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Biomedical subjects

David L Brown

Publications and source records attributed to David L Brown.

At least 37 records · Page 2Linked to original sources
PubMed2005

Are individual differences in fatigue vulnerability related to baseline differences in cortical activation?

Recent evidence suggests that underlying patterns of cortical activation may partially account for individual differences in susceptibility to the effects of sleep deprivation. Here, functional magnetic resonance imaging (fMRI) was used to examine the activation of military pilots whose sleep-deprivation vulnerability previously was quantified. A Sternberg Working Memory Task (SWMT; S. Sternberg, 1966) was completed alternately with a control task during a 13-min blood oxygen level-dependent fMRI scan. Examination of the activated voxels in response to SWMT indicated that, as a group, the pilots were more similar to fatigue-resistant nonpilots than to fatigue-vulnerable nonpilots. Within the pilots, cortical activation was significantly related to fatigue vulnerability on simulator-flight performance. These preliminary data suggest that baseline fMRI scan activation during a working memory task may correlate with fatigue susceptibility.

Adolescent↗
PubMed2004

Effect of chronic obstructive pulmonary disease on survival of patients with coronary heart disease having percutaneous coronary intervention.

There are limited data regarding the effect of chronic obstructive pulmonary disease (COPD) on the survival of patients with coronary artery disease. Prospectively developed and collected data elements on 4,284 consecutive patients who underwent percutaneous coronary intervention in 3 hospitals in 1998 and 1999 were pooled and analyzed. In-hospital major adverse cardiac outcomes were not different between groups. At 3-year follow-up, mortality for patients with COPD was 21% versus 9% for patients without COPD (log-rank p < 0.001). COPD was independently associated with a 2-fold increase in the hazard of long-term mortality (hazard ratio 2.146, 95% confidence interval 1.525 to 3.021, p < 0.001).

Aged↗
PubMed2004

Six-month outcomes after single- and multi-lesion percutaneous coronary intervention: results from the ROSETTA registry.

BACKGROUND: The American College of Cardiology/American Heart Association exercise testing guidelines suggest that routine functional testing may benefit patients at high risk of restenosis, such as those undergoing multi-lesion percutaneous coronary intervention (PCI). OBJECTIVES: To compare the six-month post-PCI clinical and procedural outcomes in patients following single- and multi-lesion PCI, and to examine the use of routine functional testing (ie, in all patients) versus selective functional testing (ie, only in those with recurrent symptoms) following multi-lesion PCI. METHODS: Six-month outcomes among 562 patients after single-lesion PCI and 229 patients after multi-lesion PCI were examined. All patients were enrolled in the Routine versus Selective Exercise Treadmill Testing after Angioplasty (ROSETTA) registry, a prospective, multicentre registry examining the use of functional testing after successful PCI. RESULTS: For single- versus multi-lesion PCI patients, respectively, rates of death (1.8% versus 2.2%, P=0.7) and myocardial infarction (0.7% versus 2.6%, P=0.03) were low in both groups. Rates of unstable angina (12.0% versus 11.7%, P=0.9) and the composite clinical end point of death, myocardial infarction or unstable angina (13.5% versus 13.9%, P=0.9) were similar. Multi-lesion PCI patients had a higher number of repeat PCI procedures (6.6% versus 13.4%, P=0.02) but there was no difference in the rates of coronary artery bypass graft surgery (3.0% versus 2.6%, P=0.7). A routine functional testing strategy was used in 28.0% of single-lesion and 31.6% of multi-lesion patients. In a multivariate analysis of the multi-lesion patients, routine functional testing was not associated with a significant reduction in the composite clinical event rate (odds ratio 0.5, 95% CI 0.2 to 1.7, P=0.27). CONCLUSIONS: During the six-month period following successful PCI, clinical event rates were similar among patients undergoing single- or multi-lesion PCI. Routine functional testing was not associated with a statistically significant benefit in patients after multi-lesion PCI. However, additional study is required to better define the role of routine functional testing in this subgroup of patients.

