Anxiolytic activity of glycine-B antagonists and partial agonists--no relation to intrinsic activity in the patch clamp

On the basis of animal models, anxiety was one of the first suggested clinical applications of partial agonists of the glycineB site coupled to the NMDA receptor. It is not certain, however, whether these findings can be extended to full glycineB antagonists and what is the relation between intrinsic activity (degree of NMDA receptor antagonism) and anxiolytic effect. In the present study several NMDA receptor antagonists, including several glycineB antagonists/partial agonists, were tested for anxiolytic activity in the Vogel conflict test and the elevated plus-maze. Additionally, the intrinsic activities of the glycineB partial agonists used [ACPC, (R,+)-HA-966 and D-cycloserine] were compared in patch-clamp experiments in cultured neurones. In the plus-maze the most striking increase in the time spent in open arms (index of anxiolytic effect) was seen after diazepam and D-cycloserine (at doses that did not change locomotion). Also reliable (dose-dependent), although weaker, anxiolytic activity was produced by the uncompetitive NMDA receptor antagonist (+)MK-801 and the competitive antagonist CGP 39551. Modest anxiolytic-like effect in the plus-maze was also observed after the glycineB antagonist L-701,324 and the partial agonist (+,R)-HA-966. Uncompetitive antagonists memantine and amantadine, the glycineB partial agonist ACPC (up to 600 mg/kg) or the full antagonists MRZ 2/570, MRZ 2/571 and MRZ 2/576 had no effect. In the Vogel conflict test neither memantine, nor any of the full glycineB antagonists tested (L-701,324 and MRZ 2/576), showed anxiolytic activity. Patch-clamp studies revealed that the intrinsic activity of (+,R)-HA-966, D-cycloserine and ACPC was 13, 57 and 92%, respectively, as compared to that of glycine itself (100%). In conclusion, for the agents tested there is no clear relation between the levels of intrinsic activity, i.e. degree of NMDA receptor inhibition, and anxiolytic activity. Moreover, L-701,324 and MRZ-type glycineB full antagonists do not exchibit anxiolytic activity in the elevated plus-maze and Vogel conflict test.     

Perceived family criticism and primary care utilization: psychosocial and biomedical pathways

We explored the relationship of perceived family criticism to subsequent healthcare utilization in patients attending a family medicine center. We examined: a) the relationship of perceived criticism to subsequent utilization for biomedical and psychosocial/somatic problems; b) the mediating effects of self-rated mental health and physical function; and c) the mediating effects of social support. The analyses were adjusted for age, sex, race, education, health insurance, and martial status. Higher perceived criticism predicted more psychosocial/somatic and biomedical visits. The relationship of perceived criticism with psychosocial/somatic visits was entirely mediated through self-rated mental health. The relationship of perceived criticism with biomedical visits was partly mediated through self-rated physical function and, in part, independent. Social support played no role in explaining these relationships. Further research is needed to determine whether lowering perceived family criticism lowers primary care utilization.     

Assessment of nutritional status in CAPD patients: serum albumin is not a useful measure

INTRODUCTION: In CAPD patients serum albumin is frequently used as an index of nutritional status, although it is recognized that hypoalbuminaemia may be caused by many factors. We have further examined the relationship between serum albumin and nutrition. METHODS: Nutritional status was assessed by biochemistry, anthropometry, mid-arm muscle circumference, muscle strength (hand grip and back), and lean body mass (from anthropometry, creatinine kinetics and bioimpedance) in a group of 76 stable CAPD patients. Correlations between biochemical and nutritional parameters were sought and data were compared between patient groups defined by serum albumin (> or = 37 vs < 37 g/l on two occasions 2 months apart) and separately according to subjective global assessment score (normal nutrition, A vs mild to moderate, B, and severe, C, malnutrition). RESULTS: In patients with a low SGA score, actual body weight, body mass index, mid-arm muscle circumference, lean body mass, subscapular skinfold thickness, hand grip strength (males and females) and iliac and triceps skinfold thicknesses and back strength (females only) were all significantly less than in patients with a normal SGA score. In contrast, none of these variables differed in either gender when patients were compared according to serum albumin. Serum albumin was correlated with serum creatinine (r = 0.45, P = 0.01), daily urine protein excretion (r = -0.42, P = 0.02) and uncorrected weekly creatinine clearance (r = -0.39) in females, but not with any index of body composition in either gender. CONCLUSION: Whilst SGA identified a patient group with significantly abnormal body mass, muscle mass and muscle strength, serum albumin did not. Serum albumin is not a useful marker of malnutrition in stable patients on CAPD.     

Outcome of subarachnoid haemorrhage. An analysis of surgical variables, cognitive and emotional sequelae related to SPECT scanning

A group of 48 patients, consecutive apart from exclusions, from a 1-year series of 60 cases of aneurysmal subarachnoid haemorrhage (SAH), was reviewed, in respect of clinical and radiological features, surgical management, clinical outcome, psychological distress and psychometric status, the neuropsychological assessment being compared with a closely-matched group of controls, the postoperative assessment being accompanied by a single positron emission computed tomogram (SPECT) scan. A review of those features which might have been expected to have a bearing on cognitive outcome (CT abnormalities at the outset, angiographic vasospasm, operative aneurysmal leakage, temporary vessel occlusion) failed to show a significant difference on cognitive tests. There was, however, a cognitive deficit shown by the patient group as a whole, when compared with the controls. Thus, SAH itself, the initial insult, would appear to be the essential factor in the production of persistent cognitive deficits.