Myocardial fibrosis and QTc are reduced following treatment with spironolactone or amiloride in stroke survivors: a randomised placebo-controlled cross-over trial.

INTRODUCTION: Myocardial fibrosis is dysrhythmogenic and may contribute to the high incidence of cardiac death in stroke survivors, especially if they have long QTc. We tested the hypothesis that procollagen-1-carboxy terminal peptide (P1CP), a biomarker of myocardial fibrosis, might be improved following treatment with spironolactone or amiloride in stroke survivors. We also tested the hypothesis that both drugs would shorten QTc. STUDY DESIGN: randomised, double-blinded, placebo-controlled, cross-over trial (spironolactone vs. amiloride vs. placebo). Duration of Study: 3 months (1 month per drug). Primary endpoints: P1CP, QTc RESULTS: 11 stroke survivors (5 female), aged 71 ± 4, BP 139/81 mmHg ± 20/11 mmHg, completed the study. Both spironolactone and amiloride significantly reduced P1CP [Spironolactone-Placebo = -24 ug/L, 95% CI = -40 to -6.9; Amiloride-Placebo = -28 ug/L, 95% CI = -44 to -11]. Spironolactone and amiloride both shortened QTc [Spironolactone vs. Placebo=-18 ms(1/2), 95% CI = -36 to -0.55; Amiloride vs Placebo = -25 ms(1/2), 95% CI = -42 to -7.5]. CONCLUSIONS: Procollagen-1-carboxy terminal peptide was reduced following treatment with spironolactone within a month. Further, this is the first study demonstrating amiloride could also improve myocardial fibrosis. The beneficial effects of both drugs on myocardial fibrosis, coupled with their effects on raising potassium translated to a shortening of QTc. Future studies should test the hypothesis that these drugs might reduce the risk of sudden cardiac death in stroke survivors.

A 12-year follow-up study of all-cause and cardiovascular mortality among 10,532 people newly diagnosed with Type 2 diabetes in Tayside, Scotland.

AIMS: To determine absolute and relative risks of all-cause and cardiovascular mortality among patients newly diagnosed with Type 2 diabetes. METHODS: In an observational cohort study using record-linkage databases, based in Tayside, Scotland, UK, we identified newly diagnosed patients with Type 2 diabetes in 1993-2004. We also identified a set of non-diabetic comparators from lists of patients registered with a general practice, individually matched to the diabetic patients by sex, age and deprivation. We followed up patients for mortality and cardiovascular mortality over a 12-year period and calculated hazard ratios using Cox regression. RESULTS: There were 10,532 patients with Type 2 diabetes and 21,056 non-diabetic comparators. Diabetic patients in every age/sex group had higher absolute mortality rates. Even taking deprivation into account, the hazard ratio for mortality was 1.32 (95% CI 1.25-1.40), decreasing to 1.15 (1.09-1.22) after adjusting for pre-existing cardiovascular disease. The hazard ratios for cardiovascular mortality were higher, decreasing from 1.51 (1.37-1.67) to 1.23 (1.11-1.36) after adjusting for pre-existing cardiovascular disease. The hazard ratios decreased with increasing age at diagnosis, although the difference in absolute rate of mortality increased slightly with age. Increased mortality risks were only evident 2 years after diagnosis and increased thereafter. CONCLUSIONS: Patients with Type 2 diabetes have an increased risk of all-cause and cardiovascular mortality compared with non-diabetic comparators, although this is not observable immediately after diagnosis. Age at diagnosis and duration of the disease independently affect absolute and relative mortality risk.

Index laparoscopic cholecystectomy for acute admissions with cholelithiasis provides excellent training opportunities in emergency general surgery.

