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Biomedical subjects

C H Gips

Publications and source records attributed to C H Gips.

At least 37 records · Page 2Linked to original sources

Bone disease after orthotopic liver transplantation.

After orthotopic liver transplantation (OLT), not infrequently a deterioration of bone disease leading to compression fractures of vertebrae is seen. In a consecutive series of 36 adult OLT patients, we studied, clinically and radiologically, the incidence and degree of bone disease before and after OLT; we also studied whether clinical, radiological and laboratory findings were related to the event of postoperative vertebral collapse. Before OLT, radiological signs of mostly slight osteoporosis were seen in a minority of patients. After OLT, 38% of patients developed vertebral collapse, mainly in the second trimester. Collapse occurred in both previously normal and abnormal vertebrae. Of the preoperative parameters sex, age, menopause, intake of prednisolone, duration and diagnosis of liver disease, duration and degree of cholestasis, bone radiology and urinary calcium, only a low urinary calcium was related to postoperative collapse. Of the postoperative parameters duration of cholestasis, urinary calcium, duration of hospital stay, prednisolone dose and outcome in terms of life and death, none was related to collapse. We conclude that vertebral collapse after OLT occurs frequently and is not easily predicted. Early prevention of bone disease in patients with chronic liver disease before OLT and a low steroid-containing immunosuppressive regimen after OLT are advocated.

Adolescent↗

Liver transplantation in a 48-year-old female with primary biliary cirrhosis.

In 1983, a Danish female with primary biliary cirrhosis underwent orthotopic liver transplantation (OLT). The transplantation took place in Groningen under a Danish-Dutch cooperation, at this writing, and more than four years after transplantation, the patient is still alive. The quality of her life has been dramatically improved, making possible her return to work. Liver tests, liver function, and biopsies are normal and without signs of development of primary biliary cirrhosis in the transplanted liver. Liver transplantation is now frequently performed at several centres throughout the world with an increasing success rate. In Scandinavia, centres have been established in Norway, Finland, and Sweden, whereas in Denmark the organisation of a programme for liver transplantation is still being discussed. Because of the extremely high costs, liver transplantation has to be approved medically and politically, and the brain death criteria have to be accepted before it can be considered as a generally accepted modality of treatment.

Female↗

Early induction of MHC antigens in human liver grafts. An immunohistologic study.

The present study documents major histocompatibility complex (MHC) Class I and II expression during early acute rejection of human liver grafts. Serial graft biopsies (pretransplant, time zero, and 1 week) were studied. Ten patients received azathioprine (AZA) and prednisone; the other six patients were treated with quadruple therapy (azathioprine, cyclosporine A, prednisone, and cyclophosphamide). To study the specificity of changes in MHC antigen expression, biopsies of six patients with minor or no morphologic abnormalities served as controls. In addition, phenotypes of inflammatory cells present during rejection were analyzed using a panel of monoclonal antibodies. The results show that during acute rejection expression of MHC Class I and II antigens increased significantly in the AZA-treated patients, in a pattern similar to that seen in the patients treated with quadruple therapy, showing enhanced MHC Class I expression on hepatocytes, bile duct epithelium, and sinusoidal endothelium, and Class II antigen on Kupffer cells and sinusoidal endothelium. Bile duct epithelium was consistently positive for Class II antigen; no significant difference with the nonrejection group was observed. T cells are the predominant inflammatory cells during rejection with equal quantities of CD4+ and CD8+ cells. A majority of the infiltrating T cells show expression of Class II antigen but do not react with anti-interleukin-2 receptor antibody. This may be the result of immunosuppressive therapy or a simple reflection of the temporary expression of interleukin-2 receptors during lymphocyte activation. The authors hypothesize that the induction of MHC antigens on bile duct epithelium leads to rejection whereas the expression on hepatocytes represents an epiphenomenon.

Adolescent↗

Comparison of the precision of seven analytical methods for the H2O concentration in human serum and urine.

