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Biomedical subjects

A Hanson

Publications and source records attributed to A Hanson.

At least 37 records · Page 2Linked to original sources

Isolation of a simian immunodeficiency virus related to human immunodeficiency virus type 2 from a west African pet sooty mangabey.

Two of 25 healthy pet sooty mangabey (SM) monkeys (Cercocebus atys) living in West Africa were seropositive by immunoblot when surveyed for antibody to simian immunodeficiency virus of macaques (SIVmac). SIVsmLIB1 was isolated from one of the pet sooty mangabeys. Nucleotide sequence data showed that this isolate is a member of the SIVsm/human immunodeficiecy virus type 2 (HIV-2)/SIVmac group of primate lentiviruses. Furthermore, sequence comparisons revealed extensive genetic diversity among SIVsm isolates similar to that observed previously in SIV isolates from naturally infected African green monkeys. These observations provide additional evidence for monkey-human cross-species transmission of SIVsm as the source of HIV-2 infection of human.

Animals↗

The value of ear lobe oximetry in the assessment of disability in asbestos-related disease.

Thirty-four asbestos workers, with either asbestosis, diffuse pleural thickening, calcified pleural plaques, or with comparable asbestos exposure but no evidence of asbestos-related disease and seven normal controls underwent a progressive exercise test. The subjects were categorized on the basis of lung function tests and PA chest X-rays. During the exercise test oxygen saturation was measured continuously by an ear lobe oximeter. The asbestosis and diffuse pleural thickening groups showed significant oxygen desaturation on exertion, confirming that both these conditions give rise to appreciable respiratory disability.

Asbestosis↗

Plasmodium falciparum-inhibitory monoclonal antibodies produced by human hybridomas.

Stable human hybridomas were generated that produced inhibitory anti-Plasmodium falciparum monoclonal antibodies. Peripheral blood lymphocytes, obtained from adults in Liberia, a malaria endemic area, were immortalized with Epstein-Barr virus and then fused with KR4, a human, lymphoblastoid cell line. Stable hybridomas that produced anti-P. falciparum monoclonal antibody were identified by an ELISA assay that used the trophozoite and schizont antigens of both the Honduras I and FCR3 parasite strains. Monoclonal antibodies produced by selected hybridomas derived from lymphocytes of two individuals were subsequently studied. The anti-parasite antibodies were produced at 1-3 micrograms/ml in culture supernatants. All of the monoclonal antibodies bound specifically to trophozoites and schizonts of both strains of parasite in an indirect immunofluorescence assay and inhibited production of ring stage parasites by more than 90% when added to trophozoite or schizont containing erythrocytes in culture. Western immunoblot analysis of antigens obtained from trophozoites and schizonts (parasite age span of 36 to 48 h) was performed using either affinity purified or ammonium sulfate-concentrated monoclonal antibody. Antibody from three hybridomas which bound primarily to antigens of the Honduras 1 strain had Mr of approximately 140,000, 130,000 and 123,000.

Animals↗

Metabolism of hydralazine in man. Part II: Investigation of features relevant to drug safety.

The metabolism of hydralazine (1-hydrazinophthalazine hydrochloride, Apresoline) was investigated in 17 hypertensive patients of known acetylator status who were chronically treated with oral doses of 50 mg b.i.d. or 100 mg b.i.d. hydralazine. The acetylator status was assessed either by the monoacetyldapsone/dapsone ratio or by the isoniazide plasma half-life. In each patient the tests were performed on two different days of treatment and they included the analyses of four hydralazine metabolites (NAc-HPZ, 3OH-MTP, MTP and TP), as well as apparent hydrazine in urine and also the determination of plasma concentrations of apparent hydralazine. All data of the two experiments performed within an interval of at least five days were in good agreement, thus indicating that the patients were in pharmacokinetic steady states. No correlation was detectable between any of the determined amounts of metabolites of hydralazine and the assigned acetylator status of the patients. On the other hand the rank order of the urinary yields of the two main metabolites NAc-HPZ and 3OH-MTP suggest to be a representative scale for the patients' status in respect to the biotransformation of the drug itself. The urinary yield of apparent hydrazine is dependent on the pH applied during the analyses and is not correlated with any of the other data recorded. The findings of the present study support the assumption that measuring a relevant prominent metabolite of the drug itself may lead to a more reliable assessment of the particular metabolic status of the patients than by classification through a non treatment related foreign compound.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

Monthly antimalarial chemotherapy to children in a holoendemic area of Liberia.

