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Biomedical subjects

R D Hamilton

Publications and source records attributed to R D Hamilton.

At least 19 recordsLinked to original sources

Prevention of tilorone developmental toxicity with progesterone.

The immunomodulator tilorone hydrochloride was administered (gastric intubation) once to time-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats in four experiments. In experiment 1, tilorone (250 or 500 mg/kg) was administered on day 10 of gestation. The dams were killed 4 or 72 hr after dosing. Interferon-like activity and drug levels were determined in maternal blood, spleen, and thymus, as well as in the embryos. In experiment 2, the test groups received progesterone (2 mg/kg), or tilorone (200 or 400 mg/kg), or progesterone and tilorone. The dams from each group were killed 24 or 48 hr after receiving tilorone. Experiment 3 was similar to experiment 2, except that the dams were killed on gestation day 20. In experiment 4, tilorone (400 mg/kg) was administered on gestation day 17, 18, or 19, and the dams were killed 24 hr after dosing or on gestation day 20. In all four experiments, tilorone-related maternal toxicity (regardless of whether progesterone also was administered) was observed, as characterized by marked decreases in weight gain, the occurrence of clinical signs, and in experiment 1 by decreased thymus weights, 72 hr post-dosing. Dose-related increases in the mean number of dead embryos and in serum interferon titers occurred 72 hr postdosing. In experiment 2, there was an increase in the number of dams in the 400-mg/kg (tilorone only) group with dead embryos only, 24 hr postdosing; similar results occurred in both the 200- and 400-mg/kg groups, 48 hr postdosing. However, in the groups that also received progesterone, a partial prevention of such embryolethality was evident. In experiment 3, embryotoxicity again was observed in both tilorone-treated groups, whereas several of the dams that were also given progesterone through day 19 of gestation experienced at least a partial prevention of the embryolethal effects of tilorone. In experiment 4, no fetotoxicity was observed despite the severe maternal toxicity evident.

Animals

Volume detection during voluntary and passive breathing.

The ability to detect small changes in tidal volume (VT) during either volitional or passive breathing was compared in seven normal subjects. Passive breathing was achieved with positive pressure applied at the mouth by a ventilator. Although baseline breathing pattern was similar for each subject during the two types of breathing, the ability of the subjects to detect changes in VT was at least as good, and in general better, during passive as compared to volitional breathing. This suggests that the generation of a motor cortical command to inspire and the resultant respiratory muscle contraction are not essential to the perception of a change in lung volume. An increase in information from receptors in the mouth, pharynx and extrathoracic airways sensitive to positive pressure may be responsible for the increased ability of most subjects to detect changes in VT during passive breathing.

Adult

Effect on breathing of raising end-expiratory lung volume in sleeping laryngectomized man.

In animals, tonic vagal activity from lung receptors provides a means by which changes in end-expiratory lung volume can influence respiratory timing. We wished to examine whether increasing the end-expiratory lung volume within the tidal volume range had a similar effect in man. In order to minimize behavioral influences on breathing, the study was performed in subjects during deep non-rapid eye movement sleep. Five laryngectomized subjects were chosen for the study since their permanent tracheal stomata allow simple, airtight connection to respiratory apparatus and avoided problems with glottic closure. During EEG-documented sleep, end-expiratory volume was increased by up to 350 ml with the addition of expiratory threshold loads of 1 to 10 cm H2O. End-expiratory volume increased linearly with expiratory pressure. Inspiratory and expiratory times (TI and TE) were not affected by increases in end-expiratory volume. Tidal volume (VT) was decreased such that end-inspiratory volume remained unchanged. The decrease in VT may result from a reduction in inspiratory muscle efficiency at a higher lung volume. The results of the study provide no evidence that tonic vagal afferent information from the lungs is important in controlling respiratory rhythm within the tidal volume range in man when behavioral control of breathing is minimized.

Adult

Bronchial reactivity in Western red cedar induced asthma.

A patient with Western red cedar induced asthma is described. The diagnosis was confirmed by a bronchial challenge with Western red cedar saw dust and the subsequent prolonged bronchial reactivity changes were measured using histamine inhalation tests.

