Muerte súbita en pacientes esquizofrénicos en tratamiento con antipsicóticos / Sudden death in schizophrenic patients in treatment with antipsychotic

La intensidad y la evolución de la esquizofrenia dependen de la alteración de determinados centros neuronales y de la interacción entre la gravedad de tales alteraciones y las fluctuaciones de diversos neurotransmisores y neuromoduladores, entre ellos, la dopamina. Quizás debido a esta complejidad y heterogeneidad tanto en su causa como en su evolución, se dan casos de pacientes tratados con antipsicóticos, fisiológicamente estabilizados y de los que no se espera una evolución desfavorable que sufren un fallecimiento inesperado. En este sentido, se considera un caso de muerte súbita en un paciente que padecía hipertensión arterial, diabetes mellitus y esquizofrenia hebefrénica en tratamiento con tioridazina, sustancia que es determinada mediante cromatografía gaseosa acoplada a espectrometría de masas (GC-MS) detectándose la presencia de tioridazina en una concentración de 2,392 mg/L de sangre. Estudiando dicho caso y teniendo en cuenta otros similares se aportan consideraciones que pueden ser de utilidad en la evaluación de estos agentes terapéuticos(AU)

Schizophrenia intensity and its evolution depend on the alteration of certain neuronal centres and on the interaction among the severity of such alterations and the fluctuations of diverse neurotransmitters and neuromodulators, among them, dopamine. Maybe due this complexity and the heterogeneity both in its origin and in its evolution, it due patients' cases treated with antipsychotic, physiologically stabilized from that there is not hoped an unfavorable evolution that they suffer an unexpected death. In this sense, one case is considered with fatal conclusion in a patient who was enduring arterial hypertens ion, diabetes mellitus and hebephrenic schizophrenia in treatment with thioridazine. This substance is analyzed by gas chromatography in tandem with mass spectrometry (GC/MS) found a sanguineous level of 2,39 mg/L. Studying the above mentioned case and taking account others similar; it can be obtained considerations that could be useful in the evaluation of these therapeutic agents(AU)

The stimulated gracilis neosphincter for fecal incontinence: a new use for an old concept.

The stimulated gracilis neosphincter is a viable procedure in selected patients with fecal incontinence. The aim of this paper is to review the technique of this staged operative procedure and review the problems and complications. Stage 1 consists of the vascular "delay" of the gracilis muscle and the creation of a temporary stoma. Stage 2 consists of transposition of the muscle around the anus with implantation of the stimulator. Low-frequency electrical stimulation is applied to the muscle for 12 weeks, after which stage 3 (stoma closure) is undertaken. From March of 1993 to March of 1995, 14 patients (9 females and 5 males) with a mean age of 44 years (range 20 to 67 years) underwent the procedure. Two patients died within 1 year of the operation from unrelated causes. Two patients developed anal stenosis and required permanent stomas. Other complications noted during ascent of the learning curve included seroma, excoriation of the skin above the stimulator, transposition of the stimulator, premature battery discharge, wound infection, rupture of the gracilis tendon, fatigue during programming sessions, and electrode displacement or fibrosis from the nerve. However, 8 of the 10 eligible patients had stoma reversal; the manometric results showed an average mean squeeze pressure that increased from 43 mmHg prior to surgery to 151 mmHg after the operation (p < 0.01). Based on an objective functional questionnaire, 60 percent of the patients who could be evaluated reported improvement in continence, social interactions, and the quality of their life. In conclusion, despite a steep learning curve, the stimulated gracilis operation is a viable operation for selected patients with severe incontinence.

Stimulated gracilis neosphincter operation. Initial experience, pitfalls, and complications.

