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Biomedical subjects

B Nashan

Publications and source records attributed to B Nashan.

At least 91 records · Page 5Linked to original sources
PubMed1992

Intragraft immune events after human liver transplantation. Correlation with clinical signs of acute rejection and influence of immunosuppression.

Evaluation of graft morphology is regarded as a cornerstone for diagnosis of acute liver graft rejection. Here we have studied the clinical relevance of biopsy findings obtained either by aspiration cytology or by histology in the first month after human liver transplantation, and have assessed the influence of immunosuppressive induction treatment on the incidence of morphological and clinical rejection. Results of 865 aspiration biopsies (TAC) and 155 core biopsies in 141 patients were correlated with the retrospective clinical diagnosis concerning the presence or absence of acute rejection. This analysis demonstrated that there are almost no false negative findings either in cytology or in histology (less than 0.1% of negative biopsies). In contrast, with both methods a large number of positive biopsy results were obtained that were without clinical correlate ("false positive" biopsies; 46% and 41% of positive cytologies and histologies, respectively). The rates of clinical and morphological acute rejections were differently influenced by the type of immunosuppressive induction protocol used. The incidence of clinical rejection was particularly low with a quadruple drug regimen when cyclosporine therapy was started immediately after transplantation (29% vs. 62% when introduction of cyclosporine was delayed for 2-5 days). Morphological rejections were similarly frequent with immediate and delayed introduction of cyclosporine at 2 mg/kg during quadruple therapy (65-75%) and were only reduced with initial high dose cyclosporine treatment (5 mg/kg) (35%). Antirejection treatment was not required in patients with morphological evidence of rejection but without clinical symptoms. The study demonstrates that cytology and histology are similarly reliable for exclusion and similarly unreliable for diagnosis of clinical acute rejection. The clinical relevance of positive biopsy findings is strongly influenced by the basic immunosuppressive treatment. Certain types of induction treatment can obviously alter the alloresponse in a way that no graft damage occurs despite the presence of marked intragraft immune activation. "False-positive" biopsy findings, therefore, seem to represent a qualitatively modified and self-limited type of intragraft alloresponse that is without clinical consequences ("incomplete" or "subclinical" rejection).

Biopsy, Needle↗
PubMed1991

Hemostatic studies of ex situ hepatic surgery.

Ex situ hepatic surgery, in which a diseased liver is resected from outside the body, was first reported in 1988. This study investigates the hemostatic changes occurring during such surgery in two cases. During the anhepatic period of more than 5 hours, veno-venous bypass without heparin was performed. The tests included platelet count, prothrombin activity (PT), partial thromboplastin time (PTT), fibrinogen (Fbg), factor II (F.II), factor V (F.V), and thromboelastography (TEG). Three to 4 hours after entering the anhepatic phase, marked fibrinolysis and a fall in the values of PT, Fbg and F.V. were observed. Every parameter temporarily deteriorated immediately after revascularization of the graft, however, all returned to almost normal values within 1-2 hours after hepatic reperfusion except for F.V and platelets. In conclusion, the coagulopathy during ex situ hepatic surgery is caused by the marked fibrinolysis and depletion of hemostatic factors which develop 3-4 hours after the onset of the anhepatic phase.

Adult↗
PubMed1991

Coagulation disorder during liver transplantation.

Detailed haemostatic changes were investigated during eight liver transplantations. The patients were divided into two groups; group 1 had minor operative bleeding (four cases) and group 2 had major bleeding (four cases). Group 2 had lower levels of platelets, fibrinogen, factor V (FV), and alpha 2-antiplasmin than group 1, and the thromboelastography showed fibrinolysis. In both groups, plasma tissue-plasminogen activator levels rose slightly. After revascularization of the graft liver, reductions in the values of PT, fibrinogen, FV and FVII were noted, along with a prolongation of the PTT and an increase in thrombin-antithrombin III complex levels. Plasma levels of protein C, protein S, antithrombin III, and plasminogen remained relatively stable throughout the operation. These results show that the preceding fibrinolysis and subsequent superimposed activation of the clotting system are the main causes of coagulopathy during liver transplantation, which correlate with the amount of operative haemorrhage and the abnormalities found in haemostatic tests.

Adult↗
PubMed1991

Differentiation of liver graft dysfunction by transplant aspiration cytology.

