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Biomedical subjects

R A Stone

Publications and source records attributed to R A Stone.

At least 37 records · Page 2Linked to original sources
PubMed2000

Computerized stereochronoscopy and alternation flicker to detect optic nerve head contour change.

PURPOSE/BACKGROUND: Stereochronoscopy, a technique previously explored but abandoned for glaucoma diagnosis, viewed optic nerve images acquired at separate points in time as if a stereo pair. Prior efforts to exploit this technique were impaired by a lack of superimposability for sequential optic nerve images. We investigated computerized registration techniques for aligning sequential, monoscopic optic disc images to facilitate sensitive detection of optic nerve head contour changes in glaucoma. DESIGN: Algorithm and software development. Comparisons with standard techniques. MATERIALS: Existing patient records from the Glaucoma Service, Scheie Eye Institute, University of Pennsylvania. METHODS: Two sets of optic disc photographs, separated in time by 1 to 18 years, of 25 eyes with and without glaucomatous optic disc progression were digitized. We developed custom software for accurate image alignment. Change in disc morphology was then judged by digital stereochronoscopy and user-controlled alternation flicker of superimposed, time-separated images on a computer monitor. Comparisons were made with standard stereoscopic comparison. MAIN OUTCOME MEASURE: Identification of change or no change in optic nerve head contour for images acquired at separate points in time. RESULTS: Image processing and registration permits accurate alignment of optic disc photographs. Alternation flicker of superimposed, sequential images facilitates image comparison and detection of change as indicated by change in vessel position, color, and other cues for contour change. A high concordance was found between standard stereoscopic comparison and alternation flicker. In several cases, reinspection of stereo comparison led to a revised judgment on the basis of disc changes rendered more obvious with alternation flicker. Digital stereochronoscopy was less concordant with standard techniques. CONCLUSIONS: Digital image processing techniques and alternation flicker provide a simple, sensitive, software-based method for detecting glaucomatous optic disc change.

Algorithms↗
PubMed2000

Descriptive epidemiology of nonsyndromic cleft lip with or without cleft palate in Shanghai, China, from 1980 to 1989.

OBJECTIVE: The purpose of this study was to characterize nonsyndromic cleft lip with or without cleft palate (CL+/- CP) in an Asian population. DESIGN: Birth prevalence was assessed in a large birth series in Shanghai, China. A 1:3 sex-age-hospital matched case-control design was used to assess the effects of parental ages and pregnancy history on risk of CL+/- CP. PARTICIPANTS: Records of live births from 1980 to 1989 in 22 hospitals in Shanghai, China, were reviewed, comprising 541,504 consecutive births, which is by far the largest such Chinese sample ever investigated. The case-control study included 528 (308 male, 220 female) nonsyndromic CL+/- CP cases and 1,563 (912 male, 651 female) controls. RESULTS: From 1980 to 1989, the overall birth prevalence was 1.2 per 1,000 live births with statistically significant seasonal variation (more CL+/- CP births in January to July). The overall male:female ratio was 1.40:1. For males, statistically significant associations were identified with maternal age for the most severe clefts (bilateral overall, and also bilateral CL+CP subgroup). For females, statistically significant association was shown for pregnancy age with birth order (overall and in most subgroups). CONCLUSIONS: The birth prevalence of CL+/- CP in this Asian population was similar to published Caucasian rates. The observed seasonal variation would be consistent with possible environmental factors. Significant associations with maternal age, pregnancy age, and birth order warrant additional study of pregnancy history in Asian CL+/- CP.

Birth Order↗
PubMed2000

Sex differences in the pharmacokinetics of dehydroepiandrosterone (DHEA) after single- and multiple-dose administration in healthy older adults.