Two hundred and eighty-two children, two to nine years old, were included in a prospective three-year study in four villages with holoendemic malaria. In three villages the children received monthly doses of either chloroquine, pyrimethamine or chlorproguanil respectively for two years. In the fourth, vitamin tablets were used as placebo. Presumptive treatment with chloroquine (10 mg base kg-1) was given to all children with fever of suspected malarial origin. The two-year drug distribution was satisfactorily fulfilled to 168 children. Surveys, including physical and laboratory examinations were performed every six months, four weeks after medication. A fifth village was only visited at the start of the study and after two years. The mean crude parasite rate was initially 92%. Plasmodium falciparum was the main species. Splenomegaly was recorded in all children. In the chloroquine-treated children, the parasite rates varied between 30% and 50% during the study. By the end of the second year the spleen rate was reduced from 100% to 50%. Reported episodes of fever were reduced to half and mean haematocrit levels increased by 6% in comparison with children receiving the placebo. Total IgG concentrations were reduced from 36.7 g l-1 to 25.9 g l-1, whereas no significant decrease was observed in malarial seropositivity as measured by indirect immunofluorescence. Chlorproguanil had a weaker impact on parasitaemia with parasite rates between 50% and 90%. However, the spleen rate was reduced to 67% and there was a significant reduction of reported fever episodes. Mean haematocrits increased by 4%. Total IgG decreased from 31.8 g l-1 to 23.8 g l-1. In contrast, in the pyrimethamine group, the placebo group and the untreated group from the fifth village, the malariometric indices after two years were comparable to each other and to the initial values. During the third year only presumptive chloroquine treatment was given, and by the end of the study all malariometric indices were again comparable. From clinical observations there was no apparent impairment of protective immunity to malaria from the two years of regular distribution of the drugs. We conclude that a certain degree of malaria control could be achieved in Liberian children by the administration of monthly doses of chloroquine 10 mg base kg-1. The administration of chlorproguanil (1.5 mg kg-1) represents an alternative regimen.

Antimalarials↗

Cost comparison of unit dose and traditional drug distribution in a long-term-care facility.

Unit dose and traditional drug distribution systems were compared in a 352-bed long-term-care facility by analyzing nursing time, medication-error rate, medication costs, and waste. Time spent by nurses in preparing, administering, charting, and other tasks associated with medications was measured with a stop-watch on four different nursing units during six-week periods before and after the nursing home began using unit dose drug distribution. Medication-error rate before and after implementation of the unit dose system was determined by patient profile audits and medication inventories. Medication costs consisted of patient billing costs (acquisition cost plus fee) and cost of medications destroyed. The unit dose system required a projected 1507.2 hours less nursing time per year. Mean medication-error rates were 8.53% and 0.97% for the traditional and unit dose systems, respectively. Potential annual savings because of decreased medication waste with the unit dose system were $2238.72. The net increase in cost for the unit dose system was estimated at $615.05 per year, or approximately $1.75 per patient. The unit dose system appears safer and more time-efficient than the traditional system, although its costs are higher.

Costs and Cost Analysis↗

Plasma fibronectin levels in acute and recovering malnourished children.

58 malnourished children (mean age 18 months) with a clinical diagnosis of marasmus or kwashiorkor were studied with respect to plasma fibronectin levels, plasma total solids, spun hematocrits, heights, weights, mid-arm circumferences, and head circumferences. Bimodal distributions were demonstrated for plasma fibronectin versus weight deficits, total solids, hematocrits, and mid-arm circumference in children 12 months of age and older (p less than 0.003 for all). The mean plasma fibronectin level for controls was 253 micrograms/ml. The mean level for the malnourished group was 96 micrograms/ml (p less than 0.0001). Malnourished children with initial plasma fibronectin levels above 100 micrograms/ml had a higher survival rate than those with levels less than 100 (92 versus 69%). With successful therapy, plasma fibronectin levels rose quickly in most children often before detectable changes were noted in clinical and other laboratory parameters. An overshoot of the mean normal levels was observed with successful treatment wherein the mean levels rose to 315 micrograms/ml (p less than 0.05). Plasma fibronectin determinations on malnourished children can serve as an important prognostic marker as well as a reliable indicator of successful therapy and recovery.

