Association of C-reactive protein with coronary heart disease risk factors in patients with type 2 diabetes mellitus

The assessment of markers of systemic inflammation, such as C-reactive protein (CRP) and interleukin 6 (IL6), could be used to identify persons at high risk of coronary heart disease (CHD). This study evaluates the relationship of CRP and IL6 with CHD risk factors in patients with type 2 diabetes mellitus (DM) with CHD and age and sex matched type 2 DM controls without CHD. CRP, IL-6, total plasma homocysteine (tHcy), lipoprotein (a) [Lp(a)] and sialic acid (SA) were determined in 55 type 2 diabetic patients with CHD and 51 age- and sex-matched type 2 diabetic controls without CHD. Multivariate and logistic regression analyses were used to relate these markers with CHD risk factors. CRP (P=0.02) and tHcy (P=0.03) were significantly higher in patients with CHD compared with the control group even after correction for age and sex. IL6, Lp(a), SA and lipid parameters were not significantly different between the two groups of patients. After adjustment for potential confounders, the odds ratio (OR) for elevated CRP was 2.00 (95% confidence interval [CI], 1.12-3.58) (P=0.02) but the OR for IL6 was 3.41 95% CI, 0.70-17.17 (P=0.14). Partial correlation analyses of CRP and IL6 with other variables showed significant correlation of CRP with tHcy, and SA in patients with CHD only. Our results support the inclusion of CRP (high-sensitivity assay), in the risk assessment of diabetic subjects.     

Tetraethylammonium: Voltage-dependent action on endplate conductance and inhibition of ligand binding to postsynaptic proteins

Tetraethylammonium (Et(4)N(+)) ions depressed the amplitude and accelerated the decay rate of spontaneously occurring and nerve-evoked endplate currents (EPCs) in frog sartorius muscle. The relationship between peak EPC amplitude and membrane potential became nonlinear in the presence of 100 muM Et(4)N(+), and with drug concentrations of 250 muM or greater the current-voltage relationship exhibited negative conductance in the hyperpolarized region. Et(4)N(+) modified the exponential dependence of the EPC decay on membrane potential such that the decays between -150 and -50 mV were abbreviated and voltage independent but remained near control levels at more positive membrane potentials. The minimal effective concentration of Et(4)N(+) for altering the EPC time course was 10, and maximal effects were attained with 100 muM. Little additional shortening in the EPC decay phase was detected on raising the drug concentration to 1000 muM. Acetylcholine noise analysis revealed a voltage-dependent reduction in the mean channel open time, which was comparable in magnitude to the shortening in the EPC decay, and a depression of single-channel conductance. In concomitant biochemical studies, Et(4)N(+) was found to inhibit the binding of both [(3)H]acetylcholine and [(3)H]perhydrohistrionicotoxin to receptor-rich membranes from the electric organ of Torpedo ocellata with K(i) values of 200 muM and 280 muM, respectively. These results suggest that Et(4)N(+) interacts with both the acetylcholine receptor and its associated ionic channel. The voltage-dependent actions of Et(4)N(+) are attributed to blockade of the ionic channel in closed as well as open conformation.     

No difference in clinical progression between patients infected with the predominant human immunodeficiency virus type 1 circulating recombinant form (CRF) 02_AG strain and patients not infected with CRF02_AG,in Western and West-Central Africa: a four-year prospective multicenter study

To compare human immunodeficiency virus (HIV) type 1 disease progression in patients infected by the predominant strain circulating recombinant form (CRF) 02_AG in western and west-central Africa and in patients infected by other strains, a prospective multicenter cohort study was conducted in Cameroon and Senegal. Among the 335 patients, a broad HIV-1 group M subtype diversity was observed in the envelope V3-V5 region, but strain CRF02_AG predominated in both Cameroon and Senegal (61.2% and 62.9%, respectively; P<.8). Multivariate analyses showed no difference between patients infected by CRF02 strains and those infected by other strains in terms of survival (adjusted hazards ratio [HR], 1.16; 95% confidence interval [CI], 0.76-1.78; P=.5), clinical disease progression (HR, 0.79; 95% CI, 0.50-1.25; P=.3), or square root CD4 cell decline (regression coefficient, -0.01; 95% CI, -0.82 to 0.81; P=.9). This study suggests that the predominance of HIV-1 CRF02_AG strain in western and west-central Africa should have no major clinical consequences.     

Increased incidence of subacute lead perforation noted with one implantable cardioverter-defibrillator.

