PubMed Health⌕ Search

Biomedical subjects

Richard A Stone

Publications and source records attributed to Richard A Stone.

At least 19 recordsLinked to original sources
PubMed2006

An early favorable outcome of streptococcal toxic shock syndrome may require a combination of antimicrobial and intravenous gamma globulin therapy together with activated protein C.

Streptococcal toxic shock syndrome (STSS) associated with a group A beta hemolytic streptococcal infection was described 18 y ago. Since then, although the pathophysiology of the syndrome has been clarified, mortality can be as high as 80%. A middle-aged female developed STSS associated with a group A streptococcal pneumonia. Laboratory studies confirmed respiratory and renal failure as well as disseminated intravascular coagulation with a striking reduction in endogenous procoagulants. The patient, probably due to her HLA DRB1*14 haplotype was unable to generate anti-streptococcal antibodies. She was treated with appropriate antimicrobial therapy together with intravenous gamma globulin and drotrecogin or activated protein C. Her response to this combined therapy was accompanied by a rapid resolution of the multiorgan failure and correction of the accompanying disseminated intravascular coagulation. This rapid response to treatment supports the hypohesis that several host factors including the immune response and loss of procoagulants determine the development and severity of the toxic shock syndromes. Further studies with this combined approach appear warranted.

Anti-Infective Agents↗
PubMed2006

Local patterns of image degradation differentially affect refraction and eye shape in chick.

PURPOSE: To evaluate visual blur as a mechanism for modulating eye shape. METHODS: Chicks wore a unilateral full goggle or one of several goggles modified with apertures. After 2 weeks, eyes were measured with refractometry, ultrasound, and calipers, and three retinal regions were assayed for dopamine and DOPAC (3,4-dihydroxyphenylacetic acid). RESULTS: Goggled eyes were diffusely enlarged or enlarged predominantly along the axial dimension, depending on the goggle. Myopia developed under goggle types inducing primarily axial growth and under some of the goggles inducing diffuse eye expansion. Enlarged eyes remained emmetropic beneath other goggles that caused diffuse eye expansion. Reductions in retinal dopamine and DOPAC were proportional to the eye growth and refraction effects. CONCLUSIONS: Localized image degradation can cause myopia with predominantly axial expansion, myopia with more diffuse vitreous chamber expansion, or eye expansion without myopia. Robust expansion of the equatorial diameter alone was not observed. The associated alterations in retinal dopamine metabolism are consistent with a hypothesized role of dopaminergic amacrine cells in the visual regulation of eye growth. Besides refraction and overall size, visual blur can affect eye shape; but the goggle responses do not correspond to a simple summation of blur signals across the retina. Therefore, other mechanisms seemingly are needed to account for the full range of refractions and ocular shapes seen in chicks and, by analogy, in humans.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Anterior segment growth and peripheral neural pathways in chick.

PURPOSE: To learn if peripheral nerve pathways are necessary for corneal expansion and anterior segment growth under a 12-hr light:dark cycle or for the inhibition of corneal expansion under constant light rearing. METHODS: Recently hatched White Leghorn chicks under anesthesia received unilateral ciliary ganglionectomy (CGx), cranial cervical ganglionectomy (Sx), or section of the ophthalmic nerve (TGx), along with sham-operated and/or never-operated control cohorts. Chicks were reared postoperatively under either a 12-hr light:dark cycle or under constant light. After 2 weeks and with the chicks under anesthesia, corneal radii of curvature and diameters were obtained with a photokeratoscope, refractometry and A-scan ultrasonography were performed, and the axial and equatorial dimensions of enucleated eyes were measured with digital calipers. Corneal areas were calculated from corneal curvatures and diameters. RESULTS: Despite the rich peripheral innervation to the eye, the selective denervations performed here exerted remarkably limited effects on corneal expansion and anterior segment development in chicks reared under either lighting condition. Ophthalmic nerve section did reverse in large part the inhibition of equatorial expansion of the vitreous chamber occurring under constant light rearing. CONCLUSIONS: The ciliary, sympathetic, or ophthalmic peripheral nerve pathways to the eye are not required either for corneal expansion and anterior segment development under a 12-hr light:dark cycle or for the inhibition of corneal expansion under constant light rearing. The ocular sensory innervation may be a means for regulating vitreous cavity shape.

