Showing papers by "World Health Organization published in 1998"

Global Burden of Diabetes, 1995–2025: Prevalence, numerical estimates, and projections

Abstract: OBJECTIVE To estimate the prevalence of diabetes and the number of people with diabetes who are ≥20 years of age in all countries of the world for three points in time, i.e., the years 1995, 2000, and 2025, and to calculate additional parameters, such as sex ratio, urban-rural ratio, and the age structure of the diabetic population. RESEARCH DESIGN AND METHODS Age-specific diabetes prevalence estimates were applied to United Nations population estimates and projections for the number of adults aged ≥20 years in all countries of the world. For developing countries, urban and rural populations were considered separately RESULTS Prevalence of diabetes in adults worldwide was estimated to be 4.0% in 1995 and to rise to 5.4% by the year 2025. It is higher in developed than in developing countries. The number of adults with diabetes in the world will rise from 135 million in 1995 to 300 million in the year 2025. The major part of this numerical increase will occur in developing countries. There will be a 42% increase, from 51 to 72 million, in the developed countries and a 170% increase, from 84 to 228 million, in the developing countries. Thus, by the year 2025, >75% of people with diabetes will reside in developing countries, as compared with 62% in 1995. The countries with the largest number of people with diabetes are, and will be in the year 2025, India, China, and the U.S. In developing countries, the majority of people with diabetes are in the age range of 45–64 years. In the developed countries, the majority of people with diabetes are aged ≥65 years. This pattern will be accentuated by the year 2025. There are more women than men with diabetes, especially in developed countries. In the future, diabetes will be increasingly concentrated in urban areas. CONCLUSIONS This report supports earlier predictions of the epidemic nature of diabetes in the world during the first quarter of the 21st century. It also provides a provisional picture of the characteristics of the epidemic. Worldwide surveillance of diabetes is a necessary first step toward its prevention and control, which is now recognized as an urgent priority.

Allergen immunotherapy: Therapeutic vaccines for allergic diseases A WHO position paper

Abstract: The World Health Organization and various allergy, asthma, and immunology societies throughout the world met on January 27 through 29, 1997, in Geneva, Switzerland to write guidelines for allergen immunotherapy. Over the ensuing year, the editors and panel members reached a consensus about the information to include in the WHO position paper "Allergen immunotherapy: Therapeutic vaccines for allergic diseases." The historical term allergen extract was changed to allergen vaccine to reflect the fact that allergen vaccines are used in medicine as immune modifiers. The document summarizes the scientific literature and rationale for the appropriate use of such therapy to treat allergic rhinoconjunctivitis, allergic asthma, and Hymenoptera hypersensitivity. It also includes recommendations to improve safety, discusses new techniques being developed that may result in better efficacy and less risk, and offers recommendations for areas of additional and necessary research.

The global burden of disease, 1990-2020.

Abstract: The authors discuss the Global Burden of Disease Study and its role in setting priorities for improving international public health into the next century * .

Zoonotic tuberculosis due to Mycobacterium bovis in developing countries

Abstract: The World Health Organization (WHO) estimates that human tuberculosis (TB) incidence and deaths for 1990 to 1999 will be 88 million and 30 million, respectively, with most cases in developing countries. Zoonotic TB (caused by Mycobacterium bovis) is present in animals in most developing countries where surveillance and control activities are often inadequate or unavailable; therefore, many epidemiologic and public health aspects of infection remain largely unknown. We review available information on zoonotic TB in developing countries, analyze risk factors that may play a role in the disease, review recent WHO activities, and recommend actions to assess the magnitude of the problem and control the disease in humans and animals.

Global Surveillance for Antituberculosis-Drug Resistance, 1994–1997

Abstract: Background Drug-resistant tuberculosis threatens efforts to control the disease. This report describes the prevalence of resistance to four first-line drugs in 35 countries participating in the World Health Organization–International Union against Tuberculosis and Lung Disease Global Project on Anti-Tuberculosis Drug Resistance Surveillance between 1994 and 1997. Methods The data are from cross-sectional surveys and surveillance reports. Participating countries followed guidelines to ensure the use of representative samples, accurate histories of treatment, standardized laboratory methods, and common definitions. A network of reference laboratories provided quality assurance. The median number of patients studied in each country or region was 555 (range, 59 to 14,344). Results Among patients with no prior treatment, a median of 9.9 percent of Mycobacterium tuberculosis strains were resistant to at least one drug (range, 2 to 41 percent); resistance to isoniazid (7.3 percent) or streptomycin (6.5 percent) ...

