The role of cerebral oximetry in combination with awake testing in patients undergoing carotid endarterectomy under local anaesthesia.

INTRODUCTION: The aim of this study is to analyse the role of cerebral oximetry in combination with awake testing in detecting cerebral ischaemia in patients undergoing carotid endarterectomy (CEA) under local anaesthesia (LA). METHODS: One hundred consecutive patients scheduled for CEA under LA were investigated. Regional oxygen saturation (rSO(2)) was measured with a cerebral oximeter. Cerebral ischaemia was assessed by awake testing in conjunction with rSO(2). Shunting was based solely on deterioration in conscious state assessed by awake testing. The correlation between awake testing and percentage fall in rSO(2) levels was statistically analysed. RESULTS: Patients requiring general anaesthesia were excluded from analysis (n = 17). Seven patients developed deterioration in conscious state and an immediate drop in rSO(2) ≥20% following carotid cross-clamping. Two patients requiring shunting for non-neurological reasons were excluded from analysis. Two patients had a drop in rSO(2) ≥20%, but remained conscious and were not shunted. There were no permanent neurological deficits postoperatively. Statistical analysis showed a sensitivity of 100% with a specificity of 96% yielding a positive predictive value of 81% and negative predictive value of 100% for a ≥19% drop in rSO(2). CONCLUSION: Cerebral oximetry using a cut off ≥19% drop in rSO(2) has a high sensitivity and specificity when compared with awake testing.

Comércio formal e perfil de consumidores de plantas medicinais e fitoterápicos no município de Itaqui - RS / Formal trade and profile of consumers of medicinal plants and phytomedicine in Itaqui Municipality, Rio Grande do Sul State, Brazil

O presente trabalho visou realizar um diagnóstico sobre os consumidores de plantas medicinais e fitoterápicos, abordando também alguns aspectos relacionados à comercialização, no município de Itaqui-RS. A coleta de dados foi efetuada em duas etapas complementares, centrada nos consumidores e estabelecimentos de comercialização, mais especificamente farmácias. Primeiramente diagnosticou-se o perfil dos usuários de plantas medicinais, através de questionário semi-estruturado que foi aplicado a 183 pessoas abordadas em áreas de circulação de moradores de todos os bairros do município; na segunda etapa, avaliou-se a comercialização e visão do comércio formal nas oito farmácias do município. De acordo com os resultados das entrevistas para a construção do perfil dos usuários de plantas medicinais observou-se que 71 por cento dos entrevistados ficaram na faixa etária de 21 a 60 anos e que a grande maioria apresenta renda mensal de até três salários mínimos; quanto ao uso de plantas na medicina popular, cerca de 82 por cento afirmaram terem obtido eficiência e que em caso de problemas de saúde 47 por cento procuram pelas plantas; quanto ao cultivo, 55 por cento dos entrevistados às cultivam em suas residências. Na segunda etapa realizada em farmácias, observou-se que a compra de fitoterápicos e plantas medicinais era realizada praticamente por mulheres, das quais 75 por cento adultas e 25 por cento idosas. Os chás mais vendidos foram principalmente os emagrecedores e digestivos e o valor gasto com esse tipo de produto ficou na faixa de R$ 1,00 a R$ 3,00. Conclui-se que existe mercado para plantas medicinais e fitoterápicos e necessidade de maiores informações referentes à forma de cultivo, correta identificação botânica, informações ao consumidor, qualidade e eficácia dos produtos e seu uso.

