Guidelines for the treatment of postmenopausal osteoporosis for general practitioners

BACKGROUND: Osteoporosis Australia has been committed to the education of general practitioners and the community with a series of updated guidelines on the management of osteoporosis. Since the last series was published in Australian Family Physician (August 2000), there have been further advances in our understanding of the treatments involved in both prevention of bone loss and the management of established osteoporosis. OBJECTIVE: This article represents updated guidelines for the treatment of postmenopausal osteoporosis to assist GPs identify those women at risk and to review current treatment strategies. DISCUSSION: Osteoporosis and its associated problems are major health concerns in Australia, especially with an aging population. While important principles of management are still considered to be maximising peak bone mass and preventing postmenopausal bone loss, new clinical trial data about drugs such as the bisphosphonates, raloxifene and oestrogen have recently become available and the relative role of various agents is gradually becoming clearer. The use of long term hormone replacement therapy has mixed risks and benefits that requires individual patient counselling.

Effects of paternal drinking, conduct disorder and childhood home environment on the development of alcohol use disorders in a Thai population

Aims To identify influences on the development of alcohol use disorders in a Thai population, particularly parental drinking and childhood environment. Design Case-control study. Setting A university hospital, a regional hospital and a community hospital in southern Thailand. Participants Ninety-one alcohol-dependents and 177 hazardous/harmful drinkers were recruited as cases and 144 non-or infrequent drinkers as controls. Measurements Data on parental drinking, family demographic characteristics, family activities, parental disciplinary practice, early religious life and conduct disorder were obtained using a structured interview questionnaire. The main outcome measure was the subject's classification as alcohol-dependent, hazardous/harmful drinker or non-/infrequent drinker. Findings A significant relationship was found between having a drinking father and the occurrence of hazardous/harmful drinking or alcohol dependence in the subjects. Childhood factors (conduct disorder and having been a temple boy, relative probability ratios, RPRs and 95% CI: 6.39, 2.81-14.55 and 2.21, 1.19-4.08, respectively) also significantly predicted alcohol dependence, while perceived poverty and ethnic alienation was reported less frequently by hazardous/harmful drinkers and alcohol-dependents (RPRS and 95% CIs = 0.34, 0.19-0.62 and 0.59, 0.38-0.93, respectively) than the controls. The relative probability ratio for the effect of the father's infrequent drinking on the son's alcohol dependence was 2.92 (95% CI = 1.42-6.02) and for the father's heavy or dependent drinking 2.84 (95% CI=1.31-6.15). Conclusions Being exposed to a light-drinking, father increases the risk of a son's alcohol use disorders exhibited either as hazardous-harmful or dependent drinking. However, exposure to a heavy- or dependent-drinking father is associated more uniquely with an increased risk of his son being alcohol-dependent. The extent to which this is seen in other cultures is worthy of exploration.

Population balance modelling of granulation with a physically based coalescence kernel

It was previously published by the authors that granules can either coalesce through Type I (when granules coalesce by viscous dissipation in the surface liquid layer before their surfaces touch) or Type II (when granules are slowed to a halt during rebound, after their surfaces have made contact) (AIChE J. 46 (3) (2000) 529). Based on this coalescence mechanism, a new coalescence kernel for population balance modelling of granule growth is presented. The kernel is constant such that only collisions satisfying the conditions for one of the two coalescence types are successful. One constant rate is assigned to each type of coalescence and zero is for the case of rebound. As the conditions for Types I and II coalescence are dependent on granule and binder properties, the coalescence kernel is thus physically based. Simulation results of a variety of binder and granule materials show good agreement with experimental data. (C) 2002 Elsevier Science Ltd. All rights reserved.

A cassette ligation strategy with thioether replacement of three Gly-Gly peptide bonds: Total chemical synthesis of the 101 residue protein early pregnancy factor [psi(CH2S)(28-29,56-57,76-77)]