The global impact of eye injuries

Abstract: Using data compiled from the ophthalmic literature and WHO's Blindness Data Bank, the available information on eye injuries from an epidemiological and public health perspective has been extensively reviewed. This collection of data has allowed an analysis of risk factors, incidence, prevalence, and impact of eye injuries in terms of visual outcome. However, most of the estimates are based on information from More Developed Countries (MDCs). The severity of eye injuries can be assessed through proxy indicators such as: (i) potentially blinding bilateral injuries; (ii) open-globe injuries; (iii) endophthalmitis; (iv) enucleation or (v) defined visual impairment. Major risk factors for ocular injuries include age, gender, socioeconomic status and lifestyle. The site where the injury occurs is also related to a risk situation. Available information indicates a very significant impact of eye injuries in terms of medical care, needs for vocational rehabilitation and great socioeconomic costs. The global patter...

Review of epidemiological studies on health effects from exposure to recreational water

Abstract: Results Most studies reported a dose-related increase of health risk in swimmers with an increase in the indicator-bacteria count in recreational waters. Relative risk (RR) values for swimming in polluted water versus clean water were often significant (usually 1.0 < RR < 3.0). The indicator microorganisms that correlate best with health outcomes were enterococci/faecal streptococci for both marine and freshwater, and Escherichia colt for freshwater. In both marine and freshwater, increased risk of gastro-intest inal symptoms was reported for water quality values ranging from only a few indicator counts/100 ml to about 30 indicator counts/100 ml. These values are low compared with the water qualities frequently encountered in coastal recreational waters. Studies which showed a higher threshold for increased risk and case-rate values in some countries may suggest immunity due to endemicity or a lower pathogen-to-indicator ratio in the natural waters. Conclusions The review strongly suggests a causal dose-related relationship between gastrointestinal symptoms and recreational water quality measured by bacterial indicator counts.

Protein Supplements Increase Serum Insulin-Like Growth factor-I Levels and Attenuate Proximal Femur Bone Loss in Patients With Recent Hip Fracture. A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: BACKGROUND Elderly persons who have osteoporotic hip fracture are often undernourished, particularly with respect to protein. Protein malnutrition may contribute to the occurrence and outcome of hip fracture. OBJECTIVE To investigate whether oral protein supplements benefit bone metabolism in patients with recent hip fracture. DESIGN 6-month, randomized, double-blind, placebo-controlled trial with a 6-month post-treatment follow-up. SETTING University orthopedic ward. PATIENTS 82 patients (mean age, 80.7 +/- 7.4 years) with recent osteoporotic hip fracture. Patients received calcium supplementation, 550 mg/d, and one dose of vitamin D, 200,000 IU (at baseline). INTERVENTION Protein supplementation, 20 g/d, or isocaloric placebo (among controls). MEASUREMENTS Bone mineral density, biochemical markers of bone remodeling, calciotropic hormone levels, biochemically evaluated nutritional and immunologic status, and muscle strength were measured every 6 months. RESULTS Compared with controls, patients who received protein supplements had significantly greater increases in serum levels of insulin-like growth factor-I (85.6% +/- 14.8% and 34.1% +/- 7.2% at 6 months; difference, 51.5 percentage points [95% CI, 18.6 to 84.4 percentage points]; P = 0.003) and an attenuation of the decrease in proximal femur bone mineral density (-2.29% +/- 0.75% and -4.71% +/- 0.77% at 12 months; difference, 2.42 percentage points [CI, 0.26 to 4.59 percentage points]; P = 0.029). Seven and 13 new vertebral deformities were found among patients who received protein supplements and controls, respectively (P > 0.2). Median stay in rehabilitation wards was shorter for patients who received protein supplements than for controls (33 days [CI, 29 to 56 days] and 54 days [CI, 44 to 62 days]; difference, 21 days [CI, 4 to 25 days]; P = 0.018). CONCLUSION Protein repletion after hip fracture was associated with increased serum levels of insulin-like growth factor-I, attenuation of proximal femur bone loss, and shorter stay in rehabilitation hospitals.