Animals↗
PubMed2006

The relation of axial length and intraocular pressure fluctuations in human eyes.

PURPOSE: To determine in human eyes whether diurnal fluctuations in axial length are related to fluctuations in intraocular pressure (IOP) by studying these fluctuations in both eyes of individual subjects and by assessing the regularity of both rhythms on two separate study days. METHODS: Ten subjects, ages 18 to 24 years, underwent serial axial length and IOP measurements using highly precise, noncontact partial coherence interferometry and Goldmann applanation tonometry, respectively. Both eyes were measured at six 3-hour intervals during each of two study days, and significant fluctuations were modeled by sine curves. RESULTS: Of the 40 data sets, 29 had significant axial length high-low differences and 32 had significant IOP high-low differences (ANOVA, P < 0.05 for each). The magnitude of the significant high-low differences were 38 +/- 22 microm for axial length and 6.0 +/- 1.9 mm Hg for IOP (mean +/- SD). Neither axial length nor IOP fluctuations necessarily occurred bilaterally on the same day, and neither rhythm was regularly observed on two separate days in individual eyes. In eyes in which both parameters fluctuated on the same day, there were no correlations in the amplitude, period or phase of the two rhythms. CONCLUSIONS: Both axial length and IOP fluctuate during the day much of the time in most subjects. However, diurnal IOP fluctuations do not appear to cause diurnal axial length fluctuations.

Adolescent↗
PubMed2006

A cohort study of incident myopia in Singaporean children.

PURPOSE: To determine the risk factors of incident myopia in a school-based cohort study in Singaporean children. METHODS: A 3-year prospective cohort study was conducted in Singaporean school children aged 7 to 9 years in three schools at entry. Chinese children without myopia at baseline (n = 994) were included in the analysis. The main outcome was incident myopia, defined as spherical equivalent (SE) at least -0.75 D based on cycloplegic autorefraction. Other definitions of incident myopia, at least -0.5 D and at least -1.0 D, were also assessed. RESULTS: After controlling for school, age, gender, income, reading in books per week and intelligence quotient (IQ) test scores, we found the relative risk (RR) of incident myopia defined as -0.75 D to be 1.55 (95% confidence interval [CI] 1.18-2.04) for two versus no myopic parents. The multivariate RR of myopia for IQ in the third versus first tertile was 1.50 (95% CI, 1.19-1.89). However, the RR of incident myopia was 1.01 (95% CI, 0.97-1.05) for every unit increase in books read per week. Similar results were obtained with definitions of -0.5 and -1.0 D for incident myopia. CONCLUSIONS: These data provide new prospective evidence of essential links between parental myopia, IQ scores and subsequent myopia development. However, reading in books per week was not associated with incident myopia.

Child↗
PubMed2006

Associations between childhood refraction and parental smoking.

PURPOSE: Motivated by pharmacologic findings linking nicotinic acetylcholine receptors to eye development in chicks, the authors studied whether the refractions of children who were passively exposed to cigarette smoke by their parents differed from those of nonexposed children. METHODS: A cross-sectional study was conducted among 323 patients (mean +/- SD age, 8.7 +/- 4.4 years; range, 1-20) in a tertiary care pediatric ophthalmology clinic. Half (162/323) of the subjects had strabismus. The accompanying parent completed a detailed questionnaire on parental smoking history and on putative risk factors for myopia. The results were compared to the subjects' cycloplegic refractions. RESULTS: If one or both parents ever smoked, their children had a lower myopia prevalence (12.4% vs. 25.4%; P = 0.004) and more hyperopic mean refractions (1.83 +/- 0.24 vs. 0.96 +/- 0.27 diopters; P = 0.02) than those whose parents never smoked. Smoking by either parent during the mother's pregnancy had a similar effect on the child's refraction. The associations largely persisted, both in multivariate models that included adjustments for the child's age, child's body mass index, child's nearwork activity, parental myopia, and parental education and also in analysis by subgroups stratified by strabismus status. CONCLUSIONS: Despite the complex constituents of cigarette smoke, neuropharmacology perspectives may prove useful in the development of new hypotheses to understand the mechanisms governing refractive development, not only in experimental animals but also in children. The associations of less prevalent myopia and a more hyperopic mean refraction with both prenatal and childhood exposures to tobacco smoke suggest that nongenetic, environmental exposures may have long-term influences on refraction and that further study of the role of nicotinic acetylcholine receptors in refractive development is warranted.

