Perfectionism in Intensive Residential Treatment of Obsessive–Compulsive Disorder

Cognitive Therapy and Research - Perfectionism is frequently noted in obsessive–compulsive disorder (OCD) and some data suggest that treatment outcomes with cognitive behavioral therapy (CBT)...     

Body dissatisfaction adjusted for weight: The body illusion index

The current study extends earlier observations that body dissatisfaction is positively associated with body weight for eating disorder patients and for nonpatient college women. An adjustment to the Eating Disorder Inventory (EDI) Body Dissatisfaction score (i.e., the “Body Illusion Index” or “Bll”) is proposed to statistically eliminate the effects of relative body weight on Body Dissatisfaction scores and to systematically increase Body Dissatisfaction scores at lower relative weights. The adjustment results in a mean adjusted body dissatisfaction score for the anorexia nervosa patients more closely resembling that for bulimia ner-vosa patients and differing significantly from normal weight college women. The “Body Illusion Index” addresses the different meanings and clinical significance that body dissatisfaction implies for individuals at different weights. © 1992 John Wiley & Sons, Inc.     

Measurent of psychometric features and their relationship to clinical outcome in the longterm course of anorexia nervosa

This study investigated the long-term outcome of anorexic patients using standardized psychometric instruments in addition to global clinical ratings. The findings suggest (1) a similar pattern of long-term outcome for both psychometric instruments that assess a variety of psychosocial paremeters and global clinical ratings and (2) recovered anorexic patients are similar to a comparison group of healthy women in terms of anorexic symptoms and psychosocial difficulties.     

耐一线药物及注射药物对耐多药结核病治疗效果的影响

背景和目的:最近的研究结果表明,对其他一线药物和注射类药物(如卡那霉素、卷曲霉素)等耐药是影响耐多药结核病(MDR-TB)患者治疗效果的独立危险因素.本研究旨在明确耐其他一线药物和注射类药物对韩国不合并人免疫缺陷病毒(HIV)感染的MDR-TB患者临床疗效的影响.方法:采用回顾性队列研究分析1996年1月至2005年12月首尔国家大学附属医院治疗的211例MDR-TB患者治疗效果,排除7例丢失和7例迁出,对197例患者进行了最终分析.     

Identification of the primary collagen-binding surface on human glycoprotein VI by site-directed mutagenesis and by a blocking phage antibody

Glycoprotein (GP) VI is the major receptor responsible for platelet activation by collagen, but the collagen-binding surface of GPVI is unknown. To address this issue we expressed, from insect cells, the immunoglobulin (Ig)-like ectodomains (residues 1-185) of human and murine GPVI, called hD1D2 and mD1D2, respectively. Both proteins bound specifically to collagen-related peptide (CRP), a GPVI-specific ligand, but hD1D2 bound CRP more strongly than did mD1D2. Molecular modeling and sequence comparison identified key differences between hD1D2 and mD1D2. Ten mutant hD1D2s were expressed, of which 4 had human residues replaced by their murine counterpart, and 6 had replacements by alanine. CRP binding studies with these mutants demonstrated that the exchange of lysine at position 59 for the corresponding murine glutamate substantially reduced binding to CRP. The position of lysine59 on the apical surface of GPVI suggests a mode of CRP binding analogous to that used by the related killer cell Ig-like receptors to bind HLA. This surface was confirmed as critical for collagen binding by epitope mapping of an inhibitory phage antibody against GPVI. This anti-GPVI, clone 10B12, gave dose-dependent inhibition of the hD1D2-collagen interaction. Clone 10B12 inhibited activation of platelets by CRP and collagen in aggregometry and thrombus formation by the latter in whole blood perfusion. Antibody 10B12 showed significantly reduced binding to the hD1D2-E59, and, on that basis, the GPVI:10B12 interface was modeled.     