Global prevalence and incidence estimates of selected curable STDs.

Abstract: Objectives To update the WHO global and regional estimates of the prevalence and incidence of syphilis, gonorrhoea, chlamydia, and trichomoniasis. Methods Prevalence estimates for syphilis, gonorrhoea, chlamydia, and trichomoniasis were generated for each of the nine UN regions for males and females between the ages of 15 and 49 in 1995 based on an extensive review of the published and unpublished medical literature since 1985. Incidence estimates were based on the prevalence figures and adjusted to take into account the estimated average duration of infection for each disease in a particular region. The latter was assumed to depend upon a number of factors including the duration of infection in the absence of treatment, the proportion of individuals who develop symptoms, the proportion of individuals treated, and the appropriateness of treatment. Results In 1995 there were over 333 million cases of the four major curable STDs in adults between the ages of 15 and 49--12 million cases of syphilis, 62 million cases of gonorrhoea, 89 million cases of chlamydia, and 170 million cases of trichomoniasis. Geographically, the vast majority of these cases were in the developing world reflecting the global population distribution. Conclusions STDs are among the most common causes of illness in the world. Estimates of the global prevalence and incidence of these infections are limited by quantity and quality of data available from the different regions of the world. Improving global STD estimates will require more well designed epidemiological studies on the prevalence and duration of infection.

Levels and patterns of intrauterine growth retardation in developing countries.

Abstract: The aim of this paper is to quantify the magnitude and describe the geographical distribution of intrauterine growth retardation (IUGR) in developing countries We estimate that at least 137 million infants are born every year at term with low birth weight (LBW), representing 11% of all newborns in developing countries This rate is approximately 6 times higher than in developed countries LBW, defined as 20%) and LBW (> 15%) cut-off levels for triggering public health action, and that population-wide interventions aimed at preventing fetal growth retardation are urgently required

A review of sex differences in the epidemiology of tuberculosis

Abstract: Globally, the prevalence of infection with Mycobacterium tuberculosis is similar in males and females until adolescence, after which it is higher in males In industrialized countries in the middle of this century (1930s to 1950s), females aged 15 to 34 years had higher tuberculosis notification rates than males of the same age However, as notification rates in these countries decreased over time, rates in males became higher than those of females for all ages over 15 Present notification rates of both sexes combined in many developing countries are similar to those of industrialized countries in the middle of the century, although the sex and age pattern is similar to that in industrialized countries at present, with men's disease rates exceeding women's after the age of 15 These findings raise the possibility that cases of tuberculosis among women are being under-reported in developing regions This is supported by the results of a study comparing active and passive case-finding in which women with tuberculosis were under-notified to public health authorities when relying on passive case-finding In addition, epidemiological evidence from the pre-human immunodeficiency virus (HIV) era shows that young to early-middle-aged women progress from infection to disease with greater frequency than do men This elevated frequency of progression among women now coincides with a peak in HIV prevalence among women of the same age National Tuberculosis Programmes must assess possible sex differences that exist in their countries In addition, information about the risks of tuberculosis in younger women should be incorporated into maternal and child health, and HIV/AIDS programmes Further research comparing sex differences in tuberculosis rates, preferably using active as well as passive case-finding, would be necessary to determine whether young women are undernotified in developing countries

Low-level exposure to radiofrequency electromagnetic fields: Health effects and research needs

