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Biomedical subjects

J Morris

Publications and source records attributed to J Morris.

At least 199 records · Page 11Linked to original sources

Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease.

Recent studies have suggested that omega 3-fats of marine origin may have a protective role in heart disease. This study aimed to compare the effects of fish or fish oil, in the setting of a high- or low-fat diet, on platelet aggregation and platelet thromboxane in men with increased risk of cardiovascular disease. One hundred twenty men who were nonsmokers, 30 to 60 years old, with mildly elevated blood pressure and cholesterol were randomly allocated to one of five high-fat (40% of daily energy) or two low-fat (30%) groups for 12 weeks. The five high-fat groups took either 6 or 12 fish oil capsules daily; fish; a combination of fish and fish oil; or placebo capsules. The two low-fat groups took either fish or placebo capsules. Fish meals provided 1.3 g of eicosapentaenoic acid daily, equivalent to 6 fish oil capsules, and contained an average of 3.65 g/d of omega 3-fatty acids. Multiple regression analysis of the combined groups showed that all groups taking omega 3-fatty acids reduced platelet aggregation to both collagen (P < .0001) and platelet-activating factor (PAF) (P < .05) and platelet thromboxane B2 responses (P < .05) to collagen-induced aggregation. The low-fat diet alone had no effect on PAF-induced platelet aggregation and only a small effect on platelet responses to collagen (P < .05). Platelet aggregation responses to PAF were reduced more by fish oil than fish in a high-fat diet, whereas fish had a greater effect when part of a low-fat rather than a high-fat diet. There was no significant difference in collagen-induced platelet aggregation or platelet thromboxane between fish and fish oils on a high or low fat intake. In conjunction with our previous findings of improvements in lipoproteins, blood pressure, and heart rate in this population, these results on platelet function suggest that dietary omega 3-fatty acids incorporated into a low- rather than a high-fat diet have a wider spectrum of more favorable effects on cardiovascular risk factors.

Adult↗

Problems in conducting economic evaluations alongside clinical trials. Lessons from a study of case management for people with mental disorders.

BACKGROUND: Case management has become the statutory basis of community care in the UK for people with long-term mental disorders, although a randomised controlled trial found no important improvements over standard care. Here we compare the costs and cost consequences of this intervention with standard care. METHOD: Resource-use data were collected over a six-month baseline period and for 14 months after randomisation on all patients in the trial. RESULTS: At 14 months the ratio of control group to treatment group weekly costs was 1.09 (95% CI 0.86-1.38) for total costs; 1.12 (0.76-1.65) for state benefits, and 1.21 (0.61-2.42) for health care costs. Costs were thus lower in the treatment group, but these differences were not significant. CONCLUSIONS: Retrospective power calculations indicated that the trial could have detected differences of 30% in total cost, but would have required 700 patients per arm to detect a 20% difference in health care costs. Hence this study, which had adequate power to detect clinically meaningful differences, was found to be far too small to detect large differences in costs. Funding agencies increasingly request that clinical trials include economic alongside clinical end-points: these findings may have important lessons for that policy.

Case Management↗

Exploratory factor analysis of the Wechsler Adult Intelligence Scale-Revised in a sample of brain-damaged women.

The first exploratory factor analysis of the WAIS-R using an exclusively female sample (N = 152) of brain-damaged patients was conducted. Means for age, education, and Full Scale IQ were 43.51 years(SD = 18.22), 12.60 years(SD = 2.47), and 86.34(SD = 13.32). Results indicated that either a two- or three-factor model was plausible for this sample. The two-factor solution supported Wechsler's (1981) Verbal and Performance IQ designations, while the three-factor model revealed Verbal-Comprehension (i.e., Information, Comprehension, Vocabulary, and Similarities), Perceptual-Organization (i.e., all Performance subtests), and Freedom From Distractibility (i.e., Digit Span) factors. Comparison of the factor structures for the present sample with those of normal women and brain-damaged men suggested factorial equivalency across groups.

Journal Article↗

Experiences and findings of a medical officer on Tristan da Cunha, February 1994-February 1995.

