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Biomedical subjects

T Myers

Publications and source records attributed to T Myers.

At least 19 recordsLinked to original sources
PubMed2000

FR901228 causes mitotic arrest but does not alter microtubule polymerization.

FR901228, a natural cyclic depsipeptide, shows high cytotoxicity against human cancer cell lines (low nM IC50 values). Cells exposed to FR901228 arrest with G1 or G2/M DNA content; S phase is depleted. G2/M cells include cells arrested in mitosis. We wished to understand the mitotic arrest by this compound. Mitotic arrest is often due to interference with microtubules and COMPARE testing in the NCI drug screen indicated a possible taxane-like mechanism. Testing of FR901228 for tubulin binding or alteration of in vitro MT assembly failed to reveal any effect. Likewise, examination of cellular microtubules following exposure to FR901228 did not reveal any change. Similar G2/M accumulation was observed in MCF7, MCF10 and PC3 cells. About 50% of G2/M cells were mitotic and contained microtubule spindles. Mitotic cells peaked at about 14-16 h drug exposure and declined to near 0% by 24-30 h. The block was at prometaphase, with numerous chromosomes unattached to the spindle. We conclude that FR901228 induces formation of aberrant spindles probably by interfering with chromosome attachment, causing mitotic accumulation without affecting mitotic microtubules.

Anti-Bacterial Agents↗
PubMed1999

Increased risk of lymphoid and nonlymphoid malignancies in patients with lymphomatoid papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) is a rare skin disease with malignant potential. The long term outcomes of patients with this disease have not been adequately assessed. METHODS: Fifty-seven patients with biopsy-proven LyP and 67 controls matched for age, gender, and race were followed prospectively from 1988 to 1996. Reported malignancies were confirmed by surgical pathology and/or autopsy reports. A search through the National Death Index through December 1995 was conducted to identify all deaths, and death certificates were procured. Expected numbers of malignancies based on SEER data were calculated for both the patient and the control groups. RESULTS: Six LyP patients (10.5%) and 1 control (1.5%) reported nonlymphoid malignancies (P = 0.047). Two patients and no controls developed lymphoid malignancies (mycosis fungoides and CD30(+) cutaneous lymphoma). The expected numbers of nonlymphoid and lymphoid malignancies in the LyP patient group, based on the SEER data, were 1.93 and 0.15, respectively, yielding a relative risk (with 95% confidence interval) of 3.11 (1.26-6.47) for nonlymphoid malignancies and 13.33 (2.24-44.05) for malignant lymphomas in the LyP patients. There was no significant difference between the observed and expected numbers of malignancies in the control group. Four LyP patients died during the follow-up, three due to malignancies; and one control died of a gunshot wound to the head (suicide). The difference in overall survival between the LyP patients and the controls was not statistically significant (P = 0. 12). CONCLUSIONS: Patients with LyP appear to have an increased risk of both lymphoid and nonlymphoid malignancies. The increased risk of nonlymphoid as well as lymphoid malignancies may suggest a basic underlying genetic defect leading to the development of malignancy in LyP patients.

Adolescent↗
PubMed1999

Mucosal injury and eicosanoid kinetics during hyperventilation-induced bronchoconstriction.

Bronchoalveolar lavage (BAL) of canine peripheral airways was performed at various times after hyperventilation, and BAL fluid (BALF) cell and mediator data were used to evaluate two hypotheses: 1) hyperventilation-induced mucosal injury stimulates mediator production, and 2) mucosal damage is correlated with the magnitude of hyperventilation-induced bronchoconstriction. We found that epithelial cells increased in BALF immediately after a 2- and a 5-min dry air challenge (DAC). Prostaglandins D(2) and F(2alpha) and thromboxane B(2) were unchanged immediately after a 2-min DAC but were significantly increased after a 5-min DAC. Leukotriene C(4), D(4), and E(4) did not increase until 5 min after DAC. Hyperventilation with warm moist air did not alter BALF cells or mediators and caused less airway obstruction that occurred earlier than DAC. BALF epithelial cells were correlated with mediator release, and mediator release and epithelial cells were correlated with hyperventilation-induced bronchoconstriction. These observations are consistent with the hypothesis that hyperventilation-induced mucosal damage initiates peripheral airway constriction via the release of biochemical mediators.

Airway Resistance↗
PubMed1998

Community pharmacist perspectives on HIV/AIDS and interventions for injection drug users in Canada.

