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Biomedical subjects

R A Stone

Publications and source records attributed to R A Stone.

At least 73 records · Page 4Linked to original sources
PubMed1995

Ciliary ganglion choline acetyltransferase activity in avian macrophthalmos.

While present evidence fails to support an etiologic mechanism for myopia based on accommodation or choroidal blood flow, atropine exhibits anti-myopia activity in many species. Accordingly, we studied choline acetyl transferase (ChAT) activity in the ciliary ganglion, uvea and retina of chicks with experimental macrophthalmos to identify a potential pathway for the moderation of eye growth by cholinergic neurons. Following unilateral lid suture or goggle, chicks were reared for 1 week under one of four lighting conditions known to induce macrophthalmos or myopia. Ocular tissues and ciliary ganglia were assayed for ChAT activity by measuring the conversion of 14C-acetyl CoA to 14C-acetylcholine. For some chicks, the goggles were removed at 1 week, and ChAT activity was measured 2 or 7 days later. Depending on the rearing condition, ciliary ganglion ChAT activity was depressed from 16 to 28% ipsilateral to the lid suture; enzyme activity also was reduced in the choroid of visually deprived eyes under most conditions. In contrast, lid suture resulted in no consistent trend in ChAT activity in either the anterior uvea or retina. For chicks wearing a unilateral goggle and reared under a 12:12 hr light/dark cycle, ChAT activity was depressed in the ciliary ganglion, anterior uvea and choroid on the visually deprived side. Following goggle removal to allow recovery from myopia. ChAT activity in the ciliary ganglion and uvea was returned toward that of the control side. The ciliary ganglion may participate in a neural pathway influencing the development of form-deprivation myopia.

Animals↗
PubMed1995

Association of intraocular pressure and myopia in children.

PURPOSE: While elevated intraocular pressure (IOP) is associated with myopia in adults, its potential influence on the growth of eyes in juveniles without glaucoma is controversial. To address this issue, a possible relation between IOP and refraction in children was sought. METHODS: A cross-sectional survey of IOP was conducted in children presenting to the Division of Pediatric Ophthalmology at The Children's Hospital of Philadelphia for a complete eye examination. Measurement of IOP was attempted in all children, including those with amblyopia, prematurity, and strabismus. Exclusion criteria were abnormalities of the posterior pole and/or conditions such as cataract that precluded assessment of refractive error. For analysis, myopia was defined as a spherical equivalent of more than 1 diopter (D) of myopia. Logistic regression was used to assess the association between other patient characteristics and presence of myopia. RESULTS: Intraocular pressure testing was attempted in all age groups, but was more successful in older children. Reliable readings were obtained on 321 subjects. The mean age was 9.8 years, with a mean IOP of 17.3 mmHg in the right eye and 17.2 mmHg in the left and a mean spherical equivalent of +0.2 D in the right eye and +0.1 D in the left. Increasing age, a family history of myopia, and amblyopia were associated myopia. Increasing IOP also was related to myopia. Even when patients with amblyopia, strabismus, and prematurity were exclude, age, family history of myopia, and IOP again were associated with myopia. CONCLUSIONS: These results indicate that IOP in children may be higher in myopic than nonmyopic eyes. Whether IOP could contribute to the mechanisms causing the abnormal eye growth of childhood myopia requires further study.

Adolescent↗
PubMed1995

Nitric oxide and choroidal blood flow regulation.

PURPOSE: Nitric oxide (NO) has been found to be an endothelial-derived relaxing factor mediating the vasodilatation that results from the stimulation of muscarinic endothelial receptors. It also has been identified as a putative neurotransmitter of parasympathetic origin in choroidal perivascular autonomic fibers. The authors investigated a potential role of NO in choroidal blood flow (ChBF) regulation. METHODS: Local ChBF in the tapetal region of 26 anesthetized cats was measured by laser Doppler flowmetry. Cats were infused through the femoral vein with increasing dosages of acetylcholine (ACh); N omega-nitro-L-arginine (NNL-A), a specific inhibitor of NO synthesis; L-arginine; and D-arginine. ChBF and mean arterial pressure (MAP) were continuously recorded. RESULTS: Infusion of 20 micrograms/minute ACh induced a 68% increase in ChBF despite a 9% decrease in MAP. Infusion of 16 mg/minute NNL-A attenuated the ACh-induced increase in ChBF by 46% and increased MAP by 40%. Infusion of different dosages of NNL-A without prior administration of ACh caused ChBF to fall below and MAP to rise above baseline in a dose-dependent fashion. Infusion of L-arginine prior to ACh infusion enhanced by 27% the ACh-induced increase in ChBF, whereas D-arginine had no effect on this increase. CONCLUSIONS: These findings suggest the presence of a local vasodilatory cholinergic mechanism in the choroid, inducing the release of NO. They also suggest that release of NO in the choroid may maintain basal blood flow to this tissue.

