Preimplantation genetic diagnosis of beta-thalassaemia major.
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Biomedical subjects
Publications and source records attributed to J Bingham.
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The neutrophil respiratory burst was examined by the technique of luminol-dependent chemiluminescence (LDCL) triggered by submaximal concentrations of N-formyl-methionyl-leucyl-phenylalanine (fMLP) in diluted whole blood. We sought to identify the chemical species responsible for LDCL in whole blood, to examine the role of leukotriene B4 (LTB4) and other arachidonic acid metabolites as mediators of the fMLP signaling pathway, and to investigate the effect of peroxynitrite on this response. Both sodium azide and taurine significantly inhibited LDCL (93% inhibition with 100 microM azide, 52% inhibition with 10 mM taurine). More modest inhibition was seen with superoxide dismutase (SOD), catalase, the nitric oxide synthase inhibitor monomethyl-L-arginine (L-NMMA), and with inhibitors of the cyclooxygenase (indomethacin), lipoxygenase (AA-861; no effect), and cytochrome P-450 (SKF 525-A) pathways of arachidonic acid metabolism. The nitric oxide donor SIN-1 (1-100 microM) and peroxynitrite (10-300 microM) also augmented fMLP-induced LDCL. The augmentation seen with peroxynitrite and SIN-1 was attenuated by SOD. Despite the increase in LDCL, peroxynitrite caused a dose-related inhibition of fMLP-stimulated LTB4 release. In summary, our results indicate that (1) LDCL elicited by fMLP in diluted whole blood appears primarily mediated by hypochlorous acid derived from myeloperoxidase; (2) pretreatment with the nitric oxide donor SIN-1 or with peroxynitrite augments LDCL; and (3) LTB4 release does not contribute to fMLP-stimulated LDCL or in the modulation of LDCL by SIN-1 or peroxynitrite.
Bone single photon emission tomography (SPET) of the knees has been shown to be of diagnostic value for the investigation of knee pain. This study compared bone SPET with magnetic resonance imaging (MRI) for the diagnosis of knee disorders. Thirty-six patients were studied with modalities, performed an average of 4 months apart (range 0-10 months). There was agreement on the presence or absence and nature of pathology in 24 (67%) patients. In a further three patients, there was an abnormal SPET with equivocal change for the same pathology on MRI. Equivocal change on both modalities for the same pathology were found in one patient. Three patients had abnormalities on MRI with normal SPET, with the remaining patients having equivocal or non-specific changes on one modality only. In the majority of patients, there was agreement on the presence or absence of pathology and the nature of pathology with both modalities. Significant pathology detected on MRI was also identified by bone SPET. This initial study suggests that further work should be undertaken to evaluate the role of bone SPET as a screening test for the evaluation of knee disorders and its role in relation to MRI is justified.
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BACKGROUND: Thiopental's myocardial depressant effects are well known and most likely involve some alteration in intracellular Ca2+ homeostasis. The aim of this study was to investigate the mechanisms of thiopental's negative inotropic effects and its underlying mechanism in isolated ferret ventricular myocardium (which shows physiologic characteristics similar to human ventricular myocardium), and in frog ventricular myocardium, in which Ca2+ ions for myofibrillar activation are derived almost entirely from transsarcolemmal influx. METHODS: The authors analyzed the effects of thiopental after beta-adrenoceptor blockade on variables of contractility and relaxation, and on the free intracellular Ca2+ transient detected with the Ca(2+)-regulated photoprotein aequorin. Thiopental's effects also were evaluated in ferret right ventricular papillary muscles in which the sarcoplasmic reticulum (SR) function was impaired by ryanodine and in frog ventricular strips with little or no SR function. RESULTS: At concentration > or = 10(-4) M, which is in the high range of the clinically encountered free plasma thiopental concentrations, thiopental decreased contractility and the amplitude of the intracellular Ca2+ transient. At equal peak force, peak aequorin luminescence in 10(-4) M thiopental and [Ca2+]0 > 2.25 mM was slightly smaller than that in control conditions at [Ca2+]o = 2.25 mM. This indicates that thiopental causes a small increase in myofibrillar Ca2+ sensitivity. After inactivation of sarcoplasmic reticulum Ca2+ release with 10(-6) M ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca2+ influx, thiopental caused a further decrease in contractility and in the amplitude of the intracellular Ca2+ transient, and thiopental's relative negative inotropic effect was not different from that in control muscles not exposed to ryanodine. Thiopental, > or = 10(-4) M, decreased contractility in frog ventricular myocardium. CONCLUSIONS: These findings indicate that the direct negative inotropic effect of thiopental results from a decrease in intracellular Ca2+ availability. At least part of thiopental's action is caused by inhibition of transsarcolemmal Ca2+ influx. These effects become apparent at concentrations routinely present during intravenous induction with thiopental.
