Left ventricular hypertrophy: reduction of blood pressure already in the normal range further regresses left ventricular mass.

OBJECTIVE: Left ventricular hypertrophy (LVH) confers high cardiovascular risk. Regression of LVH reduces risk. Patients with blood pressure in the normal range and LVH are common. We investigated whether further reduction in blood pressure would further regress LVH. METHODS: 51 subjects with blood pressure in the normal range and echocardiographic left ventricular hypertrophy were randomly assigned to active treatment (antihypertensive medication) or placebo in a ratio of 2:1. The aim was to maintain office systolic blood pressure at 10 mm Hg less than baseline in the active arm and at baseline level in the placebo arm. Cardiac magnetic resonance imaging was used to measure change in left ventricular mass index over 12 months. RESULTS: 35 subjects completed the study (active 23: placebo 12). Average mean baseline office systolic blood pressure was 122 (SD 9) mm Hg in the active group and 124 (9) mm Hg in the placebo group (p = 0.646). The mean baseline left ventricular mass index was 65.88 (11.87) g/m(2) in the active group and 59.16 (11.13) g/m(2) in the placebo group (p = 0.114). The mean difference between baseline and end of study office systolic blood pressure was -9.33 (8.56) mm Hg in the active group and -0.08 (9.27) mm Hg in the placebo group (p = 0.007). The mean change in left ventricular mass index was -4.68 (7.31) g/m(2) in the active group and +1.97 (6.68) g/m(2) in the placebo group (p = 0.014). CONCLUSIONS: Reduction in office systolic blood pressure, already in the normal range, of approximately 9 mm Hg, leads to a reduction in left ventricular mass. Further work is required to see if this also leads to a reduction in cardiovascular events. TRIAL REGISTRATION NUMBER: ISRCTN48331653.

Integrating maternal health services into a health insurance scheme: effect on healthcare delivery.

BACKGROUND: Healthcare delivery is a foremost important basic social services. OBJECTIVE: This study reviews the influence of the integration of maternal health services into the Anambra State of Nigeria government-community health care financing scheme on health service delivery at primary health care level in Igboukwu, Aguata Local Government Area of Anambra State, Nigeria. METHODS: A descriptive, cross-sectional study with an intervention component, conducted amongst 120 women of reproductive age group at Obiuno health centre, Igboukwu. RESULTS: Mean age of respondents was 30.5 +/- 6.0 years with majority, 44 (36.7%), in the age range of 26-30 years. Almost half, forty eight (40%), of the participants are of post secondary educational status; 60 (50%) are civil servants. Utilization of maternal health services % antenatal and delivery services, were significantly better at the late intervention period when compared to the early intervention period. Quality of service from clients' perspective also showed significant improvement at the late intervention period. There was an overall greater availability of maternal health service equipments, drugs and consumables, and medical records in the health facility later during the scheme. CONCLUSION: Community based health insurance schemes that focus on maternal health services ensure the provision of adequate funds for maternal health services that cover a great proportion of the rural communities.

Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels.

AIMS: To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels. METHODS: Double-blind, parallel group, placebo-controlled randomized trial. A single dose of 100,000 IU vitamin D2 or placebo was administered to patients with Type 2 diabetes over the winter, when levels of circulating 25-hydroxyvitamin D were likely to be lowest. Patients were enrolled if their baseline 25-hydroxyvitamin D level was < 50 nmol/l. Endothelial function and blood pressure were measured and fasting blood samples were taken at baseline and 8 weeks after administration of vitamin D. RESULTS: Forty-nine per cent of subjects screened had 25-hydroxyvitamin D levels < 50 nmol/l. Thirty-four subjects completed the study, with a mean age of 64 years and a baseline 25-hydroxyvitamin D level of 38.3 nmol/l. Vitamin D supplementation increased 25-hydroxyvitamin D levels by 15.3 nmol/l relative to placebo and significantly improved flow mediated vasodilatation (FMD) of the brachial artery by 2.3%. The improvement in FMD remained significant after adjusting for changes in blood pressure. Vitamin D supplementation significantly decreased systolic blood pressure by 14 mmHg compared with placebo; this did not correlate with change in FMD. CONCLUSIONS: Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotland. A single large dose of oral vitamin D2 improves endothelial function in patients with Type 2 diabetes and vitamin D insufficiency.

B-type natriuretic peptide can detect silent myocardial ischaemia in asymptomatic type 2 diabetes.

