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Biomedical subjects

R A Stone

Publications and source records attributed to R A Stone.

At least 127 records · Page 7Linked to original sources

Immunoactive atrial natriuretic peptide in the rat eye: molecular forms in anterior uvea and retina.

Acid extracts of rat anterior uvea and retina contain immunoactive atrial natriuretic peptide. Gel filtration chromatography demonstrates that the major forms of the uveal and retinal material have approximate molecular weights of 2400 and 1750 daltons respectively, similar in size to the hypothalamic form of the peptide but clearly distinguishable from the larger, cardiac form. When further analyzed by RP-HPLC, the immunoactive material from both ocular tissues elutes at a position similar to atrial natriuretic peptide-28, again distinguishing the ocular and cardiac forms of immunoactive material. These results suggest potential roles for atrial natriuretic peptide both in ocular vegetative physiology and in retinal function.

Animals↗

Evaluation of a new triphasic oral contraceptive in private practice.

We evaluated the clinical and metabolic effects of a new triphasic regimen developed in the continuing attempt to reduce the dose of estrogen and progestogen in oral contraceptives. A combination of ethinyl estradiol (EE) and levonorgestrel (LNg) was used (six tablets with 30 micrograms EE + 50 micrograms LNg, five tablets with 40 micrograms EE + 75 micrograms LNg, and 10 tablets with 30 micrograms EE + 125 micrograms LNg), also known as Triphasil (Wyeth). In a private practice, 409 subjects participated in 7,286 treatment cycles. Three pregnancies occurred, all due to subject failure. Menstrual regulation was excellent and the incidence of side effects extremely low. Withdrawals from the study for possibly drug-related medical reasons totaled 9.0% through 56 cycles of treatment. Metabolic changes also were evaluated in 14 of these women over a 6-month period. The only statistically significant increase in carbohydrate values occurred at 6 months. The mean glucose level at 30 minutes of the oral glucose tolerance test was above the baseline mean value, but serum insulin levels showed no statistically significant deviation. Lipid values presented are total lipids, total cholesterol, triglycerides, alpha-, beta-, and pre-beta-lipoproteins, and high density and low density lipoprotein cholesterol. There was no statistically significant difference between the mean values at baseline and those during treatment for any lipid variable. These results indicate that this triphasic oral contraceptive has a high degree of efficacy, a low incidence of side effects, excellent cycle control, and high subject compliance, and would seem to indicate a minimal influence on the metabolism of lipids and carbohydrates in the small number of subjects studied.

Blood Glucose↗

Neuropeptide Y and the innervation of the human eye.

Using the indirect immunohistochemical technique, neuropeptide Y as found in human ocular nerves. While limbal blood vessels were innervated and a few nerves were seen in the trabecular meshwork, the cornea proper contained no immunoreactive nerve fibers. Neuropeptide Y-like immunoreactive nerves supplied the iris dilator muscle and, to a lesser extent, the iris sphincter. Immunoreactive nerve fibers were present within the ciliary muscle and the ciliary processes. Neuropeptide Y-like immunoreactive choroidal nerve fibers were frequently associated with blood vessels. The apposition of immunoreactive nerve fibers and melanocytes occurred throughout the uvea. The distribution of neuropeptide Y-like immunoreactive nerves in the eye closely parallels the adrenergic innervation. Evidence linking neuropeptide Y to the ocular sympathetic innervation is discussed.

Adolescent↗

Neuropeptide Y and the ocular innervation of rat, guinea pig, cat and monkey.

By the immunohistofluorescence technique, peripheral nerves of the rat, guinea pig, cat and monkey eye contain a neuropeptide Y-like immunoreactive peptide. A broad distribution of immunoreactive nerve fibers is present in all four animals, innervating tissues of the aqueous humor outflow apparatus, the limbal blood vessels, and uveal blood vessels. A dense plexus of neuropeptide Y-like immunoreactive nerve fibers is present to the ciliary processes. A rich innervation exists to the iris dilator muscle, but that to the iris sphincter is modest. Throughout all regions of the uvea, neuropeptide Y-like immunoreactive nerves are associated closely with melanocytes. When acid extracts of anterior uvea and choroid from rat and guinea pig are analyzed by radioimmunoassay and reverse phase high performance liquid chromatography, the immunoreactive ocular peptide occurs in a single molecular form indistinguishable from porcine neuropeptide Y. The present findings indicate that neuropeptide Y is present in ocular nerves of rat, guinea pig, cat, and monkey. Their distribution, with a few small exceptions, closely parallels that of ocular adrenergic nerves as revealed by histofluorometric techniques. While no ocular effects of neuropeptide Y have been reported to date, its other known biological effects imply potential functions in the eye.

