Potential mechanisms connecting asthma, esophageal reflux, and obesity/sleep apnea complex--a hypothetical review

Obstructive sleep apnea (OSA) and asthma are potentially linked at several levels. The pathophysiology of these two conditions seems to overlap significantly, as airway obstruction, inflammation, obesity, and several other factors are implicated in the development of both diseases. Gastroesophageal reflux disease (GERD), cardiovascular complications, obesity itself, and the underlying inflammatory processes are all complex contributory factors that provide hypothetical links. Furthermore, a collateral rise in prevalence of both OSA and asthma has been noticed during the past few years, occurring in association with the emerging epidemic of obesity, a common risk factor for both conditions. OSA and asthma share many other risk factors as well. We propose a hypothetical OSA-asthma relationship that has implications on the diagnosis and management of patients presenting with either condition singly. Clinicians should be aware that OSA might complicate asthma management. Based on this hypothesis, we suggest that the treatment of the individual patient who experiences both asthma and OSA needs to be multidisciplinary and comprehensive. This hypothetical association of asthma and OSA, though described anecdotally, has not been systematically studied. In particular, the influence of continuous positive airway pressure therapy (for sleep apnea) on asthma outcomes (such as quality of life, steroid utilization, emergency room visits) and fatality needs to be studied further.     

Engineering neuronal nicotinic acetylcholine receptors with functional sensitivity to α‐bungarotoxin: a novel α3‐knock‐in mouse

We report here the construction of a novel knock‐in mouse expressing chimeric α3 nicotinic acetylcholine receptor (nAChR) subunits with pharmacological sensitivity to α‐bungarotoxin (αBTX). Sensitivity was generated by substituting five amino acids in the loop C (β9–β10) region of the mouse α3 subunit with the corresponding residues from the α1 subunit of the muscle type receptor from Torpedo californica. To demonstrate the utility of the underlying concept, expressed α3[5] subunits were characterized in the superior cervical ganglia (SCG) of homozygous knock‐in mice, where the synaptic architecture of postsynaptic α3‐containing nAChR clusters could now, for the first time, be directly visualized and interrogated by live‐staining with rhodamine‐conjugated αBTX. Consistent with the postsynaptic localization of ganglionic nAChRs, the αBTX‐labeled puncta colocalized with a marker for synaptic varicosities. Following in vivo deafferentation, these puncta persisted but with significant changes in intensity and distribution that varied with the length of the recovery period. Compound action potentials and excitatory postsynaptic potentials recorded from SCG of mice homozygous for α3[5] were abolished by 100 nm αBTX, even in an α7 null background, demonstrating that synaptic throughput in the SCG is completely dependent on the α3‐subunit. In addition, we observed that the genetic background of various inbred and outbred mouse lines greatly affects the functional expression of α3[5]‐nAChRs, suggesting a powerful new approach for exploring the molecular mechanisms underlying receptor assembly and trafficking. As αBTX‐sensitive sequences can be readily introduced into other nicotinic receptor subunits normally insensitive to αBTX, the findings described here should be applicable to many other receptors.     

Pseudoxanthoma elasticum with periumbilical perforation in a nullipara

Pseudoxanthoma elasticum (PXE) is an inherited multisystem disorder that primarily affects the skin and is characterized by progressive calcification and degeneration of the elastic fibers. PXE has recently been found to be caused by mutations in the ATP-binding cassette transporter C6 (ABCC6) or the multidrug resistance-associated protein 6 (MRP6) genes. Perforating PXE is a rare presentation that is usually seen in the periumbilical area in obese multiparous black women; it has distinct clinical and histopathological features and there may or may not be systemic manifestations. We report an unusual case of PXE in a nulliparous woman, with perforation in the periumbilical area and without any systemic involvement.     

Fatal Migratory Pulmonary Thromboembolism Following Successful Pericardiocentesis

Echocardiography‐guided pericardiocentesis is relatively safe with minimal risk in experienced hands. However, complications can occur because of the procedure. This report describes a unique case of an 84‐year‐old man with unanticipated fatal pulmonary thromboembolism following a successful pericardiocentesis. (Echocardiography 2010;27:E125‐E127)     

Vitamin D deficiency and calcium intake in reference to increased body mass index in children and adolescents

Vitamin D deficiency has been linked to several chronic diseases in adults. Studies focusing on children and adolescents, however, are limited. In this randomized cross-sectional study, we aimed to determine the prevalence of vitamin D deficiency and its relationship with childhood obesity and dietary calcium intake among a population of healthy urban Saudi children and adolescents. To achieve this, 331 randomly selected Saudi children (53.8% females and 46.2% males) aged 6-17 years were included. Demographic, medical, and dietary information were collected; anthropometrics were measured. Levels of serum fasting glucose, lipid profile, 25(OH) D, and for albumin corrected calcium were analyzed. Vitamin D deficiency was noted in all subjects, with girls having significantly lower vitamin D levels than boys. Mean calcium intake was found to be 60% of the required dietary allowance (RDA), while the mean vitamin D intake was 23% of RDA. Vitamin D status and calcium intake were comparable in both normal and overweight/obese children and adolescents. Vitamin D status was highest among children who had calcium intake >800 mg/day. In adolescents there was insignificant but decreasing trend in BMI, which was observed to be highest among those whose calcium intake was <250 mg/day and lowest among those taking >800 mg/day. Conclusion: results from this study suggest the importance of vitamin D fortification and increased dietary calcium in the Saudi diet to meet RDA requirements and avoid onset of vitamin D deficiency-related diseases in Saudi children and adolescents.