Abstract: The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the German and Austrian Governments jointly sponsored an international seminar in November of 1996 on the biological effects of low-level radiofrequency (RF) electromagnetic fields. For purposes of this seminar, RF fields having frequencies only in the range of about 10 MHz to 300 GHz were considered. This is one of a series of scientific review seminars held under the International Electromagnetic Field (EMF) Project to identify any health hazards from EMF exposure. The scientific literature was reviewed during the seminar and expert working groups formed to provide a status report on possible health effects from exposure to low-level RF fields and identify gaps in knowledge requiring more research to improve health risk assessments. It was concluded that, although hazards from exposure to high-level (thermal) RF fields were established, no known health hazards were associated with exposure to RF sources emitting fields too low to cause a significant temperature rise in tissue. Biological effects from low-level RF exposure were identified needing replication and further study. These included in vitro studies of cell kinetics and proliferation effects, effects on genes, signal transduction effects and alterations in membrane structure and function, and biophysical and biochemical mechanisms for RF field effects. In vivo studies should focus on the potential for cancer promotion, co-promotion and progression, as well as possible synergistic, genotoxic, immunological, and carcinogenic effects associated with chronic low-level RF exposure. Research is needed to determine whether low-level RF exposure causes DNA damage or influences central nervous system function, melatonin synthesis, permeability of the blood brain barrier (BBB), or reaction to neurotropic drugs. Reported RF-induced changes to eye structure and function should also be investigated. Epidemiological studies should investigate: the use of mobile telephones with hand-held antennae and incidence of various cancers; reports of headache, sleep disturbance, and other subjective effects that may arise from proximity to RF emitters, and laboratory studies should be conducted on people reporting these effects; cohorts with high occupational RF exposure for changes in cancer incidence; adverse pregnancy outcomes in various highly RF exposed occupational groups; and ocular pathologies in mobile telephone users and in highly RF exposed occupational groups. Studies of populations with residential exposure from point sources, such as broadcasting transmitters or mobile telephone base stations have caused widespread health concerns among the public, even though RF exposures are very low. Recent studies that may indicate an increased incidence of cancer in exposed populations should be investigated further.

Associations between wife-beating and fetal and infant death: impressions from a survey in rural India.

Abstract: Data from a 1993-94 survey of 1842 women 15-39 years old to compare women's autonomy in Uttar Pradesh and Tamil Nadu were analyzed to provide an exploratory, preliminary look at the effect of domestic violence on pregnancy outcomes. The sample included 894 women who had 1 or more pregnancies and were married 10 or fewer years. A socioeconomic profile reveals regional differences in women's decision-making authority and mobility but fewer differences in their ability to make purchases for themselves. Domestic violence affected 40-46% of the sample in Uttar Pradesh and 33-35% in Tamil Nadu and was widely accepted by women and by husbands. At least 27% of the sample reported pregnancy loss (including induced abortion), and 13% of the women who had a live birth experienced an infant death (16% from Uttar Pradesh and 10% from Tamil Nadu). Victims of domestic abuse were significantly more likely to experience fetal wastage or infant death regardless of religion or region of residence. This association survives logistic regression for other factors, such as education, age, number of children ever born, having worked for cash in the past year, number of consumer goods owned, religion, and autonomy. Strategies to combat domestic violence must deal with the root cause, which is women's powerlessness, as well as women's immediate needs. Community education programs must stress women's rights, the likely consequences of domestic violence, and the need to reverse social norms about male supremacy. Additional research is also needed on the sequelae of domestic violence and the attitudes of violent men. Language: en

Comparison of PCR and Microscopy for Detection of Cryptosporidium parvum in Human Fecal Specimens: Clinical Trial

Abstract: PCR technology offers alternatives to conventional diagnosis of Cryptosporidium for both clinical and environmental samples. We compared microscopic examination by a conventional acid-fast staining procedure with a recently developed PCR test that can not only detect Cryptosporidium but is also able to differentiate between what appear to be host-adapted genotypes of the parasite. Examinations were performed on 511 stool specimens referred for screening on the basis of diarrhea. PCR detected a total of 36 positives out of the 511 samples, while routine microscopy detected 29 positives. Additional positives detected by PCR were eventually confirmed to be positive by microscopy. A total of five samples that were positive by routine microscopy at Western Diagnostic Pathology but negative by PCR and by microscopy in our laboratory were treated as false positives. Microscopy therefore exhibited 83.7% sensitivity and 98.9% specificity compared to PCR. PCR was more sensitive and easier to interpret but required more hands-on time to perform and was more expensive than microscopy. PCR, however, was very adaptable to batch analysis, reducing the costs considerably. Bulk buying of reagents and modifications to the procedure would decrease the cost of the PCR test even more. An important advantage of the PCR test, its ability to directly differentiate between different Cryptosporidium genotypes, will assist in determining the source of cryptosporidial outbreaks. Sensitivity, specificity, ability to genotype, ease of use, and adaptability to batch testing make PCR a useful tool for future diagnosis and studies on the molecular epidemiology of Cryptosporidium infections.