BACKGROUND: The rapid evolution of implantable cardioverter-defibrillator (ICD) leads has resulted in thinner active fixation leads. While these advances have made the leads more versatile, new configurations may be associated with unforeseen complications. OBJECTIVE: The purpose of this study was to determine the incidence of perforation and dislodgement of defibrillator leads in a single center in the year 2005. METHODS: All patients who underwent percutaneous ICD implantation at the Massachusetts General Hospital using an endocardial right ventricular lead were included in this study. The specific leads analyzed were the Riata (1580/1581 and 1590/1591, St. Jude Medical, St Paul, Minnesota, USA;) and Sprint Fidelis (6949-65, Medtronic, Minneapolis, Minnesota, USA.). Information was collected retrospectively. RESULTS: A total of 130 Riata leads and 111 Sprint Fidelis leads were implanted at the Massachusetts General Hospital during this time period. A total of five lead perforations occurred in patients implanted with the Riata lead as compared with none with the Sprint Fidelis lead (3.8% vs. 0%, respectively; P <.05). Two of the five patients with perforation required pericardiocentesis for tamponade. Clinical symptoms of perforation developed 1-10 days after implant. Moreover, there were five additional lead revisions in the Riata group, which were likely due to dislodgement and/or microperforation, as compared with none in the Sprint Fidelis group (7.7% vs. 0%, respectively; P <.005). CONCLUSIONS: In 2005, at one institution, there were significantly more cardiac perforations and lead revisions with the Riata lead as compared with the Sprint Fidelis right ventricular defibrillator lead. Further data are required to determine whether certain lead characteristics are responsible for this observation.     

Factors affecting error in integration of electroanatomic mapping with CT and MR imaging during catheter ablation of atrial fibrillation

Objective Integration of 3-D electroanatomic mapping with Computed Tomographic (CT) and Magnetic Resonance (MR) imaging is gaining acceptance to facilitate catheter ablation of atrial fibrillation. This is critically dependent on accurate integration of electroanatomic maps with CT or MR images. We sought to examine the effect of patient- and technique-related factors on integration accuracy of electroanatomic mapping with CT and MR imaging of the left atrium. Materials and methods Sixty-one patients undergoing catheter-based atrial fibrillation (AF) ablation procedures were included. All patients underwent cardiac CT (n = 11) or MR (n = 50) imaging, and image integration with real-time electroanatomic mapping of the aorta and left atrium (LA). CARTO-Merge software (Biosense-Webster) was used to calculate the overall average accuracy of integration of electroanatomic points with the CT and MR-derived reconstructions of the LA and aorta. Results There was a significant correlation between LA size assessed by electroanatomic mapping (112 ± 31 ml) and average integration error (1.9 ± 0.6 mm) (r = 0.46, p = 0.0003). There was also greater integration error for patients with LA volume ≥ 110 ml (n = 31) versus < 110 ml (n = 30) (p = 0.004). In contrast, there was no significant association between average integration error and paroxysmal versus persistent AF, left ventricular ejection fraction, days from imaging to electroanatomic mapping, or images derived from CT versus MR. Conclusions Patients with larger LA volume may be prone to greater error during integration of electroanatomic mapping with CT and MR imaging. Strategies to reduce integration error may therefore be especially useful in patients with large LA volume.     

Minireview: recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners

Glucose transporter (GLUT) 4 is the major glucose transporter of muscle and adipose cells, exquisitely regulated by insulin through posttranslational events. Twenty years after the seminal observations that GLUT4 levels rapidly rise at the plasma membrane (PM) and drop in endomembranes in response to an acute insulin challenge, we are still mapping the intracellular traffic of the transporter and the regulatory events that insulin unleashes. Newly synthesized GLUT4 enters an insulin-responsive compartment aided by GGA2 (an Arf-binding protein). In cultured adipocytes and myocytes, GLUT4 concentrates in a perinuclear pole through participation of microtubules and the EHD1 Eps15 homology domain-containing protein 1. In the absence of stimuli, GLUT4 distributes between recycling endosomes and the insulin-responsive compartment. A handful of proteins that bind to GLUT4 appear to regulate its half-life (e.g. Ubc9) and tethering within endomembranes (e.g. TUG). Insulin-derived signals promote not only GLUT4 mobilization toward the PM but also its traffic between endosomal compartments and internalization from the PM. Class IA phosphatidylinositol (PI) 3-kinase plays a pivotal role at several steps of GLUT4 mobilization. The PI 3-kinase --> atypical PKC and --> Akt/PKB --> AS160 signaling cascades are major regulators of GLUT4 exocytosis aided by small GTPases. At the cell periphery, GLUT4-containing vesicles tether, dock, and fuse with the PM assisted by the exocyst complex followed by engagement of a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex [with vesicle-associated membrane protein (VAMP)2 as the vesicular (v)-SNARE and soluble NSF-attachment protein (SNAP)23 and syntaxin4 as target (t)-SNAREs] regulated by the accessory proteins Munc18c, Synip and Tomosyn. Vesicle tethering and fusion are regulated by insulin through input from class IA PI 3-kinase.     