Acetylcholine↗
PubMed1995

Propensity score adjustment for pretreatment differences between hospitalized and ambulatory patients with community-acquired pneumonia. Pneumonia Patient Outcomes Research Team (PORT) Investigators.

A primary goal of the Pneumonia Patient Outcomes Research Team (PORT) multicenter cohort study is to identify a subgroup of patients with community-acquired pneumonia (CAP) who could be safely treated on an ambulatory basis. The medical outcomes of inpatients and outpatients are to be compared. Propensity score adjustment provides a unified way to control for pretreatment differences in the analysis of all the outcomes in this nonrandomized study by defining "comparable" patients as those with the same propensity score (i.e., the same probability of hospitalization). Data for 747 patients (35.5% hospitalized) with CAP in the Pneumonia PORT study illustrate the development and assessment of a propensity score adjustment. A classification tree algorithm defined seven propensity score strata with hospitalization probabilities ranging from 6.5% to 76.5%. Statistically significant pretreatment imbalances favoring the outpatients were found for 29 of 44 baseline variables considered; after stratification on the propensity score, only 13 of the 29 imbalances remained statistically significant at the 0.05 level. Post hoc stratification on the estimated propensity score consistently reduced, but did not completely eliminate, systematic baseline differences between ambulatory and hospitalized patients with CAP. Regression adjustment can be used in conjunction with propensity score stratification to adjust further for the remaining identified imbalances.

Adult↗
PubMed1994

Galanin immunoreactivity in autonomic innervation of the cat eye.

In an immunohistochemical study, we find that galanin is much more widely distributed in the peripheral innervation of the cat eye than in other animals so far examined. Previous studies of rat and pig eyes have revealed sparse galanin-positive nerves that presumably originate in the trigeminal ganglion. In contrast, the cat has a rich supply of galanin-containing nerve fibers throughout the uvea. Galanin-positive varicose nerves concentrate densely in iris muscles and distribute more sparsely in the ciliary muscle. The ciliary processes have a plexus of galanin-positive nerves underlying the ciliary epithelium at their base and positive nerve fibers coursing within their stroma. The ciliary artery and its branch vessels in the uvea are invested with a dense plexus of galanin-positive nerves. All autonomic ganglia supplying the eye contain cells that express galanin. It is present in 97% of superior cervical ganglion cells, coexisting with both tyrosine hydroxylase and neuropeptide Y; in 80% of pterygopalatine ganglion cells, most of which also contain vasoactive intestinal peptide; and in approximately 25% of ciliary ganglion cells. After unilateral superior cervical ganglionectomy, galanin-positive nerves almost totally disappear from the iris muscles, demonstrating that they are predominantly of sympathetic origin. Galanin-positive nerves investing the ciliary artery and choroidal blood vessels are not detectably reduced by sympathectomy, indicating that perivascular parasympathetic nerves from the pterygopalatine ganglion also express galanin. Other galanin-containing nerves in the eye can originate from the trigeminal and ciliary ganglia. The prominence of galanin in the ocular autonomic innervation of the cat provides an opportunity to explore the physiological effects of this neuropeptide in the eye.

Animals↗
PubMed1994

Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson's disease and congenital dopamine beta-hydroxylase deficiency.

