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.     

Study of the arterial vascularisation of the medial tibial condyle in the fetus

Summary Varus deformity of the knee is common in young children who have suffered from fulminating purpura. This study was directed at the anatomic features of the vascularisation of the upper end of the tibia that might account for such deformation. It was based on the dissection of 28 anatomic specimens prepared by injection of Indian ink into the vascular trunk. 16 specimens were diaphanised for better analysis of the intracartilaginous distribution of the vessels. The study showed that the vascularisation of the medial condyle of the tibia is poor and of terminal nature, which may explain the occurrence of ischemic growth disorders following fulminating purpura.

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Etude de la vascularisation artérielle du condyle médial du tibia chez le foetus

Résumé Les déformations en varus du genou chez les jeunes enfants ayant présenté un purpura fulminans sont fréquentes. Ce travail a pour objet de rechercher les caractéristiques anatomiques de la vascularisation de l'extrémité supérieure du tibia qui peuvent expliquer ces déformations. L'étude porte sur la dissection de 28 pièces anatomiques préparées par injection de l'axe vasculaire à l'encre de Chine. Pour mieux analyser la répartition intra-cartilagineuse des vaisseaux, 16 pièces ont été diaphanisées. Cette étude montre que la vascularisation du condyle médial du tibia est pauvre, de type terminal, ce qui peut expliquer la survenue de troubles de croissance ischémiques dans les suites d'un purpura fulminans.

     

Urea rebound and delivered Kt/V determination with a continuous urea sensor

BACKGROUND: The recent introduction of urea sensors for dialysis monitoring has made possible new approaches to urea kinetic modelling. In this study we show how the equilibrated postdialysis urea concentration (Ceq) and Kt/V corrected for double-pool urea kinetics (Kt/Vdp) can be accurately determined using an on-line sensor providing a continuous measure of blood water urea. A modification of the Smye constant volume double-pool theory led to the following equations for Ceq and Kt/Vdp [formula: see text] where Cpre is the blood concentration measured at the start of dialysis, t is the length of the dialysis session (in min) and S(ex) is the constant slope of the blood urea logarithm concentration decline following development of the intercompartmental urea concentration gradient in the first 30-60 min of dialysis. METHODS: These equations were tested in 11 patients undergoing 165-240 min of paired filtration dialysis with continuous monitoring of blood urea concentration. Cpre was determined as the plateau concentration during a preliminary period of 15-20 min of slow isolated ultrafiltration. S(ex) was accurately determined from linear regression applied to the urea sensor data from the 80-min point to the end of dialysis. RESULTS: Ceq and Kt/Vdp determined from the above equations compared closely to values determined from 25-40 min of urea rebound monitoring with the urea sensor: 10.6 +/- 3.0 versus 10.8 +/- 2.7 mmol/l (mean +/- SD) for Ceq and 1.21 +/- 0.24 versus 1.18 +/- 0.20 for Kt/Vdp, compared to single-pool values of Kt/V = 1.34 +/- 0.23. CONCLUSION: This technique may be readily programmed into on-line urea monitors to provide current and extrapolated values of Ceq and Kt/Vdp from about the first hour of dialysis.      

Coinduction of granulocyte-macrophage colony-stimulating factor release and lymphokine-activated killer cell susceptibility in monocytes by interleukin-2 via interleukin-2 receptor beta

Human monocytes express interleukin-2 receptor beta (IL-2R beta) constitutively; however, the function of these receptors has not been fully delineated. We discovered that IL-2R beta directs two biologic activities in human monocytes, the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and increased susceptibility to lysis by lymphokine-activated killer cells (LAK) cells. Human monocytes were purified from peripheral blood mononuclear cells by plastic adherence and anti-CD2 plus complement lysis. By a 5-hour 51Cr-release assay, monocytes cultured in IL-2 were found to gain increasing susceptibility to LAK cells with time and this effect was dose dependent. Maximal susceptibility was obtained with a 4-day culture in 1,000 U/mL of IL-2. Monocytes were also found to release GM-CSF in response to IL-2 using a CSF-dependent cell line, Mo7e. Because IL-2- induced GM-CSF release coincides with LAK lysis of IL-2-cultured monocytes, we treated monocytes with anti-GM-CSF and anti-IL-2R beta to determine whether GM-CSF release and LAK susceptibility were dependent or independent events. We found that both phenomena were inhibited by either antibody. Therefore, we conclude that IL-2-induced release of GM- CSF is mediated by IL-2R beta, which then acts to modulate the susceptibility of monocytes to lysis by LAK cells.     

Residual nonunion following vascularised fibular graft treatment for congenital pseudarthrosis of the tibia: a report of two cases

Resection and reconstruction using a vascularised fibular graft is a viable alternative treatment for congenital pseudarthrosis of the tibia, although distal junctional nonunion and residual deformity are known complications that are difficult to treat. We illustrate 2 cases in which bony union was achieved following a technique using fibular grafting and intramedullary nailing, without additional bone grafting. This technique was feasible because of hypertrophy of the fibular graft.     

阿魏酸钠对花生四烯酸代谢的影响

利用放射薄层方法测定兔血小板花生四烯酸代谢产物TXB₂,PGE₂和PGF_2α。用放射免疫法测定兔血小板TXB₂及主动脉6-keto-PGF_1α。阿魏酸钠(SF,0.1～3.2 mmol/L),抑制¹⁴C-花生四烯酸转化为TXB₂,呈剂量效应关系,IC₅₀为0.762 mmol/L。SF在较高浓度(0.8～3.2mmol/L)时亦抑制PGE₂,PGF_2α的生成。用放免法观察到,SF对血小板TXB₂和动脉壁6-keto-PGF_1α的生成均有抑制作用,对TXB₂的作用较强。结果提示,SF可抑制兔血小板和动脉壁环氧酶活性。     

The relation of forearm mineral density to peripheral fractures in postmenopausal women

Forearm bone mineral density was measured in 557 postmenopausal women from whom a history of fractures was also obtained. Known cases of osteoporosis were excluded. The mean age of the subjects was 59 years. Ninety-eight of the subjects had sustained a fracture since the menopause and 37 had done so before the menopause. There had been 188 fractures in all. The mean bone density was significantly lower in the subjects who had experienced a fracture than in those who had not experienced a fracture; this was also true of subjects who had suffered a fracture before the menopause. The lowest bone densities were observed in subjects who had suffered forearm fractures, followed by those who had suffered fractures of the rib, ankle and foot. The mean bone density in subjects with more than one fracture was significantly lower than in those with only one fracture. The difference in bone density between subjects with and without a history of fractures was most significant in the younger subjects and became progressively less significant with age. The estimated relative fracture risk was 3.1 in the group with the lowest bone densities and zero in the group with the highest bone densities.