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R A Stone

Publications and source records attributed to R A Stone.

At least 55 records · Page 3Linked to original sources
PubMed1998

Neuropeptide Y-like immunoreactivity localizes to preganglionic axon terminals in the rhesus monkey ciliary ganglion.

PURPOSE: To characterize neuropeptide distribution in the ciliary ganglion of rhesus monkeys (Macaca mulatta). METHODS: Cryostat tissue sections of fixed rhesus monkey ciliary, pterygopalatine, superior cervical, and trigeminal ganglia were incubated with antisera to neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH). Antibody binding was visualized by indirect immunofluorescence. RESULTS: NPY-like immunoreactive (LI) nerve terminals surrounded 80% of ciliary ganglion cells, but ciliary ganglion cell somata were unstained. NPY-LI cells were present in the superior cervical ganglion, in which almost all cells were TH- and DBH-LI, and in the pterygopalatine ganglion, in which almost all cells were VIP-LI. Because neither TH, DBH, nor VIP immunoreactivity was detected in nerves contacting ciliary ganglion cells, the NPY-LI input to ciliary neurons does not likely derive from the autonomic ganglia. The trigeminal ganglion, another potential source, had no NPY-LI neurons. CGRP- and SP-LI axons from the nasociliary nerve traversed the ciliary ganglion; a small number of varicose axons were distributed among ganglion cells and rarely surrounded cell somata. Most ciliary ganglion cells were TH-LI, but only a few were DBH-LI. CONCLUSIONS: Based on these patterns of peptide immunoreactivities, the NPY-LI nerve fibers investing ciliary ganglion cells in the rhesus monkey are most likely preganglionic axon terminals of mesencephalic parasympathetic neurons. Although the origin and function of these NPY-LI nerves remains to be established, the present finding adds to the remarkable diversity of neuropeptide immunoreactivity so far identified in preganglionic and postganglionic cells of the ciliary ganglion in different species of birds and mammals, including primates.

Animals↗
PubMed1997

Effect of 5-HT1A receptor agonist, 8-OH-DPAT, on cough responses in the conscious guinea pig.

We have studied the role for 5-hydroxytryptamine (5-HT) in the modulation of the cough reflex by examining the effect of a selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on cough and respiratory rate in conscious guinea pigs. Animals were placed in a box and exposed to the tussive agent citric acid (0.5 M) for 10 min, 3 min after terbutaline (0.05 mg/kg i.p.) was administered to prevent bronchoconstriction. 8-OH-DPAT inhibited at low doses (0.008 and 0.016 mg/kg) but potentiated at high doses (0.25 and 0.5 mg/kg) the citric acid-induced number of coughs, but dose-dependently increased respiratory rate. Methysergide (0.05-5 mg/kg), a 5HT1 and 5HT2 receptor antagonist, and ketanserin (0.005 mg/kg), a 5HT2 receptor antagonist, had no effects on cough or respiratory rate. Methysergide inhibited the increased cough responses and respiratory rate induced by 8-OH-DPAT at high doses, while ketanserin was without effect. These results suggest that 8-OH-DPAT may induce both in inhibition and activation of the cough reflex, the latter involving central 5HT1-receptor activation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Medical outcomes and antimicrobial costs with the use of the American Thoracic Society guidelines for outpatients with community-acquired pneumonia.

