Biomedical subjects
Publications and source records attributed to T Zimmermann.
Explore the source record for details and available documents.
This study includes the first systematic comparison of an organic nitrate with the corresponding organic nitrite-isobutyl nitrate and isobutyl nitrite. The spasmolytic activity of the nitrite on isolated rabbit aortic strips was stronger, more rapid in onset, but less stable than the activity of the nitrate. In vitro tolerance to glyceryl trinitrate and isobutyl nitrite greatly weakened the activity of isobutyl nitrate, respectively, but had much less effect on isobutyl nitrite. Possible reasons for these differences are discussed.
Explore the source record for details and available documents.
Acute posttraumatic and postoperative cholecystitis is a serious and life-threatening complication with mortality rates ranging from 10 to 50%. The pathogenesis is multifactorial: possible reasons are blood transfusions, dehydration, narcotics, shock and positive end-expiratory pressure (PEEP). Between 1980 and 1990 12 patients underwent surgery for acute cholecystitis. Six of them suffered from a so-called acute acalculous cholecystitis. Two patients died postoperatively. The symptoms are that of a "common" cholecystitis with leukocytosis, fever, abdominal distension and upper right abdominal pain. Sonography is a good method to establish the diagnosis and helps in the decision for cholecystectomy. Clinicians must remember the possibility of an acute cholecystitis in any surgical patient developing abdominal pain or unexplained fever.
Microsomes and isolated hepatocytes from thioacetamide (TAA)-induced macronodularly cirrhotic rat livers were analysed for their susceptibility to unstimulated and stimulated lipid peroxidation measured as malondialdehyde (MDA) formation. In microsomes from TAA-induced macronodularly cirrhotic livers the MDA production stimulated either by ascorbate-iron or by ADP-iron in a NADPH-regenerating system was decreased. Hepatic microsomes from TAA-treated rats exhibited a reduced cytochrome P450 content and lowered activities of ethylmorphine N-demethylase, ethoxycoumarin O-deethylase and epoxide hydrolase. Besides this, the microsomal fatty acid pattern of phosphatidylcholine and phosphatidylethanolamine was significantly changed after 6 months of TAA administration. The 18:2/20:4 ratio of phospholipid fatty acids was markedly increased. In contrast to the microsomes, in isolated hepatocytes from macronodularly cirrhotic livers the iron- and ascorbate-iron-stimulated MDA formation was increased. The hepatocellular GSH content was unaffected by TAA pretreatment, whereas the GSSG content exhibited a significant increase, thus leading to a pronounced reduction of the GSH/GSSG ratio. The calcium channel blocker verapamil (200 microM), known to be able to scavenge OH' radicals produced by the Fenton reaction, revealed an inhibitory effect on ascorbate-iron- and ADP-iron-stimulated lipid peroxidation in hepatocytes from normal as well as TAA-treated livers which is attributed to its antioxidative properties. In summary, lipid peroxidation is altered in TAA-induced macronodularly cirrhotic rat livers. Furthermore, the data clearly show that isolated microsomes and parenchymal cells prepared from cirrhotic livers react differently to prooxidant stimuli.
Periportal (pp) or perivenous (pv) liver parenchymal cells from female adult Uje: WIST rats were isolated after retro- or antegrade digitonin infusion followed by collagenase perfusion in the opposite direction. The morphological results revealed a distinct acinar-related destruction of the pv- or pp-zone by digitonin. The remaining cells of the respective other zone showed a good structural maintenance. After subsequent conventional collagenase perfusion the yield, viability and structural integrity of the isolated hepatocytes were high. The zonal cell separation was indicated by significant differences in the pp marker glucose-6-phosphatase and the pv marker glutamine synthetase found in the isolated pp or pv cell populations. Under our experimental conditions including the use of female rats, the alanine aminotransferase and glutamate dehydrogenase as well as ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities were evenly distributed in both preparations. Under stimulating conditions the capacity for urea synthesis was similar in both pv and pp cells.
