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Biomedical subjects

M Levine

Publications and source records attributed to M Levine.

At least 73 records · Page 4Linked to original sources

Previous exposure to Chlamydia pneumoniae, Helicobacter pylori and other infections in Canadian patients with ischemic heart disease.

OBJECTIVE: Previous exposures to Chlamydia pneumoniae (CP), Helicobacter pylori (HP) or cytomegalovirus (CMV) have been associated with atherosclerotic heart disease. These associations were studied in Canadian patients, and the exposure to five infections measured. DESIGN: Case-control study. SETTING: In the coronary care units (Hamilton General site, Henderson General site, McMaster University Medical Centre site of the Hamilton Health Sciences Corporation and St Joseph's Hospital) and from the regional angiography suite (Hamilton General site), Hamilton, Ontario. PATIENTS AND METHODS: One hundred seven consecutive patients presenting with myocardial infarction or unstable angina (coronary care unit patients), or with previous angina or myocardial infarction (angiography suite patients), were compared with 107 family practice or outpatient clinic control subjects. INTERVENTIONS: Cardiovascular risk factors were measured, as was serology for CP, HP, CMV, adenovirus and hepatitis A virus. Statistical analysis was by logistic regression, adjusted for age and sex. RESULTS: Exposure to CP was more frequent in patients than in control subjects (85.4% versus 70.3%, adjusted odds ratio [OR] 2.3, 95% CI 1.1 to 5.1, P=0.03). Dividing CP immunoglobulin G absorbance into quarters, with the lowest quarter as the reference group, the adjusted ORs were 2.8, 3.0 and 4.3, respectively, for the second, third and fourth quarters (P=0.001 for trend). The seroprevalences of HP (61.7%), CMV (64.0%), adenovirus (75.6%) and hepatitis A virus (59.2%) were high, with no association with disease. CONCLUSIONS: An association was found between heart disease and previous exposure to CP, with a stepwise increase in ORs at higher antibody levels, whereas no association was found with HP, CMV or other infections. A prospective validation of this association is needed.

Adult↗

The 2000 Canadian recommendations for the management of hypertension: Part one--therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, there are a number of lifestyle manoeuvres and antihypertensive agents that may control blood pressure. Randomized trials evaluating first- line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS, AND COSTS: Various lifestyle manoeuvres and antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to all aspects of the therapy of patients with hypertension, including lifestyle modifications proven to lower blood pressure, treatment thresholds, target blood pressures, choice of agents in various settings and strategies to enhance adherence. Lower thresholds for blood pressure treatment are advocated for people with other cardiovascular risk factors or established hypertensive target organ damage. Implicit in the recommendations for therapy is the principle that treatment should be individualized for each patient and the choice of agent should be dictated by coexistent conditions. For the treatment of uncomplicated essential hypertension, thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors or calcium channel blockers may be appropriate, depending on individual circumstances. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually.

Adult↗

The place for prescribing guidelines and the means of their dissemination.

Practice guidelines are of potential benefit when a physician recognizes that they do not have all the facts required for providing appropriate health care. However, when guidelines for prescribing are known to the prescriber, and the physician chooses to modify or ignore them, their behaviour is being driven by personal and professional value systems that are in conflict with their knowledge base. Thus, providing practice guidelines to these physicians will not reduce suboptimal prescribing practices. In these circumstances, a number of studies suggest that addressing the social and situational involvement of physicians within the guidelines may enhance the promulgation and implementation of guidelines, and lead to more optimal prescribing choices for physicians.

Canada↗

The 2000 Canadian recommendations for the management of hypertension: part two--diagnosis and assessment of people with high blood pressure.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of high blood pressure in adults. OPTIONS: For people with high blood pressure, the assignment of a diagnosis of hypertension depends on the appropriate measurement of blood pressure, the level of the blood pressure elevation, the duration of follow-up and the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases. For people diagnosed with hypertension, defining the overall risk of adverse cardiovascular outcomes requires laboratory testing, a search for target organ damage and an assessment of the modifiable causes of hypertension. Out-of-clinic blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: People at increased risk of adverse cardiovascular outcomes and were identified and quantified. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian recommendations for the management of hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the identification of people at increased risk of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: The identification of people at higher risk of cardiovascular disease will permit counselling for lifestyle manoeuvres and the introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to aspects of the diagnosis and assessment of patients with hypertension, including the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, routine and optional laboratory testing, assessment for renovascular hypertension, home and ambulatory blood pressure monitoring, and the role of echocardiography in hypertension. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only the recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually. ENDORSEMENT: These recommendations are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control of Health Canada.