CONTEXT: The American Thoracic Society (ATS) published guidelines based on expert opinion and published data--but not clinically derived or validated--for treating adult outpatients with community-acquired pneumonia. OBJECTIVE: To compare medical outcomes and antimicrobial costs for patients whose antimicrobial therapy was consistent or inconsistent with ATS guidelines. DESIGN: Multicenter, prospective cohort study. SETTING: Emergency departments, medical clinics, and practitioner offices affiliated with 3 university hospitals, 1 community teaching hospital, and 1 health maintenance organization. PARTICIPANTS: A total of 864 immunocompetent, adult outpatients with community-acquired pneumonia: 546 aged 60 years or younger with no comorbidity and 318 older than 60 years or with 1 comorbidity or more. MAIN OUTCOME MEASURES: Patients' antimicrobial therapy was classified as being consistent or inconsistent with the ATS guidelines. Mortality, subsequent hospitalization, medical complications, symptom resolution, return to work and usual activities, health-related quality of life, and antimicrobial costs were compared among those treated consistently or inconsistently with the guidelines. RESULTS: Outpatients aged 60 years or younger with no comorbidity who were prescribed therapy consistent with ATS guidelines (ie, erythromycin with some exceptions) had 3-fold lower antimicrobial costs ($5.43 vs $18.51; P<.001) and no significant differences in medical outcomes. Outpatients older than 60 years or with 1 comorbidity or more who were prescribed therapy consistent with ATS guidelines (ie, second-generation cephalosporin, sulfamethoxazole-trimethoprim, or beta-lactam and beta-lactamase inhibitor with or without a macrolide) had 10-fold higher antimicrobial costs ($73.50 vs $7.50; P<.001); despite trends toward higher mortality and subsequent hospitalization, no significant differences in medical outcomes were observed. CONCLUSION: Our findings support the use of erythromycin as recommended by the ATS guidelines for outpatients aged 60 years or younger with no comorbidity. Although the antimicrobial therapy recommended in outpatients older than 60 years or with 1 comorbidity or more is more costly, this observational study provides no evidence of improved medical outcomes in the small subgroup who received ATS guideline-recommended therapy.

Adult↗
PubMed1997

The hospital discharge decision for patients with community-acquired pneumonia. Results from the Pneumonia Patient Outcomes Research Team cohort study.

BACKGROUND: The hospital discharge decision directly influences the length of stay in patients with community-acquired pneumonia, yet no information exists on how physicians make this decision. OBJECTIVES: To identify the factors physicians considered the factors responsible for extending length of hospital stay in clinically stable patients, and the outpatient medical services that would allow earlier hospital discharge for patients with community-acquired pneumonia. METHODS: Physicians responsible for the hospital discharge decision of patients with community-acquired pneumonia were asked to identify the factors responsible for extending stay in patients hospitalized beyond stability, and the medical services that could have allowed earlier hospital discharge to occur. RESULTS: For the 418 eligible patients with community-acquired pneumonia identified during the study, 332 questionnaires (79%) were completed by 168 physicians. Physicians believed 71 patients (22%) were discharged from the hospital 1 day or more (median, 2.5 days) after reaching clinical stability. The most common factors rated as being "very important" in delaying discharge were diagnostic evaluation or treatment of comorbid illness (56%), completion of a "standard course" of antimicrobials (15%), and delays with arrangements for long-term care (14%). Among the 302 patients with available information on both length of hospital stay and stability at discharge, median length of stay was 7.0 days for the 29 low-risk patients hospitalized beyond reaching clinical stability and 5.0 days for the remaining 128 low-risk patients (P < .005); median length of stay was 12.5 days for the 42 medium- and high-risk patients hospitalized beyond reaching clinical stability and 8.0 days in the remaining 113 medium- and high-risk patients (P < .001). Frequently cited medical services that "probably" or "definitely" would have allowed earlier discharge to occur included availability of home intravenous antimicrobial infusion (26%) and home visits by nurses (20%). CONCLUSIONS: Physicians believed that diagnostic evaluation or treatment of comorbid illness, completion of a standard course of antimicrobial therapy, and delays with arrangements for long-term care delayed hospital discharge in clinically stable patients. Addressing the efficiency of these aspects of inpatient medical care, as well as providing home treatment programs, could decrease the length of hospital stay in patients with community-acquired pneumonia.

Adult↗
PubMed1997

A case-control study of lung cancer mortality in six Gila Basin, Arizona smelter towns.

