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Biomedical subjects

P C Jackson

Publications and source records attributed to P C Jackson.

At least 37 records · Page 2Linked to original sources

The accuracy of digital subtraction angiography for the quantification of atherosclerosis.

Digital subtraction angiography (DSA) allows the degree of arterial patency or stenosis to be rapidly quantified. We have assessed the accuracy with which a single-plane DSA system is able to quantify area patency by densitometric and geometric methods. Arterial phantoms were designed to test for systematic error; intra-arterial DSA images of critical lesions of the carotid bifurcation and the lower abdominal and peripheral vessels were used to determine intra- and interobserver reproducibility. The densitometric method, which was more accurate than the geometric method, had a mean systematic error of up to 4% and a mean intra-observer variability of about 15% (coefficient of variation). We have identified the principal sources of inaccuracy and ways in which it may be reduced.

Arteriosclerosis↗

Osteoporosis and amenorrhea in young women.

Bone density of the radius was measured using both standard photon absorptiometry and X-ray computed tomography (CT) scanning, and of the femur using CT, in 21 young women with amenorrhea and estrogen deficiency due to hyperprolactinemia, 8 due to ovarian failure or weight loss, 17 postmenopausal women with bone fractures presumed to be due to osteoporosis, and 36 young normal controls. Bone density in the postmenopausal women was reduced by 18-20% in the radius and 11% in the femur (p less than 0.001). In the hyperprolactinemic group bone density was significantly reduced only in the femur (by 4%, p less than 0.01). Bone density appeared to be reduced in the other young amenorrheic women both in the radius (by 2-5%) and the femur (3%) but the difference was not significant, although the group was small. This and other studies of bone density suggest the need for prophylactic treatment to prevent osteoporosis in young women with amenorrhea and estrogen deficiency, whatever the cause.

Absorptiometry, Photon↗

Catecholaminergic properties of cholinergic neurons and synapses in adult rat ciliary ganglion.

Parasympathetic neurons of the ciliary ganglion are innervated by preganglionic cholinergic neurons whose cell bodies lie in the brain stem; the ganglion cells in turn provide cholinergic innervation to the intrinsic muscles of the eye. Noradrenergic innervation of the iris is supplied by sympathetic neurons of the superior cervical ganglion. Using immunocytochemical and histochemical techniques, we have examined the ciliary ganglion of adult rats for the expression of cholinergic and noradrenergic properties. As expected, the postganglionic ciliary neurons possessed detectable levels of choline acetyltransferase immunoreactivity (ChAT-IR). Unexpectedly, many ciliary neurons also exhibited immunoreactivity for tyrosine hydroxylase (TH-IR). Some had dopamine beta-hydroxylase-like (DBH-IR) immunoreactivity, but none contained detectable catecholamines, even after treatment with nialamide and L-DOPA. A sparse plexus of fibers exhibiting faint TH-IR was present in the irises of acutely sympathectomized rats. The terminals of preganglionic axons in the ciliary ganglion exhibited not only immunoreactivity for ChAT, but also for TH and contained stores of endogenous catecholamine. Neither ciliary neurons nor their preganglionic innervation accumulated detectable stores of exogenous catecholamines. Rats sympathectomized as neonates by treatment with 6-hydroxydopamine subsequently had a greater proportion of neurons possessing detectable TH-IR in the ciliary ganglion; both the TH-IR perikarya and their axons in the iris were more intensely immunofluorescent. TH-IR was present in the ciliary neuron cell bodies of mouse, guinea pig, and ferret. These species, however, lacked detectable TH-IR or catecholamine stores in preganglionic terminals. These observations indicate that mature, functionally cholinergic neurons from 2 different embryonic origins, postganglionic ciliary neurons derived from the neural crest and preganglionic neurons derived from the neural tube, display several catecholaminergic properties.

Animals↗

Normal electrical activity is not required for the formation of specific sensory-motor synapses.

These studies sought to determine the role of stretch-evoked electrical activity in muscle sensory axons on the formation of specific monosynaptic connections made by these neurons onto spinal motoneurons. Normal activity was disrupted by tenotomy during the developmental stages that the central connections are made. The pattern of connections was normal, suggesting that normal activity is not required in this system for the formation of specific sensory-motor connections.

Animals↗

Use of P NMR to Assess Effects of DNP on ATP Levels in Vivo in Barley Roots.