Epidemiology of glucose intolerance and gestational diabetes in women of childbearing age.

Abstract: The available data suggest that the frequency of diabetes in pregnancy is highly variable, generally reflecting the underlying pattern of NIDDM in the particular population Different ethnic groups in the same environmental setting experience widely variable risk Impaired glucose tolerance is usually more prevalent than diabetes in women of childbearing age Maternal age, overweight, parity, and family history of diabetes all predispose to gestational diabetes mellitus (GDM) Incidence of GDM is low in the absence of risk factors, suggesting that selective screening programs may be cost-effective The worldwide epidemic of glucose intolerance predicted by the latest World Health Organization studies will undoubtedly increase the burden of GDM, especially in the developing countries

Research and training in tropical diseases.

Abstract: The work of WHO's Special Programme for Research and Training in Tropical Diseases since its inception in 1975 is outlined in the present article.

Re-emergence of monkeypox in Africa: a review of the past six years.

Abstract: Human monkeypox was first identified in 1970 in the Democratic Republic of the Congo. Extensive studies of this zoonotic infection in the 1970s and 1980s indicated a largely sporadic disease with a minority of cases resulting from person-to-person transmission, rarely beyond two generations. In August 1996, an unusually large outbreak of human monkeypox was reported, and cases continued through 1997 with peak incidence in August 1996, March 1997 and August 1997. Preliminary results from the field investigations in 1997 suggest a new epidemiological pattern where a majority of secondary cases result from person-to-person transmission, and a clinically milder disease. But there is preliminary laboratory evidence of a simultaneous outbreak of varicella in the same geographic region which will undoubtedly modify these preliminary results. Since smallpox was eradicated and vaccinia vaccination terminated in this region, the population of susceptible individuals has grown. The use of vaccination to protect the population at risk, however, must take into account HIV prevalence and the risk of generalized vaccinia when using vaccinia vaccine in populations where HIV is known to be present.

Health for all in the 21st century.

Abstract: This article introduces an issue of World Health Statistics Quarterly that summarizes the activities of working groups charged by the World Health Organization (WHO) with suggesting actions for a new holistic global health policy for the 21st century. After a brief introduction the article describes implementation of the global consultative process to develop the new policy and highlights 10 selected regional and global milestones. The article then 1) identifies the interlinked values that provide the basis for the policy 2) discusses the two major policy objectives of making health central to human development and building sustainable health systems and 3) considers aspects important to the selection of disease- and intervention-specific priorities for action. Next the article presents the 10 global health targets and concludes by noting that achieving health for all will depend upon creation of a wide array of partnerships as well as the taking of decisive actions by the WHO and governments.

A comparative cost analysis of newborn screening for classic congenital adrenal hyperplasia in Texas

Abstract: OBJECTIVE: Human immunodeficiency virus (HIV) infection associated with injecting drug use has been reported in at least 98 countries and territories worldwide There is evidence that new epidemics are emerging in different regions, including Eastern Europe, Latin American, and the eastern Mediterranean The authors provide a global overview of the situation of HIV infection associated with injecting drug use and responses that have been implemented in various developing and transitional countries METHODS: Although there has been extensive documentation of the extent and nature of of HIV infection associated with injecting drug use in many developed countries and the various interventions implemented in those countries, there is very limited information on the situation in developing and transitional countries This chapter brings together information from a broad range of sources, including published literature; "gray" or "fugitive" literature; data collected by the World Health Organization (WHO), the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations International Drug Control Programme (UNDCP); personal communications; and direct observation by the authors The authors have traveled extensively to a wide range of developing and transitional countries and have accessed information not readily available to the international research community RESULTS: A wide range of HIV prevention strategies targeting injecting drug users (IDUs) has been implemented in developing countries and countries in transition Interventions include opioid substitution pharmacotherapy, needle syringe exchange and distribution, condom and bleach distribution, outreach to IDUs, peer education programs, and social network interventions In some communities, completely new models of intervention and service delivery have developed in response to specific local needs and limitations CONCLUSIONS: Although empirical data may currently be lacking to demonstrate the effectiveness of may HIV prevention programs targeting IDUs in developing and transitional countries, there is evidence that innovative HIV prevention initiatives are being implemented and sustained in a wide range of sociocultural settings

The globalization of public health, I: Threats and opportunities.

