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Biomedical subjects

J Atkinson

Publications and source records attributed to J Atkinson.

At least 91 records · Page 5Linked to original sources
PubMed1986

Oxitropium bromide. Dose-response and time-response study of a new anticholinergic bronchodilator drug.

The efficacy and side effects of oxitropium bromide, a new anticholinergic bronchodilator drug, were tested in a double-blind placebo-control study. Twenty-four men, aged 58 to 72 years, with chronic partially reversible obstruction of the airways were used as subjects. Three doses of oxitropium were tested (100 micrograms, 200 micrograms, and 300 micrograms) to determine the optimum dose by metered-dose inhaler. A comparison was also made between oxitropium, fenoterol (400 micrograms), and a combination of oxitropium (200 micrograms) and fenoterol (400 micrograms). Fenoterol produced a greater degree of maximal bronchodilatation than each of the three doses of oxitropium, and its effect was more rapid in onset (30 vs 120 minutes to peak effect); however, the duration of action of oxitropium was greater than that of fenoterol (ie, the forced expiratory volume in one second [FEV1] remained within 5 percent of peak FEV1 for three hours, compared to one hour). Oxitropium in the 100 micrograms dose was inferior to 200 micrograms and 300 micrograms in subjective efficacy scores, peak percent change in FEV1, forced vital capacity, (FVC), mean forced expiratory flow over the middle half of the FVC, and duration of action; there was no difference between 200 micrograms and 300 micrograms. The oxitropium-fenoterol combination had a rapid onset of action, and a greater peak effect was achieved than for oxitropium alone. The main unwanted effect was a mildly unpleasant taste. Anticholinergic effects were not seen in this group of elderly men. Oxitropium bromide therefore is an effective bronchodilator with slow onset but prolonged activity and few side effects when used in patients with moderately severe obstruction of the airways. An appropriate dose appears to be 200 micrograms. Addition of oxitropium to fenoterol appears to offer even greater efficacy.

Aged↗
PubMed1986

[Reduced sensitivity to noradrenaline and electric stimulation of the caudal artery of the aged rat].

UNLABELLED: Whilst arterial noradrenaline (NOR) content decreases with age (Waterson, et al. 1974; Neubauer and Christensen, 1978; Embree, et al., 1981), changes in vasoconstriction induced by NOR are equivocal (Tuttle, 1966; Cohen and Berkowitz, 1976; Scott and Reid, 1982; Duckles, et al., 1985). We have investigated changes in responsiveness to NOR in the NOR-rich rat tail artery. Two cm segments of the proximal tail artery from male Ivanos rats of 6/7, 16/17 or 30/31 months were perfused/superfused with Krebs bicarbonate (4 ml/min). Changes in perfusion pressure (mmHg) were determined after (1) electrical stimulation (1 to 30 Hz, 0.3 msec, 15 sec at supramaximal voltage, ES) followed by (2) perfusion with exogenous NOR (1 nM to 10 microM for 2 min at each concentration). Responses to ES were abolished by pretreatment with reserpine (2.5 mg/kg, i.p. at - 18 h) or perfusion with phentolamine (4 microM). They were produced therefore, by liberation of endogenous NOR. Arterial NOR content was determined by HPLC-EC following perchloric acid digestion (0.1 N). RESULTS: (Table: see text). Asterisks refer to t-test with 6/7 months age group (p less than 0.05, p less than 0.01 and p less than 0.001]. There were no differences in basal perfusion pressure before stimulation or in plateaux responses to maximal concentrations of NOR. In conclusion our results show a decrease in arterial NOR and in sensitivity to both endogenous and exogenous NOR with age.

Aging↗
PubMed1985

Attenuation of the baroreceptor reflex by general anesthetic agents in the normotensive rat.

We have investigated the effects of urethane, a urethane + allobarbital mixture, alpha-chloralose and sodium pentobarbital on baroreceptor reflex function in the normotensive rat. Results were compared to those obtained in the conscious rat. Baroreceptor reflex function was evaluated from the fall in heart rate which accompanied the rise in diastolic arterial pressure following intravenous administration of phenylephrine. All four anesthetic agents attenuated reflex function as shown by a decrease in the bradycardiac response. There was a four to five-fold attenuation with urethane and urethane + allobarbital and a two- to three-fold attenuation with alpha-chloralose and sodium pentobarbital.

Anesthetics↗
PubMed1985

The effects of trimetoquinol on the intact rabbit heart and myocardial adenylate cyclase activity: evidence for spare myocardial beta receptors.

