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Biomedical subjects

J T Rosenthal

Publications and source records attributed to J T Rosenthal.

At least 19 recordsLinked to original sources

Obesity and outcome following renal transplantation.

Single institution series have demonstrated that obese patients have higher rates of wound infection and delayed graft function (DGF), but similar rates of graft survival. We used UNOS data to determine whether obesity affects outcome following renal transplantation. From the UNOS database, we identified patients who underwent primary kidney-only transplantation between 1997 and 1999. Recipient and donor body mass index (BMI) was categorized as underweight (BMI < 18.5), normal (BMI 18.5-24.9), overweight (BMI 25-29.9), obese (BMI 30-34.9) or morbidly obese (BMI > or = 35). We correlated BMI with intermediate measures of graft outcome and overall graft survival, and created multivariate models to evaluate the independent effect of BMI on graft outcome, adjusting for factors known to affect graft success. The study sample comprised 27,377 recipients. Older age, female sex, African American race and increased comorbidity were associated with obesity (p < 0.001). Compared with normal weight patients, morbid obesity was independently associated with an increased risk of DGF (p < 0.001), prolonged hospitalization (p < 0.001), acute rejection (p = 0.006) and decreased overall graft survival (p = 0.001). Donor BMI did not affect overall graft survival (p > or = 0.07). Recipient obesity is associated with an increased risk of DGF and decreased graft survival following renal transplantation.

Adult↗

Evaluation of pre- and posttransplant donor-specific transfusion/cyclosporine A in non-HLA identical living donor kidney transplant recipients. Cooperative Clinical Trials in Transplantation Research Group.

BACKGROUND: The beneficial effects of donor specific transfusion (DST) have become controversial in the cyclosporine era. This study was performed to evaluate the potential benefits of a new protocol for administering DSTs in the perioperative period. METHODS: Non-HLA identical living donor kidney transplant recipients were randomized prospectively to control or to receive a DST 24 hr before transplant and 7-10 days posttransplant. All patients received similar immunosuppression according to protocol. RESULTS: The protocol had 212 evaluable patients (115 transfused and 97 control). There were no differences in 1- and 2-year graft and patient survival, causes of graft failure, incidence and types of infection, repeat hospitalization, or the ability to withdraw steroids. Immunological hyporesponsiveness (by mixed lymphocyte culture) occurred more frequently in transfused patients (18%) than controls (3%) (P = 0.04). Blood stored for > or =3 days was associated with fewer early rejections than blood stored < or =2 days. Overall, class II antigen mismatches were associated with more rejection episodes than class I antigen mismatches. However, transfused patients, but not control patients, with more class I antigen mismatches were more likely to have rejections. CONCLUSIONS: Administration of DSTs by the method described had no practical influence on patient or graft survival for up to 2 years. However, donor-specific hyporesponsiveness was more common in transfused patients (18 vs. 3%). Longer follow-up will be needed to determine whether DST will be associated with long-term benefit.

Blood Preservation↗

Living kidney donation: a survey of professional attitudes and practices.

Living donation is an option for meeting the needs of patients with end-stage renal disease. We surveyed kidney transplant professionals to understand their attitudes, opinions, and practices regarding living donation and to generate a rough estimate of the national potential for living related kidney donation. Although this sample of health practitioners expressed strong support for living donation, their actual professional practice does not necessarily reflect such support. Given the disparity between support and practice, we recommend that leaders in the kidney transplant community focus on several concrete objectives to optimize living donation: estimate the underlying potential for living donation; identify and implement best demonstrated practices for making the living donation request; explore and respond to the ethical issues that surround living donation; and address the needs of both donors and recipients.

Attitude of Health Personnel↗

Helical CT angiography for examination of living renal donors.

OBJECTIVE: This prospective study was intended to determine if helical CT arteriography plus conventional radiography is sufficiently accurate to replace and less costly than excretory urography and conventional renal arteriography, the techniques currently used to examine living renal donors. SUBJECTS AND METHODS: Patients underwent CT arteriography with a helical CT scanner. Conventional radiographs were obtained during the pyelographic phase to evaluate the urothelium. Findings on CT arteriograms were compared with findings on conventional arteriograms and at surgery. RESULTS: Of 57 patients who underwent CT arteriography, 46 also underwent conventional arteriography and 40 underwent surgery. For those 46 patients, we found agreement between results of CT arteriography and conventional arteriography in 89% of kidneys. For those 40 patients, we found agreement between results of CT arteriography and findings at surgery in 90% of kidneys and agreement between results of conventional arteriography and findings at surgery in 87% of kidneys. Of the 57 patients, six (11%) had findings on CT angiograms that precluded further consideration for donation. CONCLUSION: Eight to ten percent of renal arteries are not seen on renal arteriograms when compared with findings at surgery. Our results indicate that CT arteriography is as accurate as conventional arteriography at revealing the number of vessels that perfuse and drain the kidneys and can replace conventional arteriography. Use of CT angiography plus conventional radiography instead of excretory urography and conventional arteriography can result in a 35-50% reduction in cost of the imaging studies in potential renal donors.

