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Biomedical subjects

R Korte

Publications and source records attributed to R Korte.

At least 37 records · Page 2Linked to original sources

Induction of malformations in the cynomolgus monkey with 13-cis retinoic acid.

The embryotoxic and teratogenic potential of 13-cis retinoic acid was assessed in the cynomolgus macaque (Macaca fascicularis). A total of 41 animals was orally administered 13-cis retinoic acid in four sequential experiments. In Exp. 1 three dose levels, 2, 10, and 25 mg/kg, were administered on gestational day (GD) 18-28; 5 mg/kg was administered as an equally divided dose twice daily in Exp. 2 and 3 on GD 21-24 and on GD 25-27, respectively; in Exp. 4 the drug was administered at 2.5 mg/kg once daily from GD 10 to 25 and twice daily (2 x 2.5 mg/kg) on GD 26 and 27. Maternal death and toxicity, manifested as reduction in maternal weight and food consumption, and diarrhea, was observed in Exp. 1 in all three dose groups. No significant maternal toxicity was observed in the treatment groups in Exp. 2, 3, and 4 or in the control group. The primary manifestation of developmental toxicity was embryolethality in Exp. 1 and 2. The incidence of embryonic deaths in Exp. 3 was comparable to the historical controls. No malformations in GD 100 fetuses were observed in Exp. 1, 2, and 3. In Exp. 4, five of seven fetuses (71%) had malformations of both external ears, four of seven fetuses (57%) exhibited hypo- or aplasia of the thymus, and two of seven (29%) had malformations (transposition of the great vessels, ventricular septal defect) of the heart. The teratogenic dose for the cynomolgus monkey in the present study was lower than that reported for all other experimental species. Although central nervous system and craniofacial defects were not observed, the incidence of ear and thymus defects was similar to that reported for the human. The cardiovascular defects resembled those reported clinically, but the incidence was lower in the cynomolgus monkey. The similarity in teratogenic sensitivity to humans supports the use of the monkey as a model for developmental toxicity studies of vitamin A-related compounds.

Abnormalities, Drug-Induced↗

Voluntary blood donor recruitment: a strategy to reduce transmission of HIV-1, hepatitis-B and syphilis in Kinshasa, Zaïre.

We evaluated the use of voluntary blood donor recruitment in Kinshasa, Zaïre, as a means of reducing transmission of HIV-1 and other infectious agents by blood transfusion. Between January 1, 1989, and April 7, 1989, 2,237 blood donors were enrolled in the study at the transfusion centre of the Mama Yemo Hospital. Each donor was tested for antibodies to HIV-1 confirmed by IFA and Western blot, Treponema pallidum, antibodies to hepatitis B virus (HBV) core antigen and screened for the presence of the HBV surface antigen. Test results were related to the data of the blood donors: age, sex, haematocrit, voluntary blood donor, family member donor, paid donor. The serological results of all donors for Anti-HIV-1. Anti-HBc, HBsAg and TPHA were 4.8%, 70.9%, 13.1% and 13.3% respectively. Lower seroprevalence rates were found among voluntary blood donors. However, only TPHA seroprevalence was significantly lower in voluntary blood donors (8.4%, 23/275) compared with paid donors (15.2%, 87/571) (p less than 0.01). A greater proportion of voluntary donors provides a store of blood which allows more extensive screening of blood for HIV-1 and other infectious diseases. Voluntary blood donor recruitment is critical for the provision of safe blood supplies in Kinshasa.

Acquired Immunodeficiency Syndrome↗

Health impact evaluation of improved water supplies and hygiene practices in Sri Lanka: background and methodology.

