A longitudinal study of interleukin-1 gene polymorphisms and periodontal disease in a general adult population

Background: Cross-sectional studies have demonstrated that a specific polymorphism (allele 2 of both IL-1A +4845 and IL-1B +3954) in the IL-1 gene cluster has been associated with an increased susceptibility to severe periodontal disease and to an increased bleeding tendency during periodontal maintenance. The aim of the present study was to investigate the relationship between IL-1 genotype and periodontitis in a prospective longitudinal study in an adult population of essentially European heritage. Methods: From an ongoing study of the Oral Care Research Programme of The University of Queensland, 295 subjects consented to genotyping for IL-1 allele 2 polymorphisms. Probing depths and relative attachment levels were recorded at baseline, 6, 12, 24, 36, 48 and 60 months using the Florida probe. Periodontitis progression at a given site was defined as attachment loss greater than or equal to2 mm at any observation period during the 5 years of the study and the extent of disease progression determined by the number of sites showing attachment loss. Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia were detected using ELISA. Results: 38.9% of the subjects were positive for the composite IL-1 genotype. A relationship between the IL-1 positive genotype and increased mean probing pocket depth in non-smokers greater than 50 years of age was found. Further, IL-1 genotype positive smokers and genotype positive subjects with P. gingivalis in their plaque had an increase in the number of probing depths greater than or equal to3.5 mm, There was a consistent trend for IL-1 genotype positive subjects to experience attachment loss when compared with IL-1 genotype negative subjects. Conclusion: The results of this study have shown an interaction of the IL-1 positive genotype with age, smoking and P. gingivalis which suggests that IL-1 genotype is a contributory but non-essential risk factor for periodontal disease progression in this population.

Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT

Objective-To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients. Design-Cohort study. Setting-Regional cardiothoracic unit. Patients-49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress. Main outcome measures-Regional myocardial perfusion by SPECT, performed with Tc-99m tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity. Results-Normal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wail, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images. Conclusions-Myocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects.

Prediction of mortality using dobutamine echocardiography

OBJECTIVES We sought to find out whether dobutamine echocardiography (DbE) could provide independent prediction of total and cardiac mortality, incremental to clinical and angiographic variables. BACKGROUND Existing outcome studies with DbE have examined composite end points, rather than death, over a relatively short follow-up. METHODS Clinical and stress data were collected in 3,156 patients (age 63 +/- 12 years, 1,801 men) undergoing DbE. Significant stenoses (>50% diameter) were identified in 70% of 1,073 patients undergoing coronary angiography. Total and cardiac mortality were identified over nine years of follow-up (mean 3.8 +/- 1.9). Cox models were used to analyze the effect of ischemia and other variables, independent of other determinants of mortality. RESULTS The dobutamine echocardiogram was abnormal in 1,575 patients (50%). Death occurred in 716 patients (23%), 259 of whom (8%) were thought to have died from cardiac causes. Patients with normal DbE had a total mortality of 8% per year and a cardiac mortality of 1% per year over the first four years of follow-up. Ischemia and the extent of abnormal wall motion were independent predictors of cardiac death, together with age and heart failure. In sequential Cox models, the predictive power of clinical data alone (model chi-square 115) was strengthened by adding the resting left ventricular function (model chi-square 138) and the results of DbE (model chi-square 181). In the subgroup undergoing coronary angiography, the power of the model was increased to a minor degree by the addition of coronary anatomy data. CONCLUSIONS Dobutamine echocardiography is an independent predictor of death, incremental to other data. While a normal dobutamine echocardiogram predicts low risk of cardiac death ton the order of 1% per year), this risk increases with the extent of abnormal wall motion at rest and stress, (J Am Coil Cardiol 2001;37:754-60) (C) 2001 by the American College of Cardiology.

