Effectiveness of rotational atherectomy of right coronary artery ostial stenosis

Balloon angioplasty and stenting of right coronary ostial stenosis may frequently be impeded by lesion calcification, whereas rotational atherectomy, which ablates calcified plaque, should treat these lesions effectively. Accordingly, we evaluated procedural success and longterm clinical outcome of rotational atherectomy of right coronary ostial stenosis. Procedural data were obtained from a comprehensive interventional registry and follow-up information was obtained by chart review and patient enquiry. All patients who developed recurrent angina underwent angiographic restudy. During a 5-year interval, 119 patients underwent rotational atherectomy of right coronary ostial stenosis. Multilesion interventions were performed in 55% of patients. Ostial lesions were 3.73+/-3.69 mm in length (mean +/- SD), and 57.1% were significantly calcified. Reference vessel diameter was 3.42+/-0.56 mm. Maximum burr:artery ratio was 0.64+/-0.1 with adjunct balloon angioplasty in 89.1% and adjunct stenting in 9.2%. Procedural success (<50% residual stenosis without major complication) was 97.5%, with 1.7% uncomplicated failure and 0.8% Q-wave infarction. Maximum residual stenosis was 15+/-17%. During 6-month follow-up, available in 94% of patients, 82.7% remained angina-free, 10.9% developed recurrent angina due to right coronary ostial restenosis, and 6.4% developed recurrent angina due to another lesion. Two years after intervention, target lesion revascularization rate was 16%. Predictors of symptomatic angiographic restenosis were dissection >10 mm, final minimal luminal diameter <2.5 mm, lesion length >10 mm, restenotic lesion, and diabetes. We conclude that rotational atherectomy of right coronary ostial stenosis results in excellent acute procedural success and in low incidence of clinical recurrence, with a high proportion of patients remaining angina-free 2 years after intervention.     

Nicotinic acid-induced insulin resistance is related to increased circulating fatty acids and fat oxidation but not muscle lipid content

Insulin resistance is associated with increased circulating lipids and skeletal muscle lipid content. Chronic nicotinic acid (NA) treatment reduces insulin sensitivity and provides a model of insulin resistance. We hypothesized that the reduction in insulin sensitivity occurs via elevation of circulating nonesterified fatty acids (NEFAs) and an increase in intramyocellular lipid (IMCL). A total of 15 nondiabetic males (mean age 27.4 +/- 1.6 years) were treated with NA (500 mg daily for 1 week, 1 g daily for 1 week). Insulin sensitivity (glucose infusion rate [GIR]) was determined pre- and post-NA by euglycemic-hyperinsulinemic clamp. Substrate oxidation was determined by indirect calorimetry. Skeletal muscle lipid was assessed by estimation of long-chain acyl-CoA (LCACoA) and triglyceride (TG) content and by (1)H-magnetic resonance spectroscopy quantification of IMCL (n = 11). NA reduced GIR (P =.03) and nonoxidative glucose disposal (P <.01) and increased fasting NEFAs (P =.01). The decrease in GIR related significantly to the increase in fasting NEFAs (r(2) =.30, P =.03). The intrasubject increase in basal and clamp fat oxidation correlated with the decrease in GIR (r(2) =.45, P <.01 and r(2) =.63, P <.01). There were no significant changes in muscle LCACoA, TG, or IMCL content. Therefore, induction of insulin resistance by NA occurs with increased availability of circulating fatty acids to muscle rather than with increased muscle lipid content.     

Short- and long-term effects of growth hormone (GH) replacement on protein metabolism in GH-deficient adults

Reduced fat-free mass (FFM) in GH-deficient (GHD) adults is improved by GH replacement, but the protein metabolic changes are unclear. Using iv [(2)H(3)]leucine and oral l-[(13)C(1)]leucine infusions and dual emission x-ray absorptiometry, we compared leucine kinetics and body composition in eight GHD adults and eight healthy controls in the fasted and fed states, before and after 2 wk and 6 months of GH replacement. Leucine kinetics were not different between pretreatment GHD subjects and controls. After 2 wk of GH treatment, leucine oxidation decreased in the GHD subjects compared with baseline values [fasted, 41 +/- 6 vs. 30 +/- 5 micromol/kg FFM.h (P < 0.01); fed, 49 +/- 3 vs. 41 +/- 3.6 micromol/kg FFM.h (P < 0.05)], leucine balance improved [fasted, -14 +/- 4 vs. -3.5 +/- 3 micromol/kg FFM.h (P < 0.01); fed, 65 +/- 10 vs. 72 +/- 7 micromol/kg FFM.h (P = 0.07)], and protein synthesis increased [fasted, 116 +/- 5 vs. 131 +/- 6 micromol/kg FFM.h (P < 0.05); fed, 103 +/- 6 vs. 116 +/- 6 micromol/kg FFM.h (P < 0.05)]. After 6 months of GH treatment, these changes were not maintained in the fed state. The five GHD subjects with decreased FFM at baseline showed a significant increase after 6 months of GH treatment (P < 0.05). GH replacement in GHD acutely improves protein balance by stimulating synthesis and inhibiting catabolism. After 6 months, protein kinetics reached a new homeostasis to maintain the net gain in FFM.     

Oxyntomodulin suppresses appetite and reduces food intake in humans

Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg.min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 +/- 0.9 kg/m(2)) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 +/- 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 +/- 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 +/- 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.     

Preferential loss of maternal 9p alleles in childhood acute lymphoblastic leukemia.

