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Biomedical subjects

K M McCulloch

Publications and source records attributed to K M McCulloch.

27 records · Page 2Linked to original sources
PubMed1993

Influences of the endothelium and hypoxia on alpha 1- and alpha 2-adrenoceptor-mediated responses in the rabbit isolated pulmonary artery.

1. The effects of the inhibitor of nitric oxide synthase, N omega-nitro-L-arginine methylester (L-NAME, 10(-4) M), mechanical disruption of the endothelium and hypoxia on contraction to noradrenaline (alpha 1- and alpha 2-adrenoceptor agonist), phenylephrine (alpha 1-adrenoceptor agonist) and UK 14304 (alpha 2-adrenoceptor agonist) were compared in the rabbit isolated pulmonary artery. The effects of the selective antagonists rauwolscine (10(-6) M, alpha 2-adrenoceptors) and prazosin (10(-7) M, alpha 1-adrenoceptors) on the contractions to noradrenaline before and after exposure to L-NAME were also assessed. 2. Noradrenaline, phenylephrine and UK 14304 all produced concentration-dependent increases in vascular tone. The responses to noradrenaline were sensitive to both rauwolscine and prazosin (effect of prazosin >> rauwolscine). L-NAME increased the potency of both noradrenaline and UK 14304, and also the maximum tension achieved. It had no effect on the responses to phenylephrine. After L-NAME, contractions to noradrenaline, although still sensitive to both rauwolscine and prazosin, were now more sensitive to inhibition by rauwolscine. 3. Endothelium removal augmented the potency and maximum contractions to noradrenaline, phenylephrine and UK 14304. 4. Hypoxia decreased both the potency of phenylephrine and its maximum contractile response, but increased the maximum response to noradrenaline without effecting responses to UK 14304. 5. In conclusion, in the rabbit pulmonary artery, augmentation of contractile responses to noradrenaline by L-NAME involves a potentiation of alpha 2-adrenoceptor-mediated contraction probably through an effect on the synthesis of endothelium-derived nitric oxide. Experimental hypoxia had differential effects on all three agonists and did not mimic the effect of nitric oxide synthase inhibition.

Adrenergic alpha-Agonists↗
PubMed1991

Comparison of two neonatal intravenous amino acid formulations in preterm infants: a multicenter study.

Two neonatal intravenous amino acid solutions (Aminosyn-PF and Troph-Amine) were compared in 44 preterm infants. The rate of weight gain, nitrogen balance, and changes in plasma aminograms were determined over 7 days to ascertain whether different outcomes could be identified for the two solutions. At study entry, the infants received a minimum infusion of 2 g amino acid/kg/d with 50 or more nonprotein kcal/kg/d. Group mean amino acid intake over the study period was approximately 2.6 g/kg/d for both groups; nonprotein caloric intake approximated 90 kcal/kg/d. Results showed no significant differences between solutions for the rate of weight gain, nitrogen balance, and nitrogen retention, which approximated intrauterine rates. The rate of weight gain averaged nearly 15 g/kg/d for both solutions. Differences between day 0 and day 7 plasma aminograms showed significant changes between solutions for histidine, lysine, methionine, phenylalanine, threonine, and glutamic acid. However, day 7 plasma aminograms for both solutions compared favorably with those from enterally fed preterm infants reported in the literature. Failure to identify significant differences for the rate of weight gain, nitrogen balance, or nitrogen retention between the two groups suggests that differences in plasma aminograms resulting from use of one solution or the other had no short-term clinical consequences in the premature infants studied.

Amino Acids↗
PubMed1990

Prospective pneumogram recordings in preterm infants with and without clinical apnea and bradycardia.

Recordings of breathing movements and heart rate (pneumograms) were obtained prospectively in 89 preterm infants at 0-28 days of age to determine if those who develop apnea and/or bradycardia with cyanosis (Group 1) differ from those who do not (Group 2). The 148 pneumograms were blindly analyzed for periodic breathing, bradycardia, longest apnea, and quiet time. Pneumograms were compared between groups at weekly intervals during the first 4 weeks. Significant differences were found among infants who had pneumograms recorded during the 1st week of life. Although mean gestational age and mean postconceptional age at recording were similar, birthweight and weight at recording were significantly lower in Group 1 infants. Total time spent in periodic breathing and the longest episode of periodic breathing were significantly greater in Group 1 infants. Logistic regression analysis revealed significant independent relationships between birthweight and periodic breathing at less than or equal to 7 days of age and the occurrence of symptomatic apnea and/or bradycardia. It is concluded that preterm infants who develop apnea and/or bradycardia with cyanosis have a lower mean birthweight and mean weight at recording at less than or equal to 7 days of age than similar asymptomatic preterm infants. Periodic breathing at less than or equal to 7 days of age is associated with the occurrence of clinical symptoms of apnea and/or bradycardia. Normal pneumogram values for groups of 6-21 asymptomatic preterm infants are provided for the first 4 weeks of life.

Apnea↗
PubMed1989

Transplacentally acquired caffeine and the occurrence of apnea, bradycardia, and periodic breathing in preterm infants: preliminary communication.

