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Biomedical subjects

D Davis

Publications and source records attributed to D Davis.

At least 73 records · Page 4Linked to original sources

Physical activity patterns associated with cardiorespiratory fitness and reduced mortality: the Aerobics Center Longitudinal Study.

OBJECTIVES: This study examined cross sectionally the physical activity patterns associated with low, moderate, and high levels of cardiorespiratory fitness. METHODS: Physical activity was assessed by questionnaire in a clinic population of 13,444 men and 3972 women 20 to 87 years of age. Estimated energy expenditure (kcal.wk-1) and volume (min.wk-1) of reported activities were calculated among individuals at low, moderate, and high fitness levels (assessed by maximal exercise tests). RESULTS: Average leisure time energy expenditures of 525 to 1650 kcal.wk-1 for men and 420 to 1260 kcal.wk-1 for women were associated with moderate to high levels of fitness. These levels of energy expenditure can be achieved with a brisk walk of approximately 30 minutes on most days of the week. In fact, men in the moderate and high fitness categories walked between 130 and 138 min.wk-1, and women in these categories walked between 148 and 167 min.wk-1. CONCLUSIONS: Most individuals should be able to achieve these physical activity goals and thus attain a cardiorespiratory fitness level sufficient to result in substantial health benefits.

Adult↗

Does CME work? An analysis of the effect of educational activities on physician performance or health care outcomes.

OBJECTIVE: To answer the question, "does CME work?" by reviewing the effectiveness of continuing medical education (CME) and other related educational methods on objectively-determined physician performance and/or health care outcomes. These interventions include educational materials, formal, planned CME activities or programs, outreach visits such as academic detailing, opinion leaders, patient-mediated strategies, audit and feedback, reminders, or a combination of these strategies. METHODS: MEDLINE, ERIC, NTIS, the Research and Development Resource Base in CME and other relevant data sources including review articles were searched for relevant terms, from 1975 to 1994. Of those articles retrieved, randomized controlled trials of educational strategies or interventions which objectively assessed physician performance and/or health care outcomes were selected for review. Data were extracted from each article about the specialty of the physician targeted, the clinical subject of the intervention, the setting and the nature of the educational method, and the presence or degree of needs assessment or barriers to change. RESULTS: More than two-thirds of the studies (70%) displayed a change in physician performance, while almost half (48%) of interventions produced a change in health care outcomes. Community-based strategies such as academic detailing (and to a lesser extent, opinion leaders), practice-based methods such as reminders and patient-mediated strategies, and multiple interventions appeared to be most effective activities. Mixed results and weaker outcomes were demonstrated by audit and educational materials, while formal CME conferences without enabling or practice-reinforcing strategies, had relatively little impact. CONCLUSION: Strategies which enable and/or reinforce appear to "work" in changing physician performance or health care outcomes, a finding which has significant impact on the delivery of CME, and the need for further research into physician learning and change.

Clinical Competence↗

Half corneal light shield as a delivery system for standardized application of mitomycin C.

PURPOSE: The authors develop a simple and economical method of applying reproducible intraoperative doses of mitomycin C for glaucoma filtering surgery. METHODS: A three-part protocol was developed to study several properties of half corneal light shields (HCLSs). Part A tested the amount of mitomycin C (0.4 mg/ml) absorbed, the expansion dimensions attained, and the amount released to filter paper. In part B, the in vitro release of mitomycin C to an enucleated pig eye was examined. In part C, the in vivo release during intraoperative filtering surgery was tested. RESULTS: The amount of mitomycin C solution absorbed by the HCLSs ranged from 1.07 x 10(-2) mg to 1.19 x 10(-2) mg; expansion width ranged from 6.8 mm to 7.0 mm; expansion height ranged from 3.6 mm to 3.8 mm; expansion thickness was constant at 0.6 mm. The amount of solution released to filter paper ranged from 6.8 x 10(-3) mg to 8.6 x 10(-3) mg. The amount of solution transferred to the pig eye ranged from 1.0 x 10(-3) mg to 2.7 x 10(-3) mg. The amount of solution released in filtering surgery ranged from 2.0 x 10(-3) mg to 4.8 x 10(-3) mg. CONCLUSIONS: The contact surface area, the amount absorbed, and the amount released by each HCLS was reproducible. The uniform thickness theoretically provides a uniform distribution of mitomycin C. This method may allow standardization of intraoperative mitomycin C application, and may reduce the incidence of complications.

Absorption↗

Genetic variation of HIV type 1: relevance of interclade variation to vaccine development.