Adolescent↗
PubMed2005

Degradation of extracellular ATP by the retinal pigment epithelium.

Stimulation of ATP or adenosine receptors causes important physiological changes in retinal pigment epithelial (RPE) cells that may influence their relationship to the adjacent photoreceptors. While RPE cells have been shown to release ATP, the regulation of extracellular ATP levels and the production of dephosphorylated purines is not clear. This study examined the degradation of ATP by RPE cells and the physiological effects of the adenosine diphosphate (ADP) that result. ATP was readily broken down by both cultured human ARPE-19 cells and the apical membrane of fresh bovine RPE cells. The compounds ARL67156 and betagamma-mATP inhibited this degradation in both cell types. RT-PCR analysis of ARPE-19 cells found mRNA message for multiple extracellular degradative enzymes; ectonucleotide pyrophosphatase/phosphodiesterase eNPP1, eNPP2, and eNPP3; the ectoATPase ectonucleoside triphosphate diphosphohydrolase NTPDase2, NTPDase3, and some message for NTPDase1. Considerable levels of ADP bathed RPE cells, consistent with a role for NTPDase2. ADP and ATP increased levels of intracellular Ca(2+). Both responses were inhibited by thapsigargin and P2Y(1) receptor inhibitor MRS 2179. Message for both P2Y(1) and P2Y(12) receptors was detected in ARPE-19 cells. These results suggest that extracellular degradation of ATP in subretinal space can result in the production of ADP. This ADP can stimulate P2Y receptors and augment Ca(2+) signaling in the RPE.

Adenosine Diphosphate↗
PubMed2005

The cross-species A3 adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure.

PURPOSE: Antagonists to A3 adenosine receptors (ARs) lower mouse intraocular pressure (IOP), but extension to humans is limited by species variability. We tested whether the specific A3AR antagonist MRS 1292, designed to cross species, mimicks the effects of other A3AR antagonists on cultured human nonpigmented ciliary epithelial (NPE) cells and mouse IOP. METHODS: NPE cell volume was monitored by electronic cell sorting. Mouse IOP was measured with the Servo-Null Micropipette System. RESULTS: Adenosine triggered A3AR-mediated shrinkage of human NPE cells. Shrinkage was blocked by MRS 1292 (IC50 = 42 +/- 11 nM, p < 0.01) and by another A3AR antagonist effective in this system, MRS 1191. Topical application of the A3AR agonist IB-MECA increased mouse IOP. MRS 1292 reduced IOP by 4.0 +/- 0.8 mmHg at 25-microM droplet concentration (n = 10, p < 0.005). CONCLUSIONS: MRS 1292 inhibits A3AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A3 antagonist.

Adenosine↗
PubMed2005

Noninvasive intraocular pressure measurements in mice by pneumotonometry.

PURPOSE: To develop a reliable, noninvasive, continuous, and easily implemented system for measuring intraocular pressure (IOP) in mice. METHODS: Pneumotonometry was adapted for measurement of mouse IOP. Measurements were compared with those obtained with the servo-null micropipette system (SNMS) and with direct anterior chamber cannulation. Heart rate was monitored by the precordial pulse, EKG, or tail pulse in anesthetized mice. The characteristic ocular hypotensive response to mannitol was assessed as an additional validation of the METHOD RESULTS: Measurements of IOP obtained using pneumotonometry agreed closely with values measured by SNMS or by direct cannulation. IOP oscillations were synchronous with the heart rate, with a coherence peak between them of approximately 2 Hz, equal to the pulse frequency. Hypertonic mannitol reduced IOP from 13.7 +/- 0.9 mm Hg by 7.7 +/- 0.7 mm Hg after 15 minutes. CONCLUSIONS: Pneumotonometry is a reliable and noninvasive method for the measurement of IOP in mice and may permit comparisons of IOP to hemodynamic factors. This system is simpler and more adaptable for glaucoma research than previously reported methodologies for measuring IOP in mice.

