Biomedical subjects
Publications and source records attributed to J F Taylor.
Cytogenetic analysis was carried out in a prospective series of 36 children with DiGeorge syndrome. High-resolution banding (> 850 bands/haploid set) was achieved in 30 cases. Monosomy 22q11.21-->q11.23 was found in 9 of these 30 cases. In each of these cases monosomy 22q11.21-->q11.23 resulted from an interstitial deletion and not from a translocation. No other chromosome abnormalities were seen.
The effects of the potassium channel activators, cromakalim, BRL 38227 and pinacidil, and the calcium antagonist, verapamil, have been compared against various spasmogens on airway responses in vitro and in vivo in the guinea pig and also in human isolated bronchi. In guinea pig tracheal spirals, potassium channel activators generally had a greater inhibitory effect than verapamil against tone induced by a wide range of spasmogens (spontaneous, 5-hydroxytryptamine, leukotriene D4, prostaglandin E2). The potassium channel activators had very little effect against potassium chloride- and carbachol-induced tone in guinea pig tracheal spirals [e.g., cromakalim (20 microM) induced relaxations of 0.21 +/- 0.03 (relative to an isoprenaline maximum = 1.0, mean +/- S.E.M.) against carbachol, compared to 0.77 +/- 0.03 against histamine]. In vivo, the potassium channel activators prevented histamine and 5-hydroxytryptamine-induced bronchoconstrictions, but had little inhibitory effect against acetylcholine. In contrast, in human bronchi, cromakalim was capable of inducing powerful concentration-dependent relaxations against carbachol-induced tone [cromakalim (20 microM) induced relaxations of 0.77 +/- 0.09 (relative to isoprenaline = 1.0, mean +/- S.E.M.) against carbachol, compared to 0.95 +/- 0.04 against histamine]. In human bronchi, all the inhibitory agents were more potent and more effective, except that verapamil did not have an increased maximum response. We conclude that potassium channel activators should be effective at relaxing contractions induced by a wide range of spasmogens in man.
The potential of the potassium channel activator cromakalim and its active enantiomer BRL 38227 as inhaled bronchodilators has been evaluated in the guinea-pig, in comparison with nifedipine, salbutamol and aminophylline. Inhaled cromakalim and BRL 38227 prolonged the time before histamine-induced collapse in conscious guinea-pigs, BRL 38227 (ED50 250 to 500 micrograms/mL, roughly 10 to 20 micrograms per animal) being twice as potent as cromakalim. In anaesthetized guinea-pigs, BRL 38227 (inhaled and i.v.) and aminophylline (i.v.) caused similar percentage inhibitions of the increase in airways resistance and decrease in dynamic lung compliance elicited by histamine, whereas salbutamol (inhaled and i.v.) was more effective against resistance. Inhaled BRL 38227 and salbutamol were more potent against inhaled than against i.v. histamine. BRL 38227 inhibited the effects of i.v. and inhaled histamine by 67-78% when nebulized from solutions of 250 and 31 micrograms/mL respectively, but the lowest concentration that lowered blood pressure significantly was 500 micrograms/mL. In contrast, nifedipine had no effect on compliance and caused only a marginal (21%) inhibition of resistance at a dose (200 micrograms/kg i.v.) which lowered blood pressure by 44%. These results show that BRL 38227 is an effective bronchodilator when given by inhalation. It differs from salbutamol in its effects on airways dynamics, and its effect on lung compliance cannot be attributed to a pulmonary vasodilator effect. Furthermore, L-type calcium channels are not significantly involved in histamine-induced bronchoconstriction or therefore in the bronchodilator effect of BRL 38227.