Accumulating data in human immunodeficiency virus (HIV)-infected individuals support the hypothesis that in primary human immunodeficiency virus type 1 (HIV-1) isolates of different clades and phenotype (syncytium inducing [SI] and nonsyncytium inducing [NSI]) common antigenic structures must exist that can stimulate the immune response to produce a broad spectrum (cross-clade and cross SI and NSI) neutralization response. Certain vaccination regimens in chimpanzees and human volunteers with clade B SI type HIV-1 derived candidate vaccines induce neutralizing antibodies against intraclade B SI type primary HIV-1 isolates, but not against intraclade B NSI type of viruses. To be effective against the full antigenic spectrum of primary HIV-1 isolates (cross-clade--SI and NSI) candidate vaccines should contain immunogens of primary isolates representative of the whole antigenic spectrum of HIV-1. There is an urgent need to identify these immunogens and to improve their immunogenicity. As long as we have not yet characterized these cross-HIV-1 spectrum conserved immunogens, candidate vaccines against the more prevalent clades C, A, and E should be developed for evaluation in developing countries. In support of the follow-up and evaluation of the hopefully increasing number of phase 1, 2, and 3 HIV-1 vaccine trials in humans, it is considered a high priority to develop a high throughput neutralization assay, to further expand the use of a limited number of key primary HIV-1 isolates as a surrogate for neutralization of the entire HIV-1 antigenic spectrum (cross-clade--SI and NSI), to develop high throughput subtyping as well as a rapid system to monitor the immunogenic relatedness of different HIV-1 clades.

AIDS Vaccines↗

Pediatric endotracheal tube selection: a comparison of age-based and height-based criteria.

Many methods are taught and used clinically to determine what size uncuffed endotracheal tube is required for the pediatric patient. The purpose of this study was to compare the effectiveness of two methods of selection used clinically: (1) the traditional age-based (AB) formula; (age in years +16) divided by 4, and (2) the method based on body length using the Broselow pediatric resuscitation tape. Following institutional review board approval, 174 patients were prospectively studied after informed consent was obtained. Uncuffed endotracheal tube size selection was determined by randomly assigning the patient to one of the two groups. The appropriateness of the tube selection was assessed using an audible air leak around the endotracheal tube. No difference was found between the AB group and the resuscitation tape group with respect to selecting the appropriate size of endotracheal tube. Retrospective analysis of all patients found another AB formula that is occasionally used ([age in years +18] divided by 4) to be correct in only 20 (11%) of 174 cases. This was significantly different from the other methods (P < .001). Since the AB formula ([age in years +16] divided by 4) is reliable and easily applied, it appears acceptable for routine anesthesia cases in the pediatric population requiring endotracheal intubation. The AB formula ([age in years +18] divided by 4) should be used cautiously because of the high failure rate. In circumstances in which general information, such as age, is not available and endotracheal intubation is needed, the Broselow tape allows reliable endotracheal tube size identification and should be readily available.

Age Factors↗

Role of the estrogen receptor in the action of organochlorine pesticides on estrogen metabolism in human breast cancer cell lines.

As interest in the properties of xenoestrogenic compounds has grown, different in vitro cell culture systems have been proposed as models, against which to gauge relative estrogenic impact. Previous research indicated that some organochlorine-based pesticides elevated the production of 16 alpha-hydroxyestrone relative to 2-hydroxyestrone in ER+ MCF-7 breast cancer cells while phytochemicals like indole-3-carbinol reduced this ratio. That this ratio may be a biological marker of the risk of breast cancer has recently been demonstrated. In this study we have carried out the same paradigm in two ER- cell lines to examine the effect of receptor status. To determine whether the impact of chlorinated pesticides can be modulated by phytochemicals, the ability of indole-3-carbinol or brassinin to reverse the changes in metabolism was examined. Non-persisting phosphorus-based pesticides were also studied and shown not to have an effect on estrogen metabolism. The implications of these findings are examined.

Anticarcinogenic Agents↗

The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88.

