Salvinorin A reduces neuropathic nociception in the insular cortex of the rat.

BACKGROUND: Neuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors. METHODS: We evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats. RESULTS: We found a potent antinociceptive effect with the administration of SA. Moreover, this effect was blocked by the administration of a KOR antagonist as well as the administration of a CB1 antagonist. CONCLUSION: Salvinorin A has a potent antinociceptive effect when is administered centrally in the IC by the interaction with KOR and CB1 receptors. SIGNIFICANCE: We show evidence on the effectiveness of the administration of salvinorin A in the IC in a rodent model of neuropathic pain. These results support the use of novel compounds like SA as a therapeutic alternative for neuropathic pain relief.

Modification of pepsinogen I levels and their correlation with gastrointestinal injury after administration of dexibuprofen, ibuprofen or diclofenac: a randomized, open-label, controlled clinical trial.

OBJECTIVE: To assess the effect of a 2-week treatment with dexibuprofen, in comparison with ibuprofen and diclofenac, on pepsinogen plasma concentrations and gastrointestinal mucosa, as well as the correlation of these changes with gastrointestinal mucosal injury. METHODS: 60 patients with rheumatologic disease in chronic therapy with NSAID, were included. After a 7-day run-in period patients were randomly assigned to receive a 14-day treatment with dexibuprofen (Group A; Day 1 - 3 = 400 mg t.i.d; Day 4 - 14 = 400 mg b.i.d.), ibuprofen (Group B; Day 1 - 3 = 800 mg t.i.d; Day 4 -14 = 800 mg b.i.d.) or diclofenac (Group C; Day 1 - 3 = 50 mg t.i.d; Day 4 - 14 = 50 mg b.i.d.). Upper gastrointestinal endoscopy (Day 15), capsule-endoscopy (Day 16, 7 patients of each group) and determination of pepsinogen plasma concentrations were performed (basal and Day 15). A semiquantitative scale was designed for the assessment of the gastrointestinal mucosa. RESULTS: No differences in plasma pepsinogen were found between treatment groups or gastrointestinal injury grades or between basal and post-therapy determinations. Dexibuprofen showed gastroduodenal mucosal injury in fewer patients (42.1%) than was the case with ibuprofen (5%; p = 0.003) and diclofenac (30%; p = N.S.). Dexibuprofen administration was also associated with more patients having no intestinal mucosal damage (42.86% vs. 28.7% in the diclofenac group and 14.29% in the ibuprofen group; p = 0.0175). The rate of clinical adverse events was similar in Groups A, B and C (28%, 38% and 34%). CONCLUSIONS: Dexibuprofen showed a lower rate of gastroduodenal and intestinal mucosal injury. This effect was not mediated by modifications of plasma pepsinogen levels.

The value of capsule endoscopy in pediatric patients with a suspicion of Crohn's disease.

BACKGROUND AND STUDY AIMS: The aim of this study was to assess the safety and usefulness of capsule endoscopy (CE) in pediatric patients with a suspicion of Crohn's disease. PATIENTS AND METHODS: CE was used in 12 patients (four girls, eight boys; age 12-16; weight range 43-87 kg). The indication was a clinical suspicion of Crohn's disease not confirmed with traditional methods. Gastroscopy, colonoscopy, and small-bowel follow-through examinations were carried out in all of the patients, without any diagnostic findings. Ileoscopy was possible in 50 % of the patients, and the ileal mucosa and biopsies were normal in all cases. RESULTS: The capsule was easily swallowed by all of the patients. They all excreted the capsule normally, and no complications were observed in any case. CE identified lesions suggestive of Crohn's disease in seven of the 12 (58.3 %), and the majority of the lesions were in the ileum. CONCLUSIONS: CE is safe in pediatric patients over 12 years of age. The procedure appears to be a very useful diagnostic tool in children with Crohn's disease.

Usefulness of capsule endoscopy in patients with suspected small bowel disease.