Abstract: The globalization of public health poses new threats to health but also holds important opportunities in the coming century. This commentary identifies the major threats and opportunities presented by the process of globalization and emphasizes the need for transnational public health approaches to take advantage of the positive aspects of global change and to minimize the negative ones. Transnational public health issues are areas of mutual concern for the foreign policies of all countries. These trends indicate a need for cross-national comparisons (e.g., in the areas of health financing and policy development) and for the development of a transnational research agenda in public health.

Standardized tuberculosis treatment outcome monitoring in Europe. Recommendations of a Working Group of the World Health Organization (WHO) and the European Region of the International Union Against Tuberculosis and Lung Disease (IUATLD) for uniform reporting by cohort analysis of treatment outcome in tuberculosis patients

Abstract: Consensus-based recommendations have been developed by a Working Group of the World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) on uniform reporting of tuberculosis (TB) treatment outcome data in countries in Europe. The main purpose of treatment monitoring is to find out how many of the potential infectious TB patients notified were declared cured at the end of treatment. Following the uniform case definitions as defined in 1996, emphasis is placed on cohort analysis of definite cases of pulmonary TB. The Working Group recommends using a minimal set of six mutually exclusive categories of treatment outcome: cure, treatment completed, failure, death, treatment interrupted, and transfer out. More detailed subsets may be chosen. Treatment outcome is expressed as a percentage of the total number of cases notified. Analysis should be separate for new and retreatment cases. Treatment outcome data have to be collected at the local level and passed on to regional and national authorities on an ongoing basis. Evaluation of treatment results becomes, preferably, an inbuilt component of national monitoring of programme performance. Because of the long duration of treatment, it is recommended that analysis is carried out in the first quarter of the calendar year that follows a full year after the last patient was enrolled. Feedback is essential. Treatment outcome results should become an inseparable part of the annual report on tuberculosis.

Containment of antibiotic resistance

Abstract: The emergence and spread of antimicrobial resistance is a growing problem in both developing and developed countries and threatens to become a global crisis. A strategy for the containment of resistance needs to be developed, applied and evaluated. Such a strategy should focus on improving rational use of antimicrobials and reducing opportunities for spread of resistant organisms. Implementation requires education and training, surveillance, technical developments, research, and statutory regulation.

The IL-4 rapidly produced in BALB/c mice after infection with Leishmania major down-regulates IL-12 receptor beta 2-chain expression on CD4+ T cells resulting in a state of unresponsiveness to IL-12.

Abstract: Within 1 day of infection with Leishmania major, susceptible BALB/c mice produce a burst of IL-4 in their draining lymph nodes, resulting in a state of unresponsiveness to IL-12 in parasite-specific CD4+ T cells within 48 h In this report we examined the molecular mechanism underlying this IL-12 unresponsiveness Extinction of IL-12 signaling in BALB/c mice is due to a rapid down-regulation of IL-12R beta2-chain mRNA expression in CD4+ T cells In contrast, IL-12R beta2-chain mRNA expression was maintained on CD4+ T cells from resistant C57BL/6 mice The down-regulation of the IL-12R beta2-chain mRNA expression in BALB/c CD4+ T cells is a consequence of the early IL-4 production In this murine model of infection, a strict correlation is shown in vivo between expression of the IL-12R beta2-chain in CD4+ T cells and the development of a Th1 response and down-regulation of the mRNA beta2-chain expression and the maturation of a Th2 response Treatment of BALB/c mice with IFN-gamma, even when IL-4 has been produced for 48 h, resulted in maintenance of IL-12R beta2-chain mRNA expression and IL-12 responsiveness The data presented here support the hypothesis that the genetically determined susceptibility of BALB/c mice to infection with L major is primarily based on an up-regulation of IL-4 production, which secondarily induces extinction of IL-12 signaling

