The AMPA receptor potentiator LY404187 increases cerebral glucose utilization and c-fos expression in the rat.

AMPA receptor potentiators enhance AMPA receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of AMPA receptor potentiators is unknown. The aim of this study was to determine the effects of the biarylpropylsulfonamide AMPA receptor potentiator, LY404187 (0.05 to 5 mg/kg subcutaneously), upon cerebral glucose utilization and c-fos expression using 14C-2-deoxglucose autoradiography and c-fos immunocytochemistry. LY404187 (0.5 mg/kg) produced significant elevations in glucose utilization in 28 of the 52 anatomical regions analyzed, which included rostral neocortical areas and the hippocampus, as well the dorsal raphe nucleus, lateral habenula, and locus coeruleus. No significant decreases in glucose utilization were observed in any region after LY404187 administration. The increases in glucose utilization with LY404187 (0.5 mg/kg) were blocked by pretreatment with the AMPA receptor antagonist LY293558 (25 mg/kg), indicating that LY404187 acts through AMPA receptor-mediated mechanisms. LY404187 (0.5 mg/kg) also produced increases in c-fos immunoreactivity in the cortex, locus coeruleus, and the dorsal raphe nucleus. These studies demonstrate neuronal activation in key brain areas that are associated with memory processes and thus provide an anatomical basis for the cognitive enhancing effects of AMPA receptor potentiators.     

Antagonist effects of the enantiomers of 3-PPP towards alpha 1-adrenoceptors coupled to inositol phospholipid breakdown in the rat cerebral cortex

The effects of the two enantiomers of 3-PPP upon alpha 1-adrenergic and muscarinic receptors coupled to the inositol phospholipid (PI) breakdown response have been investigated. 3-PPP(-) and 3-PPP(+) were found to antagonize the noradrenaline (10 microM)-stimulated PI breakdown in rat cerebral cortical miniprisms with IC50 values of 18 and 61 microM, respectively. The dopamine receptor antagonists haloperidol and raclopride were also antagonists, with IC50 values of 0.4 and 25 microM, respectively. 3-PPP(-) and raclopride were found further to act as competitive antagonists, with pA2 values of 6.03 and 5.44, respectively. 3-PPP(-), 3-PPP(+) and haloperidol also antagonized the muscarinic receptor-mediated carbachol (50 microM)-stimulated PI breakdown in cortical miniprisms, albeit at high concentrations (IC50 values of 91, 170 and 28 microM, respectively) whereas raclopride produced only 24% inhibition at the highest concentration tested (100 microM).     

Analysis of deaths in patients awaiting heart transplantation: impact on patient selection criteria.

OBJECTIVE: To analyse the clinical characteristics of patients who died on the Stanford heart transplant waiting list and to develop a method for risk stratifying status 2 patients (outpatients). METHODS: Data were reviewed from all patients over 18 years, excluding retransplants, who were accepted for heart transplantation over an eight year period from 1986 to 1994. RESULTS: 548 patients were accepted for heart transplantation; 53 died on the waiting list, and 52 survived on the waiting list for over one year. On multivariate analysis only peak oxygen consumption (peak VO2: 11.7 (SD 2.7) v 15.1 (5.2) ml/kg/min, P = 0.02) and cardiac output (3.97 (1.03) v 4.79 (1.06) litres/min, P = 0.04) were found to be independent prognostic risk factors. Peak VO2 and cardiac index (CI) were then analysed in the last 141 consecutive patients accepted for cardiac transplantation. All deaths and 88% of the deteriorations to status 1 on the waiting list occurred in patients with either a CI < 2.0 or a VO2 < 12. In those with a CI < 2.0 and a VO2 < 12, 38% died or deteriorated to status 1 in the first year on the waiting list. Patients with CI > or = 2.0 and a VO2 > or = 12 all survived throughout follow up. Using a Cox's proportional hazards model with CI and peak VO2 as covariates, tables were constructed predicting the chance of surviving for (a) 60 days and (b) 1 year on the waiting list. CONCLUSIONS: These data provide a basis for risk stratification of status 2 patients on the heart transplant waiting list.     

Disordered vergence control in dyslexic children.

