The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study.

RATIONALE: Kava (Piper methysticum) is a psychotropic plant medicine with history of cultural and medicinal use. We conducted a study comparing the acute neurocognitive, anxiolytic, and thymoleptic effects of a medicinal dose of kava to a benzodiazepine and explored for the first time specific genetic polymorphisms, which may affect the psychotropic activity of phytomedicines or benzodiazepines. METHODS: Twenty-two moderately anxious adults aged between 18 and 65 years were randomized to receive an acute dose of kava (180 mg of kavalactones), oxazepam (30 mg), and placebo 1 week apart in a crossover design trial. RESULTS: After exposure to cognitive tasks, a significant interaction was revealed between conditions on State-Trait Anxiety Inventory-State anxiety (p = 0.046, partial ŋ² = 0.14). In the oxazepam condition, there was a significant reduction in anxiety (p = 0.035), whereas there was no change in anxiety in the kava condition, and there was an increase in anxiety in the placebo condition. An increase in Bond-Lader "calmness" (p = 0.002) also occurred for the oxazepam condition. Kava was found to have no negative effect on cognition, whereas a reduction in alertness (p < 0.001) occurred in the oxazepam condition. Genetic analyses provide tentative evidence that noradrenaline (SLC6A2) transporter polymorphisms may have an effect on response to kava. CONCLUSION: Acute "medicinal level" doses of this particular kava cultivar in naive users do not provide anxiolytic activity, although the phytomedicine also appears to have no negative effects on cognition.

Neurocognitive effects of kava (Piper methysticum): a systematic review.

RATIONALE: Kava (Piper methysticum) elicits dose-dependent psychotropic effects and thus may potentially deleteriously affect cognitive performance. Clinical trials have assessed the effects of kava on cognition, however, to our knowledge no systematic review has been conducted in this area. OBJECTIVE: To systematically review the effects of kava on cognition, providing an analysis of the individual study's methodological quality, results and effect sizes. METHODS: A systematic review was conducted of publications up to June 15th 2010, using the electronic databases MEDLINE, PsychINFO, CINAHL, Web of Science and The Cochrane Library. The search criteria involved kava and cognition related terms, e.g. memory and attention. RESULTS: Ten human clinical trials met inclusion criteria (acute n = 7, chronic n = 3). One acute study found that kava significantly improved visual attention and working memory processes while another found that kava increased body sway. One chronic study found that kava significantly impaired visual attention during high-cognitive demand. Potential enhanced cognition may be attributed to the ability of kava to inhibit re-uptake of noradrenaline in the pre-frontal cortex, while increased body sway may be due to GABA pathway modulation. CONCLUSIONS: The majority of evidence suggests that kava has no replicated significant negative effects on cognition.

Detection of autoantibodies against oxidized low-density lipoproteins and of IgG-bound low density lipoproteins in patients with coronary artery disease.

The role of oxidized low-density lipoprotein (ox-LDL) in the pathogenesis of atherosclerosis has been the object of intense investigation. It has been proposed that, due to the antigenic properties of ox-LDL, the anti-ox-LDL antibody titre could represent a useful index of in vivo LDL oxidation. On the other hand, LDL immune complexes (LDL-IC) have been demonstrated in patients with coronary disease and could play an atherogenic role. The goal of our study was to investigate anti-malondialdehyde (MDA)-LDL autoantibodies and LDL-IC in a cohort of patients with coronary artery disease. Seventy control subjects and 70 coronary angiographically documented patients were compared; in addition 32 healthy male non-smokers were compared with 32 healthy male smokers (> 10 cigarettes/day). All patients were matched for age and cholesterolemia. Enzyme-linked immunosorbent assay was used to measure anti-MDA-LDL autoantibodies and LDL-IC. Titres of anti-MDA-LDL autoantibodies were not larger in patients with documented coronary artery stenosis and in smokers than they were in controls and non-smokers. The titre of LDL-IC was not higher in patients with coronary artery stenosis than in controls. The results thus indicate that in populations matched for age and cholesterolemia the titres of anti-MDA-LDL autoantibodies and the titre of LDL-IC are not increased in patients suffering from coronary artery stenosis. Furthermore, cigarette smoking does not induce higher titres of anti-MDA-LDL autoantibodies in healthy patients.

