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Biomedical subjects

W Stille

Publications and source records attributed to W Stille.

At least 19 recordsLinked to original sources

[Enhanced lymphocyte proliferation in the presence of epidermal cells of HIV-infected patients in vitro].

Clinical observations show that the HIV infection is often associated with affections of the skin. In order to examine the involvement of the epidermal immune system in the HIV infection, we determined accessory cell function of epidermal cells from HIV-1-infected patients. For this we measured the proliferative response of enriched CD(4+)-T-lymphocytes from HIV-infected patients and noninfected controls to stimulation with anti-CD3 and IL-2 in the presence of epidermal cells; the enhancement of the response is dependent on the presence of functionally intact accessory cells. The capacity of epidermal cells to increase the anti-CD3-stimulated T-cell proliferative response was significantly enhanced in HIV patients (CDC III/IVA) as compared with noninfected donors. It is discussed, whether the increased activity of epidermal cells from HIV-infected patients may be responsible for several of the dermal lesions in the course of an HIV infection as due to an enhanced production and release of epidermal cell-derived cytokines.

Adult

Fluconazole prophylaxis of recurrent oral candidiasis in HIV-positive patients.

In a randomized, open study, the efficacy of fluconazole as a prophylaxis of recurrent oral candidiasis in patients with advanced stages of HIV-infection (CD4 cell count less than 100/mm3) was studied. For this purpose, the frequency of episodes of oral candidiasis during two different prophylaxis regimens (50 mg/day vs. 100 mg/day) were compared to an untreated control group. Sixty-five HIV-positive patients were included in the study from May, 1989 to January, 1990. Of these, 58 were evaluated over an observation time of 137-215 days. Prophylaxis with fluconazole clearly reduced the occurrence of oral candidiasis. In 20 out of 21 patients in the untreated control group, a total of 60 relapses occurred. In the prophylaxis group receiving 50 mg/day (group 2), two out of 18 patients had four relapses. In the group receiving 100 mg/day (group 3), four out of 19 patients had nine relapses in total. Of 3575 observation days in the control group, treatment due to oral candidiasis was necessary on 393 days (28%). In group 2, on 57 of 3316 days (2%), fluconazole in a higher dosage was administered for treatment. In group 3, relapse treatment with fluconazole 200 mg/day, or treatment with ketoconazole, became necessary in 116 out of 3314 observation days (3%). In all relapses, Candida albicans cfu greater than 10(3)/ml were isolated in the oral wash-outs. As compared to the untreated control group, fluconazole prophylaxis in a daily dosage of 50 as well as 100 mg led to significantly less frequent relapses of oral candidiasis (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

[Therapy of systemic mycoses in immunodeficiency].

Fungal infections have gained importance recently. The major reason for this is the increasing number of patients with immunodeficiency. Systemic treatment of invasive fungal infections up to now has been based on relatively few antimycotic agents (amphotericin B, flucytosine, as well as the azole derivatives fluconazole and itraconazole). Only a few number of fungi cause the majority of opportunistic fungal infections. Candida albicans leads to severe mucosal infections in cases of immunodeficiency. Systemic mycoses usually present as endogenous infections or are caused by an infected central venous catheter with dissemination into multiple organs. Less severe candida infections should be treated with fluconazole. A more severe candida infection still requires treatment with amphotericin B plus flucytosine. Aspergillus fumigatus, a ubiquitous mold, is the most frequent pathogen in patients with granulocytopenia. First choice treatment also is amphotericin B and flucytosine; treatment should be started despite lacking proof of pathogen in patients with immunodeficiency and typical clinical signs. Itraconazole, the azole derivative active against aspergillus, may be administered only in mild cases of aspergillus infections in immunocompromised patients. Infections with Cryptococcus neoformans, which hardly ever occur, have been observed frequently in AIDS patients. The manifestation of cryptococcosis mainly presents as chronical meningitis. Presently various treatment concepts are being clinically tested. An initial combination of amphotericin B, flucytosine, and fluconazole, followed by long-term treatment with fluconazole, is recommended.

