Atherosclerotic vascular disease is more prevalent among black ESKD patients on long-term CAPD in South Africa.

BACKGROUND: Occurrence of cardiovascular disease (CVD) in the setting of chronic kidney disease (CKD) can be described as a "cruel alliance", with CVD responsible for about half of all deaths among CKD patients. Chronic kidney disease patients are more likely to die from CVD than progress to end stage kidney disease (ESKD). Dyslipidaemia, a known traditional risk factor for CVD, is highly prevalent among CKD patients and with an even higher frequency among ESKD patients on dialytic therapies. Prolonged exposure of continuous ambulatory peritoneal dialysis (CAPD) patients to high glucose concentrations in CAPD fluid have been associated with increased risk of cardiovascular events. In this study, we investigated the relationship of atherosclerotic vascular disease (AsVD) to clinical and echocardiographic parameters among black South Africans with CKD (stage 3) and ESKD on CAPD and haemodialysis (HD). METHODS: This was a cross-sectional study of 40 adult (18-65 years) non-diabetic CKD patients (kidney disease outcome quality initiative [KDOQI] stage 3), 40 ESKD patients on CAPD, 40 ESKD patients on HD and 41 age and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants' sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Serum blood samples were analysed for creatinine, albumin and lipid profile; lipoprotein ratios, Framingham's risk score and the 10-year risk of developing coronary heart disease (CHD) were calculated. Echocardiography was performed on all patients and carotid intima media thickness (CIMT) was measured in both right and left carotid arteries at 1 cm proximal to the carotid bulb. Spearman's rank correlation and binary logistic regression were conducted to determine the relationship of AsVD to clinical and echocardiographic parameters. RESULTS: Atherosclerotic vascular disease was most prevalent among ESKD patients on CAPD (70%, n = 28/40). Chronic kidney disease and HD patients exhibited a similar prevalence (47.5%, n = 19/40), while the prevalence in controls was 17.1% (n = 7/41). Presence of AsVD was associated with significantly older age, higher waist hip ratio (WHR), left ventricular mass index (LVMI) and Framingham's 10-year risk of developing CHD. Significant differences in clinical and echocardiographic parameters were observed when the study groups were compared. Age and LVH independently predicted AsVD. CONCLUSION: Atherosclerotic vascular disease was more prevalent among CAPD patients compared to pre-dialysis CKD and HD patients. Among all lipoprotein ratios assessed, non-HDL-C showed the most consistent significant difference between the groups. Age (> 40 years) and presence of LVH were independent predictors of AsVD.

TYPES OF ALBINISM IN THE BLACK SOUTHERN AFRICA POPULATION.

BACKGROUND: Oculocutaneous albinism (OCA) is the most common inherited disorder in Southern African blacks and several types have been described. Molecular techniques, where available, can be used to confirm a clinical diagnosis and the type of OCA, if necessary, and for prenatal diagnosis. OBJECTIVES: To investigate and classify the different types of albinism commonly found and to determine the clinical implications for each type. DESIGN: A descriptive survey. SETTING: Gauteng province, South Africa, and Lesotho. SUBJECTS: Three groups of subjects with OCA (96 from a genetics clinic, 62 from a dermatology clinic, and 31 from community surveys) from the black African population participated. MAIN OUTCOME MEASURES: Subjects underwent clinical and/or dermatological examinations and were then classified according to type of OCA. RESULTS: Four forms of OCA were identified: most (82%) subjects had OCA2 (a tyrosinase- positive type) with three sub-types: those without large freckles (ephelides) on exposed areas (named OCA 2a in this study), those with such freckles (named OCA 2b), and those with brown albinism (BOCA); the remainder had red/rufous albinism, ROCA (OCA 3). The four forms could be distinguished from each other clinically without using molecular genetic testing. CONCLUSION: The most common types of albinism found in the black population of Southern Africa are OCA2 and OCA3. Given the high prevalence of the disorder, together with the high risk of skin cancer, and the recent persecution of affected individuals in certain East African countries, these findings and their clinical implications have significance in terms of both education and awareness for health professionals and lay people caring for those with albinism.

