Manual MGIT™ system for the detection of Mycobacterium tuberculosis: insights from a high TB burden setting.

OBJECTIVE: To evaluate the diagnostic performance of manual MGIT™ (MMGIT) compared to the gold standard, Löwenstein-Jensen (LJ), in the diagnosis of pulmonary tuberculosis (TB) in a high-burden setting. METHODS: Individuals with suspected TB enrolled in parallel diagnostic trials during 2007-2011 were included. Two samples were obtained from each patient and inoculated into MMGIT and LJ medium. Diagnostic tests were performed, and the incremental yield of a second test and time to detection (TTD) were calculated. Analyses were performed per patient and per sample. Gold standard was based on LJ culture. RESULTS: In the per patient and per sample analysis, we evaluated 1436 patients and 4142 samples. The sensitivity and specificity for smear and MMGIT per sample were respectively 89.9%/92.2% and 97.1%/98.9%. Contamination was observed in 1.4% of samples on MMGIT. The mean TTD (days) was 11.8 for MMGIT and 22.9 for LJ. The sensitivity and specificity for smear and MMGIT per patient were respectively 89.9% and 92.2% and 97.1% and 98.3%. A second MMGIT culture had an incremental yield of 1.6%. CONCLUSIONS: MMGIT has high sensitivity and specificity, regardless of smear result, with a 50% reduction in TTD compared to LJ. These features make MMGIT an acceptable TB diagnostic method for use in resource-limited settings.

Regression of coronary artery disease: the role of plaque biology.

Research has lead to a better understanding of the pathophysiology and history of atherosclerotic heart disease, which has reached epidemic proportions in industrialized countries in this century. Atherosclerosis should be seen as a chronic, protracted process that encompasses complex and dynamic interactions between cellular, biochemical, and biophysical factors in the microcosmos of the arterial vessel wall and blood circulation. In this context, the ultimate consequences of this disease process, namely coronary artery disease, must be seen as the "tip of the iceberg." The most dramatic manifestation of coronary artery disease, the acute coronary syndrome, usually occurs as the result of different forces and factors, which lead to abrupt plaque disruption, rupture, and vessel thrombosis. In contrast, the genesis of this atherosclerotic lesion is a slow process. Despite considerable experimental clinical evidence accrued during the past decade, atherosclerosis remains a complex pathophysiological process that is not fully understood. It is clear, however, that the interaction between the cellular elements of the vessel wall and the circulation are the determinants of atheroma formation. In this regard, the vascular endothelium appears to play a pivotal role because of its strategic location and metabolic activity. Antilipidemic therapy influences the outcome of coronary disease through a variety of mechanisms, including direct and indirect effects on the endothelium.

Volume control: a reliable option in the management of 'refractory' congestive heart failure.

CAVH can be effective in severe hypervolemic states, which are generally major hemodynamic abnormalities associated with refractory congestive heart failure, and not infrequently may have a poor renal response to diuretics and vasodilators. Reduced vascular volume with CAVH is accompanied by lower preload and afterload and thus decreased heart size. As a result, cardiac efficiency and contractility improve and oxygen demand is reduced. The temporal progression of congestive heart failure from a mild to a severe state need not be a sign of progressive pathology of heart muscle but rather a result of feedback circuits in which failure begets failure and leads to progressive cardiac enlargement, progressive hypervolemia, and peripheral edema. An appreciation of this concept permits a more optimistic approach to the management of congestive heart failure. Thus, the effective use of CAVH in reducing vascular volume and peripheral edema may reverse "refractory" congestive heart failure and prolong life.

Silent ischemia: a clinical update.

