Enhanced thrombin generation in patients with arterial hypertension.

BACKGROUND: Arterial hypertension is associated with greater risk of cardiovascular diseases and thrombotic complications, suggesting that hypertension is a prothrombotic state. OBJECTIVES: To investigate the relationship between arterial hypertension and thrombin generation, and between blood pressure level and thrombin generation in hypertensive patients. METHODS: A total of 165 hypertensive patients and 47 healthy adults controls were include in the study. Thrombin generation was assessed in both groups by the Calibrated Automated Thrombogram (CAT) method. Ambulatory blood pressure monitoring (ABPM) was also performed for all patients in the hypertensive group. RESULTS: Hypertensive patients had significantly higher levels of ETP and peak heights compared to healthy controls; means of ETP 1720.6 ±â€¯267 and 1544.7 ±â€¯302, respectively (P < 0.001) and means of peak height were 297.26 ±â€¯48 and, 273 ±â€¯53, respectively (P < 0.001). On multivariate linear regression analysis, hypertension remained independently associated with increased ETP (ß = 0.185, P = 0.047). Analysis restricted to the hypertensive group with ABPM measurement showed statistically significant correlations between all measures of diastolic blood pressure (DBP) and ETP, and multivariate analysis showed that awake DBP was significantly associated with ETP (ß = 0.194 for each 1-mm Hg increase in awake DBP, P = 0.012). Furthermore, hypertensive patients with cardiovascular complications had statistically elevated levels of peak height compared to hypertensive patients without cardiovascular complications. CONCLUSIONS: Hypertensive patients possess enhanced thrombin generation compared healthy controls. Diastolic blood pressure level is independently correlated with increased thrombin generation in hypertensive patients. These findings suggest that arterial hypertension is a prothrombotic state.

Pattern of Blood Pressure Response in Patients With Severe Asymptomatic Hypertension Treated in the Emergency Department.

Severe asymptomatic hypertension (SAH) is a common cause of emergency department (ED) visits. Despite recommendations against using short-acting blood pressure (BP)-lowering drugs in the ED, it is still a common practice. The authors characterized BP response in the ED utilizing 24-hour ambulatory BP monitoring (ABPM). Patients with SAH who were not admitted to the hospital were recruited. All patients underwent 24-hour ABPM. A total of 21 patients (14 females) with a mean age of 58±16 years were studied. BP decreased from 199±16/101±17 mm Hg to 154±34/83±23 mm Hg after 5 hours but then rose to 174±25/94±17 mm Hg after 19 hours. In 17 patients, systolic BP was ≥180 mm Hg after 6.7±5.3 hours. Two patients experienced severe hypotension (systolic BP <90 mm Hg). Thus, data from a single site in Israel support the current recommendations for management of SAH in the ED.

The association between ambulatory systolic blood pressure and cardiovascular events in a selected population with intensive control of cardiovascular risk factors.

Recent guidelines recommend a target clinic systolic blood pressure (BP) of <140 mm Hg. These recommendations are based on the relationship of office BP measurements and cardiovascular (CV) events. We evaluated the association between 24-hour ambulatory BP measurements (24H ABPM) and CV events in a selected population with intensive control of CV risk factors. We retrospectively followed all patients who had undergone 24H ABPM during 2005 at the Institute of Periodic Medical Examinations, Chaim Sheba Medical Center, Tel-Hashomer, Israel, to monitor the development of CV events. These patients were followed closely and treated meticulously in order to control CV risk factors. The study population consisted of 317 patients (81% males; mean age, 59.2 ± 9.8 years) followed for a mean period of 6.4 ± 2.1 years (median, 6 years). During follow-up, 22 patients had their first CV event. Patients who experienced CV events were significantly older, more likely diabetic, and had a history of previous CV disease. Twenty-four-hour ABPM systolic BP ≥140 mm Hg was not associated with increased CV events, whereas 24H ABPM systolic BP ≥150 mm Hg was. Logistic regression analysis showed that 24H ABPM systolic BP ≥150 mm Hg, a former smoker, old age, and a history of CV disease were associated with CV events during follow-up. We found that, in a population aggressively managed for CV risk factors, 24H ABPM systolic BP ≥150 mm Hg is associated with increased CV events.

Primary effusion lymphoma-like lymphoma in a patient with inflammatory bowel disease.

A 77-year-old man with inflammatory bowel disease (IBD) and who was treated with anti-tumor necrosis factor (TNF), 6-mercaptopurine and corticosteroids, presented with primary effusion lymphoma-like lymphoma (PEL-like lymphoma) with massive ascites. The patient's clinical course was complicated by acute renal insufficiency and hypotension, which led to death within 2 wk. In general, patients with IBD may have an increased risk for development of lymphoma, which is frequently associated with immunosuppressive and/or anti-TNF antibody therapies. PEL is a rare subset of lymphoma localized to serous body cavities, lacks tumor mass or nodal involvement, and is associated with infection by human herpes virus 8 (HHV-8). Primary neoplastic effusion may also be present in patients with large B-cell lymphoma without evidence of human immunodeficiency virus or HHV-8 infections. This type of lymphoma is classified as PEL-like lymphoma. Both PEL and PEL-like lymphoma types have been reported in patients undergoing immunosuppressive therapy, but to the best of our knowledge, the case described herein represents the first PEL-like lymphoma occurring in a patient with IBD.