Antifungal Agents

[Comparison of the effect of 2 therapy concepts in the treatment of Pneumocystis carinii pneumonia. Cotrimoxazole for 21 days versus sequential therapy with cotrimoxazole followed by pentamidine inhalation].

Standard therapy of pneumocystis carinii pneumonia with cotrimoxazole and intravenous pentamidine second line therapy both have a response rate of 75 to 90%. As severe side effects, myelotoxicity and skin reaction have been observed which may occur from treatment day 7 on. In order to prevent such side effects as well as reduce hospitalization times, an open, randomized pilot study was designed. Object of this study was the comparison of efficacy and safety of two different treatment schemes: standard therapy versus sequential treatment. Twelve patients were treated according to study design: five patients with cotrimoxazole only, and seven patients with sequential therapy consisting of cotrimoxazole followed by pentamidine aerosol. All patients were treated for 21 days. Four out of five patients with cotrimoxazole, and two out of seven patients with sequential therapy, were successfully treated and had no pneumocystis carinii pneumonia relapses within four weeks after termination of treatment. Each group had one treatment failure. Four patients under sequential treatment were not evaluable. - In spite of the rather unfavourable preliminary results, the study should be continued. However, patients with secondary opportunistic infections respectively other severe diseases should not be included into the study.

Administration, Inhalation

Change of causative organisms under antifungal treatment in immunosuppressed patients with HIV-infections.

Oral and esophageal candidosis are very common in HIV-infected patients. Due to the lack of efficacy of topical antimycotics in advanced stages of HIV-infection oral azoles are mainly used for treatment. Azoles most often used are ketoconazole and fluconazole. While Candida albicans clearly is the most frequently encountered yeast before and after treatment other species can be found somewhat less frequently after treatment. This especially applies to Candida glabrata. Candida spp. other than C. albicans obviously may cause manifest oral candidosis. This shift of microbes deserves the more interest as they are less susceptible to azole drugs.

Antifungal Agents

[Insurance legislation aspects and peculiarities of occupational legislation in AIDS and HIV infection].

Major aspects of the German insurance legislation regarding AIDS are being discussed. I. The structure of the statutory health and social security scheme is described; problems of coverage of persons with HIV Infection/AIDS in case of accident or unemployment are discussed (medical treatment, social security, pension). II. Private health insurance schemes are scrutinised as to the conditions for persons with HIV infection/AIDS. The aspect of coverage for children in private health schemes is also taken into account, and the differences between statutory and private health insurance schemes are considered. III. Criteria for life insurance contracts are described: it depends on the amount of money insured whether or not life insurance companies demand medical examination and HIV test from the policy holder. IV. Criteria for acknowledgement of AIDS as an occupational disease are pointed out. In particular, injuries at the place of work in connection with HIV-infected material, as well as methods of prevention, are discussed. V. Finally, labour legislation is investigated as to its consequences for persons with HIV infection/AIDS; the different aspects for employer and employee are considered, and problems like employment of persons with full-blown AIDS and termination of employment are explained.

Acquired Immunodeficiency Syndrome

Bactericidal activity of tigemonam, alone and in combination with gentamicin.

The in vitro bactericidal activity of tigemonam, alone and in combination with gentamicin, was evaluated against various strains of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella enteritidis, Enterobacter cloacae, Proteus mirabilis, and Proteus vulgaris. Minimum inhibitory and bactericidal concentrations were determined on three consecutive days with an inoculum of 10(5) colony-forming units (CFU)/mL or a culture in the logarithmic growth phase. The results found tigemonam to be rapidly bactericidal against most Enterobacteriaceae isolated. In addition, the killing curves indicated a synergism between tigemonam and subinhibitory concentrations of gentamicin.

Drug Combinations

[Visceral leishmaniasis (kala-azar) in acquired immunodeficiency syndrome (AIDS)].

A 32-year-old homosexual with AIDS, who until 1985 was a frequent traveller to South America and mediterranean countries, had recurrent bouts of fever, splenomegaly, arthralgias as well as granulocytopenia and anaemia. Liver and bone-marrow punctures were performed to exclude malignant lymphoma and (or) a mycobacterial infection. Both biopsies revealed Leishmania donovani. During administration of sodium stibogluconate (Pentostam) the fever disappeared for a time and there was clinical improvement, but further treatment was limited because of thrombocytopenia. In patients with AIDS who have splenomegaly with nonspecific fever, visceral leishmaniasis must be considered in the differential diagnosis even outside of endemic regions.

