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Biomedical subjects

M Tanner

Publications and source records attributed to M Tanner.

At least 217 records · Page 12Linked to original sources

Ultrasound in schistosomiasis--a critical look at methodological issues and potential applications.

This is the concluding paper of a series on the use of diagnostic ultrasound in the investigation of schistosomiasis. An earlier chapter in the volume discussed standardization of the methodology, and of recording, when ultrasound is used for epidemiological purposes. The present paper discusses some other requirements for obtaining ultrasound data which can be used to make valid comparisons within and between studies. Since there is an inherent variability in the interpretation of results from ultrasound images, quality control and the training of observers are both essential. It is also necessary to collect more information for each endemic setting about possible concomitant diseases which might lead to misinterpretation of results. Furthermore, the analysis of the data obtained must be uniform if valid comparisons are to be made. A final section considers applications of ultrasonography in research and control programmes. The technique should make it possible to obtain a better understanding of the extent and distribution of organ damage due to schistosomal infection in different geographical areas, and of the way in which lesions develop over time, or may regress in response to treatment. Since ultrasonography will always remain a relatively labour-intensive and expensive technique, it is necessary to establish, in different settings, how its findings correlate with the results of parasitological, serological and biochemical tests. The ultimate aim is to build up a body of information on the potential of ultrasonography, in combination with other procedures, in the various possible approaches to morbidity control.

Clinical Protocols↗

Distribution of repetitive and non-repetitive circumsporozoite protein epitopes on Plasmodium falciparum sporozoites and immunochemical characterization of human malaria antisera.

The presence and distribution of circumsporozoite protein (CSP) epitopes located in the repetitive and non-repetitive regions were studied in three Plasmodium falciparum strains, NF54, IFA5 and IFA6. It was found by immunofluorescence, Western blotting and immunoelectron microscopy that mAbs to epitopes of the repetitive domaine bound similarly to the CSP of all three strains. MAbs to epitopes of the flanking regions yielded either some strain differences (mAbs to the C-terminal end), or reacted only in immunofluorescence tests on whole sporozoites (mAbs to the N-terminal end). Human sera from an area endemic for malaria, two of them positive in ELISA on (NANP)40 and two negative, were tested for their reactivity with epitopes of the flanking regions of the CSP. The presence of antibodies to such epitopes could be demonstrated by Western blots and immunocytochemistry independent of the reactivity of the sera to recognize (NANP)40. All tested bound to salivary gland tissues but not to their secretory product in immunocytochemical experiments.

Amino Acid Sequence↗

Ha-ras polymorphisms in epithelial ovarian cancer.

Unusual restriction fragment length polymorphisms (RFLPs) of the Ha-ras locus have been found in DNA from leukocytes and tumor tissue of cancer patients. To determine whether rare alleles would be observed frequently in patients with ovarian cancer, Ha-ras RFLPs were studied in DNA from 42 different ovarian epithelial tumors and from the peripheral blood leukocytes of 76 normal individuals. Four common, seven intermediate, and seven rare alleles were detected overall. Similar fractions of rare alleles were found in DNA from ovarian cancers and from the peripheral blood of normal individuals. Thus, the frequency of unusual Ha-ras RFLPs did not distinguish patients with ovarian cancers from apparently healthy individuals.

Alleles↗

Gastrin induction of histamine release from primary cultures of canine oxyntic mucosal cells.

Using enzyme-dispersed canine oxyntic mucosal cells, we studied regulation of histamine release from fractions in which mast cells were largely removed by density gradient. Histamine-like immunoreactivity was demonstrated using peroxidase-anti-peroxidase immunohistochemistry. Histamine-containing cells in the small cell elutriator fractions (SCEF) were further separated by albumin step density gradients. Approximately 2.5% of cells in the low density fraction (LDF) contained histamine-like immunoreactivity; this fraction was largely depleted of the more dense mast cells (0.5%). These two fractions were cultured for 48-64 h on a Matrigel substrate. The cell content of histamine and release into the medium were measured by radioenzymatic assay. Gastrin, carbachol, and forskolin increased histamine release from the LDF. The induction of histamine release by gastrin was evident within 5 min and was sustained for at least 60 min. The response to gastrin was dose dependent between concentrations of 10(-11) and 10(-8) M. In contrast, in the mast cell-enriched SCEF, basal release was higher and gastrin was without effect; however, concanavalin A stimulated and epinephrine inhibited histamine release indicating that histamine-release mechanisms were intact in this fraction. Our methods provide a preparation of low density oxyntic mucosal histamine cells that demonstrate gastrin-responsive histamine release; we speculate that enterochromaffin-like cells account for this gastrin response.

