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Biomedical subjects

B Høgh

Publications and source records attributed to B Høgh.

31 records · Page 2Linked to original sources

Plasma, erythrocyte and urine concentrations of chlorproguanil and two metabolites in man after different doses.

Failures in the prophylactic effect of the antimalarial biguanide chlorproguanil (Lapudrine) may be caused by insufficient levels of its active metabolite chlorcycloguanil. Concentrations of chlorproguanil, chlorcycloguanil and a second metabolite, dichlorophenylbiguanide, in plasma, erythrocytes and urine, were followed in 13 volunteers, using a HPLC assay. In an initial study the basic kinetics were investigated after an oral dose of 2 mg kg-1. In the main study, the concentration-time curves were followed for 1 week after an oral dose of 20 or 80 mg chlorproguanil, respectively, after either a single dose or one weekly dose for 5 weeks. Higher concentrations of all three compounds were found in erythrocytes than in plasma. The active substance, chlorcycloguanil, was below the probably effective concentration in erythrocytes 24 h after 20 mg chlorproguanil and 72 h after 80 mg. The urinary recovery was about 45% of the dose and t1/2 31-44 h, both higher than previously reported. The apparent clearance was 0.52-0.82 l h-1 kg-1, which is lower than previously found. It is suggested that improved dose regimens, e.g. a higher dose given once a week, should be clinically tested on basis of these kinetic results.

Adult↗

[Malaria vaccines, a necessity for future control of malaria. Status and future perspectives].

Traditional malaria control is in a crisis on account of chemo-resistance of Plasmodium falciparum and insecticide-resistance of the malaria mosquito. New ways to control malaria have been opened by the possibility of producing a vaccine. Several malaria proteins (e.g. CSP, gp195, Pf155/RESA, GLURP) have been sequenced and it has been shown that most of the proteins have repetitive units. Analyses of T- and B-cell epitopes show that T-cell epitopes are mainly localized to the non-conserved parts of the antigens. Repeated malaria infections, therefore, may be seen as a number of primary infections, which partly explains the very slow development of immunity to the parasite. The initial three vaccination experiments in humans did not succeed in inducing a complete protection of the individual but it showed that partial immunization is possible.

Antigens, Protozoan↗

An epidemiological study of humoral and cell-mediated immune response to the Plasmodium falciparum antigen PF155/RESA in adult Liberians.

We investigated the seroreactivity and T cell reactivity against the Plasmodium falciparum antigen Pf155/RESA, different oligopeptides from the 3' and 5' repeat regions of the Pf155/RESA antigen, and crude Plasmodium falciparum antigens in 164 adult Liberians. We compared 2 long-term residential groups with high and low exposure to malaria. The seropositive rate to the peptides was significantly higher with increased exposure. There was no significant difference in response rates to the Pf155/RESA. This may indicate the level of persistent T cell memory in previously primed donors. The seropositive rates to 3 Pf155/RESA peptides and the rates measured by either 3H-thymidine incorporation or IFN-gamma release after stimulation with Pf155/RESA and the peptides were all lower in parasite positive individuals. Even low grade, asymptomatic parasitemia can impair the T cell response in vitro. The lower antibody response in parasite positive subjects may be explained by either antibody consumption or lower protection against malaria parasitemia in subjects with low concentrations of antibodies against the Pf155/RESA antigen.

Adult↗

The basic health care system in Botswana: a study of the distribution and cost in the period 1973-1979.

Since 1973 Botswana has developed its basic health service with an extensive network of clinics and health posts staffed with nurses, health assistants and Family Welfare Educators (11 weeks training in preventive medicine). In 1977 it was estimated that 80% of the population lived within 15km of either a health post or a clinic. In the study period the annual number of new registered outpatient diagnosis per inhabitant increased from 0.65 to 1.50, but even after the heavy investment in the rural areas the annual number of visits per rural inhabitant, was in 1979, 0.8 compared to 2.8 in the urban areas. In 1979 the per capita health expenditure was US+18.7, of which the basic health service accounted for US+8.8. The relationship between Botswana's basic health service and a primary health care system as described in the Declaration of Alma Ata is discussed.

