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Flutamide is an antiandrogen and frequently used for the treatment of prostatic cancer. Severe hepatotoxicity occurs in few patients but may be fatal. We report on two patients with prostatic cancer who received a therapy with flutamide. They showed different degrees of liver damage. One patient recovered completely after withdrawal of Flutamide under medication with steroids. Clinical symptoms and laboratory findings returned to normal within four weeks. Despite immediate withdrawal of Flutamide, the other patient showed a severe course with progressive liver dysfunction and hepatorenal syndrome. He finally died under the clinical picture of fulminant hepatic coma. This case represents the first death associated with flutamide in Germany. The literature concerning the metabolism of flutamide and the published cases of hepatotoxicity of this drug are reviewed.

A 72-year-old woman, who suffered from increasing dyspnea and productive cough was admitted to hospital. Clinical examination revealed a reduced respiratory sounds over the left lung and a painless and unmovable tumor in the area of the left hip.Apart from hypoxemia (pO2 7.81 kPa) the laboratory values did not indicate any pathological findings. The X-ray and CT-scan of the chest showed a few spotty shadows and pleura effusion on the left. No tumor cells were detected in the pleural effusion. In biopsies of the visceral and parietal pleura as well as biopsy within the tumor in the area of the left hip there were clusters of tumor cells of a granular cell tumor.Because the same tumor cell type was detected in the visceral and parietal pleura and wihtin the tumor at the left gluteus area, we diagnosed a malignant granular cell tumor. The CT-scan was suspicious of lung metastasis. The primary tumor was located in the area of left hip. The patient was in a poor general condition and she suffered from an extensive metastastic disease; curative treatment was not possible. A pleurodesis was performed. The patient died nine months after initial diagnosis.A rare malignant granular cell tumor was discovered by detecting tumor tissue of granular cell tumor in the pleura and within a tumor in the left gluteus area. Another indication of a metastatic disease were multifocal lesions in the lung detected by CT-scan. Curative treatment was not possible.

ANAMNESIS AND CLINICAL PICTURE: A 65-year old male with non-Hodgkin lymphoma developed severe invasive pulmonary aspergillosis during a state of leucopenia after chemotherapy.The initial manifestation was an infiltration in the right upper lobe of the lung, identified by lung scintigraphy as a peripheral wedge-shaped loss of perfusion. Both serum and bronchoalveolar lavage extreme high titre of Aspergillus antigen were seen as a laboratory indication of an invasive aspergillosis. The mould Aspergillus fumigatus was repeatedly isolated from bronchoalveolar lavage and bronchial secretion.Treatment was started with amphotericin B plus 5-flucytosine together with repeatedly bronchoscopic instillation of miconazole followed by thoracosurgical intervention with resection of the right upper lobe of the lung. Despite prophylaxis by itraconazole, a relapse of invasive aspergillosis occurred three months later probably due to persistence of aspergillus fungal elements in the left lung. The aspergillosis relapse was treated at first with liposomal amphotericin B. After eighteen days of treatment this was changed to a combination of 5-flucytosine with oral application of itraconazole, and cure was achieved.

Carcinomas were induced to the thyroid gland of female rats, using a method originally proposed by Thomas and Bollmann (metachronous application of nitrosomethylurea and methylthiouracil), to establish cytomorphological, histomorphological, cytochemical, and flow-cytophotometric criteria for diagnosis of thyroid carcinoma. Verification was also intended of the diagnostic value of each of the methods involved for differentiation of nodular goitre. Another purpose of the study was to find out, whether chemically induced thyroid tumours in rat were comparable to thyroid neoplasms in man. This provided to the examiners genetically coherent and morphologically comparable biological material at various stages of thyroid tumour growth which included diffuse and adenomatous hyperplasias, adenomas, and, from the 18th to 42nd experimental weeks, papillary as well as follicular carcinomas in 31 to 100% of all experimental animals involved. Cytomorphological comparability of rat thyroid material (imprint specimens) with human material (fine-needle aspiration cytology) was ensured for normal as well as for hyperplastically altered thyroid glands, including adenomatous and carcinomatous changes. Hence, group typing of thyroid cytology, originally devised for human specimens, could be easily adapted to material obtained from rat. Assessment of cytological samples by microscopic criteria yielded an accuracy of 89% in malignoma diagnosis and proved to be an approach of highly informative potential also in the context of rat experiments. Use of additional cytochemical techniques (PAS, toluidine-blue, peroxidase, alkaline and acid phosphatases, gamma-glutamyl transpeptidase) as well as quantitative DNA determination by means of flow-cytophotometry was helpful in casting light at some scattered trends of change from normal for certain stages of proliferation, but it failed to enhance information in cytomorphological diagnosis of the individual case.

