Search PubMedSearch

Biomedical subjects

C Hamilton

Publications and source records attributed to C Hamilton.

At least 55 records · Page 3Linked to original sources

The effect of nonnutritive sucking on heart rate in preterm infants.

A laboratory and a field experiment used within-subject designs to test the hypothesis that nonnutritive sucking (NNS) reduces heart rate (HR) in preterm infants. Infants in Experiment A were provided a standard pacifier nipple for 30 min under strictly controlled conditions. In the field Experiment B, nursing staff provided infants with a standard pacifier during alternate intervals in a sequence of four interfeed intervals spanning 12 hr. NNS significantly reduced average HR in each experiment. Given the strongly positive relationship between HR and energy expenditure, these results suggest that NNS reduces energy expenditure in preterm infants. Such an effect, in turn, could help to explain how the opportunity to engage in NNS enhances growth in preterms.

Arousal

The reduction of alpha-ketocarboxylic acids and alpha-dicarbonyl compounds with titanium(III) chloride.

Thirteen model alpha-ketocarboxylic acids and alpha-dicarbonyl compounds have been observed to be reduced by titanium(III) chloride. The products of these reactions were shown by melting (boiling) points, mixed melting points, derivatives, refractive indices, infrared, and NMR comparisons with authentic compounds or literature information to be the corresponding alpha-hydroxycarboxylic acids or alpha-hydroxyketones.

Carboxylic Acids

Radiotherapy for stage I seminoma testis: results of treatment and complications.

The results of treatment by infradiaphragmatic lymph node irradiation and orchiectomy in 232 patients with Stage I testicular seminoma seen between 1963 and 1983 are reported. Of this group, only five (2%) patients relapsed and none died from seminoma. Contralateral testicular tumours occurred in 12 patients and five developed second non-testicular malignancies. The acute and late morbidity of radiotherapy was low although 15 patients developed peptic ulceration. There was a significant association between prior abdominal surgery and a history of dyspepsia with ensuing peptic ulceration. Future management policy is discussed on the basis of these observations.

Adult

Mortality study of workers in the man-made mineral fiber production industry in the United Kingdom.

The workforces of two factories in the United Kingdom have been followed up to the end of 1984 as part of the collaborative European study of the health of workers in the man-made mineral fiber industry. In the cohort from an English glass-wool plant there was no suggestion of any excess mortality compared to national or local rates, except for lung cancer among men in comparison to the national level. However, the data indicate that the workers were largely local persons by place of birth, occupation, and death, and they therefore suggest that the national comparison was inappropriate. Lung cancer mortality showed little relationship to length of employment, duration of time since first exposure, occupational classification, or level of exposure. In the cohort from a continuous-filament plant in Northern Ireland no excess mortality from cancer was found. There were, however, raised death rates from violent causes and cardiovascular disease, but these rates were not exceptional for the area of the country in which the factory was located. No deaths from mesothelioma were reported in either cohort.

Construction Materials

Triazolam and ethanol interaction: kinetic and dynamic consequences.

The kinetic and dynamic consequences of the coadministration of triazolam and ethanol were investigated in six normal subjects. Each received three treatments: triazolam, 0.25 mg by mouth, preceded by 1 hour and followed for 7.5 hours by oral ethanol dosed to maintain breath concentrations of 800 to 950 mg/L; placebo and ethanol; and triazolam and orange juice. After ethanol, triazolam total AUC0-infinity increased (mean +/- SD = 21% +/- 18%). Subjects showed greater psychomotor impairment on measures of free recall, postural stability, and hand-eye coordination after the combination than after either drug alone. These dynamic interactions are greater than the kinetic changes.

Administration, Oral

Is there acute tolerance to alcohol at steady state?

