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Biomedical subjects

M R Miller

Publications and source records attributed to M R Miller.

At least 91 records · Page 5Linked to original sources
PubMed1995

Differences in output from corticosteroid inhalers used with a volumatic spacer.

Corticosteroid inhaler therapy using a spacer device is commonly used as an important part of asthma management. Increasingly, generic corticosteroid inhalers are being used with spacer devices. We have therefore tested whether these generic inhalers yield equivalence in dose when compared to the established inhalers. We measured the in vitro output, discharged into a Volumatic spacer from beclomethasone dipropionate inhalers (250 micrograms.puff-1) made by three manufacturers, Allen & Hanburys, 3M and Baker Norton. The output from 20 of each type of inhaler was sampled, in random order, by a computer driven pump system. Beclomethasone was absorbed onto a coded filter, which was analysed independently for drug content. The output per puff differed significantly between the inhalers of each manufacturer, with a 36% difference between the highest output from the Allen & Hanburys device and the lowest output device. We conclude that there are important differences in output from these inhalers when used with a spacer, and that substitution of one device with another will not necessarily give equivalent therapy to the patient.

Adrenal Cortex Hormones↗
PubMed1995

The military health services system model for pharmacoeconomic decision making.

Pharmaceutical expenditures have been increasing over the last few decades, both in the private sector and the Department of Defense (DoD). The Pharmacoeconomic Center (PEC), staffed with personnel from the Army, Navy, and Air Force, was established in 1993 to develop the means to control these pharmaceutical expenditures and to develop the DoD TriService Formulary (TSF). The TSF serves as the basis for a consistent and equitable pharmacy benefit for DoD patients. The initial TSF contains medications that are well accepted as standard therapy and are currently available at most military facilities. Revisions to the initial TSF are based on pharmacoeconomic analyses of ambulatory disease states accounting for the majority of pharmaceutical expenditures. The PEC also develops treatment guidelines, preferred drug lists, and drug use evaluation criteria based on the results of each disease state analysis.

Decision Making, Organizational↗
PubMed1995

Frequency response of variable orifice type peak flow meters: requirements and testing.

Little is known about the response of variable orifice peak flow meters to high frequency flow input. The purpose of this study was to define and test dynamic requirements for such peak flow meters. In a population sample we measured peak expiratory flow (PEF), rise time (tr), from 10-90% PEF and the duration of the flow in excess of 97.5, 95 and 90% of PEF, by use of a carefully calibrated Fleisch pneumotachograph with known and adequate frequency response. Three peak flow meters (Mini Wright, Vitalograph and Ferraris) were tested with an explosive decompression calibrator adjusted to values for PEF and tr as close as possible to the 95th and 5th percentile values, respectively, both for males and females, and with peak durations between 5 and more than 100 ms. The 95th percentile values of PEF were 597 L.min-1 for females and 894 L.min-1 for males. The 5th percentile values of tr were, respectively 55 and 45 ms. The duration of flow in excess of 95% PEF was longer than 10 ms in 99% of the subjects. For all meters, the deviation of PEF corrected for alinearity were less than 5% at a peak duration of 10 ms. We conclude that PEF, rise time, and peak duration can be used for description of dynamic properties of variable orifice meters, and that the tested meters had a satisfactory frequency response for recording PEF in mostly normal subjects.

Adult↗
PubMed1994

Characterization of cytochrome P4501A induction in medaka (Oryzias latipes) by samples generated from the extraction and processing of coal.

The objective of this study was to characterize cytochrome P4501A induction in medaka liver as a biomarker for detecting polyaromatic hydrocarbon (PAH)-type compounds in samples of processed coal or petroleum. Ethoxyresorufin-O-deethylase (EROD) activity in individual medaka livers was used to asses induction of P4501A following the addition of various samples to aquaria water. Samples included a known P4501A inducer, beta-naphthoflavone, and various processed coal samples, as well as a petroleum-pitch. The sensitivity of detecting significant EROD induction by adding samples to aquaria water was approximately 0.1 mg/L for most samples; however, a coal-tar pitch significantly increased EROD activity at 0.01 mg/L. Different samples induced EROD activity to different extents. All samples elicited a concentration-dependent increase in EROD activity, with maximum EROD induction 2 days after a single administration of xenobiotics to aquaria water. Western blot studies established that induction of EROD activity by all xenobiotics tested was associated with corresponding increased amounts of immunoreactive P4501A. EROD induction was not influenced by gender, by single or multiple xenobiotic exposures, nor by feeding or fasting animals during the course of xenobiotic exposure. The ability of xenobiotics to induce EROD activity in medaka liver did not always correlate with their genotoxic potential determined by bacterial mutagenesis assays. Induction of P4501A in medaka liver appears to provide a convenient, economical, reliable and sensitive indicator for the presence of PAH-type compounds in coal- or petroleum-derived samples.

