The influence of obesity, diabetes mellitus and smoking on fuchs endothelial corneal dystrophy (FECD).

To detect environmental factors, which may be possible risk factors in the disease course of Fuchs' endothelial corneal dystrophy (FECD). Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness, best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1-6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann-Whitney U test and chi-square test. The significance level was 5%. 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ± 10.32 (range 28-96) years. The mean age at diagnosis of those patients was 63.1 ± 13.2 years. The female-to-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m2 developed FECD significantly earlier than patients with a BMI < 30 kg/m2, p = 0.001. Patients with DM showed significantly more often an Krachmer grade of 5, p = 0.015. Smoking had a negative effect on Krachmer grading (p = 0.024). Using the mediation analysis, the presence of DM correlated Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI > 30.0 kg/m2 (p = 0.012). In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies.

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia-inducible factor-1α and its central downstream factors.

BACKGROUND: Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. OBJECTIVES: To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. METHODS: The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). RESULTS: HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV- tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV- tumours (QS: 5.40 ± 3.43, P = 0.019). CONCLUSIONS: Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV- tumours seem to show relevant differences.

Randomised clinical trial investigating self-assembling peptide P11-4 in the treatment of early caries.

OBJECTIVES: This prospective, randomised, split-mouth, clinical trial compared the efficacy of the self-assembling peptide P11-4 to fluoride varnish in the treatment of early buccal carious lesions. MATERIALS AND METHODS: Subjects presenting at least two clinically affected teeth were treated at D0 (day 0) and D90 with P11-4 (test) or fluoride varnish (control). At D180, fluoride varnish was applied on all study lesions. Standardised photographs were taken at D0, D30, D90, D180 and D360 and blindly morphometrically assessed. Hierarchical linear models (HLM) under allowance of confounders were used to compare the decrease in size between test and control groups. The visual analog scale (VAS) and Global Impression of Change Questionnaire (GICQ) were used as clinical assessments. RESULTS: Overall, 37 subjects (13-36 years) with 90 early carious lesions were included. HLM analysis showed a significant difference between test and control groups, indicating a decrease in test lesions and stabilisation of control lesions size (p = 0.001). The test lesion's mean size (SD) relative to baseline decreased to D30 = 0.936(0.127), D90 = 0.874(0.173), D180 = 0.844(0.215) and D360 = 0.862(0.352), whereas control lesions remained stable at D30 = 1.018(0.209), D90 = 1.013(0.207), D180 = 1.029(0.235) and D360 = 1.068(0.401). The effect sizes ranged from 0.47 to 0.82. CONCLUSIONS: Within the limits of this study, it was shown that the size of early carious lesions treated with P11-4 was significantly reduced; this result was superior to that of fluoride varnish treatment (DRKS00012941). CLINICAL RELEVANCE: The self-assembling peptide P11-4 is the first caries treatment approach aiming to regenerate decayed enamel. P11-4 initiates formation of de novo hydroxyapatite in the depth of early carious lesions, adding a new advanced therapy option for preventive dentistry.

[What influence do increased physical performance, age, sex and training frequency have on the effectiveness of back training?] / Welche Bedeutung haben physische Leistungssteigerungen, Alter, Geschlecht und Trainingsumfang für die Wirksamkeit eines Rückentrainings?

BACKGROUND: Active exercising can effectively reduce low back pain but the mechanisms of action are still unclear. OBJECTIVE: What are the influences of training frequency, increased physical performance, age and gender on the effectiveness of a multimodal back training? MATERIAL AND METHODS: A total of 1395 persons with back pain (mean age 46.9 ± 12.3 years, 65% female) took part in a multimodal back training over 24 months in the context of a multicenter study (39 locations). Back pain, physical capacity of strength, mobility and bilateral strength ratio of the spine stabilizing muscles were measured at the beginning of the training and after 6, 12 and 18 months. RESULTS AND DISCUSSION: The participants trained on average for 41.0 (SD ± 17.8) 60-min training units. This resulted in an increase of strength (28.1%), mobility (14.7%) and strength ratio (6.5%) compared to an age and gender-matched cohort without back pain. Back pain was reduced by 37.5%. The reduction in back pain can be ascribed to the training frequency by 70% and to increased physical performance by 30%. Age only marginally influenced the effect of training, while gender had no significant effect. CONCLUSION: Increases in physical performance have positive effects on the reduction of back pain but the number of training sessions was shown to be more relevant in the reduction of low back pain.

