A comparative study of telephone versus onsite completion of the WOMAC 3.0 Osteoarthritis Index

Objective. Outcome assessment in clinical trials using the Western Ontario and McMaster University (WOMAC 3.0) Osteoarthritis Index is traditionally achieved through self-administration of the Index. However, in other areas of clinical measurement, telephone administration has been shown to be a reliable method of acquiring data that are both accurate and complete. To address this issue in knee osteoarthritis (OA), we conducted a comparative study of telephone administration by interviewer of WOMAC LK3.0 versus onsite self-completion at the hospital. Methods. Fifty consenting patients with knee OA were randomized to complete the WOMAC LK3.0 Index by telephone interview one day, followed by onsite completion the following day, or vice versa. Neither patients nor interviewers had access to any prior scores. Results. The mean age of the 50 patients was 66.3 years (range 44-82); 34 (68%) were female and 16 (32%) male. There was excellent agreement between the mean office and telephone scores, with mean differences for the WOMAC LK3.0 pain, stiffness, and function subscale scores and total score of 0.09, 0.12, 0.78, and 0.98, respectively. These differences were well within the respective protocol defined equivalence criteria of +/- 1.7, +/- 0.9, +/- 6.4, and +/- 9.1, and represented differences from office scores of 0.9, 2.6, 2.4, and 2.2%, respectively. Conclusion. The use of telephone interviews for the WOMAC LK3.0 Index is a valid method of obtaining OA outcome measurements. These observations have important implications for designing data acquisition strategies for future OA clinical trials and for longterm observational studies.

Outcome with calcium channel antagonists after myocardial infarction: A community-based study

Objectives. We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. Background. Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. Methods. Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. Results. From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared,vith patients taking neither calcium antagonists nor beta-blockers. Conclusions. These results are consistent with randomized trial data showing benefit from beta blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists. (C) 1998 by the American College of Cardiology.

NMR study of the radiation-induced cross-linking of poly(tetrafluoroethylene-co-perfluoromethyl vinyl ether)

The gamma-radiolysis of poly(tetrafluoroethylene-co-perfuoromethyl vinyl ether) (TFE/PMVE) was investigated using solid state F-19 and C-13 NMR spectroscopy. Chain scission products identified in the polymer were saturated chain ends -CF2CF3 (G = 1.0), methyl ether end groups -CF2OCF3 (G = 0.9), acid end groups -CF2COOH (G = 0.5), and a small amount of terminal unsaturation -CF=CF2 (G = 0.2). A mechanism for the formation of these scission products was proposed and the G value for main chain scission, G(S), was determined to be 1.4. Cross-linking of TFE/PMVE was found to proceed via a Y-linking mechanism. The G value for cross-linking, G(X), was determined to be 0.9. A maximum of 0.2 mol % cross-links were formed under the experimental conditions.

Morphology of the thyroid in coastal and noncoastal populations of the koala (Phascolarctos cinereus) in Queensland

The gross morphology, histology, and ultrastructure of the thyroid gland of the koala, Phascolarctos cinereus, is described. Generally, the glands were found to contain large-diameter follicles in association with an epithelium of low height. Morphometric analysis demonstrated a high relative thyroid weight (0.3 +/- 0.2 g/kg) for koalas compared with the 0.07-0.24 g/kg typical of eutherian mammals and 0.03-0.1 g/kg found in other marsupials. The relative thyroid weight of glands (0.33 +/- 0.21 g/kg) from the coastal population (less than 28 km from the coastline) was found to be significantly higher (ANOVA: P = 0.007, significant at the 1% level) than that for glands (0.21 +/- 0.11 g/kg) of noncoastal koalas (greater than 28 km from the coastline). Follicle size was positively correlated (at the 0.1% level) with relative thyroid weight in the overall koala sample. The presence of C cells, occurring singly in the epithelial layer, was demonstrated in electron micrographs. Structural features such as low epithelial height, large follicle length and width, and large intercellular spaces in association with low concentrations of free TS (3.3 +/- 2.1 pM) and free T-3 (1.4 +/- 0.9 pM) as reported previously (Lawson et al., 1996) are consistent with an unusually low level of glandular activity in the koala thyroid even though iodine concentrations in the thyroid gland [4.7 +/- 1.6 mg/g (dry weight)] as well as leaf [0.8 +/- 0.3 mu g (dry weight)] and soil samples [3.8 mu g/g (dry weight)] from the koalas' habitat appear unremarkable. (C) 1998 Academic Press.

