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Biomedical subjects

Daniel J Brotman

Publications and source records attributed to Daniel J Brotman.

At least 19 recordsLinked to original sources
PubMed2005

Effects of short-term glucocorticoids on hemostatic factors in healthy volunteers.

OBJECTIVE: Increased circulating levels of hemostatic factors have been associated with arterial and venous thrombosis. Although in vitro evidence suggests that glucocorticoids may activate hemostasis and inhibit thrombolysis, no controlled in vivo studies have examined the effects of glucocorticoids on hemostatic factors. We hypothesized that a 5-day treatment course of dexamethasone would increase circulating levels of hemostatic and anti-fibrinolytic factors. METHODS: We randomized 24 healthy men ages 19-39 to receive either dexamethasone 3 mg twice daily versus placebo for 5 days. Parameters examined before and after the intervention included: clotting factors VII, VIII, and XI, von Willebrand factor (vWF), D-dimer, PAI-1, soluble CD40-ligand (sCD40-ligand), and fibrinogen. RESULTS: Dexamethasone tended to modestly increase clotting factors levels and fibrinogen without significantly affecting PAI-1, D-dimer or sCD40-ligand. Factor VII increased by a mean of 13% (p = 0.04 versus placebo), factor VIII by 27% (p = 0.0008), factor XI by 6% (p = 0.01), and fibrinogen by 13% (p = 0.05). CONCLUSIONS: Glucocorticoids may increase the activity of clotting factors in vivo. This may contribute to the reported increased risk of thrombosis in patients with sustained exposure to glucocorticoids.

Adult↗
PubMed2005

Effects of short-term glucocorticoids on cardiovascular biomarkers.

CONTEXT: Glucocorticoids are known to acutely increase blood pressure, suppress inflammation, and precipitate insulin resistance. However, the short-term effects of glucocorticoids on other cardiovascular risk factors remain incompletely characterized. OBJECTIVE: Our objective was to determine the effects of a short course of dexamethasone on multiple cardiovascular biomarkers and to determine whether suppression of morning cortisol in response to low-dose dexamethasone is correlated with cardiovascular risk markers in healthy volunteers. DESIGN: We conducted a randomized, double-blind, placebo-controlled study. SETTING: The study took place in a tertiary care hospital. STUDY SUBJECTS: Twenty-five healthy male volunteers, ages 19-39 yr, participated in the study. INTERVENTION: Subjects received either 3 mg dexamethasone twice daily or placebo for 5 d. Subjects also underwent a low-dose (0.5 mg) overnight dexamethasone suppression test. MEASURES: Parameters examined before and after the 5-d intervention included heart rate, blood pressure, weight, fasting lipid variables, homocysteine, renin, aldosterone, insulin resistance (homeostasis model assessment), high-sensitivity C-reactive protein, B-type natriuretic peptide, flow-mediated and nitroglycerin-mediated brachial artery dilatation, and heart rate recovery after exercise. All measurements were done in the morning hours in the fasting state. RESULTS: Dexamethasone increased systolic blood pressure, weight, B-type natriuretic peptide, and high-density-lipoprotein-cholesterol. Dexamethasone decreased resting heart rate, high-sensitivity C-reactive protein, and aldosterone and tended to attenuate nitroglycerin-mediated vasodilatation. There was no effect on flow-mediated vasodilatation, diastolic blood pressure, triglycerides, low-density-lipoprotein-cholesterol, nonesterified fatty acids, homocysteine, or heart rate recovery. The response of circulating cortisol to low-dose dexamethasone had no significant correlation with any of the cardiovascular risk markers. CONCLUSIONS: Short-term glucocorticoids elicits both favorable and unfavorable effects on different cardiovascular risk factors. Manipulation of specific glucocorticoid-responsive physiological pathways deserves further study.

Adult↗
PubMed2005

Interns' work hours.

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Data Interpretation, Statistical↗
PubMed2005

In search of fewer independent risk factors.

More than 1100 articles now appear annually investigating "independent risk factors" or "independent predictors" for various clinical outcomes. In medical research, independence is generally defined in a statistical sense: a variable is called an independent risk factor if it has a significant contribution to an outcome in a statistical model that includes established risk factors. As such, independence is based on a specific statistical model and depends on the set of established risk factors included in that model. Even when strong statistical evidence indicates that a variable is an independent risk factor for an outcome, this does not necessarily indicate that the risk factor causally contributes to the outcome. The opposite is also true: risk factors that have causal relationships with the outcome will not necessarily prove to be independent risk factors. These are basic statistical principles that are too often given short shrift in medical research. Herein, we discuss the clinical implications conferred by the above definition of independence, primarily using examples from recent cardiovascular literature. A glossary and schema are provided to help clinicians and researchers understand and discuss these matters effectively.

