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Biomedical subjects

T L Whitsett

Publications and source records attributed to T L Whitsett.

At least 19 recordsLinked to original sources

Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group.

BACKGROUND: Patients undergoing hip or knee joint replacement are at risk for venous thromboembolic complications for up to twelve weeks postoperatively. We evaluated the efficacy and safety of a prolonged post-hospital regimen of enoxaparin, a low-molecular-weight heparin, in this patient population. METHODS: Following elective total hip or knee replacement, 968 patients received subcutaneous enoxaparin (30 mg twice daily) for seven to ten days, and 873 were then randomized to receive three weeks of double-blind outpatient treatment with either enoxaparin (40 mg once daily) or a placebo. The primary efficacy end point was the prevalence of objectively confirmed venous thromboembolism or symptomatic pulmonary embolism during the double-blind phase of treatment. RESULTS: Of the 873 randomized patients, 435 underwent elective total hip replacement and 438 underwent elective total knee replacement. Enoxaparin was superior to the placebo in reducing the prevalence of venous thromboembolism in patients treated with hip replacement: 8.0% (eighteen) of the 224 patients treated with enoxaparin had venous thromboembolism compared with 23.2% (forty-nine) of the 211 patients treated with the placebo (p < 0.001; odds ratio, 3.62; 95% confidence interval, 2.00 to 6.55; relative risk reduction, 65.5%). Enoxaparin had no significant benefit in the patients treated with knee replacement: thirty-eight (17.5%) of the 217 patients treated with enoxaparin had venous thromboembolism compared with forty-six (20.8%) of the 221 patients treated with the placebo (p = 0.380; odds ratio, 1.24; 95% confidence interval, 0.76 to 2.02; relative risk reduction, 15.9%). Symptomatic pulmonary embolism developed in three patients, one with a hip replacement and two with a knee replacement; all had received the placebo. There was no significant difference in the prevalence of hemorrhagic episodes or other types of toxicity between the enoxaparin and placebo-treated groups. CONCLUSIONS: Prolonging enoxaparin thromboprophylaxis following hip replacement for a total of four weeks provided therapeutic benefit, by reducing the prevalence of venous thromboembolism, without compromising safety. A similar benefit was not observed in patients treated with knee replacement.

Adult↗

Prevention of venous thromboembolic disease following primary total knee arthroplasty. A randomized, multicenter, open-label, parallel-group comparison of enoxaparin and warfarin.

BACKGROUND: Patients treated with total knee arthroplasty are at high risk for the development of venous thromboembolism postoperatively. This study compared the efficacy and safety of two common thromboprophylactic agents, enoxaparin (a low-molecular-weight heparin) and warfarin. METHODS: Three hundred and forty-nine patients were included in a prospective, randomized, multicenter, open-label, parallel-group clinical trial. Treatment with enoxaparin (30 mg, administered subcutaneously twice daily) or warfarin (adjusted to an international normalized ratio of 2 to 3) was initiated during the immediate postoperative period, within eight hours after the surgery, and was continued for four to fourteen days. Venous thromboembolism was defined as deep-vein thrombosis documented by contrast venography, symptomatic deep-vein thrombosis documented by lower-extremity ultrasonography, or symptomatic pulmonary embolism confirmed by a positive lung scan or pulmonary angiography. RESULTS: In the all-treated-patients group, eighty (45%) of the 176 warfarin-treated patients had venous thromboembolism: fifty-nine (34%) had distal deep-vein thrombosis; twenty (11%), proximal deep-vein thrombosis; and one (0.6%), pulmonary embolism. Venous thromboembolism developed in significantly fewer (p = 0.0001) enoxaparin-treated patients (forty-four of 173; 25%): forty-one (24%) had distal deep-vein thrombosis, three (2%) had proximal deep-vein thrombosis, and none had pulmonary embolism. The enoxaparin-treated patients also had a significantly lower prevalence of proximal deep-vein thrombosis (p = 0.002). The estimated odds for the development of venous thromboembolism were 2.52 times greater (95% confidence interval, 2.00 to 3.19) with warfarin than they were with enoxaparin. Major hemorrhage occurred in four warfarin-treated patients and nine enoxaparin-treated patients; with the numbers available, this difference was not significant (p = 0.17). Clinically important operative-site hemorrhage occurred in six (3%) of the warfarin-treated patients and twelve (7%) of the enoxaparin-treated patients (p = 0.15). CONCLUSIONS: A fixed 30-mg subcutaneous dose of enoxaparin, administered twice daily, with the first dose administered within eight hours after the completion of surgery, was significantly more effective than adjusted-dose warfarin in reducing the occurrence of asymptomatic venous thromboembolism, including proximal deep-vein thrombosis, in patients undergoing total knee arthroplasty. With the numbers available, there was no significant difference between groups with regard to the occurrence of major hemorrhagic complications; however, the rate of overall hemorrhagic complications was higher in the enoxaparin group.