Randomised in situ clinical trial investigating self-assembling peptide matrix P11-4 in the prevention of artificial caries lesions.

The aim was to investigate the ability of self-assembling Peptide P11-4 Matrix (SAPM) to remineralize artificial initial caries lesions compared to the use of fluoride varnish. Volunteers were recruited for this randomised, cross-over in situ trial. Bovine specimens, half including orthodontic brackets, were recessed on the buccal aspects of mandibular appliances. Specimens included internal sound enamel control, a demineralised control and a part exposed during the in situ phase. Each phase lasted four weeks, followed by a one-week washout. Treatment groups were: A: negative control, no treatment,B: positive control, 22,600 ppm fluoride varnish,C: test group, 1,000 ppm SAPM. Laser fluorescence values (LF) were measured before/after demineralisation, and after the in situ period. Micro-CT analysis was used to assess mineral changes within the specimens after the in situ phase. In specimens without brackets, ΔLF values after in situ phase were: A: +5.28, B: +0.85, C: -2.89. Corresponding ΔLF for specimens with brackets were: A: +5.77, B: +1.30, C: -3.15. LF-values between groups significantly differed from each other (p < 0.0001) after the in situ phase. Micro-CT analysis yielded no significant difference among groups for specimens without brackets. For specimens with brackets, the test group showed significantly more remineralisation than the negative (p = 0.01) and positive control (p = 0.003). Within the limitations of the study, SAPM showed prevention of caries and remineralisation of enamel around orthodontic brackets.

[Retrospective recording of childhood ADHD symptoms : Follow-up of adults formerly diagnosed with childhood ADHD and/or childhood conduct disorder]. / Retrospektive Erfassung von ADHS-Symptomen in der Kindheit : Nachuntersuchung Erwachsener mit ADHS- und/oder Störung des Sozialverhaltens-Diagnose im Kindesalter.

BACKGROUND: The Wender Utah Rating Scale (WURS) is recommended for retrospective recording of childhood attention deficit hyperactivity disorder (ADHD) symptoms. Hence the present study explored the validity of the WURS and its short forms (WURS-25, WURS-k, WURS-15-G, IDA items) by screening adult subjects who had been diagnosed with either ADHD or conduct disorder (CD) during childhood. MATERIAL AND METHODS: From 317 contacted former patients of the department for child and adolescent psychiatry, 20 adults previously diagnosed with ADHD (20 male, mean age 27.3 years) and 20 adults previously diagnosed with CD (and concurrent exclusion of childhood ADHD, 15 male, mean age 33.5 years) took part in the follow-up examination. Besides the WURS the socioeconomic status, current ADHD symptoms and further anamnestic details were obtained. Statistical analysis was performed with SPSS Statistics. RESULTS: The five IDA items showed a greater capacity for retrospective recording of childhood ADHD symptoms than the WURS or its short forms. Only the IDA items significantly (p = 0.001) separated subjects with a diagnosis of childhood ADHD from subjects with a diagnosis of childhood CD; however, the specificity was only 40% (cut-off = 10, concurrent sensitivity = 90%). CONCLUSION: The validity of the WURS and its short forms is limited, especially if CD was present during childhood. As recommended in the guidelines, standardized instruments for retrospective recording of childhood ADHD symptoms should be supplemented with a history reported by third parties (e. g. parents) or with insight into school reports.

Time to Initiation of Clozapine Treatment in Children and Adolescents with Early-Onset Schizophrenia.