In several countries, community pharmacies play a major role in the provision of HIV prevention services to injection drug users (IDUs). In this study, results from a national Canadian Survey of Community Pharmacies and HIV/AIDS Prevention are used to describe pharmacists' perspectives on HIV/AIDS and services to IDUs, and explore the relationship between personal and organizational characteristics and the level of support for HIV/AIDS prevention initiatives. A mailed questionnaire was directed to a random sample of 2,017 pharmacist owner-managers. The response rate was 84.6%. Results suggest that current services to IDUs primarily are limited to discretionary needle and syringe sales to non-diabetics, with almost three-quarters supportive. Staff safety was an important consideration in the provision of this service (77%), while remuneration was the lowest (27%). Community pharmacists were most comfortable with the provision of counselling, advice and literature (X = 2.6) and environmental and technological interventions (X = 2.4) and least supportive of provision of services as part of a programme (X = 1.6) and legalization of drugs or prescription of methadone (X = 1.9). Female pharmacists were more likely to support preventive measures such as the provision of counselling or advice, and males were more likely to promote legislative change. Pharmacists appear generally willing to expand their services in the fight against HIV/AIDS. However, it is not feasible to expect uniform programmes to be immediately introduced. While organizational, educational and policy changes may facilitate programme development, individual pharmacy and pharmacist discretion remains important.

Canada↗
PubMed1998

Condom use among Aboriginal people in Ontario, Canada.

A survey of 658 Aboriginal men and women living in 11 reserve communities in Ontario, Canada, was utilized to collect data on patterns of condom use. Individuals who had sexual intercourse in the previous 12 months were included in the analysis (n=400). Descriptive statistics and multiple logistic regression were used to analyse condom use in the previous 12 months. Eight per cent always, 31% sometimes, and 61% never used condoms. Rates of condom use differed with the number of sex partners in the last year, age, gender, having a steady sex partner, and marital status. Multiple logistic regression revealed that people most likely to use condoms were under the age of 30, male, did not have a long-term steady sex partner, had more than one sex partner, worried about pregnancy, were knowledgeable about HIV/AIDS, and were not embarrassed to obtain condoms. Condom users who were knowledgeable about HIV/AIDS and who knew someone with HIV/AIDS were more likely to always use condoms. The most common reason for not using a condom was 'I was with my steady sex partner'. These results have implications for STD prevention efforts and for future research of sexual and STD preventive behaviour among Aboriginal people.

Adolescent↗
PubMed1997

Morphological and functional characterization of an in vitro blood-brain barrier model.

Cell culture models have been extensively used for studies of blood-brain barrier (BBB) function. However, several in vitro models fail to reproduce some, if not most, of the physiological and morphological properties of in situ brain microvascular endothelial cells. We have recently developed a dynamic, tridimensional BBB model where endothelial cells exposed to intraluminal flow form a barrier to ions and proteins following prolonged co-culturing with glia. We have further characterized this cell culture model to determine whether these barrier properties were due to expression of a BBB phenotype. Endothelial cells of human, bovine or rodent origin were used. When co-cultured with glia, intraluminally grown endothelial cells developed features similar to in vivo endothelial cells, including tight junctional contacts at interdigitating processes and a high transendothelial resistance. This in vitro BBB was characterized by the expression of an abluminal, ouabain-sensitive Na/K pump, and thus favored passage of potassium ions towards the lumen while preventing K+ extravasation. Similarly, the in vitro BBB prevented the passage of blood-brain barrier-impermeant drugs (such as morphine, sucrose and mannitol) while allowing extraluminal accumulation of lipophylic substances such as theophylline. Finally, expression of stereo-selective transporters for Aspartate was revealed by tracer studies. We conclude that the in vitro dynamic BBB model may become an useful tool for the studies of BBB-function and for the testing of drug passage across the brain endothelial monolayer.

Animals↗
PubMed1997

Decreased glucose tolerance, not decreased insulin sensitivity, is a maturational abnormality in the male offspring of a parent with early coronary artery disease.

