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Biomedical subjects

G Grant

Publications and source records attributed to G Grant.

At least 199 records · Page 11Linked to original sources

HLA typing used with cultured amniotic and chorionic villus cells for early prenatal diagnosis or parentage testing without one parent's availability.

Like fetal fibroblasts and amniotic fluid cells, cultured chorionic villus cells can also be HLA typed with selected typing sera after preincubation with gamma interferon to promote better antigen expression. A modified procedure now in use would also allow any of these cell types to be tested for the presence or absence of all known HLA A,B,C, and DR antigens with standard preplated typing trays. This procedure was used to confirm that an on-going pregnancy had resulted from the successful in vitro fertilization and implantation of an anonymous donor's ovum and could also be of major use in rape or artificial insemination cases when the identity of the possible father(s) is not known.

Amnion↗

Laminar distribution and somatotopic organization of primary afferent fibers from hindlimb nerves in the dorsal horn. A study by transganglionic transport of horseradish peroxidase in the rat.

Primary afferent nerve fibers to the spinal cord in the adult rat were labeled by applying horseradish peroxidase to the cut end of one of the following hindlimb nerves; the tibial, medial plantar, lateral plantar, common peroneal, saphenous, sural, lateral femoral cutaneous or obturator nerve. Maximal labeling intensity was found in the dorsal horn after 36-72 h survival. Labeling was observed in different dorsal horn laminae at different levels within the L1-S1 spinal cord segments, depending on which nerve horseradish peroxidase had been exposed to, probably reflecting the individual composition of afferent fiber types. Although a certain overlap was found, the central projections of the eight different nerves investigated formed well delineated three dimensional compartments within the medial 2/3 to 3/4 of the dorsal horn. This was most clearly discernible in lamina II. Although interindividual differences were present, bilaterally identical operations gave symmetrical projection patterns in the dorsal horn. The results indicate that dorsal horn projections of hindlimb nerves are organized in a highly ordered somatotopic fashion.

Afferent Pathways↗

Corneal endothelial changes in superficial epithelial keratopathy.

A series of five cases is described in which superficial punctate keratopathy was associated with endothelial cell changes. The most striking change was the presence of dark areas or blebs, usually two to four cell diameters in extent. There was also distortion and crumpling of the corneal endothelium, mild pleomorphism and polymegathism of the endothelial cells, with a reduced cell count in some cases. These blebs have previously been reported in hard and soft contact lens wearers and are due to intercellular oedema with separation of endothelial cells from Descemet's membrane. Anoxia and interference with osmosis have been proposed as possible mechanisms for the production of these blebs, but our cases demonstrate that fine disruption of the corneal epithelium can affect the integrity of the corneal endothelium and may lead to significant damage over a long period of time.

Adult↗

Changes in the iris vasculature and corneal endothelium in chronic cyclitis.

Fluorescein angiography of the iris vasculature and specular microscopy of the corneal endothelium were used to examine two important anterior chamber tissues in cases of heterochromic cyclitis, classical chronic cyclitis and some cases of iridocyclitis. The 13 cases of heterochromic cyclitis and eight cases of classical chronic cyclitis all showed vascular hypoperfusion of the iris, except for two young females with heterochromia. In these cyclitic eyes there was pupillary leakage of dye and all but one young female with heterochromia showed evidence of microneovascularization of the iris. Most patients showed evidence of abnormalities of the corneal endothelium, but this was most marked in elderly patients with heterochromic cyclitis, probably due to the long duration of the condition. Six of the patients with chronic cyclitis had bilateral disease and five of these were elderly women with glaucoma and grey irides, the group being distinct enough to form a discrete clinical entity. Seventeen of the patients with chronic cyclitis were females with grey irides suggesting that this type of patient is more susceptible to cyclitis. Patients with acute iridocyclitis showed little abnormality on fluorescein angiography, while those with recurrent or chronic disease showed vascular hypoperfusion and microneovascularization suggesting that these changes in the iris contribute to the chronicity of the condition. It is suggested that hypoperfusion and microneovascularization of the iris and abnormal permeability are important factors in the production of chronic cyclitis, and that the integrity of the corneal endothelium is affected by these changes if they operate over a long period of time.

Adult↗

Deep corneal stromal opacities with contact lenses.

Two patients with deep corneal stromal opacities occurring after prolonged contact lens wear are described. The opacities were associated with folds or striae in Descemet's membrane which they overlay. Development of the opacities was associated with ocular discomfort, photophobia, reduced vision and a history of prolonged daily wearing times. Although the corneal endothelial cell counts were within the normal range, the count was reduced in the affected eye in the patient with the unilateral deep stromal opacity and there was mild polymegathism of the endothelial cells. It is possible that the long-term effects of subtle endothelial cell changes may cause a keratopathy with later scarring and opacification. Poor oxygen transmissibility, carbon dioxide build-up, or suction effects by the lens may all be aetiological factors. Early recognition and treatment, particularly with a better fitting lens of high oxygen transmissibility is important, as once developed the opacities regress only slowly and may result in permanent visual impairment.

