Vitelline duct anomalies. Experience with 217 childhood cases

Of 217 children with vitelline duct anomalies, 85 (40%) had symptomatic lesions (mean age, 2.4 years). Forty-eight patients presented with rectal bleeding; 28, with intestinal obstruction; five, with abdominal pain; and four, with bilious umbilical drainage. An asymptomatic Meckel's diverticulum was discovered incidentally at laparotomy in 132 children. Surgical therapy included bowel resection in nine patients with volvulus, four with intussusception, seven with bleeding, three with vitelline cysts, and one with a perforation. Diverticulectomy was performed in 189 cases, and excision of a patent vitelline duct was accomplished in four neonates with umbilical drainage. Ectopic gastric mucosa was present in all 48 patients with bleeding and in four of five with inflammation but in only two asymptomatic specimens. More than one third of the cases were symptomatic and presented in younger patients. This suggests that elective resection of asymptomatic vitelline remnants in early childhood is reasonable at the time of laparotomy for other conditions.     

Effect of CGP 17/582, a selective beta-adrenoceptor antagonist, on the haemodynamic and hypokalaemic response to adrenaline.

1. CGP 17/582B is a new beta-adrenoceptor antagonist which on experimental studies appears to combine selective beta 1-adrenoceptor blockade with partial agonist activity (ISA). Assessing beta-adrenoceptor selectivity and the degree of partial agonist activity in vivo can be difficult. 2. In a double-blind placebo controlled crossover study we have compared the effect of oral pretreatment for 7 days with CGP (100 mg twice daily), with propranolol (non-selective beta-adrenoceptor blocker with no ISA) and metoprolol (selective beta-adrenoceptor blocker with no ISA) on resting heart rate and heart rate response to submaximal exercise on a bicycle ergometer to assess the degree of beta-adrenoceptor blockade and also the changes in blood pressure, heart rate and potassium during the intravenous infusion of (-)-adrenaline to determine the degree of beta 2-adrenoceptor blockade. 3. Subjects underwent submaximal exercise testing on the second and fifth day of each treatment period and on the seventh day received a 2 h infusion of (-)-adrenaline (0.06 microgram kg-1 min-1). Heart rate, blood pressure, plasma potassium and catecholamines were measured throughout the study period. 4. All three active treatments significantly reduced exercise induced tachycardia. The (-)-adrenaline infusion significantly reduced plasma noradrenaline levels following propranolol and metoprolol and to a lesser extent with placebo but were unaltered on CGP. Baseline heart rate was unaltered by CGP but was significantly reduced by metoprolol and propranolol. Adrenaline significantly reduced plasma potassium levels following placebo and CGP pretreatment but plasma potassium was unaltered by adrenaline with metoprolol and propranolol pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adherence of L1210 murine leukemia cells to sephacryl- aminopropylcobalamin beads treated with transcobalamin-II

Sephacryl beads containing an immobilized aminopropylcobalamin- transcobalamin-II complex serve as foci for the adherence of L1210 murine leukemia cells. Bead-cell interaction does not occur when (A) nonderivatized beads are used; (B) transcobalamin-II is omitted or presaturated with cyanocobalamin in the preparation of the bead complex; (C) intrinsic factor replaces transcobalamin-II; and (D) the complex is removed from beads by photolysis. These observations suggest that adherence results from the ability of transcobalamin-II to form a bridge between immobilized cobalamin on the bead and receptors in the plasma membrane of the cell.     

Nitroxergic nerves mediate vagally induced relaxation in the isolated stomach of the guinea pig.

Here we show that the relaxation induced by stimulation of the vagus nerve in the presence of cholinergic (muscarinic) and adrenergic blockade in the isolated stomach of the guinea pig is mediated by nitric oxide (NO). This is substantiated by inhibition of vagal relaxation by NG-monomethyl-L-arginine, an inhibitor of NO synthesis. The effect of NG-monomethyl-L-arginine was partially reversed by coincubation with L-arginine but not with D-arginine. NO activates soluble guanylate cyclase, and relaxation of the stomach induced by vagal stimulation was prevented by an inhibitor of soluble guanylate cyclase, methylene blue, further supporting our conclusions. The relaxant effect of vagal stimulation was also ablated by hexamethonium, an inhibitor of ganglionic nicotinic receptors, thereby showing that ganglionic transmission did not rely on NO, through its release from preganglionic neurons. However, hexamethonium did not inhibit the gastric relaxation brought about by increasing the intragastric pressure, which is also mediated by NO as previously described by us. The selective inhibition by hexamethonium of only the vagally mediated relaxation but not of the pressure-induced relaxation of the stomach indicates the existence of at least two separate neuronal pathways able to generate NO and bring about gastric accommodation of food or fluid.     

Activation of the CPP32 protease in apoptosis induced by 1-beta-D- arabinofuranosylcytosine and other DNA-damaging agents

The response of human myeloid leukemia cells to treatment with 1-beta- arabinofuranosylcytosine (ara-C) includes the induction of apoptosis. Ara-C induced apoptosis is associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) and protein kinase C (PKC) delta. However, the signals involved in this response are unknown. The present studies show that ara-C treatment of U-937 cells is associated with induction of a protease activity that cleaves the tetrapeptides Ac-DEVD- pNA and Ac-DMOD-pNA found at the cleavage sites of PARP and PKC delta, respectively. The ara-C-induced protease activity was sensitive to overexpression of the anti-apoptotic protein Bcl-xL and the baculovirus protein p35. By contrast, overexpression of the cowpox virus protein CrmA blocked apoptosis induced by engagement of the Fas receptor but not that induced by ara-C. CrmA overexpression also had no detectable effect on ara-C-induced cleavage of PKC delta. The results further show that ara-C induces activation of the CPP32 protease by a CrmA- insensitive and p35-sensitive mechanism. Similar results were obtained with cisplatinum, etoposide, and camptothecin. These findings indicate that ara-C and other DNA-damaging agents activate a CrmA-insensitive apoptotic pathway involving CPP32 and that these signals differ from those associated with apoptosis induced by the Fas receptor.