Chronic ethanol feeding produces a muscarinic receptor upregulation, but not a muscarinic supersensitivity in lower esophageal sphincter muscle.

Muscarinic acetylcholine receptors (mAChR) are important in esophageal physiology, and mAChR alterations may be involved in ethanol-induced esophageal dysfunction. We previously demonstrated that acute ethanol decreases lower esophageal sphincter pressure (LESP), whereas withdrawal from chronic ethanol results in pressure increases which are reversible by acute ethanol. To see if this increase in LESP is due to upregulation of mAChR, we evaluated both mAChR binding and dose-response curves for bethanechol and atropine-induced changes in LESP before and after acute and chronic ethanol exposure. The number of mAChR sites (Bmax) in LES (3.4 fmol/mg tissue) was lowered by acute ethanol (1.72, -50%); withdrawal from chronic ethanol raised Bmax (5.2, +54%). Acute injection of ethanol into cats in withdrawal reversed this increase in mAChR density (3.1, -10%). These changes correlated with our earlier data on ethanol-induced changes in LESP. However, the dose-response curve for bethanechol-induced pressure increases shifted to the right [ED25 (micrograms/kg); control, 8.6; withdrawal, 21.3], paralleled by an increase in the number of low-affinity agonist binding sites. Thus, 1) the withdrawal-associated increase in Bmax (up-regulation) is more likely to be a compensatory response to deficits (functional subsensitivity) distal to the receptor recognition site than to proximal deficits; 2) the increase in Bmax does not cause LESP hyperactivity; and 3) receptor binding changes do not necessarily translate into physiological changes.     

Axillary vein thrombosis as a manifestation of rapidly progressive neuropathic arthropathy of the shoulder associated with syringomyelia

Neuropathic arthropathy is a destructive joint disease associated frequently with loss of proprioception. Syringomyelia (with or without Arnold-Chiari malformation) is characterized by slow progression over many years; the joints involved most frequently are the shoulders and elbows. Neuropathic arthropathy of the hand is rare, and clinical features are vasomotor problems, digital ulcers, thickening of the fingers, and painless subluxation of the finger joints. We report an unusual case of neuropathic arthropathy of the shoulder and hands, associated with syringomyelia without Arnold-Chiari malformation. Neuropathic arthropathy of the shoulder was rapidly progressive, and axillary vein thrombosis was the first manifestation; however, neuropathic arthropathy of the hands was unrecognized for 7 years, and painless ulceration of the fingers with spontaneous amputation of the terminal phalanx and Raynaud phenomenon were the initial manifestations. To our knowledge, this is the first report of a patient with this constellation of findings.     

Development of hydrocephalus in mice lacking SOCS7

SOCS7 is a member of the suppressor of cytokine signaling (SOCS) family of proteins (SOCS1-SOCS7 and CIS). SOCS proteins are composed of an N-terminal domain of variable length, a central Src homology 2 domain, and a C-terminal SOCS box. Biochemical and genetic studies have revealed that SOCS1, SOCS2, SOCS3, and CIS play an important role in the termination of cytokine and growth factor signaling. However, the biological actions of other SOCS proteins are less well defined. To investigate the physiological role of SOCS7, we have used gene targeting to generate mice that lack expression of the Socs7 gene. Socs7-/- mice were born in expected numbers, were fertile, and did not exhibit defects in hematopoiesis or circulating glucose or insulin concentrations. However, Socs7-/- mice were 7-10% smaller than their wild-type littermates, and within 15 weeks of age approximately 50% of the Socs7-/- mice died as a result of hydrocephalus that was characterized by cranial distortion, dilation of the ventricular system, reduced thickness of the cerebral cortex, and disorganization of the subcommissural organ. In situ hybridization studies revealed prominent expression of Socs7 in the brain, suggestive of an important functional role of SOCS7 in this organ.     

Core stability measures as risk factors for lower extremity injury in athletes

INTRODUCTION/PURPOSE: Decreased lumbo-pelvic (or core) stability has been suggested to contribute to the etiology of lower extremity injuries, particularly in females. This prospective study compares core stability measures between genders and between athletes who reported an injury during their season versus those who did not. Finally, we looked for one or a combination of these strength measures that could be used to identify athletes at risk for lower extremity injury. METHODS: Before their season, 80 female (mean age = 19.1 +/- 1.37 yr, mean weight 65.1 +/- 10.0 kg) and 60 male (mean age = 19.0 +/- 0.90 yr, mean weight 78.8 +/- 13.3 kg) intercollegiate basketball and track athletes were studied. Hip abduction and external rotation strength, abdominal muscle function, and back extensor and quadratus lumborum endurance was tested for each athlete. RESULTS: Males produced greater hip abduction (males = 32.6 +/- 7.3%BW, females = 29.2 +/- 6.1%BW), hip external rotation (males = 21.6 +/- 4.3%BW, females = 18.4 +/- 4.1%BW), and quadratus lumborum measures (males = 84.3 +/- 32.5 s, females = 58.9 +/- 26.0 s). Athletes who did not sustain an injury were significantly stronger in hip abduction (males = 31.6 +/- 7.1%BW, females = 28.6 +/- 5.5%BW) and external rotation (males = 20.6 +/- 4.2%BW, females = 17.9 +/- 4.4%BW). Logistic regression analysis revealed that hip external rotation strength was the only useful predictor of injury status (OR = 0.86, 95% CI = 0.77, 0.097). CONCLUSION: Core stability has an important role in injury prevention. Future study may reveal that differences in postural stability partially explain the gender bias among female athletes.