The pharmacokinetics of exogenously administered DHEA have not been well characterized despite its increasing use in therapeutic and research investigations. The purpose of this study was to evaluate the pharmacokinetics of DHEA and its sulfated metabolite (DHEA-S) after single- and multiple-dose oral administration of DHEA 200 mg. Healthy older adult volunteers (7 women, 6 men) ages 65 to 79 years were studied on five visits separated by 1 week. Subjects received daily administration of placebo (days 1 to 7), DHEA 200 mg (days 8 to 22), and placebo (days 23 to 29). Blood samples were collected over 24 hours on days 1, 8, 15, 22, and 29 for DHEA and DHEA-S determinations by RIA. Pharmacokinetic parameter estimates were calculated by noncompartmental methods. Administration of DHEA 200 mg resulted in higher DHEA Cmax, AUC, and overall concentrations in women than in men (p < 0.03); DHEA-S parameter estimates were similar between men and women. Following a single dose of DHEA 200 mg, DHEA concentrations increased 5- to 6-fold in both men and women, and DHEA-S concentrations increased 5-fold in men and 21-fold in women relative to endogenous concentrations. The results of this study indicate that the pharmacokinetics of DHEA differ between older men and women.

Aged↗
PubMed2000

Myopia: gene-environment interaction.

INTRODUCTION: Myopia has reached epidemic proportions in Japan, Hong Kong, Taiwan and Singapore. This review summarises the evidence for environmental and genetic factors as well as gene-environment interaction for myopia for both epidemiologic studies as well as animal models. METHODS: A literature review was conducted after a Medline search on articles on the genetic or environmental aetiology of myopia in animal or epidemiologic studies. Articles on the methodology of gene-environment studies were also reviewed. All articles reviewed were articles published in peer-reviewed journals. RESULTS: Cross-sectional studies have found a positive association between myopia and near work activity such as reading and writing. Likewise, laboratory research has shown that environmental factors such as visual deprivation may lead to the development of myopia in animals. While linkage studies in humans are currently being conducted to identify possible markers for myopia in the human genome, several neurotransmitters, modulators and growth factors that influence refractive development have already been identified in animal models that may help identify candidate genes. Epidemiologic studies have also evaluated the combined effects of hereditary factors, environmental factors and gene-environment interaction on myopia development. CONCLUSIONS: Both genes and environmental factors may be related to myopia. There are no conclusive studies at present, however, that identify the nature and extent of possible gene-environment interaction. Further linkage analysis, affected sib-pair studies, and family-based association studies may better identify the nature of gene-environment interaction.

Animals↗
PubMed1999

Processes and outcomes of care for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study.

BACKGROUND: Although understanding the processes of care and medical outcomes for patients with community-acquired pneumonia is instrumental to improving the quality and cost-effectiveness of care for this illness, limited information is available on how physicians manage patients with this illness or on medical outcomes other than short-term mortality. OBJECTIVES: To describe the processes of care and to assess a broad range of medical outcomes for ambulatory and hospitalized patients with community-acquired pneumonia. METHODS: This prospective, observational study was conducted at 4 hospitals and 1 health maintenance organization in Pittsburgh, Pa, Boston, Mass, and Halifax, Nova Scotia. Data were collected via patient interviews and reviews of medical records for 944 outpatients and 1343 inpatients with clinical and radiographic evidence of community-acquired pneumonia. Processes of care and medical outcomes were assessed 30 days after presentation. RESULTS: Only 29.7% of outpatients had 1 or more microbiologic tests performed, and only 5.7% had an assigned microbiologic cause. Although 95.7% of inpatients had 1 or more microbiologic tests performed, a cause was established in only 29.6%. Six outpatients (0.6%) died, and 3 of these deaths were pneumonia related. Of surviving outpatients, 8.0% had 1 or more medical complications. At 30 days, 88.9% (nonemployed) to 95.6% (employed) of the surviving outpatients had returned to usual activities, yet 76.0% of outpatients had 1 or more persisting pneumonia-related symptoms. Overall, 107 inpatients (8.0%) died, and 81 of these deaths were pneumonia related. Most surviving inpatients (69.0%) had 1 or more medical complications. At 30 days, 57.3% (non-employed) to 82.0% (employed) of surviving inpatients had returned to usual activities, and 86.1% had 1 or more persisting pneumonia-related symptoms. CONCLUSIONS: In this study, conducted primarily at hospital sites with affiliated medical education training programs, virtually all outpatients and most inpatients had pneumonia of unknown cause. Although outpatients had an excellent prognosis, pneumonia-related symptoms often persisted at 30 days. Inpatients had substantial mortality, morbidity, and pneumonia-related symptoms at 30 days.