Eight black-backed jackals (Canis mesomelas) and seven side-striped jackals (Canis adustus) were given SAD (Berne) rabies vaccine by direct oral instillation. Three different vaccine doses were used: 10(6.3), 10(6.8) and 10(7.5) median tissue culture infectious doses. Two additional jackals were given vaccine in chicken heads. One group of jackals was challenged with a lethal dose of jackal-derived rabies virus 1 mo after vaccination and a second group 12 mo after vaccination. All 17 vaccinated jackals developed high and persistent serum neutralizing antibody titers. All challenged jackals resisted a lethal dose of rabies virus, whereas three control jackals given the same challenge succumbed to rabies.
Three cases of human rabies were diagnosed antemortem by the skin biopsy technique. The skin biopsies were taken from the nape of the neck and processed by cryosectioning and staining using the direct fluorescent antibody test (FAT). Rabies antigen was demonstrated in the network of nerve fibres surrounding the hair follicles. As the skin biopsy technique is relatively simple and cheap to perform it could be a practical technique for use in African countries, where it is not routinely used in the diagnosis of rabies in humans.
In assessing the potential of the tetracycline compounds as biomarkers in oral rabies vaccination campaigns in jackals in Zimbabwe, the natural prevalence of fluorescent compounds in bone tissue from jackals was investigated. Femur samples were taken from unbaited jackals received for routine rabies diagnosis, and thin undecalcified sections were cut and viewed under an ultraviolet microscope. Of 131 femur samples examined, 49 (37 per cent) had fluorescent markings indistinguishable from those of tetracycline. The result implies that the tetracycline compounds, which are commonly used in rabies baiting campaigns in Europe and North America, cannot be used as biomarkers in jackals in Zimbabwe.
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Cerebellar hypoplasia may present with a wide variety of neurological and systemic features, ranging from aplasia causing neonatal death to mild hypoplasia in an asymptomatic adult. MRI clearly documents the size of the cerebellum and any associated abnormalities. We describe 7 cases of cerebellar hypoplasia of varying aetiology--3 inherited, 2 associated with spinal dysraphism, 1 with Joubert's syndrome and 1 with pontine agenesis, probably as a result of basilar artery infarction in utero. T1- and T2-weighted images were obtained in each case and gadolinium-DTPA was administered in one. Associated features such as a Chiari malformation (2 cases), brain stem hypoplasia (2 cases), Dandy-Walker cyst and pachygyria (3 cases) and spinal dysraphism (2 cases) were clearly identified. Accurate documentation of these appearances assists in genetic counselling.
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Thirty eight patients with neurofibromatosis 1 (NF1) had neurological examinations, intellectual assessments and MRI scans. Increased intensity lesions on T2 weighted images were found in 13 patients. These abnormalities were more common in patients aged under 18 years. The lesions occurred predominantly in the basal ganglia, brainstem and cerebellum, and were multiple in 11 patients. They did not produce symptoms or neurological deficit in any patient and did not enhance with gadolinium-meglumine-triamine-pentaacetic acid contrast medium (Gd-DTPA). In 2 patients, however, the abnormalities exerted mass effect distorting the brain and in 3 patients they occurred in conjunction with known gliomas. The lesions remained unchanged over a three year follow up period. The nature of the lesions is uncertain but the fact that they may produce mass effect and occur in association with gliomas suggests that they have malignant potential. There was no correlation between the presence of these abnormalities and intellectual impairment.
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General practitioners and accident and emergency departments are often involved in the management of hand or finger sepsis. Such cases are usually easily diagnosed and treated. We report a more serious disorder which may mimic the condition and cause diagnostic confusion.