Adrenal Gland Neoplasms↗

Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.

Two small RNAs regulate the timing of Caenorhabditis elegans development. Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA, and transition from late larval to adult cell fates requires the 21-nucleotide let-7 RNA. The lin-4 and let-7 RNA genes are not homologous to each other, but are each complementary to sequences in the 3' untranslated regions of a set of protein-coding target genes that are normally negatively regulated by the RNAs. Here we have detected let-7 RNAs of approximately 21 nucleotides in samples from a wide range of animal species, including vertebrate, ascidian, hemichordate, mollusc, annelid and arthropod, but not in RNAs from several cnidarian and poriferan species, Saccharomyces cerevisiae, Escherichia coli or Arabidopsis. We did not detect lin-4 RNA in these species. We found that let-7 temporal regulation is also conserved: let-7 RNA expression is first detected at late larval stages in C. elegans and Drosophila, at 48 hours after fertilization in zebrafish, and in adult stages of annelids and molluscs. The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny.

Adult↗

Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes.

Dehydroascorbic acid (DHA), the first stable oxidation product of vitamin C, was transported by GLUT1 and GLUT3 in Xenopus laevis oocytes with transport rates similar to that of 2-deoxyglucose (2-DG), but due to inherent difficulties with GLUT4 expression in oocytes it was uncertain whether GLUT4 transported DHA (Rumsey, S. C. , Kwon, O., Xu, G. W., Burant, C. F., Simpson, I., and Levine, M. (1997) J. Biol. Chem. 272, 18982-18989). We therefore studied DHA and 2-DG transport in rat adipocytes, which express GLUT4. Without insulin, rat adipocytes transported 2-DG 2-3-fold faster than DHA. Preincubation with insulin (0.67 micrometer) increased transport of each substrate similarly: 7-10-fold for 2-DG and 6-8-fold for DHA. Because intracellular reduction of DHA in adipocytes was complete before and after insulin stimulation, increased transport of DHA was not explained by increased internal reduction of DHA to ascorbate. To determine apparent transport kinetics of GLUT4 for DHA, GLUT4 expression in Xenopus oocytes was reexamined. Preincubation of oocytes for >4 h with insulin (1 micrometer) augmented GLUT4 transport of 2-DG and DHA by up to 5-fold. Transport of both substrates was inhibited by cytochalasin B and displayed saturable kinetics. GLUT4 had a higher apparent transport affinity (K(m) of 0.98 versus 5.2 mm) and lower maximal transport rate (V(max) of 66 versus 880 pmol/oocyte/10 min) for DHA compared with 2-DG. The lower transport rate for DHA could not be explained by binding differences at the outer membrane face, as shown by inhibition with ethylidene glucose, or by transporter trans-activation and therefore was probably due to substrate-specific differences in transporter/substrate translocation or release. These novel data indicate that the insulin-sensitive transporter GLUT4 transports DHA in both rat adipocytes and Xenopus oocytes. Alterations of this mechanism in diabetes could have clinical implications for ascorbate utilization.

Adipocytes↗

Characterization of a maternal T-Box gene in Ciona intestinalis.

A new T-box gene, CiVegTR, was isolated in the ascidian Ciona intestinalis. CiVegTR maternal RNAs become localized to the vegetal cytoplasm of fertilized eggs and are incorporated into muscle lineages derived from the B4.1 blastomere. The CiVegTR protein binds to specific sequences within a minimal, 262-bp enhancer that mediates Ci-snail expression in the tail muscles. Mutations in these binding sites abolish expression from an otherwise normal lacZ reporter gene in electroporated embryos. In addition to the previously identified AC-core E-box sequences, T-box recognition sequences are conserved in the promoter regions of many genes expressed in B4.1 lineages in both Ciona and the distantly related ascidian Halocynthia. These results suggest that CiVegTR encodes a component of the classical muscle determinant that was first identified in ascidians nearly 100 years ago.

Amino Acid Sequence↗

The effects of radiation therapy on quality of life of women with breast carcinoma: results of a randomized trial. Ontario Clinical Oncology Group.