1. Dopamine beta-hydroxylase is stored and released with catecholamines by exocytosis from secretory vesicles in noradrenergic neurons and chromaffin cells. Although dopamine beta-hydroxylase enzymic activity is measurable in cerebrospinal fluid, such activity is unstable, and its relationship to central noradrenergic neuronal activity in humans is not clearly established. To explore the significance of cerebrospinal fluid dopamine beta-hydroxylase, we applied a homologous human dopamine beta-hydroxylase radioimmunoassay to cerebrospinal fluid, in order to characterize the properties and stability of cerebrospinal fluid dopamine beta-hydroxylase, as well as its relationship to central noradrenergic neuronal activity and its variation in disease states such as hypertension, renal failure, Parkinsonism and congenital dopamine beta-hydroxylase deficiency. 2. Authentic, physically stable dopamine beta-hydroxylase immunoreactivity was present in normal human cerebrospinal fluid at a concentration of 31.3 +/- 1.4 ng/ml (range: 18.5-52.5 ng/ml), but at a 283 +/- 27-fold lower concentration than that found in plasma. Cerebrospinal fluid and plasma dopamine beta-hydroxylase concentrations were correlated (r = 0.67, P = 0.001). Some degree of local central nervous system control of cerebrospinal fluid dopamine beta-hydroxylase was suggested by incomplete correlation with plasma dopamine beta-hydroxylase (with an especially marked dissociation in renal disease) as well as the lack of a ventricular/lumbar cerebrospinal dopamine beta-hydroxylase concentration gradient. 3. Cerebrospinal fluid dopamine beta-hydroxylase was not changed by the central alpha 2-agonist clonidine at a dose that diminished cerebrospinal fluid noradrenaline, nor did cerebrospinal fluid dopamine beta-hydroxylase correspond between subjects to cerebrospinal fluid concentrations of noradrenaline or methoxyhydroxyphenylglycol; thus, cerebrospinal fluid dopamine beta-hydroxylase concentration was not closely linked either pharmacologically or biochemically to central noradrenergic neuronal activity. 4. Cerebrospinal fluid dopamine beta-hydroxylase was not changed in essential hypertension. In Parkinson's disease, cerebrospinal fluid dopamine beta-hydroxylase was markedly diminished (16.3 +/- 2.9 versus 31.3 +/- 1.4 ng/ml, P < 0.001) and rose by 58 +/- 21% (P = 0.02) after adrenal-to-caudate chromaffin cell autografts. In congenital dopamine beta-hydroxylase deficiency, lack of detectable dopamine beta-hydroxylase immunoreactivity in cerebrospinal fluid or plasma suggests absent enzyme (rather than a catalytically defective enzyme) as the origin of the disorder. 5. We conclude that cerebrospinal fluid dopamine beta-hydroxylase immunoreactivity, while not closely linked to central noradrenergic neuronal activity, is at least in part derived from the central nervous system, and that its measurement may be useful in both the diagnosis and treatment of neurological disease.

Adult↗
PubMed1994

Renal hemodynamics in essential hypertension. Racial differences in response to changes in dietary sodium.

Previous studies have suggested striking racial differences in hypertension-related renal disease. To explore potential mechanisms responsible for these differences, we investigated changes in renal hemodynamics in white and black essential hypertensive patients in response to alterations in dietary sodium. Patients were untreated, age-matched, and blood pressure-matched white (n = 59) and black (n = 22) males with essential hypertension. Studies were conducted on an inpatient metabolic ward and included assessment of blood pressure, urinary sodium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow after 5 days each of high and low salt diets. In response to high dietary salt intake, both white and black patients demonstrated significantly higher mean arterial pressure, renal plasma flow, and renal blood flow, and there were no racial differences in the changes in these parameters. However, whites and blacks differed significantly in glomerular filtration rate, with black hypertensive patients showing an increase in glomerular filtration rate (+17.3 +/- 5.3 mL/min per 1.73 m2, F = 7.586, P = .007) and white hypertensive patients showing no change (-0.2 +/- 3.3 mL/min per 1.73 m2) in response to high dietary sodium. These data demonstrate racial differences in the autoregulation of glomerular filtration rate in response to changes in dietary sodium. These differences suggest that glomerular hyperfiltration in response to a high salt diet may be a mechanism contributing to the racial disparity in hypertension-related renal disease.

Adult↗
PubMed1994

Coughing frequency in patients with persistent cough: assessment using a 24 hour ambulatory recorder.