Beta-blocker target dosing and tolerability in a dedicated heart failure clinic in Johannesburg.

BACKGROUND: Despite the significant clinical benefits of beta-blockers in heart failure with reduced ejection fraction (HFrEF), prescription for and adherence to these agents is reported to be poor. There are few data on the use and tolerance of beta-blocker therapy in patients with HFrEF in South Africa and it is unknown whether these patients would benefit from further heart rate-lowering therapy. METHODS: Data from all patients with HFrEF attending the heart failure clinic of Charlotte Maxeke Johannesburg Academic Hospital from January 2000 to December 2014 were retrospectively collected. We first determined the rates of beta-blocker intolerance in this population and then categorised the patients according to their most recent dose of beta-blocker (low, moderate or target dose) in order to identify factors associated with beta-blocker intolerance. Lastly, we used the data to identify patients who would be suitable for further treatment with heart rate-lowering therapy. RESULTS: Five hundred patients, with a median follow up of 58.7 months, were identified during the study period. Black South Africans constituted the majority (66.4%) and most patients had HFrEF due to hypertension (32.8%). At the last recorded clinic visit at the end of the study period, 489 patients (97.8%) were taking a beta-blocker with 59.8% prescribed a beta-blocker at target dose. Consistent with previous data, bradycardia was the commonest cause for failing to reach target beta-blocker dose. Only 61 (12%) patients were on no (n = 11) or low (n = 50) dose of beta-blocker at final clinic visit. As per current guidelines, only 10.6% (n = 53) of this cohort of patients would qualify for further treatment with heart rate-lowering therapy. CONCLUSIONS: In a dedicated heart failure clinic in South Africa, beta-blockers were well-tolerated in the treatment of HFrEF. The potential role of specific heart rate-lowering therapy in patients treated adequately with heart failure medication and proper up-titration of beta-blockers is relatively small.

Mechanism of tyrosinase inhibition by deoxyArbutin and its second-generation derivatives.

BACKGROUND: Disorders, such as age spots, melasma and hyperpigmentation at sites of actinic damage, emanate from the augmentation of an increased amount of epidermal melanin. OBJECTIVES: The ineptness of current therapies in treating these conditions, as well as high cytotoxicity, mutagenicity, poor skin penetration and low stability of skin-depigmenting formulations led us to investigate new compounds that meet the medical requirements for depigmentation agents. We have shown previously that the tyrosinase inhibitor deoxyArbutin (dA) is a more effective and less toxic skin lightener than hydroquinone (HQ). METHODS: The efficacy and reversibility of dA and its derivatives on inhibiting tyrosine hydroxylase and DOPAoxidase was assessed using standard assays. RESULTS: dA and its second-generation derivatives inhibit tyrosine hydroxylase and DOPAoxidase activities of tyrosinase dose dependently thereby inhibiting melanin synthesis in intact melanocytes, when used at concentrations that retain 95% cell viability in culture. This depigmenting effect was completely reversible when the compounds were removed. Tyrosinase inhibition was also observed in vitro when tested using human and purified mushroom tyrosinase, establishing that they are direct enzyme inhibitors. Lineweaver-Burk reciprocal plot analysis using mushroom tyrosinase illustrated that dA and its derivatives are more robust competitive inhibitors than HQ, when tyrosine is used as substrate. CONCLUSIONS: Thus, dA and its second-generation derivatives, which inhibit melanogenesis at safe concentrations by specifically acting on the tyrosinase enzyme at a post-translational level, are promising agents to ameliorate hyperpigmented lesions or lighten skin.

Proteinuria, graft outcomes, and cardiovascular risk among kidney transplant recipients in a South African Public Hospital.

