Search PubMed⌕ Search

Biomedical subjects

J Grant

Publications and source records attributed to J Grant.

At least 55 records · Page 3Linked to original sources
PubMed1998

Quantitative structure-activity relationship studies of a series of sulfa drugs as inhibitors of Pneumocystis carinii dihydropteroate synthetase.

Sulfone and sulfanilamide sulfa drugs have been shown to inhibit dihydropteroate synthetase (DHPS) isolated from Pneumocystis carinii. In order to develop a pharmacophoric model for this inhibition, quantitative structure-activity relationships (QSAR) for sulfa drugs active against DHPS have been studied. Accurate 50% inhibitory concentrations were collected for 44 analogs, and other parameters, such as partition coefficients and molar refractivity, were calculated. Conventional multiple regression analysis of these data did not provide acceptable QSAR. However, three-dimensional QSAR provided by comparative molecular field analysis did give excellent results. Upon removal of poorly correlated analogs, a data set of 36 analogs, all having a common NHSO2 group, provided a cross-validated r2 value of 0.699 and conventional r2 value of 0.964. The resulting pharmacophore model should be useful for understanding and predicting the binding of DHPS by new sulfa drugs.

Dihydropteroate Synthase↗
PubMed1998

Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition?

OBJECTIVE: To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits. BACKGROUND: WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits. METHODS: We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing 1H MRS. RESULTS: WS brains exhibited significant biochemical abnormalities. All 31P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time. CONCLUSIONS: The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.

Adenosine Triphosphate↗
PubMed1997

Association of use of a log book and experience as a preregistration house officer: interview survey.

OBJECTIVE: To determine whether use of a log book improved the experiences of preregistration house officers. DESIGN: Confidential questionnaire and interview survey of preregistration house officers carried out as part of University of London inspection process. MEASURES: Preregistration house officers were asked to rate educational and pastoral elements of their posts and about the use made of previously distributed log books. SUBJECTS AND SETTING: Preregistration house officers in North Thames. RESULTS: The incumbents of 535 of 560 (95%) preregistration house officer posts in the region were surveyed between June 1994 and July 1995, 490 by questionnaire and interview, 45 by questionnaire alone. House officers who had discussed the log book with their consultant expressed more satisfaction with their induction, consultant supervision and feedback, and formal and informal education and were more likely to recommend their job to a friend. CONCLUSION: Preregistration house officers who had discussed the log book with their consultant expressed more satisfaction with the educational elements of their jobs. The structured discussion with their consultant about the job and their performance seemed to make the difference.

Consultants↗
PubMed1997

Do individuals with Williams syndrome have bizarre semantics? Evidence for lexical organization using an on-line task.

Williams syndrome, a neurodevelopmental disorder, has attracted a great deal of debate concerning the purported intactness of language in the face of other serious cognitive deficits. As more in-depth studies of specific aspects of WS language have emerged, the notion of a preserved language module has been seriously challenged. Although WS vocabulary scores are often impressive, several investigators have claimed the WS semantics are aberrant. All studies hitherto have been based on off-line experiments which necessarily involve metalinguistic processes. This clearly affects the performance of individuals with cognitive deficits. We report here an on-line study probing the semantic structure of the WS lexicon, using a task-semantic priming-which minimises metalinguistic demands. We show that WS subjects display the same taxonomic/category and thematic/functional priming effects as normal controls. The results are discussed in terms of the differences between receptive and expressive language, as well as the fact that although semantic memory and the automatic access to semantic information for individual words is normal in WS, the integration of semantic information into sentence comprehension may be abnormal. The importance of online tasks to highlight such differences is stressed.

Adolescent↗
PubMed1997

Community hospitals and general practice: extended attachments for medical students.

The first year experience of an innovative experiment in undergraduate medical education is described. The study investigated the educational effectiveness of prolonged clinical attachments for medical undergraduates in community hospital-based general practice. It has also assessed the ability of students to take some responsibility for their own learning in a clinically challenging environment. A retrospective evaluation of the experience obtained during the 3 month attachments for a self-selected group of fourth year Dundee medical school undergraduates was made. These undergraduates were placed in 10 mainly rural Scottish general practices with attached community hospitals providing a wide spectrum of inpatient and outpatient medical and surgical care. Students were assessed on the satisfactory completion of a portfolio of learning experiences and a practical clinical skills list. They were also required to submit a clinical project based on some aspect of their work during the attachment. The initial results showed a high degree of student and tutor satisfaction with the attachments. The assessment of all 10 of the students' educational achievements in their attachment were regarded as satisfactory and two were assessed as outstanding. Tutor assessment confirmed the validity of the initiative. Prolonged attachments in community hospital-based general practice for medical undergraduates have proved educationally valid and popular with both students and tutors. The development and dissemination of this model on a wider scale has resource issues which require to be addressed.

