Role of vitamin C on adrenocortical effects of etomidate]

This study was carried out to assess whether the adrenal inhibition induced by etomidate could be prevented by associating ascorbic acid with etomidate, as a protective effect of ascorbic acid administered three hours after etomidate has been described. Sixteen ASA 1 or 2 patients, less than 65 years old, free of endocrine disease, were included. At induction of anaesthesia, eight of them (group B) were given an infusion of ascorbic acid 1 g, in 500 ml of 5% glucose. Group A patients (n = 8) were given 500 ml of 5% glucose. Anaesthesia was induced with etomidate 0.3 mg.kg-1, fentanyl 0.005 mg.kg-1 and vecuronium 0.1 mg.kg-1. Maintenance was carried out using a continuous infusion of etomidate (0.1 mg.kg-1.h-1 for 10 min, followed by 0.01 to 0.02 mg.kg-1.h-1). Additional boluses of fentanyl or diazepam (10 mg) were administered when arterial blood pressure or heart rate were 20% greater than preanaesthetic values. The number of injections required was the same in both groups. Plasma cortisol concentrations were measured by radioimmunoassay (RIA) before anaesthesia (T0), 4 h (T4) and 24 h (T24) after the end of surgery. Blood ACTH levels were also assessed by RIA at T0 and T4. The adrenal insufficiency at T4 had completely ended at T24. In fact, the relative decrease in cortisol levels was greater in patients treated with ascorbic acid (T4/T0: 47.6 +/- 9% in group A vs 76.5 +/- 33% in group B, p less than 0.05); this was suggestive of a higher degree of adrenal inhibition in patients receiving ascorbic acid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Memory Enhancing Effect of Low-dose Sevoflurane Does Not Occur in Basolateral Amygdala-lesioned Rats

Background: Certain anesthetics might enhance aversive memory at doses around 0.1 minimum alveolar concentration. This issue was investigated in a rat model of learning and memory. In addition, evidence for basolateral amygdala (BLA) involvement in mediating memory enhancement was sought.

Methods: First, the memory-enhancing potential of various anesthetics was determined. Rats underwent single-trial inhibitory avoidance training (0.3 mA shock/1 s) during exposure to air, 0.11% sevoflurane, 0.10% halothane, 0.77% desflurane, or 0.12% isoflurane. Memory was assessed at 24 h. Second, the BLA contribution to sevoflurane memory enhancement was determined. Rats received bilateral excitotoxic N-methyl-d-aspartate (12.5 mg in 0.2 [mu]l per BLA) lesions of the BLA 1 week before training. Memory of lesioned and control rats was compared 24 h after training in air or sevoflurane.

Results: Sevoflurane exposure during training significantly enhanced 24-h retention performance for both nonoperated and sham-operated rats (P < 0.005 for both vs. their respective controls). Halothane, but not desflurane or isoflurane, also enhanced retention performance (P < 0.05). However, halothane-induced hyperalgesia during learning clouds interpreting enhanced retention performance solely as a memory consolidation effect. BLA lesions significantly reduced and equalized retention performance for both sevoflurane- and air-exposed animals. Lesions blocked memory enhancement without also causing a generalized inability to learn, because additional training revealed essentially normal task acquisition and 24-h memory.     

Oxygen permeability of hard gas permeable contact lens materials

Oxygen transmissibility (Dk/L) data of contact lenses enables prediction of the ocular response during wear. However, there has been difficulty in relating the data from highly permeable rigid lens materials to models predicting corneal swelling based upon the Dk/L of soft lenses. We have examined the methodology used to determine the oxygen permeability (Dk) of hard gas permeable (HGP) materials, and have applied a measurement technique that overcomes certain deficiencies of previous methods. A representative range of HGP and hydrophilic lens materials was measured. The Dk values reported here for hydrophilic materials are in close agreement with those published elsewhere. However, the Dk values of HGP materials were found to be substantially less than those reported previously, although the relative ranking appears to be independent of measurement technique. Possible explanations of these findings are presented.     

Aromatic amino analogues of artemisinin: synthesis and in vivo antimalarial activity

Nine orally active novel artemisinin derivatives were prepared from artemisinin by four-step synthesis, and the compounds were evaluated in the rodent model using multidrug resistant Plasmodium yoelii nigeriensis. All of the compounds exhibited antimalarial activities with the ED₅₀ ranging from 5.41 mg/kg–12.4 mg/kg. Among them, artemisinin derivative bearing N-(4-hydroxy-3-((4-phenylpiperazin-1-yl)methyl)phenyl) moiety (5f) was found to be the most active compound and was found to be three times more potent than artemisinin (ED₅₀ 16.4 mg/kg).     

