PubMed Health⌕ Search

Biomedical subjects

J F Neylan

Publications and source records attributed to J F Neylan.

31 records · Page 2Linked to original sources

Preemptive ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus antibody-positive renal transplant recipients. A randomized controlled trial.

OBJECTIVE: To determine whether preemptive ganciclovir therapy administered daily during antilymphocyte antibody therapy can prevent cytomegalovirus disease in renal transplant recipients who are positive for cytomegalovirus antibody. DESIGN: Randomized, controlled, multicenter trial. SETTING: 6 university-affiliated transplantation centers. PATIENTS: 113 renal transplant recipients who were positive for cytomegalovirus antibody. INTERVENTION: Patients were randomly assigned to receive either 1) ganciclovir, 2.5 mg/kg body weight administered intravenously on every day that antilymphocyte antibody therapy was administered or 2) no anticytomegalovirus therapy. MEASUREMENTS: Patients were observed for 6 months after completion of antilymphocyte antibody therapy for development of cytomegalovirus disease and cytomegalovirus viremia. RESULTS: Cytomegalovirus disease occurred in 14% of patients (9 of 64) who received preemptive ganciclovir therapy and in 33% of controls (16 of 49) (P = 0.018). Cytomegalovirus was isolated from buffy-coat specimens from 17% of patients (11 of 64) receiving preemptive ganciclovir and from 35% of controls (17 of 49) (P = 0.03). Controlling for the reason (induction or treatment of rejection) for using antilymphocyte antibodies in a Cox proportional hazards model, we found that preemptive ganciclovir still protected against cytomegalovirus disease (adjusted relative risk, 0.27; 95% CI, 0.12 to 0.64). No adverse events were attributed to preemptive ganciclovir therapy during or within 6 months of its administration. CONCLUSIONS: Preemptive ganciclovir therapy administered daily during courses of treatment with antilymphocyte antibodies reduced the excessive occurrence of cytomegalovirus disease in renal transplant recipients who were positive for cytomegalovirus antibody. This approach, which links the most potent immunosuppression to intensive antimicrobial therapy, allows preventive therapy to be given to those patients at greatest risk for developing infectious complications. These patients are likely to benefit most from the preventive strategy.

Adolescent↗

Ureteral obstruction due to calculi in the early postoperative period in renal cadaveric transplantation: a case report and discussion of ureteral obstruction in the renal transplant patient.

We report a case of obstruction secondary to multiple ureteral calculi on postoperative day 3 after cadaveric renal transplantation. Treatment consisted of ureterolithotomy with stenting of the ureteroneocystotomy and convalescence was otherwise unremarkable. Obstructive complications of the ureter after renal transplantation are reviewed.

Adult↗

Cyclosporine increases the oxidizability of low-density lipoproteins in renal transplant recipients.

Blood specimens from twenty-six renal transplant recipients treated with cyclosporine (CsA) were collected at weekly intervals, two months after transplantation. Specimens were grouped according to their CsA concentrations. Group I consisted of ten specimens with CsA concentration of >400 ng/ml; group II consisted of ten specimens with CsA concentrations ranging from 120-300 ng/ml; and group III consisted of six specimens with CsA concentrations of < 100 ng/ml. In addition, specimens from five renal transplant patients who, instead of CsA, received the immunosuppressant FK506 (group IV), and from six healty individuals were included. Plasma low-density lipoproteins (LDL) were isolated and their susceptibility to oxidation was studied by continuously monitoring the formation of conjugated dienes during copper ion-mediated oxidation. Patients with higher blood concentrations of CsA (groups I and II) had significantly higher oxidizability of LDL, as indicated by the shorter time required to start the oxidation (lag phase). The oxidizability of samples with low concentration of CsA (group III) was not significantly different from that of FK506-treated patients or healthy individuals. There was a negative correlation (r = -0702, P < 0.01) between oxidizability (lag phase) and CsA concentration in LDL. No correlation between blood CsA and plasma cholesterol or triglyceride concentration was evident during a three-month period postoperatively. Similarly, no correlation between the degree of oxidizability and plasma cholesterol or triglycerides was found at the time of the experiment. These findings suggest a prooxidant effect of CsA to plasma LDL, and may indicate that CsA is an important risk factor in the accelerated atherosclerosis of renal transplant recipients.