This study aimed to make a diagnosis of consumers of medicinal plants and phytomedicine, also addressing some aspects related to trade in Itaqui Municipality, Rio Grande do Sul State, Brazil. Data collection was performed in two complementary stages focusing on consumers and stores, especially drugstores. First, the profile of medicinal plant users was diagnosed through a semi-structured questionnaire which was applied to 183 people approached in areas frequently visited by inhabitants from different villages of the municipality; in the second stage, the trade and the view of formal trade was evaluated in the eight drugstores of the municipality. The results of interviews to build the profile of medicinal plant users showed that 71 percent interviewees were between 21 and 60 years old and most of them had monthly income of up to three minimum wages; as to the use of plants in folk medicine, around 82 percent stated to have had efficiency and, in cases of health problems, 47 percent searched for these plants; as regards cultivation, 55 percent interviewees cultivated medicinal plants in their houses. The second stage, carried out in drugstores, also indicated that phytomedicines and medicinal plants were purchased mostly by women, 75 percent adults and 25 percent elderly. The most sold teas were slimming and digestive teas, and the value paid for this type of product was between R$ 1.00 and R$ 3.00. In conclusion, there is market for medicinal plants and phytomedicine and there is also the need for further information related to their cultivation form and proper botanical identification, as well as information to users, quality and efficacy of products, and their use.

Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance.

OBJECTIVES: This study was designed to determine the effect of two weeks' treatment with L-arginine on the ratio of plasma L-arginine to asymmetric dimethylarginine (ADMA), oxidative stress, endothelium-dependent vasodilatation to acetylcholine, exercise performance and heart rate variability in men with stable angina. BACKGROUND: The ratio of plasma L-arginine:ADMA has been proposed as a determinant of endothelium-dependent dilation; dietary supplementation with L-arginine has been shown to improve endothelium-dependent vasodilation and symptoms in some conditions. METHODS: Men (n = 40) with stable angina, at least one epicardial coronary artery with a stenosis >50% and a positive exercise test were randomized to receive L-arginine (15 g daily) or placebo for two weeks according to a double-blind parallel-group design. Plasma L-arginine, ADMA, 8-epi-prostaglandin F2alpha (a marker of oxidative stress) and forearm vasodilator responses to brachial artery infusion of nitroprusside and acetylcholine (+/-L-arginine) were measured. A standard Bruce protocol exercise test was performed before and at the end of the treatment period. RESULTS: Plasma L-arginine increased after oral L-arginine, whereas ADMA remained unchanged, leading to an increase in the L-arginine/ADMA ratio of 62 +/- 11% (mean +/- SE, p < 0.01). Despite a significant enhancement in acetylcholine response by intra-arterial L-arginine at baseline, this response remained unchanged after oral L-arginine. Measures of oxidative stress and exercise performance after L-arginine/placebo were similar in placebo and active groups. CONCLUSIONS: In men with stable angina, an increase in plasma L-arginine/ADMA ratio after two weeks' oral supplementation with L-arginine is not associated with an improvement in endothelium-dependent vasodilatation, oxidative stress or exercise performance.

The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17beta-estradiol.

BACKGROUND: Genistein, a phytoestrogen, may have estrogenic cardioprotective actions. We investigated whether genistein influences endothelium-dependent vasodilation in forearm vasculature of healthy human subjects and compared the effects of genistein with those of 17beta-estradiol. METHODS AND RESULTS: The brachial arterial was cannulated with a 27-gauge needle for drug infusion. Forearm blood flow responses were measured with strain-gauge plethysmography. Genistein (10 to 300 nmol/min, each dose for 6 minutes) produced a dose-dependent increase in forearm blood flow from 3.4+/-0.3 to 9.6+/-1.3 mL x min(-1) x 100 mL forearm(-1) (mean+/-SEM) in men (n=9, P:<0.0001 by ANOVA). The mean forearm venous concentration of genistein during infusion of the highest dose was 1.8+/-0.3 micromol/L in 6 additional men. Genistein produced a similar increase in blood flow in premenopausal women. Daidzein, another phytoestrogen, was ineffective, but equimolar concentrations of 17beta-estradiol caused similar vasodilation to genistein. Responses to genistein and 17beta-estradiol were inhibited to the same degree by the NO synthase inhibitor N:(G)-monomethyl-L-arginine. A threshold dose of genistein potentiated the endothelium-dependent vasodilator acetylcholine but not the endothelium-independent vasodilator nitroprusside. CONCLUSIONS: Genistein causes L-arginine/NO-dependent vasodilation in forearm vasculature of human subjects with similar potency to 17beta-estradiol and potentiates endothelium-dependent vasodilation to acetylcholine.

