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Biomedical subjects

David Nelson

Publications and source records attributed to David Nelson.

At least 37 records · Page 2Linked to original sources

Randomized trial examining the effect of two prostate cancer screening educational interventions on patient knowledge, preferences, and behaviors.

OBJECTIVE: To assess the effect of video and pamphlet interventions on patient prostate cancer (CaP) screening knowledge, decision-making participation, preferences, and behaviors. DESIGN: Randomized, controlled trial. SETTING: Four midwestern Veterans Affairs medical facilities. PATIENTS/PARTICIPANTS: One thousand, one hundred fifty-two male veterans age 50 and older with primary care appointments at participating facilities were randomized and 893 completed follow-up. INTERVENTIONS: Patients were randomized to mailed pamphlet, mailed video, or usual care/control. MEASUREMENTS AND MAIN RESULTS: Outcomes assessed by phone survey 2 weeks postintervention included a 10-item knowledge index; correct responses to questions on CaP natural history, treatment efficacy, the prostate-specific antigen (PSA)'s predictive value, and expert disagreement about the PSA; whether screening was discussed with provider; screening preferences; and PSA testing rates. Mean knowledge index scores were higher for video (7.44; P = .001) and pamphlet (7.26; P = .03) subjects versus controls (6.90). Video and pamphlet subjects reported significantly higher percentages of correct responses relative to controls to questions on CaP natural history (63%, 63%, and 54%, respectively); treatment efficacy (19%, 20%, and 5%), and expert disagreement (28%, 19%, and 8%), but not PSA accuracy (28%, 22%, and 22%). Pamphlet subjects were more likely than controls to discuss screening with their provider (41% vs 32%; P = .03) but video subjects were not (35%; P = .33). Video and pamphlet subjects were less likely to intend to have a PSA, relative to controls (63%, 65%, and 74%, respectively). PSA testing rates did not differ significantly across groups. CONCLUSIONS: Mailed interventions enhance patient knowledge and self-reported participation in decision making, and alter screening preferences. The pamphlet and video interventions evaluated are comparable in effectiveness. The lower-cost pamphlet approach is an attractive option for clinics with limited resources.

Aged↗

The effects of rest interval length on ratings of perceived exertion during dynamic knee extension exercise.

The objective of this study was to examine the effects of rest interval length on perceived exertion and during 3 sets of 10 inertial knee extension repetitions. Thirty healthy men (n = 15) and women (n = 15) volunteers were randomly assigned to 1 of 3 groups (1-, 2-, or 3-minute rest interval length) following the establishment of each subject's 1 repetition maximum (1RM) for inertial knee extension exercise. Subjects in each group performed 3 sets of 10 repetitions at 70% of a theoretical 10RM (based on each subject's 1RM), with a 1-, 2-, or 3-minute rest interval between each set. Perceived exertion was recorded, via the Borg category-ratio scale, from each subject after each repetition of each set. The results demonstrated no significant rest interval length effect on perceived exertion across the 3 sets of 10 repetitions. The results revealed a significantly higher perceived exertion value following the first repetition in set 3 as compared to sets 2 and 1 in all groups. The increase in perceived exertion within each set, as described by the slope, was found to be significantly lowest in set 1, as compared to sets 2 and 3. The major findings of this study demonstrate that perceived exertion significantly increases in a similar manner across 3 sets of 10 knee extension repetitions, despite rest interval lengths of 1-3 minutes.

Adult↗

Cyclic variation and solar forcing of Holocene climate in the Alaskan subarctic.

High-resolution analyses of lake sediment from southwestern Alaska reveal cyclic variations in climate and ecosystems during the Holocene. These variations occurred with periodicities similar to those of solar activity and appear to be coherent with time series of the cosmogenic nuclides 14C and 10Be as well as North Atlantic drift ice. Our results imply that small variations in solar irradiance induced pronounced cyclic changes in northern high-latitude environments. They also provide evidence that centennial-scale shifts in the Holocene climate were similar between the subpolar regions of the North Atlantic and North Pacific, possibly because of Sun-ocean-climate linkages.

