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Biomedical subjects

B H Collins

Publications and source records attributed to B H Collins.

At least 19 recordsLinked to original sources
PubMed2005

Obesity predicts increased overall complications following pancreas transplantation.

PURPOSE: We sought to evaluate the role of recipient body mass index (BMI) on postoperative complications in patients receiving pancreas transplants. METHODS: A single-institution retrospective study of 145 consecutive patients undergoing either simultaneous kidney pancreas (SPK) or pancreas after kidney (PAK) transplantation from January 1997 through December 2003. Variables analyzed included: age, sex, BMI, number of prior transplants, cytomegalovirus status of donor and recipient, postoperative insulin resistance, complications, and overall patient and graft survival. Differences in continuous variables and dichotomous variables were evaluated using two-tailed t test and Fisher exact test, respectively. Univariate and multivariate logistic regression analyses were employed to identify predictors of overall complications following surgery. RESULTS: Obesity was defined by a BMI > or = 30. Of the 145 patients, 33 (23%) had a BMI > or = 30 and 112 (77%) had a BMI < 30. There was no significant difference in age or sex between obese and nonobese patients (P = .98 and P = .56, respectively). The type of transplantation, SPK or PAK, did not affect the complication rate (P = .36). Overall complications (infection, dehiscence, evisceration, ventral hernia, allograft failure, gangrene, necrotizing fasciitis, postoperative bleeding, or death) were significantly higher in the obese group (81% vs 40%, P < .001). Obesity was specifically associated with increased frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, necrotizing fasciitis, and repeat laparotomy. Obese patients also had a threefold higher rate of graft pancreatitis/enteric leak. Multivariate logistic regression analysis identified age > or = 50 and BMI > or = 30 as independent predictors of overall complications following surgery (odds ratio 4.0, P = .014 and OR 6.8, P < .001, respectively). There was no difference identified between groups with regards to allograft failure, posttransplant insulin resistance, and death. CONCLUSION: Obese patients are at increased risk of overall complications following pancreas transplantation. Specifically, obese patients experience higher frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, and necrotizing fasciitis. This study demonstrates the need for careful postoperative monitoring in the obese patient.

Adult↗
PubMed2004

Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C.

Drosophila melanogaster locomotor activity responds to different seasonal conditions by thermosensitive regulation of splicing of a 3' intron in the period mRNA transcript. Here we demonstrate that the control of locomotor patterns by this mechanism is primarily light-dependent at low temperatures. At warmer temperatures, when it is vitally important for the fly to avoid midday desiccation, more stringent regulation of splicing is observed, requiring the light input received through the visual system during the day and the circadian clock at night. During the course of this study, we observed that a mutation in the no-receptor-potential-A(P41) (norpA(P41)) gene, which encodes phospholipase-C, generated an extremely high level of 3' splicing. This cannot be explained simply by the mutation's effect on the visual pathway and suggests that norpA(P41) is directly involved in thermosensitivity.

Analysis of Variance↗
PubMed2001

A reliable method for isolation of viable porcine islet cells.

HYPOTHESIS: Mechanical injury and oxidative stress caused by reoxygenation of isolated porcine islet cells result in their unresponsiveness to glucose stimulation. DESIGN: Adult pigs (weighing 25-30 kg) were anesthetized, and following intra-arterial infusion of ice-cold University of Wisconsin solution, a complete pancreatectomy was performed. The pancreatic duct was cannulated for infusion of digestion medium containing collagenase type P, 1.5 mg/mL; deoxyribonuclease I, 10 000 U; and a water-soluble analogue of vitamin E (Trolox), 1 mmol/L. After 20-minute incubations on ice, and at 37 degrees C, the pancreas was hand shaken for 1 minute, followed by filtration and separation on an automatic cell separator (COBE 2991). Islet cells, identified by dithizone staining, were perifused at 37 degrees C. RESULTS: The mean +/- SEM yield of intact purified islet cells (50-200 microm in diameter), and mostly present in clusters, was 2398 +/- 143 cells per gram (n = 12). Glucose stimulation caused a significant increase in biphasic insulin secretion in the perifusion experiments. CONCLUSION: We have developed a simple, reproducible, and reliable procedure for isolating intact and viable porcine islet cells suitable for xenotransplantation.

Animals↗
PubMed2001

Kiwifruit protects against oxidative DNA damage in human cells and in vitro.

