2024-03-29T10:34:08Z
http://ir.lib.uwo.ca/do/oai/
oai:ir.lib.uwo.ca:physpharmpub-1010
2009-05-06T03:20:45Z
publication:physpharm
publication:physpharmpub
publication:surgerypub
publication:surgery
publication:faculties
Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection
Thulin, Pontus
Johansson, Linda
Low, Donald E.
Gan, Bing S.
Kotb, Malak
McGeer, Allison
Norrby-Teglund, Anna
Article
2006-01-17T08:00:00Z
Group A streptococcus
Streptococcal soft tissue infection
Medical Physiology
Background: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.
Methods and Findings: We characterized in vivo interactions between group A streptococci (GAS) and cells involved in innate immune responses, using human biopsies (n = 70) collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.
Conclusions: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections highlights a need for alternative therapeutic strategies.
Published in: Thulin P, Johansson L, Low DE, Gan BS, Kotb M, et al. (2006) Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection. PLoS Med 3(3): e53. doi:10.1371/journal.pmed.0030053
https://ir.lib.uwo.ca/physpharmpub/11
oai:ir.lib.uwo.ca:surgerypub-1000
2009-05-06T22:53:24Z
publication:pathol
publication:mnipub
publication:patholpub
publication:mni
publication:oncpub
publication:surgerypub
publication:surgery
publication:faculties
publication:onc
Exosomes as a Tumor Immune Escape Mechanism: Possible Therapeutic Implications
Ichim, Thomas E.
Zhong, Zhaohui
Kaushal, Shalesh
Zheng, Xiufen
Ren, Xiubao
Hao, Xishan
Joyce, James A.
Hanley, Harold H.
Riordan, Neil H.
Koropatnick, James
Bogin, Vladimir
Minev, Boris R.
Min, Wei-Ping
Tullis, Richard H.
Article
2008-07-22T07:00:00Z
Cancer therapeutics
Exosome
Exosome-immune suppression
Cancer immune suppression
Medical Immunology
Medical Microbiology
Oncology
Pathology
Surgery
Advances in cancer therapy have been substantial in terms of molecular understanding of disease
mechanisms, however these advances have not translated into increased survival in the majority of
cancer types. One unsolved problem in current cancer therapeutics is the substantial immune
suppression seen in patients. Conventionally, investigations in this area have focused on antigennonspecific
immune suppressive molecules such as cytokines and T cell apoptosis inducing
molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles
termed exosomes are involved not only in stimulation but also inhibition of immunity in
physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated
to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL.
Concentrations of exosomes from plasma of cancer patients have been associated with
spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this
paper we place the "exosome-immune suppression" concept in perspective of other tumor
immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer
immune suppression by extracorporeal removal of exosomes using hollow fiber filtration
technology.
Published in: Journal of Translational Medicine 2008, 6:37 (doi:10.1186/1479-5876-6-37). The electronic version of this article is the complete one and can be found online at: http://www.translational-medicine.com/content/6/1/37
https://ir.lib.uwo.ca/surgerypub/1
oai:ir.lib.uwo.ca:surgerypub-1001
2009-11-10T01:35:55Z
publication:surgerypub
publication:surgery
publication:faculties
Rotational Strength, Range of Motion, and Function in People with Unaffected Shoulders from Various Stages of Life
Roy, Jean-Sébastien
MacDermid, Joy C.
Boyd, Kirsty Usher
Faber, Kenneth J.
Drosdowech, Darren
Athwal, George S.
Article
2009-03-02T08:00:00Z
Rotational strength
Range of motion
Shoulder pathology
Sports Medicine, Arthroscopy, Rehabilitation, Therapy & Technology
1
4
Musculoskeletal, Neural, and Ocular Physiology
Surgery
Background: Different measurements are used to assess shoulder function, including range of motion,
strength, functional performance and self-report function. To understand disablement, it is necessary to
understand the relationship between impairments and function in persons without shoulder problems.
This study was conducted to enhance existing comparative data in subjects without upper extremity
pathology, and to assess the relationships between impairments (range of motion, strength) and selfreported
or measured function/disability. The impact of age, gender and dominance was determined.
Methods: Two-hundred ninety-four subjects with unaffected shoulders were recruited. The subjects
(mean age: 37 years old) were divided into three subgroups, 18–39, 40–59, and over 60 years of age.
During a single session, at least two of the following variables were measured: self-reported function
(shoulder disability scales), range of motion, isometric rotational strength, or upper limb functional
performance (FIT-HaNSA). Two-way analysis of variance was used to determine, for each variable, the
effects of age and gender. The relationship between the outcomes was established using Pearson product
correlations.
Results: Men were significantly stronger than women for all age categories. There was an age-related
decline in strength in men in the over-60 age category. Significant negative correlations between strength
and range of motion were demonstrated (-0.22 <r >< -0.32). Women had a significantly higher range of
motion than men for external rotation in the 40–59 age category. Furthermore, the subjects in the over-
60 age category experienced a decrease of range of motion. There was minimal disability reported in all
age groups on self-report scales. Only the Simple Shoulder Test demonstrated significant decreases in the
over-60 age category and correlated with age (r = -0.202).
Conclusion: Self-reported disability was low in individuals without upper extremity problems, although
recruitment of such individuals was difficult in the older age groups due to the high prevalence of shoulder
pathology. A low correlation between self-report disability and strength/range of motion in these
unaffected subjects reflects the lack of disability reported by all subjects without pathology despite normal
variations in strength and motion.
Published in: Sports Medicine, Arthroscopy, Rehabilitation, Therapy & Technology 2009, 1:4. doi: 10.1186/1758-2555-1-4
https://ir.lib.uwo.ca/surgerypub/2
oai:ir.lib.uwo.ca:surgerypub-1003
2009-05-12T22:30:15Z
publication:surgerypub
publication:surgery
publication:faculties
Allogeneic Endometrial Regenerative Cells: An "Off the Shelf Solution" for Critical Limb Ischemia?
Murphy, Michael P.
Wang, Hao
Patel, Amit N.
Kambhampati, Suman
Angle, Niren
Chan, Kyle
Marleau, Annette M.
Pyszniak, Andrew
Carrier, Ewa
Ichim, Thomas E.
Riordan, Neil H.
Article
2008-08-19T07:00:00Z
Critical limb ischemia
Amputation
Endometrial regenerative cell
Surgery
Critical limb ischemia (CLI) is an advanced form of peripheral artery disease which is responsible
for approximately 100,000 amputations per year in the US. Trials to date have reported clinical
improvement and reduced need for amputation in CLI patients receiving autologous bone marrow
or mobilized peripheral blood stem cells for stimulation of angiogenesis. While such treatments are
currently entering Phase III trials, practical and scientific pitfalls will limit widespread
implementation if efficacy is proven. Hurdles to be overcome include: a) reduced angiogenic
potential of autologous cells in aged patients with cardiovascular risk factors; b) invasiveness/
adverse effects of bone marrow extraction and G-CSF mobilization, respectively; and c) need for
on-site cellular manipulation. The Endometrial Regenerative Cell (ERC) is a mesenchymal-like stem
cell derived from the menstrual blood that is believed to be associated with endometrial
angiogenesis. We discuss the possibility of using allogeneic ERCs as an "off the shelf" treatment for
CLI based on the following properties: a) High levels of growth factors and matrix metalloprotease
production; b) Ability to inhibits inflammatory responses and lack of immunogenicity; and c)
Expandability to great quantities without loss of differentiation ability or karyotypic abnormalities.
Published in: Journal of Translational Medicine 2008, 6:45 (doi:10.1186/1479-5876-6-45). The electronic version of this article is the complete one and can be found online at: http://www.translational-medicine.com/content/6/1/45
https://ir.lib.uwo.ca/surgerypub/4
oai:ir.lib.uwo.ca:surgerypub-1002
2009-05-12T21:52:25Z
publication:pathol
publication:patholpub
publication:oncpub
publication:surgerypub
publication:surgery
publication:faculties
publication:onc
Feasibility Investigation of Allogeneic Endometrial Regenerative Cells
Zhong, Zhaohui
Patel, Amit N.
Ichim, Thomas E.
Riordan, Neil H.
Wang, Hao
Min, Wei-Ping
Woods, Erik J.
Reid, Michael
Mansilla, Eduardo
Marin, Gustavo H.
Drago, Hugo
Murphy, Michael P.
Minev, Boris
Article
2009-02-20T08:00:00Z
Endometrial regenerative cell
Neoangiogenesis
Multiple sclerosis
Oncology
Pathology
Surgery
Endometrial Regenerative Cells (ERC) are a population of mesenchymal-like stem cells having
pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies
suggest ERC are immune privileged and in certain situations actively suppress ongoing immune
responses. In this paper we describe the production of clinical grade ERC and initial safety
experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case
with the longest follow up, of more than one year, revealed no immunological reactions or
treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC
administration and support further studies with this novel stem cell type.
Published in: Journal of Translational Medicine 2009, 7:15 (doi:10.1186/1479-5876-7-15). The electronic version of this article is the complete one and can be found online at: http://www.translational-medicine.com/content/7/1/15
https://ir.lib.uwo.ca/surgerypub/3
oai:ir.lib.uwo.ca:surgerypub-1004
2009-05-30T01:00:50Z
publication:physpharm
publication:biochempub
publication:physpharmpub
publication:surgerypub
publication:biochem
publication:surgery
publication:faculties
Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren's Contracture
Satish, Latha
LaFramboise, William A.
O'Gorman, David B.
Johnson, Sandra
Janto, Benjamin
Gan, Bing Siang
Baratz, Mark E.
Hu, Fen Z.
Post, J. Christopher
Ehrlich, Garth D.
Kathju, Sandeep
Article
2008-04-23T07:00:00Z
Dupuytren's contracture
Significance Analysis of Microarrays
BMC Medical Genomics
1
Medical Genetics
Medical Physiology
Surgery
Dupuytren's contracture (DC) is the most common inherited connective tissue disease of humans and is hypothesized to be associated with aberrant wound healing of the palmar fascia. Fibroblasts and myofibroblasts are believed to play an important role in the genesis of DC and the fibroproliferation and contraction that are hallmarks of this disease. This study compares the gene expression profiles of fibroblasts isolated from DC patients and controls in an attempt to identify key genes whose regulation might be significantly altered in fibroblasts found within the palmar fascia of Dupuytren's patients. Total RNA isolated from diseased palmar fascia (DC) and normal palmar fascia (obtained during carpal tunnel release; 6 samples per group) was subjected to quantitative analyses using two different microarray platforms (GE Code Link™ and Illumina™) to identify and validate differentially expressed genes. The data obtained was analyzed using The Significance Analysis of Microarrays (SAM) software through which we identified 69 and 40 differentially regulated gene transcripts using the CodeLink™ and Illumina™ platforms, respectively. The CodeLink™ platform identified 18 upregulated and 51 downregulated genes. Using the Illumina™ platform, 40 genes were identified as downregulated, eleven of which were identified by both platforms. Quantitative RT-PCR confirmed the downregulation of three high-interest candidate genes which are all components of the extracellular matrix: proteoglycan 4 (PRG4), fibulin-1 (FBLN-1) transcript variant D, and type XV collagen alpha 1 chain. Overall, our study has identified a variety of candidate genes that may be involved in the pathophysiology of Dupuytren's contracture and may ultimately serve as attractive molecular targets for alternative therapies.
Published in: BMC Medical Genomics 2008, 1:10 (doi:10.1186/1755-8794-1-10). The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1755-8794/1/10
https://ir.lib.uwo.ca/surgerypub/5
oai:ir.lib.uwo.ca:biochempub-1018
2009-07-25T20:37:01Z
publication:physpharm
publication:biophysics
publication:biochempub
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:surgery
publication:biochem
publication:faculties
A Novel Mass Spectrometry-based Assay for GSK-3β Activity
Bowley, Erin
Mulvihill, Erin
Howard, Jeffrey C.
Pak, Brian J.
Gan, Bing Siang
O'Gorman, David B.
Article
2005-12-16T08:00:00Z
kinase assay
Glycogen Synthase Kinase-3beta activity
BMC Biochemistry
6
29
Biochemistry
Medical Physiology
Surgery
Background: As a component of the progression from genomic to proteomic analysis, there is a need for accurate assessment of protein post-translational modifications such as phosphorylation. Traditional kinase assays rely heavily on the incorporation of γ-P32 radiolabeled isotopes, monoclonal anti-phospho-protein antibodies, or gel shift analysis of substrate proteins. In addition to the expensive and time consuming nature of these methods, the use of radio-ligands imposes restrictions based on the half-life of the radionucleotides and pose potential health risks to researchers. With the shortcomings of traditional assays in mind, the aim of this study was to develop a high throughput, non-radioactive kinase assay for screening Glycogen Synthase Kinase-3beta (GSK-3β) activity.
Results: Synthetic peptide substrates designed with a GSK-3β phosphorylation site were assayed with both recombinant enzyme and GSK-3β immunoprecipitated from NIH 3T3 fibroblasts. A molecular weight shift equal to that of a single phosphate group (80 Da.) was detected by surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) in a GSK-3β target peptide (2B-Sp). Not only was there a dose-dependent response in molecular weight shift to the amount of recombinant GSK-3β used in this assay, this shift was also inhibited by lithium chloride (LiCl), in a dose-dependent manner.
Conclusion: We present here a novel method to sensitively measure peptide phosphorylation by GSK-3β that, due to the incorporation of substrate controls, is applicable to either purified enzyme or cell extracts. Future studies using this method have the potential to elucidate the activity of GSK-3β in vivo, and to screen enzyme activity in relation to a variety of GSK-3β related disorders.
Published in: BMC Biochemistry 2005, 6:29. doi:10.1186/1471-2091-6-29
https://ir.lib.uwo.ca/biochempub/18
oai:ir.lib.uwo.ca:oncpub-1002
2009-07-31T19:41:52Z
publication:biophysics
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
publication:onc
17561992
Tumour Dormancy in Breast Cancer: An Update
Brackstone, Muriel
Townson, Jason L.
Chambers, Ann F.
Article
2007-05-31T07:00:00Z
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Cyclophosphamide
Female
Fluorouracil
Humans
Methotrexate
Neoplasm
Residual
Recurrence
Time Factors
Breast Cancer Research
Breast Cancer Research
9
208
Medical Biophysics
Oncology
Surgery
Delayed recurrences, common in breast cancer, are well explained by the concept of tumour dormancy. Numerous publications describe clinical times to disease recurrence or death, using mathematical approaches to infer mechanisms responsible for delayed recurrences. However, most of the clinical literature discussing tumour dormancy uses data from over a half century ago and much has since changed. This review explores how current breast cancer treatment could change our understanding of the biology of breast cancer tumour dormancy, and summarizes relevant experimental models to date. Current knowledge gaps are highlighted and potential areas of future research are identified.
Published in: Breast Cancer Research, 2007, 9:208. doi:10.1186/bcr1677
https://ir.lib.uwo.ca/oncpub/2
oai:ir.lib.uwo.ca:surgerypub-1005
2009-08-04T22:55:57Z
publication:pathol
publication:mnipub
publication:patholpub
publication:mni
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
19386101
Human Embryonic Stem Cells Hemangioblast Express HLA-antigens
Basak, Grzegorz Wladyslaw
Yasukawa, Satoshi
Alfaro, Andre
Halligan, Samantha
Srivastava, Anand S.
Min, Wei-Ping
Minev, Boris
Carrier, Ewa
Article
2009-04-22T07:00:00Z
Blood Vessels
Cell Differentiation
Cell Division
Collagen
Drug Combinations
Embryonic Development
Embryonic Stem Cells
Endothelial Cells
Fluorescent Antibody Technique
HLA-A Antigens
Hemangioblasts
Hematopoiesis
Hematopoietic Stem Cells
Humans
Laminin
Proteoglycans
Journal of Translational Medicine
7
27
Surgery
Background: It has been suggested that the initial differentiation of endothelial and hematopoietic cells during embryogenesis occurs from a common progenitor, called hemangioblast (hB). We hypothesized that these cells with dual hematopoietic/endothelial potential could be used in future regenerative medicine.
Methods: We used the two-step differentiation technology to generate bipotential blast cells from human embryonic stem cells (hES). This involved short differentiation in our in vitro EB system followed by differentiation in semisolid culture medium supplemented with mixture of cytokines.
Results: The occurrence of blast-colony-forming cells (BL-CFC) during EB differentiation (day 0-6) was transient and peaked on day 3. The emergence of this event was associated with expression of mesoderm gene T, and inversely correlated with expression of endoderm gene FoxA2. Similarly, the highest BL-CFC number was associated with increase in expression of early hematopoietic/endothelial genes: CD34, CD31 and KDR. The derived colonies were composed of 30-50 blast cells on day 6 in culture. These cells had homogenous appearance in Wright-Giemsa stain, but to a different extent expressed markers of immature hematopoietic and endothelial cells (CD31, CD34, VE-cadherin, Flt-1) and mature differentiated cells (CD45, CD33, CD146). We found that some of them expressed fetal and embryonic globin genes. Interestingly, these cells expressed also HLA class I molecules, however at very low levels compared to endothelial and hematopoietic cells. The blast cells could be successfully differentiated to hematopoietic cells in a CFU assay. In these conditions, blast cells formed CFU-M colonies (63.4 +/- 0.8%) containing macrophages, BFU-E colonies (19.5 +/- 3.5%) containing nucleated red blood cells, and CFU-EM colonies (17.1 +/- 2.7%) composed of macrophages and nucleated erythrocytes. Cells of CFU-EM and BFU-E colonies expressed both epsilon - and gamma- globin genes, but not adult-type gamma-globin. When in endothelial cell culture conditions, blast cells differentiated to endothelial cells which had the ability to take up Dil-Ac-LDL and to form complex vascular networks in Matrigel.
Conclusion: 1) Hematoendothelial precursors exist transiently in early embryonic development and form single cell-derived colonies; 2) their differentiation can be tracked by the use of chosen molecular markers; 3) blast colonies consist of cells having properties of endothelial and hematopoietic precursors, however the issue of their ability to maintain dual properties over time needs to be further explored; 4) blast cells can potentially be used in regenerative medicine due to their low expression of HLA molecules.
Published in: Journal of Translational Medicine, 2009, 7:27. doi: 10.1186/1479-5876-7-27
https://ir.lib.uwo.ca/surgerypub/6
oai:ir.lib.uwo.ca:surgerypub-1007
2009-09-16T00:39:07Z
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
16390542
A Novel Method of Modifying Immune Responses by Vaccination with Lipiodol-siRNA Mixtures
Ichim, Thomas E.
Popov, Igor A.
Riordan, Neil H.
Izadi, Hamid
Zhong, Zaohui
Yijian, Li
Sher, Salman
Oleinik, Eugenia K.
Article
2006-01-03T08:00:00Z
Journal of Translational Medicine
4
2
Surgery
The dendritic cell (DC) possesses the ability to stimulate both T helper 1 (Th1) and Th2 responses depending on activation stimuli. Although it is known that chemically or genetically modified DC can be used therapeutically to steer immune responses towards either Th1 or Th2, cellular therapy with ex vivo manipulated DC is clinically difficult. Here we demonstrate a novel method of switching immune responses from Th1 to Th2 through in vivo immune modulation by administration of siRNA. We demonstrate that siRNA targeting of the IL-12p35 gene leads to a Th2 bias in vitro through an IL-10 dependent mechanism. In vivo administration of siRNA admixed with the oil-based contrast agent lipiodol in the presence of antigen and adjuvant induced a deviation in recall response to reduced production of IFN-gamma and augmented IL-4 response using either KLH or ovalbumin. This simple method of in vivo modification of immune response possesses therapeutic potential in Th1-mediated diseases such as multiple sclerosis and autoimmune diabetes.
Published in: Journal of Translational Medicine, 2006, 4:2. doi: 10.1186/1479-5876-4-2
https://ir.lib.uwo.ca/surgerypub/8
oai:ir.lib.uwo.ca:surgerypub-1006
2009-09-16T00:32:03Z
publication:physpharm
publication:mnipub
publication:biophysics
publication:biochempub
publication:mni
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:biochem
publication:surgery
publication:faculties
12866952
Elevated Levels of β-catenin and Fibronectin in Three-dimensional Collagen Cultures of Dupuytren's Disease Cells are Regulated by Tension in Vitro
Howard, Jeffrey C.
Varallo, Vincenzo M.
Ross, Douglas C.
Roth, James H.
Faber, Kenneth J.
Alman, Benjamin
Gan, Bing Siang
Article
2003-07-16T07:00:00Z
Biomechanics
Cells
Cultured
Collagen
Cytoskeletal Proteins
Dupuytren's Contracture
Fibroblasts
Fibronectins
Humans
Trans-Activators
beta Catenin
BMC Musculoskeletal Disorders
4
16
Surgery
Background: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in the development of scar-like, collagen-rich disease cords within specific palmar fascia bands. Although the molecular pathology of DD is unknown, recent evidence suggests that beta-catenin may play a role. In this study, collagen matrix cultures of primary disease fibroblasts show enhanced contraction and isometric tension-dependent changes in beta-catenin and fibronectin levels.
Methods: Western blots of beta-catenin and fibronectin levels were determined for control and disease primary cell cultures grown within stressed- and attached-collagen matrices. Collagen contraction was quantified, and immunocytochemistry analysis of filamentous actin performed.
Results: Disease cells exhibited enhanced collagen contraction activity compared to control cells. Alterations in isometric tension of collagen matrices triggered dramatic changes in beta-catenin and fibronectin levels, including a transient increase in beta-catenin levels within disease cells, while fibronectin levels steadily decreased to levels below those seen in normal cell cultures. In contrast, both fibronectin and beta-catenin levels increased in attached collagen-matrix cultures of disease cells, while control cultures showed only increases in fibronectin levels. Immunocytochemistry analysis also revealed extensive filamentous actin networks in disease cells, and enhanced attachment and spreading of disease cell in collagen matrices.
Conclusion: Three-dimensional collagen matrix cultures of primary disease cell lines are more contractile and express a more extensive filamentous actin network than patient-matched control cultures. The elevated levels of beta-catenin and Fn seen in collagen matrix cultures of disease fibroblasts can be regulated by changes in isometric tension.
Published in: BMC Musculoskeletal Disorders, 2003, 4:16. doi: 10.1186/1471-2474-4-16
https://ir.lib.uwo.ca/surgerypub/7
oai:ir.lib.uwo.ca:surgerypub-1008
2010-04-26T12:01:35Z
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
14588078
Pain and Disability Reported in the Year Following a Distal Radius Fracture: A Cohort Study
MacDermid, Joy C.
Roth, James H.
Richards, Robert S.
