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Biomedical subjects

D W Gray

Publications and source records attributed to D W Gray.

At least 37 records · Page 2Linked to original sources
PubMed1997

The factor V Leiden (R506Q) mutation and risk of thrombosis in renal transplant recipients.

BACKGROUND: Renal transplantation and chronic renal failure are associated with an increased risk of venous thrombosis and myocardial infarction (MI). We investigated whether resistance to activated protein C due to a mutation in the factor V gene (FV Leiden/FV506Q) may predispose patients to thrombosis. METHODS: Three hundred patients who had undergone renal transplantation were genotyped for the FV mutation. Seventy-seven patients who had suffered thrombotic complications (42 venous, 28 arterial, and 7 both) were compared with 223 patients free of thrombosis. RESULTS: Thirty-two patients had suffered early renal allograft thrombosis (30 venous), and 33 patients had suffered MI. A higher proportion of the patients with thrombosis, compared to those without, had a family history of arterial cardiovascular disease (42% vs. 26%, P=0.04). Eighteen (6%) patients were heterozygous for FV506Q and seven (39%) of these had suffered venous thrombosis (including four primary allograft thromboses), compared with 15% of the patients without the mutation (P<0.05). The odds ratio for risk of venous thrombosis for FV506Q carriers was 3.6 (95% confidence interval: 1.3-9.9) or 4.0 (1.2-13.8) for primary allograft thrombosis. Only one of the FV506Q carriers had suffered an MI. CONCLUSIONS: Carriers of the factor V 506Q mutation with chronic renal failure who have undergone transplantation are at an increased risk of venous but not arterial thrombosis. This mutation explained 14% of all venous and 20% of primary allograft thrombosis, suggesting that other unidentified genetic and environmental factors contribute to the risk of thrombosis in renal transplant recipients.

Adolescent↗
PubMed1997

Effect of one-HLA-haplotype-matched and HLA-mismatched blood transfusions on recipient T lymphocyte allorepertoires.

BACKGROUND: Pretransplant blood transfusion has a well-known beneficial effect on posttransplant graft survival. Recently, it has been proposed that the clinical benefit of transfusion is due to HLA-DR antigen sharing between the blood donor(s) and the recipient. Immunological studies have suggested that this might result from a functional deletion of donor-reactive cytotoxic T lymphocytes. METHODS: We investigated frequencies of alloreactive lymphocyte precursors with cytotoxic or interleukin-2-producing helper function by limiting dilution analysis in 10 renal dialysis patients before and after transfusion with fresh, allogeneic whole blood. Five patients received blood transfusions from donors matched for one HLA haplotype (or one HLA-B-DR antigen) and the other five patients received blood from fully HLA-mismatched donors. RESULTS: Contrary to some previous reports, frequency analysis of cytotoxic T lymphocyte precursors revealed no significant differences between the two treatment groups in terms of development of blood donor-specific hyporesponsiveness after transfusion. Split-well analysis of cytotoxic T lymphocyte precursors reactive with single-mismatched HLA antigens demonstrated that the effects of transfusion on alloreactive specificity are complex and may vary depending on the particular antigens mismatched between the recipient and blood donor. Analysis of donor-specific helper T lymphocyte precursor frequencies revealed a significant decrease of interleukin-2-producing cells 3 months after transfusion in the total patient population. This effect was most prominent in the recipients of HLA-mismatched blood, but it also exhibited some degree of nonspecificity, as frequencies of third-party reactive helper T lymphocyte precursors were also significantly reduced. CONCLUSIONS: Our overall results suggest that the degree of HLA matching between blood donor and recipient does not greatly influence the effect of blood transfusion on the T lymphocyte allorepertoire. The apparent induced down-regulation of helper T lymphocyte activity may play a role in the reported immunosuppressive effects of allogeneic blood transfusion.

Adult↗
PubMed1997

Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.

BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

Blood Transfusion↗
PubMed1997

Patterns of graft infiltration and cytokine gene expression during the first 10 days of kidney transplantation.