Adult↗

Cutaneous projections from the rat hindlimb foot to the substantia gelatinosa of the spinal cord studied by transganglionic transport of WGA-HRP conjugate.

The somatotopic organization of cutaneous afferent fibers from the hindlimb foot in the substantia gelatinosa of the spinal cord was investigated in adult Sprague Dawley rats following intracutaneous injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). The different parts of the foot were found to project in a precise manner to the medial two-thirds of the substantia gelatinosa of the spinal cord segments L3-L5. The projections from the digits were arranged in a consecutive row rostrocaudally, with the most medial digit in caudal L3 and the most lateral digit in caudal L4 or rostral L5. The plantar skin was found to project both rostral and caudal to the projection of the digits. The dorsal foot skin projects lateral to the digits, neighboured by the medial edge of the foot rostrally and the lateral edge caudally. Within the projection of a particular digit, the plantar skin was found medially and the dorsal skin laterally. A certain degree of overlap for the projections from the different foot skin areas was found.

Afferent Pathways↗

Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects.

Experiments were designed to investigate whether orally consumed tomato lectin could resist the digestive process and function as a lectin within the alimentary canal. Rats fed on a tomato lectin-rich diet passed faeces containing serologically detectable tomato lectin, and the lectin could be shown by immunoperoxidase staining bound to intestinal villi. Moreover, radioactivity was mainly recovered from the alimentary canal 3h after 125I-labelled tomato lectin administration with only traces in the circulation or internal organs. Radioactivity absorbed into the human circulation after consumption of 125I-labelled tomato lectin was also less than that expected for a digestable protein.

Administration, Oral↗

The reaction of primary sensory neurons to peripheral nerve injury with particular emphasis on transganglionic changes.

This paper reviews light- and electron microscopic, histochemical and physiological evidence which demonstrate that peripheral nerve injury in mammals is followed by profound structural and functional changes in the central terminals of the affected primary sensory neurons. Available evidence indicates that at least some of these so-called transganglionic changes are the result of ganglion cell degeneration and death, although other mechanisms are probably in effect as well. Existing data suggest that this ganglion cell death does not effect all types of ganglion cells equally, but do not permit a clearcut answer to the question of which kinds of ganglion cells are affected more than others. Results from studies with microtubule inhibitors and antibodies to nerve growth factor are compatible with the notion that depletion of retrogradely transported trophic factors is involved in the production of certain transganglionic changes. This issue needs further examination, however. Physiological studies indicate marked alterations in certain primary afferent synaptic connections after peripheral nerve lesions. So far, these changes have not been satisfactorily correlated with the structural changes induced by similar lesions. Further studies on the structural and functional response of primary sensory neurons to peripheral nerve injury are likely to contribute to the understanding of the frequent failure to regain normal sensory functions after peripheral nerve lesions in man, as well as of the basic aspects of lesion-induced changes in general in the peripheral and central nervous system.

Acid Phosphatase↗

A comparison between wheat germ agglutinin-and choleragenoid-horseradish peroxidase as anterogradely transported markers in central branches of primary sensory neurones in the rat with some observations in the cat.

Horseradish peroxidase conjugates of either the lectin wheat germ agglutinin or choleragenoid, the binding subunit of cholera toxin, were injected into the L5 spinal ganglion of adult rats. This enabled comparison of these two conjugates as anterograde tracers in the primary sensory system. After a postoperative survival of 4 h to 30 days, the rats were perfused and frozen sections from spinal and medullary regions receiving primary afferents were processed for horseradish peroxidase histochemistry with tetramethylbenzidine as the chromogen. Additional observations were made in two adult cats. Following injection of wheat germ agglutinin-horseradish peroxidase the labelling appeared mostly as small-sized granules. The concentration of labelled primary afferents in the grey matter of the spinal cord was greatest in the marginal zone and the substantia gelatinosa and less pronounced in the deep parts of the dorsal horn. Labelling was also found in a region lateral to the central canal and in the ventral horn. Following injection of choleragenoid-horseradish peroxidase the labelling appeared mainly as larger-sized granular profiles. The concentration of labelled primary afferents was greatest in the deep part of the dorsal horn and pronounced in a region lateral to the central canal and in the ventral horn. All these regions are known to receive large calibre fibres. The marginal zone and the substantia gelatinosa, known to receive fine calibre fibres, showed almost no labelling in the rat. In the cat, however, there was somewhat more labelling in the substantia gelatinosa. Labelling of neuronal cell bodies indicating transneuronal transport was seen after injection of wheat germ agglutinin-horseradish peroxidase. Transneuronal labelling did not seem to occur after injection of choleragenoid-horseradish peroxidase. The present findings show that wheat germ agglutinin-and choleragenoid-horseradish peroxidase give rise to markedly different labelling patterns. A possible explanation for the different labelling in the marginal zone and substantia gelatinosa could be that certain primary sensory neurones lack either receptors for choleragenoid on their neuronal plasma membrane or the ability to transport the choleragenoid-horseradish peroxidase complex.

Animals↗

Serial analysis of electrically induced ventricular arrhythmias in a canine model of myocardial infarction.