Article
2003-10-31T08:00:00Z
Activities of Daily Living
Adolescent
Adult
Aged
Cohort Studies
Disability Evaluation
Female
Humans
Male
Middle Aged
Pain
Pain Measurement
Questionnaires
Radius Fractures
Severity of Illness Index
Time Factors
BMC Musculoskeletal Disorders
4
24
http://dx.doi.org/10.1186/1471-2474-4-24
Surgery
Background: Distal radius fractures are a common injury that cause pain and disability. The purpose of this study was to describe the pain and disabilities experienced by patients with a distal radius fracture in the first year following fracture.
Methods: A prospective cohort study of 129 patients with a fracture of the distal radius was conducted. Patients completed a Patient-rated Wrist Evaluation at their baseline clinic visit and at 2, 3, 6 and 12 months following their fracture. The frequency/severity of pain and disabilities reported was described at each time point.
Results: The majority of patients experienced mild pain at rest and (very) severe high levels of pain with movement during the first two-months following distal radius fracture. This time is also associated with (very) severe difficulty in performing specific functional activities and moderate to severe difficulty in four domains of usual activity. The majority of recovery occurred within six-months, but symptoms persisted for a small minority of patients at one-year following fracture. Patients had the most difficulty with carrying ten pounds and pushing up from a chair. Resumption of usual personal care and household work preceded, and was more complete, than work and recreational participation.
Conclusions: This study demonstrated that the normal course of recovery following a distal radius fracture is one where severe symptoms subside within the first two-months and the majority of patients can be expected to have minimal pain and disability by six-months following fracture. This information can be used when planning interventions and assessing whether the progress of a patient is typical of other patients.
https://ir.lib.uwo.ca/surgerypub/10
oai:ir.lib.uwo.ca:surgerypub-1009
2009-09-22T01:21:35Z
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
18005405
Endometrial Regenerative Cells: A Novel Stem Cell Population
Meng, Xiaolong
Ichim, Thomas E.
Zhong, Jie
Rogers, Andrea
Yin, Zhenglian
Jackson, James
Wang, Hao
Ge, Wei
Bogin, Vladimir
Chan, Kyle W.
Thébaud, Bernard
Riordan, Neil H.
Article
2007-11-15T08:00:00Z
Blood
Cell Adhesion
Cell Culture Techniques
Cell Differentiation
Cell Lineage
Cell Proliferation
Endometrium
Female
Humans
Karyotyping
Menstrual Cycle
Neovascularization
Physiologic
Phenotype
Stem Cells
Journal of Translational Medicine
5
57
Surgery
Angiogenesis is a critical component of the proliferative endometrial phase of the menstrual cycle. Thus, we hypothesized that a stem cell-like population exist and can be isolated from menstrual blood. Mononuclear cells collected from the menstrual blood contained a subpopulation of adherent cells which could be maintained in tissue culture for >68 doublings and retained expression of the markers CD9, CD29, CD41a, CD44, CD59, CD73, CD90 and CD105, without karyotypic abnormalities. Proliferative rate of the cells was significantly higher than control umbilical cord derived mesenchymal stem cells, with doubling occurring every 19.4 hours. These cells, which we termed "Endometrial Regenerative Cells" (ERC) were capable of differentiating into 9 lineages: cardiomyocytic, respiratory epithelial, neurocytic, myocytic, endothelial, pancreatic, hepatic, adipocytic, and osteogenic. Additionally, ERC produced MMP3, MMP10, GM-CSF, angiopoietin-2 and PDGF-BB at 10-100,000 fold higher levels than two control cord blood derived mesenchymal stem cell lines. Given the ease of extraction and pluripotency of this cell population, we propose ERC as a novel alternative to current stem cells sources.
Published in: Journal of Translational Medicine, 2007, 5:57. doi: 10.1186/1479-5876-5-57
https://ir.lib.uwo.ca/surgerypub/11
oai:ir.lib.uwo.ca:epidempub-1009
2009-09-21T00:35:13Z
publication:epidem
publication:oncpub
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
publication:onc
publication:epidempub
15447791
Neoadjuvant or Adjuvant Therapy for Resectable Esophageal Cancer: A Clinical Practice Guideline
Malthaner, Richard A.
Wong, Rebecca K. S.
Rumble, R. Bryan
Zuraw, Lisa
Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care
Article
2004-09-24T07:00:00Z
Adenocarcinoma
Adult
Carcinoma
Squamous Cell
Chemotherapy
Adjuvant
Esophageal Neoplasms
Humans
Ontario
Population Surveillance
Radiotherapy
Adjuvant
BMC Cancer
BMC Cancer
4
67
Biostatistics
Epidemiology
Oncology
Surgery
Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. A clinical practice guideline was developed based on a systematic review investigating neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer.
Methods: A systematic review with meta-analysis was developed and clinical recommendations were drafted. External review of the practice guideline report by practitioners in Ontario, Canada was obtained through a mailed survey, and incorporated. Final approval of the practice guideline was obtained from the Practice Guidelines Coordinating Committee.
Results: The systematic review was developed and recommendations were drafted, and the report was mailed to Ontario practitioners for external review. Ninety percent of respondents agreed with both the evidence summary and the draft recommendations, while only 69% approved of the draft recommendations as a practice guideline. Based on the external review, a revised document was created. The revised practice guideline was submitted to the Practice Guidelines Coordinating Committee for review. All 11 members of the PGCC returned ballots. Eight PGCC members approved the practice guideline report as written and three members approved the guideline conditional on specific concerns being addressed. After these recommended changes were made, the final practice guideline report was approved.
Conclusion: In consideration of the systematic review, external review, and subsequent Practice Guidelines Coordinating Committee revision suggestions, and final approval, the Gastrointestinal Cancer Disease Site Group recommends the following:For adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.
Published in: BMC Cancer, 2004, 4:67. doi: 10.1186/1471-2407-4-67
https://ir.lib.uwo.ca/epidempub/10
oai:ir.lib.uwo.ca:epidempub-1010
2009-11-03T08:28:48Z
publication:epidem
publication:oncpub
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
publication:onc
publication:epidempub
15447788
Neoadjuvant or Adjuvant Therapy for Resectable Esophageal Cancer: A Systematic Review and Meta-analysis
Malthaner, Richard A.
Wong, Rebecca K. S.
Rumble, R. Bryan
Zuraw, Lisa
Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care
Article
2004-09-24T07:00:00Z
Chemotherapy
Adjuvant
Esophageal Neoplasms
Humans
Hyperthermia
Induced
Neoadjuvant Therapy
Radiotherapy
Adjuvant
Randomized Controlled Trials as Topic
BMC Medicine
BMC Medicine
2
35
Biostatistics
Epidemiology
Oncology
Surgery
Background: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis.
Methods: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced.MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports.Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios.
Results: Thirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches.Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy versus postoperative radiotherapy.- Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate.- Postoperative chemotherapy versus postoperative radiotherapy.- Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide.Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons:- Preoperative radiotherapy compared with surgery alone (five randomized trials).- Postoperative radiotherapy compared with surgery alone (five randomized trials).- Preoperative chemotherapy versus surgery alone (six randomized trials).- Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials).- Preoperative chemoradiation therapy versus surgery alone (six randomized trials).Single randomized controlled trials detected differences in mortality between treatments for the following comparison:- Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia.Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison:- Postoperative chemotherapy compared with surgery alone (two randomized trials).Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons:- Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery.- Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy.
Conclusion: For adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice.
Published in: BMC Medicine, 2004, 2:35. doi: 10.1186/1741-7015-2-35
https://ir.lib.uwo.ca/epidempub/19
oai:ir.lib.uwo.ca:patholpub-1003
2009-09-23T22:42:11Z
publication:pathol
publication:patholpub
publication:surgerypub
publication:surgery
publication:faculties
Primary PEComa of the Bladder Treated with Primary Excision and Adjuvant Interferon-alpha Immunotherapy: A Case Report
Parfitt, Jeremy R.
Bella, Anthony J.
Wehrli, Bret M.
Izawa, Jonathan I.
Article
2006-08-22T07:00:00Z
Perivascular epithelioid cell tumor
PEComa
interferon-alpha immunotherapy
BMC Urology
BMC Urology
6
20
Medical Pathology
Surgery
Urology
Background: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms of uncertain malignant potential, which have in common the co-expression of muscle and melanocytic immunohistochemical markers.
Case presentation: A 48-year-old man presented with dysuria, passage of urinary sediment and lower abdominal discomfort. A three centimeter mass was identified by cystoscopy in the posterior midline of the bladder. Computerized tomography suggested an enterovesical fistula. The patient underwent laparotomy, partial cystectomy and partial small bowel resection. Pathological examination revealed PEComa of the bladder. The patient underwent adjuvant interferon-α immunotherapy. Subsequent follow-up procedures, including cystoscopy and imaging, have not revealed evidence of recurrence. The patient is clinically free of disease 48 months after surgery.
Conclusion: This case represents the second documented PEComa of bladder and demonstrates that adjuvant therapies, including anti-angiogenic and immunotherapy, may be considered for patients with locally advanced or metastatic genitourinary PEComa.
Published in: BMC Urology, 2006, 6:20. doi: 10.1186/1471-2490-6-20
https://ir.lib.uwo.ca/patholpub/4
oai:ir.lib.uwo.ca:surgerypub-1010
2009-09-23T22:54:09Z
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
18215287
Fluid Lavage in Patients with Open Fracture Wounds (FLOW): An International Survey of 984 Surgeons
Petrisor, Brad
Jeray, Kyle
Schemitsch, Emil
Hanson, Beate
Sprague, Sheila
Sanders, David
Bhandari, Mohit
FLOW Investigators
Article
2008-01-23T08:00:00Z
Adult
Anti-Infective Agents
Local
Bacitracin
Chlorhexidine
Cross-Sectional Studies
Fractures
Open
Health Care Surveys
Humans
Hydrogen Peroxide
Iodine Compounds
Irrigation
Middle Aged
Orthopedics
Physician's Practice Patterns
Pressure
Questionnaires
Randomized Controlled Trials as Topic
Research Design
Soaps
Sodium Chloride
BMC Musculoskeletal Disorders
9
7
Surgery
Background: Although surgeons acknowledge the importance of irrigating open fracture wounds, the choice of irrigating fluid and delivery pressure remains controversial. Our objective was to clarify current opinion with regard to the irrigation of open fracture wounds.
Methods: We used a cross-sectional survey and a sample-to-redundancy strategy to examine surgeons' preferences in the initial management of open fracture wounds. We mailed this survey to members of the Canadian Orthopaedic Association and delivered it to attendees of an international fracture course (AO, Davos, Switzerland).
Results: Of the 1,764 surgeons who received the questionnaire, 984 (55.8%) responded. In the management of open wounds, the majority of surgeons surveyed, 676 (70.5%), favoured normal saline alone. Bacitracin solution was used routinely by only 161 surgeons (16.8%). The majority of surgeons, 695 (71%) used low pressures when delivering the irrigating solution to the wound. There was, however considerable variation in what pressures constituted high versus low pressure lavage. The overwhelming majority of surgeons, 889 (94.2%), reported they would change their practice if a large randomized controlled trial showed a clear benefit of an irrigating solution - especially if it was different from the solution they used.
Conclusion: The majority of surgeons favour both normal saline and low pressure lavage for the initial management of open fracture wounds. However, opinions varied as regards the comparative efficacy of different solutions, the use of additives and high versus low pressure. Surgeons have expressed considerable support for a trial evaluating both irrigating solutions and pressures.
Published in: BMC Musculoskeletal Disorders, 2008, 9:7. doi: 10.1186/1471-2474-9-7
https://ir.lib.uwo.ca/surgerypub/13
oai:ir.lib.uwo.ca:surgerypub-1011
2009-09-17T04:53:12Z
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
19393041
Non-expanded Adipose Stromal Vascular Fraction Cell Therapy for Multiple Sclerosis
Riordan, Neil H.
Ichim, Thomas E.
Min, Wei-Ping
Wang, Hao
Solano, Fabio
Lara, Fabian
Alfaro, Miguel
Rodriguez, Jorge Paz
Harman, Robert J.
Patel, Amit N.
Murphy, Michael P.
Lee, Roland R.
Minev, Boris
Article
2009-04-24T07:00:00Z
Adipose Tissue
Animals
Bone Marrow Transplantation
Dogs
Horses
Humans
Lymphocyte Activation
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
Models
Animal
Multiple Sclerosis
Stromal Cells
T-Lymphocytes
Regulatory
Tissue Therapy
Journal of Translational Medicine
7
29
Surgery
The stromal vascular fraction (SVF) of adipose tissue is known to contain mesenchymal stem cells (MSC), T regulatory cells, endothelial precursor cells, preadipocytes, as well as anti-inflammatory M2 macrophages. Safety of autologous adipose tissue implantation is supported by extensive use of this procedure in cosmetic surgery, as well as by ongoing studies using in vitro expanded adipose derived MSC. Equine and canine studies demonstrating anti-inflammatory and regenerative effects of non-expanded SVF cells have yielded promising results. Although non-expanded SVF cells have been used successfully in accelerating healing of Crohn's fistulas, to our knowledge clinical use of these cells for systemic immune modulation has not been reported. In this communication we discuss the rationale for use of autologous SVF in treatment of multiple sclerosis and describe our experiences with three patients. Based on this rationale and initial experiences, we propose controlled trials of autologous SVF in various inflammatory conditions.
Published in: Journal of Translational Medicine, 2009, 7:29. doi: 10.1186/1479-5876-7-29
https://ir.lib.uwo.ca/surgerypub/9
oai:ir.lib.uwo.ca:surgerypub-1012
2010-09-14T01:59:18Z
publication:pathol
publication:patholpub
publication:oncpub
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
publication:onc
15987509
Sentinel Node Biopsy as an Adjunct to Limb Salvage Surgery for Epithelioid Sarcoma of the Hand
Seal, Alex
Tse, Raymond
Wehrli, Bret
Hammond, Alex
Temple, Claire L. F.
Article
2005-06-29T07:00:00Z
Sentinel node
Limb salvage
Epithelioid sarcoma
World Journal of Surgical Oncology
3
41
http://dx.doi.org/10.1186/1477-7819-3-41
Oncology
Pathology
Surgery
Background: Epithelioid sarcomas of the hand are rare, high-grade tumors with a propensity for regional lymphatic spread approaching 40%.
Case Presentation: A 54-year-old male with an epithelioid sarcoma of the palm was treated with neoadjuvant radiation, wide excision, and two-stage reconstruction. Sentinel lymph node biopsy was used to stage the patient's axilla. Sentinel node biopsy results were negative. The patient has remained free of local, regional and distant disease for the follow-up time of 16 months.
Conclusion: The rarity of this tumor makes definitive conclusions difficult but SLN biopsy appears to be a useful adjunct in the treatment of these sarcomas.
https://ir.lib.uwo.ca/surgerypub/14
oai:ir.lib.uwo.ca:surgerypub-1013
2009-10-08T01:16:30Z
publication:physpharm
publication:biochempub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:biochem
publication:surgery
publication:faculties
15541177
Enhanced Dupuytren's Disease Fibroblast Populated Collagen Lattice Contraction is Independent of Endogenous Active TGF-beta2
Tse, Raymond
Howard, Jeffrey
Wu, Yan
Gan, Bing Siang
Article
2004-11-12T08:00:00Z
Antibodies
Anti-Idiotypic
Cells
Cultured
Collagen
Dose-Response Relationship
Drug
Dupuytren's Contracture
Fibroblasts
Humans
Transforming Growth Factor beta
Transforming Growth Factor beta2
BMC Musculoskeletal Disorders
5
41
Medical Biochemistry
Musculoskeletal, Neural, and Ocular Physiology
Surgery
Background: Dupuytren's disease (DD) is a debilitating fibro-proliferative disorder of the hand characterized by the appearance of fibrotic lesions (nodules and cords) leading to flexion contractures of the fingers and loss of hand function. Although the molecular mechanism of DD is unknown, it has been suggested that transforming growth factor-beta2 (TGF-beta2) may play an important role in the underlying patho-physiology of the disease. The purpose of this study was to further explore this hypothesis by examining the effects of TGF-beta2 on primary cell cultures derived from patient-matched disease and normal palmar fascia tissue using a three-dimensional collagen contraction assay.
Methods: Fibroblast-populated collagen lattice (FPCL) contraction assays using primary cell cultures derived from diseased and control fascia of the same DD patients were studied in response to exogenous TGF-beta2 and neutralizing anti-TGF-beta2 antibodies.
Results: Contraction of the FPCLs occurred significantly faster and to a greater extent in disease cells compared to control cells. The addition of TGF-beta2 enhanced the rate and degree of collagen contraction in a dose-dependent fashion for both control and diseased cells. Neutralizing anti-TGF-beta2 antibodies abolished exogenous TGF-beta2 stimulated collagen contraction, but did not inhibit the enhanced basal collagen contraction activity of disease FPCL cultures.
Conclusions: Although exogenous TGF-beta2 stimulated both disease and control FPCL contraction, neutralizing anti-TGF-beta2 antibodies did not affect the elevated basal collagen contraction activity of disease FPCLs, suggesting that the differences in the collagen contraction activity of control and disease FPCL cultures are not due to differences in the levels of endogenous TGF-beta2 activity.
Published in: BMC Musculoskeletal Disorders, 2004, 5:41. doi: 10.1186/1471-2474-5-41
https://ir.lib.uwo.ca/surgerypub/15
oai:ir.lib.uwo.ca:surgerypub-1014
2009-10-12T04:56:23Z
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
16725035
Induction of Antitumor Immunity through Xenoplacental Immunization
Zhong, Zhaohui
Kusznieruk, Kornel P.
Popov, Igor A.
Riordan, Neil H.
Izadi, Hamid
Yijian, Li
Sher, Salman
Szczurko, Orest M.
Agadjanyan, Michael G.
Tullis, Richard H.
Harandi, Amir
Reznik, Boris N.
Mamikonyan, Grigor V.
Ichim, Thomas E.
Article
2006-05-25T07:00:00Z
xenoplacental immunization
antitumor immunity
Journal of Translational Medicine
4
22
Oncology
Surgery
Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.
Published in: Journal of Translational Medicine, 2006, 4:22. doi: 10.1186/1479-5876-4-22
https://ir.lib.uwo.ca/surgerypub/17
oai:ir.lib.uwo.ca:surgerypub-1015
2009-09-23T00:46:56Z
publication:physpharm
publication:biophysics
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:surgery
publication:faculties
Wnt Expression Is Not Correlated with β-catenin Dysregulation in Dupuytren's Disease
O'Gorman, David B.
Wu, Yan
Seney, Shannon
Zhu, Rebecca D.
Gan, Bing Siang
Article
2006-08-30T07:00:00Z
Wnt expression
?-catenin
Dupuytren's Disease
Journal of Negative Results in BioMedicine
5
13
Medical Biophysics
Medical Physiology
Surgery
Background: Dupuytren's contracture or disease (DD) is a fibro-proliferative disease of the hand that results in finger flexion contractures. Increased cellular β-catenin levels have been identified as characteristic of this disease. As Wnts are the most widely recognized upstream regulators of cellular β-catenin accumulation, we have examined Wnt gene expression in surgical specimens and in DD-derived primary cell cultures grown in two-dimensional monolayer culture or in three-dimensional FPCL collagen lattice cultures.
Results: The Wnt expression profile of patient-matched DD and unaffected control palmar fascia tissue was determined by a variety of complimentary methods; Affymetrix Microarray analysis, specific Wnt and degenerative primer-based Reverse Transcriptase (RT)-PCR, and Real Time PCR. Microarray analysis identified 13 Wnts associated with DD and control tissues. Degenerate Wnt RT-PCR analysis identified Wnts 10b and 11, and to a lesser extent 5a and 9a, as the major Wnt family members expressed in our patient samples. Competitive RT-PCR analysis identified significant differences between the levels of expression of Wnts 9a, 10b and 11 in tissue samples and in primary cell cultures grown as monolayer or in FPCL, where the mRNA levels in tissue > FPCL cultures > monolayer cultures. Real Time PCR data confirmed the down-regulation of Wnt 11 mRNA in DD while Wnt 10b, the most frequently isolated Wnt in DD and control palmar fascia, displayed widely variable expression between the methods of analysis.
Conclusion: These data indicate that changes in Wnt expression per se are unlikely to be the cause of the observed dysregulation of β-catenin expression in DD.
Published in: Journal of Negative Results in BioMedicine, 2006, 5:13. doi: 10.1186/1477-5751-5-13
https://ir.lib.uwo.ca/surgerypub/12
oai:ir.lib.uwo.ca:surgerypub-1016
2009-10-10T03:22:14Z
publication:physpharm
publication:biophysics
publication:biochempub
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:biochem
publication:surgery
publication:faculties
19545383
Type-1 Collagen Differentially Alters Beta-catenin Accumulation in Primary Dupuytren's Disease Cord and Adjacent Palmar Fascia Cells
Vi, Linda
Njarlangattil, Anna
Wu, Yan
Gan, Bing Siang
O'Gorman, David B.
Article
2009-06-19T07:00:00Z
Actins
Case-Control Studies
Cells
Cultured
Collagen Type I
Dupuytren's Contracture
Fascia
Humans
Recombinant Proteins
Time Factors
Transforming Growth Factor beta1
beta Catenin
BMC Musculoskeletal Disorders
10
72
Medical Biochemistry
Medical Biophysics
Medical Physiology
Surgery
Background: Dupuytren's Disease (DD) is a debilitating contractile fibrosis of the palmar fascia characterised by excess collagen deposition, contractile myofibroblast development, increased transforming growth factor-beta levels and beta-catenin accumulation. The aim of this study was to determine if a collagen-enriched environment, similar to in vivo conditions, altered beta-catenin accumulation by primary DD cells in the presence or absence of transforming growth factor-beta.
Methods: Primary DD and patient matched, phenotypically normal palmar fascia (PF) cells were cultured in the presence or absence of type-1 collagen and transforming growth factor-beta1. beta-catenin and alpha-smooth muscle actin levels were assessed by western immunoblotting and immunofluorescence microscopy.
Results: DD cells display a rapid depletion of cellular beta-catenin not evident in patient-matched PF cells. This effect was not evident in either cell type when cultured in the absence of type-1 collagen. Exogenous addition of transforming growth factor-beta1 to DD cells in collagen culture negates the loss of beta-catenin accumulation. Transforming growth factor-beta1-induced alpha-smooth muscle actin, a marker of myofibroblast differentiation, is attenuated by the inclusion of type-1 collagen in cultures of DD and PF cells.
Conclusion: Our findings implicate type-1 collagen as a previously unrecognized regulator of beta-catenin accumulation and a modifier of TGF-beta1 signaling specifically in primary DD cells. These data have implications for current treatment modalities as well as the design of in vitro models for research into the molecular mechanisms of DD.
