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Biomedical subjects

R A Stone

Publications and source records attributed to R A Stone.

At least 109 records · Page 6Linked to original sources
PubMed1989

On statistical methods for analysing the geographical distribution of cancer cases near nuclear installations.

There is great public concern, often based on anecdotal reports, about risks from ionising radiation. Recent interest has been directed at an excess of leukaemia cases in the locality of civil nuclear installations at Sellafield and Sizewell, and epidemiologists have a duty to pursue such information vigorously. This paper sets out to show that the epidemiological methods most commonly used can be improved upon. When analysing geographical data it is necessary to consider location. The most obvious quantification of location is ranked distance, though other measures which may be more meaningful in relation to aetiology may be substituted. A test based on distance ranks, the "Poisson maximum test", depends on the maximum of observed relative risk in regions of increasing size, but with significance level adjusted for selection. Applying this test to data from Sellafield and Sizewell shows that the excess of leukaemia incidence observed at Seascale, near Sellafield, is not an artefact due to data selection by region, and that the excess probably results from a genuine, if as yet unidentified cause (there being little evidence of any other locational association once the Seascale cases have been removed). So far as Sizewell is concerned, geographical proximity to the nuclear power station does not seem particularly important.

Cluster Analysis↗
PubMed1989

The ocular hypotensive effects of demeclocycline, tetracycline and other tetracycline derivatives.

Demeclocycline, tetracycline and other tetracycline derivatives lowered intraocular pressure (IOP) in rabbits following intravitreal injection, but the onset of this effect was not evident until 1 or more days after drug administration. Of the drugs tested, demeclocycline was the most active ocular hypotensive agent. Demeclocycline caused a dose-dependent decrease in IOP. The maximum IOP decrease of approximately 12 mm Hg occurred 5 days after intravitreal administration of 0.5 mg, with the effect persisting for over a week. Demeclocycline did not alter tonographically measured aqueous humor outflow facility or episcleral venous pressure. Based on calculated aqueous humor flow rates following 0.2 mg demeclocycline, a 62% decrease in aqueous humor formation occurred 7 days after intravitreal injection. The flow-to-diffusion ratio for ascorbate was reduced 54% 6 days after the intravitreal administration of demeclocycline, a change also consistent with suppression of aqueous humor formation. Anterior chamber aqueous humor protein concentration was increased 6 days after demeclocycline administration. No histologic changes were present in the treated eyes by light microscopy. Intravitreal demeclocycline similarly lowered IOP in cats, with the duration of effect lasting up to 20 days.

Animals↗
PubMed1988

Peptide immunoreactivity of the ciliary ganglion and its accessory cells in the rat.

By means of immunohistochemistry, calcitonin gene-related peptide, Leu-enkephalin and neuropeptide Y localize to rat ciliary and accessory ganglion cells. The proportion of ciliary and accessory neurons immunoreactive to each peptide is provided and compared to previous data for vasoactive intestinal peptide. These findings indicate considerable neurochemical complexity for a parasympathetic ganglion with a small cell population.

Animals↗
PubMed1988

Pterygopalatine ganglion cells contain neuropeptide Y.

By immunohistochemistry, neuropeptide Y (NPY) localizes to neurons in the rat pterygopalatine ganglion. These cells also are intensely or moderately reactive with acetylcholinesterase histochemistry. In contrast, both tyrosine hydroxylase immunohistochemistry and glyoxylic acid-induced fluorescence for catecholamines stain smaller clustered cells, similar in appearance to small intensely fluorescent (SIF) cells and clearly distinct from the NPY-immunoreactive cells. By reverse phase high-performance liquid chromatography, the NPY-immunoreactive material in the rat pterygopalatine ganglion migrates as a single peak characteristic of the peptide. We conclude that NPY-containing cholinergic cells are present in this classical parasympathetic ganglion. NPY-like immunoreactive neurons similarly occur in the pterygopalatine ganglion of the guinea pig.

Acetylcholinesterase↗
PubMed1988

Nerve pathways between the pterygopalatine ganglion and eye in cats.

By dissection of thiocholine-stained orbital preparations, it has been determined that three different nerve pathways link the pterygopalatine ganglion and the eye in cats. 1) Nerves from the proximal half of the ganglion join a plexus of nerves and ganglion cells in the rete mirabile of the maxillary artery. Branches of the internal carotid nerve also supply this plexus. Fine nerves from the plexus travel to the optic nerve and then to the eye, accompanying both the nasociliary nerve that passes through the rete and the ciliary arteries that arise from the rete. 2) One or more nerves from the nerve of the pterygoid canal and from a prominent accessory ganglion near the orbital apex course to the inferior optic nerve surface at the optic foramen; these then run distally along the optic nerve to fuse with ciliary nerves or to accompany ciliary arteries entering the eye. 3) Other nerves from the pterygopalatine ganglion travel medially around the extraocular muscle cone to join the ethmoidal and infratrochlear branches of the nasociliary nerve; some nerves from the ganglion then take a retrograde course to the optic nerve, where they join ciliary nerves or arteries to the eye. All three pathways may transmit sympathetic, parasympathetic and somatic sensory nerve fibers.

