Search PubMed⌕ Search

Biomedical subjects

M R Miller

Publications and source records attributed to M R Miller.

At least 19 recordsLinked to original sources
PubMed2000

Novel S-nitrosothiols do not engender vascular tolerance and remain effective in glyceryl trinitrate-tolerant rat femoral arteries.

Organic nitrates, such as glyceryl trinitrate, are nitric oxide (NO) donor drugs that engender tolerance with long-term use. Here, we tested the hypothesis that our novel S-nitrosothiols, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6, tetra-O-acetyl-beta-D-glucopyranose (RIG200) and S-nitroso-N-valeryl-D-penicillamine (D-SNVP), do not induce vascular tolerance ex vivo. Femoral arteries from adult male Wistar rats were preconstricted with phenylephrine and perfused with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Perfusion pressure was measured during 20-h treatment with supramaximal concentrations of NO donor (10 microM). Perfusion with glyceryltrinitrate caused a vasodilatation, which recovered over 2-20 h. In contrast, the S-nitrosothiols caused vasodilatations that were maintained throughout the 20-h perfusion period. Responses to S-nitrosothiols were partially reversed by the NO scavenger ferrohaemoglobin and fully reversed by the soluble guanylate cyclase inhibitor [1H-[1,2,4] oxadiazole [4,3-a]quinoxaline-1-one (ODQ). Glyceryltrinitrate-tolerant vessels were fully responsive to bolus injections of S-nitrosothiols. Resistance to tolerance is an attractive property of our novel compounds, particularly in view of their sustained activity in arteries with damaged endothelium.

Animals↗
PubMed2000

S and Z alpha1-antitrypsin alleles are risk factors for bronchial hyperresponsiveness in young farmers: an example of gene/environment interaction.

Several studies have found an association between the rare Pi-alleles and asthma or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi-type on BHR among 2,308 young Danish people living in rural areas with a mean +/- SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial histamine provocation and skin-prick tests were performed. Serum alpha1-antitrypsin levels were determined and phenotyping was performed by means of isoelectric focusing and the subjects categorized into four groups: 1) MM and MX; 2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant positive trend for sensitization towards house dust mites was found, ranging from 12% in the MM group to 22% in the rare Pi-group. A positive test for trend was found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On multiple logistic regression analysis, an increased odds ratio (OR) for BHR was found among farming school attendants with the rare Pi-alleles. The OR (95% confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and 4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among the conscripts. These results show that a gene/environment interaction may exist between the farming occupation and the rare Pi-alleles, leading to a higher proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in farming school attendants, in contrast to what is found among other young people living in rural areas.

Adult↗
PubMed2000

Prevention of thromboembolism in atrial fibrillation. A meta-analysis of trials of anticoagulants and antiplatelet drugs.

OBJECTIVE: Appropriate use of drugs to prevent thromboembolism in patients with atrial fibrillation (AF) involves comparing the patient's risk of stroke and risk of hemorrhage. This review summarizes the evidence regarding the efficacy of these medications. METHODS: We conducted a meta-analysis of randomized controlled trials of drugs used to prevent thromboembolism in adults with nonpostoperative AF. Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until May 1998. MAIN RESULTS: Eleven articles met criteria for inclusion in this review. Warfarin was more efficacious than placebo for primary stroke prevention (aggregate odds ratio [OR] of stroke = 0.30, 95% confidence interval [CI] 0.19, 0.48), with moderate evidence of more major bleeding (OR 1.90; 95% CI 0.89, 4.04). Aspirin was inconclusively more efficacious than placebo for stroke prevention (OR 0.56, 95% CI 0.19, 1.65), with inconclusive evidence regarding more major bleeds (OR 0.81, 95% CI 0.37, 1.77). For primary prevention, assuming a baseline risk of 45 strokes per 1,000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was evidence suggesting fewer strokes among patients on warfarin than among patients on aspirin (aggregate OR 0.64, 95% CI 0.43, 0.96), with only suggestive evidence for more major hemorrhage (OR 1.60, 95% CI 0.77,3.35). However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared with aspirin was low (5.5 per 1,000 person-years) compared with an older group (15 per 1,000 person-years). CONCLUSION: In general, the evidence strongly supports warfarin for patients with AF at average or greater risk of stroke. Aspirin may prove to be useful in subgroups with a low risk of stroke, although this is not definitively supported by the evidence.

Anticoagulants↗
PubMed2000

Peak flowmeter resistance decreases peak expiratory flow in subjects with COPD.

