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Biomedical subjects

W Stille

Publications and source records attributed to W Stille.

At least 37 records · Page 2Linked to original sources
PubMed1996

Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies.

The efficacy of oral itraconazole 2 x 200 mg capsules daily for prevention of systemic mycoses was investigated in granulocytopenic patients with haematological malignancies. Of 241 patients, 197 were evaluable for prophylactic efficacy, and 214 for adverse events. Patients with similar characteristics receiving oral amphotericin B as antifungal prophylaxis, observed over 15 months before introduction of itraconazole, served as control group (n = 223). With itraconazole prophylaxis, 13 cases of aspergillosis (9 proven, 1 probable, 3 possible; 7%) and no systemic yeast infection occurred, compared with 14 episodes of aspergillosis (9 proven, 2 probable, 3 possible; 6%) and 3 proven systemic yeast infections (Candida albicans, Candida norvegensis, Trichosporon beigelii) in the historical group. Adverse events were observed in 13% of evaluable patients receiving itraconazole. In four patients with acute lymphoblastic leukaemia receiving itraconazole and vincristine simultaneously, severe vinca alkaloid-induced neurotoxicity occurred. Plasma concentrations of itraconazole and hydroxyitraconazole were measured in 64 patients. After eight days of itraconazole the median drug concentration was adequate (700 ng/mL), but there was a marked individual variation (229-2861 ng/mL). In comparison with a historical group, antifungal prophylaxis with itraconazole reduced the incidence of systemic yeast infections, but the frequency of aspergillosis was similar. However, a general increasing incidence of aspergillus infections at our hospital over the last four years should be considered in the assessment of study results.

Administration, Oral↗
PubMed1996

[Itraconazole suspension in the treatment of HIV-infected patients with fluconazole-resistant oropharyngeal candidiasis and esophagitis].

Forty AIDS patients suffering from fluconazole-resistant oropharyngeal candidosis were treated with oral itraconazole solution (200-800 mg/day). In 39/49 patients the disease could be initially cured or significantly improved. In contrast to the good clinical results, however, only in six patients a yeast count reduction was observed, and in four patients unchanged high yeast counts persisted. The main pathogen was C. albicans. Even in longtime treatment itraconazole solution was well tolerated. In two patients only the therapy had to be stopped due to the increase of transaminases. Considerable individual deviations in serum concentrations of itraconazole or hydroxy-itraconazole, respectively, were observed which correlated only to a minor degree with clinical and mycological results. Application of itraconazole in a soluble preparation caused an increase in efficacy due to simultaneous local and systemic action. In the case of resistance to fluconazole the itraconazole solution is a valuable alternative to the administration of amphotericin B which is rich in adverse reactions.

AIDS-Related Opportunistic Infections↗
PubMed1994

Interventional antimicrobial therapy in febrile neutropenic patients. Study Group of the Paul Ehrlich Society for Chemotherapy.

In this prospective multicenter trial, treatment strategies for 1573 patients with neutropenia < 1000/microliters and fever > or = 38.5 degrees C after cytotoxic chemotherapy were compared. Patients with unexplained fever were randomized to a three-phase sequential study for different established drug regimens. If an infection could be defined microbiologically or clinically, treatment modifications were determined. In phase I, treatment for all patients consisted of acylaminopenicillin (PEN) plus aminoglycoside (AMG); or third-generation cephalosporin (CEPH) plus AMG; or PEN plus CEPH. In 800 patients with unexplained fever the response rates were: PEN/AMG (n = 258): 74.4%, CEPH/AMG (n = 252): 73.4%; PEN/CEPH (n = 290): 70.0%. Total response rate was 72.5%. In phase II, patients not responding after 3 days received PEN/CEPH/vancomycin (n = 70) or PEN/CEPH/AMG (n = 74). The respective response rates were 52.9% and 55.4%, total 54.2%. If fever did not resolve, the patients received either PEN/CEPH (n = 40) or imipenem/cilastatin (n = 59) both in combination with amphotericin-B/5-flucytosin/rifampin. The response rates were 62.5% and 79.7%, respectively (p = 0.07), total 72.7%. No significant differences between the treatment modalities compared were found. Analyzing all three phases together, 91.3% of patients with unexplained fever were cured. The response rate was also analyzed according to patients with gram-positive bacteremia (n = 183), response rate = 82.5%; gram-negative organisms (n = 145) 78.6%; fungemia (n = 51) 43.1% (p < 0.001); lung infiltrates (n = 269) 61.3% (p < 0.001); clinically documented infections (n = 198) 84.4%; and clinically and microbiologically documented infections (n = 84) 82.1%. If infections were diagnosed after at least 5 febrile days, more lung infiltrates and fungal infections occurred (p < 0.001). Leukocytes rising above 500/mu during the infection predicted better response rates (p < 0.001): in unexplained fever 97.8% vs 86.5% and lower death rates 1.5% vs 8.5%. In documented infections the response rates were then 89.9% vs 62.3% and the death rates 7.0% vs 20.5%. Therapy of neutropenic fever and infections must be adapted according to risk factors and should include early empiric antifungal therapy. The therapeutic and prophylactic use of hematopoietic growth factors to overcome neutropenia should be evaluated.