DESIGN: A descriptive report on Tristan de Cunha, the most remote Inhabited island in the world, with emphasis on changes in health parameters since the eruption of the volcano in 1961 necessitated the evacuation of the entire island population to the UK. RESULTS: Results of a retrospective 6-month consultation analysis are given as well as the results of screening programmes, particularly for risk factors for ischaemic heart disease. FINDINGS: The high prevalence of asthma among the islanders, possibly the highest in the world, and the management thereof are described.

Adolescent↗

Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer's disease.

A placebo-controlled crossover design, with each treatment period lasting 6 weeks, was used to investigate effects of dronabinol in 15 patients with a diagnosis of probable Alzhemer's disease who were refusing food. Eleven patients completed both study periods; one patient who died of a heart attack 2 weeks before the end of the study was also included in the analysis. The study was terminated in 3 patients: one developed a grand mal seizure and 2 developed serious intercurrent infections. Body weight of study subjects increased more during the dronabinol treatment than during the placebo periods. Dronabinol treatment decreased severity of disturbed behavior and this effect persisted during the placebo period in patients who received dronabinol first. Adverse reactions observed more commonly during the dronabinol treatment than during placebo periods included euphoria, somnolence and tiredness, but did not require discontinuation of therapy. These results indicate that dronabinol is a promising novel therapeutic agent which may be useful not only for treatment of anorexia but also to improve disturbed behavior in patients with Alzheimer's disease.

Aged↗

Soluble L-selectin in peripheral arterial disease: relationship with soluble E-selectin and soluble P-selectin.

Soluble L-selectin, E-selectin and P-selectin were measured in a small case control study of 42 patients with peripheral arterial disease and 42 age and sex matched controls. Levels of soluble L-selectin were 1204 +/- 221 ng/ml (mean +/- S.D.) in the patients compared to 1256 +/- 271 ng/ml in the controls (P = 0.37). There was also no difference in levels of soluble E-selectin (57 +/- 17 ng/ml versus 51 +/- 20 ng/ml, P = 0.15) but levels of soluble P-selectin were increased (249 +/- 101 ng/ml versus 198 +/- 98 ng/ml, P = 0.011). There were no significant correlations between any of the selectins and the risk factors for atherosclerosis or with any leucocyte index. The data point to different mechanisms of release of the soluble selectins in peripheral atherosclerosis and may have important implications for leukocyte/endothelial cell interactions.

Arteriosclerosis↗

Treatment of the dying in the acute care hospital. Advanced dementia and metastatic cancer.

BACKGROUND: Most Americans die in the acute care hospital, where aggressive, life-prolonging interventions are readily performed. Although patients with incurable illness might prefer palliative care, perceived differences in prognosis by physicians may influence the type of care provided. Patients with advanced cancer and advanced dementia represent 2 extremes in the use of hospice services and may also be treated differently in the acute care hospital. We tested this hypothesis and quantitated the use of nonpalliative interventions in hospitalized, incurably ill patients. METHODS: Charts of elderly patients with advanced dementia or metastatic solid tumor malignancy who died during a 13-month period in a tertiary care acute teaching hospital were reviewed. Main outcome measures included the number of patients receiving invasive of noninvasive (but complex) diagnostic tests, invasive nonpalliative treatments, cardiopulmonary resuscitation, systemic antibiotics, and do-not-resuscitate orders. RESULTS: Charts of 164 patients (80 with dementia and 84 with cancer) were reviewed. Overall, 47% received invasive nonpalliative treatments. Controlling for age, sex, length of stay, and insurance status, the groups were equally likely to receive nonpalliative treatments (P = .75), but patients with dementia were more likely to receive new feeding tubes (P = .02). Cardiopulmonary resuscitation was attempted for 24% of each group. Patients with cancer more often received invasive (41% vs 13%; P = .002) and complex noninvasive diagnostic tests (49% vs 23%; P = .02). Overall, 88% received antibiotics, often empirically, but, controlling for neutropenia and invasive tests and treatments, patients with dementia were significantly more likely to receive antibiotics for an identifiable infection (P = .004). CONCLUSIONS: Incurably ill patients often receive nonpalliative interventions at the end of life. Patients with cancer receive more diagnostic tests, but patients with dementia receive more enteral tube feeding. Patients commonly receive systemic antibiotics, often empirically. Cardiopulmonary resuscitation is equally applied, but is out of proportion to expected survival.