Although acute tolerance to the psychomotor impairment caused by alcohol has been documented in single-dose studies, the pharmacodynamic effects of continued alcohol administration in humans have not been well studied. Six nonalcoholic men received alcohol to achieve and maintain breath alcohol levels of 80-100 mg/dl for 6 hr. The men suffered an initial impairment in word recall but improved over the next 6 hr. Measures of standing steadiness and manual tracking did not show evidence of the development of tolerance. This lack of tolerance was reflected in subjects' self-assessments of sedation and intoxication.

Adult

Experimental evaluation of iosefamate meglumine and its derivatives as hepatobiliary CT contrast agents.

Iosefamate meglumine has attracted attention as a possible hepatobiliary contrast agent for CT scanning. However, its limited hepatic opacification has prevented clinical acceptance. To find a more efficient agent, the efficacy and toxicity of six derivatives of iosefamate were compared with those of the parent compound in dogs. Twenty dogs received intravenous doses ranging from 150 to 600 mg I/kg of one of these seven water-soluble, ionic, dimeric agents. Three control animals received equivalent amounts of physiologic saline. The CT densities of liver, biliary tract, kidneys, and blood were then measured for up to 3 hr. Toxicity tests of liver and kidney function were performed for up to 3 days. Among the new agents, only MI-294, a previously unreported compound, proved to be a slightly more efficient hepatic opacifier than iosefamate (0.40 vs. 0.34 H per mg I/kg, respectively). MI-294 was also the least toxic. However, transient abnormalities in at least one liver function test were observed with every agent at some dose level. One animal died with hepatic necrosis after receiving iosefamate. No renal impairment was noted in any case. MI-294 has advantages over iosefamate as a CT liver and biliary opacifier in dogs. Potential hepatotoxicity of this class of agents needs to be more fully evaluated.

Animals

Ethanol-induced inhibition of hepatic uptake of propranolol in perfused rat liver and in man.

Studies were conducted to determine the mechanism whereby ethanol alters the hepatic disposition of propranolol. In eight isolated perfused rat livers, ethanol (mean = 40.1 mmol/l diminished the clearance of dl-propranolol (1.93 +/- 0.43 to 1.24 +/- 0.22 ml/min/g liver, p less than 0.05); increased its t1/2 (12.8 +/- 1.5 to 20.7 +/- 3.25 min, p less than 0.01); and decreased the proportion metabolized (68.7 +/- 4.7% to 34.3 +/- 10.3%, p less than 0.01). These results suggest that ethanol could substantially increase the oral bioavailability of propranolol in humans. However, in normal human volunteers administered 80 mg of propranolol orally, alone, or preceded and followed by ethanol to maintain breath ethanol concentrations of 800-1000 mg/l, increases in propranolol AUC were smaller than anticipated. Seven subjects had increases in free propranolol AUC0-8h (32%, range: 12-61%) (p less than 0.05), while total propranolol AUC0-8h increased by a mean 22% (range: -4-+49%). Propranolol free fraction varied with time and was higher after ethanol (mean = 0.090 vs 0.084) (p less than 0.077). The extent of the propranolol-induced slowing of heart rate was not influenced by ethanol (mean decrease from baseline of 13 bpm at peak propranolol effect vs 9 bpm without ethanol); mean heart rates following propranolol with ethanol were higher at all times (mean of 7.5 bpm) (p less than 0.001) than after propranolol alone. Ethanol inhibits the hepatic oxidative metabolism of propranolol in vitro; however, any effect on heart rate of higher concentrations of propranolol induced by ethanol in humans is offset by the cardio-acceleratory effect of ethanol.

Animals

Acute kinetic and dynamic interactions of zimelidine with ethanol.

The acute interaction of zimelidine (Z) with ethanol (E) was examined in six healthy men aged 20 to 37 yr who randomly received each of four treatments 1 wk apart: Z, 200 mg by mouth, preceded by 1 hr and followed for 7 hr of oral E in juice dosed to maintain blood alcohol concentrations between 800 and 1000 mg/l; placebo Z and E; Z and juice; and placebo Z and juice. E decreased the rate of biotransformation of Z to norzimelidine (NZ) by 46%, but the AUCs of Z, NZ, and their total concentration over 8 hr were not altered by E. Acetaldehyde concentrations did not change and no aversive alcohol-sensitizing reaction was detected. E-induced impairments in memory, body sway, and a manual tracking task were further enhanced by Z, as was the E-induced decrease in friendliness. Data suggest Z and E interact kinetically and dynamically and suggest a mechanism whereby Z may decrease E intake in man.