Previous work has shown that undissociated 2,4-dinitrophenol (DNP) both increases the permeability of roots to ions and alters the membrane lipids of barley roots. Anionic DNP is the main entrant form but has no effect on permeability or on the membrane lipids. The amount of anionic DNP taken up by the roots is sufficient, that were it in free solution in the cytoplasm, the DNP would uncouple oxidative phosphorylation, and thereby inhibit ATP synthesis. The present work was undertaken to assess whether DNP alters ATP levels when it is taken up by barley roots. (31)P nuclear magnetic resonance spectra were used to monitor, in vivo, levels of ATP, cytoplasmic phosphate, vacuolar phosphate, and other phosphate compounds in barley roots in the presence of 10 micromolar DNP at pH 5 and pH 7. The spectra indicate that no change in the level of ATP or the cytoplasmic pH occurred in the roots in the presence of DNP for as long as 20 hours. Thus, the effects of undissociated DNP are effects directly on the root membranes and do not involve inhibition of ATP synthesis. Furthermore, the results explain why anionic DNP has no effect on ion uptake and accumulation.

Journal Article↗

Innervation of the iris by individual parasympathetic axons in the adult mouse.

Ciliary neurones were identified electrophysiologically in isolated ganglia and the projection of individual axons to the intrinsic muscles of the eye determined by labelling identified cells with horseradish peroxidase (HRP). The ciliary ganglion of the adult mouse contains 80-100 parasympathetic neurones clustered at the point where the oculomotor nerve branches to supply the medial and inferior rectus. These nerve cells show varying degrees of dendritic complexity (zero to six primary dendrites) and differing degrees of innervation by preganglionic axons (one to seven inputs). Cells with more complex dendritic arborization generally receive synaptic input from commensurately larger numbers of preganglionic axons. The axons of individually labelled cells give rise to varicose terminals in the iris and ciliary body; in most cases a single parent axon branches only after entering the iris, producing a network of terminals in the region of both the sphincter and the antagonist dilator muscle. Cells with both simple and complex dendritic geometry show this pattern of axonal arborization. The usual net effect of stimulating a single ciliary ganglion neurone through an intracellular electrode is constriction of the pupil. Since the terminals of individual ciliary ganglion neurones are commonly distributed to both the sphincter and dilator regions of the iris, impulses invading the terminals of a single ciliary neurone cause a contraction of the sphincter muscle, perhaps accompanied by a simultaneous relaxation of the dilator. Direct examination of individually labelled neurone has revealed details of the pattern of parasympathetic axon distribution to the iris, thus accounting for the origin of cholinergic terminals in the dilator, classically considered to be primarily a target of adrenergic sympathetic neurones.

Animals↗

99mTc HMDP bone scanning in generalised nodal osteoarthritis. I. Comparison of the standard radiograph and four hour bone scan image of the hand.

The pattern of joint involvement on conventional radiographs and the four hour gammacamera image of 99Tc HMDP bone scans were studied in 33 patients with generalised nodal osteoarthritis. Both techniques showed the predominant involvement of the distal interphalangeal, scaphotrapezial, and first carpometacarpal joints. Some joints were abnormal just on one investigation: either x ray or scan alone. Others showed a marked dissimilarity in the severity of involvement on x ray compared with scan. This discrepancy between x ray and scan suggests that the scan is imaging a different process than the radiograph and offers a different way of assessing change in osteoarthritis.

Female↗

99mTc HMDP bone scanning in generalised nodal osteoarthritis. II. The four hour bone scan image predicts radiographic change.

In 14 patients with generalised nodal osteoarthritis a four hour bone scan image was found to predict the changes that occur on the radiograph at follow up between three and five years later. The scan abnormality appeared to precede the development of radiographic signs, and joints abnormal on scintigraphy showed most progression. Normal joints and joints abnormal on x ray alone showed little progression, and those that did subsequently alter became abnormal on scan. Scanning may provide a sensitive technique for monitoring osteoarthritis, it may enable a greater understanding of the underlying disease process, and allow evaluation of modifying therapeutic procedures.

Female↗

The reduction of inter- and intra-observer variability for defining regions of interest in nuclear medicine.

