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Biomedical subjects

M R Miller

Publications and source records attributed to M R Miller.

At least 55 records · Page 3Linked to original sources

The shape of the maximum expiratory flow-volume curve reflects exposure in farming.

The objective of the study was to examine the effect of farming exposure, respiratory symptoms and smoking on the shape of the MEFV-curve in 1,691 male farming students and 407 male controls and to relate the slope ratio with FEV(1) and FEV(1) /FVC. Each subject underwent a medical interview and the slope ratios from the MEFV-curve at 75 (SR75), 50 (SR50) and 25 (SR25) %FVC together with FEV1 and FVC were recorded. Histamine bronchial reactivity (Yan method) was measured and skin prick test with inhalant allergens was performed. In smokers, SR75 increased with increasing exposure to: general farming, swine and dairy cattle (p< or =0.020). SR50 increased with increasing exposure to farming (p=0.015). In non-smokers, SR25 increased with increasing exposure to swine and dairy cattle (p=0. 021) and increased SR25 was associated with sensitisation to house dust mite (p=0.017). Data revealed an interaction between smoking and exposure to farming. FEV(1) and FEV(1)/FVC was not associated with farming exposure or production animals. FEV1 and FEV(1)/FVC (p< or =0.003) were lower among subjects wi bronchial hyperresponsiveness and asthma (FEV(1) and asthma only in smokers). SR75 (p=0.037) and SR50 (p=0.024) were increased in subjects with asthma and SR75 was increased in subjects with bronchial hyperresponsiveness, but only in smokers (p=0.002). In conclusion, exposure to farming seems to influence the shape of the MEFV-curve and there are indications of interaction between exposure to organic dust and smoking. These changes are seen only in the slope ratios and not in FEV(1) and FEV(1)/FVC. However, FEV(1) and FEV(1)/FVC are superior to slope ratios in differentiating healthy subjects from those with respiratory symptoms.

Agricultural Workers' Diseases↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

The use of a neural network to detect upper airway obstruction caused by goiter.

Goiter is a common condition and can cause upper airway obstruction (UAO), which may be difficult to detect. We have studied maximal expiratory and inspiratory flow volume loops using a neural network to see if this offers a better way to identify patients with UAO. The flow-volume loops from 155 patients with goiter were assessed by a human expert and sorted into those with and without UAO. The reliability of this assessment was judged by using two observers who repeated the sorting 8 wk apart. A set of 46 patients with loops suggesting UAO and a set of 51 patients with normal flow loops were taken from these 155, and the loops from a further 50 subjects with airflow limitation caused by chronic obstructive pulmonary disease were used for training and testing the neural network. Novel and standard indices were derived from the loops and used by the neural network. The kappa score for agreement between each of the observers and the original classification were 0.5 and 0.46, respectively, with the agreement between the observers at each reading of 0.58 and 0.68. The neural network found that a combination of four novel scores for flatness of the expiratory loop, the moment ratio, and the FEV1/PEF ratio was best at identifying UAO with a kappa score of 0.81, a sensitivity of 88%, specificity of 94% and an accuracy of 92%. We conclude that a neural network using only six indices taken from the expiratory limb of a flow-volume loop was better than human experts at identifying flow loops with UAO.

Adult↗

The rise and dwell time for peak expiratory flow in patients with and without airflow limitation.

The response of peak expiratory flow (PEF) meters may be affected by the magnitude of PEF, the time taken to get to PEF, and the duration that the peak is sustained. We undertook a retrospective study to define the 10 to 90% rise time (RT) and dwell time for flow above 90% (DT90) and 95% (DT95) of PEF. Blows were analyzed that had been recorded using a pneumotachograph from 912 patients older than 17 yr of age (556 men) who routinely attended a lung function laboratory. For each subject, that blow with the largest PEF was used to derive the PEF, FEV1, FVC, RT, DT90, and DT95. The values for RT, DT90, and DT95 were negatively skewed with the median values for men of 58, 29, and 19 ms, respectively, being significantly shorter than those for the women of 67, 49, and 31 ms. From the 912 subjects, there were 277 (153 men) who had all their spirometric indices within the normal range, and 305 (220 men) had both PEF and FEV1 more than 1. 645 SD below predicted, indicating airflow limitation. For subjects with airflow limitation the median RT was significantly smaller than in the normal subjects (men: 46 versus 72 ms, women: 50 versus 72 ms), and the same was found for DT90 (men: 22 versus 40 ms, women: 27 versus 56 ms) and DT95 (men: 15 versus 26 ms, women: 18 versus 34 ms). We conclude that the dwell times for PEF are shorter in men, and the rise and dwell times are shorter in patients with airflow limitation. Profiles used to test PEF meters should encompass the range of rise and dwell times found in subjects most likely to be using PEF meters, that is, those with airflow limitation.

