Prior calcium channel blockade and short-term survival following acute myocardial infarction

There is concern over the safety of calcium channel blockers (CCBs) in acute coronary disease. We sought to determine if patients taking calcium channel blockers (CCBs) at the time of admission with acute myocardial infarction (AMI) had a higher case-fatality compared with those taking beta-blockers or neither medication. Clinical and drug treatment variables at the time of hospital admission predictive of survival at 28 days were examined in a community-based registry of patients aged under 65 years admitted to hospital for suspected AMI in Perth, Australia, between 1984 and 1993. Among 7766 patients, 1291 (16.6%) were taking a CCB and 1259 (16.2%) a betablocker alone at hospital admission. Patients taking CCBs had a worse clinical profile than those taking a beta-blocker alone or neither drug (control group), and a higher unadjusted 28-day mortality (17.6% versus 9.3% and 11.1% respectively, both P < 0.001). There was no significant heterogeneity with respect to mortality between nifedipine, diltiazem, or verapamil when used alone, or with a beta-blocker. After adjustment for factors predictive of death at 28 days, patients taking a CCB were found not to have an excess chance of death compared with the control group (odds ratio [OR] 1.06, 95% confidence interval [CI]; 0.87, 1.30), whereas those taking a beta-blocker alone had a lower odds of death (OR 0.75, 95% CI; 0.59, 0.94). These results indicate that established calcium channel blockade is not associated with an excess risk of death following AMI once other differences between patients are taken into account, but neither does it have the survival advantage seen with prior beta-blocker therapy.

Decreased perinatal sunshine duration is associated with increased non-affective but not affective psychosis birth rates

We have previously found an association between variations in schizophrenia birth rates and varyinglevels of perinatal sunshine duration. This study examines whether such an association can also be found for Ža. affective psychosis, and Žb. broadly defined nonaffective psychoses. Data for individuals born between 1931 and 1970 in Australia with ICD9 Other PsychosisŽ295–299.were obtained from the Queensland Mental Health Statistical System. ‘Affective psychosis’ included affective psychosis, schizo-affective psychosis, and depressive and excitative non-organic psychoses. ‘Non-affective psychosis’ included chizophrenia, paranoid disorders and other non-organic psychoses. Those receiving both affective and non-affective psychotic diagnoses were excluded. Rates per 10,000 live monthly general population births were calculated. For each month, we assessed the agreementŽusing the kappa statistic. between trends in Ža. birth rates and Žb. long-term trends in seasonally adjusted perinatal sunshine duration. The analyses were performed separately for males and females. There were 6265 with non-affective psychosis ŽMs3964 rate 66r10,000; Fs2299 44r10,000. and 2858 with affective psychosisŽMs1392 24r10,000; Fs1466 28r10,000.. There were no significant associations between Ža. affective psychosis birth rates for either males or females and Žb. sunshine duration. There was a significant association between nonaffective psychosis birth rates for males only and Žb. sunshine duration Žkappas0.15 p-0.001.. This suggests that, as a risk factor, the effect of reduced perinatal sunshine is specifically associated with males who develop non-affective psychosis. The Stanley Foundation supported this project.

Influence of HIV-1 coinfection on effective management of abnormal vaginal discharge

Background: Reports on microbiologic cure rates following syndromic management (SM) of women with nonulcerative sexually transmitted infections (STIs) are limited. Goal. The goal of the study was to determine the effectiveness of the drugs used in SM of nonulcerative STIs and bacterial vaginosis in women and to compare the response among those with and without HIV-1 coinfection. Study Design: This was a cohort study of women with nonulcerative STIs who were treated according to local SM protocols. Results: Of 692 women recruited, 415 (80%) returned 8 to 10 days later, and 290 (70%) consented to a second examination, in which specimens were obtained. Clinical cure was reported by 67%, and microbiologic cure ranged from 80% to 89% for the three discharge-causing STIs and was independent of HIV-1 status. Only 38% of those with bacterial vaginosis were cured, and HIV-1-infected women were less likely to be cured (28% versus 52%; P < 0.001). Conclusions: Clinical and microbiologic response to SM of the nonulcerative STIs was not affected by HIV-1 coinfection, but cure rates for bacterial vaginosis were reduced.