In order to calculate a true renal H2O clearance (U X V/P), serum and urine H2O concentrations have to be known. In this investigation we compared the precision (repeatability) and the ease of performance of 7 H2O assays in human serum and urine. The 3 gravimetric assays (oven-drying, freeze-drying or freeze-drying as well as oven-drying) had a very high precision (coefficients of variation (CV) 0.2-0.4%) and were easy to perform. The precision of mass spectrometry, gas chromatography and titrimetry (Karl Fischer) was better in urine than in serum (ranges of CV 1.2-1.5% in urine vs. 2.4-4.3% in serum), but the precision of osmometry was better in serum than in urine (CV 1.0 vs. 1.6%). Accuracy was not determined as storage effects at 4 degrees C and at -20 degrees C caused insuperable logistic problems. Only small sample volumes are used in titrimetry and gas chromatography, making them more suitable for determinations in babies and animal studies. With titrimetry determinations can be done in a short time. The gravimetric assays appear to reflect the true H2O content of serum and urine, thus enabling calculation of the true renal H2O clearance, which can be of clinical importance in liver, renal and cardiac disease.

Body Water↗

Evaluation of gravimetric assays of the H2O concentration in human serum and urine.

The oven-drying method and the combined freeze- and oven-drying method for gravimetrical measurement of human serum and urine H2O concentration, as well as two reported formulas for the calculation of the serum H2O concentration were evaluated. Day-to-day precision in serum and urine (coefficient of variation (CV) less than 0.95%), and recovery in serum (95-99%) were excellent. Storage at 4 degrees C and at -20 degrees C was safe at least for 3 wk and 2 mth, respectively. For the oven-drying method, which was the most practical, reference values after fasting overnight were determined (n = 47; 99% confidence interval; serum, 48.8-51.6 mol/l; urine, 51.2-53.8 mol/l). Patients in different disease categories were tested (n = 38), and had normal values mostly. Low serum values were found in a patient after hemodialysis with ultrafiltration (47.0 mol/l), and in two patients with an extreme hyperproteinemia (48.8 mol/l) and hypercholesterolemia (48.1 mol/l), respectively. Formulas for calculation of the serum H2O concentration proved unreliable. When direct measurement is impossible, a serum value of 50.5 mol/l can be substituted.

Adult↗

Expression of major histocompatibility complex antigens and replacement of donor cells by recipient ones in human liver grafts.

The disappearance of certain cell populations of donor origin and their replacement by recipient-specific cells constitutes a possible explanation for the relatively mild course of acute rejection despite lack of MHC compatibility in human orthotopic liver transplantation (OLT). In the present report, graft biopsies of 12 OLT patients from a total of 42 patients were studied for expression of MHC antigens after transplantation using monoclonal antibodies to HLA-ABC and HLA-DR. The patients were selected based upon donor-recipient mismatching for HLA-A2, B7, Drw52, or DQw1. Monoclonal antibodies to these 4 polymorphic HLA antigens and monoclonal antibodies to HLA-ABC and -DR were applied to frozen tissue sections and visualized using an immunoperoxidase technique. Expression of HLA-ABC and -DR on, respectively, hepatocytes and bile duct epithelium were observed in posttransplant graft conditions such as viral infections, cholangitis, and acute rejection. However, no specific pattern of MHC antigen distribution was observed for these various pathological graft conditions. Disappearance of DR-positive Kupffer cells of donor origin and immigration of recipient ones was encountered in the early posttransplant biopsies. This Kupffer cell replacement coincided with a reversible episode of acute rejection. The disappearance of highly immunogenic cellular components as HLA-DR positive Kupffer cells of graft origin may be one of the mechanisms contributing to the mild rejection response observed in human liver transplantation.

Antibodies, Monoclonal↗

Selection criteria and decisions in 375 patients with liver disease, considered for liver transplantation during 1977-1985.

