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Biomedical subjects

R A Stone

Publications and source records attributed to R A Stone.

At least 145 records · Page 8Linked to original sources

Pancreatic polypeptide-like immunoreactive nerves in the guinea pig eye.

The indirect immunofluorescence technique with antisera either to avian pancreatic polypeptide or to bovine pancreatic polypeptide stains nerve fibers in the guinea pig eye. In all regions of the uvea, immunoreactive fibers are present around large blood vessels; an association of immunoreactive nerve fibers to melanocytes is seen. Immunoreactive nerves are found throughout the choroid, including the choriocapillaris. In the ciliary body, they are seen in individual ciliary processes. The iris dilator muscle and, to a lesser degree, its sphincter are innervated. The chamber angle of the anterior segment contains immunoreactive nerve fibers, but convincing innervation to the cornea is lacking. No retinal cells stain. With some exceptions, the distribution of peripheral nerve fibers parallels that of the adrenergic innervation. Appropriate controls are negative.

Animals↗

Carboxyfluorescein. A probe of the blood-ocular barriers with lower membrane permeability than fluorescein.

We have examined the permeability of the blood-ocular barriers to carboxyfluorescein, a dye similar in spectral properties but more polar than fluorescein. Octanol-buffer partition ratios of carboxyfluorescein, measured as an indication of lipid solubility, were approximately 1,000 times lower than those of fluorescein at pH values between 6.40 and 8.03. The partition ratios of both dyes show pronounced pH dependence. We also evaluated intraocular dye distribution by fluorescence microscopy after intravenous (IV) injection in rats. Carboxyfluorescein does not penetrate ciliary or iris epithelial cells, whereas fluorescein prominently stains these cells. Quantitative measurement of fluorescence intensity demonstrates that carboxyfluorescein does not enter the retina even when high doses are administered. Fluorescein, in contrast, can be detected throughout the retina with fluorescence intensity levels proportional to the IV dose administered. The relative inability of carboxyfluorescein to penetrate the blood-ocular barriers is not caused by greater binding to plasma proteins, since the plasma concentration of free carboxyfluorescein is greater than that of fluorescein. We conclude that carboxyfluorescein has potential experimental and clinical use as a probe of the blood-ocular barriers. Because of its low membrane permeability, it may yield a better definition of the nature of barrier abnormalities than is now possible with fluorescein.

Animals↗

Substance P-like immunoreactive nerves in the anterior segment of the rabbit, cat and monkey eye.

The indirect immunofluorescence technique demonstrates a substance P-like immunoreactive innervation to the anterior segment of the rabbit, cat and monkey eye. In all three species there is a sparse, but definite, corneal innervation. For the rabbit, substance P-like immunoreactive nerves to the aqueous outflow apparatus are found chiefly in the pectinate ligament. In the cat, this innervation is somewhat more extensive, being seen in the septae of the ciliary cleft as well. The monkey has a more plentiful innervation to the outflow apparatus than either the cat or the rabbit. Substance P-like immunoreactive nerves are visible in the trabecular meshwork and at the inner and outer walls of Schlemm's canal. For all three animals, the iris contains immunoreactive nerve fibers to the sphincter muscle, to the large blood vessels and to the anterior stromal melanocytes. In the ciliary body, the ciliary processes receive a constant innervation; it is somewhat more dense in the rabbit. Some of the large ciliary body blood vessels also are innervated. Ciliary body melanocytes are innervated; it was not possible to determine whether or not immunoreactive fibers innervate the ciliary muscle cells as well. The present study extends prior knowledge of the innervation of the eye. Taken with the known physiologic effects of substance P, it indicates a series of potential roles for this peptide in the vegetative processes of the eye.

Animals↗

Hypertension in adult onset diabetes mellitus: abnormal renal hemodynamics and endogenous vasoregulatory factors.

