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Biomedical subjects

G Otto

Publications and source records attributed to G Otto.

At least 145 records · Page 8Linked to original sources
PubMed1994

FK 506 primary immunosuppression following emergency liver transplantation for fulminant hepatic failure. European FK 506 Study Liver Group.

The efficacy and safety of an FK 506-compared to a cyclosporin A based immunosuppression regimen was examined in liver recipients who underwent transplantation for fulminant hepatic failure in the European FK 506 liver study. A consistent trend towards improved patient and graft survival noted in the FK 506-treated patients was apparent from the first postoperative week (e. g. patient survival: day 7, 95.5% vs. 82.1% and month 6, 72.7% vs. 60.7%). Acute (in particular intractable) rejection was less frequent in the FK 506 group (e. g. cumulative intractable rejection rate at 6 months, 6.2% vs. 22.6%). In a single centre (Kings College Hospital), 17 patients were studied in more detail. The FK 506 treatment group had improved graft function, lower steroid requirements and episodes of infection. Accompanying these benefits, apache 111 and TISS scores were lower in this group in the early posttransplant period. Intensive care discharge was earlier and both treatment groups experienced similar toxicity.

Adolescent↗
PubMed1994

Intraoperative evaluation of big-endothelin plasma levels during liver transplantation in different vascular compartments.

Endothelin-1 (ET) is derived from its precursor big-ET, secreted by endothelial cells of multiple origin. The role of ET peptides in the physiological responses after orthotopic liver transplantation (OLT) was investigated. Venous big-ET plasma levels were analysed by RIA in 28 patients before and after OLT. Samples for analysis were taken intraoperatively from 12 patients from the caval, portal and hepatic veins and the radial artery at multiple time points. Highest caval levels were found during the anhepatic period and 60 min after reperfusion, followed by a drop and subsequent increase postoperatively. Highest levels in the hepatic and portal veins were detected during explanation and reperfusion. A different pattern was found in the radial artery. Values during rejection and infection were elevated compared with preoperative and postoperative levels. The heterogeneity of the kinetics points to different sites of ET generation, including liver and splanchnic circulation. It suggests a predominant paracrine secretion mode of ET peptides with various stimuli involved. Big-ET levels could reflect endothelial cell damage, as big-ET is generated intracellularly and biological activity is rather weak.

Adult↗
PubMed1994

Prolonged rat allograft survival induced by temporary elimination of alpha/beta T cells with monoclonal antibody.

We tested the ability of lewis (LEW; RT-1(1)) recipients to reject DA (RT-1av1) cardiac allografts following the selective elimination of alpha/beta T cells with the mouse monoclonal antibody R73. One group of adult rats (6 weeks old) received 1000 microg R73 i.p. on days 2 and 1 before transplantation, and 100 microg R73 every third day after transplantation up to day 18. Prolonged cardiac graft survival was noted (30, 30, 32, 51, 62, 108, > 500, > 500, > 500 days). Untreated controls (n = 10) rejected their grafts within 7 +/- 1 days. R73 therapy induced a dramatic decrease in alpha/beta T cells from 69% before treatment to 5% within the first 5 days, followed by an increase to 64% by day 8. The T cell increase was paralleled by the appearance of anti-mouse antibody. A second group of adult rats (10 weeks old) received the same treatment. These "older" recipients rejected their grafts within 20 +/- 5 days. Chronic R73 therapy from birth until the day of transplantation (100 microg R73 i.p. twice a week) resulted in graft survival of 37 +/- 9 days in eight animals. Two rats had a graft survival of more than 200 days. When chronic R73 therapy was continued to day 70 after transplantation, DA hearts were accepted well in all animals for more than 100 days. Alpha/beta T cells were virtually absent throughout the whole time of treatment. Antibodies against R73 were not detected. We concluded that selective elimination of alpha/beta T cells has a strong effect on allograft survival.