Volatile anesthetics differentially affect immunostimulated expression of inducible nitric oxide synthase: role of intracellular calcium.

BACKGROUND: Nitric oxide released by inducible nitric oxide synthase (iNOS) plays an important role in immune responses and systemic vasodilation in septic shock. Volatile anesthetics have been reported to interfere with signal transduction and gene expression. We studied the effect of volatile anesthetics on activity and expression of iNOS and potential mechanisms of action. METHODS: Nitrite release and iNOS expression were determined using the Griess reaction and Western and Northern blot techniques, respectively, in J774 murine macrophages stimulated with lipopolysaccharide and gamma-interferon in the absence and presence of various concentrations (0.25-2.0 minimum alveolar concentration [MAC]) of volatile anesthetics (i.e., halothane, enflurane, isoflurane, desflurane). Furthermore, potential interference of volatile anesthetics with specific signal transduction pathways was investigated. RESULTS: All volatile anesthetics, studied in a time- and dose-dependent manner, suppressed nitrite production and iNOS expression in J774 macrophages stimulated by lipopolysaccharide or gamma-interferon at clinically relevant concentrations. The inhibition was completely antagonized by ionomycin but unaffected by diacylglycerol, phorbol myristate acetate, and C2-ceramide. In contrast, in cells costimulated by lipopolysaccharide plus gamma-interferon, volatile anesthetics significantly increased nitrite production and iNOS expression independent of ionomycin and other mediators studied. CONCLUSIONS: Volatile anesthetics strongly reduced the mRNA and protein levels of iNOS and NOS activity after a single stimulation with lipopolysaccharide or gamma-interferon, most likely by attenuating intracellular calcium increase. Costimnulation with lipopolysaccharide plus gamma-interferon, however, results in maximum iNOS expression and activity, which are no longer inhibited but are potentiated by volatile anesthetics by unidentified mechanisms.

[Prognosis of children with acute myelocytic leukemia after first relapse]. / Prognose von Kindern mit AML nach dem ersten Rezidiv.

UNLABELLED: Nearly 40% of children treated within the AML BFM studies experience recurrence of their disease after having achieved remission. In our retrospective analysis we tried to estimate prognosis after relapse in children treated with intensive relapse regimens and studied the impact of prognostic factors for second remission and survival. PATIENTS: 102 patients suffering from first relapse were treated intensively according to the relapse protocols BFM REZ91 and REZ93 or intensive salvage therapy consisting of double induction with high dose Ara-C, mitoxantrone and VP-16. Once in CR, patients continued to receive a 6-week consolidation and either allogeneic or autologous bone marrow transplantation (BMT). RESULTS: Time to relapse was in median 1.1 years, range 0-8 years. Fifty-two of 102 pts. (51%) achieved 2nd remission (CR), 10 (10%) partial remission, 37 (36%) were nonresponders, and 3(3%) died early during salvage therapy. Twenty-seven were still in CR, median 2.5 years, range 0.4-7.0 years, with an overall survival of 21%, SE 5% after 5 years. The response and survival rate was similar in all treatment groups. Fifty patients were transplanted, 43 being in 2nd CR, and 7 with residual blasts. Twenty-seven patients received an allograft: Twenty-one from a matched sibling (MSD), 1 from a haploid and 5 from a matched unrelated donor (MUD); 23 received an autograft. None of the patients transplanted in partial remission survived. Whereas 7 of 16 patients were alive after MSD in 2nd CR, 1 after haploid BMT. Four of 5 patients died after MUD BMT. Multivariate risk factor analysis revealed duration until relapse to be the most important factor for survival after relapse. The maximum risk-ratio was obtained at a threshold value of 1.5 years after diagnosis resulting in a 5-year survival of 10%, SE 5% for early relapse, and 40%, SE 10% for late relapse, p logrank 0.0001. CONCLUSION: Intensive relapse regimens can induce a 2nd CR in half of the patients. Children with late relapse (> 1.5 years after diagnosis) have a realistic chance for longtime survival.

