Effects of antipsychotic treatment on polysomnographic measures in schizophrenia: a replication and extension

OBJECTIVE: The authors sought to replicate and extend previous observations of improvement in some EEG sleep measures during the course of antipsychotic treatment in schizophrenia patients. METHOD: Fourteen medication-free patients with schizophrenia underwent 2 nights of sleep EEG monitoring before and after 3-4 weeks of treatment with clinically determined doses of haloperidol or thiothixene. RESULTS: Measures of sleep continuity improved consistently. REM latency increased, although five of 14 patients continued to exhibit short REM latencies (less than 60 minutes). Stage 3 sleep increased during neuroleptic treatment, while stage 4 sleep did not change. CONCLUSIONS: These data demonstrate partial improvement of some but not all EEG sleep measures in schizophrenic patients through the course of neuroleptic treatment. They suggest that shortened REM latency and disturbed sleep continuity might represent reversible state abnormalities, while reduced slow-wave sleep may represent a more persistent trait abnormality in schizophrenia.     

Autonomic control of cardiovascular function: clinical evaluation in health and disease

The high- and low-pressure baroreceptor reflexes are integral to the control of blood pressure by the autonomic nervous system. Tests of the integrity of these baroreflexes make it possible to identify the site of autonomic dysfunction in patients with orthostatic hypotension. Clinical characteristics and typical results of autonomic testing in patients with autonomic failure, with carotid sinus hypersensitivity, and with hyperadrenergic autonomic dysfunction are described in this review.     

EIR1, a root-specific protein involved in auxin transport, is required for gravitropism in Arabidopsis thaliana

The EIR1 gene of Arabidopsis is a member of a family of plant genes with similarities to bacterial membrane transporters. This gene is expressed only in the root, which is consistent with the phenotypes of the eir1 mutants-the roots are agravitropic and have a reduced sensitivity to ethylene. The roots of eir1 mutants are also insensitive to the excess auxin produced by alf1-1 and fail to induce an auxin-inducible gene in the expansion zone. Although they fail to respond to internally generated auxin, they respond normally to externally applied auxin. Expression of the EIR1 gene in Saccharomyces cerevisiae confers resistance to fluorinated indolic compounds. Taken together, these data suggest that the EIR1 protein has a root-specific role in the transport of auxin.     

High-performance liquid chromatography determination of mycophenolic acid and its glucuronide metabolite in human plasma

Two HPLC-UV assays are reported here: one is a rapid assay for mycophenolic acid (MPA) and the other is a simultaneous assay for MPA and its metabolite mycophenolic acid glucuronide (MPAG). For both methods, plasma samples (500 microl) with added internal standard were acidified and extracted using C18 solid-phase extraction cartridges. Chromatographic separation was achieved on a C18 Novapak column using a mobile phase consisting of methanol-0.05% orthophosphoric acid (40:60, v/v) for the rapid MPA assay and 30:70 for the simultaneous MPA and MPAG assay. The assays were linear over the ranges 0.1 to 50.0 mg/l for MPA and 2.8 to 225.8 mg/l for MPAG. Mean absolute recovery for all analytes was >99%. These methods are suitable for therapeutic drug monitoring and pharmacokinetic studies.     

Native valve infective endocarditis in elderly and younger adult patients: comparison of clinical features and outcomes with use of the Duke criteria and the Duke Endocarditis Database

The effect of age on the presentation and outcome of infective endocarditis (IE) is unclear. Many of the available data are based on analyses of mixed populations of patients including intravenous drug users or those with prosthetic valve endocarditis or native valve IE. We used the Duke criteria to compare the characteristics of 44 episodes of definite native valve IE in elderly patients (> 64 years old) with the characteristics of 64 similarly defined episodes of native valve IE in younger, nonintravenous-drug-using adult patients (> 29 years and < 60 years old). Our data suggest that the clinical presentation, characteristics, and outcome of native valve IE are similar for elderly patients and younger adult patients, although elderly patients were hospitalized an average of 12 days longer. Although we found that the occurrence of renal failure and cerebral embolism during an episode of IE was associated with higher rates of death (odds ratios, 4.8 and 4.0, respectively), age was not a significant contributor to mortality.     

Utility of ischemic scores in the differential diagnosis of Alzheimer's disease and ischemic vascular dementia

Despite new developments in the concept of vascular dementia, the Hachinski Ischemic Score (HIS) and its modified versions continue to be widely used in the clinical differentiation of Alzheimer's disease (AD) and ischemic vascular dementia (IVD). The sensitivity of the HIS and two modified versions in the diagnosis of AD, IVD, and single infarcts in a large, geriatric population with mild cognitive impairment (N = 100) was evaluated. Sensitivity for identification of AD was greater than 90% but was less than 70% for IVD. Over one third of patients with one or more infarcts on computed tomographic brain scans and 63% of mixed cases were classified as having probable AD. It is concluded that ischemic scores may be useful at predicting prevalence rates if individual case accuracy is ignored. Despite being sensitive to identifying AD, ischemic scores are insensitive to both cerebral infarction and IVD and cannot reliably exclude IVD. Finally, patients with mixed dementia should not be expected to have intermediate scores.     

The influence of stereoisomerism on the pharmacokinetics of Tc radiopharmaceuticals

The influence of stereoisomerism on the pharmacokinetics of Tc mono-oxo complexes is reviewed. Tc(V) monooxo complexes formed with N/S ligands have four donor groups from the ligands in an equatorial plane; the oxo ligand coordinates in an axial position. Stereoisomerism in Tc (V) mono-oxo complexes can be centered within the ligand (carbon atom in the chelate ring or ligating nitrogen of amine donors) or at the Tc. The metal center becomes chiral when an equatorial ligand has a head and a tail (i.e., the two ends of the ligand differ). All types of stereocenters can produce significantly different pharmacokinetic profiles for individual isomers. Thus, biological evaluation of separated stereoisomers is necessary to identify the optimal sterochemical configuration, particularly for radiopharmaceuticals targeted to receptor molecules with low specificity. Because of interspecies variation, there is ultimately no substitute for human testing. Although it is possible that the increase in non-specific binding of agents incorporating L-vs D-amino acids may more than offset any increased receptor binding, much more information is needed. Stereochemical factors can also lead to unpredictable differences in coordination geometry and thermodynamic preference of a single isomer; thus chemical characterization of stereoisomers continues to be an important component of radiopharmaceutical development.