Animals↗
PubMed1988

Investigations of excess environmental risks around putative sources: statistical problems and a proposed test.

Individual reactions to a report which identifies an excess of risk near a putative source are determined mainly by some quoted significance level. One reaction, involving a commonly used 'coincidence' argument is given a simple Bayesian explanation. It is argued that interpretations of such reports should if possible allow both for data selection and for uncertainty in the null expectations underlying the significance levels. Tests are proposed, based on the first isotonic regression estimator under an order restriction, which allow for the effects of selecting a study region in the light of the data and have a simple form. Data on cancer incidence around two nuclear plants are used to illustrate.

Australia↗
PubMed1988

Increase in retinal vasoactive intestinal polypeptide after eyelid fusion in primates.

Lids were fused in six neonatal and one adult macaque monkey (Macaca mulatta and Macaca arctoides) and were kept fused for 1 to 18.5 months. The juvenile macaques, but not the adult one, developed myopia due to excessive elongation of the eye. In all animals, the immunohistochemical reactivity of the retina for vasoactive intestinal polypeptide (VIP) was much higher in the closed than in the open eyes. The neuropeptide was localized to the perikaryon and dendrites of amacrine cells. No difference was observed in substance P immunoreactivity between open and closed eyes, suggesting that the observed effect is selective. The change in VIP immunoreactivity could be the result of an increase in peptide synthesis, a decrease in peptide release, or a combination of the two. These results indicate that VIP may play a part in the regulation of postnatal ocular growth.

Animals↗
PubMed1988

Effects of systemic desmopressin on aqueous humor dynamics in rabbits.

Intravenous desmopressin, a synthetic antidiuretic hormone, resulted in a dose-dependent increase in intraocular pressure (IOP) in rabbits. IOP was increased 3.6 +/- 0.8 mm Hg 6 hr following injection of desmopressin 200 mUnits/kg with the increase lasting over 10 hr. IOP returned to baseline 24 hr after the injection. Systemic blood pressure, plasma osmolarity and arterial blood gases were not altered by desmopressin. The increased IOP was not associated with alterations in measured outflow facility or episcleral venous pressure. Five hours after desmopressin injection, calculated aqueous humor flow was increased approximately 57%. Aqueous humor ascorbate measurements for calculation of flow to diffusion ratios and anterior chamber fluorophotometry also were consistent with an increased rate of aqueous humor formation as the mechanism for the IOP elevation. Desmopressin administration did not increase aqueous humor protein or aqueous humor cyclic AMP concentration. Systemic pretreatment with indomethacin only partially blocked the IOP increase. Systemic pretreatment with demeclocycline completely blocked the desmopressin-induced increase in IOP.

Animals↗
PubMed1988

Calcitonin gene-related peptide immunoreactive nerves in human and rhesus monkey eyes.

Using immunohistochemical methods, calcitonin gene-related peptide localizes to peripheral nerve fibers of the human and rhesus monkey eye. Immunoreactive nerve fibers are found in the cornea, about limbal blood vessels and in the trabecular meshwork. Many immunoreactive iris nerve fibers are present, mostly within the stroma. A particularly dense network occurs just anterior to the iris sphincter muscle, but only a small number of immunoreactive nerve fibers are visualized within it. The ciliary muscle and ciliary processes also are innervated. Immunoreactive nerve fibers are associated with uveal blood vessels, most prominently in the choroid and ciliary body. Apposition of immunoreactive nerve fibers to uveal melanocytes is seen. In lower mammalian species, calcitonin gene-related peptide co-localizes with substance P in many ocular nerve fibers. The comparative distribution in human and monkey eyes of nerve fibers immunoreactive to these two peptides is discussed.

Adolescent↗
PubMed1988

Effects of neuropeptide Y on the isolated rabbit iris dilator muscle.

The effects of neuropeptide Y (NPY) were studied on an in vitro preparation of rabbit iris dilator muscle. NPY by itself (10(-11) M to 10(-6) M) had no effect on the resting tension or on the maximal electrically-induced response (MER) of the dilator. Phenylephrine (10(-9) M to 10(-4) M) caused a dose-dependent contraction of the dilator muscle (7.8% to 40.6% of the MER). The addition of NPY 10(-6) M enhanced the phenylephrine-induced muscle contraction (8.8% to 76.8% of the MER) without altering the EC50 value (5 X 10(-6) M) of the phenylephrine dose-response curve. These findings support a modulatory role for NPY on the iris dilator muscle.

Animals↗
PubMed1987

A quantitative correlation of substance P-, calcitonin gene-related peptide- and cholecystokinin-like immunoreactivity with retrogradely labeled trigeminal ganglion cells innervating the eye.

