Biomedical subjects

M Ruhnke

Publications and source records attributed to M Ruhnke.

At least 55 records · Page 3Linked to original sources

PubMed1994

Complicated tuberculosis and residual disease.

Complicated and extrapulmonary manifestations of tuberculosis (TB) may cause prolonged suffering for the individual patient and represent a high economic burden for the society concerned. Complications of pulmonary TB may be the consequence of reduced individual resistance, immunosuppression or specific immune defects. In HIV patients, pulmonary TB is often associated with extrapulmonary lesions, while the radiologic appearance of lung infiltrates may be less prominent compared to HIV negative persons. The present review summarizes data obtained during a 12-year study of extrapulmonary TB in Berlin, Germany, and outlines the role of residual TB lesions for disease reactivation in later life. Indications and limitations of INH preventive chemotherapy will be discussed.

HIV Seropositivity↗

PubMed1994

The pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients.

The pharmacokinetics of fluconazole after a single 100 mg i.v. dose were studied in 10 healthy subjects (5 M; 5 F) and 10 HIV-positive patients (8 M; 2 F). The mean value of plasma clearance was 25% lower in the patient groups (17 +/- 6 (s.d.) vs 23 +/- 4 ml min-1; 95% CI of difference -11 to -0.7; P < 0.05). This difference may have been related to slightly reduced kidney function in the patient group (mean creatinine clearance -18%) but is unlikely to be clinically significant. Therefore, no adjustment of the dose of intravenously administered fluconazole appears to be necessary in AIDS patients without clinical signs of enteropathy.

Acquired Immunodeficiency Syndrome↗

PubMed1994

Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection.

After repeated use of fluconazole for therapy of oropharyngeal candidosis, the emergence of in vitro fluconazole-resistant Candida albicans isolates (MIC, > or = 25 micrograms/ml) together with oral candidosis unresponsive to oral dosages of up to 400 mg of fluconazole were observed in patients with human immunodeficiency virus (HIV) infection. Antifungal susceptibility testing was done by broth microdilution and agar dilution techniques on C. albicans isolates recovered from a cohort of patients with symptomatic HIV infection who were treated repeatedly with fluconazole for oropharyngeal candidosis. In vitro findings did show a gradual increase in the MICs for C. albicans isolates recovered from selected patients with repeated episodes of oropharyngeal candidosis. Primary resistance of C. albicans to fluconazole was not seen. Cross-resistance in vitro occurred between fluconazole and other azoles (ketoconazole, itraconazole), but to a lesser extent. The results of the study suggest that the development of clinical resistance to fluconazole could be clearly correlated to in vitro resistance to fluconazole. Itraconazole may still serve as an effective antifungal agent in patients with HIV infection and oropharyngeal candidosis nonresponsive to fluconazole.

AIDS-Related Opportunistic Infections↗

PubMed1994

[Correlation between resistance testing and typing of Candida albicans--isolates from AIDS patients and chronic recurrent oral candidiasis].

In patients with AIDS and recurrent oropharyngeal candidosis results of biotyping and serotyping were compared with antifungal susceptibility testing. Biotype B1 was found predominantly with 44.3% from 169 C. albicans isolates. Serotype A was seen in 150/169 C. albicans isolates. No close correlation between high MIC values (> or = 25 micrograms/ml) for C. albicans isolates against fluconazole nor a change to a particular biotype or serotype has been observed in recurrences of oral candidosis.

AIDS-Related Opportunistic Infections↗

PubMed1993

Effects of standard breakfast on pharmacokinetics of oral zidovudine in patients with AIDS.

The influence of a standard breakfast on the single-dose pharmacokinetics of zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied in 27 subjects with advanced human immunodeficiency virus infection (Centers for Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide metabolite (GAZT) in serum and urine were measured by a high-pressure liquid chromatographic method. Pharmacokinetic analysis was done by an open one-compartment model as well as noncompartmentally. The results were summarized as medians with 50% confidence ranges because of the high degree of interindividual variability. Peak levels in plasma were moderately reduced after administration of 100 mg AZT in the nonfasting group (1.79 mumol/liter in the fasting group [F], 1.12 mumol/liter in the group that received breakfast [B]) and were markedly reduced after administration of 250 mg AZT (6.51 mumol/liter [F], 1.79 mumol/liter [B]). The terminal half-life in plasma was prolonged almost twofold after breakfast with 100 and 250 mg of AZT (100 mg, 36.4 min [F] and 51.6 min [B]; 250 mg, 35.3 min [F] and 63.6 min [B]). Recoveries (AZT and GAZT) in urine varied with both dosages, reflecting more a problem of accounting for the metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5% [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in human immunodeficiency virus-infected subjects is extremely variable, with a high degree of interindividual differences. Furthermore, breakfast had a marked influence on the absorption of AZT, suggesting that the drug should be taken in a fasting state.

