Premature ovarian insufficiency: an International Menopause Society White Paper.

The aim of this International Menopause Society White Paper on premature ovarian insufficiency (POI) is to provide the latest information regarding this distressing condition. The impact of POI has far-reaching consequences due to its impact on general, psychological, and sexual quality of life, fertility prospects, and long-term bone, cardiovascular, and cognitive health. Progress in fully understanding the etiology, diagnosis, and optimal management options has been slow thus far due to the complexity of the condition and fragmented research. Recent advances in epidemiological and genetic research have improved our understanding of this condition and randomized prospective trials are being planned to determine the intervention strategies, which will optimize quality of life and long-term well-being. The International Menopause Society has commissioned a number of experts at the forefront of their specialty to define the state of the art in the understanding of this condition, to advise on practical management strategies, and to propose future research strategies. It is hoped that a global task force will subsequently be convened in order to formulate a consensus statement across key societies, to accelerate date collection and analysis of a global POI registry, and to facilitate progress in the key defined areas of research.

ESHRE Guideline: management of women with premature ovarian insufficiency.

STUDY QUESTION: What is the optimal management of women with premature ovarian insufficiency (POI) based on the best available evidence in the literature? SUMMARY ANSWER: The guideline development group (GDG) formulated 99 recommendations answering 31 key questions on the diagnosis and treatment of women with POI. WHAT IS KNOWN ALREADY: NA. STUDY DESIGN, SIZE, DURATION: This guideline was produced by a multidisciplinary group of experts in the field using the methodology of the Manual for ESHRE Guideline Development, including a thorough systematic search of the literature, quality assessment of the included papers up to September 2014 and consensus within the guideline group on all recommendations. The GDG included a patient representative to ensure input from women with POI. After finalization of the draft, the European Society for Human Reproduction and Embryology (ESHRE) members and professional organizations were asked to review the guideline. PARTICIPANTS/MATERIALS, SETTING, METHODS: NA. MAIN RESULTS AND THE ROLE OF CHANCE: The guideline provides 17 recommendations on diagnosis and assessment of POI and 46 recommendations on the different sequelae of POI and their consequences for monitoring and treatment. Furthermore, 24 recommendations were formulated on hormone replacement therapy in women with POI, and two on alternative and complementary treatment. A chapter on puberty induction resulted in five recommendations. LIMITATIONS, REASONS FOR CAUTION: The main limitation of the guideline is that, due to the lack of data, many of the recommendations are based on expert opinion or indirect evidence from studies on post-menopausal women or women with Turner Syndrome. WIDER IMPLICATIONS OF THE FINDINGS: Despite the limitations, the guideline group is confident that this document will be able to guide health care professionals in providing the best practice for managing women with POI given current evidence. Furthermore, the guideline group has formulated research recommendations on the gaps in knowledge identified in the literature searches, in an attempt to stimulate research on the key issues in POI. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the implementation of the guideline. The guideline group members did not receive payment. Dr Davies reports non-financial support from Novo Nordisk, outside the submitted work; the other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: NA.

Which measures of adiposity predict subsequent left ventricular geometry? Evidence from the Bogalusa Heart Study.

BACKGROUND AND AIMS: Left ventricular (LV) hypertrophy increases the risk of future cardiovascular events. The relationship between obesity in young adulthood and later LV geometry is unknown. We examined the association between long-term changes in measures of adiposity and subsequent LV geometry among 1073 young adults from the Bogalusa Heart Study. METHODS AND RESULTS: Echocardiography-measured LV geometry was classified into normal (N = 796), concentric remodeling (N = 124), eccentric hypertrophy (N = 99), and concentric hypertrophy (N = 54) by integrating relative wall thickness and LV mass index. The mean age of our population was 38 years when the LV geometry was measured. Body mass index (BMI) increased by a mean of 4.9 kg/m(2) over a median of 20 years, waist circumference (WC) by 10.9 cm over 17 years, waist/hip ratio by 0.02 over 10 years, waist/height ratio by 0.06 over 17 years, abdominal height by 0.9 cm over 10 years, body fat (BF) percentage by 12.7% over 20 years, and Visceral Adiposity Index by 0.30 over 17 years. In polytomous logistic regression models corrected for multiple comparisons, participants with one-standard-deviation increases in BMI, WC, waist/height ratio, and BF had 2.00 (95% confidence interval (CI): 1.53-2.61), 1.33 (1.06-1.68), 1.35 (1.07-1.70), and 1.60 (1.26-2.03) times the risk of eccentric hypertrophy, respectively, after adjustment for demographic, lifestyle, metabolic risk factors, and follow-up time. Likewise, the rates of change in BMI, WC, waist/height ratio, and BF were associated with eccentric hypertrophy. There was no association with concentric remodeling or concentric hypertrophy. CONCLUSIONS: Our findings suggest that increases in BMI, WC, waist/height ratio, and BF were strong predictors of eccentric hypertrophy in middle age.

