Clinical utility of distributed source modelling of interictal scalp EEG in focal epilepsy.

OBJECTIVE: Assess the clinical utility of non-invasive distributed EEG source modelling in focal epilepsy. METHODS: Interictal epileptiform discharges were recorded from eight patients - benign focal epilepsy of childhood (BFEC), four; mesial temporal lobe epilepsy (MTLE), four. EEG source localization (ESL) applied 48 forward-inverse-subspace set-ups: forward - standardized, leadfield-interpolated boundary element methods (BEMs, BEMi), finite element method (FEMi); inverse - minimum norm (MNLS), L1 norm (L1), low resolution electromagnetic tomography (LORETA), standardized LORETA (sLORETA); subspace- whole volume (3D), cortex with rotating sources (CxR), cortex with fixed sources (CxN), cortex with fixed extended sources (patch). Current density reconstruction (CDR) maxima defined 'best-fit'. RESULTS: From 19,200 CDR parameter results and 2304 CDR maps, the dominant variables on best-fit were inverse model and subspace constraint. The most clinically meaningful and statistically robust results came with sLORETA-CxR/patch (lower Rolandic in BFEC, basal temporal lobe in MTLE). Computation time was inverse model dependent: sub-second (MNLS, sLORETA), seconds (L1), minutes (LORETA). CONCLUSIONS: From the largest number of distributed ESL approaches compared in a clinical setting, an optimum modelling set-up for BFEC and MTLE incorporated sLORETA (inverse), CxR or patch (subspace), and either BEM or FEMi (forward). Computation is efficient and CDR results are reproducible. SIGNIFICANCE: Distributed source modelling demonstrates clinical utility for the routine work-up of unilateral BFEC of the typical Rolandic variety, and unilateral MTLE secondary to hippocampal sclerosis.

Effects of selective and non-selective cyclo-oxygenase inhibition on endothelial function in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk that has been attributed to endothelial dysfunction and inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase (COX)-2 inhibitors have been shown in some studies to improve endothelial function in subjects without RA. The aim of this study was to investigate the effects of COX inhibition on endothelial function in patients with RA. METHODS: Patients with RA (n = 37) were randomized to receive a 2-week course of either indomethacin (75 mg bd), rofecoxib (12.5 mg bd), or placebo in a double-blind study. Endothelial function was measured using flow-mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia. Arterial stiffness was also assessed using pulse wave analysis (PWA) through the measurement of the aortic augmentation index (AIx). Measurements of vascular function and inflammatory markers were taken before and at the end of the treatment period. RESULTS: There were no significant differences in changes in FMD, AIx, blood pressure (BP), serum creatinine, erythrocyte sedimentation rate (ESR), or high-sensitivity C-reactive protein (hsCRP) between groups. However, compared with the other treatment groups, there was a tendency for systolic BP to decrease in the placebo group (p = 0.063) and for creatinine to increase in the indomethacin and rofecoxib groups after treatment (p = 0.054). CONCLUSIONS: This study suggests that COX inhibition by indomethacin or rofecoxib do not improve endothelial function in patients with RA.

Clinical utility of current-generation dipole modelling of scalp EEG.

