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Biomedical subjects

U Bienzle

Publications and source records attributed to U Bienzle.

At least 19 recordsLinked to original sources

Quinine plus clindamycin improves chemotherapy of severe malaria in children.

In a randomized trial, a 4-day quinine-clindamycin regimen was compared with the standard 7-day quinine regimen for 100 Gabonese children (50 children in each group) with severe Plasmodium falciparum malaria. In each group, only one patient died. Parasite clearance and fever clearance times were significantly shorter in the quinine-clindamycin group (P = 0.03 and P = 0.01, respectively) than in the quinine group, and significantly more recurring fever episodes occurred in the quinine group than in the quinine-clindamycin group shortly after initial fever clearance and parasite clearance (P < 0.001).

Child, Preschool

Prediction of accelerated cure in Plasmodium falciparum malaria by the elevated capacity of tumor necrosis factor production.

Cytokine regulation was compared in three groups of Gabonese patients with Plasmodium falciparum malaria before and after therapy; adults with uncomplicated malaria, children with uncomplicated malaria, and children with severe malaria. Plasma levels of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, TNF receptors (TNF R), and the TNF/TNF R ratios were significantly higher in severe malaria compared with uncomplicated malaria. High plasma levels of all immunoregulatory molecules were associated with slow cure after therapy. In all patients, phytohemagglutinin-induced cytokine production was depressed on admission compared with convalescence. A significant difference was the higher TNF production capacity in patients with severe malaria on day 2 and day 5 compared with that in patients with uncomplicated malaria. In contrast to IL-6 and IL-8, a high TNF production capacity during the acute phase of malaria predicted a rapid clinical and parasitologic cure in the patients. These findings illustrate the dual role of TNF in the protection and pathology of malaria.

Adolescent

Interferon-gamma induced lethality in the late phase of Plasmodium vinckei malaria despite effective parasite clearance by chloroquine.

A combination therapy was tested consisting of chloroquine and interferon-gamma (IFN-gamma) in the late phase of blood-stage Plasmodium vinckei malaria in BALB/c mice. When mice were treated with three times 300 micrograms chloroquine at 24-h intervals starting at a parasitemia of 30%-50%, only 5 of 14 mice (36%) died 2-4 days after initiation of therapy. However, when infected mice received chloroquine plus 1 microgram IFN-gamma at the same time, 14 of 18 mice (78%) died 0.5-3 days after start of therapy (p < 0.05) despite clearance of parasitemia. The histopathology from mice dying after combination therapy revealed interstitial leukocyte infiltration of lung tissue, severe liver cell necrosis and kidney tubular necrosis. Pretreatment of P. vinckei-infected mice with pentoxifylline, a phosphodiesterase inhibitor, led to a significant decrease of IFN-gamma-induced lethality (p < 0.05). In contrast, pretreatment with neutralizing antibodies to tumor necrosis factor or with L-N-monomethyl arginine, the latter an inhibitor of the nitric oxide synthase, significantly increased lethality (p < 0.05).

Animals

Antibody response in Plasmodium vinckei malaria after treatment with chloroquine and adjuvant interferon-gamma.

The antibody response of mice infected with Plasmodium vinckei after treatment with chloroquine either alone or in combination with interferon-gamma (IFN-gamma) was determined. Sequential serum samples were drawn from BALB/c mice receiving either 240 micrograms chloroquine on the day of infection or 120 micrograms chloroquine plus 10(4) units IFN-gamma daily for 11 days beginning on day 3 prior to infection. Mice treated with additional IFN-gamma showed an early induction of IgG2a response and a reduction in IgG1 antibodies as detected by the immunofluorescence technique at between 10 and 16 days after infection as compared with mice treated with chloroquine alone. Thus, IFN-gamma may partly exert its antimalarial activity via the induction of IgG2a antibody formation. At 4-6 weeks after infection, when mice from both groups resisted homologous re-infection, the predominant antibody isotypes found in both groups were IgG1 and IgG2a. Serum samples obtained from mice in both treatment groups at 6 weeks after infection were used for serum transfer experiments. When parasitised erythrocytes were preincubated with such immune serum, a retardation of the course of parasitaemia by 2 days was observed.

