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Biomedical subjects

L Moore

Publications and source records attributed to L Moore.

At least 73 records · Page 4Linked to original sources

Theoretical analysis of cell separation based on cell surface marker density.

A theoretical analysis was performed to determine the number of fractions a multidisperse, immunomagnetically labeled cell population can be separated into based on the surface marker (antigen) density. A number of assumptions were made in this analysis: that there is a proportionality between the number of surface markers on the cell surface and the number of immunomagnetic labels bound; that this surface marker density is independent of the cell diameter; and that there is only the presence of magnetic and drag forces acting on the cell. Due to the normal distribution of cell diameters, a "randomizing" effect enters into the analysis, and an analogy between the "theoretical plate" analysis of distillation, adsorption, and chromatography can be made. Using the experimentally determined, normal distribution of cell diameters for human lymphocytes and a breast cancer cell line, and fluorescent activated cell screening data of specific surface marker distributions, examples of theoretical plate calculations were made and discussed.

Antigens, Surface↗

Effects of the Heartbeat Wales programme over five years on behavioural risks for cardiovascular disease: quasi-experimental comparison of results from Wales and a matched reference area.

OBJECTIVE: To assess the net 5 year effects of intervention of a community based demonstration project, the Heartbeat Wales programme, on modifiable behavioural risks for prevention of cardiovascular disease. DESIGN AND SETTING: Quasi-experimental design comparing results from two independent cross sectional population surveys conducted in 1985 and 1990 in Wales and a matched reference area in north east England. SUBJECTS: Random, stratified samples of people aged 18-64 years (18,538 in 1985 and 13,045 in 1990) in Wales and in north east England (1483 and 4534, respectively). INTERVENTION: A coordinated range of activities for heart health promotion in Wales entailing public education campaigns along with supportive policy and infrastructure change. In the reference area no additional community heart health promotion was planned, though considerable activity did take place, "contaminating" the reference area. MAIN OUTCOME MEASURES: Fifteen self reported behavioural indicators relating to dietary choice, smoking, frequency of exercise, and weight. RESULTS: Positive changes (for health) in behavioural outcomes were observed among the population in Wales, including a reduction in reported smoking prevalence and improvements in dietary choice. There was no net intervention effect for the programme over and above observed change in the reference area. CONCLUSIONS: No definite conclusions can be drawn concerning the efficacy of the programme in terms of behavioural outcomes. With hindsight, the difficulties of evaluating such a complex multifaceted intervention were underestimated. Further debate on the most appropriate methods for assessing the effectiveness of community based health promotion programmes is called for.

Adolescent↗

Can the urea breath test for H.pylori replace endoscopy for the assessment of dyspepsia in primary care?

AIMS: The urea breath test may have value in the initial assessment of dyspepsia in primary care. This pilot study tracks patient and general practitioner behaviour which cannot be predicted with modelling studies. METHODS: The urea breath test was made available over a period of 18 months. The test was requested when general practitioners would normally have used a trial of medication or referred for endoscopy. Patients with a positive urea breath test had early endoscopy before treatment. Patients with a negative urea breath test were treated according to symptom response. A follow-up questionnaire was given 6-24 months after the urea breath test. RESULTS: Urea breath tests were requested on 249 patients; clinical notes and follow-up interview data were available for 207 patients (83%). The urea breath test was positive for 89 patients (43%); 70 were referred for endoscopy and peptic ulcer disease was found in 33 (47%). The urea breath test was negative for 118 patients; 14 were follow-up tests after previous H.pylori treatment. For the 104 patients with dyspepsia, a negative test and no previous treatment, 42% had 1 or more previous investigations for dyspepsia and 66% had dyspepsia symptoms for more than one year. During follow-up, 21 patients had endoscopy. Dyspepsia symptom scores were significantly lower at follow-up (p < 0.01). Using a global assessment, 66% had fewer symptoms, 22% same and 12% had more symptoms. The symptom improvement was greater if the duration of symptoms was less than one year (p < 0.05). Medication use did not change significantly. Twelve patients were dissatisfied with management; most of these would have preferred endoscopy. CONCLUSIONS: A negative urea breath test appears to have some reassurance value. The use of the urea breath test as initial assessment for dyspespia may prevent the need for some endoscopy. Further controlled studies of breath testing compared with early endoscopy are required.

Adult↗

Are giant ganglia a reliable marker of intestinal neuronal dysplasia type B (IND B)?