OBJECTIVE: To investigate the clinical utility of current-generation dipole modelling of scalp EEG in focal epilepsies seen commonly in clinical practice. METHODS: Scalp EEG recordings from 10 patients with focal epilepsy, five with Benign Focal Epilepsy of Childhood (BFEC) and five with Mesial Temporal Lobe Epilepsy (MTLE), were used for interictal spike dipole modelling using Scan 4.3 and CURRY 5.0. Optimum modelling parameters for EEG source localisation (ESL) were sought by the step-wise application of various volume conductor (forward) and dipole (inverse) models. Best-fit ESL solutions (highest explained forward-fit to measured data variance) were used to characterise best-fit forward and inverse models, regularisation effect, additional electrode effect, single-to-single spike and single-to-averaged spike variability, and intra- and inter-operator concordance. Inter-parameter relationships were examined. Computation times and interface problems were recorded. RESULTS: For both BFEC and MTLE, the best-fit forward model was the finite element method interpolated (FEMi) model, while the best-fit single dipole models were the rotating non-regularised and the moving regularised models. When combined, these forward-inverse models appeared to offer clinically meaningful ESL results when referenced to an averaged cortex overlay, best-fit dipoles localising to the central fissure region in BFEC and to the basolateral temporal region in MTLE. Single-to-single spike and single-to-averaged spike measures of concordance for dipole location and orientation were stronger for BFEC versus MTLE. The use of an additional pair of inferior temporal electrodes in MTLE directed best-fit dipoles towards the basomesial temporal region. Inverse correlations were noted between unexplained variance (RD) and dipole strength (Amp), RD and signal to noise ratio (SNR), and SNR and confidence ellipsoid (CE) volume. Intra- and inter-operator levels of agreement were relatively robust for dipole location and orientation. Technical problems were infrequent and modelling operations were performed within 5min. CONCLUSIONS: The optimal forward-inverse single dipole modelling set-up for BFEC and MTLE interictal spike analysis is the FEMi model using the combination of rotating non-regularised and moving regularised dipoles. Dipole modelling of single spikes characterises best-fit dipole location and orientation more reliably in BFEC than in MTLE for which spike averaging is recommended. SIGNIFICANCE: The clinical utility of dipole modelling in two common forms of focal epilepsy strengthens the case for its place in the routine clinical work-up of patients with localisation-related epilepsy syndromes.

Acute acetaminophen toxicity: report of a case.

A case of acetaminophen overdose in a patient presenting with a mandible fracture is presented to illustrate the clinical scenario, pathophysiology, and treatment of acute toxicity with this commonly used over-the-counter medication.

A case-control study of the androgen receptor gene CAG repeat polymorphism in Australian prostate carcinoma subjects.

BACKGROUND: The development of prostate carcinoma is androgen-dependent. The coding sequence of the androgen receptor (AR) gene contains a CAG repeat polymorphism that has been shown to influence AR activity in vitro. Studies of this polymorphism as a prostate carcinoma risk factor have been conflicting. METHODS: A matched case-control design was used in a clinic-based multicenter study of Australian prostate carcinoma subjects. Cancer subjects were matched by age and locality with controls, all of whom had a serum prostate specific antigen (PSA) level of less than 4 mg/L. Conditional logistic regression was used to determine the relative risk of prostate carcinoma dependent on AR gene CAG number. The association of disease characteristics at diagnosis with the polymorphism also was assessed. RESULTS: Five hundred forty-five cases of prostate carcinoma and 456 matched case-control pairs were recruited. Association studies of disease characteristics at diagnosis showed age at diagnosis to be associated with AR CAG number by univariate (P = 0.004) and multivariate (adjusting for PSA, stage, and grade) linear regression (P = 0.018). No association was observed between the polymorphism and disease stage (TNM-based categories; P = 0.277), histologic grade (P = 0.41), or PSA level at diagnosis (P = 0.48). In the pairwise case-control analysis, the odds ratio of prostate carcinoma for a change of 5 CAG repeats gave an odds ratio of 0.9821 (95% confidence interval, 0.84-1.15). CONCLUSIONS: In this Australian study population, the AR CAG repeat polymorphism was not a risk factor for prostate carcinoma, but a shorter repeat sequence was associated with earlier age at diagnosis.

Complementary therapies: have they become accepted in general practice?

