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K Böker

Publications and source records attributed to K Böker.

36 records · Page 2Linked to original sources
PubMed1995

A novel bioreactor design for in vitro reconstruction of in vivo liver characteristics.

We have constructed a bioreactor aimed at imitating the three-dimensional micro- and macroenvironment of the liver. In vivo hepatocytes are arranged in plates of cell monolayers and are specifically attached with both sinusoidal surfaces to the space of Disse which contains extracellular matrix. Nonparenchymal cells are located on the other side of the space of Disse toward the sinusoid. For supporting monolayer hepatocytes with bipolar attachment to the extracellular matrix, we used a double gel culture technique that sandwiches hepatocytes between two layers of collagen. In double gel cultures, albumin production increases during an adaptive period to the in vitro environment. In contrast to conventional single gel hepatocytes, double gel hepatocytes maintain expression of sinusoidal microvilli and a polyhedric cell shape in culture as seen by transmission electron microscopy. Albumin production in the bioreactor was stable. The organotypical bioreactor concept is an example of organ mimicry and may provide the basis for the organ-otypical development of a full-sized hybrid artificial liver.

Albumins↗
PubMed1995

Reconstruction of liver tissue in vitro: geometry of characteristic flat bed, hollow fiber, and spouted bed bioreactors with reference to the in vivo liver.

Bioreactors currently being developed for hybrid artificial livers vary greatly with respect to their microenvironment. The specific architecture modifies the relationship parenchymal and nonparenchymal cells have with the exchange surfaces of the bioreactor. Most designs are either based on hollow fiber, spouted bed, or flat bed devices. This diversity is contrasted by the uniform and unique organization of the in vivo liver. The liver cells are arranged as plates and both sinusoidal surfaces of the hepatocytes are enclosed within the matrix of the space of Disse. In this study we intended to define the in vivo liver tissue characteristics in a manner useful for an organotypical approach to hepatic tissue engineering. Transmission electron microscopy of an in vivo liver was utilized to describe these ratios. The ratios defined in this study are based on the constant hepatocellular expression of two sinusoidal surfaces. A relationship is established between the expression of the sinusoidal surfaces and their use as attachment and exchange surfaces inside a bioreactor. The presence of biliary surfaces and nonparenchymal cell surfaces is compared. The functional relevance of an in vivo like extracellular matrix geometry for oxidative biotransformation of primary hepatocytes in vitro was studied using the two model drugs cyclosporin and rapamycin. The generation of the hydroxylated cyclosporin metabolites AM 9 and AM 1 and four rapamycin metabolites was analyzed by high performance liquid chromatography (HPLC). It is shown that the cell-specific biotransformation rates at 1 week in culture in matrix overlayed hepatocytes was 5-10 times that of hepatocytes without matrix overlay. Bilaminar membrane (BLM) bioreactors were used to reconstruct extracellular matrix geometry, three-dimensional cell plates, and sinusoidal analogs in between cell plates.

Animals↗
PubMed1995

Clinical relevance of mutations in the precore genome of the hepatitis B virus.

A stop codon in the precore genome of the hepatitis B virus (HBV) in anti-HBe positive HBV carriers may be associated with a more progressive form of HBV infection. Earlier studies, however, were mainly performed in patients from the Mediterranean area who had severe infection. The aim of this study was to evaluate the prevalence of precore mutants in an unselected population living in northern Europe. Twenty of 42 of these patients are infected predominantly with a virus strain, which has the typical stop codon in the precore genome, characterised by a mutation at base 83. In six patients there was an additional G to A mutation at base 86 of the precore genome. Statistical analysis showed no difference between the patients with or without a stop codon in the precore genome. When patients with a double mutation at base 83 and 86 of the precore genome were compared with the other anti-HBe positive HBV carriers, however, the corresponding clinical data were worse. Therefore we suggest, that it is not the stop codon in the precore gene itself, but the occurrence of a double mutation at bases 83 and 86, which is associated with a more severe course of disease in anti-HBe positive HBV carriers.

Adult↗
PubMed1995

Recurrence of hepatitis B virus cirrhosis and hepatocellular carcinoma: an indication for retransplantation?

Hepatitis B virus reinfection as well as recurrence of hepatocellular carcinoma are frequent complications in liver allograft recipients. This is the report of a patient who had two liver transplantations with a 6-year interval, both for the same indication-postnecrotic cirrhosis and liver cancer. Following first and second transplantation, hepatitis B reinfection occurred at 12 and 6 months, and allograft cirrhosis developed after 20 and 10 months, respectively. Intrahepatic recurrence of hepatocellular carcinoma was found after 69 months. Two years following retransplantation, the patient is tumor-free, and has normal graft function. In selected patients with hepatitis B-related liver disease, and hepatocellular carcinoma liver replacement is indicated when combined with effective immunoprophylaxis, and other adjuvant therapy. Late recurrence of both diseases is unusual, and retransplantation may come into question.