Cholesterol↗

The evaluation of candidates for renal transplantation. The current practice of U.S. transplant centers.

The criteria for acceptance of candidates for renal transplantation varies throughout the United States. The Patient Care and Education Committee of the American Society of Transplant Physicians conducted a survey of all U.S. centers that participate in the United Network for Organ Sharing (UNOS) concerning their evaluation of adult candidates for kidney transplantation. The response to each question was examined according to the specialty of the individual who filled out the questionnaire, as well as the type of transplant center (university or private) and the size of the center. The response rate to the survey was 81% (147/182). We found the following: (1) university-based and larger centers accepted more medically complicated patients; (2) 83% noted that attendance to dialysis was an important indicator of compliance after transplantation; (3) 79% did not require preoperative blood transfusions for cadaver kidney recipients; (4) 66% set no specific upper age limit for transplantation; (5) 56% excluded patients with chronic active hepatitis in the setting of hepatitis B antigenemia; (6) 50% had no specific policy for evaluating hepatitis C antibody-positive patients, while 54% excluded the use of hepatitis C antibody-positive donors, and (7) 15% obtained coronary angiography on all diabetic patients. U.S. transplant centers have a heterogeneous approach to the evaluation of patients for renal transplantation, particularly in the areas of viral hepatitis, cardiovascular disease, and noncompliance. University-based centers and centers that perform a larger number of transplants accept more medically complicated patients.

Adult↗

Epitope specificity of HLA class I alloantibodies. I. Frequency analysis of antibodies to private versus public specificities in potential transplant recipients.

Sera obtained sequentially from 419 patients awaiting solid organ transplantation were screened and analyzed for HLA class I epitope specificity. Antibodies detected in each serum were defined as "private" if reactivity could only be demonstrated against a single specificity within one of the eight major CREGs, or as "public" if reactivity in a serum could be demonstrated against two or more specificities within a single CREG. A total of 139 sera contained % PRA > 0, in which 147 specific antibodies were identified. Of the 103 positive sera, 93 (90%) contained antipublic antibodies, with or without additional antiprivate antibodies, whereas just 10 (10%) sera contained only apparent antiprivate antibodies. The success rate in defining antibody specificities was low at PRA values of 1%-20% due to weak reactivity and high false-positive rates. Specificity analysis with high test sensitivity and specificity was achieved with PRA values between 40% and 80%. At PRA values > 80%, test sensitivity remained high but specificity declined. We conclude that most anti-HLA antibodies are directed against high frequency public epitope clusters (CREGs), and highly sensitized patients develop antibodies in a fairly predictable fashion, a feature that significantly improved the success rate of specificity analysis. Since high frequency antipublic antibodies are common sequelae of CREG mismatches, further definition of HLA class I public epitopes eventually may be important in donor-recipient matching.

Antibody Specificity↗

Hypertension after renal transplantation.

Hypertension is a frequent complication after organ transplantation in both children and adults and is a significant risk factor for the development of cardiovascular disease and graft dysfunction. There are multiple mechanisms responsible for the development of posttransplant hypertension. In the precyclosporine era, chronic rejection was the most common cause. The introduction of cyclosporine A has increased the prevalence of hypertension in solid organ transplant recipients. Cyclosporine increases renal vascular resistance by causing vasoconstriction of the afferent arteriole. From a pathophysiologic point of view, a calcium channel blocker should be used as the initial therapy in patients with cyclosporine-associated hypertension. Hypertension needs to be treated aggressively in all transplant recipients in an attempt to minimize allograft and cardiovascular damage.

Adult↗

Race and sex differences in the identification of candidates for renal transplantation.

The availability of renal transplantation to individuals with end-stage renal disease (ESRD) is an issue of considerable concern. The role of age, race, sex, socioeconomic status, illness severity, and comorbidity in determining access to this therapy remains unclear. We examined the influence of these factors on transplant candidacy in 8,315 patients receiving dialysis treatment for ESRD in North Carolina, South Carolina, and Georgia. We found important race-sex differences in the likelihood of being identified as a transplant candidate. These differences persisted after adjustment for other patient characteristics, including illness severity and certain comorbid conditions. Characteristics found to be positively associated with candidacy included age less than 30 years (P less than 0.00001), living with a spouse and children (P = 0.004), and employment status (P = 0.006). Characteristics and comorbid conditions that were negatively associated with candidacy included 8 years or less of formal education (P = 0.001), cancer (P = 0.0006), visual impairment (P = 0.006), congestive heart failure (P = 0.008), and peripheral vascular disease (P = 0.01). Compared with white males, after adjustment for these factors, the likelihood (95% confidence interval) of being identified as a transplant candidate was: white females, 0.88 (0.65 to 1.18); black males, 0.77 (0.59 to 0.99); and black females, 0.66 (0.51 to 0.87). We conclude that although socioeconomic and medical factors are strongly associated with transplant candidacy, these associations do not adequately explain the observed race-sex differences in transplant candidacy status.