Disequilibrium Between Alveolar and End-Pulmonary-Capillary O<Subscript>2</Subscript> Tension in Altitude Hypoxia and Respiratory Disease: An Update of a Mathematical Model of Human Respiration at Altitude

We have previously formulated and validated a mathematical model specifically designed to describe human respiratory behavior at altitude. In that model, we assumed equality of alveolar and end-pulmonary-capillary oxygen tensions. However, this equality may not hold true during rapid and prolonged changes to high altitudes producing severe hypoxia as can occur in aircraft cabin decompressions and in some respiratory diseases. We currently investigate this possibility by modifying our previous model to include the dynamics of oxygen exchange across the pulmonary capillary. The updated model was validated against limited experimental data on ventilation and gas tensions in various altitude-decompression scenarios. The updated model predicts that during rapid and sustained decompressions to high altitudes the disequilibrium of gas tensions between alveolar gas and capillary blood could be 10 Torr, or larger. Neglecting this effect underestimates the severity of a decompression and its potential to produce unconsciousness and subsequent brain damage. In light of these results, we also examined the effect of this disequilibrium on the diminished oxygen diffusion capacity that can occur in some respiratory diseases. We found that decreases in diffusion capacity which would have minimal effects at sea level produced significant disequilibrium of gas tensions and a large fall in hemoglobin oxygen saturation at a cabin altitude of 4000–8000 ft. As demonstrated, this new model could serve as an important tool to examine the important physiological consequences of decompression scenarios in aircraft and the pathophysiological situations in which the equilibrium of gas tensions along the pulmonary capillary are particularly critical.     

Effect of DPC 333 [(2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide], a human tumor necrosis factor alpha-converting enzyme inhibitor, on the disposition of methotrexate: a transporter-based drug-drug interaction case study.

DPC 333 [(2R)-2-{(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4-methylpentanamide] is a potent human tumor necrosis factor alpha-converting enzyme inhibitor with potential therapeutic implications for rheumatoid arthritis. Methotrexate (MTX), a drug for the treatment of rheumatoid arthritis, is eliminated primarily unchanged via renal and biliary excretion in humans as well as in rats and dogs. The objective of the present study was to investigate the potential effect of DPC 333 on the disposition of MTX. In dogs, DPC 333 administered orally at 1.7 mg/kg 15 min before the intravenous administration of [14C]MTX (0.5 mg/kg) did not alter the plasma concentration-time profile of MTX; however, the total amount of radioactivity excreted in urine increased from 58.7% to 92.2% of the dose, and the renal clearance increased from 1.8 ml/min/kg to 2.9 ml/min/kg, suggesting a decrease in MTX disposition via biliary excretion. The biliary excretion of MTX was investigated in isolated perfused livers prepared from wild-type and TR(-) [multidrug resistance-associated protein 2 (Mrp2)-deficient] Wistar rats in the absence and presence of DPC 333. Mrp2-mediated biliary excretion of MTX was confirmed with 95.8% and 5.1% of MTX recovered in the bile of wild-type and TR(-) Wistar rats, respectively. DPC 333 at an initial perfusate concentration of 50 microM completely blocked the biliary excretion of MTX, but not the clearance from perfusate, in both wild-type and TR(-) rats. These results suggest that the enhanced renal elimination of MTX may be due to the potent inhibition of biliary excretion and active renal reabsorption by DPC 333 and/or its metabolites.     

Comparative 13-week cigarette smoke inhalation study in Sprague-Dawley rats: evaluation of cigarettes with two banded cigarette paper technologies.

This study compared the toxicological responses of Sprague-Dawley rats exposed nose-only to mainstream smoke (MS) from Test cigarettes (1, 2, and 3) to those of Control cigarettes without banded cigarette paper technologies (BCPT). Test cigarettes 1 and 2 had bands based on one technology (different band weight application) while Test cigarette 3 had bands based on another technology. The banded papers are representative of current marketed technologies. Rats were exposed to humidified HEPA filtered air (Sham) or to MS at concentrations of 0.06, 0.20, or 0.80 mg wet total particulate matter per liter air. Each exposure group contained 30 animals/sex (sentinel had 20 animals/sex). The study had two phases (13 weeks each): MS exposure (1 h/day, 5 days/week) and recovery without smoke exposure. Endpoints included clinical observations, respiratory physiology, hematology, serum chemistry, blood carboxyhemoglobin (COHb), serum nicotine, body/organ weights, gross pathology, and histopathology. Comparisons conducted were: Sham exposed vs. all cigarettes, Control cigarette vs. all Test cigarettes, and Test 1 vs. Test 2. Control and Test MS had comparable effects on respiratory physiology, COHb, serum nicotine, serum chemistry, and hematology. While some minor differences were observed, Control and Test MS had comparable effects on clinical signs, body/organ weights, and gross pathology/histopathology. Consequently, exposure of rats to equivalent MS concentrations from the four cigarettes induced similar toxicological responses in this study.