A multicenter study about Neurobiology of Suicidal Behavior: design, development, and preliminary results.

The subproject 1.5 "Neurobiology of Suicidal Behavior" is a multicenter study assessing peripheral parameters of the serotonergic, noradrenergic, and dopaminergic transmitter systems. Additionally, stress hormones and the lipid system as well as inhibitory and excitatory amino acids will be investigated. The different parameters are collected in cerebral spinal fluid (CSF), blood, and saliva. Patients with a depressive spectrum disorder with and without a suicide attempt (during the last three weeks) and being medication free for two weeks are included in the study. So far, 103 patients and controls have been recruited. The design and development of this project as well as interconnections with the others subprojects are described. Preliminary results about the stress hormone system and suicidality are presented.     

Typ-I-Muskelfaseratrophie Wegweiser für die Diagnose einer myotonischen Muskeldystrophie mit ungewöhnlichem Phänotyp

Zusammenfassung Fallbericht. Es wird die Kasuistik eines 15-j?hrigen Patienten und seiner 45-j?hrigen Mutter vorgestellt, bei denen eine Belastungsintoleranz, eine Schw?che der Gesichtsmuskulatur und bei der Mutter auch der Schultergürtelmuskulatur sowie eine intermittierend leicht erh?hte Aktivit?t der Kreatinkinase und mentale Beeintr?chtigung des Jungen eine neuromuskul?re Erkrankung nahelegten. Die bei dem Jungen im Alter von 14 Jahren durchgeführte Biopsie aus dem M. deltoideus links zeigte eine isolierte Typ-I-Muskelfaseratrophie ohne dystrophische Ver?nderungen (zentral liegende Kerne, Nekrose, Phagozytose), Ringbinden, Kernreihen oder sarkoplasmatische Massen. Trotz des ungew?hnlichen Ph?notyps bestand aufgrund der Typ-I-Faseratrophie der Verdacht auf eine myotonische Muskeldystrophie. Die molekulargenetische Untersuchung belegte die Diagnose einer myotonischen Muskeldystrophie, die ph?notypisch wie eine fazioskapulohumerale Muskeldystrophie imponierte. Schlussfolgerung. Die Familie belegt die klinische Variabilit?t der myotonischen Muskeldystrophie. In dieser Familie mit ungew?hnlichem Ph?notyp war für die molekulargenetische Aufl?sung der muskelbioptische Befund mit isolierter Typ-I-Muskelfaseratrophie entscheidend.      

Tandemmassenspektrometrie Beitrag zum Neugeborenenscreening auf angeborene St?rungen des Stoffwechsels Beitrag zum Neugeborenenscreening auf angeborene St?rungen des Stoffwechsels

Hintergrund. Die Tandemmassenspektrometrie wurde als neue Analysetechnik für die Früherkennung angeborener Stoffwechselst?rungen im Neugeborenenscreening erprobt.     

Contraception and the Risk of Type 2 Diabetes Mellitus in Latina Women With Prior Gestational Diabetes Mellitus

Context.— Effective contraception is essential in women with prior gestational diabetes mellitus (GDM) but should not increase their already substantial risk of developing type 2 diabetes. Objective.— To determine whether exposure to low-dose oral contraceptives increases the risk of developing type 2 diabetes mellitus in women with recent GDM. Design.— Retrospective cohort study of 904 Latinas with GDM who gave birth between January 1987 and March 1994, in whom postpartum diabetes was excluded at 4 to 16 weeks post partum. Interventions.— At their initial postpartum visit, 443 women selected a nonhormonal form of contraception, 383 received a low-dose, estrogen-progestin combination oral contraceptive (OC), and 78 breast-feeding women received the progestin-only OC. When breast-feeding ended, patients initially taking progestin-only OCs were switched to combination OCs. Patients were followed up periodically with oral glucose tolerance tests for up to 7 years. Main Outcome Measures.— Person time was used to compute unadjusted average annual incidence rates of developing diabetes mellitus, as defined by the National Diabetes Data Group Criteria. Survival analysis was used to compute the unadjusted cumulative incidence rates and adjusted relative risks of diabetes mellitus. Results.— The unadjusted average annual incidence rates of type 2 diabetes mellitus were 8.7%, 10.4%, and 26.5%, respectively, for patients using nonhormonal forms of contraception, combination OCs, and progestin-only OCs. Cumulative incidence rates were virtually identical for patients with uninterrupted use of combination OCs and nonhormonal forms of contraception, but patients using progestin-only OCs developed diabetes mellitus more rapidly during the first 2 years of use. After adjustment for potential confounding factors, the use of progestin-only OCs almost tripled the risk of type 2 diabetes mellitus compared with equivalent use of low-dose combination OCs (adjusted relative risk, 2.87; 95% confidence interval, 1.57-5.27). The magnitude of this risk increased with duration of uninterrupted use. Conclusion.— Progestin-only OCs were associated with an increased risk of diabetes in breast-feeding Latinas with recent GDM and probably should be prescribed with caution, if at all, in these women. Long-term use of low-dose combination OCs did not increase the risk of type 2 diabetes compared with use of nonhormonal contraception. Thus, combination OCs do not appear to increase the risk of diabetes in non–breast-feeding women with recent GDM.      