Published in: BMC Musculoskeletal Disorders, 2009, 10:72. doi: 10.1186/1471-2474-10-72
https://ir.lib.uwo.ca/surgerypub/16
oai:ir.lib.uwo.ca:immunologypub-1007
2009-10-12T01:29:01Z
publication:pathol
publication:med
publication:mnipub
publication:patholpub
publication:mni
publication:surgerypub
publication:pmid
publication:robarts
publication:surgery
publication:immunologypub
publication:faculties
publication:institutes
publication:medpub
18522545
RIP2 Is Required for NOD Signaling But Not for Th1 Cell Differentiation and Cellular Allograft Rejection
Fairhead, T.
Lian, D.
McCully, Michelle L.
Garcia, B.
Zhong, R.
Madrenas, J.
Article
2008-06-01T07:00:00Z
Animals
Cell Differentiation
Disease Models
Animal
Graft Rejection
Mice
NF-kappa B
Oxygenases
Receptor-Interacting Protein Serine-Threonine Kinases
Signal Transduction
Th1 Cells
American Journal of Transplantation
American Journal of Transplantation
8
6
1143
1150
Immunology and Infectious Disease
Two previous reports that receptor-interacting protein (RIP)-2 knockout (RIP2-/-) mice had defective nuclear factor-kappa B (NF-kappaB) signaling and T helper (Th)1 immune responses had led us to believe that this putative serine-threonine kinase might be a possible target for transplant immunosuppression. Thus, we tested whether RIP2-/- mice were able to reject vascularized allografts. Surprisingly, we found that T cells from RIP2-/- mice proliferated and produced interferon (IFN)-gamma after allostimulation in vitro. Moreover, naïve RIP2-/- CD4+ T cells differentiated normally into Th1 or Th2 cells under appropriate cytokine microenvironments. Consistent with these findings, no difference in allograft survival was observed between wild-type and RIP2-/- recipient mice, and rejection had similar pathology and cytokine profiles in both types of recipients. RIP2 deficiency was associated with defective NOD signaling, but this did not affect T-cell receptor (TCR)-dependent activation of the canonical NF-kappaB signaling or expression of NF-kappaB genes in rejecting allografts. Our data demonstrate that RIP2-deficient mice have intact canonical NF-kappaB signaling and can mount Th1-mediated alloresponses and reject vascularized allografts as efficiently as wild-type mice, thus arguing against RIP2 as a primary target for immunosuppression.
Published in: American Journal of Transplantation,
Volume 8, Issue 6, Pages 1143 - 1150. doi: 10.1111/j.1600-6143.2008.02236.x
https://ir.lib.uwo.ca/immunologypub/7
oai:ir.lib.uwo.ca:surgerypub-1017
2009-10-13T00:03:24Z
publication:pathol
publication:mnipub
publication:patholpub
publication:mni
publication:surgerypub
publication:pmid
publication:robarts
publication:immunologypub
publication:surgery
publication:institutes
publication:faculties
17082607
Double-Negative T Cells, Activated by Xenoantigen, Lyse Autologous B and T Cells Using a Perforin/Granzyme-Dependent, Fas-Fas Ligand-Independent Pathway
Zhang, Zhu-Xu
Ma, Yuexia
Wang, Hao
Arp, Jacqueline
Jiang, Jifu
Huang, Xuyan
He, Kathy M.
Garcia, Bertha
Madrenas, Joaquím
Zhong, Robert
Article
2006-11-15T08:00:00Z
Adoptive Transfer
Animals
Antigens
CD95
Antigens
Heterophile
B-Lymphocyte Subsets
Cell Communication
Cell Death
Coculture Techniques
Cytotoxicity
Immunologic
Fas Ligand Protein
Graft Survival
Granzymes
Heart Transplantation
Lymphocyte Activation
Membrane Glycoproteins
Mice
Mice
Inbred BALB C
Mice
Inbred C57BL
Mice
Knockout
Perforin
Pore Forming Cytotoxic Proteins
Rats
Rats
Inbred BN
Rats
Inbred Lew
Signal Transduction
Spleen
T-Lymphocyte Subsets
The Journal of Immunology
177
10
6920
6929
Immunology and Infectious Disease
Pathology
Surgery
The ability to control the response of B cells is of particular interest in xenotransplantation as Ab-mediated hyperacute and acute xenograft rejection are major obstacles in achieving long-term graft survival. Regulatory T cells have been proven to play a very important role in the regulation of immune responses to self or non-self Ags. Previous studies have shown that TCRalphabeta+CD3+CD4-CD8- (double-negative (DN)) T cells possess an immune regulatory function, capable of controlling antidonor T cell responses in allo- and xenotransplantation through Fas-Fas ligand interaction. In this study, we investigated the possibility that xenoreactive DNT cells suppress B cells. We found that DNT cells generated from wild-type C57BL/6 mice expressed B220 and CD25 after rat Ag stimulation. These xenoreactive B220+CD25+ DNT cells lysed activated, but not naive, B and T cells. This killing, which took place through cell-cell contact, required participation of adhesion molecules. Our results indicate that Fas ligand, TGF-beta, TNF-alpha, and TCR-MHC recognition was not involved in DNT cell-mediated syngenic cell killing, but instead this killing was mediated by perforin and granzymes. The xenoreactive DNT cells expressed high levels of granzymes in comparison to allo- or xenoreactive CD8+ T cells. Adoptive transfer of DNT cells in combination with early immune suppression by immunosuppressive analog of 15-deoxyspergualin, LF15-0195, significantly prolonged rat heart graft survival to 62.1 +/- 13.9 days in mice recipients. In conclusion, this study suggests that xenoreactive DNT cells can control B and T cell responses in perforin/granzyme-dependent mechanisms. DNT cells may be valuable in controlling B and T cell responses in xenotransplantation.
https://ir.lib.uwo.ca/surgerypub/18
oai:ir.lib.uwo.ca:surgerypub-1018
2011-05-29T22:38:45Z
publication:pathol
publication:mnipub
publication:patholpub
publication:mni
publication:surgerypub
publication:pmid
publication:robarts
publication:immunologypub
publication:surgery
publication:institutes
publication:faculties
16539628
A Synergistic Effect Between PG490-88 and Tacrolimus Prolongs Renal Allograft Survival in Monkeys
Chen, G.
Sun, H.
Arp, J.
Garcia, B.
Wang, X.
Wise, Y.
Liu, W.
Ramcharran, S.
Huang, X.
Xiang, Y.
Yang, H.
Fang, Z.
Madrenas, J.
Sudo, Y.
Tamura, K.
Zhong, R.
Article
2006-04-01T08:00:00Z
Animals
Cell Proliferation
Diterpenes
Drug Synergism
Graft Rejection
Graft Survival
Haplorhini
Immunoglobulin M
Immunosuppressive Agents
Interferon-gamma
Interleukin-2
Kidney Transplantation
Male
NF-kappa B
NFATC Transcription Factors
T-Lymphocytes
Tacrolimus
Transcriptional Activation
American Journal of Transplantation
6
4
714
723
http://dx.doi.org/10.1111/j.1600-6143.2006.01257.x
Allergy and Immunology
Pathology
Surgery
<p>This study was undertaken to determine if PG490-88 and tacrolimus (Tac) act synergistically to prevent renal allograft rejection in monkeys and to explore possible mechanisms of synergy between these agents. MHC-mismatched renal allografts were transplanted into cynomolgus monkeys after bilateral nephrectomy. Recipients were divided into the following groups: (i) no treatment; (ii) PG490-88 (0.03 mg/kg); (iii) Tac (1 mg/kg); (iv) PG490-88 (0.01 mg/kg) + Tac (1 mg/kg) and (v) PG490-88 (0.03 mg/kg) + Tac (1 mg/kg). Through synergy PG490-88 and Tac inhibited anti-CD3/PMA-induced T-cell proliferation and IFN-gamma expression in vitro. Tac monotherapy only marginally prolonged survival (27 +/- 3.2 days), while the combination of PG490-88 and Tac significantly prolonged graft survival to a median of 99 days (PG490-88 at 0.03 mg) and 38.5 days (PG490-88 at 0.01 mg/kg). Prolonged survival correlated with inhibited IgM production as well as reduced T-cell infiltration, IL-2 protein expression and NF-AT/NF-kappaB activity. We conclude that PG490-88 and a subtherapeutic dose of Tac significantly prolong renal allograft survival in monkeys through the synergistic inhibition of T-cell activation and a decrease in IFN-gamma production and NF-AT/NF-kappaB activity.</p>
https://ir.lib.uwo.ca/surgerypub/19
oai:ir.lib.uwo.ca:oncpub-1010
2009-10-24T03:18:49Z
publication:biophysics
publication:epidem
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
publication:onc
publication:epidempub
19672424
Post-Operative Extended Volume External Beam Radiation Therapy in High Risk Esophageal Cancer Patients: A Prospective Experience
Yu, E.
Tai, P.
Younus, J.
Malthaner, R.
Truong, P.
Stitt, L.
Rodrigues, G.
Ash, R.
Dar, R.
Yaremko, B.
Tomiak, A.
Dingle, B.
Sanatani, M.
Vincent, M.
Kocha, W.
Fortin, D.
Inculet, R.
Article
2009-01-01T08:00:00Z
Pilot study
cancer
esophagus
extended volume
irradiation
Current Oncology
Current Oncology
16
4
48
54
Medical Biophysics
Oncology
Surgery
Background and purpose: Extended volume external beam radiation therapy (RT) following esophagectomy is controversial. This prospective study evaluates the feasibility of extended volume RT treatment in high-risk esophagectomy patients with cervical anastomosis receiving post–operative combined chemo-radiation therapy. Patients and methods: From 2001-2006, 15 patients with resected esophageal cancer were prospectively accrued to this pilot study, to evaluate the adverse effects of extended volume RT. Eligibility criteria were pathologically proven esophageal malignancy, T3-4, N0-1, disease amenable to surgical resection and esophagectomy with or without resection margin involvement. Patients with distant metastases (M1) and patients treated with previous RT were excluded. All 15 patients received four cycles of 5-fluorouracil-based chemotherapy. External beam RT utilized conformal computerized tomography (CT) planning, with multi-field arrangement tailored to the pathological findings with clinical target volume encompassing the primary tumour bed and anastomotic site in the neck. The radiation therapy dose was 50.40Gy at 1.8Gy per fraction, delivered concurrently with the third cycle of chemotherapy. Outcomes were disease-free survival (DFS) and overall survival (OS), calculated by Kaplan–Meier method. Treatment-related toxicities were assessed using NCI-CTC Grading System. Results: There were 10 male and 5 female patients. The median age was 64 years (ranging 48 to 80 years). The TNM stages included one T3N0, two T2N1, eleven T3N1 and one T4N1. The histopathology included 5 adenocarcinomas and 10 squamous cell carcinomas. Resection margins were clear in 10 patients. The median follow up time was 19 months (range: 3.5-53.4 months). Delay in chemotherapy occurred in 20% of patients and dose reduction was required in 13.3% of patients prior to radiation therapy. During the concurrent chemo-radiation therapy phase, 20% and 6.6% had chemotherapy delay and dose reduction, respectively. No patient experienced treatment related acute and chronic esophagitis of > Grade 2. Disease recurrence occurred in 40% (6/15) and the median time to relapse was 24 months. There was no tumour recurrence at the anastomotic site. The median DFS and OS rate were 23 months and 21 months, respectively. Conclusion: Extended volume external beam radiation therapy encompassing the tumour bed and the anastomotic site is feasible and safe after esophagectomy. These findings support proceeding with a larger trial to assess its efficacy in patients with high-risk esophageal cancer.
https://ir.lib.uwo.ca/oncpub/10
oai:ir.lib.uwo.ca:oncpub-1011
2009-10-24T03:37:20Z
publication:biophysics
publication:epidem
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
publication:onc
publication:epidempub
15542160
Is Extended Volume External Beam Radiation Therapy Covering the Anastomotic Site Beneficial in Post-esophagectomy High Risk Patients?
Yu, Edward
Dar, Rashid
Rodrigues, George B.
Stitt, Larry
Videtic, Gregory M. M.
Truong, Pauline
Tomiak, Anna
Ash, Robert
Brecevic, Ed
Inculet, Richard
Malthaner, Richard
Vincent, Mark
Craig, Ian
Kocha, Walter
Lefcoe, Michael
Article
2004-11-01T08:00:00Z
Adult
Aged
Aged
80 and over
Anastomosis
Surgical
Brachytherapy
Combined Modality Therapy
Esophageal Neoplasms
Esophagectomy
Female
Humans
Male
Middle Aged
Neoplasm Recurrence
Local
Neoplasm Staging
Probability
Prognosis
Radiotherapy Dosage
Radiotherapy
Adjuvant
Registries
Retrospective Studies
Risk Assessment
Sensitivity and Specificity
Survival Analysis
Time Factors
Treatment Outcome
Radiotherapy and Oncology
Radiotherapy and Oncology
73
2
141
148
Oncology
Surgery
Background and purpose: To assess the impact of extended volume radiation therapy (RT) with anastomotic coverage on local control in high risk post-operative esophageal cancer patients.
Patients and methods: This is a retrospective study of high risk (T(3), T(4), nodes positive, with or without margin involvement) post-operative esophageal cancer patients treated at London Regional Cancer Centre from 1989 to 1999. After esophagectomy, all patients received adjuvant combined modality therapy consisting of four cycles of fluorouracil-based chemotherapy, and loco-regional RT with or without coverage of the anastomotic site. RT dose ranged from 45 to 60 Gy at 1.8-2.0 Gy/fraction with treatment fields tailored to the pathologic findings and location of the anastomosis. CT planning was used in all patients to design spinal cord sparing beam arrangements. First relapse rate (first incidence of an event), disease specific survival and overall survival were calculated by Chi-Square, Log-Rank, and Kaplan-Meier (K-M) methods.
Results: During the study period, 72 patients had underwent esophagectomy and were considered for adjuvant chemoradiation therapy. Three patients were excluded due to disease progression prior to therapy. The 69 remaining patients formed the study cohort for the present analysis. The median age of the study group was 60 years (range 35-82 years). Pathologic stage distribution (AJCC 1997 staging) was T(2,3) N(1) in 94% patients, 65% of the cases were adenocarcinoma and had undergone transhiatal esophagectomy (86%) with positive/close margins in 34 (49%) patients. Median follow-up was 30.5 months (range 3.4-116.3 months). Two- and 5-year actuarial overall survivals rates were 50 and 31%, respectively. First relapse rate after adjuvant therapy was 63.7% (n = 44) and median time to relapse was 27.2 months. Anastomosis recurrence rates were 29% with small volume and 0% with extended volume RT (P = 0.041). Local and regional relapse occurred in 74.2% of patients treated with small volume RT compared to 15.4% in patients treated with extended volume RT (P < 0.001). After adjusting for resection margin status, the local control benefit of extended volume RT remained significant (P = 0.003). Treatment interruptions and late gastrointestinal toxicity were not significantly increased with the use of extended volume RT.
Conclusions: A significant decrease in local and regional relapse without added late toxicity was achieved with the use of extended volume RT encompassing the anastomotic site post-operatively in high risk esophageal cancer patients.
Published in: Radiotherapy and Oncology, Volume 73, Issue 2, November 2004, Pages 141-148. doi: 10.1016/j.radonc.2004.08.024
https://ir.lib.uwo.ca/oncpub/11
oai:ir.lib.uwo.ca:oncpub-1012
2009-10-26T00:13:46Z
publication:biophysics
publication:epidem
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:surgery
publication:faculties
publication:onc
publication:epidempub
Definitive Radiation Therapy Management for Medically Non-resectable Clinically Localised Non-small Cell Lung Cancer: Results & Prognostic Factors
Yu, Edward
Tai, Patricia
Ash, Robert
Lee, Michael
Stitt, Larry
Rodrigues, George
Dar, Rashid
Vincent, Mark
Inculet, Richard
Malthaner, Richard
Article
2007-01-01T08:00:00Z
radiation therapy
lung cancer
Nowotwory Journal of Oncology
Nowotwory Journal of Oncology
57
6
263
269
Epidemiology
Oncology
Surgery
The aim of this paper is to review the experience of radical radiation therapy and the prognostic factors of patient outcome for clinically localised, medically inoperable non-small cell lung cancer (NSCLC) patients. Clinically staged node-negative NSCLC patients who were not a surgical candidates due to co-morbid diseases but who were eligible for curative treatment, were reviewed in the London Regional Cancer Program (LRCP). This study population was treated between 1st Jan 1985 to 31st Jan 2004. Patients were excluded if they were previously treated with chest radiotherapy. Patients with localised disease, but who refused surgery, were also included in the study. Eligible patients received radiation therapy which was given via localised portals and underwent simulation prior to therapy. The dose prescription range was from 50 Gy in 2.5 Gy per fraction to 60 Gy in 2 Gy per fraction. Hazard ratios and P-values were determined for time to recurrence and patient survival. A total of 74 patients met the study eligibility criteria. The median age of the cohort was 70 years (range 38-92 years). The cohort consisted of 52 males and 22 females. 39/74 (53%) had a pathological diagnosis of squamous cell carcinoma. Clinical stages were 21 (28%) T1 , 40 (54%) T2 , and 13 (18%) T3 , respectively. 59/74 (78%) completed their planned radical radiotherapy but 15/74 declined radiotherapy. The median follow-up time was 17.6 months (range 0.4-123.6 months). For patients who completed radiotherapy, the two-year and five-year disease-free survival (DFS) rates were 38.1% and 11.4%. Overall survival (OS) two-year and five-year rates were 33.2% and 6.9%, respectively. The median DFS and OS for T1 , T2 , and T3 were 18.7, 14, 15 months; and 23.1, 18.5, 14.5 months, respectively. Patients who received radiotherapy compared to those who did not, had median lung cancer-specific survival (CSS) times of 21 months and 4.9 months (P<0.001); OS times of 20 months and 5 months (P<0.001), respectively. Tumour size had impact on patient survival in univariate (P=0.004) and multivariate (P=0.002) analyses. In conclusion, radical radiotherapy significantly improves survival for patients with medically inoperable clinically staged localised NSCLC, and tumour size is a predictor of patient outcome. The OS, CSS, and DFS rates for patients with tumour size greater than 6 cm are significantly worse than those with smaller size tumours.
https://ir.lib.uwo.ca/oncpub/12
oai:ir.lib.uwo.ca:oncpub-1016
2009-10-26T01:16:21Z
publication:biophysics
publication:epidem
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:surgery
publication:faculties
publication:onc
publication:epidempub
The 4th annual Ontario Thoracic Cancer Conference at Niagara-on-the-lake
Ung, Y. C.
Yu, E.
Malthaner, R.
Burkes, R.
Ellis, P.
Goss, G.
Solow, H.
Irvine, S.
Laffan, S.
Article
2009-01-01T08:00:00Z
lung cancer
esophageal cancer
molecular targeted therapies
Current Oncology
Current Oncology
16
5
111
119
Oncology
The 4th annual Ontario Thoracic Cancer Conference at Niagara-on-the-lake focused on the themes of innova- tions in the management of lung cancer, controversies in the management of esophageal cancer, and molecu- lar targeted therapies in lung cancer. This conference summary highlights the presentations and provides clinicians with a referenced update on these topics.
https://ir.lib.uwo.ca/oncpub/16
oai:ir.lib.uwo.ca:oncpub-1028
2009-11-02T00:38:49Z
publication:biophysics
publication:epidem
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:surgery
publication:faculties
publication:onc
publication:epidempub
19443337
Management and Prognosis in Synchronous Solitary Resected Brain Metastasis from Non–Small-Cell Lung Cancer
Louie, Alexander V.
Rodrigues, George
Yaremko, Brian
Yu, Edward
Dar, A. Rashid
Dingle, Brian
Vincent, Mark
Sanatani, Michael
Malthaner, Richard
Inculet, Richard
Article
2009-05-01T07:00:00Z
Adult
Aged
Brain Neoplasms
Carcinoma
Non-Small-Cell Lung
Cranial Irradiation
Humans
Infant
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
Prognosis
Retrospective Studies
Clinical Lung Cancer
Clinical Lung Cancer
10
3
174
179
Epidemiology
Oncology
Surgery
Background: Reports in the medical literature have described cases of extended survival of patients with non-small-cell lung cancer (NSCLC) with solitary metastatic disease who have received aggressive treatment both to the brain metastasis and to the local/regional disease. The objective of this research is to analyze prognostic factors that predict for outcome in this unique patient population.
Patients and methods: A single-institution, retrospective chart review was performed on 35 patients with NSCLC and a synchronous solitary brain metastasis (SSBM) treated with craniotomy and whole-brain radiation therapy. Eight patients (22.9%) had chest surgery, 24 (68.6%) had chemotherapy, and 14 (40%) had thoracic radiation as part of their local management. Fourteen had stage I/II disease (42.9%), and 20 had stage III disease (57.1%). Mean age at diagnosis was 58.5 years. Eighteen patients (56.25%) had a brain metastasis < 3 cm, and 14 patients (43.75%) had a metastasis > 3 cm.
Results: Median survival was 7.8 months, and at last follow-up, 3 patients (8.6%) were alive and well, 6 patients (17.1%) were alive and with disease, 24 patients (68.6%) had died of disease, and 2 patients (5.7%) had died of other causes. Univariate analysis demonstrated that lung surgery (P = .0033), primary lung treatment > 8 weeks after brain surgery (P = .0128), and stage I/II disease (P = .0467) were predictive of overall survival.
Conclusion: Survival remains poor for patients with NSCLC with an SSBM. However, patients with thoracic disease amenable to local resection should be considered for such therapy because a survival advantage could exist compared with patients with more locally advanced disease.
Published in: Clinical Lung Cancer, Volume 10, Number 3, May 2009, Pages 174-179. doi: 10.3816/CLC.2009.n.024
https://ir.lib.uwo.ca/oncpub/28
oai:ir.lib.uwo.ca:oncpub-1035
2009-11-08T08:35:56Z
publication:physics
publication:robartspub
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physicspub
publication:biophysics
publication:epidem
publication:robarts
publication:surgery
publication:institutes
publication:onc
publication:epidempub
17183130
3D Thoracoscopic Ultrasound Volume Measurement Validation in an Ex Vivo and In Vivo Porcine Model of Lung Tumours
Hornblower, V. D. M.
Yu, E.
Fenster, A.
Battista, J. J.
Malthaner, R. A.
Article
2007-01-07T08:00:00Z
Agar
Algorithms
Animals
Automation
Humans
Image Processing
Computer-Assisted
Imaging
Three-Dimensional
Lung
Lung Neoplasms
Neoplasm Transplantation
Phantoms
Imaging
Reproducibility of Results
Swine
Ultrasonography
Physics in Medicine and Biology
Physics in Medicine and Biology
52
1
91
106
Bioimaging and Biomedical Optics
Oncology
Surgery
The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure "tumour" volumes both in vivo and ex vivo.