A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†.

BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR). RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation. CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups. TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062.

Hepcidin levels in diabetes mellitus and polycystic ovary syndrome.

AIM: Increased body iron is associated with insulin resistance. Hepcidin is the key hormone that negatively regulates iron homeostasis. We hypothesized that individuals with insulin resistance have inadequate hepcidin levels for their iron load. METHODS: Serum concentrations of the active form of hepcidin (hepcidin-25) and hepcidin:ferritin ratio were evaluated in participants with Type 2 diabetes (n = 33, control subjects matched for age, gender and BMI, n = 33) and participants with polycystic ovary syndrome (n = 27, control subjects matched for age and BMI, n = 16). To investigate whether any changes observed were associated with insulin resistance rather than insulin deficiency or hyperglycaemia per se, the same measurements were made in participants with Type 1 diabetes (n = 28, control subjects matched for age, gender and BMI, n = 30). Finally, the relationship between homeostasis model assessment of insulin resistance and serum hepcidin:ferritin ratio was explored in overweight or obese participants without diabetes (n = 16). RESULTS: Participants with Type 2 diabetes had significantly lower hepcidin and hepcidin:ferritin ratio than control subjects (P < 0.05 and P < 0.01, respectively). Participants with polycystic ovary syndrome had a significantly lower hepcidin:ferritin ratio than control subjects (P < 0.05). There was no significant difference in hepcidin or hepcidin:ferritin ratio between participants with Type 1 diabetes and control subjects (P = 0.88 and P = 0.94). Serum hepcidin:ferritin ratio inversely correlated with homeostasis model assessment of insulin resistance (r = -0.59, P < 0.05). CONCLUSION: Insulin resistance, but not insulin deficiency or hyperglycaemia per se, is associated with inadequate hepcidin levels. Reduced hepcidin concentrations may cause increased body iron stores in insulin-resistant states.

The content validity of the Behaviour Support Plan Quality Evaluation tool (BSP-QEII) and its potential application in accommodation and day-support services for adults with intellectual disability.

BACKGROUND: The quality of support provided to people with disability who show challenging behaviour could be influenced by the quality of the behaviour support plans (BSPs) on which staff rely for direction. This study investigated the content validity of the Behaviour Support Plan Quality Evaluation tool (BSP-QEII), originally developed to guide the development of BSPs for children in school settings, and evaluated its application for use in accommodation and day-support services for adults with intellectual disability. METHOD: A three-round Delphi study involving a purposive sample of experienced behaviour support practitioners (n = 30) was conducted over an 8-week period. The analyses included deductive content analysis and descriptive statistics. RESULTS: The 12 quality domains of the BSP-QEII were affirmed as valid for application in adult accommodation and day-support service settings. Two additional quality domains were suggested, relating to the provision of detailed background on the client and the need for plans to reflect contemporary service philosophy. Furthermore, the results suggest that some issues previously identified in the literature as being important for inclusion in BSPs might not currently be a priority for practitioners. These included: the importance of specifying replacement or alternative behaviours to be taught, descriptions of teaching strategies to be used, reinforcers, and the specification of objective goals against which to evaluate the success of the intervention programme. CONCLUSIONS: The BSP-QEII provides a potentially useful framework to guide and evaluate the development of BSPs in services for adults with intellectual disability. Further research is warranted to investigate why practitioners are potentially giving greater attention to some areas of intervention practice than others, even where research has demonstrated these others areas of practice could be important to achieving quality outcomes.

