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Item does not contain fulltext OBJECTIVES: To assess the hypothesis that as lower urinary tract symptoms (LUTS) increase in severity, the impact as measured by the BPH impact index (BII) would also increase. SUBJECTS AND METHODS: The UREPIK survey collected information on this relationship from men and their partners in the Netherlands, Korea, France and the UK. Culturally and linguistically validated versions of three standard questionnaires, the SF-12, the BII and the International Prostate Symptom Score (IPSS) were used to assess the distribution of symptoms and the impact on health status. Stratified random samples of men aged 40-79 years in each community were recruited. Response rates were 72% in Boxmeer, 28% in Auxerre, 60% in Birmingham and 68% in Seoul. Regression analyses were undertaken on total SF-12, BII and IPSS. RESULTS: In all, 4800 index men and 3674 women responded; the BII increased with increasing IPSS. The correlation coefficients were; Boxmeer 0.69, Auxerre 0.56, Birmingham 0.60 and Seoul 0.68. For women, the correlations were slightly lower except in Birmingham, at 0.65 (Boxmeer), 0.44 (Auxerre), 0.71 (Birmingham), 0.57 (Korea). BII scores were higher in women than in men with the same level of IPSS. Adjusting for IPSS there was no association between age and BII. There was an association between IPSS quality-of-life (QoL) score and BII; for men the correlation was 0.62 and for women 0.60. Men and women with the same score on the IPSS QoL reported the same bother. Among those with an IPSS of 20-35 women expressed significantly more bother (P < 0.001). The SF-12 scores decreased as the IPSS and the BII increased in both men and women. Furthermore, the SF-12 mental score decreased with increasing symptoms in the partner. CONCLUSIONS: The relationship between the severity of LUTS and BII was similar in all centres. There is a clear association between the BII and the IPSS QoL question in men and women. The BII discriminates between people who are unhappy about their urinary condition compared with those who are pleased. Although designed for use in men with benign prostatic hyperplasia, the index also appears to be a useful among women. The severity of symptoms of LUTS has an adverse effect on the health status of the individual and his/her partner.

Contains fulltext : 69561tits.pdf (Publisher’s version ) (Closed access) Adiponectin is secreted from adipocytes in different multimers, of which the high molecular weight (HMW) form is supposed to mediate favorable metabolic and anti-atherogenic effects. We determined adiponectin multimers in 29 female and 22 male patients with familial combined hyperlipidemia (FCH) and 51 age-, gender-, and BMI-matched controls in relation to cardiovascular disease (CVD). We observed a clear sexual dimorphism of total adiponectin and its multimers. Female, but not male, FCH patients had significant lower total adiponectin and both HMW and low molecular weight (LMW) adiponectin than controls. The adiponectin sensitivity index (ASI), reflected by HMW/total adiponectin, and the LMW/HMW adiponectin ratio did not differ significantly between FCH females and control females. However, FCH females with CVD exhibited significantly lower ASI (34.2+/-10.1% vs 46.0+/-7.1%) and higher LMW/HMW ratio (1.5+/-0.8 vs 0.7+/-0.3) compared to FCH females without CVD, reflecting a more atherogenic adiponectin multimer distribution.

Contains fulltext : 70109.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The guanine-thymidine (GT)n repeat in the HMOX1 promoter determines the level of induction of the heme-degrading enzyme heme oxygenase 1 (HO-1), which protects against inflammatory and oxidative stress. In individuals with short (GT)n repeats (where n < 25; SS genotype), higher levels of HO-1 activity are induced more rapidly than in those with long (GT)n repeats (where n > or = 25; LL genotype). Recently, it was demonstrated that HO-1 activity protects against the onset of rheumatoid arthritis (RA). The aim of this study was to determine whether the (GT)n-repeat length within the HMOX1 promoter region is associated with RA disease severity and radiographic joint damage. METHODS: A cohort of 325 well-characterized RA patients and 273 controls was investigated by DNA fragment-length analysis for the association of (GT)n repeats in the HMOX1 promoter region with RA disease susceptibility and severity. RESULTS: Although no significant differences in genotype or allele frequency were found between controls and RA patients, the odds ratios corresponded well to those in the previously described cohort. Among patients, those carrying the SS genotype had a more favorable radiographic outcome over 9 years than those carrying the LL genotype. This was unexpected since no differences in disease activity were found between the genotypes or alleles. CONCLUSION: Patients with the SS genotype have a better long-term radiographic outcome despite poor prognostic markers at baseline and despite disease activity at followup similar to that of patients with the LL genotype. This suggests that the HMOX1/HO-1 system is involved in the uncoupling of disease activity and joint damage and may provide a novel target for the treatment of RA. 6 p.

The incidence of bladder cancer varies considerably among countries; the highest incidence rates are in Western communities. The variation in occurrence can partly be explained by differences in registration and coding practices of pTa tumours. Factors that modify the occurrence of bladder cancer are smoking and exposure to many kinds of carcinogenic substances in the workplace. Evidence also exists for radiotherapy to the pelvis, infection with Schistosoma haematobium, and certain medications as risk factors for bladder cancer. Despite enormous efforts, other important environmental or lifestyle factors that clearly and consistently increase or decrease the risk of bladder cancer have not been identified. Bladder cancer in first-degree relatives doubles the risk of bladder cancer; this increased risk might be due to high-penetrance susceptibility genes in a small subset of families, but most of this risk is probably caused by common lower-penetrance DNA variants that influence risk through one or more different cancer pathways. In the next 2 years genome-wide association scans will probably yield important new information on such variants. This might also facilitate new studies on lifestyle factors restricted to groups of susceptible people. In the future it will also be necessary to pay more attention to potential risk factors for different types of bladder cancer, more specifically low- vs high-grade cancer. The ultimate goal is to build a risk-prediction model by integrating environmental and genetic factors that can project individualized probabilities of developing bladder cancer.

Item does not contain fulltext We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07-1.41, P(trend)=0.02). After calibration to allow for measurement error, we estimated that a 35-g day(-1) increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1-72%, P(trend)=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the risk for prostate cancer.

Contains fulltext : 71001.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 71316.pdf (Publisher’s version ) (Closed access) Fecal incontinence is a common disorder in children. Many children with fecal incontinence have psychosocial co-morbidity. In this study, the effect of psychosocial co-morbidity on the treatment outcome of children with fecal incontinence was evaluated. One hundred and fifty children with fecal incontinence were treated in a multidisciplinary program. All children had been treated unsuccessfully for at least one year before entering the program. The treatment consisted of laxative treatment, psychosocial interventions, and biofeedback training. Psychosocial co-morbidity was classified according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). One hundred and forty-one children were completely analyzed (102 boys, mean age 9.6 (range 6.5-16.5) years). Of these, 31 (22%) children had fecal incontinence without constipation and 110 (78%) children had fecal incontinence associated with constipation. In 95% of children, at least one psychosocial co-morbidity was present. Treatment was successful at 12 months in 69% of patients. Treatment was less successful in children with attention deficit hyperactivity disorder (ADHD), in children with parent-child relational problems, and in mentally retarded children. The results indicate that the early assessment and treatment of psychosocial co-morbidity might improve treatment response in children with fecal incontinence. Children with fecal incontinence are treated less successfully in the first year if they have ADHD, parent-child relational problems, or mental retardation. Psychosocial evaluation and the early assessment and treatment of psychosocial co-morbidity is indicated in order to improve response rate. Family counseling--aimed at improving parent-child relations--should be an integral part of a multidisciplinary treatment program for fecal incontinence.

