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Biomedical subjects

A M Walker

Publications and source records attributed to A M Walker.

At least 37 records · Page 2Linked to original sources

Hepatitis B vaccination and the risk of multiple sclerosis.

BACKGROUND: Reports of multiple sclerosis developing after hepatitis B vaccination have led to the concern that this vaccine might be a cause of multiple sclerosis in previously healthy subjects. METHODS: We conducted a nested case-control study in two large cohorts of nurses in the United States, those in the Nurses' Health Study (which has followed 121,700 women since 1976) and those in the Nurses' Health Study II (which has followed 116,671 women since 1989). For each woman with multiple sclerosis, we selected as controls five healthy women and one woman with breast cancer. Information about hepatitis B vaccination was obtained by means of a mailed questionnaire and was confirmed by means of vaccination certificates. The analyses included 192 women with multiple sclerosis and 645 matched controls and were conducted with the use of conditional logistic regression. RESULTS: The multivariate relative risk of multiple sclerosis associated with exposure to the hepatitis B vaccine at any time before the onset of the disease was 0.9 (95 percent confidence interval, 0.5 to 1.6). The relative risk associated with hepatitis B vaccination within two years before the onset of the disease was 0.7 (95 percent confidence interval, 0.3 to 1.8). The results were similar in analyses restricted to women with multiple sclerosis that began after the introduction of the recombinant hepatitis B vaccine. There was also no association between the number of doses of vaccine received and the risk of multiple sclerosis. CONCLUSIONS: These results indicate no association between hepatitis B vaccination and the development of multiple sclerosis.

Case-Control Studies↗

Age-related differences in the distortion of the sheep lung in response to localised pleural stress.

In order for diastolic filling to occur, the heart must displace the lung. Given the changes in lung structure and compliance that follow birth, we sought to determine whether the neonatal lung resists neighbouring structures encroaching into its space more than the adult lung and whether the lung surface making up the cardiac fossa resists distortion more than the lateral surface does. Pleural distortions, induced by applied pressures (Pappl) of 20-120 g cm(-2) at airway pressures (Paw) of 2.5-15 cm H2O, were recorded in isolated lungs of adult, neonatal (4-week-old) and newborn (1-week-old) sheep. The depth of pleural distortion increased (P < 0.05, ANOVA) with increasing Pappl in all lungs. Adult lungs were significantly more distortable than newborn and neonatal lungs (P < 0.05). As Paw increased, the distortability of the adult lung decreased progressively (P < 0.05) while the distortability of the newborn and neonatal lung remained constant at Paw of 2.5 and 5 cm H2O. Adult lungs also differed from newborn and neonatal lungs in that the cardiac fossal surface was significantly less distortable than the lateral surface. As newborn and neonatal lungs are less easily distorted than adult lungs, the potential for the lungs to limit cardiac filling is greater in the newborn and neonate than in the adult.

Aging↗

Contraindicated medications dispensed with cisapride: temporal trends in relation to the sending of 'Dear Doctor' letters.

PURPOSE: 'Dear Doctor' letters alert the prescribing community of drug labeling changes that contain new contraindications, warnings, adverse reactions, and precautions. There has been little assessment of the impact of these letters. We quantified the impact of two 'Dear Doctor' letters concerning interactions between cisapride and a series of drugs. A letter in 1995 described a risk of prolonged QT intervals and serious ventricular arrhythmia in patients who received macrolide antibiotics and imidazole antifungals in conjunction with cisapride. A June 1998 letter that expanded the list of contraindicated comedications had wider distribution than an earlier one, was accompanied by substantial Internet and media coverage, and was complemented by an effort to inform large pharmacy dispensing information organizations of the warnings against concurrent use of the named drugs. METHODS: Health plan members with one or more outpatient pharmacy claims for cisapride during the period 1 January 1995 through 31 May 1999 were identified among members of a large New England health insurer. A retrospective review of concurrent and nearly concurrent dispensings of cisapride and contraindicated comedications was undertaken in the automated pharmacy claims data using both graphical and statistical time-series analysis. We tabulated by month the fraction of cisapride dispensings that occurred in close temporal relation to dispensings of contraindicated comedications. Codispensings that occurred on the same day were taken as the most direct measure of prescriber responsiveness to the letters. Codispensings that occurred in windows of plus or minus 2 weeks (29 day window) and plus or minus 4 weeks (57 day window) were taken as measures of possible simultaneous consumption. Among overlapping dispensings, we counted the proportion dispensed by the same pharmacy. Time series regression analysis of secular, seasonal, and step-effects was conducted. RESULTS: There was a steady decline in codispensing of cisapride and contraindicated medicines, and a pronounced seasonal effect, arising principally from the seasonal use of macrolide antibiotics. Against this background, the isolated Dear Doctor letter of October 1995 had no discernible effect on prescribing practices. The 1998 letter and surrounding activity, by contrast, were followed by a 66% decline in same-day dispensings and a smaller, but still pronounced decline in dispensings in the wider time windows. For most codispensings of contraindicated medications with cisapride, both medications came from the same pharmacy. CONCLUSIONS: Publicity and direct intervention with dispensing pharmacies may be an important supplement to Dear Doctor letters when the goal is to eliminate the codispensing of drugs that should not be taken together.