The synthesis of a novel series of smooth muscle relaxants which have been shown to act via the opening or activation of potassium channels is described. Compounds have been evaluated for their ability to inhibit spontaneous tone in guinea pig isolated trachealis and structure-activity relationships are discussed. One compound in particular, 1,1-dimethyl-5-nitro-3-(2-pyridon-1-yl)indan-2-ol, (16) was identified as a potent relaxant of airways smooth muscle in vitro with IC50 = 0.15 microM and was found to significantly inhibit histamine-induced dyspnoea in conscious guinea pigs when given orally 30-45 min prior to challenge.
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Previous clinical studies have studied tibiofibular torsion by measuring the angular difference between a proximal (often bicondylar) plane and a distal bimalleolar plane. We measured the angular difference between the proximal and distal posterior tibial planes as defined by ultrasound scans. We found no significant torsional difference between the right and left tibiae of 87 normal children, nor between their different age groups. The mean external torsion of 58 legs with congenital talipes equinovarus was 18 degrees; significantly less than the mean 40 degrees in the normal children and 27 degrees in the clinically normal legs of the 22 patients with unilateral congenital talipes equinovarus. We did not confirm the previously reported increase in external torsion with increasing age. The relative internal tibial torsion we have demonstrated in patients with congenital talipes equinovarus must be differentiated from the posterior displacement of the distal fibula observed by others and which may result from manipulative treatment. The relative internal tibial torsion we found in the clinically normal legs of children with congenital talipes equinovarus is further evidence that in this condition the pathology is not confined to the clinically affected foot.
Holstein sires (n = 340) with milk, milk fat, semen unit fertility, daughter stayability evaluations, and semen price for 1986 were studied. Effects of variation in sire fertility and daughter stayability on profitability of sire selection using the net present value criterion were estimated. The model estimated expected profit from a cow bred to pregnancy from future production and from cattle disposal and replacement after discounting costs and returns to the time of insemination. Effects of semen sexing and semen unit dilution on profitability to determine optimal breeding strategies for dairy herds were examined. Sire profitability increased with herd average conception rate and sire selection intensity. Daughter stayability had a greater impact on profitability than semen unit fertility when profit maximization was computed under the criterion of breeding a cow to pregnancy. Genetic progress for production was compromised when selecting to maximize profit. Dilution of semen units seems profitable only when semen availability is limited for high demand sires. The use of sexed female semen may only be appropriate when it can generate additional income from the sale of surplus heifers.
The ability of the potassium channel activator cromakalim to relax smooth muscle of the airways is now well established. The compound has been shown to be an effective bronchodilator in animal models, and more importantly, to attenuate induced bronchoconstriction and nocturnal asthma in man. Evidence now exists to suggest that BRL 38227, the 3S,4R enantiomer of cromakalim, is the predominantly active moiety and shares the same profile of activity. Further evaluation of BRL 38227 in a rat model of active peritoneal anaphylaxis provides evidence that potassium channel activators may exert beneficial effects in terms of inhibition of extravasation and inflammatory cell infiltration.
We have reviewed 82 children with congenital dislocation of the hip, after treatment by anterior open reduction followed by derotation femoral osteotomy. The clinical and radiological results were significantly better in the group that had open reduction before the appearance of the capital femoral epiphysis; this group also had a lower incidence of avascular necrosis. We conclude that, when it is clearly indicated, the earlier an open reduction is carried out the better the results.
Condensing osteitis of the clavicle was first described as a disease entity in 1974. There is painful localised swelling of the clavicle of undetermined origin, with increased radio-density, but an infective aetiology has not been excluded by previous authors. We report three children with the clinical and radiological findings of 'condensing osteitis'. Two of them had raised levels of antistaphylolysin titres and all responded to antibiotic therapy. We conclude that condensing osteitis is due to low-grade staphylococcal osteomyelitis; biopsy and treatment by antibiotics is recommended.