Advance Directives↗

Targeting delavirdine/atevirdine resistant HIV-1: identification of (alkylamino)piperidine-containing bis(heteroaryl)piperazines as broad spectrum HIV-1 reverse transcriptase inhibitors.

A novel class of bis(heteroaryl)piperazine (BHAP) analogs which possesses the ability to inhibit NNRTI (non-nucleoside reverse transcriptase inhibitor) resistant recombinant HIV-1 reverse transcriptase (RT) and NNRTI resistant variants of HIV-1 has been identified via targeted screening. Further investigation of the structure-activity relationships of close congeners of these novel (alkylamino)piperidine BHAPs (AAP-BHAPs) led to the synthesis of several compounds possessing the desired phenotype (e.g., activity against recombinant RTs carrying the Y181C and P236L substitutions). Further structural modifications were required to inhibit metabolism and modulate solubility in order to obtain compounds with the desired biological profile as well as appropriate pharmaceutical properties. The AAP-BHAPs with the most suitable characteristics were compounds 7, 15, and 36.

Animals↗

A role for CD9 molecules in T cell activation.

Costimulation mediated by the CD28 molecule plays an important role in optimal activation of T cells. However, CD28-deficient mice can mount effective T cell-dependent immune responses, suggesting the existence of other costimulatory systems. In a search for other costimulatory molecules on T cells, we have developed a monoclonal antibody (mAb) that can costimulate T cells in the absence of antigen-presenting cells (APC). The molecule recognized by this mAb, 9D3, was found to be expressed on almost all mature T cells and to be a protein of approximately 24 kD molecular mass. By expression cloning, this molecule was identified as CD9, 9D3 (anti-CD9) synergized with suboptimal doses of anti-CD3 mAb in inducing proliferation by virgin T cells. Costimulation was induced by independent ligation of CD3 and CD9, suggesting that colocalization of these two molecules is not required for T cell activation. The costimulation by anti-CD9 was as potent as that by anti-CD28. Moreover, anti-CD9 costimulated in a CD28-independent way because anti-CD9 equally costimulated T cells from the CD28-deficient as well as wild-type mice. Thus, these results indicate that CD9 serves as a molecule on T cells that can deliver a potent CD28-independent costimulatory signal.

Animals↗

Two GC boxes (Sp1 sites) are involved in regulation of the activity of the epithelium-specific MUC1 promoter.

In this report, we have analyzed the function of two Sp1 sites present in the epithelium-specific MUC1 promoter. Using promoter-reporter gene (CAT) constructs, we found that mutagenesis of either of the Sp1 binding motifs at -576/-568 and -99/-90, reduced transcription in MUC1-expressing epithelial cell lines. However, abolition of the binding site at -99/-91 by mutagenesis also resulted in increased transcriptional activity in non-epithelial cell lines, suggesting involvement of the site in tissue-specific expression. In vitro binding assays revealed a novel binding motif at -101/-89 (AGGGGGCGGGGTT), which overlaps but differs from the Sp1 consensus motif by having an adenine residue in the 5'-flanking sequence. The 5'-flanking sequence appeared to be important for binding of an Sp1-unrelated factor (SpA) but not for binding of Sp1. Site-directed mutagenesis of the motif into a site able to bind Sp1, but unable to bind SpA, resulted in an increased level of transcription of the CAT reporter gene in all cell lines tested, suggesting a repressive effect of the novel factor on transcription. The ratio between the Sp1 and SpA binding activity in nuclear extracts correlated with both promoter activity and the levels of endogenous transcription in different breast cancer cell lines. Our results are consistent with the idea that the relative activities of the two factors may be involved in the up-regulation of expression of the MUC1 gene seen in breast and other carcinomas.

Base Composition↗

Non-synaptic and dendritic exocytosis from dense-cored vesicles in the suprachiasmatic nucleus.