The use of region-of-interest (ROI) techniques to quantify data obtained in radionuclide images is commonplace. However, the reproducibility of quantitation due to inter- and intra-observer variations using particular methods of deriving ROIs is often not appreciated. We examined such variations in the results obtained by four independent observers of varying experience using four methods of depicting a ROI about an organ. The set of image data consisted of renal scans with varying target-to-background ratios, and the ROI facilities included two edge-detection methods. The results indicated that, once observers were experienced with edge-detection methods, a lower inter- and intra-observer variation could be achieved, although the technique of 'shrinking' a ROI about a subjectively chosen display level was reasonably satisfactory. In terms or reproducibility, the least satisfactory method of depicting a ROI was the commonly used manually guided 'bug' around arbitrarily chosen display levels representing the boundary of an organ.

Humans↗

Radionuclide imaging of ovarian tumours with a radiolabelled (123I) monoclonal antibody (NDOG2).

The biodistribution of a radiolabelled monoclonal antibody (123I-NDOG2) was studied in patients with ovarian tumour. It was found that the uptake patterns in known tumour sites was variable and that the clearance of the agent from the vascular pool was due to renal excretion of the radionuclide and the redistribution of the radioactively labelled compound into other compartments. The mean (+/- SD) plasma clearance time was 20.8 (+/- 2.3) h and the ratios of target (tumour) to background (thigh) ranged between 1.4 and 4.8. The ratio between the plasma radioactivity at either 3.5 or 20 h after administration was calculated relative to the initial plasma radioactivity. These values (0.79 and 0.48, respectively) were incorporated into an image-subtraction technique that allowed for redistribution outside the vascular pool. A whole-body dose equivalent to 16.3 mu Sv MBq-1 (60.4 mrem.mCi-1) was calculated.

Antibodies, Monoclonal↗

Compartmental analysis of cerebrospinal fluid transfer and absorption in simulated hydrocephalus.

A mathematical model of the cerebrospinal fluid (CSF) flow dynamics found in hydrocephalic infants with myelomeningocele lesions was constructed using criteria obtained from analogous clinical situations where 125I-labelled and 131I-labelled ortho-iodobenzoyl-amino-acetic acid (hippuran) had been employed to measure CSF flow dynamics. The quantitative results from this study allowed clinical data to be assessed and the importance of various CSF transfer mechanisms to be discussed. Our mathematical model indicates that the majority of radiopharmaceutical passes from the cerebral reservoir (the ventricles) into the blood. Experimental evidence indicates that the principal mechanism responsible for this movement is the bulk flow of CSF between its sites of production in the choroid plexus and absorption by the arachnoid villi.

Blood-Brain Barrier↗

Oesophageal function in diabetes mellitus and its association with autonomic neuropathy.

We have evaluated oesophageal function in 34 diabetics and in 16 non-diabetic controls by a timed bolus transit method derived from dynamic oesophageal scintiscans (water transit time: WTT) and barium swallow. The diabetics were screened for autonomic neuropathy using standard cardiovascular responses and 10 patients were classified as abnormal. WTT was significantly prolonged in autonomic neuropaths compared with other diabetics (p less than 0.01) and controls (p less than 0.001). Abnormal peristalsis on barium swallow was seen more frequently in autonomic neuropaths (9/10) than in other diabetics (11/24, p less than 0.002). WTTs from all diabetic patients correlated with abnormal heart rate responses at rest (Rs = - 0.49, p less than 0.005), on deep inspiration (Rs = -0.48, p less than 0.005), and on standing (Rs = -0.39, p less than 0.025) but not with the Valsalva manoeuvre. A weaker correlation was found between the postural fall in blood pressure (Rs = 0.3, p less than 0.05). Diabetics with autonomic neuropathy frequently have asymptomatic oesophageal dysfunction which may result from a vagal neuropathy in view of its association with abnormalities of vagally mediated cardiovascular responses.

Adult↗

Radionuclide imaging of ovarian tumours with 123I-labelled monoclonal antibody (NDOG2) directed against placental alkaline phosphatase.

A radiolabelled monoclonal antibody (NDOG2) directed against placental alkaline phosphatase (PLAP) was used in the radio-immunodetection of ovarian carcinoma. Tumour deposits were successfully visualized in 11 of 15 patients and the abnormalities demonstrated were classified as focal or diffuse. Of the 11 patients, eight showed focal abnormalities alone and three had a diffuse abnormality, of which two also showed a focal abnormality. False-positive results may occur not only due to uptake of 123I by gut mucosa and an inadequately blocked thyroid gland but also from activity in an incompletely emptied bladder. A false-negative result occurred due to high background activity in the liver masking a known, discrete tumour deposit.