Data analysis in multiple-frequency bioelectrical impedance analysis

The performance of three analytical methods for multiple-frequency bioelectrical impedance analysis (MFBIA) data was assessed. The methods were the established method of Cole and Cole, the newly proposed method of Siconolfi and co-workers and a modification of this procedure. Method performance was assessed from the adequacy of the curve fitting techniques, as judged by the correlation coefficient and standard error of the estimate, and the accuracy of the different methods in determining the theoretical values of impedance parameters describing a set of model electrical circuits. The experimental data were well fitted by all curve-fitting procedures (r = 0.9 with SEE 0.3 to 3.5% or better for most circuit-procedure combinations). Cole-Cole modelling provided the most accurate estimates of circuit impedance values, generally within 1-2% of the theoretical values, followed by the Siconolfi procedure using a sixth-order polynomial regression (1-6% variation). None of the methods, however, accurately estimated circuit parameters when the measured impedances were low (<20 Omega) reflecting the electronic limits of the impedance meter used. These data suggest that Cole-Cole modelling remains the preferred method for the analysis of MFBIA data.

Comparative in vitro effects of closantel and selected beta-ketoamide anthelmintics on a gastrointestinal nematode and vertebrate liver cells

PNU-87407 and PrNU-88509, beta-ketoamide anthelmintics that are structurally related to each other and to the salicylanilide anthelmintic closantel, exhibit different anthelmintic spectra and apparent toxicity in mammals, The basis for this differential pharmacology was examined in experiments that measured motility and adenosine triphosphate (ATP) levels in larval and adult stages of the gastrointestinal nematode, Haemonchus contortus, and in a vertebrate liver cell line and mitochondria, PNU-87407 and PNU-88509 both exhibited functional cross-resistance with closantel in larval migration assays using closantel-resistant and -sensitive isolates of H, contortus. Each compound reduced motility and,ATP levels in cultured adult H. contortus in a concentration- and time-dependent manner: however, motility was reduced more rapidly by PNU-88509, and ATP levels were reduced by lower concentrations of closantel than the beta-ketoamides. Tension recordings from segments of adult H, contortus showed that PNU-88509 induces spastic paralysis, while PNU-87407 and closantel induce flaccid paralysis of the somatic musculature. Marked differences in the actions of these compounds were also observed in the mammalian preparations. In Chang liver cells, ATP levels were reduced after 3 h exposures to greater than or equal to 0.25 mu M PNU-87407 1 mu M closantel or 10 mu M PNU-88509, Reductions in ATP caused by PNU-88509 were completely reversible, while the effects of closantel and PNU-87407; were irreversible. PNU-87407, closantel and PNU-88509 uncoupled oxidative phosphorylation in isolated rat liver mitochondria, inhibiting the respiratory control index (with glutamate or succinate as substrate) by 50% at concentrations of 0.14, 0.9 and 7.6 mu M respectively.

Hypothalamic dopamine D1 receptors are involved in the stimulation of prolactin secretion by high environmental temperature in the female sheep

Recent evidence suggests that dopamine, acting via its D1 receptors, may function as a neurotransmitter in intrahypothalamic pathways involved in the stimulation of prolactin secretion. Functional dopamine D1 receptors are present in the ventromedial hypothalamic nucleus (VMH) and we hypothesized that they might be part of a prolactin-stimulatory pathway activated by stress. We tested this hypothesis in a series of experiments on sheep involving two different forms of stressors, audiovisual (barking dog) and high environmental temperature. We attempted to block the stimulation of prolactin secretion by infusion into the VMH of an antagonist specific for the D1 receptor. Ovariectomised, oestradiol-implanted merino ewes were surgically implanted with bilateral guide tubes directed at the VMH. After a 180 min pretreatment period, the ewes either were or were not exposed to a stressor (30 min of barking dog or 120 min at 35 degrees C, 65% relative humidity). D1 receptor antagonist, SCH23390 or vehicle (0.9% saline) was infused into the VMH (1.7 mu l/h, 120 nmol/h) for 60 min prior to and during the stressor period. Blood was sampled every 15 min via jugular cannulae and the plasma was assayed for prolactin, cortisol and growth hormone (GH). Both stressors significantly increased prolactin concentrations over control levels. SCH23390 infusion significantly attenuated the prolactin response to high environmental temperature, but had no effect on the prolactin response to audiovisual stress. Cortisol concentrations were significantly increased by audiovisual stress only and were not affected by SCH23390, GH concentrations were not changed by either stressor or infusion. Drug infusion alone did not affect the concentration of the hormones. The data suggest that the VMH D1 receptors are involved in a prolactin stimulatory pathway in response to high environmental temperature. The inability of the D1 antagonist to affect the response to the barking dog indicates that this pathway is stress-specific, implying that there is more than one mechanism or pathway involved in the prolactin response to different stressors.