Adult↗
PubMed1999

Autonomic denervations influence ocular dimensions and intraocular pressure in chicks.

Choroidal thickness and axial eye length in the chick undergo day/night fluctuations that can also be modulated by visual experience. In the present study, we tested the effect of parasympathetic and sympathetic denervations on both day/night and image dependent changes in ocular dimensions. We also correlated such changes with fluctuations in intraocular pressure. Parasympathectomy influenced choroidal thickness and its day/night fluctuation, but had no effect on vision dependent choroidal thickness modulation. Parasympathectomy also influenced-to a lesser extent-axial length and reduced the axial growth response to form vision deprivation. Sympathectomy had little effect on ocular dimensions, but reduced the day/night differences in intraocular pressure. We conclude that (a) the parasympathetic nervous system influences both choroidal thickness and axial length and participates in the neural control mechanism leading to form deprivation myopia and, (b) the day/night fluctuations of choroidal thickness and axial length are unlikely to be explained by fluctuations in intraocular pressure. For the regulation of choroidal thickness, we hypothesize the existence of two independent mechanisms. One involves the parasympathetic nervous system; it influences the day/night choroidal thickness fluctuation. The other uses a separate pathway and is driven by visual input.

Animals↗
PubMed1999

Alprazolam increases dehydroepiandrosterone concentrations.

The gamma-aminobutyric acid (GABA) agonist alprazolam is known to decrease adrenocorticotropic hormone and cortisol concentrations. Dehydroepiandrosterone (DHEA) is secreted synchronously with cortisol by the adrenal glands and demonstrates diurnal variation. The major objective of this study was to determine whether alprazolam affects concentrations of DHEA and DHEA-S, the sulfated metabolite. In vitro studies have demonstrated that DHEA-S, and perhaps DHEA, have GABA antagonistic activity. Another objective was to determine whether DHEA-S and/or DHEA concentrations are related to psychomotor impairment after alprazolam. Thirty-eight healthy volunteers (25 young men, aged 22-35, and 13 elderly men, aged 65-75) received a single intravenous dose of alprazolam 2 mg/2 min (part 1). Fifteen young and 13 elderly men responded to alprazolam and agreed to participate in part 2 of the study, which was a crossover of placebo and alprazolam infusion to plateau for 9 hours. Plasma samples at 0, 1, 4, and 7 hours were assayed for steroid concentrations. Alprazolam produced (1) significant increases in DHEA concentrations at 7 hours in both young and elderly men; (2) significant decreases in cortisol concentrations; and (3) no change in DHEA-S concentrations. The relationship between psychomotor decrement and DHEA concentrations at 7 hours after alprazolam 2 mg/2 min was described by a u-shaped curve (p < 0.0047). Both the linear and quadratic components of the equations for the tests were significant (p < 0.002). These results suggest that alprazolam modulates peripheral concentrations of DHEA and that DHEA and/or DHEA-S may have an in vivo role in modulating GABA receptor-mediated responses.

Adult↗
PubMed1999

Effects of muscarinic cholinergic receptor antagonists on postnatal eye growth of rhesus monkeys.

PURPOSE: To study a potential role for muscarinic receptors in the inhibition of deprivation-induced excessive axial elongation and myopia in a monkey model. METHODS: The right eyes of 20 newborn rhesus monkeys were occluded with a black contact lens. In seven monkeys each, either atropine or pirenzepine was topically applied daily to the occluded eyes. The nonoccluded fellow eyes and both the occluded and nonoccluded fellow eyes of another six monkeys were treated with vehicle solution. RESULTS: After 33 to 39 weeks, in 5 monkeys of the vehicle group, occluded eyes were longer and the myopic shift significantly greater than in the nonoccluded fellow eyes. In six atropine-treated monkeys, axial length and reduction of the initial hyperopia of occluded and nonoccluded fellow eyes were not different statistically. The myopic shift of the occluded eyes was significantly smaller than in the vehicle-treated occluded eyes. In the pirenzepine-treated group, axial length of the occluded eyes was similar to the nonoccluded eyes of controls and the occluded eyes of atropine-treated monkeys. There was a trend of pirenzepine to reduce the myopic shift of the occluded eye. No effect of atropine or pirenzepine was noted on muscarinic receptor density in retina, brain, or heart, but a small increase was observed in iris + ciliary body. CONCLUSIONS: The drug treatment results implicate muscarinic receptors in postnatal eye growth regulation. Because of interanimal differences our data do not indicate whether nonselective or selective muscarinic blockade is more effective in reducing deprivation-induced myopia.

