Screening for latent tuberculosis and gastrointestinal parasite infections in Gurkha recruits: research driving policy change.

Nepalese Gurkha soldiers are recruited from a country endemic for a number of infectious diseases, including tuberculosis and gastrointestinal parasites. This article describes a prospective cohort study which investigated screening strategies for these infections among Gurkha recruits arriving in the UK to begin basic training. Several recommendations were made as a result of the study which were supported for early implementation and subsequently fully adopted. Military screening and treatment policies have been directly influenced by this research which also has translational application to similar migrant civilian populations.

Cognitive impairment in hemodialysis patients is common.

BACKGROUND: Hemodialysis patients are at high risk for cognitive impairment due to their older age and high prevalence of stroke and cardiovascular risk factors. METHODS: Using a cross-sectional design, the authors measured cognitive function in 374 hemodialysis patients aged 55 years and older and an age-matched comparison group in Minneapolis and St. Paul, MN. Cognitive performance was measured in three domains: memory, executive function, and language. Subjects were classified as having no, mild, moderate, or severe cognitive impairment. RESULTS: Of 338 subjects who completed testing in at least two of the three cognitive domains, 13.9% (95% CI 10.4, 18.1) were classified with mild impairment, 36.1% (31.0, 41.5) with moderate impairment, 37.3% (32.1, 42.7) with severe impairment, and 12.7% (9.4, 16.8) with normal cognition. Only 2.9% had a documented history of cognitive impairment. Factors associated with severe cognitive impairment on adjusted logistic regression were stroke (adjusted OR [AOR] 1.95; 95% CI 1.08, 3.49; p < 0.03), equilibrated Kt/V > 1.2 (1.67; 1.01, 2.75; p < 0.05), and education >12 years (0.32; 0.14, 0.72; p < 0.01). The AOR for severe cognitive impairment in a random sample of 101 hemodialysis patients vs an age-matched comparison group was 3.54 (1.28, 9.78; p < 0.02). CONCLUSIONS: Moderate to severe cognitive impairment is common and undiagnosed in hemodialysis patients. Further studies are needed to determine whether dialysis exacerbates the cognitive impairment attributable to underlying disease. Cognitive testing in hemodialysis patients before dialysis initiation and periodically may be warranted.

Introduction: neuropsychological assessment après Luria.

Neuropsychological assessment since Alexander R. Luria's death in 1977 has demonstrated increased sophistication and advancement, and a number of models or approaches to neuropsychological assessment are available worldwide today. This article reviews, in the context of this special issue, Luria's influence on the further development of neuropsychological assessment approaches and methods. Contemporary approaches are summarized and contrasted, and a discussion of neo-Lurian adaptations and extensions of his neuropsychological model is presented. Brief comments about the succeeding articles in this issue help to demonstrate the wide influence sustained by Luria's ideas in various regions of the world.

Introduction: Alexander Luria's continuing influence on worldwide neuropsychology.

As an introduction to this special issue, this article provides an overview of the worldwide influence of the work of Alexander R. Luria, a noted Russian neuropsychologist. Major themes and issues that he studied are reviewed, and the reasons for his strong worldwide influence are discussed. An overview of subsequent articles in this issue is provided.

Disposition and biotransformation of the antipsychotic agent olanzapine in humans.