Animals↗

Coordinate elevation of serum markers in ovarian cancer but not in benign disease.

Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (greater than 35 U/ml) were observed in 91%, CA 15-3 (greater than 30 U/ml) in 57%, TAG 72 (greater than 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer.

Alkaline Phosphatase↗

[Clinical aspects and epidemiology of cryptosporidiosis in immunocompetent children].

A prospective case-control study was performed in urban and periurban areas of Basel to investigate the epidemiology of Cryptosporidium sp., an intestinal coccidian parasite. 455 children with diarrhoea, who attended paediatric and general practices, participated in the study. Oocysts of the parasite were detected in stool specimens of 21 (4.6%) patients using auramine-fluorescence and modified Ziehl-Neelson staining. Another ten infected people were found during separate investigations of outbreaks in a Kindergarten and in two families. Serial stool stains were performed to determine the period of oocyst shedding. The median duration of diarrhoea was six days and ranged from 1 to 25 days. In contrast, shedding of oocysts of Cryptosporidium sp. lasted for 12.5 days and was significantly longer than the period of diarrhoea (p = 0.02). Compared with control patients suffering from diarrhoea of other origin, respiratory symptoms were significantly (p = 0.02) more frequent in children with cryptosporidiosis (42% vs 13%). In comparison with healthy controls, prior contact with a person suffering from diarrhoea and travel to a Mediterranean country were the most important risk factors for cryptosporidiosis. An illustrative case is described in detail. It is concluded that cryptosporidial infection of the respiratory tract may also occur in immunocompetent children. The possibility of a long period of oocyst shedding is important for the planning of hygiene measures both in individuals and public health.

Adolescent↗

Community-based questionnaires and health statistics as tools for the cost-efficient identification of communities at risk of urinary schistosomiasis.

Self-administered questionnaires, distributed by existing administrative channels to village party chairmen, head-teachers and schoolchildren, showed good diagnostic performance for the qualitative assessment of urinary schistosomiasis endemicity. At a cost 34 times below that of the WHO-recommended parasitological screening strategy, the schoolchildren's questionnaire allowed the screening of 75 out of 77 schools of a rural Tanzanian district in six weeks, and the exclusion of schools not at high risk for urinary schistosomiasis with over 90% confidence. The headteacher and party questionnaires made it possible to assess the perceived importance of a spectrum of diseases and symptoms, among which was schistosomiasis. The priority rank of schistosomiasis control was strongly correlated with the prevalence rate of the disease in the community. The questionnaires also looked for the prioritization of health among other community issues and thus contributed important information for planning at district level. Standardized monthly disease reports, sent by all primary health services, were also analysed. They allowed a zonal schistosomiasis endemicity classification.

Adolescent↗

Rapid, low-cost, two-step method to screen for urinary schistosomiasis at the district level: the Kilosa experience.

The operational and diagnostic performance of a two-step method for the cost-effective screening of urinary schistosomiasis was investigated in the Kilosa District of east-central Tanzania. In the first step a simple questionnaire was administered to 15,073 primary schoolchildren by their class teachers over a 4-week period. The answers to the questionnaires had a high negative predictive value for schistosomiasis, and this permitted the safe exclusion of schools where the risk of the disease was low. In the second step, the head-teachers of the 49 high-risk schools and of 26 low-risk schools were instructed on the use of reagent sticks to detect haematuria. Each head-teacher then performed this test on 80 children selected at random in their schools (5750 children were screened within 6 weeks). Crosschecks of the results in 18 schools confirmed the reliability of the head-teachers' testing and their findings were therefore used to prepare an epidemiological map of the district and to arrange for treatment of positive children. This two-step approach relied entirely on the existing school system and permitted screening of a rural district of area 15,000 km2 (population, 350,000) over a 4-month period at a cost of only US$3000.

Child↗

The value of questionnaires aimed at key informants, and distributed through an existing administrative system, for rapid and cost-effective health assessment.