Between January 1987 and March 1988 a Health Impact Evaluation (HIE) of the Rural Water Supply and Sanitation Project (RWSSP) was conducted in Kurunegala District. Four related activities were undertaken: 6598 children were recruited into a case-control study of diarrhoea morbidity conducted in five hospitals; an additional 1649 children from the catchment areas of three of the five hospitals were recruited as a community comparison group; environmental microbiology was performed on water samples collected during 3092 visits to the homes of children recruited into the study; diagnostic stool microbiology was performed for 371 children with diarrhoea and 121 controls. In this paper the seasonality of reported diarrhoea and the socio-demographic characteristics and health-related behaviours of each study group are examined. Cases, clinic controls and the community comparison group were all drawn from the essentially rural settlements typical of the southern part of the dry zone of Sri Lanka. The majority of households in these settlements are Sinhalese buddhist, and the main economic activity is subsitence farming. There was some evidence of differences between the three groups, community recruits tending to come from larger and wealthier households than the children recruited at the hospitals. Issues arising in the design and analysis of this Health Impact Evaluation are discussed. In particular, potential sources of bias are examined and the question of validity investigated.

Case-Control Studies↗

Magnitude, presentation, management and outcome of acute respiratory infections in children under the age of five in hospitals and rural health centres in Tanzania.

In preparation for a national control programme acute respiratory infections (ARI) were studied in children under five years of age in 14 health centres, one referral and four district hospitals in five regions of Tanzania. 10.5% of all under-fives attending these health institutions presented with symptoms of ARI. 50% of all ARI patients were less than one year old. Cough, fever and difficult breathing were the main complaints motivating consultation. On examination nearly half of ARI patients had signs of difficult breathing, which corresponded to high prevalence of pneumonia (36.8% of all diagnoses). An excessive use of antibiotics for the treatment of all kinds of ARI was observed. This may explain the low case fatality rate of 2.6% for pneumonia. Those children who died from ARI came later to the health facility, had poorer nutritional status and more severe signs on examination than those children who survived. To reduce ARI mortality further, intervention should concentrate on early diagnosis and treatment at lower, i.e. dispensary and community levels.

Acute Disease↗

The National Schistosomiasis Control Programme in Mali, objectives, organization, results.

Schistosomiasis control started regionally, in the Bandiagara district, and as a component of a dam-building project in 1978. In 1982 a national programme was created. Control was divided into three phases: Preparation, intervention and maintenance. Districts qualifyed for schistosomiasis control activities, when the prevalence for either Schistosoma haematobium or Schistosoma mansoni exceeded 20% and/or the prevalence of persons with intensive infections for either parasite exceeded 5%. Intensive infection was defined as the excretion of more than 50 eggs per 10 ml of urine or the excretion of more than 100 eggs per one gram of stool. Preparation consisted of sample surveys to identify districts that needed to be included in control operations and the training of local health personnel. Interventions were primarily mass chemotherapy, using a single dose of praziquantel (40 mg/kg), sanitation and health education. The application was still being investigated for its cost benefit. Maintenance was to be achieved through the treatment of cases at fixed centres of the basic health services. Until 1987, control activities were carried out almost entirely through a central team based in the Institut National de Recherche en Santé Publique at Bamako in a vertical fashion. The full integration into the basic health services was retarded due to the drought and famine of the years 1983 to 1985 and other factors. The programme had been active in 136 villages located in the district of Bandiagara, the Office du Niger irrigation area, the Haute Vallée Baguineda irrigation area and the Sélingué dam zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

The costs of schistosomiasis control in a Sahelian country.

The cost of schistosomiasis control in Mali was calculated on the assumption that the programme is fully nationalized and organized using the experience gained during the past seven years. In order to expand the model and to extrapolate from actual cost that arose, activities have been standardized into preparatory, baseline and follow-up sample surveys for monitoring purposes and into blanket and case mass chemotherapy for interventions. Health education is contained in them as a component, sanitation is seen as a standard item linked at a fixed cost to the duration of the intervention phase. These activities were divided into months of action and their unit cost was calculated on the basis of requirements of field allowances, transport, drugs, expendable materials, and equipment. Fixed operational costs were calculated on a yearly basis for salaries, data processing and administrative overheads. Using these unit costs, and on the basis of present knowledge of the prevalence, epidemiology and efficiency of control, the need and quantity of activities and the probable duration of a programme to achieve the goals set in the national health plan were estimated. If a population of 180,000 persons in about 300 villages is to be included in a programme that has as target to diminish the prevalence of both, Schistosoma haematobium and S. mansoni to less than 20% and that plans to diminish the prevalence of intensive infections of both parasites to less than 5%, a total amount of DM 6.9 to 7.5 million over a period of seven to nine years are required.(ABSTRACT TRUNCATED AT 250 WORDS)

Costs and Cost Analysis↗

The distribution and spread of schistosomiasis in relation to water resources development in Mali.

