Outcomes for antidepressant trials in late-life depression

Most randomized controlled trials of antidepressant efficacy in older depressive patients use outcome measures similar to those applied in younger patients. Defining subjects as geriatric based on chronological age alone misses the opportunity to study relationships among efficacy, safety, and the range of impairments associated with aging. Assessment of outcomes related to the medical comorbidities and disabilities associated with late-life depression is needed to understand the broad range of treatment effects. Assessment of changes in subjective and objective measures of functioning can address relationships between clinical state and health-related quality of life. Sensitive measurement of the number and severity of comorbid medical illnesses can precisely characterize the study sample and assess the impact of efficacious treatment on medical illnesses. In long-term studies of heterogeneous geriatric samples, use of appropriate outcome measures can determine the effect of efficacious treatment on changes in health status and functional independence.     

Trans activation of the Escherichia coli ato structural genes by a regulatory protein from Bacillus megaterium: potential use in polyhydroxyalkanoate production

A Bacillus megaterium genomic fragment, which encoded an activator homologous to sigma 54 regulators and which was capable of activating Escherichia coli ato genes in trans, was detected in a gene library of B. megaterium screened for beta-ketothiolase activity. The fragment presented only one complete open reading frame (ORF1), which encoded a protein of 398 amino acids. The recombinant plasmid complemented mutations in the Escherichia coli atoC regulatory gene. The constitutive expression of the E. coli ato operon mediated by ORF1 could be useful for the synthesis of polyhydroxyalkanoates with different flexibility properties by recombinant E. coli strains.     

Marker selection for the transmission/disequilibrium test, in recently admixed populations

Various analytical, iterative and rebinning algorithms have been proposed for 3D reconstruction in positron emission tomography. This paper examines execution times of five analytical and rebinning algorithms. Meaningful comparisons are obtained by using similar software modules in all implementations. Reconstruction times are shown to differ by vast amounts: the Favor algorithm of Defrise et al is more than twice as fast as the widely used reprojection algorithm of Kinahan and Rogers; the Fourier rebinning algorithm (Fore) recently developed by Defrise is more than 15 times faster than the reprojection algorithm.     

Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors

Homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1o and GluR3o were expressed in Spodoptera frugiperda (Sf9) insect cells. Membranes containing the recombinant receptors showed a doublet of bands of the expected size (99-109 kDa) after western immunoblotting which was shifted to a single band upon deglycosylation. In (R,S)-[3H]AMPA binding experiments, high expression was seen (Bmax = 0.8-3.8 pmol/mg protein) along with high affinity binding to a single site (Kd, nM+/-S.D.): GluR1o, 32.5+/-2.7; GluR3o, 23.7+/-2.4; GluR1o + GluR3o, 18.1+/-2.9. The pharmacological profiles of these receptors resembled that of native rat brain AMPA receptors: AMPA analogues > L-glutamate > quinoxaline-2,3-diones > kainate. In the Xenopus oocyte expression system we had previously shown that the agonist (R,S)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionate (ACPA) exhibited an 11-fold selectivity for GluR3o vs. GluR1o. In this study, it was found that ACPA has 3-fold higher affinity at homomeric GluR3o and heteromeric receptors than at homomeric GluR1o, suggesting that its efficacy and/or desensitisation properties are different at GluR1o vs. GluR3o.     

Fecal bile acids and neutral sterols in patients with familial polyposis

Fecal neutral steroids and bile acids were measured in patients with familial polyposis, family controls who are immediate relatives of patients, and controls other than relatives. All subjects were consuming a mixed Western diet at the time of collection of stool specimens. Although the total fecal neutral sterol concentrations were not different between the groups, the patients with familial polyposis excreted a high amount of cholesterol and low levels of coprostanol and coprostanone compared with other groups. Patients with familial polyposis excreted levels of total bile acids in their feces comparable to those excreted by controls; lithocholic acid excretion was decreased in patients with familial polyposis. These findings suggest that analysis of stools for cholesterol and its metabolites be useful in screening the siblings of polyposis families for latent disease.     

Fetal heart rate patterns preceding death in utero

Four cases of intrauterine fetal demise in term infants are presented. From these cases and other published reports, a sequence of fetal heart rate changes preceding intrapartum death is presented. Late or variable decelerations, if unrelieved or uncorrected, lead to baseline heart rate changes of tachycardia and loss of variability reflecting loss of fetal reserve and fetal distress. This is followed by an unstable heart rate, a sinusoidal pattern, or a rapidly changing fetal heart rate. The final event is a profound bradycardia just prior to fetal demise.