Adolescent↗

On the evaluation of drug benefits policy changes with longitudinal claims data: the policy maker's versus the clinician's perspective.

Cost containment in pharmaceutical-benefit plans are often controversially debated for their potential of unintended consequences on health and overall expenditures. Thorough evaluations are needed but hypotheses and design considerations are complex. Our objective is to provide a structured framework for the evaluation of drug-benefit changes using longitudinal claims data. Differential cost sharing (DCS) will serve as a recent example. Benefit-plan managers are mainly interested in the overall performance of their plan. In a policy model, any observed policy-related effects may be compared with what would have happened had the intervention not been implemented by extrapolating the pre-policy trend from the same patients. These estimates will reflect the global consequences of the policy maker's decision. However, such estimates represent summary effects of benefits and harms, separately identifiable in those complying with the intended policy and those not complying. Results from a policy model apply only to a specific policy implementation and tend to underestimate effects when non-compliance is high. Clinical-decision makers and patients, by contrast, are interested in the consequences of patients' actual compliance to the policy. A clinical model assesses the effects of DCS depending on the actual treatment in contrast to the treatment intended by the policy. However, this model must sometimes make, unprovable assumptions about the appropriate control of selection factors. In conclusion, both policy and clinical models should be tested with a clear understanding of their perspectives, hypotheses, and interpretations, using quasi-experimental time-series designs to evaluate the effects of drug cost-containment policies.

Attitude of Health Personnel↗

Antidepressant use and the risk of breast cancer: a non-association.

OBJECTIVE: Animal studies have suggested that some antidepressant medications may act as breast tumor promoters and recent epidemiologic studies of antidepressant use and breast cancer outcomes in humans have also reported such associations. DESIGN: Retrospective cohort study. STUDY POPULATION: 38,273 women who filled a prescription for any of a number of antidepressants and 32,949 who filled a prescription for any other medication during 1989-1991; all were > or =20, enrolled in Medicare, Medicaid or the Pharmaceutical Assistance to the Aged and Disabled (PAAD) programs of New Jersey, and free of evidence of breast cancer. DATA COLLECTION: Antidepressant use was assessed over a period lasting up to 24 months. Subjects were followed for a maximum of 7.5 years; those who had a first diagnosis of breast cancer in the New Jersey Cancer Registry at least 3 months after their index date were considered incident breast cancer cases. Other covariates, including demographic, clinical, and health care utilization variables were also assessed. MAIN OUTCOME OF INTEREST: Adjusted hazard ratio (HR) of developing breast cancer, based on multivariable proportional hazards models. RESULTS: Use of antidepressants was unrelated to the development of breast cancer (adjusted HR = 1.04; 95% CI 0.87-1.25). No elevated risks were found for specific antidepressants, including agents found to be breast tumor promoters in animal studies, as well as drugs thought to be associated with breast cancer in prior epidemiologic studies. There was no suggestion that breast cancer risks were increased with more intensive use of antidepressants or that antidepressant use is associated with a more severe stage of cancer at diagnosis. CONCLUSIONS: Despite recent reports from much smaller epidemiologic studies or laboratory animals, these results provide reassurance that antidepressant use is not associated with the development of breast cancer.

Adult↗

Discontinuation of postmenopausal hormone therapy in a Massachusetts HMO.