Schistosomiasis prevalence is known to be high in water resources development projects. Data from 225 villages and 34,434 persons were used to compare areas with irrigation in agricultural development projects, villages in the vicinity of small dams, settlements around a large artificial lake, communities along the Niger river and places in savanna areas without any irrigation programmes. For ten villages the prevalence rates before and after the creation of the large lake were analysed. In irrigated areas the risk of schistosomiasis infection was found to be six times higher than in savanna villages. Even in the vicinity of natural bodies of water the prevalence of infection was three times less than in agricultural development projects employing irrigation. A pre-valence of intense infections above 5%, indicating that schistosomiasis requires specialized interventions was observed only in areas with irrigation. Therefore schistosomiasis may be considered a man-made health problem in rural Mali although the infection is endemic in the whole country.

Agriculture↗

Embryotoxicity of sex steroidal hormone combinations in nonhuman primates: I. Norethisterone acetate + ethinylestradiol and progesterone + estradiol benzoate (Macaca mulatta, Macaca fascicularis, and Papio cynocephalus).

Two sex steroid hormone combinations which have been used clinically as tests for detection of early pregnancy were examined for embryotoxic effects in macaques and baboons. Norethisterone acetate and ethinyl estradiol (NEA + EE) were orally administered to rhesus and cynomolgus monkeys and baboons at dosages ranging from one to 1,000 times the human dose equivalent (HDE) during days 20-50 of pregnancy. Progesterone and estradiol benzoate (P + EB) were delivered by two to six intramuscular injections to rhesus and cynomolgus monkeys between gestational days 20 and 35 at 0.1-25 X HDE. Fetuses were examined following cesarean section at 100 +/- 2 days (NEA + EE) or at term (P + EB). The results showed increased embryolethality over controls at 100-1,000 X HDE (NEA + EE) and at 10 and 25 X HDE (P + EB). Besides growth retardation, isolated cases of minor nongenital malformations were observed only in cynomolgus monkeys following treatment with both hormone combinations mainly at embryolethal dose levels and were considered spontaneous in nature. Virilization of female cynomolgus fetuses following NEA + EE treatment was manifested as two cases of clitoral enlargement in the 300 X HDE group and two cases of increased anogenital distance with reduced vaginal opening in the 1,000 X HDE group. The highest dose of NEA + EE was also maternally toxic, as two maternal deaths occurred at the end of the treatment period. One dead female cynomolgus fetus exposed to P + EB (10 X HDE) also exhibited masculinized external genitalia.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

Embryotoxicity of sex steroidal hormones in nonhuman primates: II. Hydroxyprogesterone caproate, estradiol valerate.

Two sex steroid compounds which have been used clinically for parenteral supportive therapy of pregnancy were examined for embryotoxic effects in rhesus and cynomolgus macaques. Hydroxyprogesterone caproate (HPC) alone or in combination with estradiol valerate (EV) were administered intramuscularly (i.m.) to pregnant monkeys at 7-day intervals between 20 and 146 days of gestation and fetuses were examined following cesarean section at 150 +/- 2 days. HPC alone was tested in both species at doses ranging from 0.01 X to 10 X the human dose equivalent (HDE); only rhesus monkeys were exposed to the HPC + EV combination at 0.1 X to 10 X HDE. Total embryolethality resulted following the administration of HPC alone and combined with EV at 1 X and 10 X HDE in rhesus monkeys; the level of abortions in cynomolgus monkeys exposed to HPC (0.1 X to 1 X HDE) was comparable to controls. A small number of nonspecific malformations and developmental variations observed in cynomolgus fetuses after HPC exposure were considered to be incidental findings. No anomalies were found in surviving rhesus monkey fetuses treated with HPC + EV. The results indicate that long-term in utero exposure to the progestin, HPC, alone or in combination with EV in rhesus and cynomolgus monkeys, is embryolethal but not teratogenic at doses up to ten times the human therapeutic dose.

