Regional activity of galactose-1-phosphate uridyltransferase in rat brain.

The sp act of galactose-1-phosphate uridyltransferase has been measured in individual regions of adult rat brain to see if site-specific differences in enzyme activity can aid in the understanding of brain abnormalities observed in well-treated galactosemic patients. The sp act in the cerebellum, brain stem, and midbrain were higher than in the cortex, hippocampus, and striatum. Activity in the cerebellum was 2-fold greater than that found in the cortex. Steady state levels of mRNA of the enzyme in the cerebellum were twice that of the cortex corresponding to the ratio of enzyme sp act in the two regions. Measurement of the kinetic parameters in tissue from the cerebellum and cortex revealed that the regional specificity in enzyme activity observed in the brain represents differences in the Vmax. Inhibition of the enzyme by uridine and uridine triphosphate was essentially the same for all regions and was not influenced by the 2-fold differences observed in the levels of enzyme. Inhibition by uridine was significantly greater than that for uridine triphosphate.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Quality indicators for primary care mental health services

Objectives: To identify a generic set of face valid quality indicators for primary care mental health services which reflect a multi-stakeholder perspective and can be used for facilitating quality improvement.

Design: Modified two-round postal Delphi questionnaire.

Setting: Geographical spread across Great Britain.

Participants: One hundred and fifteen panellists representing 11 different stakeholder groups within primary care mental health services (clinical psychologist, health and social care commissioner, community psychiatric nurse, counsellor, general practitioner, practice nurse/district nurse/health visitor, psychiatrist, social worker, carer, patient and voluntary organisations).

Main outcome measures: Face validity (median rating of 8 or 9 on a nine point scale with agreement by all panels) for assessing quality of care.

Results: A maximum of 334 indicators were rated by panels in the second round; 26% were rated valid by all panels. These indicators were categorised into 21 aspects of care, 11 relating to general practices and 10 relating to health authorities or primary care groups/trusts. There was variation in the total number of indicators rated valid across the different panels. Overall, GPs rated the lowest number of indicators as valid (41%, n=138) and carers rated the highest number valid (91%, n=304).

Conclusions: The quality indicators represent consensus among key stakeholder groups in defining quality of care within primary care mental health services. These indicators could provide a guide for primary care organisations embarking on quality improvement initiatives in mental health care when addressing national targets and standards relating to primary care set out in the National Service Framework for Mental Health for England. Although many of the indicators relate to parochial issues in UK service delivery, the methodology used in the development of the indicators could be applied in other settings to produce locally relevant indicators.

     

Neuroendocrine response to 5-hydroxytryptophan in seasonal affective disorder

A double-blind random-ordered comparison of the effects of placebo and 5-hydroxytryptophan (200 mg, orally) in ten depressed patients with seasonal affective disorder (SAD) and ten controls disclosed slightly but significantly higher basal levels of serum prolactin and a trend toward higher basal levels of serum cortisol in the patients with SAD compared with controls. After administration of 5-HTP, the cortisol level significantly increased and the prolactin level significantly decreased in both patients and controls. No differences in the melatonin level, growth hormone level, blood pressure, or pulse rate and no side effects were noted between patients and controls in the two study conditions; the timing of basal and 5-hydroxytryptophan-stimulated hormonal secretions was similar for both groups. These results are discussed with reference to current hypotheses of the cause of SAD.     

Cognitive impairment after unilateral hemispheric injury of congenital or adult origin.

OBJECTIVE: The purpose of this study was to assess and compare cognitive functioning in adults with unilateral hemispheric injury due to either congenital damage or an ischemic event in young adulthood. METHOD: Adults with cerebral palsy resulting from left hemispheric brain damage were compared with adults who had a unilateral stroke in either the left or the right hemisphere. Our primary interest was to determine the impact on hemispheric dominance as revealed by dichotic listening, a task that assesses the bias for preferential listening and processing of sounds. Performance also was determined on a language-related task (word finding) and a spatial task (dot localization). RESULTS: Scores on the Quick Neurological Screening Test indicated that all participants demonstrated significant neuromotor deficits, whereas scores on the Barthel Index indicated that the participants were functional in basic activities of daily living. On cognitive assessments, healthy control participants demonstrated a pronounced left-hemisphere dominance and right-ear advantage; participants with injury to the left hemisphere showed a strong shift toward a right-hemisphere and left-ear dominance. In particular, injury of congenital origin appeared to foster this neural reorganization and localization of language-related functions into the healthy hemisphere. This shift was associated with a deterioration of performance on both the language and the spatial tasks. CONCLUSION: The importance of appreciating subtle deficits after unilateral injury is important in therapy. The dichotic listening test may provide a simple and useful means for evaluating persistent unilateral brain dysfunction in the clinical setting.     

The functioning and well-being of depressed patients. Results from the Medical Outcomes Study

We describe the functioning and well-being of patients with depression, relative to patients with chronic medical conditions or no chronic conditions. Data are from 11,242 outpatients in three health care provision systems in three US sites. Patients with either current depressive disorder or depressive symptoms in the absence of disorder tended to have worse physical, social, and role functioning, worse perceived current health, and greater bodily pain than did patients with no chronic conditions. The poor functioning uniquely associated with depressive symptoms, with or without depressive disorder, was comparable with or worse than that uniquely associated with eight major chronic medical conditions. For example, the unique association of days in bed with depressive symptoms was significantly greater than the comparable association with hypertension, diabetes, and arthritis. Depression and chronic medical conditions had unique and additive effects on patient functioning.     

Forensic psychiatrists' and psychologists' understanding of insanity: misguided expertise?

The ability of mental health experts to consult on insanity cases is highly dependent on their accurate understanding of the current Canadian standard. The study surveyed experienced forensic psychiatrists and psychologists and found the majority (88%) had erroneous beliefs regarding the insanity standard. Results of a discriminant analysis suggest that experience with insanity evaluations and courtroom testimony may improve experts' understanding. Implications of these results are discussed with respect to professional training and public policy.