Prediction of Heparin Induced Thrombocytopenia (HIT) Using a Combination of 4Ts Score and Screening Immune Assays.

Clinical assessment (4Ts) followed by testing for Heparin/platelet factor 4 (HPF4) antibody in intermediate and high risk patients is the standard algorithm of pretest for Heparin induced thrombocytopenia (HIT), and the diagnosis is confirmed by serotonin releasing assay (SRA) in those who have positive antibodies. We conducted a retrospective analysis in a cohort of patients treated in a community hospital who had HIT antibody test by either ELISA or a rapid Particle Immunofiltration Assay (PIFA), regardless of their 4Ts scores. Among 224 patients, 17 had HIT. The PPV for those with a 4 T score ≥4 was 10.4%, which misdianosed 3 patients with HIT who tested positive for antibodies. Combining 4 T score ≥4 AND positive HIT antibody showed a PPV of 20.3% and a sensitivity of 70.6%, misdiagnosing 5 HIT patients. Using 4Ts ≥4 OR positive HIT antibody showed 100% sensitivity and 100% negative predictive value (NPV). The ELISA test had 100% sensitivity and 100% NPV, while the PIFA test missed 2 HIT patients, with sensitivity of 60% and NPV of 96.7%. Our results suggest that SRA testing should be conducted if a patient presents with a 4 T score ≥4 OR a positive HIT antibody, and antibody tests should be conducted for every patient suspected of HIT.

Preliminary noise reduction efforts in a medical intensive care unit.

Noise is a significant contributor to sleep disruption in the intensive care unit (ICU) that may result in increased patient morbidity such as delirium and prolonged length of stay in ICU. We conducted a pre-post intervention study in a 24-bed tertiary care academic medical ICU to reduce the mean noise levels. Baseline dosimeter recordings of ICU noise levels demonstrated a mean noise level of 54.2 A-weighted decibels (dBA) and peak noise levels of 109.9 dBA, well above the Environmental Protection Agency's recommended levels. There were 1735 episodes of "defects" (maximum noise levels > 60 dBA). Following implementation of multipronged interventions, although the mean noise levels did not change significantly between pre- and post-intervention (54.2 vs 53.8 dBA; p = 0.96), there was a significant reduction in the number of "defects" post-intervention (1735 vs 1289, p ≤ 0.000), and the providers felt that the patients were sleeping longer in the ICU post-intervention.

Assessing and predicting the likelihood of interventions during routine annual follow-up visits for management of obstructive sleep.

STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) on established positive airway pressure (PAP) treatment are often advised routine annual follow-up visits to assess ongoing effectiveness and address problems associated with therapy. This study evaluates the clinical utility of annual face-to-face follow-up visits. DESIGN: We performed a retrospective chart review of OSA patients on PAP who had completed a routine annual follow-up visit. Demographics, polysomnography, PAP compliance, Epworth Sleepiness Scale (ESS), subjective complaints (efficacy and interface issues, equipment malfunction, prescription renewal), objective findings (efficacy or leak issues, equipment problems), and visit-specific interventions were recorded. We determined relationships between patient provided information and likelihood of therapeutic versus administrative interventions. SETTING: Academic sleep center. MEASUREMENTS AND RESULTS: Among 716 patients who met study criteria, we abstracted data on 180 randomly selected patients. On multivariate analyses, only subjective complaints or objective findings by providers were associated with a therapeutic intervention (p < 0.0001). Though most patients (55 of 63 patients, 87.3%) who required therapeutic interventions had objective findings, without subjective complaints, the odds of such findings were only 0.12 (95% CI = 0.06-0.24, p < 0.0001). Without subjective complaints, the likelihood of a therapeutic intervention was 0.07 (95% CI = 0.03-0.15, p < 0.001). CONCLUSION: Our data suggests that in the absence of a subjective complaint, an annual follow-up is more likely to require administrative rather than face-to-face clinical intervention. Designing a clinic model to account for this might reduce resource utilization. However, the value and optimal timing of "routine" annual follow-up visits requires further evaluation.

Periodic limb movements during sleep and their effect on the cardiovascular system: is there a final answer?

