Optimizing the detection of bidirectional block across the flutter isthmus for patients with typical isthmus-dependent atrial flutter

The purpose of this study was to show that multipolar electrographic recordings along the subeustachian isthmus (SI) can better differentiate slow conduction from complete isthmus block after atrial flutter ablation, leading to a lower incidence of recurrent atrial flutter (Afl). Despite the presence of various techniques to identify bidirectional conduction block (BDB) after isthmus ablation for typical Afl, several studies, including a report from a national registry, suggest that radiofrequency ablation is still associated with a 15% recurrence rate. Thus, techniques that can distinguish slow conduction from complete isthmus block have the potential for reducing long-term recurrences. We evaluated patients who underwent radiofrequency ablation for typical isthmus-dependent Afl. Patients were separated into 2 groups. Group A underwent assessment of BDB with conventional methods. In group B, BDB was assessed by placing a multipolar catheter along the floor of the SI, pacing adjacent to the line of radiofrequency application, and assessing electrographic activation on either side. One hundred thirty-one cases of Afl ablation were analyzed (86 in group A, 45 in group B). Over a mean follow-up period of 17 months, recurrence rates of Afl were 16.5% in group A and 4.3% in group B (p = 0.043). Thus, assessment of BDB by placement of a multipolar catheter across the SI after ablation of typical Afl is associated with a significant reduction in long-term recurrence of Afl.     

Hypoxia inducible factor 1 alpha regulates T cell receptor signal transduction

Low oxygen pressures exist in many solid tissues, including primary and secondary lymphoid organs. One key element in cellular adaptation to hypoxia is induced expression of hypoxia inducible factor (Hif) 1alpha. Here, we have examined the effect of Hif-1alpha, isolated from the myriad other effects of hypoxia, on T cell receptor (TCR) signaling in thymocytes. Because pVHL (von Hippel-Lindau protein) directs the proteolysis of Hif-1alpha under "normoxic" conditions, we achieved constitutive stabilization of Hif-1alpha through thymic deletion of Vhlh and reversed Hif-1alpha stabilization with double deletion of Vhlh and Hif-1alpha. We found that constitutive activity of Hif-1alpha resulted in diminished Ca(2+) response upon TCR crosslinking despite equivalent activation of phospholipase C(gamma1), normal intracellular Ca(2+) stores, and normal entry of Ca(2+) across the plasma membrane. Altered Ca(2+) response was instead due to accelerated removal of Ca(2+) from the cytoplasm into intracellular compartments, which occurred in association with Hif-1alpha-dependent overexpression of the calcium pump SERCA2 (sarcoplasmic/endoplasmic reticulum calcium ATPase 2). These data suggest a unique mechanism for control of TCR signaling through Hif-1alpha, which may be operative at the physiologic oxygen tensions seen in solid lymphoid organs.     

Laterality of auditory hallucinations in psychiatric patients

Twenty-nine of 54 subjects with auditory hallucinations were able, when asked, to localize the voices to the left or right ear. Subjects who heard voices on the right were found to be significantly more depressed than the others.     

Effect of chronic intracerebroventricular morphine to feeding responses in male rats

Stainless steel cannulae were implanted stereotaxically in the third ventricle of male albino rats. The rats were fed with natural food pellets and water ad lib. After seven days of cannulation, daily body weight, food intake and water intake were recorded for the first five days, which was considered the preinjection control. Then increased and repetitive injections of morphine sulphate were administered intracerebroventricularly (ICV) in dosage of 30 micrograms/2 microliter, 45 micrograms/3 microliter, 60 micrograms/4 microliter, 75 micrograms/5 microliter, 90 micrograms/6 microliter and 105 micrograms/7 microliter on each following day respectively. In a separate set of experiments, the blood glucose levels were measured in animals injected with morphine to a dose corresponding to 15 micrograms/1 microliter, 30 micrograms/2 microliter, 45 micrograms/3 microliter, 60 micrograms/4 microliter and 75 micrograms/5 microliter on days 1, 2, 3, 4 and 5 respectively. Statistically significant (p less than 0.001) decreases in the body weight, food intake, water intake and increase in blood glucose were observed. The inferences derived from the above observations for the possible involvement and interaction of opioids in the regulation of feeding mechanisms have been discussed.     