Association between HIV-1 infection, the etiology of genital ulcer disease, and response to syndromic management

Background: Reports on the effect of HIV-1 infection on healing rates of ulcers are conflicting. Goal: The goal was to determine the etiology and response to treatment of genital ulcer disease (GUD) in relation to HIV-1 infection. Study Design: This was a cohort study of patients with GUD treated with local syndromic management protocols. Results: Among the 587 recruited, the prevalences of infections due to HSV, Treponema pallidum, Chlamydia trachomatis (lymphogranuloma venereum [LGV]), Haemophilus ducreyi, Calymmatobacterium granulomatis, and HIV-1 were 48%, 14%, 11%, 10%, 1%, and 75%, respectively. The prevalence of T pallidum was higher among men (P = 0.03), and an association was seen among HIV-1-seronegatives on univariate and multivariate analyses (P < 0.001; P = 0.01). The prevalence of C trachomatis (LGV) was higher among females (P = 0.004), and an association was seen among HIV-1-seropositives on univariate analysis (P = 0.04). At follow-up, 40/407 (10%) showed a decreased healing tendency, not associated with ulcer etiology or HIV-1 seropositivity. Conclusion: Response to syndromic management of GUD was acceptable and not associated with HIV-1 coinfection.

A randomized trial comparing hormone replacement therapy (HRT) and HRT plus calcitriol in the treatment of postmenopausal osteoporosis with vertebral fractures: Benefit of the combination on total body and hip density

We report a prospective, randomized, multi-center, open-label 2-year trial of 81 postmenopausal women aged 53-79 years with at least one minimal-trauma vertebral fracture (VF) and low (T-score below 2) lumbar bone mineral density (BMD). Group HRT received piperazine estrone sulfate (PES) 0.625 - 1.25 mg/d +/- medroxyprogesterone acetate (MPA) 2.5 - 5 mg/d,- group HRT/D received HRT plus calcitriol 0.25 mug bd. All with a baseline dietary calcium (Ca) of < I g/d received Ca carbonate 0.6 g nocte. Final data were on 66 - 70 patients. On HRT/D, significant (P < 0.001) BNID increases from baseline by DXA were at total body - head, trochanter, Ward's, total hip, inter-trochanter and femoral shaft (% group mean Delta 4.2, 6.1, 9.3. 3.7. 3.3 and 3.3%, respectively). On HRT, at these significant Deltas were restricted to the trochanter and sites. si Wards. Significant advantages of HRT/D over HRT were in BMD of total body (- head), total hip and trochanter (all P = 0.01). The differences in mean Delta at these sites were 1.3, 2.6 and 3.9%. At the following, both groups Improved significantly -lumbar spine (AP and lateral), forearm shaft and ultradistal tibia/fibula. The weightbearing, site - specific benefits of the combination associated with significant suppression of parathyroid hormone-suggest a beneficial effect on cortical bone. Suppression of bone turnover was significantly greater on HRT/D (serum osteocalcin P = 0.024 and urinary hydroxyproline/creatinine ratio P = 0.035). There was no significant difference in the number of patients who developed fresh VFs during the trial (HRT 8/36, 22%; HRT/D 4/34, 12% - intention to treat); likewise in the number who developed incident nonvertebral fractures. This Is the first study comparing the 2 treatments in a fracture population. The results indicate a significant benefit of calcitriol combined with HRT on total body BMD and on BNID at the hip, the major site of osteoporotic fracture.

