Additional molsidomine in refractory unstable angina pectoris

Summary In a prospective single-blind study we examined the effects of additional molsidomine in 20 patients (63±10 years; 15 males, 5 females) with unstable resting angina (3 attacks/24 hours) refractory to triple therapy (nitrates, calcium antagonists, and beta blockers) combined with heparin or aspirin. All but one patient had coronary artery disease documented by coronarography (n=17) or by recent myocardial infarction (n=3). Two patients had angiographically documented severe coronary spasms. Patients entered the study if coronary bypass surgery or PTCA could not be performed within 3 days after angiography (n=9) or was not feasible due to anatomical or technical reasons (n=6), concomitant malignant disease (n=2), or age greater than 75 years (n=3). All patients received molsidomine orally 12 to 24 mg/day. In 15 of the 20 patients molsidomine was given i.v. initially, starting with 20 mg i.v., followed by infusion of 1 to 4 mg/hour. Heart rate and blood pressure did not change significantly, and eight patients had a slight decrease of systolic and diastolic blood pressure. Severe adverse effects did not occur, and moderate headaches were reported by five patients. In 13 patients, unstable angina could be stabilized, and they remained free of resting angina; five had a marked reduction of the frequency of anginal attacks. In two patients, molsidomine was without demonstrable beneficial effects. After a follow-up of 4 weeks, nine patients were free of symptoms after bypass surgery or PTCA, 10 continued to have angina NYHA class II or III, and one patient died due to acute myocardial infarction and cardiogenic shock 4 days after starting additional molsidomine. We conclude that molsidomine is well tolerated and has a marked beneficial effect in patients with refractory unstable angina. Molsidomine should therefore be considered for routine therapy of unstable angina, especially in those patients who are suspected of tolerance to nitrate therapy.     

Chain mobility in solid polyelectrolyte complexes

²H NMR is used to study the mobility of the alkylene chain in solid poly[(dimethyliminio)-alkylene]s (α,ω-ionenes) complexed with poly(styrenesulfonate). In 10, 10-ionene the alkylene chain motion was probed on samples selectively deuterated at the 1-, 2-, and 4-position as well as in the methyl part of the quaternary ammonium groups. ²H NMR spectra show that all positions in the polymethylene chains are involved in conformational jumps between trans and gauche states. The mobility of the methylene units adjacent to charged centres was found to be significantly reduced compared with that of units in the inner part of the chain. The charged quaternary ammonium groups themselves, however, do not take part in trans-gauche isomerization. An increase in mobility resulting from increasing the length of the alkylene chains between the charge centres was observed in 3,3-, 6,6- and 10,10-ionene complexes labelled in the 2-position. The differences in chain dynamics were also detected via EPR line shapes of small spin probe molecules incorporated into the complexes.     

An uncommon cause of recurrent strokes: Tropheryma whippelii endocarditis

BACKGROUND: Cardiac involvement in Whipple's disease is not an uncommon phenomenon in autopsies, but its clinical occurrence is often overshadowed by gastrointestinal symptoms. We report a very atypical manifestation of this disorder. SUMMARY OF REPORT: An extraordinary presentation of an extremely long-lasting, culture-negative endocarditis caused by Tropheryma whippelii is described, the clinical consequence of which has become apparent in recurrent strokes. CONCLUSIONS: Cardiac involvement of Whipple's disease should always be considered in culture and serologically negative endocarditis. The polymerase chain reaction technique may be a useful tool to confirm a presumed diagnosis of T whippelii endocarditis and consequently to apply an effective treatment regimen.     

Drug resistance of Mycobacterium tuberculosis in Malawi: a cross-sectional survey

Objective

To document the prevalence of multidrug resistance among people newly diagnosed with – and those retreated for – tuberculosis in Malawi.

Methods

We conducted a nationally representative survey of people with sputum-smear-positive tuberculosis between 2010 and 2011. For all consenting participants, we collected demographic and clinical data, two sputum samples and tested for human immunodeficiency virus (HIV).The samples underwent resistance testing at the Central Reference Laboratory in Lilongwe, Malawi. All Mycobacterium tuberculosis isolates found to be multidrug-resistant were retested for resistance to first-line drugs – and tested for resistance to second-line drugs – at a Supranational Tuberculosis Reference Laboratory in South Africa.