Effects of short-duration and long-duration exercise on lipoprotein(a)

Purpose: Most studies that use either a single exercise session, exercise training, or a cross-sectional design have failed to find a relationship between exercise and plasma lipoprotein(a) [Lp(a)] concentrations. However, a few studies investigating the effects of longer and/or more strenuous exercise have shown elevated Lp(a) concentrations, possibly as an acute-phase reactant to muscle damage. Based on the assumption that greater muscle damage would occur with exercise of longer duration, the purpose of the present study was to determine whether exercise of longer duration would increase Lp(a) concentration and creatine kinase. (CK) activity more than exercise of shorter duration. Methods: Ten endurance-trained men (mean +/- SD: age, 27 +/- 6 yr; maximal oxygen consumption [(V)over dotO(2max)], 57 +/- 7 mL(.)kg(-1) min(-1)) completed two separate exercise sessions at 70% (V)over dotO(2max). One session required 900 kcal of energy expenditure (60 +/- 6 min), and the other required 1500 kcal (112 +/- 12 min). Fasted blood samples were taken immediately before (0-pre), immediately after (0-post), 1 d after (1-post), and 2 d after (2-post) each exercise session. Results: CK activity increased after both exercise sessions (mean +/- SE; 800 kcal: 0-pre 55 +/- 11, 1-post 168 +/- 64 U(.)L(-1.)min(-1); 1500 kcal: 0-pre 51 +/- 5, 1-post 187 +/- 30, 2-post 123 +/- 19 U(.)L(-1.)min(-1); P < 0.05). However, median Lp(a) concentrations were not altered by either exercise session (800 kcal: 0-pre 5.0 mg(.)dL(-1), 0-post 3.2 mg(.)dL(-1), 1-post 4.0 mg(.)dL(-1), 2-post 3.4 mg(.)dL(-1); 1500 kcal: 0-pre 5.8 mg(.)dL(-1), 0-post 4.3 mg(.)dL(-1), 1-post 3.2 mg(.)dL(-1), 2-post 5.3 mg(.)dL(-1)). In addition, no relationship existed between exercise-induced changes in CK activity and Lp(a) concentration (800 kcal: r = -0.26; 1500 kcal: r = -0.02). Conclusion: These results suggest that plasma Lp(a) concentration will not increase in response to minor exercise-induced muscle damage in endurance-trained runners.

Simultaneous administration of a cocktail of markers to measure renal drug elimination pathways: absence of a pharmacokinetic interaction between fluconazole and sinistrin, p-aminohippuric acid and pindolol

Aims Previous studies suggest that estimated creatinine clearance, the conventional measure of renal function, does not adequately reflect charges in renal drug handling in some patients, including the immunosuppressed. The aim of this study was to develop and validate a cocktail of markers. to be given in a single administration, capable of detecting alterations in the renal elimination pathways of glomerular filtration, tubular secretion and tubular reabsorption. Methods Healthy male subjects (n = 12) received intravenously infused 2500 mg sinistrin (glomerular filtration) and 440 mg p-aminohippuric acid (PAH; anion secretion), and orally administered 100 mg fluconazole (reabsorption) and 15 mg rac-pindolol (cation secretion). The potential interaction between these markers was investigated in a pharmacokinetic study where markers (M) or fluconazole (F) were administered alone or together (M + F). Validated analytical methods were used to measure plasma and urine concentrations in order to quantify the renal handling of each marker. Plasma protein binding of fluconazole was measured by ultrafiltration. All subjects had an estimated creatinine clearance within the normal range. The renal clearance of each marker (Mean +/- s.d.) was calculated as the ratio of the amount excreted in urine and thearea-under-the-concentration-time curve. Statistical comparisons were made using a paired t-test and 95% confidence intervals were reported. Results The renal clearances of sinistrin (M: 119 +/- 31 ml min(-1); M + F: 130 +/- 40 ml min(-1); P = 0.32), PAH (M: 469 +/- 145 ml min(-1); M + F: 467 +/- 146 ml min(-1); P = 0.95), R-pindolol (M: 204 +/- 41 ml min(-1); M + F: 190 +/- 41 ml min(-1); P = 0.39; n = 11), S-pindolol (M: 225 +/- 55 ml min(-1); M + F: 209 +/- 60 ml min(-1); P = 0.27; n = 11) and fluconazole (F: 14.9 +/-3.8 ml min(-1); M + F: 13.6 +/- 3.4 ml min(-1); P = 0.16) were similar when the markers or fluconazole were administered alone (M or F) or as a cocktail (M + F). Conclusions This study found no interaction between markers and fluconazole in healthy male subjects, suggesting that a single administration of this cocktail of markers of different renal processes call be used to simultaneously investigate pathways of renal drug elimination.

