Quantitative histochemistry of brush border-associated neutral alpha-D-glucosidases in rat jejunum and kidney.
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Animals↗
Biomedical subjects
M Ruhnke
Publications and source records attributed to M Ruhnke.
[Effects of flurazepam on disturbed sleep in patients with AIDS].
Polysomnograms were recorded of twelve patients with acquired immune deficiency syndrome (AIDS) during different stages in an open design. During the first night no hypnotics were administered, during the second night 30 mg flurazepam per os were given. Flurazepam affected mainly the NREM parameters. The times "awake" during the night were reduced, sleep stage 2 showed an increase, and the effective sleep time was also increased. The increase in sleep spindle density was remarkable, however, delta sleep and generation of K-complexes were not affected. Flurazepam did not affect REM sleep at all. The amount of REM sleep showed a slight increase. REM distribution during the night did not show the "bell shaped" increase and the decrease in the morning; the degree of the illness correlated with a flattening of REM distribution.
Acquired Immunodeficiency Syndrome↗
[Hepatitis B virus antigens in liver resections from patients with hepatocellular carcinoma].
A high rate of hepatitis B virus (HBV) antigen carriers among patients with hepatocellular carcinoma (HCC) has been recorded from areas of endemic HBV infections in Africa and Asia, but there are only rare and contradictory data for Europe. 12 specimens of resected liver tissue were immunohistologically investigated for hepatitis B surface antigen (HBsAg) as well as for hepatitis B core antigen (HBcAg). HBsAg was contained in non-tumorous liver tissue in 66 per cent of these cases. In two cases detection of HBcAg in the liver provided evidence to replication of the virus. HBcAg plus HBsAg were present in tumour tissue in one case. All of the HBV antigen carriers did not have chronic hepatitis. On the other hand, all patients with chronic hepatitis had HBV antigens in their liver tissue. HBV antigens were detectable in 7 non-cirrhotic livers, but were contained in only one of two cirrhotic livers. These results are likely to suggest a possible relevance of HBV infection to the aetiology of HCC even in central Europe without customary liver cirrhosis.
Adolescent↗
[Kümmell-Verneuille syndrome, a rare, but important differential diagnostic disease].
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Diagnosis, Differential↗
Histochemical detection of alpha-D-glucosidases and their molecular forms with 5-Br-4-Cl-3-indoxyl-alpha-D-glucoside.
5-Br-4-Cl-3-Indoxyl-alpha-D-gluco(pyrano)side was found to be the most suitable synthetic substrate for the demonstration of alpha-D-glucosidases in situ. Using an azoindoxyl procedure with hexazotized pararosaniline or new fuchsine at pH 5 in freeze-dried celloidine-mounted cryostat sections acid alpha-D-glucosidase (EC 3.2.1.20) was shown for the first time in lysosomes of many cells of fetal and adult rat, mouse, guinea-pig, marmoset and human organs. At pH 6.5, in chloroform-acetone pretreated cryostat sections plasma membrane alpha-D-glucosidases were shown in the brush border of enterocytes of the small and large intestine, in the brush border of proximal renal tubule cells and in the stereocilia of the epididymal duct. In an indigogenic procedure with ferricyanide/ferrocyanide as redox catalysator plasma membrane alpha-D-glucosidases were depicted as well as with the azo-indoxyl method; the demonstration of the acid alpha-D-glucosidase was inferior to that achieved with the azo-indoxyl procedure. Using tetrazolium salts as capture reagent intracellular localization was unsatisfactory. In enterocytes, a localization in the Golgi apparatus was shown by the azo-indoxyl procedure only. Analytical isoelectric focusing revealed organ-dependent differences of plasma membrane and lysosomal alpha-D-glucosidases. Compared with the already existing methods the azo-indoxyl and indigogenic procedures are by far the most suitable techniques.
Animals↗
Proteases in the human full-term placenta.