BACKGROUND: There is minimal data on the outcome of early laparoscopic cholecystectomy (LC) for acute gallbladder disease when performed by trainees. This study assesses the outcomes of a policy of same admission LC incorporated into a surgical training programme in a major teaching hospital. METHODS: 447 index LCs performed over a 3-year period were reviewed retrospectively. The indications, operating surgeon, operating time, use of IOC, conversion rates, reasons for conversion and post-operative stay were analysed. Multivariate analysis of reasons for conversion was performed. RESULTS: 150 LCs were performed by consultants and 297 by registrars; 67 were performed by year 1-3 specialist registrars (SpR) and 230 by year 4-6 SpRs. The indications were biliary colic (n=7), acute cholecystitis (n=180), chronic cholecystitis (n=260), carcinoma (n=1). No difference was found in demographics, operating time (105 min Vs 115 min), use of IOC (34% Vs 29%; P=0.2) and post-operative stay (2 days Vs 1 day) between consultants and registrars. The conversion rates were higher for consultants compared to registrars (29 (19%) Vs 28 (9%), P=0.004). The overall conversion rate was 11%. There were no bile duct injuries. Predictors for conversion were CRP>50 at admission and acute cholecystitis. CONCLUSION: In a teaching hospital setting most acute admission LCs (66%) were performed by trainees. A step wise training programme with active consultant supervision of all index LCs results in low morbidity, low conversion rates, and a short post-operative stay for acute gallbladder disease. This model of same admission cholecystectomy provides a good training opportunity in emergency general surgery.

Incidence of symptoms in previously symptom-free impacted lower third molars assessed in general dental practice.

AIM: To determine the potential of a pathology-free impacted lower third molar to cause symptoms within a year and whether these symptoms can be linked to clinical characteristics, lifestyle or socio-demographic status. DESIGN: One-year prospective cohort study of patients registered in general dental practice in Scotland with at least one asymptomatic impacted lower third molar. METHODS: All general dental practices with panoramic radiography facilities in Tayside, Fife and Greater Glasgow (Scotland, UK) were invited to participate in the study. Orthopantomographs taken between 1995 and 2002 were reviewed and eligible patients were contacted and invited to participate. Patients were assessed in their own dental surgery by the same research dentist. In this baseline assessment, the presence of impaction was confirmed and all patients with a previous history of symptoms and/or pathology were excluded from further analysis. Clinical characteristics such as the angulation and the degree of impaction were recorded. Patients also completed a socioeconomic questionnaire. Eligible patients were re-assessed by the same research dentist one year later when they were asked about their experience of symptoms within the past year. Information was cross-referenced with patients' dental records. RESULTS: A total of 613 patients attended the baseline appointment. Of those, 30 (4.89%) had a history of symptoms and were excluded from the study, leaving 583 (95.10%) eligible patients. From those, 421 (69%) patients with a total of 676 lower third molars were examined one year later. 22.67% of all vertically impacted teeth examined had developed symptoms, along with 13.15% of all mesially impacted, 30.69% of all distally impacted and 6.45% of all horizontal third molars. This association was statistically significant (p < or =0.001). 23.05% of all partially erupted teeth and a surprising 10.49% of all unerupted teeth were associated with symptoms during the study period. This association was also significant (p < or =0.001). There was also a statistically significant inverse association between the development of symptoms and age (p = 0.0028). CONCLUSIONS: The predictability that an impacted lower third molar will develop symptoms in future remains unclear. However, some clinical characteristics such as the angulation, the degree of impaction and the patient's age could be useful in predicting the likelihood of future symptomatology.

A cohort study of the risk of cancer associated with type 2 diabetes.

BACKGROUND: There is evidence to suggest that diabetes may increase the risk of incidence and mortality from cancer. METHODS: In a cohort study using record-linkage health-care datasets for Tayside, Scotland in 1993-2004, we followed up 9577 newly diagnosed patients with type 2 diabetes, and two matched non-diabetic comparators, in the national cancer register. RESULTS AND CONCLUSIONS: The risk ratio for any cancer, adjusted for deprivation, was 0.99 (95%CI 0.90-1.09). Significantly increased risks were observed for pancreatic, liver and colon cancer.

Meta-analysis of sentinel node biopsy in ductal carcinoma in situ of the breast.