Administration, Oral

Identification of the phoM gene product and its regulation in Escherichia coli K-12.

Plasmids containing the chromosome region of Escherichia coli encoding phoM, whose product is a positive regulator of alkaline phosphatase expression, were isolated from the Clarke and Carbon plasmid bank. A 9.9-kilobase EcoRI fragment of plasmid pLC17-39 (subcloned into pBR322) was able to complement both phoM and thrB mutations. Restriction endonuclease analysis and in vitro mutagenesis of the hybird plasmids enabled the localization of the phoM gene locus to 3 kilobases of the cloned chromosomal fragment. The phoM gene product was identified, with maxicell techniques, as a protein with an approximate molecular weight of 55,000. A phoM-lacZ protein fusion was constructed by using a plasmid carrying the phoM gene and a derivative of phage lambda, lambda plac Mu2. Restriction endonuclease analysis of the plasmid carrying the fusion indicated that phoM is transcribed in a clockwise direction on the circular E. coli chromosome. Analysis of strains bearing the fusion on a multiple-copy plasmid or integrated at the lambda attachment site of the chromosome indicated that the synthesis of the phoM gene product was unaffected by phosphate limitation of growth. The expression of the phoM gene was studied in strains with mutations in genes encoding effectors of the pho regulon. A threefold increase in phoM expression was seen in a phoU strain in comparison with the wild-type strain.

Alkaline Phosphatase

Surgical management in interrupted aortic arch and atrioventricular canal.

This report concerns the management of two infants born with a combination of interrupted aortic arch with atrioventricular canal and possible left ventricular hypoplasia. Staged management including initial reconstruction of the aortic arch followed by partial intracardiac correction and, finally, closure of intentionally created atrial septal defects was successful.

Aorta, Thoracic

Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction.

Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyline free plasma concentrations were increased by a logarithmic mean of 204%, 186% and 127% at 1.5, 2, and 2.5 h, respectively, and amitriptyline free AUC0-8h was increased by 48% +/- 13% (means +/- SEM) (t = 5.21, p less than 0.01). Nortriptyline total AUC0-8h was increased by 26.6% +/- 12% (means +/- SEM) (t = 2.21, p less than 0.09). At the time of peak amitriptyline plasma concentrations, mean postural sway was increased over baseline by 92% with, and 2% without ethanol; likewise, mean short term memory (word recall) was decreased over baseline by 71% with, and 37% without ethanol. Ethanol increases free amitriptyline plasma concentrations most dramatically during the period of drug absorption; this is due to a decrease in amitriptyline hepatic clearance, resulting in decreased first-pass extraction. Together with the pharmacodynamic interaction, the kinetic changes provide a rationale for the toxicity of this combination and its deleterious effects on psychomotor skills.

Adult

DNA-DNA hybridization assay for detection of Salmonella spp. in foods.

We have developed a DNA-DNA hybridization test for the presence of Salmonella spp. in foods. This test requires an initial pre-enrichment of food samples in nutrient broth but does not require selective enrichment. Samples of food cultures are collected on membrane filters and assayed by molecular hybridization to labeled probes. The probes consist of DNA sequences which are unique to the genus Salmonella and are widely distributed in the genus. A diverse panel of foods was assayed successfully by this methodology.

Bacteriological Techniques

Evaluation of zopiclone physical dependence liability in normal volunteers.