Adult↗

Predictive value of compression ultrasonography for deep vein thrombosis in symptomatic outpatients: clinical implications of the site of vein noncompressibility.

BACKGROUND: Compression ultrasonography has a high negative predictive value for deep vein thrombosis in symptomatic outpatients. Limited data are available on factors influencing positive predictive value. The objective of this study was to evaluate the positive predictive value of compression ultrasonography according to the anatomic site of vein noncompressibility. METHODS: We performed a prospective cohort study of 756 consecutive outpatients with suspected first-episode deep vein thrombosis. Compression ultrasonography was performed at the initial visit: results were abnormal if a noncompressible segment was identified or normal if all segments were fully compressible. Venography was performed in patients with abnormal compression ultrasonography results. Positive predictive value was determined according to the site of noncompressibility: common femoral vein only, popliteal vein only, or both sites. Venography was the reference standard for the presence of deep vein thrombosis. RESULTS: Positive predictive value was 16.7% (95% confidence interval, 0.4%-64.1%) for noncompressibility isolated to the common femoral vein compared with 91.3% (95% confidence interval, 72.0%-98.9%) for the popliteal vein only and 94.4% (95% confidence interval, 72.7%-99.9%) for both sites (P<.001). Of 15 patients with isolated noncompressibility of the common femoral vein, 8 (53%) had pelvic neoplasm or abscess compared with 2 (5%) of 42 with noncompressibility of the popliteal vein only and 6 (13%) of 47 with noncompressibility of both sites (P<.001). CONCLUSIONS: The positive predictive value of noncompressibility isolated to the common femoral vein is too low to be used alone as the diagnostic end point for giving anticoagulant therapy. Noncompressibility isolated to the common femoral vein is a diagnostic marker for pelvic disease.

Adult↗

Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review.

PURPOSE: To determine the sensitivity and specificity of helical computed tomography (CT) for the diagnosis of pulmonary embolism and to determine the safety of withholding anticoagulant therapy in patients who have clinically suspected pulmonary embolism and negative results on helical CT. DATA SOURCES: The MEDLINE database was searched for all reports published from 1986 to October 1999 that evaluated the use of helical CT for the diagnosis of pulmonary embolism. Bibliographies of the retrieved articles were cross-checked to identify additional studies. STUDY SELECTION: All prospective English-language studies were selected. Retrospective studies, review articles, and case reports were excluded, and 5 of the 20 identified articles were excluded. The scientific validity of the remaining 15 articles was assessed. DATA EXTRACTION: Two of the authors used a priori, pre-defined criteria to independently assess each study. A third author resolved disagreements by adjudication. The pre-defined criteria were inclusion of a consecutive series of all patients with suspected pulmonary embolism, inclusion of patients with and those without pulmonary embolism, a broad spectrum of patient characteristics, performance of helical CT and pulmonary angiography (or an appropriate reference test) in all patients, and independent interpretation of the CT scan and pulmonary angiogram (or reference test). Specific data on sensitivity and specificity and the associated 95% CIs were recorded when available. DATA SYNTHESIS: No study met all of the predefined criteria for adequately evaluating sensitivity and specificity. The reported sensitivity of helical CT ranged from 53% to 100%, and specificity ranged from 81% to 100%. In no prospective study was anticoagulant therapy withheld without further testing for venous thromboembolism in consecutive patients with suspected pulmonary embolism. One prospective study reported the outcome of selected patients with negative results on helical CT who did not receive anticoagulant therapy. CONCLUSIONS: Use of helical CT in the diagnosis of pulmonary embolism has not been adequately evaluated. The safety of withholding anticoagulant treatment in patients with negative results on helical CT is uncertain. Definitive large, prospective studies should be done to evaluate the sensitivity, specificity, and safety of helical CT for diagnosis of suspected pulmonary embolism.

Anticoagulants↗

Additive pressor effects of caffeine and stress in male medical students at risk for hypertension.