The oncogenic nucleoporin CAN/Nup214 is essential in vertebrate cells. Its depletion results in defective nuclear protein import, inhibition of messenger RNA export and cell cycle arrest. We recently found that CAN associates with proteins of 88 and 112 kDa, which we have now cloned and characterized. The 88 kDa protein is a novel nuclear pore complex (NPC) component, which we have named Nup88. Depletion of CAN from the NPC results in concomitant loss of Nup88, indicating that the localization of Nup88 to the NPC is dependent on CAN binding. The 112 kDa protein is the human homologue of yeast CRM1, a protein known to be required for maintenance of correct chromosome structure. This human CRM1 (hCRM1) localized to the NPC as well as to the nucleoplasm. Nuclear overexpression of the FG-repeat region of CAN, containing its hCRM1-interaction domain, resulted in depletion of hCRM1 from the NPC. In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins. Lastly, hCRM1 shares a domain of significant homology with importin-beta, a cytoplasmic transport factor that interacts with nucleoporin repeat regions. We propose that hCRM1 is a soluble nuclear transport factor that interacts with the NPC.

Amino Acid Sequence↗

Intracellular volume and apparent diffusion constants of perfused cancer cell cultures, as measured by NMR.

Diffusion NMR spectroscopy was used to study intracellular volume and apparent water diffusion constants in different cell lines (DU145, human prostate cancer; AT3, rat prostate cancer; MCF-7, human breast cancer; RIF-1, mouse fibrosacroma). The cells were grown on various matrices (collagen sponge, collagen beads, polystyrene beads) which enabled continuous growth in perfused high density cell culture suitable for NMR studies. In perfused cell systems, the attenuation of the water signal versus the squared gradient strength was fitted by the sum of two decaying exponentials. For the slowly decaying component the apparent water diffusion constant at 37 degrees C was 0.22 (+/-0.02) x 10(-9) s/m2 for all cell lines at diffusion times > 100 ms. It continuously increased up to 0.47 (+/-0.05) x 10(-9) s/m2 when the diffusion time was decreased to 8 ms, indicating restricted diffusion. No significant effect of the matrices was observed. The fractional volume of the slow component as determined from the biexponential diffusion curve correlated with the relative intracellular volume, as obtained from the cell density in the sample and the cell size as measured by light microscopy. Therefore, this simple NMR approach can be used to determine intracellular volume in perfused cell cultures suitable for NMR studies. Using this information in combination with spectroscopic data, changes in intracellular metabolite concentration can be detected even when the cellular volume is changing during the experiment. The apparent diffusion constant for the fast diffusing component varied with growth matrix, cell density and cell type and also showed the typical characteristics of restricted diffusion (increase of apparent diffusion constant with time).

Animals↗

A recombinant prime, peptide boost vaccination strategy can focus the immune response on to more than one epitope even though these may not be immunodominant in the complex immunogen.

Rhesus monkeys were successfully vaccinated using a strategy of priming with a candidate envelope subunit vaccine and boosting with synthetic peptides. Priming was carried out with recombinant HIV-1 SF2 envelope glycoprotein incorporated into ISCOMs, following the attachment of a lipid tail. Peptides, covalently linked to ISCOMs, representing linear sequences with the V2 and V3 regions, were used to boost functional antibodies-to neutralizing epitopes in both of these regions. Injections with these peptide formulations substantially increased the titre of serum neutralizing antibodies from low or undetectable levels. In addition to completely neutralizing the homologous HIV-1 SF2 strain, these sera also neutralized the escape variant, HIV-1 SF13. However, no antibodies were boosted which could compete with human, neutralizing monoclonal antibodies recognising conformational epitopes. The peptides also boosted antibodies to a peptide whose sequence lies close to the V2 region neutralizing epitope but does not overlap with it. Importantly, the level of antibodies to an unrelated epitope associated with enhancement of HIV-1 SF13 continued to fall after the peptide boost. Successful protection against challenge with chimeric simian immunodeficiency virus expressing HIV-1 SF13 envelope glycoproteins (SHIV SF13) may be due to an increase in the ratio of neutralizing to enhancing antibodies by selectively boosting with peptides to critical neutralizing epitopes.

AIDS Vaccines↗

Major depression and all-cause mortality among white adults in the United States.

PURPOSE: Depression is the most common psychiatric illness affecting adults. Despite the importance of a potential link between major depression and mortality, research has been surprisingly sparse. METHODS: Information on 57,897 white adults aged 25 years and older who were included in the mental health supplement of the 1989 National Health Interview Survey was linked with the National Death Index to examine the relationship of major depression to mortality. Death status was obtained through December 1991. Sex-specific hazard rate ratios for mortality were calculated by Cox proportional hazards regression and Poisson regression to adjust for potential confounders (age, education, marital status, body mass index, and whether the target subject or a family member completed the survey about the subject). RESULTS: Major depression was reported for 223 (0.8%) of 27,345 men and 392 (1.3%) of 30,552 women. During the 2.5-year follow-up, death certificate data were obtained for 848 (3.1%) men and 651 (2.1%) women. The adjusted hazard rate ratios for all-cause mortality associated with major depression were 3.1 (95% confidence interval; 2.0-4.9) for men and 1.7 (95% confidence interval; 0.9-3.1) for women. CONCLUSIONS: These results suggest that major depression increases risk of all-cause mortality, particularly among men. Further research is needed to explain the mechanism.

