Topical ropivacaine for analgesia of aplasia cutis congenita in newborns with hereditary epidermolysis bullosa.

Aplasia cutis congenita (ACC) in patients with hereditary epidermolysis bullosa (EB) is often associated with major pain. We report our experience with using topical ropivacaine during dressing in newborns with ACC. Eight full-term newborns with EB and ACC were hospitalized in a neonatal intensive care unit for severe pain during dressing despite the use of paracetamol, opioids (n = 8) or ketamine (n = 7). Topical xylocaine was poorly tolerated and not effective. Ropivacaine 2 mg/ml was used directly in contact with the ACC, with a maximum 1 mg/kg/day, which enabled care without the child crying. No immediate or late systemic toxicity was observed. Topical ropivacaine 0.2% appears to be an interesting topical analgesic, with good clinical tolerance and rapid action, in newborns with ACC and EB. These data need to be confirmed in a prospective study including pharmacokinetics evaluations.

Selective logging, habitat quality and home range use by sympatric gorillas and chimpanzees: a case study from an active logging concession in Southeast Cameroon.

We examined range use by great apes during logging activities and investigated associations between local variations in ape abundance and changes in the structure of the habitat or in the availability of fruits after disturbances. We carried out two annual censuses of western lowland gorilla (G. g. gorilla) and chimpanzee populations (Pan t. troglodytes) in an active logging concession in Southeast Cameroon. The results suggest that gorillas may adapt their range use to avoid most recently logged compartments, while chimpanzees appear to be more spatially resilient to logging. In our study site, selective logging affected 10% of the forest. After logging, gorillas nested in all types of vegetation, while chimpanzees nested exclusively in mixed mature forest. Fruit availability was not affected by logging and did not explain the distribution of ape nests in the study area.

Estimated energy intake, macronutrient intake and meal pattern of Flemish adolescents.

OBJECTIVE: To describe the energy and macronutrient intake and the meal patterns of Flemish adolescents, aged 13-18 y. METHODS: A 7 day estimated food record was administered to the whole sample. SETTING: Secondary schools in the city of Ghent, Belgium. SUBJECTS: A total of 341 adolescents (13-18 y) selected by a multistage clustered sampling (participation: 72.7%). MAIN RESULTS: A significant increase with age was observed in total energy intake in adolescent boys (P<0.01), but not in girls. The energy distribution over the macronutrients showed no significant difference between boys and girls. On average, 35.7% (s.d. 4.81%) of energy came from total fat and 15.4% (s.d. 2.46%) from saturated fatty acids; 49.0% (s.d. 5.28%) from total carbohydrates with 25.1% (s.d. 4.49%) from complex carbohydrates and 23.9% (s.d. 5.86%) from free sugars. The energy contribution of alcohol in the 16-18 y-old-group was significantly higher as compared with the 13-15 y-old-group, for both boys and girls. Snacks between meals accounted for almost 20% of the total energy intake. Lunch and dinner were characterized by high total fat content. CONCLUSION: These students consumed a diet high in total fat and in saturated fatty acids and also high in mono- and disaccharides. Observed mean intakes deviate considerably from the Belgian dietary guidelines. A low energy intake at breakfast was observed, while a higher proportion of energy was derived from snacks.

Stir bar sorptive extraction for the determination of ppq-level traces of organotin compounds in environmental samples with thermal desorption-capillary gas chromatography--ICP mass spectrometry.

The extraction and preconcentration capabilities of a new extraction technique, stir bar sorptive extraction, were combined with the separation power of capillary gas chromatography (CGC) and the low limits of detection (LODs) of inductively coupled plasma mass spectrometry (ICPMS) for the determination of the organotin compounds tributyltin (TBuT) and triphenyltin (TPhT) in aqueous standard solutions, harbor water, and mussels (after digestion with tetramethylammonium hydroxide). Throughout, tripropyltin for TBuT and tricyclohexyltin for TPhT were used as internal standards to correct for variations in the derivatization and extraction efficiency. Calibration was accomplished by means of single standard addition. Derivatization to transform the trisubstituted compounds into sufficiently volatile compounds was carried out with sodium tetraethylborate. The compounds were extracted from their aqueous matrix using a stir bar of 1-cm length, coated with 55 microL of poly(dimethylsiloxane) (PDMS). After 15 min of extraction, the stir bar was desorbed in a thermal desorption unit at 290 degrees C for 15 min, during which the compounds were cold-trapped on a precolumn at -40 degrees C. Flash heating was used to rapidly transfer the compounds to the GC where they were separated on a capillary column with a PDMS coating. After separation, the compounds were transported to the ICP by means of a homemade heated (270 degrees C) transfer line. Monitoring of the 120Sn+ signal by ICPMS during the run of the GC provided extremely low LODs for TPhT in water: 0.1 pg L(-1) (procedure) and 10 fg L(-1) (instrumental) and a repeatability of 12% RSD (n = 10). In harbor water, concentrations of 200 pg L(-1) for TBuT and 22 pg L(-1) for TPhT were found. In fresh mussels, a concentration of 7.2 ng g(-1) (dry weight) TPhT was found. The accuracy of the method was checked by the determination of TPhT in CRM477 (mussel tissue) and comparison of the result to that of an analysis of the same material with a classical liquid/liquid extraction with isooctane.

