Platelet Reactivity in Coronary Ostial Blood: A Reflection of the Thrombotic State Accompanying Plaque Rupture and of the Adequacy of Anti-Thrombotic Therapy

Background: Optimal anti-thrombotic therapy for acute coronary syndromes (ACS) should suppress pro-thrombotic activity at the site of plaque rupture. We sought to determine whether platelet reactivity is increased in blood in the immediate vicinity of a ruptured plaque and is apparent even when blood is obtained by sampling from a catheter placed proximal to the lesion. Methods: Blood was obtained from a catheter placed in the aorta and from the same catheter after engaging the culprit coronary artery. Platelet reactivity was determined with the use of flow cytometry by surface expression of P-selectin. Results: In preliminary studies we demonstrated that a marker of thrombin activity, fibrinopeptide A, was similarly increased in blood taken from the coronary sinus and coronary arterial ostium of patients with ACS. Subsequently blood was obtained from the aorta and coronary arterial ostium through a coronary guide catheter for assessment of platelet reactivity in 23 subjects with ACS and 22 subjects with stable angina. The percentage of platelets expressing P-selectin in response to 0.2[emsp4 ]M adenosine diphosphate (ADP) was greater in coronary arterial samples from patients with ACS (aorta=6.1±1%, coronary artery=8.8±1.6%, p=0.02) compared with that in patients with stable symptoms (aorta=6.9±1.2, coronary artery=6.5±1.4, p=NS). Conclusions: Coronary arterial blood obtained from the ostium through a coronary guide catheter can be used to determine whether thrombin activity and platelet reactivity are increased in the immediate vicinity of a ruptured atherosclerotic plaque. The simplicity of the approach developed should facilitate its use in future studies designed to determine the impact of optimal suppression of platelet reactivity and the pro-thrombotic state before coronary interventions on short- and long-term clinical outcomes.     

Pseudoaneurysm of the subclavian-vertebral artery junction--case report and review of the literature

Pseudoaneurysm of the subclavian-vertebral artery junction (SVJ) is a rare complication of internal jugular vein catheter placement. Because of its retroclavicular location, arterial injury at the SVJ poses a significant therapeutic challenge. A case report and review of the literature are presented.     

Increased severity of experimental autoimmune encephalomyelitis,chronic macrophage/microglial reactivity,and demyelination in transgenic mice producing tumor necrosis factor-α in the central nervous system

Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine implicated in a number of autoimmune diseases. Apoptotic cell death is induced by TNF-α in vitro, and has been suggested as one cause of autoimmune pathology, including autoimmune demyelinating diseases where oligodendrocytes are a target of immune attack. TNF-α also regulates macrophage activity which could contribute to autoimmune inflammation. We have expressed TNF-α at disease-equivalent levels in the central nervous system of transgenic mice, using a myelin basic protein (MBP) promoter. These mice were normal and showed no spontaneous pathology, but they developed experimental autoimmune encephalomyelitis (EAE) with greater severity than nontransgenic controls when immunized with MBP in adjuvant. Unlike nontransgenic controls, EAE then progressed to a nonabating demyelinating disease. Macrophage/microglial reactivity was evident in demyelinating lesions in spinal cord, but T cells were not detected during chronic disease. The participation of TNF-α in the demyelinating process is thus more probably due to the perpetuation of macrophage/microglial activation than to direct cytotoxicity of myelin or oligodendroglia.     

Superiority of the EF-120-00-3F biopsy forceps in the histopathological evaluation of upper urinary tract specimens

Purpose

The purpose of this study was to analyze the efficacy of two different biopsy forceps with respect to their functionality and quality for histological assessment of upper urinary tract biopsies.

Methods

We compared flow rates, active deflection angle and histological quality of specimens taken from upper urinary tract biopsies of 40 consecutively treated patients between October 2011 and October 2012. Two different biopsy forceps [group A = 20 patients: “Piranha ^® ” (Boston Scientific, Natick, USA) versus group B = 20 patients: “EF-120-00-3F” (Euromedical GmbH, Siegsdorf, GER)] were assessed.

Results

The specimens obtained with the “EF-120-00-3F” were superior in terms of tissue preservation such as intact urothelium/tissue fragmentation and the prevention of artifacts due to tissue compression (existence of artifacts/nucleus evaluation). Furthermore, due to superiority of tissue preservation, tissues obtained with the “EF-120-00-3F” showed better tissue orientation in the sense of anatomic evaluation of invasion and deep layer involvement. Irrigation flow rates did not differ significantly while deflection angle was more impaired with the “Piranha” biopsy forceps. No difference was observed with the handling of both biopsy forceps.

Conclusions

We conclude that the “EF-120-00-3F” biopsy forceps represent a valuable modification of antegradely insertable instruments that qualifies for improved and correct staging as well as diagnosis of upper urinary specimens in comparison with standard biopsy forcipes.     

Safety and feasibility of elective liver resection in adult Jehovah's Witnesses: the Henri Mondor Hospital experience

Background

Elective liver resection (LR) in Jehovah’s Witness (JW) patients, for whom transfusion is not an option, involves complex ethical and medical issues and surgical difficulties.