Angina, Unstable↗
PubMed2004

Cytoskeletal interactions of synapsin I in non-neuronal cells.

Synapsin I is a neuronal phosphoprotein involved in the localization and stabilization of synaptic vesicles. Recently, synapsin I has been detected in several non-neuronal cell lines, but its function in these cells is unclear. To determine the localization of synapsin I in non-neuronal cells, it was transiently expressed in HeLa and NIH/3T3 cells as an enhanced green fluorescent protein fusion protein. Synapsin I-enhanced green fluorescent protein colocalized with F-actin in both cell lines, particularly with microspikes and membrane ruffles. It did not colocalize with microtubules or vimentin and it did not cause major alterations in cytoskeletal organization. Synapsin Ia-enhanced green fluorescent protein colocalized with microtubule bundles in taxol-treated HeLa cells and with F-actin spots at the plasma membrane in cells treated with cytochalasin B. It did not noticeably affect F-actin reassembly following drug removal. Synapsin Ia-enhanced green fluorescent protein remained colocalized with F-actin in cells treated with nocodazole, and it did not affect reassembly of microtubules following drug removal. These results demonstrate that synapsin I interacts with F-actin in non-neuronal cells and suggest that synapsin I may have a role in regions where actin is highly dynamic.

Actins↗
PubMed2004

Clinical and biochemical results of the metalloproteinase inhibition with subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS) pilot trial.

BACKGROUND: Vulnerable plaque demonstrates intense inflammation in which macrophages secrete matrix metalloproteinases (MMPs) that degrade the fibrous cap, ultimately leading to rupture, in situ thrombosis, and an associated clinical event. Thus, inhibition of MMP activity or more general suppression of vascular inflammation are attractive targets for interventions intended to reduce plaque rupture. We hypothesized that subantimicrobial doses of doxycycline (SDD) (20 mg twice daily) would benefit patients with coronary artery disease by reducing inflammation and MMP activity and thus possibly prevent coronary plaque rupture events. METHODS AND RESULTS: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study of 6 months of SDD or placebo treatment to reduce inflammation and prevent plaque rupture events. A total of 50 patients were enrolled, of whom 24 were randomized to placebo and 26 to SDD. At 6 months, there was no difference in the composite endpoint of sudden death, fatal myocardial infarction (MI), non-fatal MI, or troponin-positive unstable angina in SDD compared with placebo-treated patients (8.4% versus 0%, P=0.491). Biochemical markers of inflammation were assessed in plasma at study entry and after 6 months of therapy in 30 patients. In SDD-treated patients, high-sensitivity C-reactive protein (CRP) was reduced by 46% from 4.8+/-0.6 microg/mL to 2.6+/-0.4 microg/mL (P=0.007), whereas CRP was not significantly reduced in placebo patients. Interleukin (IL)-6 decreased from 22.1+/-3.7 pg/mL at baseline to 14.7+/-1.8 pg/mL at 6 months in SDD-treated patients (P=0.025) but did not decrease significantly in placebo-treated patients. On zymography, pro-MMP-9 activity was reduced 50% by SDD therapy (P=0.011), whereas it was unchanged by placebo treatment. CONCLUSIONS: SDD appears to exert potentially beneficial effects on inflammation that could promote plaque stability. These findings should be investigated in a larger study.

Aged↗
PubMed2004

Clinical impact of functional testing strategy among stented and non-stented patients: insights from the ROSETTA Registry.

