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Biomedical subjects

R Korte

Publications and source records attributed to R Korte.

At least 19 recordsLinked to original sources

Spontaneous pulmonary neoplasms in cynomolgus monkeys (Macaca fascicularis)--a report of two cases.

The first lung tumour-bearing animal was a 7 years and 3 months old cynomolgus monkey. Microscopic examination revealed a neoplastic mass under the pleura that consisted of squamous islands with little keratinization, multifocal mineralization of the keratin, inflammatory cell and foreign body-type giant cell infiltration. It was classified as pulmonary squamous cell carcinoma. In a second cynomolgus monkey (2 years and 10 months old) a lung mass was observed at necropsy. Microscopically the tumour consisted of numerous islands of cartilage with glandular structures lined by a cuboidal epithelium between them. The neoplasm was classified as cartilaginous hamartoma.

Animals↗

Reliability of malaria microscopy in epidemiological studies: results of quality control.

To assess the interrater reproducibility of malaria microscopy in epidemiological studies, 711 thick blood films from population-based surveys were randomly selected and reread by 4 experienced microscopists. Sample estimates of the prevalence of P. falciparum infection, geometric mean parasite density and the proportion of samples above various parasite density cut-off levels were almost identical in the routine and quality control readings. Differences were, however, encountered in the sample estimates for gametocyte ratio, proportion of mixed infection and average density index. In all three cases the quality control result was significantly higher than the routine evaluation. On the level of the individual slide there was good interrater agreement for the presence of P. falciparum infections (Kappa index kappa = 0.79) which was even better when parasite densities between 4 and 100/microl were excluded (kappa = 0.94). With respect to the assessment of parasite density, a high level of disagreement was found. While the mean difference between the two readings was not different from 0, the second reading was between 0.12 and 10 times that of the first. However, the level of disagreement significantly fell with increasing parasite densities. Thus malaria microscopy is very reliable for the estimation of parasite ratios and geometric mean parasite densities within and between studies as long as the same methodology is used, but tends to underestimate the gametocyte ratio and proportion of mixed infections. Care must be taken, however, when individual parasite density is related to other explanatory variables, due to the high degree of variability in the parasite enumeration.

Animals↗

Development of the optokinetic system in macaque monkeys.

Optokinetic nystagmus in response to horizontal movement of a whole field random dot pattern was measured in infant macaque monkeys from the first week to about 5 months after birth using electrooculography. During monocular and binocular viewing conditions stimulus velocities were varied between 10 and 120 degrees/s. Monocular stimulation in the temporonasal direction yielded slow phase gain of the optokinetic system which was relatively constant for a given stimulus velocity over the whole period of observation. Gain during nasotemporal stimulation was also clearly present but significantly lower at early stages and increased during further development. This asymmetry of monocular horizontal optokinetic nystagmus (OKN) clearly depended on the stimulus velocity. At lower stimulus velocities (10-20 degrees/s) OKN was largely symmetrical at 2-5 weeks of age. At higher stimulus velocities (40 degrees/s) symmetry was reached at about 12 weeks of age or even much later (80-120 degrees/s).

Aging↗

Financially independent primary health care drug supply system in Cameroun.

The drug supply system in the North-west Province of Cameroun differs from 'simple' health financing projects in three important respects. Firstly, the system does not promote drug sales for cofinancing purposes but aims at supporting the prescribers to provide better medical care, and patients' access to the most essential drugs at fair prices. Secondly, the project guarantees equal prices and services throughout the Province regardless of distance from the central warehouse and sales at a given location. Thirdly, along with the revolving fund-financed drug supply system, a community-based legal framework has been established. Built-in management alert mechanisms helped the project resist common causes of collapse such as uneconomic behaviour and political interference. The drug supply system has gained full independence from subsidies and external authorities. Its strong community participation promotes good governance.

Cameroon↗

Retinoid teratogenicity in the macaque: verification of dosing regimen.

To further define teratogenicity associated with 13-cis-retinoic acid (13-cis-RA) in the cynomolgus monkey, the drug was orally administered on three different treatment regimens. Experiment (Exp.) 1 (2.5 mg/kg/day, gestational day [GD] 12-27, n = 11) investigated the teratogenicity of a single daily dose of 13-cis-RA administered shortly after embryo implantation. Pharmacokinetic sampling was done to determine retinoid profiles on the first (GD12) and last (GD27) days of treatment. Exposure to 13-cis-RA during early organogenesis in Exp. 2 (2.5 mg/kg/day, GD20-27, and 2 x 2.5 mg/kg/day, GD28-30, n = 5) investigated the potential adverse effects of 13-cis-RA on the developing limb. The use of multiple doses of 13-cis-RA in Exp. 3 (2 x 2.5 mg/kg/day, GD26-27, n = 5) investigated the necessity of double dosing on the induction of retinoid embryopathy in the macaque. Malformations of retinoid target organs as well as embryolethality were most prevalent when single daily doses of 13-cis-RA were administered during pre- and early organogenesis in Exp. 1. Moreover, multiple doses on GD26-27 failed to induce any manifestation of abnormal development in Exp. 3. These results confirm that the lowest observed adverse effect level (LOAEL) in macaques is 2.5 rather than 5.0 times greater than that observed in human pregnancies. Exposure during forelimb development (GD20-30) in Exp. 2 was unsuccessful in inducing defects of this skeletal region, although defects in several retinoid target organs (i.e., cerebellum and internal ear) were present, indicating that a teratogenic threshold was achieved. Pharmacokinetic analysis of 13-cis-RA and its metabolites on GD12 and 27 in Exp. 1 showed considerable exposure to the administered drug and its 4-oxo-metabolite. In contrast, the exposure to all-trans-RA was negligible. The results support the use of a specific treatment schedule in early gestation in the macaque as the most appropriate model for characterizing the teratogenic potential of retinoids in humans.