Age Factors↗
PubMed2005

Relation of diurnal blood pressure variation and triglyceride-to-high-density lipoprotein cholesterol ratio in patients without diabetes mellitus.

A night-time decrease in systolic blood pressure that differs <10% from mean daytime values ("nondipping") is associated with increased rates of cardiovascular morbidity and mortality. We hypothesized that insulin resistance would be associated with nondipping in patients who did not have frank diabetes mellitus or hypertension. We included 106 consecutive outpatients who had been referred for 24-hour ambulatory monitoring of blood pressure. Our data suggest that insulin resistance, defined as a high ratio of triglyceride to high-density lipoprotein, is associated with blunted diurnal blood pressure variation (odds ratio 6.3, 95% confidence interval 2.6 to 16.4, p <0.0001) before the development of abnormal levels of fasting blood glucose.

Aged↗
PubMed2005

Duration of anesthesia and venous thromboembolism after hip and knee arthroplasty.

OBJECTIVE: To determine whether longer duration of anesthesia predisposes patients undergoing orthopedic surgery to venous thromboembolism (VTE). PATIENTS AND METHODS: We conducted a secondary analysis of a retrospective case-control study that examined risk factors for postoperative VTE in postmenopausal women. We matched women aged 50 years and older with radiographically confirmed postoperative VTE (cases) by age, surgeon, year of surgery, and surgical joint (knee vs hip) with women without postoperative VTE (controls). Duration of anesthesia, operative variables, demographic data, comorbid illnesses, and laboratory data were determined by medical record review. RESULTS: Eighty-eight cases were matched with 181 controls. Duration of anesthesia of 3.5 hours or longer (corresponding to the upper tertile of patients) was strongly associated with postoperative VTE compared with a shorter duration of anesthesia (odds ratio, 3.58; 95% confidence Interval, 2.11-6.16; P < .001). This relationship was maintained after controlling for multiple covariates with propensity score methods, Including type of arthroplasty, route of anesthesia, type of antithrombotic prophylaxis, and surgical approach. In multivariate analysis, the Important predictors of VTE included anesthesia duration of 3.5 hours or longer, type of antithrombotic prophylaxis, revision (vs primary) arthroplasty, and allogeneic blood transfusion. CONCLUSION: We found a marked association between the duration of anesthesia and postoperative VTE in patients undergoing Joint arthroplasty. Although it is possible that unmeasured intraoperative variables account for this relationship, we suggest that duration of anesthesia may be an important risk factor for postoperative VTE after orthopedic surgery.

Anesthesia↗
PubMed2005

Current and emerging options in the management of venous thromboembolism.

Venous thromboembolism (VTE) is a common disease whose diagnosis is challenging. The best diagnostic approaches combine the patient's pretest clinical probability of disease with D-dimer testing and/or diagnostic imaging. In light of several advantages, low-molecular-weight heparins are now recommended over unfractionated heparin for most patients with acute VTE. Newer anticoagulants such as the factor Xa inhibitor fondaparinux also show promise for acute VTE. For chronic management, the duration and intensity of warfarin therapy should be tailored to the individual patient.

Anticoagulants↗
PubMed2004

Does altered glucocorticoid homeostasis increase cardiovascular risk?

The hypothalamic-pituitary-adrenal (HPA) axis, like the sympathetic nervous system and the renin-angiotensin-aldosterone (RAA) system, sustains life in stressful situations by increasing vascular tone and ensuring fuel availability. It also modulates inflammation and tissue repair processes. Untoward cardiovascular effects of chronic sympathetic and RAA activation are well recognized, illustrating that the short-term benefit of the physiologic stress response can be detrimental in the long term. Similarly, chronic tissue exposure to glucocorticoids may lead to metabolic and vascular changes that accelerate vascular senescence. Specific situations associated with chronic activation of the HPA axis-such as major depression, inflammatory disease and perhaps the metabolic syndrome-may derive some of their associated cardiovascular risk from untoward glucocorticoid effects. Since there are no definitive clinical studies directly addressing the relationship between the HPA axis and cardiovascular disease, we present indirect evidence from two types of studies: (1) studies that examine the cardiovascular effects of exogenous glucocorticoids, and (2) studies demonstrating that endogenous glucocorticoid activity varies between individuals. The effects of physiologic increases in endogenous glucocorticoid activity may not always mirror the effects of supraphysiologic glucocorticoids. Nevertheless, the known effects of exogenous glucocorticoids provide important insights into the putative effects of endogenous glucocorticoids.