Aminopeptidase A, not yet defined aminopeptidases and endopeptidases, dipeptidyl peptidase I, II and IV, gamma-glutamyl transferase and oxytocinase were investigated in the normal human full-term placenta using qualitative (catalytic) cytochemistry, isoelectric focusing, immunocytochemistry and kinetic fluorometry. Aminopeptidase A could be visualized cytochemically in the smooth muscle cells of the chorionic plate, stem villi and basal plate blood vessels. Aminopeptidases were found in connective tissue fibres of the chorionic plate, villous stroma, basal plate and paraplacenta. Dipeptidyl peptidase IV was detected at the same sites as the aminopeptidases and, in addition, in amniotic epithelial cells, fibroblasts of the villous stroma, endothelium of chorionic plate and villous blood vessels as well as in the basophilic cytotrophoblast cells (x-cells) of the basal plate and paraplacenta, and it possibly also occurred in some domains of the plasma membrane of the syncytiotrophoblast and cytotrophoblast cells. The x-cells surrounded the fetus in the form of a dipeptidyl peptidase IV-positive shell at the border to the mother. The enzyme represented the first specific marker for x-cells. Dipeptidyl peptidase I and II were primarily found in Hofbauer cells (macrophages) of the villous stroma, but also in the syncytiotrophoblast, other villous stromal cells and cells of the chorionic and basal plate. gamma-Glutamyl transferase was present in some connective tissue elements of the chorionic plate. Oxytocinase and endopeptidases were not detected. Isoelectric focusing of proteases revealed different molecular forms of dipeptidyl peptidase IV in the paraplacenta and villous tree, while the aminopeptidases shared the same pattern in both regions.(ABSTRACT TRUNCATED AT 250 WORDS)
Aminopeptidases↗
Cytochemistry of bacterial proteases using 4-methoxy-2-naphthylamide peptides.
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Animals↗
Pharmacokinetics of cefotaxime and desacetyl-cefotaxime in cirrhosis of the liver.
In 9 patients with advanced hepatic cirrhosis and a normal serum creatinine concentration, the pharmacokinetics of cefotaxime (CTX) and its desacetyl metabolite (DACM) were examined in serum and urine after intravenous administration of 2.0 g CTX. The peak serum levels were 130.3 +/- 33.9 and 8.5 +/- 4.6 mg/l for CTX and DACM, respectively. T50% beta was calculated to be 138.1 min (69.3-245.8 min) for CTX. The approximation of the terminal half-life of DACM revealed a prolongation which exceeded 10 h. Accordingly, the AUC amounted to 255.3 +/- 92.0 and 151.9 h X mg/l, respectively. Within 24 h, 62.9% was eliminated in urine as CTX and 19.4% as DACM. The total clearance of CTX was reduced to 164.3 ml/min (58.3-296.6 ml/min), but the renal clearance was only moderately decreased to 90.0 ml/min (24.1-169.3 ml/min). These altered kinetics can be explained by altered metabolic function of the liver as well as by cirrhosis-linked alterations of renal elimination mechanisms.
Adult↗
[Autoradiographic investigations on the age dependent regeneration of parenchymal liver cells (author's transl)].
It is possible to represent the age dependent change of the ability of reproduction on the model of liver regeneration. Because of the reduced growth fraction with increasing age there is a delay of the beginning and a decrease of the maximum ascent of regeneration. In old rats the proliferating activity decreases to consistently low levels earlier than in young and adult rats. There are no age dependent differences in the total amount of regeneration 21 days after 1/3 hepatectomy. In contrast to the literature we are able to show, that already by means of 1/3 hepatectomy highest values of liver regeneration are achievable.
Age Factors↗
Intracellular bactericidal activity of fosfomycin against staphylococci: a comparison with other antibiotics.
The intracellular bactericidal activity of fosfomycin was compared to that of other anti-staphylococcal agents. Two staphylococcal strains (one isolate of Staphylococcus aureus and one isolate of Staphylococcus epidermidis) were incubated in vitro with human granulocytes isolated from volunteers. After phagocytosis and removal of residual extracellular bacteria, the cells were resuspended in the presence of clinically relevant concentrations of fosfomycin, teicoplanin, vancomycin and rifampin. The number of bacteria surviving intracellularly was determined by colony counts after osmotic lysis of the granulocytes at different time intervals. Incubation with fosfomycin resulted in a mean reduction of intracellular bacteria by approximately two logs of ten within 18 h for both staphylococcal strains. Although less effective than rifampin, fosfomycin showed a significantly higher intracellular activity than the glycopeptide antibiotics in this model.
