Increased incidence of life-threatening ventricular arrhythmias in implantable defibrillator patients after the World Trade Center attack

OBJECTIVES: This study was designed to evaluate whether the destruction of the World Trade Center (WTC) on September 11, 2001 (9/11), led to an increased frequency of ventricular arrhythmias among patients fitted with an implantable cardioverter-defibrillator (ICD). BACKGROUND: The WTC attack induced psychological distress. Because ICDs store all serious arrhythmias for months, the attack provided a unique opportunity to compare pre- and post-9/11 frequencies of potentially lethal arrhythmias among ICD patients. METHODS: Two hundred consecutive ICD patients who presented for regularly scheduled follow-up to six affiliated clinics were recruited into this observational study. The electrograms stored in the ICDs for the three months before 9/11 and 13 months thereafter were scrutinized in a blinded manner (relative to date) for all ventricular tachyarrhythmias (tachycardia or fibrillation) triggering ICD therapy. RESULTS: The frequency of tachyarrhythmias increased significantly for the 30 days post-9/11 (p = 0.004) relative to all other months between May 2001 and October 2002. In the 30 days post-9/11, 16 patients (8%) demonstrated tachyarrhythmias, compared with only seven (3.5%) in the preceding 30 days, representing a 2.3-fold increase in risk (95% confidence interval 1.1 to 4.9; p = 0.03). The first arrhythmic event did not occur for three days following 9/11, with events accumulating in a progressive non-clustered pattern. CONCLUSIONS: Ventricular arrhythmias increased by more than twofold among ICD patients following the WTC attack. The delay in onset and the non-clustered pattern of these events differ sharply from effects following other disasters, suggesting that subacute stress may have served to promote this arrhythmogenesis.     

Effects of vasoactive intestinal peptide and pancreatic polypeptide on small bowel propulsion in the rat

Vasoactive intestinal peptide (VIP) and the newly discovered pancreatic polypeptide (PP), both having been proposed as pathogenetic factors in the watery diarrhea syndrome (WDRA), were intravenously infused into rats in order to study the effect on small bowel propulsion. Simultaneously with the infusion of hormone, radioactive test substance was continuously infused into the duodenum of the conscious animal through a permanent catheter. By recording the distribution of radioactivity along the excised gastrointestinal tract, analyses of small bowel propulsion were possible. After infusion of VIP small bowel transit time was significantly prolonged, and the local propagation velocity was retarded both in the proximal and the distal part of the small bowel. PP did not alter small bowel populations. The heavily retarded transport rate after VIP is a propulsive dysfunction and not inconsistent with the clinical sign of diarrhea.     

Exposure–response for biomarkers of anticoagulant effects by the oral direct thrombin inhibitor AZD0837 in patients with atrial fibrillation

AimsAZD0837 is a novel oral anticoagulant investigated in clinical studies for stroke prevention in patients with atrial fibrillation (AF). It is bioconverted to its active form, AR‐H067637, a potent, specific and reversible thrombin inhibitor. The effects on coagulation biomarkers were correlated with the pharmacokinetic (PK) exposure of AR‐H067637 to guide selection of the effective dose regimen for a confirmatory efficacy study in AF patients.MethodsBlood samples were obtained from 601 AF patients randomized to one of four doses of AZD0837 (blinded treatment) or dose‐adjusted vitamin K antagonists (VKA, open treatment) for 3–9 months. A pharmacodynamic model was developed to describe the time course of the AR‐H067637 exposure dependent effects and the effect of VKA on fibrin D‐dimer. The thrombin generation measured ex vivo in venous plasma was also investigated.ResultsThe PK exposure of AR‐H067637 was stable with an interindividual variability of 33% and no or minor influence of patient demographics or comedications. For AZD0837, D‐dimer levels decreased with more rapid onset than for VKA. The decrease in D‐dimer levels correlated with steady‐state plasma concentrations (C _ss) of AR‐H067637, with a maximum decrease of baseline D‐dimer levels estimated to approximately 60% for both AZD0837 and VKA therapy. The effect on thrombin generation correlated closely with the plasma concentration of AR‐H067637.ConclusionsThe effects on thrombin generation and fibrin D‐dimer levels correlated with the plasma concentration of its active form and provided comparable effects to well‐controlled VKA therapy at an exposure at least corresponding to the 300 mg once daily dose of AZD0837.     