Episodes of graft dysfunction are frequently observed after liver transplantation and can be due to different causes requiring specific therapy. In this study the usefulness and reliability of liver transplant aspiration cytology (TAC) for differential diagnosis of liver graft dysfunction is assessed. Out of more than 1500 TACs performed, 292 TACs, taken during episodes of liver dysfunction due to retrospectively defined causes, were analyzed. Immune activation and parenchymal damage in the aspirates were determined cytologically. In 63 episodes of acute rejection, marked immune activation was present in aspirate but not in blood, with varying degrees of hepatocyte damage and cholestasis. No or only minimal immune activation was observed in 86 cases of toxic, ischemic, or septic liver damage, but considerable parenchymal damage and cholestasis were observed. In 3 cases of hepatitis slight-to-moderate immune activation with large granular lymphocytes was found in the aspirate, while 17 cases of viral infection presented with slight-to-moderate immune activation in aspirate and blood. After successful treatment the cytologic patterns normalized, except when the cause of liver dysfunction persisted. Moreover, typical patterns of parenchymal changes were found for preservation damage of the liver (n = 108), fatty degeneration (n = 3), obstructive cholestasis (n = 5), and acute arterial ischemia (n = 2). One case of moderate subcapsular hematoma was the only complication observed (less than 0.1%). Thus, liver TAC is an easy, safe, and clinically useful method for differential diagnosis of liver graft dysfunction. In particular, differentiation between acute rejection and nonimmunologic causes of dysfunction is very reliable, but hepatitis and viral infections also present distinctive patterns in liver TAC.

Biopsy, Needle↗
PubMed1990

Single dose pharmacokinetics of ciclosporin and its main metabolites after oral ciclosporin as oily solution or capsule.

The commercially available oily solution of ciclosporin which has to be suspended before intake is disliked by some patients for bad taste and has a variable bioavailability. In this investigation the oral pharmacokinetics of ciclosporin and its main metabolites 1 and 17 of the oily solution (Sandimmun) and a soft gelatine capsule preparation of ciclosporin were compared in a crossover fashion in 10 kidney allograft recipients. The results demonstrate a bioequivalence of both formulations. In either case metabolite 17 had a significantly longer half-life than either ciclosporin or metabolite 1. At earlier time-points the concentration of ciclosporin could be best correlated with metabolite 1 and at later time-points with metabolite 17. Both metabolites were less correlated with each other in the late absorption phase of ciclosporin.

Adult↗
PubMed1988

High incidence of monoclonal immunoglobulins in patients after liver or heart transplantation.

Sera from 56 recipients of liver or heart transplants were investigated for monoclonal immunoglobulins (mIg) by immunofixation electrophoresis (IFE) at different times during 4 years after transplantation. Transient, changing, or stable mIgs were found in 18 patients. A significantly increased mIg incidence was observed in heart Tx patients, patients over 40 years of age, and those receiving azathioprine or antithymocyte globulin in addition to prednisolone and cyclosporine as immunosuppressive treatment. No correlations could be found between the presence of mIg and the number of rejection episodes or intercurrent infections. Such serum mIg represent monoclones of at least 1 x 10(9) cells of B lymphocyte lineage that apparently proliferate without adequate suppressive control. Since immunosuppressed allograft recipients are at risk of developing B cell lymphomas, such monoclones may be regarded as prelymphomas necessitating a careful follow-up in these patients.

Antibodies, Monoclonal↗
PubMed1985

[D-Met2,Pro5]enkephalinamide activates cardioinhibitory efferents in anaesthetized dogs.

[D-Met2,Pro5]enkephalinamide (DMPEA) strongly activated cardioinhibitory vagal efferents and elicited bradycardia when perfused through the cerebroventricular system of anaesthetized dogs. These effects were concentration-dependent but plateaued at an intraventricular concentration of 200 micrograms/ml. At this maximally effective concentration, the vagal discharge rate was fourfold higher and the heart rate was lowered by 28% compared to the controls. These effects were reversed by naloxone (40 micrograms/ml). There was no significant change in blood pressure. Vagal discharge rate and heart rate correlated closely and inversely with each other with r values ranging between -0.75 and -0.95. Opiate receptors in brain structures bordering the cerebroventricular system are the most likely mediators of the effects of DMPEA. The opiate receptor/endorphin system may therefore play a role in the physiological control of cardiac vagal tone and thus of heart rate.

Action Potentials↗