Acquired Immunodeficiency Syndrome↗

PubMed1991

[Fluconazole in therapy of candidiasis of the oropharyngeal space in patients with HIV infection. Results of an open multicenter study of assessing the effectiveness and tolerance of fluconazole].

50 HIV-positive patients (CDC stage III to VI) with oral candidiasis proven by culture and typical clinical findings were treated with fluconazole (50 to 100 mg/day) over a period of eight to 22 days. After completion of treatment, clinical signs of oral candidiasis had disappeared in 45/50 patients. In 10/50 patients, however, increased concentrations of candida both in pharyngeal washes (greater than 10(2) PFU/ml) and throat swabs (greater than 20 colonies/culture) persisted. Four weeks later, clinical candidiasis had reappeared in 22/42 patients and another 14/42 patients without clinical symptoms had pathological concentrations of candida in culture. In no case did treatment with fluconazole itself have to be aborted because of adverse reactions. Most of the patients had multiple concomitant bacterial and/or viral infections requiring comprehensive medication. The side effects observed (nausea, headache, changes in the blood picture, etc.) were due to the concomitant infections and their specific therapy.

Administration, Oral↗

PubMed1991

Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal.

The systemic availability of oral zidovudine has been studied in 13 patients with the acquired immunodeficiency syndrome (AIDS) dosed either fasting or with breakfast. The mean peak plasma concentration and AUC of zidovudine were significantly 2.8- and 1.4-times higher in fasting patients than in those treated during meal. In both conditions the mean half-life was about 1.5 h and the period of plasma zidovudine concentrations greater than 1 mumol.l-1 was 2 h (NS). It is concluded that if zidovudine is taken on an empty stomach, high peak plasma concentrations and decreased variation in pharmacological parameters may be expected. Whether or not this will influence toxicity and efficacy remains to be shown.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Protection against salicylate-induced hepatic injury by zinc. A histochemical and biochemical study.

Female Wistar rats received an oral dose of 700 mg salicylic acid/kg body wt., given as sodium salicylate. Some of the salicylate-treated rats received two subcutaneous injections of 100 mumol kg-1 ZnCl2 (24 h before and simultaneously with the salicylate administration). Other animals were given one subcutaneous injection of 100 mumol kg-1 ZnCl2 simultaneously with the salicylate treatment. Control rats were similarly injected with ZnCl2. Twenty four hours after salicylate treatment, serum and livers were taken for histochemical and biochemical analysis. The most remarkable effects of the treatment were enrichment of lipid droplets and iron and a reduction of glycogen, particularly in the periportal hepatocytes. The effects of salicylate were partially prevented by two ZnCl2 injections. The protective effects of ZnCl2 may be due to lower iron uptake into hepatocytes and by the induction of zinc metallothionein, which can serve as a scavenger for oxygen radicals.

Alanine Transaminase↗

PubMed1991

Light microscopical detection of H2O2-generating oxidases using cerium ions and aqueous incubation media.

Light microscopical procedures were optimized and tested for specificity for the histochemical demonstration of D-amino acid oxidase, alpha-hydroxy acid oxidase, monoamine oxidase, and xanthine oxidase using cerium ions and a visualization step originally described by Angermüller and Fahimi (1988a, b), and modified for D-amino acid oxidase by Gossrau et al. (1989). The visualization medium contained diaminobenzidine, cobalt ions, and small amounts of hydrogen peroxide. Procedures of pretreatment of cryostat sections, types of substrate, concentrations of substrates, and cerium ions were varied. Optimum procedures are reported for the detection of these oxidases in different rat tissues. The results are compared with those obtained with other methods described for the demonstration of hydrogen peroxide-generating oxidases such as the tetrazolium, Hatchett Brown, and coupled peroxidatic methods.

Alcohol Oxidoreductases↗

PubMed1991

Inhibition of acetylcholinesterase and butyrylcholinesterase by the organophosphorus insecticide methylparathion in the central nervous system of the golden hamster (Mesocricetus auratus).