The influence of metenolone acetate (1 mg/kg b.m. orally) on intact and chronically thioacetamide-injured rat liver (experimental liver cirrhosis) was investigated over 14 d. Histological examination revealed nodular transformation of liver structure according to cirrhosis like lesions with hepatocellular and cholangiocellular proliferations. These structural alterations were more serious in the group treated with metenolone compared with the group without metenolone. Metanolone administration to animals with thioacetamide-induced experimental liver cirrhosis led to an increase in liver injury. This treatment seems to promote hepatic preneoplastic lesions induced by thioacetamide reflected by histology and induction of gamma-glutamyltranspeptidase and 7-ethoxycoumarin O-deethylase in injured livers. Metenolone did not interfere directly with the processes of connective tissue synthesis and degradation after thioacetamide pretreatment. Only little changes of the investigated biochemical parameters were seen after metenolone administration to animals with intact liver function: increases in serum cholinesterase and tissue N-acetyl-beta-D-glucosaminidase activity; decreases in N-acetyl-beta-D-glucosaminidase in serum, liver hydroxyproline content and hepatic gamma-glutamyltranspeptidase activity. The observed changes reflect hepatic adaption processes under the influence of metenolone. The results of this study indicate that the risk of anabolic steroids in adjuvant therapy of liver cirrhosis cannot be calculated at present.
Micro- and macronodular experimental cirrhosis-like liver lesion was induced in female rats by administration of 0.03% thioacetamide (TAA) in drinking water for 3 or 6 months. The activity of gamma-glutamyltranspeptidase (GGT) and the distribution pattern of this enzyme within the liver structure were investigated 14 d after withdrawal of TAA in comparison to neonatal and adult normal liver. GGT activity was extremely high at birth. Chronic TAA administration led to a strong increase in hepatic GGT activity in dependence on duration of TAA administration in comparison to adult controls. In accordance to these results we observed by enzyme-histochemistry a small to moderate hepatocellular GGT activity after 3 months of TAA treatment. GGT activity was also demonstrable in epithelia of proliferated ductuli biliferi of single enlarged portal tracts. After 6 months of TAA administration the hepatocellular GGT activity was moderate to strong. It was demonstrable both in parenchymal (preneo-plastic) nodules and in cholangiocellular/cholangioductular proliferates. A GGT activity of mesenchymal cells was not demonstrable. We conclude that the increased hepatic GGT activity after chronic TAA administration can be correlated with the process of development of preneoplastic nodules. A relation between increased GGT activity and the process of cirrhogenesis does not seem to be probable in this animal cirrhosis model.
Pancreatic secretion and hepatic removal of insulin have been measured in thioacetamide (TAA)-induced compensated rat liver cirrhosis in perfusion experiments. Peripheral plasma concentrations of glucose and insulin were slightly decreased in TAA-treated rats. Pancreatic secretion and hepatic removal of insulin remained unchanged by the TAA-treatment. Thus, even in morphologically and biochemically proven experimental liver cirrhosis, insulin secretion and removal may not be disturbed.
In the last years the number of patients with familial adenomatosis coli and metachrone carcinoma of the upper gastrointestinal tract is increasing. We describe two patients who, 9 and 15 years after colectomy for adenomatosis coli, developed a duodenal carcinoma. Each patient was treated with a partial duodeno-pancreatectomy. Another patient was resected prophylactically because of a diffuse adenomatosis of the duodenum three years after colectomy. We suggest that each patient with a history of colectomy for adenomatosis coli should have regular follow-ups including endoscopy of the upper gastrointestinal tract.