Animals↗

Argon laser trabeculoplasty in black and white patients with primary open-angle glaucoma.

The effect of argon laser trabeculoplasty (ALT) on lowering intraocular pressure (IOP) was studied retrospectively in 68 black patients and 42 white patients with uncontrolled primary open-angle glaucoma on maximally tolerated medical therapy. Patients with the diagnosis of pigmentary or pseudoexfoliation glaucoma and those having previous intraocular or laser surgery were excluded. While the mean age of the black patients (66.9 years) was lower than the white patients (72.2 years), the prelaser IOP was similar between the two groups: 26.2 mmHg for the black patients and 25.5 mmHg for the white patients. The mean IOP one year (18.4 mmHg for black patients and 18.4 mmHg for white patients) and two years (19.5 mmHg and 20.3 mmHg, respectively) after ALT was the same between the two groups of patients. A similar percentage of black (85%) and white (83%) patients showed more than a 15% decrease in IOP from their prelaser values one year after treatment. The IOP lowering effect of ALT decreased during the second post-operative year; but the diminished response was identical in patients of both races, with 71% of patients of both groups still showing greater than 15% reduction from their pre-laser IOP. We conclude that ALT is equally effective in lowering IOP for black and white patients with medically uncontrolled primary open-angle glaucoma.

Adult↗

Vasoactive intestinal polypeptide-like immunoreactive nerves to the human eye.

Using immunohistochemical techniques, vasoactive intestinal polypeptide (VIP) is visualized in nerves distributed to the human eye. Immunoreactive nerve fibers occur about limbal blood vessels and within the trabecular meshwork. In the iris, free-running stromal nerves are the most common, but nerves to both dilator and sphincter muscles are present as well. Immunoreactive nerves are seen within the ciliary muscle and occasionally within a ciliary process. Innervation to choroidal blood vessels constitutes a prominent feature; innervation to more anterior uveal blood vessels is seen only irregularly. Immunoreactive to more anterior uveal blood vessels is seen only irregularly. Immunoreactive nerves are apposed to melanocytes throughout the uvea. The present findings extend prior reports in the human eye, indicating a potential role for VIP in ocular physiology. Additional neuroanatomical, biochemical and physiological studies are necessary to define fully the ocular function of VIP and to determine ultimely whether VIP has clinical and pharmacological implications.

Aqueous Humor↗

DARPP-32 in the ciliary epithelium of the eye: a neurotransmitter-regulated phosphoprotein of brain localizes to secretory cells.

DARPP-32, a phosphoprotein enriched in dopaminoceptive brain neurons containing the D-1 receptor subtype, probably functions as an intracellular third messenger to mediate some of the physiological effects of dopamine at the D-1 receptor. By immunohistochemistry in rat, cat, Rhesus monkey, and human, we have localized DARPP-32 to the non-pigmented epithelium of the ciliary body, the innermost layer of the bi-layered epithelium responsible for secretion of aqueous humor into the eye. The immunoreactive protein in rat ciliary body, identified by immunolabeling of a ciliary body extract separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, is indistinguishable from DARPP-32 derived from rat caudatoputamen. By analogy with brain, we propose that DARPP-32 may act as a third messenger in the ciliary epithelium, probably through a dopaminergic mechanism.

Animals↗

Vasoactive intestinal polypeptide and the ocular innervation.

The indirect immunofluorescence technique with antisera to vasoactive intestinal polypeptide (VIP) stains peripheral nerve fibers in both the anterior segment and the posterior segment of rat, guinea pig, cat, and rhesus monkey eyes. While immunoreactive corneal nerves are lacking, all four species have a prominent innervation of the superficial limbal blood vessels. The aqueous humor outflow apparatus of the rat, guinea pig, and cat, but not the monkey, contain VIP-like immunoreactive nerves. All four animals have immunoreactive iris nerve fibers, tending either to surround large blood vessels or to lie as free stromal nerves. Only in the cat are immunoreactive nerve fibers seen within the iris muscles. A modest number of VIP-like immunoreactive nerves are present in the ciliary body of all four animals; immunoreactive nerve fibers within the ciliary processes occur only in the rat and guinea pig. VIP-like immunoreactive nerves are found in the choroid of all four animals. An association of immunoreactive nerve fibers to uveal melanocytes also is apparent. The present findings expand several prior immunohistochemical studies of mammalian eyes in which the VIP-like immunoreactive nerves to the choroid was emphasized.