Automated capillary gas chromatographic system to monitor ethylene emitted from biological materials.

An automated capillary gas chromatographic system to measure ethylene emitted from biological materials is presented. The system consists of an on-line sampling device, a thermodesorption preconcentration apparatus and a capillary gas chromatograph with a flame ionization detection system. The limit of detection achievable on the GC system alone is 5 pg ethylene. The use of the strong Carboxen 1000 adsorbent at a sampling temperature as low as -50 degrees C allows sampling of volumes up to a few liters. Ethylene concentrations at low ppt levels can be accurately and reproducibly determined.

A double-blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine-induced wheal and flare response for 24 h in healthy male subjects.

BACKGROUND: New H1-antagonists have become available, but there has been no comparison of their potency for inhibiting histamine in the skin. METHODS: Cetirizine 10 mg, ebastine 10 mg, epinastine 20 mg, fexofenadine 60 mg, terfenadine 60 mg, loratadine 10 mg, or placebo was given to 14 healthy male volunteers in a double-blind, crossover randomized manner. Inhibition of the wheal and flare response to epicutaneous histamine phosphate (100 mg/ml) challenge was measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after doses. RESULTS: Epinastine inhibited the wheal and flare after 30 min. Cetirizine commenced acting at 1 h and was superior to other treatments. Ebastine was no better than placebo until 4 h, but was efficacious thereafter until 24 h. Terfenadine induced potent inhibition after 1 h and was superior to its metabolite fexofenadine. Loratadine was the least potent inhibitor. Inhibition of the flare response paralleled the patterns seen for wheals. The rank order for area under the curve (0-24 h) was cetirizine, epinastine, terfenadine, ebastine, fexofenadine, loratadine, and placebo. CONCLUSIONS: The inhibition of histamine effects in the skin may be useful in predicting the clinical utility of newly introduced antihistamines in treating allergic disorders.

An evaluation of an automated anesthesia record keeping system.

Mayo Clinic makes use of an automated anesthesia record keeping system in its cardiovascular operating rooms. Over 20,000 anesthesia records have been recorded with this system since its installation in 1983. How successful is this system? Does it meet the needs of the anesthesiologist? What are their attitudes towards the computer? A questionnaire survey was conducted to solicit the experiences, opinions, and recommendations of the users of this system. The results are described in this paper. The feedback will be used to determine the tasks and their priority for improving the current system, and to define the requirements for future computerization to meet the needs of the anesthesiologist in the operating room.

Nitrogen bridgehead compounds. 66. Bronchodilator nitrogen bridgehead compounds with a pyrimidinone moiety.

New types of bronchodilator agents, bi- and tricyclic nitrogen bridgehead compounds with a pyrimidin-4(3H)-one ring, were synthesized and evaluated for bronchodilator activity against serotonin-, histamine-, and acetylcholine-induced spasms in the guinea pig Konzett-Rössler test. The structure-activity relationships are discussed. The effects of some bi- and tricyclic derivatives on the human bronchus were also investigated. The homologous tricyclic compounds 68 and 69 were tested on isolated guinea pig ileum and trachea, and the effects of compound 69 were investigated in pilocarpine-treated dogs. Azepino[2,1-b]quinazoline (69; CHINOIN-1289) was selected for further biochemical and clinical investigations.

Uncoupling between beta-adrenoceptors and adenylate cyclase in dog ischemic myocardium.