The potential of zopiclone, a non-benzodiazepine sedative hypnotic, to induce physical dependence in normal human volunteers was investigated. 9 male subjects (age range 21-39 years) participated in a 56-day double-blind study with random assignment to initial treatment A or B: (A) zopiclone 7.5 mg p.o. nightly for 21 days followed by placebo for 7 days, and (B) placebo nightly for 21 days followed by placebo for 7 days. Heart rate, blood pressure, hand tremor and auditory-evoked EEG were repeatedly measured during the withdrawal periods. No differences in any of these variables between phases were found (beta = 0.90 for mean differences of 16% between phases). Subjects slept longer (mean 28 min, p less than 0.013) on zopiclone than on placebo. Symptoms of state anxiety were greater on days 2 and 4 after discontinuing zopiclone compared to all other withdrawal days (p less than 0.0021). The mean relative increase on days 2 and 4 was 30%. Sleep depth (self-rating scale) was no deeper on drug than on placebo, but during the withdrawal phases, sleep was less deep on days 2 and 4 of withdrawal from zopiclone compared to all other withdrawal days (p less than 0.0001). Subjects were unable to identify the pattern of drug administration on withdrawal, and none reported important symptoms. Discontinuation of zopiclone (7.5 mg for 21 days) is associated with detectable increase in state anxiety and lighter sleep on days 2 and 4 of withdrawal. Quantitatively, similar changes occur with other hypnotic drugs of relatively low dependence liability.

Adult

Effects of prolonged and brief infusions of noradrenaline on arterial pressure and on the plasma concentrations of active renin, angiotensin II, aldosterone and potassium.

Conscious male beagle dogs were given constant intravenous infusions of noradrenaline for 14 days, four receiving 125 ng/kg/min and four 250 ng/kg/min. Before, during and after these infusions dose-response studies were done in which additional noradrenaline was infused at 500, 1000 and 2000 ng/kg/min, each rate for 1 h. Blood samples were taken before and during infusions for measurement of haematocrit and plasma concentrations of noradrenaline, active renin, angiotensin II, aldosterone, sodium and potassium. Fourteen-day infusion of noradrenaline at 125 ng/kg/min did not raise blood pressure significantly though infusion at 250 ng/kg/min did, but for the first week of infusion only. Heart rate decreased significantly at both rates. Arterial pressure fell markedly and significantly on stopping infusion. Mean plasma concentrations of renin, angiotensin II and aldosterone tended to be lower during prolonged infusion of noradrenaline, but only the fall of renin during the second week was significant in one group of dogs. Noradrenaline at higher rates significantly raised blood pressure and increased plasma concentrations of renin and angiotensin II. Plasma aldosterone concentration did not rise significantly, perhaps because plasma potassium concentration decreased; in support of this theory changes of plasma aldosterone correlated with changes of plasma potassium but not with changes of angiotensin II. The rise in arterial pressure during dose-response studies was related to the increase of plasma noradrenaline. Prolonged infusion of noradrenaline did not alter the dose-response relation between plasma noradrenaline concentration and arterial pressure.

Aldosterone

Recovery in vivo and in vitro of alpha-adrenoceptor responses and radioligand binding after phenoxybenzamine.

Phenoxybenzamine is an irreversible, selective alpha 1-adrenoceptor antagonist that results in long-lasting attenuation of the effects of alpha-adrenoceptor agonists in vivo and in vitro. We have studied in rabbits the time course of recovery of in vivo pressor responses to phenylephrine and in vitro contractile responses of spiral strips of renal artery to phenylephrine and noradrenaline. The maximum number of binding sites and the dissociation constant has been determined using 3H-prazosin in spleen and heart membranes prepared at intervals up to 8 days after phenoxybenzamine 5 mg/kg intravenously. In vitro contractile responses recovered over 2-3 days and by 4 days the EC50 was lower than control. In vivo pressor responses recovered over 5-8 days to control levels. The number of binding sites was only 50% of control at 8 days. It is proposed that under the conditions studied the recovery of binding sites may provide an index of turnover of alpha-adrenoceptors. The results also suggest that postreceptor mechanisms contribute to the increased responses observed in vitro.

Animals