New techniques in nutritional assessment: body composition methods

New techniques in air-displacement plethysmography seem to have overcome many of the previous problems of poor reproducibility and validity. These have made body-density measurements available to a larger range of individuals, including children, elderly and sick patients who often have difficulties in being submerged underwater in hydrodensitometry systems. The BOD POD air-displacement system (BOD POD body composition system; Life Measurement Instruments, Concord, CA, USA) is more precise than hydrodensitometry, is simple and rapid to operate (approximately 1 min measurements) and the results agree closely with those of hydrodensitometry (e.g. +/-3.4% for estimation of body fat). Body line scanners employing the principles of three-dimensional photography are potentially able to measure the surface area and volume of the body and its segments even more rapidly (approximately 10 s), but the validity of the measurements needs to be established. Advances in i.r. spectroscopy and mathematical modelling for calculating the area under the curve have improved precision for measuring enrichment of (H2O)-H-2 in studies of water dilution (CV 0.1-0.9% within the range of 400-1000 mu l/l) in saliva, plasma and urine. The technique is rapid and compares closely with mass spectrometry (bias 1 (SD 2) %). Advances in bedside bioelectrical-impedance techniques are making possible potential measurements of skinfold thicknesses and limb muscle mass electronically. Preliminary results suggest that the electronic method is more reproducible (intra-and inter-individual reproducibility for measuring skinfold thicknesses) and associated with less bias (+ 12%), than anthropometry (+ 40%). In addition to these selected examples, the 'mobility' or transfer of reference methods between centres has made the distinction between reference and bedside or field techniques less distinct than in the past.

Bioimpedance: Is it a predictor of true water volume?

Bioelectrical impedance analysis (BIA) has been reported to be insensitive to changes in water volumes in individual subjects, This study was designed to investigate the effect on the intra- and extracellular resistances (Ri and Re) of the segments of subjects for whom body water was changed without significant change to the total amount of electrolyte in the respective fluids, Twelve healthy adult subjects were recruited. Ri and Re of the leg, trunk, and arm of the subjects were determined from BIA measures prior to commencement of two separate studies that involved intervention, resulting in a loss/gain of body water effected either bt a sauna followed by water intake (study 1) or by ingestion (study 2). Ri and Re of the segments were also determined at a number of times following these interventions, The mean change in body water, expressed as a percentage of body weight, was 0.9% in study 1 and 1.25% in study 2. For each study, the results for each subject were normalized for each limb to the initial (prestudy) value and then the normalized results for each segment were pooled for all subjects, ANOVA of these pooled results failed to demonstrate any significant differences between the normalized mean values of Ri or Re of the segments measured through the course of each study, The failure to detect a change in Ri or Re is explained in terms of the basic theory of BIA.

Designs for an asymmetric gradient set and a compact superconducting magnet for neural magnetic resonance imaging

Imaging of the head and neck is the most commonly performed clinical magnetic resonance imaging (MRI) examination [R. G. Evans and J. R. G. Evans, AJR 157, 603 (1991)]. This is usually undertaken in a generalist MRI instrument containing superconducting magnet system capable of imaging all organs. These generalist instruments are large, typically having a bore of 0.9-1.0 m and a length of 1.7-2.5 m and therefore are expensive to site, somewhat claustrophobic to the patient, and offer little access by attending physicians. In this article, we present the design of a compact, superconducting MRI magnet for head and neck imaging that is less than 0.8 m in length and discuss in detail the design of an asymmetric gradient coil set, tailored to the magnet profile. In particular, the introduction of a radio-frequency FM modulation scheme in concert with a gradient sequence allows the epoch of the linear region of the gradient set to be much closer to the end of the gradient structure than was previously possible. Images from a prototype gradient set demonstrate the effectiveness of the designs. (C) 1999 American Institute of Physics. [S0034-6748(99)04910-2].

Do simple prudent health behaviours protect men from myocardial infarction?

Background We tested whether behaviours such as discarding obvious fat on meat, cessation of smoking, avoidance of passive smoking, habitual use of reduced fat milk, prudent consumption of alcohol and regular but moderate physical exercise are associated with a reduction of cardiovascular risk. Methods This was a population-based case-control study done in Perth, Western Australia. The cases (n = 336) were men aged 27-64 years with a first-ever acute myocardial infarction (AMI) during the period 1992-1993, and who survived at least 28 days. The controls (n = 735) were participants in a population-based survey of cardiovascular risk factors conducted during May-November 1994. Both groups completed the same questionnaire and the data were analysed with multiple logistic regression using backward elimination technique. Results Among men aged 27-64 years simple measures such as participation in non-vigorous exercise (odds ratio [OR] = 0.5, 95% CI : 0.4-0.7), and avoidance of added salt (OR = 0.6, 95% CI : 0.4-0.9) are associated with significant and Important protection from AMI. Conclusion After 25 years of falling mortality in Australia, lifestyles can still be significantly improved to reduce heart disease even further.

