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Biomedical subjects

T Zimmermann

Publications and source records attributed to T Zimmermann.

At least 19 recordsLinked to original sources

Equivalence of a high-performance liquid chromatographic assay and a bioassay of azithromycin in human serum samples.

Two sensitive methods for the determination of the azalide antibiotic azithromycin in human serum were compared. High-performance liquid chromatography (HPLC) and a microbiological assay were simultaneously applied to 768 serum samples obtained in a clinical study. There was excellent agreement between the azithromycin concentrations measured by HPLC and by the bioassay. The correlation coefficient for the two methods was r2 = 0.96. The precision and the sensitivity of the methods were found to be very similar.

Azithromycin

Pulmonary artery sling associated with tracheobronchial malformations.

We describe three cases of pulmonary artery slings associated with tracheal stenoses by complete cartilaginous rings and abnormalities in the tracheobronchial branching pattern. This association implicates special problems of management that are different from the simple pulmonary artery sling. Pathologic anatomy, symptoms, diagnostic procedures, and the problems of therapy are described. Considering similar cases in the literature, we conclude that thorough diagnostic evaluation of the tracheobronchial and the cardial system should be carried out in all cases of pulmonary artery sling. Simple correction of the aberrant vessel without correcting the tracheal stenosis is of no value in these cases. In some milder cases, a conservative approach is possible and probably less harmful than an operation.

Abnormalities, Multiple

Metabolic and hemodynamic responses of bivascularly perfused rat liver to nerve stimulation, noradrenaline, acetylcholine and glucagon in thioacetamide-induced micronodular cirrhosis.

Thioacetamide-induced rat cirrhosis was characterized by single-cell necroses, fibrosis, nodular parenchyma, decrease in parenchymal volume density and an increase in liver weight per body weight so that the total amount of parenchyma was not altered. The glycogen content was normal, and signs of decompensation were not found. Isolated livers were single-pass perfused by way of both the hepatic artery and the portal vein. In the normal livers stimulation of the nerve plexuses around the hepatic artery or portal vein (7.5 Hz; 2 msec) and infusions of noradrenaline (1 mumol/L) by way of either vessel and of acetylcholine (10 mumol/L) by way of the artery only increased glucose output, reduced both portal and arterial flow and increased the intravascular pressures. Glucagon (0.5 nmol/L) augmented glucose release and had no hemodynamic effects. In chronically thioacetamide-injured livers all stimuli caused smaller metabolic alterations per gram of liver weight and decreased portal flow more and arterial flow less with stronger enhancements of intravascular pressures than in the controls. The lowered metabolic responsiveness per gram of cirrhotic liver was largely compensated by the increase in liver weight. Thus despite massive histological alterations and pronounced increases in stimulation-dependent resistances - predominantly in the portal system - cirrhotic rat livers responded in their glucose metabolism to nervous and hormonal stimuli in almost the same manner as normal livers.

Acetylcholine

[Post-traumatic lesion of the distal radioulnar joint with disordered forearm pronation].

Within a period of 14 years in 27 cases operative correction of a traumatic lesion of the distal radioulnar joint has been performed at the University Clinic of Giessen. The follow-up of our results is to be confined to the last ten cases; all efforts to evaluate the outcome of 17 joints having been operated on previously unfortunately have proved to be unfeasible. Different types of corrective operative procedures have been accomplished. Improvement of wrist function, particularly of pronation and supination, was obtained in almost every case.

Humans

Quantitative studies on fatty acid metabolism in isolated parenchymal cells from normal and cirrhotic livers in rats.

Parenchymal cells isolated from normal and thioacetamide-induced micronodular cirrhotic rat livers were used to evaluate changes in hepatocellular fatty acid (FA) metabolism in cirrhosis. Exogenous free FA (FFA) are rapidly taken up by hepatocytes obtained either from normal or cirrhotic livers. They are predominantly esterified to triglycerides and accumulate intracytoplasmatically as lipid droplets with increasing cellular FFA uptake. In the parenchymal cells of cirrhotic livers, however, the following changes were observed when compared with controls: (i) decreased cellular output of esterified FA derived both from exogenous sources and from de novo FA synthesis; (ii) increased total ketone body production, mainly as beta-hydroxybutyrate; (iii) decreased cholesterol synthesis; and (iv) enhanced incorporation of newly synthesized FA into phospholipids in spite of an unaffected rate of FA synthesis. In summary, the data provide evidence for intrinsic alterations in the lipid metabolism in the parenchymal cells of cirrhotic livers which are preserved in the isolated hepatocytes under optimum incubation conditions for oxygen and substrate supply.

