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Biomedical subjects

O Bronsther

Publications and source records attributed to O Bronsther.

At least 19 recordsLinked to original sources
PubMed2001

Screening a living kidney donor for polycystic kidney disease using heavily T2-weighted MRI.

Autosomal dominant polycystic kidney disease (ADPKD) accounts for approximately 8% of those awaiting renal transplantation. Living related kidney donors for these patients require screening for ADPKD, most commonly by ultrasonography. Ultrasound has a negative predictive value (NPV) of 100% in patients aged older than 30 years, but only 96% for donors aged 20 to 30 years. This case shows that heavily T2-weighted magnetic resonance imaging (HT2MRI) may be a more sensitive screening method for ADPKD in younger kidney donors. Despite a normal screening ultrasound result, a kidney donor with a family history of ADPKD was found to have renal cysts intraoperatively, and the transplantation was canceled. Afterward, the donor was imaged with HT2MRI. In addition, the mathematical relationship between sensitivity, specificity, and NPV for ADPKD screening tests was derived. After the canceled transplantation, a second ultrasound still could not identify renal cysts. However, HT2MRI showed multiple small ( approximately 3-mm) cysts in both kidneys and a 2.5-cm cyst on the right kidney. Mathematical analysis showed that the NPV of a screening test for ADPKD was most closely related to sensitivity and that only tests with 100% sensitivity would have a 100% NPV. We conclude that ultrasound is not a sufficiently sensitive screening test for ADPKD in younger living related renal donors. HT2MRI has improved sensitivity and may be the best screening test for ADPKD in this population.

Adult↗
PubMed1999

Tolerance induction permits the development of graft-versus-host disease: donor-mediated attack following small bowel transplantation in mixed chimeras.

The induction of tolerance to organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. We have shown that tolerance induced through the creation of mixed allogeneic bone marrow chimeras allows for the long-term engraftment of cardiac and small bowel allografts across strong multiple major histocompatibility barriers. The possibility that tolerance might render the host susceptible to graft-versus-host disease (GVHD) has not been investigated in this or other models of tolerance. To test this possibility chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post bone marrow transplant (BMTx) by flow cytometry of lymphocytes from reconstituted animals. ACI/Lew chimeras (ALC), Lewis/ACI F1 (LACF1), and Lewis (LEW) rats all received heterotopic ACI vascularized small bowel grafts. A second group of chimeras received small bowel grafts from ACI rats pretreated with low dose irradiation to eliminate T-cells from the graft. LEW-->LEW small bowel isografts were also performed. Animals were examined for evidence of GVHD by clinical signs and histologic examination of biopsied tissues. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 rats developed severe lethal GVHD following ACI small bowel transplant. Bone marrow chimeras, ALC (n = 6), developed fatal GVHD in a similar fashion after receiving a small bowel transplant. LEW-->LEW isografts and chimeras receiving bowel from irradiated ACI rats survived long term without GVHD while ACI-->LEW allogeneic transplants all underwent acute rejection. GVHD or its absence was confirmed histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras (1.87) and LACF1 (5.4) receiving allografts, but not in isografts or chimeras receiving irradiated allogeneic transplants. Analysis of cytokines in the tongues of rats undergoing GVHD showed elaboration of Th1 type proinflammatory cytokines which was not seen in isografted rats or rats receiving preirradiated small bowel. These results demonstrate that tolerance induction through mixed chimerism results in susceptibility to small bowel induced GVHD. Preirradiating the donor bowel prior to SBTx can prevent GVHD.

Animals↗
PubMed1998

Tolerance induction by intrathymic inoculation prevents chronic renal allograft rejection.

BACKGROUND: These experiments investigated the ability of the donor-specific unresponsiveness created by the intrathymic inoculation of donor alloantigen to effectively prevent chronic rejection in an established rat model of chronic renal allograft rejection. METHODS: Three study groups were examined: (1) Allograft controls--F-344 rats received a Lewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls--F-344 rats received an F-344 renal isograft and low-dose CsA; (3) experimental group--F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis bone marrow. Twenty-one days after bone marrow transplant, these animals received a Lewis renal allograft. RESULTS: Allograft controls demonstrated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analysis revealed increased CD4+ T cells infiltrating the cortex of the allograft controls. Cytokine interferon-gamma and interleukin-2 transcripts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcriptase-polymerase chain reaction. Analysis of tolerant grafts by flow microfluorimetry and genomic DNA amplification could not detect chimerism to a level of < 0.1%. CONCLUSION: IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.

Animals↗
PubMed1998

An examination of the renal transplant evaluation process focusing on cost and the reasons for patient exclusion.