Characterization of an ATP-dependent pathway of activation for the heterocyclic amine carcinogen N-hydroxy-2-amino-3-methylimidazo[4,5-f]quinoline

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of several mutagenic and carcinogenic heterocyclic amines formed during the cooking process of protein-rich foods, These compounds are highly mutagenic and have been shown to produce tumours in various tissues in rodents and non-human primates. Metabolic activation of IQ is a two-step process involving N-hydroxylation by CYP1A2 followed by esterification to a more reactive species capable of forming adducts with DNA, To date, acetylation and sulphation have been proposed as important pathways in the formation of N-hydroxy esters, In this study we have demonstrated the presence of an ATP-dependent activation pathway for N-hydroxy-IQ (N-OH-IQ) leading to DNA adduct formation measured by covalent binding of [H-3]N-OH-IQ to DNA, ATP-dependent DNA binding of N-OH-IQ was greatest in the cytosolic fraction of rat liver, although significant activity was also seen in colon, pancreas and lung. ATP was able to activate N-OH-IQ almost 10 times faster than N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (7.7 +/- 0.3 and 0.9 +/- 0.1 pmol/mg protein/min, respectively). Using reported intracellular concentrations of cofactor, the ability of ATP to support DNA binding was similar to that seen with 3'-phosphoadenosine 5'-phosphosulphate and similar to 50% of that seen with acetyl coenzyme A (AcCoA), In addition to DNA binding, HPLC analysis of the reaction mixtures using ATP as co-factor showed the presence of two stable, polar metabolites, With AcCoA, only one metabolite was seen. The kinase inhibitors genistein, tyrphostin A25 and rottlerin significantly inhibited both DNA binding and metabolite formation with ATP. However, inhibition was unlikely to be due to effects on enzyme activity since the broad spectrum kinase inhibitor staurosporine had no effect and the inactive analogue of genistein, daidzein, was as potent as genistein, The effects of genistein and daidzein, which are naturally occurring isoflavones from soy and other food products, on DNA adduct formation may potentially be useful in the prevention of heterocyclic amine-induced carcinogenesis.

Screening for abdominal aortic aneurysm: lessons from a population-based study

Objectives: To test the acceptability of screening and to identify modifiable risk factors for abdominal aortic aneurysm (AAA) in men. Design: A trial of ultrasound screening for AAA in a population-based random sample of men aged 65-83 years, and a cross-sectional case-control comparison of men in the same sample. Participants: 12203 men who had an ultrasound examination of their abdominal aorta, and completed a questionnaire covering demographic, behavioural and medical factors. Main outcome measures: Prevalence of AAA, and independent associations of AAA with demographic, medical and lifestyle factors. Results: Invitations to screening produced a corrected response of 70.5%. The prevalence of AAAs (> 30 mm) rose from 4.8% in men aged 65-69 years to 10.8% in those aged 80-83 years. The overall prevalence of large (> 50 mm) aneurysms was 0.69%. In a multivariate logistic model Mediterranean-born men had a 40% lower risk of AAA (> 30 mm) compared with men born in Australia (odds ratio [OR], 0.6; 95% CI, 0.4-0.8), while ex-smokers had a significantly increased risk of AAA (OR, 2.3; 95% CI, 1.9-2.8), and current smokers had even higher risks. AAA was significantly associated with established coronary and peripheral arterial disease and a waist:hip ratio greater than 0.9; men who regularly undertook vigorous exercise had a lower risk (OR, 0.8; 95% CI, 0.7-1.0). Conclusion: Ultrasound screening for AAA is acceptable to men in the likely target population. AAA shares some but not all of the risk factors for occlusive vascular disease, but the scope for primary prevention of AAA in later life is limited.