Understanding of the events preceding acute cellular rejection of kidney transplants would be useful in the development of immunosuppressive strategies to prevent rejection. Information about these events in humans has been scarce, because of the lack of early, serial, biopsy samples. We took daily fine needle aspirates from kidney allografts for the first 10 days after transplant. Samples were analyzed by morphological cytology of graft-infiltrating cells, and reverse transcriptase-polymerase chain reaction for detection of interleukin (IL)-2, IL-4, IL-6, IL-10, and gamma-interferon gene expression. During the first 4 days, all of the grafts developed a low-grade monocyte-rich mononuclear cell infiltrate, accompanied by IL-10 gene expression. Thereafter, the infiltrates either remained stable or intensified. Of the 13 grafts with dense infiltrates, seven developed graft dysfunction. The remaining six did not, despite significant interstitial infiltrates. Both rejecting and nonrejecting dense infiltrates were associated with a biphasic pattern of IL-2 and gamma-interferon gene expression, preceding and accompanying lymphocytic graft infiltration. Grafts that did not develop dense infiltrates had no detectable IL-2 or gamma-interferon gene expression and did not suffer cellular rejection during the study period. The development of both rejecting and nonrejecting infiltrates was strongly associated with DR mismatches between donor and recipient. IL-2 and gamma-interferon gene expression are necessary, but not sufficient, for the development of acute cellular rejection in the first 10 days of kidney transplantation, and are more closely associated with the period leading up to rejection than with the period of graft dysfunction.

Acute Disease↗
PubMed1997

Encapsulated islet cells: the role of direct and indirect presentation and the relevance to xenotransplantation and autoimmune recurrence.

Immuno-isolation of islet tissue for the purpose of curing diabetes without immunosuppression is an attractive concept that has been extensively investigated over the last 20 years. Rather than give a detailed review of the past and present history of the immuno-isolation or encapsulation approach for islet transplantation, this paper will examine the concepts behind encapsulation, concentrating on the immune mechanisms involved.

Autoimmunity↗
PubMed1997

Management of severe pancreatitis in renal transplant recipients.

OBJECTIVE: The authors determine if any aspects of the treatment of renal transplant patients with pancreatitis were of particular benefit with regard to graft and patient survival. BACKGROUND: The incidence of pancreatitis in renal transplant patients is low (1%-2%), but the mortality of the disease approaches 100%. Although several descriptive reports have been published, there is no consensus-regarding management. METHODS: The authors conduct a retrospective chart review. RESULTS: Twenty-one patients were identified with posttransplant pancreatitis (1.3% incidence). The cause of pancreatitis was presumed to be maintenance immunosuppression in all cases. Patients were classified by dynamic computed tomography (CT) scans having 1) mild/edematous disease (4 patients), 2) localized abscess or pseudocyst (6 patients), or 3) severe disease (11 patients). Patients with mild/edematous pancreatitis did well with medical management. The six patients with localized abscess or pseudocyst were successfully treated with standard operative intervention. Of the 11 patients with severe disease, 6 had several days of intensive medical management before operation, and all died. The other five patients underwent early operative intervention based principally on CT scan findings, and all survived. The latter group had multiple operations and four of five had functioning renal allografts at discharge. CONCLUSION: The severity of pancreatitis in the posttranplant patients may be difficult to assess by clinical criteria. Dynamic CT scanning is, therefore, essential in defining the extent of disease. Early, and perhaps repeated, operations may be lifesaving in those patients having CT scan findings of severe pancreatitis.

Adult↗
PubMed1997

Shortening in femoral shaft fractures in children treated with spica cast.

