CSF collection time at lumbar puncture is influenced by plasma cholesterol and triglycerides

It is a fairly well-known fact that the CSF collection time (tapping time) at lumbar puncture may influence CSF levels of monoamine compounds (e.g. the serotonin metabolite 5-hydroxyindoleacetic acid, 5-HIAA) and some neuropeptides. Since serum levels of cholesterol and triglycerides and low CSF levels of 5-HIAA have been linked to violent behaviour and impulsivity, we investigated retrospectively whether serum cholesterol and triglycerides affect CSF collection time. The series consists of 14 healthy males lumbar punctured at the L(4-5) level. We found that both serum cholesterol and serum triglycerides influenced the CSF collection time for 12 ml of CSF (R = 0.77; p = 0.0067). There was no correlation between cholesterol in serum and CSF, nor between cholesterol in the CSF and collection time. However, we accidentally found a correlation between cholesterol in the CSF and age. The proposed hypothesis tries to explain why cholesterol- and triglyceride-rich lipoprotein particles modify the CSF collection time and influence endothelial function with a subsequent effect on CSF production and/or intraspinal pressure. Thus, it may be of interest to pay attention to serum cholesterol and triglycerides, their effect on CSF collection time and, in the next step, their putative impact on levels of various compounds in the CSF.     

Comparison of safety and immunogenicity of a Vi polysaccharide typhoid vaccine with a whole-cell killed vaccine in Malaysian Air Force recruits

OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine. METHODS: The study was carried out on young adult recruits (aged 18-25 years) of the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was significantly less reactogenic than the WCK vaccine with regard to systemic and local reactions. Following administration of the Vi vaccine, seroconversion rates (defined as the percentage of subjects with a 4-fold rise of baseline antibody level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective, pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The majority of subjects in this group came from a region in Malaysia which is known to have high typhoid endemicity. Interestingly, these antibody levels were boosted considerably following administration of vaccine at a level that was 5-fold higher than in subjects with low pre-immunization levels. In contrast, the seroconversion rates in those receiving the Vi vaccine were higher in subjects with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to those with protective levels of > or = 1 microgram/ml prior to immunization (48-57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi polysaccharide vaccine and identifies a hitherto unrecognized advantage in its use, i.e. it is a potent immunogen that boosted considerably the protective antibody levels among a significant number of immunologically sensitized individuals living in typhoid-endemic regions.     

Pharmacokinetics and safety of single oral doses of sirolimus (rapamycin) in healthy male volunteers

A phase I study was conducted to determine the pharmacokinetics, safety, and tolerability of sirolimus, a new immunosuppressive drug, in 45 healthy men between 19 and 36 years of age. Nine subjects in each group were randomly assigned to receive single oral doses of either sirolimus (n = 6) or placebo (n = 3) in group I (0.3 mg/m2), group II (1 mg/m2), group III (3 mg/m2), group IV (5 mg/m2) and group V (8 mg/m2). No serious adverse events occurred during the study. Twenty-eight of the 45 volunteers (62%) reported an adverse event; 19 of 30 (63%) were in the sirolimus group and 9 of 15 (60%) were in the placebo group (ns). Asthenia was the most common adverse event, occurring in 7 of 30 (23%) in the sirolimus group compared with 6 of 15 (40%) in the placebo group (ns). Absorption occurred within 1 hour in all volunteers. Whole blood peak concentration and area under the concentration-time curve increased proportionally with dose. Mean (+/- SD) whole blood terminal disposition half-life (t1/2), apparent oral dose clearance (Cl/F), and volume of distribution (Vss/F) were 82 +/- 12 hours, 278 +/- 117 mL/h x kg and 23 +/- 10 L/kg, respectively. Distribution of sirolimus into formed blood elements was extensive, with a mean whole blood-to-plasma ratio of 36. Single oral doses of sirolimus (0.3 to 8 mg/m2) solution were well tolerated in healthy male volunteers.     

Enantioselective analysis of citalopram and metabolites in adolescents.

Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.     