Calcium accretion in girls and boys during puberty: A longitudinal analysis

The primary purpose of this study was to estimate the magnitude and variability of peak calcium accretion rates in the skeletons of healthy white adolescents. Total-body bone mineral content (BMC) was measured annually on six occasions by dual-energy X-ray absorptiometry (DXA; Hologic 2000, array mode), a BMC velocity curve was generated for each child by a cubic spline fit, and peak accretion rates were determined. Anthropometric measures were collected every 6 months and a 24-h dietary recall was recorded two to three times per year. Of the 113 boys and 115 girls initially enrolled in the study, 60 boys and 53 girls who had peak height velocity (PHV) and peak BMC velocity values were used in this longitudinal analysis. When the individual BR IC velocity curves were aligned on the age of peak bone mineral velocity, the resulting mean peak bone mineral accrual rate was 407 g/year for boys (SD, 92 g/year; range, 226-651 g/year) and 322 g/year for girls (SD, 66 g/year; range, 194-520 g/year). Using 32.2% as the fraction of calcium in bone mineral, as determined by neutron activation analysis (Ellis et al., J Bone Miner Res 1996;11:843-848), these corresponded to peak calcium accretion rates of 359 mg/day for boys (81 mg/day; 199-574 mg/day) and 284 mg/day for girls (58 mg/day; 171-459 mg/day). These longitudinal results are 27-34% higher than our previous cross-sectional analysis in which we reported mean values of 282 mg/day for boys and 212 mg/day for girls (Martin et al., Am J Clin Nutr 1997;66:611-615). Mean age of peak calcium accretion was 14.0 years for the boys (1.0 years; 12.0-15.9 years), and 12.5 years for the girls (0.9 years; 10.5-14.6 years). Dietary calcium intake, determined as the mean of all assessments up to the age of peak accretion was 1140 mg/day (SD, 392 mg/day) for boys and 1113 mg/day (SD, 378 mg/day) for girls. We estimate that 26% of adult calcium is laid down during the 2 adolescent years of peak skeletal growth. This period of rapid growth requires high accretion rates of calcium, achieved in part by increased retention efficiency of dietary calcium.

Initial results of ultrasound screening for aneurysm of the abdominal aorta in Western Australia: relevance for endoluminal treatment of aneurysm disease

Background. Increased life expectancy in men during the last thirty years is largely due to the decrease in mortality from cardiovascular disease in the age group 29-69 yr. This change has resulted in a change in the disease profile of the population with conditions such as aneurysm of the abdominal aorta (AAA) becoming more prevalent. The advent of endoluminal treatment for AAA has encouraged prophylactic intervention and fuelled the argument to screen for the disease. The feasibility of inserting an endoluminal graft is dependent on the morphology and growth characteristics of the aneurysm. This study used data from a randomized controlled trial of ultrasound screening for AAA in men aged 65-83 yr in Western Australia for the purpose of determining the norms of the living anatomy in the pressurized infrarenal aorta. Aims. To examine (1) the diameters of the infra-renal aorta in aneurysmal and non-aneurysmal cases, (2) the implications for treatment modalities, with particular reference to endoluminal grafting, which is most dependent on normal and aneurysmal morphology, and (3) any evidence to support the notion that northern Europeans are predisposed to aneurysmal disease. Methods. Using ultrasound, a randomized control trial was established in Western Australia to assess the value of a screening program in males aged 65-83 yr, The infra-renal aorta was defined as aneurysmal if the maximum diameter was 30 mm or more. Aortic diameter was modelled both as a continuous tin mm) and as a binary outcome variable, for those men who had an infra-renal diameter of 30 mm or more. ANOVA and linear regression were used for modelling aortic diameter as a continuum, while chi-square analysis and logistic regression were used in comparing men with and without the diagnosis of AAA. Findings. By December 1998, of 19.583 men had been invited to undergo ultrasound screening for AAA, 12.203 accepted the invitation (corrected response fraction 70.8%). The prevalence of AAA increased with age from 4.8% at 65 yr to 10.8% at 80 yr (chi (2) = 77.9, df = 3, P<0.001). The median (IQR) diameter for the non-aneurysmal group was 21.4 mm (3.3 mm) and there was an increase (<chi>(2) = 76.0, df = 1, P<0.001) in the diameter of the infra-renal aorta with age. Since 27 mm is the 95th centile for the non-aneurysmal infra-renal aorta, a diameter of 30 mm or more is justified as defining an aneurysm. The risk of AAA was higher in men of Australian (OR = 1.0) and northern European origin (OR = 1.0, 95%CL: 0.9. 1.2) compared with those of Mediterranean origin (OR = 0.5, 99%CL: 0.4, 0.7). Conclusion. Although screening has not yet been shown to reduce mortality from AAA. these population-based data assist the understanding of aneurysmal disease and the further development and use of endoluminal grafts for this condition. (C) 2001 Published by Elsevier Science Ltd on behalf of The International Society for Cardiovascular Surgery.