Reliability and utility of the Behaviour Support Plan Quality Evaluation tool (BSP-QEII) for auditing and quality development in services for adults with intellectual disability and challenging behaviour.

BACKGROUND: Having an objective means of evaluating the quality of behaviour support plans (BSPs) could assist service providers and statutory authorities to monitor and improve the quality of support provided to people with intellectual disability (ID) who exhibit challenging behaviour. The Behaviour Support Plan Quality Evaluation Guide II (BSP-QEII) was developed to monitor and assess BSPs prepared by teachers to support children with disability in the school system. This study investigated the application of the BSP-QEII to the assessment of BSPs for adults with ID in community support services. METHOD: The inter-rater reliability of the BSP-QEII was assessed. The utility of the BPS-QEII was then investigated with reference to a time series study of matched pairs of BSPs, developed for the same clients over a period of approximately 3 years. Differences in plan quality measured across a number of service and systemic variables were also investigated. RESULTS: The BSP-QEII was found to have good inter-rater reliability and good utility for audit purposes. It was able to discriminate changes in plan quality over time. Differences in plan quality were also evident across different service types, where specialist staff had or had not been involved, and in some instances where a statutory format for the plan had or had not been used. There were no differences between plans developed by government and community sector agencies, nor were there any regional differences across the jurisdiction. CONCLUSIONS: The BSP-QEII could usefully be adopted as an audit tool for measuring the quality of BSPs for adults with ID. In addition to being used for research and administrative auditing, the principles underpinning the BSP-QEII could also be useful to guide policy and educational activities for staff in community based services for adults with ID.

Oral 11ß-HSD1 inhibitor AZD4017 improves wound healing and skin integrity in adults with type 2 diabetes mellitus: a pilot randomized controlled trial.

BACKGROUND: Chronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11ß-hydroxysteroid dehydrogenase type 1, 11ß-HSD1) impair wound healing. OBJECTIVES: Efficacy, safety, and feasibility of 11ß-HSD1 inhibition for skin function and wound healing. DESIGN: Investigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial. METHODS: Single-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11ß-HSD1 inhibitor AZD4017 (n = 14) or placebo (n = 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized. RESULTS: Exploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h ex vivoskin 11ß-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: -3.4 to 5.5) but reduced systemic 11ß-HSD1 activity by 87% (69-104%). Wound diameter was 34% (7-63%) smaller with AZD4017 at day 2, and 48% (12-85%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9/month, 27/28, and 95.3%, respectively. CONCLUSION: A phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers. SIGNIFICANCE STATEMENT: Stress hormone activation by the enzyme 11ß-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11ß-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11ß-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11ß-HSD type 1 as a novel therapeutic target forchronic wounds.

Eating behaviour and weight in children.

OBJECTIVE: To test the hypothesis that quantitative variation in eating behaviour traits shows a graded association with weight in children. DESIGN: Cross-sectional design in a community setting. SUBJECTS: Data were from 406 families participating in the Physical Exercise and Appetite in CHildren Study (PEACHES) or the Twins Early Development Study (TEDS). Children were aged 7-9 years (PEACHES) and 9-12 years (TEDS). MEASUREMENTS: Weights and heights were measured by researchers. Body mass index (BMI) s.d. scores were used to categorize participants into underweight, healthy weight, overweight and obese groups, with an additional division of the healthy weight group into higher and lower healthy weight at the 50th centile. Eating behaviour traits were assessed with the Child Eating Behaviour Questionnaire (CEBQ), completed by the parents on behalf of their child. Linear trend analyses compared CEBQ subscale scores across the five weight groups. RESULTS: Satiety Responsiveness/Slowness in Eating and Food Fussiness showed a graded negative association with weight, whereas Food Responsiveness, Enjoyment of Food, Emotional Overeating and Desire to Drink were positively associated. All effects were maintained after controlling for age, sex, ethnicity, parental education and sample. There was no systematic association with weight for Emotional Undereating. CONCLUSION: These results support the idea that approach-related and avoidance-related appetitive traits are systematically (and oppositely) related to adiposity, and not exclusively associated with obesity. Early assessment of these traits could be used as indicators of susceptibility to weight gain.