BACKGROUND: The need for sentinel lymph node (SLN) biopsy in patients with a preoperative diagnosis of ductal carcinoma in situ (DCIS) is debated. Advocates recommend such biopsy based on a high incidence of SLN involvement in some series. Opponents discourage SLN biopsy based on a perceived low incidence of nodal involvement in this setting. These contradictory arguments are generally based on small studies. The present study is a meta-analysis of the reported data on the incidence of SLN metastasis in patients with DCIS. METHODS: A search of electronic databases identified studies reporting the frequency of SLN metastases in DCIS. The random-effects method was used to combine data. RESULTS: Twenty-two published series were included in the meta-analysis. The estimate for the incidence of SLN metastases in patients with a preoperative diagnosis of DCIS was 7.4 (95 per cent confidence interval (c.i.) 6.2 to 8.9) per cent compared with 3.7 (95 per cent c.i. 2.8 to 4.8) per cent in patients with a definitive (postoperative) diagnosis of DCIS alone. This was a significant difference with an odds ratio of 2.11 (95 per cent c.i. 1.15 to 2.93). CONCLUSION: Patients with a preoperative diagnosis of DCIS should be considered for SLN biopsy.

Increasing prevalence of type 2 diabetes in a Scottish population: effect of increasing incidence or decreasing mortality?

AIMS/HYPOTHESIS: We examined incidence, prevalence and mortality from type 2 diabetes mellitus in a Scottish population over 12 years, and evaluated the effects on prevalence of increasing incidence and decreasing mortality. MATERIALS AND METHODS: We used a diabetes clinical information system in Tayside (population 387,908), Scotland, to identify new cases of type 2 diabetes between 1993 and 2004 and to calculate incidence rates and mid-year prevalence. We defined mortality rates as the number of deaths of diabetic people divided by mid-year prevalence. We used logistic and Poisson regression to analyse trends. We then modelled the increase in prevalence for each year for three scenarios, based on whether mortality or incidence rates remained unchanged from 1993. RESULTS: There was a doubling in incidence and prevalence of type 2 diabetes in Tayside over the 12 years, with statistically significant increasing trends of 6.3 and 6.7% per year respectively. The mortality rate decreased. If incidence and mortality had remained at 1993 levels, there would have been an increase in prevalence of 855 per 100,000 in 2003, accounting for 60.1% of the actual increase of 1,423 per 100,000. If there had been no mortality decrease, prevalence in 2003 would have been very similar to the actual prevalence observed. CONCLUSIONS/INTERPRETATION: Decreasing mortality rates in Tayside had less effect on the increase in prevalence than did increasing incidence. Even if incidence and mortality remain unchanged, prevalence will increase by over 20% in the next decade.

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin. SUBJECTS AND METHODS: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group. RESULTS: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA(1c), smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality. CONCLUSIONS/INTERPRETATION: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

QT interval abnormalities are often present at diagnosis in diabetes and are better predictors of cardiac death than ankle brachial pressure index and autonomic function tests.

OBJECTIVES: To study serial measures of maximum QT interval corrected for heart rate (QTc) and QT dispersion (QTD) and their association with cardiac mortality patients with non-insulin dependent diabetes and to compare QT abnormalities with other mortality predictors (ankle brachial pressure index (ABPI) and autonomic function tests) in their ability to predict cardiac death. SETTING: Teaching hospital. METHODS AND PATIENTS: QT interval analysis, heart rate (RR) variation in response to deep breathing and standing, and ABPI were analysed in 192 patients with non-insulin dependent diabetes. Cardiac death was the primary end point. RESULTS: Mean (SD) follow up was 12.7 (3.2) years (range 1.2-17.1 years). There were 48 deaths, of which 26 were cardiac. QTc and QTD were individually significant predictors of cardiac mortality throughout the follow up period (p < 0.001). The predictability of QT parameters was superior to the predictability of ABPI and RR interval analysis. Temporal changes in QT parameters showed that the mean absolute QT parameter was a significant predictor of cardiac death (p < 0.001), whereas an intraindividual change in QT parameter over time was not predictive. CONCLUSION: QT abnormalities seem to exist at the point of diagnosis of diabetes and do not appear to change between then and the subsequent cardiac death. Furthermore, the analysis of QT interval is superior to ABPI and the RR interval in identifying diabetic patients at high risk of cardiac death.