Contains fulltext : 71366.pdf (Publisher’s version ) (Closed access) BACKGROUND: Disease management of dementia in general practice (GP) is hampered by a lack of data on the prognosis of dementia. AIM: To gain more insight into the life expectancy of and the effects of cardiovascular and cerebrovascular co-morbidity in dementia patients in GP. DESIGN OF STUDY: Historical cohort. SETTING: 4 general practices in Nijmegen, The Netherlands. POPULATION: All patients in these practices participating in the Continuous Morbidity Registration (CMR). METHODS: The patient cohort was diagnosed with dementia between January 1st 1985 and December 31st 2002. The control cohort consisted of patients matched one-to-one with demented patients on age, sex, and socio-economic status. Cardiovascular and cerebrovascular co-morbidity was studied from 5 years before the diagnosis of dementia till the endpoints of data collection. RESULTS: 251 couples of patients and controls were formed (79 men, 172 women, mean age 81.4+/-7.0 years). The median life expectancy after diagnosis was 2.3 years for the dementia patients, and 3.7 years for the controls. Median time from diagnosis till nursing home placement was 1.4 years. Cerebrovascular and cardiovascular morbidity preceding dementia diagnosis decreased survival of cases with dementia with a relative risk of 1.54 (95%CI: 1.13-2.09) and in controls with a relative risk of 1.91 (95%CI: 1.48-2.46). Obesity was associated with a lower risk of dementia (RR=0.77 (95%-CI 0.63-0.94)). Hypertension and obesity diagnosed after the dementia diagnosis were significantly associated with an increase in survival. CONCLUSION: In general practice, the diagnosis of dementia is made at a late stage, when patients will continue to live at home only for a short time. Moreover, life expectancy at diagnosis is very limited and prognosis is furthermore negatively influenced by preceding cardio- and cerebrovascular co-morbidity.

Contains fulltext : 70003.pdf (Publisher’s version ) (Closed access) CONTEXT: Previous research suggests that depression is a risk factor for stroke. However, the reliability of much research is limited by the lack of documentation on the presence of preexistent cardiovascular disease and by the use of limited measures of depression or stroke. OBJECTIVES: To test the hypotheses that (1) clinically relevant depressive symptoms are an independent risk factor of incident stroke in cardiac and noncardiac patients and (2) more chronic and severe depressive symptoms are associated with incident stroke. DESIGN: A cohort of elderly Dutch people (aged > or = 55 years) was followed up for 9 years in the Longitudinal Aging Study Amsterdam (baseline measurements were taken in 1992 or 1993, and the study concluded in 2001 or 2002, respectively). SETTING: General community. PARTICIPANTS: Randomly selected population-based sample (N = 2965) without a history of stroke. MAIN OUTCOME MEASURES: The study end point was a first stroke (nonfatal or fatal). Depression was measured using the National Institute of Mental Health Diagnostic Interview Schedule and the Center for Epidemiological Studies-Depression Scale. Multivariate Cox proportional hazards regression analyses of stroke incidence were performed. The association of the chronicity and severity of depressive symptoms was studied in extended models with time-dependent variables. RESULTS: The sample's mean (SD) age was 70.5 (8.7) years, 52.1% were women, and the mean (SD) follow-up was 7.7 (3.1) years. Inclusion of an interaction between cardiac disease and clinically relevant depressive symptoms improved the model for stroke (P = .03). In participants with preexistent cardiac disease, but not in participants without cardiac disease, clinically relevant depressive symptoms at baseline (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.17-4.09) and the severity (range, 0-60; HR, 1.08; 95% CI, 1.02-1.13) and chronicity (HR, 3.51; 95% CI, 1.13-10.93) of symptoms during follow-up were associated with stroke. CONCLUSIONS: Preexistent cardiac disease moderates the association between depressive symptoms and incident stroke. In cardiac patients, baseline depressive symptoms and both the severity and chronicity of symptoms during follow-up are associated with incident stroke.

Item does not contain fulltext The study aimed to examine the relationship between spontaneous cerebral emboli (SCE), patent foramen ovale (PFO) and white matter hyperintensities (WMH) on cerebral MRI in patients with Alzheimer's disease (AD) and vascular dementia (VaD). SCE were identified by transcranial Doppler of the middle cerebral artery for 1 h. A "significant" v-aCS (venous-to-arterial circulation shunt indicative of PFO; > or =15 embolic signals within 12 cardiac cycles) was detected by intravenous injection of "air in saline" ultrasound contrast. Deep white matter hyperintensities (DWMH) and periventricular hyperintensities (PVH) were assessed using Schelten's scale. After correction for cardiovascular risk factors, both DWMH and PVH were significantly associated with the presence of a PFO in AD (beta = 0.31, p = 0.02 for DWMH, odds ratio 8.7, p = 0.011 for PVH) but not in VaD. No consistent relationship was found between SCE and WMH in AD. In VaD, the severity of DWMH was negatively correlated with SCE (beta = -0.55; p = 0.001). In conclusion, the presence of a significant venous-to-arterial shunt is associated with more severe DWMH in AD, and may play a part in the aetiology of the disorder. In addition, there is a significant negative correlation between SCE and DWMH in VaD, which supports the hypothesis that VaD may be the result of ischaemic injury, predominantly reflecting embolic aetiology.

Contains fulltext : 69250.pdf (Publisher’s version ) (Closed access) Autism spectrum disorder was diagnosed in three adults. The first patient, a married man aged 41, was referred to a psychiatrist with 'impending burn-out'. The second was a 32-year-old male student with schizophrenia and a depressive disorder who was referred to a centre for autism because a friend of his mother's knew someone with Asperger's syndrome. The third patient was a 25-year-old woman with a 'fixation on food' who was referred by her general practitioner to a psychiatrist for evaluation of longstanding use of antidepressant medication. Autism used to be thought of as a condition of childhood. Only recently has the diagnosis and treatment of autism spectrum disorders become the focus of attention in adult psychiatry. It is made all the more difficult as during development into adulthood, the expression of disorders of reciprocal social interaction, communication, imagination and repetitive stereotypical thinking and actions, change.

Contains fulltext : 69271.pdf (Publisher’s version ) (Closed access) BACKGROUND: Plasma methylmalonic acid (MMA) is a specific marker for functional cobalamin deficiency. This deficiency can give rise to non-specific but serious symptoms in childhood such as developmental delay, convulsions and failure to thrive and may even lead to irreversible neurological damage. AIM OF THE STUDY: To analyse plasma MMA concentrations in Dutch children and to evaluate possible factors influencing its concentration. METHODS: A number of 186 Dutch children aged 0-19 years were analysed cross-sectionally. Blood was collected to measure MMA, total homocysteine (tHcy), cobalamin (Cbl) and serum creatinine concentrations. In addition, information about medical history, age and sex was recorded. RESULTS: The geometric mean (GM) plasma MMA concentration was 0.17 micromol/l (95% CI 0.07-0.42) and the GM tHcy was 6.6 micromol/l (95% CI 3.1-13.9). There is a slight positive correlation between plasma MMA and age in children >1 year (r = 0.211, P < 0.05). Plasma MMA concentrations were significantly higher in children with low Cbl concentrations. No significant difference in MMA, Cbl, tHcy or creatinine concentrations between sexes could be observed. Regression analysis showed that Cbl was the strongest determinant of plasma MMA (regression coefficient -0.414, P < 0.05). The association between MMA and Cbl is stronger at increasing age (P for trend 0.045). CONCLUSIONS: Plasma Cbl is the main determinant of MMA in this group of Dutch children. The strength of the association increased with increasing age.

