Intrinsic neural circuits between dorsal midbrain neurons that control fear-induced responses and seizure activity and nuclei of the pain inhibitory system elaborating postictal antinociceptive processes: a functional neuroanatomical and neuropharmacological study

The blockade of GABA-mediated Cl(-) influx with pentylenetetrazol (PTZ) was used in the present work to induce seizures in Rattus norvegicus. The aim of this work was to study the involvement of monoamines in the antinociception induced by convulsions elicited by peripheral administration of PTZ (64 mg/kg). The analgesia was measured by the tail-flick test in seven or eight Wistar rats per group. Convulsions were followed by statistically significant increase in the tail-flick latencies (TFL), at least for 120 min of the postictal period. Peripheral administration of methysergide (0.5, 1, 2, and 3 mg/kg) caused a significant decrease in the TFL in seizing animals, as compared to controls, in all postictal periods studied. These findings were corroborated by the pretreatment with ketanserin, a 5-HT(2A/2C)-serotonergic/alpha(1)-noradrenergic receptors antagonist, at the same doses. Peripheral administration of yohimbine (0.5, 1, 2, and 3 mg/kg), alpha(2)-noradrenergic antagonist, also decreased the postictal analgesia either at initial or more terminal periods of the postictal analgesia. These data were corroborated with peripheral administrations of propranolol, a beta-noradrenergic receptor blocker that caused a decrease in the postictal analgesia consistently in later stages (after the first 20-min post-tonic-clonic convulsive reactions) of the post-seizure analgesia, except for the highest dose. These results indicate that monoamines may be involved in the postictal analgesia. The blockade of 5-HT(2A/2C)-serotoninergic, alpha(1)-noradrenergic, or alpha(2)-noradrenergic receptors before tonic clonic seizure-induced analgesia antagonized the increase in the nociceptive threshold caused by seizures in initial steps of the temporal antinociceptive curve, as compared to the blockade of beta-noradrenergic ones. These findings suggest that the recruitment of alpha-noradrenergic receptor and serotonergic receptors was made immediately after convulsions and in other initial periods of the postictal analgesia, as compared to the involvement of beta-noradrenergic receptor. Neurochemical lesions of the locus coeruleus (LC) and neuronal damage of the dorsal raphe nucleus induced a significant decrease of the postictal analgesia, suggesting the involvement of these nuclei in this antinociceptive process. The functional neuroanatomical study of the neural link between the mesencephalic tectum and nuclei of the central pain inhibitory system showed evidence for the interconnection between superior colliculus, both dorsal and ventral periaqueductal gray matter (PAG), and inferior colliculus. Defensive substrates of the inferior colliculus, also involved with wild running and epilepsy, send inputs toward dorsal raphe nucleus and locus coeruleus. Since these nuclei are rich in monoamines and send neural connections toward other monoaminergic nuclei of the brainstem involved with the control of the nociceptive inputs in the dorsal horn of the spinal cord, the present results offer a neuroanatomical and psychopharmacological basis for the antinociceptive processes following tonic-clonic seizures.     

Atrial reduction plasty Cox maze procedure: extended indications for atrial fibrillation surgery

BACKGROUND: The Cox maze procedure yields good results for atrial fibrillation (AF). However, patients with predictors of failure-chronic long-standing AF, low amplitude fibrillatory waves, and large left atriums-are generally thought not to benefit from a maze procedure. We report an aggressive approach for these patients, utilizing biatrial reduction plasty concomitantly with the Cox maze procedure for AF. METHODS: A complete Cox maze procedure utilizing supplemental RF ablation was performed in 36 patients. All underwent resection of both atrial appendages and biatrial reduction plasty encompassing resection of the left atrial posterior wall from left to right pulmonary veins and from inferior pulmonary veins to the mitral annulus, as well as removal of the right atrial lateral wall. Mitral or tricuspid valve repair, or both, was performed on 32 patients. RESULTS: These patients had a mean AF duration of 45 +/- 89 months. Their preoperative left atria measured 66 +/- 16 mm, with mean AF waves of 0.74 +/- 0.3 mm. Mean preoperative New York Heart Association class was 2.7 +/- 0.7 and left ventricular ejection fraction was 48 +/- 9. Cross clamp and bypass times were 91 +/- 35 minutes and 124 +/- 33 minutes, respectively. The average posterior left atrial tissue resected was 5.4 x 2.1 cm, and mean resected atrial weight was 10.3 +/- 2 g. There were no deaths and length of stay was 5.5 +/- 2 days. At a follow-up time of 19 +/- 16 months, 32 of the 36 patients were in normal sinus rhythm and New York Heart Association class I. CONCLUSIONS: Aggressive biatrial reduction plasty Cox maze procedure was effective in 89% of these "low success" AF patients. This simple procedure can extend utilization of the Cox maze procedure to more patients with chronic AF.     

Systemic lupus erythematosus with celiac disease: a report of five cases

Systemic lupus erythematosus and celiac disease (CD) are rarely reported in combination. We report five cases seen over a 4-year period. The two conditions occurred concomitantly in one patient, whereas the CD antedated the lupus in one patient and postdated the lupus in the remaining three patients. Villous atrophy on duodenal biopsy specimens with a favorable response to a gluten-free diet was noted in all five patients. Only four patients had positive serological tests for CD and only three had abdominal symptoms.     