The effects of caffeine on blood pressure (BP) and cortisol secretion were examined during elevated work stress in medical students at high versus low risk for hypertension. Among 31 male medical students who were regular consumers of caffeine, 20 were considered at low risk for hypertension (negative parental history and all screening BP < 125/78 mm Hg) and 11 at high risk based on epidemiologic criteria (positive parental history and average screening BPs between 125/78 and 139/89 mm Hg). Cortisol levels and ambulatory BP were measured with and without caffeine during two lectures (low work stress) and two exams (high work stress) in a randomized, double-blind, crossover trial. Caffeine consumption and exam stress increased cortisol secretion in both groups (P < .05). BP increased with caffeine or exam stress in both groups, low versus high risk, respectively (Caffeine: + 5/4 vs + 3/3 mm Hg; Stress: + 4/1 vs + 7/3 mm Hg; P < .05). The combination of stress and caffeine caused additive increases in BP (Low Risk + 9/5 mm Hg, High Risk + 10/6 mm Hg) such that 46% of high-risk participants had average systolic BP > or = 140 mm Hg. This combined effect of stress and caffeine on BP suggests that it may be beneficial for individuals at high risk for hypertension to refrain from the use of caffeinated beverages, particularly at times when work demands and attendant stressors are high. For the same reasons, recent intake of caffeine should be controlled in patients undergoing BP measurement for the diagnosis of hypertension.

Adult↗

Hypertension risk status and effect of caffeine on blood pressure.

We compared the acute effects of caffeine on arterial blood pressure (BP) in 5 hypertension risk groups composed of a total of 182 men. We identified 73 men with optimal BP, 28 with normal BP, 36 with high-normal BP, and 27 with stage 1 hypertension on the basis of resting BP; in addition, we included 18 men with diagnosed hypertension from a hypertension clinic. During caffeine testing, BP was measured after 20 minutes of rest and again at 45 to 60 minutes after the oral administration of caffeine (3.3 mg/kg or a fixed dose of 250 mg for an average dose of 260 mg). Caffeine raised both systolic and diastolic BP (SBP and DBP, respectively; P<0.0001 for both) in all groups. However, an ANCOVA revealed that the strongest response to caffeine was observed among diagnosed men, followed by the stage 1 and high-normal groups and then by the normal and optimal groups (SBP F(4),(175)=5.06, P<0.0001; DBP F(4,175)=3.02, P<0.02). Indeed, diagnosed hypertensive men had a pre-to-postdrug change in BP that was >1.5 times greater than the optimal group. The potential clinical relevance of caffeine-induced BP changes is seen in the BPs that reached the hypertensive range (SBP >/=140 mm Hg or DBP >/=90 mm Hg) after caffeine. During the predrug baseline, 78% of diagnosed hypertensive men and 4% of stage 1 men were hypertensive, whereas no others were hypertensive. After caffeine ingestion, 19% of the high-normal, 15% of the stage 1, and 89% of the diagnosed hypertensive groups fell into the hypertensive range. All subjects from the optimal and normal groups remained normotensive. We conclude that hypertension risk status should take priority in future research regarding pressor effects of dietary intake of caffeine.

Adult↗

The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis.

BACKGROUND: Ultrasonography using vein compression accurately detects proximal deep venous thrombosis in symptomatic outpatients. Repeated testing is required for patients with normal results at presentation, but the optimal management of such patients is uncertain. OBJECTIVE: To test the safety of withholding anticoagulation in outpatients suspected of having first-episode deep venous thrombosis who have normal results on simplified compression ultrasonography at presentation and on a single repeated test done 5 to 7 days later. DESIGN: Prospective cohort study. SETTING: Noninvasive vascular laboratories at a university teaching hospital and a Veterans Administration medical center. PATIENTS: 405 consecutive outpatients suspected of having first-episode deep venous thrombosis. INTERVENTION: Ultrasonography was performed at presentation. The common femoral and popliteal veins were assessed for compressibility. If the result was normal, anti-coagulation was withheld and testing was repeated 5 to 7 days later. Anticoagulation was withheld from all patients whose results remained normal according to compression ultrasonography, regardless of their symptoms. The safety of this approach was tested by follow-up lasting 3 months. MEASUREMENTS: Objective testing was done during follow-up in all patients with symptoms or signs of venous thromboembolism. The outcome measure was symptomatic venous thrombosis or pulmonary embolism during follow-up, confirmed by objective testing. RESULTS: Ultrasonography had normal results in 335 patients (83%) and abnormal results in 70 (17%). None of the patients with normal results died of pulmonary embolism. Venous thromboembolism occurred during follow-up in 2 patients with normal ultrasonographic results (0.6% [95% CI, 0.07% to 2.14%]) and in 4 patients with abnormal results (5.7% [CI, 1.58% to 13.99%]) (P = 0.009). CONCLUSIONS: It is safe to withhold anticoagulation in outpatients suspected of having first-episode deep venous thrombosis if results of simplified compression ultrasonography are normal at presentation and on a single repeated test done 5 to 7 days later.