We have compared and contrasted the actions of (-)isoproterenol and (+/-) trimetoquinol on rabbit heart preparations. In the presence of either GTP or Gpp[NH]p (guanosine-5'-(beta, gamma imino) triphosphate), trimetoquinol displayed partial agonist activity in stimulating adenylate cyclase activity in a particulate rabbit heart preparation. Trimetoquinol enhanced adenylate cyclase activity 20% or 65% of the maximum obtainable by isoproterenol in the presence of GTP or Gpp[NH]p respectively. In the presence of GTP, concentrations of catecholamines required to enhance cyclase activity 15% of the maximum obtainable with isoproterenol (EC15) were 2.0 X 10(-7) M and 5.5 X 10(-8) M for trimetoquinol and isoproterenol, respectively. In the presence of Gpp[NH]p EC30 values were 2.0 X 10(-7) and 3.5 X 10(-8) M for trimetoquinol and isoproterenol respectively. Trimetoquinol also displayed partial agonist activity for the ability to increase cAMP levels in the isolated perfused rabbit heart. By contrast trimetoquinol was equieffective to isoproterenol at increasing tension development and rate of contraction of the isolated perfused heart. Concentrations of catecholamines required to increase tension and rate of contraction 50% of the maximum obtainable with isoproterenol were 1.5 X 10(-7) M and 1.7 X 10(-8) M for trimetoquinol and isoproterenol, respectively. These data show that only a partial stimulation of adenylate cyclase activity and cAMP levels by trimetoquinol is sufficient to produce maximal changes in mechanical activity of the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1985

Involvement of the renin-angiotensin system in the dipsogenic effect of morphine.

This paper examined whether drinking elicited by morphine is dependent upon an intact renin-angiotensin system. Bilateral nephrectomy, carried out one day prior to administration of morphine, completely abolished morphine-induced water intake, pointing to involvement of the kidneys in the dipsogenic effect of morphine. Plasma and renal renin depletion were induced by the clipping of one renal artery followed, one month later, by removal of the clipped kidney. In such renin-depleted rats with subnormal plasma renin levels, morphine and isoprenaline-induced water intakes were linearly related to pre-injection basal plasma renin level. Such a relationship was not found in rats with normal renin levels. These results pointed to the existence of a permissive interaction between morphine and the renin-angiotensin system. Captopril, an inhibitor of the angiotensin converting enzyme, increased morphine-induced water intake. We interpreted this drinking response as being the sum of morphine-induced drinking (following a permissive interaction between morphine and circulating angiotensin I or renin) and captopril-induced drinking (following a captopril-induced increase in circulating renin and angiotensin I levels). The competitive antagonist of angiotensin II, saralasin, had no effect on morphine-induced drinking. This result pointed once again to a permissive interaction between morphine and circulating angiotensin I or renin.

Animals↗
PubMed1979

The renal effects of clonidine in unanesthetized rats.

Clonidine s.c. (0.01-0.3 mg/kg), in unanesthetized rats, caused an initial rise (+20 mm Hg), followed by a continuous fall of BP and a dose-dependent natriuresis and diuresis for up to 2 h. Glomerular filtration rate (GFR) (CIn) increased during the first 20 min, while effective renal plasma flow (ERPF) (CPAH) remained normal. Subsequently, between 20 and 60 min after injection, ERPF (CPAH) decreased considerably while GFR had reverted to its normal value. In saline-infused rats clonidine diuresis was accompanied by an "inappropriate" positive free water clearance. Pentobarbital anesthesia suppressed the initial BP peak and the diuresis. Phenoxybenzamine (1 mg/kg i.v.) was antinatriuretic in saline diuresis; the effect of phenoxybenzamine + clonidine on diuresis and salt excretion represented the sum of the effects of both drugs, but phenoxybenzamine enhanced the clonidine-induced increase of GFR. Neither haloperidol (1 mg/kg i.v.) nor bulbocapnine (3 mg/kg i.v.) interfered with the renal effects of clonidine. Clonidine s.c. caused hyperglycemia and glucosuria which did not account for the natriuresis. Clonidine thus appears to increase the GFR and "filtration fraction" (FF) by a phenoxybenzamine-insensitive rise of glomerular ultrafiltration, to depress ERPF by alpha-adrenergic afferent vasoconstriction, to induce natriuresis by a tubular action not blocked by phenoxybenzamine and to exert an antivasopressin effect, either by depressing pituitary vasopressin secretion or the renal response to vasopressin.

Animals↗
PubMed1979

Effect of chronic clonidine treatment and its abrupt cessation on mean blood pressure of rats with a normal or an elevated blood pressure.