AIM: To study the usefulness and safety of capsule endoscopy as a diagnostic tool in various small bowel disorders. DESIGN: A retrospective analysis of a series of cases. MATERIAL AND METHODS: Between August 2001 and August 2002, 92 capsule endoscopy procedures were performed in 88 patients (53M/39F, age: 43.87 +/- 16.78). Indications included: chronic diarrhea (n=33); unknown abdominal pain (n=29); occult gastrointestinal bleeding or iron-deficiency anemia (n=13); abdominal discomfort in NSAID takers (n=7); staging of gastrointestinal tumors (n=4), and asymptomatic controls (n=2). Previously performed gastroscopy, colonoscopy, and small-bowel follow-through were not conclusive in all patients. RESULTS: Most frequently relevant findings included: jejuno-ileal aphtas and ulcerations (29 patients), vascular malformations (13 patients), and intestinal neoplasm (6 patients). The groups with a higher rate of findings related to this indication were occult gastrointestinal bleeding (76.92%) and chronic diarrhea (67.85%), with the lowest rate in the abdominal pain group (34.48%). Therapeutic strategy was directly changed in 36 of 88 patients (40.90%) because of capsule-endoscopic findings. The only observed complication was the failed excretion of one of the capsules because of an unknown ulcerated intestinal stricture. CONCLUSIONS: Capsule endoscopy is a safe procedure which can study the entire small bowel, meaning a valuable tool for the management of patients with suggestive signs and symptoms of intestinal disorders.

Evaluación de los resultados obtenidos en el incumplimiento de citas concertadas en pacientes de una consulta de alergología, al año de la implantación de un ciclo de mejora / Evaluation of the obtained results in patient noncompliance with scheduled appointments at an allergy clinic, in the following year of implantation of an improvement cycle

Fundamento: El incumplimiento es una causa frecuente de fracaso de las actuaciones médicas, y la ausencia a los controles periódicos es una forma importante de éste. Recientemente, nuestro grupo ha publicado un estudio en el que se analiza el grado de incumplimiento de las citas concertadas de los pacientes citados en nuestra consulta de alergología (julio de 2001 a junio de 2002) y se realizaron propuestas de mejora. Objetivo: En el presente manuscrito se evalúan los resultados obtenidos en el año posterior a su puesta en marcha. Métodos: Se incluyeron los pacientes citados en consulta que acudían por primera vez o a una visita sucesiva, desde julio de 2002 a junio de 2003. Fueron objeto del estudio un total de 1.924 citaciones (441 de primera vez y 1.483 sucesivas) que no acudieron a la consulta, correspondientes a 1.762 pacientes (414 de primera visita y 1.348 sucesivas), con una media de 1,09 citas/paciente/año, 982 (55,73 por ciento) eran mujeres y 780 (44,37 por ciento) varones, con una edad media de 33,72 ñ 15,37 años. Resultados: Hubo incumplimiento en el 14,36 por ciento de las consultas. Los pacientes que incurrieron en el incumplimiento con más frecuencia fueron los varones (14,37 por ciento de los citados frente al 12,62 por ciento), los menores de 40 años (71,62 por ciento de incumplidores) y los pacientes reincidentes en el incumplimiento (8,23 frente a 91,77 por ciento). No se evidenciaron diferencias en el cumplimiento en función de la consulta, hora de citación, intervalo entre las citas o distancia desde la última consulta a demanda. No hemos encontrado un aumento significativo de las ausencias a consulta durante el período vacacional estival en ninguno de los grupos. Conclusiones: No se evidenciaron diferencias en el cumplimiento, una vez puestas en marcha las medidas propuestas a raíz de nuestro anterior estudio. Quizás, en las inasistencias jueguen cierto papel motivos de difícil control, entre los que cabe barajar la actual accesibilidad a los servicios sanitarios. Probablemente habría que estar alerta y/o tomar medidas anticipatorias en pacientes jóvenes y pacientes con incumplimientos previos. El nivel de incumplimiento es un indicador de calidad, al disminuir el rendimiento de las consultas y poner en evidencia una falta de adherencia de los ciudadanos con los equipos de atención primaria para las primeras consultas, y para la atención especializada en las consultas sucesivas. Sobre él, es difícil incidir con el fin de mejorar los índices, una vez obtenidas determinadas cuotas (AU)

Capsule endoscopy in patients with suspected Crohn's disease and negative endoscopy.