Determination of reference values for glucose tolerance, insulin tolerance, and insulin sensitivity tests in clinically normal cats

Objective-To determine reference values and test variability for glucose tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity tests (IST) in cats, Animals-32 clinically normal cats. Procedure-GTT, ITT, and IST were performed on consecutive days. Tolerance intervals tie, reference values) were calculated as means +/- 2.397 SD for plasma glucose and insulin concentrations, half-life of glucose (T-1/2glucose), rate constants for glucose disappearance (K-glucose and K-itt), and insulin sensitivity index (S-l). Tests were repeated after 6 weeks in 8 cats to determine test variability. Results-Reference values for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37 to 104 mg/dl, and 2.8 to 20.6 muU/ml, respectively. Mean values did not differ between the 2 tests. Coefficients of variation for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%, respectively. Reference values for K-itt were 1.14 to 7.3%/min, and for S-l were 0.57 to 10.99 x 10(-4) min/muU/ml. Mean values did not differ between the 2 tests performed 6 weeks apart, Coefficients of variation for K-itt and S-l were 60 and 47%, respectively. Conclusions and Clinical Relevance-GTT, ITT, and IST can be performed in cats, using standard protocols. Knowledge of reference values and test variability will enable researchers to better interpret test results for assessment of glucose tolerance, pancreatic beta -cell function, and insulin sensitivity in cats.

Can long-distance dispersal be inferred from the New Zealand plant fossil record?

New Zealand is generally thought to have been physically isolated from the rest of the world for over 60 million years. But physical isolation may not mean biotic isolation, at least on the time scale of millions of years. Are New Zealand's present complement of plants the direct descendants of what originally rafted from Gondwana? Or has there been total extinction of this initial flora with replacement through long-distance dispersal (a complete biotic turnover)? These are two possible extremes which have come under recent discussion. Can the fossil record be used to decide the relative importance of the two endpoints, or is it simply too incomplete and too dependent on factors of chance? This paper suggests two approaches to the problem-the use of statistics to apply levels of confidence to first appearances in the fossil record and the analysis of trends based on the entire palynorecord. Statistics can suggest that the first appearance of a taxon was after New Zealand broke away from Gondwana-as long as the first appearance in the record was not due to an increase in biomass from an initially rare state. Two observations can be drawn from the overall palynorecord that are independent of changes in biomass: (1) The first appearance of palynotaxa common to both Australia and New Zealand is decidedly non-random. Most taxa occur first in Australia. This suggests a bias in air or water transport from west to east. (2) The percentage of endemic palynospecies in New Zealand shows no simple correlation with the time New Zealand drifted into isolation. The conifer macrorecord also hints at complete turnover since the Cretaceous.

Effect of restricted feed intake on early reproductive development in Large White gilts

