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Biomedical subjects

T J Sutton

Publications and source records attributed to T J Sutton.

At least 19 recordsLinked to original sources
PubMed1988

Red cell haemolysis induced by SK&F 95018--a combined vasodilator and beta-adrenoceptor antagonist.

SK&F 95018, a potential antihypertensive agent with the combined properties of vasodilation and beta-adrenoceptor antagonism, induced red urine when given intravenously to a dog. Further studies revealed that in the dog, SK&F 95018 treatment led to haemoglobinaemia, haemoglobinuria and a fall in the red blood cell count. The compound was therefore suspected of causing red cell haemolysis and this was confirmed using dog blood in an in vitro haemolysis test system. Oral administration of the compound to dogs gave no indication of haemolysis, but the animals lost large portions of their dose through vomiting and the lack of effect is therefore questionable. Rats, which have no vomit reflex, were treated orally and although no direct evidence of haemolysis was obtained (e.g. haemoglobinaemia), the presence of polychromasia suggested some loss of mature red blood cells had occurred. Rat blood was haemolysed in vitro by SK&F 95018. Human red cells were also used in the in vitro haemolysis test system and these, too, were lysed by the compound. The haemolysis was shown to be related to the structure of the compound itself rather than to its pharmacological effects and development of SK&F 95018 as an antihypertensive agent was abandoned. Electron microscopy indicated that SK&F 95018 induced alterations in the red cell membrane which led to shape change, characterized by discocyte to spherocyte transformation, and finally haemolysis. The mechanism of this effect remains under investigation.

Administration, Oral↗
PubMed1986

Dyspnoea and thoracic spinal deformation in rats after oral prizidilol (SK&F 92657-A2).

Prizidilol (SK&F 92657-A2), an anti-hypertensive agent, has undergone a range of prescribed toxicity studies required for the investigation of possible adverse drug effects. During the second year of the 2-year rat oral study, a variety of symptoms were exhibited by males receiving 1600 mg of the compound day-1kg-1 by gavage. These animals became lethargic, slouched and developed dyspnoea which became progressively more severe during the course of the study. Necropsy of the affected rats revealed severely haemorrhagic lungs, cardiac hypertrophy and lordosis of the spine into the thoracic cavity. At the 2-year terminal kill, a proportion of the male rats receiving 100 and 400 mg of prizidilol day-1kg-1 were identified with similar but less severe spinal deformation. No female was found with spinal changes but all the rats receiving prizidilol showed haemorrhagic lungs and enlarged hearts. The lordosis of the affected males was always confined to the thoracic spine and this, along with the cardiac hypertrophy, presumably led to marked reduction in the volume of the thoracic cavity, inducing the dyspnoea. Thoracic vertebral body damage, possibly a precursor to the spinal deformities, was found in male rats from both drug-treated and control groups. The nature of the spinal lesion is at present under investigation.

Adrenergic beta-Antagonists↗
PubMed1982

Short-term toxicological studies with impromidine (SK&F 92676): a specific histamine H2-receptor agonist.

Impromidine is a specific, potent histamine H2-receptor agonist. The present paper describes the results of acute and short-term repeated-dose toxicity studies with impromidine in rodents and dogs. The intravenous LD50 was 9.6 mg kg-1 in male mice, 12.7 mg kg-1 in female mice and 25.5 mg kg-1 in rats. The minimum lethal dose in dogs after 30 min intravenous infusion was 27.7 mg kg-1 during the infusion and 4 mg kg-1 within 14 days. In 12- or 14-day tests in rats by the intravenous (maximum dose 3.24 mg per kg per day) and subcutaneous (maximum dose 20 mg per kg per day) routes, impromidine had no serious toxicological effects. In 12- or 14-day studies in dogs by the i.v. (maximum dose 0.259 mg per kg per day) and intramuscular (maximum dose 0.5 mg per kg per day) routes, impromidine caused vasodilation, tachycardia and vomiting. In a few dogs, at the highest dose levels, there was erosion and irritation of the gastrointestinal tract and myocardial damage. Other minor pathological changes were seen in the liver, kidneys and pancreas. No changes were seen other than those to be expected from the pharmacological actions of impromidine as an H2-receptor agonist. Studies in anaesthetized rats, either spontaneously respiring or sustained by artificial respiration, indicate that, at acute doses, impromidine causes death by respiratory failure.

Animals↗
PubMed1980

Effect of tilting on the pressor responses to McN-A-343, a muscarinic sympathetic ganglion stimulant.