Published in: Phys. Med. Biol., 52, 91-106. doi: 10.1088/0031-9155/52/1/007
https://ir.lib.uwo.ca/oncpub/35
oai:ir.lib.uwo.ca:oncpub-1045
2009-11-14T08:15:35Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:surgery
publication:onc
14630257
Patterns of Breast Recurrence in a Pilot Study of Brachytherapy Confined to the Lumpectomy Site for Early Breast Cancer with Six Years' Minimum Follow-up
Perera, Francisco
Yu, Edward
Engel, Jay
Holliday, Ronald
Scott, Leslie
Chisela, Frank
Venkatesan, Varagur
Article
2003-12-01T08:00:00Z
Adult
Aged
Aged
80 and over
Brachytherapy
Breast Neoplasms
Carcinoma in Situ
Carcinoma
Intraductal
Noninfiltrating
Chemotherapy
Adjuvant
Dose Fractionation
Female
Follow-Up Studies
Humans
Mastectomy
Segmental
Middle Aged
Neoplasm Recurrence
Local
Pilot Projects
Salvage Therapy
Treatment Failure
International Journal of Radiation Oncology, Biology, Physics
International Journal of Radiation Oncology, Biology, Physics
57
5
1239
1246
10.1016/S0360-3016(03)00816-2
Oncology
Surgery
PURPOSE: In this pilot study of high-dose-rate brachytherapy to the lumpectomy site as the sole radiation, ipsilateral and contralateral breast recurrences are documented with specific attention to the location of recurrence relative to the lumpectomy site.
METHODS: Between March 1992 and January 1996, 39 patients with T1 (32 patients) and T2 breast cancers received 37.2 Gy in 10 fractions (b.i.d.) over 1 week prescribed to a volume encompassing the surgical clips. Thirteen received adjuvant tamoxifen, and 4 received chemotherapy. Follow-up included annual bilateral mammograms and clinical breast examination every 3 to 6 months. Whereas 13 patients had intraoperative implantation of the lumpectomy site, 26 had postoperative implantation. The latter group and 7 of the former group had surgical clips marking the lumpectomy site, which allowed estimates of the distance of any ipsilateral breast recurrence from the lumpectomy site, using the mediolateral and cranio-caudad mammographic views.
RESULTS: At a median follow-up of 91 months, 33 women are alive, 4 have died of disease, and 2 have died of other causes. The 5-year actuarial rate of ipsilateral breast recurrence was 16.2%. Of 6 ipsilateral recurrences, 2 occurred within the lumpectomy site (in-field recurrences). One of the 2 patients had a 1-mm microscopic margin at initial diagnosis; the recurrence was a 3.5-mm microscopic focus of duct carcinoma in situ. The other patient had a 1.5-cm, high-grade infiltrating mammary carcinoma with no residual at wider resection at first diagnosis; the 5-mm invasive recurrence was also of high grade. Four women developed invasive recurrences at least 1.6 cm or more from the lumpectomy site (out-of-field recurrences). Two of these women had gross multifocal recurrences with two cancers in each patient; 1 of the 2 patients had an extensive intraductal component at initial diagnosis. The estimated nearest distances between the out-of-field recurrences and the surgical clips were 1.6, 5.5, 7.7, and 12.0 cm. All ipsilateral breast recurrences were salvaged by mastectomy (4 patients) or by repeat lumpectomy (2 patients) and whole-breast radiation. The interval postdiagnosis to ipsilateral recurrence ranged from 20 months to 58 months. There were two contralateral breast recurrences at intervals of 34 and 36 months; 1 of these patients also had a multifocal, ipsilateral recurrence at 58 months, as previously described. Among patients with any breast recurrence, 1 patient had a family history of prostate cancer; there was no family history of breast or ovarian cancer. Of 17 patients who received adjuvant systemic therapy, only 1 had a breast recurrence.
CONCLUSIONS: In this pilot study, breast recurrences outside of the lumpectomy site were the predominant pattern of recurrence.
https://ir.lib.uwo.ca/oncpub/44
oai:ir.lib.uwo.ca:oncpub-1047
2009-11-15T10:02:12Z
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:pmid
publication:medimaging
publication:faculties
publication:biophysics
publication:epidem
publication:medimagingpub
publication:surgery
publication:onc
publication:epidempub
12478004
Subsets More Likely to Benefit From Surgery or Prophylactic Cranial Irradiation After Chemoradiation for Localized Non-Small-Cell Lung Cancer
Keith, Bruce
Vincent, Mark
Stitt, Larry
Tomiak, Anna
Malthaner, Richard
Yu, Edward
Truong, Pauline
Inculet, Richard
Lefcoe, Michael
Dar, A. Rashid
Kocha, Walter
Craig, Ian
Article
2002-12-01T08:00:00Z
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Brain Neoplasms
Carcinoma
Non-Small-Cell Lung
Combined Modality Therapy
Cranial Irradiation
Female
Humans
L-Lactate Dehydrogenase
Lung Neoplasms
Male
Middle Aged
Multivariate Analysis
Neoplasm Recurrence
Local
Pneumonectomy
Prognosis
Radiotherapy Dosage
Radiotherapy
Adjuvant
Retrospective Studies
Risk Factors
American Journal of Clinical Oncology
American Journal of Clinical Oncology
25
6
583
587
Epidemiology
Oncology
Surgery
After chemoradiation for localized non-small-cell lung cancer, surgery and prophylactic cranial irradiation (PCI) have been used as additional therapies. Less than a third of patients develop brain recurrences, or have local recurrence as their sole initial site of recurrence; these are groups that would benefit from PCI or surgery, respectively. Pretreatment identification of patients more likely to benefit from surgery or PCI would be useful. A retrospective analysis of 80 patients was performed to determine prognostic factors for such patterns of failure. Twenty-nine patients were subsequently selected for surgery in a nonrandomized manner. Seventeen patients had isolated local initial recurrence and 15 had brain recurrences. In multivariable analysis, female gender and elevated LDH were found to be risk factors for brain recurrence. In the subset with stage III disease (n = 76), squamous cell histology was a risk factor for isolated initial local recurrence in both univariable and multivariable analysis. It is possible to identify subsets that may show increased benefit from PCI or surgery.
https://ir.lib.uwo.ca/oncpub/47
oai:ir.lib.uwo.ca:immunologypub-1022
2009-11-29T10:14:22Z
publication:mnipub
publication:surgerypub
publication:pmid
publication:immunologypub
publication:faculties
publication:medpub
publication:med
publication:mni
publication:robarts
publication:surgery
publication:institutes
15730398
Characterization of Human Peritoneal Dendritic Cell Precursors and Their Involvement in Peritonitis
McCully, M. L.
Chau, T. A.
Luke, P.
Blake, P. G.
Madrenas, J.
Article
2005-03-01T08:00:00Z
Adult
Aged
Analysis of Variance
Antigens
CD14
Case-Control Studies
Cell Differentiation
Cytokines
Dendritic Cells
Endocytosis
Female
Flow Cytometry
Humans
Immunophenotyping
Lymphocyte Count
Macrophages
Male
Microscopy
Confocal
Middle Aged
Peritoneal Dialysis
Peritoneum
Peritonitis
Th1 Cells
Clinical and Experimental Immunology
Clinical and Experimental Immunology
139
3
513
525
10.1111/j.1365-2249.2005.02713.x
Immunology and Infectious Disease
Scattered evidence suggests that the human peritoneal cavity contains cells of the dendritic cell (DC) lineage but their characterization is missing. Here, we report that the peritoneal cavity of normal subjects and of stable patients on peritoneal dialysis (PD) contains a population of CD14(+) cells that can differentiate into DCs or macrophages. Within this pool, we characterized a CD14(+)CD4(+) cell subset (2.2% of the peritoneal cells) fulfilling the definition of myeloid DC precursors or pre-DC1 cells. These cells expressed high levels of HLA-DR, CD13, CD33, and CD86, and low levels of CD40, CD80, CD83, CD123, CD209, TLR-2 and TLR-4. These cells retained CD14 expression until late stages of differentiation, despite concomitant up-regulation of DC-SIGN (CD209), CD1a, CD80 and CD40. Peritoneal pre-DC1 cells had endocytic capacity that was down-regulated upon LPS/IFN-gamma stimulation, were more potent allo-stimulators than peritoneal CD14(+)CD4(-/lo) cells and monocyte-derived macrophages, and induced Th1 cytokine responses. More importantly, the number of peritoneal pre-DC1 cells increased during PD-associated peritonitis, with a different profile for Gram positive and Gram negative peritonitis, suggesting that these cells participate in the induction of peritoneal adaptive immune responses, and may be responsible for the bias towards Th1 responses during peritonitis.
https://ir.lib.uwo.ca/immunologypub/22
oai:ir.lib.uwo.ca:immunologypub-1041
2009-11-29T12:19:27Z
publication:mnipub
publication:patholpub
publication:surgerypub
publication:pmid
publication:immunologypub
publication:faculties
publication:medpub
publication:pathol
publication:med
publication:mni
publication:robarts
publication:surgery
publication:institutes
11882031
Thymic Re-entry of Mature Activated T cells and Increased Negative Selection in Vascularized Allograft Recipients
Chau, L. A.
Rohekar, S.
Wang, J.-J.
Lian, D.
Chakrabarti, S.
Zhang, L.
Zhong, R.
Madrenas, J.
Article
2002-01-01T08:00:00Z
Animals
Antigen Presentation
Cell Death
Cell Movement
Heart Transplantation
Lymphocyte Activation
Male
Mice
Mice
Inbred BALB C
Mice
Inbred C57BL
Neovascularization
Physiologic
T-Lymphocytes
Thymus Gland
Transplantation Immunology
Transplantation
Homologous
Clinical and Experimental Immunology
Clinical and Experimental Immunology
127
1
43
52
10.1046/j.1365-2249.2002.01717.x
Immunology and Infectious Disease
Pathology
Surgery
Transplantation tolerance is a dynamic state that involves several homeostatic mechanisms intrinsic to the host. One of these mechanisms is activation-induced T cell death (AICD). However, it is unclear where AICD takes place during alloreactive responses. Since activated T cells can re-enter the thymus, we hypothesized that mature T cells activated by an allograft could be deleted upon re-entry into the thymus. To test this hypothesis, we used wild-type or 2C TCR transgenic mice receiving syngeneic or allogeneic heterotopic, vascularized heart grafts. First, we demonstrated that ex vivo CFSE-labelled T cells re-entered the thymus when transferred into allograft recipients but not when transferred into isograft recipients. Next, we compared the changes in cell subset numbers and incidence of apoptosis in the thymi and spleens of allograft or isograft recipients. Seven days after transplantation, at a time in which all the allografts were undergoing rejection, cells expressing donor-MHC class II molecules had migrated to the thymus and to the spleen. In the thymus of allograft recipients, overall cellularity was significantly reduced by 40% and associated with an increase in the number of double negative (CD4-CD8-) thymocytes and a decrease in double positive (CD4+CD8+) thymocytes, consistent with increased negative selection of thymocytes. Additionally, thymi of allograft recipients showed an increase in the number of recently activated, mature T cells (TCRhi, CD25+, CD44+) and a significant increase in the number of apoptotic cells, especially in the thymic medulla, that involved mature T cells as indicated by the TCRhi, CD44+, CD4 or CD8 single positive phenotype. Spleens of allograft recipients were increased in size and cellularity but did not show any of the changes in cell subsets seen in the thymi. Our data show that after allografting there is an increase in apoptotic cell death that is associated with negative selection of developing thymocytes as well as of alloreactive mature T cells that have re-entered the thymus upon activation in the periphery. This may occur upon migration of graft-derived antigen-presenting cells to the thymus.
https://ir.lib.uwo.ca/immunologypub/39
oai:ir.lib.uwo.ca:mnipub-1014
2010-01-24T07:47:16Z
publication:mnipub
publication:surgerypub
publication:pmid
publication:immunologypub
publication:faculties
publication:medpub
publication:med
publication:mni
publication:robarts
publication:surgery
publication:institutes
10540214
CD40-deficient Dendritic Cells Producing Interleukin-10, but not Interleukin-12, Induce T-cell Hyporesponsiveness In Vitro and Prevent Acute Allograft Rejection
Gao, J. X.
Madrenas, J.
Zeng, W.
Cameron, M. J.
Zhang, Z.
Wang, J. J.
Zhong, R.
Grant, D.
Article
1999-10-01T07:00:00Z
Adoptive Transfer
Animals
Antigens
CD40
Cells
Cultured
Dendritic Cells
Flow Cytometry
Graft Rejection
Immune Tolerance
Interleukin-10
Interleukin-12
Lipopolysaccharides
Male
Mice
Mice
Inbred BALB C
Mice
Inbred C3H
Mice
Inbred C57BL
T-Lymphocytes
Transplantation
Homologous
Immunology
Immunology
98
2
159
170
10.1046/j.1365-2567.1999.00863.x
Immunology and Infectious Disease
Microbiology
The induction of an immune response or tolerance is mediated by corresponding subsets of dendritic cells (DC). However, the property of tolerogenic DC is not clear. Recently, we have characterized a population of CD11c+ splenic DC derived from long-term mixed leucocyte culture (LT-MLC), which are able to proliferate upon stimulation and have a strong primary mixed leucocyte reaction (MLR)-stimulating activity in conventional MLR. In this study, we show that, in contrast to the irradiated ones, non-irradiated LT-MLC-derived DC induce polyclonal antigen-specific T-cell hyporesponsiveness when cocultured with allogeneic splenocytes for 3-11 days. The degree of the hyporesponsiveness increased with the length of coculture. Although these DC expressed major histocompatibility complex class II and B7 costimulatory molecules, which are down-regulated during coculture, they expressed very low or undetectable CD40 before and after coculture, respectively. The CD40-deficient DC spontaneously produce interleukin-10 (IL-10), but not IL-12. The skewed balance between IL-10 and IL-12 is associated with their capability to induce T-cell hyporesponsiveness, because a neutralizing antibody to IL-10, exogenous recombinant IL-12 or lipopolysaccharide (LPS) significantly blocked the hyporesponsiveness. Accordingly, infusion of a small number of non-irradiated LT-MLC-derived DC (5x105) significantly prolonged the survival of a vascularized heterotopic murine heart transplant, whereas irradiated DC accelerated graft rejection. These data suggest that CD40-deficient DC producing IL-10, but not IL-12 can induce T-cell hyporesponsiveness in vitro and in vivo.
https://ir.lib.uwo.ca/mnipub/17
oai:ir.lib.uwo.ca:oncpub-1063
2009-11-28T06:53:58Z
publication:robartspub
publication:biophysicspub
publication:oncpub
publication:surgerypub
publication:faculties
publication:electricalpub
publication:biophysics
publication:epidem
publication:electrical
publication:robarts
publication:surgery
publication:institutes
publication:onc
publication:epidempub
MIRA V: An Integrated System for Minimally Invasive Robot-assisted Lung Brachytherapy
Trejos, A. L.
Lin, A. W.
Mohan, S.
Bassan, H.
Edirisinghe, C.
Patel, R. V.
Lewis, C.
Yu, E.
Fenster, A.
Malthaner, R. A.
Conference Proceeding
2008-05-01T07:00:00Z
lung brachytherapy
lung cancer
robotics
IEEE International Conference on Robotics and Automation, 2008
IEEE International Conference on Robotics and Automation, 2008
2982
2987
10.1109/ROBOT.2008.4543663
Electrical and Computer Engineering
Oncology
Surgery
An integrated system for minimally invasive robot-assisted image-guided lung brachytherapy has been developed. The system incorporates an experimental setup for accurate radioactive seed placement with commercially available dosimetry planning software. The end result is a complete system that allows planning and executing a brachytherapy procedure with increased accuracy. The results of the in vitro seed placement evaluation show that seed misplacement has a significant effect on the volume receiving more than 200% of the dose (V200), and the minimum dosage received by 90% of the volume (D90).
https://ir.lib.uwo.ca/oncpub/63
oai:ir.lib.uwo.ca:surgerypub-1020
2010-01-28T06:24:42Z
publication:mnipub
publication:surgerypub
publication:pmid
publication:immunologypub
publication:faculties
publication:medpub
publication:med
publication:mni
publication:robarts
publication:surgery
publication:institutes
10188826
Surgical Technique for Vascularized Thymus Transplantation in Mice
Jiang, Jifu
Wang, Hao
Madrenas, Joaquin
Zhong, Robert
Article
1999-01-01T08:00:00Z
Animals
Endocrine Surgical Procedures
Flow Cytometry
Male
Mice
Mice
Inbred BALB C
Microsurgery
Postoperative Period
Random Allocation
Thymus Gland
Time Factors
Microsurgery
19
2
56
60
Medical Immunology
Surgery
Traditionally, mouse nonvascularized thymus implants have been used to investigate various aspects of thymus function. However, these grafts are easily damaged by ischemia and fail to reproduce the normal anatomy of the thymus. In addition, the function of these grafts has not been fully examined. We have recently developed a vascularized thymus transplant model in mice. The donor operation consists of isolating the right lobe of the thymus and creating a single vascular pathway. In the recipient surgery, end-to-side anastomoses between donor brachycephalic artery and recipient right common carotid artery, and between donor superior caval vein and recipient right external jugular vein, were performed. We performed 10 consecutive isografts in BALB/c mice with a success rate of 90%. The thymus grafts had a normal histology and function. This study illustrates that it is technically possible to transplant a mouse vascular thymus graft. This model has several advantages that make it a useful tool to study many aspects of thymus function. We plan to use this model further to study the potential for induction of tolerance by thymus grafts.
https://ir.lib.uwo.ca/surgerypub/22
oai:ir.lib.uwo.ca:surgerypub-1021
2010-01-28T06:30:40Z
publication:mnipub
publication:surgerypub
publication:pmid
publication:immunologypub
publication:faculties
publication:mni
publication:robarts
publication:surgery
publication:institutes
9203977
Generation of Dendritic Cell-like Antigen-presenting Cells in Long-term Mixed Leucocyte Culture: Phenotypic and Functional Studies
Gao, J. X.
Madrenas, J.
Zeng, W.
Zhong, R.
Grant, D.
Article
1997-05-01T07:00:00Z
Animals
Antigen Presentation
Cell Division
Cell Movement
Cell Separation
Cytokines
Dendritic Cells
Flow Cytometry
Immunophenotyping
Isoantigens
Lymphocyte Culture Test
Mixed
Lymphoid Tissue
Male
Mice
Mice
Inbred BALB C
Mice
Inbred C3H
Mice
Inbred C57BL
Immunology
91
1
135
144
10.1046/j.1365-2567.1997.00220.x
Medical Immunology
Surgery
The mechanisms contributing to the proliferation and differentiation of antigen-presenting cell (APC) precursors upon antigen stimulation or tissue injury are poorly understood. Herein, we report the induction of a population of dendritic cell-like cells (DLC) with potent antigen-presentation function from unfractionated spleen cells by means of repetitive allostimulation in long-term mixed leucocyte cultures (LT-MLC). Initially, only a few adherent DLC were observed. By 4-6 weeks, however, there were large numbers of DLC which survived persistently. Features of these DLC are closely related to dendritic cells (DC), including (1) dendritic, veiled or spiny-processed morphology; (2) expression of a wide array of leucocyte surface markers including DC-associated or restricted antigens: 33D1, NLDC-145, CD11c (N418), heat-stable antigen (HSA), CD44, B7-1 and B7-2; (3) ability to migrate to draining lymph nodes and white pulp area of spleen; (4) expression of high level of major histocompatability complex (MHC) class II molecules and (5) more potent mixed leucocyte reaction (MLR)-stimulating capacity than peritoneal macrophages and APC-enriched spleen cells. DLC-stimulated MLR was inhibited by monoclonal antibodies (mAbs) to B7-1, B7-2, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), leucocyte-function associated antigen-1 (LFA-1) or very-late activation antigen-4 (VLA-4) by 30-55%. When maintained for more than 2 months, the DLC did not lose their MLR-stimulating activity, but many surface markers were down-regulated except for Mac-2 and VCAM-1, which remained stable or were up-regulated, respectively. In short-term culture, the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin (IL)-2 enhanced proliferation of DLC, while tumour necrosis factor-alpha (TNF-alpha) and IL-4 did not. IL-4 suppressed not only 'spontaneous', but also GM-CSF-enhanced proliferation, suggesting that cytokines play a differential role in DLC proliferation. These results confirm that professional APC can proliferate in response to repetitive antigen stimulation, and their proliferation is differentially regulated by cytokines. A comparison study of DLC with typical DC is being carried out in our laboratory.
https://ir.lib.uwo.ca/surgerypub/23
oai:ir.lib.uwo.ca:biochempub-1040
2009-12-18T07:47:44Z
publication:anatomy
publication:surgerypub
publication:pmid
publication:faculties
publication:anatomypub
publication:biochempub
publication:surgery
publication:biochem
19189038
Kinetics of Calcium Oxalate Crystal Growth in the Presence of Osteopontin Isoforms: An Analysis by Scanning Confocal Interference Microcopy
Langdon, Aaron
Wignall, Geoffrey R.
Rogers, Kem
Sørensen, Esben S.
Denstedt, John
Grohe, Bernd
Goldberg, Harvey A.
Hunter, Graeme K.
Article
2009-03-01T08:00:00Z
Animals
Calcium Oxalate
Cattle
Crystallization
Kinetics
Microscopy
Confocal
Osteopontin
Protein Isoforms
Rats
Recombinant Proteins
Calcified Tissue International
84
3
240
248
http://dx.doi.org/10.1007/s00223-008-9215-5
Biochemistry
Medical Anatomy
Surgery
Proteins that inhibit the growth and aggregation of calcium oxalate crystals play important roles in the prevention of kidney stone disease. One such protein is osteopontin (OPN), which inhibits the formation of calcium oxalate monohydrate (COM) in a phosphorylation-dependent manner. To determine the role of phosphate groups in the inhibition of COM growth by OPN, we used scanning confocal interference microscopy to compare the effects of highly phosphorylated OPN from cow milk, less phosphorylated OPN from rat bone, and nonphosphorylated recombinant OPN. COM growth was measured in the principal crystallographic directions <001>, <010>, and <100>, representing lattice-ion addition to {121}, {010}, and {100} faces, respectively. While the shapes of growth curves were very consistent from crystal to crystal, absolute growth rates varied widely. To control for this, results were expressed as changes in the aspect ratios <010>/<001> and <100>/<001>. Compared to control, bone OPN increased <010>/<001> and had no effect on <100>/<001>; milk OPN had no effect on <010>/<001>and decreased <100>/<001>; recombinant OPN had no significant effect on either aspect ratio. These findings indicate that milk OPN interacts with COM crystal faces in order of preference {100} > {121} approximately {010}, whereas bone OPN interacts in order of preference {100} approximately {121} > {010}. As {100} is the most Ca(2+)-rich face of COM, while {010} is the least Ca(2+)-rich, it appears that the OPN-mediated inhibition of COM growth occurs through a nonspecific electrostatic interaction between Ca(2+) ions of the crystal and phosphate groups of the protein.
https://ir.lib.uwo.ca/biochempub/38
oai:ir.lib.uwo.ca:biochempub-1049
2023-03-16T14:02:16Z
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biochempub
publication:surgery
publication:biochem
19331810
Keloid Scarring, but Not Dupuytren's Contracture, Is Associated with Unexplained Carotid Atherosclerosis
Bhavsar, Sankalp
Nimigan, Andre
Hackam, Daniel G.
