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Biomedical subjects

S McIntosh

Publications and source records attributed to S McIntosh.

At least 19 recordsLinked to original sources
PubMed2006

Tobacco use in the Dominican Republic: understanding the culture first.

OBJECTIVE: To conduct formative research on the landscape of tobacco use to guide survey and subsequent intervention development in the Dominican Republic (DR). DESIGN: Rapid Assessment Procedures, systematic qualitative methods (participant-observations, in-depth interviewing, focus groups) using bilingual mixed age and gendered teams from the United States and DR. SUBJECTS: Over 160 adults (men and women), ages 18 to 90 years, current, former and never smokers, community members and leaders from six underserved, economically disadvantaged DR communities. MAIN OUTCOME MEASURES: Key domains: tobacco use patterns and attitudes; factors affecting smoking initiation, continuation, quitting; perceived risks/benefits/effects of smoking; and awareness/effects of advertising/regulations. RESULTS: Perceptions of prevalence varied widely. While "everybody" smokes, smokers or ex-smokers were sometimes difficult to find. Knowledge of health risks was limited to the newly mandated statement "Fumar es prejudicial para la salud" [Smoking is harmful to your health]. Smokers started due to parents, peers, learned lifestyle, fashion or as something to do. Smoking served as an escape, relaxation or diversion. Quit attempts relied on personal will, primarily for religious or medical reasons. Social smoking (custom or habit) (< 10 cigarettes per day) was viewed as a lifestyle choice rather than a vice or addiction. Out of respect, smokers selected where they smoked and around whom. Health care providers typically were reactive relative to tobacco cessation, focusing on individuals with smoking related conditions. Tobacco advertising was virtually ubiquitous. Anti-tobacco messages were effectively absent. Cultures of smoking and not smoking coexisted absent a culture of quitting. CONCLUSIONS: Systematic qualitative methods provided pertinent information about tobacco attitudes and use to guide subsequent project steps. Integrating qualitative then quantitative research can be replicated in similar countries that lack empirical data on the cultural dimensions of tobacco use.

Adolescent↗
PubMed2005

A nomogram to classify men with lower urinary tract symptoms using urine flow and noninvasive measurement of bladder pressure.

PURPOSE: Bladder pressure during voiding can be estimated by a noninvasive technique using controlled inflation of a penile cuff. This test provides a valid and reliable estimate of isovolumetric bladder pressure but to our knowledge the role of the test for the routine clinical treatment of patients with lower urinary tract symptoms (LUTS) has yet to be demonstrated. As a first step, we evaluated a proposed nomogram for the diagnosis of bladder outlet obstruction in men with LUTS using noninvasive measurements of pressure and flow. MATERIALS AND METHODS: Using a combination of theoretical calculation and experimental data the existing International Continence Society pressure flow nomogram was modified to allow noninvasive measurement of isovolumetric bladder pressure in place of detrusor pressure at maximum urine flow. Accuracy of the nomogram for classifying obstruction was then tested in a group of 144 men with LUTS who underwent an invasive and a noninvasive pressure flow study. RESULTS: The modified nomogram identified men with obstruction with 68% positive predictive value and 78% negative predictive value. Predictive accuracy could be improved by adding an additional criterion of obstruction, that is maximum urine flow less than 10 ml second, whereby an identifiable 69% of all cases could be classified as obstructed (88% positive predictive value) or not obstructed (86% negative predictive value). In the remaining 31% of patients invasive pressure flow studies would provide additional information, although some results would remain equivocal. CONCLUSIONS: The proposed nomogram combined with the additional flow rate criterion can classify more than two-thirds of cases without recourse to invasive pressure flow studies. We must now evaluate the usefulness of this classification for the treatment of men with LUTS.

Aged↗
PubMed2000

Very high Q measurements on a fused silica monolithic pendulum for use in enhanced gravity wave detectors

We present for the first time the results of very high Q factor measurements for a 2.8 kg fused silica mass suspended by two fused quartz fibers attached by a novel technique for joining fused silica or quartz. The Q for the pendulum mode at 0.93 Hz was (2.3+/-0. 2)x10(7), the highest value demonstrated to date for a mass of this size. By employing such a new suspension system the sensitivity of the gravitational wave detectors currently under construction can be increased up to 1 order of magnitude.

Journal Article↗
PubMed2000

Smokers ages 50+: who gets physician advice to quit?