Adult↗

Methodology and feasibility of a home-based examination in disabled older women: the Women's Health and Aging Study.

BACKGROUND: To ascertain disease and functional capacity in community-resident disabled older women in the Women's Health and Aging Study (WHAS), a prospective investigation of the causes and course of disability, a home-based standardized physical examination and performance test battery were developed. Thirty-nine tests were administered, 9 by a lay interviewer and 30 by a nurse. This scope and intensity of testing had not been performed previously in a home environment or on such a functionally limited population. Thus, substantial developmental work was required. This report describes the administrative procedures and field experience for each exam component, highlighting innovations pertinent to home administration. METHODS: Exclusion criteria, safety issues, administration time, completion rates, and reasons for incomplete data are reported. Administration time is based on 30 exams conducted over a 3-week period 90% of the way through baseline data collection. Completion status was determined using all 1,002 participants and is categorized as follows: complete; partial; not done, health; not done, other; and refused. RESULTS: Seventy-two percent of the screened, eligible respondents completed the 30-min interviewer-administered physical assessment and the 2-hr, 10-min nurse examination. Classifiable data were obtained for 90% of participants on 36 examination items. Lower completion rates were obtained on the other three tests primarily due to exclusions for health-related conditions; environmental constraints and participant refusal were minimal. CONCLUSION: Extensive, research-oriented physical evaluation can be successfully and safely performed in a home setting. In future studies, home-based examination may be preferable, as participation in the WHAS examination substantially exceeded rates for clinic-based exams in similar populations.

Aged↗

Anaemia of chronic disease in rheumatoid arthritis: in vivo effects of tumour necrosis factor alpha blockade.

Anaemia of chronic disease (ACD) is a common feature of active rheumatoid arthritis (RA). Inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6), are thought to contribute to the pathogenesis of ACD, possibly by inhibiting erythropoietin (EPO) production. In this study, we examined the in vivo effects of TNF-alpha blockade with a chimeric monoclonal antibody, cA2, on erythropoiesis in RA patients with ACD. Administration of cA2 led to a dose-dependent increase in haemoglobin levels compared to placebo and these changes were accompanied by a reduction in both EPO and IL-6 levels. The data support the notion that TNF-alpha is important in the causation of ACD, but suggest a mechanism independent of EPO suppression. Instead, TNF-alpha may act directly on bone marrow red cell precursors.

Anemia↗

Magnetic resonance imaging of children without sedation: preparation with simulation.

OBJECTIVE: It was hypothesized that a scanner simulator that replicates the magnetic resonance imaging (MRI) environment could be used to prepare pediatric subjects for successful completion of a diagnostic-quality MRI examination without pharmacological sedation. METHOD: Sixteen healthy children, 6 to 17 years of age, were matched for age and sex with 16 psychotropic medication-naive children with obsessive-compulsive disorder. Distress was measured throughout simulation and scanning procedures using heart rate and a self-report distress scale. Ten healthy children, 6 to 17 years of age, also underwent the same actual MRI scanning procedure but did not undergo the simulation scanning procedure. RESULTS: Significant decreases in heart rate and self-reported distress level were observed in all subjects during the simulator session that were maintained to the end of the actual scanner experience. All subjects successfully completed MRI examinations without chemical restraint. Subjects who were not trained in the simulator had higher heart rates and self-reported distress levels in the actual scanner than did simulation-trained subjects. CONCLUSIONS: Simulation without pharmacological sedation successfully prepared pediatric subjects in this pilot study for high-quality MRI studies. Subject preparation may be an alternative procedure to sedation for routine MRI examination in healthy and anxious children 6 years of age and older.

Adolescent↗

Effects of an immune-enhancing diet in critically injured patients.