O'Gorman, David B.
Gan, Bing Siang
Spence, J. David
Article
2009-01-01T08:00:00Z
Aged
Carotid Artery Diseases
Dupuytren Contracture
Female
Humans
Keloid
Male
Middle Aged
Multivariate Analysis
Regression Analysis
Risk Factors
Clinical & Investigative Medicine
32
2
95
102
Biochemistry
Surgery
<p>BACKGROUND: Atherosclerosis, a response to injury, may be thought of as scarring in the artery wall. TGF-beta and associated signaling molecules have been implicated in the pathophysiology of keloid scarring, Dupuytren's Contracture and atherosclerotic plaques in independent studies. PURPOSE: To test the hypothesis that excess cutaneous scarring and Dupuytren's contractures predispose independently to carotid atherosclerosis . METHODS: Among 1,747 patients with plaque measurements and complete data for multivariable regression analysis, 57 Caucasian patients had Dupuytren's contractures and 12 had keloid scars. Carotid total plaque area (TPA) was measured by 2-Dimensional ultrasound. RESULTS: In linear multivariable regression analysis with coronary risk factors, keloid scars were associated with TPA (P= 0.018), but Dupuytren's contractures were not. Patients with keloid scarring were younger (P < 0.0001), and more likely to be diabetic (P < 0.0001) CONCLUSIONS: Keloid scarring is a clinical clue to excess atherosclerosis not explained by traditional risk factors. Such patients may benefit from therapy directed at targets related to signalling molecules common to both the process of keloid scarring and atherosclerosis. These findings suggest previously unexplored possibilities for the prevention and treatment of atherosclerosis. The differences between Dupuytren's and keloid scars that may identify such targets are discussed.</p>
https://ir.lib.uwo.ca/biochempub/47
oai:ir.lib.uwo.ca:physpharmpub-1027
2009-12-23T21:07:48Z
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:biochem
publication:surgery
19331809
An Alternative Kinase Activity Assay for Primary Cultures Derived from Clinical Isolates
McLean, Kristopher
Wu, Yan
Gan, Bing Siang
O'Gorman, David B.
Article
2009-01-01T08:00:00Z
Biological Assay
Biotinylation
Cells
Cultured
Humans
Peptides
Phosphorylation
Proto-Oncogene Proteins c-akt
Reproducibility of Results
Spectrometry
Mass
Matrix-Assisted Laser Desorption-Ionization
Clinical & Investigative Medicine
Clinical & Investigative Medicine
32
2
84
94
Medical Biochemistry
Medical Biophysics
Medical Physiology
Surgery
PURPOSE: The measurement of protein kinase activity is central to understanding the signaling pathways that regulate cellular proliferation and apoptosis in virtually all disease processes. These measurements typically involve either indirect, time consuming assessment methods that require large amounts of sample, such as western immunoblotting, or the use of high maintenance, specialized equipment not typically available to a small clinical research facility. The purpose of this project was to determine if a benchtop Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) unit could be used to detect and directly assess kinase activity of the serine/threonine kinase Akt.
METHOD: Biotinylated substrate peptides, predicted to be recognized and phosphorylated by Akt to varying extents, were incubated in crude lysates of primary cells derived directly from clinical isolates. Streptavidin-coated chips were then used to isolate the substrate peptides from the lysates after incubation. Finally SELDI-TOF-MS was used to detect the peptide substrates and identify any changes in mass resulting from phosphorylation.
RESULTS: The biotinylated peptide substrates were readily detected and a simple, rapid procedure that allows direct measurement of Akt activity in less than 1 microg of cell lysate in a 2microL volume was developed. Further, a linear correlation between native to phospho-peptide ratios and SELDI-TOF-MS output demonstrated that this approach is semi-quantitative.
CONCLUSION: This assay avoids many of the pitfalls associated with the currently available kinase protocols as well as labour-intensive mass-spectrometry analysis by specialist laboratories. We propose that this approach may be a viable alternative for clinical research laboratories aiming to measure the activity of kinases in clinical isolates.
https://ir.lib.uwo.ca/physpharmpub/25
oai:ir.lib.uwo.ca:robartspub-1002
2009-12-27T23:57:02Z
publication:animalpub
publication:animal
publication:robartspub
publication:biophysicspub
publication:surgerypub
publication:pmid
publication:faculties
publication:biophysics
publication:biochempub
publication:robarts
publication:biochem
publication:surgery
publication:institutes
publication:campusunits
19287088
In vivo Micro-CT Analysis of Bone Remodeling in a Rat Calvarial Defect Model
Umoh, Joseph U.
Sampaio, Arthur V.
Welch, Ian
Pitelka, Vasek
Goldberg, Harvey A.
Underhill, T. Michael
Holdsworth, David W.
Article
2009-04-07T07:00:00Z
Animals
Bone Density
Bone Remodeling
Disease Models
Animal
Drug Evaluation
Preclinical
Longitudinal Studies
Male
Rats
Rats
Wistar
Sensitivity and Specificity
Skull
Time Factors
Tomography
X-Ray Computed
Physics in Medicine and Biology
Physics in Medicine and Biology
54
7
2147
2161
10.1088/0031-9155/54/7/020
Bioimaging and Biomedical Optics
Medical Biochemistry
Medical Biophysics
Surgery
The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 microm. At 6 weeks, the BMC in control animals (4.37 +/- 0.66 mg) was significantly lower (p < 0.05) than that in treated rats (11.29 +/- 1.01 mg). Linear regression between the BMC and bone fractional area, from 20 rats, showed a strong correlation (r(2) = 0.70, p < 0.0001), indicating that the BMC can be used, in place of previous destructive analysis techniques, to characterize bone growth. The high precision (2.5%) of the micro-CT methodology indicates its utility in detecting small BMC changes in animals.
https://ir.lib.uwo.ca/robartspub/3
oai:ir.lib.uwo.ca:surgerypub-1022
2010-01-01T02:38:39Z
publication:biophysicspub
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biophysics
publication:biochempub
publication:biochem
publication:surgery
19619531
Periostin Differentially Induces Proliferation, Contraction and Apoptosis of Primary Dupuytren's Disease and Adjacent Palmar Fascia Cells
Vi, Linda
Feng, Lucy
Zhu, Rebecca D.
Wu, Yan
Satish, Latha
Gan, Bing Siang
O'Gorman, David B.
Article
2009-12-10T08:00:00Z
Dupuytren's disease
palmar fascia cell
Experimental Cell Research
315
20
3574
3586
10.1016/j.yexcr.2009.07.015
Medical Biochemistry
Medical Biophysics
Medical Physiology
Surgery
Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, alpha smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.
https://ir.lib.uwo.ca/surgerypub/21
oai:ir.lib.uwo.ca:surgerypub-1023
2010-01-28T07:16:00Z
publication:surgerypub
publication:pmid
publication:faculties
publication:biochempub
publication:biochem
publication:surgery
19889147
Protein Biomarker Analysis of Primary Peyronie's Disease Cells
De Young, Ling X.
Bella, Anthony J.
O'Gorman, David B.
Gan, Bing S.
Lim, Kok B.
Brock, Gerald B.
Article
2010-01-01T08:00:00Z
Peyronie's Disease Cell Culture Models
Tunica Albuginea
Protein Expression
Wound Healing
?-catenin
Journal of Sexual Medicine
7
1 Pt 1
99
106
http://dx.doi.org/10.1111/j.1743-6109.2009.01556.x
Medical Biochemistry
Surgery
INTRODUCTION: The molecular pathogenesis of Peyronie's Disease (PD) remains unclear more than 250 years after its initial description. Because of this, no test is currently available to accurately predict PD progression among those affected.
AIM: To investigate the expression of wound healing and fibrosis-associated proteins in primary cell cultures of PD fibroblasts to determine whether altered protein expression patterns can be used as predictors of clinical course and natural history.
METHODS: Primary cell cultures derived from normal Tunica albuginea tissue and PD plaque tissue were examined by immuno-cytochemistry. Protein expression profiles were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) and Western immunoblotting.
MAIN OUTCOME MEASURES: Expression of wound healing and fibrosis-associated proteins and protein expression patterns were assessed. RESULTS: Statistically significant increases in smooth muscle alpha-actin, beta-catenin, and Heat shock proteins (Hsp47) were identified in cells derived from PD relative to cells derived from normal Tunica albuginea tissue. Changes in TGFbeta-1 receptor and Fibronectin were also observed. In addition, altered expression of additional as yet unidentified proteins at 4.7, 8.9, 10.8, 16.8, and 76.8 kDa were detected by complementary SELDI-TOF-MS approaches.
CONCLUSIONS: Primary cells derived from PD plaques display up-regulated expression of several proteins that are established components of fibrosis and wound healing. In addition, changes in other, as yet unidentified proteins were measured. It will be of interest to conduct further studies to see whether these dysregulated protein peaks represent potential biological markers of disease progression.
https://ir.lib.uwo.ca/surgerypub/24
oai:ir.lib.uwo.ca:physpharmpub-1031
2010-02-22T03:42:05Z
publication:physpharmpub
publication:surgerypub
publication:pmid
publication:faculties
publication:physpharm
publication:biochempub
publication:biochem
publication:surgery
19896280
The Potential Roles of Cell Migration and Extra-cellular Matrix Interactions in Dupuytren's Disease Progression and Recurrence
Vi, Linda
Gan, Bing Siang
O'Gorman, David B.
Article
2010-03-01T08:00:00Z
cell migration
extra-cellular matrix interactions
Dupuytren’s disease
Medical Hypotheses
Medical Hypotheses
74
3
510
512
http://dx.doi.org/10.1016/j.mehy.2009.10.009
Medical Biochemistry
Medical Physiology
Pharmacy and Pharmaceutical Sciences
Dupuytren's disease is a pathological condition of the palmar fascia characterized by the formation of contractile disease cords that result in permanent finger contracture. This condition is believed to progress from a myofibroblast-rich nodule in the early clinical stages of the disease to a contractile disease cord spanning a portion of the fascia, leading to contracture of one or more digits. The mechanism(s) by which this disease progresses from a nodule to a collagenous disease cord are poorly understood. Here, we discuss two possible models of disease progression. Firstly, disease progression might be mediated by the proliferation and outward migration of disease cells from within the nodule to populate the adjacent palmar fascia, resulting in a disease cord containing contractile cells derived from the nodule itself. Alternatively, nodular cells may secrete disease-associated factors into the surrounding extra-cellular matrix, thereby altering its composition and triggering quiescent, phenotypically normal cells in the adjacent palmar fascia to take on a proliferative and contractile phenotype. Based on the available evidence and the current state of knowledge of myofibroblast biology, we hypothesize that extra-cellular matrix interactions resulting in conversion of adjacent palmar fascia cells to a disease phenotype is more likely than cell migration from the nodule. Understanding the mechanisms of Dupuytren's disease progression will assist in the development of effective therapeutic interventions to address the high clinical recurrence rate of this condition.
https://ir.lib.uwo.ca/physpharmpub/32
oai:ir.lib.uwo.ca:ptpub-1003
2010-03-11T23:18:37Z
publication:pt
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
publication:ptpub
20047683
Effects of Low Power Laser Irradiation on Bone Healing in Animals: A Meta-analysis
Bashardoust Tajali, Siamak
Macdermid, Joy C.
Houghton, Pamela
Grewal, Ruby
Article
2010-01-04T08:00:00Z
Low Power Laser Irradiation
Bone Healing
Animals
Journal of Orthopaedic Surgery and Research
Journal of Orthopaedic Surgery and Research
5
1
http://dx.doi.org/10.1186/1749-799X-5-1
Physical Therapy
Surgery
PURPOSE: The meta-analysis was performed to identify animal research defining the effects of low power laser irradiation on biomechanical indicators of bone regeneration and the impact of dosage.
METHODS: We searched five electronic databases (MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane Database of Randomised Clinical Trials) for studies in the area of laser and bone healing published from 1966 to October 2008. Included studies had to investigate fracture healing in any animal model, using any type of low power laser irradiation, and use at least one quantitative biomechanical measures of bone strength. There were 880 abstracts related to the laser irradiation and bone issues (healing, surgery and assessment). Five studies met our inclusion criteria and were critically appraised by two raters independently using a structured tool designed for rating the quality of animal research studies. After full text review, two articles were deemed ineligible for meta-analysis because of the type of injury method and biomechanical variables used, leaving three studies for meta-analysis. Maximum bone tolerance force before the point of fracture during the biomechanical test, 4 weeks after bone deficiency was our main biomechanical bone properties for the Meta analysis.
RESULTS: Studies indicate that low power laser irradiation can enhance biomechanical properties of bone during fracture healing in animal models. Maximum bone tolerance was statistically improved following low level laser irradiation (average random effect size 0.726, 95% CI 0.08 - 1.37, p 0.028). While conclusions are limited by the low number of studies, there is concordance across limited evidence that laser improves the strength of bone tissue during the healing process in animal models.
https://ir.lib.uwo.ca/ptpub/4
oai:ir.lib.uwo.ca:surgerypub-1024
2010-03-12T22:05:29Z
publication:mnipub
publication:patholpub
publication:rwkex_researcharticles
publication:surgerypub
publication:pmid
publication:faculties
publication:rwkex
publication:pathol
publication:mni
publication:surgery
20102615
RNAi-mediated CD40-CD154 Interruption Promotes Tolerance in Autoimmune Arthritis
Zheng, Xiufen
Suzuki, Motohiko
Zhang, Xusheng
Ichim, Thomas E.
Zhu, Fei
Ling, Hong
Shunnar, Aminah
Wang, Michael H.
Garcia, Bertha
Inman, Robert D.
Min, Wei-Ping
Article
2010-01-26T08:00:00Z
RNAi-mediated CD40-CD154 interruption
autoimmune arthritis
Arthritis Research & Therapy
12
R13
http://dx.doi.org/10.1186/ar2914
Medical Immunology
Medical Microbiology
Pathology
Surgery
INTRODUCTION: We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40.
METHODS: Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses.
RESULTS: Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells.
CONCLUSIONS: These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity.
https://ir.lib.uwo.ca/surgerypub/25
oai:ir.lib.uwo.ca:surgerypub-1026
2010-03-26T21:14:59Z
publication:rwkex_researcharticles
publication:surgerypub
publication:pmid
publication:faculties
publication:stats
publication:rwkex
publication:surgery
publication:statspub
17943900
Cholecystectomy Deferral in Patients with Endoscopic Sphincterotomy
McAlister, Vivian
Davenport, Eric
Renouf, Elizabeth
Article
2007-01-01T08:00:00Z
Cholecystectomy
Choledocholithiasis
Humans
Randomized Controlled Trials as Topic
Sphincterotomy
Endoscopic
Cochrane Database of Systematic Reviews
4
CD006233
http://dx.doi.org/10.1002/14651858.CD006233.pub2
Statistics and Probability
Surgery
BACKGROUND: Cholecystectomy is not required in up to 64% of patients who adopt a wait-and-see policy after endoscopic clearance of common bile duct stones. Although reports of retrospective cohort series have shown a higher mortality among patients who defer cholecystectomy, it is not known if this is due to the patients' premorbid health status or due to the deferral of cholecystectomy. Randomised clinical trials of prophylactic cholecystectomy versus wait-and-see have not had sufficient power to demonstrate differences in survival.
OBJECTIVES: To evaluate the beneficial and harmful effects of cholecystectomy deferral (wait-and-see) versus elective (prophylactic) cholecystectomy in patients who have had an endoscopic biliary sphincterotomy.
SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Controlled Trials Register (CENTRAL) in The Cochrane Library, MEDLINE (1966 to 2007), EMBASE (1980 to 2007), and Science Citation Index Expanded without language restrictions until April 2007.
SELECTION CRITERIA: Randomised clinical trials comparing patients whose gallbladder was left in-situ after endoscopic sphincterotomy (wait-and-see group) versus patients who had cholecystectomy with either endoscopic sphincterotomy or common bile duct exploration (prophylactic cholecystectomy group), irrespective of blinding, language, or publication status.
DATA COLLECTION AND ANALYSIS: We assessed the impact of a wait-and-see policy on mortality. Secondary outcomes assessed were the incidence of biliary pain, cholangitis, pancreatitis, need for cholangiography, need for cholecystectomy, and the rate of difficult cholecystectomy. We pooled data using relative risk with fixed-effect and random-effects models.
MAIN RESULTS: We included 5 randomised trials with 662 participants out of 93 publications identified through the literature searches. The number of deaths was 47 in the wait-and-see group (334 patients) compared to 26 in the prophylactic cholecystectomy group (328 patients) for a 78% increased risk of mortality (RR 1.78, 95% CI 1.15 to 2.75, P = 0.010). The survival benefit of prophylactic cholecystectomy was independent of trial design, inclusion of high risk patients or inclusion of any one of the five trials. Patients in the wait-and-see group had higher rates of recurrent biliary pain (RR 14.56, 95% CI 4.95 to 42.78, P < 00001), jaundice or cholangitis (RR 2.53, 95% CI 1.09 to 5.87, P = 0.03), and of repeat ERCP or other forms of cholangiography (RR 2.36, 95% CI 1.29 to 4.32, P = 0.005). Cholecystectomy was eventually performed in 35% (115 patients) of the wait-and-see group.
AUTHORS' CONCLUSIONS: Prophylactic cholecystectomy should be offered to patients whose gallbladders remain in-situ after endoscopic sphincterotomy and common bile duct clearance.
This review is published as a Cochrane review in the Cochrane Database of Systematic Reviews 2007, Issue 4. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.
https://ir.lib.uwo.ca/surgerypub/28
oai:ir.lib.uwo.ca:surgerypub-1025
2010-03-26T21:16:10Z
publication:rwkex_researcharticles
publication:anesthesia
publication:surgerypub
publication:pmid
publication:anesthesiapub
publication:faculties
publication:rwkex
publication:surgery
20091580
Hypertonic Saline for Peri-operative Fluid Management
McAlister, Vivian
Burns, Karen E. A.
Znajda, Tammy
Church, Brian
Article
2010-01-01T08:00:00Z
hypertonic saline
peri-operative fluid management
Cochrane Database of Systematic Reviews
1
CD005576
http://dx.doi.org/10.1002/14651858.CD005576.pub2
Anesthesiology
Surgery
BACKGROUND: Fluid excess may place patients undergoing surgery at risk for various complications. Hypertonic saline (HS) maintains intravascular volume with less intravenous fluid than isotonic salt (IS) solutions, but may increase serum sodium.
OBJECTIVES: To determine the benefits and harms of HS versus IS solutions administered to patients undergoing surgery.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library) Issue 1, 2009; MEDLINE (1966 to 2009); EMBASE (1980 to 2009); LILACS (to August 2009) and CINAHL (1982 to 2009) without language restrictions.
SELECTION CRITERIA: We included randomized clinical trials where HS was compared to IS in patients undergoing surgery, irrespective of blinding, language, and publication status.
DATA COLLECTION AND ANALYSIS: We assessed the impact of HS administration on mortality, organ failure, fluid balance, serum sodium, serum osmolarity, diuresis and physiologic measures of cardiovascular function. We pooled data using odds ratio or mean difference (MD) for binary and continuous outcomes, respectively, using random-effects models.
MAIN RESULTS: We included 15 studies with 614 participants. One death in each group and no other serious adverse events were reported. While all patients were in a positive fluid balance postoperatively, the excess was significantly less in HS patients (standardized mean difference (SMD) -1.43L, 95% confidence interval (CI) 0.8 to 2.1 L less; P < 0.00001). Patients treated with HS received significantly less fluid than IS-treated patients (MD -2.4L 95% (CI) 1.5 to 3.2 L less; P < 0.00001) without differences in diuresis between the groups. Maximum intraoperative cardiac index was significantly increased with HS (SMD 0.6 L/min/M2 higher, 95% CI 0.1 to 1.0, P = 0.02) but Intraoperative pulmonary artery wedge pressure remained unchanged. While the maximum serum sodium and the serum sodium at the end of the study were significantly higher in HS patients, the level remained within normal limits (136 to 146 meq/L).
AUTHORS' CONCLUSIONS: HS reduces the volume of intravenous fluid required to maintain patients undergoing surgery but transiently increases serum sodium. It is not known if HS effects patient survival and morbidity but it should be tested in randomized clinical trials that are designed and powered to test these outcomes.
This review is published as a Cochrane review in the Cochrane Database of Systematic Reviews 2010, Issue 1. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.
https://ir.lib.uwo.ca/surgerypub/27
oai:ir.lib.uwo.ca:surgerypub-1027
2010-03-26T21:19:32Z
publication:rwkex_researcharticles
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:stats
publication:rwkex
publication:epidem
publication:surgery
publication:statspub
publication:onc
publication:epidempub
16827858
Cyclosporin versus Tacrolimus for Liver Transplanted Patients
Haddad, Elizabeth
McAlister, Vivian
Renouf, Elizabeth
Malthaner, Richard
Kjaer, Mette S.
Gluud, Lise Lotte
Article
2006-01-01T08:00:00Z
Acute Disease
Cyclosporine
Follow-Up Studies
Graft Rejection
Humans
Immunosuppressive Agents
Liver Transplantation
Risk Factors
Tacrolimus
Cochrane Database of Systematic Reviews
4
CD005161
http://dx.doi.org/10.1002/14651858.CD005161.pub2
Epidemiology
Oncology
Statistics and Probability
Surgery
A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring>tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients (Death: RR 0.85, 95% CI 0.73-0.99; graft loss: RR 0.73, 95% CI 0.61-0.86). Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75-0.88) and steroid-resistant rejection (RR 0.54, 95% CI 0.47-0.74) in the first year. Lymphoproliferative disorder or dialysis rates were not different but more de novo diabetes (RR 1.38, 95% CI 1.01-1.86) occurred with tacrolimus. More patients stopped cyclosporin than tacrolimus (RR 0.57, 95% CI 0.49-0.66). Treating 100 recipients with tacrolimus instead of cyclosporin would avoid rejection and steroid-resistant rejection in nine and seven patients respectively, graft loss and death in five and two patients respectively, but four additional patients would develop diabetes after liver transplantation.
This review is published as a Cochrane review in the Cochrane Database of Systematic Reviews 2006, Issue 4. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.
https://ir.lib.uwo.ca/surgerypub/29
oai:ir.lib.uwo.ca:surgerypub-1028
2010-07-20T22:40:33Z
publication:oncpub
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:surgery
publication:onc
18580208
Use of Recombinant Activated Factor VII in Patients without Hemophilia: A Meta-Analysis of Randomized Control Trials
Hsia, Cyrus C.