Previous studies have shown that the added resistance of a mini-Wright peak expiratory flow (PEF) meter reduced PEF by approximately 8% in normal subjects because of gas compression reducing thoracic gas volume at PEF and thus driving elastic recoil pressure. We undertook a body plethysmographic study in 15 patients with chronic obstructive pulmonary disease (COPD), age 65.9 +/- 6.3 yr (mean +/- SD, range 53-75 yr), to examine whether their recorded PEF was also limited by the added resistance of a PEF meter. The PEF meter increased alveolar pressure at PEF (Ppeak) from 3.7 +/- 1.4 to 4.7 +/- 1.5 kPa (P = 0.01), and PEF was reduced from 3.6 +/- 1.3 l/s to 3.2 +/- 0.9 l/s (P = 0.01). The influence of flow limitation on PEF and Ppeak was evaluated by a simple four-parameter model based on the wave-speed concept. We conclude that added external resistance in patients with COPD reduced PEF by the same mechanisms as in healthy subjects. Furthermore, the much lower Ppeak in COPD patients is a consequence of more severe flow limitation than in healthy subjects and not of deficient muscle strength.

Aged↗
PubMed2000

Peak expiratory flow profiles delivered by pump systems. Limitations due to wave action.

Pump systems are currently used to test the performance of both spirometers and peak expiratory flow (PEF) meters, but for certain flow profiles the input signal (i.e., requested profile) and the output profile can differ. We developed a mathematical model of wave action within a pump and compared the recorded flow profiles with both the input profiles and the output predicted by the model. Three American Thoracic Society (ATS) flow profiles and four artificial flow-versus-time profiles were delivered by a pump, first to a pneumotachograph (PT) on its own, then to the PT with a 32-cm upstream extension tube (which would favor wave action), and lastly with the PT in series with and immediately downstream to a mini-Wright peak flow meter. With the PT on its own, recorded flow for the seven profiles was 2.4 +/- 1.9% (mean +/- SD) higher than the pump's input flow, and similarly was 2.3 +/- 2.3% higher than the pump's output flow as predicted by the model. With the extension tube in place, the recorded flow was 6.6 +/- 6.4% higher than the input flow (range: 0.1 to 18.4%), but was only 1.2 +/- 2.5% higher than the output flow predicted by the model (range: -0.8 to 5.2%). With the mini-Wright meter in series, the flow recorded by the PT was on average 6.1 +/- 9.1% below the input flow (range: -23.8 to 2. 5%), but was only 0.6 +/- 3.3% above the pump's output flow predicted by the model (range: -5.5 to 3.9%). The mini-Wright meter's reading (corrected for its nonlinearity) was on average 1.3 +/- 3.6% below the model's predicted output flow (range: -9.0 to 1. 5%). The mini-Wright meter would be deemed outside ATS limits for accuracy for three of the seven profiles when compared with the pump's input PEF, but this would be true for only one profile when compared with the pump's output PEF as predicted by the model. Our study shows that the output flow from pump systems can differ from the input waveform depending on the operating configuration. This effect can be predicted with reasonable accuracy using a model based on nonsteady flow analysis that takes account of pressure wave reflections within pump systems.

Calibration↗
PubMed2000

Impact of correcting peak flow for nonlinear errors on air pollutant effect estimates from a panel study.

Air pollutant effects are commonly investigated using panel studies employing daily measurement of changes in peak expiratory flow (PEF). Variable orifice PEF meters are inaccurate with a nonlinear relationship to actual PEF. The impact on a panel study of correcting these errors was examined. Twice-daily PEF readings were taken by 147 9-yr old children for 8 weeks and corrected using an equation derived from the response of 32 Vitalograph meters to a servomechanism-controlled pump. Pollutant effect estimates for corrected and uncorrected readings were derived using a regression approach incorporating appropriate confounders. Correction impacted little on mean PEF values (333.1-334.2 L x min(-1)), but did alter effect sizes. Nonsignificant nitrogen dioxide estimates for the entire panel decreased by up to 73%, but, for symptomatic/atopic children, a significant 5-day mean result was lost (decrease in effect size from -2.53 to -0.90% per 10 parts per billion (ppb)) and lag 0 became significant (decrease from -0.51 to -1.22% per 10 ppb). Mass concentration estimates of particles with a 50% cut-off aerodynamic diameter of 2.5 microm moved in both directions (-0.22 changed to 0.11% per 10 microg x m(-1) lag 3 and -0.29 to -0.73% per 10 microg x m(-3) for the 5-day mean). Correction of nonlinearity of peak expiratory flow meters influenced the overall outcome of this panel study, and the changes in effect estimates would be sufficient to alter the interpretation of some studies. For adults, a greater change in effect estimates may follow the larger correction required for their usual peak expiratory flow range.