Airway-stabilizing effect of long-acting beta2-agonists as add-on therapy to inhaled corticosteroids.

BACKGROUND: The protection afforded by long-acting beta(2)-agonists against bronchoconstrictor stimuli can be regarded as a surrogate for their stabilizing effects on airway smooth muscle. AIM: To determine the magnitude of residual bronchoprotection after chronic dosing with long-acting beta(2)-agonists. DESIGN: Retrospective meta-analysis. METHODS: Medline, BIDS and Cochrane Library databases were searched from 1990. A meta-analysis was then performed of 13 eligible randomized placebo-controlled trials (596 patients) in which second-line treatment with a long-acting beta(2)-agonist (salmeterol or formoterol) was used for 1 week or more. The residual protection against bronchoconstrictor stimuli as doubling dose/dilution shift was the main outcome measure. RESULTS: Data were assessed according to Quorum criteria. Combining the results of the meta-analysis, the overall estimated protection amounted to a 0.79 (95%CI 0.63-0.96) doubling dose/dilution shift from placebo. Subgroup analysis showed greater protection at peak vs. trough, but no difference between formoterol vs. salmeterol, or between direct vs. indirect challenge. There was no evidence of significant heterogeneity across all the studies, or within any of the subgroups. DISCUSSION: When used as second-line treatment, the overall additive protective effect of long-acting beta(2)-agonists amounts to a 0.8 doubling dose/dilution shift. This stabilizing effect on airway smooth muscle may explain their beneficial effects on exacerbations.

Observer variability in the Goseki grouping of gastric adenocarcinoma in resection and biopsy specimens.

AIMS: The Goseki grouping of gastric adenocarcinoma has been suggested as a possible prognostic factor. In those centres where it is used, it may be valuable to assess the Goseki grouping of a tumour on the initial diagnostic biopsy as well as on the resection specimen since it may in theory influence management. We examined the robustness of Goseki grouping of gastric adenocarcinoma in representative sections from resection and biopsy specimens in order to assess the consistency of agreement among a group of pathologists. METHODS: A single representative block from 100 gastric resection specimens was studied using a haematoxylin and eosin and mucin (alcian blue/periodic acid-Schiff) stain. These were circulated in batches to members of a group of 12 pathologists who each completed a simple proforma confirming the presence of carcinoma and assigning a Goseki group. In a second circulation the diagnostic biopsy specimen taken prior to resection was examined in the same way. This allowed comparison of the Goseki group of the biopsy and resection specimens. RESULTS: In both studies kappa statistics showed good agreement on tubular differentiation of the carcinoma, but only moderate agreement for the intracellular mucin production, resulting in moderate agreement for the final Goseki group. Correlation between the Goseki group assigned on the biopsy and resected specimens was seen in 62% of the cases. However, the reproducibility was low (kappa 0.375). CONCLUSIONS: The Goseki grouping of resected gastric adenocarcinoma is reproducible and can be used in prognostication. Goseki grouping of biopsy specimens is of limited value in predicting the Goseki group assigned to the resected carcinoma.

Long QTc predicts future cardiac death in stroke survivors.