Proteinuria is a marker of poor long-term graft survival and an independent risk factor for total and cardiovascular mortality in the transplant population. We investigated the prevalence of proteinuria and its relationship with graft function and cardiovascular risk factors in kidney transplant recipients (KTRs). Adult KTRs at the Charlotte Maxeke Johannesburg Academic Hospital were recruited. Patients' records were reviewed for information on their posttransplant follow-up. Echocardiography and carotid Doppler were performed for the assessment of cardiac status and carotid intima-media thickness (CIMT), respectively. Proteinuria was analyzed both as a categorical and continuous variable. Graft dysfunction was defined as estimated glomerular filtration rate of <60 mL/min/1.73 m 2 based on the modification of diet in renal disease formula. Framingham's risk score was used to categorize patients' cardiovascular risk. Inferential and modeling statistics were applied as appropriate using Statistical Package for Social Sciences, and P ≤0.05 was considered statistically significant. One hundred KTRs including 63% males were recruited. Proteinuria was present in 51%, the mean ± standard deviation 24 h urinary protein excretion per day was 1.67 ± 2.0 g/day with a range of 0.4-9.4 g/day. Graft dysfunction was found in 52% of patients and 36% had high cardiovascular disease (CVD) risk. Proteinuric KTRs had high CVD risk, P = 0.002. Proteinuria was associated with graft dysfunction, increased left ventricular mass index, increased CIMT, and anemia. Proteinuria is prevalent; it is a marker of graft dysfunction and is associated with markers of atherosclerosis.

Mitral valve area calculations immediately after percutaneous balloon mitral valvuloplasty: effect of the atrial septal defect.

OBJECTIVES: The aim of this study was to assess the effect of the atrial septal defect on mitral valve area calculations after balloon mitral valvuloplasty. BACKGROUND: There is poor correlation between the hemodynamic-derived and Doppler mitral valve area immediately after mitral valvuloplasty. The reasons for this are unclear. METHODS: Twenty-five patients with severe mitral stenosis were studied. After balloon mitral valvuloplasty, serial mitral valve area calculations were performed with 1) the mitral dilating catheter across the atrial septum, 2) the 7F catheter across the atrial septum, and 3) with the atrial puncture site occluded with the balloon catheter. RESULTS: The mitral valve area determined by the Gorlin formula with balloon occlusion of the atrial septum was smaller than the mitral valve area determined without balloon occlusion (mean +/- SD 1.8 +/- 0.43 vs. 2.24 +/- 0.67 cm2, p < 0.005 for the mitral dilating catheter across the atrial septum and 1.8 +/- 0.43 vs. 2.19 +/- 0.52, p < 0.05 for the 7F catheter across the atrial septum). The mean of the differences between the mitral valve area derived by the Gorlin formula and by the Doppler pressure half-time method was smaller with the atrial septum occluded than when the dilating catheter or the 7F catheter was across the atrial septum (0.12 +/- 0.26 vs. 0.56 +/- 0.48 cm2 [p < 0.005] and 0.12 +/- 0.26 vs. 0.48 +/- 0.55 cm2 [p < 0.05]). Left to right shunting was detected less frequently by oximetry (60%), than by shunt ratios calculated by using the cardiac output measurements with and without balloon occlusion of the atrial septum (84%). CONCLUSIONS: The presence of left to right shunts after mitral valvuloplasty may account for some of the discrepancies between mitral valve area found at cardiac catheterization and that by the Doppler pressure half-time method; thus, the latter method may be reliably used to follow up patients in the long term.

Obesity and graft dysfunction among kidney transplant recipients: Increased risk for atherosclerosis.