The sites of exocytosis by dense-cored vesicles (DCVs) from neurones in the rat suprachiasmatic nucleus (SCN) were studied at the ultrastructural level. The tannic acid procedure, which stabilizes extruded proteinaceous substances, was used to demonstrate exocytosis of DCV cores. Fresh brian slices containing the SCN were incubated in media containing high levels of potassium (56 mM) or glutamate (10 mM) in the presence of tannic acid. Long-term slice explant cultures of the SCN were similarly treated. Exocytosis from DCVs occurred from axonal terminals, from dendrites, and occasionally from somata. The sites of DCV exocytosis were generally nonsynaptic or para-synaptic, including release immediately adjacent to axo-spinous synaptic densities. These observations show that, in the suprachiasmatic nucleus, neuroactive substances contained in DCVs do not necessarily function at synaptic contract zones, but could also act as neuromodulators at non-synaptic sites.

Animals↗

Risk of low red or white blood cell count related to estimated benzene exposure in a rubberworker cohort (1940-1975)

This study evaluated the relationship between benzene exposure and low white blood cell (WBC) and red blood cell (RBC) counts. Hematologic screening data collected over a 35 year period at a rubber hydrochloride manufacturing plant were analyzed; an increased risk of leukemia had been demonstrated previously among workers at the plant [Infante et al. (1977).' Lancet 2:76-78; Rinsky et al. (1981): Am J Ind Med 2:217-45 (1987): NEJM 316:1044-1050/. Hematologic screening data were available for 657 of 1,037 (63.3%) individuals employed at the plant from 1939 through 1976. There was a total of 21. 710 blood test records (range per individual 1-354). The study utilized a case-control design and estimated benzene exposures using the job exposure matrix developed by Rinsky et al. (1987): NEJM 316:1044-1050]. The effects of benzene exposure in the 30, 90, and 180 days before the blood test date, as well as cumulative exposure up until the blood test date, were examined using conditional logistic regression. For WBCs there was a strong exposure response and all of the exposure metrics selected showed a significant relationship with low blood count. For RBCs there was a weak positive exposure-response, which was significant (p = 0.03) for one of the dose metrics. The finding of an exposure-response relationship in the range of exposures represented in this study, where the maximum daily benzene exposure estimate was 34 ppm, is consistent with findings of several animal studies demonstrating a decrease in peripheral lymphocyte counts at benzene exposures as low as 10 ppm, and a stronger effect of benzene exposure on lymphocytes (as reflected in total WBC count) than on red cells. There was no evidence for a threshold for the hematologic effects of benzene exposure, suggesting that even exposure to relatively low levels of benzene (e.g., <5 ppm) may result in hematologic suppression.

Benzene↗

Neural activation during covert processing of positive emotional facial expressions.

Lesion studies indicate distinct neural systems for recognition of facial identity and emotion. Split-brain experiments also suggest that emotional evaluation of a stimulus can occur without conscious identification. The present study tested a hypothesis of a differential neural response, independent of explicit conscious mediation, to emotional compared to nonemotional faces. The experimental paradigm involved holding in mind an image of a face across a 45-s delay while regional cerebral blood flow was measured using positron emission tomography. Prior to the delay, a single face was presented with an explicit instruction to match it to one of two faces, photographed at different angles from the target face, presented at the end of the delay. Repeated blood flow measures were obtained while subjects held happy or neutral faces in mind or during a neutral control fixation condition without initial face presentation. The representation of emotional faces over a delay period, compared to either the nonemotional or the fixation condition, was associated with significant activation in the left ventral prefrontal cortex, the left anterior cingulate cortex, and the right fusiform gyrus. The findings support our hypothesis of a differential neural response to facial emotion, independent of conscious mediation, in regions implicated in the processing of faces and of emotions.

Adult↗

Prospective survey of the incidence, risk factors and outcome of hospital-acquired infections in the elderly.

Four hundred and thirty-six patient admissions to either an acute assessment or a rehabilitation ward for the care of the elderly were studied. A total of 113 episodes fitting the definition of a hospital-acquired infection (HAI) occurred in 81 (18.5%) of admissions. The global infection rate was 10.8 per 1000 patient bed days and did not differ between the wards. The chest and urinary tract were the commonest sites of infection, and 26 patients appeared to be infected at more than one site. The majority of first infections occurred within 14 days of admission. Median length of stay for patients with one or more infective episodes was significantly longer than for those who did not develop an HAI. The presence of an HAI, multiple-site infections and chest infections were significantly associated with fatal outcome. HAI occurs commonly in elderly patients and is associated with prolonged hospital stay and increased mortality.

Adult↗