Animals↗
PubMed1994

Cultured trout liver cells: utilization of substrates and response to hormones.

The characterization of a recently established system for the short-term culture of rainbow trout (Oncorhynchus mykiss) liver cells in chemically defined medium has been extended to studies on the metabolic competence of the cells and the characterization of their response to hormones. Three areas of metabolism have been addressed: a) the utilization of the exogenously added substrates fructose, lactate, glucose, dihydroxyacetone, and glycerol for glucose and lactate formation; b) the effects of the pancreatic hormones insulin and glucagon on cellular glucose formation, lactate formation, and fatty acid synthesis; and c) the effects of insulin and dexamethasone on the estradiol-dependent production of vitellogenin. Incubation of trout liver cells with fructose, lactate, glucose, dihydroxyacetone, or glycerol resulted in enhanced rates of cellular glucose and lactate production. Substrate-induced effects usually were more clearly expressed after extended (20 h) than after acute (5 h) culture periods. Addition of the hormones insulin or glucagon caused dose-dependent alterations in the flux of substrates to glucose and lactate. Rates of de novo synthesis of fatty acids from [14C]acetate were stimulated by insulin and inhibited by glucagon during acute and extended incubation periods. Treatment of liver cells isolated from male trout for 72 h with estradiol induced vitellogenin production and secretion into the medium. However, the addition of insulin or dexamethasone drastically reduced this estrogen-induced vitellogenesis. These results indicate that trout liver cells cultured in defined medium maintain central metabolic pathways, including glycolysis, gluconeogenesis, lipogenesis, and vitellogenesis as well as their responsiveness to various hormones, for at least 72 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Corticotrophin-releasing factor immunostaining is present in placenta and fetal membranes from the first trimester onwards and is not affected by labour or administration of mifepristone.

BACKGROUND AND OBJECTIVES: Corticotrophin releasing factor (CRF) is present in the human placenta and fetal membranes. Placental CRF content and plasma CRF concentrations rise throughout gestation and fall rapidly after delivery. The regulation of CRF production from the placenta is poorly understood. The objective of this study was to use the antiprogestin, mifepristone, to determine whether progesterone has a regulatory effect on CRF production in the first trimester of pregnancy. PATIENTS: Women undergoing first trimester (gestation 5-12 weeks) therapeutic abortion (by suction curettage with and without the synthetic PGE1 analogue, gemeprost (16,16-dimethyl-trans-delta 2-PGE1 methyl ester) vaginally 2-4 hours prior to the procedure; or with 600 mg mifepristone 48 hours prior to receiving 1 mg gemeprost vaginally), second trimester therapeutic abortion (600 mg mifepristone, 1 mg gemeprost), in association with preterm delivery (gestation 25-34 weeks) and at term (gestation 35-42 weeks) by spontaneous delivery, induced labour or elective Caesarean section. MEASUREMENTS: Immunohistochemical localization of CRF and quantification of CRF content by radioimmunoassay of tissue extracts, in human placenta and fetal membranes. RESULTS: CRF was immunolocalized to the syncytiotrophoblast cells of the placenta at all stages of gestation from 5 to 42 weeks. In the fetal membranes CRF immunoreactivity was localized in the epithelial and subepithelial cells of the amnion, some cells of the reticular and cellular layers of the chorion, and in decidual stroma. This pattern was seen in all tissues studied. Pretreatment with prostaglandins, mifepristone or both during the first trimester did not alter the distribution or the intensity of the CRF immunostaining. Placental CRF content rose throughout gestation but, consistent with the immunostaining results, was unaffected by the administration of mifepristone or by labour. CONCLUSIONS: CRF is localized in the syncitiotrophoblast cells of the placenta and is clearly present early in the first trimester of pregnancy. The lack of an effect of mifepristone or mode of delivery suggests that syncytiotrophoblast produces CRF constitutively throughout pregnancy.