Long-term postmenopausal hormone therapy alleviates menopausal symptoms, decreases women's risk of osteoporosis and has been shown to reduce cardiovascular morbidity and mortality in more than 30 observational studies. However, nearly half of all women initiating hormone therapy discontinue within the first year. This study was conducted to determine the rate and predictors of hormone therapy discontinuation in a clinical practice setting. We identified 992 women aged 45-59 who began hormone therapy between 1993 and 1995 in a Massachusetts health maintenance organization. Women were followed 2 years from the day they filled a prescription for estrogen. 53% discontinued hormone therapy by the end of the first year and one-fifth stopped after the first prescription. A prescription from a gynecologist (RR = 0.82, 95% CI: 0.68, 0.99) and a mammogram a year prior to initiation (RR = 0.75, 95% CI: 0.63, 0.89) were associated with a lower rate of discontinuation. Women who were using monoamine oxidase inhibitors (MAOI) or selective serotonin reuptake inhibitors (SSRI) antidepressants 3 months prior to initiation (RR = 2.07, 95% CI: 1.26, 3.39) or who had been enrolled in the health plan for less than 3 years (RR = 1.33, 95% CI: 1.10, 1.62) had an increased risk of discontinuing hormone therapy. The year a woman entered the cohort was also associated with a higher rate of discontinuation (RR = 1.40, 95% CI: 1.14, 1.74 for 1994 and RR = 1.95, 95% CI: 1.52, 2.50 for 1995). The results indicate that long-term hormone therapy use is uncommon in clinical practice, particularly when a woman or her physician attempts to use hormone therapy as an alternative to antidepressant therapy, and that the rates of discontinuation of hormone therapy were rising rapidly in the mid-1990s.

Adult↗

Finding incident breast cancer cases through US claims data and a state cancer registry.

OBJECTIVE: With the increasing availability of automated health-care data, new methods are available to screen large populations for the presence of cancer diagnoses. However, it is crucial to evaluate how completely incident cancer cases can be ascertained using these data sources. METHODS: We used capture-recapture techniques to estimate the total number of incident breast cancer cases occurring within one state during a 3-year period. We then compared the ascertainment of these cases by the following two data sources: claims for breast cancer surgery recorded in Medicaid and Medicare data vs a cancer registry in the same state. RESULTS: Medicaid-Medicare breast cancer surgery claims identified 68% of the total estimated number of incident breast cancer cases while cancer registry data identified 78%. Case ascertainment improved markedly to 91% when both registry and Medicare-Medicaid data sources were used together. The sensitivity of ascertainment was lower for Medicaid-Medicare data among those aged under 65 and non-white; ascertainment was lower for the registry among women who were aged under 65, poor, and non-white. CONCLUSIONS: Combining health insurance claims data with a population-based cancer registry improved the identification of incident cases of breast cancer, and may be particularly useful among demographic groups found to be at highest risk of under-ascertainment such as younger women, the poor, and racial minorities.

Adult↗

Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation.

Nitric oxide (NO), being produced by active neurones and also being a cerebral vasodilator, may couple brain activity and blood flow in sleep, particularly during active sleep (AS), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (CBF) compared with quiet wakefulness (QW) and quiet sleep (QS). This study examined CBF and cerebral vascular resistance (CVR) in lambs (n = 6) during spontaneous sleep-wake cycles before and after infusion of N(omega)-nitro-L-arginine (L-NNA), an inhibitor of NO synthase. L-NNA infusion produced increases in CVR and decreases in CBF during all sleep-wake stages, with the greatest changes occurring in AS (DeltaCVR, 88 +/- 19%; DeltaCBF -24 +/- 8%). The characteristic CVR and CBF differences among AS, QS, and QW disappeared within 1-3 h of L-NNA infusion, but had reappeared by 24 h despite persisting cerebral vasoconstriction. These experiments show that NO promotes cerebral vasodilatation during sleep as well as wakefulness, particularly during AS. Additionally, NO is the major, although not sole, determinant of the CBF differences that exist between sleep-wake states.

Animals↗

Right atrial pressure as measure of ventricular constraint in newborn lambs.