Animals

Inhibition of endotoxin-induced macrophage tumor necrosis factor expression by a prostacyclin analogue and its beneficial effect in experimental lipopolysaccharide intoxication.

Tumor necrosis factor (TNF), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. A stable prostacyclin analogue (iloprost) was investigated for its ability to interfere with TNF secretion of lipopolysaccharide (LPS)-stimulated macrophages. It could be demonstrated by bioassays that LPS-induced TNF production was suppressed in a dose-dependent manner when macrophages were treated with iloprost at the time of LPS stimulation. Northern blot analysis revealed that iloprost inhibited TNF production at the transcription level. In vivo, endotoxin-induced mortality rates in galactosamine-sensitized mice could be significantly (P less than .05) reduced by iloprost administration. It is assumed that prostacyclin modulates endotoxin-induced and TNF-mediated inflammation in septic shock.

Animals

A comparative study of four serological methods for diagnosis of acute and chronic Chagas' disease in Brazilian patients.

Complement fixation (CF), indirect immunofluorescence (IFAT), latex agglutination (LA) and the enzyme-linked immunosorbent assay (ELISA) were applied to assess the diagnostic value of antibody determination in Brazilian patients with acute or chronic Chagas' disease. Patients with various forms of leishmaniasis and healthy individuals from the endemic region were used as specificity controls. Whereas LA, IFAT and ELISA identified 81% of acutely ill patients, CF had no diagnostic potential in this phase of the disease. In later stages CF showed a sensitivity of 69% as compared to 100% for LA, IFAT and ELISA, irrespective whether patients presented clinically as chronic asymptomatic or chronic symptomatic cases. Cross-reactivity with anti-leishmania antibodies was observed in 23%, 38% and 77% of serum samples in LA, ELISA and IFAT, respectively, but not in CF.

Acute Disease

Interferon-gamma treatment in mice experimentally infected with Trichinella spiralis.

Interferon-tau (IFN-tau) treatment of Trichinella spiralis-infected BALB/c mice was investigated. The therapeutic regimen consisted of daily intraperitoneal injection of 10(4) U murine IFN-tau for 7 days, starting at 2 weeks post-infection. Striated muscle samples (diaphragm, thigh) were collected at 4, 8 and 12 weeks after infection. The muscle larval burden, the degree of encystation and the digestion of T. spiralis larvae were investigated. Furthermore, immunohistochemical studies of the inflammatory cell infiltrate around encysted larvae were performed. The results demonstrated an influence of IFN-tau treatment on the CD4+ and CD8+ subset distribution during the immune response but revealed no difference in the degree of encystation or digestion of encapsulated larvae as compared with control values.

Animals

Interferon-gamma enhances the effect of antimalarial chemotherapy in murine Plasmodium vinckei malaria.

Most nonimmune patients with Plasmodium falciparum infection are no longer cured by such standard antimalarial drugs as chloroquine. Thus, alternative treatment regimens are necessary. A combination therapy was tested consisting of a subcurative dose of chloroquine and interferon-gamma (IFN-gamma) in BALB/c mice with lethal Plasmodium vinckei malaria. Treatment with either agent alone prolonged median survival by 1-2 days compared with placebo-treated mice. However, a combination of 80 micrograms of chloroquine given at the time of infection plus 1 x 10(4) units of IFN-gamma/day for 11 days (starting 3 days before infection) cured 83% of infected mice. Moreover, these mice showed solid immunity when challenged with the homologous strain of P. vinckei. However, when these mice were infected with the heterologous strain of Plasmodium berghei, the same degree of parasitemia developed as did in P. berghei-infected control mice. Thus, the combination of chemotherapy with the cytokine IFN-gamma leads to substantial improvement of antimalarial treatment and to a rapid development of strain-specific immunity in murine P. vinckei malaria.

