Effects of fenfluramine on neuropsychological and communicative functioning in treatment-refractory schizophrenic patients

Reported behavioral improvement among autistic patients following feufluramine treatment and a high serotonin level among certain chronic schizophrenic patients suggested that fenfluramine treatment might be beneficial with such schizophrenic patients, especially within the realm of neuropsychological and communicative functioning. A brief neuropsychological battery was administered to eight chronic schizophrenic subjects before, during, and after fenfluramine treatment. Conversations in controlled settings were audiotaped before and during fenfluramine treatment for seven of these subjects and one additional subject. These language samples were analyzed for communicative competence and evidence of thought disorder. Overall, neuropsychological and communicative functioning was worse under the fenfluramine condition, even though blood serotonin levels were about half those at baseline conditions. The results suggest that it is not the higher levels of blood serotonin by themselves that are related to depressed neuropsychological, communicative, and other functioning. In fact, the higher levels of serotonin may well be related to adaptations for maximal level of functioning. These results suggest caution in the use of fenfluramine for other schizophrenic populations.     

The isolated bowel segment (Iowa model II): motility across the anastomosis with or without mesenteric division.

In previous reports, anastomosis has been shown to disrupt the myoelectric activity of the bowel. However, these studies have failed to delineate the role of the extrinsic nerves. Using an isolated bowel segment (IBS) and an amesenteric bowel segment (ABS), motility was evaluated by myoelectric recording across a bowel anastomosis. Ten rats were divided equally into the experimental group with the IBS and the control group with the ABS. In the IBS group, an 8-cm segment of jejunum was divided, reanastomosed, and coapted to the liver margin (Iowa model II). In the ABS group, an 8-cm segment of jejunum was coapted to the liver margin without disruption of bowel continuity (Iowa model II variant). Two weeks later, bipolar electrodes were implanted in the IBS and ABS, and normal jejunum in both groups. Mesenteric division (MD) was performed 4 weeks later to eliminate extrinsic innervation. Myoelectrical recordings were taken 2 weeks before and after MD. In the control group with IBS, incoordination in the propagation of the migrating motor complex (MMC) and reduction in the frequency of slow waves (FSW) were observed across the anastomosis and were unchanged by MD. In the control group with the ABS, the MMC and FSW were identical to that in the normal jejunum and were unaffected by MD. In both groups postprandial inhibition of the MMC was the same as in the normal jejunum and was unaffected by MD. This study confirms that incoordination in propagation of the MMC and reduction in FSW occur across a bowel anastomosis, and elimination of extrinsic innervation does not affect the autonomy of these changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of atrophy of the medial temporal lobe with reduced blood flow in the posterior parietotemporal cortex in patients with a clinical and pathological diagnosis of Alzheimer''s disease.

A combination of medial temporal lobe atrophy, shown by computed tomography, and reduced blood flow in the parietotemporal cortex, shown by single photon emission tomography, was found in 86% (44/51) of patients with a clinical diagnosis of senile dementia of the Alzheimer type (SDAT). The same combination of changes was found in four out of 10 patients with other clinical types of dementia and in two out of 18 with no evidence of cognitive deficit. Of the 12 patients who died, 10 fulfilled histopathological criteria for Alzheimer's disease, nine of them having a clinical diagnosis of SDAT, and one a clinical diagnosis of multi-infarct dementia. All 10 patients with histopathologically diagnosed Alzheimer's disease had shown a combination of hippocampal atrophy and reduced parietotemporal blood flow in life. In 10 patients (nine with SDAT) out of 12 in whom the hippocampal atrophy was more noticeable on one side of the brain than on the other the parietotemporal perfusion deficit was also asymmetrical, being greater on the side showing more hippocampal atrophy. These results suggest that the combination of atrophy of the hippocampal formation and reduced blood flow in the parietotemporal region is a feature of dementia of the Alzheimer type and that the functional change in the parietotemporal region might be related to the loss of the projection neurons in the parahippocampal gyrus that innervate this region of the neocortex.     