It has been suggested that giant ganglia are a marker for a developmental bowel disorder, intestinal neuronal dysplasia of the submucosal plexus (IND B), diagnosed in a proportion of patients with severe intractable constipation. Diagnosis of this condition, however, remains controversial with a wide variation in the frequency of diagnosis in different centres. Our aim was to assess the frequency with which giant ganglia could be found in the bowel of individuals who did not give a history of life-long constipation. We also aimed to assess the reproducibility of giant ganglia counts. For this two pathologists independently assessed pieces of normal bowel taken away from the site of the lesion in patients who had undergone surgery for colorectal carcinoma. Giant ganglia containing seven or more ganglion cells were found in 76 and 78% of subjects by each of the two pathologists. There was 1 giant ganglion per 10 ganglia counted in those patients in whom they were identified and 1 giant ganglion per 10.9 ganglia overall. Sections from eight patients in whom there was a history of constipation and/or melanosis coli did not show a greater number of giant ganglia. We conclude therefore that so-called "giant ganglia" are a common feature in the submucosa of normal bowel and that the presence of occasional giant ganglia cannot be considered diagnostic of IND B.

Colorectal Neoplasms↗

Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension.

OBJECTIVES: Inhaled nitric oxide (NO) reduces pulmonary hypertension in acute respiratory failure. Soluble nitric oxide donors (NO/nucleophile adducts-NONOates) are less cumbersome to deliver and may offer clinical advantage compared with inhaled NO. The objective of this study was to examine the pulmonary and systemic hemodynamic effects of tracheal aerosolization of a new class of NONOates in a porcine model of experimentally induced pulmonary hypertension. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Yorkshire pigs (n = 18), weighing 11.4 to 16.4 kg. INTERVENTIONS: In anesthetized, mechanically ventilated, instrumented pigs, steady-state pulmonary hypertension (SSPH) was induced using a thromboxane agonist (U46619). Control animals received tracheal aerosolization of saline (n = 6); EP/NO animals received tracheal aerosolization of ethylputreanine NONOate (EP/ NO, n = 6); and DMAEP/NO animals received aerosolized 2-(dimethylamino) ethylputreanine NONOate (DMAEP/NO, n = 6). MEASUREMENTS AND MAIN RESULTS: Mean pulmonary (MPAP) and mean systemic arterial pressures (MAP), atrial pressures, cardiac output, and arterial blood gases were measured following drug instillation. DMAEP/NO animals had significant reductions in pulmonary vascular resistance index (PVRI) and MPAP at all time points compared with SSPH and control animals (p < .05), while systemic vascular resistance index did not change. EP/NO animals had a significant reduction in PVRI and MPAP at some time points compared with SSPH and control animals. For both NONOate-treated animal groups, MAP and cardiac index did not change significantly compared with SSPH and control animals (p < .05). CONCLUSIONS: In this porcine model of pulmonary hypertension, intratracheal aerosolization of soluble NO donors results in sustained reduction of pulmonary hypertension without reducing systemic arterial pressure. Intermittent aerosolization of NONOates may be an alternative to continuously inhaled NO in the treatment of acute pulmonary hypertension.

Acute Disease↗

Follow up after successful eradication of Helicobacter pylori: symptoms and reinfection.

The important long-term outcomes after Helicobacter pylori eradication are the proportion of patients with continuing symptoms, and the rate of recrudescence of the infection. Patients with proven H. pylori infection prior to treatment and a negative urea breath test at least 4 weeks after completing treatment were invited to return for a further urea breath test and a questionnaire. There were 167 patients and the mean interval since the post-treatment urea breath test was 16 months. The endoscopic diagnoses were duodenal ulcer 72, duodenitis 17, gastric ulcer 26, normal or oesophagitis 52. The ethnic groups were European 86, Maori 25, Pacific Island 28 and other ethnic groups 28. Ten patients (6%) had a positive urea breath test at follow up. The proportion of patients showing recrudescence of H. pylori was related to the delta value (delta) of the post-treatment urea breath test: delta 0-2, five of 146 (3.4%); delta 2-3, two of 18 (11%); and delta 3-4, three of five (60%). A symptom questionnaire was given to 147/157 patients with a persistently negative breath test; 60 had no symptoms, 31 had heartburn, 30 had epigastric pain, 15 had both heartburn and epigastric pain, and 11 had nausea or other symptoms. There were fewer symptoms in patients with gastric ulcer (GU) compared with patients with duodenal ulcer (DU) and non-ulcer patients. Twenty-four patients (16%) were taking H2-antagonists (including seven DU and five GU), 15 were taking antacids and four were taking omeprazole. There was no difference in medication use between diagnostic groups. Eighteen of the 46 patients (39%) with heartburn stated that this was a new symptom. Heartburn was a common symptom for duodenal ulcer patients after eradication (24/74, 32%). A second urea breath test 6-12 months after eradication is required to definitely prove eradication. Patients with a breath test delta value of 2-4 should have a repeat urea breath test.

Anti-Bacterial Agents↗

Cyclin partners determine Pho85 protein kinase substrate specificity in vitro and in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10.