BACKGROUND: The purpose of this study was to evaluate the effect of breast irradiation on quality of life, including cosmetic outcome, for patients enrolled in a clinical trial. METHODS: Between 1984 and 1989, a randomized trial was conducted in Ontario, Canada, in which women with lymph node negative breast carcinoma who had undergone lumpectomy and axillary lymph node dissection were randomized to either breast irradiation or no further treatment. A modified version of the Breast Cancer Chemotherapy Questionnaire (BCQ) was administered to women at baseline, 1 month (4 weeks), and 2 months (8 weeks) after randomization. Irritation of the skin of the breast, breast pain, and appearance of the breast to the patient were also assessed every 3 months for the first 2 years of the study. RESULTS: Of 837 patients, 416 were randomly allocated to radiation therapy and 421 to no further treatment. The mean change in quality of life from baseline to 2 months was -0.05 for the radiation group and +0.30 for the control group. The difference between groups was statistically significant (P = 0.0001). Longer term radiation therapy increased the proportion of patients who were troubled by irritation of the skin of the breast and breast pain. Radiation therapy did not increase the proportion of patients at 2 years who were troubled by the appearance of the treated breast; 4.8% in irradiated and nonirradiated patients (P = 0.62). CONCLUSIONS: Breast irradiation therapy had an effect on quality of life during treatment. After treatment, irradiated patients reported increased breast symptoms compared with controls. However, no difference was detected between groups at 2 years in the rates of skin irritation, breast pain, and being upset by the appearance of the breast.

Breast Neoplasms↗

Characterization of the promoter of the human ribonucleotide reductase R2 gene.

We describe here cloning and characterization of the promoter region of the human ribonucleotide reductase R2 gene. Primer extension and sequence data indicated that two different transcripts were produced via using two different promoter regions. Promoter activity of the 5' flanking region of the first transcript was approximately 100-fold higher than controls, and that of the second transcript was approximately 30-fold higher than controls. Particularly, the proximal region of the first transcript, -125 to +1 bp, was responsible for approximately a 50-fold increase in promoter activity, compared to controls. This region had three CCAAT sequences, each of which contributed similarly to promoter activity. When all three CCAAT sequences were mutated, promoter activity declined 80%. In addition, the promoter region -125 to +1 bp was responsible for cell-cycle-specific expression. These data provided essential information concerning regulatory mechanisms of cell-cycle-specific expression of human ribonucleotide reductase R2.

Base Sequence↗

The family group conference in the New Zealand children, young persons, and their families act of 1989 (CYP&F): review and evaluation.

The family group conference is an innovation introduced into New Zealand law as a means of resolving child protection and youth justice cases. The law requires the conference to include the offender, the victim, the extended family, and other relevant parties. This article reviews New Zealand research and commentary, and publications reporting on experiences with the methods in other countries. The discussion emphasizes problems in adapting a method based on one culture to a different culture and social organization. The article also considers the law from the viewpoint of therapeutic jurisprudence. Although the research is sparse, the FGC has strong promise for resolving problems, enhancing the sense of community and participation, and empowering families.

Adolescent↗

A cross-cultural consumer-based decision aid for screening mammography.

BACKGROUND: "Women should have mammograms" is the usual perspective of educational interventions about screening. The perspective that "women should be informed" about potential risks and benefits so they can make value- and evidence-integrated personal decisions has recently been advocated. However, this perspective has not previously been operationalized. We developed an evidence-based cross-cultural mammography decision aid (MDA), for European American and Mexican American women who are 50-70 years old, at average risk of breast cancer, of varying educational levels, and English- or Spanish-speaking. METHODS: MDA development included: (1) content development by a multidisciplinary team and lay women and (2) testing for validity and reliability. Four parts include: (1) introduction; (2) information about logistics (cost, time, discomfort) and risks (sequelae of false-positive or negative results; (3) probability of developing breast cancer; and (4) benefit of mammography regarding breast cancer outcomes (e.g., death and recurrence). We assessed reliability (stability of decisions with the same information) after 1-2 weeks. We assessed validity (comprehension of information) quantitatively (probabilities were changed to see whether preferences changed predictably) and qualitatively (focus groups, standardized probes for comprehension). Subjects were a convenience sample of 49 European American (50-81 years old) and 54 Mexican American (49-89 years old) women from administrative staff at a medical school, the waiting room of an indigent primary care clinic, and a community center. RESULTS: Reliability was 100%. In quantitative validity testing, 22 of 28 women (89%) changed preference as predicted with changed probabilities. Comprehension was confirmed qualitatively in all phases of testing with both Spanish and English versions. CONCLUSION: The decision aid is valid and reliable in English and Spanish for southwestern Mexican American and European American women at average risk of breast cancer, including those of low educational levels.

Aged↗

Predicting hand preference with performance on motor tasks.