The requirement for a careful interview set-up in the classical key-informant approach considerably limits its extension to a larger scale. However, the administration of simplified questionnaires entirely through an existing administrative system can provide an alternative approach and become a valuable tool for fast and cost-efficient community health assessment. This methodology relies on a well-structured and working administrative system, and is restricted to health problems that are well and distinctly perceived by community members. It gives mainly qualitative results, and can therefore be used to single out rapidly and inexpensively high-risk and low-risk units. The biomedical screening of a large number of negative units can thus be avoided, and available resources can be concentrated on the positive ones. An extensive validation of this "indirect" approach by standardized biomedical measurements is a crucial requirement for its usefulness. In addition to biomedical information, questionnaires also provide information on the perception and prioritization of community health problems, which is of interest for health planning.

Child↗

Childhood vaccination in a squatter area of Manila: coverage and providers.

In 1988 a vaccination coverage cluster survey was performed in a squatter area of Manila, Philippines. 24% of the surveyed children (aged 1-2 years) were fully immunized and 19% not immunized. 60% of the children were vaccinated through private organization. The dropout rates of these children were significantly lower than those of the children vaccinated through governmental agencies. This suggests that services have to be provided by agencies that are based in the squatter area. Efforts for improved coverage should focus on lowering the high dropout rates and strengthening coordination between the governmental and the various private health agencies that provide vaccination service in this squatter area. The survey also indicated approaches to strengthening collaboration between different service providers.

Child Health Services↗

Symptoms and transmission of intestinal cryptosporidiosis.

Cryptosporidium spp are a cause of diarrhoea in toddlers. Symptoms and routes of transmission were investigated in a prospective case-control study in the city and surroundings of Basel, Switzerland. Twenty one (4.6%) out of 455 children with diarrhoea who attended paediatric and general practices from June to September 1988 were positive for cryptosporidium. The mothers of each case, of two controls with diarrhoea of another origin, and of two healthy controls were interviewed with a standardised questionnaire. In comparison with controls with diarrhoea of another origin, respiratory symptoms were significantly more frequent in children with cryptosporidiosis: eight of 19 (42%) compared with five of 38 (13%). In comparison with healthy controls, preceding contact with a person suffering from diarrhoea was associated with the greatest relative risk for cryptosporidiosis, followed by travel in a Mediterranean country. Transient cryptosporidial infection of the respiratory tract may be common in immunocompetent children. In the area investigated person to person transmission may account for most cases.

Case-Control Studies↗

Training of village health workers in Tanzania; a comparison of two approaches.

The paper compares the costs of training for two groups of Village Health Workers (VHWs) in Tanzania, where the policy of developing a system based on Primary Health Care principles will require the training of more than 16,000 VHWs during the next decade. In the Kilombero District, one group of VHWs was trained according to the guidelines of the National Programme of the Ministry of Health, and another group followed the training programme of the Kilombero Project, based on the Swiss Tropical Institute Field Laboratory. The training scheme of the Kilombero project cost almost 80% less for one VHW, largely because it depended on on-the-spot training by local staff. The results of a first investigation of the efficacy of the training were encouraging; a long-term evaluation is in progress. The curricula for the two programmes also differed; the Kilombero programme had shorter blocks of theory, interspersed with supervised practical work, and introduced curative medicine earlier in the course. The advantage and disadvantages of the two programmes are discussed, not only in terms of cost but also in terms of their efficacy in training VHWs who will be motivated, efficient and accepted by the community.

Community Health Workers↗

Antibody responses to Plasmodium falciparum and P. vivax sporozoites in areas with stable and unstable malaria.