The punctates of the biochemical joint function test contain hydroxyethyl starch which disturbs the assay of uronic acid and glucosamine for the estimation of hyaluronate. Therefore hyaluronate (0.03-0.75 g/l) was estimated by precipitation with Alcian blue on cellulose acetate membranes and measuring of the absorbance at 678 nm after dissolution in aqueous SDS (75 g/l). The gel-filtration HPLC separates the high-molecular-mass hyaluronate from low-molecular-mass impurities of biological samples. By comparing with a standard curve (0.5-2.5 g/l hyaluronate) the concentration can be determined. The results obtained by the two methods were significantly correlated (p less than 0.05). The Alcian blue technique is useful for rapid screening, the HPLC technique to confirm these values.

A report is given on three rare tumor types that developed in chronic lung scars. There were a malignant mucoepidermoid tumor, a carcinosarcoma, and a mixed tumor consisting of a carcinomatous and a mesenchymal part. The scar is regarded as the realizing factor in these tumors.

Irrigation of the knee joint in haemarthrosis during acute arthroscopy, as well as the continuous flow of liquid during surgical arthroscopy via motor-driven roller pumps and dialysis tubes, are described in this article.

The radial diffusion assay is a very useful method for detection of low amounts of proteinase inhibitors in biological materials. The determination of low molecular weight (LMW) inhibitors in the presence of high molecular weight inhibitors is possible by the combination of radial diffusion and ultrafiltration. Using this method LMW trypsin inhibitors could be demonstrated in human articular cartilage, but not in human synovial fluid. In cow, pig and sheep a LMW trypsin inhibitor could be found in both the articular cartilage and in the synovial fluid. On the other hand, a LMW trypsin inhibitor could not be found neither in the canine cartilage nor in the canine synovial fluid. The method allows also the direct determination of LMW trypsin inhibitors in cartilage extracts in the presence of 4 M guanidinium hydrochloride or 6 M urea. Therefore, the method is recommended for direct determination of LMW inhibitors by column chromatographic separations of inhibitors.

Basing on several international studies on the light microscopic pattern of acute non-A, non-B hepatitis we tried to discover the histological criteria of its chronic course by means of a detailed analysis of 181 liver biopsies of 94 patients suffering from chronic non-A, non-B hepatitis (a homogeneous group without competing noxious agents). In accordance with the relevant literature we found a rate of chronic courses of about 60% with chronic persistent hepatitis (2/3) and chronic lobular hepatitis (1/3) predominating. A transition into liver cirrhosis was not stated. As changes typical of the chronic non-A, non-B hepatitis cell ballooning (89%), changes of cell nuclei (88%), eosinophilic changes of cytoplasm (73%), focal sinusoidal cell activation (92%) and microvesicular steatosis (59%) were ascertained with the chronological analysis showing that there were no changes of these criteria up to the 6th year of disease. Its cause is seen in an incomplete elimination of the hepatitis viruses as a result of inefficient immune defence.

In two patients with chronic pulmonary fibrosis their history and findings of autopsy suggested, that X-ray therapy in a 31-year old male and Cytostatica-drug therapy in a 52 years old female have had an influence to development of a scar cancer. These cases are discussed with informations of the literature.

From 1973 to 1978 in the dissection material of the Medical Clinic in 78 deceased a stenosis of the aortic valve was diagnosed. Clinically diagnosed was the failure of the aortic valve, however, only in 33 cases. The retrospective analysis of the dissection material showed from the clinical point of view that the old age of the patients at admission (x = 70 years), the short stay in the ward and the reduced general condition were factors which rendered difficult the diagnosis of a stenosis of the aortic valve. On the basis of our results we are of the opinion that when a systolic murmur is present above the basis in connection with signs of the load of the left heart in the ECG in every case the diagnosis of the stenosis of the aortic valve is to be included into the diagnostic considerations also when a picture of heart complaints is not present in older persons.