Physical Functioning,Mental Health,and Quality of Life in Different Congenital Heart Defects: Comparative Analysis in 3538 Patients From 15 Countries

BackgroundWe compared physical functioning, mental health, and quality of life (QoL) of patients with different subtypes of congenital heart disease (CHD) in a large international sample and investigated the role of functional class in explaining the variance in outcomes across heart defects.MethodsIn the cross-sectional Assessment of Patterns of Patient-Reported Outcome in Adults with Congenital Heart Disease-International Study (APPROACH-IS), we enrolled 4028 adult patients with CHD from 15 countries. Diagnostic groups with at least 50 patients were included in these analyses, yielding a sample of 3538 patients (median age: 32 years; 52% women). Physical functioning, mental health, and QoL were measured with the SF-12 health status survey, Hospital Anxiety and Depression Scale (HADS), linear analog scale (LAS) and Satisfaction with Life Scale, respectively. Functional class was assessed using the patient-reported New York Heart Association (NYHA) class. Multivariable general linear mixed models were applied to assess the relationship between the type of CHD and patient-reported outcomes, adjusted for patient characteristics, and with country as random effect.ResultsPatients with coarctation of the aorta and those with isolated aortic valve disease reported the best physical functioning, mental health, and QoL. Patients with cyanotic heart disease or Eisenmenger syndrome had worst outcomes. The differences were statistically significant, above and beyond other patient characteristics. However, the explained variances were small (0.6% to 4.1%) and decreased further when functional status was added to the models (0.4% to 0.9%).ConclusionsSome types of CHD predict worse patient-reported outcomes. However, it appears that it is the functional status associated with the heart defect rather than the heart defect itself that shapes the outcomes.     

Controlled treatment of primary hypertension with propranolol and spironolactone: A crossover study with special reference to initial plasma renin activity

Twenty-seven patients with hypertension were randomly allocated to a 10 month crossover study. Treatment consisted of spironolactone (200 mg/day for 2 months), propranolol (320 mg/day for 2 months) and combined administration of both drugs at half the dosage. Between treatment periods placebo was given for 2 months. Fourteen patients were previously untreated. The average pretreatment blood pressure for the entire group was 188/114 ± 16/7 (mean ± standard deviation) mm Hg supine and 188/118 ± 20/9 mm Hg standing. Both spironolactone and propranolol reduced blood pressure significantly in both the supine and standing positions.Upright plasma renin activity was determined by radioimmunoassay of angiotensin I. The average initial level was 1.9 ± 1.2 (range 0.4 to 5.0) ng/ml/hr. There was a close correlation between plasma renin activity and the effects of the drugs: With increasing renin level the response to propranolol was better whereas the opposite was true for spironolactone. The combination of spironolactone and propranolol decreased the blood pressure still further in the supine and standing positions, irrespective of initial plasma renin activity. All patients achieved a normal supine pressure. Blood pressure and plasma renin activity returned toward pretreatment values during placebo administration. It is concluded that pretreatment levels of plasma renin activity can predict the antihypertensive response to propranolol and spironolactone. The combination of the two drugs, which have different modes of action, will effectively reduce blood pressure in hypertension. The results support the concept that the renin-angiotensin-aldosterone system may be involved in primary hypertension.     

Granzyme D Is a Novel Murine Mast Cell Protease That Is Highly Induced by Multiple Pathways of Mast Cell Activation

Granzymes are serine proteases known mostly for their role in the induction of apoptosis. Granzymes A and B have been extensively studied, but relatively little is known about granzymes C to G and K to M. T cells, lymphohematopoietic stromal cells, and granulated metrial gland cells express granzyme D, but the function of granzyme D is unknown. Here we show that granzyme D is expressed by murine mast cells and that its level of expression correlates positively with the extent of mast cell maturation. Coculture of mast cells with live, Gram-positive bacteria caused a profound, Toll-like receptor 2 (TLR2)-dependent induction of granzyme D expression. Granzyme D expression was also induced by isolated bacterial cell wall components, including lipopolysaccharide (LPS) and peptidoglycan, and by stem cell factor, IgE receptor cross-linking, and calcium ionophore stimulation. Granzyme D was released into the medium in response to mast cell activation. Granzyme D induction was dependent on protein kinase C and nuclear factor of activated T cells (NFAT). Together, these findings identify granzyme D as a novel murine mast cell protease and implicate granzyme D in settings where mast cells are activated, such as bacterial infection and allergy.     

Swedish Universities Scales of Personality: Relation to Other Personality Instruments

ObjectiveTo investigate associations between Swedish universities Scales of Personality (SSP) and scales of the following personality instruments: Structured Clinical Interview for DSM-III-R axis II screening questionnaire (SCID-II screen), revised NEO personality inventory (NEO-PI-R), revised Chapman scales (Chapman) and the psychotic traits questionnaire (STQ). MethodsHealthy individuals (n=406) completed self-report personality questionnaires including SSP and at least one more personality inventory. Correlations were calculated between the 13 different SSP subscales as well as SSP’s three factors and factors and scales/subscales in SCID-II screen, NEO-PI-R, Chapman and STQ. The main factors of the various instruments were factor analysed. ICC were calculated. ResultsSSP Neuroticism factor correlated with SCID-II cluster C (r=0.71), NEO Neuroticism (r=0.80) and Chapman Social anhedonia (r=0.62). SSP Extraversion factor correlated with NEO Extraversion (r=0.63) and SSP Aggressiveness factor with NEO Agreeableness (r=-0.62). Strong correlations between SSP factors and scales and scales of the other instruments were sparse, although weaker correlations were common. ConclusionSSP is a useful investigation tool when measuring personality traits related to temperament-like features. SSP partly correlates well to especially three of the NEO-PI-R factors. The different personality inventories are not completely comparable to each other. Instead, they measure personality aspects in partly different ways.