Forty-five Large White gilts were used to study the effect of energy intake from 28 to 176 d of age on body composition and reproductive development. From 28 to 60 d, the gilts were fed ad libitum a 16.6 MJ DE/kg, 24% crude protein and 1.3% total lysine diet. From 61 d of age three dietary treatments were used; 1) ad libitum access to feed (15.6 MJ DE/kg, 21% crude protein and 1.07% total lysine) (H), 2) feed offered at 75% (M) of the previous days intake of H, and 3) feed offered at 60% (L) of the previous days intake of H. ADG from 61 to 176 d of age was (p <0.05) affected by treatment. Although live weight at 176 d of age did not differ (p >0.1) the H gilts had higher (p <0.08) carcass weights than the M or L gilts. Back fat depths were similar (p >0.1) for all treatments at 115 d of age, however by 176 d of age M and H gilts were fatter (p <0.1) than L gilts. The mean lipid deposition (LD) from 115 to 176 d of age for L gilts (78.9 g/d) was less (p <0.05) than for M gilts (143.6 g/d) and H gilts (135.6 g/d). There were no differences between treatments for protein deposition (PD) over the same period. More (p <0.05) H gilts (n=8) attained puberty (first observed estrus) than either M gilts or L gilts (n=4 for both). Follicle numbers were similar (p >0.1) across treatments. For gilts that attained puberty, H gilts had fewer (p <0.05) follicles (13.5) than M gilts (19.7) and L gilts (21.3). For gilts with follicular development, H gilts had the heaviest (458.7 g) reproductive tract weight (RTW). However, for those that attained puberty, L gilts had the heaviest RTW. RTW were lowest for those with no follicular development. Energy restriction had a negative impact on puberty attainment, i.e. it took longer to reach puberty. However, for gilts that attained puberty, the number of follicles was greater for those on lower feed intakes. It would appear that rate of fat deposition, but not necessarily the total amount of fat, plays an important role in puberty attainment.

An aggregate sales model for consumer durables incorporating a time-varying mean replacement age

Forecasting category or industry sales is a vital component of a company's planning and control activities. Sales for most mature durable product categories are dominated by replacement purchases. Previous sales models which explicitly incorporate a component of sales due to replacement assume there is an age distribution for replacements of existing units which remains constant over time. However, there is evidence that changes in factors such as product reliability/durability, price, repair costs, scrapping values, styling and economic conditions will result in changes in the mean replacement age of units. This paper develops a model for such time-varying replacement behaviour and empirically tests it in the Australian automotive industry. Both longitudinal census data and the empirical analysis of the replacement sales model confirm that there has been a substantial increase in the average aggregate replacement age for motor vehicles over the past 20 years. Further, much of this variation could be explained by real price increases and a linear temporal trend. Consequently, the time-varying model significantly outperformed previous models both in terms of fitting and forecasting the sales data. Copyright (C) 2001 John Wiley & Sons, Ltd.

The BRCA2 372 HH genotype is associated with risk of breast cancer in Australian women under age 60 years

The BRCA2 N372H nonconservative amino acid substitution polymorphism appears to affect fetal survival in a sex-dependent manner, and the HH genotype was found to be associated with a 1.3-fold risk of breast cancer from pooling five case-control studies of Northern European women. We investigated whether the BR 2 N372H polymorphism was associated with breast cancer in Australian women using a population-based case-control design. The BRCA2 372 genotype was determined in 1397 cases under the age of 60 years at diagnosis of a first primary breast cancer and in 775 population-sampled controls frequency matched for age. Case-control analyses and comparisons of genotype distributions were conducted using logistic regression. All of the statistical tests were two-tailed. The HH genotype was independent of age and family history of breast cancer within cases and controls, and was more common in cases (9.2% versus 6.5%). It was associated with an increased risk of breast cancer, 1.47-fold unadjusted (95% confidence interval, 1.05-2.07; P = 0.02), and 1.42-fold (95% confidence interval, 1.00-2.02; P = 0.05) after adjusting for measured risk factors. This effect was still evident after excluding women with any non-Caucasian ancestry or the 33 cases known to have inherited a mutation in BRCA1 or BRCA2, and would explain similar to3% of breast cancer. The BRCA2 N372H polymorphism appears to be associated with a modest recessively inherited risk of breast cancer in Australian women. This result is consistent with the findings for Northern European women.