Racial differences in blood pressure control.

Children from an entire biracial geographical population were examined for blood pressure. A sample of 278 children, stratified by diastolic blood pressure, was reexamined 1 to 2 years later. Dopamine beta-hydroxylase, renin activity, and resting heart rate were observed in black and white children. In the group with high blood pressure, whites had higher heart rates and greater renin activity than blacks. Dopamine beta-hydroxylase concentrations in blacks were lower than in whites over the entire spectrum of blood pressure levels. High blood pressure seems to have a different metabolic background in the two races which may influence the early natural history of essential hypertension. Therefore, the rationale of prevention, and possibly treatment, of early hypertension in blacks and whites may differ.

Early predictors of anastomotic leaks after colectomy.

BACKGROUND: An anastomotic leak after colorectal surgery is associated with significant morbidity and decreased survival. Our aim was to identify the early predictors of anastomotic leaks. METHODS: The records of patients undergoing restorative resection for colorectal disease from January 2000 to November 2005 were reviewed. Demographics, clinical events, and laboratory parameters were recorded. RESULTS: A total of 311 patients were included. An anastomotic leak was identified in 25 patients (8%). A leak was suspected and diagnosis confirmed at a mean of 10+/-1 days postoperatively. More respiratory and neurological events occurred in patients with an anastomotic leak (p<0.001). These events occurred early in the postoperative course and were usually the first signs and symptoms of a leak. More patients with a leak had absence of bowel activity by postoperative day 6 compared to patients without a leak (p<0.0001). Elevations of the white blood cell count or temperature were a late finding. CONCLUSION: The earliest clinical predictors of an anastomotic leak are pulmonary and/or neurological. Awareness of these findings might help in early diagnosis and treatment of an anastomotic leak.

Adiposity and 'eating in the absence of hunger' in children.

OBJECTIVE: To examine the association between eating in the absence of hunger (EAH) and adiposity in children. DESIGN: Two cross-sectional studies in community settings. SUBJECTS: For study 1, 348 children (178 girls and 170 boys) aged 7-9 years were recruited as part of the Physical Exercise and Appetite in Children Study. In study 2, participants were a subsample of children aged 9-12 years (N=316; 192 girls and 124 boys) from the Twins Early Development Study. MEASUREMENTS: EAH was operationalized as intake of highly palatable sweet snacks after a mixed meal at school (study 1) or home (study 2). Weight (kg) and height (m) measurements were used to calculate the body mass index (BMI) s.d. scores. Children were grouped using the standard criteria for underweight, healthy weight, overweight and obesity. The healthy weight range was further subdivided into lower healthy weight (50th centile) to examine the distribution of EAH across the adiposity continuum. RESULTS: In both studies, EAH showed a significant positive association with adiposity in boys after adjusting for covariates (P<0.001), with a linear increase in the intake across underweight, healthy weight and overweight groups. The association between EAH and adiposity was not significant in girls in either study, although in study 1, results showed a quadratic trend, with EAH increasing through the underweight and healthy weight ranges and decreasing in overweight and obese groups. CONCLUSION: EAH is a behavioural phenotype that is not specific to overweight children but instead shows a graded association with adiposity across the weight continuum, particularly in boys. In this study, the effect was less pronounced in girls, which may reflect social desirability pressures constraining food intake among heavier girls.

Origins of the "black/white" difference in blood pressure: roles of birth weight, postnatal growth, early blood pressure, and adolescent body size: the Bogalusa heart study.