Summary Objectives: In this study, we evaluated the internal validity of EPICON, an application for grouping ICPCcoded diagnoses from electronic medical records into episodes of care. These episodes are used to estimate morbidity rates in general practice. Methods: Morbidity rates based on EPICON were compared to a gold standard; i.e. the rates from the second Dutch National Survey of General Practice. We calculated the deviation from the gold standard for 677 prevalence and 681 incidence rates, based on the full dataset. Additionally, we examined the effect of casebased reasoning within EPICON using a comparison to a simple, not case-based method (EPI-0). Finally, we used a split sample procedure to evaluate the performance of EPICON. Results: Morbidity rates that are based on EPICON deviate only slightly from the gold standard and show no systematic bias. The effect of case-based reasoning within EPICON is evident. The addition of case-based reasoning to the grouping system reduced both systematic and random error. Although the morbidity rates that are based on the split sample procedure show no systematic bias, they do deviate more from the gold standard than morbidity rates for the full dataset. Conclusions: Results from this study indicate that the internal validity of EPICON is adequate. Assuming that the standard is gold, EPICON provides valid outcomes for this study population. EPICON seems useful for registries in general practice for the purpose of estimating morbidity rates.

Contains fulltext : 70771.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To investigate functional consequences of the Toll-like receptor 4 (TLR4) variant (Asp299Gly) in rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cells from 28 patients with RA carrying or not carrying the TLR4 variant were incubated with lipopolysaccharide (LPS) and heat shock protein B8 (HSPB8). Concentrations of interleukin 6 (IL-6), tumor necrosis factor-alpha(TNF-alpha), and IL-10 were determined along with TLR4 and CD14 expression. RESULTS: TLR4 expression was similar in patients carrying or not carrying the variant. In contrast, both LPS and HSPB8 resulted in significantly lower secretion of IL-6, TNF-alpha, and IL-10 in those who carried the variant, whereas the frequency of CD14+ cells was higher in these individuals. CONCLUSION: TLR4 variant clearly reduces its potency to mediate signaling. Correction for CD14+ cells is necessary in comparable experiments.

Contains fulltext : 70089.pdf (Publisher’s version ) (Closed access) BACKGROUND: Several studies have shown that adults who develop schizophrenia and commit a criminal offence may already have shown behaviour problems in childhood or adolescence. It is less clear whether such problems follow a particular pattern in such patients. AIMS: To examine the utility of the Child Behavior Checklist (CBCL) among offenders, to test whether externalizing behaviour problems, as measured by the CBCL, are more frequent in psychotic offenders than in non-offenders with psychosis, and to investigate relationships between early behavioural problems and adult personality disorder in psychotic offenders. METHODS: Three groups of violent offenders detained under the Dutch Entrustment Act (TBS-detainees)(n = 78) and one group of psychotic patients in general psychiatry (n = 16) were rated from case records on the CBCL. RESULTS: There was a significant difference between psychotic offenders with a personality disorder (n = 25) and the non-offender patients with psychosis (n = 16) on the 'delinquent behavior' scale, but no such difference between psychotic offenders with (n = 25) and without (n = 21) personality disorder. A hierarchic cluster analysis revealed significantly higher scores for externalizing behaviour in all TBS-detainees with a personality disorder. Those starting to offend early had higher scores for externalizing behaviour than late starters. CONCLUSIONS: Psychotic and non-psychotic offenders with personality disorder resemble one another in their early childhood behaviour problems; psychotic offenders without a personality disorder differ from these two groups but resemble non-offenders with psychosis. In contrast to findings in non-forensic populations, there were no differences on other problem scales of the CBCL. Given the small sample sizes, replication is needed, but the findings lend weight to treatment models which focus on the psychosis in the latter two groups but extend also to personality disorder in the former.

Contains fulltext : 71081.pdf (Publisher’s version ) (Closed access) The treatment of lumbar spinal stenosis is either conservative or surgical decompression. Recently, an interspinous decompression device (X-Stop) has been developed as an alternative. Patients treated with an X-Stop between 2003 and 2006 are subject of this study. The SF-36 Health Survey and Zurich Questionnaires are used. The data of pre- and post-operative self-rated questionnaires are collected and analysed by independent investigators. The data were statistically analysed. A good outcome was defined when the mean score at the ZQ for satisfaction was at maximal 2.0, and the mean improvement of the severity score was at least 0.5, and also for vitality score. For relations between outcome and gender, smoking, BMI, orthopaedic co-morbidity, number of implanted X-Stops were sought. The change in SF-36 scales was related to the outcome. Sixty-five patients did undergo implantation of an X-Stop. The mean age was 64.4 +/- 10.0 years (range: 37.0-85.0 years). 31.1% Of the patients had a good outcome. A good outcome was not related to smoking, BMI, number of implanted X-Stops. However, a good outcome was related to the absence of orthopaedic co-morbidity or male gender. Patients with a good outcome had significantly a better improvement of the scales of the SF-36 concerning physical pain or impairment. The X-Stop does improve the clinical situation. However, a good outcome is achieved less often than previously reported. Probable explanations are discussed.

BackgroundA number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales.MethodThe 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery–Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores.ResultsThe MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely ‘observed mood and anxiety’, ‘cognitive’ and ‘neurovegetative’, provided a more detailed description of depression severity.ConclusionsThe MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.

Contains fulltext : 71472.pdf (Publisher’s version ) (Closed access) Play helps to develop social skills. Children with autism show deviances in their play behavior that may be associated with delays in their social development. In this study, we investigated manipulative, functional and symbolic play behavior of toddlers with and without autism (mean age: 26.45, SD 5.63). The results showed that the quality of interaction between the child and the caregiver was related to the development of play behavior. In particular, security of attachment was related to better play behavior. When the developmental level of the child is taken into account, the attachment relationship of the child with the caregiver at this young age is a better predictor of the level of play behavior than the child's disorder.

Contains fulltext : 69584.pdf (Publisher’s version ) (Closed access) Deficits in Joint Attention (JA) may be one of the earliest signs of Autism Spectrum Disorders (ASD). In this longitudinal study we investigated several types of JA behaviors at the age of 24 and 42 months, and their development over time. Eleven children with ASD, 10 children with other developmental disorders, and eight children without a developmental disorder participated. It was found that children with ASD showed significantly less JA at the age of 24 months. At this age, the various types of JA (Basic Joint Attention, Associated Joint Attention, Joint Visual Attention) were correlated with developmental level and number of autistic characteristics. However, at the age of 42 months, these associations were absent. Although children with ASD may show less JA at the age of 24 months compared to other groups of children, by the age of 42 months they reach about the same level of JA, except for joint visual attention. In fact, at both ages, children with ASD differed consistently only on JVA from the other groups. JVA may be a core component of an early screening device for ASD.