Cough is an important symptom of many respiratory disorders. We determined the frequency and diurnal variation of cough in normal subjects and in patients with asthma or with persistent cough of unknown cause. We used a portable, solid-state, multiple-channel recorder to record cough sounds over a 24 h period. The audio-signal was recorded from a unidirectional microphone strapped over the chest wall, and electromyographic (EMG) signals from the lower respiratory muscles were simultaneously registered with surface electrodes. The recorded digital data were examined on an IBM-compatible computer, and the typical signals induced by cough (as assessed by voluntary or experimentally-induced cough) were counted. In 12 normal subjects, only 0-16 coughs were recorded over 24 h. In 21 stable asthmatics with a history of chronic cough ("asthma") the median number was 282 (ranges: 45-1,577), and in 14 patients with the predominant symptom of daily dry coughs ("chronic coughers") the median number was 794 (64-3,639). In both groups of patients, there was a diurnal variation of coughs, such that the least numbers occurred between 2 and 5 a.m. (< 3% of total). In the asthma group, there was no significant correlation between forced expiratory volume in one second (FEV1) (% predicted) or diurnal variation of peak expiratory flow and cough frequency. In the chronic coughers, there was a significant correlation between daytime cough numbers and daytime cough symptoms scores but not for the night-time values. Our data show that cough frequency is not determined by the severity of asthma in relatively stable asthmatics on inhaled steroids, and is reduced during sleep in both asthmatics and chronic cough patients. This portable cough recorder may be useful in the assessment of drug therapy for chronic cough.

Adult↗
PubMed1994

Statistical power to detect occupationally related respiratory cancer risk in a cohort of female employees in the US man-made vitreous fiber industry.

The current update of the US man-made vitreous fiber production worker cohort includes women for the first time. Preliminary comparisons of 3,820 female and 27,767 male workers from 11 participating fibrous glass plants show different hiring patterns during World War II. The gender-specific person-year distributions are similar with respect to duration of employment and time since first employment. The current follow-up of 118,559 person-years for women provides an estimated 80% power to detect a threefold relative risk of respiratory cancer for women who worked more than 14 years in these plants, based on a Poisson regression analysis of the cohort rates. When women comprise a small fraction of the cohort, the statistical power may be inadequate to detect risks of the magnitude typically of interest in studies of men.

Aged↗
PubMed1993

Enhanced expression of nitric oxide synthase by rat retina following pterygopalatine parasympathetic denervation.

Removal of the pterygopalatine ganglion enhanced the expression of nitric oxide synthase (NOS) in the ipsilateral rat retina and optic nerve by immunohistochemical and biochemical criteria. The denervation procedure did not alter the apparent histochemical reactivity of retinal cells normally immunoreactive for NOS but did induce expression in retinal ganglion cells and their axons in the retinal nerve fiber layer and optic nerve. After denervation, the induced NOS immunohistochemical reactivity was consistently visualized by day 7, reached a maximum intensity during days 14 to 28, and thereafter gradually attenuated to become barely detectable by microscopy at 10 weeks. Biochemical assays performed two weeks after pterygopalatine denervation confirmed the immunohistochemical observations, especially with regard to the optic nerve. The induced enzyme activity in both retina and optic nerve showed calcium dependency. These results point towards interactions of the ocular parasympathetic innervation and the retina, between which no known neuronal connections exist.

Amino Acid Oxidoreductases↗
PubMed1993

Expansion of the retinal pigment epithelium in experimental myopia.

Expansion of the retinal pigment epithelium was studied in neonatal chicks after one or two weeks of unilateral form vision deprivation to investigate altered ocular growth mechanisms in this experimental model of myopia. The area of individual retinal pigment epithelial (RPE) cells, measured in tangential sections, was greater in myopic eyes than in contralateral control eyes at both times. The mean RPE cell area in myopic eyes increased to the same extent as the area of the retinal pigment epithelium as a whole. In control eyes between one and two weeks, RPE cell expansion occurred predominantly in the periphery; in myopic eyes, it occurred more generally across the epithelium but was less pronounced in the temporal region. Given the absence of detectable mitotic figures in control and myopic eyes, expansion of the epithelial layer is attributable to passive stretch or growth of existing cells. Whether scleral growth or stretch occurs selectively beneath the areas of more pronounced RPE cell expansion is unknown.

Animals↗
PubMed1993

Chromogranin A immunoreactivity in human cerebrospinal fluid: properties, relationship to noradrenergic neuronal activity, and variation in neurologic disease.