Non-therapeutic anti-FXa levels are common among medical ward patients treated with enoxaparin.

Thromboembolism is treated with a weight-adjusted enoxaparin dose without the need for laboratory monitoring. This study aims to determine the prevalence of sub and supra-therapeutic anti-factor Xa (aFXa) levels among medical ward patients treated with enoxaparin, and to identify potential factors associated with non-therapeutic aFXa levels. aFXa levels were measured in a cohort of medical ward patients treated with curative enoxaparin regimen (1 mg/kg bid) in the Ha'emek Medical Center in the northeastern area of Israel. The relative risk (RR) ratio for sub and supra-therapeutic aFXa levels was estimated in demographic and clinical subgroups. Of the 294 included patients, only 78.6% had therapeutic aFXa levels, while 13.3% and 8.1% had sub and supra-therapeutic levels, respectively. On univariate analysis, females, smoking, BMI ≥ 30, and cancer were significantly associated with supra-therapeutic aFXa levels; fibrates and warfarin use were significantly associated with sub-therapeutic aFXa levels (P < 0.05). On multivariate analysis, females and patients with cancer were independently at increased risk for supra-therapeutic levels RR 3.35(95% CI 1.50, 7.48), RR 3.61(95% CI 1.50, 8.70), respectively. Fibrates and warfarin were associated with sub-therapeutic levels RR 2.99(95% CI 1.44, 6.20), RR 3.42(95% CI 1.73, 6.76), respectively. Standard curative enoxaparin regimen is associated with increased risk for supra-therapeutic aFXa levels in females and patients with cancer and sub-therapeutic levels in patients treated with fibrates and warfarin. This may suggest the need for anticoagulation monitoring in high-risk patients with these conditions.

Haloperidol-induced neuroleptic malignant syndrome complicated by hyperosmolar hyperglycemic state.

Neuroleptic malignant syndrome (NMS) is a life-threatening neurologic emergency that may be caused by neuroleptic agents of any class. The association with hyperosmolar hyperglycemic state (HHS) is rare and carries a grave prognosis. We describe the case of a 25-year-old male patient with haloperidol-induced NMS complicated by HHS that culminated in the patient's death despite all treatment efforts. Physicians caring for diabetic psychiatric patients who are treated with neuroleptic agents should be aware of this association that may be prevented by tight glycemic control.

Pulmonary hypertension in a patient with Schmidt syndrome.

We describe a 26-year-old patient with long-standing autoimmune hypothyroidism. She was doing well until she developed Addisonian crisis accompanied by severe metabolic acidosis, hypoglycemia, hypomagnesemia, and hypokalemia. Subsequently she developed a life-threatening cardiac arrhythmia due to QT prolongation secondary to electrolyte imbalance. The association of autoimmune hypothyroidism and adrenal insufficiency in our patient suggests the diagnosis of autoimmune polyglandular syndrome type II or Schmidt syndrome. An echocardiography that was performed detected pulmonary hypertension without apparent cardiac or lung pathology. The association of pulmonary hypertension and Schmidt syndrome is rare and may be explained by a generalized immune activation leading to pulmonary endothelial damage or dysfunction.

Effects of date ( Phoenix dactylifera L., Medjool or Hallawi Variety) consumption by healthy subjects on serum glucose and lipid levels and on serum oxidative status: a pilot study.

The present pilot study analyzed, for the first time, the in vivo effect of Medjool or Hallawi date consumption by healthy subjects on serum glucose, lipids, and oxidative stress. Total phenolics concentration in the Hallawi versus Medjool dates was greater by 20-31%. The major proportion of the soluble phenolics in both date varieties consisted of phenolic acids, mainly ferulic acid and coumaric acid derivatives, and also chlorogenic and caffeic acid derivatives. Unlike the Medjool dates, Hallawi dates contained a significant proportion of catechins as well. In addition, both varieties contained a quercetin derivative. Both date varieties possess antioxidative properties in vitro, but the ferric ion reducing antioxidant power of Hallawi versus Medjool dates was higher by 24%. Ten healthy subjects consumed, for a period of 4 weeks 100 g/day of either Medjool or Hallawi dates. The date consumption did not significantly affect the subjects' body mass index (BMI), their serum total cholesterol, or their cholesterol levels in the VLDL, LDL, or HDL fractions. Most important, fasting serum glucose and triacylglycerol levels were not increased after consumption of either date variety, and serum triacylglycerol levels even significantly (p < 0.05) decreased, by 8 or 15% after Medjool or Hallawi date consumption, respectively. Basal serum oxidative status was significantly (p < 0.01) decreased by 33%, as compared to the levels observed before consumption, after Hallawi (but not Medjool) date consumption. Similarly, the susceptibility of serum to AAPH-induced lipid peroxidation decreased by 12%, but only after Hallawi date consumption. In agreement with the above results, serum activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) significantly increased, by 8%, after Hallawi date consumption. It is concluded that date consumption (and mainly the Hallawi variety) by healthy subjects, despite their high sugar content, demonstrates beneficial effects on serum triacylglycerol and oxidative stress and does not worsen serum glucose and lipid/lipoprotein patterns, and thus can be considered an antiatherogenic nutrient .

