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Biomedical subjects

J L Wright

Publications and source records attributed to J L Wright.

At least 91 records · Page 5Linked to original sources
PubMed1996

Assessment of General Dental Services orthodontic standards: the Dental Practice Board's gradings compared to PAR and IOTN.

The subjective grading of cases at the Dental Practice Board of England and Wales was compared to the Peer Assessment Rating Index (PAR) and Index of Orthodontic Treatment Need (IOTN) in assessing 1505 cases sampled at the Board between late 1990 and mid-1991. Whilst some criteria are common to both systems, case by case there is only limited agreement; sources of disagreement are evaluated. The indices are essentially epidemiological tools; whilst they have short-comings in assessing individual cases, they are related to peer opinion, and show good reliability when used on samples of cases. They can be readily updated, as findings of research or future peer opinion may dictate. Use of PAR and IOTN at the Board, instead of subjective gradings, would require a departure from decisions on withholding payment on a case by case basis. If, however, they were used on samples of practitioners' caseloads to assess reduction of malocclusion, and residual malocclusion and need for treatment, practitioners fees could be up- or down-graded periodically according to their overall performance, to encourage more to adopt higher standards. Allowances could be made, however, for 'limited objective treatments' and cases where poor co-operation had impaired the result.

Dental Health Surveys↗
PubMed1996

A critical assessment of orthodontic standards in England and Wales (1990-1991) in relation to changes in prior approval.

Targeting, use of appliances, and standards of outcome for General Dental Service orthodontic cases collected between 1990 and 1991 were compared with a sample of cases from an earlier study, collected between 1987 and 1988, using the PAR index and IOTN. Comparisons are made generally and in relation to the changes in prior approval regulations for cases started since October 1987. More lower-need cases were treated, but there were no more "unnecessary' treatments and there has been a limited improvement in outcomes, as assessed by the indices, associated with increased use of fixed appliances since 1987. Prior approval appeared to give no tangible benefits in terms of levels of unnecessary treatment or quality of outcome.

England↗
PubMed1996

Cigarette smoke-induced emphysema in guinea pigs is associated with diffusely decreased capillary density and capillary narrowing.

There is little information about whether alveolar capillaries are altered in emphysema. To examine this question, we used scanning electron microscopic morphometry of microvascular corrosion casts to evaluate capillary structure in a guinea pig model of cigarette smoke-induced emphysema. After 6 months, the mean airspace size in the smoke-exposed animals was 157 +/- 31 microns and 106 +/- 11 microns (p < 0.001) in the control (air-exposed) animals. Because previous results from our laboratory had shown differences in size and density between central and peripheral capillaries in normal guinea pigs, these two areas were sampled separately in the present study. Capillaries in the emphysematous animals were narrowed compared with those in the control animals in both the center (mean diameter, 7.51 +/- 1.95 versus 8.93 +/- 2.01 microns, p < 0.001) and periphery (mean diameter, 8.52 +/- 2.13 versus 10.15 +/- 2.16 microns, p < 0.001) of the lobule. Smoke-exposed animals had a decreased capillary density in both the center (0.73 +/- 0.06 versus 0.79 +/- 0.05, p < 0.001) and periphery (0.77 +/- 0.07 versus 0.84 +/- 0.04, p < 0.001) of the lobule. We conclude that cigarette smoke-induced emphysema is associated with a diffuse and relatively uniform narrowing of capillaries with loss of capillary density throughout the lung. These findings may reflect diffuse smoke-induced abnormalities in the alveolar wall matrix with stretching of capillaries over enlarged airspaces and may partially explain the alteration of ventilation perfusion distribution in cigarette smoke-induced emphysema.

Animals↗
PubMed1996

Perceptions of the risks and benefits of orthodontic treatment.