Contains fulltext : 52450.pdf (Publisher’s version ) (Closed access) FcgRIIa and FcgRIIIa are potent modulators of the immune system which bind (auto)antibodies and activate immune cells. The FcgRIIa*A519G and FcgRIIIa*A559C functional variants have been associated with several immune-related diseases. We studied FcgRIIa*A519G and FcgRIIIa*A559C SNPs in type 1 diabetes (T1D), celiac disease (CD) and rheumatoid arthritis (RA) patients and controls and included a meta-analysis of all recent studies of FcgRIIIa*A559C and RA. Our cohorts comprised 350 T1D, 519 CD, 639 RA patients and 1359 controls, who were genotyped for FcgRIIa*A519G and FcgRIIIa*A559C variants. Regression and expectation maximization (EM) algorithm-based haplotype analyses were used for the data analysis. We found significant differences in genotype frequencies of FcgRIIa between controls and patients with T1D (P = 0.04), CD (P = 0.000005) and RA (P = 0.04). The FcgRIIa*519GG genotype showed an increased risk for both T1D [odds ratio (OR) = 1.51; 95% confidence interval (95% CI) 1.08-2.12; P = 0.015] and CD (OR = 1.81; 95% CI 1.35-2.37; P = 0.000004), but not for RA. There was no difference in the frequency of FcgRIIIa*A559C genotypes or allelotypes between controls with T1D, CD and RA. We found that FcgRIIa and FcgRIIIa haplotype frequencies differed significantly between controls and patients with T1D (P = 0.05) and with CD (P = 0.00038) but not with RA. Our meta-analysis showed a significant 1.37(95% CI 1.14-1.66)-fold increased risk of RA for the FcgRIIIa*559CC (158VV) genotype (P = 0.001). This is the first report that the FcgRIIa*519GG genotype predisposes to T1D and CD. We confirmed that the FcgRIIIa*559CC genotype is associated with RA. If replicated, our findings would suggest FcgRIIa*519G as a common risk factor for auto-immune diseases. This may have clinical implications with regard to efficacy or safety of antibody-based immuno-modulator therapies.

Contains fulltext : 53340.pdf (Publisher’s version ) (Open Access) AIMS: In patients with coronary artery disease, the 34C > T variant of the adenosine mono-phosphate deaminase gene (AMPD1), encoding a dysfunctional protein, predicts improved survival. We hypothesized that in subjects with this variant allele, ischaemia-induced intracellular adenosine formation is increased, augmenting reactive hyperaemia and ischaemic tolerance. METHODS AND RESULTS: We selected 10 healthy subjects with the CT genotype and 10 CC controls. The forearm vasodilator response to 2 and 5 min of ischaemia (venous occlusion plethysmography, expressed as percentage of maximum blood flow after 13 min of ischaemia) was higher in the CT group 56% (49-74%) and 77% (71-86%) vs. 49% (42-53%) and 60% (55-70%) in the CC group [median (interquartile range), P = 0.01]. Additionally, ischaemia-reperfusion injury was assessed in the thenar muscle using (99m)Tc-annexin A5 scintigraphy after forearm ischaemic exercise to detect externalized membrane phosphatidylserines. At reperfusion, (99m)Tc-annexin was administered intravenously. The change in annexin targeting between 1 and 4 h post-injection was -2.3% (interquartile range -2.4 to -1.6%) in the CT group vs. -0.3% (-0.6 to 1.3%) in controls (n = 7 in both groups, P = 0.03). CONCLUSION: The 34C > T variant of AMPD1 augments vasodilation and reduces tissue injury in response to forearm ischaemia. These mechanisms could contribute to the survival benefit of cardiovascular patients with this variant allele.

Contains fulltext : 52551.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Testing the hypothesis that depressive symptoms in dementia reflect dysfunction in fronto-subcortical pathways. BACKGROUND: Both depression and dementia can be the result of vascular damage of the brain. The nature of the depressive symptomatology seems to be related to concommittant cognitive disturbances in that subjects show more so-called motivational symptoms of depression. These symptoms can be the result of frontal-subcortical dysfunction. It could be very helpful for clinical practice if these subjects could be identified by simple diagnostic procedures. METHODS: Associations were computed between measures of depressive symptoms and a set of neuropsychological tests in a sample of 54 subjects with a post-stroke dementia. RESULTS: Although we used an extensive set of neuropsychological tests, most subjects were able to participate only in a small part of them, because of disease severity. Our hypothesis was supported by a negative correlation between scores on the verbal semantic fluency task and the total numbers of motivational depressive symptoms. None of the neuropsychological tests was significantly related to the number of mood symptoms neither did they correlate with the total number of depressive symptoms. CONCLUSION: This study gives further evidence for the assumption that motivational-based depressive symptoms partially originate from fronto-subcortical dysfunction.

Contains fulltext : 55343.pdf (Publisher’s version ) (Closed access) Atypical lateralization, as indicated by mixed-handedness, has been related to diverse psychopathologies. Maternal prenatal stress has recently been associated with mixed-handedness in the offspring. In the present study, this relationship was investigated further in a prospective, methodologically comprehensive manner. Stress levels were determined three times during pregnancy by means of questionnaires and measurements of cortisol levels. The handedness of 110 6-y-old children (48 boys) was determined by independent observers. Mixed handedness was defined as using the opposite hand for one or more of the tested activities. Logistic regression analysis showed that more maternal daily hassles in late pregnancy and maternal mixed-handedness increased the chance of mixed-handedness in the offspring. In contrast, more pregnancy-related fear in late pregnancy and a longer duration of gestation were associated with a smaller chance of being mixed-handed. Prenatal stress measured during the first two periods of pregnancy or determined by cortisol was not related to mixed-handedness in the offspring. In conclusion, reported and physiologic measures of prenatal stress in a moderately stressed pregnant population were only partly related to offspring mixed-handedness. 5 p.

Contains fulltext : 52748.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To examine the prevalence of the use of health care services and psychotropic medication within a community sample (N = 283) of 9-year-old school children and, more specifically, to evaluate the use of prescribed stimulants. METHODS: Data from the second follow-up phase of the "Study of Attention Deficit Maastricht" (SAM) were analysed. Assessments at age 9 included a structured psychiatric interview with parents, behaviour and family situation questionnaire, IQ estimate and global assessment scale. Use of health care services and medication was obtained by the DICA-R and from the Youth Health Care records. RESULTS: About 190 children of the selected sample had at least one child psychiatric diagnosis, 26 (14%) of them were clinically referred and 12 (6%) received stimulants. Of the children with ADHD (N = 45), 10/45 (22%) received stimulants. Conversely, 2 out of 12 children who were treated with stimulants did not meet full DSM-IV diagnostic criteria, but were subthreshold ADHD cases. The treatment status was highly dependent on being clinically referred. CONCLUSION: The major finding of our survey is a lack of referral to child mental health services, and associated underdiagnosis and undertreatment, particularly in children with ADHD. There is a critical need to translate and implement the diagnostic and treatment guidelines to clinical practice.

