Relationship between haloperidol plasma concentration, debrisoquine metabolic ratio, CYP2D6 and CYP2C9 genotypes in psychiatric patients

BACKGROUND: Around seven percent of Caucasians are poor metabolizers of cytochrome P450, CYP2D6 due to genetically impaired activity of the enzyme. Haloperidol in vitro and in vivo inhibits the activity of CYP2D6 and also the involvement of the enzyme in haloperidol metabolism has been reported. The present study was aimed to evaluate the possible inhibition of CYP2D6 during haloperidol treatment, and to determine the effect of CYP2D6 and CYP2C9 genotypes on the plasma concentration of haloperidol. METHODS: Thirty Caucasian psychiatric patients under haloperidol monotherapy were studied. CYP2D6 activity was evaluated by the debrisoquine metabolic ratio (MR), subjects with MR > 12.6 were named as poor metabolizers. Haloperidol plasma concentration was determined by high performance liquid chromatography. RESULTS: The number of patients with debrisoquine MR > 12.6 was higher than the expected comparing to healthy volunteers (13 % vs. 6.6 %, respectively). Debrisoquine MR was correlated with the dose of haloperidol (r = 0.40, p < 0.05), and also with the plasma concentration (r = 0.58, p < 0.001). Additionally, three patients comedicated with inhibitors of CYP2D6 were studied, all of them had a debrisoquine MR > 12.6, however only one was genetically poor metabolizer of CYP2D6. CYP2D6 and CYP2C9 genotypes were not related to the dose or plasma concentration of haloperidol. CONCLUSIONS: The present data support the dose-dependent inhibitory effect of haloperidol on CYP2D6, and the influence of this enzyme activity on haloperidol plasma concentration under steady-state conditions. The inhibitory effect of haloperidol on CYP2D6 enzyme activity may result in drug interactions and unexpected high plasma concentrations when drugs metabolized by the same enzyme are given concomitantly with haloperidol.     

Role of a minimally invasive approach in the management of laparoscopic adjustable gastric banding postoperative complications

HYPOTHESIS: Complications after laparoscopic adjustable gastric banding as treatment for morbid obesity may require a major reintervention. A minimally invasive approach represents an attractive management alternative for such complications. DESIGN: Prospective case series. SETTING: Major academic medical and surgical center. PATIENTS: From January 1996 to July 2003, 47 patients who had undergone laparoscopic adjustable gastric banding were operated on again. Considering the causes for reoperation, the patients were divided into 4 groups: group A had major complications (n = 26); group B, minor complications (n= 11); group C, psychological problems (n=6); and group D, insufficient weight loss (n=4). INTERVENTIONS: Forty-three procedures, 38 using general anesthesia (groups A, C, and D) and 5 using local anesthesia (group B), were performed. MAIN OUTCOME MEASURES: Feasibility, safety, and effectiveness of a minimally invasive approach in the treatment of laparoscopic adjustable gastric banding complications. RESULTS: In group A, 9 of 10 patients with irreversible gastric pouch dilatation and 15 of 16 with intragastric band migrations were treated laparoscopically. In group B, 5 ports were substituted and 2 reconnections of the catheter-port system were performed. In group C, 6 laparoscopic band removals were carried out. In group D, 4 laparoscopic revision procedures for insufficient weight loss were performed. The operative mortality was nil. The most frequent cause of reoperation was intragastric migration (37.2%). A minimally invasive approach was adopted in 94.7% of cases. CONCLUSION: Laparoscopy is safe and effective, even as a second operative procedure.     