Weight gain after kidney transplant is common, and may be related to graft dysfunction and high cardiovascular risk. We investigated the prevalence of obesity and evaluated the relationship between obesity and graft dysfunction in kidney transplant recipients (KTRs). All patients who received kidney transplant at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) between January 2005 and December 2009 were recruited. Information on demographics, clinical characteristics and post-transplant care were documented. All patients underwent transthoracic echocardiography and carotid Doppler ultrasound for the assessment of cardiac status and carotid intima-media thickness (cIMT), respectively. Inferential and modelling statistics were applied. One hundred KTRs were recruited, of which 63 were males. The mean age was 42.2 ± 12.42 years with a range of 19-70 years. The mean body mass index and waist circumference of the recipients were 26.4 ± 4.81 kg/m(2) and 90.73 ± 14.76 cm, respectively. Twenty-nine patients (29%) were obese; of these, 24 (82.8%) had moderate obesity, 4 (13.8%) had severe obesity, and 1 (3.4%) had morbid obesity. Graft dysfunction was present in 52%. Obese patients were older (P < 0.0001), had graft dysfunction (P = 0.03), higher mean arterial blood pressure (P = 0.022), total cholesterol (P = 0.019), triglycerides (P < 0.0001), left ventricular mass index (P = 0.035) and cIMT (P = 0.036). Logistic regression showed obesity to be independently associated with graft dysfunction (P = 0.033). Obesity after kidney transplantation is common and is associated with graft dysfunction and markers of atherosclerosis.

Exercise capacity and skeletal muscle structure and function before and after balloon mitral valvuloplasty.

This study evaluated the effects of balloon mitral valvuloplasty (BMV) on exercise capacity and skeletal muscle structure and function in 10 subjects with mitral stenosis (mean age +/- SD 33 +/- 5.5). Measurements were obtained before, and 2 weeks and 4 months after BMV to provide baseline data, to examine the effects of improved hemodynamics, and to examine the effects of resumption of normal physical activity, respectively. Valvuloplasty caused an increase in mitral valve area (0.89 +/- 0.04 to 1.75 +/- 0.07 cm2; mean +/- SE), and an increase in resting cardiac output (3.8 +/- 0.18 to 4.6 +/- 0.19 L/min, p < 0.05). At early follow-up after 2 weeks, subjects did more work (31% increase, p < 0.01) and had greater maximal oxygen consumption (11% increase, p < 0.01). However, measurements reflecting skeletal muscle histology, biochemistry, and function were unaltered at this stage. Four months after BMV, subjects had a further increase in exercise capacity compared with both baseline (58% increase, p < 0.01) and early follow-up (20% increase, p < 0.05). There were associated late increases compared with baseline in quadriceps cross-sectional area (66 +/- 5.8 vs 61 +/- 5.5 cm2, p < 0.05) and torque production (125 +/- 14 vs 118 +/- 16 Nm, p < 0.05). The percentage of slow twitch type I fibers increased compared with baseline (41 +/- 2.0% vs 33 +/- 3.1%, p < 0.05), as did the size of type II fibers (5.9 +/- 0.49 vs 4.9 +/- 0.57 microns2 x 10(3), p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The transformation of Zimbabwe's health care system: a review of the White Paper on health.

In a recently released White Paper on health, the Government of Zimbabwe details its plans to transform the colonial health care system it inherited at the time of independence to one consonant with its commitment to socialist development. The essence of the transformation can be described in terms of several key ideas. First, there is a commitment to develop an integrated non-racial health care system. Second, there is a concerted attempt to develop a primary health care system throughout Zimbabwe. Third, there is a deliberate attempt to 'redistribute' health care resources by making sure that additional or new resources are largely devoted to the rural populations. Fourth, the government is committed, and has acted on the commitment, to ensure equitable access to health services. Fifth, the government is taking a variety of measures to limit the size and influence of the private medical sector. Sixth, there is a serious intent to involve local populations in the health planning and programming. Seventh, human resource development must be consistent with the primary health care system the government wishes to establish throughout the country. It is suggested that while the White Paper is unclear and uncertain about some important aspects of the transformation, for example, with regard to the private sector and the financing of the National Health Service, most of its proposed changes are well within the realm of feasibility.

Salmonella endocarditis: successful treatment with parenteral ampicillin and oral amoxicillin.

We describe a case of Salmonella typhimurium endocarditis involving the mitral valve secondary to infection with Salmonella typhimurium. The presence of the infective agent was confirmed by blood cultures and the endocarditic lesions by cross-sectional echocardiography. Successful therapy was achieved with parenteral ampicillin and amoxicillin.

Primary leiomyosarcoma of the pulmonary trunk.