UNLABELLED: The clinical utility of routine functional testing following percutaneous coronary intervention (PCI) among patients with and without coronary stenting is unclear. We established an international registry to evaluate the functional testing strategies following successful PCI. Among patients treated with stents, adverse cardiovascular outcomes were similar between those who underwent routine or clinically-driven functional testing. Conversely, among those who were not treated with stents, the rate of death, myocardial infarction or unstable angina was lower than those who underwent routine functional testing (14.8% vs. 6.6%; P=0.033). Our study suggests that routine functional testing may be beneficial to patients not treated with stents. BACKGROUND: The role of routine functional testing following successful PCI is unclear. By improving patient outcomes with coronary stenting, the value of such a strategy may diminish. HYPOTHESIS: To determine the clinical utility of routine functional testing following PCI between patients with and without stenting. METHODS: The routine versus selective exercise testing after angioplasty (ROSETTA) Registry was established to evaluate the utilization of functional testing following PCI. Use of functional testing, either routine or selective (clinically-driven), was left to the discretion of the attending physician. RESULTS: Of 791 patients enrolled, 462 (58%) underwent coronary stenting. Stented patients were less likely to suffer from concomitant diseases but had more complex angiographic morphological characteristics. Between the groups of patients with and without stents, there was no difference in the proportion of patients undergoing routine functional testing (24% vs. 36%) or subsequent cardiac procedures (18.4% vs. 16.0%). Among patients with stents, outcomes at 6 months were similar between the groups undergoing routine and selective functional testing, including death (0% vs. 1.7%), myocardial infarction (0.9% vs. 2.0%), unstable angina (9.9% vs. 13.7%), repeat angiography (16.2% vs. 16.9%) and revascularization procedures (11.7% vs. 10.8%). However, among non-stented patients, selective functional testing was associated with a higher occurrence of death, myocardial infarction or unstable angina (14.8% vs. 6.6%; P=0.033). There was also no difference in the rates of repeat coronary angiography or revascularization procedures between these two strategies. CONCLUSION: Although routine functional testing has little impact on outcomes among patients treated with coronary stents, non-stented patients may derive particular benefit.

Angioplasty, Balloon, Coronary↗
PubMed2004

Race, ethnicity, and sociocultural characteristics predict noncompliance with lipid-lowering medications.

BACKGROUND: Sociocultural factors that predict noncompliance with lipid-lowering medications are not well understood. METHODS: Interviews and medical record review were conducted for 510 patients treated with lipid-lowering medications. Compliance with lipid-lowering medications was measured by patients' self-assessment of medication-taking practices. RESULTS: Adjusted for age and sex, there was a higher frequency of noncompliance among Black and Hispanic subjects. Adjusted for age, sex, and race/ethnicity, noncompliance was associated with medication side effects, feelings of sadness or depression, fair or poor health status, primary use of a language other than English, single or divorced status, fewer and less frequent contact with friends, children in the household, and lower education. Independent predictors of noncompliance in multivariate models were side effects (OR = 3.9, P < 0.01), sadness or depression (OR = 1.9, P = 0.05), Black (OR = 3.7, P < 0.01, vs. White), Hispanic (OR = 6.3, P < 0.01, vs. White), single or divorced (OR = 2.1, P < 0.01), children in the household (OR = 1.5 per child, P < 0.01), and lack of health insurance (OR = 2.4, P = 0.05). CONCLUSIONS: Unmarried status, feelings of sadness or depression, lack of insurance, and children in the household were independently associated with poorer compliance with lipid-lowering medications in this urban population. Nonetheless, higher noncompliance among minority patients persisted independently of these and other specific social, cultural, and economic factors.

Adult↗
PubMed2004

Effect of diabetes on long-term mortality following contemporary percutaneous coronary intervention: analysis of 4,284 cases.

