[Fatal familial insomnia--a rare differential diagnosis in dementia]. / Letale familiäre Insomnie--Eine seltene Differenzialdiagnose in der Demenzabklärung.

Fatal familial insomnia (FFI)--first reported in 1986--is a hereditary prion disease with autosomal-dominant inheritance, caused by a missense-mutation at codon 178 of the prion-protein gene (PRNP) on chromosome 20. A methionine-valine polymorphism at codon 129 of PRNP expresses different phenotypes. The clinical features of FFI are characterized by a disrupted sleep-wake cycle with resulting fluctuations of vigilance, autonomic hyperactivation, myoclonus, motor abnormalities and by cognitive disturbances. The age of onset is between middle to late adulthood (51 +/- 7.1 years), disease duration varies between 8 and 72 months (18.4 +/- 17.3 months) and is ultimately fatal. We report the case of a 57-year-old man with a diagnosed FFI by molecular-genetic investigation who suffered from increasing memory- and sleep-disturbance as well as physical restlessness and impotence for 9 months. Clinical features were motor symptoms, generalized myoclonus and hyperactivity with reduced attention and concentration. The neuropsychological findings were a severe disturbance of attention and memory as well as incipient deficits in executive functions. The cranial MRI and repeated EEG were normal; in detailed laboratory tests including CSF no abnormalities were detected. The clinical course was characterized by rapid decline of the motor and cognitive skills; the patient died 15 months after onset. Histological analysis showed the typical changes of FFI (spongiform changes at hippocampus and regio entorhinalis, severe gliosis in the thalamus and mild deposits of abnormal prion protein).

The role of research in a technical assistance agency: the case of the 'German Agency for Technical Co-operation'.

Technical assistance agencies have a sustainable impact on the health systems of the countries they are operating in. As well as policy-makers at the national level, technical assistance agencies see themselves confronted that their interventions should be based on evidence, usually meaning the results of research. This study has the aim to analyse role of research in the implementation of technical assistance. We sent a questionnaire to all health project managers of the 'German Agency for Technical Co-operation' and performed a qualitative case study in one of the health projects. Forty-seven of 80 (58.8%) of the questionnaires were completed and sent back. The managers considered publications of International Organisations (IOs), scientific articles and local research as most important for their work. The case study showed application problems in the daily work. Research use not only depends on the relevance of the data but also on analytical skills, linguistic barriers and technical access to research by the potential users. The role of knowledge and information management has to be clearly defined in an organisation of technical assistance. The specific needs at the different levels have to be analysed so that skills and resources can be allocated adequately.

Lack of neuroprotection by an ACTH (4-9) analogue. A randomized trial in patients treated with vincristine for Hodgkin's or non-Hodgkin's lymphoma.

PURPOSE: This randomized, double-blind, placebo-controlled study evaluates the effect of the corticotropin (4-9) analogue Org 2766 on the neuropathy-free interval in patients receiving vincristine (VCR) containing chemotherapy for Hodgkin's or non-Hodgkin's lymphoma. PATIENTS AND METHODS: In a longitudinal design, 150 patients were evaluated by interview, neurological examination, and neurophysiological techniques. Patients with an expected cumulative VCR dose of at least 8 mg received a single dose of Org 2766 or placebo before and after each intravenous VCR injection and 3-4 weeks after cessation of VCR. The final patient assessment was performed 1 month after discontinuation of study medication. The neuropathy-free interval as the major end point of this study was defined as the first occurrence of bilateral paresthesias and expressed as the administered cumulative VCR dose. This bi-center study represents the largest cohort of patients monitored for the effect of an ACTH-analogue on VCR neurotoxicity. RESULTS: A total of 147 patients were included in the final analysis. No significant differences were observed between the placebo and actively treated group for the major and secondary endpoints. CONCLUSION: Contrary to a single previous pilot study in patients receiving VCR-based chemotherapy, in our study the ACTH (4-9) analogue Org 2766 did not provide protection from VCR-induced neuropathy.

Attitude of women in western Uganda towards pre-packed, unit-dosed malaria treatment for children.