Animals↗
PubMed2004

Emmetropisation under continuous but non-constant light in chicks.

It has been suggested that ambient lighting at night influences eye growth and might play a causal role in human myopia. To test this hypothesis, we reared newly hatched chicks under 12 hr light-dark or light-dim cycles with a light phase intensity of 1500 microW/cm(2) and variable dim phase intensities between 0.01 and 500 microW/cm(2). Other chicks were reared under constant light conditions with intensities between 1 and 1500 microW/cm(2). After three weeks, the chicks were examined by refractometry, ultrasound and caliper measurements of enucleated eyes. To relate ocular parameters with a retinal neurotransmitter likely involved in eye growth control, retinal and vitreal levels of dopamine and its principal metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were measured by high performance liquid chromatography with electrochemical detection in the light, dark and dim phases. Diurnal fluctuations in axial length and choroidal thickness also were measured twice daily by partial coherence interferometry (PCI) in chicks under light-dark and the two brightest light-dim conditions. The eyes of chicks reared under most light-dim conditions had refractions and ocular dimensions comparable to those reared under light-dark conditions. At dim phase light intensities of 10 microW/cm(2) and above, the day-night changes in retinal dopamine metabolism were not observed. The daily fluctuations of axial length and choroidal thickness were altered with rearing under the two brightest dim light intensities, compared to the light-dark condition. Rearing under constant light with intensities ranging between 1 and 1500 microW/cm(2) produced a shallow anterior chamber and other eye alterations previously described for constant light rearing even though rearing under continuous light that fluctuated between these same intensities generally permitted normal eye growth. Thus, continuous but fluctuating light exerts different developmental effects on the eye than constant non-fluctuating light. Light-dim rearing may be more relevant to daily human light exposures than other laboratory lighting conditions and may provide an opportunity to study developmental interactions of visual quality (e.g. blur, defocus, etc.) and features of the light-dark cycle under conditions that perturb daily rhythms in dopamine metabolism and ocular dimensions. Such studies also could provide mechanistic insights into whether and how daily rhythms in retinal dopamine metabolism, axial length or choroidal thickness modulate refractive development.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2004

Clinical experience with drotrecogin alfa in treating gram-positive and -negative pathogens in patients with severe sepsis.

BACKGROUND: Newer concepts in the management of severe sepsis and, in particular, in the understanding of the relationship between proinflammatory and procoagulant activities during severe infection have led to the introduction of activated protein C (drotrecogin) into the therapeutic program. The combination of effective antimicrobial therapy, aggressive supportive care, and efforts to antagonize procoagulants and inhibitors of fibrinolysis was used in this study. METHODS: We treated 12 patients with severe sepsis using this combination of antimicrobial agents and drotrecogin. All patients presented with hypotension and organ failure and some with multiple organ failure. Infected patients were separated into those with gram-positive and those with gram-negative infections. RESULTS: In contrast to an expected mortality rate of nearly 40% in this group of patients, only 2 (9%) expired. Both deaths were due to infection by gram-negative organisms in patients with complicated abdominal infections and concurrent cancer. All patients with gram-positive organisms survived. CONCLUSION: Those patients with infections caused by gram-positive organisms seemed to have a better prognosis than those with gram-negative infections, perhaps because their illnesses are less complicated by local disease. Although our study is small, it suggests that activated protein C will have a significant beneficial effect on the future treatment of severe sepsis and can reduce the mortality rate significantly. Further improvement in survival rates will require more effective treatment of local disease and associated noninfectious ailments.

Adult↗
PubMed2004

Diurnal axial length fluctuations in human eyes.