Abnormalities, Drug-Induced↗

The future of tropical medicine in Europe. Opportunities for intersectoral cooperation.

The author provides a brief history of tropical medicine and describes how it has evolved since its creation at the end of the 19th century. The author proposes a working definition of tropical diseases, including their geographical distribution and their socioeconomic conditions prevailing in these regions. Currently tropical medicine is in danger of fragmenting into a number of subspecialties or being absorbed into the subspecialties of other medical sectors. The broad interdisciplinary nature of tropical medicine may be its weakness, but also its particular strength. The effective interplay between four major areas of work makes it different from other specialties. These are biomedical sciences, medical care, epidemiology and the social sciences. This intersectoral approach should also lead to stronger synergisms between scientists in Europe and institutions in the South.

Europe↗

Urinary tract morbidity due to Schistosoma haematobium infection in Mali.

A total of 824 Malian villagers in a region endemic for Schistosoma (S.) haematobium were examined clinically, parasitologically and by abdominal ultrasound. Systematic schistosomicidal treatment had never been applied to this population. Prevalence of S. haematobium infection ranged from 77% in adolescents to 51% in adults older than 40 years. Intensity of infection was generally mild, 91% of all patients excreting less than 100 ova/10 ml urine. Bladder wall enlargement and irregularities, bladder masses, pseudopolyps and dilation of the upper urinary tract were found ultrasonographically in about one third of infected individuals. Bladder lesions were more frequent in children than in adults and correlated with the intensity of infection in younger age groups only. Hydronephrosis was rare (7 of 824) and never seen in uninfected individuals. Prevalence of urinary tract pathology dropped significantly with age (P < 0.001) and was lowest in patients older than 40 years. Logistical regression identified age and infection as independent parameters affecting the prevalence of urinary tract pathology (P < 0.001). We conclude that Schistosoma haematobium infection causes substantial morbidity in children and younger adults. The reduction of urinary tract morbidity with age despite a considerable prevalence of infection in older age groups suggests spontaneous resolution during adulthood in most cases.

Adolescent↗

Estimating the number of HIV transmissions through reused syringes and needles in the Mbeya Region, Tanzania.

OBJECTIVE: HIV infection attributable to medical injections is suspected to be low, although case-control studies have not provided definite results. This study aims to determine the number of HIV infections caused by the reuse of syringes and needles in the Mbeya Region, Tanzania. METHODS: The direct identification or detection of HIV in syringes and needles under field conditions was not appropriate, therefore a surrogate marker consisting of two components for possible HIV transmission was used: insufficient sterilization, and blood remaining from a previous patient. The assumption was that HIV infection can only occur if both markers are positive. Samples were collected in nine health-care facilities. All syringes and needles prepared for use in these facilities were collected without prior notification. The samples were rinsed and the resulting fluid was cultured for bacteria. Traces of blood were detected by urine stick test for haemoglobin volumes > 0.0015 microliters. RESULTS: Bacterial contamination was found in 32.8% of the total 1219 syringes and needles; 67% was caused by improper handling of the equipment after sterilization. Blood was detected in 12.5% of the samples. In the following three sampling strata, both contamination criteria were positive either on the syringe or the needle: wards/outpatient departments (OPD), 1.39%; laboratories, 7.45%; expanded programme on immunization (EPI), < 0.1%. We calculated that from 1.1 million patients injected in wards/OPD in any 1 year, fewer than 13 become infected, in laboratories fewer than 12 (160,000 blood-taking procedures), and less than one child in the EPI (850,000 vaccinations). CONCLUSION: With an established AIDS intervention programme supporting the health system, less than 0.4% of the total annual incidence of 4500-8500 is attributable to medical injections in the Mbeya Region.

Case-Control Studies↗

Importance of early exposure to 13-cis retinoic acid to induce teratogenicity in the cynomolgus monkey.