Animals↗
PubMed1999

A3 adenosine receptors regulate Cl- channels of nonpigmented ciliary epithelial cells.

Adenosine stimulates Cl- channels of the nonpigmented (NPE) cells of the ciliary epithelium. We sought to identify the specific adenosine receptors mediating this action. Cl- channel activity in immortalized human (HCE) NPE cells was determined by monitoring cell volume in isotonic suspensions with the cationic ionophore gramicidin present. The A3-selective agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) triggered shrinkage (apparent Kd = 55 +/- 10 nM). A3-selective antagonists blocked IB-MECA-triggered shrinkage, and A3-antagonists (MRS-1097, MRS-1191, and MRS-1523) also abolished shrinkage produced by 10 microM adenosine when all four known receptor subtypes are occupied. The A1-selective agonist N6-cyclopentyladenosine exerted a small effect at 100 nM but not at higher or lower concentrations. The A2A agonist CGS-21680 triggered shrinkage only at high concentration (3 microM), an effect blocked by MRS-1191. IB-MECA increased intracellular Ca2+ in HCE cells and also stimulated short-circuit current across rabbit ciliary epithelium. A3 message was detected in both HCE cells and rabbit ciliary processes using RT-PCR. We conclude that human HCE cells and rabbit ciliary processes possess A3 receptors and that adenosine can activate Cl- channels in NPE cells by stimulating these A3 receptors.

Adenosine↗
PubMed1998

Bone mineral density and risk of breast cancer: differences by family history of breast cancer. Study of Osteoporotic Fractures Research Group.

Recent studies have suggested that bone mineral density (BMD) is related to risk of breast cancer in elderly women. This study investigated whether the level of breast cancer risk associated with BMD in women with a positive family history of breast cancer is different from that in women without a family history of breast cancer. Radial and calcaneus BMD were measured at baseline (1986-1988) in 7,250 elderly white women enrolled in the Study of Osteoporotic Fractures, and initial breast cancer status was ascertained at year 1 of follow-up. After a mean of 3.2 years of additional follow-up, 104 incident breast cancer cases, 20 of which appeared in women with a family history of breast cancer, were identified and confirmed by medical record review. Modification of the BMD effect by family history status was assessed by inclusion of interaction terms in proportional hazards regression models. Among women without a family history of breast cancer, those with a proximal radius BMD in the highest tertile were at a 1.48-fold increased risk compared with women in the lowest tertile; among women with a positive family history of breast cancer, those with highest tertile BMD were at a 3.41-fold increased risk compared with women in the lowest tertile. These results suggest that the association between BMD and breast cancer may be different in subgroups of women defined by family history.

Aged↗
PubMed1998

A release mechanism for stored ATP in ocular ciliary epithelial cells.

Purines can modify ciliary epithelial secretion of aqueous humor into the eye. The source of the purinergic agonists acting in the ciliary epithelium, as in many epithelial tissues, is unknown. We found that the fluorescent ATP marker quinacrine stained rabbit and bovine ciliary epithelia but not the nerve fibers in the ciliary bodies. Cultured bovine pigmented and nonpigmented ciliary epithelial cells also stained intensely when incubated with quinacrine. Hypotonic stimulation of cultured epithelial cells increased the extracellular ATP concentration by 3-fold; this measurement underestimates actual release as the cells also displayed ecto-ATPase activity. The hypotonically triggered increase in ATP was inhibited by the Cl--channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) in both cell types. In contrast, the P-glycoprotein inhibitors tamoxifen and verapamil and the cystic fibrosis transmembrane conductance regulator (CFTR) blockers glybenclamide and diphenylamine-2-carboxylate did not affect ATP release from either cell type. This pharmacological profile suggests that ATP release is not restricted to P-glycoprotein or the cystic fibrosis transmembrane conductance regulator, but can proceed through a route sensitive to NPPB. ATP release also was triggered by ionomycin through a different NPPB-insensitive mechanism, inhibitable by the calcium/calmodulin-activated kinase II inhibitor KN-62. Thus, both layers of the ciliary epithelium store and release ATP, and purines likely modulate aqueous humor flow by paracrine and/or autocrine mechanisms within the two cell layers of this epithelium.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Ocular axial length and choroidal thickness in newly hatched chicks and one-year-old chickens fluctuate in a diurnal pattern that is influenced by visual experience and intraocular pressure changes.