Findings

Overall, M. tuberculosis was isolated from 1777 (83.8%) of the 2120 smear-positive tuberculosis patients. Multidrug resistance was identified in five (0.4%) of 1196 isolates from new cases and 28 (4.8%) of 581 isolates from people undergoing retreatment. Of the 31 isolates from retreatment cases who had previously failed treatment, nine (29.0%) showed multidrug resistance. Although resistance to second-line drugs was found, no cases of extensive drug-resistant tuberculosis were detected. HIV testing of people from whom M. tuberculosis isolates were obtained showed that 577 (48.2%) of people newly diagnosed and 386 (66.4%) of people undergoing retreatment were positive.

Conclusion

The prevalence of multidrug resistance among people with smear-positive tuberculosis was low for sub-Saharan Africa – probably reflecting the strength of Malawi’s tuberculosis control programme. The relatively high prevalence of such resistance observed among those with previous treatment failure may highlight a need for a change in the national policy for retreating this subgroup of people with tuberculosis.     

The Malawi National Tuberculosis Programme: an equity analysis

Background  

Until 2005, the Malawi National Tuberculosis Control Programme had been implemented as a vertical programme. Working within the Sector Wide Approach (SWAp) provides a new environment and new opportunities for monitoring the equity performance of the programme. This paper synthesizes what is known on equity and TB in Malawi and highlights areas for further action and advocacy.     

Characteristics of patients with abnormal stress technetium Tc 99m sestamibi SPECT studies without significant coronary artery diameter stenoses

BACKGROUND: Single-photon emission computed tomography (SPECT) sestamibi (MIBI) is an excellent tool for detection of coronary artery disease (CAD), preoperative risk assessment, and follow-up management after coronary revascularization. While the sensitivity of MIBI SPECT for detecting CAD has been reported to exceed 90%, the specificity ranges between 53-100%. HYPOTHESIS: The study was undertaken to assess characteristics of patients with abnormal stress technetium Tc99m sestamibi SPECT (MIBI) studies without significant coronary artery diameter stenoses (< 50%). METHODS: Between January 1999 and November 2000, 270 consecutive patients were referred for coronary angiography due to reversible MIBI uptake defects during exercise. In 41 patients (15%; 39% women, mean age 59 +/- 9 years), reversible MIBI uptake defects were assessed although coronary angiography showed no significant CAD. These patients were compared with age- and gender-matched patients with perfusion abnormalities (39% women, mean age 60 +/- 9 years), due to significant CAD (coronary artery stenosis > 50%). RESULTS: There were no significant differences between the two groups regarding body mass index, left bundle-branch block (LBBB), or method of stress test (dipyridamole in patients with LBBB or physical inactivity [n = 11] and exercise in all the others [n = 30]). Left ventricular hypertrophy (44 vs. 23%, p = 0.05) and left anterior fascicular block (LAFB) (17 vs. 0%, p = 0.005) were more common in patients with perfusion abnormalities with no significant CAD, whereas ST-segment depression during exercise (17 vs. 37% p = 0.05) and angina during exercise (15 vs. 29%, p = 0.02) were significantly less common than in patients with abnormal MIBI perfusion studies and angiographically significant CAD. Sestamibi uptake defects during exercise were significantly smaller in patients without significant CAD than in matched controls with significant CAD (p < 0.0004). CONCLUSION: Of 270 consecutive patients, 41 (15%) referred to coronary angiography due to reversible MIBI uptake defects showed coronary artery stenoses < 50%. Twenty-six (10%) of these presented angiographically normal coronary arteries. The significantly higher proportion of left ventricular hypertrophy and LAFB in patients with reversible MIBI uptake defects without significant CAD suggest microvascular disease, angiographically underestimated CAD, and conduction abnormalities as underlying mechanisms.