Periodic limb movements during sleep (PLMS) is a sleep-related movement disorder characterized by repetitive limb movements during sleep, seen predominantly in the legs but also occasionally involving the arms. These movements may be associated with arousals that can lead to increases in sympathetic tone, resulting in tachycardia and elevated systolic blood pressure. Chronic sustained tachycardia and elevated systolic blood pressure are known to be associated with the development of arrhythmias, hypertension, left ventricular hypertrophy, and congestive heart failure. However, the data are not entirely clear on whether untreated PLMS is associated with these cardiovascular risks. This review examines the current evidence on whether PLMS has any effect on the cardiovascular system.

Molecular and functional asymmetry at a vertebrate electrical synapse.

Electrical synapses are abundant in the vertebrate brain, but their functional and molecular complexities are still poorly understood. We report here that electrical synapses between auditory afferents and goldfish Mauthner cells are constructed by apposition of hemichannels formed by two homologs of mammalian connexin 36 (Cx36) and that, while Cx35 is restricted to presynaptic hemiplaques, Cx34.7 is restricted to postsynaptic hemiplaques, forming heterotypic junctions. This molecular asymmetry is associated with rectification of electrical transmission that may act to promote cooperativity between auditory afferents. Our data suggest that, in similarity to pre- and postsynaptic sites at chemical synapses, one side in electrical synapses should not necessarily be considered the mirror image of the other. While asymmetry based on the presence of two Cx36 homologs is restricted to teleost fish, it might also be based on differences in posttranslational modifications of individual connexins or in the complement of gap junction-associated proteins.

Effect of obstructive sleep apnea on type 2 diabetes mellitus: A comprehensive literature review.

Obstructive sleep apnea (OSA) is frequently associated with obesity and metabolic syndrome. Also frequently associated with metabolic syndrome is type 2 diabetes mellitus (T2DM). Therefore, it is common to find OSA and T2DM together in individuals with metabolic syndrome. Additionally, both OSA and T2DM have a common pathophysiological link with development of insulin resistance. Individuals with severe insulin resistance are likely to have inadequate glycemic control. Long standing poorly controlled T2DM is associated with debilitating microvascular complications such as retinopathy, nephropathy, neuropathy and macrovascular complications such as coronary artery and cerebrovascular disease. There is extensively published literature exploring the cause-effect relationship between OSA and T2DM. In this article we provide an in-depth review of the complex pathophysiological mechanisms linking OSA to T2DM. Specifically, this review focusses on the effect of OSA on the microvascular complications of T2DM such as retinopathy, nephropathy and neuropathy. Additionally, we review the current literature on the effect of continuous positive airway pressure use in individuals with T2DM and OSA.

Trafficking of gap junction channels at a vertebrate electrical synapse in vivo.

Trafficking and turnover of transmitter receptors required to maintain and modify the strength of chemical synapses have been characterized extensively. In contrast, little is known regarding trafficking of gap junction components at electrical synapses. By combining ultrastructural and in vivo physiological analysis at identified mixed (electrical and chemical) synapses on the goldfish Mauthner cell, we show here that gap junction hemichannels are added at the edges of GJ plaques where they dock with hemichannels in the apposed membrane to form cell-cell channels and, simultaneously, that intact junctional regions are removed from centers of these plaques into either presynaptic axon or postsynaptic dendrite. Moreover, electrical coupling is readily modified by intradendritic application of peptides that interfere with endocytosis or exocytosis, suggesting that the strength of electrical synapses at these terminals is sustained, at least in part, by fast (in minutes) turnover of gap junction channels. A peptide corresponding to a region of the carboxy terminus that is conserved in Cx36 and its two teleost homologs appears to interfere with formation of new gap junction channels, presumably by reducing insertion of hemichannels on the dendritic side. Thus, our data indicate that electrical synapses are dynamic structures and that their channels are turned over actively, suggesting that regulated trafficking of connexons may contribute to the modification of gap junctional conductance.

Variability of distribution of Ca(2+)/calmodulin-dependent kinase II at mixed synapses on the mauthner cell: colocalization and association with connexin 35.