The 101 residue protein early pregnancy factor (EPF), also known as human chaperonin 10, was synthesized from four functionalized, but unprotected, peptide segments by a sequential thioether ligation strategy. The approach exploits the differential reactivity of a peptide-NHCH2CH2SH thiolate with XCH2CO-peptides, where X = Cl or I/Br. Initial model studies with short functionalized (but unprotected) peptides showed a significantly faster reaction of a peptide-NHCH2CH2SH thiolate with a BrCH2CO-peptide than with a CICH2CO-peptide, where thiolate displacement of the halide leads to chemoselective formation of a thioether surrogate for the Gly-Gly peptide bond. This rate difference was used as the basis of a novel sequential ligation approach to the synthesis of large polypeptide chains. Thus, ligation of a model bifunctional N-alpha-chloroacetyl, C-terminal thiolated peptide with a second N-alpha-bromoacetyl peptide demonstrated chemoselective bromide displacement by the thiol group. Further investigations showed that the relatively unreactive N-alpha-chloroacetyl peptides could be activated by halide exchange using saturated KI solutions to yield the highly reactive No-iodoacetyl peptides. These findings were used to formulate a sequential thioether ligation strategy for the synthesis of EPF, a 101 amino acid protein containing three Gly-Gly sites approximately equidistantly spaced within the peptide chain. Four peptide segments or cassettes comprising the EPF protein sequence (BrAc-[EPF 78-101] 12, ClAc-[EPF 58-75]-[NHCH2CH2SH] 13, ClAc-[EPF 30-55]-[NHCH2CH2SH] 14, and Ac-[EPF 1-27]-[NHCH2CH2SH] 15) of EPF were synthesized in high yield and purity using Boc SPPS chemistry. In the stepwise sequential ligation strategy, reaction of peptides 12 and 13 was followed by conversion of the N-terminal chloroacetyl functional group to an iodoacetyl, thus activating the product peptide for further ligation with peptide 14. The process of ligation followed by iodoacetyl activation was repeated to yield an analogue of EPF (EPF psi(CH2S)(28-29,56-57,76-77)) 19 in 19% overall yield.

Comparison of two population pharmacokinetic programs, NONMEM and P-PHARM, for tacrolimus

Objectives: To compare the population modelling programs NONMEM and P-PHARM during investigation of the pharmacokinetics of tacrolimus in paediatric liver-transplant recipients. Methods: Population pharmacokinetic analysis was performed using NONMEM and P-PHARM on retrospective data from 35 paediatric liver-transplant patients receiving tacrolimus therapy. The same data were presented to both programs. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F). Covariates screened for influence on these parameters were weight, age, gender, post-operative day, days of tacrolimus therapy, transplant type, biliary reconstructive procedure, liver function tests, creatinine clearance, haematocrit, corticosteroid dose, and potential interacting drugs. Results: A satisfactory model was developed in both programs with a single categorical covariate - transplant type - providing stable parameter estimates and small, normally distributed (weighted) residuals. In NONMEM, the continuous covariates - age and liver function tests - improved modelling further. Mean parameter estimates were CL/F (whole liver) = 16.3 1/h, CL/F (cut-down liver) = 8.5 1/h and V/F = 565 1 in NONMEM, and CL/F = 8.3 1/h and V/F = 155 1 in P-PHARM. Individual Bayesian parameter estimates were CL/F (whole liver) = 17.9 +/- 8.8 1/h, CL/F (cutdown liver) = 11.6 +/- 18.8 1/h and V/F = 712 792 1 in NONMEM, and CL/F (whole liver) = 12.8 +/- 3.5 1/h, CL/F (cut-down liver) = 8.2 +/- 3.4 1/h and V/F = 221 1641 in P-PHARM. Marked interindividual kinetic variability (38-108%) and residual random error (approximately 3 ng/ml) were observed. P-PHARM was more user friendly and readily provided informative graphical presentation of results. NONMEM allowed a wider choice of errors for statistical modelling and coped better with complex covariate data sets. Conclusion: Results from parametric modelling programs can vary due to different algorithms employed to estimate parameters, alternative methods of covariate analysis and variations and limitations in the software itself.

Impact numbers: measures of risk factor impact on the whole population from case-control and cohort studies

Objective: To describe new measures of risk from case-control and cohort studies, which are simple to understand and relate to numbers of the population at risk. Design: Theoretical development of new measures of risk. Setting: Review of literature and previously described measures. Main results: The new measures are: (1) the population impact number (PIN), the number of those in the whole population among whom one case is attributable to the exposure or risk factor (this is equivalent to the reciprocal of the population attributable risk),- (2) the case impact number (CIN) the number of people with the disease or outcome for whom one case will be attributable to the exposure or risk factor (this is equivalent to the reciprocal of the population attributable fraction); (3) the exposure impact number (EIN) the number of people with the exposure among whom one excess case is attributable to the exposure (this is equivalent to the reciprocal of the attributable risk); (4) the exposed cases impact number (ECIN) the number of exposed cases among whom one case is attributable to the exposure (this is equivalent to the reciprocal of the aetiological fraction). The impact number reflects the number of people in each population (the whole population, the cases, all those exposed, and the exposed cases) among whom one case is attributable to the particular risk factor. Conclusions: These new measures should help communicate the impact on a population, of estimates of risk derived from cohort or case-control studies.