OBJECTIVE: To find out whether B-type natriuretic peptide (BNP) detects silent myocardial ischaemia in patients with type 2 diabetes, since many of these patients have silent ischaemia leading to unexpected cardiac deaths. DESIGN: Prospective cross-sectional study with consecutive recruitment of patients. SETTING: Outpatient, single centre. PATIENTS: 219 patients with type 2 diabetes. Patients were excluded if they had a history or evidence of cardiac failure. OUTCOME MEASURES: BNP, echocardiography and exercise tolerance test (ETT). BNP was compared with the ETT result in all patients and specifically in those who had no apparent ischaemic heart disease (IHD). RESULTS: 121 patients had no history of IHD or cardiac failure and of these patients 85 had a clearly abnormal or normal ETT result. BNP was higher in patients with an abnormal than with a normal ETT (mean 58.2 (SD 46.3) v 24.4 (SD 15.7) pg/ml, p < 0.001). In univariate analysis BNP was an independent predictor of an abnormal ETT (p < 0.001). In multivariate analysis BNP remained an independent predictor of the ETT result. BNP concentration over 20 pg/ml predicted an abnormal ETT result with a sensitivity of 87% and specificity of 37%, and BNP over 40 pg/ml had a sensitivity of 63% and a specificity of 81%. CONCLUSION: BNP is of value in predicting silent ischaemia on exercise testing in asymptomatic patients with type 2 diabetes.

The role of RhD agglutination for the detection of weak D red cells by anti-D flow cytometry.

Anti-D flow cytometry is an accurate method for quantifying feto-maternal haemorrhage (FMH). However, weak D red cells with <1000 RhD sites are not detectable using this methodology but are immunogenic. As quantitation of RhD sites is not practical, an alternative approach is required to identify those weak D fetal red cells where anti-D flow cytometry is inappropriate. We describe a simple algorithm based on RhD agglutination and flow cytometry peak separation. All weak D (n = 34) gave weak agglutination with RUM-1 on immediate spin (grading

Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Aldosterone blockade has followed in the footsteps of ACE inhibition in reducing mortality in patients with heart failure. This is associated with its beneficial effects on endothelial function and heart rate variability. Diabetes is another area, where angiotensin II withdrawal has proven to be of particular value. We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients. METHODS: We assessed endothelial function by forearm venous occlusion plethysmography in 42 patients with type 2 diabetes mellitus after 1 month of treatment with spironolactone or placebo allocated in a randomised double-blind trial. Of the 42 patients, 20 were on ACE inhibitor therapy. We also assessed heart rate variability, HbA1c and plasma angiotensin II levels at the end of each treatment period. RESULTS: Compared to placebo, spironolactone decreased forearm blood flow response to acetylcholine by 44.56+/-14.56% (p=0.003) in the group as a whole and by 57.61+/-15.56% (p<0.001) in the 20 patients on ACE inhibition. Spironolactone also worsened heart rate variability parameters, with root mean squared standard deviation decreased by 1.99+/-0.93 ms (p=0.03), low-frequency normalised power increased by 2.00+/-0.91 normalised units (nu) (p=0.03), high-frequency normalised power decreased by 1.98+/-0.94 nu (p=0.04) and the low frequency : high frequency ratio increased by 0.40+/-0.19 (p=0.04). HbA1c and angiotensin II increased during treatment with spironolactone by 0.26+/-0.07% (p=0.001) and 8.12+/-1.94 pg/ml (p=0.001) respectively. CONCLUSIONS/INTERPRETATION: Spironolactone worsened endothelial function and heart rate variability in patients with type 2 diabetes. These findings are possibly due to the worsening of glycaemic control and increase in plasma angiotensin II that were seen with spironolactone treatment. Thus the prescription of spironolactone to diabetic patients without heart failure does not seem to be justified.

Hypothetical economic analysis of screening for left ventricular hypertrophy in high-risk normotensive populations.

BACKGROUND: Left ventricular hypertrophy (LVH) measured by echocardiography is a powerful independent marker of increased cardiovascular risk. The prevalence of echocardiographic LVH in patients with high cardiovascular risk appears to be high, even in patients currently considered normotensive. AIM: To ascertain the likely costs of screening for and treating echocardiographic LVH in normotensive patients at high risk of cardiovascular events. DESIGN: Hypothetical economic analysis. METHODS: Cost analyses were based on known costs of echocardiography, costs of selected cardiovascular medications and prevalence of normotensive LVH in at-risk populations, combined with treatment effect data from studies of hypertensive patients with echocardiographic LVH. RESULTS: Screening costs per case for echocardiographic LVH are likely to be low, because of the high prevalence of the condition and the low unit cost of echocardiography. Treatment costs are likely to be comparable to those currently deemed acceptable in treating high-risk cardiovascular populations, e.g. the HOPE study population. DISCUSSION: The costs of screening for and treating LVH in normotensive patients at risk of cardiovascular events do not appear to be prohibitively high. Trials of screening and treatment for normotensive LVH seem therefore to be warranted.

Detection of massive transplacental haemorrhage by flow cytometry.

Flow cytometry has been shown to be a more accurate and sensitive method than the Kleihauer-Betke test for the measurement of feto-maternal haemorrhage in Rh(D) incompatibility. This report describes the successful use of flow cytometry to detect and monitor the management of a massive transplacental haemorrhage (105 ml) of fetal Rh(D) positive cells in a Rh(D) negative woman. The report highlights the accuracy and reproducibility of the test and the stability of a blood sample when transferred 596 kilometres to a central testing facility.