The teratogenic potential of 13-cis retinoic acid (13-cis RA) was further assessed in cynomolgus macaques (Macaca fascicularis) following exposure to two different regimens during the preorganogenic period to determine the influence of time of treatment on the 13-cis RA malformation syndrome established previously (Hummler et al., Teratology, 42:263-272, 1990). In experiment (Exp) 1, 13-cis RA was orally administered once daily (2.5 mg/kg) on gestational day (GD) 16-25 and twice daily (2 x 2.5 mg/kg) on GD 26-27. In Exp 2, the same oral dose was administered once daily on GD 10-20 and twice daily on GD 21-24. Although the ear was affected at about the same incidence (6/9, 67%) in Exp 1 as previously reported, the defects were less severe. Except for hypoplastic vermis of the cerebellum (2/9, 22%), no other defects were seen. In Exp 2, the teratogenic effects of 13-cis RA on the craniofacial skeleton (1/9, 11%), external ear (5/9, 56%), and heart (2/9, 22%) were similar to that reported by Hummler et al.; however, no thymus or cerebellar malformations were observed. Analysis of the three different treatments (GD 16-27 in Exp 1, GD 10-24 in Exp 2, and GD 10-27 in Hummler et al.) suggests that the sensitive periods in the macaque are 1) craniofacial skeleton and heart GD 10-24, 2) thymus and cerebellum > GD 24, and 3) external ear GD 16-24, although the defects are less severe following the shorter exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

Primary health workers in north east Brazil.

One approach to providing primary health care in developing countries is to implement programs which rely on minimally trained primary health workers (PHWs). Originally, such programs were primarily designed for rural areas with intact social structures--where a community--based PHW could easily establish a link between the community and the conventional health services (delivery programs). However, faced with increasing migration of the rural population to urban centers in developing countries, the present need for elementary health care in urban slums raises the question of whether PHWs can also provide health assistance to the population there. This paper deals with the issue of whether PHWs in North East Brazil can improve health care delivery and the health situation of the poor population in rural and urban areas. The investigations covered both PHWs and the population. Questionnaire-guided interviews and participant observation were used as research tools. The conclusion is drawn that the PHW-program there has succeeded, if the PHWs have increased the coverage of the health service delivery and also the level of health-related knowledge, attitudes and practices (KAP) in the population--although with significant differences between rural and urban areas (higher coverage and higher KAP in rural areas). The quality of training and supervision and the characteristics of the area and local framework were also found to influence the quality of the work (performance) of the PHWs.

Brazil↗

Financing health services in Sub-Saharan Africa: options for decision makers during adjustment.

The financing of health services has become an increasingly critical and urgent issue in many developing countries particularly in Sub-Saharan Africa. This paper analyses options available to policy makers. The possible effects and side effects of strategies are described based on the experience from different countries. The dangers of simplistic solutions are discussed. A cautious approach is recommended taking into consideration the lessons learned in other regions accompanied by a careful ongoing evaluation especially regarding the ability to pay of the poorer sections of the population. Providing for equity in health care should be an important guiding principle. It therefore appears to be necessary to find an appropriate mix of public and private sector interventions with elements of cost-sharing for services and drugs, insurance schemes and more efficient use of available resources.

Africa↗

Risk of transfusion-associated HIV transmission in Kinshasa, Zaire.

Between 5 March and 12 April 1990, we assessed transfusion practices and the risk of transfusion-associated HIV transmission in all the hospitals and medical centres in Kinshasa, Zaire. Of the 733 hospitals and medical centres surveyed, 62 (8.5%) transfuse blood. Of 3741 units of blood transfused in February 1990, 1045 (27.9%) were not screened for HIV infection. Eighteen out of 62 centres (29%) received HIV test kits on a regular basis. Twenty of the centres (32.3%) recorded HIV test results. Major blood group cross-matching was done by 9.7% (six out of 62) of the centres. Bacteriological results indicated contamination in 17% (four out of 23) of stocked blood units, 6.4% (four out of 62) of solutions for disinfections, and 22% (13 out of 59) of sterilized instruments (possessed by 59 centres only). Transfusion practices in Kinshasa are associated with considerable health risks. The establishment and appropriate supervision of HIV screening facilities should be integrated into primary health-care programmes in order to increase safe transfusions in Kinshasa.

Academic Medical Centers↗

Strategies to maintain health in the Third World.

International cooperation with Third World countries aims at reducing the high morbidity and mortality of the population to a tolerable level. The main health problems are caused by poverty. Thus, the range of diseases in tropical countries can be explained more readily by the socio-economic situation than solely by the climate. Health services, in Africa in particular, have had to reduce drastically their budgets in the last ten years and now have only approximately 1/1000th of the funds usually available in industrialised countries. High population growth reduces the resources available per head, increases infection potential and worsens living conditions. Control strategies must take account of these circumstances in order to achieve the required sustained effect within the framework of primary health care. The example of the control of several infectious diseases, such as schistosomiasis, pneumonia, malaria and AIDS, is used to show that control programmes can be effective but, in the current conditions, can hardly be maintained without outside support. In the future, diseases caused by environmental problems and new life styles as a result of industrialization, urbanization and slum growth will move dramatically into the foreground.

Acquired Immunodeficiency Syndrome↗

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↗