1. Clonidine (6 mg of base/l of water) was given as drinking fluid to normotensive rats or rats with established or early hypertension. 2. Spontaneous hypertensive rats (6 months old: average dose of clonidine, 0.6 mg 24 h-1 kg-1) showed a sustained fall in blood pressure over 3 weeks. 3. The same clonidine solution given for 6 weeks to two-kidney Goldblatt rats with early-stage hypertension (average dose of clonidine: 1 mg 24 h-1 kg-1) or spontaneously hypertensive rats (clonidine dose: 1 mg) induced a fall in mean blood pressure, but no change in normotensive rats. 4. Replacement of clonidine by water induced hypertension and lability which led to death in hypertensive but not in normotensive rats.

Animals↗
PubMed1979

The role of circulating renin in drinking in response to isoprenaline.

1. In nephrectomized rats, S.C. (0.12 mg. kg body wt.(-1)) or intracerebroventricular (I.C.V.: 0.03 mg. kg(-1)), isoprenaline failed to elicit drinking. However, when preceded (5-20 min) by a non-dipsogenic dose of I.V. pig renin, S.C. isoprenaline induced a marked, and I.C.V. isoprenaline a smaller drinking response. 2 hr after I.V. renin, S.C. isoprenaline no longer caused drinking.2. Pig renin did not enhance drinking in response to 0.12 mg. kg(-1) isoprenaline S.C. in intact or sham-operated rats.3. Isoprenaline (0.12 mg. kg body wt.(-1), S.C.) caused a larger fall of blood pressure in unanaesthetized nephrectomized than in intact unanaesthetized rats, but it was not the resulting hypotension that interfered with the nephrectomized rats' ability to drink, since intact rats with similar falls in blood pressure drank avidly in response to large doses of isoprenaline.4. Since the rate of inactivation of pig renin in nephrectomized rats was not modified by isoprenaline, drinking in nephrectomized animals in response to renin+isoprenaline was not attributable to increased plasma renin levels.5. Since isoprenaline induces drinking in the presence of circulating renin, but in the absence of renin release from kidneys, renin plays a permissive role in isoprenaline-induced drinking. Angiotensin and isoprenaline may interact at the level of intracranial receptors.

Animals↗
PubMed1979

Hexobarbital blood levels and effects on EEG in the presence and absence of caffeine.

The interaction of caffeine and hexobarbital in the rat with spinal cord transection was studied. Duration of hexobarbital effect on the brain was taken as the time from the injection of hexobarbital (i.v.) to the return of pre-injection cortical voltage. Hexobarbital distribution and elimination was estimated by application of a two-compartmental model to values for blood hexobarbital concentration (determined by a direct gas chromatographic method after extraction). Caffeine caused a shift in the dose-response curve for hexobarbital but no changes in hexobarbital distribution and elimination. Results are interpreted on the basis of a central interaction of caffeine with hexobarbital at a brain receptor level.

Animals↗
PubMed1979

Contrast sensitivity of the human neonate measured by the visual evoked potential.

Visual evoked potentials (VEPs) were recorded from a total of 97 1- to 10-day-old infants, with phase-reversing sinusoidal grating stimuli. The grating contrast or spatial frequency for which 50% of infants gave a statistically significant VEP was taken as a measure of threshold. This procedure yielded an estimate of neonatal acuity of 0.85 cycles/degree and an optimal contrast threshold of 50%. VEPs from an older infant showed good agreement with behavioral measures of sensitivity on the same individual. Comparison of the neonatal VEP results with behavioral data from 5-week-old infants, suggests little change in visual performance over the first month of life.

Evoked Potentials↗
PubMed1978

Infant astigmatism measured by photorefraction.

Photorefraction of a sample of 93 infants of ages 1 day to 12 months showed that 63 percent of the subjects had astigmatism of 0.75 diopter or greater, and 12 percent greater than 2 diopters. Seventy percent of these astigmatisms were in the horizontal-vertical meridians. By comparison, only 8 percent of a sample of 26 adults tested by the same method showed astigmatism (all 0.75 to 1 diopter). The high incidence of infant astigmatism has implications for critical periods in human visual development and for infant acuity.

Adult↗
PubMed1978

Comparison of effects of quinidine and dihydroquinidine on canine heart.

Various cardiac effects of quinidine and dihydroquinidine were tested in isolated dog hearts and in vivo in dogs. No significant differences were found in the negative inotropic, chronotropic, and dromotropic effects. Dihydroquinidine was more potent than quinidine in decreasing coronary arterial pressure.

Animals↗