Early spica cast treatment is one method used for children's femoral shaft fractures; it is increasingly advocated as treatment that allows early hospital discharge. The outcome of early spica cast treatment in 100 children, ages 2 to 10 years, with uncomplicated and isolated closed femoral shaft fractures treated at Johns Hopkins Hospital between October 1987 and March 1994 were analyzed. The objective was to identify those children who can be treated safely and dependably with early spica casting without excessive shortening of the fracture fragments. Eighty-one (81%) children had an acceptable outcome and 19 (19%) had an unacceptable outcome by the definition of more than 25 mm of fracture fragment overlap after clinical healing. A new clinical test, the telescope test, was statistically significant for correlation with spica cast outcome. Age, gender, fracture, location, mechanism of injury, fracture type, and resting radiograph of fracture fragment overlap were not statistically significant. The telescope test had a sensitivity of 80% and a specificity of 85% for predicting outcome. The relative risk for failure of spica cast treatment with a positive telescope test was 20.4 (95% confidence limits = 2.7-225.1). Children 2 to 10 years of age with uncomplicated femoral shaft fractures and a negative telescope test can be treated appropriately in most cases with early application of a spica cast.

Casts, Surgical↗
PubMed1996

Preemptive cadaveric renal transplantation--clinical outcome.

Preemptive cadaveric renal transplantation (PCRT) maximizes the chance of maintaining high quality of life and may avoid the morbidity of dialysis and the associated financial costs. These benefits are offset by disadvantages, which include the possibility of transplantation many months before the need for dialysis, resulting in wasted organ function; an immediate risk of graft failure with conversion to a dialysis-dependent state; and uncertainty of the safety of PCRT. Patients who underwent PCRT between June 1976 and December 1994 at the Oxford Transplant Centre were compared with a matched cohort of first cadaveric transplant recipients who were dialysis-dependent when transplanted. The 116 patients in the PCRT cohort were well matched to the control group with respect to sex, age, blood group, HLA match, degree of sensitization, donor age, immunosuppression, and year of transplantation. Patient and graft survival were significantly better in the PCRT group. The difference in graft survival did not appear to be completely explained by better patient survival, as suggested by a trend toward better graft survival after excluding death with a functioning graft as a cause of failure. Among surviving grafts there were no significant differences in graft function as assessed by 1, 2, and 3 year plasma creatinine levels. In conclusion, PCRT appears to be safe and may even be associated with superior graft survival when compared with conventional transplantation. Early inclusion on a transplant waiting list with a view to PCRT can be justified with respect to the clinical outcome but the financial costs and implications for the utilization of cadaveric donor kidneys must also be considered.

Adolescent↗
PubMed1996

Late reflush in clinical renal transplantation. Protection against delayed graft function not observed.

Mechanical flushing of cadaveric kidneys with organ preservation fluid immediately before transplantation has been reported to be associated with improved early graft function. We report here the results of a prospective randomized controlled study of cadaveric renal transplantation after late reflush with organ preservation fluid in which no benefit with respect to delayed graft function was observed and, indeed, the protocol may have been harmful. The study was terminated after recruitment of only 18 patients (9 to each arm) because postreperfusion biopsies of reflushed kidneys contained unusual features, including abnormal cellular debris within the tubules or eosinophilic proteinaceous material within Bowman's capsule. These features were not present in the control kidneys. Acute tubular necrosis and biopsy-proven acute rejection episodes were more frequently seen in the reflushed kidneys, but at 1 year there was no significant difference in the function of the surviving grafts.

Adult↗
PubMed1996

Cytomegalovirus infection and colonic perforation in renal transplant patients.

Cytomegalovirus (CMV) infection in immunocompromised patients is a major cause of morbidity and mortality. A well-documented manifestation of gastrointestinal CMV infection is gastrointestinal haemorrhage. In contrast, CMV-associated intestinal perforation has rarely been reported after transplantation, although it is well documented in AIDS patients. Three patients are reported who received their first cadaveric renal transplant in 1994 and subsequently developed CMV disease. During the course of their CMV illness, which was treated with ganciclovir, each presented with clinical suspicion of peritonitis and proceeded to laparotomy. All three were found to have sigmoid colon perforations with histological evidence of CMV infection. Following bowel resection and defunctioning, two patients made an uneventful recovery and have had the continuity of their bowel restored, but one died of overwhelming sepsis within hours of surgery. The explanation for the apparent clustering of this rare condition in transplant patients is uncertain.