A nonrandomized comparison of the clinical outcome of ocular involvement in patients with mucous membrane (cicatricial) pemphigoid between conventional immunosuppressive and intravenous immunoglobulin therapies

The purpose of this study was to compare the clinical outcomes of intravenous immunoglobulin (IVIg) therapy to conventional immunosuppressive therapy in patients with mucous membrane pemphigoid (MMP), also known as cicatricial pemphigoid (CP), whose disease progressed to involve the eye. Before ocular involvement, all the patients in this study were diagnosed and treated with immunosuppressive agents, for biopsy-proven MMP, affecting the skin and/or mucous membranes, other than the conjunctiva. Eight patients in group A were treated with IVIg after the diagnosis of ocular cicatricial pemphigoid (OCP) was established. The efficacy and safety of IVIg therapy were compared to a clinically similar group of eight patients treated with conventional immunosuppressive therapy (group B). The inclusion criteria for both groups were: (1). presence of MMP at extraocular sites confirmed by biopsy before entry into the study; (2). entry into the study occurred when ocular involvement was noted and confirmed by biopsy; (3). presence of conventional immunosuppressive therapy at the time of ocular involvement; (4). a minimum of 18 months of follow-up after diagnosis of ocular involvement. The mean length of the therapy, after the onset of ocular involvement, was 24 months (range 16-30) in group A and 45 months (range 21-90) in group B. The median time between initiation of therapy and clinical remission in group A and group B was 4 and 8.5 months, respectively. This difference was statistically significant (P < 0.01). No recurrence of ocular inflammation was recorded in any of the patients in group A. On the contrary, at least one recurrence (median 1) was recorded in five patients in group B (range 0-4). This difference was statistically significant (P < 0.05). All eight patients in group A and group B presented to the ophthalmologist in stage 2 of OCP at the time of the initial visit. At the last follow-up visit, no progression to advanced stages of OCP was recorded in all eight patients in group A. On the contrary, only four patients in group B remained in stage 2 of OCP at the last follow-up exam. The conjunctival scaring progressed from stage 2 to stage 3 in the remaining four patients of group B. At the last follow-up visit, both eyes of each patient in group A were free of inflammation. Some level of conjunctival inflammation at the last follow-up visit was noted in five patients in group B (range 0-1.5, P < 0.05). Both groups of patients were studied during the same time period. The results of this study suggest that ocular involvement in patients with MMP may be considered an indication for initiating IVIg therapy, since it was more effective in arresting progression of OCP, when compared to conventional immunosuppressive therapy. These data indicate that IVIg produced a faster control of the acute inflammation and that no recurrences were observed during the follow-up. This clinical difference could be because of the reduced production of pathogenic antibody, and/or restoration of the immunoregulation, which may have been disturbed.     

Mechanical ventilation in intensive care units: indications, modalities and complications. Results of a prospective multicenter survey in Tunisia

The survey was performed during the month of March 1998 and concerned 9 ICUs located in teaching hospitals. To be included each ICU had to MV for more than 12 hours were included in the study and had a 28 day follow-up in the ICU or until hospital discharge. Collected parameters were indications of MV, modalities of MV and of weaning, complication and outcome at hospital discharge. Assist-control ventilation was the most used ventilation modality (69.8%). Weaning of MV was performed in 63% of the study patients and was based on a once-a-day attempt of spontaneous breathing through a T-piece (59.5%) and a combination of intermittent mandatory ventilation with pressure support (IMV-PS: 27%) or pressure support alone (11.2%). Mean length of hospital stay was 19.7 +/- 15.9 days of which 11.6 days were spent in the ICU. Fifty nine patients (54%) were alive at discharge form the ICU of whom 4 ultimately died during their hospital stay. MV practice as well as ICU facilities are not homogenous in Tunisia. Recommendations and guidelines should be built in order to standardize MV practice in Tunisia.     

Metoclopramide attenuates iminodipropionitrile-induced oxidative stress and neurobehavioral toxicity in rats

Metoclopramide (MET) has long been used as a neuroleptic and antiemetic drug in clinical practice. Motor impairment and dyskinesia have been reported in some patients following chronic treatment with MET. Occasionally, the adverse symptoms may appear even after acute exposure to MET in more susceptible population (such as elderly individual) or due to concomitant exposure to MET and certain neurotoxins. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been shown to produce dyskinetic syndrome in rodents. This study reports the effect of concomitant exposure of rats to MET and IDPN on behavioral abnormalities in rats namely excitation, circling and chorea (ECC) syndrome. Four groups of female Wistar rats (aged 3 months) were given MET (0, 10, 40 and 80 mg/kg, i.p., for 11 days) 30 min before IDPN (100 mg/kg, i.p. for 8 days). Two additional groups of rats were treated with either saline (control group) or 80 mg/kg of MET (drug alone group). The animals were observed for neurobehavioral abnormalities including dyskinetic head movement, circling, tail hanging, air righting reflex and contact inhibition of righting reflex. Horizontal and vertical locomotor activities and fore limbs grip strength were also measured. On day 12, the animals were sacrificed and brains were collected for biochemical analysis. MET significantly and dose-dependently protected the animals against IDPN-induced ECC syndrome, motor impairment and deficiency in grip strength. MET also protected the animals against IDPN-induced oxidative stress.