Biomedical subjects
O Klinge
Publications and source records attributed to O Klinge.
[Successful therapy of persistent androgen-induced cholestasis with ursodeoxycholic acid].
Drug-induced cholestasis can rarely persist for a considerable time period even after withdrawal of the drug. We report the case of a 55-year-old man with progressive jaundice after oral therapy with 17-alpha-methyltestosterone. Under empiric therapy with ursodeoxycholic acid the condition resolved completely. According to this observation, we suggest a therapeutic trial with ursodeoxycholic acid in cases of prolonged androgen-induced cholestasis.
Fatal hepatotoxicity in a child treated with vigabatrin.
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[Intrahepatic cholangitis with presumably immunologic bases].
An overview is given on three topics of chronic cholangitides, namely 1. chronic non destructive cholangitis, i.e. primary biliary cirrhosis, 2. immunocholangitis, 3. primary sclerosing cholangitis including the liver-colitis-syndrome, each of which will lead into primary biliary cirrhosis within a commonly long period. The histological patterns are well defined in chronic non destructive cholangitis and primary sclerosing cholangitis. Clinical features, laboratory data and histologic pattern concerning the immunocholangitis will have to be evaluated in more precise ways in the future. As with all immunological diseases it is not always clear whether findings are causative or merely secondary consequences of the disease in question. Nevertheless compelling evidence for an immunologically related pathogenesis comes from immunohistochemical studies. Results of electronmicroscopic and histochemical studies of basement membranes in sclerosing cholangitis did not refer to their considerable role in the initiation of the disease. The role of vascular lesions in bile duct destruction and scar formation seems to be negligible. Neoformation of ducts and duct like structures which regularly precede fibre formation are the consequence of hepatocellular metaplasia.
[Capillary hemangioma of the heart: a case report].
In a 52-year-old man, within the left ventricle, a globular mass 1.5 cm in diameter was detected incidentally by echocardiography. Selective coronary angiography showed a mobile patch of hypervascularity suggesting the vascular nature of the cardiac mass. The patient was operated and a pedunculated tumor originating from the anterolateral papillary muscle was removed. Histological examination revealed a benign capillary hemangioma. Six months after surgery the patient was reevaluated by echocardiography. There was no evidence of tumor recurrence.
[Vitamin A poisoning as a cause of isolated gamma-GT increase].
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[Variability of Jeune syndrome. Lung hypoplasia, renal failure and direct hyperbilirubinemia in a newborn infant].
Asphyxiating thoracic dysplasia (Jeune-syndrome) is an autosomal inherited disease which is characterized by bone dysplasia, renal and hepatic malformations of various expressivity. Newborns who have serious thoracic dysplasia with associated lung hypoplasia normally die during the neonatal period. Patients without signs of pulmonary defects may develop progressive renal failure due to an interstitial fibrosis. In addition, liver- and pancreas fibroses are found. We recently observed the greater variability of clinical manifestation in two patients with Jeune-syndrome. The first patient, a mature male newborn infant, presented early signs of respiratory disease and, more interestingly, had high serum levels of 5.1 mg/dl conjugated bilirubin at day 1; the maximal bilirubin-concentration was 26.5 mg/dl at day 9. Additionally, he developed progressive renal failure (maximal serum creatinin: 2.7 mg/dl at day 13). The patient eventually died of respiratory failure. To our knowledge such an early onset of severe hepato-renal manifestation has not been observed in patients with this disorder. A second term newborn infant with typical radiological signs of Jeune-syndrome and severe lung hypoplasia died within hours after birth. No hepato-renal defects could be documented in this patient.
[Clinico-pathological conference. Cholangiectasis and cholelithiasis in primary sclerosing cholangitis].
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[Adenomatosis of the bile ducts as a rare cause of cholestasis].
Biliary obstruction of uncertain aetiology in a 69-year-old women led to a cholecystectomy and exploration of the bile tract: a nearly complete cast of the hepatic ducts and intrahepatic bile ducts was extracted. Histological examination of the gall bladder and liver biopsy failed to provide a diagnosis, but a bile duct biopsy taken at the time of an endoscopic retrograde cholangiography revealed the diagnosis of papillomatosis. This disease has a poor prognosis because there is no known cure.
[The injection abscess--a sequela of unsuitable cannulas?].
Skin-cylinders punched out by hypodermic needles, are discussed as an influencing factor in abscess forming after injection. Up to now these skin-cylinders are regarded as unavoidable. The authors show, that with different types of hypodermic needles the frequency of skin-cylinders widely differs. They resume, that the frequency of post injection abscesses could be reduced by the use of better suitable needles.
[Biocompatibility and mechanical strength of various dura mater preparations after intraperitoneal implantation in rats].
Biocompatibility and mechanical strength of 3 different dura mater preparations were studied during 1, 2 and 4 weeks in a rat model. Two preparations produced by conventional methods did not markedly differ, whereas the third one, which had been freeze-dried after addition of glycerol, exhibited some special properties, showing higher mechanical strength throughout the whole period of implantation, and lower tendency to form adhesions, and inducing weaker leucocytic reaction. For certain surgical problems this soft, strong and compatible dura preparation could be an appropriate alternative.