OBJECTIVES: To describe Victorian general practitioners' attitudes towards and use of a range of complementary therapies. DESIGN: A self-administered postal survey sent to a random sample of 800 general practitioners (GPs) in Victoria in July 1997. PARTICIPANTS: 488 GPs (response rate, 64%). MAIN OUTCOME MEASURES: GPs' knowledge; opinions about harmfulness and effectiveness; appropriateness for GPs to practise; perceived patient demand; need for undergraduate education; referral rates to complementary practitioners; and training in and practice of each therapy. RESULTS: Acupuncture, hypnosis and meditation are well accepted by the surveyed GPs, as over 80% have referred patients patients to practitioners of these therapies and nearly half have considered using them. General practitioners have trained in various therapies--meditation (34%), acupuncture (23%), vitamin and mineral therapy (23%), hypnosis (20%), herbal medicine (12%), chiropractic (8%), naturopathy (6%), homoeopathy (5%), spiritual healing (5%), osteopathy (4%), aroma-therapy (4%), and reflexology (2%). A quarter to a third were interested in training in chiropractic, herbal medicine, naturopathy and vitamin and mineral therapy. General practitioners appear to underestimate their patients' use of complementary therapies. CONCLUSIONS: There is evidence in Australia of widespread acceptance of acupuncture, meditation, hypnosis and chiropractic by GPs and lesser acceptance of the other therapies. These findings generate an urgent need for evidence of these therapies' effectiveness.

Primer postcard improves postal survey response rates.

OBJECTIVE: This study measures the effect of an intervention to improve mailed survey response rates. METHOD: A randomised controlled trial of a 'primer' postcard was performed as part of a large survey in Victoria in 1997. Prior to the survey mailout, half the sample of 800 general practitioners supplied by the Health Insurance Commission was sent, at random, a primer card to request prompt return of the survey. RESULTS: The intervention resulted in a more rapid return of the survey and improved overall response rates from 60% to 66%. The increased cost per returned survey (40 cents) was largely offset by fewer non-responders requiring follow-up. CONCLUSIONS: A primer postcard is a time and cost-efficient method to increase response rates in general practitioner surveys. IMPLICATIONS: Public health researchers should consider implementing this intervention to improve response rates to postal surveys. Reports of other response maximising strategies should report the cost per returned survey to allow better comparison.

Helicobacter pylori infection is not a correlate of plasma fibrinogen in the Australian population.

Plasma fibrinogen concentration is an important independent risk factor for cardiovascular disease. Studies into whether Helicobacter pylori infection and fibrinogen are associated have yielded inconsistent results. Despite the geographical variation in fibrinogen and prevalence of H. pylori infection, all studies to date have been undertaken in the United Kingdom or Italy. The association between H. pylori infection and fibrinogen was investigated in 324 adults, 65% of a random sample, in an Australian regional city. The mean plasma fibrinogen concentration in 98 infected participants (2.52 g/l) was similar to that in 226 non-infected subjects (2.58 g/l, P = 0.51); 95% confidence interval on the difference was -0.23-0.11 g/l. After including all potential confounding factors in a backward multiple linear regression analysis, H. pylori was still not associated with fibrinogen (P = 0.084). Any association between H. pylori and cardiovascular disease in Australia is not mediated through fibrinogen.

Passive ventricular constraint amends the course of heart failure: a study in an ovine model of dilated cardiomyopathy.

OBJECTIVE: Dilated cardiomyopathy (DCM) is associated with a progressive deterioration in cardiac function. We hypothesised that some of the deleterious effects of DCM could be reduced by mechanically limiting the degree of cardiac dilatation. METHODS: A Transonic 20A cardiac output (CO) flow-probe was implanted in the pulmonary artery of 12 adult (52 +/- 4 kg) sheep. Early heart failure was created by rapid right ventricular (RV) pacing for 21 days at a rate which resulted in an initial 10% decrease in CO (to a maximum of 190 bpm). A custom polyester jacket (Acorn Cardiovascular, St Paul, MN) was then placed, via a partial lower sternotomy, on the ventricular epicardium of all sheep. Animals were randomised either to jacket retention (wrap) or removal (sham). Pacing was recommenced at a higher rate (that initiated a further 10% decrease in CO) for 28 days. Haemodynamic and echocardiographic parameters were determined at baseline, implant and at termination. RESULTS: At termination, the left ventricular fractional shortening was significantly higher (p = 0.03), the degree of mitral valve regurgitation lower (scaled 0-3) (p = 0.03) and the left ventricular long axis area smaller (p = 0.02) in the wrap animals compared with sham. CONCLUSIONS: In this model of heart failure, ventricular constraint with a polyester jacket diminished the deterioration in cardiac function associated with progressive dilated cardiomyopathy. These results suggest that maintainance of a more normal cardiac size and shape may be beneficial in patients with dilated cardiomyopathy.

