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.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.