Reproducibility of the cycling time to exhaustion at VO(2)peak in highly trained cyclists

The purpose of the present study was to examine, in highly trained cyclists, the reproducibility of cycling time to exhaustion (T-max) at the power output equal to that attained at peak oxygen uptake ((V) over dot O(2)peak) during a progressive exercise test. Forty-three highly trained male cyclists (M +/- SD; age = 25 +/- 6yrs; weight = 75 +/- 7 kg; (V) over dot(2)peak = 64.8 +/- 5.2 ml.kg(-1) . min(-1)) performed two T-max tests one week apart. While the two measures of T-max were strongly related (r = 0.884; p < 0.001), T-max from the second test (245 +/- 57 s) was significantly higher than that of the first (237 +/- 57 s; p = 0.047; two-tailed). Within-subject variability in the present study was calculated to be 6 +/- 6%, which was lower than that previously reported for Tmax in sub-elite runners (25%). The mean T-max was significantly (p < 0.05) related to both the second ventilatory turnpoint (VT2; r = 0.38) and to (V) over dot O(2)peak (r = 0.34). Despite a relatively low within-subject coefficient of variation, these data demonstrate that the second score in a series of two T-max tests may be significantly greater than the first. Moreover the present data show that T-max in highly trained cyclists is moderately related to VT2 and (V) over dot O(2)peak.

Colonization and risk factors for Brachyspira aalborgi and Brachyspira pilosicoli in humans and dogs on tea estates in Assam, India

The prevalence of colonization with the anaerobic intestinal spirochaetes Brachyspira aalborgi and Brachyspira pilosicoli was investigated in humans (n = 316) and dogs (n = 101) living on three tea estates in Assam, India. Colonization was detected using PCR on DNA from faeces. Nineteen (6%) human faecal samples contained B. aalborgi DNA, 80 (25.3%) contained B. pilosicoli DNA, and 10 (3.2%) contained DNA from both species. One canine sample contained DNA from B. pilosicoli. Significant factors for B. aalborgi colonization in logistic regression were: infection of family members with B. aalborgi (P < 0.001), being a resident of Balipara (P = 0.03), and use of water treatment (P = 0.03). For B. pilosicoli, significant factors were: other family members being positive for B. pilosicoli (P < 0.001), water obtained from a well (P = 0.006), water treatment (P = 0.03), and not having visited a doctor in the previous 12 months (P = 0.03).

Recruitment of single human low-threshold motor units with increasing loads at different muscle lengths

We investigated the recruitment behaviour of low threshold motor units in flexor digitorum superficialis by altering two biomechanical constraints: the load against which the muscle worked and the initial muscle length. The load was increased using isotonic (low load), loaded dynamic (intermediate load) and isometric (high load) contractions in two studies. The initial muscle position reflected resting muscle length in series A, and a longer length with digit III fully extended in series B. Intramuscular EMG was recorded from 48 single motor units in 10 experiments on five healthy subjects, 21 units in series A and,27 in series B, while subjects performed ramp up, hold and ramp down contractions. Increasing the load on the muscle decreased the force, displacement and firing rate of single motor units at recruitment at shorter muscle lengths (P < 0.001, dependent t-test). At longer muscle lengths this recruitment pattern was observed between loaded dynamic and isotonic contractions, but not between isometric and loaded dynamic contractions. Thus, the recruitment properties of single motor units in human flexor digitorum superficialis are sensitive to changes in both imposed external loads and the initial length of the muscle. (C) 2003 Elsevier Ltd. All rights reserved.

