Search PubMed⌕ Search

Biomedical subjects

L Moore

Publications and source records attributed to L Moore.

At least 73 records · Page 4Linked to original sources

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↗

Health locus of control and value for health in smokers and nonsmokers.

A representative sample of 11,401 persons completed a questionnaire, including measures of health locus of control, value for health, and smoking frequency. Smokers held stronger internal, chance, and powerful others beliefs than never smokers. Ex-smokers had lower scores on internal and chance dimensions and placed a higher value on their health than smokers. The interaction between chance health locus of control and value for health was a significant predictor of smoking status, suggesting that health value may moderate the relationship between health locus of control and smoking status. Within smokers, the health locus of control dimensions and value for health explained less than 1% of the variance in smoking frequency, with only the chance dimension emerging as a significant predictor.

Adolescent↗

Dietary energy and nutrients in relation to preclinical prostate cancer.

Previous studies of diet and prostate cancer have focused on advanced disease and have suggested a positive association with saturated fat intake. We report a study assessing the relationship between diet and preclinical prostate cancer. A total of 215 men with preclinical prostate cancer and 593 controls with no evidence of cancer participated in a case-control study conducted in Quebec City between October 1990 and May 1993. The study population comprised two groups: men treated surgically for benign prostatic hypertrophy and participants in a prostate cancer screening program. Trained nutritionists interviewed the participants on their usual diet using a diet history questionnaire. Odds ratios for prostate cancer associated with quartiles of dietary intake and P values for trend were estimated by logistic regression while controlling for age, education, group, and family history of prostate cancer. A positive association was observed between total energy intake and preclinical prostate cancer (p = 0.004). The odds ratios for prostate cancer increased with each quartile of energy intake: 1.00, 1.77, 1.90, and 2.67. After adjustment for energy, nutrients were not associated with prostate cancer. This study provides some evidence that total energy intake is related to preclinical prostate cancer and suggests that diet could be involved earlier than thought in the occurrence of prostate cancer.

Aged↗

Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration.

Initial toxicity testing of neostigmine for intrathecal (IT) injection was performed with preservative-free isobaric solution, yet currently available formulations contain the preservatives methyl- and propylparaben and are usually mixed with glucose to yield hyperbaric solutions. Since it has been proposed that preservatives and hyperbaricity increase the risk of neurotoxicity after IT injection, we examined the safety of chronically administered IT neostigmine containing these additives in sheep and rats. Rats receiving daily IT injections of glucose alone or of glucose with preservative-containing neostigmine, 5 and 10 microg, exhibited dose-related antinociception, tremor, and rigidity. In comparison to our previously published study of neostigmine injection in solution without glucose, rats receiving IT neostigmine with glucose displayed less rigidity, tremor, and salivation. Sheep receiving daily injection of glucose alone or with preservative-containing neostigmine, 1 mg, for 14 days exhibited no histologic evidence of neurotoxicity, nor did they exhibit abnormalities in cerebrospinal fluid chemistry aside from those caused by inflammation. Spinal cord histologic examination in both species revealed fibrosis and inflammation secondary to the catheter without evidence of neuronal damage. These studies support the safety of paraben- and glucose-containing IT neostigmine.

Analgesia, Epidural↗

Circulating methemoglobin and nitrite/nitrate concentrations as indicators of nitric oxide overproduction in critically ill children with septic shock.

OBJECTIVES: To examine the relationship between circulating methemoglobin and nitrite/nitrate concentrations and to compare these markers of nitric oxide overproduction with clinical variables in children diagnosed with septic shock. DESIGN: Prospective, controlled, clinical study. SETTING: Pediatric intensive care unit and outpatient clinic in a children's hospital. PATIENTS: Twenty-two children diagnosed with septic shock and ten age-matched healthy control patients. INTERVENTIONS: Patients diagnosed with septic shock had blood specimens taken on study entry and every 6 hrs for 72 hrs for methemoglobin and nitrite/nitrate determinations. Single blood specimens were obtained from controls. MEASUREMENTS AND MAIN RESULTS: Circulating methemoglobin and nitrite/nitrate concentrations were significantly higher in children diagnosed with septic shock in comparison with healthy control children (p = .01 and .05, respectively). Peak nitrite/nitrate concentrations correlated with serum creatinine (r2 = .19; p = .04) and were inversely correlated with arterial pH (r2 = .28; p = .01) and urine output (r2 = .21; p = .03) when analyzed by log-linear regression. There were no significant relationships between methemoglobin and nitrite/nitrate or between methemoglobin and any other clinical variable. CONCLUSIONS: Circulating methemoglobin and nitrite/nitrate concentrations are increased in children diagnosed with septic shock. Plasma nitrite/nitrate values correlate with selected clinical variables in these children. Circulating methemoglobin measurements are not superior to plasma nitrite/nitrate concentrations as an indicator of endogenous overproduction of nitric oxide in children diagnosed with septic shock. A need remains to develop markers of endogenous nitric oxide activity that have greater accuracy and reliability.

Adolescent↗