OBJECTIVE: Diabetic patients are known to have reduced long-term survival following percutaneous transluminal coronary angioplasty compared with nondiabetic patients. However, it is unknown whether this survival disadvantage has persisted in the era of contemporary percutaneous coronary intervention (PCI) techniques, which include the widespread use of stents and the availability of platelet glycoprotein (GP) IIb/IIIa inhibitors. RESEARCH DESIGN AND METHODS: Three hospitals in New York City contributed prospectively defined data on 4,284 patients undergoing PCI. The primary end point was all-cause mortality following hospital discharge for PCI. RESULTS: Hypertension, renal insufficiency, and renal failure requiring dialysis were all more common in diabetic patients, whereas active smoking was less frequent. Congestive heart failure on admission was more common in diabetic than nondiabetic patients (7.7 vs. 4.0%, P < 0.001). Stents were placed in 78% of nondiabetic patients and 75% of diabetic patients (P = 0.045). Platelet GP IIb/IIIa antagonists were administered to 23% of nondiabetic and 24% of diabetic patients (P = NS). At a mean follow-up of 3 years, mortality was 8% among nondiabetic patients and 13% for diabetic patients (P < 0.001). After adjustment for differences in baseline characteristics between nondiabetic and diabetic patients, diabetes remained a significant independent hazard for late mortality (hazard ratio 1.462, 95% CI 1.169-1.828; P = 0.001). CONCLUSIONS: Following contemporary PCI, diabetic patients continue to have worse survival than nondiabetic patients.

Aged↗
PubMed2004

Utility of routine functional testing after percutaneous transluminal coronary angioplasty: results from the ROSETTA registry.

BACKGROUND: There is little consensus regarding the use of functional testing after percutaneous transluminal coronary angioplasty (PTCA). Some physicians employ a routine functional testing strategy, and others employ a symptom-driven strategy. OBJECTIVE: To examine the effects of routine post-PTCA functional testing on the use of follow-up cardiac procedures and clinical events. METHODS: The Routine versus Selective Exercise Treadmill Testing after Angioplasty (ROSETTA) Registry is a prospective multicenter observational study examining the use of functional testing after PTCA. A total of 788 patients (pts) were enrolled in the ROSETTA Registry at 13 clinical centers in 5 countries. The frequencies of functional testing, cardiac procedures and clinical events were examined during the first 6 months following a successful PTCA. RESULTS: Patients were predominantly elderly men (mean age, 61+/-11 years; 76% male) who underwent single-vessel PTCA (85%) with stent implantation (58%). During the 6-month follow-up, a total of 237 pts were observed to undergo a routine functional testing strategy (100% having functional testing for routine follow-up), while 551 pts underwent a selective (or clinically-driven) strategy (73% having no functional testing and 27% having functional testing for a clinical indication). Patients in the routine testing group underwent a total of 344 functional tests compared with 165 tests performed in the selective testing group (mean, 1.45 tests/patient versus 0.3 tests/patient; p<0.0001). There was little difference in the rates of follow-up cardiac procedures among the pts undergoing the routine and selective testing strategies [cardiac catheterization, 13.9% versus 17.5% (p=NS); percutaneous coronary intervention (PCI), 8.4% versus 8.7% (p=NS); coronary artery bypass graft surgery, 2.1% versus 3.3% (p=NS)]. However, clinical events were less common among pts who underwent routine functional testing, e.g., unstable angina (6.1% versus 14.4%; p=0.001), myocardial infarction (0.4% versus 1.6%; p=NS), death (0% versus 2.2%; p=0.02) and composite clinical events (6.3% versus 16.3%; p<0.0001). After controlling for baseline clinical and procedural differences, routine functional testing had a persistent independent association with a reduction in the composite clinical event rate (odds ratio, 0.45; 95% confidence interval, 0.24-0.81; p=0.008). CONCLUSION: Routine functional testing after PTCA is associated with a reduction in the frequency of follow-up clinical events. This association may be attributable to the early identification and treatment of pts at risk for follow-up events, or it may be due to clinical differences between pts who are referred for routine and selective functional testing.

Angioplasty, Balloon, Coronary↗
PubMed2004

Modafinil's effects on simulator performance and mood in pilots during 37 h without sleep.