Animals↗

Substance P-like immunoreactive nerves in the human eye.

Using immunohistochemical methods, substance P is localized to nerves of the human eye. Immunoreactive nerve fibers occur in the cornea, about limbal blood vessels, and within the trabecular meshwork. Substance P-like immunoreactive nerve fibers surround uveal blood vessels, especially in the choroid and ciliary body. Immunoreactive nerves are seen in ciliary processes. The ciliary muscle is innervated, as are the iris dilator and sphincter muscles. Apposition of immunoreactive nerves to uveal melanocytes is apparent. The distribution of substance P-like immunoreactive nerves in the human eye parallels that found in other mammals. While substance P probably has important neurotransmitter or neuromodulator roles in the eye, further physiologic studies are required to define its ocular function.

Adolescent↗

Acute intraocular pressure response to argon laser iridotomy.

Argon laser iridotomy (ALI) was performed in 50 eyes for prophylactic treatment of anatomically narrow iridocorneal angles and in 50 eyes for therapy of chronic angle-closure glaucoma. Intraocular pressure was increased 6 mmHg or more 1 to 2 hours after ALI in 19 of 50 eyes with anatomical narrow iridocorneal angles and in 23 of 50 eyes with chronic angle-closure glaucoma. Increases greater than 20 mmHg over baseline value occurred in 5 of 50 eyes with narrow iridocorneal angles and in 7 of 50 eyes with chronic angle-closure glaucoma. A clinically significant increase in intraocular pressure (defined as a pressure 30 mmHg or greater and 40% or more increased over the pre-laser value) occurred 1 to 2 hours after ALI in 11 of 50 eyes with narrow iridocorneal angles and in 17 of 50 eyes with chronic angle-closure glaucoma. There was no statistical difference (chi square P greater than 0.3) in the incidence of this complication in the two groups. Additional medical therapy was effective in lowering the acute laser-induced elevation in intraocular pressure. Patient diagnosis, patient demographics, preoperative glaucoma medication and laser treatment parameters did not predict which eyes would develop this complication. Eyes which did not have a clinically significant elevation in intraocular pressure 1 to 2 hours after ALI did not show a later increase at 24 hours.

Female↗

Flexible sigmoidoscopy as a screening procedure for asymptomatic colorectal carcinoma in patients with inguinal hernia.

In patients about to have hernia repair, preoperative screening studies for early colorectal cancer using the rigid proctosigmoidoscope and barium enema have previously shown minimal cost effectiveness and poor patient acceptance. Flexible sigmoidoscopy may be more acceptable to patients and of greater diagnostic value. Between October 1980 and December 1983, 100 consecutive asymptomatic male surgical patients were examined using the Olympus 60 flexible proctosigmoidoscope. All patients were admitted for elective hernia repair. Age ranged from 21 to 88 years (mean 59.7). All patients with stool positive for occult blood on admission were excluded from this study. In addition, patients with any gastrointestinal symptoms, history of colorectal disease, or family history of colorectal polyps or carcinoma were excluded. Examinations were done under direct supervision of an attending surgeon (W.W. or C.S.C.). Of the 22 patients who had one or more benign polyps, three had villous adenomas. Two additional patients had carcinoma. Results of examination were completely normal in 63, while 13 patients were found to have hemorrhoids or diverticular disease. There were no complications and the procedure was well tolerated by all patients.

Adenoma↗

Presence of an alpha-melanocyte-stimulating hormone-like epitope in the 150,000 dalton neurofilament subunit from diverse regions of the central nervous system: an immunohistochemical and immunoblot study in guinea pig.