PURPOSE: This study sought diurnal variations of eye length in human subjects, analogous to those reported in laboratory animals. METHODS: Seventeen subjects, ages 7 to 53 (median 16) years and mean spherical equivalent refractive error -0.68 D (range, -3.00 to +1.00 D), underwent axial length measurements at multiple times during the day between 7 AM and 1 AM the following day, using partial coherence interferometry (PCI), a highly precise, noncontact method. Diurnal axial length measurements were obtained on two or more days in 10 of these subjects. RESULTS: During at least 1 day, 15 subjects showed a statistically significant (ANOVA, P < 0.05) diurnal fluctuation of axial length, with a magnitude generally between 15 and 40 microm. From the diurnal tracings that fit a sine curve using statistical criteria, the mean period of fluctuation was 21.6 +/- 4.33 hours (SD), the mean amplitude was 27.1 +/- 11.9 microm (SD; range, 12.8-41.4 microm), and the maximum axial length tended to occur at midday. Each of the subjects with multiple daily measurements showed axial length fluctuations on at least 1 day, but there were day-to-day differences in the diurnal variations: most notably, four subjects showed axial length fluctuations on each day; in others, the fluctuations were not observed on each testing day. CONCLUSIONS: The human eye undergoes diurnal fluctuations in axial length, with a pattern suggesting maximum axial length at midday. Based on repeated measurements, these daily fluctuations may not appear regularly in all subjects, suggesting the possibility of physiologic influences that must be defined.

Adolescent↗
PubMed2004

IQ and the association with myopia in children.

PURPOSE: To evaluate the association between intelligence and myopia in children. METHODS: Cycloplegic refraction and ocular biometry parameters, including axial length, vitreous chamber depth, lens thickness, anterior chamber depth, and corneal curvature were obtained in 1204 Chinese school children aged 10 to 12 years from three schools who were participants in the Singapore Cohort Study Of the Risk Factors for Myopia (SCORM). Intelligence quotient (IQ) was assessed using the nonverbal Raven Standard Progressive Matrix test. RESULTS: After controlling for age, gender, school, parental myopia, father's education, and books read per week, myopia (spherical equivalent [SE]) of at least -0.5 D was associated with high nonverbal IQ (highest quartile) versus low IQ (lowest quartile) (odds ratio = 2.4; 95% confidence interval, 1.7-3.4). Controlling for the same factors, children with higher nonverbal IQ scores had significantly more myopic refractions (-1.86 D for children with nonverbal IQ in the highest quartile compared with -1.24 D for children with nonverbal IQ in the lowest quartile; P = 0.002) and longer axial lengths (24.06 mm versus 23.80 mm; P = 0.022). Nonverbal IQ accounted for a greater proportion of the variance in refraction compared with books read per week. CONCLUSIONS: Nonverbal IQ may be an independent risk factor of myopia, and this relationship may not be explained merely by increased reading (books per week) among myopes. An interesting observation is that nonverbal IQ may be a stronger risk factor for myopia compared with books read per week. The complexity of the relationships between nonverbal IQ, reading, and myopia warrant additional studies to clarify any cause-effect relationship.

Books↗
PubMed2003

Highly precise eye length measurements in children aged 3 through 12 years.

OBJECTIVE: To determine the feasibility, reliability, and validity of using partial coherence interferometry, a noncontact method that detects interference patterns from various layers of the eye, to measure axial length in young children. METHODS: The right eye of 64 subjects (mean age, 8.4 y; age range, 3.4-12.9 y; best-corrected visual acuity >or=20/30) was measured. Subjects fixated monocularly on the collimated light pattern from a laser diode (the alignment beam) and the operator used a video monitor to align the corneal reflection in the optical path. Axial length was measured during an 0.8-second scan using interference patterns from a collimated short coherence superluminescence diode aligned coaxially with the laser diode. Five series of 16 readings each were obtained. The average axial length for each of the 5 series of readings was calculated. Main Outcome Measure Axial length. RESULTS: Within-subject precision of axial length measurements was high, with an overall SE of measurement of 8 micro m for individual subjects across the 5 sessions (95% confidence interval, +/-16 micro m). Subgroup analysis showed that sex, age, spherical equivalent, and refractive error exerted statistically significant effects on precision, but all of the differences among subgroups were 3 micro m or less and likely to be insignificant clinically. Axial length measured by partial coherence interferometry varied systematically, with factors known to influence eye length (ie, age and refractive error), further validating the measurement method. CONCLUSION: The partial coherence interferometry technique provides reproducible, extraordinarily precise eye length measurements in young children and should enable novel approaches to study eye growth and refractive development.

Body Weights and Measures↗
PubMed2003

Myopia and natural lighting extremes: risk factors in Finnish army conscripts.

