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Biomedical subjects

D J Jones

Publications and source records attributed to D J Jones.

At least 163 records · Page 9Linked to original sources

Cardiovascular responses to diazepam and midazolam maleate in the dog.

Previous clinical studies establishing the efficacy of midazolam maleate (RO 21-3981), a new water-soluble benzodiazepine for induction of anesthesia, have not critically evaluated the effects of this agent on the cardiovascular system. The present study compares the cardiovascular effects of midazolam maleate and diazepam in conscious dogs. Systemic arterial, pulmonary arterial and central venous pressures, cardiac output, LVmax dP/dt, heart rate and regional coronary blood flow were measured 3 min following intravenous administration of diazepam (0.5, 1.0, and 2.5 mg/kg) or midazolam maleate (0.25, 1.0, and 10.0 mg/kg). Midazolam maleate increased heart rate 10--20 per cent with all three doses and decreased mean arterial blood pressure approximately 10--20 per cent at 1.0 and 10 mg/kg. Cardiac output was increased 10--12 per cent with all three doses of midazolam maleate, and LVmax dP/dt was decreased 13--16 per cent at the two higher doses. Diazepam at all three doses did not alter heart rate or mean arterial blood pressure. Diazepam, 1.0 and 2.5 mg/kg, produced significant (17 per cent) decreases in LVmax dP/dt, and 2.5 mg/kg produced a significant (10 per cent) increase in cardiac output. Neither drug in any dosage altered regional coronary blood flow, systemic or coronary vascular resistance, stroke volume, or stroke work. Maximum alterations in cardiovascular variables occurred with doses of midazolam maleate that are 10--15 times the recommended clinical induction dosage. It is concluded that in concentrations necessary for induction of anesthesia midazolam maleate has minimal effects on cardiovascular function.

Animals↗

Anticonvulsant drug actions on in vitro and in vivo levels of cyclic AMP in the mouse brain.

Injections of pentylenetetrazol to mice produced a rise in steady state levels of cyclic AMP in the cerebrum and cerebellum subsequent to sacrifice by focused microwave irradiation. One hour pretreatment with anticonvulsant drugs--phenytoin, phenobarbital, carbamazepine, clonazepam, and diazepam--prevented this pentylenetetrazol-induced rise in cyclic AMP. Anticonvulsant agents which alone depressed steady state levels of cyclic AMP were phenytoin and carbamazepine in the cerebral cortex and carbamazepine in the cerebellum while elevations in the cyclic nucleotide were evoked by clonazepam in the cerebrum and cerebellum or diazepam and phenytoin in the cerebellum. Under in vitro conditions, in which incubated tissue slices of mouse cerebral cortex were used, the stimulation of cyclic AMP by norepinephrine was blocked by carbamazepine greater than phenobarbital greater than phenytoin. Inhibition of adenosine-induced accumulation of cyclic AMP was observed with phenobarbital greater than carbamazepine greater than phenytoin. Clonazepam enhanced this response to adenosine. Ouabain stimulation of cyclic AMP was prevented by carbamazepine, phenytoin greater than clonazepam greater than phenobarbital greater than diazepam. Only the highest concentrations (0.5 mM) of phenytoin, phenobarbital, and carbamazepine reduced the action of KCl on cyclic AMP elevation. Clonazepam and diazepam elevated the basal levels of the cyclic nucleotide.

Adenosine↗

Role of neuroleptic agents on mouse pulmonary cyclic nucleotide systems.

The norepinephrine (NE)-induced accumulation of cyclic AMP in incubated tissue slices of mouse lung was inhibited by chlorpromazine (CPZ) and to a lesser extent by haloperidol. In particulate lung fractions both agents blocked dopamine-sensitive adenylate cyclase to a greater degree than the NE-responsive enzyme. Again CPZ was more potent than haloperidol. Acute injections (1/2--8h) of the neuroleptics usually resulted in lower steady state levels of pulmonary cyclic AMP and cyclic GMP following rapid (0.5 sec) tissue inactivation by microwave irradiation. On a subchronic injection schedule, the in vivo levels of pulmonary cyclic AMP tended to increase.

Adenylyl Cyclases↗

Cyclic nucleotides and prostaglandins (PGs) produced by the rabbit oviduct: effects of estrogen treatment.

Levels of cyclic AMP and cyclic GMP have been measured in oviducts of rabbits killed 68 hr after injection of human chorionic gonadotrophin (HCG) to induce ovulation. cAMP and cGMP levels were higher in the isthmus than in the ampulla. Estrogen treatment given at the same time as HCG increased cGMP levels. Levels of PGE and PGF in blood draining the oviduct were low and showed no effect of estrogen treatment at 68 hr after HCG.

Animals↗

Hypersensitivity pneumonitis after exposure to isocyanates.

Four patients exposed to isocyanate vapour developed dyspnoea associated with restriction and reduced gas transfer as well as moderate airways obstruction on lung function testing. In one patient bilateral radiographic shadowing was present and an open lung biopsy was performed. The microscopic appearances ranged from acute inflammation to end-stage fibrosis but the centribular accentuation of disease and the presence of areas resembling bronchopulmonary aspergillosis suggested that the process was a hypersensitivity response to inhaled allergen. Challenge tests with albumin and toluene diisocyanate-albumin were carried out in sensitized and control rabbits. The sensitized animals developed extensive lung damage of the type associated with an Arthus reaction. It is suggested that patients exposed to isocyanates may occasionally develop a hypersensitivity pneumonitis rather than the more usual asthmatic syndrome.

Animals↗

Effects of chronic morphinization on calcium membrane interaction.

Tolerance to morphine proceeds with an adaptation in the nerve membrane causing an increase in endogenously bound calcium. Our data on calcium binding is compatible with Collier's hypothesis (10) for drug induced changes in number and/or types of receptors. The results demonstrating naloxone reversal of this membrane adaptation suggest that opiate antagonist action may be to maintain the opiate macromolecule portion of the membrane in a Ca++ associated homeostatic state. Lack of effects of Na+ on opiate treated SPM suggest that cellular adaptation to morphine proceeds in vivo through a change in membrane binding of calcium.

Animals↗

The Kmif (Kveim-induced macrophage migration inhibition factor) test in sarcoidosis.

Circulating lymphocytes from 30 patients with sarcoidosis when stimulated in vitro with Kveim-induced macrophage migration factor, the Kmif test, produced a guinea-pig macrophage migration inhibition factor in 21 of 30 cases (70%). In those patients not on steroids the results showed a good correlation with the cutaneous Kveim test. One positive test was found in 16 normal subjects. Our results suggest that the Kmif test may prove a useful rapid alternative to the Kveim test.

Adult↗

Diagnosis of established deep vein thrombosis with the 125 I fibrinogen uptake test.

One hundred and two patients with clinical signs indicating a possible diagnosis of deep vein thrombosis were studied with the fibrinogen uptake test and phlebography to assess the reliability of the test as a means of diagnosing established venous thrombosis. The test gave a correct diagnosis in 78% of the 85 legs shown to contain thrombus by phlebography and only 19 (10%) false-negative results in the 195 legs examined. The duration of the symptoms, the administration of anticoagulants, and mild leg swelling did not affect the accuracy of the test. Very old thrombus, phlebographically more than 11 days old, was associated with an increased false-negative rate.The fibrinogen uptake test is accurate enough to make it a valuable method of clinical investigation.

Adult↗