Introduction: Early-onset schizophrenia (EOS) has a poor prognosis and is difficult to treat, which often leads to the initiation of clozapine treatment. Studies in adults have shown that the initiation of clozapine treatment is often delayed. There is a lack of studies concerning the initiation of clozapine in children and adolescents with EOS. The aim of this study was to investigate the time span from first EOS-related psychiatric hospitalization to clozapine initiation. Methods: We retrospectively studied a consecutive cohort of children and adolescents with EOS and first-time clozapine prescriptions from a tertiary care child and adolescent psychiatric center in Germany. Results: Clinical records with data on clozapine initiation were available for 112 patients (35.7% females, mean age: 15.2±1.6 years). The mean time from first EOS-related hospitalization to clozapine initiation was 1.1 (±1.0) years, with an average of 2.3 (±1.1) prior antipsychotic treatment episodes. Higher age and higher IQ predicted earlier clozapine initiation. At the time of clozapine initiation, 40.2% of patients received antipsychotic polypharmacy. Prior to clozapine, 33.9% of patients had received 3 or more antipsychotic treatment episodes. Discussion: In our study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS. The significant portion of patients undergoing 3 or more antipsychotic trials or antipsychotic polypharmacy prior to clozapine may indicate a need for improved dissemination of knowledge on the effectiveness of clozapine in treatment-resistant schizophrenia in order to promote timely clozapine prescriptions in these cases.

[Evaluation of an Intensified Dental Preventive Programme Aimed at Children with Increased Caries Risk]. / Evaluation eines zahnmedizinischen Präventionsprogramms für Kinder mit erhöhtem Kariesrisiko.

Our study investigated the effect of a selective intensive prevention (SIP) programme on dental health of pupils in comparison to a control group. While no differences were observed in respect to dental health of first graders, the DMF-T values of fourth and 6 graders participating in SIP were significantly lower. Concerning the psychometric variables only few differences were found. The fourth and 6 graders in the test group reported less dental fear than the pupils in the control group.

Efficacy of the self-assembling peptide P11-4 in constructing a remineralization scaffold on artificially-induced enamel lesions on smooth surfaces.

OBJECTIVES: The management of white-spot lesions remains a challenge, especially during and after fixed orthodontic treatment. The aim of this in vitro study was to evaluate the efficacy of the newly introduced self-assembling peptide P11-4 (Curodont™) for regenerating demineralized tooth tissue on smooth surfaces. Another aim was to evaluate whether the DIAGNOdent (DD) and VistaProof (VP) fluorescence systems are suitable for differentiating between demineralized and remineralized enamel. MATERIALS AND METHODS: A total of 40 sound samples (buccal surfaces) of extracted human posterior teeth were artificially demineralized. The samples were examined visually as well as via DD and VP. Curodont was applied to 30 samples which were then stored in a remineralizing agent (test group). In control group 1, Curodont was applied to 5 samples which were then stored in water. Control group 2 consisted of 5 samples stored in the remineralizing agent only. Sample surfaces were examined visually and by means of DD and VP after 1 week (t1), 8 weeks (t2), and 12 weeks (t3). All fluorescence measurements were taken twice. Sample surfaces were viewed using a scanning electron microscope (SEM). Statistical analysis was conducted using the IBM SPSS® Statistics and MedCalc® programs. The fluorescence measurements' reproducibility was calculated using the intraclass correlation coefficient (ICC). A χ(2) test was applied to detect any significant differences between the fluorescence measurements of the test and control groups at each examination. Receiver operating characteristic (ROC) curves of DD and VP were constructed and areas under the ROC curve (AUC) were compared (α = 0.05) between the two fluorescence devices. RESULTS: Reproducibility of DD was moderate at t3, while the ICC values were high for all other measurements. Significant differences between the fluorescence measurements at t2 and t3 between the test and control groups (p < 0.001 for DD and VP, respectively) were observed. The performance (AUC) of DD was significantly higher than VP (visual inspection: p = 0.017; SEM: p = 0.030). At t3, all test-group samples displayed a shinier surface than the surface after demineralization. The SEM images of 28 test-group samples exhibited extensive signs of remineralized enamel. CONCLUSION: Based on visual inspection, Curodont proved to be efficacious in all samples. The SEM images revealed large areas of remineralized enamel surface in 93 % of the samples. Both fluorescence systems enabled the detection of differences between the measurements of the test and control groups after 8 and 12 weeks.

[Dental health in 12-year-old children including initial lesions and dentine caries]. / Zahngesundheit bei 12-Jährigen unter Einbeziehung von Initialläsionen und Dentinkaries.

