Why sequence the genome of Mycobacterium tuberculosis?

Radical measures are required to prevent the grim predictions of the World Health Organisation for the deterioration of the global tuberculosis epidemic in the next century from becoming reality. Study of the nerve centre of the tubercle bacillus, its genome, by means of systematic deoxyribonucleic acid sequence analysis will provide a wealth of information about Mycobacterium tuberculosis that will undoubtedly fuel the next generation of research. In the coming year, this highly cost-effective approach will deliver an unprecedented amount of knowledge to catalyse the development of new, more efficient diagnostic tools and therapeutic interventions to detect, control and, ultimately, eliminate tuberculosis.     

Does the rennin inhibitor aliskiren offer promising novel opportunities in the treatment of cardiovascular diseases?

The renin-angiotensin-aldosterone system (RAAS) plays an important part in the pathogenesis of arterial hypertension and the complications it causes in organs (the heart, the circulatory system, the brain, the kidneys), heart failure and kidney diseases. Materials that block the most upstream point of the RAAS cascade (ACE inhibitors - ACEI, AT1,-receptor (AT1R) blockers, aldosterone receptor blockers) have greatly expanded our options in the treatment and primary and secondary prevention of cardiovascular and renal diseases. ACEI and AT1R blockers interrupt the normal feedback provided by the release of renin into the circulatory system from the kidneys. After they are applied the reactive increase in active circulating renin leads to increased creation of angiotensin I and angiotensin II and the subsequent return of aldosterone secretions to pre-treatment values ("escape" phenomenon). The possible negative effect of these intermediary products of an incomplete blockade of RAAS on organ complications lead to an effort to develop a material that could block the renin-angiotensin cascade at its first stage--i.e. a renin blocker. The first efforts with renin antibodies or peptide analogues of renin prosegments failed to satisify the basic requirements for long-term medication--effectiveness when used orally. In recent years the first non-peptidic, oral renin ihibitor providing sustained effects has been developed, aliskiren fumarate. Aliskiren reduces BP depending on the dose (50-300 mg/day) in monotherapy or in combination with hydrochlorothiazide. Aliskiren lowers plasma renin activity (PRA) and neutralises the activation of the RAAS triggered by hydrochlorothiazide. Ambulatory BP monitoring has shown that taking the medicine once a day has a 24-hour effect and its continued residence in the kidneys suggests renoprotective effects. The compound is in the third stage of clinical tests as a monotherapy or in combination for the treatment of hypertension. It has also been shown to have an influence on the regression of cardiac hypertrophy (Aliskiren in Left-Ventricular Hypertrophy trial - ALLAY), the treatment of heart failure (Aliskiren Observation of Heart Failure Treatment trial - ALOFT) and diabetic (Aliskiren in the Evaluation of Proteinuria in Diabetes trial - AVOID). In April 206, the FDA permitted the use of aliskiren in the USA for the treatment of high BP and it is currently undergoing testing in Europe. The renin inhibitor has minimal undesirable side effects, like AT1-receptor blockers. The slightly lower effectiveness ofaliskiren than AT1-receptor blockers in reducing BP is caused by the fact that it does not block bradykinins. It is recommended as a monotherapy for clinical use or in combination with other antihypertensive medicines for conditions with high levels of PRA including its rise after diuretics, ACEI and AT1-receptor blockers. Aliskiren could therefore be used primarily with young patients, Caucasians, persons with ACEI intolerance, and also in diseases where angiotensin II is involved in the pathogenesis and the secondary prevention of cardiovascular disease. It is also safe for persons with concurrent renal problems, because it is mainly removed by the liver without great interference with other materials. Like ACEI, the renin inhibitor has a vasodilatory effect which could potentially improve the elasticity of arteries. The medicine has the same limitations and contraindications as ACEI and AT1R blockers, such as pregnancy and bilateral renal artery stenosis. A definitive assessment of the benefit of this new class of medicines and its broad application in the treatment of cardiovascular and other diseases will require demonstration of its long-term effect on morbidity and mortality, as well as comparison with other RAAS blockers in long clinical studies, which represent research programmes lasting another 7 to 8 years.     

Does gastrojejunostomy for unresectable cancer of the gastric antrum offer satisfactory palliation?

BACKGROUND/AIMS: Gastrojejunostomy is the procedure of choice for patients with obstruction or stenosis of the gastric outlet or duodenum. However, the palliative benefits of this procedure in gastric cancer remain uncertain. Thus, the present study was performed to address this problem. METHODOLOGY: In the present study, 52 patients who had undergone gastrojejunostomy for unresectable cancer of the gastric antrum at Kitasato University Hospital and Kitasato University East Hospital in Japan between 1972 and 1994 were examined. RESULTS: The median survival time in these 52 patients was 5.0 months. The duration of palliation ranged from 0-13 months, with an average of 2.8 months. No significant difference between clinicopathologic factors and duration of palliation was found and location of tumor was the only independent prognostic factor (coefficient: 0.890; hazard ratio: 2.435). CONCLUSIONS: Although gastrojejunostomy for unresectable cancer of the gastric antrum is the procedure most often chosen at laparotomy, the palliative benefits of gastrojejunostomy do not sufficiently compensate for the patients' limited post-operative survival and quality of life.     

Do hemodynamics matter in the treatment of patients with submassive pulmonary emboli?

• The present article examines the right heart (RH) pressures of patients with submassive pulmonary embolism before and after catheter‐directed thrombolysis (CDT).
• 40% of patients had a low cardiac output (CI ≤1.8 L/min/m²) despite normally preserved blood pressure. After thrombolysis, CI increased and pulmonary artery pressures decreased.
• Although routine RH pressure measurements may help in CDT management and possibly serve as a surrogate outcome measure, more comprehensive pulmonary embolism trials are needed to solidify the role of hemodynamics in this setting.