Prevention of alcohol withdrawal seizures with carbamazepine and valproic acid

To evaluate the value of the nonsedative anticonvulsants carbamazepine and valproic acid a controlled study including drug monitoring was carried out. Intoxicated alcoholics (n = 138) were admitted for inpatient detoxication and randomly assigned to either carbamazepine (n = 43), sodium valproate (n = 46) or placebo (n = 49) in a double-blind fashion. Drug treatment lasted for four days and the daily doses of both drugs amounted to 1200 mg in the beginning of the study. Sodium valproate induced gastric distress, nausea and vomiting more frequently than placebo. About half of the subjects had to stop carbamazepine because of intolerable side-effects including vertigo, nausea, vomiting, diplopia and rash. Serum carbamazepine levels (18-89 mumol/l) were found to be high (greater than 40 mumol/l) in many but not all of these subjects. Seizures occurred in 3 subjects on placebo, 2 on carbamazepine and 1 on sodium valproate. Delirium tremens developed in 2 on sodium valproate and 1 on placebo. The study demonstrates that drug side-effects may seriously hamper the utility of carbamazepine and sodium valproate as routine treatment for the prevention of alcohol withdrawal symptoms.     

Altered cardiovascular autonomic regulation after salmeterol treatment in asthmatic children

The effects of therapeutic 4 weeks' inhaled salmeterol treatment on the cardiovascular and respiratory autonomic nervous regulation was studied in 11 asthmatic children using inhaled corticosteroid medication. The study followed a randomized, double-blind, placebo-controlled cross-over design. The salmeterol dose was 50 μg twice daily. The 4-week salmeterol treatment increased baseline heart rate, low-frequency/high-frequency (LF/HF) variability ratio of R–R intervals, LF variability of systolic arterial pressure (SAP) and maximum tidal volume during the deep breathing test, as well as morning and evening peak expiratory flow (PEF) values. The 4-week salmeterol treatment decreased baseline HF variability of R–R intervals. As a response to the acute 600 μg of salbutamol, the changes in heart rate, HF variability of R–R intervals and diastolic blood pressure were significantly smaller after 4 weeks' salmeterol treatment. In conclusion, 4 weeks' therapeutic salmeterol treatment decreases basal cardiovagal reactivity, increases sympathetic dominance in the cardiovascular autonomic balance and improves pulmonary function. A tolerance develops in the cardiovascular response but not in the bronchodilatory response.     

Growth differentiation factor-9 induces Smad2 activation and inhibin B production in cultured human granulosa-luteal cells

The TGF beta family member growth differentiation factor-9 (GDF-9) is an oocyte-derived factor that is essential for mammalian ovarian folliculogenesis. GDF-9 mRNAs have been shown to be expressed in the human ovarian follicle from the primary follicle stage onward, and recombinant GDF-9 has been shown to promote human ovarian follicle growth in vitro. In this study with primary cultures of human granulosa-luteal (hGL) cells, we investigated whether recombinant GDF-9 activates components of the Smad signaling pathways known to be differentially activated by TGF beta and the bone morphogenetic proteins (BMPs). As with TGF beta, GDF-9 treatment caused the phosphorylation of endogenous 53-kDa proteins detected in Western blots with antiphospho-Smad2 antibodies (alpha PS2). However, unlike BMP-2, GDF-9 did not activate the phosphorylation of antiphospho-Smad1 antibody (alphaPS1)-immunoreactive proteins in hGL cells. Infection of hGL cells with an adenovirus expressing Smad2 (Ad-Smad2) confirmed that GDF-9 activates specifically phosphorylation of the Smad2 protein. Infection of hGL cells with Ad-Smad7, which expresses the inhibitory Smad7 protein, suppressed the levels of both GDF-9-induced endogenous and adenoviral alpha PS2-reactive proteins. Furthermore, GDF-9 increased the steady state levels of inhibin beta(B)-subunit mRNAs in hGL cells and strongly stimulated the secretion of dimeric inhibin B. Again, Ad-Smad7 blocked GDF-9-stimulated inhibin B production in a concentration-dependent manner. We identify here for the first time distinct molecular components of the GDF-9 signaling pathway in the human ovary. Our data suggest that GDF-9 mediates its effect through the pathway commonly activated by TGF beta and activin, but not that activated by many BMPs. The results are also consistent with the suggestion that in addition to endocrine control of inhibin production by gonadotropins, a local paracrine control of inhibin production is likely to occur via oocyte-derived factors in the human ovary.     

Short-Term Bone Biochemical Response to a Single Bout of High-Impact Exercise

Bone response to a single bout of exercise can be observed with biochemical markers of bone formation and resorption. The purpose of this study was to examine the response of bone biochemical markers to a single bout of exhaustive high-impact exercise. 15 physically active young subjects volunteered to participate. The subjects performed continuous bilateral jumping with the ankle plantarflexors at 65 % of maximal ground reaction force (GRF) until exhaustion. Loading was characterized by analyzing the GRF recorded for the duration of the exercise. Venous blood samples were taken at baseline, immediately after, 2h and on day 1 and day 2 after the exercise. Procollagen type I amino terminal propeptide (P1NP, marker of bone formation) and carboxyterminal crosslinked telopeptide (CTx, marker of bone resorption) were analyzed from the blood samples. CTx increased significantly (32 %, p = 0.015) two days after the exercise and there was a tendensy towards increase seen in P1NP (p = 0.053) one day after the exercise. A significant positive correlation (r = 0.49 to 0.69, p ≤ 0.038) was observed between change in P1NP from baseline to day 1 and exercise variables (maximal slope of acceleration, body weight (BW) adjusted maximal GRF, BW adjusted GRF exercise intensity and osteogenic index). Based on the two biochemical bone turnover markers, it can be concluded that bone turnover is increased in response to a very strenuous single bout of exhaustive high-impact exercise.