Journal Article↗

Baseline abdominal pressure and valsalva leak point pressures-correlation with clinical and urodynamic data.

AIMS: To characterize the factors contributing to changes in baseline abdominal pressure (P(abd)) and the correlation between DeltaVLPP, VLPP(tot), and other clinical and urodynamic variables. METHODS: Two hundred sixty-four female patients who had undergone an anti-incontinence procedure between February 1994 and October 1999 were retrospectively reviewed. The urodynamics performed for each patient included abdominal and vesical pressures measured in a standardized manner with the patient sitting upright and the pressure sensors maintained at the level of the symphysis pubis. VLPP was determined at bladder volumes of 200 mL during a gradually increasing Valsalva maneuver. RESULTS: Baseline P(abd) varied between 10 and 55 cm H(2)O (mean, 32.7 +/- 8.8) and were significantly correlated with patient weight (P<0.001) and with patient body mass index (P<0.001). Baseline P(abd) was not found to be correlated with patient age, Baden and Walker Classification of the grading of pelvic floor prolapse, degree of incontinence (determined by the number of pads used per day), or prior surgical procedures for stress incontinence. Higher baseline P(abd) were significantly correlated with the peak abdominal pressure reached during the Valsalva maneuver (P<0.0001) and with VLPP(tot) (P<0.0001) but not with DeltaVLPP. Higher VLPP(tot) significantly correlated with decreased age (P=0.004), less severe incontinence (P=0.004), higher peak Valsalva pressure (P<0.0001), and the ability to increase abdominal pressure for a longer period of time (time to peak P(abd) during Valsalva). VLPP(tot) and DeltaVLPP had similar statistical correlation with all the clinical variables examined and neither could predict the outcome of any anti-incontinence surgery. By using a VLPP of 60 cm H(2)O as a cutoff to differentiate severe ISD from GSUI, 211 (67.4%) of the patients would be categorized as having ISD according to their DeltaVLPP compared with only 106 (40.1%) by using the VLPP(tot). CONCLUSIONS: Baseline P(abd) varies considerably among patients, is correlated with patient weight and habitus. In addition, it varies with both the ability to be increased for longer periods of time and with VLPP(tot). Looking at VLPP(tot) and DeltaVLPP will result in a different categorization of the type of incontinence in at least 25% of patients and, thus, affect the physician's selection of an anti-incontinence procedure for an individual patient.

Abdomen↗

ARF after open-heart surgery: Influence of gender and race.

BACKGROUND: Both acute renal failure (ARF) and female sex are strongly associated with mortality after open-heart surgery. This study analyzes the effect of sex and race on the incidence of ARF after open-heart surgery and its influence on mortality. METHODS: A total of 24,660 patients underwent open-heart surgery at the Cleveland Clinic Foundation (Cleveland, OH) from 1993 to 2000. The primary outcome was ARF defined as ARF requiring dialysis, 50% or greater decline in glomerular filtration rate (GFR) not requiring dialysis, or 50% or greater decline in GFR relative to baseline or requirement of dialysis. The secondary outcome was all-cause hospital mortality. RESULTS: The overall frequency of ARF requiring dialysis after open-heart surgery was 1.82%. The frequency was greater in women (2.36%) than men (1.60%; P < 0.0001) and blacks (2.94%) than nonblacks (1.70%; P < 0.0001) by univariate analysis. By multivariate analysis, risk for ARF requiring dialysis in women was 1.61 (confidence interval [CI], 1.27 to 2.05; P < 0.0001), but race was not a risk factor. The overall postoperative mortality rate was 2.2%, and for patients with ARF requiring dialysis, it was 61.2% (women, 68.6% versus men, 56.5%; P = 0.01) with an odds ratio of 49.29, whereas in patients with ARF not requiring dialysis, it was 14.1% (women, 13.3% versus men 14.6%; P = 0.63) with an odds ratio of 7.18. CONCLUSION: Female sex is an independent risk factor for developing ARF after open-heart surgery. The influence of race on risk for ARF is less clear. Regardless of its definition, ARF is strikingly associated with a high risk for mortality.