OBJECTIVES: To test the hypothesis that the QTc of any lead of the ECG predicts death after stroke, and to determine which lead of the ECG carries the greatest risk of cardiac death when its QTc is measured. DESIGN: Standard 12 lead ECGs were analysed by one observer who was blind to patient outcome. SETTING: A major teaching hospital in Scotland. PATIENTS: 404 stroke survivors were studied at approximately one year after the cerebrovascular event and followed for up to 6.3 years. OUTCOME MEASURES: Death from any cause and cardiac mortality. RESULTS: The QTc measured from any lead of the ECG (except aVR) was associated with death from any cause. A prolonged QTc in limb lead III and chest lead V6 carried the highest relative risk of cardiac death (a 3.1-fold incease). After adjusting for overt ischaemic heart disease, pulse pressure, glucose, and cholesterol, a prolonged QTc in lead V6 was associated with a relative risk of cardiac death of 2.8 (95% confidence interval (CI) 1.1 to 7.3) (p = 0.028) and of death from all causes of 2.9 (95% CI 1.6 to 5.3) (p < 0.001). If the QTc in V6 exceeded 480 ms, then the specificity of predicting cardiac death within five years after the stroke was 94%. CONCLUSIONS: Although treatment of the conventional modifiable risk factors is important, stroke survivors with a prolonged QTc in lead V6 are still at a high risk of cardiac death and may need more intensive investigations and treatments than are currently routine practice.

Urate predicts subsequent cardiac death in stroke survivors.

AIMS: To test the hypothesis that urate predicts cardiac death after stroke independent of conventional risk factors of atherosclerosis, creatinine and diuretic use. METHODS AND RESULTS: Serum urate concentration was measured in an unselected cohort of 354 stroke survivors who were followed-up for a median of 2.8 years. Cardiac death was the primary end-point. Urate was associated with a statistically significant threefold increase in relative risk of cardiac death even after adjustment for other conventional risk factors. In the subgroup of patients who were not on diuretics, raised urate was associated with a 12-fold significant increase in relative risk of cardiac death after adjusting for renal function and other conventional risk factors. A urate concentration of greater than 0.31 mmol. l(-1) was 78% sensitive at predicting cardiac death within 5 years after stroke, but was only 54% specific. If urate exceeded 0.38 mmol. l(-1), specificity of predicting cardiac death within 5 years after stroke was 88%. CONCLUSIONS: Elevated serum urate concentration may be used to stratify risk of future cardiac death after stroke. This appeared to be true even in stroke survivors who were not on diuretic therapy.

Identifying populations at risk from environmental contamination from point sources.

OBJECTIVES: To compare methods for defining the population at risk from a point source of air pollution. A major challenge for environmental epidemiology lies in correctly identifying populations at risk from exposure to environmental pollutants. The complexity of today's environment makes it essential that the methods chosen are accurate and sensitive. METHODS: Environmental and mathematical methods were used to identify the population potentially exposed to a point source of airborne pollution emanating from a waste incinerator. Soil sampling was undertaken at 83 sites throughout the city and environs. The concentrations of arsenic and copper were measured at each site. Computer software produced smoothed contour plots of the distribution of arsenic and copper in the soil based on the information derived from the sampling sites. The population at risk was also identified using concentric rings of varying radii, with the source of pollution at the centre. Lastly, we used the sites that had previously been selected and measured the frequency of wind direction, speed and distance from the source of pollution at each site. Theoretical contour plots were constructed using the distance from the source of pollution at each site, with and without incorporating wind frequency as a function of direction. RESULTS: Each method identified different populations at risk from airborne pollution. The use of circles was a very imprecise way of identifying exposed populations. Mathematical modelling that incorporated wind direction was better. Soil sampling at many sites was accurate, as the method is direct; but it is very costly and the close proximity of high and low concentrations hindered interpretation. The smoothed contour plots derived from the soil sampling sites identified an exposed population that was similar to that derived from the spot sampling. CONCLUSIONS: Using circles as the only means of identifying the exposed population leads to dilution of the potential health effect. The best approach is to use local knowledge about wind direction and speed to estimate the population likely to be at risk; to back up this estimate by judicious use of soil sampling; to use contour mapping to guide the final selection of exposed and non-exposed populations; and finally, to interpret the populations identified as being at risk by incorporating information about other potential sources of pollution (past and present) in the area.