Acute intestinal obstruction provoked by intraperitoneal secretion of ovarian tumor. A clinical case

We report here of the case of a 53-year-old woman who presented with intestinal obstruction without response to medical treatment. Exploratory laparotomy produced a moderate quantity of yellowish-green liquid and agglutination of semi-dough-like material. Separation of the flaps of intestine and colon was easily done by the fingers. A grayish white mass of 10 x 15 cm was seen in the left annex, with a perforation which released the semi-dough-like material. Wide resection of the corresponding annex was carried out. Anatomopathologic examination revealed malignant thecoma with resected free borders of at least 2 cm which was moderately differentiated. Because endometrial biopsy was normal, we decided against further hysterectomy. The patient was referred to an oncologist who did not recommend chemotherapy. The patient was reviewed one year later and was found to be free of tumor and in good condition although with some evidence of occlusive blocking. There have been only four similar cases in the literature in which intestinal obstruction by the same mechanism appeared, also indicating that the finding of malignant thecoma is rare.     

Functional sequelae of tuberculous pleurisy in patients correctly treated

STUDY OBJECTIVES: To assess the functional sequelae (FS) of patients with tuberculous pleurisy (TP), to analyze the influence of different factors in the occurrence of these FS, and, finally, to evaluate the relationship between the FS and roentgenographic sequelae. DESIGN: An observational, retrospective study. SETTING: A community teaching hospital in Alicante, Spain. PATIENTS AND METHODS: From April 1986 to July 2000, all patients with a firmly established diagnosis of TP, who had been functionally studied at the end of follow-up, were included in the study. A diagnosis of TP was considered to be definitive when the presence of granuloma on a pleural biopsy specimen was demonstrated or when a culture was positive for Mycobacterium tuberculosis in pleural fluid (PF) or tissue. The general characteristics of the study population and PF were compared in patients with or without restrictive FS (ie, FVC or TLC < 80%), looking for risk factors for developing this complication. RESULTS: Eighty-one of 150 patients who had been treated for TP were eligible for the study. At the end of follow-up, eight patients (10%) had a restrictive FS. These patients had a lower PF lactate dehydrogenase concentration (p < 0.001), a higher PF concentration of cholesterol (p < 0.03) and triglycerides (p < 0.03), and a higher percentage of lymphocytes (p < 0.04). A weak correlation was found between the FVC and the intensity of radiographic pleural thickening (r = - 0.298; p < 0.01). CONCLUSIONS: The FS in patients with TP is restrictive in type, infrequent, and usually mild. A higher PF lipid content or a more chronic inflammatory pleural reaction at diagnosis appear to be risk factors for developing a FS. The correlation between FS and roentgenographic sequelae is poor.     

A study of age-related IgE pathophysiological changes

The literature on immunosenescence has focused mainly on T cell impairment. However, it is well known that B function is also profoundly affected. In particular, several studies have shown age-related changes in immunoglobulin serum levels. Concerning allergic diseases, the incidence of onset of allergic symptoms, as well as their severity, seems to decrease with age. So, the decline of onset of allergic symptoms observed in ageing might result from a decrease of serum total IgE due to an unbalance of cytokines and soluble factors involved in its production. To gain insight into the mechanisms of age related incidence of onset of allergic symptoms, as well as their severity, in this study we have evaluated in a sample of young (12 females and 15 males, range 20-64 years) and old (42 females and 20, males range 70-93 years) individuals serum values of IgE and sCD23 and in vitro Type 2 cytokine production. Total serum IgE levels were quantified by CAP-system fluorescence enzyme immunoassay. Serum CD23 levels were measured by a sandwich enzyme-linked immunoassay. Enzyme immunoassay tests have been used to quantify IL-4, IL-10 and IL-13 on mitogen-stimulated cultures. Serum total IgE and sCD23 in the two groups of young and old subjects were not significantly different. No detectable levels of IL-4, IL-10 and IL-13 were observed in supernatants from unstimulated cultures in all the subjects tested. After 48 h stimulation with PHA, cytokine amounts became detectable in all subjects. However, the values of the cytokines under study were not significantly different between young and old subjects. In our study, we have not been able to show no impairment in the afferent (type 2 cytokine production) and in the central (serum IgE and sCD23 levels) branch of allergic responses. Previous studies have shown that the efferent branch, at least studied as basophil releasability and bronchial responsiveness, is not impaired in elderly. In conclusion, as suggested from the present and previous papers it is questionable whether there is sufficient information to validate the statement that the incidence of allergic diseases decreases with age.