The treatment of aging rats with 100 or 300 mg/kg "essential" phospholipids (EPL) for 10 weeks significantly changed the microsomal concentration of phosphatidyl serine plus phosphatidyl inositol. The most marked alterations of the phospholipid fatty acid pattern predominantly observed with unsaturated fatty acids were detectable even 7 days after cessation of EPL application. Ultrastructurally, an enrichment in the hepatocytes with rough endoplasmic reticulum was visible which was more prominent in acinus zone 3. The changes after EPL administration are regarded as the expression of an increased membrane fluidity.
In 1973 the observation was published that in patients who had received non specific blood transfusions before kidney transplantation graft survival was improved. An immunosuppressive effect of blood transfusion was suggested. Indeed, modulation on the cellular and humoral immunologic system has been demonstrated during the last decade. But this immunomodulation effect might worsen the prognosis after cancer surgery. Whereas in several experimental studies in animals the negative influence was confirmed, clinical investigations on the other hand are contradictive. In our retrospective study we analysed the follow-up of 273 patients (158 men, 115 women; average age 66 years) on which we had performed a curative resection of their colorectal carcinoma. 182 patients had received nonspecific random blood transfusions. The survival rate for patients with blood transfusions was significantly worse in comparison to the non-transfused group (43% versus 73%, respectively). Even when we subdivided our patients into tumor stage, differentiation and localisation, the negative influence of transfused blood was confirmed. We conclude that beside the risk of transmitting hepatitis or HIV the immunosuppressive effect is a strong argument to restrict the indication for blood transfusion.
Patients suffering from mucoviscidosis can improve their quality of life and can cope with greater physical load if they undergo intensive treatment. This can be objectively confirmed by measuring the lung function, by performing a blood gas analysis and by means of a self-rating mood scale. Load tests can be performed additionally, e.g. by a treadmill ergometer. Only two of 22 patients attained a level of 1 w/kg, in 21 patients the pulse rate increased partly long before the end of the test to more than 130 beats per minute. The rate at which the test was discontinued, was attained by all the patients. There was a significant volume increase after load. Blood gas pCO2 dropped significantly afterload, whereas pO2 did not change.
The effect of the calcium channel blocker verapamil on structure, formation and secretion of very-low-density lipoproteins (VLDL) from rat hepatocytes in suspension was examined. After 30 min incubation at a verapamil dose of 200 microM neither free fatty acid (FFA) uptake nor triglyceride (TG) and phospholipid (PL) secretion into the incubation medium were significantly changed. After 90 min incubation the TG secretion was inhibited by about 60%, whereas the PL output was only insignificantly lowered, indicating the secretion of abnormally composed lipoprotein particles. Morphologically, after 30 min incubation the hepatocytes had lost their microvillous border and exhibited a 2-3-fold increase in volume density and average size of the lysosomes. In the Golgi-containing regions an accumulation of smooth-surfaced microvesicles was regularly evident. The configuration of the Golgi complexes was normal. After 90 min incubation the lysosomes showed a further significant elevation in volume and size. The Golgi complexes exhibited only minor changes, but their content in VLDL particles was reduced per microns 2 Golgi complex by about 75%. Commonly, the VLDL were larger and more heterogenous in size. The diameter of those VLDL secreted into the incubation medium ranged from 31 to 84 nm, thus surpassing the control values by 2-3 times. The secretion of large-sized VLDL was regularly associated with the intracytoplasmic appearance of dilated smooth-surfaced vesicles filled with size-modified VLDL. These vesicles were concentrated within Golgi-containing areas from where they were widely dispersed towards the cell periphery.(ABSTRACT TRUNCATED AT 250 WORDS)
A method for simultaneous determination of cardiac output and regional blood flow distribution in a chronically instrumented, unrestrained rat preparation for different experimental conditions (i.e. conscious, free movement; general anesthesia) and in an experimental chronic liver injury model is described. The use of a modified radioactive microsphere reference sample method using 99mTc labelled HSA-microspheres provides valid measurements of cardiac output [255 +/- 21.6 ml/(min.kg b.wt.)] and of the determined blood flow rates of abdominal organs (with separate determination of arterial and portal-venous hepatic blood flow rates; the latter by means of arterial blood flow measurement of the gastrointestinal tract and the spleen), the myocard, the adrenals, the kidneys, and various brain regions. Furthermore, it is demonstrated that this measuring approach with chronical preparation can also advantageously be used in pharmacological or pathogenetical studies, especially because of the simple measuring equipment and the comparatively low costs that offer a broader application.
