Special Issue: The Fourteenth Annual New York State Office of Mental Health Research Conference: Introduction

Psychiatric Quarterly -     

Assessment and diagnosis of borderline personality disorder

Borderline personality disorder is common in treatment settings and may be so in the general population. In this guide to assessment strategies for diagnosing borderline personality disorder, the authors discuss the reliability and validity of structured interviews and self-report instruments and suggest the use of a self-report questionnaire as a cost-effective screening test. Assessment problems, such as the need for longitudinal observation, are reviewed. Essential features of the recommended diagnostic approach include clarity about the diagnostic concept, consideration of the full range of diagnostic criteria, incorporation of recently developed diagnostic methodologies, care in distinguishing personality disorders from comorbid axis I syndromes, and complete assessment of the full range of axis II disorders.     

Uninformed Decisionmaking The Case of Surrogate Research Consent

A New York court recently struck down state Office of Mental Health regulations governing research involving subjects with impaired decisionmaking capacity. The court held that neither incapacitated adults nor minors could participate in any research protocol that contained a nontherapeutic element, irrespective of possible benefits to the subject or the importance of the knowledge to be gained. Although the decision rested on a technical point of law and dealt only with psychiatric research, the court's holding has significantly broader implications.     

Chronic bronchitis in textile workers

BACKGROUND: Exposure to cotton is known to produce a specific occupational disease known as byssinosis. A large population of textile workers was investigated to determine whether such exposure was also associated with chronic bronchitis once other possible aetiological factors had been accounted for. METHODS: A total of 2991 workers were investigated for the presence of symptoms compatible with chronic bronchitis. An MRC adapted respiratory questionnaire and MRC definition of chronic bronchitis were used for diagnostic labelling. Current and lifetime exposure to dust was estimated by personal and work area sampling, and the use of records of retrospective dust levels previously measured over the preceding 10 years. Airborne endotoxin exposure was measured using a quantitative turbidometric assay. Lung function tests were performed to measure forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). A control group of workers exposed to man-made fibre textiles was identified. The comparative prevalence of chronic bronchitis in the two populations was assessed, allowing for sex, age, smoking habit, and ethnic origin. Two case referent studies were also performed; cases of chronic bronchitis were separately matched with controls from the cotton and control populations to determine the effect of the symptomatic state on lung function. RESULTS: After controlling for smoking (pack years), workers in a cotton environment were significantly more likely to suffer from chronic bronchitis and this was most marked in workers over 45 years of age (odds ratio 2.51 (CI 1.3 to 4.9); p < 0.01). Regression analysis of all possible influencing parameters showed that cumulative exposure to cotton dust was significantly associated with chronic bronchitis after the effects of age, sex, smoking, and ethnic group were accounted for (p < 0.0005). In the intra-cotton population case control study a diagnosis of chronic bronchitis was associated with a small decrement in lung function compared with controls: percentage predicted FEV1 in cases 81.4% (95% CI 78.3 to 84.6), controls 86.7% (84.9 to 88.5); FVC in cases 89.9% (95% CI 87.0 to 92.9), controls 94.6% (92.8 to 96.4). After controlling for cumulative past exposure and pack years of smoking the effect of the diagnostic state remained significant for both FEV1 (p < 0.01) and FVC (p < 0.05). CONCLUSIONS: Chronic bronchitis is more prevalent in cotton workers than in those working with man-made fibre and exposure is additive to the effect of smoking. The diagnosis of chronic bronchitis is associated with a small but significant decrement in lung function.


     

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.     

Diazepam metabolism in cultured hepatocytes from rat, rabbit, dog, guinea pig, and man

Diazepam metabolism has been investigated in cultured hepatocytes from rat, rabbit, dog, guinea pig, and man. The metabolite profile obtained by HPLC analysis of the culture medium indicated that substantial differences exist corresponding to known species differences in the metabolite profile of diazepam in vivo. These differences were attributed to a combination of the rate at which a metabolite was formed and the rate at which it is removed from the medium by further metabolism. The intrinsic clearance of nordiazepam in hepatocytes from each of the species exhibited the most marked species variation (rat much greater than guinea pig greater than rabbit greater than human greater than dog). Species that exhibited a high intrinsic clearance for nordiazepam were also those species that exhibited significant hydroxylation at the 4'-site of the molecule. The disappearance of diazepam was rapid in rat, dog, and guinea pig hepatocytes, but slow in human hepatocytes. Moreover, rat and human hepatocytes exhibited different saturability of diazepam clearance with respect to diazepam concentration accounting, at least in part, for the different rates of diazepam metabolism in the different species. These results support the value of hepatocytes in drug metabolism studies and especially in studies of species differences in metabolism.     

Activation of complement by hydroxyl radical in thermal injury

Complement activation resulting from local burn injury of skin and other soft tissues can be linked to systemic complications, such as intravascular hemolysis, neutrophil activation, and acute lung injury. This study was designed to clarify the relationship between cutaneous thermal injury, oxygen radical formation, and complement activation in vivo. A model for "selective" venous sampling from the area of a partial-thickness cutaneous burn over 25% to 30% of the total body surface in the rat was developed. Interventions involving oxygen radical scavengers, antioxidant enzymes, xanthine oxidase inhibitors, an iron chelator, complement depletion, and neutrophil depletion were used to probe the nature of the oxygen products involved in complement activation. Plasma from the area of burn was examined for total hemolytic complement activity, content of C5a-related chemotactic peptide, and relationship of oxygen products to appearance of this peptide. Xanthine oxidase inhibitors, hydroxyl radical scavengers, and complement depletion diminished the generation of C5a activity at the burn site, whereas neutrophil depletion was without effect. These data suggest that C5a activity may be related to oxygen products from xanthine oxidase. The catalase sensitivity and iron dependency of C5a generation suggest that hydroxyl radical may be related to complement activation and C5a appearance. This is the first report to directly link oxygen radical generation and complement activation in vivo.     

Noise in polymer gel measurements using MRI

With the development of conformal radiotherapy, particularly intensity modulated radiation therapy (IMRT), there is a clear need for multidimensional dosimeters. A commercial polymerizing gel, BANG-2 gel (MGS Research, Inc., Guilford, CT), has recently been developed that shows potential as a multi-dimensional dosimeter. This study investigates and characterizes the noise and magnetic resonance (MR) artifacts from imaging BANG-2 gels. Seven cylindrical vials (4 cm diam, 20 cm length) were irradiated end on in a water bath and read using MRI (B0=1.5 T, TE=20 ms/100 ms, TR=3000 ms). The gel calibration compared the measured depth-dose distributions in water against the change in solvent-proton R2 relaxivity of the gel. A larger vial (13 cm diam, 14 cm length) was also irradiated to test the calibration accuracy in a vial of sufficient volume for dose distribution measurements. The calibration curve proved accurate to within 1.3% in determining the depth dose measured by the larger vial. An investigation of the voxel-to-voxel (IXIX 3 mm3) noise and sensitivity response curve showed that the voxel-to-voxel variation dominated the dose measurement uncertainty. The voxel-to-voxel standard deviation ranged from 0.2 Gy for the unirradiated gel to 0.7 Gy at 20 Gy. Slice-to-slice R2 magnitude deviations were also observed corresponding to 0.2 Gy. These variations limited the overall accuracy of the gel dose measurements and warrant an investigation of more accurate MR readout sequences.