Infrarenal aortic diameter predicts all-cause mortality

Objective - To assess the relationship between infrarenal aortic diameter and subsequent all-cause mortality in men aged 65 years or older. Methods and Results - Aortic diameter was measured using ultrasound in 12 203 men aged 65 to 83 years as part of a trial of screening for abdominal aortic aneurysms. A range of cardiovascular risk factors was also documented. Mortality over the next 3 to 7 years was assessed using record linkage. Initial aortic diameter was categorized into 10 intervals, and the relationship between increasing diameter and subsequent mortality was explored using Cox proportional hazard models. Median diameter increased from 21.4 mm in the youngest men to 22.1 mm in the oldest men. The cumulative all-cause mortality increased in a graded fashion with increasing aortic diameter. Using the diameter interval 19 to 22 mm as the reference, the adjusted hazard ratio for all-cause mortality increased from 1.26 (95% CI: 1.09, 1.44; P = 0.001) for aortic diameters of 23 to 26 mm to 2.38 (95% CI: 1.22, 4.61; P = 0.011) for aortic diameters of 47 to 50 mm. Analysis of causes of death indicated that cardiovascular disease was an important contributor to this increase. Conclusion - Infrarenal aortic diameter is an independent marker of subsequent all-cause mortality.

Behavioural abnormalities of the hyposulphataemic Nas1 knock-out mouse

We recently generated a sodium sulphate cotransporter knock-out mouse (Nas1-/-) which has increased urinary sulphate excretion and hyposulphataemia. To examine the consequences of disturbed sulphate homeostasis in the modulation of mouse behavioural characteristics, Nas1-/- mice were compared with Nas1+/- and Nas1+/+ littermates in a series of behavioural tests. The Nas1-/- mice displayed significantly (P < 0.001) decreased marble burying behaviour (4.33 +/- 0.82 buried) when compared to Nas1+/+ (7.86 +/- 0.44) and Nas1+/- (8.40 +/- 0.37) animals, suggesting that Nas1-/- mice may have decreased object-induced anxiety. The Nas1-/- mice also displayed decreased locomotor activity by moving less distance (1.53 +/- 0.27 m, P < 0.05) in an open-field test when compared to Nas1+/+ (2.31 +/- 0.24 m) and Nas1+/- (2.15 +/- 0.19 m) mice. The three genotypes displayed similar spatiotemporal and ethological behaviours in the elevated-plus maze and open-field test, with the exception of a decreased defecation frequency by the Nas1-/- mice (40% reduction, P < 0.01). There were no significant differences between Nas1-/- and Nas1+/+ mice in a rotarod performance test of motor coordination and in the forced swim test assessing (anti-)depressant-like behaviours. This is the first study to demonstrate behavioural abnormalities in the hyposulphataemic Nas1-/- mice. (C) 2004 Elsevier B.V. All rights reserved.

Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men

The epsilon4 allele of apolipoprotem E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, arnyloid beta1-40 (Abeta40) and homocysteine, (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) mumol/L. The MTHFR genotype had no obvious impact on Hey levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hey and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95% CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hey and Alzheimer's disease.

Evaluating curriculum changes in undergraduate cancer education

Background. Previous studies have indicated that Australian medical schools have not adequately prepared our graduating doctors to care for patients with cancer. The University of Western Australia (UWA) introduced a two-week clinical attachment in cancer medicine for fifth-year students in 2000 and a four-day clinical attachment in palliative care for sixth-year students in 2001. This article evaluates the introduction of these dedicated clinical attachments in cancer and palliative care. Method. The Australian Cancer Society's Cancer Education Survey was administered to the UWA graduates starting their intern year in teaching hospitals in Perth, Western Australia, in 2002. Their responses were compared with data collected in a similar national survey of Australian and New Zealand interns in 2001. Results. The response rate was 56% (n = 70). When compared with the national data for 2001, more UWA interns (2002) would refer a newly diagnosed breast cancer patient to a multidisciplinary breast clinic (97% vs. 74%, P<.001). Fewer UWA 2002 interns rated their training as poor or very poor in the management of patients with incurable cancer (19% vs. 35%, P=.008) and the management of symptoms in patients dying from cancer (10% vs. 37%, P<.001), but they were more likely to rate their training in assisting a patient to stop smoking as poor or very poor (54% vs. 21%, P<.001). Only a quarter of the UWA 2002 interns had examined a patient with a cancer of the mouth or tongue (25% vs. 49%, P<.001), and only two thirds had examined a patient with lymphoma (64% vs. 83%, P<.001). Conclusions. Our data reflect changes in the final two years of the medical course at UWA and suggest that the introduction of dedicated attachments in cancer and palliative care has better prepared graduating doctors to care for patients with cancer.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p < 0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p < 0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p = 0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p = 0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes. (C) 2004 Elsevier Ltd. All rights reserved.