Acquired Immunodeficiency Syndrome

4-quinolones inhibit biotransformation of caffeine.

The pharmacokinetics of caffeine, including formation of its major metabolite paraxanthine in plasma, has been investigated in 12 healthy males (age 20-40 years) alone and during co-administration of the 4-quinolones ofloxacin, norfloxacin, pipemidic acid, ciprofloxacin, and enoxacin; ciprofloxacin and enoxacin were given in 3 different dose levels. The naphthyridine derivative enoxacin and the pyrido-pyrimidine derivative pipemidic acid had caused marked inhibition of caffeine and paraxanthine metabolism, whereas the genuine quinolone derivatives norfloxacin and ciprofloxacin had little effect, and the pyrido-benzoxacine derivative ofloxacin had no detectable effect. The different molecular and spatial structures of the compounds appear to be responsible for the differences in inhibitory potency.

Adult

Clinical efficacy and safety of teicoplanin.

This was an open efficacy and safety study in 310 hospitalized patients (187 male and 123 female) with infection by Gram-positive bacteria. The age range was 12-88 years (mean 49.8 years), and 80 of the patients were older than 65 years. Teicoplanin was given either by fast iv or by im injection, in most cases at a dose of 200 or 400 mg every 24 h with an initial dose of 400 mg. For both routes of administration the mean total daily dose was 286 +/- 5 mg/day. The mean duration of treatment was 8.2 days (range 1-37 days). The infections comprised 133 skin or soft tissue, 53 joint or bone, 40 urinary tract, 39 upper respiratory tract, 21 lower respiratory tract, nine septicaemia, four gastro-intestinal tract and 11 miscellaneous. All Gram-positive bacteria isolated were sensitive to teicoplanin. Teicoplanin was the sole antimicrobial agent given in 269 of the 310 patients. Clinical cure occurred in 79.7%, and improvement in 13.6%. Adverse events related to teicoplanin occurred in 7.7% of the patients. Most were minor and in only six patients was treatment discontinued because of adverse events (three allergy, two bronchospasm, one tremor). The laboratory values and audiometry indices in 67 patients showed no significant changes. Teicoplanin was considered an effective and well-tolerated treatment for Gram-positive infections in this study.

Adolescent

[Ciprofloxacin in combination with other antimicrobial substances].

The antibacterial activity of ciprofloxacin, either alone or in combination with azlocillin, imipenem, mezlocillin or tobramycin, was tested against enterococcus and pseudomonas species. No synergy or antagonism was found by means of the checkerboard titration method used. Subsequently, the bactericidal activity of ciprofloxacin (2 x minimal inhibitory concentration, MIC), azlocillin, imipenem, mezlocillin or tobramycin (2 x MIC) either alone or in combination (1 x MIC each of each substance) was tested against individual strains. No reduction of bactericidal activity in comparison with the effect of the single substances at higher concentration was found, even though the concentrations of each substance were halved. An antagonism is unlikely when ciprofloxacin is combined with one of the beta-lactams studied or with tobramycin. More likely is a slight synergistic effect.

Anti-Bacterial Agents

Autopsy findings in AIDS--a histopathological analysis of fifty cases.

Fifty consecutive AIDS autopsy cases were evaluated. All subjects showed one or more opportunistic infections and malignancies included in the AIDS case definition with cytomegalovirus and Kaposi's sarcoma being most prevalent. Mycobacterial and cryptococcal infections occurred only infrequently. Most patients of our series after successful treatment of Pneumocystis carinii pneumonia or cerebral toxoplasmosis later succumbed to less treatable conditions like disseminated cytomegalovirus or fungal infections or malignant lymphoma. In the absence of specific treatment for the HIV infection leading to these lethal complications special emphasis must be put on the prevention of HIV transmission and spread.

Acquired Immunodeficiency Syndrome