Aged↗
PubMed1996

A ten year audit of surgery for vascular trauma in a British teaching hospital.

Vascular trauma is uncommon in the U.K. with the exception of Northern Ireland. In marked contrast to North America, gunshot wounds are rare and stabbings are infrequent. A 10 year audit was carried out in a regional vascular referral unit to determine the mechanisms, treatment and outcome of vascular injuries. Forty-seven patients were operated on during the period. The median age was 26 years (range 7-85 years); two-thirds were men. Road traffic accidents accounted for 21 (45%) of injuries, other accidents 15 (32%) and stabbings 11 (23%). There were no gunshot wounds. Most injuries were penetrating with no associated fracture. Commonly injured vessels were the brachial (30%) and superficial femoral (15%) arteries. Fifty-three primary operations were performed, 10 were vein interpositions and 21 were bypass grafts. There were three primary amputations (6%). Eleven patients suffered a complication including one death. One graft occluded requiring a further bypass. Two patients required fasciotomy as a secondary procedure. Median follow-up was 6 months. Eighty-one percent of patients were symptom free at last follow-up. There were no late vascular complications. Our experience is likely to represent that of other vascular units in countries with strict gun control legislation, little civil violence and modest levels of road traffic accidents.

Accidents, Traffic↗
PubMed1996

The role of zinc in solutions used for cold preservation of pancreatic islets.

Advances in the field of organ transplantation have been made possible by progress in cold preservation as well as advances in immunosuppression, postoperative surgical care, and refinement of surgical techniques. The optimal solution for cold storage of pancreatic islets has not been defined, although recent studies have suggested that University of Wisconsin (UW) solution or derivatives may be significant advances. Zinc has a central role in the storage, synthesis, and secretion of insulin and is taken up preferentially by isolated islets to levels 30-fold higher than those of extracellular zinc. Since the currently used cold storage solutions do not contain zinc, we have investigated the effect of adding zinc to Hanks and UW solution and assessed the viability status of the islets at 0 h and at 1, 3, and 6 days. Islets of standard diameter were suspended in four solutions: Hanks solution, Hanks +20 microM zinc, UW solution, and UW +20 microM zinc. Viability was assessed by supravital staining, and each islet was scored at 0 h and at 1, 3, and 6 days. The results showed that UW solution was superior to Hanks solution for the preservation of pancreatic islets up to 6 days, but the addition of zinc was not beneficial. Despite the integral role of zinc in islet metabolism, we were unable to find a beneficial role for zinc in cold storage solutions for the purposes of islet preservation.

Animals↗
PubMed1996

Hepatic cystic disease in an adult polycystic kidney disease transplant population.

BACKGROUND: A study of the incidence of polycystic liver in a transplant population and an assessment of the impact of this disease on the group was undertaken. Clinical presentation, investigation and treatment of hepatic polycystic disease are explored. METHODS: The study examined the morbidity incurred by polycystic liver disease in patients, patient and graft survival, incidence of hepatic cysts and presentation, investigation and management of morbid hepatic cystic disease. One hundred and eleven patients were studied. RESULTS: It was found that hepatic cysts occurred in the majority of patients that underwent transplants for renal failure because of polycystic kidney disease at this institution. Symptomatic hepatic cystic disease was found to be primarily responsible for three deaths and affected between 15 and 20% of the group. Gall bladder disease was found to be associated with highly symptomatic hepatic cystic disease. CONCLUSION: Hepatic cystic disease is common in patients that have had kidney transplants because of polycystic kidney disease. Morbidity is likely to increase as patients survive for longer periods. Cholecystectomy should be considered in patients with significant hepatic cystic disease.

Adult↗