BACKGROUND: The determinants of differences in blood pressure that emerge in adolescence between black Americans of predominantly African descent and white Americans of predominantly European descent are unknown. One hypothesis is related to intrauterine and early childhood growth. The role of early blood pressure itself is also unclear. We tested whether differences in birth weight and in carefully standardized subsequent measures of weight, height, and blood pressure from 0 to 4 or 5 years were related to black/white differences in blood pressure in adolescence. METHODS AND RESULTS: Two Bogalusa cohorts who had complete follow-up data on birth weights and early childhood and adolescent anthropometric and blood pressure measures were pooled. One hundred eighty-five children (48 black and 47 white boys and 41 black and 49 white girls) were followed up and studied after 15 to 17 years. Birth weights were a mean 443 and 282 g lower in black boys and girls, respectively, than in whites (P<0.001). Blood pressures in adolescence were 3.4/1.9 and 1.7/0.6 mm Hg higher, respectively, and tracked from early childhood. In regression analyses, birth weight accounted for the ethnic difference in adolescent blood pressure, which was also independently predicted, in decreasing impact order, by adolescent height, adolescent body mass index, and systolic blood pressure at 4 to 5 years and inversely by growth from 0 to 4 to 5 years. CONCLUSIONS: If these results can be replicated in larger and independent samples, they suggest that efforts to improve intrauterine growth in black infants as well as lessen weight gain in adolescence might substantially reduce excess high blood pressure/hypertension in this ethnic group.

TopCount coupled to ultra-performance liquid chromatography for the profiling of radiolabeled drug metabolites in complex biological samples.

The recent commercial availability of small particle packed columns (<2microm) and associated instrumentation capable of withstanding the high pressures of such columns, has lead to an increase in the application of so called ultra-performance liquid chromatography (UPLC). It has recently been shown that the improved efficiency, resolution and peak capacity of these columns, when coupled to mass spectrometry, provides particular benefit for the identification of drug metabolites in complex biological samples. In this work, the ability of TopCount, a microplate scintillation counter, to act as a suitable radiodetection system for ultra-performance liquid chromatography methods is tested. TopCount, has innumerable benefits over more traditional on-line radioactivity flow detection methods, when dealing with the narrow peak widths and small peak volumes associated with the enhanced efficiency of sub-2microm columns. The system is tested for robustness and sensitivity, and then used to undertake successful metabolite profiling of actual samples, and the data compared to traditional HPLC with on-line radioactivity flow detector.

Multicenter evaluation of a new 4th generation HIV screening assay Elecsys HIV combi.

Fourth-generation screening assays which permit a simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody reduce the diagnostic window on average by four days in comparison to third-generation antibody assays. Recently, the new automated Elecsys HIV combi was compared in a multicenter study to alternative fourth- and third-generation assays, p24 antigen test and HIV-1 RNA RT-PCR. A total of 104 serocon-version panels, samples of the acute phase of infection after seroconversion (n = 33), anti-HIV-1 positive specimens (n = 572) from patients in different stages of the disease, 535 subtyped samples from different geographical locations, including group M (subtypes A-J) and group O, anti-HIV-2 positive sera (n = 364), dilutions of cell culture supernatants (n = 60) infected with different HIV-1 subtypes, selected performance panels, 8406 unselected samples from blood donors originating from different blood transfusion centers, 3810 unselected sera from daily routine and from hospitalized patients, 9927 unselected samples from South Africa and 1943 potentially interfering samples were tested with the Elecsys HIV combi. Elecsys HIV combi showed a comparable sensitivity to HIV-1 Ag stand-alone assays for early detection of HIV infection in seroconversion panels. The mean time delay of Elecsys HIV combi (last negative sample + 1 day) in comparison to HIV-1 RT-PCR for 92 panels tested with both methods was 3.23 days. The diagnostic window was reduced with Elecsys HIV combi between 1.56 and 5.32 days in comparison to third-generation assays. The specificity of Elecsys HIV combi in blood donors was 99.80% after repeated testing. Our results show that a fourth-generation assay with improved specificity and sensitivity like the Elecsys HIV combi is suitable for blood donor screening due to its low number of false positives and since it detects HIV p24 antigen with a comparable sensitivity to single antigen assays.

A new human breast carcinoma cell line (PMC42) with stem cell characteristics. I. Morphologic characterization.

