A mouse model of AChR deficiency syndrome with a phenotype reflecting the human condition

The two subtypes of mammalian muscle nicotinic acetylcholine receptors (AChR) are generated by the substitution of the epsilon (adult) subunit for the gamma (fetal) subunit within the AChR pentamer. Null mutations of the adult AChR epsilon-subunit gene are the most common cause of the AChR deficiency syndrome. This is a disorder of neuromuscular transmission characterized by non-progressive fatigable muscle weakness present throughout life. In contrast with the human disorder, mice with AChR epsilon-subunit null mutations die between 10 and 14 weeks of age. We generated transgenic mice that constitutively express the human AChR gamma-subunit in an AChR epsilon-subunit 'knock-out' background. These mice, in which neuromuscular transmission is mediated by fetal AChR, live well into adult life but show striking similarities to human AChR deficiency syndrome. They display fatigable muscle weakness, reduced miniature endplate potentials and endplate potentials, reduced motor endplate AChR number and altered endplate morphology. Our results illustrate how species differences in the control of ion-channel gene expression may affect disease phenotype, demonstrate that expression of adult AChR subtype is not essential for long-term survival, and suggest that in patients with AChR deficiency syndrome, up-regulation of the gamma-subunit could be a beneficial therapeutic strategy.     

Angiography in poor-risk patients with massive nonvariceal upper gastrointestinal bleeding

The purpose of this retrospective study was to determine the diagnostic and therapeutic usefulness of gut angiography in patients with massive upper gastrointestinal bleeding from a nonvariceal source. All patients (n = 64) in this category who underwent a gut angiogram between 1980 and 1986 were studied. Pre-angiogram endoscopy was attempted in all patients and was nondiagnostic in 14 (22%). Contrast extravasation at angiography was seen in 25 of 64 patients (39%), and in over half of these patients endoscopy was nondiagnostic (n = 11) or wrong (n = 3). Attempts to control bleeding in this group by selective arterial embolization (n = 14) or intra-arterial vasopressin (n = 11) successfully averted operation in 13 of 25 patients (52%) and was associated with a 50% reduction in mortality (83% versus 38%). Selective embolization of vessels thought to be bleeding on clinical grounds without evidence of contrast extravasation (i.e., "blind" embolization) was not helpful in controlling hemorrhage. Urgent gut angiography in patients with massive upper gastrointestinal bleeding of arteriocapillary source is a useful diagnostic and therapeutic maneuver and warrants continued application in this group of poor-risk patients.     

Transoesophageal echocardiography detects residual ductal flow during video-assisted thoracoscopic patent ductus arteriosus interruption

This report describes transoesophageal echocardiographic (TEE) monitoring in a one-year-old boy undergoing patent ductus arteriosus (PDA) interruption. After application of a first vascular clip, echocardiographic monitoring detected incomplete interruption of ductal flow, prompting the surgeon to add a second clip to the ductus. The procedure was performed via a new surgical technique: video-assisted thoracoscopic surgery (VATS). This innovative approach offers many advantages to patient care including reduced postoperative pain and better preservation of pulmonary function. We conclude that the use of TEE monitoring during PDA interruption via the VATS procedure may improve the surgical result, and eliminate reintervention and the complications associated with residual ductal flow.     

PPOs are beginning to plug into age of automation

As relative latecomers to the computer age, most preferred provider organizations are just beginning to see the value of automation in gaining a competitive advantage. In addition to using electronic data interchange to automate claims processing, some forward-thinking PPOs are using automation to provide quick confirmation of patient eligibility for coverage or to streamline utilization review.