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Frankfurt am Main, Germany

Bonnet F.,University of Rennes 1 | Ducluzeau P.-H.,Angers University Hospital Center | Gastaldelli A.,CNR Institute of Clinical Physiology | Laville M.,French Institute of Health and Medical Research | And 5 more authors.
Diabetes | Year: 2011

OBJECTIVE - The pathophysiological mechanisms to explain the association between risk of type 2 diabetes and elevated concentrations of γ-glutamyltransferase (GGT) and alanineamino-transferase (ALT) remain poorly characterized. We explored the association of liver enzymes with peripheral and hepatic insulin resistance, insulin secretion, insulin clearance, and glucagon concentration. RESEARCH DESIGN AND METHODS - We studied 1,309 nondiabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study; all had a euglycemic-hyperinsulinemic clamp and an oral glucose tolerance test (OGTT) with assessment of insulin secretion and hepatic insulin extraction. The hepatic insulin resistance index was calculated in 393 individuals. RESULTS - In both men and women, plasma concentrations of GGT and ALT were inversely related with insulin sensitivity (M/I) (all P < 0.01). Likewise, the hepatic insulin resistance index was positively correlated with both GGT (r = 0.37, P < 0.0001, men; r = 0.36, P < 0.0001, women) and ALT (r = 0.25, P = 0.0005, men; r = 0.18, P = 0.01, women). These associations persisted in multivariable models. Increased GGT and ALT were significantly associated with higher insulin secretion rates and with both reduced endogenous clearance of insulin and hepatic insulin extraction during the OGTT (P = 0.0005 in men; P = 0.003 in women). Plasma fasting glucagon levels increased over ALT quartiles (men, quartile 4 vs. quartile 1 11.2 ± 5.1 vs. 9.3 ± 3.8 pmol/L, respectively, P = 0.0002; women, 9.0 ± 4.3 vs. 7.6 ± 3.1, P = 0.001). CONCLUSIONS - In healthy individuals, increased GGT and ALT were biomarkers of both systemic and hepatic insulin resistance with concomitant increased insulin secretion and decreased hepatic insulin clearance. The novel finding of a positive correlation between ALT and fasting glucagon level concentrations warrants confirmation in type 2 diabetes. © 2011 by the American Diabetes Association. Source


Background: The purpose of this study was to evaluate the outcome and complication rates of different cranioplastic procedures. Patients and methods: This study retrospectively reviewed 242 consecutive patients who underwent cranioplasty. The indications for craniectomy, the timing and materials employed for the cranial repair procedures were analysed in all patients as well as their early and long-term results. The immediate patient's outcome after cranioplasty was assessed by reviewing medical records and the late outcome was evaluated with a telephone questionnaire. The patients were divided into three groups depending on the timing of cranioplasty [ultra early group (until 6 weeks), early group (7-12 weeks) and delayed group (after 13 weeks following craniectomy)]. Results: The ultra early cranioplasty in the form of reimplantation of the patient's own skull flap led to a rapid improvement of the patient's neurological function and late outcome. The analysis of the registered postoperative complications revealed that there were no significant differences between the groups examined. Conclusion: This study found that ultra early cranioplasty by reimplanting the patient's own previously removed and frozen skull bone was a safe and successful strategy. © Springer-Verlag 2012. Source


Stadler C.,University of Basel | Stadler C.,Goethe University Frankfurt | Kroger A.,Goethe University Frankfurt | Clement H.-W.,Albert Ludwigs University of Freiburg | And 2 more authors.
Kindheit und Entwicklung | Year: 2012

In the treatment of conduct disorders, multimodal behavioural therapeutic approaches have been proven effective. This study aims to investigate the effectiveness for the multimodal day-care approach VIA in a waiting-list control approach with regard to specific effects and more global measures for therapy success, such as parenting and family life quality. Since many studies have shown that therapeutic interventions are less effective in a subgroup of patients characterized by low emotional and psychophysiological responsiveness, it was additionally asked whether callous unemotional traits and cortisol reactivity were significant predictors for therapy success. Statistical analyses yielded evidence for a significant reduction of specific conduct disorder symptoms in the intervention group compared to the waiting-list group. In regard to more global indices for therapy success, it was shown that effective parenting strategies enhanced after VIA training, whereas family life quality did not improve in a statistically significant extent. Additionally, it was revealed with a logistic regression analysis that patients with a positive course (defined by a 25 % symptom reduction) are characterized by low callous unemotional traits and high cortisol reactivity.This study supports that that VIA is an effective approach in treating patients with conduct disorder. However, for conduct disorder patients with high callous unemotional traits additional therapeutic intervention options focusing on enhancing empathy and emotional responsiveness are recommended. © Hogrefe Verlag, Göttingen 2012. Source