Although measurement of chromogranin A in the bloodstream is of value in sympathoadrenal investigations, little is systematically known about chromogranin A in cerebrospinal fluid, despite substantial knowledge about its occurrence and distribution in brain. We therefore applied a homologous human chromogranin A radioimmunoassay to cerebrospinal fluid, in order to evaluate the properties and stability of cerebrospinal fluid chomogranin A, as well as its relationship to central noradrenergic neuronal activity, to peripheral (plasma) chromogranin A, and to disease states such as hypertension, renal failure and Parkinsonism. Authentic, physically stable chromogranin A immunoreactivity was found in cerebrospinal fluid (at 37-146 ng/ml; mean, 87.0 +/- 6.0 ng/ml in healthy subjects), and several lines of evidence (including 3.39 +/- 0.27-fold higher chromogranin A in cerebrospinal fluid than in plasma) indicated that it originated from a local central nervous system source, rather than the periphery. Cerebrospinal fluid chromogranin A values were not influenced by administration of effective antihypertensive doses of clonidine or propranolol, and were not related to the cerebrospinal fluid concentrations of norepinephrine, methoxyhydroxyphenylglycol, or dopamine-beta-hydroxylase; thus, cerebrospinal fluid chromogranin A was not closely linked to biochemical or pharmacologic indices of central noradrenergic neuronal activity. Cerebrospinal fluid chromogranin A was not changed (P > 0.1) in essential hypertension (84.2 +/- 14.0 ng/ml) or renal failure (72.2 +/- 13.4 ng/ml), despite a marked (7.1-fold; P < 0.001) increase in plasma chromogranin A in renal failure, and a modest (1.5-fold; P = 0.004) increase in plasma chromogranin A in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

The localization of nitric oxide synthase in the rat eye and related cranial ganglia.

Nitric oxide synthase is the biosynthetic enzyme for the free radical neurotransmitter nitric oxide. Using an affinity-purified antiserum, nitric oxide synthase was found to be localized to peripheral ocular nerve fibers, related cranial ganglia, and the retina of the rat. In the eye, nitric oxide synthase-like immunoreactive peripheral nerve fibers were visualized mainly in the choroid and about limbal blood vessels. The anterior uvea was quite sparsely innervated, and the cornea was negative. Many principal neurons in the pterygopalatine ganglion were immunoreactive for nitric oxide synthase while very few cells stained in the superior cervical and trigeminal ganglia. Virtually all nitric oxide synthase-like immunoreactive pterygopalatine cells were also immunostained for vasoactive intestinal polypeptide; nitric oxide synthase also partially co-localized with neuropeptide Y in some of the neurons of this ganglion. Pterygopalatine ganglionectomy significantly reduced the number of peripheral nitric oxide synthase-like immunoreactive nerve fibers in the eye. A variety of immunoreactive retinal cells were seen. Most cells in the inner nuclear layer or ganglion cell layer corresponded morphologically to amacrine cells and displaced amacrine cells. Interplexiform cells and occasional faintly stained cells in the outer portion of the inner nuclear layer also were visualized. Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry generally stained cells of similar distribution but did reveal somewhat more extensive localizations in peripheral ocular tissues, the ciliary ganglion, and the retina, compared with nitric oxide synthase immunohistochemistry. Nitric oxide synthase thus localizes to peripheral ocular nerve fibers, chiefly parasympathetic in nature and derived from the pterygopalatine ganglion, and to several cell types in the retina. Nitric oxide probably acts as a choroidal vasodilator of parasympathetic origin in the eye; the neuropeptide co-localizations in the pterygopalatine ganglion suggest complex neuromodulatory interactions. The retinal localizations imply potential neurotransmitter functions for nitric oxide in this tissue.

Amino Acid Oxidoreductases↗
PubMed1993

Effects of 5-hydroxytryptamine and 5-hydroxytryptophan infusion on the human cough reflex.

In some species serotonin (5-HT) has been shown to act as a central modulator of the cough reflex. To investigate whether serotonergic mechanisms influence the control of the human cough reflex, we have induced cough responses before and during infusions of 5-HT; its precursor 5-hydroxytryptophan (5-HTP), which, in contrast to 5-HT, crosses the blood-brain barrier; and saline control. At the start of each study day, eight normal male volunteers were challenged with a single inhalation of a solution lacking chloride ions (0.15 M sodium bicarbonate) and a single breath of capsaicin during a sham infusion. After 3 h they received repeat cough challenges during experimental infusions of 5-HT, 5-HTP, or saline control, which were given randomly and single blind. Heart rate, respiratory rate, and blood pressure were measured before, during, and after each infusion. Both 5-HT and 5-HTP reduced cough responses to the chloride-deficient solution (P = 0.035 and P = 0.017, respectively) with respect to saline control, whereas neither infusion reduced responses to capsaicin. 5-HT caused a transient increase in heart rate that was not observed with a similar dose of 5-HTP or saline (P < 0.01). Respiratory rate and blood pressure were not affected by experimental infusions but rose during cough challenge. We conclude that 5-HT exerts an inhibitory influence over the human cough reflex at peripheral and possibly central sites.