Adolescent↗

Stress-like adrenocorticotropin responses to caffeine in young healthy men.

The effects of oral caffeine (3.3 mg/kg, equivalent to 2-3 cups of coffee) on plasma adrenocorticotropin (ACTH) and cortisol (CORT) were tested in 47 healthy young men at rest in a double-blind, placebo-controlled, crossover study. Following caffeine, ACTH was significantly elevated at all times from 30 min to 180 min, and CORT was elevated from 60 min to 120 min (Fs > or = 8.4, ps < 0.01). Peak increases relative to placebo were: ACTH, 33% (+5.2 pg/ml) and CORT, 30% (+2.7 micrograms/dl) at 60 min postcaffeine. The results suggest that caffeine can activate important components of the pituitary-adrenocortical response in humans during the resting state. Caffeine's known ability to increase CORT production appears at least partly due to an increase in ACTH release at the pituitary.

Administration, Oral↗

Pseudotumor cerebri. A complication of catheter-induced subclavian vein thrombosis.

Pseudotumor cerebri is frequently the only clinical clue to the presence of cerebral venous thrombosis, a potentially devastating condition. We report a case of pseudotumor cerebri associated with thrombosed dural venous sinuses caused by propagation of a catheter-related subclavian vein thrombus. The findings and clinical course in this case alert us to a complication of central venous catheter use that responds well to treatment if recognized early.

Aged↗

Prolonged increase in blood pressure by a single oral dose of caffeine in mildly hypertensive men.

Caffeine is known to raise blood pressure (BP). We examined a single oral dose of caffeine (3.3 mg/kg, equivalent to 2 to 3 cups of coffee) on BP in 18 hypertensive (HTN) and 12 age-matched, normotensive (NT) men for 3 h. Systolic BPs were significantly higher after caffeine for both groups (P < .001) for the entire 3 h. The HTN group showed persistent elevation in diastolic BP for 3 h, whereas the increment of diastolic BP became smaller in the NT group 90 min after caffeine ingestion. Our results suggest that caffeine consumption may affect both diagnosis and treatment of hypertension and abstinence from caffeine may be beneficial, especially for hypertensive individuals.

Administration, Oral↗

Survival factors in a canine septic shock model.

Physiological indicators of tissue perfusion in a canine septic shock model have been examined. An early death (ED) group and a combined late death and survivor group (LDS) were defined and the corresponding data compared. It was found that the LDS group had less reductions in mean systemic arterial pressure (P less than 0.05), transcutaneous oxygen pressure (P less than 0.05), and red blood cell deformability (P less than 0.001); a smaller increase in hematocrit (P less than 0.05); and a lower concentration of white blood cells (P less than 0.05), relative to the ED group, at 6 hr after an infusion of Escherichia coli organisms. These results suggest that dogs in the LDS group have better tissue perfusion than those in the early death ED group. Post-treatment of dogs with pentoxifylline did not improve survival time or enhance flow factors.

Animals↗

Accelerated thrombolysis and reperfusion in a canine model of myocardial infarction by liposomal encapsulation of streptokinase.

The aim of thrombolytic therapy for acute myocardial infarction with plasminogen activators such as streptokinase is to lyse the coronary thrombus and reestablish blood flow as quickly as possible so that heart tissue loss is minimized and mortality rates are improved. Streptokinase has been encapsulated in large unilamellar phospholipid vesicles and tested in an animal model of acute myocardial infarction. The time required to restore vessel patency has been reduced more than 50% when compared with findings for free streptokinase. The total dosage of streptokinase required was lower, and smaller remnant thrombi were observed with the encapsulated agent. Results from this initial unoptimized study may have significant implications for further reduction in mortality from heart attacks by therapy with plasminogen activators.

Animals↗

Erythrocyte deformability in canine septic shock and the efficacy of pentoxifylline and a leukotriene antagonist.

Decreased microcirculatory flow in the case of endotoxic shock has been extensively reported. The flexibility of the red blood cell plays an important role in tissue perfusion. The present study with a canine shock model was designed to investigate the changes in erythrocyte flow properties during septic shock. Deformabilities of canine erythrocytes were found to decrease considerably 6 hr after infusion of Escherichia coli organisms (P less than 0.05). Pretreatment of dogs with pentoxifylline reduced the effect by improving erythrocyte deformability significantly and by increasing animal survival times. The leukotriene antagonist LY171883 also increased survival time, but did not change red cell filterability. The mortality of the dogs was not affected by either pentoxifylline or the leukotriene antagonist. Both drugs aided the concentration recovery of circulating leukocytes by 6 hr post-E. coli infusion.

Acetophenones↗