A new human breast carcinoma cell line (PMC42) was established from a pleural effusion from a woman with metastatic breast cancer. The cells were significantly pleomorphic even after 3.5 years in continuous culture. Eight different cell types could be characterized morphologically in monolayer culture. Cells cloned in agar and replated in monolayer culture were equally heterogenous. Cells also grew in suspension in papillary clusters that structurally resembled glandular organoids. Electron microscopy confirmed the differentiated structure of these cells in which many of the features of lactating breast tissue were evident. It is proposed that this is a culture derived from a malignant breast stem that has retained its ability to differentiate in vitro.

A new human breast carcinoma cell line (PMC42) with stem cell characteristics. II. Characterization of cells growing as organoids.

A new human breast carcinoma cell line (PMC42) has been further characterized. The cells can grow either as monolayers or as floating cords of cells. The cords grow in suspension for long periods but may spontaneously attach and grow out to form a typical PMC42 monolayer. Ultrastructurally, the cells resemble breast ductal cells in many respects. Both epidermal growth factor (EGF) and prolactin induce ultrastructural changes, and lipid production is stimulated markedly by both factors. EGF also promoted the attachment of the floating cords and the growth of cells from these cords as monolayer cultures. The karyotype of the cord cells is different from that previously described for the monolayer cultures. Cord cells are hypodiploid (mode 39), whereas the monolayer cultures are subtriploid (mode 66). Although the ploidy is different, the karyotypes are related with 9 marker chromosomes being common to both populations. In addition, cultures in which cords have attached and in which cells are growing out as monolayers are bimodal with 10-20% of the cells becoming pseudotetraploid with a mode of 77.

Childhood obesity patterns and relation to middle-age sleep apnoea risk: the Bogalusa Heart Study.

BACKGROUND: Obese adults have a higher risk of obstructive sleep apnoea (OSA); however, the relationship between childhood obesity and adult OSA risk is unclear. Objectives This study aimed to examine overweight/obesity (OW) in childhood and risk of OSA in middle age. METHODS: Childhood OW status was classified as never OW, weight cycling, persistent OW and incident OW. After 35 years of follow-up, high risk for OSA was determined by a positive score in ≥2 domains on the Berlin Questionnaire with obesity removed from scoring. RESULTS: At initial assessment, mean (SD) age was 9.9 (2.9) years, and 23.9% were OW. Overall, 25.7% had scores indicating a high risk for OSA. Compared with participants who were never OW, those with persistent OW and incident OW were 1.36 (95%CI: 1.04-1.77) and 1.47 (1.11-1.96) times more likely to be high risk for OSA, after adjustment for multiple risk factors and adult OW status. Participants with an OW duration of 1-4 years, 5-8 years, and 8+ years were 0.96 (0.44-2.09), 1.20 (0.70-2.04) and 1.52 (1.22-1.90) times more likely to be high risk for OSA compared with those who were never OW (P for trend: 0.0002). CONCLUSIONS: These results suggest that childhood OW is associated with a high risk of OSA in middle age.

Nuclear changes in oral mucosa of alcoholics and crack cocaine users.

The effects of drugs of abuse on oral mucosa are only partly understood. The aims of the present study were to: (1) evaluate the frequency of nuclear changes in normal-appearing oral mucosa of alcoholics and crack cocaine users and (2) assess their association with cell proliferation rate. Oral smears were obtained from the border of the tongue and floor of the mouth of 26 crack cocaine users (24 males and 2 females), 29 alcoholics (17 males and 12 females), and 35 controls (17 males and 18 females). Histological slides were submitted to Feulgen staining to assess the frequency of micronuclei (MN), binucleated cells (BN), broken eggs (BE), and karyorrhexis (KR). A significant increase in the frequency of MN was observed in cells exfoliated from the tongue of crack cocaine users (p = 0.01), and alcoholics showed a higher frequency of KR in cells obtained from the floor of the mouth (p = 0.01). Our findings suggest that the use of crack cocaine induces clastogenic effects, whereas alcoholism is associated with higher degrees of keratinization in the floor of the mouth.