BACKGROUND: Smoking-related morbidity and mortality, and benefits associated with quitting, extend across the life span. Health care provider interventions enhance quitting. The present study examined perceived influence of physician advice to quit and characteristics of subjects receiving this advice. METHODS: Subjects were 1,454 smokers ages 50+ with at least one physician visit in the past year. Subjects were surveyed at baseline for receipt of and reactions to physician advice to quit and for smoking, health, and demographic characteristics. RESULTS: Over half of subjects welcomed physician advice to quit, about half said the advice influenced their quitting decision "extremely" or "quite a lot," and about one-third indicated that it increased their confidence in quitting. Physicians were more likely to advise sicker patients, indicated by poorer health status, at least one past year hospitalization, and presence of cardiovascular, cerebrovascular, or respiratory diseases. CONCLUSIONS: Midlife and older smokers reacted generally favorably to physician advice to quit. Physicians were more likely to advise patients with commonly recognized smoking-related diseases. Discrepancies were noted in advice given to sicker vs healthier patients. Additional physician training in less commonly recognized smoking-related illnesses, intervening with healthier patients to prevent disease, and enhancing patients' confidence in quitting may improve outcomes.

Aged↗
PubMed2000

Recruitment strategies and success in a multi-county smoking cessation study.

The current paper focuses on the process evaluation of recruitment strategies and success in a large study of self-help smoking interventions with mid-life and older smokers in a 15-county area. Recruitment 'channels' were examined: (1) multiple paid newspaper advertisements, (2) free media (i.e., TV and radio), (3) referrals, (4) HMO newsletters, (5) targeted mailings, (6) face-to-face, and (7) passive recruitment. Data were analyzed to determine (1) which channels produced the greatest numbers of information requests, or initial 'recruits', and (2) which produced the greatest number of enrolled subjects. Overall, four channels resulted in the enrollment of 96.4% of the final sample of 1972 subjects. The most reliable, cost-controlled channel was paid newspaper advertisements ($18-19 per enrolled subject), while face-to-face recruitment was inefficient and costly (over $140 per subject). Results can be used to help guide other studies in selecting recruitment strategies for large, geographically diverse, smoking intervention trials.

Aged↗
PubMed1999

Carotid sinus hypersensitivity--a modifiable risk factor for fractured neck of femur.

BACKGROUND: the potential impact on morbidity, mortality and health care economics makes it important to identify patients at risk of fracture, in particular fractured neck of femur (FNOF). Older patients with carotid sinus hypersensitivity (CSH) are more likely to have unexplained falls and to experience fractures, particularly FNOF. Our objective was to determine the prevalence of CSH in patients with FNOF. DESIGN: case-controlled prospective series. METHODS: consecutive cases were admissions over 65 years with FNOF. Controls were consecutive patients admitted for elective hip surgery, frail elderly people admitted to hospital medical wards and day-hospital patients. All patients had a clinical assessment of cognitive function, physical abilities and history of previous syncope, falls and dizziness, in addition to repeated carotid sinus massage with continuous heart rate and phasic blood pressure measurement. RESULTS: heart rate slowing and fall in systolic blood pressure was greater for patients with FNOF than those admitted for elective hip surgery (P < 0.05 and P < 0.001). CSH was present in 36% of the FNOF group, none of the elective surgery group, 13% of the acutely ill controls and 17% of the outpatients. It was more likely to be present in FNOF patients with a previous history of unexplained falls or an unexplained fall causing the index fracture. The heart rate and systolic blood pressure responses to carotid sinus stimulation were reproducible. CONCLUSION: older patients with an acute neck of femur fracture who do not give a clear history of an accidental fall or who have had previously unexplained falls are likely to have CSH. CSH may be a modifiable risk factor for older patients at risk of hip fracture.

Accidental Falls↗
PubMed1998

Syndet, an adipocyte target SNARE involved in the insulin-induced translocation of GLUT4 to the cell surface.