OBJECTIVE: To determine the effects of an immune-enhancing experimental diet (XD = supplemental arginine, trace elements, and increased omega-3 fatty acids) versus standard diet (SD), on immune cell function and clinical outcome of critically injured patients. DESIGN: Prospective randomized clinical trial of patients admitted to the surgical intensive care unit after trauma (Injury Severity Score > 13). MATERIALS AND METHODS: Patients received early enteral nutrition with either XD or SD for a minimum of 5 days. MEASUREMENTS: Mortality, intensive care unit, ventilator, and hospital days, as well as incidence of adult respiratory distress syndrome (ARDS) and infectious complications were recorded. Nutritional parameters were also studied. Peripheral blood leukocytes were isolated from normal volunteers and from patients on days 1, 6, and 10 of feeding. MAIN RESULTS: Demographics and injury severity were similar in both groups. Both SD (n = 21) and XD (n = 22) groups revealed depressed monocyte function (tumor necrosis factor, prostaglandin E2, and procoagulant activity) on day 1 compared with a reference group (p < 0.05). However, monocytes from XD patients began to "normalize" their response (tumor necrosis factor, prostaglandin E2, and procoagulant activity) by day 6. Although ARDS occurred more frequently in the XD group (45 vs. 19%), the majority of ARDS in both groups occurred very early, with only three patients in the XD (13.6%) and one patient in the SD (4.7%) groups developing ARDS after study entry. XD patients remained on the ventilator longer (16.4 vs. 9.7 days) and in the hospital longer (32.9 vs. 22 days) compared with the SD group, but overall mortality was nearly identical (4.5 vs. 5%). CONCLUSION: The exact role and timing for diets with immune-enhancing effects has yet to be defined.

Adjuvants, Immunologic↗

Munchausen syndrome presenting as trauma.

Rarely, a patient with Munchausen syndrome will present with apparent trauma. A computerized literature search from 1966 until the present discovered only three such case reports, none of which appeared in a surgical journal. We report a fourth case. The characteristics of Munchausen syndrome are illustrated. The possibility that such a patient may have a true injury is also discussed.

Adult↗

Intraoperative microvascular Doppler sonography in aneurysm surgery.

OBJECTIVE: The goal was to evaluate the efficacy and reliability of intraoperative microvascular doppler sonography for the assessment of cerebral hemodynamics in aneurysm surgery. METHODS: For 35 patients who underwent surgery for the treatment of 42 intracranial aneurysms, microvascular doppler sonography with a 20-MHz probe (1-mm diameter) was used before and after clip application, to confirm the obliteration of aneurysms. Assessment of the patency of the parent vessels and all branching arteries was performed. The findings from doppler sonography were confirmed with either intraoperative angiography or immediate postoperative angiography. RESULTS: The 1-mm microprobe was able to insonate all vessels of the circle of Willis and their major branches; furthermore, perforating arteries were reliably insonated. For 11 patients (31%), doppler sonography exposed parent artery or branching artery stenosis or occlusion and guided the immediate adjustment of aneurysm clip placement. The findings from intraoperative microvascular doppler sonography correlated with findings from angiography in all cases. There were no complications of microvascular doppler probe use. CONCLUSION: Intraoperative microvascular doppler sonography is a safe, instantaneous, effective, reliable, and cost-effective method for documenting the patency of parent vessels, arterial branches, and major perforators and the complete occlusion of cerebral aneurysms. This technique can be reliably used, in many instances, instead of intraoperative angiography for the surgical treatment of aneurysms.

Aged↗

Determination of cerebral glucose transport and metabolic kinetics by dynamic MR spectroscopy.

A new in vivo nuclear magnetic resonance (NMR) spectroscopy method is introduced that dynamically measures cerebral utilization of magnetically labeled [1-13C]glucose from the change in total brain glucose signals on infusion. Kinetic equations are derived using a four-compartment model incorporating glucose transport and phosphorylation. Brain extract data show that the glucose 6-phosphate concentration is negligible relative to glucose, simplifying the kinetics to three compartments and allowing direct determination of the glucose-utilization half-life time [t1/2 = ln2/(k2 + k3)] from the time dependence of the NMR signal. Results on isofluorane (n = 5)- and halothane (n = 7)-anesthetized cats give a hyperglycemic t1/2 = 5.10 +/- 0.11 min-1 (SE). Using Michaelis-Menten kinetics and an assumed half-saturation constant Kt = 5 +/- 1 mM, we determined a maximal transport rate Tmax = 0.83 +/- 0.19 mumol.g-1.min-1, a cerebral metabolic rate of glucose CMRGlc = 0.22 +/- 0.03 mumol.g-1.min-1, and a normoglycemic cerebral influx rate CIRGlc = 0.37 +/- 0.05 mumol.g-1.min-1. Possible extension of this approach to positron emission tomography and proton NMR is discussed.

Animals↗