An unusual case of leiomyosarcoma of the pulmonary trunk in a 33-year-old woman is described. Angiography suggested a large pulmonary embolus. The patient was referred for surgery and the diagnosis was made histologically. The surgical management and postoperative course are described.

Comparative results of percutaneous balloon mitral valvuloplasty using the Trefoil/Bifoil and Inoue balloon techniques.

This study compared the results in 150 consecutive patients with rheumatic mitral stenosis who underwent percutaneous balloon mitral valvuloplasty by means of a Trefoil/Bifoil balloon catheter (n = 100, Group 1) or the Inoue balloon catheter (n = 50, Group 2). There was significant improvement in mitral valve area after valvuloplasty in both groups: in Group 1 mitral valve area improved from 0.92 +/- 0.22 to 2.14 +/- 0.64 cm2 (P < 0.001) and in Group 2 from 1.0 +/- 0.26 to 2.06 +/- 0.59 cm2 (P < 0.001). There was no significant difference in the mitral valve area, mean diastolic gradient or mean left atrial pressure between Group 1 and Group 2 patients after valvuloplasty. There was a higher complication rate in Group 1 patients but this was largely related to our early learning experience with the procedure. The Trefoil/Bifoil catheter technique is more complex and involved a longer screening time: Group 1 (39 +/- 15 min) vs. Group 2 (22 +/- 10 min); P < 0.001. The cost of the Inoue balloon technique, however, was almost twice that of the Trefoil/Bifoil technique. This may have important implications for developing countries with limited health care budgets and a high prevalence of rheumatic heart disease.

Pulmonary arterial aneurysms in Marfan's syndrome.

We report the case of a 23-year-old man with Marfan's syndrome and saccular aneurysms of the pulmonary arteries. The importance and possible complications of this finding are discussed.

The quadrileaflet mitral valve: follow-up in rheumatic heart disease.

This prospective study evaluated the clinical performance of a novel stentless quadrileaflet bovine pericardial mitral valve implanted at one center since December 1996. After giving informed consent, patients were included in the study if they required isolated mitral valve replacement. All underwent comprehensive clinical evaluation, as well as transthoracic M-mode, two-dimensional and Doppler (pulsed, continuous, and color) echocardiography preoperatively and postoperatively at 1 month, 3 months, and annually thereafter. Mitral valve area was derived by planimetry, the pressure half-time method, and the continuity equation. The degree of mitral regurgitation was semi-quantitated using color Doppler. In all 38 patients with rheumatic valvular heart disease (mean age 35+/-13 years) were monitored for 13.8+/-7.5 months (range, 1 to 29 months). All but three patients are alive and symptomatically improved (functional New York Heart Association class I or II). One valve was explanted because of early prosthetic valve endocarditis. There were no episodes of thromboembolism or anticoagulation-related hemorrhage. Left ventricular function was maintained with increased cardiac output and low transmitral pressure gradients. The mitral valve area was larger when measured by pressure half-time and planimetry than by the continuity equation (P<.05). In an independent clinical evaluation of a subset of 30 patients, mitral stenosis was considered absent in 33%, mild in 30%, mild to moderate in 26%, and moderate in 10% of cases. No or less than or equal to mild mitral regurgitation was noted in the majority of patients postoperatively, both clinically and echocardiographically. We are encouraged by the clinical performance of the quadrileaflet mitral valve and with patient outcome. Long-term follow-up data are needed to assess durability.

The stentless quadrileaflet bovine pericardial mitral valve: echocardiographic assessment.