17 alpha-Hydroxyprogesterone Caproate↗

Cost and effectiveness of different approaches to schistosomiasis control in Africa.

In order to analyze the cost-effectiveness of selected mass-chemotherapy, a model is used to compare the treatment of urinary schistosomiasis with metrifonate (3 dose regimen, fortnightly intervals) and praziquantel (one dose regimen). The model was applied to two situations. Setting I, based on experiences in the Peoples Republic of the Congo, assumes that the average distance between the project base and the area of intervention is 80 km, the other, setting II, based on the situation in Mali, assumes an average distance of 250 km. The aim of the project is defined as the reduction of a prevalence of 50% to less than 5% in the absence of reinfection. Using metrifonate, the cost per person rendered negative is calculated at DM 12.57 for the Congo and at DM 32.52 for Mali. Prevalence will be 4.2% after intervention. Using praziquantel, the costs are DM 8.36 and 11.47, respectively, and the prevalence reached at the end of the intervention will be 1.1%. The cost difference is mainly due to the high operational cost incurred by the 3 dose regimen. Once low prevalence levels are reached, operational cost further outweigh drug expenses.

Congo↗

Myocardial lactate extraction: multi-determined metabolic function.

Myocardial lactate production indicates anaerobic metabolism resulting from hypoxia or anoxia. Clinically, myocardial lactate extraction of less than 10% has also been used as an indicator of ischemia. Sixteen healthy young male volunteers underwent coronary sinus and aterial catheterization. A coronary sinus pacing catheter was used to obtain blood samples and increase the heart rate to twice the resting rate. Hemodynamic measurements and blood samples for lactate, free fatty acids and glucose were obtained at rest and during pacing. Seven of 16 sujects (44%) had lactate extraction of less than 10% at rest and/or at miximal pacing. No subject produced lactate. There was no correlation between myocardial lactate extraction and arterial glucose. However, lactate extraction correlated inversely with the arterial levels of free fatty acids (r = 0.67; p less than 0.01). In addition, a positive correlation was present between lactate extraction and the arterial lactate level (r = 0.78; p less than 0.01). In conclusion, myocardial lactate extraction is dependent on multiple metabolic parameters and any absolute value short of production cannot be considered abnormal.

Adolescent↗

[Detoxification of staphylococcal-enterotoxin B in water (author's transl)].

Staphylococcal enterotoxin B contaminated water has been detoxified with calcium hypochlorite used in the water treatment procedure which is available now in order to get drinking water from surface water in emergency cases. Changes in toxin-activity were measured serologically by agar-gel-immuno-precipitation as well as biologically by the "monkey-feeding test" with young macaca mulatta. With an initial concentration of 50 ppm chlorine in tap water resp. 200 ppm in native surface water concentrations of toxin up to 40 fold average emetic dose of rhesus monkey could be inactivated safely. It was pointed out an obvious conformity between precipitation test and monkey-feeding test. The clinical efficiency of SEB on rhesus monkeys has been investigated and discussed subsequently.

Animals↗

Protein versus energy in Papua New Guinea.

Protein deficiency has in the past generally been considered the main nutritional problem in the world. This has unduly detracted attention from the need for an adequate energy intake. Using surveys from different areas in Papua New Guinea, it is shown that deteiled investigations are needed to determine actual nutritional needs. In the Sepik a severe energy deficiency was found to be the principal problem. In some Highland areas, on the other hand, a distinct protein deficiency was observed, compounded by a low energy intake in the under 5-years age group. These distinct dietary patterns require a vastly different approach to nutrition intervention. It is shown that nutritional needs in the Sepik could in principle be met by increasing the availability of staple foods. An emphasis on protein would be a misdirected effort for most areas there. In the Highlands emphasis should be placed on legumes particularly those with a high energy value. This could close the protein gap and help to meet the caloric needs of young children.

Adolescent↗