Predicting plant leaf area production: shoot assimilate accumulation and partitioning, and leaf area ratio, are stable for a wide range of sorghum population densities

Predicting plant leaf area production is required for modelling carbon balance and tiller dynamics in plant canopies. Plant leaf area production can be studied using a framework based on radiation intercepted, radiation use efficiency (RUE) and leaf area ratio (LAR) (ratio of leaf area to net above-ground biomass). The objective of this study was to test this framework for predicting leaf area production of sorghum during vegetative development by examining the stability of the contributing components over a large range of plant density. Four densities, varying from 2 to 16 plants m(-2), were implemented in a field experiment. Plants were either allowed to tiller or were maintained as uniculm by systematic tiller removal. In all cases, intercepted radiation was recorded daily and leaf area and shoot dry matter partitioning were quantified weekly at individual culm level. Up to anthesis, a unique relationship applied between fraction of intercepted radiation and leaf area index, and between shoot dry weight accumulation and amount of intercepted radiation, regardless of plant density. Partitioning of shoot assimilate between leaf, stem and head was also common across treatments up to anthesis, at both plant and culm levels. The relationship with thermal time (TT) from emergence of specific leaf area (SLA) and LAR of tillering plants did not change with plant density. In contrast, SLA of uniculm plants was appreciably lower under low-density conditions at any given TT from emergence. This was interpreted as a consequence of assimilate surplus arising from the inability of the plant to compensate by increasing the leaf area a culm could produce. It is argued that the stability of the extinction coefficient, RUE and plant LAR of tillering plants observed in these conditions provides a reliable way to predict leaf area production regardless of plant density. Crown Copyright (C) 2002 Published by Elsevier Science B.V. All rights reserved.

Testing the applicability of molecular genetic markers to population analyses of scleratinian corals

The abundance of coral reefs worldwide is in decline, and despite the ecological importance of reefs, only a limited number of DNA markers have been identified for scleractinian coral genetic studies. This paper addresses the search for new coral molecular markers and investigates the applicability of the cytochrome c oxidase subunit I (COI), the internal transcribed spacer region 1 (ITS1), and the pocilloporin gene to the question of intraspecific variation in the scleractinian coral Pocillopora verrucosa along the southeast African coastline. The COI fragment was 710 bp long and was identical for P. verrucosa (n = 10) and P. damicornis (n = 3). Only two different ITS1 sequences were found (differing by 13 bp insertion), but more importantly, 24% of the sequences were heterogenous indicating that different multiple copies of the sequence exist. Pocilloporin is an intronless gene that was absolutely conserved throughout all P. verrucosa populations (n = 50). Thus, the three DNA regions studied appear unsuitable for the population genetic analyses of P. verrucosa.

Tillering in grain sorghum over a wide range of population densities: Identification of a common hierarchy for tiller emergence, leaf area development and fertility

Most studies of tiller development have not related the physiological and morphological features of each calm to its subsequent fertility. This introduced problems when trying to account for the effects of tillering on yield in crop models. The objective of this study was to detect the most likely early determinants of tiller fertility in sorghum by identifying hierarchies for emergence, fertility and grain number of tillers over a wide range of assimilate availabilities. Emergence, phenology, leaf area development and dry weight partitioning were quantified weekly for individual tillers and main culms of tillering and uniculm plants grown at one of four densities, from two to 16 plants m(-2). For a given plant in any given density, the same tiller hierarchy applied for emergence of tillers, fertility of the emerged tillers and their subsequent grain number. These results were observed over a range of tiller fertility rates (from 7 to 91%), fertile tiller number per plant at maturity (from 0.2 to 4.7), and tiller contribution to grain yield (from 5 to 78%). Tiller emergence was most probably related to assimilate supply and light quality. Development, fertility and contribution to yield of a specific tiller were highly dependent on growing conditions at the time of tiller emergence, particularly via early leaf area development of the tiller, which affected its subsequent leaf area accumulation. Assimilate availability in the main culm at the time of tiller emergence was the most likely early determinant of subsequent tiller fertility in this study. (C) 2002 Annals of Botany Company.