Clinical and morphological findings of 406 patients who fell ill from a virus hepatitis were established according to the data and statistically evaluated to find relations between clinical, serochemical and histological criteria. The results were tested statistically. Clinical and paraclinical findings at the end of the hospital treatment give no evidence concerning the histological degree of cure of the acute virus hepatitis. In normalised clinical and serochemical findings we could morphologically prove an acute hepatitis still in 27.4%. Anamnestic data and severity of the clinical course have no relation to the histological diagnosis at the end of the hospital treatment with clinical and serochemical recovery. Therefore, at the end of the hospital treatment we recommend the liver biopsy as final examination. The most favourable date of the liver biopsy would, however, be between the 6th and 12th week after discharge.

The basis of the results are histological investigations of the preparations of liver biopsy of 134 donors who were evident in the SGPT-screening and of 100 patients with viral hepatitis after normalisation of the clinical and the laboratory-chemical findings. The liver casts were got by means of Menghini's method. In patients with hepatitis we found in 43% and in donors in 44% a small-droplet to medium size droplet fatty change in the liver cells. A large-droplet fatty change in the liver cells occurred in the patients with hepatitis only in 2% of the cases, in the donors, however, in 25%. Factors which favour the fatty change in the liver cells, such as adiposis, alcohol and prednisone therapy, were excluded. Our results increase the suspicion that in one part of the clinically healthy donors who are evident in the SGPT-screening we have to do with persons who are in the healing phase of a viral hepatitis with abortive course. Therefore, these persons should be excluded from blood donation. Donors and patients with the findings of a large-droplet fatty change in the liver cells must be investigated systemically. Blood donors with the findings of a fatty liver may remain in the team of donors.

During 23 years in the County Hospitel St. Georg Leipzig 500 nephrostomies were performed. A definitive balloon catheter nephrostomy was performed 58 times. Exclusively the open transparenchymatous establishment was carried out. If no malignant basic disease shortens the survival time, the renal fistulae are tolerated for many years without greater restriction of the renal function. The longest time of observation of a fistulated solitary kidney is about 17 years. The complication rate is small and the psychic stress of the patient as well as the quality of life obtained are tolerable. A preoperative intensive talk with the patient with adequate explanation and alternative demonstration is necessary in every case. An epithelial lining of the channel of the fistula does not take place even after years. The squamous cell epithelium of the external skin and the urothelium of the renal calyces grow only a few centimeters into the fistula. This is lined by inflammatory granulation tissue.

The clinical findings of 28 diabetic females with suspicion of diabetic nephropathy were compared with the findings of 27 decreased female diabetics with ascertained diabetic glomerulosclerosis. In the two groups above all elderly female diabetics were concerned with an average duration of diabetes of more than 10 years. Of the parameters examined duration of diabetes and diabetic retinopathy still possessed the greatest diagnostic certainty. All the other symptoms (particularly proteinuria, hypertension) were only signs of reference. On account of the difficult differential diagnosis of the diabetic nephropathy an undiscriminating use of the notion should be avoided, above all then when a bioptical clarification is not possible.

By means of a long-term analysis of histological and clinical-biochemical data taken of a group of patients (n = 38) having contracted an acute viral hepatitis non-A, non-B with a uniform parenteral source of infection evidence is given concerning the dynamic processes in the course of chronic non-A, non-B hepatitis. The analysis was therefore not based on the total biopsy material but on a section of 143 liver biopsies of patients who had been punctured at least 3 times (up to 6 times) in the 7 years of examination. A rate of 57,2% chronic persistent and 42,8% chronic lobular hepatitis was ascertained. A chronic active hepatitis or liver cirrhosis were not found. Both the histological activity degrees and ALAT-mean values were declining during the follow-up study though attacks (ALAT) and histological reactivations were observed in the 7th year, too. The data suggest that the chronic liver changes that developed in this type of non-A, non-B hepatitis proved to be extremely lingering but as a whole a regressive tendency could be observed.

Activity of plasminogen activator in synovial fluids of patients with osteoarthritis was determined by a radial diffusion assay. Synovial fluid from human knee joints was obtained by joint lavage with 35 ml physiological saline containing 0.5% hydroxyethyl starch. Synovial fluids from contralateral, healthy knee joints served as controls. The activity of plasminogen activator in synovial fluid from activated (painful) osteoarthritis is significantly higher than in cases of latent osteoarthritis, whereas the activity of controls is significantly lower as in latent osteoarthritis. The findings are helpful for the discovery of patients with enhanced plasminogen activator levels in synovia which should be treated therapeutically.