AIM: The aim of this study was to assess caries prevalence among 12-year-olds, including initial lesions and dentine caries (ICDAS-II criteria, Codes 0-6). METHODS: The study was conducted in 2 regions of Hesse with different group prevention programmes (in region 1 children receive regular school-based prophylaxis using fluoride varnish twice a year from 1(st)-6(th) grade, in region 2 there is no use of fluoride varnish in schools. The samples were selected by a random sampling procedure using a list of all public schools. Dental caries was recorded on surface base and the presence of sealants was recorded. Additionally, a school-based analysis was performed. Statistical analysis was performed using SPSS 17.0. To compare the mean caries scores of the subgroups, non-parametric tests were performed (α=0.05). RESULTS: 270 12-year-olds were examined in each region. Mean DF-S values were: Region 1: D1-6FS=1.61; D1+2FS=1.5; D3-6FS=0.84; D5+6FS=0.74. Region 2: D1-6FS=2.8; D1+2FS=2.3; D3-6FS=1.1; D5+6FS=0.72. In region 2 significantly more initial lesions were assessed (p=0.01, D1+2FS). The difference between the regions was not statistically significant at the level of dentine caries (p=0.531, D3-6FS and p=0.113, D5+6FS). In region 1 mean DFS values differ significantly between children with and without fissure sealants at all levels (p<0.05). The analysis for region 1 based on the type of school visited showed a significant difference of mean D1+2F-S and D1-6F-S values (p=0.01 and p=0.012, respectively). CONCLUSION: In total, the caries prevalence in both regions was low. Differences between mean DFS values were clearer when initial lesions were included. The results point out the impact of assessing initial lesions for evaluation of prevention programs.

Trying to optimise the German version of the OPTION scale regarding the dyadic aspect of shared decision making.

OBJECTIVES: The OPTION scale ("observing patient involvement in decision making") assesses the extent to which clinicians involve patients in decisions across a range of situations in clinical practice. It so far just covers physician behavior. We intended to modify the scoring of the OPTION scale to incorporate active patient behavior in consultations. METHODS: Modification was done on scoring level, attempting a dyadic, relationship-centred approach in that high ratings can be evoked also by the behaviour of active patients. The German version of the OPTION scale was compared with a modified version by analysing video recordings of primary care consultations dealing with cardiovascular prevention. Fifteen general practitioners provided 40 videotaped consultations. Videos were analysed by two rater pairs and two experts in shared decision making (SDM). RESULTS: Reliability measures of the modified version were lower than those of the original scale. Significant associations of the dichotomised scale with the expert SDM rating as well as with physicians' expertise in SDM were only found for the modified OPTION scale. Receiver Operating Characteristic (ROC) analyses confirmed a valid differentiation between the presence of SDM (yes/no) on total score level, even though the cut-off point was quite low. Standard deviations of the single items in the modified version were higher compared to the original OPTION scale, while the means of total scores were similar. CONCLUSIONS: The original OPTION scale is physician-centered and neglects the activity and a possible self-involvement of the patient. Our modified instruction was able to capture the dyadic element partially. The development of a separate dyadic instrument might be more promising.

Effect of different time intervals between examinations on the reproducibility of ICDAS-II for occlusal caries.

AIM: To evaluate intra- and interexaminer reproducibility of ICDAS-II on occlusal caries diagnosis when different time intervals were allowed to elapse between examinations. A subsidiary aim was to determine whether collapsing the codes would influence this reproducibility. METHODS: The occlusal surfaces of 50 permanent posterior teeth were investigated by 3 trained examiners using ICDAS-II at baseline, 1 day, 1 week and 4 weeks after baseline. RESULTS: Weighted kappa values for intra- and interexaminer reproducibility were 0.76-0.93. CONCLUSION: The time span did not have a major impact on assessing intra- and interexaminer reproducibility. Collapsing ICDAS-II codes had no impact on examiner reproducibility.

Body weight gain induced by atypical antipsychotics: an extension of the monozygotic 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. METHODS: Twin and sib pairs were identified by a telephone screening. Measured data on weight and other clinical variables were obtained cross-sectionally and retrospectively from medical records. In seven monozygotic twin pairs and 12 sib pairs (total number of patients treated: n = 38, mean age 29.5 +/- 9.5, range 13.7-54.3 years), the similarity in BMI (kg/m(2)) change under these atypical antipsychotics (atypical Delta BMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total Delta BMI) was explored. RESULTS: For total Delta BMI we found greater similarity in antipsychotic-induced BMI change in MZ twin pairs than in sib pairs (intrapair difference) with a heritability of h(2) = 0.6, but not for atypical Delta BMI, possibly because of a genetically influenced weight plateau achieved under antipsychotic medication. CONCLUSION: The results of the present and our previous report suggest a contribution of genetic factors in antipsychotic-induced weight gain of 60-80%.