Recent National Health Service changes have brought about a greater involvement of the consumers of medical and dental care in decision making regarding their treatment. The aim of this study was to investigate the level of awareness of the risks and benefits of orthodontic treatment among potential consumers and their referring dentists. Parents of patients referred for orthodontic treatment were issued with a questionnaire about the risks and benefits of treatment and the reason the child had been referred. Study models were also made of the child's teeth. The patients' dentists were issued with a similar questionnaire. The results revealed that most of the parents were aware of the benefits of treatment in general and the reason that their own child required it. This awareness was greater where the orthodontic need on aesthetic grounds was greater. There was less awareness of the risks of treatment though again this was greater among those with a greater need for treatment. When the perceptions of the dentists were evaluated, they were more aware of the risks but were not communicating this to the parents. Since for some patients the risks of treatment may outweigh the benefits, it would be helpful if dentists could provide this information for patients before referral.

Adolescent↗
PubMed1996

Writer's block.

Explore the source record for details and available documents.

Adenocarcinoma↗
PubMed1995

Identification, characterization and pharmacological profile of three metabolites of (R)-(+)-1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenylcyclohexen-1- yl)methyl]pyridine (CI-1007), a dopamine autoreceptor agonist and potential antipsychotic agent.

Liquid chromatographic-mass spectrometric (LC-MS) analysis of plasma taken from cynomolgus monkeys dosed orally with (R)-(+)-1,2,3,6-tetrahydro-4-phenyl-1-[(3-phenylcyclohexen-1- yl)methyl]pyridine (1), a dopamine (DA) autoreceptor agonist and potential antipsychotic agent, revealed several metabolites. The molecular masses of three major metabolites suggested that they were mono- and dihydroxylated derivatives of 1. We synthesized compounds 2 and 3, the two possible mono-p-hydroxyphenyl derivatives of 1, along with the bis-p-hydroxyphenyl derivative 4. These compounds coeluted by HPLC with the three hydroxylated metabolites of 1. Compounds 2-4 all had high affinities for DA D2 and D3 receptors and moderate affinities for D4 receptors. Like 1, compound 2 decreased DA synthesis and neuronal firing in rat brain, indicative of DA autoreceptor activation. Compound 2 inhibited exploratory locomotor activity in rodents and was active in the Sidman avoidance test in squirrel monkeys, predictive of antipsychotic activity in humans. Compounds 3 and 4 showed weak activity in all these tests. After squirrel monkeys were dosed with 1 orally at the ED100 dose of the Sidman avoidance test, the plasma concentration of 2 was below the limit of quantitation. Therefore, these metabolites are unlikely to contribute greatly to the potent activity seen with 1 in the Sidman avoidance test.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Invasive pulmonary aspergillosis in AIDS: radiographic, CT, and pathologic findings.

PURPOSE: To review the radiographic and computed tomographic (CT) manifestations of invasive pulmonary aspergillosis and to correlate the imaging and pathologic findings in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Chest radiographs, CT scans, and pathologic specimens were reviewed retrospectively in 10 AIDS patients with proved invasive pulmonary aspergillosis. RESULTS: The most common radiographic finding was the presence of thick-walled cavitary lesions. Less common findings included nodules, consolidation, and pleural effusion. CT depicted more nodules and cavities than did radiography. The predominant pathologic abnormalities consisted of tissue invasion and abscess formation and angioinvasion with or without infarction. All patients had infection with Aspergillus fumigatus as well as other pathogens, the most common being cytomegalovirus and Pseudomonas aeruginosa. CONCLUSION: Thick-walled cavitary lesions are the most common radiologic manifestation of invasive pulmonary aspergillosis in AIDS. The findings are more numerous and better defined on CT scans. The radiologic findings reflect a spectrum of pathologic abnormalities.

AIDS-Related Opportunistic Infections↗
PubMed1995

Smoke-induced emphysema in guinea pigs is associated with morphometric evidence of collagen breakdown and repair.