A working group of histopathologists with specialised liver training has established guidelines for a nomenclature of drug-induced liver lesions. It is recommended to use the term of drug-induced hepatitis for all cases of virus hepatitis-like picture. The most frequent type is that of hepatitis with confluent necrosis. This type of hepatitis was subdivided into three subtypes of diagnostic probability for differential diagnosis versus virus hepatitis.

It is reported on a 79-year-old female patient who died from coma hepaticum. As evoking cause an immunesuppressive treatment with cyclophosphamide or prednisolone, respectively, on account of chronic lymphadenosis with excessive thrombocytopenia is discussed. An accessible preliminary lesion of the liver after an infectious jaundice with persistence of the HBs-antigen from which the patient formerly suffered is probable. It is referred to the combination of the chronic aggressive hepatitis with malignant systemic diseases and immunopathy, taking into consideration the decision of therapy.

Pathophysiology, clinical picture with grading and in some cases controversial possibilities of treatment are described. We report on our experience in treatment of 21 cases of frostbite on hands and feet. Widening by DSA of the diagnostic spectrum of late sequelae is emphasized.

n the basis of clinical case reports on liver disintegration comata in foudroyant virus hepatitis the coma therapy was explained which was performed in the clinic for infectious and tropic diseases of the County Hospital St. Georg Leipzig in 1981 and this therapy was compared with the possibilities mentioned in literature. The aim of the article was to determine the present position of a county hospital in the great number of forms of therapy proposed. The basic therapy aimed at the reduction of neurotoxic protein metabolites and the application of intensive-medical therapeutic methods in interdisciplinary cooperation of internal specialist, specialist in dialysis and haemostaseologist are valuated as successful. The combined haemoperfusion/haemodialysis--two out of three patients treated survived--as a constituent of the present concept of therapy is assessed positively.

Our analysis showed that in of more than 80% of the patients admitted to the infection hospital because of suspicion of viral hepatitis there is also an anamnesis of one or several drugs. Among 2944 patients, admitted with being suspect of having viral hepatitis, there were 128 patients (adequate to 4.4%) with a drug-induced liver injury diagnosed in the result of all clinical, serological, histological and immunological findings. Inducing noxes were - in accordance to the frequency of ordination - ovulation inhibitors followed by Berlocombin, Ketazon, Depressan and Obsidan. In view of a clinic for infectious diseases it has to be pointed to the necessity of a high degree of security in the differential diagnosis of the drug-induced liver injury in relation to the viral hepatitis and one has to consider the great responsibility of the clinician. Often a decision may only be taken in close interdisciplinary collaboration of gastroenterologists, pathologists, epidemiologists and immunologists.

Prerequisite of a scientific and rational liver diagnostics is the knowledge of the physician of function and structure of the liver. The laboratory demand should always be an accomplishment of the physician and should be performed only upon such a scale that it is also followed by therapeutic consequences and/or consequences concerning the expert's opinion. The biochemical blood analysis gives information about the size of the injury to the parenchyma and about the disturbance of the various partial functions of the liver. In this case is to be taken into consideration that biochemical and histological parameters are no concurrent, but supplementing diagnostic methods. A progress in liver diagnostics is the use of the isoenzymes of the aspartate aminotransferase and the lactate dehydrogenase as well as of the enzymes of the metabolism of the connective tissue. With the entering into selected parameters of the liver diagnostics possibilities to the establishment of the disturbed liver metabolism by means of markers are shown and at the same time recommendations for the praxis of the liver diagnostics are derived.

A deteriorating nutritional condition combined with the loss of body mass is one of the most noticeable symptoms of cancer. In order to answer the question to what extent absorption disorders in the small intestine are responsible for the malnutrition which develops, we studied 54 oncologic patients using modified D-xylose absorption tests. After the oral and intravenous administration of 10 g D-xylose at different times, the degree of absorption dependent on time was determined on the basis of a biophysical model. When accompanied by general nonspecific tumor symptoms, the frequency of absorption restrictions was increased. An established relation was found between the extent of small intestinal absorption, on the one hand, and the degree of spreading (staging) and the degree of histological differentiation of the carcinoma, on the other hand. Enteral absorption disorders represent a partial cause for the development of malnutrition in cancer patients and must be viewed as a result of a metabolic situation which is distinctly catabolic.