Immunophenotyping in Tourette syndrome--a pilot study.

BACKGROUND AND PURPOSE: The cause of Tourette syndrome (TS) is not precisely known, although several lines of evidence point at an involvement of the immune system in its pathogenesis. RESULTS: Here, we report the results of a pilot study investigating frequently analysed lymphocyte surface markers in 20 adult patients with TS (16 males; 37.3 +/- 15.8 years) and 20 matched controls (16 males; 37.5 +/- 15.3 years). Statistical analysis revealed significant differences for the investigated lymphocyte surface markers. The difference in CD69+/CD22+-B cells (23.0 +/- 10.5% vs. 13.1 +/- 6.1%; P = 0.001) and in CD95+/CD4+-T cells (41.5 +/- 12.1% vs. 24.6 +/- 10.0%; P = 0.0001) was still significant after Bonferroni-Holm correction. CONCLUSION: Our preliminary data indicate that TS may be associated with an increased peripheral immune activity.

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 (r(s) = 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.

Prevalence of dental fluorosis in German schoolchildren in areas with different preventive programmes.

In a retrospective study in two different regions of Germany, 1,041 fifteen-year-old pupils were examined for dental fluorosis. The adolescents had taken part in different caries prevention programmes. There were 746 subjects in the study group and 295 subjects in the control group. For each participant, specific aspects of early development, diet and fluoride exposure in group prevention programmes and at home were determined by means of questionnaires. The Thylstrup-Fejerskov index was used to classify the fluorosis scores on the buccal surfaces of teeth 11, 12, 13, 14, 15 and 16 after compressed air drying of the teeth. Binary logistic stepwise regression analyses were conducted to identify associations between fluorosis and potential influence factors. A distinction was made between early and late developing tooth parts. The significance level was set at alpha = 0.05. Fluorosis prevalence in the regions studied was 7.1 and 11.3%, respectively. The difference was not statistically significant (p = 0.052; chi square). Binary logistic stepwise regression analysis revealed that 'early start of toothbrushing' was a statistically significant predictor of dental fluorosis in the early-mineralizing enamel (OR = 1.99, p = 0.027). For the late-mineralizing enamel no single independent variable was identified as a significant predictor of dental fluorosis.

Clozapine/olanzapine-induced recurrence or deterioration of binge eating-related eating disorders.

OBJECTIVE: To explore the association between eating disorders (EDs) prior to the use of clozapine/olanzapine (pre-clozapine/olanzapine EDs) and after initiation of these antipsychotics (post-clozapine/olanzapine EDs). METHOD: Sixty-four consecutively admitted patients receiving clozapine/olanzapine were screened using the M-Composite International Diagnostic Interview (M-CIDI) to identify subjects with pre-clozapine/olanzapine EDs (DSM-IV criteria). We investigated post-clozapine/olanzapine EDs and binge eating behavior using the Questionnaire on Eating and Weight Patterns (QEWP) and used the Naranjo probability scale as objective causality assessment. RESULTS: Post-clozapine/olanzapine EDs were significantly more frequent in patients with pre-clozapine/olanzapine EDs (5 of 6) when compared to patients without pre-clozapine/olanzapine EDs (4 of 58) [chi(2) = 26.29; df = 1; p < 0.001] [odds ratio (OR) 67.5; 95% CI: 6.3-725.8]. According to the Naranjo probability scale, recurrence or deterioration of EDs in patients with prior EDs was definitely (n = 1) or probably (n = 4) related to the intake of clozapine/olanzapine. CONCLUSION: Clozapine/olanzapine may induce recurrence or deterioration of binge eating symptomatology or full-blown EDs in patients with prior EDs.

Local irradiation prior to stem cell harvest has no influence on CD34+ yield: a quantitative analysis.