To investigate factors related to lung cancer mortality in six Arizona copper smelter towns, we identified 185 lung cancer cases and two matched controls per case from decedent residents during 1979-1990. Detailed information on lifetime residential, occupational, and smoking history was obtained by structured telephone interviews with knowledgeable informants. Interviews were completed for 82% of 183 eligible cases and 88% of the targeted number (366) of controls. Estimated historical environmental exposures to smelter emissions, based on atmospheric diffusion modeling of measured SO2 concentrations, were linked with residential histories to derive individual profiles of residential exposure. Occupational histories were characterized by potential exposure to smelter emissions, asbestos, and ionizing radiation. Conditional logistic regression was used to compare study factors in cases and controls with adjustment for potential confounding factors: gender, Hispanic ethnicity, and smoking. In overall and gender-specific analyses, no statistically significant associations were observed between lung cancer risk and any of the measures of residential exposure to smelter emissions considered (town of residence at time of death, highest level of exposure, and duration or cumulative exposure above background levels), or any of the estimated occupational exposures (definite or potential asbestos, potential ionizing radiation, definite or potential smelter). Among male residents of some, but not all, towns, there was some evidence of a positive association between lung cancer risk and reported copper smelter-related employment (reported as definite), with the highest risk observed for Miami, Arizona. This study provided little evidence of a positive association between lung cancer mortality and residential exposure to smelter emissions. Specific factors associated with the apparent heterogeneity in lung cancer risk across study towns cannot be identified in this community-based study.

Arizona↗
PubMed1997

Retinal dopamine in the recovery from experimental myopia.

PURPOSE: To address further a possible role for retinal dopamine in postnatal eye growth, we studied the response of retinal dopamine in eyes of chicks recovering from myopia. METHODS: Newborn chicks either received a unilateral translucent goggle to induce form deprivation myopia or were reared with unimpaired visual input. The goggle was removed from half of the chicks on day 7. Myopic, recovering and control never-goggled chicks were studied on days 7, 9 and 14. Eyes were enucleated postmortem and measured in axial and equatorial dimensions with calipers. Retinal levels of dopamine and its principal metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were assayed by high performance liquid chromatography with electrochemical detection. RESULTS: Compared to contralateral and control eyes, retinas of goggled eyes at each time point had reduced levels of dopamine and DOPAC and a lowered calculated DOPAC/dopamine ratio, an index of dopamine metabolism. In eyes recovering from myopia, all biochemical parameters showed prominent increases by 2 days after goggle removal and had reached the level of both contralateral eyes and control eyes by one week after goggle removal. As evidence of a contralateral effect, the retinas of open eyes of chicks wearing a unilateral goggle demonstrated equal dopamine levels but reduced DOPAC compared to eyes of never-goggled chicks. CONCLUSION: An early rise and eventual normalization of retinal dopamine, DOPAC and the DOPAC/dopamine ratio correlate with recovery from myopia. Combined with recent results from lens rearing experiments, these findings suggest that dopaminergic amacrine cells may participate in visually guided eye growth regulation and not just in the myopia response to visual form deprivation. The retinal biochemical alteration in eyes contralateral to a goggle identifies a previously unappreciated binocular interaction in the chick.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Mortality among chemical workers in a factory where formaldehyde was used.

OBJECTIVES: An independent and updated historical cohort mortality study was conducted among chemical plant workers to investigate further an association between exposures to formaldehyde and particulates and cancers of the nasopharynx and lung reported in an earlier National Cancer Institute study of the same plant. METHODS: Subjects were 7359 workers who were first employed between 1941 and 1984 in a factory in Wallingford, Connecticut where formaldehyde was used. Vital status was determined on 31 December 1984 for 96% of the cohort and death certificates were obtained for 93% of 1531 known deaths. Exposures of individual workers were estimated quantitatively for formaldehyde, product particulates, and non-product particulates, and qualitatively for pigment. Statistical analyses focused on 6039 white men in 1945-84. Cohort data that could not have been included in the National Cancer Institute study were also analysed separately. RESULTS: Mortality among long term workers (employed > or = 1 y) was generally similar to or more favourable than that of the general population, and there was little evidence of a relation between either rates of lung cancer or standardised mortality ratios (SMRs) and several measures of exposure to formaldehyde, particulates, and pigment. For several causes including lung cancer, death rates among short term workers (employed < 1 y) were significantly increased. Short term workers did not seem to differ from long term workers for the exposures considered. Among all white men, a significant SMR of 550 (local comparison) for nasopharyngeal cancer (NPC) was based on the same four index cases identified in the earlier study of this plant. Only one case of nasopharyngeal cancer had any appreciable exposure to formaldehyde. No new cases of nasopharyngeal cancers were found among the cohort data that could not have been included in the National Cancer Institute study--that is, extended observation time and additional study members. CONCLUSIONS: Among workers employed for at least one year, this study provides little evidence that the risk of lung cancer is associated with exposure to formaldehyde alone or in combination with particulates or pigment. The significant increases in both the rates and SMRs for lung cancer seem to be primarily a phenomenon of short term workers, but the possibility remains that unmeasured occupational or non-occupational factors may have played a part.