Mortality in various types of osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a group of closely related inherited diseases characterized by abnormal bone fragility. The current clinical classification system delineates 6 types, one of which (type II) is so severe that mortality is 100%, either intrauterine or perinatal. The types are differentiated by clinical groups, by severity, and by the presence or absence of other features such as blue sclerae or dentinogenesis imperfecta. There are no known previous studies of mortality in OI. RESULTS: From a registry created in association with the Brittle Bone Society, 743 patients with OI in England and Wales were observed in the period 1980-1993. These were classified into 3 groups (type IA, type III, and types IB, IVA, and IVB combined). Average annual mortality rates were determined in each group by sex and attained age. These rates were compared with 1981 rates in the population of England and Wales, matched by sex and age. Results are given in terms of exposures, observed and expected deaths, and 2 indices of excess mortality: mortality ratios and excess death rates per 1000 person-years. CONCLUSION: In type IA, 51.5% of the OI cases overall, there was no significant excess mortality (mortality ratio 108%, based on 15 deaths). In type III, on the other hand, excess mortality was very high in children and still significantly high at ages 15-34 years. In the combined group of types IB, IVA, and IVB, the mortality ratio was 157% in patients aged 45 and up (not significant at the 95% confidence level), but higher ratios at younger ages were significant, even though based on a total of only 5 deaths.

A case-control study examining the role of physical trauma in the onset of rheumatoid arthritis.

OBJECTIVE: To investigate whether physical trauma may precipitate the onset of rheumatoid arthritis (RA). METHOD: In a case-control study comparing RA out-patients with controls attending non-rheumatology out-patient clinics, 262 patients and 262 age- and sex-matched controls completed a postal questionnaire or were interviewed about any physical trauma in the 6 months before the onset of their symptoms. RESULTS: Fifty-five (21%) of the RA patients reported significant physical trauma in the 6 months before the onset of their disease, compared with only 17 (6.5%) of the controls (P<0.00001). A preceding history of physical trauma was significantly more common in RA patients who were seronegative for rheumatoid factor (P=0.03), but was not significantly associated with sex (P=0.78), age (P=0.64), a family history of RA (P=0.07) or type of occupation, defined as manual or sedentary (P=0.6). CONCLUSION: Physical trauma in the preceding 6 months is significantly associated with the onset of RA.

"Ethnic" variation in childhood lung function may relate to preventable nutritional deficiency.

UNLABELLED: This study aimed to define the differences in lung function between British Caucasian and rural eastern Indian children, and to test the hypothesis that nutrition could account for such "ethnic" variation. To exclude confounders, a rural Indian setting was identified and children were screened for respiratory illness before lung function and nutritional characteristics were measured. Regression equations for this population have already been published. In this study, the lung function differences between rural eastern Indian (n=391) and mean predicted lung function for Caucasian children were characterized, matched for height and sex. In addition, stepwise multiple regression models were fitted to investigate the relative associations of lung function differences with body mass index (BMI), occipitofrontal circumference and age. Although the largest differences in the forced expiratory volume in 1 s (FEV1) [girls 28.7 (27.3-30.1), boys 23.4 (22.2-24.6)] and forced vital capacity [girls 27.9 (26.4-29.4), boys 30.7 (29.6-31.9)] [values as mean difference in % predicted (95% confidence intervals)] ever reported between two populations were observed, differences in peak expiratory flow rate (PEFR) were small. BMI was strongly associated with inter-racial differences for FEV1 for both sexes (boys beta = -0.227, girls beta = -0.353. p < 0.001) and PEFR for girls (beta = -0.200, p < or = 0.05) (beta = standardized coefficient). CONCLUSION: Preventable nutritional factors may play a causal role in determining the FEV1 differences between rural Indian and Caucasian children. As peak FEV1 in youth influences respiratory morbidity in later life, it is important to define specific nutrient deficiencies that may relate to poor FEV1 growth in these children.

Effect of phenylephrine with and without atropine on QT dispersion in healthy normotensive men.