Carcinoma, Hepatocellular↗
PubMed1994

Auxiliary partial orthotopic liver transplantation for acute liver failure: the Hannover experience.

APOLT has been developed both to enable the native liver to regenerate in acute liver failure and to avoid the risks of long-term immunosuppressive therapy. We present our experience with APOLT in 4 patients with acute liver failure. The patients were 33, 18, 5, and 34 years of age, respectively. The causes of hepatic failure were: one HELLP syndrome, one paracetamol intoxication, and 2 causes which remained undetermined. All patients were in coma before transplantation. First symptoms had occurred 13, 2, 30, and 20 days prior to APOLT, respectively. In all cases, segments II and III of the recipient's own liver were resected before implanting the auxiliary liver orthotopically. The auxiliary graft consisted of segments II and III in 2 cases and of II, III, and IV in the other 2 patients. The auxiliary graft showed good initial function in all cases. All 4 patients are alive 5 years, 15 months, 6 months, and one month after transplantation. In the last patient, an arterial thrombosis of the graft on the 5th postoperative day required retransplantation. The immunosuppressive therapy could be stopped in 3 cases and the graft was removed in 2 patients 15 and 40 days after APOLT, respectively. This shows that APOLT represents an effective treatment for patients with acute liver failure, which enables restoration of native liver function. Thus, APOLT should be considered in every patient with acute and potentially reversible liver failure in whom a transplantation is indicated.

Acetaminophen↗
PubMed1994

The Budd-Chiari syndrome: clinical presentation and diagnostic findings in 45 patients treated by surgery.

We report on the clinical presentation and diagnostic findings in 45 patients with Budd-Chiari syndrome. The diagnosis was confirmed by histology at the time of liver transplantation (n = 37) or shunt surgery (n = 8). An underlying disorder could be established only in half of the patients, oral contraceptives as predisposing factor were known in 18 cases. Clinically, abdominal pain and distension as well as hepatomegaly and ascites were most frequent findings, whereas changes in laboratory data were more or less unspecific. By use of repeated ultrasound, a definite diagnosis of a Budd-Chiari syndrome could be confirmed in all cases by obligatory demonstration of obstruction or thrombosis of at least one major liver vein. Hepatic venography revealed only one false-negative result. Celio-mesenteric arteriography plus portography, cavography and preoperative liver biopsy did not present additional diagnostic information. These techniques may contribute to treatment planning of portosystemic shunt surgery or hepatic transplantation. In conclusion, the presence of hepatosplenomegaly, ascites, abdominal pain and distension, especially in combination with a known hypercoagulable state, should alert to the possibility of a Budd-Chiari syndrome. Ultrasound is the diagnostic tool of choice. Hepatic venography should only be performed if even repeated ultrasound is not conclusive.

Adolescent↗
PubMed1992

[Experimental studies of the inhibition of fibrogenesis].

Colchicine as well HOE 077 were found to be effective in the inhibition of hepatic collagen accumulation after bile duct ligation in rats. The effect was additive and was truly reflected by changes in the serum PIIIP and 7s-collagen (IV) concentration. Extrahepatic effects on collagen synthesis were not detected when HOE 077 was used. Thus further studies on the potential clinical usefulness of these compounds are clearly indicated.

Animals↗
PubMed1991

Fibrosis of the liver in rats induced by bile duct ligation. Effects of inhibition by prolyl 4-hydroxylase.

The model of biliary cirrhosis by bile duct ligation was further characterized using PIIIP, 7S-collagen as well as standard enzymes in the serum, prolyl 4-hydroxylase and total hydroxyproline in the liver and light microscopical histology. Five weeks after bile duct ligation there was an increase in total collagen content of the liver to 510% of initial values accompanied by an increase of serum-PIIIP (225%) and 7S-collagen (389%). The time-course of this connective tissue proliferation was biphasic with an initial phase of cholestasis and cellular damage followed by rapidly increasing collagen accumulation. The novel prolyl 4-hydroxylase inhibitor HOE 077 reduced the accumulation of collagen in the liver over 6 weeks by 48%. There were no apparent side effects and treated animals showed a tendency towards less functional impairment. The drug's effects, however, were not dose-dependent between daily doses of two times 2 mg/kg and two times 10 mg/kg. These results emphasize the usefulness of the bile duct ligation model for studies of collagen metabolism. They show HOE 077 to be a promising agent for the inhibition of hepatic fibrosis.

Animals↗
PubMed1991

Liver transplantation in HBs antigen (HBsAg) carriers. Prevention of hepatitis B virus (HBV) recurrence by passive immunization.