To evaluate the intraganglionic organization of ocular sensory neurons in the guinea pig, we studied the retrograde axonal transport from the eye to the trigeminal ganglion of cholera toxin B subunit and then applied immunohistochemistry for substance P, calcitonin gene-related peptide and cholecystokinin. Retrogradely labeled cells were observed only in the anteromedial portion of the ipsilateral ganglion. We observed no somatotopical organization to trigeminal neurons containing any of these three peptides, either for cells projecting to the eye or for the ganglion as a whole. The relative proportion of neurons immunoreactive for each of these three peptides was similar among the population of neurons retrogradely labeled with cholera toxin B and among the population of neurons without direct projections to the eye.

Animals↗
PubMed1987

Autonomic neurons supplying the rat eye and the intraorbital distribution of vasoactive intestinal polypeptide (VIP)-like immunoreactivity.

We traced the origin and path of autonomic nerves to the rat eye using, as an aid to dissection, a modified thiocholine method for the histochemical demonstration of cholinesterase. When applied to whole nerves and ganglia supplying the rat eye, this procedure is not specific for cholinergic neurons; instead it stains both sympathetic and parasympathetic nerves, many of which are otherwise too fine to identify in dissection. We found that nerves from the superior cervical and pterygopalatine ganglia form a plexus at the orbital apex corresponding to the retro-orbital plexus found in rabbit, monkey and man. In the rat, nerves from the retro-orbital plexus travel peripherally to the superior surface of the optic-nerve sheath. Here, they fuse with long ciliary nerves and the post-ganglionic nerves from the ciliary ganglion to form another dense nerve-fiber plexus that ultimately supplies the eye. Importantly, the plexus on the optic nerve contains many isolated or aggregated ganglion cells. These are comparable in number to those in the ciliary ganglion itself and are assumed to be accessory ciliary neurons. Using immunohistochemistry, we also sought evidence for vasoactive intestinal polypeptide in these ganglia and nerves. As previously known, many pterygopalatine ganglion cells are immunoreactive for this peptide. Vasoactive intestinal polypeptide (VIP)-like immunoreactive nerve fibers are present in nerves from the retro-orbital plexus to the optic-nerve sheath plexus, in most nerves of the latter plexus, and in most nerves entering the eye. Furthermore, a small proportion of nerve cells in the main and accessory ciliary ganglia also are immunoreactive for VIP. We conclude that in addition to the pterygopalatine ganglion, the ciliary ganglion and its accessory ganglia are sources of VIP-like immunoreactive nerves in the rat eye.

Acetylthiocholine↗
PubMed1987

Distinct substance P and calcitonin gene-related peptide immunoreactive nerves in the guinea pig eye.

Using a double labeling indirect immunofluorescent technique, we studied the guinea pig trigeminal ganglion and eye for co-localization of substance P and calcitonin gene-related peptide. In the trigeminal ganglion, the number of neurons immunoreactive for calcitonin gene-related peptide significantly outnumber those immunoreactive for substance P, but virtually all substance P positive neurons are immunoreactive for calcitonin gene-related peptide. In the eye, a complex pattern of co-localization is present; both peptides co-localize in most immunoreactive nerve fibers. Nerve fibers immunoreactive only for calcitonin gene-related peptide tend to be concentrated in the cornea and posterior ciliary body. Nerve fibers immunoreactive only for substance P are present in relation to both iris muscles. Sensory denervation by intracranial transection of the ophthalmic and maxillary nerves fails to eliminate these substance P positive but CGRP negative iris nerve fibers. These findings indicate an alternative origin for substance P immunoreactive nerves supplying the iris muscles in this species.

Animals↗
PubMed1986

Cholecystokinin-like immunoreactivity occurs in ocular sensory neurons and partially co-localizes with substance P.

Based on immunohistochemical analysis of the trigeminal, superior cervical, ciliary and sphenopalatine ganglia and of the eye after sensory denervation and sympathectomy, cholecystokinin (CCK)-like immunoreactive nerves in the guinea pig eye derive from the trigeminal ganglion. Substance P (SP) also occurs in some ocular sensory neurons, suggesting the possible co-localization in this system of CCK- and SP-immunoreactivities. A double-labeling immunofluorescence technique stained 3 types of trigeminal cells and ocular nerve fibers: some immunoreactive for both peptides, some immunoreactive only for CCK and some immunoreactive only for SP.

Animals↗
PubMed1986

Neuropeptide immunoreactivity of pericellular baskets in the guinea pig trigeminal ganglion.

Using immunohistochemical techniques, calcitonin gene-related peptide, substance P and cholecystokinin localize to baskets of fine nerve fibers that completely surround occasional neurons in the guinea pig trigeminal ganglion. These observations, viewed with prior neuroanatomical studies indicating an intrinsic origin for these structures, raise again the possibility of intraganglionic communication within the trigeminal ganglion.

Animals↗