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Biomedical subjects

J F Taylor

Publications and source records attributed to J F Taylor.

At least 127 records · Page 7Linked to original sources

Inhibition of mammalian 5-lipoxygenase by 2-benzylaminophenols.

A number of 2-benzylaminophenols, prepared from the corresponding 2-aminophenols by reductive alkylation, have been identified as highly potent inhibitors of 5-lipoxygenase with IC50 values in the nanomolar range. Most compounds were also shown to inhibit the release of the peptidoleukotrienes when administered intraperitoneally in a rat model of peritoneal anaphylaxis. Two compounds evaluated for their effects on anaphylactic contractions in isolated human lung were shown to attenuate the leukotriene-induced component of the response.

Aminophenols↗

Evaluation of the potassium channel activator cromakalim (BRL 34915) as a bronchodilator in the guinea-pig: comparison with nifedipine.

1. The potential of the potassium channel activator, cromakalim (BRL 34915), as a bronchodilator has been evaluated in guinea-pig models in comparison with nifedipine. Some effects of the compounds on guinea-pig tracheal spirals have been studied in an attempt to elucidate their different efficacies in vivo. 2. When given by the intraduodenal route to anaesthetized guinea-pigs, cromakalim (3 and 10 mg kg-1) inhibited 5-hydroxytryptamine (5-HT)-induced bronchospasm for at least 60 min. When given by the i.v. route, the dose of cromakalim producing 50% inhibition of the 5-HT response was 84 micrograms kg-1. Nifedipine failed to show any protective effect up to 100 micrograms kg-1, i.v. and was lethal at higher dose levels. 3. Cromakalim protected conscious guinea-pigs from asphyxic collapse in response to histamine aerosol. The maximal effect occurred 60 min following oral dosing, with 2.5 mg kg-1 providing complete protection for almost half of the animals. Nifedipine had only a weak protective effect even at a high dose level of 50 mg kg-1, p.o. 4. Cromakalim prolonged the time before convulsive cough in response to an antigen challenge in actively sensitized guinea-pigs. Its minimum protective dose was 1 mg kg-1, p.o. Nifedipine (50 mg kg-1, p.o.) was ineffective. 5. Cromakalim inhibited both spontaneous and prostaglandin E2-induced tone in guinea-pig isolated tracheal spirals with IC50 values, relative to the maximum inhibition achieved by isoprenaline (10(-3)M), of 1.1 x 10(-6)M and 8.9 x 10(-7)M, respectively. Its maximal effect was 89% of that produced by isoprenaline. Removal of the epithelium did not influence its activity. Studies using the two enantiomers showed that the activity of cromakalim resided almost entirely in the (-)-enantiomer. 6. Nifedipine (2 x 10-SM) achieved only 49% of the relaxant effect of 10 -3M isoprenaline in isolated tracheal spirals. Addition of cromakalim (10- 5 M) at the end of the nifedipine concentrationresponse experiment caused further relaxation to 94% of the effect of isoprenaline. 7. It is concluded that cromakalim has greater potential than nifedipine as a bronchodilator. It appears that opening of potassium channels, with consequent hyperpolarization and stabilization of the membrane potential, prevents calcium entering the cytosol through routes that are unaffected by calcium entry blockers.

Animals↗

Small feet and Perthes' disease. A survey in Liverpool.

There is a high incidence of Perthes' disease among the children of unskilled manual workers in underprivileged urban areas in Britain. The skeletal measurements of 38 Liverpool children with Perthes' disease were compared with those of their siblings and of normal children from the inner and outer city. Children in families where Perthes' disease occurs have retarded growth of the trunk, with reduced sitting height and bi-acromial diameter. Among those who develop the disease there is also retarded limb growth, most evident as unusually small feet.

Anthropometry↗

Novel 1H-benzimidazol-4-ols with potent 5-lipoxygenase inhibitory activity.