Asthma

Chronic extradural hematoma: case report.

A recent experience with a chronic extradural hematoma found unexpectedly during an evaluation for an enlarged sella turcica is reported. This case, as well as pertinent literature, demonstrates the variability of the classical signs in the chronic lesion. Our experience suggests that the diagnosis of patients with persistent symptoms after head injury may be clarified by computerized tomographic scanning, which in the present case revealed chronic extradural hematoma.

Adult

Pineal apoplexy.

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Brain Neoplasms

Arterial blood gas analysis: potential errors due to the addition of heparin.

The effect of sodium heparin on the determination of the major arterial blood gas parameters was studied. The addition of heparin produced errors in all three parameters tested, i.e. PO2, PCO2 and pH. The PCO2 determination was most affected, a 12% decrease being introduced into a 1.5 ml blood sample by the volume of heparin which fills the deadspace of a syringe and needle. Small but statistically significant errors were also produced in PO2 and pH by this heparin concentration. The clinical implications of these findings are discussed and certain measures outlined to avoid such errors.

Arteries

Purification of human interferons by antibody affinity chromatography.

Human Leukocyte Interferon, Human Fibroblast Interferon and Namalva-interferon was purified on an antibody affinity colomn up to 2-20 X 10 IFU/mg protein with recoveries in the 80-120% range. The colomn was made by coupling highly absorped anti-leukocyte interferon immunoglobulins to Sepharose 4B. The absorption was performed by means of crude human leukocyte interferon covalently bound to Sepharose 4B.

Antibodies

Transverse fractures of the sacrum. A report of six cases.

The diagnosis of transverse sacral fracture was made in six patients. All patients initially had evidence of urinary retention, a decrease in anal sphincter tone, or both. Diagnostic confirmation was established by tomography in four patients and by cystometric examination in two. All patients who had transverse sacral fractures with displacement of the fragments had resolution of their neurological deficit following posterior sacral laminectomy and decompression.

Adult

Halofenate in the treatment of type II hyperlipoproteinemia. Double blind comparison with clofibrate.

A double-blind study comparing halofenate, a new lipid-lowering investigation drug, with an established drug, clofibrate, was conducted on 33 clinic patients with Type II hyperlipoproteinemia for a period of 48-96 weeks. All but 10 patients had some type of symptomatic major vascular disease. With respect to serum cholesterol levels, a comparable proportion (56-59%) of patients in each group responded to the respective treatment but the magnitude of lowering was substantially less for the halofenate responders (12% mean decrease versus 25%). Type IIa patients in both groups were more likely than Type IIb patients to have a favorable cholesterol-lowering response. Weight gain of 5% or greater was prejudicial to cholesterol lowering. In the case of serum triglycerides, the proportion of patients responding to clofibrate treatment was somewhat greater (87% versus 57% for halofenate) but the mean magnitude of lowering (27-34%) was comparable for responders in the two groups. Weight gain did not influence appreciably the triglyceride-lowering effect. Elevated concentrations of triglyceride (Type IIb) in the control period favored a triglyceride lowering response by clofibrate but was only a moderate influence on the response to halofenate.

Adult

Reflection on the 1976 Toronto Olympiad for the physically disabled.

A report is given on the various aspects of the 1976 Olympiad of the Physically Disabled. The aspects discussed are the historical background, planning and preparation of the Games, accommodation for amputees, blind and paraplegics, transport, games site, organisation of sports events, medical supervision, publicity of the Games, standards of performance and records and last, but by no means least, politics and sport.

Canada

Aquatic acetylene-reduction techniques: solutions to several problems.

Previous methods of performing aquatic acetylene-reduction assays are described and several problems associated with them are discussed. A refinement of these older techniques is introduced and problems that it overcomes are also discussed. A depth profile of nitrogen fixation (C2H4 production), obtained by the refined technique, is shown for a fertilized Canadian Shield lake in the Experimental Lakes Area of northwestern Ontario.

Acetylene