Chemical Industry↗
PubMed1996

The ciliary ganglion and vitreous cavity shape.

PURPOSE: To learn the influence of the ciliary ganglion on the postnatal growth of eyes with unimpaired visual input and of eyes beneath an image diffusing goggle. METHODS: Newborn chicks received unilateral ciliary ganglionectomy or unilateral sham operation and were reared either with or without a goggle ipsilateral to the surgical procedure. Ocular refractions and ultrasound measurements were made on anesthetized chicks; eyes enucleated postmortem were measured in axial and equatorial dimensions with calipers and studied histologically. RESULTS: Excessive growth of open eyes in the equatorial dimensions followed ciliary ganglionectomy and became more pronounced as the chicks grew older. There was only a modest increase in axial growth. Ganglionectomy also induced relative hyperopia; lens thinning contributed to this effect and likely was a direct result of disrupted parasympathetic input to the ciliary muscle. Ganglionectomy also slightly increased the thickness of the choroid in the posterior pole but not in more peripheral locations. CONCLUSION: We conclude that the ciliary ganglion exerts an inhibitory influence on the postnatal growth of open eyes; the main effect is in the equatorial dimension of the vitreous cavity, with a smaller effect on axial length. Ciliary ganglionectomy exerted minimal influence on the development of experimental myopia, known to be induced by the goggle regimen. The amount of equatorial expansion in goggle-induced myopia was greater than after ganglionectomy alone, indicating that other factors besides the ciliary ganglion can influence the equatorial dimension of the vitreous cavity.

Animals↗
PubMed1996

Validation of laser Doppler interferometric measurements in vivo of axial eye length and thickness of fundus layers in chicks.

Purpose. Laser Doppler interferometry (LDI) permits the measurement of intraocular distances to a precision of better than 20 microm. The signal complex from the posterior segment of the eye consists of four peaks in the chick, an animal frequently used in ocular development studies. The present study sought to identify anatomical landmarks corresponding to these LDI peaks. Methods. Distances obtained with LDI at the posterior pole were compared to axial length components measured with three independent methods: vernier calipers, tissue sections and high frequency A-scan ultrasound. Results. LDI reflections appear to originate from the retinal inner limiting membrane, Bruch's membrane and the inner and outer scleral surfaces. Conclusions. The non-invasive and highly precise nature of LDI measurements enables repetitive and accurate assessment of intraocular distances. Such measurements should prove particularly useful for the assessment of short-term cyclic variations in intraocular distances as well as post-natal eye growth.

Animals↗
PubMed1996

Peptidergic innervation of the primate meibomian gland.

PURPOSE: To localize and characterize nerves in primate meibomian glands using immunohistochemical staining for neuropeptides and neuronal enzymes. METHODS: Upper eyelids were obtained from seven rhesus monkeys (Macaca mulatta) and one cynomolgous monkey (Macaca fascicularis). The tissues were fixed either by immersion in Zamboni's fixative or by transcardiac perfusion with paraformaldehyde and glutaraldehyde and were then postfixed. Cryostat tissue sections of the lids were stained by immunohistochemistry using rabbit antisera to neuron-specific enolase (NSE), tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and substance P (SP), followed by a fluorescence visualization system. RESULTS: Used as a marker for the overall nerve distribution, NSE antibodies revealed abundant smooth and varicose nerve fibers closely apposed to the basement membranes of acini of the meibomian glands. Numerous nerve fibers near the meibomian gland acini were immunoreactive for NPY and VIP, but nerve fibers containing TH, CGRP, and SP were more sparse in the meibomian glands. Nerve fibers also were visualized in other eyelid structures, including conjunctiva, epidermis, hair follicles, and subconjunctival lymphoid follicles. CONCLUSIONS: The meibomian glands of rhesus and cynomolgous monkeys are richly innervated by diverse nerve fiber types. The immunohistochemical staining suggests a largely parasympathetic origin for this innervation, with relatively smaller contributions from sympathetic and sensory sources. These findings also suggest that meibomian gland secretion is under the control of diverse neurotransmitter-neuromodulator mechanisms.