Automated reticulocyte counting: evaluation of the Coulter STKS Haematology Analyser reticulocyte counting function.

This study evaluated reticulocyte counting with the automated reticulocyte function of the Coulter STKS Haematology Analyser. This is an upgrade option for Coulter STKS and MAXIM haematology analysers. Reticulocyte counts obtained with the automated reticulocyte counting function were compared with those obtained by visual counting. Reticulocyte counting with both methods gave excellent comparability with a correlation coefficient of 0.98. Results were consistent with the well documented imprecision of the manual method with a coefficient of variation (CV) of 16-22%. In contrast, the automated reticulocyte counting function was more precise with a CV of 12.3%. In both cases, counts were stable after storage for 24 h at room temperature and 4 degrees C. Our results suggest that the use of this upgrade will be beneficial for many laboratories.

Reduced susceptibility to oxidative damage of erythrocyte membranes from medicated schizophrenic patients.

Susceptibility to non-enzymatic peroxidation of erythrocyte membranes from medicated schizophrenic patients relative to healthy control subjects was investigated by measuring internalization into erythrocytes of ethylene glycol, cellobiotol or mannitol, with or without preincubation with cumene hydroperoxide or with chlorpromazine. The main finding was that erythrocytes from schizophrenic patients were less susceptible than those from control subjects to non-enzymatic oxidative damage from cumene hydroperoxide, as measured by internalization of cellobiotol and mannitol. At baseline before incubation, there was reduced internalization of cellobiotol and mannitol and this was reduced even further by preincubation with chlorpromazine. It is suggested that previous findings of fatty acid deficits in erythrocyte membranes from neuroleptic-treated schizophrenic patients are unlikely to have resulted from non-enzymatic oxidative damage of the membrane. Furthermore, it is suggested that depleted erythrocyte membrane essential fatty acids are more likely to be the result of the schizophrenic process rather than antipsychotic drug treatment, and that antipsychotic drugs may even offer protection against membrane lipid peroxidation.

Zopiclone poisoning: tissue distribution and potential for postmortem diffusion.

Zopiclone is the first cyclopyrrolone hypnotic and is chemically unrelated to any existing drug. The authors studied the tissue distribution and postmortem redistribution of zopiclone in a fatal suicidal overdose. A 29-year-old female weighing 64 kg had cardiac blood ethanol 153 mg% and zopiclone blood concentrations in the range 0.9-2.0 microgram/ml in 10 distinct sampling sites. After 40 h at room temperature the range was 0.9-1.8 micrograms/ml in 15 samples. Portal venous blood and urine concentrations were 3.0 and 10.5 micrograms/ml, respectively. Tissue concentrations (microgram/g) were spleen 5.8, peri-renal fat 5.0, psoas muscle 3.3, brainstem 2.8, gastrocnemius muscle 1.9, myocardium 1.6, and kidney 1.7. Eight liver samples had concentrations in the range 0.5-4.9 micrograms/g, with highest concentrations in the left lobe and adjacent to the gallbladder, probably reflecting postmortem diffusion from gastric residue (700 ml, 55.1 micrograms/ml) and bile (14.1 micrograms/ml). Of six lung samples, paired upper and middle samples had concentrations in the range 2.1-2.3 micrograms/g, the right postero-basal 1.3 micrograms/g and the left postero-basal 3.4 micrograms/g. Drug concentration in putrefactive pleural fluid was also higher on the left (2.1 micrograms/ml) than the right (1.4 micrograms/ml), probably reflecting postmortem diffusion from gastric residue. The authors conclude that zopiclone showed little preferential concentration in solid organs and consequently has relatively stable postmortem blood concentrations, with little drug redistribution artefacts. Postmortem diffusion from gastric drug residue elevates drug levels in the left lobe of the liver and left lung lower lobe.

The sequestration of [3H]spiperone by lymphocytes in schizophrenics and their first-degree relatives: a limited vulnerability marker?

The sequestration of [3H]spiperone by lymphocytes was studied in preserved cells obtained from 22 schizophrenic subjects and 40 of their relatives, and the results were compared with those obtained from 25 healthy control subjects. Mean displaceable sequestration values, obtained from measurements made at a single radioligand concentration (1nM) which optimised the relative contribution of "high affinity" sequestration, were found to be similar for all groups of subjects. Furthermore, displaceable spiperone sequestration was abnormally high in only a small proportion of the schizophrenics (13.6%) and their relatives (5%). There was no evidence that either exposure to neuroleptic medication or duration of illness had an effect on sequestration values. The results suggest that, at least until the required experimental conditions are better established, [3H]spiperone sequestration by lymphocytes does not offer a useful vulnerability marker for schizophrenia.