In contrast to chemical transmission, few proteins have been shown associated with gap junction-mediated electrical synapses. Mixed (electrical and glutamatergic) synaptic terminals on the teleost Mauthner cell known as "Club endings" constitute because of their unusual large size and presence of connexin 35 (Cx35), an ortholog of the widespread mammalian Cx36, a valuable model for the study of electrical transmission. Remarkably, both components of their mixed synaptic response undergo activity-dependent potentiation. Changes in electrical transmission result from interactions with colocalized glutamatergic synapses, the activity of which leads to the activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII), required for the induction of changes in both forms of transmission. However, the distribution of this kinase and potential localization to electrical synapses remains undetermined. Taking advantage of the unparalleled experimental accessibility of Club endings, we explored the presence and intraterminal distribution of CaMKII within these terminals. Here we show that (1) unlike other proteins, both CaMKII labeling and distribution were highly variable between contiguous contacts, and (2) CaMKII was not restricted to the periphery of the terminals, in which glutamatergic synapses are located, but also was present at the center in which gap junctions predominate. Accordingly, double immunolabeling indicated that Cx35 and CaMKII were colocalized, and biochemical analysis showed that these proteins associate. Because CaMKII characteristically undergoes activity-dependent translocation, the observed variability of labeling likely reflects physiological differences between electrical synapses of contiguous Club endings, which remarkably coexist with differing degrees of conductance. Together, our results indicate that CaMKII should be considered a component of electrical synapses, although its association is nonobligatory and likely driven by activity.

The yeast dynamin-like protein Vps1:vps1 mutations perturb the internalization and the motility of endocytic vesicles and endosomes via disorganization of the actin cytoskeleton.

Mammalian dynamin is responsible for scission of endocytic vesicles from the plasma membrane. A previous study showed that Vps1, a yeast dynamin-like protein, plays an important role in pheromone receptor internalization (Yu and Cai, 2004; J. Cell Sci. 117, 3839-3853). However, the details of how Vps1 acts in various phases of endocytosis including early internalization of the endocytic vesicle are poorly understood. To investigate the potential roles of Vps1 in both endocytic vesicle formation/maturation on the plasma membrane and endocytic vesicle internalization, time-lapse fluorescent images of GFP-tagged endocytic markers in live cells were analyzed using a particle tracking software. The loss of Vps1 leads to a robust increase in the lifespan of newly forming cortical endocytic vesicles carrying Las17-GFP, Ede1-GFP, Sla1-GFP, and Abp1-GFP, indicating that Vps1 is required for the proper assembly and maturation of endocytic vesicles. Particle track analysis revealed that Abp1-GFP vesicles in vps1 null cells moved a relatively short distance away from the cell membrane due to their non-directional movement. Furthermore, we found that the GTPase and the GED domains of Vps1 are required for the proper endocytic function of Vps1. Our tracking analysis data also revealed that the post-internalized vesicle motility en route to the vacuole was decreased significantly, perhaps due to severe disruption of the actin cables in Vps1 mutant cells.

Elevated B-type natriuretic peptide level: use with caution in patients with multiple co-morbidities and presenting with dyspnea.

BACKGROUND AND AIM: While the effect of age, gender, body mass index and renal failure on B-type natriuretic peptide (BNP) has been studied individually in different trials, the influence of all these co-morbidities in patients with dyspnea needs to be evaluated. The objective of our study was to examine the effect of age, gender, obesity and co-morbid conditions on the evaluation of higher BNP levels in patients presenting with dyspnea. METHODS: A total of 382 patients admitted with shortness of breath and suspected to have congestive heart failure were included in the study. The co-morbid conditions studied were pulmonary hypertension, pleural effusion, obesity, renal failure and chronic obstructive pulmonary disease. RESULTS: The mean BNP levels significantly increased with age. Women tended to have slightly higher mean BNP levels than men, but the differences were not statistically significant. The body mass index had an inverse correlation with the BNP level. Regression analysis demonstrated that the most significant predictors of a higher BNP were the lower left ventricular ejection fraction (OR 6.2: 95% CI 2.74-14.02), renal failure (OR 3.88: 95% CI 1.9-7.91) and pulmonary hypertension (OR 2.28: 95% CI 1.14-4.54). CONCLUSION: A lower left ventricular ejection fraction, renal failure and pulmonary hypertension were the most significant predictors of an increased BNP level. Age, gender, obesity and pleural effusion minimally influenced the BNP level and were not significantly predictive of congestive heart failure.