By October 31st 2014, pharmaceuticals have passed 104 benefit assessment by the federal joint committee according to the AMNOG ("Act on the Reform of the Market for Medicinal Products") since January 1st 2011. The assessment is transparent to the public. In contrast to drug approval by the EMA (European medicines agency) and comparable institutions which is based on the proof of efficacy, tolerability and safety essentially in comparison to placebo, benefit assessment addresses the benefit in comparison to an active so-called appropriate comparator treatment. For orphan-drugs - 14 assessments by now - "only" the size of the benefit is to be defined as long as the sales do not exceed 50 million Euro per year. For 56 pharmaceuticals, the reimbursement ("price") has been negotiated. Four pharmaceuticals have been assigned to a reference price group. Five assessments were discontinued prematurely because the legislator in 2014 has exempted pharmaceuticals launched before 2011. Six pharmaceuticals have been withdrawn by the manufacturers because of not expecting any fair price. None has gained the highest degree of benefit, the considerable (major) added benefit, yet. A moderate added benefit was conceded to 19 pharmaceuticals in 20 comparisons. 27 pharmaceuticals gained a minor benefit at least in one of the comparisons. 38 pharmaceuticals were decided to have no added benefit at all. The underlying legal regulations, principles, methodological issues and problems encountered, especially concerning the number and choice of the appropriate comparator treatments, are reviewed, where possible from a neuropsychopharmacological perspective. If the legislator had not exempted drugs launched before 2011 from assessment it would be logical and high time to clear office-based physicians from the charges of prescription limits in conjunction with utilization review. Benefit assessment in Germany probably will not affect innovation readiness of the international pharmaceutical industry adversely. Research promotion is a task for society as a whole and to be financed from taxes accordingly. Patients affected by mental disorders are in special need for psychopharmacotherapeutic innovation and thus deserve focussed public funding of drug research. © 2015, Wissenschaftliche Verlagsgesellschaft MBH. All rights reserved. Source


Kaur P.,Panjab University | Kaur P.,University of Wurzburg | Zeh A.,University of Wurzburg | Zeh A.,Free University of Berlin | And 3 more authors.
Precambrian Research | Year: 2011

In situ U-Pb-Hf isotope analyses of detrital zircons from the Alwar quartzite, the oldest member of the North Delhi fold belt in the Aravalli mountain range, indicate that the basement of NW India shares a common Archaean-Palaeoproterozoic evolutionary history, and is a consequence of several crust-forming and crust-reworking events between 3.70 and 1.71 Ga. This is suggested by a zircon age spectrum with most ages at 1.87-1.71 Ga (75%), minor age peaks at 2.5-2.2 and 2.9-2.7 Ga, and Palaeoarchaean ages of 3.27-3.23 Ga. Lu-Hf isotope data reveal that the oldest crust, either in the Aravalli mountain range or in its hinterland, was formed from a depleted mantle source at around 3.7 Ga. Furthermore, the data also indicate that the hinterland of the Alwar sediments was affected by several periods of new "juvenile" crust formation at 3.25, 2.89, 2.67, 2.51, and 1.87-1.80 Ga, while crustal reworking was predominant at 2.62-2.45, 2.2 and 1.87-1.77 Ga. Zircons with xenocrystic cores and metamorphic overgrowths, additionally suggest that the source region was affected by high-grade (?) metamorphic events at 2.5 and 2.2 Ga. Based on our new data, in conjunction with field relationships and existing zircon ages in the Archaean basement of NW India, it can be concluded that the Palaeo- to Neoarchaean detritus (3.3-2.5 Ga) in the Alwar quartzite stems from proximal sources. The predominant late Palaeoproterozoic zircon detritus (1.87-1.71 Ga) was supplied from a nearby basement, which was affected by subduction-accretion tectonics at around 1.85 Ga, and by a first, perhaps post-collisional rift-related phase at 1.77 Ga. The latter event is unrecognized so far, and predates a second phase of rift-related A-type magmatism at 1.72-1.70 Ga. The youngest detrital zircon age of ca. 1.71 Ga suggests that the sedimentation and metamorphism in the North Delhi fold belt postdate the second phase of rift-related A-type magmatic activity. © 2011 Elsevier B.V. Source

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