In adipocytes, insulin stimulates the translocation of the glucose transporter, GLUT4, from an intracellular storage compartment to the cell surface. Substantial evidence exists to suggest that in the basal state GLUT4 resides in discrete storage vesicles. A direct interaction of GLUT4 storage vesicles with the plasma membrane has been implicated because the v-SNARE, vesicle-associated membrane protein-2 (VAMP2), appears to be a specific component of these vesicles. In the present study we sought to identify the cognate target SNAREs for VAMP2 in mouse 3T3-L1 adipocytes. Membrane fractions were isolated from adipocytes and probed by far Western blotting with the cytosolic portion of VAMP2 fused to glutathione S-transferase. Two plasma membrane-enriched proteins, p25 and p35, were specifically labeled with this probe. By using a combination of immunoblotting, detergent extraction, and anion exchange chromatography, we identified p35 as Syntaxin-4 and p25 as the recently identified murine SNAP-25 homologue, Syndet (mSNAP-23). By using surface plasmon resonance we show that VAMP2, Syntaxin-4, and Syndet form a ternary SDS-resistant SNARE complex. Microinjection of anti-Syndet antibodies into 3T3-L1 adipocytes, or incubation of permeabilized adipocytes with a synthetic peptide comprising the C-terminal 24 amino acids of Syndet, inhibited insulin-stimulated GLUT4 translocation to the cell surface by approximately 40%. GLUT1 trafficking remained unaffected by the presence of the peptide. Our data suggest that Syntaxin-4 and Syndet are important cell-surface target SNAREs within adipocytes that regulate docking and fusion of GLUT-4-containing vesicles with the plasma membrane in response to insulin.

3T3 Cells↗
PubMed1997

Characterization of Munc-18c and syntaxin-4 in 3T3-L1 adipocytes. Putative role in insulin-dependent movement of GLUT-4.

We have previously identified three mammalian Sec1/Munc-18 homologues in adipocytes (Tellam, J. T., McIntosh, S., and James, D. E. (1995) J. Biol. Chem. 270, 5857-5863). These proteins are thought to modulate the interaction between vesicle membrane and target membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and thus regulate intracellular vesicular transport. This study aimed to further characterize these Munc-18 isoforms and to define their potential role in the trafficking of GLUT-4 in adipocytes, a process reported to involve the vesicle membrane SNARE, VAMP-2. Using an in vitro binding assay with recombinant fusion proteins, we show that Munc-18a and Munc-18b bind to syntaxin-1A, -2, and -3, while Munc-18c binds only to syntaxin-2 and -4. The specific interaction between Munc-18c and syntaxin-4 is of interest because aside from syntaxin-1A, which is not expressed in adipocytes, syntaxin-4 is the only syntaxin that binds to VAMP-2. Using a three-way binding assay, it was shown that Munc-18c inhibits the binding of syntaxin-4 to VAMP-2. The subcellular distribution of syntaxin-4 and Munc-18c was almost identical, both being enriched in the plasma membrane, and both exhibiting an insulin-dependent movement out of an intracellular membrane fraction similar to that observed for GLUT-4. Munc-18b had a similar distribution to Munc-18c and so may also be involved in vesicle transport to the cell surface, whereas Munc-18a was undetectable by immunoblotting in adipocytes. Microinjection of a syntaxin-4 antibody into 3T3-L1 adipocytes blocked the insulin-dependent recruitment of GLUT-4 to the cell surface. These data suggest that syntaxin-4/Munc-18c/VAMP-2 may play a role in the docking/fusion of intracellular GLUT-4-containing vesicles with the cell surface in adipocytes.

3T3 Cells↗
PubMed1995

Molecular identification of two novel Munc-18 isoforms expressed in non-neuronal tissues.

Munc-18, also known as n-Sec1 or rbSec1, is a syntaxin-binding protein thought to play a role in regulating synaptic vesicle exocytosis. Although a gene family of syntaxins has been identified, only a limited subset bind to Munc-18. This implicates the existence of other mammalian Munc-18 homologues that may be involved in a range of vesicle transport reactions. The purpose of the present study was to identify other members of the Munc-18 family by cDNA cloning. Three distinct Munc-18 isoforms, Munc-18a, previously identified in neuronal tissue, and two novel isoforms, Munc-18b and Munc-18c, were isolated from a 3T3-L1 adipocyte cDNA library by screening with a rat brain Munc-18 DNA probe. Munc-18a is identical to Munc-18 and by Northern analysis is expressed predominantly in brain and to a lesser extent in testis and 3T3-L1 cells. Munc-18b is 62% identical to Munc-18 at the amino acid level and is expressed in testis, intestine, kidney, rat adipose tissue, and 3T3-L1 cells. Munc-18c is 51% identical to Munc-18 and is ubiquitously expressed. It is likely, based on these findings, that unique Munc-18/syntaxin interactions may play an important role in generating a combinatorial mechanism for the regulation of vesicle transport in mammalian cells.