Animals↗
PubMed1995

Nitric oxide synthase in autonomic innervation of the cat carotid body.

In the cat carotid body, nitric oxide synthase (NOS) immunoreactivity and NADPH diaphorase activity localize in nerve fibers mainly associated with blood vessels and occasionally lying close to glomus cells. The NOS-positive innervation originates in part from multipolar ganglion cells scattered in and around the carotid body and in the glossopharyngeal nerve. In the superior cervical ganglion, NOS and diaphorase staining localizes to many preganglionic axons and also to a small population of vasoactive intestinal peptide-positive, presumably cholinergic, ganglion cells. Positively stained ganglion cells are absent in the petrosal ganglion and very rare in the nodose ganglion, although both sensory ganglia display characteristic distributions of cells immunoreactive for calcitonin gene-related peptide, substance P and tyrosine hydroxylase. The NOS-positive innervation of the carotid body thus appears to be autonomic, originating mainly from a population of dispersed ganglion cells, and probably parasympathetic in nature. The superior cervical ganglion also may supply some pre- or postganglionic NOS-positive axons. Nitric oxide released from these nerves could affect glomus cell activity directly or indirectly by vasoregulation.

Animals↗
PubMed1995

Helospectin-like immunoreactivity in the rat eye and pterygopalatine ganglion.

Helospectin I and II, nearly identical peptides isolated from lizard venom, show close sequence homology with vasoactive intestinal peptide (VIP). In mammals, the helospectins have been localized immunohistochemically to neurons of the brain, digestive tract and respiratory system, commonly co-existing with VIP. Using an antiserum that recognizes both forms of the peptide, we localized helospectin-like immunoreactivity in the rat eye and pterygopalatine ganglion. In the eye, helospectin-positive nerve fibers were evident mostly in the choroid, associated with small arterial vessels or distributed diffusely in the stroma; they were only occasionally seen in the anterior uvea. All of the helospectin nerve fibers also appeared to be immunoreactive for VIP. In the pterygopalatine ganglion, the principal source of VIP-containing innervation of the posterior uvea, approximately 25% of ganglion cells were helospectin-positive; all helospectin-reactive cells were also strongly positive for VIP. This immunohistochemical localization of helospectin indicates possible involvement in ocular autonomic functions, particularly regulation of blood flow.

Animals↗
PubMed1995

Comparison of a disease-specific and a generic severity of illness measure for patients with community-acquired pneumonia.

OBJECTIVE: To compare the performances of a disease-specific severity of illness index and a prototypical generic severity of illness measure, MedisGroups Admission Severity Groups (ASGs), for patients with community-acquired pneumonia. DESIGN: A retrospective database study. PATIENTS: Adult patients (aged > or = 18 years) with an ICD-9-CM principal diagnosis of pneumonia in 78 MedisGroups Comparative Database hospitals. METHODS: The pneumonia severity of illness index (PSI) was developed to predict hospital mortality using logistic regression analyses in a 70% random sample of study patients. The performances of the PSI and the generic severity measure were assessed among the remaining 30% of patients by comparing observed mortalities within the five PSI and ASG severity classes, and areas under their receiver operating characteristic (ROC) curves. Both the PSI and the generic severity measure were used to estimate the 95% confidence interval of the expected number of deaths in each of the 78 study hospitals. Hospitals with an observed number of deaths outside these limits were identified as outliers. RESULTS: There were 14,199 study patients who had community-acquired pneumonia, and 1,542 (10.9%) died during hospitalization. In comparison with the generic severity measure, the PSI more accurately identified patients at extremely low risk of death, and had a larger area under its ROC curve (0.84 vs 0.79; p < 0.0001). Of the 78 study hospitals, 17 (21.8%) were classified as outliers for mortality by at least one severity adjustment system. Among the 11 low-outlier hospitals, six were classified by the generic severity measure alone, two by the PSI alone, and three by both systems; among the six high-outlier hospitals, one was classified by the generic measure alone, three by the PSI alone, and two by both systems. CONCLUSIONS: The PSI provided more accurate estimates of hospital mortality and classified different hospital outliers for mortality than did the generic severity of illness measure for patients with community-acquired pneumonia.