Age Factors↗
PubMed1994

Heart allograft survival in rats following immunization with soluble peptide MHC class I donor antigens: evidence for the role of indirect recognition in rejection.

The current series of experiments addressed the question of whether indirect priming with donor MHC antigens affects heart allograft survival. LEW (RT-1(1)) rats were immunized with a mixture of two peptides corresponding to the variable region of MHC class I locus Aa antigen (alpha1 and alpha2 domain). The recipients were transplanted with a DA (RT1-1a) heart 1 month after immunization, and graft survival was closely monitored by ECG. All peptide-treated recipients presented with anti-peptide antibodies at the time of transplantation and developed a strongly accelerated graft rejection. These findings indicated that indirect recognition of MHC I donor antigens promotes heart allograft rejection.

Amino Acid Sequence↗
PubMed1994

Laparoscopic versus open appendicectomy for suspected appendicitis: a prospective study.

Despite recent advances in minimally invasive surgery, laparoscopic appendicectomy has been questioned as a feasible method of treating patients with suspected appendicitis because open appendicectomy carries few risks and complications. Between February 1992 and January 1993 a non-randomized prospective study comparing open and laparoscopic appendicectomy was designed to assess differences in postoperative morbidity, pain, inpatient hospital stay and a return to normal lifestyle. One hundred and sixty-seven patients with suspected clinical appendicitis were assigned to open (n = 74) or laparoscopic (n = 93) appendicectomy. Six patients were excluded due to the presence of other significant pathology such that the appendix was not removed. Eighty-seven patients underwent attempted laparoscopic appendicectomy, of which 81 were completed. The diagnosis of appendicitis was confirmed histologically in 63.5% of patients undergoing open appendicectomy and 63% of patients undergoing laparoscopic appendicectomy. There were no significant differences in anaesthetic times, postoperative morbidity and analgesic requirements. There was a significant reduction in both postoperative inpatient stay (P < 0.0001) and time taken to return to work or normal activities (P < 0.0001) for the laparoscopic group. The use of laparoscopy for patients with suspected appendicitis aids definitive diagnosis and should reduce the negative appendicectomy rate to an acceptable figure. The results suggest that laparoscopic appendicectomy is safe and offers advantages over open appendicectomy in the management of patients with suspected appendicitis.

Adolescent↗
PubMed1994

Animal and public health implications of gastric colonization of cats by Helicobacter-like organisms.

The bacterial genus Helicobacter contains a number of species which colonize the gastric mucosa of mammals. Natural and/or experimental gastric pathology has been correlated with colonization in humans and a wide variety of animal species. Historical reports in the literature suggest that a high percentage of cats are colonized by large, spiral, gastric helicobacter-like organisms (GHLOs). One of these bacteria (Helicobacter felis) has been isolated on artificial media and has experimentally caused gastritis in gnotobiotic dogs. This study surveyed the prevalence of helicobacter colonization in random-source cats by using the urease assay. Histologic examination was performed to determine the degree of associated pathology present. GHLOs associated with chronic gastritis were present in 70% of the juvenile and 97% of the adult cats studied. Although further study is needed to determine specifically what role GHLOs play in feline gastrointestinal disease, these results indicate that helicobacter colonization should be considered in the pathogenesis of feline gastroenteropathy. Furthermore, the high prevalence of feline infection is interesting because cats have recently been implicated as a potential reservoir for human infection by helicobacter-like organisms.

Animals↗
PubMed1994

[Liver transplantation after surgical shunt or transjugular intrahepatic portasystemic shunt].

The goal of this study was to assess the influence of prior treatment of bleeding esophageal varices on liver transplantation. After sclerotherapy the results of liver transplantation were identical to those achieved in patients without previous variceal hemorrhage (74% 1-year survival). The results of liver transplantation to patients who already had surgical shunts were dismal. Four of nine patients with portocaval or Warren shunts were long-term survivors. In comparison, the intraoperative course in five patients with transjugular intrahepatic portosystemic stent shunts (TIPSS) was uneventful and four of these were long-term survivors. This has led us to adopt TIPSS as the treatment modality of choice for patients with bleeding varices awaiting liver transplantation.