Item does not contain fulltext This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis colorectal cancer-related mutation. Family functioning, differentiation to parents, hereditary cancer-related family communication and perceived support from relatives were assessed in 271 participants for genetic testing before test result disclosure. Hereditary cancer distress (assessed by the Impact of Event Scale) and cancer worry (assessed by the Cancer Worry Scale) were assessed before, 1 week after, and 6 months after test result disclosure. Participants reporting more cancer-related distress over the study period more frequently perceived the communication about hereditary cancer with relatives as inhibited, the nuclear family functioning as disengaged-rigid or enmeshed-chaotic, the support from partner as less than adequate and the relationship to mother as less differentiated. Especially, open communication regarding hereditary cancer and partner support may be important buffers against hereditary cancer distress. Identifying individuals with insufficient sources of support and addressing the family communication concerning hereditary cancer in genetic counseling may help the counselee to adjust better to genetic testing.

Contains fulltext : 52445.pdf (Publisher’s version ) (Closed access) TGF-beta1 has a dual role in carcinogenesis. In this gene, a leucine to proline substitution in codon 10 leads to higher circulating levels of TGF-beta1. This variant has been studied in relationship to the risk for breast cancer yielding contradicting results. We aim to unravel the relationship of this polymorphism and the risk of breast cancer. Women participating in the Rotterdam Study including 143 patients with incident breast cancer were genotyped for this polymorphism. We carried out a logistic regression and a survival analysis using age as the time variable. The logistic regression analysis showed an increased risk of breast cancer for Proline carriers (OR=1.4; 95% confidence interval (CI)=1.1-2.0) versus non-carriers. The survival analysis showed that carriers of the same allele had an increased risk of breast cancer (HR=1.4, 95% CI=1.1-2.0) against non-carriers. Our data suggest that the TGF-beta1 Leu10Pro polymorphism might play a role in breast cancer risk.

Contains fulltext : 34983.pdf (Publisher’s version ) (Closed access) OBJECTIVE: The primary purpose of this study was to confirm the association of a specific haplotype of the dopamine transporter gene and attention deficit hyperactivity disorder (ADHD), which could be one source of the heterogeneity seen across published studies. METHOD: The authors previously reported the association of ADHD with a subgroup of chromosomes containing specific alleles of two variable-number tandem repeat polymorphisms within the 3' untranslated region and intron 8 of the dopamine transporter gene. They now report on this association in a sample of ADHD combined-type probands. RESULTS: The original observations were confirmed, with an overall odds ratio of 1.4 across samples. CONCLUSIONS: These data challenge results of meta-analyses suggesting that dopamine transporter variation does not have an effect on the risk for ADHD, and they indicate that further investigation of functional variation in the gene is required.

Contains fulltext : 73204.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Craving for benzodiazepines has never been examined as a factor of relapse after successful benzodiazepine discontinuation. In this study, we examined the predictive value of craving on benzodiazepine relapse. METHOD: A stepped-care intervention trial aimed to discontinue long-term benzodiazepine use in general practice. The first step was the sending of a letter to users advising them to gradually quit their use by themselves (i.e., minimal intervention). The second step, a supervised tapering-off program, was offered to those unable to discontinue by themselves. Craving was assessed by means of the Benzodiazepine Craving Questionnaire (BCQ). Multiple Cox proportional hazards regression analyses were performed to examine the effect of craving on subsequent relapse during a 15-month follow-up period in patients who had successfully quit their benzodiazepine use by themselves after the minimal intervention (N = 79) and in those patients who had successfully quit after the supervised tapering-off program (N = 45). Data were collected from August 1998 to December 2001. RESULTS: Thirty-five (44%) and 24 (53%) patients had relapsed after the minimal intervention and tapering-off program, respectively. Patients able to quit by themselves experienced very little craving. In this sample, craving was not related to relapse (p = .82). In patients who needed an additional supervised tapering-off program, higher craving scores were significantly related to relapse (hazard ratio = 1.26, 95% CI = 1.02 to 1.54, p = .029), when corrected for benzodiazepine characteristics, psychopathology, and personality characteristics. CONCLUSION: Craving is an independent factor of subsequent relapse after successful benzodiazepine discontinuation in long-term benzodiazepine users who are not able to quit their usage of their own accord.

Contains fulltext : 52985.pdf (Publisher’s version ) (Closed access) BACKGROUND: Skin diseases are a substantial part of the problems dealt with by general practitioners. Although the psychosocial consequences of skin diseases in secondary care has been extensively studied, little is known about the psychosocial well-being of patients with skin diseases in primary care. OBJECTIVE: To investigate the psychosocial well-being of patients with skin diseases in primary care. PATIENTS/METHODS: Questionnaires about the psychosocial consequences of skin diseases were sent to patients with a skin disease who were registered within a research network (continuous morbidity registration) of general practices that continuously have recorded morbidity data since 1971. Questionnaires completed by 532 patients were eventually suitable for analyses. RESULTS: Compared with the general population, patients with skin diseases reported significantly lower scores for psychosocial well-being. Furthermore, a lower psychosocial wellbeing was significantly related with higher levels of disease-severity, lower disease-related quality of life, longer disease duration, more comorbidity and more physical symptoms of itch, pain and fatigue. After demographic variables and comorbidity were controlled for, sequential regression analyses showed that disease duration, disease severity and physical symptoms (itch, pain and fatigue) were significant predictors of psychosocial well-being. CONCLUSION: The psychosocial well-being of patients with skin diseases in primary care is lower than that of the general population. Special attention has to be directed to those patients with lowered psychosocial well-being who might be at risk of developing severe psychosocial impairments such as clinical depression.

Contains fulltext : 53203.pdf (Publisher’s version ) (Closed access) To identify interacting loci in genetic epidemiological studies the application of multi-locus methods of analysis is warranted. Several more advanced classification methods have been developed in the past years, including multiple logistic regression, sum statistics, logic regression, and the multifactor dimensionality reduction method. The objective of our study was to apply these four multi-locus methods to simulated case-control datasets that included a variety of underlying statistical two-locus interaction models, in order to compare the methods and evaluate their strengths and weaknesses. The results showed that the ability to identify the interacting loci was generally good for the sum statistic method, the logic regression and MDR. The performance of the logistic regression was more dependent on the underlying model and multiple comparison adjustment procedure. However, identification of the interacting loci in a model with two two-locus interactions of common disease alleles with relatively small effects was impaired in all methods. Several practical and methodological issues that can be considered in the application of these methods, and that may warrant further research, are identified and discussed.

Contains fulltext : 51958.pdf (Publisher’s version ) (Closed access) This study on sensitivity and attachment included 55 toddlers and their parents. Samples included children with autism spectrum disorder (ASD), mental retardation, language delay, and typical development. Children were diagnosed at 4 years of age. Two years before diagnosis, attachment was assessed with the Strange Situation procedure, and parental sensitivity and child involvement during free play were assessed with the Emotional Availability Scale. Parents of children with ASD were equally sensitive as parents of children without ASD, but their children showed more attachment disorganization and less child involvement. More sensitive parents had more secure children, but only in the group without ASD. Less severe autistic symptoms in the social domain predicted more attachment security. Autism challenges the validity of attachment theory.

