The effects of feedback on the behavior of depressed inpatients in two structured interactions.

This study examined the responsivity of depressives' behavior to contingent social feedback within the framework of Coyne's and Lewinsohn's models of depression. Subjects included 10 depressed inpatients, 8 nondepressed psychiatric inpatients, and 10 nondepressed individuals. Each subject participated in two structured interactions with an experimenter in baseline phases and phases in which ongoing contingent feedback was provided by a pair of observers. The results revealed that the behavior of all three subject groups was responsive to the feedback in both interactions. The results are consistent with past research demonstrating social skills problems among depressed individuals but do not support the notion of a social skill deficit in depression. The results are consistent with Coyne's model of depression and suggest that the problematic social behavior often associated with depression may be modifiable by immediate veridical feedback from others.     

Comparison of a carboxypeptidase E-like enzyme in human, bovine, mouse, Xenopus, shark and Aplysia neural tissue

Several diverse species contain an enzyme with many properties in common with those of bovine carboxypeptidase E (CPE), a neuropeptide processing carboxypeptidase B-like enzyme. This enzyme has been designated EC 3.4.17.10, and is also known as enkephalin convertase and carboxypeptidase H. All tissues that are known to contain bioactive peptides also contain CPE-like enzymatic activity. In Xenopus laevis, enzyme activity is highest in the brain and pituitary, lower in the skin, and undetectable in liver and gut. In Aplysia californica, enzyme activity is highest in the atrial gland, but is also present in moderate amounts in the various neural tissue. CPE extracted from human, bovine, mouse, Xenopus, shark, and Aplysia neural tissue is substantially purified using substrate affinity chromatography and concanavalin A sepharose columns. The partially purified enzyme from all species examined possess very similar enzymatic properties. These properties include a pH optimum of 5.6, a stimulation by cobalt chloride, and an inhibition by chelating agents (1,10-phenanthroline). Arginine-derived active site-directed inhibitors show similar inhibition constants (Ki's) towards enzyme from the various species, whereas lysine-derived inhibitors are substantially less potent towards the Aplysia carboxypeptidase than towards enzyme isolated from the other species. The similar properties of the carboxypeptidase isolated from the various species suggests that a CPE-like is involved in the biosynthesis of many peptide neurotransmitters and hormones in a wide range of organisms.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Extraneural metastases in ependymoma

Summary Ependymomas, glial neoplasms usually arising in the posterior fossa or spinal cord, rarely metastasize outside the central nervous system. We have reviewed all 81 ependymomas evaluated at MSKCC between 1956–1989. Five (6.2%) had extraneural metastases (ENM). The primary tumor was in spinal cord in 3 patients and the cerebral hemisphere in 2. Two tumors were histologically anaplastic; 3 were histologically benign. The 5 patients were 3, 3, 3.5, 16 and 37 years old. Time from initial diagnosis to development of ENM was 0, 15, 35, 40, and 288 months. At the time of ENM the primary tumor was progressing in 4/5 patients. Prior therapy had included resection plus radiation therapy (RT) (1), RT plus chemotherapy (1), resection plus RT plus chemotherapy (2). One patient had not received prior therapy because ENM were present at diagnosis. The sites of ENM included lung and thoracic lymph nodes (2), pleura and peritoneum (2), and liver (1). Both patients with peritoneal ENM had had ventriculoperitoneal shunts. ENM did not correlate with histologic grade, age, or degree of surgical resection. When patients with ependymoma develop signs or symptoms of systemic disease such as abdominal pain, cough, or adenopathy, ENM should be considered.     

Deep venous thrombosis: rate of spontaneous lysis and thrombus extension.

AIM: Although recanalization occurs after an episode of venous thrombosis, the exact timing for this process, the rate of clearing at the different venous segments and the nature of the mechanisms involved and their progression are not well known. Recognition of these competing events is important in understanding the natural history and the mechanisms responsible for lysis of the thrombus and for the development of the post-thrombotic syndrome METHODS: During the course of 5 consecutive years, 110 patients (126 legs) with deep vein thrombosis (DVT) were prospectively followed using ultrasonic duplex. Follow-up studies were performed at intervals of 1 and 7 days, 1 month, every 3 months for the 1(st) year, and yearly thereafter. Mean duration of follow-up was 329 days. RESULTS: When only legs with initial complete occlusion are considered, the prevalence of occlusion progressively decreases to 33% after 6 months, 17% after the 1(st) year, and 0% after 3 years. Recanalization of individual segments occurred even more rapidly. After 3 months, recanalization of completely occluded segments was present in 93% of common femoral veins, 79% of superficial femoral veins (proximal segment), 84% of popliteal veins, and 72% of posterior tibial veins. The rate of recanalization was highest for multisegmental disease. Propagation of thrombi to adjacent venous segments occurred in 15% of the limbs. Propagation was usually limited to 1 or 2 adjacent segments. CONCLUSION: Lysis occurred early and was progressive. After 1 year most legs have recanalized. After 3 years recanalization occurred in all legs although residual thrombosis (partial obstruction) was still present in 50% of the limbs. Propagation of the thrombus was a limited process.     

Differential effect of catechol-O-methyltransferase Val158Met genotype on emotional recognition abilities in healthy men and women.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism modulates executive functions and working memory and recent neuroimaging studies implicate an association with emotional processing. We examined the relationship between the COMT Val158Met polymorphism and facial emotion recognition and differentiation in 100 healthy individuals. Compared to Met homozygosity, Val homozygosity was associated with better and faster recognition of negative facial expressions such as anger and sad. Our study provides evidence for a possible influence of the COMT polymorphism on emotion recognition abilities in healthy subjects. Additional research is needed to further define the neurocognitive phenotypes associated with COMT polymorphisms.