By means of a synoptophore vergence eye movements were recorded in dyslexic and normal children while they were attempting to track small targets moving in simulated depth. Of the dyslexic children 64% were unable to make proper vergence movements when macular sized fusion targets (2 1/2 degrees) were employed, but their vergence control was better for larger (7 degrees) targets. The normal readers and the remaining dyslexics showed normal vergence responses for both large and small moving fusion stimuli. The results suggest that many dyslexics suffer a disorder of visuomotor control and perception for stimuli falling on the macula; this may explain their characteristic visual problems when reading. Hence recording vergence eye movement responses to small moving fusion stimuli may be useful in the investigation and treatment of children with reading difficulties.     

Effectiveness of training health professionals to provide smoking cessation interventions: systematic review of randomised controlled trials.

OBJECTIVE--To assess the effectiveness of interventions that train healthcare professionals in methods for improving the quality of care delivered to patients who smoke. DESIGN--Systematic literature review. SETTING--Primary care medical and dental practices in the United States and Canada. Patients were recruited opportunistically. SUBJECTS--878 healthcare professionals and 11,228 patients who smoked and were identified in eight randomised controlled trials. In each of these trials healthcare professionals received formal training in smoking cessation, and their performance was compared with that of a control group. MAIN MEASURES--Point prevalence rates of abstinence from smoking at six or 12 months in patients who were smokers at baseline. Rates of performance of tasks of smoking cessation by healthcare professionals, including offering counselling, setting dates to stop smoking, giving follow up appointments, distributing self help materials, and recommending nicotine gum. METHODS--Trials were identified by multiple methods. Data were abstracted according to predetermined criteria by two observers. When possible, meta-analysis was performed using a fixed effects model and the results were subjected to sensitivity analysis. RESULTS--Healthcare professionals who had received training were significantly more likely to perform tasks of smoking cessation than untrained controls. There was a modest increase in the odds of stopping smoking for smokers attending health professionals who had received training compared with patients attending control practitioners (odds ratio 1.35 (95% confidence interval 1.09 to 1.68)). This result was not robust to sensitivity analysis. The effects of training were increased if prompts and reminders were used. There was no definite benefit found for more intensive forms of counselling compared with minimal contact strategies. CONCLUSIONS--Training health professionals to provide smoking cessation interventions had a measurable impact on professional performance. A modest, but non-robust, effect on patient outcome was also found, suggesting that training alone is unlikely to be an effective strategy for improving quality of care, unless organisational and other factors are also considered.     

Isoperistaltic intestinal lengthening for short bowel syndrome

Because of improvements in supportive care, many infants now survive massive intestinal loss and have short bowel syndrome. Unfortunately, some survivors are left with an insufficient amount of intestine and cannot be weaned from total parenteral nutrition. An isoperistaltic intestinal lengthening procedure was used to treat surgically two such infants with 25 centimeters of remaining small intestine and absent ileocecal valves. This surgical technique longitudinally divides the short, dilated small intestine into two smaller, parallel lumens that are anastomosed end to end. This procedure preserves all mucosa, prolongs transit time by doubling intestinal length and corrects the ineffective peristalsis by tapering the dilated intestine. The lengthening technique can be performed because of the anatomic division of the intestinal vasculature within two leaves of the mesentery. Longitudinal division between the two leaves maintains vasculature to each side of the intestine. The isoperistaltic intestinal lengthening procedure, as it was successfully applied to two infants, is described in detail.     

Assessment of toroidal surfaces by the measurement of curvature in three fixed meridians

A method is described where the surface curvatures and axis orientation of a toroidal surface can be determined by measuring the lens in three fixed orientations. This method also has possible applications in the measurement of progressive addition lenses.     

L/M speed-matching ratio predicts reading in children.

PURPOSE: Many behavioral studies have found impaired perception of dynamic visual stimuli in dyslexia and several neuroimaging studies have found reduced activation of the human motion area MT+ in dyslexia. These results are often interpreted as a magnocellular (MC) deficit in dyslexia. It has also been claimed that colored filters can help dyslexics to read. One defining feature of the MC-pathway is a greater weight for L-cone input than M-cone input, and at most very weak S-cone input. We measured the subjective speed matches between L-, M-, and S-cone isolating stimuli in good and poor readers. METHODS: Subjects performed a speed-matching task with drifting cone-isolating stimuli to find the point of subjective equality between two drifting patterns. Such a task is known to activate cortical area MT+, presumably via the MC-pathway. RESULTS: L- to M-cone speed-match ratios were negatively correlated with single-word (r=-0.46) and irregular-word reading (r=-0.56) but not with non-word reading. CONCLUSIONS: Results suggest that relative L-cone sensitivity within the MC-pathway may limit orthographic reading performance.