Lack of effect of vitamin E on L-arginine-responsive endothelial dysfunction in patients with mild hypercholesterolaemia and coronary artery disease.

1. Dietary supplementation with vitamin E reduces ischaemic events in patients with established coronary artery disease and improves endothelial function in cholesterol-fed rabbits. We examined whether such dietary supplementation with vitamin E improves endothelial function in patients with mild hypercholesterolaemia and coronary artery disease. 2. Twenty patients (total cholesterol 6.8 +/- 1.1 mmol/l, mean +/- SD) with angiographically documented coronary artery disease were randomly allocated to receive placebo (n = 10) or vitamin E, 400 i.u. daily, (n = 10) for 8 weeks. Endothelium-dependent and independent vasodilatation within forearm vasculature was assessed by brachial artery infusion of acetylcholine (co-infused with saline vehicle and L-arginine) and nitroprusside before and after supplementation. 3. Plasma concentrations of vitamin E increased from 32.9 +/- 3.8 to 69.1 +/- 11.8 mumol/l (means +/- SE) in the vitamin E-supplemented group (P < 0.01) but did not change significantly in the placebo group. Lipid profiles remained similar before and after supplementation in both groups. Forearm blood flow responses to acetylcholine (7.5 and 15 micrograms/min) and nitroprusside (3 and 10 micrograms/min) were similar before and after supplementation in both groups. Acute intra-arterial administration of L-arginine (10 mg/min) augmented the response to acetylcholine (15 micrograms/min) in both groups before and after supplementation to a similar degree (mean augmentation: 60 +/- 18%, P < 0.01). 4. Acute administration of L-arginine reverses endothelial dysfunction in forearm vasculature of patients with mild hypercholesterolaemia and coronary artery disease but supplementation with vitamin E (400 i.u. daily) for 8 weeks does not reverse L-arginine-responsive endothelial dysfunction.

In vivo 31P NMR spectroscopy of human musculoskeletal tumors as a measure of response to chemotherapy.

The value of in vivo 31P NMR spectroscopy to provide indicators of response to cytostatic chemotherapy was studied in patients with malignant musculoskeletal tumors. Characteristics of untreated cancers were strong signals of PME and PDE, moderately increased Pi and low PCr. The intracellular pH was slightly alkaline. The intracellular concentration of free magnesium was 70% of that in muscle. Spectroscopic findings at different times of therapy were compared with the percentage of tumor necrosis after surgical resection in 28 patients. In follow-up studies, energy-rich phosphates declined in nonresponders, while PME, Pi and frequently PDE increased. Treatment response appeared to involve the reversal of these trends. In five responders, a biphasic pattern was observed, i.e. initially the spectrum changed into that of severely ischemic cell injury followed by a successive phase of apparent 'tumor activation'. Pretreatment levels of (PCr+Pi)/total phosphate > or = 0.35 and PCr/ alpha-NTP > or = 1.5, an accelerated increase in total low-energy phosphates/total high-energy phosphates (> or = 3.0%/day) after the initial drug application, and a long-term decrease (< or = -0.4%/day) during later therapy were highly indicative of tumor response to chemotherapy. Such spectroscopic predictors for treatment response proved to be superior to currently used indices such as tumor size.

Vaginal lubricants for the infertile couple: effect on sperm activity.

