Pharmacogenetics of antipsychotic adverse effects: Case studies and a literature review for clinicians

There is a growing body of literature supporting the contribution of genetic variability to the mechanisms responsible for the adverse effects of antipsychotic medications particularly movement disorders and weight gain. Despite the current gap between research studies and the practical tools available to the clinician to identify such risks, it is hoped that in the foreseeable future, pharmacogenetics will become a critical aid to guide the development of personalized therapeutic regimes with fewer adverse effects. We provide a summary of two cases that are examples of using cytochrome P450 pharmacogenetics in an attempt to guide treatment in the context of recent literature concerning the role of pharmacogenetics in the manifestation of adverse effects of antipsychotic therapies. These examples and the review of recent literature on pharmacogenetics of antipsychotic adverse effects illustrate the potential for applying the principles of predictive, preventive, and personalized medicine to the therapy of psychotic disorders.     

LAPAROSCOPIC CHOLECYSTECTOMY: THE EXPERIENCE OF A COMMUNITY HOSPITAL

Background: The practice of laparoscopic cholecystectomy in a community hospital is presented. The morbidity of the procedure is analysed and recommendations for improvement are made. Laparoscopic cholecystectomy was introduced into this 200 bed community hospital in October 1990. All five general surgeons accredited to the hospital agreed to participate in a quality assurance programme to determine the incidence of complications and to make recommendations for improvement. Methods: The records of all 534 patients having laparoscopic cholecystectomy between October 1990 and September 1993 were reviewed, and all complications recorded. Results: Of the 534 cases reviewed in the study 470 were considered uncomplicated and 64 patients experienced a total of 85 postoperative complications. The death of one patient was caused by a pulmonary embolus and another patient experienced a myocardial infarction. Twenty patients has postoperative atelectasis or pneumonia and urinary infection or retention occurred in seven. Complications of laparoscopic cholecystectomy requiring a conversion to open cholecystectomy occurred in eight patients, biliary complications occurred in 18 and 11 patients required re-operation. Conclusions: Three areas of concern were identified. They were the incidence of major biliary injury (0.37% of all cases) and its management, the role of cholangiography. and the incidence and prophylaxis of deep venous thrombosis and pulmonary embolism. Recommendations for improvement in these areas were made.     

Permeability of pure lipid bilayers to melatonin

Abstract: Melatonin, the chief hormone of the pineal gland, has been reported to interact with a variety of different cells. This ubiquitously acting hormone has been found to interact with protein receptors both at the cell membrane and in the nucleus. Moreover, melatonin was recently shown to be a very potent hydroxyl radical scavenger. The present work focuses on the interaction of melatonin with pure lipid bilayers. It is shown that melatonin can cross multilamellar lipid vesicles, which are used here as model systems for the lipid phase of biological membranes. Thus, the data prove that melatonin can easily pass through the cell membrane and bath every part of the cell, as previously suggested in the literature. Melatonin lipid association constant was calculated based on the change of the hormone fluorescence intensity due to its penetration into the hydrophobic lipid phase. Though melatonin was recently shown to be highly soluble in aqueous media, its lipid association constant is rather high, indicating that the biological action of the hormone is likely to be at the membrane level, either via its interaction with membrane receptors, and/or as a lipoperoxidation radical scavenger.     

Evaluation of a Commercial PCR Kit for Diagnosis of Cytomegalovirus Infection of the Central Nervous System

We evaluated the AMPLICOR cytomegalovirus (CMV) PCR kit for the diagnosis of neurologic CMV infections on 43 positive and 112 negative archived cerebrospinal fluid specimens originally tested by an in-house PCR method. The AMPLICOR kit showed sensitivity and specificity of 95 and 100%, respectively, versus the home-grown assay, indicating its utility in this clinical setting.     

The importance of vaginal mucosal folds at the urethral external meatus

We report on the vaginal mucosal folds (VMF) at the urethral external meatus. Resection of the VMF reduces the dispersed micturition and other urinary symptoms. EDITORIAL COMMENT: The investigators describe the presence of a vaginal mucosal fold (VMF) just dorsal to the urethral meatus and its relationship to voiding abnormalities. VMF were found on physical examination in 8.9% of the clinic population, all of whom complained of dispersed micturition, and 79% also experienced other voiding abnormalities. The complaint of dispersed micturition was successfully treated with excision of the VMF, and the other associated symptoms were improved. This structure should be routinely looked for on physical examination, especially in patients with voiding symptoms. Only further investigation of this newly described entity at other centers around the world will determine the incidence of the anatomic finding and the prevalence of associated voiding disturbances across different populations.     

The effect of desmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure

Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. All had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (2-4 micrograms given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fall, especially in the morning, when patients were often at their worst. Desmopressin may be a useful alternative to, or may supplement, other forms of treatment in some patients with autonomic failure.     

Analgesic activity and release of [MET5]enkephalin-Arg6-Gly7-Leu8 from rat spinal cord in vivo

Rat spinal cord contains the opioid peptide including [Met5]enkephalin-Arg6-Gly7-Leu8 (YGGFMRGL) and a higher molecular weight (HMW) immunoreactive peptide which is an N-terminal extended molecular form of YGGFMRGL. Since a high proportion of tissue immunoreactivity resides in the HMW component we have determined whether this form is released during perfusion of the spinal cord subarachnoid space in vivo while (1) electrically stimulating the sciatic nerves bilaterally or (2) superfusing with substance P. We have found that YGGFMRGL and the HMW immunoreactivity are released by both types of stimuli. The HMW material appeared to be the more stable of the two species of immunoreactivity; its presence in the superfusate was more consistently observed than that of YGGFMRGL itself. Injection of YGGFMRGL into the spinal subarachnoid space in chronically catheterized rats produced a suppression of the tail-flick response. This effect of YGGFMRGL was reversed by naloxone suggesting an action mediated by spinal opiate receptors. These data suggest that YGGFMRGL plays an integral role in the neurotransmission process between spinal neurons storing enkephalin and other neurons. The possibility that enkephalin-mediated neurotransmission includes multiple chemical signals can be entertained.     

Experimental study of the efficacy of the endoluminal prosthesis in colonic anastomoses

Colorectal surgery is still associated with a significant morbidity and mortality rate, mostly related to suture failure. We have carried out a randomized experimental study in dogs on colonic anastomoses exposed to a number of anastomotic risk situations. A total of 42 dogs was used. They were divided into three study groups (control, occlusion and diverticulitis), with and without an endoluminal tube. The aim was to assess the efficacy of the endoluminal prosthesis using clinical and radiological assessment of anastomotic healing. Pre- and post-anastomotic intraluminal pressures were also measured to determine whether these might be a factor in suture failure. There were significant differences in suture failure in animals in which the endoluminal tube was used. Mean duration of placement was 10.5 days. In the colon healing study, no significant differences were found between the groups in the pathological examination or in the assay of hydroxyproline content. The presence of the endoluminal tube may increase the maximum pressure applied on the colon wall. No significant differences were found in the intracolonic pressure differentials between the different groups or after the inclusion of the endoluminal prosthesis. The results obtained establish the efficacy of the endoluminal prosthesis in protecting the colonic anastomosis, and could be a valuable technique in colonic anastomoses with a high risk of suture dehiscence.