In Saccharomyces cerevisiae, PHO85 encodes a cyclin-dependent protein kinase (Cdk) with multiple roles in cell cycle and metabolic controls. In association with the cyclin Pho80, Pho85 controls acid phosphatase gene expression through phosphorylation of the transcription factor Pho4. Pho85 has also been implicated as a kinase that phosphorylates and negatively regulates glycogen synthase (Gsy2), and deletion of PHO85 causes glycogen overaccumulation. We report that the Pcl8/Pcl10 subgroup of cyclins directs Pho85 to phosphorylate glycogen synthase both in vivo and in vitro. Disruption of PCL8 and PCL10 caused hyperaccumulation of glycogen, activation of glycogen synthase, and a reduction in glycogen synthase kinase activity in vivo. However, unlike pho85 mutants, pcl8 pcl10 cells had normal morphologies, grew on glycerol, and showed proper regulation of acid phosphatase gene expression. In vitro, Pho80-Pho85 complexes effectively phosphorylated Pho4 but had much lower activity toward Gsy2. In contrast, Pcl10-Pho85 complexes phosphorylated Gsy2 at Ser-654 and Thr-667, two physiologically relevant sites, but only poorly phosphorylated Pho4. Thus, both the in vitro and in vivo substrate specificity of Pho85 is determined by the cyclin partner. Mutation of PHO85 suppressed the glycogen storage deficiency of snf1 or glc7-1 mutants in which glycogen synthase is locked in an inactive state. Deletion of PCL8 and PCL10 corrected the deficit in glycogen synthase activity in both the snf1 and glc7-1 mutants, but glycogen synthesis was restored only in the glc7-1 mutant strain. This genetic result suggests an additional role for Pho85 in the negative regulation of glycogen accumulation that is independent of Pcl8 and Pcl10.

Cyclin-Dependent Kinases↗

Community perceptions of health, illness and care: identifying issues for indigenous communities.

Community meetings, interviews with key informants, and focus groups were used to document major health concerns and problems among Indigenous women in Queensland, as part of the Australian Longitudinal Study on Women's Health. In this article, we analyze understandings of "community" as used in Australian health research and among Indigenous women. We then examine health issues as identified and experienced by women and explore the gaps that exist between community concerns, individual health status, and service delivery.

Adolescent↗

Quebec prostate cancer mortality dropped in 1996.

OBJECTIVE: To monitor incidence and mortality rates of prostate cancer in the province of Quebec. DESIGN: Population-based incidence and mortality trends. SETTING: Entire population of the province of Quebec between 1979 and 1996. MAIN OUTCOME MEASURES: Age-standardized incidence rates and mortality for prostate cancer. RESULTS: Prostate cancer mortality increased regularly until 1989, were stable between 1989 and 1995 and dropped in 1996 by 15%. Incidence rates increased steadily from 1989 until 1993 by an average of 9% per year. CONCLUSION: The rise in incidence is due to the increasing use of prostate specific antigen as a screening test for prostate cancer. The reasons for the reduction in prostate cancer mortality are unknown but are likely to reflect improved treatment modalities.

Age Factors↗

Dietary fat and advanced prostate cancer.

PURPOSE: We identify the dietary factors, particularly fat intake, associated with advanced prostate cancer. MATERIALS AND METHODS: We performed a case series analysis restricted to prostate cancer cases recruited in a hospital based, case control study evaluating the influence of diet on the development of prostate cancer. Patients eligible for study inclusion were 45 years old or older with prostate cancer who had been hospitalized for initial surgical treatment or radiotherapy between October 1990 and December 1992 at 1 of 8 hospitals in the Quebec City area. A diet history questionnaire was administered to 427 patients with prostate cancer of whom 384 (90%) had completed a reliable questionnaire, including 142 with advanced and 242 with local stages I and II disease. Logistic regression analysis was used to evaluate the associations between dietary intake and advanced prostate cancer. Odds ratios and trend odds ratios were adjusted for patient age, energy intake, method of cancer detection and cancer treatment. RESULTS: There was a moderate, not statistically significant relation to total fat (trend odds ratio 1.15, confidence interval [CI] 0.95 to 1.39). Cases in the highest quartile of saturated fat consumption had a statistically significant odds ratio of 2.15 (CI 1.14 to 4.04). In addition, the relation increased proportionally and significantly with saturated fat intake (trend odds ratio 1.24, CI 1.02 to 1.51). Inverse associations of borderline significance were observed between advanced cancer, and polyunsaturated fat (trend odds ratio 0.88, CI 0.73 to 1.07) and linoleic acid intake (trend odds ratio 0.86, CI 0.71 to 1.04). A positive trend was observed for total animal fat intake (trend odds ratio 1.20, CI 0.99 to 1.46), while a negative trend was noted for total vegetable fat intake (trend odds ratio 0.84, CI 0.70 to 1.01). CONCLUSIONS: This study suggests an association between saturated fat consumption and prostate cancer progression. If cohort studies performed on patients with local prostate cancer confirm these results, dietary fat intake modification may be a promising intervention to prevent prostate cancer progression.