Adult↗
PubMed2000

Parental preferences for primary and specialty care collaboration in the management of teenagers with congenital heart disease.

OBJECTIVES: We examined parental preferences for locus of service delivery for their teenager's congenital heart disease (CHD) and the influence of disease severity, sociodemographic factors, and insurance on these preferences. METHODS: A consecutive sample of parents of teenagers followed in a pediatric cardiology clinic completed a mailed questionnaire. Disease severity was classified as low (</=1 cardiovascular procedure), moderate (>1 cardiovascular procedure), and high (cyanosis or single ventricle physiology). RESULTS: Eighty-six of 148 parents responded (58%): 40, low severity; 36, moderate severity; and 10, high severity of illness. Parents preferred using primary care providers (PCPs) as a point of first contact for all 11 of 11 general health concerns and 5 of 7 potential cardiovascular-related concerns: chest pain (52%), syncope (73%), seeming seriously ill (79%), sports physical examination (79%), and endocarditis prophylactic antibiotics (94%). Increasing disease severity was significantly associated with preferring cardiologists for 6 of 7 cardiovascular-related concerns. Overall, 58% of parents viewed their care as a PCP-cardiologist comanagement model versus a cardiologist-dominated model. Lower family income (odds ratio [OR]: 1.5; confidence interval [CI]: 1.0-2.2) and severity of illness (OR: 2.1; CI: 1.0-4.4) were associated with a comanagement model of health care versus a cardiologist-dominated model. CONCLUSIONS: This study suggests that the majority of parents of teenagers with CHD prefer to use their teenager's PCP for all routine health care needs and many cardiovascular health needs. Severity of illness and family income are positively associated with greater preference for cardiologist care.

Adolescent↗
PubMed2000

The evidence regarding the drugs used for ventricular rate control.

OBJECTIVE: Our goal was to determine what drugs are most efficacious for controlling the ventricular rate in patients with atrial fibrillation. SEARCH STRATEGY: We conducted a systematic review of the literature published before May 1998, beginning with searches of The Cochrane Collaboration's CENTRAL database and MEDLINE. SELECTION CRITERIA: We included English-language articles describing randomized controlled trials of drugs used for heart rate control in adults with atrial fibrillation. DATA COLLECTION/ANALYSIS: Abstracts of trials were reviewed independently by 2 members of the study team. We reviewed English-language abstracts of non-English-language publications to assess qualitative consistency with our results. MAIN RESULTS: Forty-five articles evaluating 17 drugs met our criteria for review. In the 5 trials of verapamil and 5 of diltiazem, heart rate was reduced significantly (P <.05), both at rest and with exercise, compared with placebo, with equivalent or improved exercise tolerance in 6 of 7 comparisons. In 7 of 12 comparisons of a beta-blocker with placebo, the beta-blocker was efficacious for control of resting heart rate, with evidence that the effect is drug specific, as nadolol and atenolol proved to be most efficacious. All 9 comparisons demonstrated good heart rate control with beta-blockers during exercise, although exercise tolerance was compromised in 3 of 9 comparisons. In 7 of 8 trials, digoxin administered alone slowed the resting heart rate more than placebo, but it did not significantly slow the rate during exercise in 4 studies. The trials evaluating other drugs yielded insufficient evidence to support their use, but those drugs may yet be promising. CONCLUSIONS: The calcium-channel blockers verapamil or diltiazem, or select beta-blockers are efficacious for heart rate control at rest and during exercise for patients with atrial fibrillation without a clinically important decrease in exercise tolerance. Digoxin is useful when rate control during exercise is less a concern.

Adrenergic beta-Antagonists↗
PubMed1999

Acetaminophen-induced proliferation of breast cancer cells involves estrogen receptors.