Acute Kidney Injury↗

Evaluation of a worksheet to structure teaching and learning outpatient internal medicine.

The Worksheet for Ambulatory Medicine (WAM) is an educational tool designed to enhance teaching and learning outpatient internal medicine. It was developed to identify student learning needs, focus teaching, and structure educational and patient care activities in a clinic setting. The purpose of the study was to assess the feasibility and educational value of using the WAM with medical students and preceptors. Sixty-five third- and fourth-year medical students and 12 supervising faculty at two university-based general medicine outpatient clinics used the WAM during required internal medicine clerkships. Students and faculty completed written evaluations. Results are reported as percentages of respondents agreeing or disagreeing with a variety of statements, and mean rating scores for several questions designed to assess the feasibility and educational value of using the worksheet. Student response rate was 89%; 83% found the WAM easy to use; 65% found it too structured. Half said the worksheet helped diagnostic decision making and note writing, and two-thirds thought it promoted careful thinking about differential diagnosis and aided in identifying learning issues. Some 56% said using the WAM motivated outside reading. Most students found it helpful for identifying patient agendas and focusing case presentations (61% and 67, respectively). Only 36% said the WAM helped with time management. Most preceptors thought the WAM helped identify earning issues, focus case presentations and clarify student expectations. There was less agreement among preceptors that it allowed them to demonstrate clinical reasoning or provide students with more autonomy in decision making. Nearly half the preceptors did not find it helpful with time management. Both students and preceptors rated the overall value and usefulness of the WAM as good to very good, and a majority recommended that others use it. Using the Worksheet for Ambulatory Medicine was feasible and educationally valuable for many third- and fourth-year medical students and their preceptor in a required ambulatory internal medicine clerkship.

Ambulatory Care↗

Patch-testing practices of American Contact Dermatitis Society members: a cross-sectional survey.

BACKGROUND: Patch testing is an example of how medicine blends art and science, resulting in differences among practitioners in methods of history taking, application of patch tests, and interpretation of results. OBJECTIVE: To evaluate the "art" of patch testing (specifically, the prevalence of Thin-Layer Rapid Use Epicutaneous (T.R.U.E.) TEST use, photopatch testing, patch testing to dust mites, and immediate testing for latex allergy) as practiced by American Contact Dermatitis Society (ACDS) members and to compare the results of this survey with those of similar studies among United States dermatologists and allergists. METHODS: A cross-sectional survey of all 322 members of the ACDS. RESULTS: The response rate was 46%. The largest proportions of respondents were male, had practiced for 11 to 20 years, were located in the northeast United States, and were in private practice. Forty percent of respondents used T.R.U.E. TEST, and 65% performed photopatch testing. Seventy percent of respondents evaluated patients for latex allergy, and 15% patch-tested to dust mites. CONCLUSIONS: As expected, respondents reported significantly higher prevalences of patch testing, photopatch testing, and evaluation for latex allergy than did United States dermatologists generally. Respondents reported significantly lower prevalences of single patch-test readings and use of T.R.U.E. TEST than did either general United States dermatologists or general United States allergists.

Allergens↗

A macromolecular complex of beta 2 adrenergic receptor, CFTR, and ezrin/radixin/moesin-binding phosphoprotein 50 is regulated by PKA.