Adolescent↗

Cyclofenil in childhood scleroderma.

Treatment with cyclofenil for 9 months of a 10-year-old girl with localized scleroderma is reported. No clinical improvement was achieved. The drug was discontinued due to hepatotoxicity.

Child↗

A longitudinal study of antibodies to the Plasmodium falciparum antigen Pf155/RESA and immunity to malaria infection in adult Liberians.

118 adult Liberians from 2 villages were studied prospectively for one year with monthly blood examinations for malaria parasites. The crude parasite rate was 41.5% and the crude gametocyte rate was 6.1%. The inoculation rate varied between 0.075 in the dry season and almost 0.4 in the rainy season, which is in accordance with other data from holoendemic areas. 47.5% (56) had a titre to the Pf155/RESA antigen less than or equal to 1/50 ('low responders') and 52.5% (62) had a titre of greater than or equal to 1/250 ('high responders'). The response was not age-dependent in this adult population, which may suggest that genetic factors are determining whether the individual become a high or low responder. Antibodies against the Pf155/RESA antigen were measured in 2 surveys 8 months apart, and the mean antibody response to Pf155/RESA and its EENV sequence was constant without seasonal variation. Pf155/RESA high responders had lower parasite densities during all 3 seasons surveyed, and Pf155/RESA high responders, with high antibody reactivity against the (EENV)6 sequence from the 3' repeat region of Pf155/RESA, had significantly lower parasite densities in the rainy season of 1987. The data suggest that high titres of antibodies to the Pf155/RESA antigen, and especially to its EENV sequence, might play a role in protective immunity in adults.

Adult↗

Aminopropeptide of human procollagen type I: a marker for the identification of blood from children in the mosquito blood meal.

A capture enzyme-linked immunosorbent assay (ELISA) to distinguish between blood from children and adults in the mosquito blood meal was examined using the alpha 1 chain of the aminopropeptide of human procollagen type I (PINP) as antigenic marker. Rabbit anti-human PINP (alpha 1) antibody was used as catching antibody, and either normal serum from 288 African and 58 Caucasian children and adults, or blood meals from 93 fed Aedes aegypti, were examined. PINP in excess of 40 optical density units (ODU) was detected in all children aged 0-13 years, whereas adults aged 21-77 years had PINP levels less than 25 ODU. In the transitional age group (14-20 years), the PINP levels ranged from 1 to 166 ODU. The PINP levels in 95% of the mosquito blood meals obtained from children exceeded the control levels, using 13 ODU as a cut-off value, whereas none of the blood meals from adults exceeded 13 ODU. The PINP levels in the mosquito blood meals were constant 1 and 8 h after ingestion, but they had decreased significantly after 16-19 h. Our data suggest that the test can be used to identify host preferences in studies of mosquitoes collected within 16 h after the blood meal. A field evaluation is necessary to determine the potential of the antigenic marker PINP as a tool in the identification of mosquito host preference.

Adolescent↗

The mosquito transmission of malaria: the effects of atovaquone-proguanil (Malarone) and chloroquine.

Despite its recognized importance, the prevention of patients with malaria from continuing to infect mosquitoes after treatment is not always achieved in practice. An inevitable consequence of the prolonged life-span and relative metabolic stasis of the mature gametocytes of Plasmodium falciparum is that they are not cleared by most antimalarials, and few antimalarials block infection in the mosquito vector. Previous research on the constituents of Malarone, a new 'combined antimalarial', suggested that the active components, atovaquone and proguanil, might inhibit infectivity of gametocytes to mosquitoes. We contrast here the impact of atovaquone-proguanil and chloroquine on the transmission of P. falciparum and P. berghei. While chloroquine enhanced infectivity of P. falciparum, atovaquone-proguanil caused a significant reduction. Surprisingly, sporontocidal activity against the rodent parasite persisted long after the levels of the constituent drugs would have been expected to have fallen below effective plasma concentrations on the basis of the established pharmacokinetics of atovaquone and proguanil. The P. berghei model may thus have provided a sensitive bioassay, detecting drug(s) at levels below that normally found with the usual chemical assays.

Animals↗