Cardiovascular Diseases↗
PubMed2004

Acute splenic sequestration crisis resembling sepsis in an adult with hemoglobin SC disease.

Acute splenic sequestration crisis (ASSC) is a common complication of sickle cell anemia in children. ASSC is generally not seen in adults with the SS genotype but occasionally can be seen in adults with the SC genotype. We present a case of fulminant ASSC in an adult with hemoglobin SC who developed high fever, intense abdominal pain, leukocytosis, and jaundice.

Abdominal Pain↗
PubMed2004

Postmenopausal hormone replacement and venous thromboembolism following hip and knee arthroplasty.

Hormone replacement therapy has been associated with venous thromboembolism. Controversy exists regarding the appropriate management of hormone replacement in the perioperative setting and in other situations--such as acute illness--predisposing to acute venous thromboembolism. We performed a case-control study to determine whether perioperative hormone replacement is associated with venous thromboembolism following hip and knee arthroplasty. 108 patients with postoperative venous thrombosis were matched by age, date and type of surgery, and surgeon with 210 controls without thrombosis. Perioperative hormone replacement use was no more prevalent in patients with postoperative thrombosis than those without. Eighteen (16.7%) women with post-operative thrombosis had taken perioperative hormone replacement compared to 49 (23.3%) of controls: odds ratio = 0.66; (95% CI 0.35-1.18; p=0.17). After multivariate analysis, the adjusted odds ratios were similar. Variables predicting post-operative thrombosis included: prior venous thromboembolism (OR = 2.3; p = 0.02), rheumatologic disease (OR = 2.2; p = 0.03), and absence of pharmacologic antithrombotic prophylaxis (OR = 13.4; p = 0.005). Cases and controls were otherwise similar. Users of hormone replacement were similar to non-users except that they were less likely to have coronary disease (OR 0.34; p = 0.03) or prior thrombosis (OR = 0.28; p = 0.04), and were younger (median age 67 versus 74 years; p <0.0001). We found no association between perioperative hormone replacement and post-operative thrombosis in patients undergoing major orthopaedic surgery. Routine discontinuation of these medications preoperatively--and possibly in other situations predisposing to thrombosis, such as acute medical illness--may be unnecessary in patients receiving appropriate pharmacologic antithrombotic prophylaxis.

Acute Disease↗
PubMed2004

Warfarin prophylaxis and venous thromboembolism in the first 5 days following hip and knee arthroplasty.

Many orthopaedic surgeons use warfarin to prevent venous thromboembolism (VTE) following hip or knee arthroplasty. Since warfarin's antithrombotic effects are delayed, we hypothesized that early VTE (occurring within 5 days post-operatively) would be more common in arthroplasty patients receiving warfarin monotherapy compared to those receiving enoxaparin. We performed a secondary analysis of a case-control study examining risk factors for post-operative thrombosis in postmenopausal women. We defined cases as patients who were diagnosed with thrombosis within 5 days of surgery. Controls without thrombosis were matched with cases by age, surgeon, year of surgery and surgical joint. 84 women with early post-operative thrombosis (cases) were matched with 206 controls. 18 cases (21.4%) had been prescribed warfarin mono-therapy, compared with 7 controls (3.4%). 58 (69.1%) cases and 195 (94.7%) controls had been prescribed subcutaneous enoxaparin 30 mg twice daily, starting 12-24 hours after surgery. The odds ratio for any early thrombosis in patients receiving warfarin as opposed to enoxaparin 30 mg twice daily was 8.6 (p<0.0001). For proximal thrombosis, the odds ratio was 11.3 (p<0.0001). Multivariate analysis did not alter these findings. Warfarin's delayed antithrombotic effects may not provide adequate VTE prophylaxis in the immediate post-operative setting. We suggest caution in employing warfarin monotherapy following joint arthroplasty.

Aged↗