Chin-Yee, Ian H.
McAlister, Vivian C.
Article
2008-07-01T07:00:00Z
Erythrocyte Transfusion
Factor VIIa
Hemorrhage
Hemostasis
Humans
Randomized Controlled Trials as Topic
Recombinant Proteins
Thromboembolism
Annals of Surgery
248
1
61
68
http://dx.doi.org/10.1097/SLA.0b013e318176c4ec
Surgery
CONTEXT: Benefits of recombinant activated factor VII (rFVIIa) in hemorrhage may be lost because of thromboembolic events (TAE).
METHOD: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index Expanded, clinicaltrials.gov were searched for placebo controlled trials of rFVIIa in patients without hemophilia. Reports of 22 randomized controlled trials were selected for analysis. Results were pooled using random effects models to calculate the odds ratios (OR) with 95% confidence interval (CI). Subgroup analyses were predetermined.
RESULTS: Among 3184 participants, 478 (15.0%) died and 249 (7.8%) had TAE. Additional blood transfusion was required in 517 (41.2%) of 1256 subjects. Patients receiving rFVIIa were less likely to need additional blood transfusions (OR, 0.54; 95% CI, 0.34-0.86) than patients receiving placebo. Mortality was not increased but may be reduced (OR, 0.88; 95% CI, 0.71-1.09). Reduction in mortality was more likely if rFVIIa was given therapeutically (OR, 0.87; 95% CI, 0.70-1.09) rather than prophylactically (OR, 1.00; 95% CI, 0.37-2.68). Differences in the pooled analysis of TAE were not statistically significant (OR, 1.17; 95% CI, 0.87-1.58) but the incidence of arterial TAE was likely higher in patients receiving rFVIIa (OR, 1.50; 95% CI, 0.93-2.41) although no differences were seen with respect to venous TAE (OR, 0.76; 95% CI, 0.49-1.15).
CONCLUSIONS: Use of rFVIIa reduces the need for blood transfusion and it may reduce mortality, especially if the dose of rFVIIa is limited to therapeutic doses of 90 mug/kg. It does not increase the risk of venous thrombosis but it may increase the risk of arterial thrombosis.
https://ir.lib.uwo.ca/surgerypub/26
oai:ir.lib.uwo.ca:surgerypub-1030
2010-05-13T23:53:27Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
19503659
Catastrophe Surgery: Response to Multiple Casualties or Individual Patients with Devastating Injuries
McAlister, Vivian C.
Article
2009-06-01T07:00:00Z
Canada
Humans
Mass Casualty Incidents
Military Medicine
Traumatology
Canadian Journal of Surgery
52
3
175
176
Surgery
https://ir.lib.uwo.ca/surgerypub/31
oai:ir.lib.uwo.ca:surgerypub-1029
2010-05-13T23:37:06Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
19865541
A Surgical Review of the Priority Caims Attributed to Abraham Groves (1847-1935)
Geddes, Christopher R.
McAlister, Vivian C.
Article
2009-10-01T07:00:00Z
Appendectomy
General Surgery
Gloves
Surgical
History
19th Century
History
20th Century
Humans
Ontario
Physician's Role
Radiotherapy
Surgical Procedures
Operative
Canadian Journal of Surgery
52
5
E126
E130
Surgery
BACKGROUND: The practice of surgery had changed little over millennia when Abraham Groves and William Osler attended medical school together in Toronto, Ontario. The invention of anesthesia sparked such rapid development that by the time of Groves' and Osler's deaths, surgical practice resembled the current model. Several priority claims have been attributed to Groves' life in surgery, including aseptic surgery (1874), suprapubic lithotomy (1878), appendectomy (1883), surgical gloves (1885) and cancer radiotherapy (1903). These claims arise from an autobiography written by Groves at the age of 87 years in 1934.
METHODS: The purpose of this paper is to assess these priority claims from a modern surgical perspective. We did a systematic search of contemporary (1873-1934) and modern journals for articles by or about Groves. We searched relevant archives and museums. We reviewed the 1934 autobiography, notes held by descendants, reminiscences by contemporaries and collateral information. We assessed the information not only for priority but also for the development of organized surgical thought.
RESULTS: Groves published frequently throughout his career; thus far we have located 36 papers, almost all of which were published in Canadian journals. He spoke regularly at regional meetings in Ontario. Many medical students apprenticed with him (including his brother, son and grandson), he established a hospital and he founded a school of nursing. His contemporaries published complimentary reminiscences, but no correspondence with his classmate, William Osler, is known. Groves' priority claims for aseptic surgery, suprapubic lithotomy and radiotherapy are supported by contemporary publications. Groves independently developed an organized surgical system that remains valid today. Priority claims for appendectomy and the use of surgical gloves are entirely consistent with that system.
CONCLUSION: Although Groves' impact was reduced by his location and the limited circulation of the journals in which he wrote, he demonstrated a systematic understanding of modern surgery well ahead of his contemporaries.
https://ir.lib.uwo.ca/surgerypub/30
oai:ir.lib.uwo.ca:surgerypub-1031
2010-05-13T23:40:12Z
publication:surgerypub
publication:pmid
publication:faculties
publication:military_medicine
publication:surgery
publication:campusunits
18031633
Origins of the Canadian School of Surgery
McAlister, Vivian Charles
Article
2007-10-01T07:00:00Z
Canada
Education
Medical
General Surgery
History
16th Century
History
17th Century
History
18th Century
History
19th Century
History
20th Century
Journalism
Medical
Periodicals as Topic
Canadian Journal of Surgery
50
5
357
363
Surgery
Background: Since its inception 50 years ago, the Canadian Journal of Surgery has published articles under the banner "History of Canadian Surgery." Because no comprehensive history of surgery in this country has yet been written, these articles may provide its basis.
Method: The Canadian Journal of Surgery was searched from October 1957 to August 2007 for articles on the practice of surgery in Canada before 1957. Articles regarding the development of surgery in provinces, universities, hospitals and surgical specialty societies were included, as well as biographies and obituaries of surgeons.
Results: Thirty-six articles dealing with the lives of 57 Canadian surgeons were located. Three periods of Canadian surgery were covered: the French regime (1535–1759), the transition period (1759–1870) and the early modern period (1870–1945). The review shows that persistent efforts were made in Canada to develop surgical education and to regulate the practice of surgery. Isolation forced a spirit of adaptability that led to innovation and progress.
Conclusion: The practice of surgery in Canada today can be traced back to contributions made by pioneering surgeons over the entire history of modern Canada. An archive of materials related to the history of surgery in Canada is being created at www.historyofsurgery.ca to facilitate further research.
https://ir.lib.uwo.ca/surgerypub/32
oai:ir.lib.uwo.ca:surgerypub-1032
2010-05-13T23:42:11Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
17550716
Influence of Local Provision of Specialty Health Care Service on Patient Access to Care
McAlister, Vivian C.
Article
2007-04-01T07:00:00Z
Adult
Canada
Catchment Area (Health)
Cross-Sectional Studies
Female
Health Services Accessibility
Humans
Liver Diseases
Liver Transplantation
Male
Middle Aged
Registries
Retrospective Studies
Severity of Illness Index
Canadian Journal of Surgery
50
2
124
128
Surgery
Introduction: The impact of local provision of specialty service on patients' access to care was studied in Canada's 13 health care jurisdictions where distance may be a barrier limiting access.
Methods: A cross-sectional study of routinely collected registry data in Ontario and Nova Scotia was performed. Liver transplant was chosen as an indicator service. Transplant rate, disease severity, urgency and outcome were studied in adult recipients of first liver transplants from 1993 to 2002. Provinces that provided liver transplants were compared with those that did not; Ontario regions that provided the service were compared with those that did not; and the period of time when liver transplants were available in Nova Scotia was compared with the time when they were not.
Results: Use varied widely between jurisdictions but was consistently higher in provider provinces, at 10.9 per million population (pmp) compared with 8.9 pmp in nonprovider provinces (p < 0.005). Use was higher in district health councils of Ontario that provided transplantation. A larger proportion of patients in provider regions had viral or alcoholic etiologies of disease than did those from nonprovider regions, who tended to have superior survival after transplant. Service interruption in Nova Scotia did not change use rates, with transplant rates remaining above average, at 12.0 pmp.
Conclusions: Differences in use between provider and nonprovider regions may reflect local service availability as well as local patterns of disease and patient referral. Expectations of patients that are established by local service availability persist after service is removed.
https://ir.lib.uwo.ca/surgerypub/33
oai:ir.lib.uwo.ca:surgerypub-1033
2010-05-13T23:44:39Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
17391611
The Role of Prophylactic Cholecystectomy versus Deferral in the Care of Patients after Endoscopic Sphincterotomy
Archibald, Jason D.
Love, Jonathan R.
McAlister, Vivian C.
Article
2007-02-01T08:00:00Z
Age Factors
Aged
Cause of Death
Cholangiopancreatography
Endoscopic Retrograde
Cholecystectomy
Cholecystolithiasis
Cholelithiasis
Cohort Studies
Follow-Up Studies
Humans
Middle Aged
Patient Compliance
Physical Fitness
Retrospective Studies
Severity of Illness Index
Sphincterotomy
Endoscopic
Survival Rate
Treatment Outcome
Treatment Refusal
Canadian Journal of Surgery
50
1
19
23
Surgery
Introduction: Prophylactic cholecystectomy (PC) is advised after ES and clearance of ductal calculi on the basis of a randomized controlled trial that showed a requirement for cholecystectomy in 36% of patients who defer surgery. Other studies suggest the cholecystectomy rate to be as low as 8%.
Methods: To determine the proportion of patients who deferred cholecystectomy and the outcome, we reviewed 870 consecutive patients who underwent endoscopic retrograde cholangiography and sphincterotomy; the gallbladder of 420 of these remained in situ. Patients were assigned to PC or deferred cholecystectomy (DC) groups.
Results: Cholecystectomy was deferred in 180 of 310 eligible patients. DC patients were significantly older (66.4 v. 49.8 yr) and sicker (according to the American Society of Anesthesiology [ASA] physiological status score) and had a significantly higher mortality rate than did PC patients. Deaths were principally cardiovascular and not biliary related. After a follow-up of 24.2 (< 1–82.3) months, eventual cholecystectomy was required in 46 (24.7%) DC patients at a mean of 6 months after ES. The subgroup undergoing eventual cholecystectomy was younger (57.6 v. 69.4 yr; p < 0.001) fitter (ASA score of 1.98 v. 2.26; p = 0.015) and more likely to have residual cholecystolithiasis than were those who continued deferral. Recurrent pancreatitis was more common in DC (30%) than in PC (4.8%) patients if pancreatitis was the indication for sphincterotomy.
Discussion: PC is advised for patients with residual cholecystolithiasis after ES. In patients with relative contraindications, the choice is balanced in favour of cholecystectomy if there is a history of pancreatitis and in favour of deferral if more than 6 months have elapsed since ES.
https://ir.lib.uwo.ca/surgerypub/34
oai:ir.lib.uwo.ca:surgerypub-1034
2010-05-13T23:55:09Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
17391608
William Harvey, Fabricius ab Acquapendente and the Divide between Medicine and Surgery
McAlister, Vivian C.
Article
2007-02-01T08:00:00Z
Anatomy
Europe
General Surgery
History of Medicine
History
16th Century
History
17th Century
Humans
Canadian Journal of Surgery
50
1
7
8
Surgery
https://ir.lib.uwo.ca/surgerypub/35
oai:ir.lib.uwo.ca:surgerypub-1035
2010-05-13T23:57:57Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
16417047
Common Sense for a Common Problem: The Question of Screening the Average-risk Population for Colorectal Neoplasia
Vinden, Chris
McAlister, Vivian C.
Article
2005-12-01T08:00:00Z
Colonoscopy
Colorectal Neoplasms
Female
Health Care Surveys
Health Education
Humans
Male
Mass Screening
Ontario
Physician's Practice Patterns
Preventive Medicine
Risk Assessment
Sensitivity and Specificity
Canadian Journal of Surgery
48
6
431
432
Surgery
https://ir.lib.uwo.ca/surgerypub/36
oai:ir.lib.uwo.ca:surgerypub-1036
2010-05-13T23:50:27Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
15540684
Multivariate Analysis of Technical Variables in Pancreaticoduodenectomy: The Effect of Pylorus Preservation and Retromesenteric Jejunal Position on Early Outcome
Butler, Trevor J.
Vair, D. Brock
Colohan, Shannon
McAlister, Vivian C.
Article
2004-10-01T07:00:00Z
Adult
Aged
Aged
80 and over
Canada
Female
Humans
Jejunum
Male
Middle Aged
Multivariate Analysis
Pancreaticoduodenectomy
Postoperative Complications
Pylorus
Registries
Regression Analysis
Treatment Outcome
Canadian Journal of Surgery
47
5
333
337
Surgery
Background: To evaluate the effect of technical modifications to pancreaticoduodenectomy (PD) on postoperative outcome, we established a register of all patients undergoing PD at Victoria General Hospital (Queen Elizabeth II Health Sciences Centre), a tertiary care, university-affiliated hospital.
Patients and method: Data from 78 consecutive patients who underwent PD from January 1998 through November 2000 were collected for univariate and multivariate analyses of clinical and technical factors on early outcome after PD, including duration of gastric stasis, development of complications and length of hospital stay.
Results: Two patients (2.6%) died; complications were recorded in 43 (55%). Upon univariate analysis, 3 factors (a diagnosis of chronic pancreatitis, pylorus preservation, and route of the jejunal limb) significantly affected duration of gastric stasis; but on multivariate analysis, only pylorus preservation and jejunal-limb route remained significant. Retromesenteric jejunal-limb placement was associated with longer periods of gastric stasis (mean 11.9 d, standard deviation [SD] 8.1 d) than the antemesenteric (retrocolic) route (mean 7.2, SD 3.6 d; p < 0.05); likewise pyloric preservation (mean gastric stasis 10.4 d, SD 5.9 d) compared with resection of the pylorus (mean 7.0 d, SD 3.2 d; p < 0.05). Pancreatic leaks occurred in 18% of retromesenteric and 8% of antemesenteric reconstructions (p = 0.3). Fewer patients with mucomucosal pancreaticojejunostomy suffered complications than those with invaginated anastomoses, but their hospital stays were similar in length.
Conclusion: Route of the jejunal efferent limb and preservation of the pylorus are independent technical variables affecting early outcome after PD.
https://ir.lib.uwo.ca/surgerypub/37
oai:ir.lib.uwo.ca:surgerypub-1038
2010-04-01T06:07:08Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
19858268
H1N1-related SIRS?
McAlister, Vivian C.
Letter to the Editor
2009-10-27T07:00:00Z
Age Factors
Comorbidity
Female
Follow-Up Studies
Health Status
Humans
Immunocompromised Host
Influenza A Virus
H1N1 Subtype
Influenza
Human
Male
Pregnancy
Risk Assessment
Severity of Illness Index
Systemic Inflammatory Response Syndrome
CMAJ
181
9
616
617
Surgery
https://ir.lib.uwo.ca/surgerypub/39
oai:ir.lib.uwo.ca:surgerypub-1037
2010-05-13T23:59:49Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
14997917
Maimonides’s Cooling Period and Organ Retrieval
McAlister, Vivian
Article
2004-02-01T08:00:00Z
Attitude to Death
Brain Death
Canada
Female
History
20th Century
History
21st Century
Humans
Informed Consent
Male
Organ Transplantation
Terminal Care
Tissue and Organ Procurement
Canadian Journal of Surgery
47
1
8
9
Surgery
https://ir.lib.uwo.ca/surgerypub/38
oai:ir.lib.uwo.ca:surgerypub-1039
2010-04-01T06:13:35Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
16461979
Regression of Cutaneous and Gastrointestinal Telangiectasia with Sirolimus and Aspirin in a Patient with Hereditary Hemorrhagic Telangiectasia
McAlister, Vivian C.
Letter to the Editor
2006-02-07T08:00:00Z
Anti-Inflammatory Agents
Non-Steroidal
Aspirin
Female
Humans
Immunosuppressive Agents
Liver Transplantation
Middle Aged
Remission Induction
Sirolimus
Telangiectasia
Hereditary Hemorrhagic
Annals of Internal Medicine
144
3
226
227
Surgery
https://ir.lib.uwo.ca/surgerypub/40
oai:ir.lib.uwo.ca:surgerypub-1040
2010-04-01T06:18:33Z
publication:surgerypub
publication:faculties
publication:surgery
A History of Surgery, Harold Ellis
McAlister, Vivian C.
Book Review
2006-04-01T08:00:00Z
history of medicine
history of surgery
Canadian Bulletin of Medical History
23
1
270
272
History of Science, Technology, and Medicine
Surgery
https://ir.lib.uwo.ca/surgerypub/41
oai:ir.lib.uwo.ca:surgerypub-1041
2010-04-01T06:24:47Z
publication:surgerypub
publication:faculties
publication:psychologypub
publication:psychology
publication:surgery
Twice Dead: Organ Transplants and the Reinvention of Death, Margaret Lock
Gordon, Robert
McAlister, Vivian C.
Book Review
2003-01-01T08:00:00Z
ethics of surgery
Canadian Bulletin of Medical History
20
1
211
212
History of Science, Technology, and Medicine
Surgery
https://ir.lib.uwo.ca/surgerypub/42
oai:ir.lib.uwo.ca:surgerypub-1042
2010-04-03T20:21:27Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
16021982
Sacred Disease of Our Times: Failure of the Infectious Disease Model of Spongiform Encephalopathy
McAlister, Vivian
Article
2005-06-01T07:00:00Z
Animals
Behavior
Cannibalism
Communicable Diseases
History
18th Century
History
20th Century
History
Ancient
Humans
Models
Theoretical
Prion Diseases
Clinical and Investigative Medicine
28
3
101
104
Surgery
BACKGROUND: Public health and agricultural policy attempts to keep bovine spongiform encephalopathy out of North America using infectious disease containment policies. Inconsistencies of the infectious disease model as it applies to the spongiform encephalopathies may result in failure of these policies.
METHODS: Review of historical, political and scientific literature to determine the appropriate disease model of spongiform encephalopathy.
PRINCIPAL FINDINGS: Spongiform encephalopathy has always occurred sporadically in man and other animals. Hippocrates may have described it in goats and cattle. Transmission of spongiform encephalopathy between individuals is too uncommon for it to be usefully considered an infection. Spongiform encephalopathy is a somatic disorder whose dissemination within a host or transmission between individuals is more like cancer than infectious disease. Spongiform encephalopathy transmission within a species is facilitated in comparison to transmission between species so that cannibalism may amplify the prevalence of the disease.
CONCLUSION: Agricultural policy should be directed toward an absolute prohibition on occult cannibalism and away from surveillance, quarantine and slaughter, the principal measures of infectious disease containment used to control bovine spongiform encephalopathy.
https://ir.lib.uwo.ca/surgerypub/43
oai:ir.lib.uwo.ca:surgerypub-1043
2010-04-03T20:25:36Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
17330453
Control of Coagulation: A Gift of Canadian Agriculture
McAlister, Vivian
Article
2006-12-01T08:00:00Z
Agriculture
Animals
Anticoagulants
Canada
Coagulants
Heparin
History
20th Century
Humans
Thrombosis
Vitamin K
Warfarin
Clinical and Investigative Medicine
29
6
373
377
Surgery
Vitamin K, heparin and their antagonists remain the basis of coagulation therapies today, more than half a century after their discovery. Failure of blood clotting in chicks that were fed a fat-depleted diet was observed by William McFarlane, William Graham Jr. and Frederick Richardson of the Ontario Agricultural College; it led to the search that yielded vitamin K. Investigation of hemorrhagic disease in cattle by Francis Schofield of the Ontario Veterinary College found an anti-thrombin substance in spoiled clover which was later characterized as dicoumarol, a vitamin K antagonist, and led to the development of warfarin. In Toronto, a systematic approach lead by Charles Best resulted in the world's first plentiful supply of purified heparin. Clinical usefulness of heparin in thrombosis, embolism, cardiovascular surgery, dialysis and transplantation was demonstrated first by Gordon Murray and Louis Jaques. The roles and the careers of Canadian coagulation research pioneers are briefly presented in this review, which shows how clinical medicine benefited by the systematic development of agricultural science in Guelph, Ontario.
https://ir.lib.uwo.ca/surgerypub/44
oai:ir.lib.uwo.ca:surgerypub-1045
2010-04-05T20:05:35Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
10559451
Alloimmune Thrombocytopenia after Organ Transplantation
West, Kenneth A.
Anderson, David R.
McAlister, Vivian C.
Hewlett, Thomas J. C.
Belitsky, Philip
Smith, James W.
Kelton, John G.
Article
1999-11-11T08:00:00Z
Adult
Antigens
Human Platelet
Blood Platelets
Female
HLA Antigens
Histocompatibility Testing
Humans
Isoantibodies
Kidney Transplantation
Liver Transplantation
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism
Restriction Fragment Length
Purpura
Thrombocytopenic
Idiopathic
Radioimmunoprecipitation Assay
Tissue Donors
Transplantation Chimera
New England Journal of Medicine
341
20
1504
1507
Nephrology
Surgery
Urology
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/46
oai:ir.lib.uwo.ca:surgerypub-1044
2010-04-03T20:35:07Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
15930433
Correction of Factor XI Deficiency by Liver Transplantation
Ghosh, Nina
Marotta, Paul J.
McAlister, Vivian C.
Letter to the Editor
2005-06-02T07:00:00Z
Carcinoma
Hepatocellular
Factor XI Deficiency
Hepatitis C
Humans
Liver Cirrhosis
Liver Neoplasms
Liver Transplantation
Male
Middle Aged
New England Journal of Medicine
352
22
2357
2358
Surgery
https://ir.lib.uwo.ca/surgerypub/45
oai:ir.lib.uwo.ca:surgerypub-1046
2010-04-05T20:17:00Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
15453152
Utility of MELD and Child-Turcotte-Pugh Scores and the Canadian Waitlisting Algorithm in Predicting Short-term Survival after Liver Transplant
Bazarah, Salem M.
Peltekian, Kevork M.
McAlister, Vivian C.
Bitter-Suermann, Heinrich
MacDonald, Alan S.
Article
2004-08-01T07:00:00Z
Adult
Algorithms
Canada
Female
Graft Survival
Humans
Liver Transplantation
Male
Middle Aged
Models
Statistical
Outcome Assessment (Health Care)
Retrospective Studies
Survival Analysis
Waiting Lists
Clinical & Investigative Medicine
27
4
162
167
Surgery
BACKGROUND: The Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores are important predictors for survival after liver transplantation (LT). The objective of this study was to compare the utility of MELD and CTP scores with Canadian waitlisting algorithm in transplantation (CanWAIT) status for predicting 90-day survival after LT.