Contains fulltext : 53071.pdf (Publisher’s version ) (Closed access) BACKGROUND: The aim of this study was to assess the incidence, characteristics, treatment, and survival of patients with tracheal malignancies in the Netherlands. METHODS: All cases of tracheal cancer entered into the database of the Netherlands Cancer Registry in the period 1989-2002 were selected. Data on histological type, age at time of diagnosis, treatment, and survival were analyzed retrospectively. RESULTS: The annual incidence was 0.142 per 100,000 inhabitants (308 cases, of which 15 were found incidentally at autopsy). Of these, 72% were men. In 52.9%, the histological type was squamous cell carcinoma and in only 7.1% adenoid cystic carcinoma (ACC). Mean age at time of diagnosis was 64.3 years. Of the 293 patients diagnosed while alive, 34 patients underwent surgical resection (11.6%), 156 patients received radiotherapy (53.2%), and 103 patients neither (35.4%). Median survival of all 293 patients was 10 months (mean 28 months) with 1-year, 5-year, and 10-year survival rates of 43%, 15%, and 6%, respectively. The prognosis of patients with ACC was significantly better. The 5-year survival rate in patients who underwent surgical resection was 51%, and the 10-year survival rate in these patients was 33%. CONCLUSION: The prognosis of patients with a tracheal malignancy is usually poor. Surgical treatment, however, can lead to good survival rates; still, this is currently only used in selected patients, even though it would seem to be possible in more cases in view of the technical advances in the field of tracheal surgery. Centralizing the care and treatment of tracheal cancers and implementing a more assertive attitude towards this disease could make surgery accessible to a larger number of patients. Data from the literature show that this would lead to better survival in patients with a tracheal malignancy.

Contains fulltext : 51000.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Most studies on tobacco smoking have focused on daily-smokers. Occasional smokers, who have never smoked daily, have often been included in the reference group of never-smokers. We have investigated the association between occasional smoking and cancer of the bladder, kidney, pancreas, upper aero-digestive tract and lung. METHODS: The study population consisted of 158,488 persons, who provided information on occasional smoking, within the European Prospective Investigation into Cancer and Nutrition (EPIC), 780 of whom developed a smoking-related cancer. We used Cox proportional hazard model, stratified by gender and country to estimate incidence rate ratios (IRR) for smoking-related cancers. RESULTS: The results suggest that occasional smokers have a higher risk of bladder cancer (IRR: 1.92, 95% confidence interval (CI) 0.93-3.98) and of the major smoking-related cancers combined (IRR: 1.24, 95% CI 0.80-1.94) than true never-smokers. Including occasional smokers in the reference group resulted in a lower risk estimate for former and current smokers. CONCLUSIONS: Occasional smoking should be discouraged.

Contains fulltext : 49679.pdf (Publisher’s version ) (Closed access) Accurate prediction of tumor recurrence in patients with superficial urothelial cell carcinoma (UCC) might result in a significant reduction of invasive follow-up cystoscopies. A recent study identified a panel of 26 genes from a large cDNA microarray analysis of bladder tumors that discriminated between early- and late-recurring patients with superficial Ta tumors (Dyrskjot et al., Nat Genet 2003;33:90-6). We aimed to validate this panel of genes in 44 primary Ta UCCs (23 and 21 tumors from patients with short or prolonged recurrence-free periods, respectively), by real-time quantitative PCR. Statistical analysis showed marginal significant different mRNA expression levels between the 2 patient groups. To evaluate a supplementary effect of genes for the identification of patients with short or prolonged recurrence-free intervals, forward logistic regression analysis was applied. This revealed that a combination of the expression profiles of the genes HNRPK, LTB4DH and ANP32B resulted in the best performance, although the combination only marginally increased the predictive value of HNRPK alone. Comparing the receiver-operating-characteristic curves for HNRPK expression among patients with short or prolonged recurrence-free periods, revealed an area under the curve of 0.696 (95% CI, 0.537-0.855). Using the median HNRPK expression level as cut-off, a sensitivity of 69.6% and a specificity of 71.4% were obtained for the identification of patients with short or prolonged recurrence-free periods, respectively. In conclusion, we were not able to confirm the microarray gene expression pattern of the 26 genes shown by Dyrskjot et al. The discovery of accurate recurrence predictive markers, therefore, remains a challenge.

Contains fulltext : 53651.pdf (Publisher’s version ) (Closed access) The use of antipsychotics is associated with an increased risk of obesity. This consideration makes it important to search for determinants that can predict the risk for antipsychotic-induced obesity. In this cross-sectional study, we investigated whether polymorphisms in the HTR2C gene were associated with obesity (body mass index >30 kg/m2) in patients using antipsychotics. We examined polymorphisms in the promoter region of the HTR2C gene ((HTR2C:c.1-142948(GT)n, rs3813928 (-997 G/A), rs3813929 (-759 C/T), rs518147 (-697 G/C)) and an intragenic polymorphism (rs1414334:C>G). The results of the logistic regression were expressed as adjusted odds ratios (OR). In total, we included 127 patients mainly diagnosed with schizophrenia or schizoaffective disorder (89%). The results indicate that a combined genotype carrying the variant HTR2C:c.1-142948(GT)n 13 repeat allele, the common allele rs3813929 C, the variant allele rs518147 C and the variant allele rs1414334 C is significantly related to an increased risk of obesity (OR 3.71 (95% confidence interval: 1.24-11.12)).

The aim of this study was to determine the prevalence of expectation of secondary gain among first-generation immigrant Turkish patients referred to a psychiatric hospital and whether this prevalence differs from that of Dutch outpatients. The study was carried out in the outpatient department of a Dutch psychiatric hospital. Expectation of secondary gain was assessed by directly asking the patients, via questionnaires whether they hoped to gain specific "benefits" from being in therapy. The study found that 31.7% of the Turkish patients reported holding expectations of secondary gain while being in therapy versus 42.2% of the Dutch patients. Our finding of a large proportion of Turkish patients with expectations of secondary gain is consistent with the results of an earlier study of Dutch patients. However, in contrast to the findings of empirical research, Turkish immigrants were not found more than Dutch patients to have expectations of secondary gain. In fact, such expectations were more common among Dutch patients.

Item does not contain fulltext BACKGROUND: There are considerable overlaps between vascular dementia and Alzheimer's disease (AD), with a suggestion that cerebrovascular disease (CVD) contributes to the neurodegenerative pathology of AD. Paradoxical embolization of venous emboli into the systemic circulation through a venous to arterial circulation shunt (v-aCS), the most commonly a patent foramen ovale (PFO), is known to cause cryptogenic stroke in younger people. We reviewed the potential role of paradoxical embolization in AD. METHODS: A review of the literature on paradoxical embolization in neurological disorders and techniques to detect v-aCS and PFO, supplemented by data from our own studies. RESULTS: Before our research, the role of paradoxical embolism in dementia had not been studied. The potential role of embolization in cerebral damage was highlighted by studies in patients undergoing coronary artery bypass or carotid surgery. Paradoxical embolization was found to occur in patients with cryptogenic stroke, migraine, decompression sickles and during hip surgery. The methods for detecting v-aCS or PFO had not been standardized. We found 'significant' v-aCS (equivalent to PFO) in 32% of AD patients compared with 22% of controls, but the study was not sufficiently powered to test the statistic significance of this difference. In AD, there was evidence of an association between 'significant' v-aCS and the severity of white matter hyperintensities on magnetic resonance imaging (MRI). CONCLUSION: Paradoxical embolization through a v-aCS may be a potentially preventable or treatable cause of CVD in AD.