PURPOSE: To establish whether features of environmental lighting in far northern latitudes might be associated with prevalence of myopia. METHODS: Using both questionnaires and military medical examinations, this cross-sectional survey of Finnish conscripts assessed both light exposure and conventional risk factors for myopia. RESULTS: While myopia was not associated with the month of birth, there was a trend towards a higher prevalence of myopia among conscripts living above the Arctic Circle, consistent with the hypothesis that ambient lighting might influence refractive development. Other novel associations with myopia were decreased sunglasses use and brown iris colour. As indicated by other reports, myopia was found to be associated with family history, education and nearwork. CONCLUSION: Although constraints inherent in surveying this military population may have limited our ability to detect associations, the positive findings suggest that studying northern populations may prove useful in clarifying any potential role of the light/dark cycle in refractive development.

Adolescent↗
PubMed2003

Noninvasive assessment of aqueous humor turnover in the mouse eye.

PURPOSE: To develop a noninvasive test for monitoring changes in aqueous humor turnover in the mouse eye. METHODS: After topical instillation of fluorescein, the rate of decay of fluorescence from aqueous humor and cornea was monitored in Black Swiss, C57 Bl6, and DBA 2J mice with a microscope equipped with epifluorescence and a charge-coupled device (CCD) camera. RESULTS: The rate of decay of fluorescence was identical in right and left eyes over an approximately 70-minute measurement period. The rate of decay was similar in normal mice aged 2 and 18 months. Pilocarpine and latanoprost, known to enhance aqueous humor outflow in humans, accelerated the decay of fluorescence. Levobunolol, known to inhibit aqueous humor inflow in humans, slowed decay. Dimethylamiloride, an inhibitor of the Na(+),H(+) exchanger that is known to act on cultured cells of both the ciliary epithelium and trabecular meshwork and to lower mouse intraocular pressure (IOP), enhanced decay. DBA 2J mice, in which secondary glaucoma develops, displayed a slower decay of fluorescence at 18 months of age than age-matched unaffected animals. CONCLUSIONS: Monitoring decay of fluorescence provides a noninvasive index of aqueous humor dynamics in the mouse eye that facilitates study of ocular hypotensive drugs and mouse models of glaucoma. Coupled with knowledge of IOP, it permits semiquantitative conclusions about the relative roles of aqueous humor inflow and outflow in conditions with altered IOP. Based on this approach, dimethylamiloride appears to lower mouse IOP primarily by enhancing outflow of aqueous humor.

Amiloride↗
PubMed2003

GABA, experimental myopia, and ocular growth in chick.

PURPOSE: To learn whether gamma-aminobutyric acid (GABA) participates in retinal mechanisms that influence refractive development. METHODS: White leghorn chicks, some of which wore a unilateral goggle to induce myopia, received daily intravitreal injections of agonists or antagonists to the major GABA receptor subtypes. Eyes were studied with refractometry, ultrasound, and calipers. Retinas of other chicks wearing unilateral goggles were assayed for GABA content. RESULTS: Antagonists to GABA(A) or GABA(A0r) (formerly known as GABA(C)) receptors inhibited form-deprivation myopia. GABA(A) antagonists showed greater inhibition of myopic growth in the equatorial than the axial dimension. A GABA(A0r) antagonist displayed parallel inhibition in the axial and equatorial dimensions. A GABA(A0r) agonist but not GABA(A) agonists altered the myopic refraction of goggled eyes. GABA(B) receptor antagonists, more so than an agonist, also slowed development of myopia, inhibiting axial growth more effectively than equatorial expansion of goggled eyes. When administered to nongoggled eyes, GABA(A) or GABA(A0r) agonists or antagonists also altered eye growth, chiefly stimulating it. Only a GABA(A) agonist induced a myopic refraction. Several of these agents stimulated eye growth in the axial, but not the equatorial, dimension. Retinal GABA content was slightly reduced in goggled eyes. CONCLUSIONS: GABA(A), GABA(A0r), and GABA(B) receptors modulate eye growth and refractive development. The anatomic effects of these drugs reinforce the notion that eye shape and not just eye size is regulated. A retinal site of action is consistent with the known ocular localizations of GABA and its receptors and with the altered retinal biochemistry in form-deprived eyes.

Animals↗