Monoclonal antibodies specific for the two higher molecular weight neurofilament (NF) subunits (NF200 and NF150), and antiserum to alpha-melanocyte-stimulating hormone (alpha-MSH) were used to probe the distribution of an alpha-MSH-like epitope in NF proteins of the guinea pig central nervous system using immunoblot and immunohistochemical methods. The anti-alpha-MSH antiserum recognized the same protein band as an anti-NF150 monoclonal antibody in immunoblots of proteins extracted from guinea pig cerebellum, spinal cord, retina, optic nerve, and neurohypophysis; it also stained axons and dendrites in sections of cerebellum, retina, and optic nerve. Although all cells of the pars intermedia and some in the pars distalis exhibited immunoreactivity with this antiserum, it did not stain axons in the neurohypophysis. Our immunoblot data demonstrate an alpha-MSH-like epitope in NF150 extracted from each of the regions studied. The lack of in situ recognition of this alpha-MSH-like epitope in neurophypophyseal axons, using the same immunohistochemical methods that demonstrate this epitope in axons of the cerebellum, retina, and optic nerve, suggests that NF150 is immunochemically heterogeneous in different regions of the guinea pig central nervous system.

Animals↗

Retinal autoregulation in open-angle glaucoma.

The macular blood flow response to an induced change in intraocular pressure (autoregulation) was studied using the blue field entopic phenomenon in 11 open angle glaucoma patients, eight glaucoma suspects and 13 normal volunteers. A suction cup was used to raise the intraocular pressure (IOP) above its resting state (IOPrest). IOPmax, the highest acutely increased IOP for which blood flow can be maintained constant by autoregulation, was 24.9 +/- 1.5 mmHg (+/- 1 SD) in the glaucoma patients, 30.8 +/- 4.6 mmHg in the glaucoma suspects and 29.9 +/- 3.6 mmHg in the normal subjects. The values for IOPmax - IOPrest were 3.7 +/- 4.3 mmHg, 4.7 +/- 3.3 mmHg, and 14.3 +/- 3.1 mmHg, respectively. After the release of the suction cup, a hyperemic response was observed by 16 of 17 normal eyes, 10 of 14 glaucoma suspect eyes and only 9 of 19 glaucomatous eyes. These results suggest an abnormal autoregulation of macular retinal blood flow in open-angle glaucoma.

Adult↗

Steroid effects on uveal transport.

Hydrocortisone (10(-4)M) causes a significant depression of cholic acid accumulation by the isolated rabbit ciliary body-iris while causing little, if any, depression of p-aminohippuric acid uptake and not affecting alpha-aminoisobutyric acid uptake. Because no lag period is present for this inhibition and because cyclohexamide pretreatments fails to eliminate it, the hydrocortisone effect does not appear to be mediated by a protein synthesis mechanism. Deoxycorticosterone (10(-4)M) not only inhibits cholic acid uptake but also depresses p-aminohippuric acid uptake; no deoxycorticosterone effect on alpha-aminoisobutyric acid uptake is seen.

Aminoisobutyric Acids↗

Neuron-specific enolase-containing cells in the rhesus monkey trabecular meshwork.

Neuron-specific enolase (NSE) localizes immunohistochemically to a discontinuous band of cell clusters in the trabecular meshwork of the anterior segment of the rhesus monkey eye. To date, this enolase isomer has been found exclusively in neurons or in cells of the diffuse neuroendocrine system. On this basis, its presence provides presumptive evidence for neuroregulatory cells in the primate trabecular meshwork.

Animals↗

Baroreflex dysfunction in patients with adult-onset diabetes and hypertension.

Ten patients with adult-onset diabetes in whom diabetes antedated the appearance of hypertension were evaluated. These patients had evidence of diabetic autonomic neuropathy, including significant orthostatic hypotension (four patients), impotence (three patients), and evidence of diabetic peripheral sensorimotor neuropathy (nine patients) in clinical testing and nerve conduction study results. Baroreflex function was evaluated by multiple hemodynamic tests, including inhalation of amyl nitrite and intravenous administration of phenylephrine, before and after parasympathetic blockade with atropine, and the cold pressor test; results were compared with results in normal control subjects, patients with essential hypertension, and two subgroups of uremic patients undergoing maintenance hemodialysis. Baroreflex function was significantly abnormal in the diabetic patients and was consistent with combined parasympathetic and sympathetic motor nerve (efferent) dysfunction in the baroreflex arc. There was a significant inverse correlation between the degree of orthostatic hypotension in the diabetic patients and their baroreflex response to phenylephrine (r = -0.680, p less than 0.05). There was no significant correlation between supine hypertension in the patients with diabetes and any of the hemodynamic or biochemical parameters examined. The results suggest that orthostatic hypotension in these patients is related to baroreflex dysfunction. However, baroreflex dysfunction does not appear to be a factor in the development of hypertension in these patients, although more studies with normotensive diabetic patients are needed to confirm this point.

Aged↗