Maternal factors influencing development of embryos from mice superovulated with gonadotropins

In NMRI mice superovulation with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) increased mating rate, number of implantation sites, rate of advanced and delayed resorptions, as well as retarded sternebral ossification and cleft palate. On day 3 of gestation in preimplantation embryos, cell number and mitotic index were lower after superovulation than after spontaneous ovulation. However, when preimplantation embryos from superovulated and control females were transferred on day 3 of pregnancy to pseudopregnant recipients (10 embryos per female) no differences could be detected between the two groups of fetuses at term. The results of the embryo transfer experiments indicate that abnormal embryonic development after superovulation with gonadotropins is predominantly induced by effects of the hormone treatment on the maternal uterine environment.     

Aktualisierte Kurzfassung der Leitlinien zur Pr?vention, Diagnostik und Therapie der nosokomial erworbenen Pneumonie

Hintergrund:  

Die nosokomiale Pneumonie gehört zu den häufigsten nosokomialen Infektionen und ist die häufigste auf der Intensivstation. Die nosokomiale Pneumonie ist mit einer signifikanten Mortalität und Morbidität assoziiert, und ihr Auftreten verschlechtert die Prognose des Patienten deutlich. Nach der Definition der DRGs auch im deutschen Krankenhaussystem ist die nosokomiale Pneumonie überwiegend Sache des Krankenhauses und kann somit nicht nur das Ergebnis der Patientenbehandlung, sondern auch das finanzielle Ergebnis des Krankenhauses beeinträchtigen.     

Modelling Germline Mosaicism and Different New Mutation Rates Simultaneously for Appropriate Risk Calculations in Families with Duchenne Muscular Dystrophy

For several genetic diseases two biological phenomena have been recognised as important: germline mosaicism; and different new mutation rates in males and females depending on mutation type. Both principles have been investigated separately and their influence on risk estimation in families has been exemplified in the literature. The aim of this paper is to present a general model that includes mosaicism and different new mutation rates. Mosaicism is introduced by defining additional alleles at the disease locus in combination with adapted segregation rules. Taking Duchenne muscular dystrophy as an example, we derive the conditions which have to be fulfilled for a population in mutation selection equilibrium. Our approach describes the model at the population level and not in individual subjects. This has the advantage of being able to use well known algorithms for the calculation of likelihoods in pedigrees, and to include additional diagnostic information such as marker genotypes and carrier deletion test results. We demonstrate the impact of the new model on a typical pedigree. In families where the patient is not available, the distinction between point mutations and deletions is important, since often molecular diagnostic tests for females can only screen for deletions. Negative deletion test results can now be included in the risk calculations.     

Extensive pectoral muscle necrosis after defibrillation: nonthermal skeletal muscle damage caused by electroporation

A 37-year-old Italian male developed a myocardial infarct with subsequent ventricular fibrillation. He was defibrillated seven times with up to 360 Joules. Thirteen days later the patient died of recurrent myocardial infarct due to thrombotic occlusion of the left circumflex coronary artery. At autopsy, necrosis of the right pectoralis muscle was observed. Electroporation is the pathogenetic mechanism of skeletal muscle damage due to multiple defibrillations with high energy levels. Received: 8 January 1998 Accepted: 15 April 1998     

Scoliosis in pediatric spinal cord-injured patients

One hundred thirty children who sustained spinal cord injuries between birth and age 21 years were reviewed to determine the progression rate of paralytic scoliosis and the effects of bracing and surgery. Patients were divided into two groups: those injured before and those injured after the adolescent growth spurt. Scoliosis developed in 97 and 52%, respectively. Bracing was effective in delaying progression in the preadolescent group. The progressive paralytic spinal deformity did not appear to be related to the level of injury. The older patient is at much less risk for paralytic scoliosis, but still requires routine examination.     

Effect of Bupivacaine and Levobupivacaine on Exocytotic Norepinephrine Release from Rat Atria

Background: The cardiotoxic mechanism of local anesthetics may include interruption of cardiac sympathetic reflexes. The authors undertook this investigation to determine if clinically relevant concentrations of bupivacaine and levobupivacaine interfere with exocytotic norepinephrine release from cardiac sympathetic nerve endings.