It has been demonstrated previously that both the cystic fibrosis transmembrane conductance regulator (CFTR) and beta(2) adrenergic receptor (beta(2)AR) can bind ezrinradixinmoesin-binding phosphoprotein 50 (EBP50, also referred to as NHERF) through their PDZ motifs. Here, we show that beta(2) is the major adrenergic receptor isoform expressed in airway epithelia and that it colocalizes with CFTR at the apical membrane. beta(2)AR stimulation increases CFTR activity, in airway epithelial cells, that is glybenclamide sensitive. Deletion of the PDZ motif from CFTR uncouples the channel from the receptor both physically and functionally. This uncoupling is specific to the beta(2)AR receptor and does not affect CFTR coupling to other receptors (e.g., adenosine receptor pathway). Biochemical studies demonstrate the existence of a macromolecular complex involving CFTR-EBP50-beta(2)AR through PDZ-based interactions. Assembly of the complex is regulated by PKA-dependent phosphorylation. Deleting the regulatory domain of CFTR abolishes PKA regulation of complex assembly. This report summarizes a macromolecular signaling complex involving CFTR, the implications of which may be relevant to CFTR-dysfunction diseases.

Animals↗

Knockout mouse model for Fxr2: a model for mental retardation.

Fragile X syndrome is a common form of mental retardation caused by the absence of the FMR1 protein, FMRP. Fmr1 knockout mice exhibit a phenotype with some similarities to humans, such as macro-orchidism and behavioral abnormalities. Two homologs of FMRP have been identified, FXR1P and FXR2P. These proteins show high sequence similarity, including all functional domains identified in FMRP, such as RNA binding domains. They have an overlap in tissue distribution to that of FMRP. Interactions between the three FXR proteins have also been described. FXR2P shows high expression in brain and testis, like FMRP. To study the function of FXR2P, we generated an Fxr2 knockout mouse model. No pathological differences between knockout and wild-type mice were found in brain or testis. Given the behavioral phenotype in fragile X patients and the phenotype previously reported for the Fmr1 knockout mouse, we performed a thorough evaluation of the Fxr2 knockout phenotype using a behavioral test battery. Fxr2 knockout mice were hyperactive (i.e. traveled a greater distance, spent more time moving and moved faster) in the open-field test, impaired on the rotarod test, had reduced levels of prepulse inhibition, displayed less contextual conditioned fear, impaired at locating the hidden platform in the Morris water task and were less sensitive to a heat stimulus. Interestingly, there are some behavioral phenotypes in Fxr2 knockout mice which are similar to those observed in Fmr1 knockout mice, but there are also some different behavioral abnormalities that are only observed in the Fxr2 mutant mice. The findings implicate a role for Fxr2 in central nervous system function.

Animals↗

Cost-effectiveness of gemfibrozil for coronary heart disease patients with low levels of high-density lipoprotein cholesterol: the Department of Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial.

BACKGROUND: Although numerous clinical trials and economic analyses have established the efficacy and cost-effectiveness of lowering cholesterol for the prevention of coronary heart disease, there are few data on the role of raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglyceride levels. The US Department of Veterans Affairs (VA) Cooperative Studies Program HDL-C Intervention Trial (VA-HIT) was a multicenter, randomized trial of gemfibrozil, an agent that raised HDL-C levels and lowered triglyceride levels, yet had no effect on low-density lipoprotein cholesterol (LDL-C) levels. The study showed that gemfibrozil therapy significantly reduced major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in patients with coronary heart disease, low HDL-C levels, and low LDL-C levels. OBJECTIVE: To report the results of a cost-effectiveness study based on the results of the VA-HIT. METHODS: The cost per year of life gained with gemfibrozil therapy was calculated. Hazard functions were estimated, and the resulting probabilities were used in a Markov model simulation to estimate the effect of gemfibrozil on life expectancy and costs over a simulated lifetime. Sensitivity analyses were used to account for uncertainty. RESULTS: Using the prices of gemfibrozil that were negotiated by the VA, gemfibrozil was cost saving. Using drug prices found outside the VA, a quality-adjusted life-year saved by gemfibrozil therapy cost between $6300 and $17 100. CONCLUSIONS: Gemfibrozil reduces major cardiovascular events in male coronary heart disease patients with low levels of HDL-C and low levels of LDL-C and would result in cost saving at annual drug costs of $100 or less in 1998 dollars. Even at the higher drug prices represented by the average wholesale price in the United States, the cost of a life-year saved is well below the threshold that would be deemed cost-effective. To our knowledge, this is the first economic analysis based on clinical trial data to assess the cost-effectiveness of raising HDL-C levels and lowering triglyceride levels in a setting in which LDL-C levels were not lowered.