[Hepar lobatum carcinomatosum].
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[A chronic destructive non-suppurative cholangitis-like disease picture with antinuclear antibodies (immunocholangitis)].
Three females had suffered, two for many years, from bouts of a liver disease of unknown origin, which clinically, histologically and biochemically fulfills the criteria of chronic destructive non-suppurative cholangitis. None of the patients had antimitochondrial antibodies, but all had antinuclear antibodies at high titres. Two of them are mother and daughter; the latter has two daughters (aged 10 and 12 years), both of whom have antinuclear antibodies at low titres but no abnormal liver function tests. The female family members of the third patient also had antinuclear antibodies in their serum with normal liver enzyme tests. None of the patients was taking any drugs. Contrary to true chronic destructive nonsuppurative cholangitis (primary biliary cirrhosis), in the three patients immunosuppressive treatment with azathioprine (Imurek) and prednisone (Decortin) was successful. It is suggested that the described disease be called immunocholangitis.
Prognostic relevance of serum inhibitory factors (SIF) in protracted and persistent hepatitis B.
In a follow-up study of 3 years' duration, serum inhibitory factors (SIF) were analysed in 23 patients with a protracted course of viral hepatitis B (PVH) and 12 patients with chronic persistent hepatitis (CPH). Four patients showed a progressive course, developing chronic active hepatitis, and one died of liver failure. All 4 patients had high and persisting SIF activity. The other patients were either SIF negative or lost SIF during the observation period. The inhibitory moiety was isolated from an albumin-rich serum fraction, indicating that the factor was of the same nature as previously described in patients with acute viral hepatitis B. SIF was also demonstrated in other viral infections but was absent or of low activity in autoimmune, toxic or nutritive disorders. These results suggest that SIF may act as an immunoregulatory molecule protecting the liver from exaggerated immune response.
[Intrahepatic sclerosing cholangitis. Morphology, morphogenesis and diagnosis].
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Hereditary hypofibrinogenemia with fibrinogen storage in the liver.
A family with hereditary autosomal dominant hypofibrinogenemia is described. The outstanding feature is massive deposition of fibrinogen/fibrin within hepatocytes, faintly visible in routine microscopic sections, but clearly demonstrable by immunohistologic techniques. Circulating fibrinogen shows normal electrophoretic mobility of A alpha-, B beta-, and gamma-chains. We assume that the hereditary defect in this family interferes with fibrinogen release from hepatocytes. Clinically there are fluctuating slight elevations of serum transaminase levels. Hemostasis and wound healing are undisturbed.
Safety and potency aspects in the preparation of an experimental HBsAg vaccine.
No experimental setting is available to exclude residual infectivity in HBsAg vaccines derived from human plasma. Thus, safety can be achieved only by means of their preparation. To reduce infectivity of the starting material, only plasma from healthy anti-HBe positive donors was used. In the FRG, 50% of all healthy HBsAg carriers with anti-HBe have a suitable serum level of 5 to 20 micrograms/ml. The purification procedure removed hepatitis B virus by a factor greater than 10(4). The purified product contained only the HBsAg proteins and no serum protein, as shown by SDS gel electrophoresis. The pure HBsAg was treated with formalin 1:500 at 37 degrees C for 4 days. A loss of 30 to 50% antigenicity was tolerated to achieve the highest possible destruction of known and unknown infectious agents. After inactivation, the HBsAg was bound to aluminium hydroxide gel. The gel was washed repeatedly to remove the formalin. Doses of 40 micrograms or 20 micrograms absorbed HBsAg protein were given to greater than 2500 persons without serious side effects. In greater than 97% anti-HBs was formed with a median titer of 1900 I.U./ml.
[Preparation and testing of a hepatitis B vaccine (author's transl)].
Starting with 41.5 l of plasma from anti-HBe positive carriers of HBs antigen, 11,400 doses of a hepatitis B vaccine with 42 micrograms HBsAg-protein and 11,300 national units HBsAg activity per dose were obtained. After purification, HBsAg is obtained in 99% purity with a yield of more than 90% protein. A possible residual infectivity was inactivated by a diluted formalin solution. The infectivity test in chimpanzees confirmed the absence of infectious hepatitis viruses (HBV and nonA-nonB). In guinea pigs the immunogenicity of the vaccine was comparable to that of the reference preparation from the U.S. National Institute of Health. The presence of Al(OH)3 in the vaccine increased the anti-HBs titre by factors of 30-50. After vaccination with two doses 41 of 45 persons became anti-HBs positive, with three doses 42 of 45 persons developed anti-HBs. Median anti-HBs titre after the third doses: schedule I (three doses in intervals of 6 weeks) 427 mWHO-U/ml; schedule II (two doses at an interval of 4 weeks, third doses 4 months after the first doses) 1535 mWHO-U/ml. The vaccine was well tolerated. There were minor local reactions only.