Measuring tuberculosis burden, trends, and the impact of control programmes.

The targets for tuberculosis control, framed within the United Nations' Millennium Development Goals, are to ensure that the incidence per head of tuberculosis is falling by 2015, and that the 1990 prevalence and mortality per head are halved by 2015. In monitoring progress in tuberculosis control, the ultimate aim for all countries is to count tuberculosis cases (incidence) accurately through routine surveillance. Disease prevalence surveys are costly and laborious, but give unbiased measures of tuberculosis burden and trends, and are justified in high-burden countries where many cases and deaths are missed by surveillance systems. Most countries in which tuberculosis is highly endemic do not yet have reliable death registration systems. Verbal autopsy, used in cause-of-death surveys, is an alternative, interim method of assessing tuberculosis mortality, but needs further validation. Although several new assays for Mycobacterium tuberculosis infection have recently been devised, the tuberculin skin test remains the only practical method of measuring infection in populations. However, this test typically has low specificity and is therefore best used comparatively to assess geographical and temporal variation in risk of infection. By 2015, every country should be able to assess progress in tuberculosis control by estimating the time trend in incidence, and the magnitude of reductions in either prevalence or deaths.

[Burn shock fluid resuscitation and hemodynamic monitoring]. / Flüssigkeitstherapie und hämodynamisches Monitoring im Verbrennungsschock.

Successful surgical and intensive care treatment of severely burned patients requires adequate prehospital management and fluid resuscitation adjusted to individual needs of the patient. Burn shock fluid resuscitation is now predominantly performed utilizing crystalloid solutions. Whenever possible, colloid solutions should not be given in the first 24 h after burn injury. The rate of administration of resuscitation fluids should maintain urine outputs between 0.5 ml/kg per h and 1 ml/kg per h and mean arterial pressures of >70 mmHg. Extended hemodynamic monitoring can provide valuable additional information, if burn resuscitation is not proceeding as planned or volume therapy guided by these typical vital signs is not attaining the desired effect. We recommend this in patients with TBSA burns of >30%. Inhalation injuries, pre-existing cardiopulmonary diseases, or TBSA burns of >50% definitely require extended hemodynamic monitoring during burn shock resuscitation. The Swan-Ganz catheter or less invasive transcardiopulmonary indicator dilution methods can be utilized to assess hemodynamic data.

Fibroblast growth factor signaling and basement membrane assembly are connected during epithelial morphogenesis of the embryoid body.

Fibroblast growth factors and receptors are intimately connected to the extracellular matrix by their affinity to heparan sulfate proteoglycans. They mediate multiple processes during embryonic development and adult life. In this study, embryonic stem cell-derived embryoid bodies were used to model fibroblast growth factor signaling during early epithelial morphogenesis. To avoid redundancy caused by multiple receptors, we employed a dominant negative mutation of Fgfr2. Mutant-derived embryoid bodies failed to form endoderm, ectoderm, and basement membrane and did not cavitate. However, in mixed cultures they displayed complete differentiation induced by extracellular products of the normal cell. Evidence will be presented here that at least one of these products is the basement membrane or factors connected to it. It will be shown that in the mutant, collagen IV and laminin-1 synthesis is coordinately suppressed. We will demonstrate that the basement membrane is required for embryoid body differentiation by rescuing columnar ectoderm differentiation and cavitation in the mutant by externally added basement membrane proteins. This treatment induced transcription of Eomesodermin, an early developmental gene, suggesting that purified basement membrane proteins can activate inherent developmental programs. Our results provide a new paradigm for the role of fibroblast growth factor signaling in basement membrane formation and epithelial differentiation.

Evaluating the impact of tuberculosis control: number of deaths prevented by short-course chemotherapy in China.

BACKGROUND: Tuberculosis (TB) is still amongst the most important causes of human morbidity and mortality, killing approximately two million people each year. Standard short-course chemotherapy (SSCC) can rapidly control illness and dramatically reduce the chance of death, but the impact of treatment has rarely been evaluated in these terms. METHOD: We developed a mathematical model that makes use of routinely-collected data to calculate the number of deaths directly prevented by TB treatment (i.e. excluding those due to reduced transmission). The method was applied to the world's largest TB control programme covering over 500 million people in 12 provinces of China. RESULTS: Counties which had been enrolled in the programme since 1991 were, by 1997, preventing at least 46% (37-56%) of the TB deaths that would otherwise have occurred. If replicated across the entire TB control programme area, this would amount to 30 000 (range 26 000-59 000) deaths directly prevented each year. CONCLUSIONS: Short-course chemotherapy has substantially reduced TB mortality in half of China. The analytical method described here could be applied to TB control operations in many other countries, and should help to quantify the true burden of tuberculosis alleviated by SSCC.

The early operation for acute severe cholecystitis: the Riedel paper; an introduction and translation.

BACKGROUND: For acute cholecystitis in the latter 19th century and early 20th century, the diagnosis was difficult and the management not defined. METHODS AND RESULTS: Bernhard Riedel of Jena in Germany documented his patients, analysed his results, and described his method of cholecystectomy. CONCLUSIONS: Riedel advocated early operation for acute cholecystitis when the conditions were favourable, as for acute appendicitis. He stressed the importance of good lighting, an experienced surgeon and trained assistants. He advocated conservative treatment for minor cholecystitis (biliary colic) until the diagnosis was certain, followed by elective cholecystectomy to reduce the risk of subsequent acute cholecystitis or bile duct stones. Caution was advised when analysing previous statistics, to ensure appropriate patient comparison.

Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance and Monitoring Project.

OBJECTIVE: To estimate the risk and prevalence of Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB) incidence, prevalence, and mortality, including disease attributable to human immunodeficiency virus (HIV), for 212 countries in 1997. PARTICIPANTS: A panel of 86 TB experts and epidemiologists from more than 40 countries was chosen by the World Health Organization (WHO), with final agreement being reached between country experts and WHO staff. EVIDENCE: Incidence of TB and mortality in each country was determined by (1) case notification to the WHO, (2) annual risk of infection data from tuberculin surveys, and (3) data on prevalence of smear-positive pulmonary disease from prevalence surveys. Estimates derived from relatively poor data were strongly influenced by panel member opinion. Objective estimates were derived from high-quality data collected recently by approved procedures. CONSENSUS PROCESS: Agreement was reached by (1) participants reviewing methods and data and making provisional estimates in closed workshops held at WHO's 6 regional offices, (2) principal authors refining estimates using standard methods and all available data, and (3) country experts reviewing and adjusting these estimates and reaching final agreement with WHO staff. CONCLUSIONS: In 1997, new cases of TB totaled an estimated 7.96 million (range, 6.3 million-11.1 million), including 3.52 million (2.8 million-4.9 million) cases (44%) of infectious pulmonary disease (smear-positive), and there were 16.2 million (12.1 million-22.5 million) existing cases of disease. An estimated 1.87 million (1.4 million-2.8 million) people died of TB and the global case fatality rate was 23% but exceeded 50% in some African countries with high HIV rates. Global prevalence of MTB infection was 32% (1.86 billion people). Eighty percent of all incident TB cases were found in 22 countries, with more than half the cases occurring in 5 Southeast Asian countries. Nine of 10 countries with the highest incidence rates per capita were in Africa. Prevalence of MTB/HIV coinfection worldwide was 0.18% and 640000 incident TB cases (8%) had HIV infection. The global burden of tuberculosis remains enormous, mainly because of poor control in Southeast Asia, sub-Saharan Africa, and eastern Europe, and because of high rates of M tuberculosis and HIV coinfection in some African countries.