Antioxidant micronutrients may account for the beneficial effects of fruits on human health. A direct demonstration that consumption of fruit decreases oxidative DNA damage in human cells would support this hypothesis. Kiwifruit was taken as an example of a food with putative antioxidant properties, and its effectiveness at decreasing oxidative DNA damage was assessed in ex vivo as well as in vitro tests. The comet assay (single-cell gel electrophoresis) was used to measure DNA damage in lymphocytes collected during a human supplementation trial with a single 0.5-liter drink of kiwifruit juice (with water as a control). The comet assay was also modified to assess the antioxidant effect of kiwifruit in vitro by measuring the ability of an extract to interfere with oxidative damage to DNA induced by H2O2. Ex vivo, consumption of kiwifruit led to an increased resistance of DNA to oxidative damage induced by H2O2 in isolated lymphocytes, in comparison with lymphocytes collected after a control drink of water. No effect was seen on endogenous DNA damage. In vitro, a simple extract of kiwifruit, buffered to pH 7, was more effective than a solution of vitamin C (of equivalent concentration) at protecting DNA from damage, whereas at the highest concentrations tested, neither kiwi extract nor vitamin C had a protective effect. We have demonstrated significant antioxidant activity of kiwifruit ex vivo and in vitro, not attributable entirely to the vitamin C content of the fruit. Our dual approach is appropriate for testing other fruit and vegetable products for potential antioxidant effects.

Actinidia↗
PubMed2001

Islet cell transplantation for the treatment of diabetes mellitus.

Diabetes mellitus is estimated to affect at least 16 million individuals in the United States and 135 million persons worldwide. It is a significant cause of morbidity and early mortality. The related expenses are astronomical with at least 15% of healthcare expenditures in the United States being used for the treatment of diabetes and its complications, a figure that approaches US$100 billion annually. The Diabetes Control and Complications Trial (DCCT) convincingly showed that intensive glucose management delays the onset and slows the progression of diabetic complications. Numerous studies have shown that pancreas transplantation not only delays the onset and progression of diabetic complications, but in some cases reverses some of the effects of diabetes. Human islet cell transplantation provides an alternative, less invasive alternative to whole organ transplantation. Human islet allotransplantation would only exacerbate the organ shortage, as recipients usually require islets from more than one pancreas. Xenotransplantation of porcine islets is a more attractive option; however, the recipient's immune response to xenografted tissue would be a formidable obstacle. Microencapsulation of the islets is a method of immunoisolation that would prevent the need for immunosuppressive drugs and the risks associated with their long-term use and have the potential to make xenoislet transplantation a clinical reality.

Animals↗
PubMed2000

Long-term results of liver transplantation in older patients 60 years of age and older.

BACKGROUND: Advances in perioperative care and immunosuppression have enabled clinicians to broaden the indications for organ transplantation. Advanced age is no longer considered a contraindication to transplantation at most centers. Although short-term studies of elderly liver transplant recipients have demonstrated that the incidence of complications and overall patient survival are similar to those of younger adults, transplant center-specific, long-term data are not available. METHODS: From August of 1984 to September of 1997, 91 patients 60 years of age or older received primary liver transplants at the University of Wisconsin, Madison. This group of patients was compared with a group of younger adults (n=387) ranging in age from 18 to 59 years who received primary liver transplants during the same period. The most common indications for transplantation in both groups were Laennec's cirrhosis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis, and cryptogenic cirrhosis. There was no difference in the preoperative severity of illness between the groups. Results. The length of hospitalization was the same for both groups, and there were no significant differences in the incidence of rejection, infection (surgical or opportunistic), repeat operation, readmission, or repeat transplantation between the groups. The only significant difference identified between the groups was long-term survival. Five-year patient survival was 52% in the older group and 75% in the younger group (P<0.05). Ten-year patient survival was 35% in the older group and 60% in the younger group (P<0.05). The most common cause of late mortality in elderly liver recipients was malignancy (35.0%), whereas most of the young adult deaths were the result of infectious complications (24.2%). CONCLUSION: Although older recipients at this center did as well as younger recipients in the early years after liver transplantation, long-term survival results were not as encouraging.

Aged↗
PubMed2000

Using renal transplantation to evaluate a simple approach for predicting the impact of end-stage renal disease therapies on patient survival: observed/expected life span.