Cesarean Section↗
PubMed1994

Prevention of thermal and condensation errors in pneumotachographic recordings of the maximal forced expiratory manoeuvre.

When recording respiratory manoeuvres using a pneumotachograph (PT), it is customary to heat the pneumotachograph head to avoid condensation errors. It is technically demanding to heat the PT correctly, and this increases the complexity of the equipment. We have studied whether a simpler method can eradicate condensation errors and preserve thermal stability of the PT. We tested the accuracy of a PT by recording the discharge of 1,000 ml of air through the PT before and after a subject had blown through it, thus causing both condensation within the PT and a rise in its temperature. We then determined whether the thermal and condensation errors could be avoided by placing the PT, between blows, on a fan that was blowing air at a constant 1.65 l.s-1. With ambient temperature at 20 degrees C, a single blow through the PT was found to cause a subsequent 4% over-reading in volume, due to condensation and temperature changes in the PT. After five consecutive blows the error was 7%. Placing the PT on the fan for 15 s after a single blow abolished these errors, whereas a wait of 15 s did not. At an ambient temperature of 14 degrees C there was a 5% over-reading of volume after a single blow, and an over-reading of 9% after five blows. At an ambient temperature of 26 degrees C these errors were 3 and 5%, respectively. All of these errors were abolished by placing the PT on the fan for 15 s and 30 s, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1994

Portable peak flow meters: physical characteristics, influence of temperature, altitude, and humidity.

Little is known about the linearity of portable peak flow meters, or about physical gas factors affecting peak expiratory flow (PEF) readings. We therefore tested five portable peak flow meters of three types in an altitude chamber (sea level to 5,500 m) and in a climate chamber at sea level (7-37 degrees C) to determine the influence of the physical conditions of the gas on the reading of the meters. The nonlinear response of the variable orifice meters was confirmed and, when this was corrected for, the readings of these meters were found to be significantly reduced by higher altitude and lower temperature. The readings from a turbine type of peak flow meter were not affected by altitude but were reduced at low temperature. A mathematical model for the variable orifice meters could correct for both their nonlinear behaviour and the effect of gas density (altitude, temperature and humidity). The model showed that correction is not necessary for the differences in gas conditions between calibration and taking of measurements under normal laboratory conditions. All the meters tested had impedances higher than recommended (0.05 kPa.l-1.s) and this may influence PEF at high flows. The mean uncorrected PEF of six healthy subjects when measured with a Mini Wright peak flow meter at sea level and at 3,000 m fell by 5%, but the mean corrected PEF increased by 12%. This increase in PEF was about 60% of that predicted for fully density-dependent flow and agreed with the findings of other similar studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Effect of profound hearing loss on a central auditory nucleus.

The present study was designed to investigate the type and extent of degeneration occurring in the human central auditory system subsequent to profound hearing loss. The authors have examined the size of one population of neurons in the ventral cochlear nucleus in seven subjects with profound hearing loss (audiometric responses poorer than 90-100 dB HL). Six normal subjects, ages 35-78, were used as controls. Cell size in the hearing-impaired subjects ranged from normal to reduced by more than 50 percent. Two factors appear to contribute to the variability in cell size reduction. The correlation coefficient (Spearman rs) of cell size with duration of profound deafness was -0.48, indicating a moderate tendency for neurons to become smaller with longer periods of deafness. The correlation coefficient of cell size with number of surviving cochlear ganglion cells was 0.73, indicating a stronger tendency for neurons to be larger with greater eighth nerve innervation of the cochlear nucleus. Two cases of Scheibe degeneration showed the most severe degenerative change in the central auditory system.

Adult↗
PubMed1993

Lack of association of human immunodeficiency virus seroconversion with visits to foreign ports in US Navy personnel.