BACKGROUND AND STUDY AIMS: The aim of the present study was to assess the value of capsule endoscopy in the diagnostic work-up of patients in whom there is a clinical suspicion of small bowel Crohn's disease that cannot be confirmed using traditional techniques. PATIENTS AND METHODS: A total of 21 patients (14 men, seven women; mean age 43 +/- 8 years) with a clinical and biochemical suspicion of Crohn's disease were included in the study. Conventional imaging work-up, including upper and lower endoscopy, as well as a small-bowel follow-through, was carried out in all of the patients. RESULTS: Pathological findings were not observed in 12 of the 21 patients (57 %). In the other nine patients (43 %), lesions supporting the diagnosis of Crohn's disease were seen. The most frequent findings were located in the distal ileum and included aphthae, lineal and serpiginous ulcers, and fissures. Four patients had lesions in the jejunum. One patient showed erosions in the distal duodenum, jejunum, and ileum. No adverse effects of the technique were observed in any of the patients. CONCLUSIONS: Capsule endoscopy is a valuable diagnostic tool in patients with suspected Crohn's disease that has not been confirmed using standard imaging techniques.

Short- and medium-term clinical efficacy of three endoscopic therapies for achalasia: a single-blinded prospective study.

OBJECTIVE: to compare the efficacy of three endoscopic therapies for achalasia and to identify predictors of response. DESIGN: prospective, single-blinded study at short and medium term. MATERIAL AND METHODS: 22 patients (9M/13 F; mean age: 47.45 +/- 21.01 years) with confirmed clinical and manometric achalasia were randomised in three groups: intrasphincteric injections of botulinum toxin (group 1: 10 patients ), injections of 1% polidocanol (group 2:6 patients), and a combined therapy with both of them (group 3: 6 patients). Clinical response was evaluated by a score (0-5) of tested symptoms (dysphagia, regurgitation and chest pain) at 1 and 24 weeks post-treatment. RESULTS: at 24 weeks post-treatment group 2 had the best complete response (CR) rate (33.33%), whereas CR in both the botulinum toxin and combined therapy groups was 10 and 0%, respectively. Groups 1 and 2 got an overall improvement in clinical score at 1 (p= 0.02) and 24 weeks (p= 0.04). Five patients (50%) in group 1, two patients (33.33%) in group 2, and three patients (50%) in group 3 needed other therapies (dilation or surgery) because of treatment failure. Separately, neither age nor sex, time from diagnosis or type of therapy could distinguish responders from non-responders in these three groups. However, absence of response within the first week, and an initial clinical score above 7 were predictive factors of poor response at six months. CONCLUSIONS: short- and medium-term clinical response to these endoscopic therapies was limited. The absence of response at seven days and a severe initial clinical score were predictive factors of poor medium-term response.

Gestión de pacientes en las agendas de una consulta de alergología. Propuestas de mejora / Management of patients on the appointment book of an Allergy service. Improvement proposals

