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Biomedical subjects

R Lew

Publications and source records attributed to R Lew.

At least 19 recordsLinked to original sources
PubMed2005

The foundation and launch of the Melbourne Interventional Group: a collaborative interventional cardiology project.

The Melbourne Interventional Group (MIG) is a voluntary collaborative venture of interventional cardiologists practicing at 12 major public and private hospitals in Victoria, designed to record data pertaining to percutaneous coronary interventions (PCI) and perform long-term follow-up. The potential advantages of collaboration involve large-scale analysis of current interventional strategies (e.g. drug-eluting stents, evaluation of new technologies and cost-effective analysis), provide a basis for multi-centred clinical trials and allow comparison of clinical outcomes with cardiac surgery. The established registry documents demographic, clinical and procedural characteristics of consecutive patients undergoing PCI and permits analysis of those characteristics at 30 days and 12 months. The registry is co-ordinated by the Centre of Clinical Research Excellence (CCRE), a research body within the Department of Epidemiology and Preventive Medicine (Monash University, Melbourne). The eventual goal of MIG is to provide a contemporary appraisal of Australian interventional cardiology practice, with opportunities to improve in-hospital and long-term outcomes of patients with coronary artery disease.

Angioplasty, Balloon, Coronary↗
PubMed2002

Human esophageal cancer is distinguished from adjacent esophageal tissue by tissue cysteine concentrations.

Recent studies have suggested that cysteine, in addition to glutathione, may play a role in the genesis, pathobiology, and treatment response of rodent and human cancers. We examined the relative concentrations of cysteine and glutathione in human esophageal cancer and adjacent, minimally involved esophageal tissue. Small biopsies from tumors and adjacent esophageal tissues were placed into cold acid to allow extraction of low-molecular-mass compounds and simultaneous precipitation of macromolecules. Supernatants were analyzed by high-performance liquid chromatography with electrochemical detection for thiol content. While there was no statistically significant difference between the glutathione content of tumor versus adjacent tissue (2.2 mM vs 2.1 mM, respectively), tumor tissue had significantly higher levels of cysteine than adjacent tissue (0.21 mM vs 0.13 mM, respectively). In conclusion, cysteine content distinguishes tumor from adjacent more normal tissue.

Adenocarcinoma↗
PubMed2002

Targeting of Asian Americans and Pacific Islanders by the tobacco industry: results from the Minnesota Tobacco Document Depository.

OBJECTIVE: The study objective was to review internal tobacco industry documents written between 1985 and 1995 regarding the Asian American and Pacific Islander (AAPI) population in the USA. These documents detail opportunities and barriers to promotion of tobacco products, as viewed by the tobacco industry and its market research firms. DATA SOURCES: /methods: Researchers reviewed tobacco industry documents from the document depository in Minneapolis, Minnesota and the tobacco industry's website, The Tobacco Archive, in a systematic fashion. A combined technique was employed using title keywords, dates, and names to search the 4(b) index. FINDINGS: A review of internal tobacco company documents reveal that during the late 1980s, the industry and its market research firms recognised the importance of the AAPI community as a potential business market. Documents describe the population growth in this community, the high prevalence of smoking in countries of origin, high purchasing power of AAPI immigrants, cultural predisposition to smoking, opportunities afforded by the high proportion of retail businesses under AAPI ownership, barriers to developing the AAPI market, comprehensive campaigns, and political and lobbying efforts. Comprehensive campaigns were designed to integrate promotion efforts in AAPI consumer, retail, and business communities. CONCLUSIONS: The documents show that the tobacco industry developed specific promotion strategies to target the AAPI population. Tobacco control initiatives in the AAPI group have been slower to develop than in other targeted ethnic groups, and may benefit by increased awareness of industry methods to promote tobacco use.

Advertising↗
PubMed2001

Gender-dependent enhanced adult neurotoxic response to methamphetamine following fetal exposure to the drug.