5-Hydroxytryptophan↗
PubMed1993

Effect of frusemide on cough responses to chloride-deficient solution in normal and mild asthmatic subjects.

We studied the tussive effects of a chloride-deficient solution (1.26% sodium bicarbonate). Nine normal volunteers and 10 mild asthmatic subjects were studied. In two double-blind, placebo-controlled, cross-over studies, we assessed the profile of any inhibitory effects that inhaled frusemide had over these responses. Baseline cough challenge was followed by inhalation of either frusemide (40 mg), or 0.15 M NaCl control. Cough was then induced at 0.5, 2, 4 and 6 h after treatment. Forced expiratory volume in one second (FEV1) was measured before and after each challenge. Changes from the baseline cough response due to drug or control were compared nonparametrically at each time point. There was no difference in the sensitivity of normal and asthmatic subjects to the cough challenge (median cough response 15 and 14.5 on control day, 12 and 15 on frusemide day). Frusemide caused sustained inhibition of the cough response in normal subjects (p < 0.05 at 2 h, p < 0.01 at 4 h), but had only a small, nonsignificant effect in asthmatic subjects at 30 min. Falls in FEV1 of asthmatic subjects due to the chloride-deficient solution were not significant, and did not correlate with number of coughs. We conclude that mild asthmatic subjects are less sensitive than normal subjects to the influence of frusemide against low chloride challenge. This observation is not explained by bronchoconstrictor effects of the cough challenge in asthmatic subjects.

Adult↗
PubMed1992

Lung cancer mortality among industrial workers exposed to formaldehyde: a Poisson regression analysis of the National Cancer Institute Study.

The Formaldehyde Institute (FI) sponsored additional Poisson regression analysis of lung cancer mortality data from the joint National Cancer Institute (NCI)/FI cohort study of workers exposed to formaldehyde to investigate the previously reported effects of plant and latency period and to assess the impact of short-term workers (under 1 yr employment) on the results. There were 242 lung cancer deaths in this cohort of 20,067 white male workers. With OCMAP software, lung cancer death rates for the white males in this cohort were computed by plant, age, calendar time, and job type for several time-dependent formaldehyde exposures, including formaldehyde exposure in the presence of 12 selected co-exposures: ammonia (AM), antioxidants (AN), asbestos (AS), carbon black (CB), dyes/inks/pigments (DY), hexamethylenetetramine (HX), melamine (ME), particulates (PT), phenol (PH), plasticizers (PL), urea/urea compounds (UR), wood dust (WD), and a composite co-exposure (X5) involving AN, HX, ME, PH, and UR.A 1.6-fold increase in lung cancer risk was found, beginning approximately 16-20 yr after first employment in the study plants with no evidence of a differential effect of latency between hourly and salaried workers or among the various categories of formaldehyde exposure as measured by cumulative average intensity or length of exposure. The statistically significant heterogeneity in lung cancer risk among the 10 plants could not be explained by interplant differences in cumulative or average intensity of exposure to formaldehyde, either without regard to co-exposures or in the presence of any of the 12 co-exposures considered individually. Plant was not a statistically significant predictor of lung cancer risk when cumulative exposure to the composite X5 was included in the model, suggesting that some component of X5, or a correlate, could at least partly account for the overall heterogeneity. No significant associations were found for cumulative, average, or length of exposure to formaldehyde without regard to co-exposure, but positive associations were found for cumulative exposure to formaldehyde in the presence of several co-exposures (AN, HX, ME, PH, and UR). For workers who were never exposed to any of 10 co-exposures associated with an increased lung cancer risk, there was a decreasing pattern of estimated lung cancer risk ratios relative to cumulative formaldehyde exposure. Similar patterns were seen when the analysis was restricted to the long-term workers. Analysis of the internal cohort rates corroborates previous analyses of NCI/FI cohort data in that significant positive associations were found between the risk of lung cancer and cumulative exposure to formaldehyde in the presence of several of the same co-exposures. No such associations were found in the absence of these co-exposures.

Adult↗