Estimating gene penetrance from family data

Family data are useful for estimating disease risk in carriers of specific genotypes of a given gene (penetrance). Penetrance is frequently estimated assuming that relatives' phenotypes are independent, given their genotypes for the gene of interest. This assumption is unrealistic when multiple shared risk factors contribute to disease risk. In this setting, the phenotypes of relatives are correlated even after adjustment for the genotypes of any one gene (residual correlation). Many methods have been proposed to address this problem, but their performance has not been evaluated systematically. In simulations we generated genotypes for a rare (frequency 0.35%) allele of moderate penetrance, and a common (frequency 15%) allele of low penetrance, and then generated correlated disease survival times using the Clayton‐Oakes copula model. We ascertained families using both population and clinic designs. We then compared the estimates of several methods to the optimal ones obtained from the model used to generate the data. We found that penetrance estimates for common low‐risk genotypes were more robust to model misspecification than those for rare, moderate‐risk genotypes. For the latter, penetrance estimates obtained ignoring residual disease correlation had large biases. Also biased were estimates based only on families that segregate the risk allele. In contrast, a method for accommodating phenotype correlation by assuming the presence of genetic heterogeneity performed nearly optimally, even when the survival data were coded as binary outcomes. We conclude that penetrance estimates that accommodate residual phenotype correlation (even only approximately) outperform those that ignore it, and that coding censored survival outcomes as binary does not substantially increase the mean‐square errror of the estimates, provided the censoring is not extensive. Genet. Epidemiol. 34: 373–381, 2010. © 2010 Wiley‐Liss, Inc.     

Assessment of dσ*/dtmax, a Load Independent Index of Contractility, in the Canine

The search for a load-independent index of myocardial contractility has been a focus for nearly 100 years. Nearly all of the parameters developed have yielded insight into cardiac function but their clinical utility has been limited. A new index, dσ*/dt _max, has been proposed to be useful in the clinic. This parameter is expressed as the maximum time rate of change of the pressure normalized circumferential wall stress (σ* = σ _θ /P, where σ _θ is circumferential wall stress and P is pressure) for a thick walled sphere model of the left ventricle (LV). This definition for a contractility index renders dσ*/dt _max dependent only on LV wall volume (V _m) and maximum time rate of change of the ventricular volume, dV/dt _max. The index dσ*/dt _max has been studied in patients with echocardiogram-derived volume, but up until this point its characteristics in canines have remained unknown. Validating this index in the canine will allow for a more intensive and wide-range investigation of the index that is not available with humans. The purpose of this study was to validate dσ*/dt _max as a load-independent measure of contractility in the canine heart with the hope that it was a noninvasive assessment of contractile function. To assess the load independence of dσ*/dt _max, the index was estimated over a range of preloads (end diastolic volume, EDV) during a vena caval occlusion (VCO). The study was conducted in five canines under various pacing modes [right atrial (RA), right ventricular (RV), left ventricular (LV), and biventricular (BV)] at rates of 90 or 100, and 160 bpm. The animals’ ventricular volume measurements were assessed by conductance catheter, calibrated with echocardiography. A 50 Hz filter was applied to the volume signal before differentiation to obtain dV/dt _max. Echocardiography was used to calculate left ventricle mass and V _m. In eight of ten cases, dσ*/dt _max was significantly correlated with decreasing EDV (p < 0.05). There was also a significant correlation between dσ*/dt _max and dP/dt _max. With a strong correlation between the values of dσ*/dt _max, dP/dt _max, and EDV in all five subjects, dσ*/dt _max is not load independent in the canine heart when preload is altered by a VCO. Further evaluation of this index is required to delineate the situations where dσ*/dt _max can be accurately applied.     

NK cell function in a patient with IgM monoclonal antibody against myelin-associated glycoprotein

Anti-Leu 7 antibody reacts with determinants on a subset of natural killer (NK) cells and myelin-associated glycoprotein (MAG). In a patient patient with peripheral neuropathy and IgM autoantibodies against MAG, we found the distribution and functions of NK cells to be normal.