Adolescent↗
PubMed1994

Uptake and killing of Candida by human peritoneal macrophages and amphotericin B.

The effects of amphotericin B at subinhibitory and inhibitory concentrations on ingestion and intracellular killing of C. albicans ATCC 10,231 and C. tropicalis ATCC 13,803 by human peritoneal macrophages in vitro was investigated. Peritoneal macrophages were harvested from overnight peritoneal dialysate of 26 patients undergoing regular continuous ambulatory peritoneal dialysis (CAPD) using a new simple isolation technique. Macrophages were suspended with Candida (1:2-3) together with pooled human serum and with or without amphotericin B at various concentrations. Vital staining with acridine orange at a very low concentration using the metachromatic property of the dye allowed simultaneous assessment of ingestion and intracellular viability of the yeasts. Counts of Candida in 100 macrophages were performed at 1, 2, 3, 4, 6 and 24 h under a fluorescence microscope at 1000x and the ratios of living to dead intracellular Candida were calculated. Amphotericin B was added at concentrations of 0.1, 1 and 10 times the MIC. Ingestion was rapid and complete, while intracellular killing ranged from 4-69% for C. albicans and from 9-48% for C. tropicalis. Amphotericin B at 1 MIC enhanced the killing of C. tropicalis (factor 1.32) but reduced killing of C. albicans (factor 0.6) after 6 h.

Adult↗
PubMed1993

Control of intracellular growth of Mycobacterium fortuitum by human monocytes in vitro.

The ability of human monocytes to phagocytize and respond to infection by Mycobacterium fortuitum was tested using the method of Crowle and May. The monocytes were obtained from heparinized donor blood samples and separated from lymphocytes by adherence to plastic surfaces. M. fortuitum infection was performed immediately. Intracellular viability was indicated by colony forming units (CFU) done at 2 hour intervals. Monocytes were found to cause a rapid reduction in CFU during the first 2 hours of incubation. The rate of killing of M. fortuitum decreased thereafter but continued for the entire 8-hour study period. In parallel tests, ciprofloxacin and ofloxacin were added to the culture medium. Increased intracellular killing was observed with drug concentrations above 2 x MIC in both cases. Ofloxacin showed better antimycobacterial effects than ciprofloxacin.

Ciprofloxacin↗
PubMed1993

The efficacy and safety of zidovudine alone or as cotherapy with acyclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind randomized trial. European-Australian Collaborative Group.

OBJECTIVE: To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC). DESIGN: Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy. SETTING: Teaching hospital ambulatory clinics in eight European countries and Australia. SUBJECTS: A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988. MAIN OUTCOME MEASURES: Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts. RESULTS: During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients. CONCLUSION: These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

AIDS-Related Complex↗
PubMed1993

[Bovine spongiform encephalopathy].

The bovine spongiform encephalopathy, a new bovine disease, was diagnosed first in the U.K. in 1985. Primarily an object of interest to scientific and news media, it has become a subject of research to some specialists only. Some aspects seem to point out the importance and potential danger of this disease to humans, too. Its similarity to other chronic degenerative forms of central nervous diseases is discussed.

Animals↗
PubMed1993

[Results of studies from the AIDS counseling center of the Frankfurt/M. city health office January 1990 to December 1991].

Between January 1990 and December 1991 5854 clients entered the AIDS-Counselling Service of the Municipal Health Department in Frankfurt/M; 1997 (34%) of them were female and 3857 (66%) male. In 5228 cases blood samples were examined for HIV-antibodies and the prevalence of positive tests was 84 (1.6%). Among the subjects who were seropositive for HIV, 51 (61%) were homosexual, 9 (11%) bisexual and 11 (13%) heterosexual men, furthermore 5 (6%) heterosexual women. 8 (9%) seropositive persons were intravenous drug abusers (5 male, 3 female). With the aid of an anonymous questionnaire that was filled in voluntarily by the clients, information about the sexual anamnesis, reasons for wanting the test, and whether they had been already tested for HIV in the past, could be gained. During the examined period, safer sex has been practiced by 414 (58%) of 712 homosexual men and by 1183 (24%) of 4867 heterosexuals (2923 male, 1944 female). By reason of a new partner 141 (19%) homosexuals and 1261 (26%) heterosexuals wanted to be tested for HIV; 529 (74%) homosexuals and 1806 (37%) heterosexuals had been already tested for HIV in the past. Summing up we can state, that the large attendance of the AIDS-Counselling Service, now as before, could be traced back to great acceptance and trust placed the population in the Municipal Health Department. HIV-testing is accepted by heterosexual and homosexual couples as well, and often performed at the beginning or at the end of a partnership. Safer-sex plays, now as before, a subordinate role among heterosexuals in comparison to homosexuals.

AIDS Serodiagnosis↗
PubMed1992

[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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1990

[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↗
PubMed1989

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↗
PubMed1989

[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↗
PubMed1989

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↗
PubMed1988

[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↗