Troponin-T: improved diagnostic assessment of myocardial damage in childhood

Troponin-T (cTnT) as a marker of myocardial damage is well established in adults, but not yet in children. cTnT was measured in 85 children (aged 1 day-204 months, mean 46 months). Twenty-five children were non-surgical patients, with possible myocardial damage suspected on clinical grounds. The other 60 patients had cardiac surgery leading to a defined myocardial damage. In these children, troponin-T (cTnT), creatine kinase activity (CK), creatine kinase-MB activity (CK-MB), and creatine kinase-MB-Mass (CK-MB-Mass) were measured preoperatively and 3–4 times during the first 55 postoperative h. Except in four children with probable preoperative myocardial damage, all troponin-T values were in the normal range (< 0.1 μig/1). All children with intracardiac surgery showed a postoperative increase in troponin-T. Children with extracardiac surgery of the great vessels showed no postoperative increase of troponin-T. For the assessment of myocardial damage, troponin-T was more specific and more sensitive than the other markers tested, troponin-T might significantly improve the diagnostic assessment of myocardial damage in children.     

Metabolism of carcinogenic heterocyclic and aromatic amines by recombinant human cytochrome P450 enzymes

The N-hydroxylation of carcinogenic arylamines represents an initial step in their metabolic activation. Animal studies have shown that this reaction is catalyzed by the cytochrome P450 (P450) enzymes P450 1A1 and P450 1A2. In this study, utilizing enzymes expressed in Escherichia coli (and purified) or in human B-lymphoblastoid cells, the catalytic activities of recombinant human P450 1A1, P450 1A2, and P450 3A4 for N- hydroxylation of several carcinogenic arylamines were determined. P450 1A2 from both expression systems catalyzed the N-hydroxylation of 4- aminobiphenyl and the heterocyclic amines, 2-amino-3-methylimidazo[4,5- f/quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rates were similar, with values of 1.1-7.8 nmol/min/nmol P450. In contrast, P450 1A1 catalyzed N-hydroxylation of only PhIP, and no activity was observed with P450 3A4. Further kinetic analysis with purified P450 1A2 showed similar Km and Vmax values for N-hydroxylation of the arylamines. Furafylline and fluvoxamine, inhibitors of P450 1A2 activity in human liver microsomes, were found to be inhibitory of the recombinant P450 1A2 N-hydroxylation activity. Results from this study are supportive of a major role for human P450 1A2 in the metabolic activation of arylamines.      

An attenuated aroA Salmonella typhimurium vaccine elicits humoral and cellular immunity to cloned beta-galactosidase in mice

beta-Galactosidase (GZ) is an intracellular protein that is frequently used to express cloned antigens as fusion proteins in Escherichia coli. Salmonella typhimurium strain SL3261, an attenuated aroA vaccine strain, was used as a carrier for the plasmid pXY411, which directs the expression of GZ in salmonellae (which do not normally produce this protein). The resulting strain--SL3261(pXY411)--expressed GZ as an intracellular antigen. The plasmid was stable in vitro and in vivo and did not significantly alter the behavior of strain SL3261 in mice. Animals intravenously vaccinated with this construct developed circulating antibodies to GZ, as measured by ELISA, and delayed hypersensitivity to the antigen injected in the footpad. These results indicate that attenuated salmonellae may be expected to elicit both humoral and cellular responses to intracellular cloned antigens.     

Hormonal studies in women with premenstrual tension

Summary. Serum hormone concentrations were determined at intervals during the last 17 days of the menstrual cycle in 35 patients with premenstrual tension (PMT) and 11 control subjects without symptoms. The maximum mean concentration of oestradiol occurred 17 days before menstruation in the patients and 14 days before in the controls. The maximum concentrations of progesterone were similar in the two groups but the mean concentrations rose carlier in the cycle in the patients with PMT. These results suggested that the patients tended to ovulate earlier in the cycle than the controls and on the basis of the ovulatory surge in gonadotrophins two groups could be identified, group A who showed signs of ovulation 14 days or less before menstruation (17 patients, 9 controls) and group B who ovulated more than 14 days before menstruation (18 patients, 2 controls). There were no significant differences between the groups in prolactin, thyroid stimulating hormone or testosterone levels, but cortisol concentrations were uniformly higher in both groups of patients compared with those in the controls. Follicular growth was assessed with ultrasound in 18 patients and 16 control subjects. Mean follicular diameters were significantly lower in the patients than in the control group at the time of ovulation. Oestradiol determinations done at the same time correlated with the diameters and were also significantly lower in the patient group. The results suggest that ovulation tends to occur prematurely in women with PMT.     

The incidence of acute neonatal respiratory disorders in Padova county: an epidemiological survey

The aim of this study was to determine the incidence of respiratory diseases in newborns and the mortality rate caused by the same disorders in an area-based survey conducted during the period extending from June 1, 1993, to May 31, 1994. These rates were related to sex, gestational age, birth weight, Apgar score, mode of delivery and obstetric pathologies. A total of 7588 newborns were studied. A simple diagnostic system was used, which was based on clinical, laboratory and instrumental criteria. The incidence of respiratory disorders was 3.3%; the overall mortality rate was 0.28% and the case fatality rate for respiratory distress syndrome was 14.8%. Neonatal asphyxia was frequently associated with respiratory diseases.     

Metabolic activation of aromatic amines by human pancreas

Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas. Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens. Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O- deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4- (methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA- dependent DNA-binding of [3H]N-hydroxy-ABP) of pancreatic cytosols was high, about twothirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using 32P-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP- DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.      

Heart transplantation for terminal congestive heart failure in an acromegalic patient

Dilated hypokinetic cardiomyopathy in an acromegalic patientis an uncommon event. Specific hormonal therapy with octreotide(a somatostatin analogue) is now recognized as able to improvecardiac failure. A case of worsening of cardiac function undersuch a therapy is described in this report. Octreotide was finallydiscontinued and a cardiac transplantation performed. Soon aftersurgery, treatment with octreotide was started again and noother adverse reaction was noticed. Furthermore, no deleteriousor synergistic interaction between the somatostatin analogueand cyclosporine A was detected. A pharmacological hypothesisis given to explain the inability of octreotide to counteractcardiac failure. The patient died 6 months after surgery probablybecause of an acute episode of arrhythmia.     

Ma-huang strikes again: ephedrine nephrolithiasis

Ephedrine and its metabolites are naturally occurring alkaloids that can be derived from evergreens worldwide and have been used as medicinals for hundreds of years. Because they have "real" pharmacological alpha and beta catecholamine effects and are "natural" products, the alternative medicine industry has popularized them for multiple uses, including asthma, weight loss, energy and sexual enhancement, and euphoria. Several recent reviews have documented the dangerous nature of using these "drugs" unsupervised, including multiple deaths, and the FDA is currently reviewing ephedrine's use in the alternative medicine industry. We report a new toxicity, ephedrine nephrolithiasis, in a patient using an energy supplement, Ma-Huang extract, which contains ephedrine. Although previously not reported, the Louis C. Herring and Company kidney stone database show that this is an endemic complication of ephedrine with hundreds of previous episodes. Using gas chromatography (GC) mass spectrometry, we were able to positively identify the chemical structure of our patient's stone, as well as other similar stones from Louis Herring, as containing ephedrine, norephedrine, and pseudoephedrine.