In patients with multiple myeloma, irradiation of bone marrow prior to mobilization of autologous peripheral blood progenitor cells (PBPCs) may lead to a reduced yield of CD34+ cells. Quantitative effects have not been sufficiently assessed. We retrospectively performed a multivariate analysis in 114 patients (67 men, 47 women) with multiple myeloma, of whom 53 (47%) patients had been irradiated prior to mobilization chemotherapy. High-dose cyclophosphamide followed by granulocyte colony-stimulating factor was used for mobilization in 84% of patients. In addition to previous chemotherapy, we quantitatively evaluated the dose and fractionation of prior irradiation, the volume of the irradiated bone marrow, and the time interval between radiation therapy and mobilization of PBPCs. The median volume of irradiated bone marrow was 9% (range 1-30%) of the estimated total hematopoietic bone marrow. The irradiated bone marrow volume and the number of CD34+ cells per kilogram of body weight in the first leukapheresis product showed no correlation. However, the time between irradiation and mobilization seemed to influence the yield of CD34+ cells. A comparison of irradiated patients with nonirradiated patients revealed no differences with respect to the CD34+ cell counts. We did not find a significant influence of the extent or the total dose of irradiation on the yield of CD34+ cells in the first leukapheresis product in patients with multiple myeloma. However, there may be an inverse correlation between the time elapsed since the last irradiation and the number of mobilized CD34+ cells.

[Prevalence of melanocortin 4 receptor (MC4R) mutations and polymorphismsin consecutively ascertained obese children and adolescents from a pediatric health care utilization population]. / Prävalenz von Melanocortin-4-Rezeptor(MC4R)-Mutationen und Polymorphismen bei adipösen Kindern und Jugendlichen in einer konsekutiven pädiatrischen Inanspruchnahmepopulation.

BACKGROUND: The prevalence of childhood obesity is steadily increasing. Weight regulation and food intake are subject to complex regulatory mechanisms. The leptinergic-melanocortinergic system is known to be of major importance. AIM OF THE STUDY: Identification of mutations in the melanocortin 4 receptor gene (MC4R) and of phenotypic effects of detected mutations in German obese children and adolescents. Family specific and cardiovascular risk factors were also analysed. PATIENTS: Consecutive ascertainment of 90 obese children and adolescents with a medium BMI SDS of + 2.6, age range 3 to 16 years. METHODS: Mutation screen within the MC4R was carried out by denaturing high performance liquid chromatography (dHPLC) and re-sequencing of samples with aberrant dHPLC patterns. Eating behaviour and obesity-associated diseases within the families were evaluated by semi-structured interviews. Metabolic evaluation included: oral glucose tolerance test (OGTT, WHO criteria) for calculation of insulin resistance (Homeostasis Model Assessment, HOMA) and insulin sensitivity index (ISI), lipid panel for lipid status, blood pressure measurement and abdominal ultrasound. RESULTS: Three patients were heterozygous MC4R mutation carriers (Thr112Met, Ala175Thr and Gly181Asp). Gly181Asp leads to a complete loss of function; whereas Thr112Met and Ala175Thr lead to a reduced receptor function. The patients with heterozygous MC4R mutations had BMIs, cholesterol levels and waist to hip ratios (W/H) that did not differ from the rest of our study group. The overall occurrence of hypertriglyceridemia (34 %) and hypercholesterinemia (22 %) was correlated with the W/H-ratio. The overall incidence of impaired glucose tolerance was 12 %. In those with a normal glucose tolerance 68 % already had an increased HOMA (mean 3.12; reference value < 1.9) and decreased ISI (mean 4.3; reference value > 7.2). The patients with MC4R mutations had a normal glucose tolerance with similar HOMA and ISI values compared to the rest of the patients. Hypertension was found in 24 % of all cases and blood pressure was correlated with BMI (r+ 0.8). None of the patients with MC4R mutations were hypertensive. Leptin levels did not discriminate between patients with MC4R mutations and the other patients. Five patients harboured one of the MC4R polymorphisms (Val103Ile, Ile251Leu). These were phenotypically indistinguishable from the individuals without MC4R variants. CONCLUSION: We detected MC4R mutations (Thr112Met, Ala175Thr and Gly181Asp) in 3.3 % and MC4R polymorphisms (Val103Ile, Ile251Leu) in 5.5 % of the analysed obese children and adolescents, respectively. The patients with MC4R mutations did not show a higher metabolic risk compared to obese children and adolescents without mutations. However the total study group is prone to an increased risk for developing metabolic and cardiovascular diseases.

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

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.