Methamphetamine use by females of child-bearing age has become a major public health concern in terms of the long-term risk to the exposed fetus. We examined the possibility of enhanced adult neurotoxic potential of the drug in offspring that had been exposed to methamphetamine in utero during gestational days 7 to 18. While basal levels of monoamines were not affected by prenatal exposure to methamphetamine, we observed an enhanced neurotoxicity in adult male offspring following drug challenge with effects localized primarily to the dopaminergic nigrostriatal projection. This was evidenced by greater methamphetamine-induced reductions of dopaminergic markers in the striatum [dopamine (DA), dihydroxyphenylacetic acid, homovanillic acid (HVA), and 3-methoxytyramine (3-MT)] and ventral brainstem (DA) of prenatal methamphetamine-treated males compared with saline-treated animals. Some effects of prenatal methamphetamine exposure were observed in female offspring, but these were limited to striatal levels of 3-MT and HVA. Differential gender sensitivity to the neurotoxic effect of methamphetamine was shown to be correlated with hyperthermic response. Hyperthermic effects, however, do not account for the increased susceptibility of prenatal methamphetamine-treated males to drug-induced striatal DA neurotoxicity since methamphetamine challenge did not evoke a significantly greater hyperthermic response in these animals compared with prenatal saline-treated males. The findings raise the concern that male methamphetamine abusers may be at risk for an enhanced neurotoxic risk if they were exposed to the drug in utero.

Animals↗
PubMed2000

A design for testing interventions to improve adherence within a hypertension clinical trial.

The Potassium Adherence Clinical Trial (PACT) incorporates one randomized clinical trial within another. A randomized trial of interventions to increase adherence to medication is nested within a second randomized clinical trial testing hypotensive effect of supplemental oral potassium. The trial aims principally to compare the effects of three intervention strategies: two sessions of individual patient counseling, two telephone contacts, or standard care. The trial aims secondarily to evaluate the effect of 60 mEq supplemental oral potassium daily on sitting systolic and diastolic blood pressure in hypertensive patients on established drug therapy. Therefore, it organizes the patients given potassium into three study groups for adherence interventions, and the patients assigned to placebo into a further three. We evaluate adherence primarily by means of the Medication Event Monitoring System (MEMS), an electronic system that records the date and time that the container of study medication is opened. Additional measurements, such as assessments of change in levels of urinary potassium, pill counts, appointment records, self-reporting by patients, and estimates by physician of adherence, are used and correlated with MEMS data. At a single center, the trial enrolled 107 participants between the ages of 26 and 80. This paper describes the background to this trial within a trial, details its design, documents the baseline characteristics of participants enrolled, and describes issues experienced during implementation of the trial.

Adult↗
PubMed1999

N-(6-18F-fluorohexyl)-N-methylpropargylamine: a fluorine-18-labeled monoamine oxidase B inhibitor for potential use in PET studies.

We have synthesized N-(6-18F-fluorohexyl)-N-methylpropargylamine (18F-FHMP) as a positron emission tomography (PET) radiotracer for monoamine oxidase B (MAO-B). The radiosynthesis was carried out by a fluorine-for-bromine substitution in 30-40% radiochemical yield in specific activities of 1-2 Ci/micromol. Selectivity for MAO-B was demonstrated by the high affinity of (R)-deprenyl (IC50 = 6.8 nM) and lower affinity of clorgyline (IC50 = 1.2 microM) for the inhibition of 18F-FHMP binding in vitro in rat brain homogenates. In vitro autoradiographic studies in rat brain slices showed localization of 18F-FHMP in regions such as the ependyma of the lateral ventricle, dorsal raphe, area postrema, and other regions such as the cerebellum. The specific binding observed in the autoradiograms was displaced by preincubation with (R)-deprenyl. In in vivo experiments, the uptake of 18F-FHMP in the rat brains was high (0.10-0.20% injected dose/g). The binding of 18F-FHMP in the rat brain correlated with the general distribution of MAO-B and was displaced completely by preadministration of 10 microM (R)-deprenyl. These results suggest that 18F-FHMP is a potential PET radiotracer for MAO-B for use in in vitro and in vivo experiments.

