PubMed Health⌕ Search

Biomedical subjects

M R Miller

Publications and source records attributed to M R Miller.

At least 19 recordsLinked to original sources
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

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↗
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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Spirometry with a Fleisch pneumotachograph: upstream heat exchanger replaces heating requirement.

The exact temperature of the head of an unheated Fleisch pneumotachograph (PT) during recording is not known, and variation in its temperature may lead to errors in measuring spirometric indexes. We measured PT head temperature during blows from five normal subjects, recorded by using a PT with and without an upstream heat exchanger to condition the air to the ambient temperature that was set in a climate chamber. Group mean (+/- SD) temperature of a thermocouple (TC) placed inside the PT head was 11.8 +/- 1.9 degrees C with 7 degrees C ambient, 25.4 +/- 1.3 degrees C at 23 degrees C, and was 37.2 +/- 0.3 degrees C at 37 degrees C. The between-subject range of temperature for this TC was 7.5 degrees at 7 degrees C, 5.5 degrees at 23 degrees C, and 1.1 degrees at 37 degrees C. The mean within-subject within-blow variation of temperature for this TC was 10.0 degrees and 3.3 degrees C for ambient of 7 degrees and 23 degrees C, respectively. At the usual ambient temperature in a laboratory, these differences in temperature lead to a 3.6% between-subject bias in recording, and the within-subject differences lead to 2.6% underreading of peak expiratory flow and a 0.5% overreading later in the blow, which makes ATPS-to-BTPS correction erroneous or difficult to perform. With the use of an upstream heat exchanger, the group mean temperature was 8.7 +/- 0.4 degrees, 23.2 +/- 0.2 degrees, and 37.1 +/- 0.2 degrees C at the three ambient temperatures, respectively, and the within-subject within-blow variation was reduced to < 1 degrees C. A heat exchanger placed upstream of the PT satisfactorily conditioned expired air to the ambient temperature and removed the error.

Adult↗
PubMed1997

Gas compression in lungs decreases peak expiratory flow depending on resistance of peak flowmeter.

It has recently been shown (O. F. Pedersen T. R. Rasmussen, O. Omland, T. Sigsgaard, P. H. Quanjer. and M. R. Miller. Eur. Respir. J. 9: 828-833, 1996) that the added resistance of a mini-Wright peak flowmeter decreases peak expiratory flow (PEF) by approximately 8% compared with PEF measured by a pneumotachograph. To explore the reason for this, 10 healthy men (mean age 43 yr, range 33-58 yr) were examined in a body plethysmograph with facilities to measure mouth flow vs. expired volume as well as the change in thoracic gas volume (Vb) and alveolar pressure (PA). The subjects performed forced vital capacity maneuvers through orifices of different sizes and also a mini-Wright peak flowmeter. PEF with the meter and other added resistances were achieved when flow reached the perimeter of the flow-Vb curves. The mini-Wright PEF meter decreased PEF from 11.4 +/- 1.5 to 10.3 +/- 1.4 (SD) l/s (P < 0.001), PA increased from 6.7 +/- 1.9 to 9.3 +/- 2.7 kPa (P < 0.001), an increase equal to the pressure drop across the meter, and caused Vb at PEF to decrease by 0.24 +/- 0.09 liter (P < 0.001). We conclude that PEF obtained with an added resistance like a mini-Wright PEF meter is a wave-speed-determined maximal flow, but the added resistance causes gas compression because of increased PA at PEF. Therefore, Vb at PEF and, accordingly, PEF decrease.

Adult↗
PubMed1997

Effect of adult-onset deafness on the human central auditory system.

Degenerative change in the central auditory system was assessed in seven subjects with profound bilateral adult-onset deafness. The degree of transneuronal atrophy was determined by measuring cell size at three levels of the brain stem auditory pathway (anteroventral cochlear nucleus, medial superior olivary nucleus, and inferior colliculus). Within subjects, the relative degree of cell shrinkage was similar across all levels of the central pathway. Across subjects, the best neuronal preservation was seen in a case of viral labyrinthitis with 1 year of bilateral dearness and a near-normal population of cochlear ganglion cells. Reduction in cell size was greatest in cases of bacterial labyrinthitis or Scheibe degeneration with reduced populations of ganglion cells and longer periods of deafness. At the level of the cochlear nucleus, there was no consistent difference in cell size between the side stimulated by a functioning prosthetic device and the nonstimulated side.

Adult↗
PubMed1997

Preoperative risk factors for surface disease after penetrating keratoplasty.

We sought to identify the types of, prevalence of, and predisposing factors for the development of surface keratopathy after penetrating keratoplasty. We reviewed the records of 120 corneal grafts performed over a 15-month period. Twenty patients were excluded from the study. Fifty-three men and 47 women composed the group studied. All transplants were performed by the same surgeon. Retrospective data from patients' records were gathered preoperatively and from postoperative visits at 1 week and at 1, 2, 3, and 4 months. Data included preoperative medical and demographic data, operative time, postoperative medication regimens, assessment of the presence and degree, if present, of punctate epithelial keratopathy (PEK), hurricane keratopathy, macroepithelial defects, microcystic edema, bullous edema, and filamentary keratitis. In addition, information on the donor material was recorded. Surface disease and normal groups were compared to identify risk factors for the occurrence of surface abnormalities. Thirty-three of the patients demonstrated persistent surface abnormalities. Coarse PEK was the most common surface abnormality in the sample studied and was most prominent in the first week after surgery. Postoperative surface keratopathy was not statistically associated with preoperative diagnosis, donor age, death-to-preservation time, preservation-to-surgery time, or donor epithelial status. However, corneal recipients in the group with surface keratopathy were significantly older (mean, 68.7 years) than patients in the group with no surface abnormalities (mean, 52.6 years; Mann-Whitney U test, p < 0.001). Although many factors may contribute to the normal integrity of the corneal surface after keratoplasty, recipient age is of key importance in the development of surface disease.

Aged↗