Adult↗

Chronic obstructive pulmonary disease and '150 years of blowing'.

Spirometry is now an established and important aspect of investigation of many lung diseases. This article considers the history of spirometry, how we come to use the current indices of dynamic lung function, and the role of spirometry in the management of patients with chronic obstructive pulmonary disease.

Forced Expiratory Flow Rates↗

Hypoxia, hypocapnia and spirometry at altitude.

1. Both hypoxia and hypocapnia can cause broncho-constriction in humans, and this could have a bearing on performance at high altitude or contribute to altitude sickness. We studied the relationship between spirometry, arterial oxygen saturation and end-tidal carbon dioxide (ETCO2) concentration in a group of healthy lowland adults during a stay at high altitude, and then evaluated the response to supplementary oxygen and administration of a beta 2 agonist. 2. We collected spirometric data from 51 members of the 1994 British Mount Everest Medical Expedition at sea level (barometric pressure 101.2-101.6 kPa) and at Mount Everest Base Camp in Nepal (altitude 5300 m, barometric pressure 53-54.7 kPa) using a pocket turbine spirometer. A total of 205 spirometric measurements were made on the 51 subjects during the first 6 days after arrival at Base Camp. Further measurements were made before and after inhalation of oxygen (n = 47) or a beta 2 agonist (n = 39). ETCO2 tensions were measured on the same day as spirometric measurements in 30 of these subjects. 3. In the first 6 days after arrival at 5300 m, lower oxygen saturations were associated with lower forced expiratory volume in 1 s (FEV1; P < 0.02) and forced vital capacity (FVC; P < 0.01), but not with peak expiratory flow (PEF). Administration of supplementary oxygen for 5 min increased oxygen saturation from a mean of 81%-94%, but there was no significant change in FEV1 or FVC, whilst PEF fell by 2.3% [P < 0.001; 95% confidence intervals (CI) -4 to -0.7%]. After salbutamol administration, there was no significant change in PEF, FEV1 or FVC in 35 non-asthmatic subjects. Mean ETCO2 at Everest Base Camp was 26 mmHg, and a low ETCO2 was weakly associated with a larger drop in FVC at altitude compared with sea level (r = 0.38, P < 0.05). There was no correlation between either ETCO2 or oxygen saturation and changes in FEV1 or PEF compared with sea-level values. 4. In this study, in normal subjects who were acclimatized to hypobaric hypoxia at an altitude of 5300 m, we found no evidence of hypoxic broncho-constriction. Individuals did not have lower PEF when they were more hypoxic, and neither PEF nor FEV1 were increased by either supplementary oxygen or salbutamol. FVC fell at altitude, and there was a greater fall in FVC for subjects with lower oxygen saturations and probably lower ETCO2.

Administration, Inhalation↗

Western Australian Health Department recommendations for fruit and vegetable consumption--how much is enough?

In 1989 the Nutrition Program of the Health Department of Western Australia determined a minimum recommended daily intake of fruit and vegetables for use in promotion of increased fruit and vegetable consumption. Considerations in the development of this recommendation included: a review of existing recommendations; the protective effects of fruit and vegetables; specification of fruit and vegetables separately or together; classification of fruit and vegetables; definition of a serve; and practical considerations for the implementation of the recommendation. This paper outlines the development of the recommendation to eat at least two average-sized (120-150 g) pieces of fruit and five average-sized (60-90 g) serves of vegetables daily.

Fruit↗