Low coherence laser Doppler interferometry (LDI) allows high precision measurements of the axial length of the eye and of the thickness of the individual layers of the ocular fundus. Here, we used LDI to monitor diurnal changes in these dimensions in eyes of newly hatched chicks and one-year-old chickens with normal or altered visual input. In chicks and chickens with normal visual experience, axial eye length displays diurnal fluctuations increasing during the light phase. Choroidal thickness also exhibits a diurnal pattern, shrinking during the day and expanding during the night. Retinal thickness does not vary. Based on the pressure compliance of the enucleated chick eye, the diurnal intraocular pressure (IOP) fluctuation could contribute both to the increase in axial length and to daytime choroidal shrinkage. Following deprivation of form vision by unilateral goggle wear, occluded chick eyes demonstrate enhanced axial elongation. Diurnal fluctuations in axial length but not in choroidal thickness are temporarily disrupted. The retina of form deprived eyes thins approximately 10% in five days. In contralateral eyes, the diurnal patterns of both axial length and choroidal thickness fluctuations are also disrupted. Following occluder removal in chicks, choroidal thickness increases for several days during both the light and dark phase, leading to its overall expansion. Retinal thickness returns to baseline. When deprived of form vision for five days, the eyes of year-old chickens do not exhibit measurable axial elongation. Diurnal patterns of fluctuation in axial length and choroidal thickness are however disrupted. After goggle removal, axial length fluctuation is restored to normal, but the diurnal choroidal thickness pattern is inverted. In contralateral eyes, choroidal thickness exhibits normal diurnal fluctuations both during and after form vision deprivation. In conclusion, axial length and choroidal thickness fluctuations are influenced by visual experience in both newborn chicks and one-year-old chickens. In selected instances a binocular interaction regarding axial length and choroidal thickness changes is suggested, the effect weakening with age.

Animals↗
PubMed1998

Induction of axial eye elongation and myopic refractive shift in one-year-old chickens.

Depriving the eyes of neonatal animals of form vision induces axial eye elongation and ipsilateral myopia. We studied one-year-old chickens, an age at which full body growth has been attained, to learn if form deprivation myopia can develop at a later stage. We found that ocular reactivity to visual form deprivation continues in one-year-old chickens; but both the growth stimulation and the myopic shift in refraction are attenuated compared with newly hatched birds. Neurochemical changes in visually deprived eyes of one-year-old chickens parallel those in newly hatched chicks: ipsilateral decreases in retinal dopamine and in the activity of ciliary ganglion and uveal choline acetyltransferase. These findings strengthen the relevance of the form deprivation model to more common human myopia and suggest a common eye growth control mechanism at both ages.

Aging↗
PubMed1998

Prevalence of myopia between 3 months and 5 1/2 years in preterm infants with and without retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity Cooperative Group.