INTRODUCTION: Modafinil is a relatively new alertness-enhancing compound of interest to the military aviation community. Although modafinil has been well-tested in clinical settings, additional studies are required to establish its safety and efficacy for use in pilots. OBJECTIVE: The purpose of this study was to determine whether modafinil (100 mg after 17, 22, and 27 h without sleep) would attenuate the effects of fatigue on fighter-pilot mood and performance during 37 h of continuous wakefulness. METHODS: A quasi-experimental, single-blind, counterbalanced design tested the effects of modafinil in 10 Air Force F-117 pilots. RESULTS: Modafinil attenuated flight performance decrements on six of eight simulator maneuvers. Overall, modafinil maintained flight accuracy within approximately 15-30% of baseline levels, whereas performance under the no-treatment/placebo condition declined by as much as 60-100%. Modafinil decreased self-ratings of depression and anger, while improving ratings of vigor, alertness, and confidence. Benefits were most noticeable after 24 to 32 h of continuous wakefulness. One potential drawback of modafinil was that, at least at the 100-mg dose level, the drug's effects were not subjectively salient. Since this may lead personnel to escalate the dose without flight surgeon approval, personnel should be cautioned regarding this particular drug characteristic. CONCLUSION: Although modafinil did not sustain performance at predeprivation levels, the present study suggests that modafinil should be considered for the military's armament of short-term fatigue countermeasures. Future research will evaluate whether 200-mg doses are more beneficial than the 100-mg doses used here.

Adult↗
PubMed2003

Management of patients undergoing percutaneous coronary revascularization.

While performance of percutaneous coronary intervention (PCI) remains the domain of specialized cardiologists, patients undergoing PCI are cared for by noninvasive cardiologists, internists, and primary care physicians. Therefore, patient care is optimized when the entire patient care team understands procedural risks and complications as well as optimum patient management before, during, and after PCI. Before PCI, patients with contrast dye allergies should be identified and pretreated with steroids and an H1-blocker. Hydration should be initiated and maintained before and after the procedure to minimize the risks for contrast nephropathy. Periprocedure, patients should be monitored clinically for evidence of ischemia. In patients with significant groin, flank, abdominal, or back pain, as well as those with decrease in hematocrit or unexplained hypotension, the diagnosis of groin or retroperitoneal hematoma should be considered and promptly evaluated. Groin tenderness, pulsatile mass, or bruit should prompt evaluation for possible femoral pseudoaneurysm or arteriovenous fistulae. After the procedure, all patients treated with coronary stents should receive aspirin plus clopidogrel. Patients who develop typical anginal symptoms between the 1st and 6th to 8th months after PCI are likely to have restenosis and can be evaluated by an imaging study or repeated catheterization.

Angioplasty, Balloon, Coronary↗
PubMed2003

Diagnosis and management of syphilis.

Syphilis is a sexually transmitted disease with varied and often subtle clinical manifestations. Primary syphilis typically presents as a solitary, painless chancre, whereas secondary syphilis can have a wide variety of symptoms, especially fever, lymphadenopathy, rash, and genital or perineal condyloma latum. In latent syphilis, all clinical manifestations subside, and infection is apparent only on serologic testing. Late or tertiary syphilis can manifest years after infection as gummatous disease, cardiovascular disease, or central nervous system involvement. Neurosyphilis can develop in any stage of syphilis. The diagnosis of syphilis may involve dark-field microscopy of skin lesions but most often requires screening with a nontreponemal test and confirmation with a treponemal-specific test. Parenterally administered penicillin G is considered first-line therapy for all stages of syphilis. Alternative regimens for nonpregnant patients with no evidence of central nervous system involvement include doxycycline, tetracycline, ceftriaxone, and azithromycin. In pregnant women and patients with neurosyphilis, penicillin remains the only effective treatment option; if these patients are allergic to penicillin, desensitization is required before treatment is initiated. Once the diagnosis of syphilis is confirmed, quantitative nontreponemal test titers should be obtained. These titers should decline fourfold within six months after treatment of primary or secondary syphilis and within 12 to 24 months after treatment of latent or late syphilis. Serial cerebrospinal fluid examinations are necessary to ensure adequate treatment of neurosyphilis.