Consumption of wonderful variety pomegranate juice and extract by diabetic patients increases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities.

Association of paraoxonase 1 (PON1) with high-density lipoprotein (HDL) stabilizes the enzyme. In diabetic patients, PON1 dissociates from HDL and, as a consequence, is less biologically active. Our aim was to investigate the effects of Wonderful variety pomegranate juice (WPJ) and pomegranate polyphenol extract (WPOMxl) consumption on PON1 association with HDL in diabetic patients. Thirty patients with type 2 diabetes mellitus participated in the study. Ten male patients and 10 female patients received concentrated WPJ (50 mL/day for 4 weeks), while another group of 10 male patients received WPOMxl (5 mL/day for 6 weeks). There were no significant effects of WPJ or WPOMxl consumption on fasting blood glucose or hemoglobin A1c levels. After 4 weeks of WPJ consumption by male patients, basal serum oxidative stress was significantly decreased by 35%, whereas serum concentrations of thiol groups significantly increased by 25%. Moreover, HDL-associated PON1 arylesterase, paraoxonase, and lactonase activities increased significantly after WPJ consumption by 34-45%, as compared to the baseline levels. PON1 protein binding to HDL was significantly increased by 30% following WPJ consumption, and the enzyme became more stable. In male patients that consumed WPOMxl and in female patients that consumed PJ, a similar pattern was observed, although to a lesser extent. We conclude that WPJ as well as WPOMxl consumption by diabetic patients does not worsen their diabetic parameters. Furthermore, WPJ as well as WPOMxl consumption contribute to PON1 stabilization, increased association with HDL, and enhanced catalytic activities. These beneficial effects of pomegranate consumption on serum PON1 stability and activity could lead to retardation of atherosclerosis development in diabetic patients.

Correction of HDL dysfunction in individuals with diabetes and the haptoglobin 2-2 genotype.

OBJECTIVE: Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction. RESEARCH DESIGN AND METHODS: Hb and lipid peroxides were assessed in HDL isolated from diabetic individuals or mice with the Hp 1-1 or Hp 2-2 genotypes. HDL function was assessed based on its ability to promote cholesterol efflux from macrophages. A crossover placebo-controlled study in Hp 2-2 diabetic humans and in Hp 1-1 and Hp 2-2 diabetic mice assessed the ability of vitamin E to favorably modify these structural and functional parameters. RESULTS-Hb and lipid peroxides associated with HDL were increased and HDL function was impaired in Hp 2-2 diabetic individuals and mice. Vitamin E decreased oxidative modification of HDL and improved HDL function in Hp 2-2 diabetes but had no effect in Hp 1-1 diabetes. CONCLUSIONS: Vitamin E significantly improves the quality of HDL in Hp 2-2 diabetic individuals.

Ten years surveillance of antimicrobial susceptibility of community-acquired Escherichia coli and other uropathogens in northern Israel (1995-2005).

BACKGROUND: In an era of increasing antimicrobial resistance, knowledge of local antimicrobial susceptibility patterns of common uropathogens is essential for prudent empiric therapy of community-acquired urinary tract infections. OBJECTIVES: To define antimicrobial susceptibility of Gram-negative uropathogens in northern Israel over a 10 year period and to compare it with patterns of antibiotic use in the same community. METHODS: We tested the susceptibility of all Gram-negative urinary isolates from outpatients at HaEmek Medical Center over the years 1995, 1999, 2002 and 2005 to common antimicrobial agents. MIC90 of Escherichia coli to some of these agents was determined and antibiotic consumption data over the years 2000-2005 (DDD/1000/day) were obtained. RESULTS: We observed a rise in susceptibility rates of E. coli to amoxicillin-clavulanate, trimethoprim-sulfamethoxazole and nitrofurantoin and of other Gram-negative isolates to amoxicillin-clavulanate, ceftriaxone and cephalothin. Susceptibility rates of all Gram-negative uropathogens to ciprofloxacin decreased significantly. MIC90 of E. coli for all drugs tested remained stable. There was a significant decrease in the use of nitrofurantoin and TMP-SMX and a significant increase in the use of ampicillin, cephalothin and ceftriaxone. CONCLUSIONS: Antibiotic resistance patterns mostly remained unchanged or improved slightly. There was, however, a constant decrease in susceptibility of all Gram-negative uropathogens to ciprofloxacin. Antibiotic use patterns could not explain the changes seen in antibiotic susceptibility patterns.