Expression Cloning of a Novel Estrogenic Mouse 17β-Hydroxysteroid Dehydrogenase/ 17-Ketosteroid Reductase (m17HSD7), Previously Described as a Prolactin Receptor-Associated Protein (PRAP) in Rat

Abstract: 17β-Hydroxysteroid dehydrogenases/17-ketosteroid reductases (17HSDs) modulate the biological activity of certain estrogens and androgens by catalyzing reductase or dehydrogenase reactions between 17-keto- and 17β-hydroxysteroids. In the present study, we demonstrate expression cloning of a novel type of 17HSD, chronologically named 17HSD type 7, from the HC11 cell line derived from mouse mammary gland. The cloned cDNA, 1.7 kb in size, encodes a protein of 334 amino acids with a calculated molecular mass of 37,317 Da. The primary structure contains segments characteristic of enzymes belonging to the short-chain dehydrogenase/reductase superfamily. Strikingly, mouse 17HSD type 7 (m17HSD7) shows 89% identity with a recently cloned rat protein called PRL receptor-associated protein (PRAP). The function of PRAP has not yet been demonstrated. The enzymatic characteristics of m17HSD7 and RT-PCR-cloned rat PRAP (rPRAP) were analyzed in cultured HEK-293 cells, where both of the enzymes efficiently catalyzed conver...

New tools for the diagnosis of tuberculosis: the perspective of developing countries.

Abstract: New diagnostics for tuberculosis are urgently needed to replace or facilitate acid-fast bacilli (AFB) microscopy for the identification of smear-positive cases, and to improve the diagnosis of AFB smear-negative cases. These need to be appropriate for use in low income countries. Tests to replace or facilitate AFB microscopy must offer improvements to this test, including increased sensitivity, speed, ease of use, and safety. Products to improve the identification of smear-negative cases should focus on the diagnosis of patients with paucibacillary pulmonary disease, including children and human immunodeficiency virus (HIV) infected persons, and those with extrapulmonary forms of tuberculosis.

Development of a clinical prediction model for an ordinal outcome: the World Health Organization Multicentre Study of Clinical Signs and Etiological Agents of Pneumonia, Sepsis and Meningitis in Young Infants

Abstract: This paper describes the methodologies used to develop a prediction model to assist health workers in developing countries in facing one of the most difficult health problems in all parts of the world: the presentation of an acutely ill young infant. Statistical approaches for developing the clinical prediction model faced at least two major difficulties. First, the number of predictor variables, especially clinical signs and symptoms, is very large, necessitating the use of data reduction techniques that are blinded to the outcome. Second, there is no uniquely accepted continuous outcome measure or final binary diagnostic criterion. For example, the diagnosis of neonatal sepsis is ill-defined. Clinical decision makers must identify infants likely to have positive cultures as well as to grade the severity of illness. In the WHO/ARI Young Infant Multicentre Study we have found an ordinal outcome scale made up of a mixture of laboratory and diagnostic markers to have several clinical advantages as well as to increase the power of tests for risk factors. Such a mixed ordinal scale does present statistical challenges because it may violate constant slope assumptions of ordinal regression models. In this paper we develop and validate an ordinal predictive model after choosing a data reduction technique. We show how ordinality of the outcome is checked against each predictor. We describe new but simple techniques for graphically examining residuals from ordinal logistic models to detect problems with variable transformations as well as to detect non-proportional odds and other lack of fit. We examine an alternative type of ordinal logistic model, the continuation ratio model, to determine if it provides a better fit. We find that it does not but that this model is easily modified to allow the regression coefficients to vary with cut-offs of the response variable. Complex terms in this extended model are penalized to allow only as much complexity as the data will support. We approximate the extended continuation ratio model with a model with fewer terms to allow us to draw a nomogram for obtaining various predictions. The model is validated for calibration and discrimination using the bootstrap. We apply much of the modelling strategy described in Harrell, Lee and Mark (Statist. Med. 15, 361-387 (1998)) for survival analysis, adapting it to ordinal logistic regression and further emphasizing penalized maximum likelihood estimation and data reduction.