Effects of left atrial dilatation on the endocardial atrial defibrillation threshold: a study in an ovine model of pacing induced dilated cardiomyopathy.

Left atrial (LA) dilation is a common finding in patients with chronic atrial fibrillation (AF). Progressive dilatation may alter the atrial defibrillation threshold (ADFT). In our study, epicardial electrodes were implanted on the LA free wall and right ventricular apex of eight adult sheep. Large surface area, coiled endocardial electrodes were positioned in the coronary sinus and right atrium (RA). LA dilatation was induced by rapid ventricular pacing (190 beats/min) for 6 weeks and echocardiographically assessed weekly along with the ADFT (under propofol anesthesia). LA effective refractory period (ERP) was measured every 2-3 days using a standard extra stimulus technique and 400 ms drive. The AF cycle length (AFCL) was assessed from LA electrograms. During the 6 weeks of pacing the mean LA area increased from 6.1 +/- 1.5 to 21.3 +/- 2.4 cm2. There were no significant changes in the mean ADFT (122 +/- 15 V), circuit impedance (46 +/- 5 omega), or LA AFCL (136 +/- 23 ms). There was a significant increase in the mean LA ERP (106 +/- 10 ms at day 0, and 120 +/- 13 ms at day 42 of pacing). In this study, using chronically implanted defibrillation leads, the minimal energy requirements for successful AF were not significantly altered by ongoing left atrial dilatation. This finding is a further endorsement of the efficiency of the coronary sinus/RA shock vector. Furthermore, the apparent stability of the AF present may be a further indication of a link between the type of AF and the ADFT.

Helicobacter pylori infection: an added stressor on iron status of women in the community.

OBJECTIVE: To explore a possible association between Helicobacter pylori infection and iron status. DESIGN: Cross-sectional study. SETTING: Ballarat (a major regional city in Victoria), population 78000, October November 1997. PARTICIPANTS: 160 women and 152 men, a subsample of participants in a cardiovascular disease risk factor prevalence survey for whom frozen plasma was available. MAIN OUTCOME MEASURES: H. pylori IgG antibody status by enzyme immunoassay; iron intake; plasma iron, transferrin and ferritin concentrations. RESULTS: 28% of women and 33% of men were infected with H. pylori. The mean (SEM) plasma ferritin concentration of infected women (59.3 [7.6] microg/L) was significantly lower than for non-infected women (88.8 [7.9] microg/L; P=0.002), after adjusting for age. Mean daily dietary iron intakes were similar in infected and non-infected women. CONCLUSIONS: H. pylori infection appears to be an additional stressor on women's iron status, but the mechanism remains to be determined.

Age-standardised mortality and proportional mortality analyses of aboriginal and non-aboriginal deaths in metropolitan, rural and remote areas.

The study's aim was to assess how much of the variation in disease-specific mortality between metropolitan, rural and remote areas is specific to those diseases or reflects the all-cause mortality pattern. The ranges and variances of disease-specific standardised proportional mortality ratios between geographical areas were compared to those of the corresponding standardised mortality ratios. For most chapters in the International Classification of Diseases, the ranges and variances of the standardised proportional mortality ratios were less than 40% of those of the corresponding standardised mortality ratios. Only a small proportion of the variation in mortality can therefore be attributed to a specific disease component; the remainder must be attributed to an underlying 'force of mortality'. Research, programs and policies addressing the socio-economic disadvantages of living in remote areas may lead to a greater improvement in mortality than those targeting specific diseases.