PURPOSE: The stimulated gracilis neosphincter is accepted as a viable option in select patients with fecal incontinence. The aim of this study was to review the initial problems and complications. METHODS: A prospective analysis of all patients who underwent this procedure was undertaken. Stage I consisted of the distal vascular delay of the muscle and creation of a temporary stoma. Stage II was the transposition of the muscle and implantation of the stimulator and electrodes. Low frequency electrical stimulation was applied to the muscle for 12 weeks, after which Stage III (stoma closure) was undertaken. RESULTS: From March 1993 to December 1995, 17 patients (9 females and 8 males) with a mean age of 42.2 (range, 19-72) years underwent the procedure. One patient died from pancreatitis and another from small-bowel adenocarcinoma, three and six months after the procedure, respectively. Two patients (one with Crohn's disease) required permanent stomas. One additional patient required a permanent stoma because of lead fibrosis. Other complications noted during ascent of the learning curve included seroma of the thigh incision, excoriation of the skin above the stimulator, fecal impaction, anal fissure, parastomal hernia, rotation of the stimulator, premature battery discharge, fracture of the lead, perineal skin irritation, perineal sepsis, rupture of the tendon, tendon erosion, muscle fatigue during programming sessions, and electrode displacement from the nerve or fibrosis around the nerve. However, ultimately after rectification of these problems, 13 of the 15 eligible patients had stoma reversal. Manometric results showed an average basal pressure of 43 mmHg and an average maximum squeeze pressure that increased from 36 mmHg before surgery to 145 mmHg by stimulation (P < 0.01). Based on objective functional questionnaires, 9 of 15 (60 percent) evaluable patients reported improvement in continence, social interactions, and quality of life. Three of these nine patients require daily use of enemas. CONCLUSION: Although the stimulated gracilis operation is a feasible procedure for selected patients with severe incontinence, the learning curve is steep. Although the ultimate outcome in a selected group of patients can be very gratifying, major technical modifications are required before use beyond a research protocol setting. Furthermore, patients must have the psychological strength, emotional commitment, and financial resources that may be necessary for multiple revisional surgeries or ultimate device failure.

Depression of liver microsomal glucose 6-phosphatase activity in carbon tetrachloride-poisoned rats. Potential synergistic effects of lipid peroxidation and of covalent binding of haloalkane-derived free radicals to cellular components in the process.

Depression of liver microsomal glucose-6-phosphatase (G6Pase) activity is a relevant feature of CCl4 poisoning. In vitro studies from several laboratories led to the hypothesis that a CCl4 promoted lipid peroxidation (LP) process is responsible for that effect. In vivo studies from our laboratory with potent antioxidants in dosage regimes inhibiting LP, however, were in contrast with that hypothesis. In this work we studied the potential preventive effects of Pyrazole (Pyr), alpha-tocopherol (alpha T), and 3-amino-1,2,4-triazole (AT) against CCl4-induced depression of G6Pase activity. Pyr decreases the intensity of the covalent binding (CB) of CCl4 reactive metabolites to cellular components but does not inhibit LP in vitro or in vivo. alpha T inhibits LP in vitro and in vivo and AT inhibits both CB and LP. Our present studies give evidence that AT but neither Pyr nor alpha T are able to prevent the CCl4-induced depression of G6Pase activity. Results are compatible with the hypothesis that the cooperation of both factors is critical to explain the observed effects, and suggest that under in vitro experimental conditions used by others the relevance of LP might be artifactually promoted.

Late preventive effects of quinacrine on carbon tetrachloride induced liver necrosis.

We have previously reported that treatments stimulating phospholipid (PL) synthesis or preventing PL degradation were late preventive agents against CCl4-induced liver necrosis. Later studies by others postulated that stimulation of phospholipase A2 (PLA2) plays a role in PL degradative processes responsible for CCl4 damage. Quinacrine (QUIN) is a well known inhibitor of PLA2. In this work we report that QUIN (150 mg/kg i.p.) partially prevents CCl4-induced liver necrosis at 24 h when given 30 min before or 6 or 10 h after CCl4 (2.5 ml/kg p.o.) QUIN administration does not modify at 1 or 3 h after poisoning CCl4 levels reaching the liver, covalent binding of CCl4 reactive metabolites to proteins or lipids, CCl4-induced lipid peroxidation process, CCl4-induced decreases in body temperature, or glutathione levels in liver. QUIN concentrations in liver at times from 1 to 24 h are well over those required to inhibit PLA2 activity. Results are compatible with the hypothesis that CCl4 activation of PLA2 at late stages of poisoning plays a role in CCl4-induced liver necrosis.