Monika Heinzel-Gutenbrunner

Reproducibility and Accuracy of the ICDAS-II for Detection of Occlusal Caries in vitro

Aim: The aim of this study was to assess inter- and intra-examiner reproducibility and accuracy in the detection and assessment of occlusal caries in extracted human teeth using a newly developed visual method for caries diagnosis (International Caries Detection and Assessment System, ICDAS-II). Serial sectioning and microscopy were used as the ‘gold standard’. Methods: The occlusal surfaces of 100 teeth were examined by 4 dentists using the ICDAS-II graded scores 0–6. Thereafter the teeth were serially sectioned and assessed for depth of the lesion with two histological classification systems. Results: The weighted kappa values for inter- and intra-examiner reproducibility for the ICDAS-II examination were 0.62–0.83. There was a moderate relationship between the visual and both histological examinations (rs = 0.43–0.72). At the D1 diagnostic threshold (enamel and dentine lesions) specificity was 0.74–0.91 and sensitivity was 0.59–0.73. At the D3 diagnostic threshold (dentine lesions) specificity was 0.82–0.94 and sensitivity was 0.48–0.83 for the 4 examiners. Conclusion: The ICDAS-II system has demonstrated reproducibility and diagnostic accuracy for the detection of occlusal caries at varying stages of the disease process which are comparable to previously reported data using similar visual classification systems.

Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index

The melanocortin-4 receptor gene ( MC4R ) is involved in central energy homeostasis and body weight regulation. Both endogenous anorexigenic and orexigenic ligands bind to the receptor.1 Under normal conditions, the anorexigenic tone prevails as revealed by the fact that Mc4r knock-out mice2 develop elevated body weight. Mc4r−/− mice show higher food intake but a similar metabolic rate and similar decreased physical activity compared to wild type (WT) mice of the same strain.2–4 In comparison to a standard low fat diet, this deviant regulation of energy homeostasis is even more pronounced upon intake of a moderately fat diet,5 which leads to an even higher body mass. In all studies, the effect on body weight is smaller in heterozygous than in homozygous knockout mice, but the exact degree of dominance is not clear. In heterozygous Mc4r+/− animals, body mass is increased on average by about 7–45% and in homozygous Mc4r−/− by 50–100% compared to WT2–5 with substantial overlap between groups. The mutations might have a sex dependent effect, but the results are contradictory. In one study, the effect in males was only about half of that in females.2 However, two studies did not detect a sex by genotype interaction in this Mc4r−/− strain.4,5 One study in a different knockout line of the same inbred strain found a sex by genotype interaction in the opposite direction, with only a marginal effect in heterozygous females whereas heterozygous males had a body weight intermediate between WT and homozygous knockouts.3 The first mutations in the human MC4R gene were reported in extremely obese probands.6–8 Since then, several other studies investigated the association of different MC4R mutations with obesity. According to a recent overview,9 at least 34 putatively functionally relevant …

Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations

Recently, Branson and coworkers reported a strong association between binge-eating disorder (BED) and variants in the melanocortin-4 receptor gene (MC4R). In the current study, we compared the eating behavior of 43 obese probands with functionally relevant MC4R mutations and of 35 polymorphism carriers (V103I or I251L) with wild-type carriers. The module for eating disorders of the Composite International Diagnostic Interview was used to identify binge-eating behavior. The Three-Factor Eating Questionnaire and the Leeds Food Frequency Questionnaire were used to assess restrained eating, disinhibition, hunger and percent total energy intake as fat. No significant differences between carriers of MC4R variants and wild-type carriers were detected. In particular, we found no evidence for an increased rate of binge-eating behavior in obese carriers of MC4R variants. Our findings do not support the strong association between BED and MC4R carrier status.

Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and clozapine-induced weight gain among German schizophrenic individuals.

Weight gain is a major side effect of treatment with clozapine and other antipsychotics. Recent studies suggest an important role of the serotonin type 2C receptor gene (5-HT2CR) in antipsychotic-induced weight gain. However, investigations pertaining to a possible association between a –759C/T polymorphism (C allele) of the 5-HT2CR and weight gain induced by clozapine and/or other antipsychotics have yielded inconsistent results. We investigated the –759C/T polymorphism of the 5-HT2CR in relation to clozapine-induced change in body mass index (BMI) (kg/m2) in 97 German patients with schizophrenia and found no association between the –759C allele and weight gain after 12 weeks of clozapine treatment. In addition, confounding effects of initial BMI, age, sex and duration of illness on change in BMI could not be detected by multiple linear regression analysis. Our data do not support an involvement of the –759C/T polymorphism of the 5-HT2CR in clozapine-induced weight gain in German patients with schizophrenia. Further pharmacogenetic studies pertaining to antipsychotic-induced weight gain are warranted.