The toxic effects of the organophosphorus pesticide methylparathion are primarily caused by the inhibition of acetylcholinesterase activity in the central nervous system, whereas the relationship between butyrylcholinesterase and poisoning symptoms is unclear. The presumed different effects of methylparathion on acetylcholinesterase in various regions of brain and spinal cord suggest differences in the distribution of molecular enzyme forms. In the present work, the in vitro and in vivo effects of methylparathion on acetylcholinesterase and butyrylcholinesterase were studied in whole brain homogenates of golden hamsters with biochemical methods. Furthermore, acetylcholinesterase activity was determined in regions of the nervous system by quantitative histochemistry (microdensitometry). Biochemically, very low IC50 values of the hydrophilic and lipophilic fractions of both enzymes were measured. Analysis of the time course of enzyme inhibition revealed maximum inhibition 45 min after methylparathion application. Using microdensitometry different degrees of acetylcholinesterase inhibition were found in various areas of the brain. The highest inactivation was observed in the Substantia nigra and in thalamic nuclei; in several regions of the cerebellum, the inhibition rate was comparatively lower. In conclusion, methylparathion acts as an potent inhibitor of acetylcholinesterase and butyrylcholinesterase in the hamster nervous system. The region-specific different inactivation of acetylcholinesterase might be caused by the existence of multiple forms of the enzyme in various brain regions.

Acetylcholinesterase↗

PubMed1991

The efficacy and safety of zidovudine with or without acyclovir in the treatment of patients with AIDS-related complex. The European-Australian Collaborative Group.

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

AIDS-Related Complex↗

PubMed1990

Direct tissue isoelectric focusing on ultrathin polyacrylamide gels. Applications in enzyme, lectin and immunohistochemistry.

Application of cryostat sections directly onto ultrathin polyacrylamide gels and subsequent isoelectric focusing allows elution of proteins, glycoproteins and peptides out of the sections into the gels. The eluted compounds reveal clearly delineated band patterns in the polyacrylamide gels. The advantage of this method is that enzyme histochemical reactions can be directly performed in the gel and in the electroeluted tissue sections. Therefore, this method is suitable for specifying, in more detail, histochemical enzyme reactions and for detecting multiple forms of enzymes even from a single tissue section. Furthermore, the transfer of proteins, glycoproteins and peptides from the gel onto nitrocellulose by a modified Western blot procedure offers the possibility of checking findings obtained by lectin histochemistry and immunohistochemistry.

Animals↗

PubMed1990

[Multiple amebic liver abscesses: ultrasound diagnosis and ultrasound-controlled puncture].

Amebic colitis and amebic liver abscess were diagnosed in a 45-year-old patient who had returned from Thailand. Ultrasound scans performed after starting treatment with metronidazole showed an abscess located above the right kidney that had enlarged to a maximum diameter of 9.7 cm. Since rupture of this lesion was felt to be imminent, ultrasound-guided needle biopsy was performed and 300 ml of abscess fluid evacuated. The patient experienced rapid relief of his symptoms. The role of ultrasound imaging in the diagnosis and follow-up of amebic liver abscesses and the indications for ultrasound-guided needle aspiration are discussed.

Animals↗

PubMed1990

Pharmacokinetics of ciprofloxacin in liver cirrhosis.

The pharmacokinetics of ciprofloxacin were evaluated in 11 patients (3 patients with impaired renal function) with advanced liver cirrhosis after a single oral dose of 500 mg. Mean serum peaks were 2.80 +/- 1.00 mg/l in 64 +/- 37 min after intake in patients with normal renal function. Elimination was reduced in comparison with healthy volunteers: t1/2 beta 510 +/- 158 min with a total area under the curve of 18.2 +/- 10.3 mg x h/l. Mean recovery of the parent compound from urine was 38 +/- 9% of the dose. In 3 patients with cirrhosis plus poor renal function, elimination was markedly reduced. In patients under 60 years with good renal function, the standard does not require a reduction.

Administration, Oral↗

PubMed1990

[Immunohistologic differentiation of interstitial infiltration cells in biopsies of transplanted kidneys].