Aged↗

Prevalence and methodology of evaluation for latex allergy among allergists in the United States: results of a cross-sectional survey.

BACKGROUND: Natural rubber latex allergy is a potentially life-threatening, Type I, immediate allergic reaction. Despite great strides in identification of high-risk groups, methods for diagnosis remain limited in the United States. OBJECTIVE: The objective of this study was to estimate the prevalence of evaluation for latex allergy and methodologies used by allergists in the United States. METHODS: A cross-sectional survey of all US Fellows of the American Academy of Allergy, Asthma and Immunology was conducted. RESULTS: Of 1,239 questionnaires mailed, 519 (42%) were returned. Ninety-five percent of responding allergists reported evaluating patients for latex allergy. RAST and skin prick testing were the most commonly used tests. Sixty-two percent of respondents reported performing prick testing for latex allergy, with those in academic practices significantly more likely to do so. Whereas respondents practicing in the Northern United States were significantly more likely to evaluate for latex allergy than those in the Southern United States, no associations were found between practice location and prick testing for latex allergy. There was no association between practice type and evaluation for latex allergy. Only 6% of allergists reported ever witnessing a patient with anaphylaxis during latex allergy testing. CONCLUSIONS: Almost all responding allergists evaluated patients for latex allergy, with approximately two thirds utilizing prick testing.

Confidence Intervals↗

Prevalence and methodology of patch testing by allergists in the United States: results of a cross-sectional survey.

BACKGROUND: Patch testing is considered the gold standard for the diagnosis of allergic contact dermatitis. Whereas previous surveys have evaluated the patch testing practices of dermatologists, little information is available on the use of patch testing by allergists. OBJECTIVE: The objective of this study was to examine the prevalence of patch testing and associated methodologies used by allergists in the United States. METHODS: A cross-sectional survey of all US Fellows of the American Academy of Allergy, Asthma and Immunology was conducted. RESULTS: Of 1,239 questionnaires mailed, 519 (42%) were returned. Fifty-three percent of allergists reported performing patch testing. The majority (89%) patch tested 5 or fewer patients per month. Allergists who evaluated for latex allergy were twice as likely to patch test than those who did not. The most common patch test reading schedule was at both 48 and 72 hours (48%). Thirty-three percent of respondents performed only a single patch test reading. The majority (72%) used TRUE Test. Only 4% patch tested for Type IV allergy to dust mites. CONCLUSION: Many more allergists patch test than initially hypothesized. The patch testing methodologies used by allergists are similar to those of dermatologists.

Allergens↗

Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema.

OBJECTIVE: To investigate the relation between outcomes of children with diabetic ketoacidosis (DKA)-related cerebral edema and baseline clinical features and therapeutic interventions for treatment of cerebral edema. STUDY DESIGN: All children </=18 years old with DKA and cerebral edema (n = 61) were retrospectively identified from 10 pediatric centers between 1982 and 1997. Demographic, biochemical, and therapeutic data were collected. Ordinal logistic regression analysis was used to identify factors associated with the clinical outcome (death or persistent vegetative state; mild to moderate neurological disability; or normal) after adjusting for known risk factors for the development of cerebral edema as well as the degree of neurologic depression at the time of diagnosis of cerebral edema. RESULTS: Seventeen (28%) children died or survived in a vegetative state; 8 (13%) survived with mild to moderate neurologic disabilities; and 36 (59%) survived without sequelae. Factors associated with poor outcomes included greater neurologic depression at the time of diagnosis of cerebral edema, a high initial serum urea nitrogen concentration, and intubation with hyperventilation to a PCO (2) <22 mm Hg. CONCLUSIONS: After adjusting for potential confounding variables and the degree of neurologic compromise at the initiation of therapy, intubation with hyperventilation is associated with adverse outcomes of DKA-related cerebral edema. Greater neurologic depression at the time of diagnosis of cerebral edema and a higher initial serum urea nitrogen concentration are also associated with poor outcome.