We have previously shown that chronic cigarette smoke exposure produces emphysema and airflow obstruction in the guinea pig. To further examine the changes in the connective tissue matrix associated with emphysema in this model, we used ultrastructural morphometry to determine the volume proportions of collagen and elastin in the alveolar walls of animals exposed to smoke or air (control) for 1, 3, 6, and 12 mo. After 1 mo of smoke exposure, there was a statistically significant (P < 0.001) decrease in the volume proportion of collagen in the smoke-exposed animals, whereas by 6 and 12 mo of smoke exposure, the proportion of collagen had significantly (P < 0.02, P < 0.03, respectively) increased. The volume proportion of elastin was increased in the smoke-exposed animals at the 12-mo time period. While our results do not exclude reorganization of elastin within the alveolar wall, we conclude that, in this model, cigarette smoke-induced emphysema appears to be associated with collagen breakdown and repair. We suggest that the currently accepted proteolysis-antiproteolysis theory is too narrow in its focus on elastin destruction as the major contributor to emphysema and should be broadened to the concept that smoke-induced emphysema reflects breakdown and resynthesis (possibly overproduction in the form of scarring) of a variety of connective tissue proteins in addition to elastin.

Animals↗
PubMed1995

Pulmonary function alterations after 3 wk of exposure to hypobaria and/or hypoxia in growing rats.

We studied lung growth in rats between 4 and 7 wk of age under different conditions. There were five groups, seven animals in each: 1) general controls (ambient pressure and room air, food ad libitum); 2) hypobaric normoxic [barometric pressure (PB) 410 mmHg, PO2 153 Torr]; 3) normobaric hypoxic (ambient pressure, PO2 80 Torr); 4) hypobaric hypoxic (PB 410 mmHg, PO2 80 Torr); and 5) weight-matched controls to hypobaric hypoxic. Residual volume, functional residual capacity, vital capacity, and total lung capacity grew 10-20% more in both hypoxic groups than in weight-matched and general controls. Expiratory flow rates corrected for forced vital capacity decreased, and specific airway resistance increased significantly. In addition, the ratio of forced expiratory volume in 0.1 s to %forced vital capacity, peak expiratory flow rate, and forced maximal midexpiratory flow were also lower in normobaric hypoxic animals compared with weight-matched controls. Above a transpulmonary pressure of 6 cmH2O, flows were reduced in both hypoxic groups. No differences were observed between hypobaric normoxic and general control groups for lung volume and lung function. In weight-matched animals, total lung capacity decreased but lung function remained unchanged. We conclude that accelerated lung growth in hypobaric hypoxia and normobaric hypoxia is dysanaptic. Lung growth in hypobaric hypoxia is primarily induced by low oxygen, but differences between hypobaric hypoxia and normobaric hypoxia suggest a beneficial effect of low pressure.

Animals↗
PubMed1995

Density dependence of pulmonary resistance: correlation with small airway pathology.

The density dependence of maximal expiratory flow is not an effective test of the site of airway narrowing in obstructive lung disease. We hypothesized that the density dependence of pulmonary resistance (DD,RL) would be more closely related to the degree of airway narrowing and peripheral airway pathology in smokers. We measured maximal expiratory flow at 50% vital capacity (V'max50) and lung resistance (RL) breathing air and 80% helium-20% oxygen, and calculated density dependence of V'max50 and RL in 40 patients who had moderate airflow obstruction and in 10 normal subjects. We compared the density dependence of RL and V'max50 with the degree of airway obstruction and bronchiolar pathology scores in 27 patients with resected lung specimens. There were no differences in DD of V'max50 or RL between normal subjects and patients, and no relationship between the degree of obstruction or the bronchiolar pathology score and the DD of these measurements. There were significant relationships between V'max50, RL and the bronchiolar pathology scores. In conclusion, lung resistance and maximal expiratory flow are related to the severity of peripheral airway pathology, but there is no relationship between the severity of obstruction or the severity of peripheral airway pathology and the density dependence of maximal expiratory flow or lung resistance.

Adult↗
PubMed1995

Emphysema: concepts under change--a pathologist's perspective.

The diagnosis of pulmonary emphysema is often neither as obvious nor as easy as is generally assumed. In this review, the methodologies are discussed by which emphysema can be accurately diagnosed. The classification of emphysema is outlined, with the salient gross and microscopic features listed.