Absence of relationship between plasma Lp(a), Lp-AI, anti-oxidized LDL autoantibodies, LDL immune complexes concentrations and restenosis after percutaneous transluminal coronary angioplasty.

To determine the relation between the concentration of Lp(a), LpAI, immunological markers of LDL oxidation (antioxidized-LDL autoantibodies (LDL-AB), LDL immune complexes (LDL-IC)) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) in a Caucasian population (France), we studied 77 consecutive patients who successfully underwent PTCA. All were evaluated by follow-up angiography at an average of 6 months after PTCA and were divided into two groups: existence of restenosis (32 patients, group (G+)) and absence of restenosis (45 patients, negative group (G-)). The prevalence of diabetes mellitus was higher in the restenosis positive group than in the negative group (28% versus 2% respectively, P=0.001). Before and after adjustment in diabetes mellitus frequency there was no difference in the usual lipid parameters (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, phospholipids, apolipoprotein AI, apolipoprotein B) between the two groups of patients nor in the other parameters (Before adjustment: Lp(a): 0.306+/-0.352 g/l (G+) vs. 0.263+/-0.270 g/l (G-); LpAI: 0.414+/-0.126 g/l (G+) vs. 0.390+/-0.092 g/l (G-); LDL-AB: arbitrary unit (AU) 3.75+/-1.91 (G+) vs. 3.67+/-1.24 (G-); LDL-IC: (AU) 0.93+/-0.82 (G+) vs. 0.86+/-0.44 (G-)). Spearman correlation coefficients did not report any correlation between late loss, loss index, gain and the above mentioned plasma parameters. In conclusion, usual tested plasma lipids, Lp(a), LpAI and in vivo markers of LDL oxidation (LDL-AB and LDL-IC) are not risk factors for restenosis after PTCA in this French population.

[Imaging problems in endoscopic surgery]. / Problèmes d'imagerie en chirurgie endoscopique.

In this article, we analyse some problems related with the use of optic endoscopes in surgery and we point possible solutions. The lack of perception and spatial orientation in video vision are some drawbacks of endoscopic surgery. The role of light multi-incidence on objects as a determining factor to locate objects in space is underlined. The use of a rotating microcamera placed at a high point inside the abdominal cavity might be a useful watch during operation. Alternative digitalized imaging is most likely the future of minimally invasive surgery.

Does a medicinal dose of kava impair driving? A randomized, placebo-controlled, double-blind study.

OVERVIEW: Increasing concerns over the potentially impairing effects of prescriptive sedative drugs such as benzodiazepines on driving have been raised. However, other alternatives such as natural medicines may also carry similar risks with respect to driving safety. Kava (Piper methysticum) is a psychotropic plant commonly used both recreationally and medicinally in the United States, Australia, and the South Pacific to elicit a physically tranquilizing effect. To date no controlled study has tested a medicinal dose of kava versus placebo and a standard sedative drug on driving ability and driving safety. OBJECTIVE: Due to the need to establish the safety of kava in operating a motor vehicle, we compared the acute effects of the plant extract versus the benzodiazepine oxazepam and placebo using a driving simulator. METHODS: A driving simulator (AusEd) was used by 22 adults aged between 18 and 65 years after being randomly administered an acute medicinal dose of kava (180 mg of kavalactones), oxazepam (30 mg), or placebo one week apart in a crossover design trial. RESULTS: No impairing effects on driving outcomes were found after kava administration compared to placebo. Results on specific driving outcome domains revealed that the oxazepam condition had significantly slower braking reaction time compared to the placebo condition (p =.002) and the kava condition (p =.003). The kava condition had significantly fewer lapses of concentration compared to the oxazepam condition (p =.033). No significant differences were found between conditions for steering deviation, speed deviation, and number of crashes. Results were not modified by driving experience. On the Bond-Lader visual analogue sub-scale of alertness, a significant Treatment × Time interaction (p =.032) was found, with a significant reduction over time for oxazepam decreasing alertness (p <.001), whereas no significant reduction was found in the kava or placebo conditions. CONCLUSION: The results indicate that a medicinal dose of kava containing 180 mg of kavalactones does not impair driving ability, whereas 30 mg of oxazepam shows some impairment. Research assessing larger recreational doses of kava on driving ability should now be conducted.

