João V. Busnello

High power setting argon plasma coagulation for the eradication of Barrett’s esophagus

OBJECTIVE:The term Barretts esophagus refers to a premalignant condition that is characterized by the replacement of the esophageal squamous mucosa by a columnar-lined one. Preliminary studies have demonstrated reversal of Barretts mucosa after endoscopic coagulation with different techniques associated with acid inhibition. However, most of these studies have shown that residual Barretts glands are found underneath the new squamous epithelium in up to 40% of patients. The goal of our study is to verify whether complete restoration of Barretts mucosa can be achieved by the combination of high power setting argon plasma coagulation and omeprazole.METHODS:A total of 33 patients (mean age: 55.2 yr, range: 21–84 yr; 21 men and 12 women) with histologically demonstrated Barretts esophagus (mean length: 4.05 cm, range: 0.5–7 cm) were treated. Fourteen cases presented with low-grade dysplasia and one with high-grade dysplasia. All of the extent, or until a maximum of 4 cm, of the Barretts mucosa was cauterized in each session using argon beam coagulation at a power setting of 65–70 W. All patients received 60 mg omeprazole during the treatment period.RESULTS:Complete restoration of squamous mucosa was obtained in all 33 cases after a mean of 1.96 sessions (range, 1–4). Endoscopic results were histologically confirmed. Nineteen (57.5%) patients experienced moderate to severe chest pain and odyno-dysphagia lasting for 3–10 days after the procedure. Five of these cases experienced high fever and a small volume of pleural effusion, and three patients developed esophageal strictures that needed to be dilated. Another patient developed pneumomediastinum and subcutaneous emphysema without evidences of perforation. After a mean follow-up of 10.6 months there was one endoscopic, as well as histological, recurrence of Barretts mucosa in a patient with an ineffective laparoscopic fundoplication.CONCLUSIONS:High power setting argon plasma coagulation combined with intensive acid suppression is an effective treatment for the total endoscopic ablation of Barretts esophagus, at least in the short term. Long-term follow-up of treated patients in whom gastroesophageal reflux is surgically or medically alleviated seems mandatory before drawing definitive conclusions about this therapy.

The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans

The hypothesis that brain-derived neurotrophic factor (BDNF) is involved in the pathogenesis of major depression is supported by several research findings; however, genetic studies assessing the relationship between BDNF and psychiatric disorders have produced conflicting results. We examined the effect of a BDNF polymorphism on depression susceptibility in Mexican-Americans. The single nucleotide polymorphism (Val66Met), which has been shown to have functional and behavioral effects, was genotyped in 284 depressed participants and 331 controls, showing association with depression (P=0.005). Individuals homozygous for the major allele (GG) had an increased chance of being depressed (OR=1.7 95% CI 1.17–2.47). Our findings support the association of BDNF single nucleotide polymorphism rs6265 and depression, suggesting that this polymorphism may increase susceptibility to major depression in Mexican-Americans.

Mirtazapine versus fluoxetine in the treatment of panic disorder

Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents (selective serotonin reuptake inhibitors) used in the treatment of panic disorder. The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind, randomized, flexible-dose trial conducted with outpatients. After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P < or = 0.01). ANOVA showed no significant differences between the two treatment groups in number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas measures of patient global evaluation of phobic anxiety were significantly different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the 22 patients who completed the study, the mean daily dose of mirtazapine was 18.3 +/- 1.3 vs 14.0 +/- 1.0 mg for fluoxetine at the endpoint. Weight gain occurred more frequently in the mirtazapine group (50 vs 7.7%, P = 0.04) and nausea and paresthesia occurred more often in the fluoxetine group (P = 0.01). Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder.

The anticonvulsant compound gabapentin possesses anxiolytic but not amnesic effects in rats.

This report describes the effects of the antiepileptic agent gabapentin on anxiety and memory. Male Wistar rats received intraperitoneal administrations of gabapentin (10, 30 and 100 mg/kg), diazepam (1 mg/kg), saline or diazepam vehicle 30 minutes prior to experimental procedures. Animals were: (1) tested on step‐down inhibitory avoidance (footshock 0.3 mA) and habituation to an open‐field for memory assessment; and (2) submitted to the elevated plus‐maze to evaluate the potential anxiolytic effects of gabapentin. Animals treated with gabapentin showed a reduction in anxiety similar to the that observed in animals treated with diazepam. Memory was not affected by gabapentin in any of the tests, but was impaired by diazepam. The lack of effects of gabapentin on memory suggest a potential advantage of this drug over compounds with previously known anxiolytic property, which have amnesic effects at doses used for the treatment of anxiety disorders.

Behavioural effects of acute tryptophan depletion in healthy male volunteers.

Acute tryptophan depletion (ATD) studies have been used to assess the role of the serotonergic system in various aspects of human behaviour. Changes in mood have already been described in selected groups of individuals submitted to ATD. The present study was a randomized, double-blind, cross-over trial designed to evaluate the effects of ATD on mood, memory, attention and induced anxiety in normal male volunteers. Twelve healthy male volunteers were submitted to two separate sessions of ATD, 1 week apart. Drinks containing either a balanced mixture of amino acids (B) or a similar mixture devoid of tryptophan (T–) were administered in each session. Mood was assessed using self-rating scales. Attention and memory were assessed using a battery of psychological tests. Anxiety induction was carried out using a simulation of public speaking. Blood levels of tryptophan were assessed before and after the B and T– drinks. Results showed that ATD markedly decreased plasma tryptophan (p< 0.0001). Mood ratings, memory and attention were not changed by the T– drink. There was no difference among the anxiety levels measured under T– or B mixtures. These data supports the notion that ATD does not change mood and cognitive function in healthy subjects.