Adolescent↗
PubMed1995

Photoperiod, early post-natal eye growth, and visual deprivation.

(1) We studied the influence of photoperiod and unilateral lid suture on post-natal ocular growth in two types of White Leghorn chicks previously reported to respond differently to visual deprivation, Truslow and Cornell K chicks. We analyzed the chicks after 2 weeks of rearing, a time period commonly used in neuropharmacological studies of eye growth but much shorter than in most prior studies of photoperiod effects on the chick eye. (2) Altering the photoperiod length significantly influenced the refraction and growth of both open and sutured eyes even at this early time, with differences between the two types of chicks. (3) The most prominent effect on the open eyes was the development of hyperopia with rearing under constant light, a response especially prominent in the Cornell K chicks. In the open eyes under this condition, the anterior chamber shallowed and the vitreous chamber elongated in the axial dimension only, reciprocal changes that resulted in no net alteration of axial length at 2 weeks. A high variability in refraction of open eyes reared with constant illumination suggests the need for a dark period in the regulation of eye growth. (4) Compared to contralateral open eyes, the lid-sutured eyes of both types of chicks developed longer total axial lengths and enlarged vitreous chambers in both axial and equatorial dimensions under each photoperiod. The effects on anterior chamber depth and refraction were complex and differed between the two types of chicks. (5) The responses in open eyes support the notion that growth of the vitrious chamber of the chick eye is differentially regulated in the axial and equatorial dimensions, previously indicated by pharmacological studies. The responses in both open and sutured eyes indicate different control mechanisms for anterior chamber and vitreous cavity growth.

Animals↗
PubMed1995

Factitious pheochromocytoma: novel mimickry by Valsalva maneuver and clues to diagnosis.

Factitious pheochromocytoma usually occurs in patients surreptitiously ingesting adrenergic medications. We encountered a case of factitious pheochromocytoma where in the subject mimicked hemodynamic (profound hypertension) and biochemical (plasma catecholamine elevation) manifestations of the illness by consciously altering autonomic function with Valsalva maneuver. Clues to this presentation included visible performance of Valsalva maneuver, marked disparity between blood pressures recorded in the presence and absence of the subject's knowledge, normal urinary catecholamine and metabolite excretion, and normal plasma chromogranin A. We reproduced, in part, the hemodynamic and biochemical manifestations of this presentation with Valsalva maneuver in healthy subjects.

Adrenal Gland Neoplasms↗
PubMed1995

Sex differences in chick eye growth and experimental myopia.

Stimulated by reported sex differences in eye size and refraction in humans, we compared refractions and ocular size measurements of male and female chicks. Chicks were reared under a 12-hr light/dark cycle with one eye open and the other occluded by a goggle or lid suture, each well-established means of inducing ipsilateral myopia. While the open eyes of the two sexes emmetropized equally well, both ultrasound and caliper measurements demonstrated that on average males have larger eyes. Although statistically significant for defined populations, the sex differences in open eyes were to small to be diagnostic for individual birds. The visually-deprived eyes of male chicks were more reactive than those of females, especially following deprivation by a goggle. Consistently, the anterior chamber of visually-deprived eyes of males was deeper than those of the females regardless of the means of impairing vision. With a goggle, males also developed more myopia and a deeper vitreous chamber than females similarly occluded. When goggles were removed, rapid recovery occurred in 2 weeks irrespectively of sex.

Animals↗