Association study of functional polymorphisms of dopaminergic pathway in epilepsy-related factors of temporal lobe epilepsy in Brazilian population.

BACKGROUND AND PURPOSE: There are few data about the role of neurotransmission modulated by dopamine in epilepsy, especially temporal lobe epilepsy (TLE). This is the first study that aimed to analyze the dopaminergic polymorphisms in an etiologically homogeneous group of patients with TLE with hippocampal sclerosis. Selected polymorphisms were: (i) the most expressed D2-like receptors in the limbic system (DRD2/ANKK1 TAQ-1A, D4_VNTR and D4_rs1800955); (ii) the dopamine transporter (DAT) 3'-untranslated region and intron 8; and (iii) two degrading enzymes regulating the synaptic activity, i.e. the main metabolizer of dopamine, catechol-O-methyltransferase, and monoamine oxidase A. METHODS: We assessed 119 patients with unequivocal TLE with hippocampal sclerosis and 112 healthy volunteers. Individuals were genotyped for the polymorphisms of the gene encoding dopaminergic pathway transporter DAT haplotype, dopaminergic receptors, catechol-O-methyltransferase and monoamine oxidase A. We also evaluated epilepsy-related factors (e.g. seizure frequency, age of onset, duration and status epilepticus). RESULTS: There was no difference between the groups for the studied polymorphisms. The polymorphism DRD4_VNTR was associated with family history of epilepsy (P = 0.003), DRD2_rs1800497 was related to status epilepticus (P = 0.022), and intron 8 VNTR DAT was related to higher seizure frequency (P = 0.019) and family history of epilepsy (P = 0.011). CONCLUSIONS: Our findings demonstrated that polymorphisms of the dopaminergic pathway are associated with significant clinical features of this form of epilepsy, such as seizure frequency, family history of epilepsy and status epilepticus.

Laparoscopic cholecystectomy in a patient with Steinert myotonic dystrophy. Case report.

Myotonic dystrophy (MD) is a serious multi-systemic autosomal dominant disease. The estimated incidence is 1 in every 8000 births, with an estimated prevalence of between 2.1 and 14.3 cases per 100,000 inhabitants. Signs and symptoms vary from a severe form of congenital myopathy, present from birth and often fatal, to a classic form and a delayed form, which generally presents after the age of 50 and in which the only sign is a cataract and life expectancy is completely normal. We describe the clinical case of a 40-year-old woman with Steinert myotonic dystrophy who underwent laparoscopic cholecystectomy (under general anesthesia) for symptomatic gallbladder stones. The conduct of anesthesia in such patients must be carefully considered, as hypothermia, shivering, electrical and mechanical stimulation, and the drugs used can all trigger myotonia.

Metabolic myopathies: functional evaluation by different exercise testing approaches.

Metabolic myopathies are a clinically and etiologically heterogeneous group of disorders due to defects in muscular energy metabolism. They include glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders. The typical manifestations of a metabolic myopathy are exercise-induced myalgias, exercise intolerance, and cramps. Evaluating subjects with such symptoms is not easy because of the frequent lack of clinical features. Exercise tests are, therefore, reliable screening tools. Here, we discuss the possible role of such exercise testing techniques in the diagnostic approach of a patient with suspected metabolic myopathy.

[The role of the anesthesiologist in secondary hyperparathyroidism]. / Il ruolo dell'anestesista nell'iperparatiroidismo secondario.

In the last years the increasing of diabetes and hypertension has produced a considerable increase of patients with chronic renal failure; secondary hyperparathyroidism is one of the major complications. The resection of hyperfunctioning parathyroid tissue is the ultimate goal of the treatment. The preoperative examination by the anesthetist is the starting-point of the treatment. The anesthetist programs hemodialysis, the correction of fluid and electrolyte abnormalities and of the anaemia. In the operating room the anesthetist is involved in the careful monitoring of liquid infusion and anesthesiological procedure. The intraoperative parathyroid hormone (PTH) assay is an essential tool because the stress of orotracheal intubation elicits the raising of the catecholamine levels, and the catecholamines stimulates PTH secretion. Propofol can interfere with the intraoperative PTH assay causing an artificial reduction of PTH levels. This study highlights the difficulty in the application of anesthesiological protocol in the uremic patient.

Multiple nucleosome positioning with unique rotational phasing on multimers of the light-responsive elements of pea rbcS-3A and rbcS-3.6 genes: comparison between experimental and theoretical mapping.

Nucleosome positioning along two DNA tracts, corresponding to tetramers of the light-responsive elements of pea rbcS-3A and rbcS-3.6 genes, were studied by experimental (exonuclease III mapping and band shift electrophoresis) as well as theoretical methods. Multiple nucleosome positioning with unique rotational phase was derived from both methods in satisfactorily good agreement, if nucleosome dyad axis positions are considered. Theoretical and experimental distributions of nucleosome frequencies appear different, probably on account of DNA sequence dependent digestion kinetics of exonuclease III.

Regression models for calculating gas fluxes measured with a closed chamber.