OBJECTIVE: To determine the effects of natural vegetable oils and vaginal lubricants on sperm motion and viability. DESIGN: Four widely used vaginal lubricants (K-Y Jelly, Astroglide, Replens, and Touch) and two vegetable oil products that have been used as vaginal lubricants were purchased through local vendors. Sperm was obtained by masturbation without lubrication from normal, healthy donors. Lubricants were mixed with sperm from individual donors and the effects on sperm motility were determined at 1, 15, 30, and 60 minutes. SETTING: Southwestern Fertility Associates of The University of Texas Southwestern Medical Center at Dallas. MAIN OUTCOME MEASURES: Sperm motility was evaluated by manual motility counts and by computer-assisted semen analysis. Sperm viability was evaluated with Hoechst 33258 dye. The effects of the various lubricants were compared with those of a spermicidal agent, Gynol II (negative control) and Ham's F-10 (positive control). RESULTS: Commercial lubricants inhibited sperm motility by 60-100% after 60 minutes of incubation. Sperm exposed to Replens or Astroglide were nonmotile and nonviable after incubation for 60 minutes, similar to the control, nonoxynol-9 containing product Gynol II. Canola oil had no detrimental effects and was indistinguishable from Ham's F-10 in terms of sperm viability and motility. CONCLUSIONS: For couples with infertility, the use of vaginal lubricants during intercourse is not recommended. In cases where a lubricant is required, careful selection can maximize sperm motility and viability.

A continuous microtiter plate assay for screening nucleotide sugar-synthesizing nucleotidyltransferases.

A continuous microtiter plate nucleotidyltransferase substrate screening assay (NUSSA) is described which allows the identification of nucleotide sugar-synthesizing enzyme activities. The assay is accomplished by the determination of the common product of these enzymes PPi with a PPi-dependent phosphofructokinase. A subsequent enzyme reaction cascade leads to the production of 2 mol NAD per mol PPi. PPi-dependent phosphofructokinase was purified from potato with respect to contaminating enzyme activities which would disturb NUSSA performance. NUSSA allows the quick, simultaneous, and comprehensive check of different sugar 1-phosphate and nucleoside triphosphate substrates using purified pyrophosphorylases or crude extracts of plants, microorganisms, and mammalian tissues. Moreover, NUSSA will assist to evaluate these enzymes for the synthesis of important nucleotide sugars which serve as substrates of glycosyltransferases in carbohydrate syntheses.

Inhibition of acetylcholinesterase selectively potentiates NG-monomethyl-L-arginine-resistant actions of acetylcholine in human forearm vasculature.

1. NG-monomethyl-L-arginine (L-NMMA, a nitric oxide synthase inhibitor) inhibits vasodilator responses to acetylcholine but not methacholine in human forearm vasculature. To investigate whether this difference results from the relative susceptibility of these agonists to hydrolysis by acetylcholinesterase, we studied vasodilator responses to brachial artery administration of acetylcholine alone and in the presence of the acetylcholinesterase inhibitor edrophonium. 2. Vasodilator responses to constant-rate brachial artery infusions of acetylcholine were biphasic, with an initial peak response fading over 2 min to a plateau. Fade [(peak-plateau)/peak x 100%] was dose dependent (P < 0.02), ranging from 43 +/- 7% (mean +/- SEM) at low dose (16 nmol/min) to 9 +/- 8% at high dose (83 nmol/min). 3. Edrophonium (0.5 mumol/min intra-arterially) alone produced no change in forearm blood flow but increased blood flow responses to acetylcholine (P < 0.01), causing an approximately 10-fold reduction in the dose required to increase plateau blood flow by 10 ml min-1 100 ml-1. 4. Responses to low doses of acetylcholine alone (16 and 41 nmol/min) faded more (P < 0.01) than those to doses of acetylcholine with edrophonium chosen to produce similar plateau blood flows. Responses to acetylcholine (41 nmol/min) also faded more (P < 0.01) than those to methacholine (5 nmol/min), producing matched plateau flows. 5. Peak and plateau responses to acetylcholine (41 nmol/min) were reduced (P < 0.01) by similar amounts (47 +/- 15%, and 37 +/- 13% respectively, P = 0.39) by coinfusion of L/NMMA (4 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS)

[EEG-slowing after high-dose Methotrexate with citrovorumfactor-rescue. A spectralanalytic study (author's transl)]. / EEG-Verlangsamung nach hochdosiertem Methotrexat mit Citrovorumfaktor-Schutz. Eine spektralanalytische Untersuchung.