The effectiveness of therapy for a chronic disease can be assessed by evaluating the length of time that a patient survives after receiving treatment. We used a novel means for measuring the effectiveness of renal replacement therapy for patients with end-stage renal disease (ESRD): the ratio of observed life span divided by expected life span. This ratio incorporated observed life span for patients from the time of ESRD and expected life span based on state-specific life-table analyses. A total of 3,782 individuals with ESRD were analyzed (average follow-up, 14.2 +/- 4.9 years); 3, 192 patients in that group received a kidney transplant at some point during their course of ESRD. For each patient, we determined a curve of observed/expected life span. Separate patient groups were analyzed to determine the median population observed/expected life span or the percentage of patients who reached 0.5 observed/expected life span. Younger transplant recipients (<21 years) had a median observed/expected life span of 67%, significantly greater than the median observed/expected life span for those aged 21 to 40 years (49%; P = 0.01) and 41 to 60 years (47%; P = 0.01). Surprisingly, 57% of the patients aged older than 60 years reached their median observed/expected life span (P = 0.02 versus <21 years; P = not significant against all others). A Cox proportional hazards model identified era of immunosuppression (hazards ratio, 0.32) and atherosclerotic vascular disease-related ESRD (hazards ratio, 2.07) as significant variables influencing patient survival and observed/expected life span. This simple ratio is easy to use and may be a helpful tool for assessing the survival benefits of risk-factor modifications and therapeutic advances in transplantation and ESRD care.

Adult↗
PubMed2000

Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease.

BACKGROUND: Diabetic renal disease continues to be the most significant cause of end-stage renal disease (ESRD) in the United States. Renal transplantation improves diabetic ESRD patient survival; however, the diabetic state remains associated with poor patient survival. Simultaneous pancreas-kidney (SPK) transplantation can restore normoglycemia and thus may improve outcomes. METHODS: We assessed the impact of SPK on age-range-matched type 1 diabetic patients who underwent renal transplantation at a single center. The observed/expected life span and annual mortality rates (AMRs) were used as measures of survival. A Cox proportional hazards analysis was used to analyze the impact of potential variables on mortality in SPK recipients. RESULTS: SPK transplantation (N = 335) increased the observed/expected life span compared with diabetic cadaveric (DM-Cad, N = 147) and live-donor (DM-Live, N = 160) transplant recipients (P = 0.004) and significantly reduced the AMRs (SPK, 1. 5%; DM-Cad, 6.27%; DM-Live, 3.65%, P = 0.008, SPK vs. other DM). Moreover, the SPK observed/expected life span and AMR were not significantly different from that of age-range-matched nondiabetic transplant recipients (N = 492). The only variable that was significantly associated with patient survival was discharge serum creatinine (relative risk 1.16, P < or = 0.0154). CONCLUSION: These data demonstrate that SPK improves the ability for type 1 diabetic patients to live more of their expected life span. This suggests that glycemic control, even as a late intervention in a diabetic patient's lifetime, may beneficially affect survival.

Adult↗
PubMed1999

The impact of hypoalbuminemia in kidney-pancreas transplant recipients.

BACKGROUND: Hypoalbuminemia is associated with poorer outcomes in renal transplantation. Diabetes can compound hypoalbuminemia's detrimental effects. Kidney-pancreas transplantation alters the diabetic milieu; yet, some patients continue to be hypoalbuminemic. METHODS: We retrospectively analyzed 232 patients who underwent simultaneous kidney-pancreas transplantation (SPK) between 1993 and 1997 to determine the incidence and clinical correlates of hypoalbuminemia in SPK recipients. Post-SPK hypoalbuminemia was defined as a serum albumin level < or =3.5 g/dl. Univariate analyses were performed to determine whether post-SPK hypoalbuminemia was associated with pre-SPK variables. The effect of albumin level and hypoalbuminemia on the risk of post-SPK events (cardiac events, cytomegalovirus [CMV] infection, rejection, readmission, kidney and pancreas graft failure, and death) was examined with a Cox proportional hazards model. RESULTS: The study population consisted of 149 men and 83 women. Average follow-up was 2.0+/-1.3 years. Hypoalbuminemia (serum albumin level < or =3.5 g/dL) was most common early after SPK (3 months: 44% of evaluable patients were hypoalbuminemic; 12 months: 15.3%; 36 months: 8.3%). Acute rejection episodes and readmission were the most common adverse events after SPK transplantation. There were 24 episodes of renal allograft loss and only 5 cardiac events. Ten SPK recipients died during the study time period. SPK-related hypoalbuminemia was associated with an increased risk for CMV infection (risk ratio [RR] 2.5; P<0.02), renal graft failure (RR 2.41; P=0.05), pancreas graft failure (RR 3.66; P=0.01), and a trend toward an increased risk for death (RR 2.8; P=0.19). CONCLUSIONS: Post-SPK hypoalbuminemia resolves over time in many patients. Persistent post-SPK hypoalbuminemia is associated with an increased risk for CMV infection, graft loss, and a trend toward decreased survival. Efforts to improve nutrition, as it may affect hypoalbuminemia in SPK recipients, may be one strategy for improving SPK outcomes.