Plasma factor VII and thrombin–antithrombin III levels indicate increased tissue factor activity in sickle cell patients

Although the mechanisms involved in the persistent clinical complications of sickle cell disease have not yet been fully delineated, previous studies suggest that sickle cell (HbSS) patients have a disposition to generate more thrombin and plasma in vivo than normal subjects. The reasons for the impaired regulation of haemostasis in HbSS patients is poorly understood. We report studies evaluating the extent to which in vivo coagulation and fibrinolysis are altered in HbSS patients in steady state. The concentrations of total factor VII (F(VII)t), factor VII zymogen (F(VII)z), thrombin-antithrombin III (TAT), fibrinopeptide A(FPA), and fibrin D-dimer in plasmas of 50 normal controls (HbAA) and 45 HbSS steady state patients, were measured using sensitive and specific enzyme-linked immunoassays. The average plasma concentration of F(VII)t, in sickle cell plasma was significantly lower than that of the control subjects (0.70 +/- 0.19 U/ml versus 1.16 +/- 0.41 U/ml), whereas F(VII)z in the patients and controls were 0.47 +/- 0.15 U/ml and 1.15 +/- 0.33 U/ml respectively, P < 0.001. Both measures of factor VII suggest a higher factor VII turnover in sickle cell disease. The mean concentration of TAT in the plasma of HbSS patients were significantly higher than those of HbAA controls (371 +/- 44 pM versus 42 +/- 2 pM) (P < 0.001), a difference that is strongly indicative of higher rates of in vivo thrombin generation by HbSS patients. Plasmas of HbSS patients had significantly higher concentrations of FPA compared to those of the control subjects (12.85 +/- 1.96 ng/ml versus 4.22 +/- 0.37 ng/ml) (P < 0.001). The D-dimer levels were also higher in the HbSS than control plasmas (1029.6 +/- 58.6 ng/ml versus 224.3 +/- 27.6 g/ml) (P < 0.001), with the patients' values being indicative of enhanced fibrinolysis. These results strongly suggest accelerated in vivo coagulation and fibrinolysis in HbSS patients even during steady state. They are consistent with the hypothesis that haemostasis is less tightly regulated in the HbSS patients than in HbAA controls. The altered regulation of haemostasis may contribute to the initiation of vaso-occlusive processes associated with sickle cell painful episodes.     

Open conformation tissue transglutaminase testing for celiac dietary assessment

ObjectivesAnti tissue-transglutaminase antibody is the mainstay of celiac disease serologic testing. Whilst it has high sensitivity in patients on an unrestricted diet, sensitivity is poor for evaluation of gluten free diet adherence.AimTo assess the utility of a novel assay measuring Immunoglobulin-A antibodies to catalytically active open conformation tissue-transglutaminase in assessment of ongoing gluten exposure in celiac disease patients on an alleged gluten free diet.MethodsThrough prospective assessment, 147 patients with celiac disease were divided into good and poor adherence. Open and closed (conventional) tissue-transglutaminase titres were measured using standard enzyme linked immunosorbent assay. 50 patients with inflammatory bowel disease served as disease controls.ResultsOverall 128 patients had been on gluten free diet for more than six months and 19 were found to be poorly adherent on dietary review. Within this group 13 (68.4%) and 10 (52.6%) patients respectively were positive for the open conformation and conventional assay (p = 0.51). Two and one control patients tested positive for closed and open assays respectively.ConclusionsCompared to native assays open conformation tissue-transglutaminase may have higher sensitivity in the poor gluten free diet adherence group and higher specificity in the control population. Larger population studies are warranted to assess whether the open conformation tissue-transglutaminase assay may be superior to the conventional assay.     

Difference in the respiratory variation between pulmonary venous and mitral inflow Doppler velocities in patients with constrictive pericarditis with and without atrial fibrillation

OBJECTIVES: The goal of this study was to evaluate the difference in the respiratory change from expiration to inspiration (%E) between pulsed Doppler mitral inflow (MV) and pulmonary venous flow (PV) velocities in patients with constrictive pericarditis (CP) and to describe the influence of atrial fibrillation (AF). BACKGROUND: The difference in %E between MV and PV velocities as well as the influence of AF on %E has not been well described. METHODS: Pulsed-wave Doppler transesophageal echocardiography (TEE) was performed with respiratory monitoring in 31 patients with CP and sinus rhythm (SR) and in 10 patients with CP and AF. The MV early (E) and late diastolic (A) velocities and their velocity time integral (VTI) as well as PV systolic (S) and diastolic (D) velocities and their VTI were measured. RESULTS: Regardless of the cardiac rhythm: 1) The MV-E velocity and E-VTI as well as PV-D velocity and D-VTI significantly decreased from expiration to inspiration; 2) the %E in PV-D velocity (27% in SR and 35% in AF) and D-VTI (38% in SR and 45% in AF) was significantly greater than that in MV-E velocity (18% in SR and 15% in AF) and E-VTI (21% in SR and 19% in AF), respectively; 3) the PV S/D and S/D-VTI significantly increased from expiration to inspiration. CONCLUSIONS: A significant respiratory variation was observed in both MV and PV velocities in CP, not only in patients with SR but also in those with AF. Moreover, the %E was greater in the PV velocities than it was in the MV velocities. Evaluation of the %E in the PV velocities using TEE can be a sensitive diagnostic strategy for evaluation of patients with CP, even in patients with AF.