Disposition and biotransformation of the new antipsychotic agent olanzapine (OLZ) were studied in six male healthy volunteers after a single oral dose of 12.5 mg containing 100 microCi of [14C]OLZ. Biological fluids were analyzed for total radioactivity, the parent compound (GC/MS), and metabolites (electrospray LC/MS and LC/MS/MS). Mean radiocarbon recovery was approximately 87%, with 30% appearing in the faces and 57% excreted in the urine. Approximately half of the radiocarbon was excreted within 3 days, whereas > 70% of the dose was recovered within 7 days of dosing. Circulating radio-activity was mostly restricted to the plasma compartment of blood. Mean peak plasma concentration of OLZ was 11 ng/ml, whereas that of radioactivity was 39 ng eq/ml. Mean plasma terminal elimination half-lives were 27 and 59 hr, respectively, for OLZ and total radioactivity. With the help of NMR and MS data, a major metabolite of OLZ in humans was characterized as a novel tertiary N-glucuronide in which the glucuronic acid moiety is attached to the nitrogen at position 10 of the benzodiazepine ring. Another N-glucuronide was detected in urine and identified as the quaternary N-linked 4'-N-glucuronide. Oxidative metabolism on the allylic methyl group resulted in 2-hydroxymethyl and 2-carboxylic acid derivatives of OLZ. The methyl piperazine moiety was also subject to oxidative attack, giving rise to the N-oxide and N-deemethyl metabolites. Other metabolites, including the N-deemethyl-2-carboxy derivative, resulted from metabolic reactions at both the 4' nitrogen and 2-methyl groups. The 10-N-glucuronide and OLZ were the two most abundant urinary components, accounting for approximately 13% and 7% of the dose, respectively. In fecal extracts, the only significant radioactive HPLC peaks were due to 10-N-glucuronide and OLZ representing, respectively, approximately 8% and 2% of the administered dose. Semiquantitative data obtained from plasma samples from subjects given [14C]OLZ suggest that the main circulating metabolite is 10-N-glucuronide. Thus, OLZ was extensively metabolized in humans via N-glucuronidation, allylic hydroxylation, N-oxidation, N-dealkylation and a combination thereof. The 10-N-glucuronidation pathway was the most important pathway both in terms of contribution to drug-related circulating species and as an excretory product in feces and urine.

Converging impressions in Russian and American neuropsychology: discussion of a clinical case.

We report the case of FR, a 50-year-old woman who suffered a closed head injury in a motor vehicle accident. FR was evaluated approximately two months post-injury using a combined Russian and North American assessment approach with test methods applied from each country. The case is thoroughly discussed qualitatively and quantitatively using the Lurian principle of syndrome analysis to illustrate the findings. The logical-conceptual understanding of the case as different findings were revealed is presented to demonstrate the benefit of the application of a process oriented analysis to assist in the functional description of the case and the development of rehabilitative strategies. We believe that this is one of the first cases to be described that has used a combined Russian and American approach to assessment.

Synthesis of disulfide-bridged fragments of omega-conotoxins GVIA and MVIIA. Use of Npys as a protecting/activating group for cysteine in Fmoc syntheses.

The 3-nitro-2-pyridinesulphenyl (Npys) moiety is finding increasing utility as a protecting-activating group for cysteine, particularly in the synthesis of cyclic and unsymmetrical disulfides using the Boc strategy. This chemistry has been extended to peptides assembled by the Fmoc strategy. N-Terminal Cys(Npys) is introduced via Boc-Cys(Npys)-OPfp. Non-N-terminal Cys(Npys) is incorporated by reacting a resin-bound, fully protected Cys(Acm) peptide with NpysCl. This approach has been applied to the synthesis of four disulfide-bridged fragments of omega-conotoxins GVIA and MVIIA.

Synthesis and dopamine antagonist activity of 2-thioether derivatives of the ergoline ring system.

A series of 2-thioether derivatives of a number of clavine alkaloid (ergoline) ring systems have been synthesized and tested for dopamine antagonist activity. Of the compounds tested 2-(methylthio)-agroclavine (8,9-didehydro-6,8-dimethyl-2-(methylthio)ergoline) (6) was the most potent and had a profile of activity in animal models indicative of potential antipsychotic activity. The synthesis and biological activity of a number of metabolites of 6, including the 13-hydroxy derivative, are also reported.

Quality assurance in an acute geriatric ward.

A multi-disciplinary problem oriented patient record was introduced on to a 24-bed geriatric ward, replacing separate professional records. A Clinical Psychologist and Quality Assurance Consultants assisted with implementation. A Master Problem List with care plans consisting of goal setting and goal achievement analysis were used. Doctors justified use of medications and radiological investigations. Audit indicators were developed for completion of documentation, goal achievement, functional status at discharge, medication and radiology usage. Thirty four per cent of patients' records showed at least one goal not achieved and 45% not reached by review date. Twenty per cent of patients had lower functional status on discharge. Medication cost per patient fell by 10.8% compared with the year prior to introduction. On a similar ward, medication cost rose by 6.7%. This problem resolution approach helped to assure safer discharge and improved team communication. Prescribing behaviour was modified.

