Portal and mesenteric thrombosis associated with protein S deficiency]

INTRODUCTION: liver cirrhosis is the main cause of portal thrombosis (PT), while hypercoagulability syndromes are rarely found as the etiology of PT. We report a case of portal and mesenteric thrombosis secondary to protein S deficiency. CASE REPORT: a 74-year-old woman was admitted with melena secondary to upper gastrointestinal bleeding. She reported mild, diffuse abdominal pain in the last 2 weeks. Endoscopy revealed ruptured esophageal varices. Doppler ultrasonography and CT demonstrated a heterogeneous liver, splenomegaly and ascites, and complete non-occlusive PT involving the hilum and portal branches, as well as the superior mesenteric vein, with portosystemic collaterals. At this point a complete study for cirrhosis etiologies was negative, including a liver biopsy that showed nonspecific architectural changes secondary to diminished blood flow, which suggested non-cirrhotic portal hypertension. The search for hypercoagulability states determined a deficiency of S protein, with total pS = 107% and free pS = 56%. The patient was started on anticoagulant treatment and no other thrombotic events occurred. DISCUSSION: PT usually manifests without specific symptoms. The most common presentation is upper gastrointestinal bleeding, as occurred in our patient. Liver cirrhosis is one of the most frequent cause of PT. Up to 65% of these patients present an associated prothrombotic state, including protein S deficiency. Our case reminds us of the importance of a systematic search for hipercoagulability syndromes in patients with TP, even when the etiology can be conferred to liver cirrhosis.     

Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism

OBJECTIVES: The purpose of this research was to determine the levels of platelet, leukocyte, and endothelial activation and markers of cellular interactions in patients with venous thromboembolism (VTE). BACKGROUND: The details of interactions between endothelium, platelets, and leukocytes in VTE are not well understood. METHODS: We studied 25 patients with VTE and compared 25 healthy controls. We used flow cytometry to measure: 1) endothelial microparticles (EMP) identified by CD31+/CD42b- (EMP(31)) or E-selectin (EMP(62E)); 2) platelet microparticles (CD31+/CD42b+); 3) surface expression of P-selectin in platelets and CD11b in leukocytes; 4) EMP-monocyte conjugates (percentage of monocytes positive for E-selectin); and 5) platelet-leukocyte conjugates (PLC) expressed as percentage of leukocytes positive for CD41. RESULTS: Patients with VTE had marked elevations of EMP(31) (2,193 vs. 383 counts/microl; p = 0.003), EMP(62E) (368 vs. 223 counts/microl; p = 0.001), and EMP-monocyte conjugates (3.3% vs. 2.5%; p = 0.002), as well as increased activation of platelets (35.2 vs. 5.0 fluorescence intensity units for P-selectin; p < 0.0001) and leukocytes (13.9 vs. 7.7 U for CD11b; p = 0.004). Also elevated in VTE were PLC (61.7% vs. 39.6%; p = 0.01). Expression of CD11b in leukocytes strongly correlated with PLC (r = 0.74; p < 0.0001). CONCLUSIONS: Marked activation of endothelium, platelets, and leukocytes occurs in VTE, and VTE, or the accompanying inflammatory process, involves the release of EMP and formation of EMP-monocyte conjugates and PLC. These findings support prior studies suggesting that release of EMP and their binding to monocytes are key events in thrombogenesis. Our findings also support the concept that the formation of PLC regulates leukocyte activation and participates in linking thrombosis with inflammation.     

Correlation between apoptotic endothelial microparticles and serum interleukin-6 and C-reactive protein in healthy men

Inflammation has been associated with increased cardiovascular risk, and endothelial cell (EC) apoptosis has been implicated in atherogenesis. The correlation between circulating concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and endothelial microparticles (EMPs) expressing an apoptotic (EMP31) or activation (EMP62E) phenotype in 20 middle-aged healthy men was investigated. IL-6 was significantly correlated with EMP31 (r = 0.6, p = 0.004), which persisted after adjusting for body mass index and CRP. CRP was significantly correlated with body mass index (r = 0.49, p = 0.02) but not with EMP31 or EMP62E. EC apoptosis is associated with IL-6 levels in men and might be partially responsible for the increased cardiovascular risk associated with subclinical inflammation.     

Short term serum pharmacokinetics of diammine silver fluoride after oral application

Background

There is growing interest in the use of diammine silver fluoride (DSF) as a topical agent to treat dentin hypersensitivity and dental caries as gauged by increasing published research from many parts of the world. While DSF has been available in various formulations for many years, most of its pharmacokinetic aspects within the therapeutic concentration range have never been fully characterized.

Methods

This preliminary study determined the applied doses (3 teeth treated), maximum serum concentrations, and time to maximum serum concentration for fluoride and silver in 6 adults over 4 h. Fluoride was determined using the indirect diffusion method with a fluoride selective electrode, and silver was determined using inductively coupled plasma-mass spectrometry. The mean amount of DSF solution applied to the 3 teeth was 7.57 mg (6.04 μL).