During human and experimental liver fibrogenesis, the pattern of glycosaminoglycans in fibrotic liver matrix is greatly changed by severalfold increases of hyaluronic acid, chondroitin sulfate, and dermatan sulfate, respectively. The present study aimed to determine whether hepatocytes take part during fibrogenesis in the alteration of the glycosaminoglycan profile in liver matrix. Rats received thioacetamide orally for 2 and 10 weeks, respectively. After 10 weeks a typical micronodular cirrhosis had developed. Hepatocytes isolated at these time points were characterized by light and electron microscopy and incubated for up to 4 h in suspension cultures in [35S]-sulfate and [3H]-glucosamine containing medium to study the synthesis and intra-/extracellular distribution of total and specific types of glycosaminoglycans. A biphasic change of glycosaminoglycan synthesis in hepatocytes was found. After 2 weeks of TAA-treatment parenchymal cells synthesized about 25% more labeled glycosaminoglycans than control liver cells, but at 10 weeks the synthesis was reduced by more than 40%. Thus, between 2 and 10 weeks of TAA-treatment hepatocellular glycosaminoglycan synthesis decreased by more than 50%. The major portion of newly synthesized glycosaminoglycans was nitrous acid labile and, hence, identified as heparan sulfate. Its fractional synthesis decreased from 0.90 in control cells to 0.84 (2 weeks TAA) and 0.76 (10 weeks TAA), respectively. Thus, the absolute synthesis of heparan sulfate was reduced by 50% in hepatocytes from cirrhosis liver. Eighty to 90% of labeled glycosaminoglycans remained cell-associated. Hyaluronic acid was detected neither in normal hepatocytes nor in hepatocytes from injured liver. We conclude from these data that parenchymal liver cells will not contribute actively to the accumulation of galactosaminoglycans (chondroitin sulfate, dermatan sulfate) and hyaluronic acid in the extracellular matrix during fibrogenesis. The diminished rate of synthesis of heparan sulfate in hepatocytes from cirrhotic liver might explain its fractional decrease in cirrhotic liver matrix.
Over the last seven years, there has been an increase in the number of children admitted to our hospital because of aspirated foreign bodies. An inhaled foreign body can become a serious matter if it results in acute respiratory distress or if it remains unrecognized for a long period in the bronchial system. Then, as a result of inflammatory tissue reactions, it can be extracted only with great difficulty. Of our 94 children with foreign body aspiration, 24% had been treated initially on the basis of a different diagnosis. In 30% of all cases, the children were admitted more than 3 days after aspiration. One third of the patients already had signs of marked inflammation on admission. Early treatment, under general anaesthesia, proved to be safe even for small babies. Bronchoscopic examinations should not last more than approximately 1 hour. All children who had complications after bronchoscopy (6%) recovered fully after treatment, except for one child who died of respiratory failure. A diminution of complications in children with inflammatory signs on admission was observed when they were treated before the operation with antibiotics and methylprednisolone.
Between 1980 and 1989, 69 children underwent lung resection in our department. 45 of them (25 boys, 20 girls, age 0-9 years) presented with atelectatic areas of the lung parenchyma, which had been demonstrated preoperatively in only 76%. Resections were performed for bronchial malformations (n = 7), sequestration (6), cysts (6), aspiration (1), pyocele following pulmonary artery ligation (1), upper lobe torsion (1), chronic pneumonia and/or bronchiectasis (14) and lobar emphysema with lung compression (10). The overall mortality was 4/45. Indications are discussed with special reference to the persistent or recurrent atelectasis.