Notch in T-ALL: new players in a complex disease

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy of thymocytes affecting preferentially children and adolescents. The disease is heterogeneous and characterized by a large set of chromosomal and genetic alterations that deregulate the growth of maturing thymocytes. The identification of activating point mutations in NOTCH1 in more then 50% of all T-ALL cases highlights the NOTCH1 cascade as a central player of T-ALL pathogenesis. In this review, we summarize and update more recent findings on the molecular mechanisms of T-ALL with a particular emphasis on the oncogenic properties of aberrant NOTCH1 signaling.     

Familial cardiac valvulopathy due to filamin A mutation

We report on the clinical findings in siblings affected by the recently characterized X-linked form of hereditary cardiac valvular dystrophy or cardiac valve disease (OMIM 314400) due to mutations in the FLNA gene and review the literature on this condition. Although FLNA related cardiac valve disease is presumed to be a rare disorder, it is likely underdiagnosed. Several features of this condition may aid in its identification. FLNA related valvular disease can be recognized on the basis of its distinctive inheritance, early age of onset, and frequent multi-valve involvement.     

Is Sanfilippo type B in your mind when you see adults with mental retardation and behavioral problems?

Sanfilippo type B is an autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by deficiency of N-acetyl-alpha-D-glucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulfate. It is characterized by neurologic degeneration, behavioral problems, and mental decline. Somatic features are relatively mild and patients with this disorder can reach late adulthood. It is the most common subtype of MPS in the Netherlands and probably underdiagnosed in adult persons with mental retardation (MR). In order to increase knowledge on the adult phenotype and natural history in Sanfilippo type B, we present the clinical data of 20 patients with this disorder. Sixteen of them were followed for one to three decades. Six died between 28 and 69 years of age, mainly from pneumonia and cachexia; the surviving patients were 18-63 years old. Apart from the youngest, they had lost mobility at 36-68 years. Most had developed physical problems, in particular in the 4th-6th decade of life: cardiac disease (cardiomyopathy, atrial fibrillations), arthritis, skin blistering, swallowing difficulties requiring feeding by a gastrostomy tube, and seizures. The course of the disease was dominated in most of them by challenging behavioral problems with restlessness, extreme screaming and hitting, difficult to prevent or to treat pharmaceutically. Even in absence of knowledge of the history of an elderly patient with MR, the presence of behavioral problems should prompt metabolic investigation for MPS.     

The effect of electrochemically simulated titanium cathodic corrosion products on ROS production and metabolic activity of osteoblasts and monocytes/macrophages

Nowadays aseptic loosening is the most common cause of orthopaedic implant failure. Some of its reasons have already been described up to now; however, others remain still hypothetical. Besides the inflammatory response to wear particles originating at different sources, the role of reactive oxygen species as products of cellular reactions and/or as a result of the process of corrosion of an implant leading to implant failure has recently been discussed too. In the present study, we used a galvanostatic polarization to simulate the cathodic partial reaction of the corrosion process at a titanium alloy surface. With respect to cells occurring at the interface of a metal implant, the behaviour of osteoblasts and monocytes/macrophages was investigated. It has been found that cathodic polarization of Ti6Al4V induces an increase in the level of intracellular reactive oxygen species as well as suppressing the metabolic activity of cells in a dose-dependent manner. This is in agreement with the results obtained with cells after external addition of hydrogen peroxide as another kind of oxidative stress. In both approaches, monocytes/macrophages show a higher tolerance to oxidative stress than osteoblasts. It could be concluded that the electrochemical setup developed induced intracellular changes occurring during oxidative stress and it could be used for future detailed analysis of the consequences of corrosion processes for cellular reactions.