In 23 treatment courses of high-dose Methotrexate (MTX) with Leukovorin-rescue for osteogenic sarcoma serial EEG-examinations before and after MTX-infusion were done. In 11 course Vincristine had been administered additionally. Frequency-analysis of EEG-background activity was performed by computer-based FFT. At the end of the MTX-infusion EEGs were unchanged, compared with the findings before start of treatment. At 24 and 48 hours after start of infusion, there was a slight but statistically significant slowing, recognizable from an increase of the theta/alpha-ratio (median + 48%, range -7% to + 373%) and a drop of dominant frequency (median-8%, range +12% to -53%). There was a stronger trend towards normalisation in patients, not having received Vincristine. The greatest changes were found in a patient, whose serum-MTX-concentration at 24 hours exceeded the upper therapeutic limit. The EEG-findings are discussed as an equivalent of a subclinical MTX-encephalopathy. Acute encephalopathies with severe EEG-changes and morphological changes on CT have been observed in MTX-intoxications.

Use of fracture mechanics theory in lifetime predictions for alumina and bioglass-coated alumina.

The fatigue behavior of alumina and bioglass-coated alumina was determined in air and biological test environments by the dynamic fatigue test technique in which strength is measured as a function of stressing rate. The good correlation found between the test data and fracture mechanics theory indicates that fatigue failure is controlled by the slow crack growth of preexisting flaws and that fracture mechanics theory can be used in making failure predictions for alumina and bioglass-coated alumina in biological environments. Thus, it is believed that lifetime predictions can be made for ceramic implants on the basis of short-term test data utilizing fracture mechanics principles.

[Histochemistry of cholinergic systems in the CNS. I. Topochemical and quantitative changes in acetylcholinesterase activity in the limbic cortex after septal lesions in the rat (author's transl)]. / Zur Histochemie cholinerger Systeme im ZNS. I. Topochemische und quantitative Veränderungen der AChE-Aktivität im limbischen Cortex bei Ratten nach Septumläsion

In brains of female albino rats the influence of septal and paraseptal lesions on the activity of acetylcholinesterase in the limbic cortex (hippocampal formation, regio limbica anterior et posterior, regio retrosplenialis) was investigated topochemically and also by a quantitative histophotometrical method. On the 4th day after bilateral lesion of the nuclei septi mediales the AChE-activity was diminished to residual values of 10 to 20% in comparison with sham-operated animals in all regions and layers of hippocampus and area dentata. Unilateral lesions of ncl. septi medialis cause stronger decreases in activity only ipsilaterally. Lesions surrounding the medial septal nuclei (ncl. septi lateralis, rostral septum, lateral hypothalamus, area preoptica especially) did not influence the enzyme activity in the hippocampal formation. After lesions in the rostral part of septum with intact medial nuclei, a reduced activity was found ipsilaterally in the layers of cingular cortex with residual values of 25 to 75% of the unaffected contralateral side. After destruction of the gyrus cinguli itself significantly lesser residual activities could be detected in this region caudal to the lesion. Quantitative estimations showed that 80 to 90% of the AChE-activity which was established by histochemical means in the hippocampal formation is immediately related to septal neurones. From these results it is evident that the hippocampal formation receives nearly all its cholinergic innervation from the medial septum exclusively. However, the cingular cortex seems to be an integrating field of other cholinergic afferences.