We investigated whether the male offspring of a parent with early coronary artery disease (before the age of 60; n = 61) exhibit decreased insulin sensitivity compared with controls matched for age and body mass index (BMI) (n = 39). The insulin sensitivity index (S[I]) was determined by the minimal modeling method of Bergman from a frequently sampled intravenous glucose tolerance test with intravenous tolbutamide. Offspring and controls had a similar S[I], insulin-independent glucose utilization (S[G]), first-phase insulin response (AIR[G]), and area under the glucose curve. When subjects were separated into two age groups, younger subjects aged 15 to 30 years and older subjects aged 31 to 45 years, important differences were seen. S[G] was significantly increased in younger offspring compared with controls (22.8 +/- 2.3 v 16.8 +/- 2.3 x 10(-3) x min(-1), P < .05). Older offspring had a significantly increased area under the glucose curve compared with controls (18,250 +/- 322 v 17,225 +/- 347 mg/dL x min(-1), P < .05). Older offspring also had decreased S[I] compared with younger offspring (5.0 +/- 0.4 v 6.6 +/- 0.9 x 10(-4) x min(-1) x micro U/mL, P < .05), but this difference was eliminated after adjusting for BMI and waist to hip ratio (5.5 +/- 0.4 v5.8 +/- 0.9 x 10(-3) x min(-1), nonsignificant). This study does not support the concept that insulin resistance is an early atherogenic risk factor in offspring at risk for coronary disease because of their family history. However, it does point to the importance of maturational changes in glucose homeostasis in these offspring.

Adolescent↗
PubMed1997

Effects of increasing airway pressure and PEEP on the assessment of cardiac preload.

BACKGROUND: Cardiac preload is most commonly assessed by pulmonary artery wedge pressure. It was postulated that the right ventricular end-diastolic volume index (RVEDVI) derived by thermodilution would be a better predictor of preload in trauma patients with high airway pressures associated with positive pressure ventilation and positive end-expiratory pressure. METHODS: Volumetric thermodilution catheters were placed in 52 mechanically ventilated trauma patients. Regression analysis was performed on 986 sets of hemodynamic data comparing pulmonary artery wedge pressure and RVEDVI to cardiac index (CI) at various airway pressures. RESULTS: There was much better correlation between RVEDVI and CI (r = 0.41) than with pulmonary artery wedge pressure and CI (r = -0.06). This was true of all levels of airway pressure tested. When analyzed by the degree of right ventricular dysfunction, as indexed by right ventricular ejection fraction, the strongest correlation between RVEDVI and CI was noted when right ventricular ejection fraction was > 30%. CONCLUSIONS: Unlike the pulmonary artery wedge pressure, RVEDVI is as reliable indicator of preload in the mechanically ventilated trauma patient. This is especially true when the right ventricular ejection fraction is not severely depressed.

Adult↗
PubMed1997

Differences in sexual risk-taking behavior with state of inebriation in an aboriginal population in Ontario, Canada.

OBJECTIVE: This article describes the self-reported use of substances, participation in unprotected intercourse and differences in sexual risk-taking behavior with state of inebriation among a group of aboriginal (First Nations) people in Ontario. And, in so doing, attempts to answer some of the questions about the association between the use of alcohol and sexual risk taking in this population. METHOD: The project was developed in a partnership between an aboriginal steering committee and university researchers. Data were collected via interview from 658 randomly selected status First Nations people living within 11 reserve communities in the province. RESULTS: Of the 426 individuals included in the within subject analysis 9.6% reported variation in their participation in sex, 13.8% variation in their participation in intercourse and 10.3% variation in their participation in unprotected intercourse with inebriation. An examination of individual behavior across "sober" and "drunk or high" states showed that there were almost equal proportions of respondents who only participated in unsafe sex when sober and respondents who only participated in unsafe sex when drunk or high. Where significant differences occurred, individuals were more likely to report a shift towards no sex or no intercourse with inebriation, not towards unprotected intercourse. CONCLUSIONS: Since a large proportion of individuals in this study engage in unprotected intercourse, the small proportion of individuals reporting different sexual behavior were more likely to report participation in a safe activity rather than an unsafe activity while "drunk or high." Stereotypes and assumptions may lead educators and researchers to feel the need to focus their messages on the relationship between drug and alcohol consumption and unsafe sex; however, the amount of unsafe sexual intercourse that occurs only while individuals are inebriated suggests that this focus is not of principal concern.

Adolescent↗
PubMed1997

Understanding the intention of gay and bisexual men to take the HIV antibody test.

This study offers an explanation for the intention of 1,512 gay and bisexual men to be tested for the HIV antibody. Participants were recruited through 125 gay-identified venues (bars, bathhouses, community dances) across Canada. Self-administered questionnaires assessed respondents' intention to take the test in the next year, predictor variables (e.g., attitudes, the perceived social norm of the gay community, perceived behavioral control, and other constructs such as reasons for not being tested and importance of aspects of the test such as confidentiality), and sociodemographic variables. For this analysis, two groups were formed: men who had taken the HIV test in the past with negative or unknown results (Group A) and men who had not taken the test (Group B). The proportions of men who intended to take the test in the next year were 84.8% and 53.3% for groups A and B, respectively. For both groups, logistic regression indicated that the most important factors explaining intention were attitudes toward taking the test and perceived behavioral control. Additional variables specific to each group also contributed to explain intention. Thus, to enhance test-seeking among this population requires a consistent program of health education and facilitative policies.