We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior descending coronary in 5 anesthetized dogs. Crude cardiac membrane preparations were isolated from control and ischemic areas of ventricular myocardium and tested for: 1. L-(125I)iodocyanopindolol binding, in the absence and presence of +/- -isoprenaline and GTP, and 2. adenylate cyclase activity. The density of beta-adrenoceptors increased by 35% in membranes from ischemic areas while the proportion of receptors in a high affinity state for +/- -isoprenaline decreased from 43% to 20%. Adenylate cyclase activities in the basal state and under stimulation with NaF, forskolin, Gpp(NH)p, +/- -isoprenaline and VIP were all markedly and similarly reduced, being only about 30% of comparable activities in membranes from control areas. The +/- -isoprenaline subsensitivity of cardiac adenylate cyclase can, thus, be attributed to a defective enzymatic system and not to a reduction in the number of beta-adrenoceptors implying that the internal components of the system were more sensitive to acute ischemia than the outward oriented hormone receptors. It is tempting to ascribe this uncoupling to a functional depletion in the guanine nucleotide-binding regulatory protein Ns that might reflect a loss of high energy phosphate stores including GTP.

Amiodarone. Biochemical aspects and haemodynamic effects.

The mechanisms underlying the non-competitive beta-antagonistic properties of amiodarone were investigated, and the haemodynamic responses to exercise following the administration of oral amiodarone or intravenous propranolol were compared in dogs with a healed myocardial infarction submitted to a graded treadmill exercise. In radioligand binding studies, amiodarone, up to 10 mumol/L did not compete with 125I-iodocyanopindolol for binding to rat heart beta-adrenoceptors. Exposure of cardiac membranes to greater concentrations of amiodarone induced a significant decrease in the number of beta-adrenoceptors without affecting their affinity for 125I-iodocyanopindolol. Similar results were observed ex vivo, in rats after single or multiple dose administration. When added in vitro to rat heart membranes, amiodarone non-competitively inhibited the activation of adenylate cyclase by isoprenaline, glucagon and secretin. Stimulation of adenylate cyclase by those agents which act at more internal sites in the sarcolemmal membrane such as GppNHp, sodium fluoride or forskolin, was much less affected by amiodarone. In dogs performing at a submaximal work level, amiodarone significantly reduced heart rate and tended to increase coronary flow and to reduce left ventricular end-diastolic pressure, but did not affect left ventricular dP/dt. During submaximal exercise, propranolol had similar effects on heart rate, but dramatically reduced myocardial contractility.

Nitrogen bridgehead compounds. 38. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 3.

The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid (4) on the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of appropriate functional groups into position 9 of the pyridopyrimidine ring. The most active 9-substituted pyridopyrimidinecarboxylic acids contained an oxime, a phenylamino, or a (phenylamino)thioxomethyl group in position 9. The 9-phenylcarboxamido and 9-phenylhydrazono moieties may be regarded as bioisosteric groups in the pyridopyrimidinone series. In the series of 9-(arylamino)dihydropyridopyrimidines, the structure-activity relationship study revealed similar relationships as found for the 9-(arylhydrazono)tetrahydropyridopyrimidines. The biological activity was due to the 6S enantiomers. A monosubstituted arylamino moiety in position 9 was necessary for the intravenous activity. The most active compound, 9-[(3-acetylphenyl)amino]-6-methyl-4-oxo-6,7,8,9-tetrahydro-4H- pyrido[1,2-a]pyrimidine-3-carboxylic acid (40) was three times as active as the reference sodium chromoglycate (DSCG) in the passive cutaneous anaphylaxis (PCA) test.

Nitrogen bridgehead compounds. 33. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 2.

A series of 9-hydrazono-4H-pyrido[1,2-a]pyrimidin-4-ones was prepared. The compounds were evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. Structure-activity relationship studies revealed that the presence of a monosubstituted hydrazone moiety in position 9 and an unsubstituted 2-position are necessary for the intravenous activity.

Nitrogen bridgehead compounds. 18. New antiallergic 4H-pyrido[1,2-a]pyrimidin-4-ones. 1.

A new type of antiallergic agent, 9-hydrazono-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-ones, was synthesized and evaluated for inhibitory effects in the rat reagenic passive cutaneous anaphylaxis (PCA) screen. Several racemic 6-methyl derivatives were found to be more potent than disodium chromoglycate intravenously and some were also active orally. Structure-activity relationships are discussed. High stereospecificity was observed in the 6-methyl series between the enantiomers with 6S and 6R absolute configuration, the former being more active. Compound 17, (+)-6(S)-methyl-9-(phenylhydrazono)-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid [Chinoin-1045; UCB L140], has an ED50 value of 1.0 mumol/kg po and is now under clinical investigation.