Animals↗
PubMed1999

Preliminary assessment of extrastriatal dopamine D-2 receptor binding in the rodent and nonhuman primate brains using the high affinity radioligand, 18F-fallypride.

We have identified the value of 18F-fallypride [(S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide], as a dopamine D-2 receptor radiotracer for the study of striatal and extrastriatal receptors. Fallypride exhibits high affinities for D-2 and D-3 subtypes and low affinity for D-4 (3H-spiperone IC50s: D-2 = 0.05 nM [rat striata], D-3 = 0.30 nM [SF9 cell lines, rat recombinant], and D-4 = 240 nM [CHO cell lines, human recombinant]). Biodistribution in the rat brain showed localization of 18F-fallypride in striata and extrastriatal regions such as the frontal cortex, parietal cortex, amygdala, hippocampus, thalamus, and hypothalamus. In vitro autoradiographic studies in sagittal slices of the rat brain showed localization of 18F-fallypride in striatal and several extrastriatal regions, including the medulla. Positron emission tomography (PET) experiments with 18F-fallypride in male rhesus monkeys were carried out in a PET VI scanner. In several PET experiments, apart from the specific binding seen in the striatum, specific binding of 18F-fallypride was also identified in extracellular regions (in a lower brain slice, possibly the thalamus). Specific binding in the extrastriata was, however, significantly lower compared with that observed in the striata of the monkeys (extrastriata/cerebellum = 2, striata/cerebellum = 10). Postmortem analysis of the monkey brain revealed significant 18F-fallypride binding in the striata, whereas binding was also observed in extrastriatal regions such as the thalamus, cortical areas, and brain stem.

Animals↗
PubMed1999

Early immune activation in acute dengue illness is related to development of plasma leakage and disease severity.

T lymphocyte activation and increased cytokine levels have been described in retrospective studies of children presenting with dengue hemorrhagic fever (DHF). Serial plasma samples obtained in a prospective study of Thai children presenting with <72 h of fever were studied. Plasma levels of 80-kDa soluble tumor necrosis factor receptors (sTNFRs) were higher in children who developed DHF than in those with dengue fever (DF) or other nondengue febrile illnesses (OFIs) and were correlated with the degree of subsequent plasma leakage. Soluble CD8 and soluble interleukin-2 receptor levels were also elevated in children with DHF compared with those with DF. Interferon-gamma and sTNFR 60-kDa levels were higher in children with dengue than in those with OFIs. TNF-alpha was detectable more often in DHF than in DF or OFIs (P<.05). These results support the hypothesis that immune activation contributes to the pathogenesis of DHF. Further studies evaluating the predictive value of sTNFR80 for DHF are warranted.

Acute Disease↗
PubMed1999

CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups.

We examined CD4+ T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4+ TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4+ T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells.

Adult↗
PubMed1999

A computer based intervention to reduce unnecessary serologic testing.

OBJECTIVE: Laboratory testing is important in the evaluation of patients with possible systemic rheumatic disease, but uncritical use of any test may result in misleading information and unnecessary costs. We attempted to reduce the number of unnecessary antinuclear antibody, rheumatoid factor, and complement level tests ordered by house officers at a large teaching hospital, where inpatient orders are written through a computer based order entry system. METHODS: We conducted a prospective cohort study of an interactive test ordering program. The intervention consisted of displaying post-test probability estimates during the usual physician order entry session. These estimates were based on pretest probabilities entered by the ordering physician and sensitivities and specificities derived from a literature review. Another group of test orders did not prompt the intervention and were considered controls. The outcome of interest was the percentage of tests canceled in the intervention group versus the control group. RESULTS: Eleven percent (11/99) of intervention orders were canceled, versus only one order among 236 controls (p = 0.001). However, there was no association between the physicians' pretest probability estimates and whether test orders were canceled (p = 0.59). Additionally, 43 of the 335 orders (13%) yielded positive tests, but only 4 patients (1%) were given new diagnoses of rheumatic disease. CONCLUSION: The computer based intervention significantly reduced orders for antinuclear antibody and rheumatoid factor levels by 10%. Further reductions without clinical harm are probably possible, since the yield of testing for new rheumatic diseases was low.