BACKGROUND AND AIMS OF THE STUDY: Recently, a stentless chordally supported quadrileaflet mitral valve (QMV) bioprosthesis made of selected tanned bovine pericardium treated to minimize calcification, has become available for clinical trial. The aim of this study was to report both the echocardiographic appearance and hemodynamic performance of this valve by means of echocardiography. METHODS: The QMV was implanted in 22 patients (mean age 38 +/- 12 years) requiring isolated mitral valve replacement for valve lesions not deemed suitable for repair. Echocardiography was performed pre-operatively, and at one and three months postoperatively. Transthoracic echocardiography (TTE) was used to monitor mean instantaneous pressure gradient as calculated from the long modified Bernoulli equation, cardiac index (CI), pressure half-time and effective orifice area (EOA) using the Hatle and continuity equations. Regurgitation patterns were sought by color Doppler transesophageal echocardiography in all valves intraoperatively following valve implantation, and by TTE in the outpatient clinic at follow up. RESULTS: After a mean follow up of 8.3 months (range: 1 to 18 months), all patients were well and symptomatically improved. At three months postoperatively, the mean pressure gradient ranged from 1.7 to 2.2 mmHg. The EOA was larger using the Hatle as compared with the continuity equation (2.4 +/- 0.7 cm2 versus 1.8 +/- 0.5 cm2, respectively; p < 0.005). Mitral regurgitation was trivial in 77% and mild in 14% of patients at 3 months after surgery; moderate mitral stenosis was noted in one patient. The CI improved significantly postoperatively (p < 0.005), and left ventricular function was maintained. CONCLUSIONS: The hemodynamic performance of this novel prosthesis is favorable. Although follow up is too short to assess durability, it is hoped that the unique design and improved valve preservation technique of this device will enhance long-term durability.

The Quattro valve and active infective endocarditis of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: Even today, infective endocarditis remains a therapeutic challenge. Active endocarditis at the time of valve implantation is an important risk factor for the development of prosthetic valve infection. This study reports results following implantation of the Quattro valve, a stentless chordally supported quadrileaflet mitral valve made from bovine pericardium. METHODS: The Quattro valve was implanted in seven patients (four females, three males; mean age 34 years) requiring isolated mitral valve replacement for active bacterial endocarditis. All had congestive heart failure; two were in cardiogenic shock. The diagnosis of active endocarditis was based on clinical and echocardiographic findings, together with macroscopic evidence of acute infection at surgery, blood culture or histopathological evidence of valve infection. Postoperatively, all patients received at least four weeks of parenteral antibiotic therapy. RESULTS: Congestive heart failure (and large pedunculated vegetations and mobile septic left atrial thrombi in two patients) prompted early surgical intervention. Patients underwent surgery at a mean of 7 days (range: 1-16 days) after admission. Endocarditis was caused by Gram-positive cocci in all patients except one. At a mean follow up of 15 months (range: 6-24 months) all patients were alive and symptomatically improved. To date, all remain free of prosthetic valve endocarditis, reoperation and thromboembolism. CONCLUSION: The Quattro valve can be implanted safely in patients with acute bacterial endocarditis. The results also reflect the benefit of early surgical intervention in patients with infective endocarditis complicated by congestive heart failure, with or without large vegetations.

The stentless quadrileaflet bovine pericardial mitral valve: early clinical results.

BACKGROUND AND AIMS OF THE STUDY: Although bioprosthetic valves currently in use have low thrombogenicity, durability remains very unsatisfactory. Valve failure occurs early from calcification, and later from tissue wear. Stentless design lessens the latter, and anticalcification treatments the former. Recently, a stentless chordally supported quadrileaflet mitral valve (QMV) bioprosthesis made of selected tanned bovine pericardium, treated to minimize calcification, has become available for clinical study. The aim of this study was to report the early results relating to valve performance, and patient outcome. METHODS: Since December 1996, the QMV has been implanted in 23 patients (mean age 38 +/- 12 years) requiring isolated mitral valve replacement for valve lesions not suited for repair. All patients were symptomatic (three in NYHA functional class II, 16 in class III, four in class IV). Preoperatively, all underwent full clinical and echocardiographic assessment, and intraoperative transesophageal evaluation immediately after valve implantation. Blood tests for hemolysis were performed preoperatively and at 3 months after surgery. RESULTS: After a mean follow up of 8.3 months (range: 1 to 18 months), 22 patients were alive and symptomatically improved (NYHA class I or II). One patient died of sternal sepsis soon after surgery. There have been no reoperations, nor cases of infective endocarditis or thromboembolism. Subclinical hemolysis was shown pre- and postoperatively in 35% and 32% of cases, respectively. Intraoperative transesophageal echocardiography post valve implantation demonstrated mitral regurgitation which was trivial in 15 patients (78%) and mild in five (22%). CONCLUSIONS: The QMV can be implanted safely, and the early clinical results relating to patient outcome and valve performance are encouraging.