Acute Disease↗

Long-term clinical experience with mexiletine.

Mexiletine was given to 12 patients for different periods of time varying from 4 to 96 months, with a mean of 47.8 months. At the latest follow-up in August 1983, five patients had been taking mexiletine for 74 to 96 months (mean 85 months). Mexiletine was well tolerated and serious side effects were not seen. In particular, there was no rise in antinuclear factor titer. The serum level of mexiletine was easily maintained within the therapeutic range, and most side effects correlated closely with the drug level. It is concluded that mexiletine can be administered for a long time as a safe alternative to other antiarrhythmic drugs.

Administration, Oral↗

Incidental teaching of mentally retarded students within a token system.

Six mentally retarded students were taught to name sight words during the token-exchange periods of a token-reinforcement system. Words appeared on 25% of the tokens, and a student was given two opportunities to name a word written on a token before the token could be exchanged. Sequential teaching of new sets of sight words via a multiple-baseline design was used to evaluate the procedure. Five of the 6 students acquired sight-word vocabularies. The data support the contention that token-exchange periods may be used for educational purposes.

Adolescent↗

Pharmacokinetics of oral hydralazine in chronic heart failure.

The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine ("apparent" and "real" hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III-IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.

Administration, Oral↗

Studies on the epidemiology of schistosomiasis in Liberia: the prevalence and intensity of schistosomal infections in Bong County and the bionomics of the snail intermediate hosts.

Urine samples from 3548 individuals residing in six of the eight districts which comprise Bong County, Liberia, the project area of the Bong County Agricultural Development Project (BCADP), and fecal specimens from 3408 of these individuals were examined for schistosome ova. A total of 164 water sites, including rice paddies, were surveyed for schistosome vector snails and monthly changes in snail population density and infection rate were determined in selected water sites. Bulinus globosus was more widely distributed than Biomphalaria pfeifferi but the latter species showed a higher infection prevalence (12.3%) than the former one (10.3%). Snail population density and infection rate fluctuated with season, being higher in the dry season and lower during periods of heavy rainfall. Dessication and/or heat stress may have contributed to the contraction of snail population size at the end of the dry season. More water sites contained infected snails during December through February than at any other time of the year. In selected water sites examined at monthly intervals, mean snail density was higher in rice paddies than in other water contact sites but the latter showed a higher prevalence of infected snails than the former. The overall prevalence of Schistosoma mansoni (24.8%) was significantly higher than that of S. haematobium (22.7%) but the difference in prevalence rates of two species in school children was not statistically significant. The intensity of S. haematobium infection (13.2 means G) was significantly higher than that of S. mansoni (6.3 means G). Mixed infections in school children did not have a significant effect on egg output. The prevalence and intensity of S. haematobium showed a dramatic decline between the age groups 0-15 and 20-50 + years old; the differences between these age groups in S. mansoni infection were unremarkable. In Zota, Jorquelle and Kokoya Districts, prevalence rates of S. haematobium were higher than those of S. mansoni; the reverse was observed in Suakoko and Panta-Kpai Districts but relative prevalence rates varied according to specific locality in each district. A south to north stratification of schistosomal infection prevalence was observed similar to the west to east gradient reported by Saladin et al. (1980). New rice paddies developed during the three year operational period of the BCADP contained little or no vector snails and schistosomal infections in farm families of these paddies reflected the characteristic of the disease in corresponding localities.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

A pilot control trial of schistosomiasis in central Liberia by mass chemotherapy of target populations, combined with focal application of molluscicide.