Adult↗
PubMed1998

Lack of cardiac manifestations among patients with previously treated Lyme disease.

BACKGROUND: Cardiac involvement is common in acute Lyme disease, and case reports suggest that cardiac abnormalities might also occur years after the primary infection. OBJECTIVE: To determine the prevalence of cardiac abnormalities in persons with previously treated Lyme disease. DESIGN: Population-based, retrospective cohort study with controls. SETTING: Nantucket Island, Massachusetts. PARTICIPANTS: From among 3703 adult respondents to a total-population (n = 6046) mail survey, 336 (176 case-patients and 160 controls) were randomly selected for clinical evaluation. MEASUREMENTS: Current cardiac symptoms and major or minor abnormal electrocardiographic features, including heart rate; rhythm; axis; PR, QRS, and QT intervals; QRS structure; atrioventricular blocks; and ST-segment and T-wave changes. RESULTS: Persons with Lyme disease (case-patients, n = 176) (mean duration from disease onset to study evaluation, 5.2 years) and persons without evidence of previous Lyme disease (controls, n = 160) did not differ significantly in their patterns of current cardiac symptoms and electrocardiographic findings, including heart rate (P > 0.2), PR interval (P = 0.15), QRS interval (P > 0.2), QT interval (P > 0.2), axis (P > 0.2), presence of arrhythmias (P > 0.2), first-degree heart block (P = 0.12), bundle-branch block (P > 0.2), and ST-segment abnormalities (P > 0.2). In multivariate analyses that adjusted for age, sex, and previous heart disease, a history of previously treated Lyme disease was not associated with either major (odds ratio, 0.78; P > 0.2) or minor (odds ratio, 1.09; P > 0.2) electrocardiographic abnormalities. CONCLUSION: Persons with a history of previously treated Lyme disease do not have a higher prevalence of cardiac abnormalities than persons without a history of Lyme disease.

Adult↗
PubMed1998

Consensus workshop on the toxic effects of long-term PUVA therapy.

The possibility that there is an increased risk of melanoma in patients with psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the part of physicians and patients about the long-term safety of this treatment. In response to this concern, the National Psoriasis Foundation sponsored a workshop at which invited participants with expertise in PUVA therapy, psoriasis treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical trials were asked to develop a consensus on the following 3 issues: the risk of long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and melanoma skin cancer; the guidelines for physicians and patients for selection and use of PUVA therapy with consideration of the risk-benefit ratio of this treatment compared with the risk-benefit ratios of alternative treatments; and the directions for further evaluation of the long-term effects Of PUVA therapy.

Humans↗
PubMed1998

Evaluation of the binding of the radiolabeled antidepressant drug, 18F-fluoxetine in the rodent brain: an in vitro and in vivo study.

We have developed 18F-fluoxetine as a radiotracer analog of the antidepressant drug fluoxetine (Prozac). In vitro saturation experiments of 18F-fluoxetine were carried out on rat midbrain tissue and citalopram was used for measuring nonspecific binding. A saturation curve for the binding of 18F-fluoxetine was not obtained. Even when fluoxetine (10 microM) was used for measurements of nonspecific binding, a saturation curve was difficult to obtain. Other compounds, such as deprenyl, clorgyline, amphetamine, and reserpine were also not able to reduce the binding of 18F-fluoxetine. Ex vivo autoradiographic experiments with 18F-fluoxetine did not reveal any specific uptake in various brain regions. In vivo administration of 18F-fluoxetine in rats showed similar uptake in all the brain regions with little regional selectivity. A subcellular analysis of rat brain tissue after intravenous (IV) administration of 18F-fluoxetine indicated significant amounts of binding in mitochondria and synaptosomes. In summary, in vitro experiments with 18F-fluoxetine indicate little specific binding. Binding to the serotonin transporter was not identifiable. High nonspecific binding of the tracer resulting from its subcellular nature in the brain masks the ability to detect binding to the serotonin uptake sites in vivo. These findings indicate that a large portion of the binding of 18F-fluoxetine in rat brains is subcellular and clears slowly out of the cells. Other sites, such as monoamine oxidase, may also play a significant role in the action of fluoxetine.