Adolescent↗

Atrial natriuretic factor does not improve the outcome of cadaveric renal transplantation.

Atrial natriuretic factor (ANF) ameliorates renal damage in animal models of acute ischemic renal failure. Consequently, ANF could blunt acute tubular necrosis related to ischemia that occurs frequently in cadaveric renal transplants. Ten pairs of cadaveric kidneys were transplanted into 20 recipients. Paired recipients received either alpha-human ANF (hANF) or vehicle alone in a prospective, double-blind protocol. Upon revascularization of the allograft, either hANF or vehicle was administered intravenously as a 50-micrograms bolus, followed by a 4-h infusion (0.1 microgram/kg/min). Glomerular filtration rate ([125I]iothalamate clearance) was measured between 4 and 7 days posttransplant and again between 14 and 21 days posttransplant. Serum creatinine was measured daily when patients were in the hospital, then twice weekly as patients were examined in the outpatient clinic. Between the groups, there was no significant difference in age of the recipients or donors, cold ischemia time, or histocompatibility leukocyte antigen match. Infusion of hANF had no adverse effects. When subjects receiving hANF were compared with those treated with vehicle alone, there were no significant differences in serum creatinine or glomerular filtration rate. Three hANF and four vehicle recipients required dialysis postoperatively. At 1 month posttransplant, 19 of 20 patients had functioning allografts; an allograft from one hANF recipient never functioned. It was concluded that hANF, when given by the protocol of this study, had no beneficial effect on the outcome of cadaveric renal transplantation in humans.

Acute Kidney Injury↗

Diagnosis of pancreatic transplant dysfunction: value of gadopentetate dimeglumine-enhanced MR imaging.

Sixteen MR studies performed in four patients who had undergone combined pancreatic and renal transplantation were reviewed retrospectively to determine if dynamic gadopentetate dimeglumine-enhanced gradient-echo imaging is useful in the early diagnosis of pancreatic transplant rejection. The MR studies were performed between 3 days and 6 months after transplantation and consisted of T1- and T2-weighted spin-echo images as well as a gradient-echo image prior to administration of an IV bolus of gadopentetate dimeglumine (0.1 mmol/kg). After injection of gadopentetate dimeglumine, a static dynamic gradient-echo scan was obtained. Signal-intensity measurements were determined for each of the gradient-echo images and used to generate an enhancement curve. Because T2 values have previously been used as an objective indicator of rejection, the mean T2 of each pancreatic transplant was calculated also. The MR results were compared with clinical and laboratory data and/or percutaneous biopsy results. In six studies of normally functioning pancreatic allografts, the percent enhancement during the first minute of the enhancement curve was 98 +/- 23% (1 SD). In six episodes of acute dysfunction (rejection or infarction), the first-minute enhancement was 42 +/- 20%. In four cases of dysfunction, the finding of an abnormal enhancement curve preceded a significant drop in urinary amylase by 1-4 days. The calculated T2 value was prolonged in only two cases in which biopsy-proved pancreatic infarction had occurred. No prolongation of T2 was evident in four cases of rejection alone. These results suggest that mean T2 calculation at 1.5 T may not be a reliable indicator of pancreatic transplant rejection, but that gadopentetate dimeglumine-enhanced gradient-echo MR imaging of the pancreatic transplant may be a reliable early indicator of pancreatic transplant dysfunction.

Adult↗

Conclusions: the maintenance of allograft acceptance.

This article summarizes all of the findings of the authors in this issue who examined various laboratory procedures used to implement and monitor transplantation treatment strategies. Histocompatibility matching, crossmatching, monitoring immunosuppression and rejection, and immunologic monitoring of allograft rejection and acceptance are reviewed.

Graft Rejection↗