Animals

Pentoxifylline prevents murine cerebral malaria.

Pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (CM) in Plasmodium berghei ANKA-infected CBA/Ca mice. Nine of 12 control mice developed neurologic signs and died from CM approximately 2 weeks after infection. All 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop CM. All surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. In pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM.

Animals

Prevention of murine cerebral malaria by a stable prostacyclin analog.

Iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice. Malaria antigen-induced tumor necrosis factor (TNF) production could be inhibited by iloprost in vitro and in vivo. Northern analysis of TNF mRNA revealed that malaria antigen-induced TNF expression was suppressed at the transcription level.

Animals

Characterization of erythrocytic glucose-6-phosphate dehydrogenase in a mouse strain with reduced G6PD activity.

Erythrocytic glucose-6-phosphate dehydrogenase (G6PD) of a mutant mouse strain with X-linked G6PD-deficiency was purified and compared with the wildtype G6PD by biochemical and physiological characteristics. The red cell G6PD activity of the mutant was 20% of the wildtype. The Michaelis constant (Km) of the substrate glucose-6-phosphate (G6P) was higher (90 microM) for the mutant than for the wildtype (56 microM). The isoelectric focusing with a pH range from 3 to 10 showed one more enzymatically active band for the wildtype G6PD compared to the mutant enzyme. Other enzyme characteristics, however, such as Km for nicotinamide adenine dinucleotide phosphate (NADP), utilisation of 2-deoxy-glucose-6-phosphate (2dG6P) and deamino-NADP, heat stability, pH optimum, molecular weight, and glucose metabolisation via the pentosephosphate pathway were similar in mutant and wildtype enzyme.

Animals

Sequelae after infection with Trichinella spiralis: a prospective cohort study.

It is still a matter of debate whether or not infection with Trichinella spiralis is followed by long lasting sequelae. A common source epidemic of trichinosis which occurred in Bitburg, FRG, in October 1982 gave us the opportunity of performing a controlled cohort study (171 patients and 51 controls). 145 patients and 44 controls completed the 3 year follow-up. Complaints persisted in 36% of patients aged less than 30 years and in 100% of patients aged greater than 50 years. Complaints in order of frequency were: muscular complaints 84%, ocular complaints 63%, cardiac complaints 48%, cephalgia 43%, neurological complaints 35%, gastrointestinal complaints 18%, m fatigue and weakness 18%, oedema 12% and fever less than 1%. IgG antibodies to T. spiralis were still present in all but 5 patients 3 years after infection. IgM antibodies were either low or absent. In our patients the frequency and pattern of complaints and the correlation to the specific antibody response provide evidence that trichinosis causes long-lasting disease. Yet, from our data we were unable to draw conclusions as to the causative pathophysiological mechanisms.

Adolescent

Behavioral characteristics and laboratory parameters in homo- and bisexual men in West Berlin: an evaluation of five years of testing and counselling on AIDS.

Sera of 1980 homo- and bisexual men who visited the Landesinstitut für Tropenmedizin Berlin (West) between April 1983 and December 1987 were tested for HIV antibodies; 24.3% were positive. Of HIV-antibody-positive men, 78.9% reported both active and passive anal intercourse, 58.8%, rectal enemas, and 53.3%, use of butyl nitrite. There was a sexual partner with known positive HIV-antibody status or AIDS in 33.9%, and in 32.4% there was a history of sexual activity in the USA. In the year before the test, 18.8% had had more than 50 partners. All these behavioral characteristics were found to be significantly correlated to HIV antibodies. We noted a substantial reduction of high-risk behavior from 1983 to 1987. The most important behavioral factor for HIV infection in 1983 and 1984 was sexual activity in the USA, and from 1984 to 1987, the numbers of lifetime partners. Persons infected with HIV were significantly more often carriers of antibodies against HAV, HBV, CMV, EBV, and syphilis. Prevalence of antibodies against HIV, HAV, HBV, and syphilis increased with age, duration of homosexual practice, and the number of partners. Overall crude prevalence rates of HIV antibodies, anti-HBc, anti-HAV, and antibodies to syphilis declined during the observation period. Clinical findings such as fever, oral lesions, and lymphadenopathy syndrome (LAS) were found to be highly indicative of HIV infection. Lower hemoglobin values, a reduced white cell count, and hyperimmunoglobulinemia were significantly more frequent in subjects with HIV antibodies.