The present study examined if changes in cardiac after-load would affect QT interval dispersion. QT dispersion (QTd) on the 12-lead electrocardiogram is believed to be a noninvasive measure of electrical inhomogeneity in the heart and has recently been identified as a sensitive predictor of sudden cardiac death. In experimental models, an increase in cardiac afterload has been shown to alter action potential durations through mechanoelectrical feedback. This may result in an altered dispersion of action potential repolarization in the ventricle. Until now, there has been little evidence for this occurring in man in vivo. In the present study, the effects of afterload on QTd were examined in 10 healthy male volunteers (mean age [SD] 25 years [4.5]) who received an intravenous infusion of phenylephrine (0.2 to 3.6 microg/kg/min) given in incremental doses, and placebo in a blinded, crossover fashion. Because phenylephrine is known to alter heart rate (HR) significantly (via a reflex vagal response), the study was performed with and without atropine. We found a significant positive correlation between acute changes in blood pressure (BP) and changes in all QTd indexes (deltaQTd/delta systolic BP and deltaQTcd/deltasystolic BP r values 0.67 and 0.60, respectively; p <0.001). This relation was independent of HR changes or reflex vagal activity. Atropine had no significant effect on QTd. These observations have important clinical implications and may partly account for why sudden deaths and arrhythmic complications occur so frequently in conditions associated with increased after-load, such as hypertension and heart failure.

The relationship between ocular toxoplasmosis and levels of specific toxoplasma antibodies.

The relationship between ocular toxoplasmosis and levels of toxoplasma specific antibodies was examined in 195 patients. Using clinical information collected by questionnaires, patients were divided into: 97 with ocular toxoplasmosis (group 1) and 98 with ocular lesions not due to toxoplasma (group 2). The geometric mean of dye test titres (+/-S.D. natural log titre) in group 1 was 53.2 (+/-0.95) compared with 24.6 (+/-1.11) in group 2 (P < 0.001). Young females tended to have more active lesions compared with young males (P < 0.05). There was an age-dependent difference in dye test titres between the groups (P < 0.001). Group 1 showed a decline in titre with age compared with an increase in group 2. Ocular toxoplasmosis was diagnosed most frequently among 21-30 year olds. More group 1 patients had dye test titres > or = 65 iu/ml than group 2 (P < 0.05). Dye test titres > or = 65 iu/ml support a diagnosis of ocular toxoplasmosis whereas lower titres suggest other causes for eye lesions.

QT dispersion in patients with chronic heart failure: beta blockers are associated with a reduction in QT dispersion.

OBJECTIVE: To compare QT dispersion in patients with impaired left ventricular systolic function and in matched control patients with normal left ventricular systolic function. DESIGN: A retrospective, case-control study with controls matched 4:1 for age, sex, previous myocardial infarction, and diuretic and beta blocker treatment. SETTING: A regional cardiology centre and a university teaching hospital. PATIENTS: 25 patients with impaired left ventricular systolic function and 100 patients with normal left ventricular systolic function. MAIN OUTCOME MEASURES: QT and QTc dispersion measured by three methods: the difference between maximum and minimum QT and QTc intervals, the standard deviation of QT and QTc intervals, and the "lead adjusted" QT and QTc dispersion. RESULTS: All measures of QT/QTc dispersion were closely interrelated (r values 0.86 to 0.99; all p < 0.001). All measures of QT and QTc dispersion were significantly increased in the patients with impaired left ventricular systolic function v controls (p < 0.001): 71.9 (6.5) (mean (SEM)) v 46.9 (1.7) ms for QT dispersion, and 83.6 (7.6) v 54.3 (2.1) ms(-1-2) for QTc dispersion. All six dispersion parameters were reduced in patients taking beta blockers (p < 0.05), regardless of whether left ventricular function was normal or impaired-by 9.4 (4.6) ms for QT dispersion (p < 0.05) and by 13.8 (6. 5) ms(-1-2) for QTc dispersion (p = 0.01). CONCLUSIONS: QT and QTc dispersion are increased in patients with systolic heart failure in comparison with matched controls, regardless of the method of measurement and independently of possible confounding factors. beta Blockers are associated with a reduction in both QT and QTc dispersion, raising the possibility that a reduction in dispersion of ventricular repolarisation may be an important antiarrhythmic mechanism of beta blockade.