Clozapine-induced weight gain: a study in monozygotic twins and same-sex sib pairs.

To assess the relative contribution of genetic factors in antipsychotic-induced weight gain, we explored the similarity in body mass index (BMI) (kg/m2) change under clozapine only (clozapine ΔBMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total ΔBMI) of five monozygotic twins in comparison with seven same-sex sibs. Twin and sib pairs were identified by a telephone screening of 786 office-based psychiatrists. Measured data on weight and other clinical variables were obtained cross-sectionally and retrospectively from medical records. We found greater similarity in total ΔBMI in monozygotic twins (intrapair difference 2.78±3.41 kg/m2) than in same-sex sibs (5.55±4.35 kg/m2), resulting in heritability estimates of h2=0.8 and A=0.45 (ACE twin model). However, intrapair differences in clozapine ΔBMI were similar between twins (4.18±4.27 kg/m2) and sibs (4.68±4.88 kg/m2). We hypothesize that the weight plateau achieved under clozapine is influenced by genetic factors. The weight gain achieved during pretreatment with other antipsychotics seems to limit clozapine-induced weight gain, thus presumably explaining why heritability/similarity in monozygotic twins in comparison with same-sex sibs is greater for total ΔBMI than for clozapine ΔBMI. An important caveat is that, owing to the sample size, the heritability estimates have a large standard error and thus have to be interpreted with caution.

Body weight gain induced by atypical antipsychotics: an extension of the monocygotic twin and sib pair study

Background and objective:  In our original study based on five monozygotic twin pairs and seven same‐sex sib pairs, we previously showed that genetic factors contribute to body weight gain induced by the atypical antipsychotic clozapine. We aim to study this further by including patients treated with the atypical antipsychotics olanzapine or risperidone as well as opposite‐sex sib pairs.

Ruling out coronary artery disease in primary care: development and validation of a simple prediction rule

Background: Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care. Methods: We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain (n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort). Results: The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83–0.91) for the derivation cohort and 0.90 (95% CI 0.87–0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3–5 points; negative result ≤ 2 points), which had a sensitivity of 87.1% (95% CI 79.9%–94.2%) and a specificity of 80.8% (77.6%–83.9%). Interpretation: The prediction rule for coronary artery disease in primary care proved to be robust in the validation cohort. It can help to rule out coronary artery disease in patients presenting with chest pain in primary care.

Categorical and Dimensional Structure of Autism Spectrum Disorders: The Nosologic Validity of Asperger Syndrome

There is an ongoing debate whether a differentiation of autistic subtypes, especially between Asperger Syndrome (AS) and high-functioning-autism (HFA) is possible and if so, whether it is a categorical or dimensional one. The aim of this study was to examine the possible clustering of responses in different symptom domains without making any assumption concerning diagnostic appreciation. About 140 children and adolescents, incorporating 52 with a diagnosis of AS, 44 with HFA, 8 with atypical autism and 36 with other diagnoses, were examined. Our study does not support the thesis that autistic disorders are discrete phenotypes. On the contrary, it provides evidence that e.g. AS and autism are not qualitatively distinct disorders, but rather different quantitative manifestations of the same disorder.

A prospective study of serum ghrelin levels in patients treated with clozapine

Summary.We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

The influence of social status on pre-school children’s eating habits, caries experience and caries prevention behavior

ObjectivesTo assess the prevalence of Early Childhood Caries (ECC) in a county in Northern Hesse and to correlate this parameter to various independent variables. Additionally to investigate the relationship between preventive measures and the socioeconomic status (SES).MethodsIn spring 2006, 1,082 preschool children were examined. According to WHO-criteria d3+4mft scores were recorded. Information about eating habits and preventive measures were collected by structured questionnaires. To compare the mean caries scores and preventive measures of various subgroups, non-parametric tests were performed. Variables associated with caries were included in a binary stepwise backward logistic regression analysis.ResultsThe mean d3+4mft score amounted to 1.88. Children with high SES had significantly less caries than children with low SES. Significant positive and negative associations of feeding practices and preventive measures to d3+4mft scores were observed. Differences between feeding practices and preventive measures were dependent on SES.ConclusionsLong-term use of baby bottles at night is the most important factor of ECC. Differences in feeding practices and preventive measures in the various SES groups are evident but not that significant as supposed.