Aged↗
PubMed1999

Peripheral vascular disease and renal transplant artery stenosis: a reappraisal of transplant renovascular disease.

BACKGROUND: Renal transplant artery stenosis (RTAS) continues to be a problematic, but potentially correctable, cause of post-transplant hypertension and graft dysfunction. Older transplant recipients, prone to peripheral vascular disease (PVD), may have pseudoRTAS with PVD involving their iliac system. METHODS: We retrospectively analyzed 819 patients who underwent kidney transplantation between 1993 and 1997 to determine the contribution of pseudoRTAS to renal transplant renovascular disease. Univariate analyses were performed for donor and recipient variables, including age, weight, gender, race, renal disease, cholesterol and creatinine values, human leukocyte antigen (HLA) matching, cytomegalovirus (CMV) infection, and immunosuppressive medications. Significant variables were then analyzed by a Cox proportional hazards model. RESULTS: Ninety-two patients (11.2%) underwent renal transplant arteriogram (Agram) or magnetic resonance angiography (MRA) for suspected RTAS. RTAS or pseudoRTAS, defined as one or more hemodynamically significant lesions in the transplant artery or iliac system, was evident in 44 patients (5.4%). Variables significantly associated with RTAS by univariate analysis were weight at the time of transplant (p = 0.0258), male gender (p = 0.034), discharge serum creatinine > 2 mg/dL (p = 0.0041), and donor age (p = 0.0062). Variables significantly associated with pseudoRTAS by univariate analysis were weight at the time of transplant (p = 0.0285), recipient age (p = 0.0049), insulin-dependent diabetes mellitus (IDDM; p = 0.0042), panel reactive antibody (PRA) at transplant (p = 0.018), and body mass index (p = 0.04). Weight at transplant and donor age remained significantly associated with an increased risk for RTAS in a multivariate stepwise Cox proportional hazards model. IDDM, transplant PRA, weight at transplant, and donor age were significantly associated with an increased risk for pseudoRTAS in a multivariate stepwise Cox proportional hazards model. Importantly, both RTAS and pseudoRTAS were associated with poorer graft survival (p < 0.007 for each). CONCLUSIONS: Renal transplant renovascular disease encompasses pre-existing PVD acting as pseudoRTAS, as well as classical RTAS. Efforts to identify and correct renal transplant renovascular disease of either nature are important, given its negative impact on graft survival.

Adult↗
PubMed1998

Living unrelated renal donation: the University of Wisconsin experience.

BACKGROUND: Living unrelated renal donation (LURD) has the potential to reduce the current waiting list significantly for kidney transplantation. The purpose of this study was to examine the long-term results of 150 LURDs performed at our center during a 16-year period. METHODS: From Dec 23, 1981, to Feb 13, 1998, 150 LURDs, 219 human leukocyte antigen (HLA)-identical, 577 haploidentical, and 1789 cadaveric kidney transplant procedures were performed. Surgical complications, rejection episodes, infectious complications, and the cause of graft loss and death were examined. Ten-year patient and graft survival rates between groups were compared. RESULTS: Fourteen surgical complications including lymphocele (n = 7), ureteral stricture (n = 4), and ureteral leak (n = 3) were seen. Seventy-eight patients (52%) had 123 rejection episodes and 66 patients (44%) had 1 or more infections. Thirty-six allografts were lost and 25 deaths occurred. Patient survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaveric transplant procedures were 86%, 82%, 63%, and 64%, respectively. Allograft survival rates at 10 years for HLA-identical, haploidentical, LURD, and cadaver transplant procedures were 75%, 59%, 56%, and 44%, respectively. CONCLUSIONS: Long-term LURD allograft survival rates are lower than those for HLA-identical but equivalent to those of haploidentical and better than those of cadaveric kidney transplantations. Spousal and nonspousal LURDs should be actively encouraged to help alleviate the current donor kidney shortage.