Although the lungs and pericardium constrain the heart and limit cardiac output, no method exists to assess this constraint in sick newborns. We hypothesize that a useful estimate of ventricular constraint may be obtained by measuring right atrial pressure (P(RA)) in the newborn. To test this hypothesis, we measured P(RA), thoracic inferior vena caval pressure (P(IVC); saline-filled catheters), and ventricular constraint (pericardial pressure, P(PER); liquid-containing balloon) in 4-wk-old (neonatal, n = 12) and 3-day-old (newborn, n = 6) anesthetized lambs. The measurements were made while LV filling pressure was altered (0-20 mmHg) and while positive end-expiratory pressure (PEEP) was maintained at 2.5 or 15 cmH2O. In all of the lambs, a strong linear relationship (r) existed between P(RA) and P(PER) (P(RA) = 1.19 P(PER) + 0.0, r = 0.99) and between P(IVC) and P(PER) (P(IVC) = 1.24 P(PER) + 0.1, r = 0.99; PEEP of 2.5 cmH2O). Similar relationships were also observed with increased PEEP (P(RA) = 1.29 P(PER)-1.2, r = 0.98 and P(IVC) = 1.32 P(PER)-1.2, r = 0.97). Because P(RA) provides an accurate measure of ventricular constraint in the normal lamb, it may be a useful measure of ventricular constraint in the sick newborn.

Animals↗

Unmodified and phosphorylated prolactin and gamma delta T cell development and function.

This manuscript discusses our studies to date concerning the effects of unmodified prolactin (PRL) and phosphorylated PRL on immune function. Most of the discussion refers to effects of changing the ratio of these two forms in maternal PRL on gamma delta T cell development in rat pups in utero, but limited experiments where adult animals have been directly treated are also discussed. The manuscript begins with some general background on gamma delta T cells and the different forms of PRL and then proceeds to a discussion of experimental findings. Results demonstrate that the ratio of unmodified to phosphorylated PRL during rat pregnancy is crucial to normal epidermal gamma delta T cell development in the pup thymus. Elevation of phosphorylated PRL in the dams, by administration of a recombinant molecular mimic of phosphorylated PRL, produces a defect in epidermalgamma delta T cell seeding and subsequent function in the offspring. In contrast, a functional defect is not seen for uterine gamma delta T cells in the offspring, a finding likely reflective of the continued availability of precursors to these cells after the fetal period. Preliminary results from treatment of the NZB/NZW mouse model of lupus with the two forms of PRL suggest opposing effects of unmodified and phosphorylated PRL on one measure of the disease.

Animals↗

Administration of unmodified prolactin (U-PRL) and a molecular mimic of phosphorylated prolactin (PP-PRL) during rat pregnancy provides evidence that the U-PRL:PP-PRL ratio is crucial to the normal development of pup tissues.

During rat pregnancy initial high concentrations of prolactin (PRL) decline by about day 9, concomitant with an increase in the ratio of unmodified to phosphorylated PRL. The physiological significance of both the decline in total PRL and the change in ratio of the two PRLs is unknown. To test the importance of each, either unmodified PRL (U-PRL) or a molecular mimic of phosphorylated PRL (PP-PRL) were continuously administered to rats throughout pregnancy. A dose of 6 microg/24 h resulted in circulating concentrations of 50 ng/ml of each administered PRL and had little effect on the pregnancy itself. After birth, pups were killed and various tissues examined. In the pup lungs, exposure to additional PP-PRL caused a reduction in epithelial integrity and an increase in apoptosis, whereas exposure to additional U-PRL had beneficial, anti-apoptotic effects. In the heart, PP-PRL caused an apparent developmental delay, whereas U-PRL promoted tissue compaction. In the blood, U-PRL increased the number of mature red blood cells at the expense of white blood cell production. Within the white blood cell population, myelopoiesis was favored at the expense of lymphopoiesis. PP-PRL, in contrast, had a less dramatic influence on the hematopoietic compartment by promoting red blood cell maturation and granulocyte production. In the thymus, exposure to PP-PRL caused accumulation of apoptotic thymocytes in enlarged glands, whereas exposure to U-PRL resulted in smaller thymi. In the spleen, exposure to U-PRL increased cellularity, with the majority of cells belonging to the erythroid series - a finding consistent with increased red blood cells in the circulation. Exposure to PP-PRL was without discernible effect. In all of these tissues, the contrasting effects of the two PRLs indicate that the absolute concentration of PRL is not crucial, but that the ratio of U-PRL to PP-PRL has a profound effect on tissue development. In brown fat, both PRL preparations decreased the number of lipid droplets. This result is therefore probably a consequence of the increase in total PRL. The results of this study attest to the importance of the U-PRL:PP-PRL ratio normally present during pregnancy and have provided clues as to the possible pathogenesis of a variety of neonatal problems.

