Background-TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathyassociated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Here, we sought to characterize the frequency, spectrum, and phenotype associated with HCMassociated mutations in these three genes in a large cohort of unrelated patients evaluated at a single tertiary outpatient center.

Urinary bladder wall muscle (i.e., detrusor smooth muscle; DSM) contracts in response to a quick-stretch, but this response is neither fully characterized, nor completely understood at the subcellular level. Strips of rabbit DSM were quick-stretched (5 ms) and held isometric for 10 s to measure the resulting peak quick-stretch contractile response (PQSR). The ability of selective Ca2+ channel blockers and kinase inhibitors to alter the PQSR was measured, and the phosphorylation levels of myosin light chain (MLC) and myosin phosphatase targeting regulatory subunit (MYPT1) were recorded. DSM responded to a quick-stretch with a biphasic response consisting of an initial contraction peaking at 0.24 ± 0.02-fold the maximum KCl-induced contraction (Fo) by 1.48 ± 0.17 s (PQSR) before falling to a weaker tonic (10 s) level (0.12 ± 0.03-fold Fo). The PQSR was dependent on the rate and degree of muscle stretch, displayed a refractory period, and was converted to a sustained response in the presence of muscarinic receptor stimulation. The PQSR was inhibited by nifedipine, 2-aminoethoxydiphenyl borate (2-APB), 100 μM gadolinium and Y-27632, but not by atropine, 10 μM gadolinium, LOE-908, cyclopiazonic acid, or GF-109203X. Y-27632 and nifedipine abolished the increase in MLC phosphorylation induced by a quick-stretch. Y-27632, but not nifedipine, inhibited basal MYPT1 phosphorylation, and a quick-stretch failed to increase phosphorylation of this rhoA kinase (ROCK) substrate above the basal level. These data support the hypothesis that constitutive ROCK activity is required for a quick-stretch to activate Ca2+ entry and cause a myogenic contraction of DSM.

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onography has high sensitivity for detecting intravascular gas. Historically, most attention in the literature has focused on portal venous gas, an increasingly common finding with myriad causes, both benign and catastrophic. 1 However, there are only a few reported cases of systemic and hepatic venous gas, rare findings associated with iatrogenic causes and more serious medical conditions. 2,3 We report the sonographic findings of systemic and hepatic venous gas secondary to hemodialysis.Received November 20, 2008, Case ReportA 55-year-old man with a complex medical history including active intravenous drug use, critical aortic stenosis, congestive heart failure, and chronic kidney disease was admitted to the San Francisco Veterans Affairs Medical Center with sepsis secondary to lower extremity cellulitis. His hospital course was complicated by acute renal failure requiring hemodialysis. On hospital day 30, he was transferred to the intensive care unit for respiratory failure, hypotension, and critical anion gap metabolic acidosis. Before intubation, the patient reported new severe diffuse abdominal pain.A physical examination at this time revealed an intubated, sedated, and ventilated patient. He was afebrile and normotensive on a norepinephrine drip. An abdominal examination revealed tenderness to palpation in both upper quadrants but was otherwise unremarkable. Laboratory test results revealed a pH of 7.09, a lactate value of 13.2 mmol/L, mild leukocytosis, and a slight elevation in total bilirubin and alkaline phosphatase levels.

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