[Osteoarticular tuberculosis: a differential diagnosis of idiopathic juvenile arthritis]. / Oligo-arthrite tuberculeuse : un diagnostic différentiel de l'arthrite juvénile idiopathique.

UNLABELLED: We report a case of extrapulmonary tuberculosis with oligoarthritis and synovitis in a 6-year-old girl with undiagnosed disseminated tuberculosis. CLINICAL CASE: The child, adopted from Ethiopia, was admitted to the pediatric rheumatology unit for suspected idiopathic juvenile arthritis. She presented with clinical signs of subacute arthritis of the right knee. Joint symptoms began insidiously and followed a short period of fever and pain in the right hip. Clinical examination showed voluminous cervical lymphadenitis, night sweats, and a moderate alteration of the child's general condition. The medical history revealed that since her arrival in France, 2 years before, she had had febrile subacute pneumonia. A review of the chest x-ray diagnosed primary pulmonary tuberculosis. An intradermal tuberculin test confirmed the diagnosis with a phlyctenular response and a diameter exceeding 20mm. Additional evaluation showed cervical lymphadenitis and intense synovitis of the right hip and knee joints. With an appropriate antitubercular regimen, her condition improved within a few months. After 1 year of treatment, magnetic resonance imaging (MRI) showed normalization of the impaired joints with no functional sequelae. DISCUSSION: Although the spine is a common target for osteoarticular tuberculosis (OAT), peripheral involvement in this case underlines the polymorphism of OAT in children. It illustrates a case of OAT strictly located to the synovial membranes, which usually occurs in one-third of OAT cases. In addition, MRI showed tenosynovitis of the quadriceps. The child presented with unilateral oligoarthritis instead of chronic insidious monoarthritis or symmetrical oligoarthritis as usually described in pediatric OAT. When available, MRI is the best way to evaluate OAT lesions. Mycobacterium tuberculosis can be isolated from sputum, gastric aspiration, and joint fluid or synovial biopsy. Histological lesions can reveal advanced tuberculosis with the presence of caseous follicular lesions. Rapid bacterial detection using polymerase chain reaction remains insufficiently useful in those situations. The recommended therapeutic regimen consists of 3 months with four antitubercular agents (rifampicin, isoniazid, pyrazinamide, and ethambutol) followed by 9 months of a dual therapy (isoniazid, rifampicin).

[Retro- and parapharyngeal infections: standardization of their management]. / Infections rétro- et parapharyngées: vers une harmonisation des pratiques.