3T3 Cells↗
PubMed1994

Incidence of complications after carotid sinus massage in older patients with syncope.

OBJECTIVE: To review the incidence of neurological complications occurring after carotid sinus massage performed for diagnostic purposes. DESIGN: Case review and comparison with previously published work. SETTING: Syncope Clinic, Royal Victoria Infirmary, Newcastle-upon-Tyne, and Chelsea and Westminster Hospital, London. PARTICIPANTS: Patients undergoing investigation of dizziness, syncope, or unexplained falls. METHODS: Carotid sinus massage performed for 5 seconds in both supine and erect postures, both before and after atropine. Contraindications to carotid sinus massage were the presence of carotid bruits, recent myocardial or cerebral ischemia, or previous ventricular tachyarrhythmias. RESULTS: Two cases of neurological complications were reported from a total of 500 patients (2000 massage episodes) investigated in one center, giving an incidence of 0.1%. Combining this data with another center performing investigations in a similar fashion, seven neurological complications arose from a total of 5000 massage episodes, an incidence of 0.14%. Reported complications were pyramidal signs in five cases and visual field defects in two. Pyramidal weakness persisted in one case with a pre-existing stroke on the same side, and a visual field loss was permanent in one. CONCLUSIONS: Neurological complications following carotid sinus massage for diagnosis of the carotid sinus syndrome are uncommon and usually transient. Contraindications to carotid sinus massage should be respected and the standardized technique used.

Aged↗
PubMed1993

Outcome of an integrated approach to the investigation of dizziness, falls and syncope in elderly patients referred to a 'syncope' clinic.

Sixty-five consecutive elderly patients (mean age 78 years) referred to a 'syncope' clinic over a six-month period were prospectively studied. Initial evaluation included ambulatory electrocardiography, carotid sinus massage before and after atropine and prolonged head-up tilt. Diagnostic criteria for causes of syncope were assigned at the beginning of the study. Overall, a diagnosis was attributed to symptoms in 92% of patients; overlap was present in a quarter. Diagnoses were cardioinhibitory carotid sinus syndrome (CSS; 5%), vasodepressor CSS (26%), mixed CSS (14%), orthostatic hypotension (32%), vasodepressor vasovagal syncope (11%), cardiac arrhythmia (21%), epilepsy (9%), cerebrovascular disease (6%) and others (12.5%). Sixty per cent of patients with vasodepressor CSS also had orthostatic hypotension or vasodepressor vasovagal syncope suggesting a common aetiology. Using an integrated approach incorporating head-up tilt and carotid sinus massage in a selected group of elderly patients referred to a 'syncope' clinic, the diagnostic yield was high.

Accidental Falls↗
PubMed1993

Benefits of fludrocortisone in the treatment of symptomatic vasodepressor carotid sinus syndrome.

OBJECTIVE: To assess treatment with fludrocortisone in vasodepressor carotid sinus syndrome. PATIENTS AND METHODS: Eleven patients, mean (SD) age 83 (5) years, with daily dizzy episodes and a median of five (range two to 20) syncopal episodes over a median of one year were studied. All had vasodepressor carotid sinus syndrome (> 50 mm Hg fall in systolic blood pressure during carotid sinus massage independent of bradycardia). Carotid sinus massage was carried out while the patient was supine and upright (tilt table) before and after 600 micrograms intravenous atropine. Phasic heart rate and blood pressure recordings were monitored throughout. The study was repeated after 100 micrograms of fludrocortisone daily by mouth for two weeks. Patients continued to take fludrocortisone for a six month follow up period. RESULTS: Baseline systolic blood pressure was (mean (SD)) 169 (31) mm Hg and the RR interval was 770 (150) ms. After carotid sinus massage, systolic blood pressure fell to 113 (27) mm Hg (p < 0.01) and RR was 1060 (210) ms (NS). The vasodepressor response was 56 (12) mm Hg. Baseline systolic blood pressure after two weeks of fludrocortisone treatment was 171 (37) mm Hg (NS); but the fall in systolic blood pressure during carotid sinus massage was significantly reduced (32 (14) mm Hg; p < 0.01). At six months follow up, two patients complained of intermittent dizziness and no patients had syncope. CONCLUSION: Fludrocortisone effectively reduces the vasodepressor response and relieves the symptoms of vasodepressor carotid sinus syndrome.

Aged↗