Adolescent↗

Relationship between oxidative stress and embryotoxicity of hydrosalpingeal fluid.

BACKGROUND: Oxidative stress mechanisms are involved in the pathophysiology of many reproductive disorders. The objective of this study was to characterize oxidative stress parameters in hydrosalpingeal fluid (HSF) and examine their possible role in early embryo development. METHODS AND RESULTS: HSF was aspirated at laparoscopic salpingectomy in 11 infertile women. Reactive oxygen species (ROS), total (non-enzymatic) antioxidant capacity (TAC) and lipid peroxidation (LPO) were assayed. Two-cell mouse embryos were incubated with 25, 50 or 75% HSF and the blastocyst development rate was observed. ROS was detected in five of 11 (45%) HSF samples with a mean of 4.2 x 10(4) c.p.m. LPO was detected in all samples at a mean (+/- SD) value of 5575.4 +/- 6091.9 micromol/l malonaldehyde. The mean blastocyst development rate at 25, 5+/- 0 and 75% HSF and in the control group was 88.9 +/- 9.4, 65.7 +/- 19.1, 45.7 +/- 5.7 and 96.7% respectively (P < 0.0001). The blastocyst development rate was positively correlated to ROS concentrations (P < 0.02) but was not significantly related to LPO. CONCLUSIONS: The blastocyst development rate decreased with increasing concentrations of HSF. For the first time, the presence of ROS, LPO and TAC activity in human HSF was characterized. A possible role of oxidative stress in the embryotoxicity of HSF is suggested.

Animals↗

Environmental regulation and differential production of members of the Bdr protein family of Borrelia burgdorferi.

Borrelia burgdorferi B31MI carries 18 plasmid-carried genes that form the bdr gene family. The bdr genes of B. burgdorferi encode proteins that form three distinct subfamilies, the BdrD, BdrE, and BdrF subfamilies. bdr orthologs have been demonstrated to be carried by all Borrelia species analyzed, and their widespread distribution suggests that they play an important genus-wide functional role. The biological rationale for maintaining 18 bdr alleles has not been defined. It is our hypothesis that specific paralogs function in different environments and are differentially expressed in response to environmental conditions. As a first step in testing this hypothesis, the production patterns of the Bdr proteins in spirochetes grown under a variety of conditions were assessed through immunoblot analyses. The influence of temperature, serum deprivation, tick feeding, and the mammalian environment on Bdr production was evaluated. These analyses revealed that the synthesis of some Bdr paralogs is environmentally regulated. The production of BdrF(2,) BdrF(1), BdrE(4), and BdrE(5) were upregulated in host-adapted bacteria, while the production levels of other Bdr paralogs were influenced by temperature and serum starvation. These observations suggest that different Bdr paralogs function in different biological environments and provide insight into the biological basis for maintaining multiple members of this gene family.

Amino Acid Sequence↗

Pulmonary edema caused by inhaled nitric oxide therapy in two patients with pulmonary hypertension associated with the CREST syndrome.

Pulmonary arterial hypertension (PAH) is commonly associated with the CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome. Inhaled nitric oxide (iNO) is often used to assess acute vasoresponsiveness in patients with PAH, and reports of adverse reactions have been infrequent. We describe two of nine patients with PAH and CREST syndrome who had pulmonary edema develop during acute iNO testing. This complication was not encountered in the 46 patients with other forms of PAH tested with iNO. We suggest that iNO should be used with caution, if at all, to test acute vasoreactivity in patients with CREST syndrome.

Administration, Inhalation↗