A rapid solid-phase extraction and HPLC/DAD procedure for the simultaneous determination and quantification of different benzodiazepines in serum,blood and post-mortem blood

Summary A rapid and quantitative method for the determination of benzodiazepines using high-performance liquid chromatography (HPLC) with diode-array detection (DAD) is reported. The drugs were extracted from serum, blood or post-mortem blood using C₁₈ extraction columns. Brotizolam was used as internal standard. Experiments with spiked serum/blood samples resulted in recoveries between 75% and 94% for all investigated benzodiazepines. Excellent linearity was obtained over the concentration range 5–1500 ng benzodiazepine/ml. The limit of detection was approximately 2 ng/ml. The detection of low therapeutic serum levels of highly potent benzodiazepines is also possible.      

Hypoxische pulmonale Vasokonstriktion

Hypoxic pulmonary vasoconstriction (HPV) was first described by von Euler and Liljestrand in 1946 and is still the only known vascular feedback control mechanism in the lung. This technique results in a redistribution of blood flow away from poorly ventilated areas into better ventilated regions, thus reducing shunt. HPV functions as a local mechanism that acts in response to alveolar hypoxia but in the smallest areas of the lung, making it an important mechanism in all situations where ventilation perfusion mismatch occurs. To be effective, HPV needs normal pulmonary areas into which blood flow can be diverted. This explains why the efficacy of the treatment depends on the area that is vasoconstricted. The effect on PaO₂ is maximal when the amount of the hypoxic lung ist 30–70%. If the area in vasoconstriction is small, the influence on PaO₂ is negligible. On the other hand, when most of the lung is hypoxic, there is no significant normoxic region to which the hypoxic region can divert flow. In that case it does not matter, in terms of PaO₂, whether the hypoxic region has active hypoxic pulmonary vasoconstriction or not. In this situation HPV becomes a rather detrimental mechanism, because it causes an increase in pulmonary arterial pressure. At some stage a turning point, where the gain in PaO₂ is lost due to an increase in right ventricular afterload, inducing a decrease in CO. The reaction is diminished by exogenous manipulations, drugs (inhalation anesthetics, direct vasodilators), endotoxin, very low PaO₂ values, vasodilating mediators and changes in the acid-base balance. Acidosis and alcalosis inhibit HPV. Factors like spontaneous or mechanical ventilation, PEEP, open or closed chest, and the type of hypoxia (atelectasis or nitrogen) have no influence on HPV. The small arteries, those less than 500?μm in diameter, were identified as the location of the hypoxic constriction. Pulmonary vascular smooth muscle cells in pure culture undergo reversible and repeated hypoxic constriction. Examination of a histological lung section emphasizes that the small arteries are closely surrounded by alveoli gas on the outside and by mixed venous blood on the inside. Thus, the response is believed to be accounted for by each smooth muscle cell in the pulmonary arterial wall responding proportionally to the local oxygen tension in its vicinity and depending on alveolar as well as mixed venous oxygen pressure. The biochemical intracellular mechanism remains unknown.     

Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Hinweise auf belastungsdeformationen an skelettresten aus prähistorischen brandbestattungen

Zusammenfassung Aus Leichenbränden werden einige Skelettelemente mit Verformungen vorgelegt, die durch äußere Einwirkungen während des Festigkeitsminimums der Knochensubstanz zwischen 400–500°C entstanden sein müssen. Derartige Belastungsdeformationen konnten bisher in einigen Fällen an Gelenkregionen verschiedener Langknochen sowie häufiger an Arcusteilen größerer Wirbel beobachtet werden. Als Ursache wäre eine beabsichtigte Beschwerung der Gelenkregionen zu ihrer Fixierung während der Kremation denkbar sowie aufgrund der an den Corpus vertebrae herangedrückten Arcusteile nur der unterern (!) Wirbel eine Rückenlage des Leichnams auf der Verbrennungsstelle. Experimentelle Verbrennungen, um den erforderlichen Gewichtsdruck zur Erzeugung von Belastungsdeformationen zu ermitteln, wären wünschenswert.     

Fahrunsicherheit durch Drogen und Medikamente

Zusammenfassung Medikamente – insbesondere solche mit zentralnervöser Wirkung – können einerseits die Fahrsicherheit einschränken, andererseits kann durch eine Arzneimitteltherapie eine krankheitsbedingt eingeschränkte Fahrsicherheit gebessert bzw. eine Fahreignung wiederhergestellt werden. Für die verschiedenen verkehrsmedizinisch bedeutsamen Arzneimittelgruppen werden im Folgenden die relevanten Leistungseinbußen dargestellt. Die dem Arzt im Zusammenhang mit einer Arzneimitteltherapie obliegenden umfangreichen Beratungs- und Hinweispflichten für seinen Patienten werden ebenfalls vorgestellt.     

腹泻型与便秘型肠易激综合征直肠肛管动力和感觉功能的不同特点

目的 研究腹泻型与便秘型肠易激综合征（IBS）病人直肠肛管动力和直肠感觉功能的不同特点。方法 选择IBS病人85例，分成两组。其中腹泻组52例，便秘组33例，20例健康志愿者为对照组，采用PC Polygraf ID高分辨率多道胃肠功能测定仪，分别测定直肠肛管压力、直肠感知阈值、排便阈值、最大耐受量和直肠肛门抑制反射最低充气量。结果IBS病人的直肠静息压、肛管静息压和直肠肛门抑制反射最低充气量与健康对照组比较无显著性差异。腹泻组的最大缩窄压和排便阈值显著低于健康对照组。便秘组的松弛压、直肠感知阈值、排便阈值和最大耐受量显著高于健康对照组。结论腹泻型IBS病人的症状与最大缩窄压和排便闽值降低有关；而便秘型则与松弛压、直肠感知阈值、排便阈值和最大耐受量显著增高有关。     

Orofaziale Regulationstherapie nach Castillo Morales

The goal of Castillo-Morales’ orofacial therapy is to improve the coordination of oral motor functions in cooperation with other body systems. The processes involved in sucking, biting, chewing and swallowing are stimulated by specific techniques of sensory stimulation such as touching, stroking, stretching, exerting pressure or the vibration of mimic and tongue-bone musculature, as well as massage of the gums and palate or the application of technical apparatus. Sufficient head and posture control is fundamental and must be the first goal. Successful therapy, especially for ICP-children, has been documented in progress reports and case studies. As yet, however, there is no evidence of specific effects on eating and speech functions. Therefore, the therapy can be recommended only in order to achieve specific goals and for a limited time, being aware of the risk of overstimulation.