METHODS: Retrospectively, we analyzed all 228 liver transplants performed in adults by the Atlantic Liver Transplant Program since 1985. These cases included combined transplants, retransplants and those after fulminant liver failure. MELD and CTP scores were calculated, and CanWAIT status and waiting time on the day of LT determined. We used c-statistic for 90-day outcome as the endpoint (survival), comparing areas under the receiver operating characteristic (ROC) curves for MELD and CTP scores and CanWAIT status.
RESULTS: Mean (and standard deviation [SD]) MELD score was 18 (SD 12); CTP score, 10 (SD 3); and waiting time, 97 (SD 132) days. At the time of LT, 54% were in CanWAIT status 1; 4% in 1T; 14% in 2; 11% in 3; 6% in 3F; 4% in 4; and 7% in status 4F. Overall 90-day survival was 80% (95% confidence interval [CI] 75%-85%), exceeding the predicted survival by MELD scale with transplant of only 51% (CI 47%-55%). By c-statistic, CanWAIT is a clinically relevant predictor of 90-day outcomes in LT. By multivariate regression analysis, only CanWAIT status and age were found to have independent associations for short-term outcomes after LT.
INTERPRETATION: CanWAIT status stratifies LT patients better and predicts short-term outcome more accurately than MELD or CTP scores, and so should not be replaced by MELD or CTP scores. This observation should be confirmed by a prospective and multicentre study in Canada.
https://ir.lib.uwo.ca/surgerypub/47
oai:ir.lib.uwo.ca:surgerypub-1047
2010-04-05T20:29:03Z
publication:surgerypub
publication:faculties
publication:surgery
In Search of the Anglophone Doctor in Jacques Ferron’s Story “Le petit William”
McAlister, Vivian C.
McAlister, Christiane I.
Article
2006-04-01T08:00:00Z
canadian fiction
francophone
Quebec
physician writer
Gaspe
Dalhousie Medical Journal
34
1
23
30
French and Francophone Literature
Surgery
The story of ‘Le Petit William’ (Contes anglais, 1964) is based on Ferron’s experiences as a general practitioner in the Gaspé in 1946. A medical event, use of the maternal left lateral position by a sage-femme to deliver a baby boy, becomes allegory. The sage-femme had learned the technique from a visiting Anglophone doctor. A simple joke, which superficially appears to be the story’s culmination, takes on a sombre political tone when considered in the light of the Latin epigraph. Trips to the Gaspé, a review of the history of obstetrics and speculation are used in this paper to understand the realities upon which Ferron’s fantastic literature is based.
A la recherche du médecin « anglais » dans ‘Le petit William’ de Jacques Ferron
L'histoire de « Le Petit William » (Contes anglais,1964) est basée sur les expériences de Ferron comme médecin de campagne en Gaspésie en 1946. Un événement médical, l'usage de la posture obstétricale « position latérale gauche » par une sage-femme lors de la naissance d’un petit garçon, donne lieu à une allégorie. La sage-femme avait appris la technique d'un accoucheur « anglais», de passage dans la région. Une plaisanterie simple, qui semble à première vue être la culmination de l'histoire, prend un ton politique plutôt sombre quand on la considère à la lumière de l'épigraphe latine. Partant de renseignements recueillis lors de voyages en Gaspésie, d’une revue de l'histoire obstétricale, et de la spéculation, nous essaierons de comprendre les réalités sur lesquelles la littérature fantastique de Ferron est basée.
The article is also available online at: <a href="http://edmj.medicine.dal.ca/archives/Spring_2006.pdf">http://edmj.medicine.dal.ca/archives/Spring_2006.pdf</a>
https://ir.lib.uwo.ca/surgerypub/48
oai:ir.lib.uwo.ca:surgerypub-1048
2010-07-20T22:48:47Z
publication:surgerypub
publication:faculties
publication:surgery
Myopia of Health-Care Reform Using Business Models
Kenneth, MacInnes
McAlister, Vivian C.
Article
2001-02-01T08:00:00Z
heath care economics
econometrics
economic models
Annals of the Royal College of Physicians and Surgeons of Canada
34
1
20
22
Econometrics
Economic Policy
Health and Medical Administration
Surgery
Background: Health-care institutions have looked to business for models to respond to the requirement for reform. This has changed the perspective of institutions that were founded on charitable principles, and managed with liberal employment policies and deficit budgeting. Using lesions from supply-side management, hospitals are fragmenting into independent programs with demands to balance budgets regardless of the source of cost.
Methods: Costs from the institution’s perspective are compared with those of the payer (province) using an example of a proposal to reduce costs in the surgical program by buying disposable drapes.
Results: The actual cost of disposable drapes bought from the United States seems favourable at $100,000 per annum compared with $110,000 for the purchase and laundry of reusable linen. However, 80 per cent of the reusable system’s costs are generated by wages, which from the province’s perspective, should be reduced by income tax, by total consumption taxes and by other impacts of employment. The net cost to the province of the reusable system is $62,348 accounting for taxes alone. The disposable system would represent a loss of $37,652 to the province.
Interpretation: Cost-referenced decisions in health care may differ depending on the perspective taken. Discounting labour costs by taxes collected may enable governments to understand the impact of such decisions.
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/49
oai:ir.lib.uwo.ca:surgerypub-1049
2010-05-06T01:28:07Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
20346159
Metastatic Breast Carcinoma of the Coracoid Process: Two Case Reports
Benson, Eric C.
Drosdowech, Darren S.
Article
2010-03-26T07:00:00Z
Metastatic disease
Breast carcinoma
Coracoid
Journal of Orthopaedic Surgery and Research
5
22
http://dx.doi.org/10.1186/1749-799X-5-22
Surgery
BACKGROUND: The coracoid process of the scapula is a rare site of involvement for metastatic disease or for primary tumors. We are unaware of any reports in the literature of pathologic coracoid process fractures and only one report of metastatic disease to the coracoid.
METHODS AND RESULTS: In this case report, we present two cases with metastatic breast carcinoma of the coracoid process, one of which presented with a pathologic fracture of the coracoid.
CONCLUSIONS: An orthopaedic surgeon must be aware of the potential for metastatic disease to the coracoid as they may be the first medical provider to encounter evidence of malignant disease.
https://ir.lib.uwo.ca/surgerypub/50
oai:ir.lib.uwo.ca:surgerypub-1051
2010-07-20T20:32:04Z
publication:surgerypub
publication:faculties
publication:surgery
Canadians' Agricultural Research Contributed to Vitamin K Discovery
McAlister, Vivian
News Article
2007-05-08T07:00:00Z
Vitamins
Nutrition
Graduate studies
Agriculture
Medical Post
43
17
26
27
Nutrition
Surgery
https://ir.lib.uwo.ca/surgerypub/51
oai:ir.lib.uwo.ca:surgerypub-1052
2010-07-29T03:45:55Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
16105541
Clinical Kidney Transplantation: A 50th Anniversary Review of the First Reported Series
McAlister, Vivian Charles
Article
2005-09-01T07:00:00Z
History
20th Century
Humans
Kidney Transplantation
Ontario
Renal Dialysis
American Journal of Surgery
190
3
485
488
http://dx.doi.org/10.1016/j.amjsurg.2005.04.016
History of Science, Technology, and Medicine
Surgery
BACKGROUND: Histories of kidney transplantation rarely mention a series reported by Gordon Murray of Toronto and published by the American Journal of Surgery 50 years ago.
METHODS: The papers and biographies of Gordon Murray were reviewed in the context of knowledge at that time about renal failure management to determine their contribution to transplantation research and to current practice.
RESULTS: Murray proceeded from a unique leadership position in vascular surgery, anticoagulation therapy, and dialysis to undertake a rational series of animal experiments and human trials of kidney transplantation that led him to the practices of graft irrigation, cold storage, pelvic graft placement, renal-to-iliac vascular anastomoses, and ureterovesical anastomosis that continue to be used today. His animal studies included the first attempts to use immunosuppression and total body irradiation to prevent rejection. His observation that rejection may result in graft thrombosis and his attempts to prevent it with heparin anticipated current efforts to use newer agents for the same purpose in sensitized allotransplantation and xenotransplantation.
CONCLUSIONS: Modern renal transplantation is founded on many of the principles expounded by Gordon Murray 50 years ago.
Dr. Vivian McAlister has been granted a license by the journal publisher (Elsevier) to make the pdf file of this article available online. License no.: 2414910756898
https://ir.lib.uwo.ca/surgerypub/52
oai:ir.lib.uwo.ca:surgerypub-1053
2023-03-10T15:01:22Z
publication:surgerypub
publication:pmid
publication:faculties
publication:military_medicine
publication:surgery
publication:campusunits
20453775
In-theater Peritoneal Dialysis for Combat-related Renal Failure
Pina, Joseph S.
Moghadam, Soraya
Cushner, Howard M.
Beilman, Greg J.
McAlister, Vivian C.
Article
2010-05-01T07:00:00Z
Adult
Afghan Campaign 2001-
Causality
Child
Dialysis Solutions
Hospitals
Packaged
Humans
Iraq War
2003 -
Kidney Failure
Acute
Male
Medical Audit
Military Medicine
Military Personnel
Multiple Trauma
Operating Rooms
Peritoneal Dialysis
Progressive Patient Care
Transportation of Patients
Treatment Outcome
United States
War
Wounds
Gunshot
The Journal of Trauma
68
5
1253
1256
http://dx.doi.org/10.1097/TA.0b013e3181d99089
Surgery
<p>BACKGROUND: Complications of renal failure may prevent timely evacuation of injured soldiers. Conventional renal replacement therapy is not available in forward surgical units. METHODS: Records of in-theater improvised peritoneal dialysis (IPD) in level III hospitals or forward surgical units in Iraq or Afghanistan were reviewed to determine the following: cause of renal failure and associated injuries; type of dialysate, peritoneal access, and exchange technique; and patient outcome. These data were used to propose method for IPD using commonly available materials. RESULTS: IPD is described in four patients. Abdominal or chest drains were used with either improvised dextrose-electrolyte solution or commercial dialysate. Exchanges were successful, despite fresh surgical wounds including full laparotomy, removed excess fluid and restored acid and electrolyte balance, but did not correct azotemia. Open abdominal packing prevented continuation of IPD after 48 hours. Two patients fully recovered, one died, and one patient with a poor prognosis was lost to follow-up. CONCLUSION: IPD can be delivered effectively using readily available materials in forward surgical units and level III combat support hospitals.</p>
https://ir.lib.uwo.ca/surgerypub/54
oai:ir.lib.uwo.ca:surgerypub-1054
2010-08-07T20:50:25Z
publication:rwkex_researcharticles
publication:surgerypub
publication:pmid
publication:faculties
publication:rwkex
publication:surgery
20648949
Management of Devastating Ocular Trauma--Experience of Maxillofacial Surgeons Deployed to a Forward Field Hospital
Ansell, M. J.
Breeze, J.
McAlister, Vivian C.
Williams, M. D.
Article
2010-06-01T07:00:00Z
Eye trauma
Combat surgery
The Journal of the Royal Army Medical Corps
155
2
106
109
Ophthalmology
Surgery
Combat-related eye injuries continue to increase in frequency and are generally secondary to Improvised Explosive Devices. Many ocular injuries are potentially preventable by the wearing of ballistic eye protection. The management of penetrating eye trauma is normally outside the routine practice of maxillofacial surgeons in the UK. The aim of this paper is to describe the surgical techniques used in the modern management of devastating ocular trauma including selected case examples managed by British military maxillofacial surgeons deployed to Afghanistan.
https://ir.lib.uwo.ca/surgerypub/53
oai:ir.lib.uwo.ca:surgerypub-1055
2010-08-07T20:47:50Z
publication:surgerypub
publication:faculties
publication:surgery
Sinister Surgery
McAlister, Vivian C.
Response or Comment
2005-01-05T08:00:00Z
Surgery
British Medical Journal
Surgery
Online response to "<a href="http://dx.doi.org/10.1136/bmj.330.7481.10-f">The loneliness of the left handed surgeon</a>" by Roger Dobson.
https://ir.lib.uwo.ca/surgerypub/55
oai:ir.lib.uwo.ca:surgerypub-1056
2010-08-09T00:11:18Z
publication:surgerypub
publication:faculties
publication:surgery
A History of Neuro-Oncology
McAlister, Vivian
Book Review
2007-02-01T08:00:00Z
Surgery
Oncology
Canadian Journal of Surgery
50
1
71
71
Surgery
https://ir.lib.uwo.ca/surgerypub/56
oai:ir.lib.uwo.ca:surgerypub-1059
2010-08-17T23:26:52Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
11289353
Repopulation of Liver Endothelium by Bone-marrow-derived Cells
Gao, Z.
McAlister, Vivian C.
Williams, G. M.
Article
2001-03-24T08:00:00Z
Vascular Endothelium
Liver Regeneration
Liver Transplantation
Transplantation Chimera
Transplantation Tolerance
The Lancet
357
9260
932
933
http://dx.doi.org/10.1016/S0140-6736(00)04217-3
Pathology
Surgery
The mechanism underlying the immunological advantage of hepatic allografts relative to other organs is incompletely understood. We used molecular probes for the repetitive units on the Y chromosome, to identify an increasing number of male liver venous endothelial cells in needle biopsy samples of men who received female donor liver grafts. We have also shown repopulation of liver endothelium by bone marrow derived cells in a male to female mouse bone marrow transplant model. We conclude that the liver has unique venous endothelium characterised by turnover and replacement by bone marrow derived cells.
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/58
oai:ir.lib.uwo.ca:surgerypub-1058
2010-08-17T23:26:04Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
11360956
Circulating Endothelial Cells after Transplantation
Salazar, A. B.
McAlister, Vivian C.
Gupta, R.
MacDonald, A. S.
Article
2001-05-05T07:00:00Z
Vascular Endothelium
Graft Rejection
Kidney Transplantation
Transplantation Chimera
The Lancet
357
9266
1450
1450
http://dx.doi.org/10.1016/S0140-6736(00)04607-9
Surgery
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/57
oai:ir.lib.uwo.ca:surgerypub-1060
2010-08-16T21:48:26Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
10665560
Sirolimus-tacrolimus Combination Immunosuppression
McAlister, Vivian C.
Gao, Zuhua
Peltekian, Kevork
Domingues, Javier
Mahalati, Kamrar
MacDonald, Allan S.
Article
2000-01-29T08:00:00Z
Drug Therapy
Graft Rejection
Immunosuppressive Agents
Kidney Transplantation
Liver Transplantation
Pancreas Transplantation
Sirolimus
Tacrolimus
The Lancet
355
9201
376
377
http://dx.doi.org/10.1016/S0140-6736(99)03882-9
Surgery
A series of 32 recipients of liver, kidney, or pancreas transplants who were treated with sirolimus and low-dose tacrolimus experienced a low rate of rejection and excellent graft function without drug-related toxic effects.
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/59
oai:ir.lib.uwo.ca:surgerypub-1061
2010-08-16T21:56:55Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
17993733
Endoscopic Fenestration of a Duodenal Duplication Cyst to Resolve Recurrent Pancreatitis
Rockx, Marie-Antoinette J.
McAlister, Vivian
Article
2007-01-01T08:00:00Z
Cholangiopancreatography
Endoscopic Retrograde
Duodenum
Endoscopy
Digestive System
Pancreatitis
Journal of the Pancreas
8
6
795
798
Surgery
Non-invasive tools such as endoscopic ultrasound and magnetic resonance cholangiopancreatography have assisted the diagnosis of unexplained or recurrent acute pancreatitis prior to endoscopic retrograde cholangiopancreatography (ERCP). The majority of these patients are improved by endoscopic therapy with ERCP. Duodenal duplication cyst is a known but rare cause of recurrent acute pancreatitis that is also amenable to ERCP. We document the diagnosis and treatment of a 26-year-old man who had six episodes of pancreatitis that were found to be due to a duodenal duplication cyst. The pancreatico-biliary tree emptied into the cyst, which caused episodic obstruction and reflux contaminated juice resulting in pancreatitis. The patient also complained of persistent epigastric discomfort between attacks. Video demonstration of the technique for fenestration of the cyst is presented. Free emptying of bile and pancreatic juice from the cyst has resulted in elimination of the patient's persistent epigastric discomfort and attacks of pancreatitis.
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/60
oai:ir.lib.uwo.ca:surgerypub-1062
2010-08-16T22:06:30Z
publication:surgerypub
publication:pmid
publication:medimaging
publication:faculties
publication:medimagingpub
publication:surgery
16184595
Association of Recanalization of the Left Umbilical Vein with Umbilical Hernia in Patients with Liver Disease
Shlomovitz, Eran
Quan, Douglas
Etemad-Rezai, Roya
McAlister, Vivian C.
Article
2005-10-01T07:00:00Z
Hepatocellular Carcinoma
Functional Laterality
Hepatitis C
Liver Failure
Liver Neoplasms
Liver Transplantation
Liver Transplantation
11
10
1298
1299
http://dx.doi.org/10.1002/lt.20579
Surgery
https://ir.lib.uwo.ca/surgerypub/61
oai:ir.lib.uwo.ca:surgerypub-1064
2010-08-16T22:13:42Z
publication:mnipub
publication:surgerypub
publication:pmid
publication:faculties
publication:mni
publication:surgery
15738463
Demarcated Truncal Jaundice: A Sign of Retroperitoneal Bile Leakage
McAlister, Vivian C.
Sener, Alp
Article
2005-03-01T08:00:00Z
Bile
Cholecystectomy
Jaundice
Retroperitoneal Space
Annals of Internal Medicine
142
5
389
389
Surgery
The characteristic feature of the clinical sign described here is the demarcation between jaundiced and unaffected areas of the body. The flanks and the genitalia are stained more than would be expected by examination of the sclera or estimation of bilirubin level. Superiorly, a horizontal line about 3 cm below the clavicles, corresponding to the insertion of the fascia of Scarpa into the clavipectoral fascia, allows an easy comparison between the jaundiced trunk and unaffected adjacent areas, such as the neck, shoulder, and arm. Similarly, a line 3 cm below the groin skin crease corresponds to the insertion of the fascia of Scarpa into the fascia lata of the thigh. In former times, such a sign might have been called icterus marginatus.
https://ir.lib.uwo.ca/surgerypub/62
oai:ir.lib.uwo.ca:surgerypub-1065
2010-08-18T00:34:22Z
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:surgery
20334741
Kidney and Liver Transplants from Donors after Cardiac Death: Initial Experience at the London Health Sciences Centre
Hernandez-Alejandro, Roberto
Caumartin, Yves
Chent, Cameron
Levstik, Mark A.
Quan, Douglas
Muirhead, Norman
House, Andrew A.
McAlister, Vivian
Jevnikar, Anthony M.
Luke, Patrick P. W.
Wall, William
Article
2010-04-01T07:00:00Z
Heart Arrest
Kidney Transplantation
Length of Stay
Life Support Care
Liver Transplantation
Postoperative Complications
Time Factors
Tissue Donors
Tissue and Organ Procurement
Canadian Journal of Surgery
53
2
93
102
Nephrology
Surgery
Urology
BACKGROUND: The disparity between the number of patients waiting for an organ transplant and availability of donor organs increases each year in Canada. Donation after cardiac death (DCD), following withdrawal of life support in patients with hopeless prognoses, is a means of addressing the shortage with the potential to increase the number of transplantable organs.
METHODS: We conducted a retrospective, single-centre chart review of organs donated after cardiac death to the Multi-Organ Transplant Program at the London Health Sciences Centre between July 2006 and December 2007. In total, 34 solid organs (24 kidneys and 10 livers) were procured from 12 DCD donors.
RESULTS: The mean age of the donors was 38 (range 18-59) years. The causes of death were craniocerebral trauma (n = 7), cerebrovascular accident (n = 4) and cerebral hypoxia (n = 1). All 10 livers were transplanted at our centre, as were 14 of the 24 kidneys; 10 kidneys were transplanted at other centres. The mean renal cold ischemia time was 6 (range 3-9.5) hours. Twelve of the 14 kidney recipients (86%) experienced delayed graft function, but all kidneys regained function. After 1-year follow-up, kidney function was good, with a mean serum creatinine level of 145 (range 107-220) micromol/L and a mean estimated creatinine clearance of 64 (range 41-96) mL/min. The mean liver cold ischemia time was 5.8 (range 5.5-8) hours. There was 1 case of primary nonfunction requiring retransplantation. The remaining 9 livers functioned well. One patient developed a biliary anastomotic stricture that resolved after endoscopic stenting. All liver recipients were alive after a mean follow-up of 11 (range 3-20) months. Since the inception of this DCD program, the number of donors referred to our centre has increased by 14%.
CONCLUSION: Our initial results compare favourably with those from the transplantation of organs procured from donors after brain death. Donation after cardiac death can be an important means of increasing the number of organs available for transplant, and its widespread implementation in Canada should be encouraged.
https://ir.lib.uwo.ca/surgerypub/63
oai:ir.lib.uwo.ca:medpub-1041
2010-08-18T00:25:26Z
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:surgery
19302454
Recombinant Activated Factor VII in the Treatment of Non-haemophilia Patients: Physician Under-reporting of Thromboembolic Adverse Events
Hsia, C. C.
Zurawska, J. H.
Tong, M. Z. Y.
Eckert, K.
McAlister, Vivian C.
Chin-Yee, I. H.
Article
2009-02-01T08:00:00Z
Drug Toxicity
Recombinant Proteins
Risk Management
Survival Rate
Thromboembolism
Transfusion Medicine
Transfusion Medicine
19
1
43
49
http://dx.doi.org/10.1111/j.1365-3148.2009.00913.x
Surgery
The objective of this study was to determine if clinically important thromboembolic adverse events (TAEs) because of recombinant activated factor VII (rFVIIa) administration are being under-reported. rFVIIa is a potent haemostatic agent with a short half-life of 2.6 h that is increasingly used in 'off-label' situations. Retrospective review of 94 patients who received rFVIIa during 1 January 2003 to 30 June 2007 was carried out at a tertiary care centre. Sixty-nine patients, 32 females and 37 males, mean age 55 years (18-84 years), satisfied study criteria of off-label usage. This was a high-risk population with 33 (48%) deaths. A mean dose of 8.2 mg (2.4-19.2 mg) was administered in two average divided doses. Thirty-six potential TAEs were identified in 29 patients, and of these, 12 patients had TAEs deemed to be rFVIIa related and were identified on average 8.8 days after exposure to rFVIIa. Forty-eight (70%) physician questionnaires were completed; however, no TAEs were reported in these questionnaires or on chart review. Potential clinically significant TAEs are being under-reported by treating physicians. Until further evidence, we suggest the urgent need to develop consensus recommendations for utilization and required follow up to monitor the safety of rFVIIa and that at a minimum, all use of rFVIIa should be regulated through a gate-keeping mechanism that ensures adherence to these policies. Furthermore, prospective registries and trials are necessary to evaluate the efficacy and safety of rFVIIa in off-label settings.
https://ir.lib.uwo.ca/medpub/35
oai:ir.lib.uwo.ca:surgerypub-1066
2010-08-19T00:37:14Z
publication:mnipub
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:mni
publication:surgery
19034018
Perfusion of Renal Allografts with Verapamil Improves Graft Function
Nguan, Chris Y.