BACKGROUND: The US Navy visits ports on all continents and many islands of the world, many of which are reported to have a high endemicity of human immunodeficiency virus (HIV) infection. The objective of this study was to determine whether visits to foreign ports by active-duty navy personnel were associated with increased risk of HIV infection. METHODS: The Naval Health Research Center in San Diego, Calif, maintains records of all HIV enzyme-linked immunosorbent assay and Western blot tests given in the navy. This information, along with career histories and ship movement data, was used in a nested case-control design to examine the relationship between visits to the 100 foreign ports most frequently visited by the navy and risk of HIV seroconversion. All visits to a port and total time in each port during the study period were examined. A total of 813 seroconverters were matched to 6993 seronegative active-duty controls by age, race, sex, occupational group, home port, and year of test. RESULTS: Estimated relative risks of seroconversion associated with visits to foreign ports showed no statistically significant excess risk of HIV infection for navy personnel after visits to any foreign port. CONCLUSIONS: These results do not imply that an individual's risk of acquisition of HIV would be less in a foreign port if the individual engaged in high-risk activity there. Rather, they imply that despite the mobility of the US Navy and the large variation in HIV seroprevalence rates throughout the world, navy personnel generally do not appear to be acquiring HIV infections abroad.

Adolescent↗
PubMed1993

Hepatic cellular distribution of cytochrome P-450 IA1 in rainbow trout (Oncorhynchus mykiss): an immunohisto- and cytochemical study.

Monoclonal antibody 1-12-3 reactive against scup (Stenotomus chrysops) cytochrome P450 E (a teleost CYP IA1) has been used to immunohistochemically localize CYP IA1 within hepatocytes and presumably sinusoidal endothelial and biliary epithelial cells of scup and trout. The goal of the present study was to extend immunohistochemical studies to the ultrastructural level determining intracellular locations of CYP IA1 in fish liver. Juvenile trout (5-10 g) were given i.p. injections once (50 micrograms/g b beta-naphthoflavone in cod liver oil; 0.5-ml injectate volume). After 5 days, livers were fixed (0.25% glutaraldehyde) via vascular in situ perfusion, removed, cut in 100-microns slices, infiltrated, and embedded in LR White monomer. Ultrathin sections of exposed livers were incubated in monoclonal antibody 1-12-3, rabbit anti-mouse IgG, and protein G colloidal gold. Membranes of granular endoplasmic reticulum in perinuclear regions of hepatocytes were consistently labeled. In addition, hepatocyte plasma membrane, particularly microvilli at bile canaliculi, was labeled. Biliary epithelial cells were labeled on luminal plasma membrane surrounding biliary passageway. Plasma membrane facing sinusoid and immediately subjacent cytoplasm was labeled in endothelial cells. Presence of CYP IA1 in sinusoidal endothelium could contribute to detoxication and/or bioactivation of blood borne chemicals. Granular endoplasmic reticulum was not uniformly labeled in hepatocytes. Rather, distribution seemed sequestered within highly specific regions and not dispersed along all membrane surfaces. Localization within biliary epithelial cells could signify potential of this cell type to bioactivate polycyclic aromatic hydrocarbons and may explain the common finding of biliary as well as hepatocytic tumors of trout liver.

Animals↗
PubMed1993

Acetaminophen toxicity in cultured trout liver cells. I. Morphological alterations and effects on cytochrome P450 1A1.

To better characterize the hepatotoxicity of acetaminophen, the effects of this drug were investigated on isolated liver cells from a species relatively resistant to acetaminophen toxicity, rainbow trout. At high concentrations of acetaminophen (2-10 mM), pathologic effects were detected, including loss of lactate dehydrogenase from cells, disruption of cell-cell aggregation, cell death, and distinctive alterations in cell morphology, as demonstrated by light and electron microscopic examination. Most striking was the acetaminophen-induced rearrangement of mitochondria, which were clustered adjacent to the nucleus and rarely seen at cell periphery. The endoplasmic reticulum was also altered by acetaminophen treatment. In the middle portion of the cytoplasm, parallel arrays of endoplasmic reticulum cisternae were abundant; however, the peripheral cytoplasm was restricted to vesicular profiles of endoplasmic reticulum. Although nuclei in acetaminophen-treated cells displayed peripheral heterochromatin aggregation, acetaminophen did not produce detectable DNA fragmentation, in contrast to effects reported for mouse liver cells. Thus DNA fragmentation does not appear to be required for acetaminophen to manifest cytotoxic effects. In addition, immunohistochemical studies indicated that toxic concentrations of acetaminophen which altered the endoplasmic reticulum helped maintain cytochrome P450 1A1 in liver cells from beta-naphthoflavone-induced trout.