Portable closed chambers provide a valuable tool for measuring crop photosynthesis and evapotranspiration. Typically, the rates of change of CO2 and water vapor concentration are assumed to be constant in the short time required to make the closed-chamber measurement, and a linear regression model is used to estimate the CO2 and H2O fluxes. However, due to the physical and physiological effects the measurement system has on the measured process, assuming a constant rate and using a linear model may underestimate the flux. Our objective was to provide a model that estimates the CO2 and H20 exchange rates at the time of chamber closure. We compared the linear regression model with a quadratic regression model using field measurements from two studies. Generally, 60 to 100% of all chamber measurement data sets were significantly nonlinear, causing the quadratic model to yield fluxes 10 to 40% greater than those calculated with the linear regression model. The frequency and degree of nonlinearity were related to the measured rate and chamber volume. Closed-chamber data should be tested for nonlinearity and an appropriate model used to calculate flux. The quadratic model provides users of well-mixed closed chambers an alternative to a simple linear model for data sets with significant nonlinearity.

Midazolam does not influence intravenous fentanyl-induced analgesia in healthy volunteers.

The effects of saline and intravenous midazolam (0.5, 1, and 2 mg per 70 kg) in combination with intravenous fentanyl (0.1 mg/70 kg) were examined on pain induced by a cold pressor test. Healthy volunteers (six females, six males) were enrolled in a prospective, double-blind, randomized, crossover trial in which mood and psychomotor performance were also examined. Five minutes and 135 min postinjection subjects immersed their forearm in ice cold water for 3 min while assessments of pain were recorded. During the first immersion, subjects reported significantly lower pain intensity and bothersomeness ratings after having been injected with fentanyl, relative to the saline condition, but the addition of midazolam neither increased nor decreased pain reports. During the second immersion (approximately 2.5 h postinjection) pain ratings did not differ between the drug and saline conditions. Mood-altering and psychomotor-impairing effects of the drug combination were dose related. We conclude that midazolam at the doses and route of administration tested neither potentiates nor decreases the analgesia produced by fentanyl in a cold-pressor pain assay.

The effects of transnasal butorphanol on mood and psychomotor functioning in healthy volunteers.

Transnasal butorphanol is effective in relieving migraine and postoperative pain. The extent to which this drug preparation impacts on cognitive and psychomotor performance, as well as mood, has not been examined. Accordingly, the cognitive and psychomotor, subjective, and physiological effects of two clinically relevant doses of transnasal butorphanol (1 and 2 mg) were compared to that of placebo, and a common analgesic drug combination given for pain relief in ambulatory settings, 600 mg of acetaminophen and 60 mg of codeine, in healthy volunteers (n = 10). The larger transnasal butorphanol dose impaired psychomotor performance for up to 2 h, and produced subjective effects for up to 3 h. The smaller dose had no psychomotor-impairing effects, but had subjective effects (including increased ratings of "sleepy"). All three active drug conditions including miosis. These laboratory results suggest that patients should use caution when using the 1-mg dose of transnasal butorphanol, and should curtail certain activities if they administer the 2-mg dose of transnasal butorphanol for analgesia.

Examining the subjective, psychomotor and reinforcing effects of nitrous oxide in healthy volunteers: a dose-response analysis.

The present study examined the subjective, psychomotor and reinforcing effects of 10%, 20%, 30% and 40% nitrous oxide in oxygen in 16 healthy volunteers using a choice procedure in which sampling (e.g. 20% nitrous oxide and oxygen-placebo) and choice trials (e.g. 20% nitrous oxide vs. oxygen placebo) were within the same session. Across the four-session study, nitrous oxide dose was varied. Nitrous oxide in a dose-related manner altered subjective effects (e.g. increased visual analog scale ratings of "high", "stimulated" and "tingling") and decreased performance on the Digit Symbol Substitution Test. 10%, 20%, 30% and 40% nitrous oxide were chosen over oxygen by 6, 7, 7 and 8 subjects, respectively. We conclude that nitrous oxide across a range of subanesthetic doses did not function as reinforcer in the majority of subjects tested.

Premixed insulin at ratio 3/7 and regular + isophane insulins at mixing ratios from 2/8 to 4/6 achieve the same metabolic control.

The insulin regimen with two daily injections is still that more frequently used. Often regular and NPH insulins are mixed at different ratios according to the patient's need; however, the mixture preparation can involve several errors. Efficacy, safety and compliance were evaluated comparing a premixture 3/7 (Actraphane HM) with extemporary mixtures of regular + NPH at mixing ratios ranging from 2/8 to 4/6, in a cross-over study of 8 weeks involving 20 insulin dependent diabetics. Metabolic control, hypoglycaemic episodes, insulin dose and proportions were similar with both treatments while a higher compliance was achieved with the premixture. In conclusion, premixture 3/7 and extemporary mixture (from 2/8 to 4/6) obtain the same efficacy and safety but the former shows a higher acceptability.

A simple computer program for insulin dose adjustment in diabetic patients.

A program is described for the adjustment of insulin dose in diabetic patients. The program is written in BASIC and runs on a Casio FX-770P portable computer. On the basis of the maximum daily dose variation allowed, seven twice-daily glucose determinations and the previous insulin dose, the program generated 'cautious' and 'normal' insulin dose adjustment for 66 patients which correlated well with the judgements made by four expert diabetologists.