Adult↗
PubMed1994

[Shunt surgery in portal hypertension. Pathophysiology and indications].

Portosystemic shunts are well established methods of avoiding recurrent hemorrhage from esophageal varices. Hemodynamic aspects and clinical results suggest that distal splenorenal shunts should be preferred over non-selective shunts. The functional capacity of the liver is crucial for any type of shunt. In patients with Child C cirrhosis, mortality is known to be particularly high following an emergency shunt so that, this procedure is recommended only as a rescue operation. Although prophylactic shunting decreases the risk of bleeding from varices, it leads to higher liver-related mortality. Prophylactic shunts are, therefore, indicated only in exceptional cases.

Catheterization↗
PubMed1994

Acetylsalicylic acid in the prevention of early stenosis and occlusion of transjugular intrahepatic portal-systemic stent shunts: a controlled study.

Stenosis or occlusion of the transjugular intrahepatic portal-systemic stent shunt may be initiated by aggregation and activation of thrombocytes on the surface of the metallic stent material. To find effective prevention of this event, we conducted a controlled trial administering acetylsalicylic acid for 3 mo. Forty-four patients (8 women and 36 men) with portal hypertension were included in this study. The patients were randomized into a group receiving 100 mg acetylsalicylic acid/day (n = 21) or into a control group (n = 23). Treatment was started immediately after transjugular intrahepatic portal-systemic stent shunt. Three months after transjugular intrahepatic portal-systemic stent shunt, 15 patients in the acetylsalicylic acid group and 19 patients in the control group underwent clinical reevaluation, gastroscopy and recatheterization with determination of the portal-systemic pressure gradient. No variceal bleeding occurred in any patients. In four patients in the acetylsalicylic acid group, erosive gastritis was observed in gastroscopy in contrast to only one patient in the control group. Complete patency of the stent was noted in 10 of 15 patients in the acetylsalicylic acid group and in 14 of 19 patients in the control group. Transjugular intrahepatic portal-systemic stent shunt restenosis associated with a significant increase of the portal-systemic gradient occurred in five patients in the acetylsalicylic acid group, which required redilation in all and additional stent placement for expansion of the stented tract in two patients. In the control group, redilation was necessary in five patients with additional stent extension in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

p53 overexpression is frequent in European hepatocellular carcinoma and largely independent of the codon 249 hot spot mutation.

Mutations in the p53 tumour suppressor gene have been recently described in hepatocellular carcinomas (HCC) from high risk areas such as China and South Africa. Our study was designed to assess the importance of p53 aberrations in HCCs from Europe, where the major risk factors in hepatocarcinogenesis, aflatoxin exposure and chronic hepatitis B virus (HBV) infection, do not play a dominant role. We investigated 22 HCCs and, as controls, their corresponding tumour-free liver tissues, seven livers with primary biliary cirrhosis and four morphologically normal livers. p53 overexpression, which is usually associated with point mutations of the p53 gene, was detected in 10 of the 22 HCCs by immunoblotting and immunohistochemistry. p53 expression was restricted to the nucleus in the positive cells, while all cells in the control tissues were negative. There was no obvious etiological preference in the p53 positive tumours. Particularly, underlying chronic HBV infection did not appear to be associated with an increased rate of p53 overexpression in European HCCs. SSCP and sequence analysis of exons 5-8 of the p53 gene revealed point mutations in six out of eight tumours with increased steady state levels of p53. In conclusion, our study demonstrates increased p53 levels due to point mutations in a significant proportion of European HCCs. The codon 249 mutation, which was detected in one of the cases, is not predominant in these tumours.

Adult↗
PubMed1993

Identification and propagation of a putative immunosuppressive orphan parvovirus in cloned T cells.