The synthesis and structure--activity profile of 2-substituted benzimidazol-4-ols as inhibitors of cell-free RBL-1 5-lipoxygenase are discussed, and their potency is compared with that of the standard inhibitors phenidone, AA 861, BW 755C, and nordihydroguaiaretic acid. In contrast to the standard compounds, most did not inhibit the release of slow-reacting substance of anaphylaxis (SRS-A) in vivo when administered at 200 microM ip to rats subjected to peritoneal anaphylaxis, although five compounds containing a methoxylated benzyl group (compounds 36, 39, 42, and 43) or hydroxylated benzyl group (41) showed similar activity to that of phenidone, nordihydroguaiaretic acid, and AA 861. Of the many compounds tested, two, 5-tert-butyl-7-methyl-2-(trifluoromethyl)-1H-benzimidazol-4-ol (57) and 2-(4-methoxybenzyl)-7-methyl-1H-benzimidazol-4-ol (36), like dexamethasone, inhibited monocyte accumulation in a pleural exudate model of inflammation. Standard lipoxygenase inhibitors such as phenidone, BW 755C, and AA 861 were inactive in this system.

Animals↗

Vision and driving.

The major studies on the inter-relationship between visual performance and road accident records are briefly reviewed. Statutory standards of vision for vehicle drivers are discussed, together with the responsibilities of the driver, Licensing Authority and those offering advice to drivers on their standards of vision.

Accidents, Traffic↗

Infective endocarditis in children with congenital heart disease: comparison of selected features in patients with surgical correction or palliation and those without.

The diagnostic and prognostic features of 44 episodes of infective endocarditis in 42 children with congenital heart disease were reviewed. Endocarditis occurred in 18 patients who had not had surgical correction or palliation of the defect (non-operated group). There were 26 episodes in 24 patients who had been treated surgically (operated group) (16 open and eight closed cardiac operations). Endocarditis occurred soon after open heart surgery in eight patients and as a late complication in the other 16. It recurred in two patients (operated group). Invasive monitoring and low cardiac output were consistent features in those patients who had endocarditis soon after open heart surgery whereas dental treatment was a common feature in non-operated cases and after closed cardiac operations. Late cases of endocarditis after open heart surgery had various microbiological features that were not typical of infection after dental problems. Gram positive infections occurred in non-operated patients and in those who had had closed cardiac operations. The group that had open heart surgery had infections caused by Gram positive, Gram negative, and anaerobic bacteria and fungi. Fever, anaemia, leucocytosis, and positive blood cultures were the only consistent findings. Vegetations were seen in nine of 12 patients at cross sectional echocardiography. All 12 (four non-operated, one closed, and seven open cases) needed acute surgical treatment. The mortality from infective endocarditis was 17% for non-operated cases, 0% for those who had had closed heart surgery, and 50% for those who had had open heart surgery. Infective endocarditis after open heart surgery differs from that in the other subgroups in terms of microbiology, source of infection, and outcome and its early diagnosis depends on a thorough investigation of minimal symptoms and signs.

Adolescent↗

Response of the growth plates to tibial osteotomy in rats.

The parameters of cellular proliferation and growth in the growth plates of immature rats were measured after unilateral tibial osteotomy and used to calculate growth rates. Distal osteotomy of one tibia was followed by a bilateral increase in the calculated growth rate of the distal growth plates. However, the ipsilateral distal growth plate grew faster than the contralateral between 12 and 18 days after operation, which appeared to be related to increased cell proliferation and height. Proximal osteotomy led to an increase in growth rates proximally which was more marked on the contralateral side. The lesser response of the ipsilateral growth plate may have been due to local impairment of blood supply, or to greater local release of metabolites after bony damage. Distal tibial osteotomy gave similar results to circumferential release of the distal tibial periosteum. Proximal osteotomy, however, produced a relative impairment of growth on the operated side. This may be of importance in the correction of childhood deformities associated with inequality of leg length.

Animals↗

Periosteal division and longitudinal growth in the tibia of the rat.

