Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo.

An experimental drug, 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine, that facilitates glutamatergic transmission in brain after systemic administration was tested for its effects on the induction of long-term potentiation in the hippocampus of rats. Intraperitoneal injections of the drug markedly increased the degree and duration of long-term potentiation; similar results were obtained with an analogue of 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine that was also found to improve retention of memory in a radial maze task and in an odor-matching problem. These results define tools for enhancing long-term potentiation in vivo and confirm an important prediction from the hypothesis that long-term potentiation is a substrate of memory.     

Regional preferences of AMPA receptor modulators determined through agonist binding autoradiography

Autoradiographic techniques were used to test if positive modulators of AMPA-type glutamate receptors have regionally differentiated effects on ligand binding. Cyclothiazide, a drug with ten fold greater effects on `flip' than `flop' splice variants of the receptors, had unequal effects across the subdivisions of hippocampus; i.e., it reduced [³H]AMPA binding in field CA3 with an EC₅₀ of 24 μM and in field CA1 and dentate gyrus with EC₅₀s between 60 and 100 μM. The EC₅₀ for the drug's influence on binding was also significantly lower in the superficial than in the deeper layers of the neocortex, though these differences were not as pronounced as those in the hippocampus. The ampakine CX614, a compound with a modest preference for flop variants, had a slightly lower EC₅₀ for its effects on [³H]AMPA binding in CA1 than in CA3. This result was confirmed with [³H]fluorowillardiine binding. The effects of the ampakine in neocortex tended to be greater in the deeper than superficial layers but this did not reach statistical significance. These results indicate that differential effects of modulators on AMPA receptor subunits are reflected in their relative potency across brain subdivisions. This raises the possibility that subclasses of positive modulators will exhibit a measurable degree of selectivity in their physiological and behavioral influences.     

Dissociation Between Changes in Intramyocardial Function and Left Ventricular Volumes in the Eight Weeks After First Anterior Myocardial Infarction

Objectives. We sought to examine the relation between regional changes in intramyocardial function and global left ventricular (LV) remodeling in the first 8 weeks after reperfused first anterior myocardial infarction (MI).

Background. Because of limitations in imaging methods used to date, this relation has not been thoroughly evaluated.

Methods. We studied 26 patients (21 men, 5 women; mean age 51 years) by magnetic resonance imaging (MRI) on day 5 ± 2 (mean ± SD) and week 8 ± 1 after their first anterior MI. All patients had single-vessel left anterior descending coronary artery disease and although they had received reperfusion therapy, all had regional LV dysfunction and an initial ejection fraction (EF) ≤50%. Short-axis magnetic resonance tagging was performed spanning the LV. Percent intramyocardial circumferential shortening (%S) on a topographic basis, LV mass index, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index and LV ejection fraction (LVEF) were measured.

Results. Left ventricular mass index tended to decrease, whereas the LVEDVI increased from 82 ± 24 to 96 ± 27 ml/m² (p = 0.002). Left ventricular end-systolic volume index remained unchanged, whereas LVEF increased from 39 ± 12% to 45 ± 14% (p = 0.002). Apical %S improved from 9 ± 6% to 13 ± 5% (p < 0.0001), as it did in the midanterior (6 ± 6% to 10 ± 7%, p < 0.02) and midseptal regions (8 ± 7% to 12 ± 6%, p < 0.02). Early dysfunction in remote midinferior and basal lateral regions resolved by 8 weeks. By multivariate analysis, the only significant predictor of an increase in LVEDVI over the study period was peak creatine kinase (p = 0.04).

Conclusions. In the first 8 weeks after a large, reperfused anterior MI, %S improved in the apex, midanterior and midseptal regions and normalized in remote noninfarct-related regions, but LV end-diastolic volumes also increased. This increased LVEDVI correlated with infarct size by peak creatine kinase and was not related to changes in global and regional LV function.     

Sociodemographic and behavioral characteristics of HIV antibody-positive blood donors.

This paper describes the sociodemographic and behavioral characteristics of 173 blood donors who were confirmed by Western blot tests to have antibodies to human immunodeficiency virus (HIV), the etiologic agent for acquired immunodeficiency syndrome (AIDS). Seropositive donors were predominantly young, unmarried, and male, and major risk factors could be identified for almost all donors. However, more than 20 per cent of the study participants were women, and many participants were not aware that they were at risk of infection. The heterogeneity of the study population, the lack of awareness among many subjects of risk factors and self-exclusion procedures, and the high level of distress among many subjects after notification, emphasize the need for intensive, well-designed education and support programs.     

Early abdominal complications of intestinal surgery: the radiologist's role in management

Abdominal complications of intestinal surgery are an important cause of postoperative morbidity and mortality. We define early complications as those occurring within the first 30 days after surgery. The radiological contribution towards prompt and accurate diagnosis of common complications is discussed and the radiologist's role in non-operative management is outlined.     

Endocrinology: Immunohistochemical sex steroid receptor distribution in endometrium from long-term subdermal levonorgestrel users and during the normal menstrual cycle

The bleeding problems experienced by users of subdermal levonorgestrelimplants (Norplant) remain unexplained. The aim of the presentstudy was to investigate the oestrogen (ER) and progesteronereceptor (PR) distribution in levonorgestrel-treated endometrialbiopsies from 31 subjects recruited in Jakarta, Indonesia, andto compare the sex steroid receptor immunostaining with thatof endometrium from 58 normally cycling women from Melbourne,Australia. Sex steroid receptor immunoreactivity was additionallycompared with days of exposure to subdermal levonorgestrel,serum oestradiol and progesterone levels and days of bleedingduring a 90-day reference period. An immunohistochemical techniquewith an alkaline phosphatase anti-alkaline phosphatase (APAAP)detection system for use in formalin-fixed paraffin wax embeddedendometrial tissue was employed. Significantly greater meanimmunostaining scores of stromal PR were observed in Norplantcompared with control endometrium at all stages across the cycle.No significant correlations were demonstrated between sex steroidreceptor immunostaining and days of exposure to subdermal levonorgestrel,serum oestradiol or progesterone concentrations or days of bleedingduring a 90-day reference period. Whether the elevated stromalPR immunostaining in Norplant-treated endometrium is a consequenceof increased synthesis or reduced turnover of receptor remainsunclear. As yet it is undetermined whether increased PR immunoreactivitycorresponds to an increase in number of functional PR.