1 In anaesthetized cats and dogs treated with mecamylamine, the pressor response to McN-A-343 was increased when the animals were changed from a supine to a head-up, tilted position. This potentiation was not seen in rats. 2 The potentiation of the McN-A-343 pressor response was not affected by propranolol, destruction of the brain, or removal of the intestines, spleen or adrenal glands. It was promptly abolished by applying pressure to the lower half of the tilted animal. No increase in the pressor response to McN-A-343 occurred when cats were tilted head down. The potentiated response in tilted cats was abolished by atropine. 3 The pressor effects of adrenaline, noradrenaline, tyramine and angiotensin in cats treated with mecamylamine were either reduced or unchanged when the animal was changed from the supine to the tilted position. In one cat not treated with mecamylamine in which orthostatic hypotension occurred, tilting potentiated the pressor responses to dimethyl phenylpiperazinium iodide. 4 In cats anaesthetized with chloralose, the reflex pressor response to bilateral carotid occlusion was reduced by tilting. After mecamylamine treatment the residual atropine-sensitive response to carotid occlusion was potentiated when the animal was placed in the tilted position. 5 These results suggest that muscarinic stimulation of sympathetic ganglia by McN-A-343 raises blood pressure by predominantly reducing venous capacity, in contrast to noradrenaline and angiotension which increase blood pressure mainly by arterial vasoconstriction. 6 It is not clear whether this is a general property of sympathetic ganglionic stimulation or is restricted to stimulation of muscarinic sites.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1977

Radiological manifestations of neonatal renal vein thrombosis on follow-up examinations.

Renal atrophy involving all or part of one or both kidneys was found in 10 children with renal vein thrombosis who had been given conservative treatment. This appearance is nonspecific and can be found in any condition which disturbs the renal parenchyma. However, in a significant number of patients calcification produced a pathognomonic radiological pattern. Awareness of these late radiological manifestations may help in recognizing those cases in which renal vein thrombosis went unnoticed in the neonatal period and the patient is now found to have a perplexing radiological appearance.

Female↗
PubMed1977

[Pyelocalyceal submucosal hemorrhage in a child treated with oral anticoagulants].

A 15 1/2-year-old girl with disseminated lupus erythematosus presented with acute flank pain and hematuria during oral anticoagulant therapy for thrombophlebitis of the lower extremities. The intravenous pyelogram demonstrated multiple filling defects of the renal collecting system interpreted as pyelocalyceal submocosal hemorrhage. This benign complication disappeared following adjustment of the anticoagulant therapy. An identical appearance has been described in a case of aplastic anemia, Henoch-Schonlein purpupa, and in renal truma. Submocosal hemorrhage of the renal collecting system is to be differentiated from pyeloureteritis cystca, uroepithelial tumor, vascular impressions from collateral circulation and submucosal edema.

Administration, Oral↗
PubMed1976

Prolactin-secreting pituitary microadenomas.

Prolactin-secreting pituitary microadenomas have been surgically selectively removed in 20 patients presenting an amenorrhea-galactorrhea syndrome, hyperprolactinemia and radiological modifications of the sella turcica. In these patients, the sella was of normal size but hypocyloidal tomography evidenced subtle changes characterizing pituitary microadenomas. The surgical intervention has been based on the twin criteria of hyperprolactinemia and sellar findings.

Adenoma↗
PubMed1975

Two unusual conditions simulating ectopic ureterocele. Unilateral hydrometrocolpos with ipsilateral renal agenesis or hypoplasia, and ectopic ureteral opening into a seminal vesicle.

The clinical and radiologic findings in two infants are presented, one with unilateral hydrometrocolpos and ipsilateral renal agenesis or hypoplasia and the other with ureteral duplication with one of the ureters opening into a cystically dilated seminal vesicle. The excretory urograms of both infants suggested ectopic ureterocele. Further radiologic investigation, including lateral views of the bladder, led to the correct preoperative diagnosis. Both conditions are relatively rare, and their appearance simulating ectopic ureteroceleis even more uncommon.

Female↗
PubMed1975

[Renal localization of lymphosarcoma in the child (author's transl)].

Eight children with renal localization of a lymphosarcoma are presented. Intravenous pyelography is generally carried out in the systematic full check-up of a known case of lymphosarcoma, in order to determine the degree of extension of the disease and in order to adapt chemotherapy. The different radiological appearances are discussed. They more frequently lead to the diagnosis of more well known conditions when the diagnosis of lymphosarcoma has not yet been established.

Adolescent↗