We evaluated 10 adult onset diabetics who developed hypertension well after the onset of glucose intolerance. Systemic and renal hemodynamics, intravascular volume, the renin-angiotensin-aldosterone axis, and the renal kallikrein-kinin system were examined at extremes of sodium intake, and compared to results from matched normotensive and essential hypertensive subjects. On unrestricted sodium diet, the diabetics, compared to normotensives, had significantly decreased blood volume (p less than 0.01), and preservation of renal plasma and blood flow, but significantly elevated renal vascular resistance (p less than 0.05), decreased creatinine clearance (p less than 0.01), and decreased filtration fraction (p less than 0.01). On restricted sodium intake, diabetics, compared to normotensives, had reduced urinary kallikrein activity (p less than 0.01) and reduced ambulatory plasma renin activity (p less than 0.01). Essential hypertensives were similar to diabetics in that both had reduced intravascular volume, elevated renal vascular resistance, and reduced levels of stimulated urinary kallikrein and ambulatory renin activities, but plasma aldosterone concentrations were reduced in diabetics compared to both normotensives and essential hypertensives under all dietary conditions. The ratio urinary kallikrein activity/supine plasma renin activity in diabetics correlated with renal blood flow (p less than 0.05), and inversely with renal vascular resistance (p less than 0.05). We conclude that these hypertensive diabetics have multiple abnormalities in intrarenal hemodynamics that may be related, in part, to abnormal activities of the renal enzymes renin and kallikrein. The kallikrein defect may be an etiologic factor in their hypertension.

Aldosterone↗

Amitriptyline stimulates weight gain in hemodialysis patients.

Sixteen chronic hemodialysis patients were enrolled in a double blind 13 week study of amitriptyline vs. placebo in non-crossover design. Patients receiving active drug reached therapeutic serum concentrations at doses of 50 to 200 mg/day, but antidepressant effect was not demonstrable. Patients receiving active drug had slightly greater fluctuation in weight pre- vs. Post-dialysis and had slightly greater postural hypotension post-dialysis than control patients. The trend in post-dialysis weight indicated gain in the active drug group and loss in the placebo group; this difference was highly statistically significant. Weight gain in depression and anorexia nervosa patients treated with amitriptyline is reviewed and it is suggested that amitriptyline may be a useful agent in stimulating appetite in other diseases also.

Adult↗

Fluorescein transport in the anterior uvea.

Rabbit ciliary body-iris preparations accumulate 14C-fluorescein against a concentration gradient when incubated in Tyrode's solution at 37 degrees C and pH 7.4 for 1 hr. Under these conditions, fluorescein metabolism is negligible. This accumulation is depressed by cyanide, dinitrophenol, iodoacetate, by incubation in glucose-free medium, and by incubation at 0 degrees C. This uptake is not inhibited significantly by incubation in sodium-free medium, and relatively high concentrations of ouabain are necessary to cause inhibition. Initial uptake studies show saturation kinetics with half-saturation concentration = 0.12 mM and maximum accumulation rate = 2.3 mmoles/hr/kg wet tissue weight. Fluorescein thus appears to accumulate by a carrier-mediated active uptake process. On the basis of series of competition experiments, it is concluded that fluorescein uptake and p-aminohippurate uptake occur by similar, although not identical, mechanisms.

Animals↗

Long-term clonidine effects on autonomic function in essential hypertensive man.

Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 +/- 0.15 mg/day) alone in 13 essential hypertensive men, assessing several biochemical indices of sympathetic function, as well as physiologic parameters, including baroreflex sensitivity, the cold pressor test, and the hypotensive response to alpha adrenergic blockade. Clonidine diminished mean arterial pressure (from 104 +/- 5 to 84 +/- 3 mmHg; p less than 0.01), without associated changes in several biochemical parameters of sympathetic outflow (urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid; all p greater than 0.1). Circulatory baroreflex function was not enhanced by clonidine, during either the amylnitrite test or the phenylephrine test, before or after parasympathetic blockade with atropine. The cold pressor test, an index of efferent sympathetic pressor function, was also unaltered. The enhanced mean arterial pressure response to phentolamine during clonidine therapy (from a fall of 14.8 +/- 4.3 to 39.4 +/- 5.2 mmHg, p less than 0.01), suggested an increase in alpha adrenergic vascular tone, perhaps mediated by clonidine's alpha agonist properties in vascular smooth muscle. The antihypertensive mechanism of longterm low dose clonidine cannot reliably be ascribed either to baroreflex enhancement or to suppression of sympathetic outflow.