PURPOSE: The purpose of the study was to examine spherical equivalent refractive errors, especially myopia, at six ages between 3 months and 5 1/2 years post-term in preterm children with birth weights of less than 1251 g. DESIGN: A cohort study. PARTICIPANTS: There were a total of 827 participants in the multicenter study of cryotherapy for retinopathy of prematurity (ROP). Approximately one third of the eyes did not develop ROP, whereas two thirds developed mild-to-severe ROP. None of the eyes underwent cryotherapy. INTERVENTION: Refractive error was measured at 3 months, 1 year, and 5 1/2 years term due date at the five long-term follow-up centers. In most eyes, refractive error also was measured at 2, 3 1/2, and 4 1/2 years. MAIN OUTCOME MEASURE: Myopia was defined as 0.25 diopter (D) or greater with high myopia as 5 D or greater. RESULTS: The proportion of eyes with myopia in this preterm population was increased compared to published data on full-term children and was related to severity of both acute-phase and cicatricial-phase ROP. The percentage of eyes with myopia varied little across ages, ranging from 21.2% at 1 year to 15.7% at 4 1/2 years. The percentage of eyes with high myopia doubled from 1.8% to 3.9% between 3 months and 1 year and remained stable thereafter. The distribution of refractive errors in eyes with mild acute-phase ROP was similar to that of eyes with no ROP. In contrast, eyes with moderate or severe acute-phase ROP showed an increased prevalence of high myopia. The distribution of refractive errors changed between 3 months and 1 year with little change after 1 year. This pattern of refractive development differs from that of full-term infants. Birth weight, severity of ROP, and degree of myopia at 3 months predicted the presence of myopia and high myopia at 5 1/2 years of age. CONCLUSIONS: The distribution of refractive errors in preterm infants from age 3 months to 5 1/2 years varies with severity of acute-phase ROP and cicatricial disease. Changes in refractive error distribution occur primarily between 3 months and 1 year and involve a decrease in the proportion of eyes with hyperopia and an increase in the proportion with high degrees of myopia.

Acute Disease↗
PubMed1998

Fenoldopam, a selective dopamine-1 receptor agonist, raises intraocular pressure in males with normal intraocular pressure.

Recent studies have suggested that intravenous infusion of fenoldopam, a selective dopamine-1 receptor agonist, elevates intraocular pressure (IOP) in man. This study evaluated the effect of intravenous fenoldopam on IOP, aqueous humor outflow facility and gonioscopy in 12 healthy human subjects. Three doses (0.2, 0.5 and 1.0 microg/kg/min) were infused for 120 minutes in a double masked, placebo controlled, four-way crossover design. IOP was measured every 20 minutes in the supine position and every 40 minutes while sitting during the drug and placebo infusions. Tonography and gonioscopy were performed at baseline and after 120 minutes of infusion. Compared to placebo, IOP increased by 3.5 mm Hg (32%) for the lowest dose, 5.8 mm Hg (46%) for the intermediate dose, and 6.9 mm Hg (55%) for the highest dose (p<0.05 for all three doses). IOP returned to baseline within 30 minutes of stopping the infusion. The outflow facility decreased from baseline by 26% after 120 minutes of infusion for all drug doses. In contrast, outflow facility increased from baseline by 11% during placebo infusion. Compared to placebo, the fenoldopam induced changes in outflow were statistically significant (p<0.05). There was no change in the gonioscopic appearance of the anterior chamber angle during the infusion. This study shows that systemic administration of a selective dopamine-1 receptor agonist causes a significant dose-dependent increase in IOP that can be explained in part by diminished outflow facility. These results support a role for the dopamine-1 receptor in the modulation of IOP in general and suggest modulation of aqueous humor outflow by dopaminergic receptors.

Adult↗
PubMed1998

OCMAP-PLUS: a program for the comprehensive analysis of occupational cohort data.

The Occupational Cohort Mortality Analysis Program (OCMAP) has been redesigned for optimal microcomputer use and extended to include new computing algorithms. The new program, OCMAP-PLUS, offers a comprehensive, flexible, and efficient analysis of incidence or mortality rates and standardized measures in relation to multiple and diverse work history and exposure measures. New features include executable code, minimization of memory requirements, disk file storage of person-day arrays, stratified analyses by geographic area, employment status and up to eight exposure variables, a data imputation algorithm for study members with unknown race, and enhanced algorithms for constructing several time-dependent exposure measures. New modules create grouped data files for Poisson and logistic regression and risk set files for use in relative risk regression analysis. The Mortality and Population Data System (MPDS) provides external comparison rates and proportional mortalities. Analysis from two recent cohort mortality studies illustrate several new features.

Cohort Studies↗