Emphysema↗
PubMed1994

The discovery and structure-activity relationships of 1,2,3,6-tetrahydro-4-phenyl-1-[(arylcyclohexenyl)alkyl]pyridines. Dopamine autoreceptor agonists and potential antipsychotic agents.

A novel dopamine (DA) autoreceptor agonist, 1,2,3,6-tetrahydro-4-phenyl-1- [(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine (14), was identified. The structure-activity relationships surrounding this compound were studied by synthesis of analogues and evaluation of their dopaminergic activity. The cyclohexene substitution pattern was varied along with the length of the chain connecting the 1,2,3,6-tetrahydro-4-phenylpyridine to the cyclohexene. Compound 14, having the 1,3-substitution pattern and a single methylene chain, was the most potent. The 1,2,3,6-tetrahydro-4-phenylpyridine could be replaced by other aryl-cyclic amines with a slight loss in activity. The phenyl group on the cyclohexene ring could be para substituted; electron-donating groups were better tolerated than electron-withdrawing groups. Finally, the enantiomers of 14 were resolved via the 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate salts. Although both isomers were partial DA agonists, the (+)-enantiomer had higher intrinsic activity than the (-)-enantiomer. Syntheses were developed that allowed rapid preparation of analogues. An X-ray crystal structure determination of an intermediate identified the (+)-isomer of 14 as having R configuration. This compound, designated CI-1007 (PD 143188), was found to have antipsychotic-like activity in behavioral tests; in particular, it was orally active in the conditioned avoidance test in squirrel monkeys with an ED50 of 0.6 mg/kg. The overall profile suggests that (R)-(+)-14 may be a clinically useful antipsychotic agent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Gender-related subcomponent differences in high type A subjects.

Thirty Type A males and 30 Type A females were administered an expanded version of the Structured Interview designed to assess 11 Type A subcomponents. The purpose was to determine whether males and females follow different subcomponent routes in achieving their Type A status. As predicted, males scored higher than females on two of four anger-related variables. Contrary to prediction, males scored higher than females on the subcomponent of exaggerated social control. These findings were interpreted as providing some support for the notion of differing gender-related subcomponent routes for achieving Type A status. These findings also may have implications for the higher incidence of coronary heart disease in high TABP males vs. females.

Adolescent↗
PubMed1994

Estimation and correlation of drug water solubility with pharmacological parameters required for biological activity.

A procedure for estimating the molar water solubility (S) for a series of structurally related drug compounds is presented. HPLC methods for the determination of partition coefficients (P) are combined with semiempirical calculations for S. Multidimensional plots are developed with the physical constants S and P along the x and y axes and with a biological response, e.g. IC50 or ED50, along the z axis. Other attributes, e.g. bioavailability or biodistribution, can be added by color coding, shading, or numbering. Since the methods have a high throughput capability, parameters governing the events leading to pharmacological action [i.e. gastrointestinal dissolution (S), absorption (P), blood level (bioavailability), and biological action (IC50, EC50)] can be correlated for drug series comprising large numbers of compounds.

Chemistry, Pharmaceutical↗
PubMed1994

Kainic acid and 1'-hydroxykainic acid from Palmariales.

The distribution of kainic acid among various red algae was investigated. Analysis of free amino acids from different populations of Palmaria palmata showed that some were unable to accumulate kainic acid to detectable concentrations, whereas in two dwarf mutants it was a major component of the free amino acid composition. The amino acid profiles were also examined for unknown amino acids in the search for possible intermediates in kainic acid biosynthesis. The only unknown amino acid present in P. palmata extracts was isolated and identified by NMR spectroscopy as 1'-hydroxykainic acid. This compound was found in all samples that contained kainic acid. To investigate the effect of growth conditions on kainic acid production different strains of P. palmata were grown at 5, 10, and 15 degrees C with or without added nitrate. No effect on production was observed, suggesting that the growth conditions in these experiments do not affect the level of gene expression in the pathway of kainic acid biosynthesis. Furthermore, changing the growth conditions did not induce synthesis of kainic acid in the non-producing strains of Palmariales.

Amino Acids↗