Rupture of the sinus of valsalva (RSOV) is an uncommon condition with a variety of manifestations ranging from an asymptomatic murmur to cardiogenic shock. This retrospective 10-year review (1985-1995) of 18 patients from a single institution revealed that 6 (33%) were female and 12 (67%) were male with a mean age of 37.6 +/- 13.4 years and that 72% were Chinese by ethnic descent with the remaining 28% being Malay. Eight patients (44.4%) presented with an asymptomatic murmur, 4 (22.2%) with acute chest pain, 4 (22.2%) with mild heart failure, 2 (11.1%) with severe heart failure, and 2 (11.1%) with cardiogenic shock. Rupture of the right aneurysmal coronary cusp (RCC) made up 15 (83.3%) while those of the non-coronary cusp (NCC) made up the remaining. Most of the RCC ruptures were directed into the right ventricle and all of the NCC ruptures were into the right atrium. Ventricular septal defects (VSDs) were found in 9 (50%) of the patients, (although detected by echocardiography in only one third of those patients), aortic regurgitation in 6 (33.3%) and aortic valve vegetations in 2 (11.1%). Echocardiography was found to be accurate in diagnosing RSOVs with 100% diagnostic accuracy after 1990 with four misdiagnoses before 1990. Of these four patients, two were misdiagnosed as having VSDs, one as having a coronary arteriovenous fistula and one as having a patent ductus arteriosus. The anatomical structure of the "windsock" was seen in 64% of the patients who were correctly diagnosed. The pattern of colour flow and spectral Doppler was seen in all patients and helped to localise the site of rupture and the direction of flow. In summary, echocardiography is a simple and accurate way of diagnosing and defining RSOVs and is the imaging modality of choice.
The pharmacokinetics of propofol was studied in 11 Asian patients with fentanyl-isoflurane anaesthesia during cardiopulmonary bypass (CPB) and undergoing elective coronary artery bypass grafting (CABG). Instead of the usual increments of morphine and a benzodiazepine, propofol (4 mg/kg/h) was initiated at the start of CPB and ceased at CPB separation. Whole blood propofol concentrations were determined during and postinfusion using high-performance liquid chromatography with fluorescence detection. Data from four patients seemed to fit a two-compartment model, whereas those from seven patients were significantly (F test, p < 0.05) better fitted to a three-compartment model. The pharmacokinetic parameters were as follows: The mean (SD) of the initial distribution phase t1/2 pi, intermediate distribution phase t1/2 alpha, and elimination phase t1/2 beta were 2.22 (1.04) min, 42.9 (16.4) min, and 370 (138) min, respectively. The mean clearance of 1.31 (0.50) L/min was lower than those reported from other studies, whereas the mean blood concentration of 2.2 (1.0) mg/L at the 1-h infusion period was higher. The mean calculated apparent Css was 3.9 (1.5) mg/L. The low clearance is likely to be due to hemodynamic changes during CPB and CABG, thereby affecting drug distribution and blood flow to the liver.
Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson's disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann-Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.