Susceptibility to atrial fibrillation: a study in an ovine model of pacing-induced early heart failure.

INTRODUCTION: The development of susceptibility to atrial fibrillation (AF) is a common consequence of many forms of cardiovascular disease, especially heart failure. In this study we used a sheep model of pacing-induced stable early heart failure to describe, quantify, and relate the level of susceptibility to AF to changes in structural and electrophysiologic parameters. METHODS AND RESULTS: Epicardial electrodes were implanted on the atria and right ventricles of nine sheep. The AF threshold, atrial vulnerability period, atrial effective refractory period (ERP), and interatrial conduction time were examined during control and over a 6-week period of ventricular pacing at 190 beats/min. Left atrial (LA) area and left ventricular (LV) fractional shortening were monitored using echocardiography. There were significant increases in LA susceptibility to AF (P < 0.0003), LA area (P < 0.0002), and LA ERP400 (P < 0.0002). Rate of increase in LA area was related positively to AF susceptibility (P = 0.02) and inversely to LA ERP400 (P = 0.002). LV fractional shortening decreased to approximately 50% of control value (P < 0.00001). No changes were observed in right atrial electrophysiology. CONCLUSION: In this study, susceptibility (the ability of an extrastimulus to induce AF) was rigorously measured within a predetermined format. Significant relationships were found to exist between susceptibility, certain of the observed changes in atrial electrophysiology and structure.

Comparison of unsafe drinking between a rural and metropolitan area.

Factors associated with unsafe drinking in a rural area were identified and the prevalence of unsafe drinking and alcohol related mortality compared with a metropolitan area. Alcohol consumption data were collected from a random sample of adults in Greater Ballarat. Odds ratios of demographic factors associated with unsafe drinking were estimated by logistic regression. Compared with males and 20-29-year-olds, females and 30-59-year-olds had a significantly lower prevalence of 'intermediate' or higher risk drinking and binge-only drinking. Rural-metropolitan ratios for the prevalence of unsafe drinking and alcohol related mortality were also greatest in young adults. Young adults must adopt safer drinking habits if the rural excess in mortality is to be reduced.

The influence of preoperative antibiotics on success of endosseous implants up to and including stage II surgery: a study of 2,641 implants.

According to the American College of Surgeons, complex oral surgical procedures, including the transoral placement of endosseous implants, are of the type that may require prophylactic antibiotics. However, the routine use of prophylactic antibiotics in the field of dental implantology continues to be controversial, and their utilization varies widely. No data from a randomized prospective clinical study of the prophylactic use of antibiotics in implant surgery have been previously published. As part of the comprehensive Dental Implant Clinical Research Group clinical implant study, the preoperative or postoperative use of antibiotics, the type used, and the duration of coverage was left to the discretion of the surgeon. These data were recorded and correlated with failure of osseointegration during healing (stage I) and at stage II surgery (uncovering). The results showed that significantly fewer failures occurred when preoperative antibiotics were used.

Bone quality and implant design-related outcomes through stage II surgical uncovering of Spectra-System root form implants.

Failure rates at second-stage surgery were reported for the ongoing Dental Implant Clinical Research Group studies of the Spectra-System (Core-Vent Corporation, Las Vegas, NV) implants. As of May 1995, 69 implants failed out of 2,633 placed and uncovered. The overall failure rate was 2.6%, with 3.6% in bone quality 1 (BQ-1), 2.4% in BQ-2, 2.5% in BQ-3, and 3.1% in BQ-4. HA-coated cylinders had the lowest number of failures and titanium alloy baskets the highest. The basket design failed more often in the posterior jaw areas; 9 of 32 clinical centers (28%) accounted for 72% of these failures.

Helicobacter pylori infection in an Australian regional city: prevalence and risk factors.