In an area of high transmission of Schistosoma haematobium and S. mansoni in Central Liberia, populations of five villages and intermediate host snails were surveyed for two years. In three of these villages focal application of molluscicide (niclosamide) in the main transmission sites was combined with mass chemotherapy of a target population representing 76 to 90% of the contamination index. In the two other villages, which served as control, the prevalence indexes remained stable or increased a little during the period of this study. A three dose metrifonate mass treatment was applied in one village with only S. haematobium infections. The compliance was very poor for the second and third dose but the quantity of eggs eliminated by the whole population present before and after mass treatment was reduced by 50%. No snails were found after molluscicide applications but as the incidence remained unchanged it is suspected that inhabitants have been reinfected by going to their fields. Concurrent metrifonate and niridazole mass treatment in one dose was applied in another village with only S. haematobium infections. Molluscicide applications reduced the snail population by 80% but did not affect the transmission. Prevalence indexes were almost the same before and after this intervention. In the last village, praziquantel (40 mg/kg in 1 dose) was used because both S. haematobium and S. mansoni infections were present. Molluscicide applications reduced the snail population by 99% and 87% for Bulinus globosus and Biomphalaria pfeifferi, respectively. This intervention stopped the transmission of S. haematobium for at least one year and reduced the prevalence from 21% to 4.6%. On the contrary for S. mansoni infections, the incidence remained very high (50%) and the prevalence was unchanged after one year follow-up. This could be explained by lower efficacy of praziquantel against S. mansoni (cure rate: 53%) and of molluscicide application against B. pfeifferi, which are highly susceptible to S. mansoni (infection rate 44%). The importance of migration in these villages is emphasized. Prevalence indexes were largely influenced by the arrival of newcomers who played a more important role in the maintenance of transmission after target mass chemotherapy than the infected persons excluded from this treatment. The costs per capita protected were 3.33 US $ for metrifonate, 1.53 for metrifonate and niridazole combined and 1.67 US$ for praziquantel. These figures do not include costs for parasitological examinations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Transplacental passage and breast milk concentrations of hydralazine.

The concentration of "real" and "apparent" (= "real" hydralazine + acid-labile hydrazones) hydralazine in maternal and umbilical plasma obtained at delivery of 6 women treated with hydralazine and atenolol for pregnancy hypertension were measured by gas chromatography. In one of the patients, the concentrations of the same substances were subsequently measured in breast milk. "Apparent" hydralazine reached higher levels in umbilical than in maternal blood. The concentration of "real" hydralazine seemed to be at least as high in the fetus as in the mother. On the other hand, even though the fraction of "real" (i.e. presumably active) hydralazine was greater in milk than in plasma, the total concentration was smaller, and the estimated dose per milk feed of 75 ml would not exceed 0.013 mg. Thus, hydralazine treatment of the pregnant woman would expose her fetus to effective concentrations of the drug, but breast feeding would not result in a clinically relevant concentration in the infant.

Adult↗

Influence of food on the bioavailability of "real" and "apparent" hydralazine from conventional and slow-release preparations.

The influence of concomitant food intake on the bioavailability of hydralazine was studied in healthy volunteers following single-dose administrations in the fasting state and together with a standardized breakfast meal of 1840 kJ (440 kcal). Both "real" (presumably active) and "apparent" (= total = "real" hydralazine + acid-labile hydrazones formed after hydralazine ingestion) hydralazine were determined by gas chromatography. Concomitant food intake seemed to enhance the bioavailability of both "apparent" and "real" hydralazine following ingestion of conventional hydralazine tablets. On the other hand, food intake did not significantly affect hydralazine bioavailability from a slow-release preparation. The enhanced effect of food on hydralazine bioavailability from the conventional preparation is probably due to reduced first-pass metabolism.

Acetylation↗

Acetylator phenotyping: a comparison of the isoniazid and dapsone tests.

A comparison was made between the results of acetylator phenotyping by isoniazid (INH) half-life measurements based on 5 samples (0-6 h), and by determination of the ratio of monoacetylated (MAD) to unchanged dapsone (DDS) in a single sample obtained 3 h after dapsone intake. In each of 44 subjects examined, there was unequivocal agreement about classification of the subject as a rapid (INH t1/2 less than 2 h; MAD/DDS greater than 0.3) or slow (INH t1/2 greater than 2 h; MAD/DDS less than 0.3) acetylator. It appears that the single-sample (3 h) dapsone test is as reliable as the more laborious and time-consuming INH test for acetylator phenotyping.

Acetylation↗