Interleukin-6 and interleukin-6 promoter polymorphism (-174) G > C in patients with spontaneous venous thromboembolism

Increased levels of interleukin-6 (IL-6) have been reported in patients with a history of venous thromboembolism (VTE); however, prospective studies did not confirm an association between inflammatory markers that are highly correlated with IL-6 and the risk ofVTE. It was the aim of our study to investigate the association of IL-6 and its promoter polymorphism (-174) G > C with the risk of spontaneousVTE. IL-6 was measured in 128 patients with deep venous thrombosis (DVT,70 w/58 m),105 with pulmonary embolism (PE, 58 w/47 m) and 122 healthy controls (60 w/62 m) with a highly sensitive ELISA (Quantikine HS Human IL-6 Immunoassay, RnDSystems). The promoter polymorphism was determined by genotyping, allele specific PCR was followed by high resolution gel-electrophoresis. Median concentrations [interquartile ranges] were 2.37 [1.51-3.89] (pg/ml) in patients with DVT, 2.83 [1.83-4.87] in those with PE and 2.51 [1.71-4.78] in controls (p = 0.6, p = 0.4). Hetero- or homozygous carriers of the C allele (71% in DVT, 67% in PE and 59% among controls) did not have higher IL-6 levels than homozygous carriers of the G allele (median 2.60 vs. 2.59 pg/ml, p = 0.7). In conclusion, we found no association of IL-6 and its promoter polymorphism (-174) G > C with the risk of spontaneous VTE.     

Contribution of thromboxane a₂ in rat common carotid artery response to serotonin

Serotonin is a vasoactive substance that in different blood vessels mostly induces vasoconstriction. Considering the important role of common carotid artery in brain blood supply, the aims of this study were to investigate the effect of serotonin on isolated rat common carotid artery and also to examine participation of intact endothelium, cyclooxygenase products, Ca(++) channels and 5-HT(2) receptors in serotonin-evoked action. Endothelium was mechanically removed from some vascular rings. Circular artery segments were placed in organ baths containing KrebsaRinger bicarbonate solution. Cumulative concentration-contraction curves for serotonin were obtained in rings previously equilibrated at basal tone. Serotonin produced concentration-dependent contraction, which was unaltered by endothelial denudation. Serotonin-induced effect was notably and comparably reduced by indomethacin (cyclooxygenase inhibitor) or OKYa046 (thromboxane A(2)-synthase inhibitor) on intact or denuded rings. Nifedipine (Ca(++) channel blocker) or ketanserin (5-HT(2) receptor antagonist) strongly reduced serotonin-evoked effect. Our results suggest that serotonin produced concentration-dependent and endothelium-independent contraction of carotid artery, which was initiated by activation of 5-HT(2) receptors located on smooth muscle cells and mediated via L-type Ca(++) channels. Thromboxane A(2) from smooth muscle cells notably contributed to the overall contraction of carotid artery induced by serotonin.     

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy

Polyomavirus BK (BKV) is the cause of polyomavirus‐associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.     

Race/ethnicity,nativity, and lifetime risk of mental disorders in US adults

Social Psychiatry and Psychiatric Epidemiology - There has been no comprehensive examination of how race/ethnicity and nativity intersect in explaining differences in lifetime prevalence of mental...     

Treatment and outcome of subdural hematoma in patients with spontaneous intracranial hypotension: a report of 35 cases

Spontaneous intracranial hypotension (SIH) is characterized by orthostatic headache, low CSF pressure and diffuse pachymeningeal enhancement on brain MRI. SIH results from spontaneous CSF leakage leading to brain sag. Sometimes, tearing of bridging veins may produce subdural hematomas (SDHs). Patients with SDH were identified retrospectively from 212 consecutive SIH patients. Data were collected on demographics, clinical courses, neuroimaging findings, treatment and outcome of SDH. Thirty-five patients (16%), (6 women, 29 men; aged 33–68; mean, 50 years) with SDH were recruited. They were divided into two groups: initially withSIH diagnosed (n = 29) and undiagnosed (n = 6). After conservative treatment, the first group underwent a lumbar epidural blood patch (EBP) (n = 27) and emergent evacuation of symptomatic SDH (n = 2). After EBP, ten patients had enlarged SDH. Nine of them underwent evacuation of symptomatic SDH with mass effect (ME). In the second group, three patients with clinical worsening from SIH underwent, erroneously, evacuation of mild SDH. They worsened after the evacuation; after SIH diagnosis was made, they underwent one EBP (n = 2) and three EBPs (the patient with coma). The other three cases with symptomatic SDH with ME underwent evacuation with recurrence of SDH (n = 2). All 35 patients enjoyed a good outcome. If conservative treatment is insufficient, EBP should be performed prior to hematoma irrigation. When an emergent evacuation is necessary before EBP, it is preferable to perform, after surgery, one early EBP before the patient gets up to prevent frequent recurrences of SDH by underlying CSF leakage.     

Influence of farnesol on the morphogenesis of Aspergillus niger

Farnesol was the first quorum-sensing regulator to be found in eukaryotic cells. In Candida albicans, a dimorphic fungal human pathogen, farnesol blocks the yeast-to-filamentous growth transition. Here we show that in Aspergillus niger farnesol acts as an inhibitor of conidiation: Colonies grown on media containing farnesol were unable to develop conidia. Although farnesol treated A. niger cultures exhibited a colony morphology resembling the "fluffy" phenotype of A. nidulans, which is caused by a hyperactive G-protein/cAMP pathway, the intracellular level of cAMP in A. niger mycelia grown in presence of farnesol is greatly diminished. Furthermore, whereas inhibiting adenylyl cyclase led to a farnesol-like effect, the addition of external cAMP inhibited conidiation without causing a "fluffy" phenotype. This suggests that the mechanisms regulating conidiation in A. niger and A. nidulans are different.     

Adaptive support ventilation versus conventional ventilation for total ventilatory support in acute respiratory failure

Objective

To compare the short-term effects of adaptive support ventilation (ASV), an advanced closed-loop mode, with conventional volume or pressure-control ventilation in patients passively ventilated for acute respiratory failure.

Design

Prospective crossover interventional multicenter trial.

Setting

Six European academic intensive care units.

Patients

Eighty-eight patients in three groups: patients with no obvious lung disease (n = 22), restrictive lung disease (n = 36) or obstructive lung disease (n = 30).

Interventions

After measurements on conventional ventilation (CV) as set by the patients’ clinicians, each patient was switched to ASV set to obtain the same minute ventilation as during CV (isoMV condition). If this resulted in a change in PaCO₂, the minute ventilation setting of ASV was readjusted to achieve the same PaCO₂ as in CV (isoCO₂ condition).

Measurements and results

Compared with CV, PaCO₂ during ASV in isoMV condition and minute ventilation during ASV in isoCO₂ condition were slightly lower, with lower inspiratory work/minute performed by the ventilator (p < 0.01). Oxygenation and hemodynamics were unchanged. During ASV, respiratory rate was slightly lower and tidal volume (Vt) slightly greater (p < 0.01), especially in obstructed patients. During ASV there were different ventilatory patterns in the three groups, with lower Vt in patients with restrictive disease and prolonged expiratory time in obstructed patients, thus mimicking the clinicians’ choices for setting CV. In three chronic obstructive pulmonary disease patients the resulting Vt was unacceptably high.

Conclusions

Comparison between ASV and CV resulted either in similarities or in minor differences. Except for excessive Vt in a few obstructed patients, all differences were in favor of ASV.