Growth at the proximal tibial epiphyseal plate of the rat has been measured following three different growth-stimulating procedures. These were proximal periosteal release, distal periosteal release and full periosteal stripping of the diaphysis. A new radiographic method using a photographic technique has made it possible to take accurate measurements of the rate of long-bone growth in small experimental animals. From the results of this animal series we conclude that proximal tibial periosteal division is likely to be the most effective of the three procedures when used to correct leg-length discrepancy in the growing child.

Animals↗

[Mitral valve atresia with normal aortic valve and pulmonary atresia. A case with pulmonary collateral vascular perfusion by systemic pulmonary arteries].

A case of mitral atresia with normal aortic valve, situs solitus, d-loop, ASD, VSD, DORV and atresia of the pulmonary valve is presented. Systemic-pulmonary collateral arteries were the single source of collateral lung perfusion. These vessels are often found in patients with tetralogy of Fallot and pulmonary atresia with VSD. The case favours the idea that these vessels are not specific for the above mentioned cardiac anomalies. It supports the theory that they represent true embryonal vessels which can persist in cases of an inadequate or completely missing connection of the sixth aortic arch derivates with the pulmonary vascular bed.

Cardiac Catheterization↗

Evaluation of long-term results of homograft and heterograft valves in extracardiac conduits.

Between 1971 and 1982, 249 patients received right heart extracardiac conduits. The 173 patients who survived 30 days were reviewed retrospectively; 72 had antibiotic-sterilized aortic homografts, 97 had xenografts of various types, and four had valveless tubes. Reoperation for conduit obstruction was required as early as 13 months after the original operation, but actuarial analysis showed no differences in overall performance of homograft and heterograft conduit groups with respect to late death or survival free of conduit obstruction. More important risk factors for late death or the need for reoperation were the severity of the underlying cardiac lesions and the influence of early postoperative complications. When analyzed statistically, the performance of conduits bearing homografts was disappointing, influenced sometimes by complications in the Dacron extension tubes. Repairs dispensing with conduits entirely should be evaluated.

Actuarial Analysis↗

The response of the rat tibial growth plates to distal periosteal division.

The growth plate chondrocytes have been examined in the tibiae of normal immature rats and in similar rats after circumferential distal periosteal release. In control rats, calculation of the growth rate as the product of the rate of cell proliferation and the maximum hypertrophic cell height correlated with gross measurements. The labelling index also correlated with the calculated growth rate. During the period 28 to 46 days of age there was little change in the growth rate but a diminution in the height of the hypertrophic cells. Unilateral circumferential periosteal division produced bilateral increases in tibial growth rate and in the activity of both the proliferative and hypertrophic zones as part of the systemic response to the trauma. There was a 1% ipsilateral increase in tibial length, as compared to the contralateral side, which appeared to be related principally to an increase in the number of proliferative cells. This simple method of stimulating bone growth can usefully be undertaken at the same time as other operative procedures.

Animals↗

Facet joint injection for low back pain. A clinical study.

Therapeutic injection of facet joints is now widely practised, but British experience has been infrequently reported. We studied the results of injecting facet joints with a corticosteroid preparation in 50 patients suffering from the "facet syndrome". Our series included a number of extra-articular injections and these "failed injections" provide a useful control group. Results indicate that only intra-articular injections are effective; certainty of joint penetration can be ensured only by the routine use of joint arthrography.

Adult↗

Costectomy as the first stage of surgery for scoliosis.

Preliminary costectomy before Harrington instrumentation and fusion for idiopathic scoliosis allows direct excision of the rib prominence and better correction at the second-stage operation. The excised rib fragments are used as grafts, thus avoiding the need for a separate pelvic incision. The management regime and the technique of costectomy are described. The results in 42 children, most suffering from adolescent idiopathic scoliosis and all treated by this method, have been reviewed. Respiratory function in a group of these children has been compared with that of a group treated by Harrington instrumentation alone. Costectomy produced a significantly greater reduction in total lung capacity and peak expiratory flow rate but, providing the preliminary lung function tests were reasonably normal, the cosmetic and psychological effects of costectomy were very rewarding.