Methods: Rat atria were prepared for measurements of twitch contractile force and 3[H]-norepinephrine release. After nerve endings were loaded with 3[H]-norepinephrine, the tissue was electrically stimulated in 5-min episodes during 10 10-min sampling periods. After each period, a sample of bath fluid was analyzed for radioactivity and 3[H]-norepinephrine release was expressed as a fraction of tissue counts. Atria were exposed to buffer alone during sampling periods 1 and 2 (S1 and S2). Control atria received saline (100 [mu]l each, n = 6 atria) in S3-S10. Experimental groups (n = 6 per group) received either bupivacaine or levobupivacaine at concentrations (in [mu]M) of 5 (S3-S4), 10 (S5-S6), 30 (S7-S8), and 100 (S9-S10).

Results: Bupivacaine and levobupivacaine decreased stimulation-evoked fractional 3[H]-norepinephrine release with inhibitory concentration 50% values of 5.1 +/- 0.5 and 6.1 +/- 1.3 [mu]m. The inhibitory effect of both local anesthetics (~70%) approached that of tetrodotoxin. Local anesthetics abolished the twitch contractions of atria with inhibitory concentration 50% values of 12.6 +/- 5.0 [mu]m (bupivacaine) and 15.7 +/- 3.9 [mu]m (levobupivacaine). In separate experiments, tetrodotoxin inhibited twitch contractile force by only 30%.     

The aesthetics of hair restoration

The hairline and frontal hair volume are frequently overlooked aspects of attractive facial proportion and overall facial aesthetics. The author contends that patient benefit from hair restoration surgery is significant, and these procedures should be routinely considered as part of a complete facial rejuvenation.     

Toll-like receptor 9 ligand blocks osteoclast differentiation through induction of phosphatase.

CpG-ODN, in addition to stimulation of osteoclastogenic signals in early osteoclast precursors, also induces phosphatase, shifting the pattern of ERK phosphorylation from sustained to transient. This shift results in the degradation of c-fos, an essential molecule for osteoclast differentiation. Therefore, CpG-ODN blocks osteoclast differentiation. INTRODUCTION: Activation of either Toll-like receptor 9 (TLR9) or RANK induces similar responses in osteoclast precursors. Paradoxically, activation of TLR9 results in inhibition of RANKL-induced osteoclastogenesis. MATERIALS AND METHODS: We used bone marrow-derived osteoclast precursors. Analyses of signaling molecules phosphorylation were performed using Western blotting. Different levels of gene expression analyses were performed using RT-PCR, Northern, and run-on analyses (for RNA), and EMSA, Western, and pulse-chase experiments (for protein). Phosphatase activity was measured spectrophotometrically. RESULTS: We found that RANKL and TLR9 ligand, oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG-ODN), induce sustained and transient extracellular signal-regulated kinase (ERK) phosphorylation, respectively. Furthermore, together they induce a transient phosphorylation of ERK. The duration of ERK phosphorylation is a key factor in determining induction of c-fos, a protein critical for osteoclastogenesis. Indeed, we found that CpG-ODN does not induce c-fos and inhibits its induction by RANKL by enhancing c-fos mRNA and protein degradation. Our observation that CpG-ODN, but not RANKL, induces the expression of the phosphatase PP2A suggests that CpG-ODN exerts its inhibitory activity by induction of ERK dephosphorylation. Moreover, together with the phosphatase inhibitor okadaic acid, CpG-ODN induces sustained ERK phosphorylation and c-fos expression. CONCLUSIONS: Our findings suggest that the increased rate of c-fos degradation by the TLR9 ligand mediates the inhibition of RANKL-induced osteoclast differentiation. The TLR9 ligand, through induction of dephosphorylation, prevents the sustained ERK phosphorylation needed for maintaining high c-fos levels that are essential for osteoclast differentiation.