Availability of synthetic and recombinant peptides reproducing the repetitive regions of the circumsporozoite (CS) proteins of Plasmodium falciparum and P. vivax has allowed the development of assays for the detection of specific antibodies and of potential subunit vaccines. Knowledge of the immune responses to malaria sporozoites is a prerequisite for the optimal design of a sporozoite antigen-based vaccine. Studies carried out in areas with stable P. falciparum malaria (United Republic of Tanzania) have shown that antibodies against the synthetic peptide (NANP)40 increase as a function of age. Cluster analysis revealed marked inter-household variation of the anti-sporozoite antibody response, despite comparable risks of exposure to infectious bites. An age-related prevalence of anti-P. vivax sporozoite antibodies has been observed in an area of Sri Lanka with unstable malaria, using a 45-mer synthetic peptide reproducing a defined sequential array of the two main 9-mer variants of the P. vivax CS protein. In this area, anti-(NANP)40 antibodies became detectable after the first epidemic of P. falciparum malaria. Interestingly, their prevalence also increased with age. Since this population had not been exposed to P. falciparum malaria for at least 10 years previously, one can suggest that anti-sporozoite antibodies reflect the relative exposure to infectious bites in the different age groups, and, in turn, the transmission of the disease. This can be particularly useful in areas where entomological indices of transmission tend to be unreliable because of the low vectorial capacity and wide fluctuations in vector densities.

Age Factors↗

Measurement of schistosomiasis-related morbidity at community level in areas of different endemicity.

Among the indicators of schistosomiasis morbidity currently used in control programmes, ultrasound has been found to be a safe, non-invasive and efficient technique for detecting schistosomiasis-related lesions and for assessing the effect of treatment on their resolution. Three case-studies from East Africa, in areas of different endemicity for Schistosoma haematobium, using ultrasound are described and their results related to indirect measurements of the disease (e.g., haematuria, egg counts). This review reveals that cross-sectional ultrasound surveys can be used to quickly assess subsamples of populations in areas of different endemicity, in order to make decisions about sampling strategies in control programmes. The association between the intensity of infection and urinary tract abnormalities is reviewed and evaluated. One case study provides information on the resolution of S. haematobium-related uropathy after treatment; this information is crucial in order to maintain low levels of morbidity in a community. The role of ultrasound is further discussed, particularly as a tool to complement and validate indirect morbidity control measurements. The validation of such indirect measurements for use as a basis for public health decisions is important because they can be carried out by existing health care services in many areas.

Adolescent↗

[From tropical medicine to medicine in the tropics--priorities in the control of transmissible diseases].

The major health problems of developing countries are still caused by communicable diseases. Along with the raise of the living standards and substantial urbanization processes in many parts of the third world, a shift towards chronic noncommunicable diseases of adults, which are costly to control, can be expected. Health priorities are not only determined by the biomedical view assessing morbidity and mortality patterns, but also by the ranking of perceived health problems, symptoms and signs by the population concerned. Incorporating these aspects greatly increases the acceptance of health interventions and can stimulate community involvement. The recent advances in the field of diagnosis, therapy, prophylaxis as well as in the implementation of primary health care imply the need to emphasize the operational aspects of intervention programmes such as diagnostic accuracy, compliance of providers and users and coverage. These elements are the crucial determinants of the community effectiveness of any technology and will provide the cornerstones for sustainability besides careful evaluation and monitoring of a health intervention.

Communicable Disease Control↗

Preoperative serum tumor-associated antigen levels in women with pelvic masses.

Preoperative sera were assayed for tumor-associated antigens CA 125, TAG 72, and CA 15-3 in 100 women with pelvic masses. Serum CA 125 levels were elevated above 65 U/mL in 83% of 42 patients with ovarian malignancies, in 58% of 12 patients with nonovarian malignancies, and in 17% of 46 patients with benign pelvic masses. Elevations of TAG 72 and CA 15-3 levels occurred less frequently in all groups of patients. Serum CA 125 levels distinguished most effectively between patients with malignant pelvic masses and those with benign pelvic masses, having a sensitivity of 78% and a specificity of 83% at a threshold level of 65 U/mL. When comparing 33 patients with epithelial ovarian carcinomas to 46 patients with benign masses, the CA 125 level alone yielded a sensitivity of 88% with a specificity of 83%. Coordinate elevations of CA 125 (above 65 U/mL) and TAG 72 (above 10 U/mL) or CA 15-3 (above 30 U/mL) distinguished ovarian epithelial carcinomas from benign masses with a sensitivity of 73% and a specificity of 98%, which improved to 81 and 100%, respectively, among patients over 50 years of age. Given the marked increase in specificity observed with this panel of three serum tumor-associated antigens, use of multiple markers might facilitate screening for ovarian carcinoma and appropriate referral of patients with pelvic masses for cytoreductive operations.

Antigens, Tumor-Associated, Carbohydrate↗