A medical evaluation of prospective renal transplant recipients is performed to identify conditions that may exclude patients from transplantation because of unacceptable risks. Protocols for evaluating potential transplant candidates are available, but there is little information about reasons for excluding patients from transplantation. To assess the effectiveness and cost of our renal transplant-recipient evaluation process, we retrospectively reviewed patients excluded from renal transplantation between January 1993 and December 1995 to categorize the reasons for exclusion. We also examined the costs of the evaluation. The study group included all adults referred for kidney-only transplantation during the study period who were excluded from transplantation (n=125). Demographics of the 160 patients with end-stage renal disease (ESRD) who underwent renal transplantation during the study period were also examined. Compared with the patients who underwent transplantation, the excluded patients were older (48+/-14 v 43+/-12 years; P=0.006) and more likely to be women (66 of 125 patients; 53% v 57 of 160 patients; 36%; P=0.005) and diabetic (59 of 125 patients; 47% v 30 of 160 patients; 19%; P=0.005). The most common reason for excluding patients was medical contraindication (46%), followed by patient declined (25%), obesity (10%, defined as a body mass index [BMI] > or = 35), patient death (6%), and insurance/financial (5%). The medical reasons for exclusion were heart disease (38%), noncompliance (28%), miscellaneous (22%), and cancer (12%). Tests performed after the initial evaluation included cardiac testing (stress thallium or echocardiography and coronary angiography) in 50 patients, Doppler studies of the lower extremities in 28 patients, and hepatitis C polymerase chain reaction (PCR) or recombinant immunoblot assay (RIBA) assays in 8 patients. The cost of standard pretransplantation blood work for selected tests (ABO blood group typing, HLA, hepatitis B and C, and cytomegalovirus) was $709. Deferring such routine pretransplantation blood work until after the patient education session and history and physical examinations by nephrology and surgery in the 31 patients (25%) who declined transplantation at the initial visit would have resulted in considerable savings. Our evaluation process now includes prereferral information on a prospective recipient's medical problems, height and weight, and basic screening laboratory tests. This protocol has resulted in a more efficient and cost-effective evaluation process. Further examination of the cost-effectiveness of the transplant evaluation process is warranted.

Adult↗
PubMed1998

Use of intraoperative ultrasonography during hepatic transplantation.

The aim of this study was to evaluate if intraoperative vascular ultrasonography is of clinical value in the perioperative management of hepatic transplant patients. Fifteen intraoperative ultrasonographic examinations were performed on 13 patients (five female, eight male) during transplantation. These patients had clinically suspected vascular compromise. Among the 13 patients studied intraoperatively, five were correctly diagnosed as having hemodynamically significant vascular compromise. Of the intraoperative vascular sonographic examinations, the results of 13 were in concordance with the surgical impression as to whether further intervention was necessary or if the procedure could be terminated. Intraoperative sonography demonstrates potential to be of aid to the surgeon in recognition of vascular compromise.

Adult↗
PubMed1997

The hyperventilation of cirrhosis: progesterone and estradiol effects.

Progesterone and estradiol are metabolized in the liver and are elevated in patients with cirrhosis. Progesterone stimulates ventilation by activating progesterone receptors in the central nervous system; estradiol may facilitate progesterone's actions by increasing progesterone receptors. This study evaluated whether progesterone and estradiol contribute to the respiratory alkalosis common in cirrhotic patients. Arterial blood gases and progesterone and estradiol levels were obtained in 50 patients with cirrhosis. Multiple linear regression revealed a statistically significant correlation between PaCO2 and progesterone and estradiol (r = .54, P < .05). Patients with severe hyperventilation (PaCO2 < or = 30 mm Hg) had statistically higher levels of progesterone and estradiol than did patients with mild hyperventilation (30 < PaCO2 < or = 35) or normal ventilation (PaCO2 > 35) (P < .05). Although the progesterone levels were two orders of magnitude lower than those associated with hyperventilation in pregnant patients, the increased ventilatory effect may be because of the altered blood-brain barrier (BBB) present in cirrhotic patients. Progesterone and estradiol appear to contribute to the hyperventilation in cirrhotic patients.

Adult↗
PubMed1997

Graft versus host disease in rats made tolerant for organ allografts.