Energy cost of activity assessed by indirect calorimetry and a (CO2)-C-13 breath test

Purpose: The aim of this study was to assess the accuracy of a (CO2)-C-13 breath test for the prediction of short-duration energy expenditure. Methods: Eight healthy volunteers walked at 1.5 km.h(-1) for 60 min followed by 60-min recovery. During this time, the energy cost of physical activity was measured via respiratory calorimetry and a C-13 bicarbonate breath test. A further eight subjects were tested using the same two methods during a 60-min cycle at 0.5 kp. 30 ipm followed by a 60-min recovery. The rate of appearance of (CO2)-C-13, (RaCO2) was measured and the mean ratio, (V) over dot CO2/RaCO2 was used to calculate energy expenditure using the isotopic approach. Results: As would be expected, there was a significant difference in the energy cost of walking and cycling using both methods (P < 0.05). However. no significant differences were observed between respiratory calorimetry and the isotope method for measurement of energy expenditure while walking or cycling. Conclusions: These data suggest that the C-13 breath test is a valid method that can be used to measure the energy cost of short duration physical activity in a field setting.

Accumulation of human heat shock protein 60-reactive T cells in the gingival tissues of periodontitis patients

Heat shock protein 60s (hsp60) are remarkably immunogenic, and both T-cell and antibody responses to hsp60 have been reported in various inflammatory conditions. To clarify the role of hsp60 in T-cell responses in periodontitis, we examined the proliferative response of peripheral blood mononuclear cells (PBMC), as well as the cytokine profile and T-cell clonality, for periodontitis patients and controls following stimulation with recombinant human hsp60 and Porphyromonas gingivalis GroEL. To confirm the infiltration of hsp60-reactive T-cell clones into periodontitis lesions, nucleotide sequences within complementarity-determining region 3 of the T-cell receptor (TCR) beta-chain were compared between hsp60-reactive peripheral blood T cells and periodontitis lesion-infiltrating T cells. Periodontitis patients demonstrated significantly higher proliferative responses of PBMC to human hsp60, but not to P. gingivalis GroEL, than control subjects. The response was inhibited by anti-major histocompatibility complex class 11 antibodies. Analysis of the nucleotide sequences of the TCR demonstrated that human hsp60-reactive T-cell clones and periodontitis lesion-infiltrating T cells have the same receptors, suggesting that hsp60-reactive T cells accumulate in periodontitis lesions. Analysis of the cytokine profile demonstrated that hsp60-reactive PBMC produced significant levels of gamma interferon (IFN-gamma) in periodontitis patients, whereas P. gingivalis GroEL did not induce any, skewing toward a type1 or type2 cytokine profile. In control subjects no significant expression of IFN-gamma or interleukin 4 was induced. These results suggest that periodontitis patients have human hsp60-reactive T cells with a type I cytokine profile in their peripheral blood T-cell pools.

Energy intake and energy expenditure in elite lightweight female rowers

Purpose: The training program undertaken by many athletes will affect directly the total, habitual energy requirements of that individual. Unless that energy requirement is met via the diet and or supplementation, chronic negative energy balance will ensue, which will have both short-term and long-term effects not only on performance but also on general health. The aim of this research was therefore to determine the energy expenditure (EE) and hence energy requirements of lightweight female rowers and, further, to compare this with their self-reported energy intake (EI). Methods: The El of seven lightweight female rowers was measured using a self-reported 4-d weighed dietary record. EE was determined using the doubly labeled water (DLW) technique over a 14-d period. Results: The mean (+/-SD) age, height, and weight of the subjects was 20 (+/-1.1) yr, 168.8 (+/-4.7) cm, and 60.9 (+/-23) kg, respectively. The rowers self-reported El was 2214 (+/-313) kcal.d(-1) and their total EE was 3957 (+/-1219) kcal.d(-1). After adjusting total EE for changes in body weight (mean (+/-SD) - 1.2 (+/-1.2) kg), the comparison between adjusted El and reported showed a bias to underreporting of 1133 (+/-1539) kcal.d(-1) or 34%. The bias was not consistent across adjusted El, and two of the seven subjects overreported their intake. Conclusions: Due to the underreporting of EI, diet recording may not be an appropriate way of assessing energy requirements in lightweight female rowers. A benefit of accurately determining energy requirements, as with DLW, is that female lightweight rowers will be able to successfully manipulate their EI and achieve the set weight cut-off for participation without compromising their health or performance.