Treatment of depression with E-10-hydroxynortriptyline — a pilot study on biochemical effects and pharmacokinetics

The major metabolite of nortriptyline, i.e. E-10-hydroxynortriptyline (E-10-OH-NT), was given as a racemate in increasing doses from 75 to 225 mg/day to five patients with major depressive episode. Plasma concentrations of both the (–)- and (+)-enantiomers were linearly related to the doses. The mean ratio between them was 3.6±0.53, indicating stereospecific kinetics during maintenance treatment. Lumbar punctures were performed in four of the patients before and after 3 weeks of E-10-OH-NT treatment. There was a 18% mean decrease (P<0.01) in the noradrenaline metabolite HMPG in cerebrospinal fluid (CSF), supporting previous in vitro data showing that E-10-OH-NT inhibits noradrenaline uptake in vivo. During treatment, the median depression score measured by the Montgomery-Åsberg Depression Rating Scale declined from 32 to 14 (P<0.05). As the study was open, the clinical outcome is not conclusive but does not contradict the hypothesis that E-10-OH-NT has antidepressant properties. If present at all, side effects were mild and did not interfere with the treatment.     

Intrafascicular multi-unit recordings from the human infra-orbital nerve

Intrafascicular micro-electrode recordings were made from the human infra-orbital nerve close to the infra-orbital foramen. The fascicular organization was studied and multi-unit activity from low-threshold mechanoreceptive afferents was recorded during tactile stimuli, vibration and facial movements. Attempts were also made to record C-fibre activity. Innervation zones corresponding to 66 fascicles were mapped with tactile stimuli on facial hairy skin and the red zone of the lip. Most of these fields were located on the upper lip, where they overlapped, indicating a high innervation density. The fields had a median size of 3.8 cm2. Skin indentation evoked dynamic on- and off-responses and a much less pronounced static discharge. The afferent double-peaked responses to an oscillating probe applied to the peri-oral region induced similar grouping of the EMG activity during sustained lip protrusion. Contraction of facial muscles and stretching of the skin evoked on- and off-responses, whereas the static discharge was less pronounced, especially during sustained stretching. The dynamic sensitivity to minor variations in contraction and stretching was high, and during normal facial movements, as in speech, there was a barrage of impulses originating from mechanoreceptors within large facial areas. Functional implications of these sensorimotor interactions are discussed. Sympathetic C-fibre activity, frequently seen in recordings from the supra-orbital nerve, was never encountered in the infra-orbital nerve recordings, indicating a lack of such fibres. Failure to detect afferent C-fibre activity could be explained by methodological difficulties.     

Postoperative autotransfusion of concentrated drainage blood in cardiac surgery. Experience with a new autotransfusion system

A new autotransfusion system was evaluated postoperatively in six patients undergoing aortocoronary bypass surgery. A hollow fiber hemofilter was integrated in the system, making it possible to concentrate the shed blood. The device functioned well, 825 ml diluted mediastinal drainage blood with a hematocrit of 23 was concentrated to a volume of 475 ml with a hematocrit of 36 and retransfused. Proteins were preserved, thus albumin concentration increased from 23 to 37 g/l in the autotransfusate. No negative side effects were registered after autotransfusion. A thorough coagulation study after retransfusion did not reveal any sign of activation of the coagulation cascade, nor were there any signs of an increased fibrinolysis.     

Acute phase reactants and suppressive E-receptor factor in various groups of patients receiving autolymphocyte therapy.

The levels of selected acute phase proteins (APP) and of tumor-associated suppressive E-receptor factor (SER) were determined in sequential serum specimens from (1) cancer patients under treatment with autolymphocyte therapy (ALT) or plasmapheresis, (2) patients with acute infections, (3) patients with autoimmune disorders, and (4) other nonmalignant diseases. The absolute serum levels of APP, including SER, and their patterns of change over time are shown to differ significantly between cancer and non-cancer patients. The absolute levels of APP and the patterns of change over time appear to be useful indicators of immune status and predictors of antitumor response to autolymphocyte (and possibly other anti-cancer) therapy.     

Course and Prognostic Factors for Neck Pain in the General Population

European Spine Journal - Best evidence synthesis. To undertake a best evidence synthesis on course and prognosis of neck pain and its associated disorders in the general population. Knowing the...     

The Burden and Determinants of Neck Pain in Workers

European Spine Journal - Systematic review and best evidence synthesis. To describe the prevalence and incidence of neck pain and disability in workers; to identify risk factors for neck pain in...