We performed a prospective study on 375 patients with liver disease, 60% female, for whom orthotopic liver transplantation (OLT) was considered during 1977-1985. Fifty-four per cent had cirrhosis, 8.5% congenital/hereditary disorders, 25% malignant tumour, 6% benign tumour, 2% Budd-Chiari syndrome, 1.5% acute hepatic failure, 3% other diagnoses, and 10% were under 15 years of age. As of July 1st, 1985, 99 patients (47 chronic active/inactive cirrhosis (CAC/CIC), 28 primary biliary cirrhosis (PBC), five hepatocellular carcinoma (HCC), 19 other diagnoses) were accepted for OLT (median age 40 years, 10% under age 15). By that date, 45 patients (median age 42), had had an OLT (20 CAC/CIC, 15 PBC, three biliary atresia, two HCC, five other diagnoses). Fifty-four per cent (201 patients) were rejected for transplantation. The primary reasons for rejection were: no indication (11%), age (5%), other surgical procedures possible (3%), severe liver failure (14%), extrahepatic spread of liver tumour (11%), cardiovascular or pulmonary problems (2%), severe hepatic bone disease (1%), and miscellaneous (7%). Thirty per cent of the patients with CAC/CIC, 38% with PBC, 88% with HCC and 71% with biliary atresia were rejected. In the CAC/CIC, PBC and biliary atresia patients severe liver failure was the most frequent reason for rejection (62%, 50% and 60%, respectively). In HCC, extrahepatic tumour spread was the most frequent reason (72%) for rejection. In this category only two patients (7%) ultimately underwent liver transplantation.

Adolescent↗

Evaluation of the UV-340 spectrophotometric determination for pseudocholinesterase activity (EC 3.1.1.8) in human serum.

A pseudocholinesterase catalytic activity assay using p-hydroxybenzoylcholine as substrate and measuring the decrease of NADPH at 340 nm was compared with a colorimetric method using acetylthiocholine as substrate. The assay is simple, uses 50 microliters serum and is performed at 37 degrees C. Precision of the UV-340 method was good except at low ranges. The catalytic activity was depressed by the anticoagulants citrate and fluoride but not by EDTA or heparin. The reference values obtained with the evaluated UV-340 method are somewhat higher than those with the colorimetric method. As the results with both methods are comparable, the choice of procedure will depend on the local facilities.

Butyrylcholinesterase↗

Composition of bile after orthotopic liver transplantation.

In 20 adult patients undergoing orthotopic liver transplantation (OLT), we studied longitudinally for the first 3 weeks after OLT the composition of bile with regard to differences between surviving and non-surviving patients and between patients with more or less rejection and the relation between bile and serum concentrations. The analyzed biliary components were bilirubin, cholesterol, bile acids, phospholipids, copper, iron, glucose, urea, creatinine, ammonia, protein, sodium, potassium, chloride, pH, bicarbonate, calcium and phosphate. After the 1st day the composition of bile was often different from reference values. In most patients deviations of the hepatic excretion function were found. Especially, a sharp fall was noticed in the biliary concentrations of cholesterol and copper. The composition of bile was not helpful in predicting the histologic degree of rejection or the ultimate outcome of the patients. Changes in bile glucose, electrolyte, urea, and creatinine concentrations were positively related to serum concentrations. We conclude that for the compounds analyzed the composition of bile after OLT is not only influenced by the state of the liver but also by the overall metabolic state of the patient.

Adolescent↗

Ammonia kinetics in eight patients with liver disease and in dogs.

Pharmacokinetic parameters of ammonia were calculated from a constant-rate infusion of ammonium chloride in 8 patients with chronic liver disease, and in 19 healthy mongrel dogs. In the animal group, the median half-life of the infused ammonia was approximately 4 minutes (range 3.5-5 minutes). The median ammonia clearance was 4.4 l/min (range 3.3-9.2 l/min). The median volume of distribution was approximately 28 liters. In the animal group, the median half-life of the infused ammonia was one minute (range less than 1-4 minutes). The median clearance was 2.2 l/min (range 1.2-4.2 l/min). The median volume of distribution was 3.1 liters. The short half-life and the high clearance of ammonia underscore the importance of the extrahepatic ammonia removal mechanisms.

Ammonia↗

Pancreatic and duodenal ammonia in dogs: lowering by glucose infusion.