Analog language teaching versus natural language teaching: Generalization and retention of language learning for adults with autism and mental retardation

Examined the effects of two instructional methods on language generalization and longterm retention in 23 adults with autism and severe to profound mental retardation. Analog language teaching employed discrete trials in a controlled setting concentrating on discrimination and identification of materials. Natural language teaching emphasized instruction through interactions that occurred incidentally to training students in the use of materials to perform functional tasks. Assessments were conducted under conditions favoring analog teaching to assure against partiality toward natural language teaching. Under such disadvantageous conditions, the methods of natural language teaching would be supported by results showing either no difference or an advantage in their favor. Both techniques increased initial and long-term generalization though the results suggest no relative superiority for either method under these assessment conditions. A significant interaction was found between prior functioning level and sequence of instruction. Because natural language teaching has many strengths, few drawbacks, and produces equal generalization and retention under disadvantageous conditions, it is strongly supported as preferable for people with autism and mental retardation.The authors acknowledge the important assistance provided by the following people: the staff and management of the Behavior Development and Learning Center at CSH/DC directed by Israel Perel, Lisa Kramer, Steve Hafferkamp, James Lowdermilk, and, finally, and especially, to the participants themselves.     

Management of common bile duct stones

Conclusions Choledocholithiasis remains a complicated and challenging disease process for today’s clinicians. Transabdominal ultrasound and ERC are the most common preoperative imaging modalities with endoscopic ultrasound, MRCP, and HCT emerging as potentially more accurate and less invasive tools. Intraoperatively, LUS and IOC are complimentary in detecting CBD stones, while laparoscopic CBDE is commonly and safely performed by surgeons comfortable with advanced laparoscopic techniques. Postoperative ERC is effective with failure of laparoscopic CBDE, surgeon inexperience, and unfavorable anatomy and patient selection. Open CBDE should never be looked upon as a failure, while sphincterotomy, sphincteroplasty, and choledochoenterostomy remain necessary operations for certain patients. The proposed algorithm is only a guideline, and ultimate treatment depends on physician experience and available resources.     

Continued maturation of thymic emigrants in the periphery

Developing thymocytes are selected for recognition of molecules encoded by the major histocompatibility complex, purged of self-reactive cells and committed to either the CD4 or CD8 lineage. The 1% of thymocytes that complete these tasks emigrate and join the population of peripheral lymphocytes. Whether T cell maturation is complete at the time of thymic exit has been a subject of debate. Using mice transgenic for green fluorescent protein driven by the recombination activating gene 2 promoter to identify recent thymic emigrants, we now show that T cell differentiation continues post-thymically, with progressive maturation of both surface phenotype and immune function. In addition, the relative contribution of CD4 and CD8 recent thymic emigrants was modulated as they entered the peripheral T cell pool. Thus, T cell maturation and subset contribution are both finalized in the lymphoid periphery.     

Mutagenicity of bisphenol A (4,4'-isopropylidenediphenol) in vitro: effects of nitrosylation

Bisphenol A (4,4'-isopropylidenediphenol) is a common component of polycarbonate plastics and epoxy resins. Since bisphenol A-containing plastics and resins have found uses in food-contact items, its potential migration into foodstuffs and possible health consequences have been the focus of many recent studies. However, the potential mutagenic activation of bisphenol A by nitrosylation has received little attention. Incubation of bisphenol A with sodium nitrite under acidic conditions produced a yellow-brown product. When nitrosylated bisphenol A was tested in the Ames Salmonella/microsome assay at 100 ng to 1 mg/plate, dose-dependent increases in mutagenicity were found in both TA98 and TA100 Salmonella strains. These results indicated the presence of a direct-acting mutagenic activity causing both frameshift and base pair mutations, respectively. When compared to colony formation in untreated controls, the addition of rat liver S9 for metabolic activation had little influence on revertant colony formation. Unreacted bisphenol A dissolved in DMSO, acidic buffer, or inactivated nitrosylation solution showed negligible mutagenicity. When the nature of the mutagenic changes was examined using the Ames II trade mark Assay, a variety of base pair changes was found including T:A to A:T - S9, G:C to A:T +/- S9,C:G to A:T +/- S9 and C:G to G:C +/- S9. Bisphenol A also induced frameshift mutations at G:C sites. In addition, the presence of electrophiles was shown by the production of an intensely coloured orange-red product upon incubation of nitrosylated bisphenol A with the nucleophile 4-(4'-nitrobenzyl)pyridine. These findings suggest that migration of bisphenol A into nitrite containing foodstuffs, or its ingestion in the presence of nitrite, could lead to the formation of mutagenic compounds.