BACKGROUND: The factors associated with initial periodontitis are not well understood and cannot be identified by cross-sectional studies. AIM: To identify the factors associated with the initiation of chronic periodontitis using ante-dependence modelling. MATERIAL AND METHODS: A 26-year longitudinal study of the natural history of periodontitis served as the basis for the study. In 1969, 565 Norwegian men aged 16-34 years were surveyed. Subsequent surveys were performed in 1971, 1973, 1975, 1981, 1988 and finally in 1995, with 223 remaining subjects. Plaque (PlI), gingival (GI) and calculus indices (CI) and loss of attachment (LoA) were recorded. Ante-dependence modelling using a Markov chain enabled the results of this sequence of examinations to be analysed longitudinally, taking into account serial dependence, describing temporal changes in patients' levels of disease and allowing for both progression and regression between disease categories. RESULTS: With age, the rate of disease regression decreased. Increasing calculus accumulation and smoking increased the rate of disease progression, while increasing GI increased the rate of regression. CONCLUSIONS: Increased mean CI and smoking were significant predictive covariates for progression, while increased mean GI and younger age predicted regression of initial periodontitis.

BACKGROUND AND OBJECTIVE: Interleukin-10 is a key immunoregulatory cytokine that may be of significance in the immunopathogenesis of chronic inflammatory diseases such as periodontal disease. Molecular genetic studies have defined a number of haplotypes that may be associated with differing levels of interleukin-10 secretion. The present study investigated the possible association between interleukin-10 gene polymorphism and periodontal disease progression. MATERIAL AND METHODS: Genomic DNA was obtained from 252 adults who were part of a prospective longitudinal study on the progression of periodontal disease in a general adult Australian population. Single nucleotide polymorphisms at positions -592 and -1082 in the interleukin-10 promoter were analysed using an induced heteroduplex methodology and used to determine interleukin-10 promoter haplotypes in individual samples. Periodontitis progression was assessed by measuring probing depths and relative attachment levels at regular intervals over a 5-year period. A generalized linear model was used to analyse the data, with age, gender, smoking status, interleukin-1 genotype and Porphyromonas gingivalis included as possible confounders. RESULTS: There was a significant (p approximately 0.02) main effect of interleukin-10 haplotypes, with individuals having either the ATA/ACC or the ACC/ACC genotype experiencing around 20% fewer probing depths of >or= 4 mm compared to individuals with other genotypes. Age and smoking had significant (p < 0.001) additional effects. CONCLUSION: These data suggest that the interleukin-10 genotype contributes to the progression of periodontal disease.

BACKGROUND: Serum anti-Müllerian hormone (AMH) levels are highly correlated with antral follicle counts (AFC), while being menstrual cycle independent and easily measurable. However, AMH, unlike AFC, has not been tested as yet as a predictor of reproductive status. By relating AMH levels to the age distribution of reproductive events like onset of menopause we tested this hypothesis. METHODS: AMH levels were measured in 144 fertile normal volunteers and used to determine an estimate of mean AMH as a function of age. Data on onset of menopause were obtained from the population-based Prospect-Epic cohort. Estimation of an AMH threshold to predict menopause was done by maximum likelihood using the observed (EPIC) and predicted (AMH) distributions of age at menopause. Predictions of age at menopause follow from an individual woman's AMH relative to percentiles of the distribution of AMH for a given age, and the corresponding percentiles of the predicted distribution of age at menopause. RESULTS: There was good conformity between the observed distribution of age at menopause and that predicted from declining AMH levels. CONCLUSION: The similarity between observed and predicted distributions of age at menopause supports the hypothesis that AMH levels are related to onset of menopause. Results of this study suggest that AMH is able to specify a woman's reproductive age more realistically than chronological age alone.

OBJECTIVES: To use multi-state Markov chain modelling to analyse data on geriatric patient care, and to make comparisons between male and female patients. METHODS: Estimation, from observed data, of covariate (age of patient and date of admission to hospital or community care) dependent parameters of statistical models for time in care and subsequent events. RESULTS: Differential effects of these covariates shown on the parameters of the models for female and male patients, where these parameters can be interpreted as affecting different features of the distributions of time in care. CONCLUSIONS: Multi-state modelling is an appropriate means of analysing data on geriatric patient care and can reveal underlying patterns of differential effects, some of which may not be apparent from more routine data processing.

BACKGROUND: Premature ovarian failure (POF) before 40 years of age from natural causes affects approximately 1% of adult women, with minor variations between ethnic groups. A recent case of ovarian transplantation between young monozygotic (MZ) twins in which one had undergone unexplained POF at 14 years has prompted a study of the prevalence of POF. METHODS: Menopausal ages of 832 Australian and UK female twin-pairs were extracted from volunteer national twin registry databases containing medical, reproductive and lifestyle data surveyed by mail questionnaire. Surgical menopause was an exclusion criterion. RESULTS: The prevalence of POF in both MZ and dizygotic (DZ) twins was similar in both registries and 3- to 5-fold greater than the general population at age thresholds 40 and 45 years. No specific factors were found to account for the higher risk of early menopause. Some twins of both zygosities were highly discordant for menopausal age (>/=10 years). Nevertheless, there was significant intra-twin dependence, especially for MZ twins, and the average age difference at last menses was greater in DZ twin-pairs. CONCLUSION: Both MZ and DZ twins are at higher risk of POF. Despite some striking differences within MZ twin-pairs, menopausal ages were more concordant than for DZ twin-pairs, confirming that the timing of menopause has a heritable component.