A putative parvovirus related to minute virus of mice (MVM), but distinct from MVM-prototype and MVM-immunosuppressive, was identified, using serologic techniques and Southern blot analysis, in maintenance cultures of established T cell clones. This putative viral agent resulted in a lytic infection of cloned L3 cytotoxic T cells but was unable to produce a productive infection in BHK.21 or EL-4(G) cells. Moreover, maintenance cultures of several distinct subsets of cloned T cells apparently contaminated with this putative viral agent contained poorly growing cells and erythrocyte aggregates. The aggregation of mouse erythrocytes appeared to be a reliable indicator of infection with this putative virus and may be related to the ability of this agent to agglutinate mouse erythrocytes. This putative virus also was found to inhibit the proliferative response of certain cloned T cells to IL-2 and Ag. Viremic mice and secondary MLC supernatant were identified as two potential sources of contamination and represent ways of propagating this agent in vitro. The finding that this agent interferes with the ability of T cell clones to thrive and, therefore has the potential to alter immune responses, emphasizes the importance of identifying and excluding parvoviral infections in cultures of murine T lymphocytes.

Animals↗
PubMed1993

Inhibition by cyclosporin A of adenosine triphosphate-dependent transport from the hepatocyte into bile.

BACKGROUND: Immunosuppressive treatment with cyclosporin A may be associated with impaired hepatobiliary elimination of bile salts and with cholestasis. Inhibition by cyclosporin A of the primary-active adenosine triphosphate (ATP)-dependent transport systems responsible for excretion of bile salts and cysteinyl leukotrienes across the hepatocyte canalicular membrane into bile may explain the cholestatic side effect. METHODS: ATP-dependent transport of bile salt and of cysteinyl leukotrienes was studied in human liver plasma membrane vesicles and additionally in rat liver plasma membrane vesicles enriched in canalicular membranes. RESULTS: Inhibition of ATP-dependent taurocholate transport in human liver by 50% was measured at 3 mumol/L cyclosporin A and at 4 mumol/L fujimycin. Kinetic analyses in rat liver indicated non-competitive inhibition by cyclosporin A with respect to ATP and competitive inhibition with respect to taurocholate with inhibition constant (Ki) values of 1.0 and 0.3 mumol/L, respectively. CONCLUSIONS: The ATP-dependent export carriers for bile salts and cysteinyl leukotrienes in the hepatocyte canalicular membrane are novel targets for inhibitory side effects of cyclosporin A. Inhibition of ATP-dependent bile salt transport may induce cholestasis.

Adenosine Triphosphate↗
PubMed1993

Supplemental dietary calcium fails to alter the acute effects of 1,2-dimethylhydrazine on O6-methylguanine, O6-alkylguanine-DNA alkyltransferase and cellular proliferation in the rat colon.

Prior studies from our laboratory have demonstrated that K-ras G to A mutations were detectable in a high percentage of carcinomas which developed in the colons of animals treated with the known colonic procarcinogen, 1,2-dimethyl-hydrazine (DMH). Moreover, in this model, the incidence of these mutations was decreased by a supplemental dietary calcium regimen which concomitantly decreased the frequency of rats with multiple tumors as well as tumor size. In an attempt to clarify the possible mechanism(s) involved in this antimutagenic effect of supplemental calcium, two groups of Sprague-Dawley rats were fed semisynthetic diets containing either 0.87 or 1.80% calcium by weight for 3 weeks, s.c. injected with 100 mg/kg of DMH and killed prior to and at various time periods (16-144 h) after injection. The colons of animals were analyzed and compared with respect to O6-methylguanine content in DNA, O6-alkylguanine-DNA alkyltransferase levels as well as cellular proliferation, as assessed by immunohistochemical staining of colonic crypts by bromodeoxyuridine. In certain experiments, these parameters were also analyzed in the proximal and distal colon before and at various times after administration of DMH. The results of these experiments demonstrated that supplemental dietary calcium was not found to influence significantly O6-methylguanine levels, alkyltransferase levels or cellular proliferation in the entire colon or in either colonic segment before or after the acute administration of DMH. DMH did, however, differentially alter all three of these biochemical parameters in the colonic segments (distal > proximal), possibly due to a greater degree of metabolic activation in the distal colon.