The KIDROP model of combining strategies for providing retinopathy of prematurity screening in underserved areas in India using wide-field imaging,tele-medicine,non-physician graders and smart phone reporting

Aim:

To report the Karnataka Internet Assisted Diagnosis of Retinopathy of Prematurity (KIDROP) program for retinopathy of prematurity (ROP) screening in underserved rural areas using an indigenously developed tele-ROP model.

Materials and Methods:

KIDROP currently provides ROP screening and treatment services in three zones and 81 neonatal units in Karnataka, India. Technicians were trained to use a portable Retcam Shuttle (Clarity, USA) and validated against ROP experts performing indirect ophthalmoscopy. An indigenously developed 20-point score (STAT score) graded their ability (Level I to III) to image and decide follow-up based on a three-way algorithm. Images were also uploaded on a secure tele-ROP platform and accessed and reported by remote experts on their smart phones (iPhone, Apple).

Results:

6339 imaging sessions of 1601 infants were analyzed. A level III technician agreed with 94.3% of all expert decisions. The sensitivity, specificity, positive predictive value and negative predictive value for treatment grade disease were 95.7, 93.2, 81.5 and 98.6 respectively. The kappa for technicians to decide discharge of babies was 0.94 (P < 0.001). Only 0.4% of infants needing treatment were missed. The kappa agreement of experts reporting on the iPhone vs Retcam for treatment requiring and mild ROP were 0.96 and 0.94 (P < 0.001) respectively.

Conclusions:

This is the first and largest real-world program to employ accredited non-physicians to grade and report ROP. The KIDROP tele-ROP model demonstrates that ROP services can be delivered to the outreach despite lack of specialists and may be useful in other middle-income countries with similar demographics.     

Acute inhibition of PRL and TSH secretion after intraventricular injection of PRL in ovariectomized rats

Prolactin (PRL) is under short-loop inhibitory control via the hypothalamus. However, earlier studies evaluated the effects on PRL secretion of PRL levels elevated for periods of days. In this study we evaluated the acute effects of intraventricular and systemic injection of PRL on the release of a variety of pituitary hormones. Ovariectomized (OVX) rats, bearing implanted third ventricular and jugular cannulas were used. Blood was withdrawn in unanesthetized, freely moving animals before and after intraventricular injection of 0.9% NaCl or 1 or 3 micrograms of bovine (b) or ovine (o) PRL. Prolactin was also administered intravenously in doses of 3 or 6 micrograms. No effect on plasma levels of any of the pituitary hormones occurred after intraventricular or systemic injection of saline. Intraventricular injection of both doses of bPRL or oPRL significantly lowered plasma PRL within 15-30 min. In animals with elevated initial PRL values because of stress or estradiol (E) priming, greater lowering of PRL occurred. Inconsistent reductions in plasma PRL occurred after intravenous injection of oPRL but not bPRL, which elevated PRL values via cross-reaction in the immunoassay. In contrast, only small and inconsistent declines in luteinizing hormone (LH) were seen after intraventricular injection of PRL in either OVX or OVX E-primed rats. Plasma follicle-stimulating hormone (FSH) and growth hormone (GH) were not affected by PRL in any of the experiments; however, a significant lowering of thyrotropin (TSH) occurred in OVX or OVX E-primed rats within 30 min after intravenous injection of 3 micrograms of oPRL, but no change occurred after intravenous PRL. The data indicate that PRL can acutely inhibit PRL and TSH release via a hypothalamic action, whereas release of LH is only slightly inhibited and that of FSH and GH is unaltered.     

Emergency Neurological Life Support: Severe Traumatic Brain Injury

Severe traumatic brain injury (TBI) causes substantial morbidity and mortality, and is a leading cause of death in both the developed and developing world. The need for a systematic evidence-based approach to the care of severe TBI patients within the emergency setting has led to its inclusion as an Emergency Neurological Life Support topic. This protocol was designed to enumerate the practice steps that should be considered within the first critical hours of neurological injury from severe TBI.