Impact of voluntary folate fortification on plasma homocysteine and serum folate in Australia from 1995 to 2001: a population based cohort study

Study objective: To investigate the effect of the voluntary folate fortification policy in Australia on serum folate and total plasma homocysteine (tHcy) concentrations. Design: Population based cohort study. Setting: Perth, Western Australia. Participants: Men and women aged 27 to 77 years (n = 468), who were originally randomly selected from the Perth electoral roll. The cohort was surveyed in 1995/96 before widespread introduction of folate fortification of a variety of foods, and followed up on two occasions, firstly in 1998/99 and again in 2001, when a moderate number of folate fortified foods were available. Subjects with abnormal serum creatinine concentrations at baseline were excluded from this analysis. Main results: Repeated measures analysis of variance was used to determine changes in serum folate and tHcy over the three surveys and to assess whether time trends were related to age, sex, MTHFR C677T genotype, or consumption of folate fortified foods. An increase (38%) in mean serum folate (p < 0.0005) and a decrease (21%) in mean tHcy (p < 0.0005) were seen after introduction of the voluntary folate fortification policy in Australia. Serum folate was consistently higher (p = 0.032) and tHcy was consistently lower (p = 0.001) in subjects who consumed at least one folate fortified food compared with subjects who did not consume any folate fortified foods in the previous week. The time related changes in serum folate and tHcy were affected only by intake of folate fortified foods (p < 0.0005) and not by any other measured variables including age, sex, or MTHFR genotype. Conclusion: Voluntary fortification of foods with folate in Australia has been followed by a substantial increase in serum folate and decrease in tHcy in the general population.

Refining the perfusion-diffusion mismatch hypothesis

Background and Purpose-The Echoplanar Imaging Thrombolysis Evaluation Trial ( EPITHET) tests the hypothesis that perfusion-weighted imaging (PWI)-diffusion-weighted imaging (DWI) mismatch predicts the response to thrombolysis. There is no accepted standardized definition of PWI-DWI mismatch. We compared common mismatch definitions in the initial 40 EPITHET patients. Methods-Raw perfusion images were used to generate maps of time to peak (TTP), mean transit time (MTT), time to peak of the impulse response (Tmax) and first moment transit time (FMT). DWI, apparent diffusion coefficient ( ADC), and PWI volumes were measured with planimetric and thresholding techniques. Correlations between mismatch volume (PWIvol-DWIvol) and DWI expansion (T2(Day) (90-vol)-DWIAcute-vol) were also assessed. Results-Mean age was 68 +/- 11, time to MRI 4.5 +/- 0.7 hours, and median National Institutes of Health Stroke Scale (NIHSS) score 11 (range 4 to 23). Tmax and MTT hypoperfusion volumes were significantly lower than those calculated with TTP and FMT maps (P < 0.001). Mismatch >= 20% was observed in 89% (Tmax) to 92% (TTP/FMT/MTT) of patients. Application of a +4s ( relative to the contralateral hemisphere) PWI threshold reduced the frequency of positive mismatch volumes (TTP 73%/FMT 68%/Tmax 54%/MTT 43%). Mismatch was not significantly different when assessed with ADC maps. Mismatch volume, calculated with all parameters and thresholds, was not significantly correlated with DWI expansion. In contrast, reperfusion was correlated inversely with infarct growth (R= -0.51; P = 0.009). Conclusions-Deconvolution and application of PWI thresholds provide more conservative estimates of tissue at risk and decrease the frequency of mismatch accordingly. The precise definition may not be critical; however, because reperfusion alters tissue fate irrespective of mismatch.