BackgroundThe vascular depression hypothesis and our recent findings of increased frequency of spontaneous cerebral emboli in dementia suggest that such emboli may be involved in the causation of depressive symptoms in dementia.AimsTo evaluate the association between spontaneous cerebral emboli and depressive symptoms in Alzheimer's disease and vascular dementia.MethodIn a cohort of 142 patients with dementia (72 with Alzheimer's disease and 70 with vascular dementia), the association between spontaneous cerebral emboli and clinically relevant depressive symptoms was examined using multiple logistic regression analyses.ResultsSpontaneous cerebral emboli were significantly more frequent in the patients with clinically relevant depressive symptoms (66 v. 37%, P=0.03). After adjustment for age, gender, Mini-Mental State Examination score, type of dementia and significant cardiovascular risk factors, the relationship remained significant (OR=3.47, 95% CI 1.10–10.97).ConclusionsSpontaneous cerebral emboli are associated with clinically relevant depressive symptoms in dementia, and further research is needed to explore the nature of this relationship.

Contains fulltext : 52360.pdf (Publisher’s version ) (Closed access) While angiotensinogen (AGT) seems to have anti proliferative properties, angiotensin II (ATII) is a potent growth factor and it mediates its actions through the angiotensin type 1 receptor (AGTR1). In the AGT gene, the M235T polymorphism has been associated with the variation in angiotensinogen levels and in the AGTR1 gene; the C573T variant is associated with different pathologies. We aimed to evaluate the relationship of these two variants and the risk of breast cancer. These polymorphisms were genotyped in 3787 women participating the Rotterdam Study. We performed a logistic regression and a disease free survival analysis by genotype. The logistic regression yielded an odds ratio of 1.4 (95% CI: 1.1-1.9) for the MM genotype carriers versus the T allele carriers. The breast cancer free survival by AGT genotype was significantly reduced in MM genotype carriers compared to non-carriers (hazard ratio (HR) = 1.5; 95% CI: 1.1-2.2). We did not find any association of the AGTR1 polymorphism and breast cancer risk or disease free survival. Our results suggest that AGT plays a role in breast cancer risk in postmenopausal women, whereas the role of AGTR1 needs further studying.

Contains fulltext : 50178.pdf (Publisher’s version ) (Closed access) A two-stage protocol for screening for autistic spectrum disorders (ASD) was evaluated in a random population of 31,724 children aged 14-15 months. Children were first pre-screened by physicians at well-baby clinics using a 4-item screening instrument. Infants that screened positive were then evaluated during a 1.5-h home visit by a trained psychologist using a recently developed screening instrument, the 14-item Early Screening of Autistic Traits Questionnaire (ESAT). Children with 3 or more negative scores were considered to be at high-risk of developing ASD and were invited for further systematic psychiatric examination. Eighteen children with ASD were identified. The group of children with false positive results had related disorders, such as Language Disorder (N = 18) and Mental Retardation (N = 13).

Contains fulltext : 50140.pdf (Publisher’s version ) (Closed access) BACKGROUND: While (partial) recovery of spermatogenesis, observed by means of standard semen analysis, has been seen in testicular cancer patients after chemotherapy with cisplatin, sperm genomic integrity and its implication for the patient's fertility are poorly understood. METHODS: Semen and serum from 22 patients treated for testicular cancer were analysed pre- and post-chemotherapy. Besides routine semen analysis, sperm samples were evaluated by computerized karyometric image analysis (CKIA), chromomycin-A3 assay (CMA3, chromatin condensation) and TdT-mediated dUTP nick-end labelling assay (TUNEL, DNA damage). Serum FSH, LH and testosterone concentrations were measured. RESULTS: Ejaculate volume decreased post-chemotherapy (P

Background: Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer. The mechanism through which physical inactivity affects breast cancer risk is not clear. The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk. Methods: We did a cross-sectional study in 620 women, of ages 49 to 68 years and participants of the Dutch Prospect-European Prospective Investigation into Cancer and Nutrition cohort. A self-administered questionnaire was used to obtain information on duration and intensity of physical activity (recreational, household, and occupational) during the year preceding study recruitment. A total activity index (inactive, moderately inactive, moderately active, and active) was estimated by combining all activity types. Percent and absolute breast density were determined on screening mammograms using a computer-aided method. Multivariate linear regression was used to examine the association between physical activity and breast density. Results: Mean percent density was 35.3% [95% confidence interval (95% CI), 31.8-38.8] for the inactive category compared with 36.1% (95% CI, 33.0-39.2) for the active category. Mean absolute density values for the inactive and active category were 45.8 cm2 (95% CI, 40.9-50.7) and 42.6 cm2 (95% CI, 38.3-47.0), respectively. Subgroup analysis for postmenopausal women showed similar results, as did separate analyses for recreational and household activity. Conclusions: The result does not support a relation between current physical activity and mammographic density in postmenopausal women. (Cancer Epidemiol Biomarkers Prev 2006;15(3):456–60)

Lignans are biphenolic compounds that occur in foods of plant origin such as whole grains, seeds, fruits and vegetables, and beverages, such as coffee and tea. Plant lignans are converted by intestinal bacteria into the enterolignans, enterodiol and enterolactone. Enterolignans possess several biological activities, whereby they may influence carcinogenesis. We studied the associations between plasma enterolignans and the risk of colorectal adenomas in a Dutch case-control study. Colorectal adenomas are considered to be precursors of colorectal cancer. Cases (n = 532) with at least one histologically confirmed colorectal adenoma and controls (n = 503) with no history of any type of adenoma were included. Plasma enterodiol and enterolactone concentrations were measured by liquid chromatography with tandem mass spectrometry. Associations were stronger for incident than for prevalent cases. When only incident cases (n = 262) were included, high compared to low plasma concentrations of enterodiol were associated with a reduction in colorectal adenoma risk after adjustment for confounding variables. Enterodiol odds ratios (95% confidence intervals) were 1.00, 0.69 (0.42-1.13), 0.60 (0.37-0.99), and 0.53 (0.32-0.88) with a significant trend (P = 0.01) through the quartiles. Although enterolactone plasma concentrations were 10-fold higher, enterolactone's reduction in risk was not statistically significant (P for trend = 0.09). Use of oral antibiotic therapy could decrease the plasma concentrations of enterolactone. Exclusion of antibiotic users resulted in similar odds ratios for both enterolignans, but the association for enterolactone became somewhat stronger (P = 0.05 versus P = 0.09). We observed a substantial reduction in colorectal adenoma risk among subjects with high plasma concentrations of enterolignans, in particular, enterodiol. These findings could be important in the prevention of colorectal adenomas. (Cancer Epidemiol Biomarkers Prev 2006;15(6):1132–6)