In the context of a larger study on malaria related knowledge, attitudes, practices and beliefs in western Uganda 813 women aged 15-49 years were shown a sample of a pre-packed, unit-dosed malaria treatment for children, its use was explained and attitudes of the women were investigated. Of all women, 90.5% (86% urban, 92% rural) said they would prefer the pre-packed over the conventional type of treatment and 93.9% of these were willing to pay between 0.17 (rural) and 0.29 (urban) US dollars more for this treatment. Two-thirds (67.8%) thought that they would not have to ask their spouses before making a decision on the kind of treatment and 59.5% said they would rather stock the treatment at home than buy it when a child gets sick. The most mentioned reason for preferring pre-packs was their safety and cleanliness, while ease of application, dosing and compliance were secondary. We conclude that pre-packed, unit-dosed malaria treatment is accepted by the caretakers of children in the area studied and that they readily understand and accept its concept. This indicates a high potential for this approach to improve the home management of malaria fevers and reduce malaria-related morbidity and mortality if adequate coverage can be achieved and if the intervention is embedded into an appropriate programme of behavioural change communication and provider training.

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.

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.

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).

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.

Resistance in vivo of Plasmodium falciparum to co-trimoxazole in western Uganda.

In the context of the 'integrated management of childhood illnesses' (IMCI) programme the World Health Organization recommends treating children in malarious areas presenting with fever and respiratory symptoms with co-trimoxazole. In order to verify its effectiveness in uncomplicated Plasmodium falciparum malaria we carried out a study in vivo in western Uganda: 180 children under 5 years old were enrolled and treated with 40/8 mg/kg/d co-trimoxazole over 5 d, and 159 could be followed on days 3, 7 and 14. Effectiveness of treatment was found to be significantly different in various parts of the study area. In Bundibugyo District, bordering République Democratique du Congo (Zaire), 59.1% (39/66) of children were clinically cured after 14 d and 56.1% were parasitologically cured. In the east of Kabarole District (43 children), the figures were 76.7% and 65.1%, respectively. In western Kabarole (50 children) the rates were 96.0% and 90.0%, respectively. We conclude that, in view of the high level of clinical failures in parts of the study area, co-trimoxazole should not be used in the IMCI programme for combined treatment of malaria and pneumonia in the region. Assessment of therapeutic effectiveness of antimalarial drugs needs to consider the microepidemiology of resistance.

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.

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.

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.

Predictors of nutritional status among participants in a rice irrigation scheme in Kenya.

PIP: Over the short term, irrigation projects often negatively influence the nutrition and health of target populations through factors which are either directly or indirectly related to the development process of the project. A cross-sectional survey of 187 households in, and 168 households from surrounding areas of the Mwea-Tebere rice irrigation scheme (MTIS) in Kenya was conducted to study the individual and social characteristics associated with childhood malnutrition. The cultivated area in the MTIS grew from 7000 acres in 1965 to 31,000 in 1987. However, during the same period, the population grew from 16,000 to 40,000, with most or all of the tenants' children continuing to live with their parents and overcrowding scheme villages. The proportion of under-fives who had weight/age, weight/height, and height/age indices under -2 standard deviations of the WHO-NCHS reference values was higher among MTIS residents than among nonresidents. Maternal education was the only variable significantly associated to all indicators of malnutrition used in the study. the area of residence, the number of resident dependents upon proceeds from the same farm, recent episode of diarrhea, child's age, mother's occupation, mother's age, type of caretaker of the child in the mother's absence, and mother's marital status were associated to one or two indicators of malnutrition. The level of maternal education is significantly higher at MTIS than off-scheme. However, the influence of MTIS' crowding and poor sanitation conditions is strong enough to make the nutritional status of preschool children worse within the scheme. Maternal education should be promoted, facilities provided to improve sanitary conditions, and programs launched to control population density in on-scheme villages.^ieng

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.

Pattern of sexually transmitted diseases in a Malagasy population.

BACKGROUND: Data concerning the spectrum and antimicrobial susceptibility of STDs in Madagascar are scarce. OBJECTIVES: Improvement of STD patient management in Madagascar. GOAL OF THE STUDY: Assessment of the spectrum of STDs and improvement of therapy. STUDY DESIGN: Etiologic study of 400 patients (169 men, 231 women) under consultation at the major STD service in Antananarivo for one or more of the STD syndromes, urethral discharge, cervicovaginal discharge, genital ulcers, or condylomata according to a fixed diagnostic schedule. RESULTS: Of genital ulcers, syphilis accounted for 46%, lymphogranuloma venereum for 24%, chancroid for 16%, and herpes for 1%. Of the syphilis cases, 51% presented as condyloma lata. Discharge was found in 124 men and 210 women. Counting concomitant infections separately, gonorrhea occurred in 69% of the men and 20% of the women with discharges, chlamydia infection in 42% and 52%, trichomoniasis in 9% and 31%, candidiasis in 12% and 30%. Bacterial vaginosis was found in 37% of the women with discharges. In 32% of male and 71% of female gonorrhea cases, there was concurrent chlamydia infection. Infection with HIV 1 or 2 was not detected. Determination of the antibiotic susceptibility of Neisseria gonorrhoea revealed high efficacy of ampicillin, ciprofloxacin, and spectinomycin; but frequent resistance to tetracycline and cotrimoxazole. CONCLUSIONS: High priority should be given to the management of infections with chlamydia and with Treponema pallidum as well as to educational measures to increase awareness of genital ulcer disease.