OBJECTIVE: To investigate the prevalence of Helicobacter pylori infection and potential risk factors for infection in an adult Australian population. DESIGN: Cross-sectional study. SETTING: Ballarat, a major regional city in Victoria (population, 78,000; 92% bom in Australia), November 1994 to July 1995. PARTICIPANTS: 217 adults randomly selected from the electoral roll. MAIN OUTCOME MEASURES: H. pylori IgG antibody status by enzyme immunoassay; amount of dental plaque; sociodemographic and other potential risk factors; odds ratios for risk factors determined by logistic regression analysis. RESULTS: Age-standardised prevalence of H. pylori infection was 30.6%. After adjustment for age, sex and socioeconomic index, positive H. pylori status was significantly associated with increasing number of tooth surfaces with a high plaque score (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.7), increasing number of years in a job with public contact (OR, 1.7; 95% CI, 1.3-2.3), blood group B antigen (OR, 3.1; 95% CI, 1.1-9.1), and having lived in a household with more than six members during childhood (OR, 2.5; 95% CI, 1.1-5.5). Negative H. pylori status was significantly associated with increasing education, having ever lived on a farm, and having teeth scaled less than once a year. CONCLUSIONS: H. pylori infection is common. Dental plaque may be a reservoir for H. pylori, which is probably transmitted by person-to-person contact, and blood group B antigen may predispose to infection. Community education about effective oral hygiene and adoption of good hygiene practices by those with regular public contact may be important to prevent acquisition and transmission of H. pylori.

Predictive value of MCV for hazardous drinking in the community.

A recent study suggested that general practitioners (GPs) do not see the necessity of investigating MCVs which unexpectedly and only slightly exceed the reference limit, despite the association between MCV and alcohol abuse. Because a literature search could not find a study of the predictive value of the MCV for hazardous drinking in the community, such a study was undertaken among a random sample of 338 adults living in a regional Australian city. Twenty-nine of the adults admitted drinking hazardously. The MCV with the optimum sensitivity and specificity for identifying the hazardous drinkers was determined. An MCV of > 94 fl identified as many as 35% of the hazardous drinkers whilst misclassifying only 6% of the non-hazardous drinkers. The predictive value was even greater among males, 67%. We conclude that inquiring into MCVs > 94 fl will lead to GPs identifying a significant proportion of adults in the community admitting to hazardous drinking.

Blepharospasm and hemifacial spasm. Randomized trial to determine the most appropriate location for botulinum toxin injections.

PURPOSE: The purpose of the study is to analyze the effectiveness and side effects of botulinum toxin using four different treatment site applications to determine the most successful treatment regime with the least side effects. METHODS: In a prospective trial, 92 patients (50 blepharospasm and 42 hemifacial spasm) were assigned randomly to 1 of 4 different treatment groups (standard [S], brow [B], inner orbital [IO], or outer orbital [OO]). Each treatment group had a different pattern of injection sites in the orbicularis. A total of 285 treatments were given, and the mean follow-up time was 16.4 months. RESULTS: In the blepharospasm group, patients assigned to the standard group had a significantly longer duration of effect than for those in the brow, inner orbital, and outer orbital groups (8.1 weeks compared with 4.5, 4.2, and 3.1 weeks, respectively; P < 0.001). In the hemifacial spasm group, patients in the outer orbital group had significantly shorter duration of effect than those in standard, brow, or inner orbital group (7.2 weeks compared with 12.6, 12.8 and 10.4 weeks, respectively; P < 0.001). The four major complications of botulinum toxin treatment were epiphora, ocular irritation, ptosis, and diplopia. The inner orbital treatment produced significantly more episodes of ptosis (13% of treatments). However, the standard treatment produced the most epiphora and ocular irritation (18% of treatments). CONCLUSIONS: The position of the injection sites around the orbicularis influences the effectiveness and side effects of botulinum toxin treatment for patients with blepharospasm and hemifacial spasm. The further the treatment is away from the eyelid margin, the lower the risk of ocular side effects. The standard treatment produces the longest duration of effect in the blepharospasm group but with the most transient ocular irritation and epiphora. In the hemifacial spasm group, the brow treatment has an equally long duration of effect as that of the standard treatment with fewer side effects.