Key points

• Studies on bone acute biochemical response to loading have yielded unequivocal results.
• There is a paucity of research on the biochemical bone response to high impact exercise.
• An increase in bone turnover was observed one to two days post exercise.

Key words: Bone biochemical marker, jumping, bone turnover, osteogenic index     

Psychotic boys performing well in school are at increased risk of suicidal ideation

Aim:  This study investigated how the level of school performance is associated with suicidal behavior and psychiatric disorders among adolescent psychiatric inpatients aged 12–17 years.
Methods:  Data were collected from 508 adolescents (300 girls, 208 boys; age 12–17 years) admitted to inpatient psychiatric hospitalization between April 2001 and March 2006. Information on the adolescents' school performance, suicidal ideation, suicide attempts and self-mutilation as well as psychiatric DSM-IV diagnoses was obtained using the Schedule for Affective Disorder and Schizophrenia for School-Age Children.
Results:  An elevated risk of suicidal ideation (OR = 3.6, 95% CI 1.3–10.2, P  = 0.017) and of psychotic disorders (OR = 3.2, 95% CI 1.0–10.0, P  = 0.048) was observed among male adolescents performing well in school. In addition, adolescents with poor school performance had an increased likelihood of substance-related disorder both in boys (OR = 2.6, 95% CI 1.1–6.1, P  = 0.027) and girls (OR = 2.5, 95% CI 1.2–5.1, P  = 0.011).
Conclusions:  Our findings indicate that psychotic inpatient male adolescents performing well in school are at an elevated risk of suicidal ideation. Although good school performance is often considered a marker of high intelligence and good general ability, symptoms of major psychiatric disorders and suicidality need to be taken very seriously among adolescents performing well in school.     

Staphylococcal chromosomal cassette mec type I, spa type, and expression of Pls are determinants of reduced cellular invasiveness of methicillin-resistant Staphylococcus aureus isolates

We have shown previously that pls, which codes for the surface protein Pls of methicillin-resistant Staphylococcus aureus (MRSA), reduces adhesion to immobilized fibronectin, fibrinogen, laminin, and immunoglobulin G as well as invasion of host cells. Here, we tested a collection of 66 clinical MRSA isolates--48 negative for pls/Pls (pls(-)/Pls(-)), 15 positive for pls/Pls (pls(+)/Pls(+)), and 3 harboring the pls gene but not expressing Pls (pls(+)/Pls(-))--for cellular invasiveness. Invasion of 293 cells by pls(+)/Pls(+) strains was lower than that by the pls(-)/Pls(-) strains (median [range], 36% [22%-70%] vs. 93% [25%-162%]). The 3 pls(+)/Pls(-) strains (median [range], 95% [63%-103%]) were as invasive as the pls(-)/Pls(-) strains. In addition, we identified a pls(+)/Pls(+) staphylococcal chromosomal cassette mec (SCCmec) IV strain. In conclusion, 3 properties--pls/Pls, SCCmec type, and spa type--strongly predicted the cellular invasiveness of MRSA strains, as indicated by good clustering. In contrast, the spa type-deduced multilocus sequence typing clonal complex (MLST-CC) was not able to predict the invasiveness of MRSA strains equally well. The underlying mechanism remains to be elucidated.     

Effects of xenon anesthesia on cerebral blood flow in humans: a positron emission tomography study

BACKGROUND: Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in patients with cerebral pathology could be compromised by deleterious effects on regional cerebral blood flow (rCBF). METHODS: 15O-labeled water was used to determine rCBF in nine healthy male subjects at baseline and during 1 minimum alveolar concentration (MAC) of xenon (63%). Anesthesia was based solely on xenon. Absolute changes in rCBF were quantified using region-of-interest analysis and voxel-based analysis. RESULTS: Mean arterial blood pressure and arterial partial pressure for carbon dioxide remained unchanged. The mean (+/-SD) xenon concentration during anesthesia was 65.2+/-2.3%. Xenon anesthesia decreased absolute rCBF by 34.7+/-9.8% in the cerebellum (P<0.001), by 22.8+/-10.4% in the thalamus (P=0.001), and by 16.2+/-6.2% in the parietal cortex (P<0.001). On average, xenon anesthesia decreased absolute rCBF by 11.2+/-8.6% in the gray matter (P=0.008). A 22.1+/-13.6% increase in rCBF was detected in the white matter (P=0.001). Whole-brain voxel-based analysis revealed widespread cortical reductions and increases in rCBF in the precentral and postcentral gyri. CONCLUSIONS: One MAC of xenon decreased rCBF in several areas studied. The greatest decreases were detected in the cerebellum, the thalamus and the cortical areas. Increases in rCBF were observed in the white matter and in the pre- and postcentral gyri. These results are in clear contradiction with ketamine, another N-methyl-D-aspartate antagonist and neuroprotectant, which induces a general increase in cerebral blood flow at anesthetic concentrations.