Some observations on the use of the Woodcock-Johnson Tests of Cognitive Ability in adults with head injury.

Current research specifies the varied cognitive and psychoeducational deficits in the adult with head injury, and the clinical assessment of this population is widespread, though often only traditional intellectual measures are used. This article provides descriptive data in the first reported study using the Woodcock-Johnson Tests of Cognitive Ability (WJTCA) (Woodcock & Johnson, 1977) in an outpatient sample of 39 adults with closed head injury. The study also addressed (a) the relationships between the various cognitive clusters of the WJTCA and a measure of injury severity (coma duration) and (b) the relationships between the WJTCA and several Halstead-Reitan neuropsychological measures. Correlational analyses indicated significant relationships between coma duration and performance on the Perceptual Speed and Memory clusters of the WJTCA. No relationships were found between the Halstead Category test and any of the WJTCA cognitive clusters, though the Trail Making test correlated significantly with many of the WJTCA clusters. Time since injury did not correlate with any of the WJTCA test results. Other findings are presented, and the advantages and disadvantages of this set of cognitive tests in relation to other psychoeducational and cognitive measures are reviewed.

Methodological considerations in the use of attribute variables in neuropsychological research.

This paper examines the conceptual and statistical difficulties created when neuropsychological research uses attribute variables in traditional orthogonal experimental designs. It is argued that attribute variables, as a result of their statistical and theoretical nonindependence, break the underlying assumptions of these traditional designs, and may lead to incorrect inferences being drawn. These difficulties are illustrated in a consideration of the typical use of analysis of variance designs, matched groups designs, and the analysis of covariance. Finally, a plea is made for the explicit consideration of the assumptions underlying the design models used in neuropsychological research, and a suggestion is made regarding the more appropriate use of correlational techniques in neuropsychology.

4-Piperazinyl-10H-thieno[2,3-b][1,5]benzodiazepines as potential neuroleptics.

A series of 4-substituted 10H-theino[2,3-b][1,5]benzodiazepines has been synthesized. These compounds have been assessed for their ability to block a conditioned avoidance response (CAR) and to produce catalepsy in rats and have been compared with several typical and atypical neuroleptics. The compounds which inhibit CAR at doses which produce no catalepsy are believed to cause less extrapyramidal side effects in the clinic. A number of compounds (9, 12, 17, 29, and 34) show potent neuroleptic activity, yet maintain a favorable separation of activity on these two parametrs. Three 5-piperazinyl-10H-thieno[2,3-b][1,4]benzodiazepine derivatives (46-48) analogous to compounds in the [1,5] series have been prepared for comparison and were found to be inactive.

10-Piperazinyl-4H-theino[3,2-b][1,5]- and -[3,4-b][1,5]benzodiazepines as potential neuroleptics.

The synthesis of 10-piperazinyl-4H-thieno[3,2-b][1,5]benzodiazepines is described. The activity of these compounds has been assessed on the basis of their ability to produce hypothermia in mice and block a conditioned avoidance response (CAR) and produce catalepsy in rats, and the results are compared with various classical and nonclassical neuroleptic drugs. A number of compounds (6, 17, 21, and 22) demonstrate potency greater than clozapine and also show low degree of catalepsy. It is believed that this profile of activity, unlike standard neuroleptics, is associated with the relative lack of extrapyramidal side effects in the clinic. The corresponding 9-piperazinyl-4H-thieno[1,4]benzodiazepines (12 and 35, limited analogues prepared in the respective series, were inactive.

Utility of the neurological examination in rats.

This study presents general observations of neurological examination in rats after various CNS manipulations. The examination consisted of neurologic reactions as described in Bures and co-workers. Subjects studied were controls, hippocampal irradiates, and animals with cerebellar lesions or midline cerebellar transplants. Utility of the procedure as an adjunct to more detailed testing is discussed.

Adamantane and protoadamantanealkanamines as potential anti-Parkinson agents.

The synthesis of 2-halo-1-adamantanemethanamines, 4-protoadamantanemethanamines, and 4-protoadamantaneamines is described. The anti-Parkinson activity of these amines in terms of reversal of reserpine-induced catalepsy in rats has been evaluated and compared with amantadine. 2-Bromo- and 2-chloro-1-adamantanemethanamines are shown to be twice as active as amantadine.