Results

Over the 4 hour observation period, the mean maximum serum concentrations were 1.86 μmol/L for fluoride and 206 nmol/L for silver. These maximums were reached 3.0 h and 2.5 h for fluoride and silver, respectively.

Conclusions

Fluoride exposure was below the U.S. Environmental Protection Agency (EPA) oral reference dose. Silver exposure exceeded the EPA oral reference dose for cumulative daily exposure over a lifetime, but for occasional use was well below concentrations associated with toxicity. This preliminary study suggests that serum concentrations of fluoride and silver after topical application of DSF should pose little toxicity risk when used in adults.

Clinical trials registration

NCT01664871.

     

Arterial properties as determinants of time-varying myocardial stress in humans

Myocardial and arterial load are time-varying phenomena. Despite their importance in myocardial function, the arterial properties that determine time-resolved myocardial wall stress are unknown. We aimed to assess arterial properties as determinants of time-resolved myocardial stress among 1214 men and women enrolled in the Asklepios Study. Time-resolved central pressure, flow, and left ventricular geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography, respectively, for computation of arterial load and ejection-phase time-varying myocardial wall stress. For any given end-diastolic left ventricular geometry and cardiac output, peak myocardial stress correlated directly with systemic vascular resistance (standardized β=1.12; P<0.0001) and aortic characteristic impedance (standardized β=0.17; P<0.0001). The ejection-phase stress-time integral correlated with systemic vascular resistance (standardized β=1.06; P<0.0001), lower total arterial compliance (standardized β=-0.13; P=0.0008), and earlier return of wave reflections (standardized β=-0.10; P<0.0001) but not with reflection magnitude, whereas end-systolic wall stress correlated with systemic vascular resistance (standardized β=1.06; P<0.0001) and reflection magnitude (standardized β=0.12; P<0.0001). After adjustment for age, all of the measured arterial properties, end-diastolic left ventricular geometry, and cardiac output, women demonstrated greater peak (534 versus 507 kdyne/cm(2); P<0.0001), end-systolic (335 versus 320 kdyne/cm(2); P<0.0001), and ejection-phase stress-time integral (157 versus 142 kdyne · s · cm(-2); P<0.0001). In conclusion, different arterial properties have selective effects on time-resolved ejection-phase myocardial wall stress, which are not apparent from single-time point measurements. Women demonstrate less efficient myocardial-arterial coupling, with higher wall stress development for any given left ventricular geometry, arterial properties, and flow output. These observations may relate to the differential susceptibility of women to heart failure.     

Metabolic Syndrome in Andean Populations

The metabolic syndrome, a cluster of metabolic abnormalities, has been linked to both cardiovascular disease and type 2 diabetes mellitus risk. Several studies have shown that ethnicity is an important determinant for risk of developing the metabolic syndrome; therefore, further understanding of the prevalence and presentation of the metabolic syndrome in various ethnic groups is needed. Latin American communities, and particularly Andean countries, are largely understudied in relation to the metabolic syndrome and until recently, the prevalence of this metabolic disturbance in Andean Hispanics was unknown. Nonetheless, recent (and ongoing) population studies are providing important data regarding the prevalence and patterns of the metabolic syndrome in various Andean countries. This review aims to summarize and interpret the information provided by these studies in an effort to better characterize the metabolic syndrome in Andean Hispanics.     

Stroke etiology among Haitians living in Miami

The black Caribbean population continues to grow in the US and little is known about stroke etiologies in that community. We examined stroke subtypes in 175 consecutive Haitian-born patients living in Miami, admitted for acute stroke. Ischemic stroke was diagnosed in 72%. Small vessel occlusion was the most frequent stroke subtype. There was a high prevalence of hypertension, medication noncompliance and intracranial atherosclerosis. Hypertension was the only cardiovascular risk factor significantly associated with small vessel infarction when compared with non-small vessel infarcts.     

Localization of species conserved zona pellucida antigens in mammalian ovaries

The mammalian zona pellucida (ZP) consists of three glycoproteins (ZP1, ZP2 and ZP3), which are variably conserved among species at the genomic and amino acid levels. In order to evaluate the expression of ZP during ovarian development, a population of antibodies was selected that recognize species conserved antigenic domains of the three ZP proteins. Domain specific antibodies were selected from sera of rabbits immunized with all three native pig ZP proteins by elution of antibodies bound to each of the three human ZP recombinant proteins expressed from cDNAs, using the baculovirus expression system in insect cells. Immunoblot analysis was used to characterize the specificity of the antibodies and immunohistochemistry was used to evaluate the stage specific expression of ZP proteins during ovarian follicular development of the mouse, baboon and human. This study demonstrates that the conserved domains of all three ZP proteins are localized in the oocyte extracellular ZP matrix as well as in a subset of granulosa cells. However, this expression does vary among species with respect to the stage and cell type during early stages of ovarian follicular development. These antibodies should serve as excellent markers for evaluating early stages of human ovarian follicular development and in the development of contraceptive agents.