Anti-Bacterial Agents↗
Teicoplanin: 10 years of clinical experience.
The teichomycin antibiotics have been discovered and chemically purified in the late 1970s. Teicoplanin, one of the major derivatives of this group, has been introduced into clinical use in 1984. In Germany, teicoplanin was licensed in 1988 and now ranks among the antimicrobial agents most frequently used in intensive care units. Due to its reduced rate of side effects compared to vancomycin, its longer serum half-life and a simplified mode of application, teicoplanin has become the glycopeptide of choice in many hospitals. The present review summarizes in vitro activity data, pharmacokinetics, and clinical experience with teicoplanin, with special consideration of currently recommended doses and serum levels.
Clinical Trials as Topic↗
A case of rhinoscleroma cured with ciprofloxacin.
The diagnosis of rhinoscleroma was confirmed in a 17-year-old female patient from Tehran, Iran, suffering from a roundish tumour of the nose. Prior treatment with streptomycin and tetracycline had been unsuccessful. A three-month course of high-dose oral ciprofloxacin (750 mg b.i.d.) led to prompt cessation of the growth of the granuloma which was removed later by plastic surgery. Although serology alone appeared to have little value for the specific diagnosis of rhinoscleroma, a significant increase of IgG antibodies during treatment with ciprofloxacin confirmed infection by Klebsiella rhinoscleromatis in this case.
Adolescent↗
Recent trends in antimycotic chemotherapy.
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AIDS-Related Opportunistic Infections↗
Fluconazole therapy of oral candidiasis in HIV-infected patients: results of a multicentre study.
In an open phase-III study 103 HIV-positive patients with oral candidiasis were treated with oral fluconazole 100 mg/day for 7-21 days (mean 12.2 +/- 6.1 days). Ninety per cent of the patients presented with the full clinical picture of AIDS, in 83% CD4-lymphocytes were < 100/mm3. Clinical and mycological (smear and mouth rinsing) examinations were performed at the start of therapy, after weeks 1, 2, and 3, and at the end of therapy. The clinical findings showed fluconazole therapy to have achieved cure in 71% of the patients and improvement in 16%. Therapy failed in 13%. Mycological tests revealed elimination in 57% and reduction in colony counts in 23% of patients. Therapy failure according to mycological criteria was observed in 20% of all subjects. Adverse events were recorded for 26% of all patients. A causal connection with study therapy was considered as "unlikely" in 20 cases, "questionable" in 17 cases, and "likely" in three cases. Premature discontinuation of fluconazole therapy was required in seven patients, in three of them because of adverse events due to fluconazole. Even in patients with advanced HIV infection and consequently severe immunodeficiency, fluconazole is an important improvement of the therapeutic spectrum.
AIDS-Related Opportunistic Infections↗
Correlation between antifungal susceptibility testing of Candida isolates from patients with HIV infection and clinical results after treatment with fluconazole.
In an open-label controlled study 23 HIV-infected patients (CDC IV A-E) with documented oropharyngeal candidosis were treated with 100 mg fluconazole orally over 5 days (53 episodes; 1-6 treatments/patient). Efficacy data were compared with a control group of 21 patients who received treatment for 10-21 days with 100 mg fluconazole for candidosis. Candida isolates were repeatedly recovered from patients before and after treatment with fluconazole and antifungal susceptibility testing (microbroth-dilution) was done. Inoculum size, medium pH, incubation time and temperature were standardized. Up to 85% of patients responded to therapy clinically and mycologically. Candida albicans was the most important yeast (86%) isolated from cultures of oral washings. In 90% of C. albicans isolates MIC to fluconazole were low (< or = 1.56 mg/l). Primary resistance to fluconazole was not seen, but secondary resistance occurred in two cases clinically and in vitro (MIC > or = 25 mg/l). Short treatment for 5 days was as successful as for 10 to 21 days without leading to significantly more recurrences of oral candidosis in these patients. Selection of Candida spp. other than C. albicans (e.g. Candida krusei, Torulopsis glabrata) under repeated fluconazole treatment occurred rarely. One patient developed clinical signs of chronic recurrent candidiasis, where only C. krusei could be cultured repeatedly.
AIDS-Related Opportunistic Infections↗
Reaction rate measurements of proteases and glycosidases with chromogenic methods.