Handedness may be defined as preference or hand-differences in task performance. The strength and significance of the relationship between hand preference and hand performance asymmetries have been contested. To evaluate this relationship, we administered the Edinburgh Handedness Inventory and measured asymmetries in finger tapping, Purdue Pegboard, and grip strength in 30 subjects who prefer their right hand and 30 subjects who prefer their left hand. Hand asymmetries in finger tapping, Purdue Pegboard, and grip strength each predicted hand preference scores. However, a multiple regression equation best predicted hand preference by using performance of each task. Hand asymmetries in finger tapping correlated strongly with asymmetries in Purdue Pegboard performance, but neither of these asymmetries correlated strongly with asymmetries in grip strength. These findings indicate that hand preference and asymmetries in motor proficiency are strongly related, but suggest that preference and proficiency for different aspects of motor performance may be independently lateralized.

Adult↗

Mental health professionals' experiences reporting suspected child abuse and maltreatment.

OBJECTIVE: The purpose of this study was to provide systematic data on the experiences of mental health professionals (e.g., psychiatrists, psychologists, and social workers) who reported cases of suspected child abuse and maltreatment concerning their clients. METHOD: Mail surveys were completed by 258 mental health professionals known to have reported a case of suspected child abuse and maltreatment to the New York State Central Register (NYSCR) in 1993. Subjects were asked to complete a survey describing their experience with making reports, referring to a specific case they reported. RESULTS: About 40% did not inform the client about the limits of confidentiality until reportable material came up. Most clinicians reported that informing clients about the limits of confidentiality did not deter them from entering treatment. Many clinicians learned about abuse/maltreatment after approximately 3 months into therapy. Even very experienced clinicians usually consulted with others before making the report. Clinicians most typically informed the client about the report directly and before it was made, but did not call the NYSCR in the presence of the client. Following the report, most clinicians performed additional activities such as calling clients and scheduling additional sessions. When clients evidenced resistance to continuing therapy, it usually dissipated after a brief period of time. In over 72% of the cases, making the report did not disrupt the relationship and in many instances it was helpful in the therapeutic process; about 27% were continuously resistant or terminated therapy shortly after the report was made. CONCLUSIONS: Implications for practice, training, program development, and research are discussed.

Adolescent↗

Reevaluation of ascorbate in cancer treatment: emerging evidence, open minds and serendipity.

Some clinicians and alternative therapy practitioners advocate megadose intravenous and oral ascorbate treatment of cancer. Randomized control studies using oral ascorbate showed no benefit. Recent data show that intravenous but not oral administration of ascorbate can produce millimolar plasma concentrations, which are toxic to many cancer cell lines. We propose that ascorbate treatment of cancer should be reexamined by rigorous scientific scrutiny in the light of new evidence.

Administration, Oral↗

Intracellular accumulation of ascorbic acid is inhibited by flavonoids via blocking of dehydroascorbic acid and ascorbic acid uptakes in HL-60, U937 and Jurkat cells.

In HL-60, U937 and Jurkat cells, the intracellular accumulation of ascorbic acid occurred via uptakes of both dehydroascorbic acid (an oxidized metabolite of ascorbic acid) and ascorbic acid (vitamin C). Dehydroascorbic acid and ascorbic acid were transported into cells by sodium-independent glucose transporters (GLUT 1 and GLUT 3) and sodium-dependent ascorbic acid transporters, respectively. Flavonoids inhibited the intracellular accumulation of ascorbic acid by blocking dehydroascorbic acid and ascorbic acid uptakes in the transformed cells. At flavonoid concentrations of 10-70 micromol/L, approximately 50% of dehydroascorbic acid uptake was inhibited in the cells. In Jurkat cells, two potent flavonoids (myricetin and quercetin) competitively inhibited dehydroascorbic acid uptake, and K(i) values were approximately 14 and 15 micromol/L, respectively. Because GLUT 1 and GLUT 3 transport dehydroascorbic acid, the inhibition of dehydroascorbic acid uptake by flavonoids was investigated by using Chinese hamster ovary cells overexpressing rat GLUT 1 or human GLUT 3. Myricetin at concentrations of 22 and 18 micromol/L, respectively, inhibited half of dehydroascorbic acid uptake in the cells overexpressing GLUT 1 and GLUT 3. Myricetin also inhibited ascorbic acid uptake; inhibition was noncompetitive with K(i) = 14 micromol/L in Jurkat cells. These data indicate that flavonoids inhibit both ascorbic acid and dehydroascorbic acid uptake but do so by different mechanisms. These data may contribute to new understanding of the biological effect of flavonoids on the intracellular accumulation of ascorbic acid in human cells.

Animals↗