Effects of gabapentin on anxiety induced by simulated public speaking.

The effects of gabapentin, 400 mg and 800 mg, on anxiety induced by simulated public speaking (SPS) were investigated. Thirty-two normal male volunteers (aged 17-30 years) had their anxiety and mood evaluated by self-scales [Visual Analogue Mood Scale (VAMS) and Profile of Mood State (POMS)] during the SPS procedure. Physiological measures (heart rate and blood pressure) were taken. Treatment with gabapentin at 800 mg attenuated the anxiety of subjects that had a decrease on the VAMS item calm-excite. In addition, volunteers that received gabapentin at 400 mg and 800 mg showed a decrease in the hostility score in POMS. Our results suggest, in agreement with other studies, an anxiolytic potential to gabapentin.

USE AND MISUSE OF BENZODIAZEPINES IN BRAZIL: A REVIEW

Benzodiazepines are among the most prescribed and consumed medication groups in the world. Although benzodiazepines are used in the treatment of several psychiatric and non-psychiatric disorders, and are generally safe and well-tolerated, the potential for misuse and abuse is considerable. This makes the study and regulation of benzodiazepine prescription and consumption an item of concern in public health around the world. Most developed countries have consistent data of benzodiazepine sales and consumption; however, data from developing countries is scarce, making health policies on the use of benzodiazepines a much tougher issue in these countries. This article aims to review the epidemiology of benzodiazepine use in Brazil, as well as to analyze how legislation, physician misinformation and economic factors might contribute to making benzodiazepine abuse a problem in the country.

Effects of leptin replacement on macro-and micronutrient preferences

Background:The mechanisms underlying food choices are complex and involve neuroendocrine and biochemical signaling. Among neuroendocrine signals, leptin may play a prominent role in food preference.Objective:This study was designed to obtain an understanding of the effects of leptin replacement on macro- and micronutrient preferences in leptin-deficient adults.Design:We studied the effects of leptin replacement on three adults with genetic leptin deficiency during the initial 12 months of treatment. Dietary intake was measured in our study by weighed food consumption records. Nutrient intake was calculated using a nutrition analysis software.Results:After leptin replacement was started, all patients had initially a marked reduction in food intake. The reduction in caloric intake differentially affected intake of macro- and micronutrients. There was an initial shift toward a higher percentage consumption of fats and a decrease in the intake of carbohydrates. Significant differences also occurred in 7 distinct types of macronutrients, 12 vitamins, 11 minerals and 1 amino acid.Conclusions:We documented several specific leptin-induced changes in macro- and micronutrients intake during the course of leptin-replacement treatment, the majority of which were not related to the decrease in total caloric consumption.

Peripheral nucleotide hydrolysis in rats submitted to a model of electroconvulsive therapy

Electroconvulsive therapy (ECT) is an efficacious and safe method for the treatment of mood disorders. Its utilization is accompanied by a myriad of biochemical and cellular changes, which are far from fully understood. The present work investigates in rat serum the effects of seizures induced by electroconvulsive shocks (ECS), an animal model of ECT, on enzymes that hydrolyze ATP, ADP and AMP to adenosine. Two different models of ECS were used, consisting in the application of one or eight ECS sessions, and respectively named acute or chronic. Serum samples were collected at several time points after the single shock in the acute and after the eighth and last shock in the chronic model. A single shock produced a sudden and short-lived inhibition of enzymatic activity (P<0.01 for ADP and AMP), whereas in the chronic model significant increases were noticed starting as early as 12 h after the last shock, remaining significantly elevated until the last measurement 7 days later for ATP and ADP. Analysis of hydrolysis was assessed at the selected time point of 7 days in cerebrospinal fluid samples, also demonstrating a significant activation in the chronic model (P<0.0001 for ATP and ADP). These results support the idea that adenosine nucleotides may be involved in the biochemical mechanisms underlying longer lasting therapeutic effects associated with ECT, and suggest that peripheral markers can possibly contribute to the evaluation of activity in the central nervous system.

Evoked potentials for the evaluation of latent hepatic encephalopathy in pediatric liver transplant candidates

Background Visual evoked potentials (VEPs) and brain stem auditory evoked potentials (BAEPs) have been proposed as tools in the diagnosis of subclinical hepatic encephalopathy (HE). However, little information exists to determine their usefulness in pediatric patients. This study was undertaken to evaluate both methods in the detection of subclinical HE in pediatric liver transplant candidates. Methods VEPs and BAEPs were recorded in 15 pediatric liver transplant candidates with no clinical signs of HE. The wave latencies found in these examinations were then compared with those in 16 healthy controls of similar age. Laboratory data on liver function and electroencephalographic data from the patients were also recorded to examine their correlation with the evoked potentials results. Results No differences were found in the BAEP results between patients and controls. However, in the VEPs, the liver transplant candidates had significantly prolonged N1 (N75) latencies when compared with controls; no significant delay was found in the other waves. In contrast, among the children with liver disease, higher BAEP peak latencies correlated positively with electroencephalographic abnormalities, but this correlation was not observed in VEPs. Conclusions Evoked potentials might be of use in detecting alterations related to HE in children. However, further studies are necessary to determine their sensitivity and specificity in this situation.