Animals↗
PubMed1998

Haemorphin peptides may be endogenous ligands for brain angiotensin AT4 receptors.

1. Angiotensin IV (AngIV), the (3-8) fragment of AngII, was previously believed to be an inactive metabolite. However, specific binding sites, termed AT4 receptors, have been identified in the brain and peripheral organs and the peptide has been reported to enhance memory recall in passive avoidance studies and to dilate pial and renal cortical vessels. 2. AT4 receptors are distinct from AngII AT1 and AT2 receptors with respect to function, ligand specificity and distribution. 3. In the brain, AT4 receptors are abundant in cerebral and cerebellar cortex, hippocampal formation and cholinergic systems, as well as sensory and motor systems. However, the peptide AngIV is low or undetectable in the central nervous system. This led us to search for an alternative peptide ligand of the AT4 receptor. 4. The decapeptide LVVYPWTQRF was isolated from cerebral cortex and binds with high affinity to brain AT4 receptors. This peptide sequence corresponds to an internal sequence of beta-globin and has previously been named LVV-haemorphin 7. 5. Haemorphin may represent a new class of endogenous neuropeptides, some of which interact potently with the brain AT4 receptor to elicit a range of actions.

Angiotensin II↗
PubMed1998

Rates and independent correlates of Pap smear testing among Korean-American women.

OBJECTIVES: This study reports population estimates of Pap smear testing among Korean-American women and evaluates correlates of testing. METHODS: Korean Americans in 2 California counties were surveyed by telephone. Frequencies were age-adjusted to the 1990 census to produce population estimates of testing. Logistic regression models were used to evaluate independent correlates of testing RESULTS: Only 50% of the Korean-American women surveyed had a Pap test in the previous 2 years. The strongest independent correlate was having had a regular check-up in the previous 2 years (odds ratio 7.2, 95% confidence interval 4.2, 12.1). CONCLUSIONS: Rates of Pap testing among Korean-American women are well below national objectives. Collaboration and community-sensitive research are essential to collect data and design programs to improve the health of ethnic minority communities.

Asian↗
PubMed1997

A controlled trial of an educational program to prevent low back injuries.

BACKGROUND: Low back injuries are common and costly, accounting for 15 to 25 percent of injuries covered by workers' compensation and 30 to 40 percent of the payments made under that program. The high costs of injury, the lack of effective treatment. and the evidence that there are behavioral risk factors have led to widespread use of employee education programs that teach safe lifting and handling. The effectiveness of those programs, however, has received little rigorous evaluation. METHODS: We evaluated an educational program designed to prevent low back injury in a randomized, controlled trial involving about 4000 postal workers. The program, similar to that in wide use in so-called back schools, was taught by experienced physical therapists. Work units of workers and supervisors were trained in a two-session back school (three hours of training), followed by three to four reinforcement sessions over the succeeding few years. Injured subjects (from both the intervention and the control groups) were randomized a second time to receive either training or no training after their return to work. RESULTS: Physical therapists trained 2534 postal workers and 134 supervisors. Over 5.5 years of follow-up, 360 workers reported low back injuries, for a rate of 21.2 injuries per 1000 worker-years of risk. The median time off from work per injury was 14 days (range, 0 to 1717); the median cost was $204 (range, zero to $190,380). After their return to work, 75 workers were injured again. Our comparison of the intervention and control groups found that the education program did not reduce the rate of low back injury, the median cost per injury, the time off from work per injury, the rate of related musculoskeletal injuries, or the rate of repeated injury after return to work; only the subjects' knowledge of safe behavior was increased by the training. CONCLUSIONS: A large-scale, randomized, controlled trial of an educational program to prevent work-associated low back injury found no long-term benefits associated with training.

Adolescent↗