Liver transplantation in HBs-antigen (HBsAg) positive allograft recipients is associated with a high risk of HBV recurrence some time after surgery. So far, results of measures to prevent recurrent HBV-infection by means of treatment with interferon, hepatitis B vaccination and short-term passive immunization with hepatitis B immunoglobulin (HBIg) or monoclonal antibody to HBsAg (anti-HBs) have been disappointing. In the present study the results of long-term, anti-HBs monitored passive immunization with HBIg is reported. In 23 HBsAg-positive liver transplant recipients an anti-HBs level of greater than or equal to 100 IU/l was maintained for 6 or 12 months, respectively. The rate of recurrent infection was found to be less than 20% under HBIg substitution, whereas 11 graft recipients with no or only short-term HBIg prophylaxis were reinfected by month 15 after transplantation. HBV recurrence was associated with chronic liver disease and recurrent cirrhosis in the allograft.

Adolescent↗
PubMed1991

Renal failure is a common complication in non-immune Europeans with Plasmodium falciparum malaria.

Renal failure in malaria appears to be a complication less well known than anaemia and cerebral malaria. Thirty-one non-immune patients treated for Plasmodium falciparum malaria at Hannover Medical School were reviewed. Nine patients (29%) had acute renal failure, seven of whom required dialysis, and five patients needed mechanical ventilation. Cerebral symptoms were seen in nine patients, and three of the patients died. In a second series, information about patients who died of malaria in Germany and Austria was gathered. Thirty-six reports were obtained and analysed retrospectively. Thirty-four patients (94%) had acute renal failure. Eighteen patients received dialysis while five other patients with high central venous pressure or hyperkalaemia would have benefitted from dialysis. Cerebral involvement was seen in 34 patients, and 20 patients showed respiratory failure. It was concluded that renal failure in P. falciparum malaria is as common in non-immune adults as cerebral malaria. As untreated renal failure may have a deleterious influence on cerebral and respiratory functions, early dialysis-treatment in patients with severe P. falciparum malaria and signs of deteriorating renal function is recommended.

Acute Kidney Injury↗
PubMed1986

Human atrial natriuretic peptide (ANP) for the treatment of patients with liver cirrhosis and ascites.

The acute effects of human atrial natriuretic peptide (ANP) were investigated in 10 patients with liver cirrhosis and ascites. In all patients, diuresis and natriuresis were stimulated with a wide individual variation (50 to 500%) in response to a bolus injection of 30 micrograms ANP. No side effects of treatment were observed. Continuous infusion of ANP (300 micrograms/10 h/d) in a patient with liver cirrhosis and ascites, resistant to conservative forms of diuretic therapy, resulted in an initial increase of diuresis and natriuresis which subsequently returned to pretreatment levels. After initiation of pulsatile nocturnal treatment (5 pulses of 30 micrograms ANP every 3 h), diuresis increased, leading to a persistent normalization of sodium and chloride excretion. The patient lost 8 kg of weight during 16 days of treatment. Out of 3 additional patients on the same therapeutic regime, only one experienced a weight loss of 5 kg due to increased natriuresis and chloruresis. The remaining 2 patients did not respond during 5 resp. 7 days of therapy.

Adult↗
PubMed1982

[Day-clinic treatment in geropsychiatry (author's transl)].

In a retrospective study the author reports on the results of the first four years in the geropsychiatric day clinic of the general hospital "Ochsenzoll" in Hamburg. After a survey of the literature on the history and indication of day-clinic therapy for aged people, the author describes that in a chiefly psychotherapeutic and sociotherapeutic setting patients are treated who had formerly belonged to the category of inpatients, as well as patients without previous psychiatric experience. The main tasks to be performed in a day-clinic attached to a large hospital, are rehabilitation and prevention. These tasks cover different groups of patients which are characterized in the article. Pointers to factors which make it difficult to transfer some patients to day care results from the consideration which must be given to yet another group of patients who, although they participated in the therapeutic programme, could eventually not be transferred to the day hospital. A separate section deals with patients having psychogenic and organic disturbances, and experiences are communicated from day-clinic practice while referring to data taken from literature. It is finally underlined that the value of day-clinic therapy cannot be assessed in terms of money or economy.

Aged↗
PubMedDate not supplied

Subacute liver failure induced by phenprocoumon treatment.

We report on a 39-year-old woman suffering from deep venous thrombosis due to a heterozygous factor-V-Leiden mutation with resistance to activated protein C. Four months after beginning oral anticoagulation, generalized jaundice appeared. Subsequently, subacute liver failure developed necessitating an orthotopic liver transplantation. Histopathology showed features of extensive liver cell necrosis without evidence of a substantial inflammatory infiltrate. Based on histopathology and exclusion of other liver diseases, phenprocoumon-induced liver failure was diagnosed. Five months after transplantation the patient is well with normal liver function tests. Because of the widespread use of oral anticoagulants, not only bleeding complications but also hepatotoxicity should be considered in therapy supervision.

Adult↗