Adolescent↗

Surgical treatment of absent pulmonary valve syndrome.

The absent pulmonary valve syndrome includes agenesis of the pulmonary valve, annular stenosis, and pulmonary insufficiency. The pulmonary arteries are aneurysmal and usually compress the tracheobronchial tree. These features are associated with a ventricular septal defect and right ventricular hypertrophy. Nineteen children aged 5 days to 11 years were treated between 1976 and 1983. Nine were younger than 1 year. Intractable respiratory symptoms and heart failure were the main features in the infant group; five required preoperative assisted ventilation. Older children had decreased exercise tolerance and repeated respiratory infections. Several surgical techniques were used in this series. The best results were achieved when the size of the main, right, and left pulmonary arteries was reduced by extensive anterior resection; the ventricular septal defect was closed; and an aortic homograft was interposed between the right ventricle and the pulmonary artery. Four infants and four children treated in this way survived the operation. Five of the nine operated infants died (56%); all older children survived the operation. At follow-up, six children were asymptomatic and one was in New York Heart Association Class II. All four infants were progressing satisfactorily although all had some residual pulmonary symptoms. Closure of the ventricular septal defect, reduction of the size of the pulmonary arteries, and insertion of an aortic homograft was the optimal treatment in our series.

Aneurysm↗

Long-term results of the "palliative" Mustard operation.

A long-term follow-up study after 41 palliative Mustard operations for transposition of the great arteries and pulmonary vascular obstructive disease is presented. The operations were performed from 1973 to 1980. Mean pulmonary arteriolar resistance was 13.96 +/- 6.7 Um2. A ventricular septal defect was not closed in 34 patients; in 7 it was created at operation. There were three hospital and two late deaths. Survivors were followed up for 3 to 10 years (mean 76.7 +/- 22.8 months). Before operation 4 children were in New York Heart Association functional class IV and 33 were in class III. Mean hemoglobin concentration was 19.43 +/- 3.14 g/dl and arterial oxygen saturation was 63.44 +/- 11.29%. After operation 18 patients were in functional class I, 17 in class II and only 1 in class III. Hemoglobin level decreased to 14.19 +/- 2.3 g/dl and arterial oxygen saturation improved to 89.12 +/- 7.25%. Cardiac catheterization in 21 survivors confirmed no change in pulmonary artery pressure and resistance. Effective pulmonary blood flow improved from 1.39 +/- 0.39 before to 2.6 +/- 0.78 liters/min per m2 after operation. The palliative Mustard operation carries a low risk and provides excellent symptomatic improvement up to 10 years in patients with transposition of the great arteries and pulmonary vascular disease.

Adolescent↗

Percutaneous balloon valvuloplasty for pulmonary valve stenosis in infants and children.

Pulmonary valve stenosis was relieved by balloon dilatation during cardiac catheterisation on 27 occasions in 23 infants and children aged 7 days to 12 years, median 31 months (three aged less than 2 weeks). Pulmonary valve diameter was estimated by cross sectional echocardiography to assist in the choice of balloon size. Before dilatation the right ventricular systolic pressure ranged from 41 to 190 (median 92) mm Hg and was suprasystemic in 10 patients. There were significant reductions in the ratio of right ventricular to systemic systolic pressure and pulmonary systolic pressure gradients immediately after balloon dilatation. Twelve patients underwent recatheterisation (11 at six months and one at one week after balloon dilatation), which showed further improvement with significant reductions in right ventricular pressure or pulmonary valve gradient or both, particularly in the patients with the least satisfactory initial results. This improvement was attributed to resolution of the obstruction at infundibular level. Repeat pulmonary valve dilatation was successfully performed in four patients who had poor results after initial dilatation. Balloon pulmonary valvotomy appears to provide good short term and medium term relief of pulmonary valve stenosis and may obviate the need for surgery in many cases. An apparently poor immediate haemodynamic result does not preclude a good longer term result.

Angiography↗