Adult↗

The role of whole organ pancreas transplantation in the treatment of type I diabetes.

UNLABELLED: BACKGROUND AND DEMOGRAPHICS: Clinical course was reviewed for 19 whole organ pancreas transplant recipients at UCLA between 11/14/93 and 5/31/95, 18 of which were simultaneous pancreas kidney transplants and 1 of which was an isolated pancreas after kidney transplant. The initial 4 pancreatic grafts were procured by classical warm dissection techniques while the remaining 15 were procured by rapid en bloc technique. Mean recipient age, duration of diabetes, and daily insulin requirements were 38 years, 25 years, and 45 units, respectively. Bladder drainage of exocrine secretions was used primarily in 18 cases and primary enteric drainage in one. RESULTS: All recipients manifested immediate dialysis and insulin independence. Actuarial patient and graft survival were 100% and 89%, respectively, at a mean follow-up of 396 days (range, 150-660 days). Mean maximal serum amylase on the first postoperative day was 366 U/dL. There were no instances of pancreatic graft vascular thrombosis. Three patients experienced pancreatic leaks (16%), 1 of which resulted in graft loss. Six month posttransplant Hgb A1c was within normal range and significantly lower than pretransplantation values (5.1 vs 10.7, P = 0.002). Mean length of initial hospitalization was 15 days, with 100% of patients requiring at least one read mission. Fifty-eight percent of patients experienced rejection episodes. Ninety-one percent of patients responding to a quality of life survey reported improvement in general sense of well-being after transplantation. CONCLUSIONS: It is concluded that high rates of success may be possible with whole organ pancreas transplantation, even in new programs. Rapid en bloc dissection is a safe, expeditious method of pancreas procurement. Successful pancreatic transplantation is associated with freedom from exogenous insulin administration, normalization of glycated hemoglobin, and subjective improvement in quality of life. However, this modality is associated with higher rates of rejection and readmission, and longer duration of hospitalization when compared with isolated kidney transplantation.

Adult↗

Adenoviral-p53 gene transfer to orthotopic and peritoneal murine bladder cancer.

PURPOSE: This study was designed to examine the potential for adenoviral-mediated gene therapy in primary and metastatic bladder cancer. MATERIALS AND METHODS: Orthotopic and intraperitoneal bladder tumors were established after delivery of 1 x 10(6) MBT-2 cells into syngeneic mice. Gene transfer was accomplished via intravesical or intraperitoneal instillation by using an E-1 deleted adenovirus encoding LacZ or human p53. Successful tumor transduction was confirmed in tumor DNA and mRNA by polymerase chain reaction. Detection of recombinant gene product was detected by histochemical staining (X-gal) and Western blot. RESULTS: Palpable tumors developed 18 days following implantation. LacZ and p53 mRNA were present in tumor and adjacent normal tissue after bladder and intraperitoneal vector administration. Recombinant gene products were identified by histochemistry and Western blot. CONCLUSION: Bladder tumor-directed gene transfer using adenoviral vectors is an efficient and powerful tool for evaluating the adjuvant role of therapeutic gene products.

Adenoviridae↗

Adenoviral-mediated gene transfer to bladder in vivo.

This study was designed to examine the potential for gene therapy in bladder in vivo using adenoviral vectors. Gene transfer to rat bladders was accomplished via direct intravesical instillation using a replication-defective adenoviral vector containing a marker gene encoding for Escherichia coli beta-galactosidase (beta-gal). Successful gene transfer was confirmed by analyzing bladder samples for DNA and RNA using polymerase chain reaction (PCR) with primers specific for beta-gal and adeno sequences, detecting beta-gal in full-thickness bladder wall using specific histochemical staining (X-gal) and documenting recombinant protein production. Bladder architecture was preserved, without evidence of distant spread of virus as assessed by PCR. Gene expression was evident for at least 7 days. In summary, bladder cells can be genetically altered using replication-deficient adenoviral vectors via simple intravesical instillation of vector. Introduction of exogenous genetic material is a potentially powerful therapeutic modality for immunomodulation of bladder neoplasms.

Adenoviridae↗

Developments and dilemmas in renal transplantation.