Objetivo: El objetivo de la asistencia sanitaria en Alergología es proveer a los pacientes alérgicos de aquellos servicios que mejor preserven o restauren su estado de salud.Pacientes y método: Se revisaron los pacientes que fueron citados en nuestra Unidad desde julio de 2001 a junio de 2002. La gestión administrativa de los pacientes en el Área de Consultas Externas, se realiza en HP-HIS1® por el módulo de Consultas Externas.Resultados: Los 8.785 pacientes asistidos generaron 13.578 visitas sucesivas, lo que supone 1,55 visitas/paciente. De los pacientes programados a través del centro de programación del servicio de admisión de consultas externas, no asistieron a la consulta 1.769 (15,89 por ciento), trescientos veintiséis (14,3 por ciento) de los citados como primera vez y 1.443 (16,3 por ciento) de los que lo fueron como sucesiva. De las 16.125 visitas previstas (2.547 visitas de primera vez y 13.578 de sucesivas), sólo se realizaron 14.314, lo que supone el 88,77 por ciento de las visitas previstas (87,20 por ciento de primera vez y 89,37 por ciento de sucesivas).Doscientos sesenta y cinco (10,40 por ciento) pacientes de primera visita fueron citados directamente desde la consulta de alergología; 79 procedentes de equipos de atención primaria o centros de atención especializada extrahospitalaria, en 18 casos se trataba de profesionales del hospital o sus familiares, y sólo en uno se trató de una hoja de interconsulta de otra unidad asistencial del hospital. De los 287 pacientes remitidos por el servicio de urgencias del hospital, 120 (41,81 por ciento) fueron citados por el centro de programación y 167 (58,19 por ciento) por las administrativas de la consulta, con el fin de ser asistidos en las horas siguientes a su asistencia en el área de urgencias.La demora de los pacientes que consultan por primera vez, oscila entre 1,47 y 70,88 días.Conclusiones: a) Una vez estabilizadas las agendas mejora la satisfacción de los usuarios; b) es previsible que la carga administrativa disminuya en los dos niveles de asistencia; c) en función de la demora se puede llevar a cabo una redistribución de las citas entre agendas de la unidad; d) existen debilidades del proceso que es necesario resolver a corto plazo, y e) el sistema de información ha permitido efectuar las primeras descargas de datos que cumplen las exigencias de información corporativas y que nos han servido para elaborar estos resultados (AU)

Incumplimiento a citas concertadas en pacientes de una consulta de alergología / Patient noncompliance with scheduled appointments at an allergy clinic

Fundamento: El incumplimiento es una causa frecuente de fracaso de las actuaciones médicas, y la ausencia a los controles periódicos es una forma importante del mismo. El objetivo ha sido conocer el grado de incumplimiento a citas concertadas de los pacientes citados en nuestra consulta de Alergología y realizar propuestas de mejora. Métodos: Se incluyeron los pacientes citados en consulta que acudían por primera vez o a una visita sucesiva, desde julio de 2001 hasta junio de 2002. Fueron objeto del estudio un total de 1.769 citaciones (326 de primera vez y 1.443 sucesivas) que no acudieron a la consulta, correspondientes a 1.626 pacientes (294 de primera visita y 1.332 sucesivas), con una media de 1,09 citas por paciente y año. Novecientos cincuenta y nueva (58,98 por ciento) eran mujeres y 667 (41,02 por ciento) varones, con una edad media de 33,46+/-15,35 años. Resultados: Existió incumplimiento en el 13,06 por ciento de las consultas. Los pacientes que incurrieron en el incumplimiento con más frecuencia fueron las mujeres (58,98 frente a 41,02 por ciento), los menores de 40 años (72,34 por ciento de incumplidores) y los pacientes reincidentes en el incumplimiento (8,16 frente al 91,84 por ciento). No se evidenciaron diferencias en el cumplimiento en función de la consulta, hora de citación, intervalo entre las citas o distancia desde la última consulta a demanda. No se encontró un aumento significativo de las ausencias a consulta durante el período vacacional estival en ninguno de los grupo. Conclusiones: Probablemente habría que estar alerta y/o tomar medidas anticipatorias en mujeres jóvenes y pacientes con incumplimientos previos. El nivel de incumplimiento es un indicador de calidad, al disminuir el rendimiento de las consultas y poner en evidencia una falta de adherencia de los ciudadanos con los Equipos de Atención Primaria para las primeras consultas y para la Atención Especializada en las consultas sucesivas (AU)

Lesion and electrical stimulation of the ventral tegmental area modify persistent nociceptive behavior in the rat.