Adult↗

Safety and effectiveness of concomitant administration of dipivefrin and timolol maleate.

Dipivefrin, an epinephrine prodromal drug, was used in conjunction with timolol maleate to evaluate the safety and effectiveness of combined therapy. Seventeen patients who had used timolol maleate for at least six months added dipivefrin (Group 1) and seven patients who had used dipivefrin for at least six months added timolol maleate (Group 2). Intraocular pressure decreased further in both groups. Side effects were most prominent in Group 1.

Adult↗

A clinicopathologic study of four cases of primary open-angle glaucoma compared to normal eyes.

Eight eyes obtained at autopsy from four patient who had chronic open-angle glaucoma were compared to eyes with normal aging changes. Three cases were characterized by early and pronounced abnormalities in the uveal portion of the drainage angle. The findings consisted of formation of an exaggerated scleral spur upon the scleral roll by accretion and compaction of the overlying uveal meshwork, hyalinization and atrophy of the adjacent ciliary muscle, and atrophy of the iris root. The fourth case showed widespread proliferation of endothelium into the lumen of Schlemm's canal. We concluded that the predominant histologic findings in eyes with open-angle glaucoma consists of an exaggeration of normal aging processes, ranging in a spectrum from excessive involvement of the uveal pathway to excessive involvement of the canal of Schlemm pathway.

Aged↗

Renal papillary necrosis in thyroid carcinoma.

A thirty-four-year-old man with progressive visual impairment was found to have thyromegaly and renal insufficiency at the time of admission. Subsequent evaluation demonstrated bilateral optic neuritis and a thyroid nodule which proved to be a follicular carcinoma. Nephrologic studies revealed bilateral papillary necrosis and chronic interstitial nephritis on biopsy. The patient's renal function stabilized and twenty-four-hour protein excretion diminished after hemithyroidectomy. Carcinoma-related protein production may have played a role in the development of the observed renal lesions. Carcinoma should be a consideration in patients with unexplained papillary necrosis.

Adenocarcinoma↗

Studies of the renal vasoactive systems in hyporeninemic hypoaldosteronism.

Plasma renin activity, total renin, active renin, and aldosterone were measured as well as urinary prostaglandin E2 and kallikrein in a group of patients with hyperkalemia (6.1-7.7 mEq per liter) and hyporeninemic hypoaldosteronism. Plasma renin activity and aldosterone were low and the response was markedly blunted to upright posture, and furosemide. The rise in cortisol but not aldosterone was normal following ACTH stimulation. Active renin was depressed; however, total renin was normal. Urine PGE was variable including some low values, but the mean of the group was normal (p greater than 0.1). Urine kallikrein excretion was markedly diminished and undetectable in most cases. Fludrocortisone normalized potassium but minimally increased kallikrein in the patients. The possibility exists that kallikrein deficiency in these patients may underlie the inability to generate active renin.

Adrenocorticotropic Hormone↗

Periorbital scleroderma associated with heterochromia iridis.

Two patients had biopsy-proven linear scleroderma, associated with a pigmentary abnormality of the anterior segment of the eye. One patient had heterochromia iridis, atrophy of the upper eyelid, a typical coup de sabre lesion, and a markedly asymmetric pigmentary glaucoma. The second patient had bilateral scalp involvement, paresis of the extraocular muscles, blepharoptosis, and heterochromia iridis.

Adolescent↗

Effects of zinc in chronic hemodialysis.

Ten male patients requiring maintenance hemodialysis were given zinc in the dialysate (400 micrograms/liter) or placebo in a double-blind crossover experiment. Sexual activity, depression ratings, and hematocrit were unchanged while subjective appreciation of food taste and smell was significantly less during zinc than placebo condition. No patients who were sexually inactive while receiving placebo became sexually active while receiving zinc.

Adult↗