Ammonia is produced by some organs and removed by others. Glucose may influence ammonia formation. The contribution of the pancreas to ammonia metabolism is unknown. This study compares pancreatic and duodenal venous ammonia to arterial ammonia in dogs. Pancreatic venous ammonia exceeds arterial ammonia by a factor of 2.8 (range 1.3-9.3); and duodenal ammonia by a factor of 1.1 (range 0.9-2.8). Duodenal venous exceeds arterial ammonia by a factor of 2.4 (range 0.8-5.8). High-dose glucose infusion decreased pancreatic venous ammonia by approximately one-third and duodenal venous ammonia by approximately one quarter, but left arterial ammonia virtually unaltered. The mechanism of pancreatic ammonia production is unknown. We postulate that it may be related to pancreatic bicarbonate synthesis, binding the hydrogen ions which are liberated during this process.

Ammonia↗

The psycho-social impact of a liver transplant programme.

Through in-depth interviews, an inventory has been made of the experiences of 18 liver patients who have been considered for or undergone a liver transplant. Interviews were also held with the patients' relatives. Chronic patients especially seem to regard a transplant as their last chance, and all their hopes become based on it. The strict selection procedure is distressing, and being turned down causes negative feelings. As far as the operation itself is concerned, patients are inclined to create high success rates for themselves in relation to their survival chances and the expectations of quality of life. For some patients a transplant means a marked improvement in the various aspects of their functioning. Others are not so fortunate, but do not give up hope of improvement. From the relatives of the patients who had died post-operatively, no negative feelings were encountered over the 'failure' of the technology'.

Adolescent↗

Hepatic disease in erythropoietic protoporphyria.

A standardized hepatological investigation was performed in 9 unselected patients with erythropoietic protoporphyria (EPP). The aim of this study was to detect early liver involvement due to EPP and to determine the significance of several diagnostic procedures. Scintigraphy revealed slight enlargement of liver and spleen in all cases. Light microscopic examination of liver tissue in 7 patients showed protoporphyrin deposition in 4 and signs of fibrosis in 3 cases. Cirrhosis was not found. Electron microscopical examination (EM) of all 7 cases was negative and needle-shaped crystals were not found. Therefore we regard EM of little diagnostic value in the detection of early liver involvement. The literature on fatal and asymptomatic cases of liver involvement in EPP is discussed with emphasis on possible predictive and provocative factors. A proposal for EPP patients intending to reduce possible risk factors is made.

Adolescent↗

Measurements of prednisolone and some of its metabolites, in urine of patients after orthotopic liver transplantation, as a means of monitoring prednisolone absorption.

In patients who had undergone orthotopic liver transplantation, malabsorption of prednisolone or increased metabolism of prednisolone was suspected. In order to rule out this possibility, urinary prednisolone, and some of its metabolites, viz prednisone and 6 beta-hydroxyprednisolone, were determined by means of a gas chromatographic assay. To evaluate this assay aliquots of a pooled urine from several of our patients were analysed in multiplicate (n = 10). Mean prednisone, prednisolone and 6 beta-hydroxyprednisolone concentrations of 1.9 mg/l, 6.3 mg/l and 4.1 mg/l, respectively, were found with the following respective day-to-day coefficients of variation: 12.3%, 5.2% and 5.3%. Amounts of prednisolone metabolites excreted in the urine of these patients were correlated with the ingested daily dose of prednisolone. It was concluded that overall absorption of prednisolone in these patients was adequate and not influenced by shortage of bile acids in the gastro-intestinal tract, or by steatorrhoea, both caused by external bile drainage. In addition there was no evidence for increased metabolism of prednisolone.

Adolescent↗

Change in alpha 1-antitrypsin phenotype after orthotopic liver transplant.

The aim of the present study was to determine the interval after orthotopic liver transplant during which the alpha 1-AT phenotype in the serum changes. Eleven patients could be evaluated because the donor and recipient had different alpha 1-AT phenotypes. The results showed that within 1 to 3 days of the transplant donor alpha 1-AT is already present in the serum of the recipient, and subsequently the transplanted liver continued to synthesize alpha 1-AT of the donor phenotype. The result confirmed that liver parenchymal cells are the main site of alpha 1-AT synthesis.

Humans↗