The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study

OBJECTIVES: To estimate the incidence and determine predictors of venous stasis syndrome and venous ulcers after deep venous thrombosis and pulmonary embolism. PATIENTS AND METHODS: This population-based retrospective cohort study reviewed medical records of 1527 patients with incident deep venous thrombosis or pulmonary embolism between 1966 and 1990. We recorded baseline characteristics, event type (deep venous thrombosis with or without pulmonary embolism or pulmonary embolism alone), leg side and site of deep venous thrombosis (proximal with or without distal deep venous thrombosis vs distal deep venous thrombosis alone), and venous stasis syndrome and venous ulcer. RESULTS: Two hundred forty-five patients developed venous stasis syndrome. One-year, 5-year, 10-year, and 20-year cumulative incidence rates were 7.3%, 14.3%, 19.7%, and 26.8%, respectively. By 20 years the cumulative incidence of venous ulcers was 3.7%. Patients with deep venous thrombosis with or without pulmonary embolism were 2.4-fold (95% confidence interval, 1.7-fold-3.2-fold) more likely to develop venous stasis syndrome than patients with pulmonary embolism and no diagnosed deep venous thrombosis. In patients aged 40 years or younger with proximal compared with distal-only deep venous thrombosis, venous stasis syndrome was 3.0-fold more likely (95% confidence interval, 1.6-fold-4.7-fold). In patients with unilateral leg deep venous thrombosis, venous stasis syndrome usually developed in the concordant leg (P < .001). There was a 30% (95% confidence interval, 2%-62%) increased risk for venous ulcer per decade of age at the incident venous thromboembolism. CONCLUSIONS: The cumulative incidence of venous stasis syndrome continues to increase for 20 years after venous thromboembolism. Pulmonary embolism alone is less likely to cause venous stasis syndrome.     

Is phenytoin contraindicated in patients receiving cranial irradiation ?

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation.     

Early versus delayed feeding with an immune-enhancing diet in patients with severe head injuries

BACKGROUND: Although early enteral feeding clearly reduces septic morbidity after blunt and penetrating trauma, data for head-injured patients are conflicting. This study examines the effects of early vs delayed enteral feedings on outcome in patients with severe closed-head injuries with a Glasgow Coma Scale (GCS) score greater than 3 and less than 11. METHODS: Thirty patients were prospectively randomized to receive an immune-enhancing diet (Impact with fiber) early (initiated < 72 hours after trauma) delivered via an endoscopically placed nasoenteric tube (Stay-Put) or late (administered after gastric ileus resolved). This formula was continued for 14 days or until the patient tolerated oral feeding. Goal rate of nutrition was 21 nonprotein cal/kg/d and 0.3 g N/kg/d. RESULTS: Two patients in the early group were excluded due to inability to place the tube, and one patient in the late group died before 72 hours. Five of the remaining 27 died, 1 in the early group and 4 in the late group. There were no significant differences between the groups in length of stay, intensive care unit (ICU) days, significant infection, or GCS score. However, major infection correlated inversely with admission GCS score (R = -0.6, p < .003). Time to reach a GCS score of 14 was significantly longer in patients with significant infections compared with those without (p < .02). CONCLUSIONS: No difference in length of stay or infectious complications is shown in patients with severe closed-head injury when they are given early vs delayed feeding using an immune-enhancing formula. Severity of the head injury is closely associated with significant infection.     

Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine

BACKGROUND: Certain foods, such as grapefruit juice, are known to substantially alter the bioavailability of some drugs. These effects may be mediated by interactions with enzyme systems, such as cytochrome P450, or with active transporter systems, such as P-glycoprotein and organic anion transporting polypeptides. OBJECTIVE: To assess the effect of consumption of grapefruit juice on the oral bioavailability of two nonsedating antihistamines, fexofenadine and desloratadine. DESIGN: Non-blinded, randomised, single-dose, four-way crossover study. PARTICIPANTS: Twenty-four healthy adult volunteers. INTERVENTIONS: Single oral doses of desloratadine 5mg and fexofenadine 60mg taken without and with grapefruit juice (pretreatment with 240ml of double-strength juice three times daily for 2 days prior to administration of study drug, plus the same amount simultaneously with, and 2 hours after, the drug dose). Each treatment was separated by at least 10 days. MAIN OUTCOME MEASURES: Log-transformed pharmacokinetic parameters [peak plasma concentration (C(max)) and area under the curve (AUC)], time to maximum concentration, elimination half-life and electrocardiographic (ECG) parameters. RESULTS: Comparing the ratio of the pharmacokinetic parameter means (C(max) and AUC) with and without grapefruit juice (expressed as a percentage), the rate (C(max)) and extent (AUC) of absorption of fexofenadine were reduced by 30% by consumption of grapefruit juice. In contrast, the bioavailability of desloratadine was unaffected by grapefruit juice. No clinically significant changes in ECG parameters were observed following coadministration of grapefruit juice with desloratadine or fexofenadine compared with either antihistamine given alone. CONCLUSION: The bioavailability of drugs that do not undergo significant intestinal or hepatic metabolism, such as fexofenadine, may be altered when administered with agents that influence drug transport mechanisms.     

Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin

AIMS: The primary aims of these two single-centre, randomized, evaluator-blind, placebo/positive-controlled, parallel-group studies were to evaluate the potential for pharmacodynamic and pharmacokinetic interaction between ezetimibe 0.25, 1, or 10 mg and simvastatin 10 mg (Study 1), and a pharmacodynamic interaction between ezetimibe 10 mg and simvastatin 20 mg (Study 2). Evaluation of the tolerance of the coadministration of ezetimibe and simvastatin was a secondary objective. METHODS: Eighty-two healthy men with low-density lipoprotein cholesterol (LDL-C) >or=130 mg dl-1 received study drug once daily in the morning for 14 days. In Study 1 (n=58), five groups of 11-12 subjects received simvastatin 10 mg alone, or with ezetimibe 0.25, 1, or 10 mg or placebo. In Study 2 (n=24), three groups of eight subjects received simvastatin 20 mg alone, ezetimibe 10 mg alone, or the combination. Blood samples were collected to measure serum lipids in both studies. Steady-state pharmacokinetics of simvastatin and its beta-hydroxy metabolite were evaluated in Study 1 only. RESULTS: In both studies, reported side-effects were generally mild, nonspecific, and similar among treatment groups. In Study 1, there were no indications of pharmacokinetic interactions between simvastatin and ezetimibe. All active treatments caused statistically significant (P<0.01) decreases in LDL-C concentration vs placebo from baseline to day 14. The coadministration of ezetimibe and simvastatin caused a dose-dependent reduction in LDL-C and total cholesterol, with no apparent effect on high-density lipoprotein cholesterol (HDL-C) or triglycerides. The coadministration of ezetimibe 10 mg and simvastatin 10 mg or 20 mg caused a statistically (P<0.01) greater percentage reduction (mean -17%, 95% CI -27.7, -6.2, and -18%, -28.4, -7.4, respectively) in LDL-C than simvastatin alone. CONCLUSIONS: The coadministration of ezetimibe at doses up to 10 mg with simvastatin 10 or 20 mg daily was well tolerated and caused a significant additive reduction in LDL-C compared with simvastatin alone. Additional clinical studies to assess the efficacy and safety of coadministration of ezetimibe and simvastatin are warranted.     

Functional genomics of the endocrine pancreas: the pancreas clone set and PancChip,new resources for diabetes research

Over the past 5 years, microarrays have greatly facilitated large-scale analysis of gene expression levels. Although these arrays were not specifically geared to represent tissues and pathways known to be affected by diabetes, they have been used in both type 1 and type 2 diabetes research. To prepare a tool that is particularly useful in the study of type 1 diabetes, we have assembled a nonredundant set of 3,400 clones representing genes expressed in the mouse pancreas or pathways known to be affected by diabetes. We have demonstrated the usefulness of this clone set by preparing a cDNA glass microarray, the PancChip, and using it to analyze pancreatic gene expression from embryonic day 14.5 through adulthood in mice. The clone set and corresponding array are useful resources for diabetes research.