The ventral tegmental area (VTA) has been traditionally related with the control of motor responses. However, some studies show that this area is also involved in the processing of nociceptive information. It has been reported that this nucleus participates in the dissociative analgesia phenomenon. In the few works where electrical stimulation and lesion of the VTA have been performed, evaluated with persistent or chronic pain related behaviors, contradictory results have been obtained. Thus, a more detailed analysis of the role of the VTA in persistent pain is needed. Two series of experiments were performed: lesions of this nucleus were done with radiofrequency, (bilaterally at two points per side using a temperature range from 50 to 80 degrees C), and the VTA was electrically stimulated (10 min daily over 5 days, 2 ms rectangular pulses at 100 Hz during 1 s every 5 s) using two different schemes:10 min before the induction of the nociceptive stimulus and 90 min after the induction of the nociceptive stimulus. The latter allowed us to distinguish if the VTA electrical stimulation had a distinctive antinociceptive effect when applied before or after the induction of the nociceptive stimulus on a persistent pain related behavioral response in the rat, the self injury behavior (SIB). Our results showed that VTA lesions enhanced the occurrence of SIB; while activation of this same nucleus by electrical stimulation after the nociceptive stimulus, but not before, facilitates the analgesic process, expressed as a 1 day delay in SIB onset. These results indicate that the VTA is a brain structure that plays a key role in the processing and modulation of persistent pain information. Data are discussed in terms of the relationship of the VTA with the affective component of pain.

Toluene increases acute thermonociception in mice.

Toluene is an abused solvent widely used in several commercial products. Recent evidence indicates that this solvent is a non-competitive inhibitor of NMDA receptors. Since NMDA receptors have been implicated in pain, this paper describes studies of the effects of increasing concentrations of inhaled toluene on nociception. Swiss Webster mice were exposed to toluene (500-8000 ppm) in static exposure chambers for 30 min. After completing the exposure period, animals were tested for nociception using the hot plate test. Toluene dose-dependently increased nociception as reflected by shorter latencies for the reflex, paw-lick and escape responses in toluene-treated mice with respect to their controls (animals exposed to air). In order to determine the possible role of opioids in this response, morphine (1-10 mg/kg) was injected before toluene inhalation. Toluene was not able to block morphine-induced antinocieption, however, it produced a shift of the morphine dose-response curve to lower effects, suggesting a physiological antagonism. No potentiation was seen when toluene was administered in combination with naloxone. Present results suggest that toluene increases nociception via neurotransmitter systems others than the glutamatergic.

Effect of red peppers (Capsicum frutescens) intake during gestation on thermonociceptive response of rat offspring.

Oral administration of aqueous red pepper (Capsicum frutescens, Cf) solution and low capsaicin (8-methyl-N-vanillyl-6-nonenamide) doses during gestation produces an increase in the latency of the thermonociceptive escape response of rat offspring. The present work shows that different amounts of Cf (10%, 25% and 50%) incorporated to normal food of gestating rats modify in a dose-dependent manner the flexion reflex latency (R), as well as the latency of appearance of antialgesic behaviours expressed as paw lick (P) and escape response (E) using the hot plate test (53 degrees C+/-0.5 degrees C). The latency of the same parameters was tested in the same subjects 55 days later to determine the persistence of this effect. Results show an increase in latency of the three parameters R, P and E in all experimental groups with respect to controls. Animals (Cf, 25% group) tested 55 days after the first test exhibited latencies similar to controls, which suggests that the process is reversible.

Long-term management of GERD. Why using endoscopy just now?

Early results with the use of endoscopic techniques in the treatment of gastro-oesophageal reflux disease (GERD) have been recently reported. Methods used are an injection of biocompatible substances within the lower oesophageal sphincter (LES), LES ablation using radio-frequency, and suture of folds in the area distal to the Z-line. The latter--endoscopic gastroplasty--is most difficult, but this technique has been most widely accepted by gastroenterologists to this date. Effectiveness of these endoscopic management systems in the long-term control of GERD has never been compared to a control group. This fact, together with the proven efficacy of anti-secretory drugs and the refinement of laparoscopic surgery during the past few years, has led physicians to be more demanding regarding early results. This review will discuss each method available, and issues answered by reported studies to this day are approached.

Stimulation of the medical preoptic area facilitates sexual behavior but does not reverse sexual satiation.