AIDS Serodiagnosis↗
PubMed1996

A novel catecholamine, arbutamine, for a pharmacological cardiac stress agent.

Arbutamine, developed for use as a cardiac stress agent, was compared with isoproterenol and dobutamine in anesthetized dogs for cardiovascular actions prior to and after beta-adrenergic blockade with propranolol. The efficacy and safety of arbutamine were also evaluated in a canine model of myocardial ischemia obtained by partially occluding the left anterior descending coronary artery. Comparison of hemodynamic variables in normal dogs showed that arbutamine was approximately equipotent to isoproterenol in increasing heart rate and cardiac contractility, and in decreasing total peripheral vascular resistance and mean arterial blood pressure. Arbutamine was 210 times more potent than dobutamine in increasing cardiac contractility by 70%; however, at this dose dobutamine exhibited a negative chronotropic response. Beta-adrenergic blockade with propranolol shifted the agonist's dose-response curves for heart rate and contractility to the right; however, low doses of dobutamine exhibited a negative chronotropic effect and increased the total peripheral vascular resistance. In dogs subjected to partial left anterior descending coronary artery occlusion, arbutamine produced significant ST-segment deflections, beginning at a dose of 0.1 nmol/kg/min. Impairment of segment shortening, reflecting cardiac wall motion abnormality, was evident at a dose of 0.3 nmol/kg/min. Isoproterenol did not cause significant changes in these parameters. These results show that arbutamine is capable of producing graded increments in cardiac contractility and rate before and after beta-adrenergic blockage in normal dogs. In dogs subjected to coronary artery occlusion, it is capable of provoking myocardial ischemia at dose levels devoid of toxicity.

Animals↗
PubMed1996

Sexual risk and HIV-testing behaviour by gay and bisexual men in Canada.

Behavioural epidemiology is an important aspect of HIV research, particularly among marginalized populations where measurement of rates of infection have not been conducted. This Canadian study provides a country-wide analysis of the characteristics and behaviours of gay and bisexual men, and examines the influence of geographic, socio-demographic and lifestyle influences on sexual behaviour and test-seeking. A purposive sample of 4,803 men was recruited through gay-identified venues. In order to provide national representation seven sampling strata were defined. Data were collected by self-completed questionnaire. A three-level hierarchical logistic regression analysis is used to model two behaviours, unprotected anal intercourse and test-seeking. The results showed that, nationally, 22.9% of respondents reported at least one episode of unprotected anal intercourse in the previous 3 months, and 63% had been tested. Characteristics and behaviours of men varied across the country. Geographic differences appear to be less important in explaining unprotected anal intercourse than test-seeking. In conclusion, policy, programmes and social environment appear to exert an important influence on test-seeking, whereas cultural and psychosocial dimensions appear to have a greater influence on sexual behaviour.

AIDS Serodiagnosis↗
PubMed1996

Heparinase-guided thrombelastography in an anticoagulated parturient.

We describe the use of heparinase-guided thrombelastography in the assessment of a parturient who had been anticoagulated with heparin for suspected thromboembolic disease. Reversal of the heparin effect in the heparinase-treated sample facilitated administration of protamine and successful subarachnoid analgesia for delivery.

Adult↗
PubMed1996

Fracture and migration of a pacemaker atrial lead retention wire found by fluoroscopic screening in an asymptomatic patient.

We present the case of a woman who had an Accufix atrial "J" pacemaker lead implanted in 1990. Subsequently, Telectronics Pacing Systems recalled two models of the atrial leads after problems with fracture and malfunction were reported. One of these models was used in our case. Fifty-two months after implantation, following recommended fluoroscopic screening, our patient was found to have a complete fracture of the "J" retention wire with one fragment protruding from the sheath in the right atrium and another fragment of the wire lodged in the right ventricle. The pacemaker had continued to function normally and there was no clinical evidence to suggest such a potentially disastrous fracture. Our report emphasizes the importance of fluoroscopic screening of all patients with atrial leads involved in the recall.

Aged↗
PubMed1996

In utero exposure to ethanol alters mRNA for insulin-like growth factors and insulin-like growth factor-binding proteins in placenta and lung of fetal rats.