Previous studies have shown that acetaminophen, a common analgesic/antipyretic, induces proliferation of cultured breast cancer cells containing both estrogen and progesterone receptors (ER+/PR+). The main objective of this study was to evaluate the involvement of ERs in this effect. First, the effects of therapeutic acetaminophen concentrations were compared in breast cancer cells with high ERs and in T47Dco cells with lower ERs, to determine if acetaminophen-induced proliferation depends on ER levels. Second, the effects of two antiestrogens (ICI 182,780 and 4'-hydroxytamoxifen) on acetaminophen-induced proliferation were determined in three human breast cancer cell lines: two ER+/PR+ (MCF7, T47D) and one ER-/PR- (MDA-MB-231). Third, ER binding assays were performed in MCF7 cells to determine if acetaminophen competed with estradiol for binding to ERs. Proliferation endpoints monitored included percent cells in the DNA synthesis phase of the cell cycle, 3H-thymidine incorporation into DNA, and cell number. Acetaminophen did not induce DNA synthesis in T47Dco cells, but did in cells with higher ER levels, suggesting high ER levels are necessary for acetaminophen to induce proliferation. Antiestrogens inhibited acetaminophen-induced proliferation in ER+/PR+ cells while no effects were observed in ER-/PR- cells, further supporting ER involvement. However, acetaminophen did not compete with estradiol for binding to ERs in ER+/PR+ cells. Collectively, these data suggest that acetaminophen induces breast cancer cell proliferation via ERs without binding to ERs like estradiol. The second purpose of this study was to determine if acetaminophen is estrogenic/antiestrogenic in vivo (uterotrophic assays). Acetaminophen has no antiestrogenic/estrogenic activity in mice or rats uteri.

Acetaminophen↗
PubMed1999

Positional isomers of acetaminophen differentially induce proliferation of cultured breast cancer cells.

This study demonstrates that acetaminophen (p-acetamidophenol) stimulates proliferation of estrogen-responsive cultured breast cancer cells and assesses if the proliferative activity of p-acetamidophenol is influenced by the -OH moiety position on the benzene ring. The effects of p-, m-, and o-acetamidophenol on cell number and on percentage cells in S phase of the cell cycle were determined for two estrogen receptor positive, human breast cancer cell lines, T47D and MCF7. Therapeutic concentrations of p-acetamidophenol (0.1 mM) significantly increased breast cancer cell proliferation. The relative order of potency of isomers in stimulating proliferation in both cell types was p- > m- > o-acetamidophenol, indicating the -OH position on the benzene ring influences the proliferation output in cultured breast cancer cells.

Acetaminophen↗
PubMed1999

Effective management of spinal pain in one hundred seventy-seven patients evaluated for manipulation under anesthesia.

OBJECTIVE: To demonstrate that manipulation under anesthesia (MUA), a conservative treatment modality, is both safe and efficacious in the treatment of both acute and chronic spinal pain disorders in appropriately selected patients. MUA can be safely used to treat pain arising from the cranial, cervical, thoracic, and lumbar spine, as well as the sacroiliac and pelvic region. SETTING: An ambulatory surgical center. SUBJECTS: The treatment group consisted of 177 patients between ages 17 and 65 years. Evaluation followed a treatment algorithm created by the authors as a multidisciplinary approach to patient selection, evaluation, treatment, and timing of specialized referral, in consideration of previously published algorithms. Prior forms of treatment, both conservative and surgical in nature, had failed in these patients. INTERVENTION: Patients underwent three sequential manipulations under intravenous sedation, followed by 4 to 6 weeks of skilled spinal manipulation and therapeutic modalities. OUTCOME MEASURES: Data regarding changes in Visual Analog Scale (VAS), range of motion, medication needs, and return to work status were used to document progress. All patients had follow-up for 6 months. RESULTS: On average, VAS ratings improved by 62.2% in those patients with cervical pain problems. On average, VAS ratings improved by 60.1% in those patients with lumbar pain problems. There was a near-complete reversal in patients out of work before MUA (68.6%) and those returning to unrestricted activities at 6 months after MUA (64.1%). There was a 58.4% reduction in the percentage of patients requiring prescription pain medication from the pre-MUA period to 6 months after MUA. Additionally, 24.0% of the treatment group required no medication at 6 months after MUA. CONCLUSION: A multidisciplinary approach to evaluation and treatment, including MUA, offers patient benefits above and beyond what can be obtained through the individual providers working alone.

Adolescent↗
PubMed1999

Risk factors in microbial keratitis leading to penetrating keratoplasty.