Animals↗

Folic acid antagonists during pregnancy and the risk of birth defects.

BACKGROUND: Multivitamin supplementation in pregnant women may reduce the risks of cardiovascular defects, oral clefts, and urinary tract defects in their infants. We evaluated whether the folic acid component of multivitamins is responsible for the reduction in risk by examining the associations between maternal use of folic acid antagonists and these congenital malformations. METHODS: We compared data on exposure to folic acid antagonists that act as dihydrofolate reductase inhibitors and to certain antiepileptic drugs for 3870 infants with cardiovascular defects, 1962 infants with oral clefts, and 1100 infants with urinary tract defects with data for 8387 control infants with malformations the risk of which is not reduced after vitamin supplementation. Mothers were interviewed within six months after delivery about their medication use. RESULTS: The relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors during the second or third month after the last menstrual period, as compared with infants whose mothers had no such exposure, were 3.4 (95 percent confidence interval, 1.8 to 6.4) and 2.6 (95 percent confidence interval, 1.1 to 6.1), respectively. The relative risks of cardiovascular defects, oral clefts, and urinary tract defects after maternal exposure to antiepileptic drugs were 2.2 (95 percent confidence interval, 1.4 to 3.5), 2.5 (95 percent confidence interval, 1.5 to 4.2), and 2.5 (95 percent confidence interval, 1.2 to 5.0), respectively. Use of multivitamin supplements containing folic acid diminished the adverse effects of dihydrofolate reductase inhibitors, but not that of antiepileptic drugs. CONCLUSIONS: Folic acid antagonists, which include such common drugs as trimethoprim, triamterene, carbamazepine, phenytoin, phenobarbital, and primidone, may increase the risk not only of neural-tube defects, but also of cardiovascular defects, oral clefts, and urinary tract defects. The folic acid component of multivitamins may reduce the risks of these defects.

Abnormalities, Drug-Induced↗

Influence of prenatal adrenaline infusion on arterial blood gases after caesarean delivery in the lamb.

The efficacy of pulmonary gas exchange immediately after delivery is inversely related to the volume of liquid in the lung at birth, but aspiration of as much liquid as possible from the lung before Caesarean delivery fails to improve postnatal oxygenation (Pa,O2) to the level achieved after spontaneous term delivery. We hypothesised that the differing respiratory benefit of aspiration and vaginal delivery results from the differing volume of lung liquid remaining after aspiration (17 ml (kg body weight)-1) and labour (7 ml kg-1). We addressed this hypothesis by reducing lung liquid volume to an estimated 7 ml kg-1 by infusing adrenaline to seven fetal lambs at 140 days gestation (term is 147 days) before performing Caesarean delivery and obtaining postnatal blood gases for comparison with samples from lambs delivered vaginally. Infusion of adrenaline to fetuses caused a progressive decline in arterial O2 saturation (Sa, O2), pH and base excess, but no change in arterial partial pressure of O2 (Pa,O2) or CO2 (Pa,CO2). After birth, Pa,O2 rapidly rose to the same level in adrenaline-treated and vaginal-delivery groups. A severe acidosis occurred in the adrenaline-treated group and this appeared to be related to a higher Pa,CO2 and a transiently lower Sa, O2 in this group. We conclude that adrenaline infusion can enhance postnatal Pa,O2 levels in the newborn lamb, but this beneficial effect may be outweighed by the severe acidosis that develops after prolonged prenatal adrenaline treatment.

Acidosis↗

Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies.