AIM: To analyze the changes in the management of retropharyngeal and parapharyngeal infections and propose a decisional algorithm for their diagnosis and treatment. PATIENTS AND METHODS: A retrospective survey was carried out in a tertiary care pediatric hospital between January 2001 and December 2005. All children aged less than 15 years and affected by a retro- or parapharyngeal infection were included. Clinical, biological, and radiological data, medical and surgical treatment, and complications were extracted from the review of medical charts. The results of the surgical findings were correlated with a cervical computed tomographic scan (CT scan). RESULTS: Thirty-one patients were included, 64.5% during the last 2 years of the study period. All children presented fever and a stiff neck. The pharyngeal examination revealed a retropharyngeal bulge in a quarter of the population and an upper respiratory tract infection was concomitant in 68% of cases. A CT scan was carried out in 29 of 31 children (93.5%), with the radiological diagnosis of an abscess in 16 children (55.2%), presuppurative adenitis in 8 children (27.6%), and cellulitis in 5 children (17.2%). The CT scan was performed within 0.75 days of admission in 2001 and 2.3 days in 2005. All children were treated with intravenous antibiotic therapy: an association of amoxicillin/clavulanic acid and an aminoglycoside in most cases. The mean duration of intravenous antibiotic therapy was 5.2 days. Seventeen patients (93.5%) underwent surgical drainage and purulent material was found in 82.3% of cases. The accuracy of the CT scan, confirmed by surgical finding of a purulent material, was 71.4% in correctly identifying an abscess. The mean duration of surgical treatment after admission increased from 1.7 days in 2001 to 3.3 days in 2005. The number of patients who underwent surgery was divided by a factor of 3 in the second period of the study. Two groups were compared: group A (n=12) treated with antibiotic therapy and group B (n=17) treated with antibiotics and surgical drainage. No significant difference was found between the two groups considering the duration of parenteral and oral antibiotic therapy, the standardization of cervical mobility, the mean time for apyrexia, and the length of hospitalization. There was one recurrence in group B 1 month later, and one case of sepsis in group A. None of the patients with retropharyngeal infection died. CONCLUSION: Without clinical evidence of severe sepsis, parenteral antibiotic therapy is recommended as the first-line treatment for children over 6 months of age presenting with retropharyngeal and parapharyngeal infections. If the clinical and/or biological conditions do not improve within 48-72h, a CT scan is indicated to assess the extent of infection and exclude complications. The decision to initiate surgical drainage depends on the patient's clinical status and the accessibility of the abscess.

Rapid quantification of alpha-tocopherol in plasma and low- and high-density lipoproteins.

We have developed two methods for measuring the alpha-tocopherol content in plasma and lipoproteins (LDL and HDL). In procedure 1, plasma or lipoproteins are deproteinized with ethanol containing delta-tocopherol as internal standard and then extracted with hexane or ethyl acetate. The organic layer is removed and evaporated, and the residue is redissolved in methanol and injected into a reversed-phase HPLC. In procedure 2, plasma or lipoproteins are diluted in a methanol and ethanol mixture containing the same internal standard. The solution is vortex-mixed, centrifuged, and directly injected into the column. The tocopherols are eluted with an isocratic methanol mobile phase at a flow rate of 1 mL/min and detected by fluorescence (lambda(exc)= 295 nm, lambda(em)= 330nm). Recoveries are approximately 100% in both cases. Between-run CVs were 8.39% for procedure 1 and 6.55% for procedure 2. Small sample requirement, simplicity of sample preparation, short assay time, and good reproducibility make procedure 2 ideal for clinical or research use. This method was applied to determination of alpha-tocopherol in plasma of patients whose diet was supplemented with alpha-tocopherol and in LDL and HDL.

Oxidized high-density lipoproteins modulate endothelin secretion by adult bovine aortic endothelial cells.

BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are well established as an inverse risk factor for atherosclerosis. This fact is probably related to the ability of HDL to induce cholesterol efflux from the vascular cell. It is also possible that HDL affects the production of different mediators implicated in the development of atheroslerosis. Endothelin is a vasconstricting mitogenic peptide involved in the development of atherosclerosis. We studied whether native HDL, oxidized HDL and tetranitromethane HDL modulate the endothelin secretion of cultured adult bovine aortic endothelial cells. METHODS: We determined the effect of native HDL and modified HDLs (oxidized HDL and tetranitromethane HDL) on the secretion of endothelin by cultured adult bovine aortic endothelial cells. An endothelin radioimmunoassay system was used to quantify levels of immunoreactive endothelin in the cultured media. RESULTS: Native HDL, tetranitromethane HDL and oxidized HDL produced a highly significant stimulation of endothelin secretion (maximum 294% of control), even at low concentrations (10 and 20 micrograms/ml). Oxidized HDL2 and oxidized HDL3 produced a biphasic effect, with maximum secretion occurring with 100 micrograms/ml oxidized HDL3 (294% of control) and 50 micrograms/ml oxidized HDL2 (252% of control). The secretion of the peptide decreased with higher concentrations of oxidized HDL2 and oxidized HDL3. CONCLUSION: Because modified HDLs (oxidized HDL and tetranitromethane HDL) do not bind to the 'HDL receptor' to stimulate endothelin secretion, we propose that the stimulation of secretion is mediated by unspecific binding of the lipoprotein to the cell membrane. Nevertheless, oxidized HDL and tetranitromethane HDL may stimulate endothelin secretion via the scavenger-receptor pathway. Our results suggest that HDL and modified HDL participate in the regulation of vascular tone.

A high concentration of melatonin inhibits in vitro LDL peroxidation but not oxidized LDL toxicity toward cultured endothelial cells.

The pineal hormone, melatonin, was recently found to be a potent free scavenger for hydroxyl and peroxyl radicals. Melatonin also inhibits neuronal and thymocyte damage due to oxidative stress. Atherosclerosis development is mediated by low-density lipoprotein (LDL) oxidation and the endocytosis of oxidized LDL by resident macrophages in the subendothelial vascular wall. Furthermore, the cytotoxic effect of oxidized LDL increases atherogenicity. The goal of this study was to compare the antioxidant activities of melatonin and vitamin E against in vitro LDL oxidation and their cytoprotective actions against oxidized LDL-induced endothelial cell toxicity. An attempt at loading LDL with melatonin by incubating human plasma with an ethanolic melatonin solution gave only low protection against Cu2+-induced LDL oxidation in comparison with vitamin E and gave no detectable incorporation of melatonin into LDL, measured by high-performance liquid chromatography (HPLC) coupled to UV detection. High concentrations of melatonin (10-100 microM) added to the oxidative medium induced a clear inhibition of Cu2+-induced LDL oxidation, characterized as an increase in the lag-phase duration of conjugated diene formation and decreases in the maximal rate of the propagation phase and in the maximal amount of conjugated diene formation. Determination of the median efficacious dose (ED50) of melatonin and vitamin E by their ability to increase lag-phase duration showed that melatonin was less active than vitamin E (ED50, 79 vs. 10 microM, respectively). Melatonin was also less active than vitamin E in limiting the formation of thiobarbituric acid-reactive substances (TBARS) and LDL fluorescence intensity increase in the medium during Cu2+-induced LDL oxidation. Cu2+-induced LDL oxidation in the presence of 100 microM melatonin produced oxidized LDLs that were less recognizable for the scavenger receptors of J774 macrophages than were untreated LDLs. Vitamin E, 10 microM, was more active than 100 microM melatonin in inhibiting LDL oxidation and the resulting lipoprotein alterations leading to binding internalization and degradation by the J774 macrophages. Vitamin E, 100 microM, inhibited the pursuit of the oxidation of oxidized LDL mediated by bovine aortic endothelial cells (BAECs) in a culture medium containing Cu2+, whereas 100 microM melatonin had no antioxidant effect. Melatonin, 100 microM, as well as 100 microM vitamin E inhibited intracellular TBARS formation during the incubation of BAECs with highly oxidized LDL but had no influence on the increase in glutathione (GSH) concentration during this lengthy exposure (16 h) of BAECs to highly oxidized LDL. During this period, the same dose of vitamin E but not of melatonin tended to limit the decrease in adenosine triphosphate (ATP) concentration. Vitamin E, 100 microM, did not significantly reduce cellular lactate dehydrogenase (LDH) release in the culture medium during the incubation of oxidized LDL with BAECs, whereas 100 microM melatonin dramatically increased this release. These data show that melatonin is less active than vitamin E in inhibiting in vitro LDL oxidation and does not inhibit the cytotoxicity of oxidized LDL toward cultured endothelial cells. The concentrations necessary to inhibit LDL oxidation are far beyond those found in human plasma (100 microM vs. 100 pM). Therefore our results indicate that the pineal hormone melatonin per se appears to have little antiatherogenic property in the in vitro oxidation of LDL and the cytoprotective action against the toxicity of oxidized LDL. Nevertheless, in vivo LDL oxidation takes place in the subendothelium of the artery wall, and nothing is known about the concentration of melatonin or its catabolites in this environment.