Community Medicine↗
PubMed1997

The prevalence of serological markers for syphilis amongst a sample of Spanish prostitutes.

The results of a multicentre study of 1668 Spanish prostitutes are described with regard to syphilis infection. For those women who permitted serological tests (n = 1095), 30.59% (confidence interval (CI): 30.55%-30.63%) were positive for markers indicating current or prior infection. After adjustment was made for other variables, a significant association with syphilis infection was observed for periods of exposure (i.e. age and years working as a prostitute). No significant associations were detected for either intravenous drug use, or educational attainment. The results of this study are similar to those of some other investigations into the prevalence of syphilis amongst prostitutes.

Adolescent↗
PubMed1997

Language and Williams syndrome: how intact is "intact"?

It has been claimed that Williams syndrome (WS), a rare neurodevelopmental disorder, is characterized by serious cognitive deficits alongside intact language. The syndrome is often used as a prime example of the modularity of an innate faculty for morphosyntactic rules. We challenge this claim and hypothesize that morphosyntax, although surprisingly good given WS level of mental retardation, is by no means intact. We make an initial test of this hypothesis through an analysis of the receptive language of a group of English-speaking WS individuals on a standardized morphosyntactic test. We then present an experimental study of expressive language that examines grammatical gender assignment in French-speaking WS patients. Despite a Verbal Mental Age selected to be higher than the chronological age of the young control group, these people with WS continue even in adulthood to show clear-cut deficits in their production of an aspect of morphosyntax that normal children acquire effortlessly very early. The results of the 2 studies, one focusing on receptive language and the other on expressive language, challenge the notion that comprehension and use of morphosyntactic rules in WS individuals are intact. The Within-domain dissociations regarding the use of grammatical gender assignment across several sentence clements and their difficulties in understanding embedded sentences-two quintessentially linguistic skills-suggest that we must rethink the notion of spared, modular, language capacities in Williams syndrome. We conclude that WS language follows a different path to normal acquisition and may turn out to be more like second language learning.

Adolescent↗
PubMed1996

Management of acute myocardial infarction in Auckland.

AIM: To analyse the utilisation of therapies in coronary care units for patients with acute myocardial infarction. METHODS: An evaluation form was completed prospectively by a designated nurse in each coronary care unit of the four Auckland hospitals in 1993. RESULTS: One thousand and eighty one patients who were admitted with definite or probable acute myocardial infarction had a coronary care unit stay of 63.4 (SD 49.3) hours, and hospital stay of 7.3 (5.1) days. The mortality for definite myocardial infarction was 13.7% (< 70 years 7.1%). Coronary angiography was performed on 10% of patients during their hospital admission, and 4.9% underwent revascularisation. Thrombolytic therapy was administered to 52% (495/948) of patients with definite infarction and 4% had contraindications. Patients aged > or = 70 years (47% vs 55% p = 0.02) or diabetics (46% vs 56%, p = 0.04) were less likely to receive thrombolysis. The utilisation of aspirin and oral beta-blockers was 86% and 40%, respectively, in patients with definite infarction and both were used less frequently in patients > or = 70 years. Intravenous beta-blockers were administered to < 1% of patients. Angiotensin converting enzyme (ACE) inhibitors were prescribed in 21%, intravenous or long acting nitrates in 41% and calcium antagonists in 14%; the latter two therapies were used more frequently in patients > or = 70 years. There was no evidence of gender or ethnic bias for either investigation or treatment. CONCLUSION: On the basis of results of recent clinical trials, there may be under utilisation of some treatments for acute myocardial infarction including aspirin, thrombolytic therapy, beta-blockers and ACE inhibitors, while calcium antagonists may be over used.

Adrenergic beta-Antagonists↗
PubMed1996

Rethinking metalinguistic awareness: representing and accessing knowledge about what counts as a word.

Developmentalists have argued that young children have a confused notion of the metalinguistic concept word and that they cannot focus on single word boundaries when words occur in normal syntactic/semantic frames. We challenge these assumptions and present a new technique which engages normal syntactic-semantic processing but which, once it is interrupted on-line, introduces a metalinguistic component. In three experiments, children listened to a story in which the narrator paused on open or closed class words and then asked children to repeat "the last word" or "the last thing" that she had said each time she stopped. The results show that children as young as 4 1/2-5 years treat both open and closed categories as words and clearly differentiate word and thing. We conclude by suggesting that the new technique may be useful for enhancing early reading readiness and for reassessing the relationship between literacy and metalinguistic awareness.

