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Biomedical subjects

C Hamilton

Publications and source records attributed to C Hamilton.

At least 73 records · Page 4Linked to original sources

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↗

Prolonged infusion of norepinephrine in the conscious dog: effects on blood pressure, heart rate, renin, angiotensin II, and aldosterone.

Eight conscious beagle dogs were given continuous intravenous infusions for 4 weeks: 0.9% NaCl solution was given for the first week; norepinephrine for the following 2 weeks, (at 125 ng/kg/min or at 250 ng/kg/min each in four dogs), 0.9% NaCl for the final week. Norepinephrine at the lower dose did not raise blood pressure but did reduce heart rate significantly. The higher rate of norepinephrine infusion raised blood pressure, but for the first week of infusion only, and again heart rate was reduced significantly during both weeks. Blood pressure fell on stopping infusion whether or not it had been raised previously. Plasma concentrations of renin, angiotensin II, and aldosterone were reduced, but the changes were of borderline significance only. These changes occurred when plasma concentrations of norepinephrine were increased four-sevenfold. The acute response to high infusion rates of norepinephrine (500, 1,000, and 2,000 ng/kg/min each for 1 h) was tested at weekly intervals in each dog. At each of these high rates of infusion, blood pressure, renin and angiotensin II, and haematocrit increased while plasma potassium concentration and heart rate fell. These changes occurred with increases of plasma norepinephrine greater than 14-fold. Prolonged infusion of norepinephrine did not alter the relation between plasma norepinephrine and arterial pressure as assessed by these dose-response studies.

Aldosterone↗

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↗

The use of prostaglandin E1 and Blalock-Taussig shunts in neonates with cyanotic congenital heart disease.

Six unselected neonates with cyanotic congenital heart disease and life-threatening degrees of arterial oxygen desaturation have been managed by a protocol that includes administration of prostaglandin E1 (PGE1) and early Blalock-Taussig shunting. In 5 patients (seven paired observations) partial pressure of arterial oxygen (PaO2) rose from 19 mm Hg to a mean of 32.9 mm Hg within 20 minutes of initiation of PGE1 (0.1 to 0.2 microgram/kg/hr), infused intravenously or through an aortic catheter placed at ductal level or with both methods. The nonresponsive patient was older than the patients showing a positive response (1 month versus 24 to 96 hours). Following catheterization, immediate palliative operation including a Blalock-Taussig shunt was carried out. Although all had a satisfactory PaO2 (mean, 49 mm Hg) postoperatively, the PGE1-nonresponsive patient experienced serious intraoperative bradycardia, hypotension, and acidosis in contrast to the PGE1-responsive group. In this study, the use of PGE1 was not associated with any apparent serious side effects.

Drug Evaluation↗

Sequential evaluation of the supine hypertension or 'roll-over' test in a high risk population.

The supine hypertensive or 'roll-over' test (ROT) was performed serially in 24 primigravid patients between 27 and 35 weeks of gestational age. Pregnancy-induced hypertension (PIH) developed in 3 women (12.5%). Test producibility one week to the next in the same patient was poor. A false-positive ROT was noted for 83% of our patients a false-negative test for 12.5%. We conclude that serial testing reveals marked variations in response that reflect inherent biologic fluctuations that limit the predictive value of the ROT for screening outpatients.

Adolescent↗

Topical analgesia before tracheal intubation.

The major toxic effects of local analgesic drugs are regarded as due to over-dosage. A technique of topical analgesia for tracheal intubation using lignocaine is described based on spraying the pyriform fossae to effect a superior laryngeal nerve block combined with topical analgesia of larynx and trachea which avoids excessive exposure of the lowere airway to the local analgesic. The results show lower levels of venous blood lignocaine with slower absorption of the agent than when similar doses are applied to the trachea. This method is accordingly recommended.

Administration, Topical↗

The anterior band of the inferior glenohumeral ligament: biomechanical properties from tensile testing in the position of apprehension.

The shoulder is the most commonly dislocated joint in the body. The primary restraint to anterior instability is the anterior band of the inferior glenohumeral ligament, where lesions are found after dislocation. The amount of surgical plication required to eliminate instability and maintain full range of shoulder motion remains unclear. We performed tensile testing with the shoulder in abduction and external rotation in 11 human, fresh-frozen, cadaveric glenohumeral joints to improve understanding of the glenoid origin of the anterior band of the inferior glenohumeral ligament and to quantify midsubstance irrecoverable elongation. After measuring the length, width, and thickness of the anterior bands with digital micrometry, biomechanical properties were obtained on bone-ligament-labrum-bone (b-l-l-b) complexes. The complexes were aligned for tensile testing with the humerus abducted 60 degrees and externally rotated. The b-l-l-b complexes were then loaded to failure at a strain rate of 100%/sec. Seven of the complexes failed at the glenoid insertion site (representing the Bankart lesion), 2 at the humeral insertion site, and 2 at the anterior band midsubstance. The ultimate load for the b-l-l-b complexes was 353+/-32 N (mean+/-SE), and tensile stress at failure of the glenoid insertion site averaged 9.6+/-2.1 MPa. When the complex failed at the glenoid insertion site, total elongation of the b-l-l-b complex was 9.1+/-0.5 mm, and the ligament midsubstance strain was 13.0%+/-1.8%. Irrecoverable elongation was only 0.8 mm when failure occurred at the glenoid insertion site. Our results indicate patients with initial anterior glenohumeral instability have small irrecoverable capsuloligamentous elongation so that meaningful plication in addition to repair of the Bankart lesion may be unnecessary.

Cadaver↗