Animals↗
PubMed1993

Virulence factors and pap genotype in Escherichia coli isolates from women with acute pyelonephritis, with or without bacteremia.

Bacteremia develops in a subgroup of patients with acute pyelonephritis. This study examined isolates of Escherichia coli from the urine and the blood of 25 bacteremic and 67 nonbacteremic women with this acute disease. P-fimbriated strains were found in 100% of bacteremic patients without complicating factors but in only 71% of nonbacteremic patients without complications (P < .05). Non-P-fimbriated strains were only found to cause bacteremia in three patients with compromising host factors. Strains from the bacteremic group and those from the nonbacteremic group did not differ significantly in terms of hemolysin or aerobactin production or of serum resistance. The P-fimbriated strains from both groups of patients carried pap DNA sequences of the papGIA2 adhesin type; prsGJ96 homologous DNA sequences were rare. The results suggested that P fimbriae and compromising host conditions independently increase the risk for bacteremia during acute pyelonephritis.

Acute Disease↗
PubMed1993

Remission of severe rheumatoid arthritis following liver transplantation.

We present the case of a 32-year-old male who suffered from severe RA from the age of 21 years. After 9 years of active disease and poor response to therapy the patient developed severe hepatitis induced by the NSAID pirprofen. He went into fulminant hepatic failure necessitating emergency liver transplantation. Liver transplantation was followed by clinical and laboratory remission of his RA and he has remained virtually asymptomatic for more than 3.5 years. The possibility that this favourable clinical course was due to the immunosuppressive effect of the liver transplant rather than the ensuing immunosuppressive therapy is discussed.

Adult↗
PubMed1993

Effects of Carolina rinse and adenosine rinse on microvascular perfusion and intrahepatic leukocyte-endothelium interaction after liver transplantation in the rat.

Flushing hepatic grafts immediately before revascularization with a specially designed rinse solution such as "Carolina rinse" has been reported to improve survival after liver transplantation in the rat. This study investigated the influence of Carolina rinse and adenosine rinse on early graft function, microcirculation, and leukocyte (WBC)-endothelial cell interaction of arterialized syngeneic orthotopic liver transplants in Lewis rats. Livers were preserved for 24 hr in University of Wisconsin solution and flushed immediately before reperfusion with either Ringer's lactate (group A: n = 7), Ringer's lactate + 0.2 mmol/liter adenosine (group B: n = 6), or Carolina rinse (group C: n = 7). Microvascular perfusion and WBC accumulation were assessed by intravital fluorescence microscopy. In group C, acinar perfusion was significantly improved, accompanied by a lower percentage of nonperfused sinusoids 1 hr after reperfusion (mean +/- SEM: 26 +/- 2% [group A], 21 +/- 2% [B], 11 +/- 1% [C], P < 0.01 for C vs. A or B). In addition, Carolina rinse and, to a lesser extent, adenosine rinse reduced the number of WBC sticking in sinusoids and postsinusoidal venules. Better graft function in group C was indicated by increased bile flow during the observation period of 90 min after reperfusion (0.5 +/- 0.3 ml/100 g liver [group A], 1.5 +/- 0.7 [B], 3.7 +/- 0.6 [C], P < 0.01 for C vs. A or B). We conclude that Carolina rinse is able to improve early excretory hepatocellular function, microvascular perfusion, and intrahepatic WBC accumulation after prolonged cold ischemia and reperfusion, but adenosine is unlikely to be the key component of this rinse solution.

Adenosine↗