Adolescent

HIV infection in intravenous drug abusers in Berlin: risk factors and time trends.

To investigate the epidemiology of HIV infection among intravenous drug abusers (IVDA) in Berlin (West), from October 1984 to October 1988, 741 heterosexual IVDA were recruited from facilities for drug treatment and counseling. In this group 22.8% were seropositive for antibodies against HIV, representing 21.1% of the females and 23.5% of the males. Seroprevalences of hepatitis B, hepatitis A, and lues were 67.7%, 40.1%, and 4.0%, respectively. Seropositivity for HIV antibodies correlated with positive seromarkers for hepatitis B and A, and with certain behavioral and social features such as sharing of injection equipment, imprisonment, and intravenous drug use in prison. The crude time trend of HIV seroprevalence shows an increase from 17.1% in those subjects who discontinued i.v. drug abuse in 1983 or earlier to 31.5% in 1985, and a decrease over the past 3 years to 14.1% in 1988. After adjusting for temporary changes in the study group, the estimated HIV seroprevalence odds show an almost steady increase and were significantly higher for those who were injecting drugs in 1987 and 1988 compared with those who stopped i.v. drug use before 1984. Thus IVDA with a persistent risk profile are at a still-increasing risk of acquiring HIV infection.

Age Factors

Mixed Schistosoma haematobium and S. mansoni infection: effect of different treatments on the serum level of circulating anodic antigen (CAA).

In this study, levels of circulating anodic antigen (CAA) in serum were investigated after differential treatment of 160 Sudanese patients with mixed Schistosoma haematobium and S. mansoni infections. The patients were randomly divided into four groups, which were treated with metrifonate (two doses of 10 mg/kg bodyweight), oxamniquine (60 mg/kg), praziquantel (40 mg/kg), or a multivitamin preparation, respectively. Serum, stool and urine samples were taken prior to treatment as well as one month and five months after chemotherapy. Before chemotherapy CAA levels were similar in the four groups. Antigenemia remained unchanged in the control group. In patients treated with praziquantel or oxamniquine the concentration of CAA decreased to a similar extent. However, whereas in the praziquantel group absence of CAA was already observed one month after treatment, clearing of CAA from the circulation seemed to take longer in patients treated with oxamniquine. Treatment with metrifonate did not result in a reduction of the CAA titres.

Animals

Time trends of HIV-I antibody prevalence in homosexual men.

1840 homosexual and bisexual men were tested for human immunodeficiency virus type I (HIV) infection at the Landesinstitut für Tropenmedizin, Berlin between April 1983 and December 1987. A total of 25.1% were seropositive for HIV, but the percentage was seemingly declining. During the study period we observed also a steady decrease in the prevalence of lymphadenopathy syndrome (LAS), antibodies to hepatitis B and syphilis, and high-risk sexual behaviour in the study population. By adjusting for these changes of population characteristics we assessed the odds of HIV infection which had more than doubled between 1983 and 1986 (prevalence odds ratio 2.43, 95% confidence interval 1.58 to 3.76). In 1987 the HIV prevalence odds showed a drop which, however, was not significant (p = 0.34) when compared with the odds in 1986. Methodological aspects of time trend estimation based on data of voluntary HIV testing are discussed.

Adolescent