Adolescent↗
PubMed1997

Effect of continuous complement inhibition using soluble complement receptor type 1 on survival of pig-to-primate cardiac xenografts.

A single bolus of soluble complement (C) receptor type 1 (sCR1, TP-10) has been shown to delay hyperacute rejection (HAR) of porcine cardiac xenografts (Xgs) by primate recipients. In these recipients, C activity slowly returned and C deposition was noted in the Xgs at rejection. To evaluate the effect of sustained C inhibition using sCR1 on HAR, two additional cynomolgus monkeys received porcine cardiac Xgs and a continuous infusion of sCR1. In the first recipient, Xgs survival was 5 days (120+ hr), whereas in the second, Xg survival was 7 days (168+ hr). Serial biopsies of the Xgs were remarkable for an increasing cellular infiltrate composed predominantly of neutrophils and macrophages, and the development of edema, hemorrhage, and myocyte necrosis. These findings suggest that once C-mediated HAR has been inhibited, infiltration of the Xg by these cells may lead to accelerated acute rejection, which is an additional barrier to successful longer term Xg survival.

Animals↗
PubMed1996

Quality of life after treatment for pancreatitis.

OBJECTIVE: The authors evaluated the morbidity, mortality, and quality of life after pancreatic debridement for necrosis and compared these values to those for quality of life after elective medical and surgical management for chronic pancreatitis. SUMMARY BACKGROUND DATA: Quality of life after pancreatic debridement for necrosis has received little attention. Although quality of life after other pancreatic surgery has been evaluated and is though to be good, management of patients with pancreatic necrosis can be labor intensive and require extraordinary resources. Therefore, further evaluation of the quality of life achieved after treatment is appropriate. METHODS: Forty patients (group 1) underwent operative debridement for necrosis between 1986 and 1994. Medical records of these patients were reviewed for morbidity, mortality, and in-hospital costs. Follow-up of quality of life was assessed by the Short Form-36 Health Survey. Patients in group 2 (n = 89) underwent medical management of chronic pancreatitis. Group 3 included 47 patients who underwent elective operations for ductal abnormalities. The Short Form-36 Health Surveys were administered to all three groups and compared statistically. RESULTS: Mortality and morbidity from pancreatic debridement was 18% and 77%, respectively. Quality-of-life evaluations in groups 1 through 3 and age-matched controls were statistically similar. CONCLUSIONS: Pancreatic debridement for necrosis requires intense application of resources and is associated with a high mortality and morbidity. Long-term follow-up shows good quality of life for patients who survive this morbid disease. This study supports the continued aggressive approach to the management of pancreatic necrosis, given that long-term outcome about quality of life is good.

Chronic Disease↗
PubMed1995

The humoral immune response in humans following cross-perfusion of porcine organs.

A major question in xenotransplantation is the nature of the humoral response that would occur following the transplantation of a xenogeneic organ into an immunosuppressed recipient as such a response could mediate delayed types of injury to the graft. To begin to address this issue we characterized the changes in the properties of xenoreactive antibodies occurring in patients exposed to porcine organs under conditions simulating transplantation. In two patients whose blood had been cross-perfused through porcine livers as a treatment for hepatic failure, the titer of xenoreactive IgM increased by four-fold and the titer of xenoreactive IgG increased by sixty-fold within ten days after perfusion procedures. The xenoreactive IgM and IgG antibodies were specific for Gal alpha 1-3Gal based on binding to porcine endothelial cells and bovine thyroglobulin, which express this determinant, and on the decrease in binding following treatment of porcine endothelial cells or bovine thyroglobulin with alpha-galactosidase. The sequential addition to endothelial cells of amounts of serum known to saturate antibody-binding sites obtained before and ten days after perfusion of porcine organs revealed no increase in binding of IgM above the level observed with serum obtained before perfusion, suggesting that new determinants were not identified. Moreover, the functional avidity of binding to porcine endothelial cells of IgM in serum obtained before and ten days after perfusion of porcine organs was unchanged. Even at later times, the presence of newly elicited antibodies against porcine aortic endothelial cell targets was not detected. Thus, exposure to porcine antigens in a vascularized organ results in increases in the levels of xenoreactive IgM and IgG antibodies--however, these antibodies exhibit properties similar to natural antibodies.

Adult↗