Investigations on organ-specific metabolism and genotoxic effects of the urinary bladder carcinogen N-nitrosobutyl-3-carboxypropylamine (BCPN) and its analogs N-nitrosodibutylamine (NDBA) and N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA)

N-Nitrosodibutylamine (NDBA) and its omega-oxidized metabolites N-nitrosobutyl-4-hydroxybutylamine (4-OH-NDBA) and N-nitrosobutyl-3-carboxypropylamine (BCPN) are potent urinary bladder carcinogens. To study putative organ specific activation of BCPN, its alpha-oxidation by liver and urinary bladder microsomal fractions was investigated in comparison to NDBA and 4-OH-NDBA. Additionally, induction of DNA single strand breaks (SSB) was monitored in hepatocytes and in a human lymphoblastoid cell line (Namalva) in the presence and absence of external metabolic activation, including N-nitroso-t-butyl-n-butylamine as a negative control. BCPN was alpha-hydroxylated and dealkylated at both alkyl chains in small rates (about 1 nmol x mg protein-1 x 60 min-1) by microsomes from rat liver and pig urinary bladder epithelium. NDBA and 4-OH-NDBA were dealkylated at similarly low rates by pig urinary bladder microsomes, in strong contrast to the high debutylation rates observed for rat liver microsomes. Correspondingly, SSB induction by NDBA and 4-OH-NDBA was observed in Namalva cells with NDBA and 4-OH-NDBA in the presence of PB-induced rat liver microsomes but not with urinary bladder microsomes or without external activation. BCPN did not induce DNA-damage in Namalva cells (with or without external activation) or in rat hepatocytes. Significant induction of sister chromatid exchanges (SCEs) and micronuclei, however, was observed in Namalva cells after incubation with NDBA and BCPN. Our data suggest activation of BCPN via alpha-oxidation in the urinary bladder, even though activation rate in-vitro is so low that a positive response is not detectable by several short-term tests.     

Multidisciplinary approach in the long-term management of intrahepatic stones: Indian experience.

BACKGROUND: Intrahepatic stones, though common in East Asia, are uncommon in India. There is paucity of data from India regarding the treatment and long-term outcome of patients with intrahepatic stones. METHODS: We retrospectively analyzed medical records of 35 patients with intrahepatic stones who had been treated surgically. Endoscopic biliary drainage had been used in patients who presented with acute cholangitis. Intraoperative stone clearance was confirmed by choledochoscopy and intraoperative cholangiography. Outcome of surgery, frequency and subsequent management of recurrent intrahepatic stones, and factors associated with stone recurrence and cholangitis were analyzed. RESULTS: Twenty-one (60%) patients had bilobar disease. Eight patients underwent hepatectomy and 16 hepatico-jejunostomy with access loop; 12 of these were jejuno-duodenal anastomoses. Postoperative morbidity was observed in 10 patients (29%). Recurrence of stones occurred in 12 patients (34%) and cholangitis in 9 patients (26%). Presence of bilobar disease and associated biliary strictures were associated with recurrent cholangitis (p< 0.05). Two patients (6%) required re-operation for recurrent cholangitis. Complete removal of recurrent stones using conventional endoscope was possible through jejuno-duodenostomy in all 5 cases who had this type of access loop construction. CONCLUSION: Surgical treatment for intrahepatic stones depends on the site of involvement. Construction of a jejuno-duodenal access loop in patients with bilobar disease and intrahepatic strictures is helpful in facilitating postoperative stone clearance. A multidisciplinary approach is beneficial especially when the disease is bilobar and recurrent in type.     

The myocardial performance index during low-dose dobutamine echocardiography in control subjects and patients with a recent myocardial infarction: a new index of left ventricular functional reserve?

BACKGROUND: Wall-motion analysis during low-dose dobutamine echocardiography (LDDE) is a semiquantitative measure of left ventricular contractile reserve after myocardial infarction (MI). The Doppler echocardiographic myocardial performance index (MPI) is a quantitative measure of combined left ventricular systolic and diastolic function. We sought to characterize the changes in MPI during LDDE in control subjects and patients with MI, and to describe the relation of these changes to changes in regional systolic function. METHODS: MPI was obtained at rest and during LDDE (10 microg/kg/min) in 25 healthy volunteers (group 1) and 50 patients with a recent MI. Patients were divided into two subsets; those with (n = 23; group 2A) and those without (n = 27; group 2B) a contractile reserve defined as an improvement of wall motion in more than two contiguous infarct-zone segments during LDDE. DeltaMPI was defined as the change from rest to LDDE. RESULTS: MPI decreased significantly during LDDE in groups 1 and 2A, whereas MPI increased in group 2B (DeltaMPI = 0.12 +/- 0.04 and 0.10 +/- 0.08 vs -0.03 +/- 0.08, P <.0001). On multivariate analysis, Deltawall-motion score index predicted DeltaMPI (beta = 0.65, P <.0001) independently of age, sex, and the dobutamine-induced change in heart rate and systolic blood pressure. CONCLUSIONS: Data suggest that the change in MPI during LDDE may provide a simple and quantitative measure of overall left ventricular functional reserve in patients with a recent MI.     