Insulin-like growth factors I and II (IGF-I and IGF-II) play a role in regulating fetal growth and development. Their actions in target tissues are modulated in part by binding to IGF binding proteins 1 and 2 (IGFBP-1 and IGFBP-2). In this study, we examined the effect of fetal exposure to alcohol IGF-I and on IGF-II and IGFBP-1 and IGFBP-2 mRNA in placenta and fetal lung tissue. Timed-pregnant Sprague-Dawley dams were fed a diet consisting of 35% ethanol-derived calories [alcohol-fed (AF)], an Isocaloric diet with sucrose substituted for alcohol (pair-fed; PF), or ad libitum rat chow (CF). Alcohol feeding began on gestational age (G) 14. At G20, dams were killed, and we examined placenta and fetal lung for the steady-state levels of mRNA for IGF-1 and IGF-II and for IGFBP-1 and IGFBP-2. In all dams, body weight increased throughout gestation, and there were no differences between the three groups. At G20, the mean weight for the fetuses from the AF group was lower (p < 0.001) than the fetuses from the CF and PF groups. Steady-state mRNA levels were detected in fetal lung and in placentas by Northern-blot hybridization analysis and semiquantitated by slot-blot hybridization analysis. Multiple transcripts for IGF-I and IGF-II, 1.8 kb species for IG-FBP-1 and 1.6 kb species for IGFBP-2 were detected from total RNA isolated from the fetal lung and placenta, Slot-blot hydridization analysis of fetal lung RNA showed that IGF-I mRNA was significantly increased (p < 0.001) in AF males and females by 4.0 +/- 0.28-fold and by 3.25 +/- 0.2-fold, respectively. IGF-II transcript levels were not affected. IGFBP-1 and IGFBP-2 were increased in AF males, whereas only IGFBP-2 was increased in AF females. In the placenta, there was a significant increase in IGFBP-1 and IGFBP-2 transcripts [(p < 0.001) 1.75 +/- 0.5-fold and 3 +/- 0.53-fold increase, respectively]. No differences between the groups in serum levels of IGFBP-1 or -2 were detected when measured by Western-blot analysis. The increased gene expression for IGFBPs within fetal lung and placenta may decrease bioavailability of locally synthesized, IGFs that may contribute to the fetal growth retardation observed in this model system.

Animals↗
PubMed1996

The role of policy in community pharmacies' response to injection-drug use: results of a nationwide Canadian survey.

The response rate to this survey reflects the salience of the topic and the professional concern about and interest in issues presented by HIV. The HIV/AIDS epidemic has presented pharmacists with one of the greatest challenges to their professional training, ethics, and practice. It further expedites a current re-examination that is occurring among community pharmacies concerning their roles in community health practices. In response to HIV there have been dramatic and unprecedented changes in pharmacy policy and practices. Clearly, some community pharmacies have led the way and influenced policy and practices. In view of the recent introduction of many of these policies and practices, it is likely that change will continue. Survey respondents were, in general, very comfortable with an expanded role involving counseling, health promotion, and disease prevention, consistent with a broader role for community pharmacies in general that has been recently advocated. Community pharmacies serve all areas of the country, in communities large and small; many are open seven days a week, and some provide extended hours of service. Community pharmacies may provide an important complement to community outreach programs as a source of clean needles and syringes for IDUs in most communities, and as an alternative service in some communities where more elaborate programs are not feasible. Safer needle use, as part of a health-promotion approach, is divergent from conventional practice. While major changes have occurred, it appears that there has been some polarization of attitudes and response. The explanation for this is not simple, and further analysis is required to determine the full impact from several ethical perspectives that include professional, business, and public health viewpoints. We have highlighted the role that policy has in moving toward preventive and harm-reduction approaches. From a policy perspective, we have found that support from the federal government, regulatory bodies, and professional associations may be an important catalyst to pharmacists' participation in programs. Further, it does not appear to be possible to implement such policies without professional development and continuing education, and collaboration with the community. Based on data on knowledge and educational need, we believe that our study population's lowest levels of information were in such areas as the role of methadone in HIV prevention and the availability of needle-exchange programs. As with other health-promotion campaigns, additional skills training may be important. Movement forward with expanded preventive and harm-reduction strategies by pharmacies will require careful planning. It is anticipated that change in this area will be incremental in nature, and that it is necessary to introduce programs and services into community pharmacies gradually. Successful implementation will require extensive community development and collaboration with other health professionals, public health officials, police, groups who represent IDUs, and persons living with HIV/AIDS. Careful monitoring and evaluation of these programs will be necessary to enhance their effectiveness.

Canada↗