OBJECTIVE: The triggers that induce antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (APV) are largely unknown. However, there have been reports suggesting that hydralazine, propylthiouracil, and several other drugs may cause some cases of APV, and the majority of these cases have been associated with antimyeloperoxidase (anti-MPO) ANCA. Our experience led us to hypothesize that cases of high titers of anti-MPO antibodies are often drug-associated. METHODS: In this study, we determined the prevalence of exposure to hydralazine, propylthiouracil, and other drugs previously implicated in APV among 30 patients with vasculitis and the highest titers of anti-MPO antibodies newly detected in our laboratory between 1994 and 1998. The clinical, histologic, and other serologic features of these 30 patients were also examined. RESULTS: The 30 study patients accounted for 12% of the 250 new patients with APV and anti-MPO who were tested during the study period. All 30 study subjects had anti-MPO titers that were more than 12 times the median titer of the 250 patients. Ten (33%) of the 30 patients had been exposed to hydralazine and 3 (10%) had been exposed to propylthiouracil. An additional 5 patients (17%) had been exposed to 1 of the other previously reported candidate drugs: 2 to penicillamine, 2 to allopurinol, and 1 to sulfasalazine. One of the patients exposed to hydralazine had also been exposed to allopurinol. In all cases, the clinical and histologic findings were typical of APV. There was a strong association between the presence of antielastase and/ or antilactoferrin antibodies and exposure to candidate drugs. CONCLUSION: These data suggest that a sizable proportion of cases of APV with high titers of anti-MPO antibodies are drug-associated, especially following exposure to hydralazine or propylthiouracil. We recommend that the use of these drugs should be sought in cases of anti-MPO-positive vasculitis, particularly among patients with high titers of these antibodies.

Adolescent↗

Association between intraocular pressure and budesonide inhalation therapy in asthmatic patients.

BACKGROUND: The extent to which inhaled glucocorticoids increase the risk of intraocular pressure elevation has been controversial. OBJECTIVE: The authors attempt to assess such risk attributable to budesonide, an inhaled glucocorticoid for asthma therapy. METHODS: Data were pooled from four prospective, randomized, double-blind, parallel-group, placebo-controlled, multicenter clinical trials of 12 to 20 weeks in duration. One thousand two hundred and fifty-five patients, 6 to 70 years of age whose intraocular pressures (IOPs) were less than 23 mmHg at screening were randomized to receive placebo or inhaled budesonide at doses ranging from 100 to 800 microg, administered twice daily. Intraocular pressure was measured at screening and at the end of double-blind treatment. Intraocular change was compared between budesonide and placebo, accounting for the confounding effects of gender, race, age, history of diabetes, history of hypertension, clinical trial, systemic glucocorticoid use during the trials, ophthalmic glucocorticoid use during the trials, and prior oral glucocorticoid use. RESULTS: No budesonide treatment effect on the IOP was evident either in the crude analysis or after adjustment for possible confounding factors. For patients exposed to budesonide at a total daily dose of 1600 microg for 20 weeks, there was no difference in IOP change compared with the placebo controls. CONCLUSIONS: No association with an increased IOP was observed in asthmatic patients treated with budesonide at daily doses ranging from 200 to 1600 microg for durations of 12 to 20 weeks. The subgroup analysis, which focused on the highest dose and longer term therapy was reassuring, as was the overall result.

Administration, Inhalation↗

True hermaphroditism.

OBJECTIVE: True hermaphroditism is a rare cause of atypical genitalia which presents significant diagnostic and management challenges. We present the clinical and laboratory findings and management of four patients with true hermaphroditism. METHODOLOGY: Case studies from a teaching hospital and literature review. RESULTS: All four patients had atypical genitalia identified at birth. All had a palpable gonad, only one of which was palpable at birth. Three patients were 46XX (SRY -ve) and one 46XY (SRY +ve). Three patients were raised as females (two 46XX and one 46XY) and one as a male. All four patients were found to have an ovotestis present. CONCLUSIONS: The management of true hermaphroditism is controversial and requires a multidisciplinary approach. It has many implications for both the parent and child. We discuss the issues involved for the patients and their parents.

Disorders of Sex Development↗

Refractory ceramic fiber: toxicology, epidemiology, and risk analyses--a review.

Refractory ceramic fiber (RCF) is an energy-efficient, high-temperature insulation, used principally in industrial furnaces, heaters, and reactors. Prior to the 1980s, there were few publications dealing with the potential health effects of this material. However, with the advent of higher energy costs and the need for thermally efficient high-temperature insulating materials, production of RCF grew rapidly, as did interest in its potential health effects. This article provides a comprehensive and integrated review of the toxicology (in vitro and in vivo), epidemiology, and risk analysis literature of RCF. Based on the available literature, we conclude that an occupational exposure of 0.5 fibers per cubic centimeter (cm(3)) [8-h time-weighted average (8-h TWA)] results in an occupational health risk no greater than 9.1 x 10(-5).

Administration, Inhalation↗