Exercise-induced hyperkalemia and concentration of Na,K-pumps in skeletal muscle in mitral stenosis: effect of balloon mitral valvotomy.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to examine the effects of balloon mitral valvotomy (BMV) on exercise-induced hyperkalemia, and on changes in the concentration of Na,K-pumps in skeletal muscle, as an exaggerated exercise-induced rise in potassium concentration ([K+]) may contribute to exertional fatigue and breathlessness. METHODS: Eight subjects were evaluated with mitral stenosis (mean age 34 +/- 5.2 years) before, and at two weeks and four months after BMV. Subjects underwent incremental exercise to exhaustion for exercise-induced rise in [K+] and vastus lateralis biopsy for concentration of Na,K-pumps. RESULTS: Mean (+/- SE) valve area increased from 0.89 +/- 0.03 cm2 before to 1.75 +/- 0.05 cm2 after BMV. There was a progressive increase in VO2,max (15.3 +/- 1.6, 17.2 +/- 1.4 and 19.9 +/- 1.9 l/kg/min) at baseline, early after and later after BMV, respectively (p < 0.01). The rise in [K+] with absolute workload fell progressively at early and late follow up post-BMV (p < 0.05), but was unchanged when plotted against percentage of VO2,max to match for relative workload. The concentration of Na,K-pumps was similar to baseline at early follow up (233 +/- 10 versus 228 +/- 15 pmol/g wet weight), but was significantly increased at late follow up after four months (265 +/- 17 pmol/g; p < 0.05). When the relationship between the concentration of Na,K-pumps and the exercise-induced rise in [K+] was studied, a negative correlation was found. However, correlation analysis for the effects of changes in Na,K-pumps on changes in exercise hyperkalemia after BMV was not significant. CONCLUSIONS: The progressive reduction in exercise-induced rise in [K+] after BMV may contribute to the progressive improvement in exercise performance. The increased concentration of Na,K-pumps in skeletal muscle may assist in this improvement, and emphasizes the importance of peripheral adaptations in clinical improvement after BMV.

Doppler frequency ratio and peak frequency in the assessment of carotid artery disease: a comparative study with angiography.

A retrospective analysis compared the sensitivity, specificity, and predictive value of two methods using noninvasive Doppler ultrasound for detecting the severity of carotid artery disease. Doppler spectral analyses were used in determining the peak systolic frequency (PF) found within the stenosis, as well as the ratio of the peak systolic frequency distal to the stenosis, to the peak systolic frequency within the stenosis (f2/f1). The results of the noninvasive tests were compared with carotid arteriography. The sensitivity of the two methods were similar, but the specificity of f2/f1 was much higher (98%) than PF (88%) with stenosis greater than 50%, and marginally better, 97 and 94%, respectively, with stenosis greater than 75%. The positive predictive value was also better for f2/f1 than PF; 91% and 71% for stenosis greater than 50%, and 77% and 67%, respectively for stenosis greater than 75%. The use of Doppler frequency ratio in conjunction with peak frequency measurements provide a quantitative and fairly accurate evaluation of the severity of carotid artery disease.

Euthanasia and medically assisted suicide--the case for legalizing physician assisted suicide.

Ethical and legal debates over ending life are inescapably emotive, controversial and complex. It is, however, increasingly urgent to resolve the debate over the legalization or continued prohibition of physician assisted suicide for a number of reasons, not least of which is the changing public and professional opinion and the growing concern over what may be actually but quietly and surreptitiously occurring in medical practice. The paper assesses the arguments for and against the legalization of this special case of euthanasia and concludes that with appropriate and well-defined criteria, guidelines, review and reporting requirements, the legalization of physician assisted suicide is not only ethical defensible but practical.