Simultaneous azo-coupling and indigogenic methods were evaluated for the quantitative histochemical assay of the plasma membrane proteases gamma-glutamyl transpeptidase (EC 2.3.2.2) and dipeptidyl peptidase IV (EC 3.4.14.5) and the glycosidases maltase-glucoamylase and glucoamylase (EC 3.2.1.20) in decidual cells, jejunal enterocytes and renal proximal tubulocytes. Using kinetic (continuous) microdensitometry, a linear increase in the final reaction product was found from 3 up to 10 min, depending on the substrate concentration and the plasma membrane glycosidase or protease under investigation. Combined continuous and end point (static) microdensitometry revealed a linear relationship between the section thickness (enzyme concentration) and final reaction product up to 12 microns for the proteases and up to 16 microns for the glycosidases. Apparent Km and Vmax values were calculated with a computerized version of the direct linear plot and compared with the results obtained with the linear transformations according to Lineweaver-Burk, Eadie-Hofstee and Hanes. Apparent Km and Vmax values for the proteases were calculated separately for each animal and were 1.82 mM and 1.02 mM and 2.43 arbitrary units (a.u.) and 1.67 a.u. (gamma-glutamyl transpeptidase, decidua) and 0.42 mM and 0.38 mM and 0.29 and 0.26 a.u. (dipeptidyl peptidase IV, decidua). For the alpha-D-glucosidases, the corresponding values were 0.23 mM and 0.15 a.u. (kidney) and 0.55 mM and 0.20 a.u. (jejunum). The results show the suitability of the indigogenic methods for quantitative histochemical measurements of plasma membrane alpha-D-glucosidases, whereas the simultaneous azo-coupling procedures seemed to be less suitable for the quantification of surface membrane proteases, due to, for example, interactions of diazonium salts with amino acid or peptide substrates, reaction products and peptide activators.
Animals↗
Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial.
BACKGROUND: Voriconazole has proven efficacy against invasive aspergillosis and oesophageal candidiasis. This multicentre, randomised, non-inferiority study compared voriconazole with a regimen of amphotericin B followed by fluconazole for the treatment of candidaemia in non-neutropenic patients. METHODS: Non-neutropenic patients with a positive blood culture for a species of candida and clinical evidence of infection were enrolled. Patients were randomly assigned, in a 2:1 ratio, either voriconazole (n=283) or amphotericin B followed by fluconazole (n=139). The primary efficacy analysis was based on clinical and mycological response 12 weeks after the end of treatment, assessed by an independent data-review committee unaware of treatment assignment. FINDINGS: Of 422 patients randomised, 370 were included in the modified intention-to-treat population. Voriconazole was non-inferior to amphotericin B/fluconazole in the primary efficacy analysis, with successful outcomes in 41% of patients in both treatment groups (95% CI for difference -10.6% to 10.6%). At the last evaluable assessment, outcome was successful in 162 (65%) patients assigned voriconazole and 87 (71%) assigned amphotericin B/fluconazole (p=0.25). Voriconazole cleared blood cultures as quickly as amphotericin B/fluconazole (median time to negative blood culture, 2.0 days). Treatment discontinuations due to all-cause adverse events were more frequent in the voriconazole group, although most discontinuations were due to non-drug-related events and there were significantly fewer serious adverse events and cases of renal toxicity than in the amphotericin B/fluconazole group. INTERPRETATION: Voriconazole was as effective as the regimen of amphotericin B followed by fluconazole in the treatment of candidaemia in non-neutropenic patients, and with fewer toxic effects. RELEVANCE TO PRACTICE: There are several options for treatment of candidaemia in non-neutropenic patients, including amphotericin B, fluconazole, voriconazole, and echinocandins. Voriconazole can be given both as initial intravenous treatment and as an oral stepdown agent.
APACHE↗
Candida dubliniensis candidemia in patients with chemotherapy-induced neutropenia and bone marrow transplantation.
The recently described species Candida dubliniensis has been recovered primarily from superficial oral candidiasis in HIV-infected patients. No clinically documented invasive infections were reported until now in this patient group or in other immunocompromised patients. We report three cases of candidemia due to this newly emerging Candida species in HIV-negative patients with chemotherapy-induced immunosuppression and bone marrow transplantation.
Adult↗