The number of patients waiting for a kidney transplant is about three times greater than the number of transplants performed each year. This article highlights current immunosuppression protocols and the newer immunosuppressive drugs under investigation in a number of multicenter trials. These hold out the promise of reducing the frequency of acute rejection and of prolonging graft survival. They are divided into three groups. The first, like cyclosporine, interferes with the action of interleukin 2. The second, like azathioprine, are antimetabolites; and the third, new monoclonal antibodies. The use of antibody-induction therapy is compared with standard regimens. There are risks related to prednisone withdrawal protocols and inadequate cyclosporine dosing that may lead to accelerated graft loss. Cardiovascular disease is a significant problem in older diabetic patients for whom coronary angiography is recommended. A defined set of risk factors is outlined that predicts which younger diabetic patients should have a cardiovascular evaluation. Chronic liver disease is a growing problem and rational strategies are emerging from studies of patients with biopsy-proven active hepatitis. The presence of hepatic inflammation is associated with progressive liver disease and patients must be made aware of this risk when seeking transplantation. A large number of studies of various prophylactic regimens are starting to provide data on the cost-effective reduction of cytomegalovirus disease in transplant recipients. It is recommended that patients receiving antibody therapy also receive preemptive gangciclovir. The issue of chronic allograft rejection is discussed briefly. The most important predictors of chronic allograft rejection are the frequency of acute rejection, inadequate immunosuppression, and infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Therapy, Combination↗

Expanded criteria for cadaver organ donation in renal transplantation.

Although the demand for kidneys has risen steadily, the number of organs available has not increased significantly. In an attempt to alleviate this shortage of organs, the criteria for acceptance of cadaver organs has been expanded. Extremes of donor age and other medical conditions that would have excluded donors in the past are now being accepted cautiously.

Cadaver↗

Positron emission tomography: a new method for determination of renal function.

Positron emission tomography (PET) is a newly evolving diagnostic modality that has been widely used in many facets of clinical medicine, but whose use in the diagnosis and management of disorders of the kidney has not been previously described. Employing the radiotracer N-13 ammonia, flow-dependent extraction of this compound after intravenous injection was used to measure renal blood flow (RBF) in a swine model (N = 10). A mean baseline value of 3.16 ml./min./gm. kidney was obtained with this method, in close agreement with values previously reported using established invasive techniques. Four conditions known to affect RBF were also studied to determine the ability of PET to detect changes in RBF. Kidneys were subjected to varying durations of warm ischemia, demonstrating a progressive decrease in RBF with increasing ischemic insult, with return to normal significantly impaired in animals exposed to the greatest degree of ischemia (180 minutes versus 150 or 120 minutes ischemia). Cross-transplant between animals produced acute allograft rejection and a corresponding marked decrease in RBF that failed to normalize. After unilateral nephrectomy, RBF increased two-fold in the remaining kidney by 7 days (R = 0.79), as predicted for compensatory renal hypertrophy. Lastly, there was an inverse, linear relationship between toxic cyclosporine level and RBF (R = 0.68), indicative of vascular-mediated cyclosporine nephrotoxicity. Positron emission tomography is safe and efficient, and yields an accurate measurement of RBF in several important physiologic states. The development of PET as a quantitative measure of renal function is promising.

Animals↗

Exogenous epidermal growth factor fails to accelerate functional recovery in the autotransplanted ischemic pig kidney.

The reversibility of ischemic renal injury is dependent on epithelial cell regeneration and repopulation of the nephron. Renal cells produce and respond to many growth factors. In the rat, epidermal growth factor (EGF) is mitogenic for tubular cells and accelerates renal recovery after ischemia. We used a pig renal autotransplant model to evaluate the effect of exogenous EGF on renal recovery in a large animal more analogous to man. Group 1 animals underwent left autotransplant after 120 minutes of warm ischemia and received either a single intra-arterial dose of recombinant human EGF (EGF, 10(-7) M.) (N = 11) or vehicle alone (N = 6). Group 2 animals underwent left autotransplant after 72 hours of cold preservation with Collins' solution and received a similar intra-arterial dose plus a subcutaneous dose of EGF (0.5 ml. of 10(-3) M.) (N = 8) or vehicle alone (N = 6). Contralateral nephrectomy was performed in all animals. Daily creatinine measurements revealed no beneficial effect from EGF on recovery of renal function in Group 1 or 2 animals. Studies of EGF on pig proximal tubular cells demonstrated in vitro mitogenesis; autoradiography with 125I-EGF revealed binding of EGF throughout the kidney. Immunohistochemistry showed significant tubular cell proliferation in response to ischemic injury, without further enhancement from EGF. Thus, although exogenous EGF bound to pig kidney cells and stimulated cell proliferation, we were unable to demonstrate a clinically significant acceleration of recovery from ischemic injury.

Animals↗

The challenge of kidney transplant nephrectomy.

During a 5-year-period 92 kidney transplant nephrectomies were performed and 87% of these kidneys were removed by a subcapsular technique. Surgical complications occurred in 4% of the cases. Renal allograft nephrectomy is a more complex and riskier operation than simple native nephrectomy.

Adult↗