OBJECTIVE: To determine the characteristics of infectious corneal ulcers at the time of presentation to the cornea specialist associated with a favorable response to medical therapy versus a poor outcome manifested by the need for penetrating keratoplasty for therapy or visual rehabilitation. DESIGN: Retrospective, case-control study. PARTICIPANTS: A total of 162 patient records were reviewed, including the study group of 30 patients and the control group of 132 patients. INTERVENTION: A retrospective review of all cases of microbial keratitis presenting to the Cornea Service between January 1, 1989 and December 31, 1995 was conducted. The cases were divided into two groups. The study group consisted of patients with microbial keratitis who failed medical therapy and required penetrating keratoplasty. The control group included patients with infectious ulcers who responded to medical therapy alone. MAIN OUTCOME MEASURES: The influence of demographics, medical and ocular history, delay in presentation to the primary ophthalmologist or the corneal specialist, topical medications, and contact lens usage were compared. Visual acuity and ulcer characteristics were recorded. The statistical significance was evaluated by the chi-square test for independence and multiple logistic regression. RESULTS: Older age (P=0.001), delay in referral to the corneal specialist (P<0.03), and treatment with topical steroids prior to presentation (P<0.0001) were statistically significant factors associated with the need for penetrating keratoplasty. Steroid use and the delay in referral were correlated. A past history of ocular surgery (P=0.01), poor visual acuity at presentation (P<0.001), and ulcer characteristics, including central location (P<0.0001), large size (P<0.0001), presence of perforation or descemetocele (P<0.0001), limbal involvement (P<0.0001), and hypopyon (P=0.05), were all associated with the need for penetrating keratoplasty. CONCLUSIONS: Older age, delay in referral to the corneal specialist, topical steroid treatment, past ocular surgery, poor vision at presentation, large size, and central location of the ulcer are risk factors for poor outcome of microbial keratitis, as indicated by the need for penetrating keratoplasty.

Age Factors↗
PubMed1999

Endogenous prostaglandin formation in the field-stimulated guinea-pig vas deferens: comparison of the inhibitory effects of indomethacin and NS-398.

Prostaglandin (PG) E2 inhibited both phases of contraction produced by electrical field stimulation of the guinea-pig vas deferens. PGF2alpha and PGD2 were without effect on this preparation. Carbacyclin (a PGI2) analogue inhibited the first phase of contraction at higher concentrations, whereas U46619 (a thromboxane mimetic) potentiated both phases of contraction. As exogenous arachidonic acid inhibits both phases of contraction of the electrically field-stimulated guinea-pig vas deferens, it is likely that the arachidonic acid is converted to PGE2 in the vas deferens. Indomethacin, a non-specific inhibitor of prostaglandin H synthase (PGHS), attenuated the inhibitory actions of exogenous arachidonic acid when examined on the first phase of contraction. NS-398, a relatively specific inhibitor of PGHS-2, also prevented the inhibitory action of exogenous arachidonic acid. However, NS-398 was much less effective than indomethacin in this respect even though NS-398 and indomethacin inhibit PGHS-2 with similar potencies. Consequently, the findings suggest that exogenous arachidonic acid is converted to PGE2 in the guinea-pig vas deferens by the actions of PGHS-1 and, to a lesser extent, by PGHS-2.

Animals↗
PubMed1999

Acetaminophen alters estrogenic responses in vitro: inhibition of estrogen-dependent vitellogenin production in trout liver cells.

The purpose of this study was to determine if acetaminophen altered estrogen-dependent vitellogenin production in isolated trout liver cells. Estrogen-induced vitellogenesis was studied in liver cells isolated from male trout and cultured in defined medium; vitellogenin secreted into culture medium was quantitated using immunological procedures. Vitellogenin production was absolutely dependent on the addition of estradiol (10(-6) M) to liver cells from male trout. Acetaminophen produced a dose-dependent inhibition of vitellogenin production; approximately 50% inhibition was achieved with 0.05 mM acetaminophen, while 0.3 mM acetaminophen inhibited secreted vitellogenin to undetectable levels. In contrast, these concentrations of acetaminophen (< or = 1 mM) did not significantly alter the production of secreted albumin, determined immunologically, or cause detectable toxicity. Higher doses of acetaminophen were toxic, but did not induce DNA fragmentation in the trout liver cells. Acetaminophen reduction of estradiol-induced vitellogenin production was accompanied by a dose-dependent decrease in vitellogenin mRNA, indicating acetaminophen inhibited a step prior to, or during, formation of vitellogenin mRNA. Estrogen receptor-binding assays demonstrated that acetaminophen did not reduce binding of [3H]-estradiol to trout liver estrogen receptor. In addition, catabolism of estradiol to water-soluble metabolites was not significantly altered by acetaminophen. These studies indicate that non-toxic concentrations of acetaminophen specifically inhibit estrogen-dependent vitellogenin synthesis and suggest that this commonly used drug may alter estrogen-regulated processes.