Decreased Intrinsic Factor Secretion in AIDS: Relation to Parietal Cell Acid Secretory Capacity and Vitamin B12 Malabsorption

AIDS-associated gastric secretory failure has been characterized by decreased secretion of acid, pepsin, and gastric juice volume. To determine whether decreased intrinsic factor secretion and vitamin B12 malabsorption occur in this entity, we performed prospective measurements of maximal acid output, intrinsic factor output, vitamin B12 absorption, serum vitamin B12, and holotranscobalamin II in 10 consecutive AIDS patients. Four of 10 patients had low maximal acid output, i.e., < or = 1.5 mEq/h (control = 12.8 +/- 9.0, range 2.5-25 mEq/h). Four patients had low intrinsic factor output, i.e., < or = 1.1 microgram/h (control = 8.2 +/- 6.9, range 3.1-19.4 micrograms/h). One patient with low intrinsic factor output had low serum vitamin B12 and a Schilling test consistent with pernicious anemia. A second patient with very low intrinsic factor output (0.16 micrograms/h) had low parts I and II Schilling tests; malabsorption most likely resulted from both low intrinsic factor secretion and ileal disease. One of three vitamin B12 malabsorbing patients, with normal serum vitamin B12, had low holotranscobalamin II, 25 pg/ml (control holotranscobalamin II = 76 +/- 44, range 44-152 pg/ml). Maximal acid output and intrinsic factor output did not correlate in AIDS (r = 0.36, p = 0.30) in contrast to the expected correlation in controls (r = 0.91, p = 0.03). We conclude that low intrinsic factor secretion is common in AIDS and contributes to vitamin B12 malabsorption. Decreased parietal cell secretion of intrinsic factor and acid may occur independently in human immunodeficiency virus-associated gastric secretory failure. Low holotranscobalamin II, an early manifestation of vitamin B12 malabsorption, results in decreased delivery to vitamin B12-dependent tissues prior to depletion of serum vitamin B12. Regular supplementation with vitamin B12 may therefore be warranted in patients with advanced HIV infection.     

Impact of the driving pressure on mortality in obese and non-obese ARDS patients: a retrospective study of 362 cases

Purpose

The relation between driving pressure (plateau pressure-positive end-expiratory pressure) and mortality has never been studied in obese ARDS patients. The main objective of this study was to evaluate the relationship between 90-day mortality and driving pressure in an ARDS population ventilated in the intensive care unit (ICU) according to obesity status.

Methods

We conducted a retrospective single-center study of prospectively collected data of all ARDS patients admitted consecutively to a mixed medical-surgical adult ICU from January 2009 to May 2017. Plateau pressure, compliance of the respiratory system (Crs) and driving pressure of the respiratory system within 24 h of ARDS diagnosis were compared between survivors and non-survivors at day 90 and between obese (body mass index?≥?30 kg/m²) and non-obese patients. Cox proportional hazard modeling was used for mortality at day 90.

Results

Three hundred sixty-two ARDS patients were included, 262 (72%) non-obese and 100 (28%) obese patients. Mortality rate at day 90 was respectively 47% (95% CI, 40–53) in the non-obese and 46% (95% CI, 36–56) in the obese patients. Driving pressure at day 1 in the non-obese patients was significantly lower in survivors at day 90 (11.9?±?4.2 cmH₂O) than in non-survivors (15.2?±?5.2 cmH₂O, p?<?0.001). Contrarily, in obese patients, driving pressure at day 1 was not significantly different between survivors (13.7?±?4.5 cmH₂O) and non-survivors (13.2?±?5.1 cmH₂O, p?=?0.41) at day 90. After three multivariate Cox analyses, plateau pressure [HR?=?1.04 (95% CI 1.01–1.07) for each point of increase], Crs [HR?=?0.97 (95% CI 0.96–0.99) for each point of increase] and driving pressure [HR?=?1.07 (95% CI 1.04–1.10) for each point of increase], respectively, were independently associated with 90-day mortality in non-obese patients, but not in obese patients.

Conclusions

Contrary to non-obese ARDS patients, driving pressure was not associated with mortality in obese ARDS patients.