3-Hydroxybutyric Acid

Treatment of ruptures of the symphysis and iliosacral joint in pediatric patients.

The three osseous parts of the human pelvis form a continuous structure because of the symphysis and both iliosacral joints that-owing to their mobility-make possible a shock-absorption of vertical forces. The goal in the treatment of ruptures of the symphysis and/or of the sacroiliac joints is the restoration of functioning joints. Especially in the adolescent, a stiffening of these joints has to be avoided. Therefore, we treat ruptures of the pelvic joints with an overbridging banding that preserves the function of shock absorption. Due to utilisation of a banding, made up of polydioxanone, another operation to remove internal fixation material is not necessary. Rupture of the symphysis or iliosacral joint in the pediatric patient is very rare. Only three among the 67 patients whom we operated on because of a rupture of the symphysis or iliosacral joints between 1984 and 1990 were children. These were an eleven-year-old girl and a nine-year-old boy, who had suffered a rupture of the symphysis, and an eight-year-old boy with a disrupted iliosacral joint. In these children a banding with PDS suture was performed. At a follow-up examination, the children were free from pain and did not feel restricted in their daily routine or their physical activities.

Child

Liver function after bilateral nephrectomy.

Consequences of bilateral nephrectomy (NX) for liver functions and for hepatic excretion of various endogenous substances were characterized in rats 24 h after NX. Plasma concentrations of urea, creatinine, fibrinogen, and glutathione increased significantly after NX, whereas the concentrations of total protein, albumin, and lipids decreased. The hepatic excretion of urea, creatinine, phospholipids, cholesterol, and aldosterone significantly increased in uremia, and excretions of protein and glutathione diminished. Active biliary transport can be diminished after NX by the effects of uremic toxins on the liver cells or by the competition phenomena between endogenous substances, which are normally excreted in urine, at the hepatocellular level. Reduced glutathione content and increased lipid peroxidation in hepatocytes have been found. Changes in lipid and protein metabolism after NX can be proved.

Albumins

Relative bio-availability of sultamicillin in healthy volunteers following administration of two tablet formulations.

The pharmacokinetics of both ampicillin and sulbactam obtained from a balanced, open two-way crossover study in 20 normal adult volunteers receiving a single 375 mg oral tablet of sultamicillin administered as two different formulations--the original product (Duocid) and a generic formulation that is commercially available in Turkey--were compared. Pharmacokinetic parameters for the two formulations and for both ampicillin and sulbactam were tested for bio-equivalence by the two one-sided Student's t-test (80-120% range; P < 0.1). Area under concentration--time curves and maximum concentrations for both components were found to be non-equivalent for the two formulations, the generic formulation having consistently lower mean values. The results were consistent with studies of the in vitro release of sultamicillin from the two tablets. It is concluded that the generic formulation is pharmacokinetically inferior to the original product.

Adult

Comparison of isobutyl nitrate and isobutyl nitrite: tolerance and cross-tolerance to glyceryl trinitrate.

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.

Animals

[Acute stress-induced cholecystitis].

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.

Acute Disease

Lipid peroxidation in thioacetamide-induced macronodular rat liver cirrhosis.

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.

Animals

Biochemical and morphological studies on perivenous and periportal liver parenchymal cells from female rats isolated by digitonin-collagenase method.

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.

7-Alkoxycoumarin O-Dealkylase

Experimental treatment of thioacetamide-induced liver cirrhosis by metenolone acetate. A morphological and biochemical study.

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.

7-Alkoxycoumarin O-Dealkylase

Gamma-glutamyltranspeptidase (GGT) in experimental liver cirrhosis induced by thioacetamide: a biochemical and enzymehistochemical study.

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.

Animals

Secretion and elimination of insulin by the in vitro perfused pancreas and liver of rats with thioacetamide-induced liver cirrhosis.

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.

Animals