Tolerance for organ allografts would eliminate acute and chronic rejection as well as the need for nonspecific immunosuppression. A potential hazard of tolerance is the susceptibility to graft vs host disease (GVHD) due to unresponsiveness to alloantigen. This study sought to determine if our model of tolerance induction results in susceptibility to GVHD. Chimeras were created by transplantation of T-cell depleted ACI and Lewis bone marrow into lethally irradiated Lewis rats. Chimerism was determined post-BMTx by flow cytometric analysis of recipient spleens for the presence of ACI cells. ACI/Lew chimeras (ALC), animals that reconstituted only with syngeneic (Lewis) marrow (so-called failed chimeras), and ACI/Lew F1 (LACF1) hybrid rats were all given 200 x 10(6) ACI splenocytes i.v. Animals were examined for evidence of GVHD. GVHD was quantified using the popliteal lymph node enlargement assay. All LACF1 (n = 6) rats developed severe lethal GVHD following ACI splenocyte injection. Similarly, ALC (n = 6) developed fatal GVHD. Animals that reconstituted only with syngeneic Lewis marrow (failed chimeras) showed no signs of illness. GVHD was confirmed histologically and immunohistochemically. Failed chimeras receiving ACI splenocyte challenge showed no evidence of GVHD histologically. Popliteal lymph node enlargement indices reflected the presence of GVHD in the chimeras and hybrids but not in the failed chimeras. We conclude that tolerance induction by mixed chimerism results in susceptibility to GVHD if enough donor lymphoid tissue is given to the host at the time of organ transplant. Animals that are not mixed chimeras (failed bone marrow transplant) rejected the allogeneic splenocytes as evidenced by their lack of disease. Tolerance may therefore make the host defenseless against fatal GVHD.

Animals↗
PubMed1995

Experience with liver and kidney allografts from non-heart-beating donors.

Given the shortage of cadaveric organs, we began a study utilizing NHBD for OLTx and KTx. There were 24 NHBD between January 1989 and September 1993. These donors were divided into 2 groups: uncontrolled NHBD (G1) (n = 14) were patients whose organs were recovered following a period of CPR; and controlled NHBD (G2) (n = 10) were patients whose organs were procured after sustaining cardiopulmonary arrest (CA) following extubation in an operating room setting. Eight kidneys and 5 livers were discarded because of macroscopic or biopsy findings. In G1, 22/27 (81.5%) kidneys were transplanted; 14/22 (64%) developed ATN; 20/22 (95%) recipients were off dialysis at the time of discharge. With a mean follow-up of 32.7 +/- 21.1 months, sixteen (73%) kidneys are still functioning, with a mean serum creatinine of 1.7 +/- 0.6 mg/dl. The one-year actuarial patient and graft survivals are 95% and 86%. In G2, 17/20 (85%) kidneys were transplanted; 13/17 (76%) kidneys experienced ATN. All patients were off dialysis by the time of discharge. With a mean follow-up of 17.6 +/- 15.4 months, twelve (70%) kidneys are still functioning, with a mean serum creatinine of 2.5 +/- 2.1 mg/dl. The one-year actuarial patient and graft survivals are 94% and 82%, respectively. In G1, 6/10 (60%) livers were transplanted; 3/6 (50%) livers functioned, the other 3 patients required ReOLTx in the first week postoperatively because of PNF (n = 2) and inadequate portal flow (n = 1). Two functioning livers were lost due to HAT (n = 1) and CMV hepatitis (n = 1). In G2, 6/7 (85.7%) livers were transplanted. All the livers (100%) functioned. 2 patients required ReOLTx for HAT at 0.9 and 1.0 months. Both patients eventually died. One patient with a functioning liver died 2 months post OLTx. The remaining 3 patients are alive and well at 27 months of follow-up. This study shows that the procurement of kidneys from both uncontrolled and controlled NHBD leads to acceptable graft function despite a high incidence of ATN. The function of liver allografts is adequate in the controlled NHBD but suboptimal in the uncontrolled NHBD, with a high rate of PNF.

Adolescent↗
PubMed1995

Immunoglobulin G lymphocytotoxic antibodies in clinical liver transplantation: studies toward further defining their significance.