Acetaminophen↗
PubMed1999

Food service in long day care centres--an opportunity for public health intervention.

OBJECTIVE: To determine the characteristics of long day care centre operations, food service management practices, and nutrition resources use and needs. METHOD: In October 1996, all 330 long day care centres in Western Australia were surveyed by telephone to gather information to help develop strategies for food service improvement. RESULTS: The response rate was 85%. An accreditation committee directed operations in 76% of centres. Most centres employed a cook with limited or no cooking training. Coordinators identified training needs for cooks that are specific to the National Childcare Accreditation Council's Quality Improvement and Accreditation System (QIAS) guidelines: food hygiene; nutritional and food requirements of children; menu planning; and multicultural cooking. CONCLUSIONS: National standards for the quantification of foods to meet children's nutritional requirements in long day care would allow for consistency in educating child care workers, training cooks, and establishing and assessing government regulations and the QIAS guidelines. Nine recommendations for strategies to improve food service in long day care are presented. IMPLICATIONS: There are two main messages for public health practitioners working to improve the quality of food served to children in long day care: the strong influence of the QIAS guidelines, and the need for specific nutrition recommendations.

Child↗
PubMed1999

Lung status in young Danish rurals: the effect of farming exposure on asthma-like symptoms and lung function.

The aim of this study was to assess the prevalence of asthma (self-reported) and relate this to lung function and factors associated with asthma in young farmers. Two hundred and ten female and 1,691 male farming students together with 407 males controls were studied. Each subject underwent a medical interview; forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were recorded using a dry wedge spirometer. Histamine bronchial reactivity was measured using the Yan method. Skin prick testing was performed using inhalant allergens. Nonsmokers had lower prevalence of asthma (5.4-10.8%) than smokers (11.3-21.0%) (p<0.05). Females reported symptoms of asthma nearly twice as often as males. Sex, smoking and a family history of asthma/allergy were significantly associated with asthma. Controls had higher standardized FEV1 and FVC residuals than male students, both nonsmokers (0.21 and 0.24) versus (-0.06 and -0.05) and smokers (0.29 and 0.33) versus (-0.11 and 0.13) (p<0.032). Bronchial hyperresponsiveness, asthma, siblings with allergy and working with cattle (controls only) were significantly associated with reduced lung function. In conclusion, the prevalence of asthma was significantly related to smoking, female sex, family history of asthma and allergy. Whilst bronchial hyperresponsiveness was associated with reduced lung function and lung function was slightly reduced in the male farming students, there was no association found between occupational farming exposure and either lung symptoms or lung function.

Adolescent↗
PubMed1998

Acetaminophen alters estrogenic responses in vitro: stimulation of DNA synthesis in estrogen-responsive human breast cancer cells.

A limited number of studies have investigated the estrogenic potential of acetaminophen but none has reported its effects on breast cells. Many compounds that alter estrogen-mediated processes in various tissues contain p-phenolic moieties. Acetaminophen is a commonly used analgesic/antipyretic that also contains a p-phenol. This study tested the hypothesis that therapeutic concentrations of acetaminophen alter estrogen-responsive human breast cancer cell DNA synthesis. To this end, a modified E-screen assay was developed to determine the response to acetaminophen of two dichotomous types of human breast cancer cell lines: estrogen-responsive (MCF7, T47D, ZR-75-1) and estrogen-nonresponsive (MDA-MB-231, HS578T). Cells were placed in estradiol-free medium and then exposed to 3 nM estradiol or 0.03-1 mM acetaminophen. The proliferative response was assessed by determining [3H]thymidine incorporation into DNA and by determining the percentage of cells in the DNA synthesis (S) phase of the cell cycle. Concentrations of acetaminophen commonly attained in human plasma with therapeutic doses of this drug (approximately 0.1 mM) were found as effective as estradiol in stimulating DNA synthesis in estrogen-responsive breast cancer cells. Higher acetaminophen concentrations (1 mM) stimulated estrogen-responsive cells to a lesser extent. The combination of estradiol and acetaminophen did not stimulate DNA synthesis in estrogen-responsive cells more than either agent alone. Neither acetaminophen nor estradiol stimulated DNA synthesis in estrogen-nonresponsive human breast cancer cells. These novel findings demonstrate that therapeutic acetaminophen concentrations specifically stimulate estrogen-responsive breast cancer cell DNA synthesis, suggesting that this drug may exert estrogenic effects.

Acetaminophen↗