Despite known morphological criteria of kidney allograft rejection a definite diagnosis of interstitial rejection in not possible in each case. Therefore, by an enzyme histological differentiation of infiltrating cells in the transplant biopsy specimen this problem should be solved. It was used the PAP method against pan T lymphocytes, T4 and T8 lymphocytes, monocytes and granulocytes. An acute interstitial rejection can be verified if 1. the number of lymphocytes and their subpopulations did increase over the maximum values, 2. without vascular rejection is the T4/T8 ration less than 1 and 3. in the presence of vascular rejection is the T4/T8 ratio greater than 1. Additional information about cyclosporin injury or viral infections may be possible. It is possible increase markedly the rate of safer diagnosis by immunohistological differentiation of infiltrating cells.

Biopsy↗

PubMed1990

[Randomized comparative study of secondary prevention of Pneumocystis carinii pneumonia in patients with acquired immunologic deficiency syndrome].

Pneumocystis carinii pneumonia is one of the most frequent infectious complications in patients with the acquired immunodeficiency syndrome (AIDS). A prospective trial was initiated to compare azidothymidine alone with azidothymidine plus aerosolized pentamidine as a secondary prophylaxis for pneumocystis carinii pneumonia. 27 patients (24 male, three female, average age 39 years) were enrolled, 14 patients receiving azidothymidine and pentamidine aerosol and 13 azidothymidine alone. After 166 days of follow-up, this trial had to be terminated prematurely, since the efficacy of pentamidine aerosol in the prevention of pneumocystis carinii pneumonia was clearly demonstrated in two recently published studies. Two patients died during the study period, one in either group, but neither due to pneumocystis carinii pneumonia. Two patients developed histologically proven pneumocystis carinii pneumonia; both patients were allocated to the azidothymidine arm. Pneumocystis carinii pneumonia was suspected clinically but not proven in four patients, three were randomized in the azidothymidine arm. Pentamidine was well tolerated and produced no severe side effects. The sample size is too small to draw definitive conclusions concerning the efficacy of pentamidine aerosol in AIDS patients.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Penetration of ciprofloxacin into the spinal fluid in patients with viral and bacterial meningitis.

Cerebrospinal fluid (CSF) concentrations of ciprofloxacin (Ciprobay) were measured by high performance liquid chromatography (HPLC) in 20 patients with varying degrees of meningeal inflammation. Underlying clinical syndromes were viral meningitis (n = 10), convalescent phase of acute bacterial meningitis (n = 9), and acute phase of bacterial meningitis (n = 1). CSF concentrations following an intravenous dose of 200 mg ranged between 0.028 and 0.11 mg/l (5.8-26.8% of corresponding serum levels) in patients with viral meningitis, and between 0.049 and 0.389 mg/l (5.9-77.0% of corresponding serum levels) in patients with bacterial meningitis. Taken together with the findings of other authors, the results indicate a potential usefulness of ciprofloxacin as an alternative agent for treatment of meningitis due to susceptible gram-negative microorganisms.

Adult↗

PubMed1989

Kinetic and end-point microdensitometry (section biochemistry) of gamma-glutamyl transpeptidase and dipeptidyl peptidase IV in the mature mouse decidua and visceral yolk sac.

gamma-Glutamyl transpeptidase (EC 2.3.2.2) and dipeptidyl peptidase IV (EC 3.4.14.5) were measured in mature mouse decidual and visceral yolk sac epithelial cells by means of kinetic (continuous) and end-point (static) microdensitometry (section biochemistry). For continuous measurements a new device for starting the enzyme reaction allowed the first readings to be made already during its very early phase. Since the initial reaction rates of both peptidases were very different in the plasma membrane of decidual and also in the visceral yolk sac epithelial cells, it was difficult to select a sufficient number of cells of the same activity for representative measurements on the basis of kinetic microdensitometry. Static section biochemistry was performed also for statistical reasons, i.e., in order to obtain information about the distribution of the activities of the decidual and visceral epithelial cells and the number of measurements required to guarantee valid data. Various groups of decidual and visceral yolk sac epithelial cells with different gamma-glutamyl transpeptidase and dipeptidyl peptidase IV activities were formed. In this way, different activities of gamma-glutamyl transpeptidase were measured in the plasma membrane of the cells of the antimesometrial, intermediate, and mesometrial decidua. Compared with dipeptidyl peptidase IV, gamma-glutamyl transpeptidase was significantly more active in the plasma membrane of the antimesometrial decidual cells and microvillous zone of the visceral yolk sac epithelial cells.

Animals↗