Does gravidity influence the success of in vitro fertilization-embryo transfer cycles?

OBJECTIVE: To evaluate the influence of gravidity on the results of in vitro fertilization (IVF)-embryo transfer (ET) cycles. PATIENTS AND METHODS: All consecutive women aged <35 years admitted to our IVF unit from January 2002 to December 2004 were enrolled in the study. Only patients undergoing one of their first three IVF cycle attempts were included. Gravidity, ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and clinical pregnancy rate were assessed. RESULTS: Three hundred and forty-two consecutive IVF cycles were evaluated. One hundred and sixty-one cycles were from nulligravidas and 181 from women with a history of at least one previous clinical pregnancy. Forty-eight (29.8%) clinical pregnancies were observed in the nulligravida group and 56 (30.9%) in the gravida group. There were no differences between nulligravidas and gravidas in causes of infertility, length of ovarian stimulation, peak estradiol and progesterone levels, number of oocytes retrieved, fertilization rate and number of embryos transferred. Gravidas were significantly older (30.4 vs. 27.6 years, p < 0.001) and used more gonadotropin ampoules (36.1 vs. 31.8, p < 0.004) compared with the nulligravidas. CONCLUSIONS: Patient gravidity has no influence on the likelihood of achieving pregnancy in IVF-ET cycles.     

Cluster headache: phospholipid metabolism in polymorphonuclear cells

Our group has previously reported significant changes in the incorporation of precursors into glycerophospholipids, particularly phosphatidylserine, in polymorphonuclear cells obtained from the peripheral blood of cluster headache patients, when compared with controls. The potential of these results led to further work using both the previous methodology and a modified isolation technique to obtain polymorphonuclear cells in as pure a state as possible. Neither the new results obtained using the original technique, nor the results with high purity polymorphonuclear cells from controls and cluster headache patients, confirm the marked changes in precursor uptake into glycerophospholipids originally reported.     

Inhaled steroid delivery from small-volume holding chambers depends on age, holding chamber, and interface in children.

The relationship between the amount of inhaled steroids delivered from pressurized metered-dose inhalers used with their recommended holding chambers and age of the patients using these devices was studied in an open randomised cross-over filter study. We recruited 1-2-month-old healthy infants (n = 21), 2-3-year-old asthmatics (n = 13), 4-6-year-old asthmatics (n = 15), and 10-15-year-old asthmatics (n = 20). Each child inhaled two puffs, administered by a single investigator, of both budesonide through Nebuchamber and fluticasone propionate through Babyhaler, on two occasions. Moreover, the 4-6-year-old group inhaled via both facemask and mouthpiece. Drug, collected on a filter interposed between holding chamber and patient, was analysed by high performance liquid chromatography. Filter dose, expressed in percent of the nominal dose, was analysed in a mixed effect linear regression model with age group, holding chamber and inhalation interface (facemask or mouthpiece) as fixed effects and subject as random effect. Filter dose from both holding chambers increased significantly with age, from 3% with Babyhaler and 7% with Nebuchamber in the youngest children, to 40-41% with both holding chambers in adolescents. Nebuchamber delivered more drug than Babyhaler (p = 0.002), but variability in drug delivery (about 11%) was similar between holding chambers. Filter dose decreased from 35% to 22% with Babyhaler, and from 42% to 27% with Nebuchamber when using a mouthpiece rather than a facemask (p < 0.0001). Delivery of inhaled steroids used with their recommended holding chambers depends from age and holding chamber, but also from the inhalation interface. Lung deposition and clinical studies comparing inhalation from holding chambers with mouthpiece and facemask are urgently required.     

Risk factors for asthma in adolescents in a large urban region of Brazil.

BACKGROUND: Identify risk factors for asthma in adolescents from S?o Paulo, Brazil. METHODS: total of 528 adolescents (141 asthmatics, 387 control subjects) from the ISAAC study (phase III) were submitted to a complementary questionnaire to evaluate risk factors, through response to questions regarding personal history, environment, and diet and an agreement to undergo the skin prick test (SPT) for aeroallergens. RESULTS: Positive SPT to at least one allergen occurred in 49.4% adolescents. The risk factors for asthma were: prematurity (OR: 3.84, 95% CI: 1.54-9.64), rhinitis (OR: 3.18, 95% CI: 1.71-5.91), positivity in the SPT (OR: 2.81, 95% CI: 1.48-5.32), eczema in characteristic skin-folds (OR: 2.86, 95% CI: 1.13-7.26), and an allergic mother (OR: 2.01, 95% CI: 1.02-3.93). The consumption of cooked vegetables was a protective factor for asthma (OR: 0.37, 95% CI: 0.18-0.79) CONCLUSIONS: Asthma is a multifatorial disease. An allergic mother, aeroallergen sensitization, rhinitis, eczema and prematurity were considered risk factors and the consumption of cooked vegetables was considered a protective factor for asthma in this population.