Sener, Alp
Karnik, Vaishali
Caumartin, Yves
House, Andrew A.
McAlister, Vivian C.
Luke, Patrick P. W.
Article
2008-11-27T08:00:00Z
ABO Blood-Group System
Calcium Channel Blockers
Cohort Studies
Creatinine
Drug Therapy
Graft Survival
Hypertension
Immunosuppressive Agents
Kidney Transplantation
Perfusion
Verapamil
Transplantation
86
10
1463
1467
http://dx.doi.org/10.1097/TP.0b013e3181889979
Allergy and Immunology
Surgery
The effect of adding a calcium channel antagonist to kidney allograft perfusate solution was assessed. All renal transplants in which both kidneys from the same donor used for transplantation were studied between November, 2003 and August, 2005 (n=46). The first renal allograft was perfused on the backtable with 1 L of histidine-tryptophan-ketoglurate solution and the second with 1 L of histidine-tryptophan-ketoglurate with 5 mg/L of verapamil. Both organs were transplanted in the usual manner. Baseline demographic parameters were similar between first and second kidney recipients other than BMI and cold ischemic time. At 6 and 12 months, renal function was significantly improved in the verapamil versus control cohort (creatinine clearance 73.8+/-23.5 mL/min vs. 55.8+/-17.0 mL/min, P<0.05 and 87.5+/-28.4 mL/min vs. 59.7+/-21.3 mL/min, P<0.05 respectively). Additionally, rates of hypotension during graft reperfusion and other adverse reactions were similar in both groups. In conclusion, verapamil supplemented perfusate significantly improved renal function posttransplantation.
https://ir.lib.uwo.ca/surgerypub/64
oai:ir.lib.uwo.ca:medpub-1042
2010-08-19T00:26:43Z
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:surgery
19938124
Long-term Outcomes of Emergency Liver Transplantation for Acute Liver Failure
Chan, Gabriel
Taqi, Ali
Marotta, Paul
Levstik, Mark
McAlister, Vivian
Wall, William
Quan, Douglas
Article
2009-12-01T08:00:00Z
Brain Edema
Emergency Treatment
Kaplan-Meiers Estimate
Liver Failure
Liver Transplantation
Nervous System Diseases
Proportional Hazards Models
Risk Assessment
Time Factors
Tissue Donors
Treatment Outcome
Liver Transplantation
Liver Transplantation
15
12
1696
1702
http://dx.doi.org/10.1002/lt.21931
Medicine and Health Sciences
Surgery
Acute liver failure continues to be associated with a high mortality rate, and emergency liver transplantation is often the only life-saving treatment. The short-term outcomes are decidedly worse in comparison with those for nonurgent cases, whereas the long-term results have not been reported as extensively. We report our center's experience with urgent liver transplantation, long-term survival, and major complications. From 1994 to 2007, 60 patients had emergency liver transplantation for acute liver failure. The waiting list mortality rate was 6%. The mean waiting time was 2.7 days. Post-transplantation, the perioperative mortality rate was 15%, and complications included neurological problems (13%), biliary problems (10%), and hepatic artery thrombosis (5%). The 5- and 10-year patient survival rates were 76% and 69%, respectively, and the graft survival rates were 65% and 59%. Recipients of blood group-incompatible grafts had an 83% retransplantation rate. Univariate analysis by Cox regression analysis found that cerebral edema and extended criteria donor grafts were associated with worse long-term survival. Severe cerebral edema on a computed tomography scan pre-transplant was associated with either early mortality or permanent neurological deficits. The keys to long-term success and continued progress in urgent liver transplantation are the use of good-quality whole grafts and a short waiting list time, both of which depend on access to a sufficient pool of organ donors. Severe preoperative cerebral edema should be a relative contraindication to transplantation.
https://ir.lib.uwo.ca/medpub/36
oai:ir.lib.uwo.ca:medpub-1043
2010-08-19T00:45:58Z
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:surgery
18342169
Prospective Comparison of Magnetic Resonance Angiography with Selective Renal Angiography for Living Kidney Donor Assessment
Neville, Christopher
House, Andrew A.
Nguan, Christopher Y.
Beasley, Kenneth A.
Peck, David
Thain, Lisa M. F.
Rankin, Richard
McAlister, Vivian C.
Spouge, Alison R.
Luke, Patrick P. W.
Article
2008-03-01T08:00:00Z
Kidney Transplantation
Living Donors
Magnetic Resonance Angiography
Renal Artery
Sensitivity and Specificity
Urology
Urology
71
3
385
389
http://dx.doi.org/10.1016/j.urology.2007.10.030
Medicine and Health Sciences
Surgery
OBJECTIVES: For years, the reference standard in the evaluation of living donor vascular anatomy has been selective renal angiography (SRA). Because of the potential morbidity associated with SRA, we prospectively evaluated magnetic resonance angiography (MRA) in the assessment of renal donors.
METHODS: All patients had SRA and 53 renal units were prospectively evaluated by MRA. We used SRA supplemented by findings at donor nephrectomy (DN) as our standard. We defined a positive test as the detection of any abnormality in the number of renal arteries.
RESULTS: Selective renal angiography yielded a sensitivity of 86%, specificity of 95%, positive predictive value (PPV) of 75%, and negative predictive value (NPV) of 97% compared with findings at DN. MRA had a sensitivity of 64%, 88% specificity, 58% PPV, and 90% NPV. MRA correctly identified only 7 of 11 renal units with accessory arteries. MRA also incorrectly identified 5 accessory arteries not present on SRA or DN. Two patients diagnosed with fibromuscular dysplasia by SRA were missed using MRA.
CONCLUSIONS: We have shown that MRA is not capable of replacing SRA as the reference standard in renal donor imaging.
https://ir.lib.uwo.ca/medpub/37
oai:ir.lib.uwo.ca:surgerypub-1067
2010-08-23T01:11:14Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
17188102
Treatment of Renal Transplant Complications with a Mesh Hood Fascial Closure Technique
Nguan, Christopher Y. C.
Beasley, Kenneth A.
McAlister, Vivian C.
Luke, Patrick P. W.
Article
2007-01-01T08:00:00Z
Compartment Syndromes
Kidney Transplantation
Prostheses and Implants
Reoperation
Retroperitoneal Space
Surgical Mesh
Suture Techniques
The American Journal of Surgery
193
1
119
121
http://dx.doi.org/10.1016/j.amjsurg.2006.03.008
Surgery
Early renal allograft dysfunction may be caused by a number of technical factors including thrombosis, kinking of vessels, and a Page kidney situation in which the allograft is compressed within a shallow false pelvis and limited retroperitoneal space. Without early recognition, compromised graft function, obstruction, or graft loss may ensue. We describe a technique using a polypropylene-assisted mesh hood fascial closure (MHFC) to prevent and treat this potential complication. MHFC was performed both primarily to prevent this phenomenon, and secondarily to treat this complication. Between April 2001 and October 2002, 16 patients undergoing 17 renal transplants underwent MHFC. The mean recipient body weight was 17% less than the mean donor weight. The mean follow-up period was 9 months. The mean serum creatinine level after primary MHFC was 148.4 micromol/L. Three of 4 patients with early allograft dysfunction regained function after secondary MHFC and had a mean serum creatinine level of 155.3 micromol/L. Wound complications were seen in 5 (31%) patients with no wound or mesh infections and 1 patient was diagnosed with a lymphocele. We conclude that the use of mesh in the primary closure of the incision after renal transplantation is safe and has minimal complications.
https://ir.lib.uwo.ca/surgerypub/65
oai:ir.lib.uwo.ca:surgerypub-1068
2010-08-23T00:30:02Z
publication:rwkex_researcharticles
publication:surgerypub
publication:pmid
publication:faculties
publication:stats
publication:rwkex
publication:surgery
publication:statspub
16827858
Cyclosporin versus Tacrolimus as Primary Immunosuppressant after Liver Transplantation: A Meta-analysis
McAlister, Vivian C.
Haddad, E.
Renouf, E.
Malthaner, R. A.
Kjaer, M. S.
Gluud, L. L.
Article
2006-07-01T07:00:00Z
Cyclosporine
Graft Rejection
Immunosuppressive Agents
Liver Transplantation
Risk Factors
Tacrolimus
American Journal of Transplantation
6
7
1578
1585
http://dx.doi.org/10.1111/j.1600-6143.2006.01360.x
Statistics and Probability
Surgery
A systematic review of randomized clinical trials (RCT) was undertaken to evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients. MEDLINE, EMBASE, Cochrane Central and Hepato-Biliary Group Controlled Trials Registers were searched. Using fixed and random effects model, relative risk (RR), values <1 favoring>tacrolimus, with 95% confidence intervals (CI) were calculated. Of 717 potentially relevant references, 16 RCTs were eligible for inclusion. Mortality and graft loss at 1 year were significantly reduced in tacrolimus-treated recipients (Death: RR 0.85, 95% CI 0.73-0.99; graft loss: RR 0.73, 95% CI 0.61-0.86). Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75-0.88) and steroid-resistant rejection (RR 0.54, 95% CI 0.47-0.74) in the first year. Lymphoproliferative disorder or dialysis rates were not different but more de novo diabetes (RR 1.38, 95% CI 1.01-1.86) occurred with tacrolimus. More patients stopped cyclosporin than tacrolimus (RR 0.57, 95% CI 0.49-0.66). Treating 100 recipients with tacrolimus instead of cyclosporin would avoid rejection and steroid-resistant rejection in nine and seven patients respectively, graft loss and death in five and two patients respectively, but four additional patients would develop diabetes after liver transplantation.
https://ir.lib.uwo.ca/surgerypub/66
oai:ir.lib.uwo.ca:surgerypub-1069
2010-08-23T00:42:49Z
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:surgery
16421486
Intravenous Immunoglobulin as a Treatment for BK Virus Associated Nephropathy: One-Year Follow-Up of Renal Allograft Recipients
Sener, Alp
House, Andrew A.
Jevnikar, Anthony M.
Boudville, Neil
McAlister, Vivian C.
Muirhead, Norman
Rehman, Faisal
Luke, Patrick P. W.
Article
2006-01-15T08:00:00Z
BK Virus
Creatine
Graft Rejection
Immunoglobulins
Intravenous
Kidney Transplantation
Polyomavirus Infections
Time Factors
Transplantation
Homologous
Tumor Virus Infections
Transplantation
81
1
117
120
http://dx.doi.org/10.1097/01.tp.0000181096.14257.c2
Surgery
BK virus associated nephropathy (BKVAN) has emerged as an important cause of renal allograft dysfunction and graft loss. Although several treatment strategies have been proposed, the rate of graft loss remains high. We studied the outcome of renal transplant patients with BKVAN treated with IVIG. After 11.4 +/- 3.9 months (mean +/- SEM) from the time of transplantation, 8 renal allograft recipients were diagnosed with BKVAN. In addition to a reduction of immunosuppressive therapy, patients received 2 g/kg IVIG. After a mean follow-up of 15 months, all except one patient are currently off dialysis. In summary, after IVIG therapy, 88% of patients still have functioning grafts, although renal function continues to be impaired. The benefit of concomitant IVIG and reduction of immunosuppressive therapy in BKVAN needs to be further addressed in randomized, multicentered trials.
https://ir.lib.uwo.ca/surgerypub/67
oai:ir.lib.uwo.ca:surgerypub-1070
2010-08-23T00:52:14Z
publication:patholpub
publication:surgerypub
publication:pmid
publication:faculties
publication:pathol
publication:surgery
16236113
Catastrophic Microangiopathy Induced by High-titre Factor VIII Inhibitors after Liver Transplantation for Haemophilia A with Cirrhosis
Khakhar, A. K.
Chan, N. G.
Allan, D. S.
Chakrabarti, S.
McAlister, Vivian C.
Article
2005-11-01T08:00:00Z
Factor VIII
Fatal Outcome
Hemophilia A
Hemorrhagic Disorders
Hepatitis C
Liver Cirrhosis
Liver Transplantation
Haemophilia
11
6
623
628
http://dx.doi.org/10.1111/j.1365-2516.2005.01145.x
Pathology
Surgery
Liver transplantation may induce immune tolerance to factor VIII inhibitors but de novo development of inhibitors after transplantation may cause intractable haemorrhage. We report a patient with mild haemophilia A and high-titre FVIII inhibitors who received an orthotopic liver transplantation for complications of hepatitis C virus cirrhosis. Recombinant activated FVII was used in addition to routine haemostatic agents. Conventional immunosuppression was supplemented with antithymocyte globulin and cyclophosphamide. FVIII inhibitors disappeared from the circulation with liver transplantation but they were found to have bound to the graft endothelium, which became activated and induced catastrophic microangiopathy. A subsequent anamnestic response resulted in FVIII inhibitor titres of 1000 Bethesda Units. Uncontrollable haemorrhage persisted until the recipient's death. In patients with high-titre FVIII inhibitors resilient desensitization is required before liver transplantation.
https://ir.lib.uwo.ca/surgerypub/68
oai:ir.lib.uwo.ca:surgerypub-1071
2010-08-23T15:11:05Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
16035095
Efficacy and Safety of Repeated Perioperative Doses of Recombinant Factor VIIa in Liver Transplantation
Lodge, J. Peter A
Jonas, Sven
Jones, Robert M.
Olausson, Michael
Mir-Pallardo, José
Soefelt, Soeren
Garcia-Valdecasas, Juan Carlos
McAlister, Vivian
Mirza, Darius F.
Article
2005-08-01T07:00:00Z
Dose-Response Relationship
Double-Blind Method
Erythrocyte Transfusion
Factor VII
Factor VIIa
Liver Cirrhosis
Liver Transplantation
Postoperative Care
Premedication
Prothrombin Time
Recombinant Proteins
Treatment Outcome
Liver Transplantation
11
8
973
979
http://dx.doi.org/10.1002/lt.20470
Surgery
Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.
https://ir.lib.uwo.ca/surgerypub/69
oai:ir.lib.uwo.ca:surgerypub-1072
2010-08-23T15:20:12Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
15659130
A Prospective 3-yr Evaluation of Tacrolimus-based Immunosuppressive Therapy in Immunological High Risk Renal Allograft Recipients
Zaltzman, Jeffrey S.
Boucher, Anne
Busque, Stephan
Halloran, Phillip F.
Landsberg, David N.
McAlister, Vivian C.
Russell, David
Shoker, Ahmed
Shapiro, Jean
Tchervenkov, Jean I.
Ferguson, Ralph
Article
2005-02-01T08:00:00Z
Graft Rejection
Graft Survival
Immunosuppressive Agents
Kidney Transplantation
Prospective Studies
Survival Analysis
Tacrolimus
Treatment Outcome
Clinical Transplantation
19
1
26
32
http://dx.doi.org/10.1111/j.1399-0012.2005.00275.x
Surgery
BACKGROUND: There have been no published data on use of the the newer immunosuppressants tacrolimus and mycophenolate mofetil (MMF) in high immunological risk renal transplantation. We therefore undertook a prospective study to systematically assess outcomes using these agents as part of an aggressive immunosuppressive regimen.
METHODS: Fifty-nine high-risk renal allograft recipients were enrolled at 10 Canadian sites and given a regimen of: a biological induction agent, tacrolimus, MMF, and corticosteroids. Patients included 10 (17%) who had lost a previous graft to rejection <1 >yr, 31 (53%) with a current panel reactive antibody (PRA) >30%, 47 (80%) with a historic PRA >50%, four (7%) who had a positive historical T-cell crossmatch with the current donor, and six (10%) with a current positive B-cell crossmatch. The mean peak PRA was 76 +/- 33%.
RESULTS: The estimated 3-yr Kaplan-Meier patient and graft survival estimates were 89% and 75%, respectively. There were nine graft losses other than deaths with a functioning graft, of which six were preceded by delayed graft function (p = 0.01, chi2). Sixteen (27%) recipients experienced at least one episode of biopsy-confirmed acute rejection. Infections included cytomegalovirus in 16 patients, eight of whom had tissue-invasive disease. Only one malignancy occurred.
CONCLUSIONS: The immunosuppressive strategy investigated is effective and displays a satisfactory safety profile in high immunological risk renal allograft recipients.
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/70
oai:ir.lib.uwo.ca:medpub-1044
2010-08-23T15:28:35Z
publication:surgerypub
publication:pmid
publication:faculties
publication:medpub
publication:med
publication:surgery
15350012
Prospective Evaluation of the Role of Quantitative Doppler Ultrasound Surveillance in Liver Transplantation
Stell, David
Downey, Donal
Marotta, Paul
Solano, Edward
Khakhar, Anand
Quan, Douglas
Ghent, Cam
McAlister, Vivian
Wall, William
Article
2004-09-01T07:00:00Z
Blood Flow Velocity
Hepatic Artery
Liver Cirrhosis
Liver Transplantation
Portal Vein
Postoperative Period
Prospective Studies
Regional Blood Flow
Ultrasonography
Doppler
Vascular Resistance
Liver Transplantation
Liver Transplantation
10
9
1183
1188
http://dx.doi.org/10.1002/lt.20231
Medicine and Health Sciences
Surgery
Doppler ultrasound (DUS) is able to measure parameters of blood flow within vessels of transplanted organs, and vascular complications are associated with abnormal values. We analyzed the findings of 51 consecutive patients who underwent DUS on 2 occasions in the first postoperative week following liver transplantation for cirrhosis to determine the range of values in patients following liver transplantation. Three patients developed early vascular thromboses that were detected by the absence of a Doppler signal. In patients making an uneventful recovery, the arterial velocity tended to increase and the resistive index (RI) to decrease during the first postoperative week. All recipients were shown to have high-velocity segments within the hepatic artery, without an increase in flow resistance. Assessment of the portal vein revealed narrowing at the anastomosis, associated with a segmental doubling of flow velocity, and the mean portal venous flow decreased by approximately 20% in the first postoperative week. In conclusion, a wide range of abnormalities occurs in the vessels of liver transplant recipients, which were not associated with the development of vascular complications or affect patient management.
https://ir.lib.uwo.ca/medpub/38
oai:ir.lib.uwo.ca:surgerypub-1073
2010-08-23T15:41:12Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
15390333
Immunoglobulin-G Subclass Antidonor Reactivity in Transplant Recipients
Gao, Zu-hua
McAlister, Vivian C.
Wright, James R.
McAlister, Chloe C.
Peltekian, Kevork
MacDonald, Allan S.
Article
2004-08-01T07:00:00Z
Graft Rejection
Immunoglobulin G
Immunoglobulin M
Isoantibodies
Kidney Transplantation
Liver Transplantation
Pancreas Transplantation
Postoperative Period
Transplantation Immunology
Homologous Transplantation
Liver Transplantation
10
8
1055
1059
http://dx.doi.org/10.1002/lt.20154
Pathology
Surgery
Outcomes may differ after kidney transplantation compared to combined liver-kidney transplantation. In animal models, distinct patterns of antidonor immunoglobulin (Ig) G subclasses are associated with either rejection or transplant tolerance. Flow cytometry has increased the sensitivity of antidonor immunoglobulin detection. We compared antidonor IgG subclass responses in kidney transplant recipients to those in recipients of liver or multiorgan grafts. In this study of 19 organ (kidney, liver, pancreas) transplantations, recipient serum incubated with donor splenocytes was tested by flow cytometry for the presence of IgM, IgG, or IgG subclass 1-4. Sera before transplantation and 10 days and 100 days after transplantation were used. No differences were seen in antidonor IgM, IgG, or IgG subclass antibodies among recipients of kidney transplants and liver grafts or combination grafts, either before or after transplantation. IgG4 gradually but significantly increased after transplantation in all groups. High levels of antidonor IgG3 either before transplantation or produced after it were found in 3 kidney recipients who experienced acute rejection. No other patients experienced rejection, and no other increase in IgG3 was seen. In conclusion, antidonor IgG subclass profiles may be useful to distinguish populations at risk of rejection but they do not differentiate the immunological response after kidney transplantation from that after liver or combined transplantation. A late rise in antidonor IgG4 is consistent with decreased antidonor reactivity thought to occur late after transplantation.
https://ir.lib.uwo.ca/surgerypub/71
oai:ir.lib.uwo.ca:surgerypub-1075
2010-08-26T01:06:54Z
publication:surgerypub
publication:pmid
publication:faculties
publication:surgery
14762873
Protective Anti-donor IgM Production after Crossmatch Positive Liver-kidney Transplantation
McAlister, Chloe C.
Gao, Zu-Hua
McAlister, Vivian C.
Gupta, Rekha
Wright, James R.
MacDonald, Allan S.
Peltekian, Kevork
Article
2004-02-01T08:00:00Z
Antibodies
Anti-Idiotypic
Blood Group Incompatibility
Complement C1q
Complement System Proteins
Immunologic Cytotoxicity
Flow Cytometry
Graft Rejection
Immunoglobulin G
Immunoglobulin M
Kidney Transplantation
Liver Transplantation
Tissue Donors
Treatment Outcome
Liver Transplantation
10
2
315
319
http://dx.doi.org/10.1002/lt.20062
Pathology
Surgery
The mechanism by which a liver transplantation might protect a simultaneous kidney transplant in a crossmatch-positive recipient is unknown. Flow cytometry crossmatch (FCXM) has increased the sensitivity of donor-specific antibody (DSA) detection compared with complement-dependant cytotoxicity (CDC). Here we compare the outcome of a liver-kidney transplantation (LKT), which was CDC and FCXM positive, to the mate-isolated kidney transplantation (KT), which was CDC negative but FCXM positive, from the same donor. Immunoglobulin G (IgG) and immunoglobulin M (IgM) DSAs were measured by FCXM using splenocytes and purified T cells. The KT graft was hyperacutely rejected and removed, but the LKT graft survived without episodes of rejection. Both the KT and the LKT recipients had high levels of circulating antidonor IgG, but not IgM, before transplantation. By day 3, antidonor IgG and IgM in the LKT recipient increased 2 and 7 fold respectively, whereas the KT recipient maintained the high IgG level but did not increase IgM. Histology of the KT graft showed IgG and complement (C1q) deposition, but in the LKT grafts, IgM was deposited without IgG or C1q. Circulating IgG and IgM DSAs returned to background by day 10 and were still at background on day 100. We report a crossmatch-positive LKT where posttransplantation production of IgM DSA, which failed to fix complement, appeared to protect the grafts.
Dr. Vivian McAlister is currently a faculty member at The University of Western Ontario.
https://ir.lib.uwo.ca/surgerypub/74
839693/simple-dublin-core/100//