Contains fulltext : 50798.pdf (Publisher’s version ) (Open Access) OBJECTIVE: This pilot study examined the effects of atomoxetine on attention-deficit/hyperactivity disorder (ADHD) symptoms and autistic features in children with pervasive developmental disorders (PDD). METHOD: Twelve children (aged 6-14 years) with PDD accompanied by ADHD symptoms entered a 10-week open-label study with atomoxetine (1.19 +/- 0.41 mg/kg/day). Response was assessed by using parent and clinician rating scales with change in the ADHD-Rating Scale (ADHDRS) as primary outcome measure. RESULTS: Atomoxetine reduced ADHD-symptoms as measured by the ADHDRS (44% decrease vs. baseline, p < 0.003), the Conners' Parent Rating Scale-R:S (CPRS-R) (25% in the subscale "Cognitive Problems," p < 0.028; 32% in "Hyperactivity," p < 0.030; and 23% in "ADHD index," p < 0.023). We found a reduction of 21% (p = 0.071) for changes in the subscale "Hyperactivity" of the Aberrant Behavior Checklist (ABC). No change was found in any of the other ABC subscales, nor in the subscale "Oppositional" of the CPRS-R. Five patients (42%) discontinued because of side effects. Gastrointestinal symptoms, irritability, sleep problems, and fatigue were the most frequent side effects. CONCLUSIONS: These preliminary findings indicate that atomoxetine may be a promising new agent in the treatment of ADHD symptoms in children with PDD. However, children with PDD may have a higher vulnerability for some of the known side-effects of atomoxetine.

Contains fulltext : 49338.pdf (Publisher’s version ) (Closed access) STUDY DESIGN: Prospective inception cohort study. OBJECTIVE: To investigate prospectively whether pain-related fear predicts future perceived disability and participation in patients with acute low back pain (LBP). SUMMARY OF BACKGROUND DATA: There are indications that fear of movement/(re)injury, as measured by the Tampa Scale for Kinesiophobia, is present early in an episode of LBP, and that it might be a predictor of future perceived disability and participation. METHODS: A cohort of 555 patients with acute LBP included by general practitioners and physical therapists in primary care settings was followed for 6 months. RESULTS: Results indicate that baseline fear of movement/(re)injury was predictive of future perceived disability and, to a lesser extent (and together with duration and radiation), of participation. CONCLUSIONS: The results suggest that interventions aimed at reducing pain-related fear in the acute stage of LBP might prevent restrictions of activity and participation because of pain, and might be a way of preventing the transition from acute to chronic LBP.

Contains fulltext : 51396.pdf (Publisher’s version ) (Closed access) Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with

Contains fulltext : 51073.pdf (Publisher’s version ) (Closed access) Toll-like receptor (TLR)-4 is an important pattern recognition receptor for Candida albicans, playing a role in innate host defense. We investigated whether there is an association between the TLR4 Asp299Gly or TLR4 Thr399Ile polymorphism, and the occurrence of Candida bloodstream infection. We performed a case-control study, involving 43 patients with a Candida bloodstream infection and 166 healthy individuals. TLR4 Asp299Gly and Thr399Ile polymorphisms were assessed, as well as cytokine production after stimulation of peripheral blood mononuclear cells (PBMC) with Candida albicans. We observed that the prevalence of TLR4 Asp299Gly polymorphism was found to be higher in patients with Candida bloodstream infection than in controls (26% versus 10%; OR 3.0; 95%CI 1.3-6.9). All patients bearing the Asp299Gly polymorphism were also positive for the Thr399Ile allele, a linkage well described in literature. IL-10 production was higher in C. albicans-stimulated PBMC from volunteers bearing the TLR4 Asp299Gly polymorphism, and a similar tendency was observed in TLR4 Asp299Gly heterozygous patients who had recovered from candidemia. These findings show that the TLR4 Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility to Candida bloodstream infections, and an increased production of IL-10 is probably involved in this effect.

Contains fulltext : 51210.pdf (Publisher’s version ) (Closed access) BACKGROUND: To study the possible involvement of an (im)balance between oxidants and antioxidants in pre-eclampsia concentrations of intra- and extracellular blood antioxidants in women with uncomplicated and hypertensive pregnancies, they were studied preconceptionally and throughout pregnancy. METHODS: In uncomplicated pregnancies (n = 19) and hypertensive pregnancies (n = 6) concentrations of whole blood and plasma thiols, plasma vitamins/E and C, hemoglobin, and hematocrit were assessed at preconception, 6, 10, 20, and 37 weeks of gestational age, as well as six weeks postpartum. A repeated mixed model was used for statistical analysis. RESULTS: Vitamin C and most whole blood and plasma thiol concentrations decreased during pregnancy, while vitamin E, whole blood oxidized cysteinyl-glycine and the ratio of free to oxidized homocysteine revealed a linear increase during pregnancy. Postpartum plasma cysteine and vitamin C levels and the ratio of free to oxidized levels of cysteine, cysteinyl-glycine, and glutathione were significantly (p

Contains fulltext : 49558.pdf (Publisher’s version ) (Closed access) The objective of this study was to determine whether postmenopausal asymptomatic women with normal endometrial cells in their smear are at higher risk for endometrial pathology compared with women without these cells. Histologic follow-up outcome and otherwise cytologic follow-up of 29,144 asymptomatic postmenopausal women was determined. Presence of normal endometrial cells, age, use of hormones, and reported elevated maturation index were assessed. The effect of each variable on outcome as well as the combined effect were evaluated. Prevalence rate of (pre)malignant uterine disease was significantly higher when normal endometrial cells were found in the cervical smear (6.5%) as compared to smears without these cells (0.2%), resulting in a relative risk of 40.2 (95% CI 9.4-172.2). Neither age nor hormone use or elevated maturation index showed significant impact on the outcome. Asymptomatic postmenopausal women with normal endometrial cells in their smear are at significant higher risk for (pre)cancerous endometrial lesion than women without these cells. These cases should be reported to the physician with an explicit comment that normal endometrial cells in a smear of a postmenopausal woman is an abnormal finding, possibly associated with significant endometrial pathology. It raises the question whether further gynecological examination would be more appropriate.

Contains fulltext : 49535.pdf (Publisher’s version ) (Closed access) PURPOSE: To assess the occurrence of high-risk epithelial lesions in women of breast cancer families with and without a BRCA mutation. PATIENTS AND METHODS: Prospective study of women at very high risk of breast cancer undergoing prophylactic mastectomy (68 BRCA1 mutation carriers, 14 BRCA2 mutation carriers and 24 non-BRCA mutation carriers). RESULTS: The prevalence of high-risk lesions is equal in women with a BRCA1 or a BRCA2 mutation, but is higher in non-BRCA mutation carriers: all lesions 43% versus 71% (p=0.02), atypical lobular hyperplasia 26% versus 67% (p=0.001), atypical ductal hyperplasia 17% versus 42% (p=0.01), lobular carcinoma-in situ 15% versus 29% (p=0.10) and ductal carcinoma-in situ 9% versus 17% (p=0.25). The presence of high-risk lesions is related to absence of a BRCA mutation and to age over 40 years. CONCLUSION: Women with an autosomal dominant family history for breast cancer, with and without a BRCA mutation are prone to develop high-risk epithelial lesions, especially over 40 years.