Silent ischemia is a common finding in coronary artery disease and occurs more frequently than painful episodes in the total ischemic burden. Since painless ischemia places limits on the history, it can encourage physicians to spend more time studying and treating the electrocardiogram and less time with patients, potentially leading to a deterioration in doctor-patient relationship and care. Silent ischemia should be considered only in patients 35 years of age or older who: (a) have a strong family history of early coronary artery disease, or (b) have two major coronary risk factors. Verification is made by performing an electrocardiographic exercise stress test and followed by a thallium-201 electrocardiographic stress test when the electrocardiograms are equivocal. In females it is best to proceed directly to a thallium-201 electrocardiographic stress test because of the frequency of false positives on the exercise electrocardiograms. The results will help determine the indications for further studies and subsequently the need for drug or interventional management. Frequently a history in which symptoms of lower esophageal disorders, hiatal hernia, gastric disease and arthritic pains mimic angina or in fact coexist with ischemic heart disease makes the clinical diagnosis of angina more elusive and difficult. However, a careful unhurried history and an exercise stress test can often differentiate the etiology of the chest pains. A 24-hour ambulatory electrocardiographic recording aids in measuring the total ischemic burden. When the diagnosis and severity of the ischemic syndrome is established, a course of medical therapy tailored to the symptoms and with defined end points is initiated. Since silent ischemia and angina frequently coexist, suppression of the frequency and severity of the anginal episodes will also reduce the episodes of silent ischemia. Symptomatic improvement is thus a guide in the treatment of the total ischemic syndrome. Drug management will usually consist of two or more of the following drugs: a nitrate, beta blocker, calcium channel blocker, and aspirin. A 24-hour ambulatory electrocardiographic recording is helpful in assessing the efficacy of medical management of silent ischemia. Failures in drug management should proceed with coronary angiography, and when indicated, followed by percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery.

Circadian influence on coronary events.

The circadian variation of major cardiovascular disorders, that is, TMI, AMI, SCD, and stroke, reflects an increased vulnerability to myocardial and cerebral ischemia and myocardial dysfunction in the early hours of the morning after awakening and rising. A comprehensive approach to treatment in patients with ischemic heart disease must take into consideration the chronobiology of the cardiovascular system and its relevance to the underlying disease process that affects the cardiovascular system.

Electrolyte imbalances in cardiovascular disease: the forgotten factor.

Hypomagnesemia is not an infrequent finding in diuretic-induced hypokalemia. Potassium replacement therapy in these cases may be ineffective in raising serum potassium levels unless normal magnesium concentrations are restored.

An acute cardiovascular event in an endurance-trained athlete.

In athletes, symptoms and electrocardiographic patterns may mimic an acute coronary event. In addition, endurance athletes show significantly elevated heart-specific serum CK-MB enzyme activity in the first week after athletic competition. Also, cellular control of the CK-MB enzyme is consistently elevated in skeletal muscles of trained endurance athletes. Thus, all three criteria used in diagnosis of acute myocardial infarction may be found in the athlete's heart. Awareness of these potential findings in athletes as "heart patients" and curtail unnecessary hospitalizations.

Effective technique of controlling volume in refractory congestive heart failure.

Continuous arteriovenous hemofiltration can be very effective in severe hypervolemic states associated with refractory CHF and limited renal response to diuretics and vasodilators. A reduced vascular volume is accompanied by a lower preload and afterload and thus a decrease in heart size. As a result cardiac efficiency and contractility improve, and oxygen demands are reduced. The temporal progression of CHF from a mild to a severe state need not be a sign of progressive pathology of heart muscle, but rather a result of feedback circuits where failure begets failure and leads to progressive cardiac enlargement, progressive hypervolemia, and peripheral edema. An appreciation of this concept permits a more optimistic approach to the management of CHF. Thus, the effective use of CAVH in reducing vascular volume and peripheral edema may in some patients reverse "refractory" CHF and prolong life.

A correctable complication of advanced congestive heart failure.

Hyponatremia is a common complication of chronic advanced CHF unresponsive to the usual therapeutic measures. Thus low levels of serum sodium are a significant marker for severe CHF refractory to the more conventional measures. The combined use of ACE inhibitors and diuretics is generally very effective in correcting the hyponatremic state and often helpful in reversing CHF.