The aim of the present study was to establish whether electrical and/or drug stimulation of the medial preoptic area/anterior hypothalamus (mPOA/AH) surmounts the sexual behavior inhibition that results from copulation to exhaustion. Thus, intermittent electrical stimulation of the mPOA/AH (alone or combined with the systemic injection of yohimbine or apomorphine, at doses that were subthreshold for reversing sexual exhaustion) or intrapreoptic treatments to block GABAergic transmission were applied to sexually satiated rats. The results suggest that the mPOA/AH is not responsible for male sexual behavior inhibition or for the pharmacologically induced sexual behavior expression in satiated rats. Data are discussed in terms of the roles ascribed to the mPOA/AH, both in the control of sexual behavior expression and in the regulation of the postejaculatory interval.

Electric stimulation of the cingulum bundle precipitates onset of autotomy induced by inflammation in rat.

The purpose of this work was to test if electric stimulation of the cingulum bundle in animals subjected to a hindpaw inflammatory process precipitates the onset and enhances autotomy behaviour. Wistar rats were implanted with bipolar parallel electrodes in the boundary of the cingulum bundle. The inflammatory process was induced in all subjects by injection of carrageenan. The groups were: A, sham; B, implanted and stimulated 10 min daily for 7 days; C, implanted and stimulated 2 h daily, for 7 days. Both groups were injected with CAR 2 days after ending the stimulation period; and D, implanted and stimulated 10 min daily for 5 days, the first stimulation being simultaneous to CAR injection. Results show that 100% of the subjects in stimulated groups presented autotomy as compared with 66% in the sham group. A significant shortening of the onset and increased rates in autotomy were observed in experimental groups (B, C and D) as compared to the sham group. We did not find differences between groups B and C, but there was an increment of autotomy in group D when compared with both B and C groups. We conclude that it is possible to facilitate the onset and to increase the intensity of the autotomy triggered by the inflammatory process with cingulum bundle electrical stimulation. The results also suggest that a fundamental condition to the development of the autotomy in this model is the presence of the noxious inflammatory process. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Self-mutilation in the Lesch-Nyhan syndrome: a corporal consciousness problem?--a new hypothesis.

The Lesch-Nyhan syndrome (LNS) has been extensively studied from the genetic and biochemical point of view. The main characteristic of the syndrome is the self-mutilation feature, which has been poorly studied and understood. We propose a new hypothesis about the self-mutilation physiopathology, which is related to the supersensitivity of the dopaminergic D1 receptors in the neuromatrix found in the cingulum cortex region. The LNS shows an increase of uric acid levels as a result of the deficiency of hypoxanthine phosphoribosyltransferase enzyme. This increase could induce damage to dopaminergic neurons. As a consequence, a decrease in dopamine synthesis during gestation and the early postnatal period could occur, producing a functional dopaminergic denervation of the D1 receptors, located on the prefrontal cortex, specifically in the cingulum bundle projections. This phenomenon could induce a codification disturbance in the 'genetic body' of the neuromatrix, that could be expressed functionally as anosognosia, giving rise to self-mutilation. We suggest that this self-mutilation is a pain consciousness problem.

Capsaicin or feeding with red peppers during gestation changes the thermonociceptive response of rat offspring.

Capsaicin is responsible for the pungent sensation produced by red peppers on the body's mucous membranes. This substance is found naturally in the gender Capsicum, widely used in the diet of different cultures in America, Asia, and Africa. In this paper we used the hot plate model (53 +/- 0.5 degrees C) to study the effect of acute thermonociceptive stimulus on escape response latency in the offspring of rats that were treated during gestation, either with an aqueous red pepper solution (Capsicum frutescens, approximately 2.75 mg of capsaicin in 1 ml/day, by gavage during the second week), or with capsaicin (0.5 mg/day SC, during the second week). These groups were compared with their respective controls. We found that the difference between the manipulated control group and the one given the aqueous red pepper solution was 41.33%, and between the vehicle control and the one treated with capsaicin was 30.59%. These increments on the escape response latency were statistically significant. Our results show that both treatments, the aqueous red pepper extract and low doses of capsaicin on pregnant rats. produce an increment on escape response latency due to a thermonociceptive stimulus.