Cord blood caffeine concentrations were measured by high-pressure liquid chromatography in 79 preterm infants. Eleven infants (14%) had detectable caffeine concentrations ranging from 1.1 to 3.7 micrograms/mL (means +/- SD = 2.5 +/- 0.8), and 68 infants had no measurable caffeine. Seven infants with detectable caffeine (group 1) had impedance pneumograms recorded before 2 weeks of age. Each infant in group 1 was matched with two infants without detectable caffeine by birthweight, gestational age, and chronologic age at pneumogram recording to yield a control group (group 2) of 14 infants. Comparison of the groups using quantitative measures of apnea, bradycardia, and periodic breathing obtained from pneumogram analysis and the incidence of monitor alarms on bedside nursing records showed no significant differences. Thus, caffeine was present infrequently and at low concentrations at birth in 79 preterm infants. The amount of apnea, bradycardia, and periodic breathing experienced before 2 weeks of age in 7 preterm infants with detectable cord blood caffeine was not different from that in 14 similar infants without caffeine. Future studies are planned to examine the relationship between postnatal changes in transplacentally acquired methylxanthine concentrations and quantitative measures of apnea, bradycardia, and periodic breathing in a larger number of preterm infants without cardiorespiratory disease.

Apnea↗
PubMed1987

Double-blind controlled trial of single-dose treatment with bovine surfactant in severe hyaline membrane disease.

In a double-blind clinical trial the effects of a single dose of reconstituted bovine surfactant ('Surfactant TA') were assessed in 30 premature infants (birthweight 751-1750 g) with severe hyaline membrane disease. 17 infants had a sonicated saline suspension of 100 mg/kg surfactant phospholipid instilled into the trachea at 5.0 (SD 0.7) hours of age and 13 infants received saline by the same route at 4.3 (1.1) hours of age. In the surfactant-treated group there was early improvement in oxygenation and ventilation. Haemodynamically significant patent ductus arteriosus occurred more often in the surfactant group; pneumothorax and pulmonary interstitial emphysema occurred less often. The combined incidence of death and severe bronchopulmonary dysplasia was significantly lower in the surfactant group (3/17) than in the placebo group (9/13).

Animals↗
PubMedDate not supplied

Effect of novel mixed ETA/ETB antagonists on responses to ET-1 in human small muscular pulmonary arteries.

Selective ETA and ETB receptor antagonists do not fully inhibit responses to ET-1 in human small pulmonary arteries. Here, we have compared the influence of the novel mixed ETA/ETB antagonists SB/217242, SB/234551 and SB/209670 on ET-1-mediated vasoconstriction in these vessels. ET-1 was a potent vasoconstrictor (pEC50: 8.14+/-0.05, n=5) and the concentration-response curve to ET-1 was biphasic in nature. All three mixed antagonists (1 microM) inhibited the responses to ET-1, abolishing the biphasic form of the concentration response curve. The order of potency was SB 209670>SB 234551>/=SB 217242 with estimated pKb values of 8.0+/-0.20, 6.8+/-0.17 and 6. 6+/-0.11 respectively (n=3-5).

Carboxylic Acids↗
PubMedDate not supplied

Intrauterine cocaine exposure and the risk for sudden infant death syndrome: a meta-analysis.

OBJECTIVE: To determine whether an association exists between intrauterine cocaine exposure and sudden infant death syndrome (SIDS). STUDY DESIGN: A meta-analysis of 10 published studies that reported the incidence of SIDS in infants born to mothers who used cocaine during pregnancy. We computed the rates of SIDS in cocaine-exposed infants for each of the 10 studies and in comparison groups for each of the eight studies that reported the incidence of sudden infant death syndrome in comparison groups. We also computed odds ratios and 95% confidence intervals individually for the eight studies with comparison groups. Then we computed adjusted overall odds ratios (Mantel-Haenszel) by combining the eight studies with comparison groups; combining three of these studies in which the comparison group infants were exposed to illicit drugs other than cocaine (polydrug controls); and combining the other five studies in which the comparison group infants were not exposed to illicit drugs (drug-free controls). RESULTS: For all 10 studies combined, SIDS occurred in 84 of 12,163 infants with intrauterine cocaine exposure; the variance weighted estimate for incidence was 5.2 per 1000 with a 95% confidence interval of 4 and 7 per 1000. The combined odds ratio for SIDS in cocaine-exposed versus all comparison group infants was 3.9 (95% confidence interval 3 and 5), a significantly increased risk. However, in a subset analysis we found that the odds ratio for SIDS in cocaine-exposed versus the polydrug comparison group infants was 2.7 (95% confidence interval 0.9 and 8.2), not a significantly increased risk. Whereas in a subset analysis comparing risk for SIDS in cocaine-exposed versus the drug-free comparison group infants, the odds ratio was 4.1 (95% confidence interval 3.2 and 5.3), indicating a highly significant effect of cocaine exposure on SIDS risk. CONCLUSION: After we controlled for the confounding variable of concurrent use of other drugs, the increased risk for SIDS could not be attributed to intrauterine cocaine exposure alone. The increase in risk for SIDS was found not to be specific to cocaine but to intrauterine exposure to illicit drugs in general.

Cocaine↗