15 cases of lethal gas gangrene infections were found in 15,024 autopsies from 1970 to 1975. The infection mode via gastro-intestinal tract is very likely in two thirds of the cases. In particular tumor diseases of intestine are able to yield these base for gas gangrene infection by infiltration of the muscular system in the abdomen.

The analysis of 284 resected small-cell bronchial cancers from 4 Lung clinics has shown that these represent 11% of all resected lung cancers. The 5-year survival rate was 24%. The male-to-female ratio was 9.5: 1. Two-thirds were detected by X-ray mass screening. The majority of them (60%) were peripheral tumors. 50% of the patients had a stage Ia cancer and showed a 5-year survival of 40%! This result speaks for the primary surgical therapy even for stage I small-cell bronchial cancers, and for a 6-month screening interval of the respective risk groups. Patients with stage II or III cancers showed a 5-year survival rate of only 10%. In such cases postoperative adjuvant chemotherapy should be carried out. But such a therapy seems to be little effective in stage Ia patients.

An acute coma hepaticum was produced in 8 pigs by means of one intraperitoneal dose of thioacetamide. Distinct changes in the behaviour of the animals, changes of the biochemical parameters inclusively the enzyme pattern with a typical lesion pattern of the liver parenchyma and a displacement of the plasma amino acids were shown. All pathological changes in comparison with the normal animal characterize the liver insufficiency after 24 hours as a comatose state. This acute toxic model serves as the base for investigations within the physiology of nutrition about parenteral feeding of L-amino acid mixtures in coma hepaticum. The nearly exclusive hepatotropic lesion degree of thioacetamide is suitable as an experimental model for this purpose.

37 patients with clinically and histologically ascertained acute virus hepatitis (51% virus hepatitis B) underwent a bicycle-ergometric load a short time after admission to hospital and 17 of them were subsequently submitted to a training from twice a day to 30 minutes with 70% of the submaximal steady state effect. After their discharge from hospital all patients were repeatedly examined in the outpatient department for on an average 2.7 years; 20 patients (8 in the load group, 12 in the comparative group) were submitted to a liver biopsy on an average after one year. In 11 of the other patients the result of a histological examination of the liver from the end of the clinical treatment was present. The comparison of the training group and the control group showed nearly the same percentage of cures for the two groups as well as no transitions into chronic hepatitis in the training group. Also clinical and biochemical relapses did not appear in the load group. In a follow-up observation up to five years in the training group did not appear any disadvantage concerning the complete cure of virus hepatitis so that we apparently do not fear any negative sequels of physical activity in the acute phase of virus hepatitis. A forced immobilisation of the body--after proved ineffectiveness of diet and medicamentous treatment last support of the therapeutic regime--thus seems no more be indicated, since it is also accompanied by impairing reduction of the bodily function.

It is reported on a 46-year-old woman who died of a haemorrhage of the cerebral matter in renally fixed hypertension and severe arteriosclerosis of the arteries of the basis of the brain. The possible connection between hypertension, arteriolosclerosis of the kidneys and arterioclerosis of the arteries of the brain basis and an intake of ovulation inhibitors lasting 10 years is critically discussed.A 46 year old woman who used oral contraceptives (OCs) for 10 years developed severe arteriosclerosis of the base of the brain and renally fixed hypertension. She subsequently died of cerebral hemorrhage. The relationship between o.c. use and hypertension is discussed. A thorough family and personal anamnesis must be taken for women who want to use o.c.s; hypertension, kidney ailments, obesity, or diabetes mellitus require particular attention. Blood pressure should be checked for the first 3 months of o.c. use and every 6 months thereafter. Weight gain during o.c. use may serve as a warning symptom. Hypertension or several other difficulties require discontinuation of o.c. use to determine whether they may be caused by o.c.s.

Possible actions of artificial short-time hyperglycaemia, which is tested as an adjunctive measure in various therapeutical concepts of tumours (for instance in combination with oncolytic apathogenic Clostridia), were checked by histomorphological investigations in Jensen sarcoma of rats. The glucose-induced hyperglycaemia caused a considerable increase of the extend of necrosis in the whole tumour. These morphological findings gave evidence of the high tumour selectivity of the provable effects of artificial short-time hyperglycaemia.