Summary. A model for binary trials based on a bivariate generalization of the Poisson process for both the number of successes and number of trials with the transition rates dependent on the accumulating numbers of successes and trials is used to reanalyze some recently published data of Zhu, Eickhoff, and Kaiser (2003, Biometrics59, 955-961). This modeling admits alternative distributions for the numbers of trials and the numbers of successes conditional on the number of trials which generalize the Poisson and binomial distributions, without some of the restrictions apparent in the beta-binomial-Poisson mixed modeling of Zhu et al.(2003). Some quite marked differences between the results of this analysis and those described in Zhu et al.(2003) are apparent.

A group of scientists from Harvard Medical School (Johnson et al., 2004) claims to have "established the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary," expressing no doubts about their methods, results and conclusion. Johnson et al. based their conclusions of oocyte and follicular renewal from existing germline stem cells (GSC) in the postnatal mouse ovary on three types of observations:(1) A claimed discordance in follicle loss versus follicle atresia in the neonatal period and in the following pubertal and adult period;(2) immunohistochemical detection of proliferating GSC with meiotic capacity using combined markers for meiosis, germline, and mitosis; and (3) neo-folliculogenesis in ovarian chimeric grafting experiments with adult mice. Oogenesis is the process that transforms the proliferative oogonium into an oocyte through meiosis, followed by folliculogenesis and follicular and oocyte maturation. The most crucial part in producing a functional oocyte is firstly, initiation and completion of the first meiotic prophase, and secondly, enclosure of the resulting diplotene oocyte in a follicle. Neither of these two events has been shown to take place in Johnson et al.'s study of the postnatal mouse ovary. We hereby address the observations underpinning their hypothesis and conclude that it is premature to replace the paradigm that adult mammalian neo-oogenesis/folliculogenesis does not take place.

OBJECTIVES: To show that Markov chain modelling can be applied to data on geriatric patients and use these models to assess the effects of covariates. METHODS: Phase-type distributions were fitted by maximum likelihood to data on times spent by the patients in hospital and in community-based care. Data on the different events that ended the patients' periods of care were used to estimate the dependence of the probabilities of these events on the phase from which the time in care ended. The age of the patients at admission to care and the year of admission were also included as covariates. RESULTS: Differential effects of these covariates were shown on the various parameters of the fitted model, and interpretations of these effects made. CONCLUSIONS: Models based on phase-type distributions were appropriate for describing times spent in care, as the ordered phases had an interpretable structure corresponding to increasing amounts of care being given.

OBJECTIVE: The variability in ultrasound-based antral follicle counts sized 2-10 mm after allowing for age-related decline is considerable. This may represent differences in actual reproductive age among women. This hypothesis was tested by cohort comparison for distribution of age at occurrence of reproductive events. DESIGN: A model with a nonlinear mean decline with age was fitted to antral follicle counts (AFC) obtained in 163 regularly cycling fertile volunteers. Ages at last child birth and menopause were predicted from the individual AFC by using thresholds to represent these events and the model for decline with age. Distributions of the observed ages at last childbirth (proxy variable for loss of natural fertility) and ages at menopause were obtained from the BALSAC demographic database and the Prospect-EPIC study, respectively. The observed distributions were compared with the predicted distributions by using visual comparison and quantile-quantile plots. Predictions of age at last child and age at menopause were done using percentiles of the modeled AFC distribution for given age, and corresponding percentiles of the predicted distributions of age at these reproductive events, with predictions following from the position of a woman's AFC relative to these percentiles. RESULTS: The predicted distributions of age at last child and age at menopause showed good agreement with the observed distributions in the BALSAC and EPIC cohort. Compared with age alone, antral follicle counts gave some additional information for individual prediction of age at last child and menopause. CONCLUSIONS: The link between declining antral follicle counts and reproductively significant events like loss of natural fertility and menopause is strengthened by the high degree of similarity among the predicted and observed age distributions. Predictive usefulness of this relationship in a clinical setting may be more marginal, except in the case of women who have low AFCs for their age.

OBJECTIVES: The present study describes the natural history of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans and Prevotella intermedia over a 5-year period and the effect of a triclosan/copolymer dentifrice on these organisms in a normal adult population. MATERIAL AND METHODS: Subgingival plaque samples were collected from 504 adult volunteers. Probing pocket depths (PPD) and relative attachment levels were measured using an automated probe. Participants were matched for disease status (CPI), plaque index, age and gender, and allocated to receive either a triclosan/copolymer or placebo dentifrice. Re-examination and subgingival plaque sampling was repeated after 1, 2, 3, 4 and 5 years. P. gingivalis, A. actinomycetemcomitans and P. intermedia were detected and quantitated using an enzyme linked immunosorbent assay. Logistic regression and generalised linear modelling were used to analyse the data. RESULTS: This 5-year longitudinal study showed considerable volatility in acquisition and loss (below the level of detection) of all three organisms in this population. Relatively few subjects had these organisms on multiple occasions. While P. gingivalis was related to loss of attachment and to PPD >/=3.5 mm, there was no relationship between A. actinomycetemcomitans or P. intermedia and disease progression over the 5 years of the study. Smokers with P. gingivalis had more PPD >/=3.5 mm than smokers without this organism. There was no significant effect of the triclosan dentifrice on P. gingivalis or A. actinomycetemcomitans. Subjects using triclosan were more likely to have P. intermedia than those not using the dentifrice; however this did not translate into these subjects having higher levels of P. intermedia and its presence was uniform showing no signs of increasing over the course of the study. CONCLUSION: The present 5-year longitudinal study has shown the transient nature of colonisation with P. gingivalis, A. actinomycetemcomitans and P. intermedia in a normal adult population. The use of a triclosan-containing dentifrice did not lead to an overgrowth of these organisms. The clinical effect of the dentifrice would appear to be independent of its antimicrobial properties.