Single-sire natural mating data from a beef cattle herd in tropical Australia were used to estimate heritabilities of cow fertility (hc2), heritabilities of bull fertility (hb2) and genetic correlations between cow and bull fertility (rg) within each of six genotypes. Estimates of hc2 and hb2 were low, averaging .11 and .08, respectively. The pooled estimate of rg was 0.16, indicating that cow and bull fertility are favorably genetically correlated and therefore that cow fertility could be genetically improved by indirect selection on bull fertility, or some more heritable component of bull fertility.
The growth of the immature rat tibia has been measured following five different growth stimulating procedures. These comprised proximal periosteal release, proximal periosteal release with insertion of dissimilar metal wire, repeated proximal periosteal release, distal periosteal release and full periosteal stripping of the diaphysis. The new radiographic method of measurement employed, utilizes a photographic technique. A reproducible measurement of the rate of long bone growth in the small experimental animal is possible.
Percutaneous balloon dilation was attempted in three patients with mid baffle pulmonary venous pathway obstruction after the Mustard operation for transposition of the great arteries. The procedure was unsuccessful in a 3 year old boy. Evidence for relief of obstruction in the other two patients (7 and 14 years old, respectively) consisted of angiographic demonstration of improved caliber at the site of the pulmonary venous pathway narrowing, improvement in the Doppler spectral signal at this site from an "obstructed" to a "normal" pattern as well as symptomatic improvement. Balloon dilation was performed twice in one of these patients. The Doppler and symptomatic improvement were sustained in both patients at short-term follow-up (5 and 6 months, respectively). This technique may offer effective relief of pulmonary venous pathway obstruction in some patients with this complication of the Mustard operation.
The aetiology of Perthes' disease of the hip, avascular necrosis of the head of the femur, is unknown. Children with the disease have a generalised abnormality of growth. A similar disproportionate growth is found in chicks given a diet deficient in manganese. In Liverpool, which has the highest incidence of Perthes' disease reported anywhere in the world, children with the disease were shown to have lower blood manganese levels than controls. This is evidence that manganese deficiency around the time of birth may be a cause of Perthes' disease, but the results require confirmation.
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Seven members of four families had nystagmus noted by 4 months of age, poor vision, photophobia, and a markedly reduced or absent electroretinogram. Six of these patients had a life threatening episode of cardiac failure in infancy. There were also two neonatal deaths, and one of the affected children died at 2 years and one at 19 years. The five surviving children are well, remain with nystagmus, and have visual acuities of less than 6/60, with the eldest two having lost perception of light. They have a short obese habitus distinct from that of their unaffected siblings and parents.
Balloon dilatation of the aortic valve was attempted in 34 consecutive children aged 16 months to 17 years (median 7 years), weight range 9-60 (median 22) kg. Previous surgical valvotomy had been performed in two patients (twice in one of them). The valve was not crossed in one patient. In the remaining 33 patients the pressure difference between the left ventricle and the ascending aorta during systole was reduced from 71 (30) to 28 (19) mm Hg. In 24 patients recatheterisation 2-19 (mean 9) months later showed gradients that were similar to those immediately after balloon dilatation (35 (20) v 31 (20) mm Hg). The two patients with the highest residual gradients immediately after balloon dilatation showed a spontaneous reduction in gradient at repeat catheterisation, whereas the patient who had twice had previous surgical valvotomy showed an increase in gradient from 37 to 99 mm Hg over nine months and required aortic root replacement. Balloon dilatation was repeated in two patients and this caused a further reduction in gradient. New aortic regurgitation occurred in nine (27%) patients (grade I, 8; grade II, 1) and aortic regurgitation was exacerbated (grade I to II) in two of the nine with pre-existing aortic regurgitation. External iliac artery avulsion occurred in one (3%) patient and two (6%) required intravenous streptokinase because the femoral artery became occluded. There were no other complications. Open valvotomy was performed in the child in whom the valve was not crossed, but no other child required aortic valve operation. Balloon dilatation of the aortic valve gave reasonable short term palliation and was well tolerated. It is an alternative to surgical valvotomy for initial palliation of congenital aortic stenosis in many children.
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