Twenty-two consecutive liver allograft recipients, who tested positive for immunoglobulin G (IgG) lymphocytotoxicity were subjected to pretransplantation and posttransplantation immunologic monitoring of anti-donor IgG lymphocytotoxic antibody titers, total hemolytic complement activity (CH100), circulating immune complexes (CIC), and platelet counts in an effort to improve our understanding of the preformed antibody state in clinical hepatic transplantation. Ten contemporaneous liver transplant recipients whose crossmatch results were negative and who experienced severe hepatocellular damage early after transplantation were included as controls. Crossmatch test results were negative 1 day after transplantation and during the 1 month follow-up remained negative in 14 of 22 (64%) sensitized recipients, most of whom had relatively low (< or = 1:16) anti-donor IgG antibody titers before transplantation. After transplantation, this group and the control group experienced no thrombocytopenia, no increase of CIC, and a gradual increase in CH100 activity that reached normal levels within 1 week. A strong negative correlation between prothrombin time (PT) and CH100 activity in these groups of patients suggested that changes in CH100 activity (P < .0005) were tightly linked to liver synthetic function. In contrast, the crossmatch test results remained positive after transplantation in 8 of 22 (36%) sensitized recipients, all of whom had relatively high (> 1:32 to 1024) pretransplantation titers of anti-donor IgG antibodies. After transplantation these patients developed a syndrome that was characterized by decreased CH100 activity and increased CIC compared with pretransplantation levels and refractory thrombocytopenia that was associated with a 50% allograft failure rate because of biopsy-proven humoral and acute (cellular) rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Liver transplantation for HBV-related disease under immunosuppression with tacrolimus: an experience with 78 consecutive cases.

Hepatitis B viral liver disease (HBVLD) is a major worldwide health problem. It is estimated over 300 million people have had hepatitis B virus infection and that one-third of these have chronic HBVLD. Little effective therapy exists for HBVLD even though high dose interferon (IFN) has been advocated. For those who either are untreated or do not respond to IFN, HBVLD is steadily progressive and orthotopic liver transplantation (OLTx) is the only available therapy. Until quite recently, all OLTx recipients received cyclosporine (CyA) and prednisone. The consequence of OLTx for HBV disease in individuals immunosuppressed with tacrolimus has not previously been reported. A total of 78 consecutive patients with HBV-related liver diseases who were transplanted between January 1, 1990, and December 31, 1991, and treated with tacrolimus were studied. The clinical records of these patients were reviewed retrospectively. HBV disease recurrence was documented with serologic and histologic methods. As of April 1, 1993, 57 of 78 (73%) of the patients were still alive. Thirty-one of the alive patients have documented HBV recurrence. Eighteen of these 31 patients, however, have normal liver function. With a median follow-up of 24 months, 8 patients (10.9%) have died of recurrent HBVLD. Seven of 8 patients, who preoperatively were HBeAg+, developed recurrence and 4 of these patients have already died of recurrence. Patients who were HBsAg+ rarely recurred (1 of 16 patients). The use of HBIG did not prevent recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Can adenine nucleotides predict primary nonfunction of the human liver homograft?

Sixty-eight primary liver grafts were analyzed to see whether adenine nucleotides (AN: ATP, ADP, and AMP) or purine catabolites (PC: adenosine, inosine, hypoxanthine, and xanthine) of tissue or effluent can predict primary graft nonfunction. AN, PC, and nicotinamide adenine dinucleotide, oxidized form (NAD+) of the tissue before (pretransplant) and after graft reperfusion (post-transplant) and of the effluent were analyzed. The graft outcome was classified into two groups (group A: successful, n = 64; group B: primary nonfunctioning, n = 4). No significant differences were observed in pretransplant measurements between groups A and B, whereas ATP, ADP, total AN, total AN + total PC (T) and NAD+, in post-transplant tissues, were significantly higher in group A. Xanthine in the effluent was significantly higher in group B than in group A. ATP, ADP, total AN, T, and NAD+ in post-transplant tissue were significantly associated with primary graft nonfunction by logistic regression analysis.

Adenine Nucleotides↗
PubMed1994

Disease gravity and urgency of need as guidelines for liver allocation.

One thousand one hundred and twenty-eight candidates for liver transplantation were stratified into five urgency-of-need categories by the United Network for Organ Sharing (UNOS) criteria. Most patients of low-risk UNOS 1 status remained alive after 1 yr without transplantation; the mortality while waiting was 3% after a median of 229.5 days. In contrast, only 3% of those entered at the highest risk UNOS 5 category survived without transplantation; 28% died while waiting, the deaths occurring at a median of 5.5 days. The UNOS categories in between showed the expected gradations, in which at each higher level fewer patients remained as candidates throughout the 1-yr duration of study while progressively more died at earlier and earlier times while waiting for an organ. In a separate study of posttransplantation survival during the same time period, the best postoperative results were in the lowest-risk UNOS 1 and 2 patients (88% combined), and the worst results were those in UNOS 5 (71%). However, a relative risk cross-analysis showed that a negative benefit of transplantation may have been the result in terms of 1-yr survival for the low-risk elective patients, but that a gain in life extension was achieved in the potentially lethal UNOS categories 3, 4 and 5 (greatest for UNOS 3). These findings and conclusions are discussed in terms of total care of patients with liver disease, and in the context of organ allocation policies of the United States and Europe.

Adult↗