Alkaline Phosphatase↗

Temporal and spatial constraints on the collateral sprouting of low-threshold mechanosensory nerves in the skin of rats.

We have studied the collateral sprouting of intact low-threshold mechanosensory nerves into adjacent denervated skin in rats. An "isolated" field was produced by extensive denervations of the surrounding skin; sprouting of the remaining cutaneous nerve supplying the field was looked for in the form of field expansion into the surrounding denervated territory at various postoperative intervals. Such isolated fields failed to expand in the adult rat for periods up to at least 85 days. "Nonfunctional" sprouting is unlikely to explain this failure. However, similar experiments done in very young animals gave a different result. In rat pups aged less than 20 days, isolated fields did expand, but this ceased at about 20 days, and attempts to evoke it after this time were unsuccessful. There seems to be a critical period for sprouting of these touch-sensitive nerves into denervated skin, and our evidence suggests that it may not begin until about 15 days of age. Within this developmental window the sprouting that occurs is spatially constrained, an isolated field expanding preferentially into denervated skin of the parent dermatome; if only skin of neighboring dermatomes is available there is no expansion. In contrast, low-threshold nerves regenerated readily after a crush at all ages studied, and the mechanosensory fields established by regenerating nerves expanded progressively into denervated skin without apparent constraints at dermatomal boundaries. The temporal and spatial constraints found for the sprouting of intact low-threshold axons are in marked contrast to their absence for the well-described sprouting of high-threshold (nociceptive) nerves.

Age Factors↗

Impulse activity evokes precocious sprouting of nociceptive nerves into denervated skin.

We have studied the sprouting of intact high-threshold mechanosensory nerves into adjacent denervated trunk skin in adult rats behaviorally, histologically, and electrophysiologically. In the anesthetized animal, stimulation of high-threshold endings in back skin by localized pinching elicits a bilateral reflex excitation of the underlying skeletal muscle, the cutaneous trunci muscle (CTM), visible as a twitch-like puckering of the skin. The reflex was also evoked by electrical excitation of A delta and of C fibers in the dorsal cutaneous nerves (DCNs), with characteristic latencies of 7-20 msec and 40-60 msec, respectively; excitation of low-threshold (A alpha) fibers was ineffective. After cutting selected DCNs, the deprived skin became insensible, but pinch responsiveness gradually recovered over the following 2 weeks. Regeneration of cut axons was not responsible for this recovery; when neighboring intact DCNs were cut, however, all responses were abolished in the recovered skin that had been initially denervated. By 3-5 days after denervation, axons in the dermis were all histologically absent or degenerating; when pinch sensitivity was restored to such skin, silver-stainable axons reappeared in the formerly empty Schwann tubes. During the work we noticed that the periodic examination by pinching, used to follow the time course of recovery of function in individual animals, led to an earlier development of this recovery than in animals that were examined only once at a specified time after denervation. This apparent acceleration in the redevelopment of pinch sensitivity was correlated with the appearance of axons in the recovered skin, and was shown to be due to the impulse activity evoked in the remaining nerves by the periodic pinching; it did not occur when the nerves were blocked by tetrodotoxin (TTX), and it was mimicked by a brief (10-min) period of electrical excitation of the A delta fibers in a remaining nerve carried out at the time when the denervation of skin was done. The time course of the phenomenon suggested that the principal effect of the impulses was to shorten the latency to the onset of sprouting in the activated A delta axons; that is, they induced precocious sprouting. The impulses needed to be conducted centrally for the effect to occur, and precocious sprouting failed to occur if the impulses were allowed to proceed only distally toward the skin. It seems that a brief conditioning burst of impulses in A delta axons sensitizes the neurons to the influence of a sprouting stimulus that appears when skin is denervated.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

The potential of phase and amplitude images in determining the boundary of the left ventricle.

The phase and amplitude images derived from multiple gated blood pool studies of the heart have been used to aid the delineation of the boundary of the left ventricle. The results of left ventricular ejection fraction (LVEF) using this method have been compared with those obtained using edge detection algorithms, dual region of interest techniques, and x-ray contrast ventriculography, in a series of patients with well documented left ventricular wall motion. The results indicate that the sole use of phase and amplitude images does not improve the correlation or accuracy of LVEF estimation in relation to those obtained by x-ray contrast ventriculography, and that the dual region of interest technique is likely to remain the preferred method.

Adult↗