Awareness↗
PubMed1996

Dizocilpine-like discriminative stimulus effects of low-affinity uncompetitive NMDA antagonists.

The dizocilpine-like discriminative stimulus effects of a variety of channel blocking (uncompetitive) N-methyl-D-aspartate (NMDA) receptor antagonists were examined in rats trained to discriminate dizocilpine (0.17 mg/kg, i.p) from saline in a two-lever operant procedure. The dissociative anesthetic-type NMDA antagonists dizocilpine (ED50 0.05 mg/kg), phencyclidine (ED50 3.4 mg/kg) and ketamine (ED50 14 mg/kg) showed complete substitution without producing significant decreases in response rates, whereas dexoxadrol (ED50 4.3 mg/kg) also produced complete substitution with a concomitant decrease (35%) in response rate. Similarly, the low-affinity antagonist memantine resulted in complete substitution (ED50 9.7 mg/kg) at doses that significantly reduced (68%) the response rate. All other low-affinity antagonists resulted in either partial or no substitution for the discriminative stimulus effects of dizocilpine at doses that significantly decreased average response rates. These include (ED50 values in parentheses) remacemide (29 mg/kg), the remacemide metabolite 1,2-diphenyl-2-propylamine (ARL 12495) (14 mg/kg), phencylcyclopentylamine (25 mg/kg), dextromethorphan (46 mg/kg), (+/-)-5-aminocarbonyl-10,11-dihydro -5H-dibenzo-[a,d]cyclohepten-5,10-imine (ADCI; no substitution) and levoxadrol (no substitution). We conclude that low-affinity uncompetitive NMDA antagonists have discriminative stimulus properties distinct from dissociative anesthetic-type uncompetitive NMDA antagonists. The lowest-affinity antagonists show virtually no substitution for dizocilpine, whereas the relatively more potent low-affinity antagonists (such as memantine) exhibit greater substitution, but complete substitution is obtained only at rate-reducing doses.

Acetamides↗
PubMed1996

Freeman-Sheldon syndrome (whistling face syndrome) and cranio-vertebral junction malformation producing dysphagia and weight loss.

The whistling face syndrome has been reported, with complications of the respiratory system and feeding problems due to microstomia, since 1938. Dysphagia, however, has not previously been reported as a complication of whistling face syndrome. We report a 13-year-old with the whistling face syndrome and dysphagia of late onset who has the typical whistling face, scoliosis and multiple joint contractures. Dysphagia occurred as a result of compression at the cervicomedullary junction by a cranio-vertebral junction malformation and impingement by the tip of the odontoid process. This child had undergone multiple surgical procedures for cleft palate, clubfeet, contractures of the hip and knee and scoliosis. Halo traction and posterior occipital-cervical decompression and fusion successfully treated the dysphagia.

Adolescent↗
PubMed1996

Content of a trainer's report for summative assessment in general practice: views of trainers.

BACKGROUND: Summative assessment of doctors completing general practice vocational training will become compulsory for those completing training after 1 September 1996. One component of the assessment will be a trainer's report. AIM: A study set out to consider the content of the trainer's report. It aimed to determine which elements of general practice general practitioner trainers believe are the most important for independent general practice; to seek the views of trainers as to the most appropriate methods for assessing these elements in summative assessment of general practitioner registrars; and to determine how frequently trainers have been sufficiently concerned about the performance of registrars to consider not signing the form denoting satisfactory completion of the training year. METHOD: A questionnaire was sent to 1296 general practitioner trainers in the United Kingdom. The main outcome measures used were: the percentage of respondents indicating that an element was very important/crucial for independent general practice; the percentage of respondents indicating a favoured method of assessment that did not include a trainer's report at all; and the proportion of trainers who had ever considered not signing the form denoting satisfactory completion of the training year. RESULTS: The response rate was 78%. Of 75 elements examined, 31 were considered important for independent general practice by 70% or more of respondents. For 29 of these 31 elements, fewer than 30% of respondents would choose a method of assessment that did not include a trainer's report at all. Twenty-six per cent of respondents had considered not signing the form denoting satisfactory completion of the training year, which represents a trainer considering not signing this form once every 29 years. CONCLUSION: These results provide a basis for the content of a structured trainer's report for summative assessment in general practice; such a report is likely to contain about 30 items. Data from the Joint Committee on Postgraduate Training for General Practice and the present study suggest that, for every form not signed, trainers considered not signing the forms of another 13 general practitioner registrars. This highlights the need for a report that will help trainers to make the difficult decision as to whether or not a registrar is ready for independent practice.

Education, Medical, Graduate↗