To determine the rate of induction, specificity and evolution of electrically induced postmyocardial infarction ventricular arrhythmias, 10 dogs that underwent a sham operation and 20 dogs with experimental transmural apical myocardial infarction underwent serial closed chest electrophysiologic studies with programmed ventricular stimulation under light anesthesia 1, 2, 4 and 6 weeks after the operation. The reproducibility of the electrically induced ventricular arrhythmias was at a maximum when three extrastimuli were used during ventricular pacing for induction. The reproducibility of the arrhythmias was also a function of the age of the infarct. Electrically induced sustained monomorphic ventricular tachycardia, observed in 45 to 50% of the animals, was a highly specific postinfarction finding (0% specificity in control animals, regardless of the mode or timing of programmed cardiac stimulation), whereas nonsustained polymorphic ventricular tachycardia was not. The specificity of induced ventricular fibrillation was a function of the mode and timing of programmed stimulation. The rate of induction of the electrically induced ventricular arrhythmias did not change significantly during the 6 week period after myocardial infarction. A large infarct size (determined by postmortem examination) and a low left ventricular ejection fraction (determined during premortem cardiac catheterization) were the only variables identified that predisposed the animals to electrically induced sustained monomorphic ventricular tachycardia. These factors, however, did not correlate with the presence of electrically induced ventricular fibrillation or nonsustained ventricular tachycardia.

Animals↗

Determinants of the outcome of electrophysiologic study in patients with ventricular tachyarrhythmias.

To determine those factors predictive of the ability to both initiate and suppress ventricular tachyarrhythmias during electrophysiologic study, the results of programmed cardiac stimulation were evaluated in 261 patients: 66 presenting with nonsustained ventricular tachycardia, 91 with sustained ventricular tachycardia and 104 with ventricular fibrillation. Multivariate logistic regression analysis revealed that the presenting arrhythmia was a potent and independent predictor of the ability to provoke ventricular arrhythmias at electrophysiologic study; a history of myocardial infarction and male sex were also significant independent predictors. Of patients presenting with sustained ventricular tachycardia, 89% (81 of 91) had inducible ventricular arrhythmias compared with 61 (40 of 66) and 66% (69 of 104) of patients with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Complete suppression of inducible arrhythmias could be achieved in only 52% (34 of 66) of patients with sustained ventricular tachycardia, compared with 73 (24 of 33) and 75% (46 of 61) of patients presenting with nonsustained ventricular tachycardia and ventricular fibrillation, respectively. Multivariate analysis showed that the major independent determinants of the ability to suppress inducible arrhythmias were the number of drug trials performed before electrophysiologic study (inversely correlated) and the nature of the induced arrhythmia. The nature of the presenting clinical arrhythmia is, therefore, a highly significant and independent predictor of the ability to induce ventricular arrhythmias during electrophysiologic testing and an important determinant of the ability to suppress induced arrhythmias in patients with spontaneous ventricular tachyarrhythmias.

Adolescent↗

Current problems in continuous ambulatory peritoneal dialysis.

In spite of multiple problems, continuous ambulatory peritoneal dialysis is now an acceptable alternative treatment for end-stage renal failure. With proper care and attention to detail, many of its problems can be reduced or eliminated. It is particularly suitable for the very old, the very young and the patient living a long distance from the centre, and it is the treatment of choice for diabetes mellitus prior to transplantation.

Chronic Kidney Disease-Mineral and Bone Disorder↗

The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord.

A laminar cytoarchitectonic scheme of the lower thoracic and lumbosacral segments of the rat spinal cord is presented in which Rexed's principles for the cat are applied. The material consists of 80-micron-thick sections stained with toluidine blue or according to van Gieson and 2-micron-thick sections stained with p-phenylenediamine or toluidine blue. The cytoarchitectonic organization of the rat spinal cord was found to be basically similar to that of the cat, although certain differences exist--for example, in the extension of the laminae. In addition to the laminar scheme, the distribution of certain cell groups, Lissauer's tract, and the pyramidal tract were investigated.

Animals↗

Long-term clinical outcome of ventricular tachycardia or fibrillation treated with amiodarone.

The determinants of long-term clinical outcome were studied in 42 patients with recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) who were treated with amiodarone as the sole antiarrhythmic agent. Of the 42 patients, 11 (26%) either died suddenly or had recurrent, symptomatic, sustained VT during a mean follow-up period of 10 months (range 0.3 to 45). Of the 19 patients without inducible VT/VF during electrophysiologic study while receiving amiodarone, 1 patient died suddenly but no patient had recurrent VT/VF. Ten of the 23 patients (43%) with persistently inducible arrhythmia have died suddenly or have had recurrent VT/VF. Using survival and stepwise logistic regression analyses, 2 significant independent predictors of recurrent arrhythmia were identified; persistently inducible VT during electrophysiologic testing in patients receiving amiodarone therapy (p less than 0.002) and the left ventricular ejection fraction at rest (p less than 0.05). The predictive accuracy of the response to serial electrophysiologic testing during amiodarone therapy was 67%, the sensitivity was 58% and the specificity was 91%. Thus, serial electrophysiologic testing is useful for determining the prognosis in patients with inducible VT/VF treated with amiodarone.

Aged↗