Germ-line events, such as paternal mutation or genomic imprinting, contribute to the early onset of childhood cancers such as retinoblastoma, Wilms tumors, and neuroblastoma. Given the high frequency of deletion involving chromosome 9p in childhood acute lymphoblastic leukemia (ALL), this study investigated whether 9p deletion might reflect preexisting germ-line gene inactivation. To do this the parental origin of deletion was determined in 10 cases of ALL with 9p21 loss of heterozygosity. Of these cases, 9 showed loss of the maternally derived allele, suggesting that a germ-line event involving a 9p gene may play a role in the onset of childhood ALL.     

Effect of interferon-gamma on allergic airway responses in interferon-gamma-deficient mice

Interferon (IFN)-gamma reduces airway responses after allergen challenge in mice. The mechanisms of this effect are not clear. These studies investigate whether IFN-gamma can reverse prolonged airway responses after allergen challenge in IFN-gamma-deficient (IFN-gammaKO) mice. Sensitized mice (IFN-gammaKO and wild-type [WT]) were challenged with ovalbumin. Airway responsiveness, eosinophils in bronchoalveolar lavage fluid, and lung lymphocyte subsets (CD4(+) and CD8(+)) were measured 24 hours and 8 weeks after challenge. In further experiments, we treated IFN-gammaKO mice with recombinant IFN-gamma starting 4 weeks after the challenge for 1 week or 4 weeks. Airway responsiveness, bronchoalveolar lavage eosinophils, and lung CD4(+) cells were increased 8 weeks after challenge in IFN-gammaKO but not WT mice. IFN-gamma treatment returned lung CD4(+) cell numbers to values obtained in unchallenged mice. One week of IFN-gamma treatment also returned airway responsiveness to baseline levels; however, 4-week treatment with IFN-gamma failed to decrease airway responsiveness below levels observed in untreated animals. This suggests that IFN-gamma plays an essential role in reversing allergen-induced airway inflammation and hyperresponsiveness and that it may have dual actions on the latter. Observations that IFN-gamma reverses airway responses, even when administered after challenge, suggests that IFN-gamma treatment could control allergic disease, including asthma.     

Fibrin Glue as an Adjunct to Flap Repair of Anal Fistulas: A Randomized, Controlled Study

Purpose Both flap repair and fibrin glue are accepted sphincter-preserving techniques for managing anal fistulas. Additionally, the two techniques are not mutually exclusive and can be combined. This trial was undertaken to determine whether the combination of flap repair and fibrin glue resulted in better outcomes than flap repair alone. Methods Between July 2000 and March 2004, patients with transsphincteric anal fistulas were randomly assigned to advancement flap repair alone or flap repair combined with fibrin glue obliteration of the fistula tract. Data regarding age, gender, fistula anatomy, race, and previous repairs were collected. Fistulas managed by fistulotomy or caused by Crohn’s disease, acute obstetric trauma, or radiation were excluded from this study. Results There were 58 patients randomized to flap repair alone or flap repair with fibrin glue (47 males; median age, 47 (range, 29–68) years). Mucosal advancement flap was performed in 36 patients and anodermal advancement flap was performed in 22. The median follow-up was 22 (range, 12–36) months. Total fistula recurrence rate for all patients was 32.6 percent. The recurrence rate for fistulas repaired by advancement flap alone was 20 percent, whereas the recurrence rate for fistulas repaired by advancement flap with fibrin glue was 46.4 percent (P < ;0.05). Conclusions The data fail to show improved outcomes when fibrin sealant is used in combination with an advancement flap compared with advancement flap alone for the management of complex anal fistulas. Read at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004. Reprints are not available.     

Ovine concanavalin A-induced suppressor cells: generation, assay, age-related effects and re-evaluation of mechanism of suppression.

Preactivation of ovine peripheral blood and lymph node mononuclear cells with mitogenic doses of concanavalin A (Con A) induced cells which suppressed mitogen-stimulated proliferative responses of untreated autologous and allogeneic responder cells. The degree of suppression varied with preactivating doses of Con A, length of preactivation time, and ratio of preactivated to responder cells. The role of macrophages in generation of suppressor cells was not evaluated. However, macrophages were not required to mediate suppression in cocultures, as lymphoblasts depleted of macrophage by plastic adherence and nylon wool columns mediated equal, and often greater, suppression than unseparated, preactivated cells. Suppressor cell activity in peripheral blood increased from the neonatal period to adulthood. Supernatants from Con A preactivated cell cultures with detectable interleukin-2 activity abrogated suppression when added at 0 and 24 hr of the 72 hr coculture period, suggesting that Con A-induced suppressor cells exert their function by decreasing available levels of IL-2 in the cocultures.     

Expression of sperm antigens during spermatogenesis and maturation detected with monoclonal antibodies

The expression of hamster sperm antigens was investigated during spermatogenesis and sperm maturation with the use of monoclonal antibodies generated in culture from mice immunized with hamster cauda epididymal spermatozoa or sperm heads. Antigens were localized by immunofluorescence and immunoperoxidase techniques which were first visualized on isolated spermatids over the developing acrosome. In one case, antibody inhibited fertilization in vitro although localization on testicular or epididymal spermatozoa was minimal compared with the early spermatid. Antibodies also recognized surface antigens first expressed in the epididymis whose localization on the spermatozoon altered during epididymal transit or incubation in capacitating medium. The results were discussed in relation to the expression and function of surface determinants on the haploid germ cell.