Metabolic syndrome among Caribbean-born persons living in the U.S. Virgin Islands

OBJECTIVES. To determine the frequency of the metabolic syndrome (MS) among four subpopulations in the United States Virgin Islands and to estimate the risk for the MS that is associatd with waist circumference cutpoints among overweight and obese individuals. CONCLUSIONS. The frequency of the MS among Caribbean-born persons in the U.S. VirginIslands is comparable to the frequency of the MS among the general population on the mainland of the United States. Among Caribbean-born persons living in the U.S. Virgin Islands, those who are Hispanic blacks may have a greater risk of cardiovascular disease than do other groups (AU)

Nuevas tecnologías aplicadas a la cirugía laparoscópica. telecirugía y robótica / New technologies applied to laparoscopic surgery: telesurgery and robotics

Un repaso a la situación actual de nuestros quirófanos demuestra la continua inclusión de nuevos aparatos. La cirugía laparoscópica ha saturado el espacio de la sala de operaciones, creando un sinfín de incomodidades a todo el personal. La introducción de las nuevas tecnologías en nuestros hospitales facilita la labor diagnóstica y terapéutica al médico, al verse ampliado el abanico de posibilidades, y comporta beneficios para el paciente ya que permite un proceso más rápido y preciso y un acto terapéutico menos agresivo, menos traumático, con una recuperación más rápida y cómoda. Quizá valga la pena señalar las desventajas que también conlleva su uso, como son el encarecimiento del tratamiento por el coste del material y del personal que debe manejarlo, o la necesaria reorganización del modelo asistencial que conlleva una reubicación de los recursos, incluidos los profesionales. A éstos se les exige el esfuerzo continuado para estar al día, superar las incomodidades derivadas del manejo de instrumentos y aparatos insuficientemente desarrollados y aprovechar estas nuevas posibilidades en la atención a sus pacientes. La aplicación de la informática y de nuevas vías de comunicación hará que el escenario de nuestras actuaciones varíe, tanto en el aspecto externo como en la composición de los equipos quirúrgicos, en los que personal que actualmente cumple una función asistencial será sustituido por otro especializado en informática, ingeniería, psicología, etc. El futuro permitirá que las máquinas colaboren activamente en el desarrollo de los procedimientos terapéuticos, e incluso lleven a cabo los mismos actos que hoy día realiza el hombre, pero de forma mucho más rápida y precisa, sin el cansancio o el relajamiento y falta de atención, implícitos en la condición humana (AU)

Consideracoes propedeuticas e terapeuticas. Acerca de reticuloendoteliose leucemica. Relato de um caso. / Propedeutic and therapeutic considerations on leukemic reticuloendotheliosis. Report of a case

E relatado um caso de reticuloendoteliose leucemica ("hairy-cell leukaemia"), no qual a propedeutica hematologica foi realizada atraves de diversos aspectos: imunologico, citologico, citoquimico e morfologico por microscopia eletronica. Salienta-se as dificuldades diagnosticas e peculiaridade do tratamento pela cirurgia, incomum nos outros tipos de leucemia