Aged↗

A motility function for the paraflagellar rod of Leishmania parasites revealed by PFR-2 gene knockouts.

We demonstrate a functional role for the paraflagellar rod (PFR) in motility of Leishmania mexicana. The PFR is a complex cytoskeletal structure running parallel to the axoneme in the flagella of kinetoplastid protozoa. The PFR is composed of a latticework of protein filaments whose major constituents are two related proteins (PFR-1 and PFR-2 in Leishmania). The molecular details of their assembly into PFR filaments are unknown as is the biological function of the PFR. As an approach to understanding the structure and function of the PFR in Leishmania, we made L. mexicana null mutants of PFR-2. PFR-2 minus parasites grow and divide normally in culture and still express the PFR-1 protein. They lack most of the PFR structure demonstrating that the PFR-2 protein is an essential constituent of the PFR. Detailed ultrastructural analysis of the PFR-2 null mutant reveals the presence of a residual inner substructure of the PFR which contains PFR-1 protein, indicating that PFR-1 can polymerize in the absence of PFR-2. The PFR-2 null mutant displays pronounced changes in flagellar beat waveform and forward swimming velocity, compared to wild type parasites consistent with decreased internal elastic bending resistance in PFR-lacking flagella, and indicating a functional role for the PFR in the motility of Leishmania.

Animals↗

Co-occurrence of AIDS and tuberculosis: results of a database "match" and investigation.

PURPOSE: To conduct a match between the AIDS and Tuberculosis (TB) Registries in Philadelphia. METHODS: Database extracts for the year 1993 were prepared manually and matched by name, birth date, and social security number. Reported cases not matching with those on the primary registry were investigated. Proportion levels of comorbidity were calculated. Predictors of comorbidity were evaluated separately for the TB sample and for the AIDS sample. RESULTS: The proportion of comorbid patients with AIDS alive at midyear was 4.7%; 17.1% of TB cases were also HIV-positive. Twenty-three percent of AIDS cases were falsely reported as having active TB; the false-positive rate in TB Control for HIV seropositivity was 4.2%. Having public or no health insurance, injection drug use (IDU) or heterosexual risk background (HET), and being nonwhite and female were significant predictors of active TB in persons with AIDS. CONCLUSIONS: A registries' data match can provide useful information and result in improved validity for both registries. Although women with AIDS initially appeared to have a higher risk of having active TB, additional parallel analyses suggested that this effect was primarily the result of the 1993 expansion of the definition of AIDS.

Acquired Immunodeficiency Syndrome↗

Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland.

The incidence of natural scrapie in sheep is associated with polymorphisms of the PrP gene, particularly those at codons 136, 154 and 171. In many breeds, the PrP allele encoding valine at codon 136 confers an extremely high risk of scrapie, but in Suffolk sheep this allele is vanishingly rare. In this study of a single closed flock of Suffolk sheep in Scotland, scrapie occurred primarily in animals which were homozygous for glutamine at codon 171, a genotype which was significantly less frequent in healthy flockmates. However, the apparent linkage between glutamine at codon 171 and scrapie was not completely recessive because two of 64 scrapie cases were heterozygous glutamine/arginine. These results suggest that breeding for increased resistance to scrapie in Suffolks by the selection of animals according to their PrP genotype is a feasible option.

Alleles↗

Disappearing suprarenal masses in fetuses and infants.

This paper presents 12 infants (9 boys, 3 girls) in whom the diagnosis of a suprarenal mass (10 left, 2 bilateral) was made on antenatal sonography. All were otherwise healthy neonates who were born at term after a normal pregnancy, labor and delivery. The masses ranged from 1 to 3.5 cm in diameter on initial scans at gestational ages of 19-35 weeks. Eleven masses were hyperechoic and 4 of these contained small, well-defined cysts. The 12th was hypoechoic. Follow-up sonography showed complete disappearance of the mass antenatally in 1 case and postnatally by 4-6 months in 5 cases; there was marked diminution in the size of the mass by 2 months of age in 4 infants, by 4 months in 1 case and by 15 months in 1 case. Eleven were managed nonoperatively. Laparotomy (after disappearance of the mass) in the 12th case revealed only some fibrous tissue. The 11 echogenic masses resemble previously reported imaging findings in infants with histologically proven intra-abdominal sequestrated lung. Conservative management with careful sonographic follow-up should, therefore, be considered in otherwise healthy fetuses or neonates with these imaging findings. We are less certain what the hypoechoic mass represented.

Bronchopulmonary Sequestration↗