PIP: Between November 1992 and April 1993, interviews were conducted with 400 patients (169 men, 231 women) aged 14-52 years at the sexually transmitted disease (STD) clinic of the Institut d'Hygiene Sociale in Antananarivo, Madagascar, to determine the pattern of STDs and to improve treatment of the leading STDs. The 400 patients presented with 434 syndromes. 124 men had urethral discharge. 210 women had cervicovaginal discharge. 43 men and 18 women had genital ulcers. Clinicians could not establish a diagnosis in 33 patients. 171 patients had more than one infection. Chlamydia infection was the most common infection associated with another STD (gonorrhea in 22% of men and 11% of women with discharge, trichomoniasis in 2.4% of men and 13% of women, candidiasis in 1.6% of men and 9% of women, and bacterial vaginosis in 15% of women with discharge). Gonorrhea was the most common etiology for male discharge (69%) while chlamydia infection was for female discharge (52%). Women with discharge were more likely than men with discharge to have chlamydia infection (52% vs. 42%), trichomoniasis (30% vs. 9%; p 0.00001), and candidiasis (32% vs. 12%; p 0.00001). 37% of women with discharge had bacterial vaginosis. Chlamydia infection was the most common STD in this population (45%). 32% of male and 71% of female gonorrhea cases also had chlamydia infection. 70 patients had syphilis. 36 of them had secondary stage syphilis. No one had HIV-1 or HIV-2 infection. The most efficacious antibiotics for gonorrhea were ampicillin, ciprofloxacin, and spectinomycin (100% susceptibility). 31% and 26% of isolates were susceptible to tetracycline and cotrimoxazole, respectively. Public facilities in Madagascar do not have the capabilities to diagnosis chlamydia, resulting in many untreated chlamydia cases. These findings stress the need to improve combined treatment of gonorrhea and chlamydia infection and for educational efforts to increase awareness of genital ulcer disease.

[Obstetrics in the Third World]. / Geburtshilfe in der Dritten Welt.

PIP: According to the World Health Organization, between 1980 and 1985 the total fertility rate was 2.0 in the wealthy countries and 4.1 in the less developed countries. The highest rate was found in Kenya with 8.1. The risk of maternal mortality in connection with pregnancy and childbirth was 1/10,000 in Northern Europe, but 1/21 in Africa. Every year about 500,000 women die because of complications before, during, or after delivery. The maternal mortality rate (30/100,000 live births in Europe) is still 500-800/100,000 in the developing countries, although Tanzania has succeeded in cutting its rate from 450/100,000 to 170/100,000. The main causes of maternal mortality are: 1) unrecognized obstructed labor, 2) postpartum bleeding that could be managed by massaging the uterus, administration of oxytocin or by the manual removal of the placenta, 3) postpartum infections that could be treated by timely administration of antibiotics, 4) preeclampsia that could be detected and treated, and 5) abortion complications requiring effective treatment. Among indirect causes of death is anemia: 66% of pregnant women in developing countries are anemic, compared to 14% in industrialized countries. So far the cause of the reduction of partial immunity against malaria parasites in primiparas has not been explained. A significant percentage of deaths (11-47%) can be traced to unqualified and negligent personnel, especially in the slums and rural areas. Only 52% of deliveries are attended by well-trained health personnel, although in 10% of pregnancies complications arise. Young age is another factor: in 1989 in Tanzania the first pregnancy occurred on the average at age 17.6 years compared to 27 years in England. In the beginning of the 1990s there were an estimated 3 million HIV-infected women, therefore maternal mortality as a consequence of AIDS is going to increase. In high prevalence areas the population growth rate will decline from 3% to 2.4%. Traditional birth attendants could be trained and used effectively to reduce maternal mortality by 3-11% as part of a functioning referral system.^ieng

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.

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)