Diagnosis, Differential↗
PubMed2003

A propensity analysis of the impact of platelet glycoprotein IIb/IIIa inhibitor therapy on in-hospital outcomes after percutaneous coronary intervention.

It is unknown whether the benefits of parenteral platelet glycoprotein (GP) IIb/IIIa inhibitors as an adjunct to percutaneous coronary intervention (PCI) demonstrated in randomized clinical trials extend to patients treated outside the setting of clinical trials. A contemporary registry of 10,847 consecutive PCI procedures was analyzed to determine the effect of GP IIb/IIIa inhibitor treatment on in-hospital major adverse coronary events ([MACEs] composite of death, urgent coronary artery bypass surgery, periprocedural myocardial infarction, abrupt closure, and stent thrombosis). In this registry, GP IIb/IIIa inhibitors were administered to 20.1% of patients. These patients were younger, more often men, and less often hypertensive than untreated patients. GP IIb/IIIa inhibitor-treated patients were more likely to present with acute myocardial infarction or unstable angina. Stents were placed in 79% of patients treated with GP IIb/IIIa inhibitors. MACEs occurred in 7.8% of GP IIb/IIIa inhibitor-treated patients compared with 3.8% of untreated patients (p <0.001). After multivariable adjustment for the propensity of GP IIb/IIIa inhibitor treatment as well as other possible confounders and interactions known to influence MACEs, GP IIb/IIIa inhibitor treatment was associated with a 57% increase in the risk of a MACE (odds ratio 1.57, 95% confidence interval 1.22 to 2.03; p = 0.0004). In a data set consisting of patients with a high degree of acuity predominantly treated with stent placement, GP IIb/IIIa inhibitor treatment is associated with an increase in thrombotic complications of PCI.

Abciximab↗
PubMed2003

Vitamin B12 deficiency.

Vitamin B12 (cobalamin) deficiency is a common cause of macrocytic anemia and has been implicated in a spectrum of neuropsychiatric disorders. The role of B12 deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Diagnosis of vitamin B12 deficiency is typically based on measurement of serum vitamin B12 levels; however, about 50 percent of patients with subclinical disease have normal B12 levels. A more sensitive method of screening for vitamin B12 deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B12 deficiency. Use of the Schilling test for detection of pernicious anemia has been supplanted for the most part by serologic testing for parietal cell and intrinsic factor antibodies. Contrary to prevailing medical practice, studies show that supplementation with oral vitamin B12 is a safe and effective treatment for the B12 deficiency state. Even when intrinsic factor is not present to aid in the absorption of vitamin B12 (pernicious anemia) or in other diseases that affect the usual absorption sites in the terminal ileum, oral therapy remains effective.

Humans↗
PubMed2003

In-hospital outcomes of contemporary percutaneous coronary interventions in the very elderly.

Coronary heart disease is the leading cause of death among the elderly (> 65 years) and the very elderly (> 85 years). Little information is available regarding the outcome of very elderly patients referred for PCI in the current era of improved techniques, devices, and pharmacotherapy. The objective of the current study was to evaluate the clinical characteristics and outcomes of very elderly patients > or = 85 years of age in a large, contemporary, multi-institutional PCI database. Five hospitals in the New York City metropolitan area contributed these prospectively defined data elements on consecutive patients undergoing PCI from 1 January 1998 to 1 October 1999. Of 10,847 patients, 5,341 (49%) were younger than 65 years, 3,342 (31%) were 65-74 years, 1,885 (17%) were 75-84 years, and 279 (2.6%) were at least 85 years of age. Following PCI, the very elderly developed stroke (P < 0.001) and renal failure requiring dialysis (P = 0.002) more commonly than younger patients following PCI. The very elderly had a significantly increased in-hospital mortality rate at 2.5% (P < 0.001). However, on multivariate analysis, age > or = 85 years was not an independent predictor of in-hospital mortality (OR = 1.22; 95% CI = 0.37-4.07). The very elderly should not be refused PCI on the basis of advanced age alone.

Age Factors↗