An evidence-based, systematic approach using physician-pharmacist comanagement for patients with uncontrolled hypertension resulted in improved blood pressure control and reduced average visit costs/patient.

A revision of an "excitotoxic hypothesis" of schizophrenia is summarized. The hypothesis suggests that in, at least, a subtype of patients with schizophrenia, progressive excitotoxic neuronal cell death in hippocampal and cortical areas occurs via "disinhibition" of glutamatergic projections to these areas. Patients who have excitotoxic damage would be expected to have poor outcomes characterized, perhaps, by anatomic evidence of progressive neurodegeneration, pronounced negative symptoms and cognitive deficits, and profound psychosocial deterioration. Disinhibited glutamatergic activity could result from inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission and a consequent failure to stimulate inhibitory gamma-aminobutyric acid (GABA)-ergic interneurons, and/or anatomic degeneration of inhibitory GABAergic interneurons. The result of these hypothesized mechanisms is excessive stimulation of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate class of glutamate receptor complexes. In turn, this excessive stimulation of AMPA/kainate receptors could lead to disruption of ionic gradients, depletion of energy reserves expended in an attempt to restore and maintain the ionic disequilibrium across neuronal membranes, generation of reactive oxygen species, and cell death from apoptotic and other mechanisms. The postulated existence of disinhibited glutamatergic neurotransmission and the subsequent cascade of excitotoxic events resulting from NMDA receptor hypofunction (NRH), anatomic degeneration of inhibitory GABAergic interneurons, or a combination of the two has suggested a diverse variety of experimental therapeutic interventions for schizophrenia. These interventions include facilitation of NMDA receptor-mediated neurotransmission, potentiation of GABAergic neurotransmission, antagonism of AMPA/kainate receptors, and "quenching" of locally generated reactive oxygen species. In fact, several of these approaches have already been pursued or are proposed as part of a systematic clinical investigation of the revised excitotoxic hypothesis of schizophrenia.

We tested the ability of d-cycloserine, a partial glycine agonist acting at the N-methyl-D-aspartate (NMDA) receptor complex, to improve implicit memory in Alzheimer patients in a parallel-group, placebo-controlled, double-blind study. One-hundred eight patients with probable Alzheimer's disease of mild to moderate severity received d-cycloserine (5, 15, or 50 mg) or placebo twice daily for 10 weeks. We then evaluated their ability to identify perceptually degraded words, some of which were repeated over multiple trials across 3 days. Implicit memory performance of words repeated across trials was significantly enhanced for the patients who received 15 mg d-cycloserine compared with those who received placebo. These findings support development of NMDA receptor-mediated glutamatergic interventions for the treatment of Alzheimer-related memory disorders.

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