Acetaminophen↗
PubMed1993

Acetaminophen toxicity in cultured trout liver cells. II. Maintenance of cytochrome P450 1A1.

Acetaminophen was demonstrated to maintain cytochrome P450 1A1 (P450 1A1) in isolated rainbow trout liver cells cultured in serum-free medium. This novel finding was characterized in detail. Cultured trout liver cells retained their ability to respond to typical 1A1 inducers in vitro; induction of ethoxyresorufin O-deethylase (EROD) activity was readily demonstrated by exposing liver cells from control trout to beta-naphthoflavone (BNF), Aroclor 1254, or 7,12-dimethylbenz[a]anthracene. BNF was the most potent inducer studied and was used in further experiments. High levels of EROD activity, immunoreactive 1A1, and 1A1 mRNA were expressed in liver cells prepared from trout pretreated with BNF. However, all of these 1A1-specific indicators rapidly declined when cells from BNF-treated trout were placed in culture, and BNF in culture medium was not effective in maintaining EROD activity. Immunohistochemical studies suggested that addition of acetaminophen to liver cells prepared from BNF-induced trout helped maintain elevated levels of P450 1A1. Total cytochrome P450, EROD activity and immunoreactive P450 1A1 were retained in liver cells from BNF-induced trout by the addition of acetaminophen, in a dose-dependent manner. The concentrations of acetaminophen most effective in maintaining P450 1A1 produced cytotoxic effects, including vesiculation of endoplasmic reticulum. Furthermore, the acetaminophen maintenance of P450 1A1 was primarily attributed to elevated levels of P450 1A1 mRNA. In contrast to BNF, acetaminophen was not capable of inducing 1A1 in liver cells prepared from control trout. This is the first report to demonstrate that acetaminophen can help maintain P450 1A1 and that this effect is exerted at the level of P450 1A1 mRNA.

Acetaminophen↗
PubMed1993

Development of an accurate portable recording peak-flow meter for the diagnosis of asthma.

This article describes the systematic design of an electronic recording peak expiratory flow (PEF) meter to provide accurate data for the diagnosis of occupational asthma. Traditional diagnosis of asthma relies on accurate data of PEF tests performed by the patients in their own homes and places of work. Unfortunately there are high error rates in data produced and recorded by the patient, most of these are transcription errors and some patients falsify their records. The PEF measurement itself is not effort independent, the data produced depending on the way in which the patient performs the test. Patients are taught how to perform the test giving maximal effort to the expiration being measured. If the measurement is performed incorrectly then errors will occur. Accurate data can be produced if an electronically recording PEF instrument is developed, thus freeing the patient from the task of recording the test data. It should also be capable of determining whether the PEF measurement has been correctly performed. A requirement specification for a recording PEF meter was produced. A commercially available electronic PEF meter was modified to provide the functions required for accurate serial recording of the measurements produced by the patients. This is now being used in three hospitals in the West Midlands for investigations into the diagnosis of occupational asthma. In investigating current methods of measuring PEF and other pulmonary quantities a greater understanding was obtained of the limitations of current methods of measurement, and quantities being measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1993

Alterations in the pulmonary microsomal cytochrome P-450 system after exposure of rats to silica.

Because some evidence indicates that there is an increased incidence of lung cancer in silicosis, we studied the effects of exposing rats to silica on the pulmonary microsomal cytochrome P-450 system. Rats were exposed to silica by intratracheal administration, lung microsomes were obtained from untreated and silica-treated animals, and the amount of microsomal tissue, the level of total cytochromes P-450 (all isozymes), the activity of NADPH cytochrome P-450 reductase, the metabolism of two xenobiotics, and the relative amounts of cytochrome P-4502B1 and P-4501A1 were measured. Lungs from silica-treated rats were almost 2-fold heavier and contained more than 10 times more alveolar phospholipids than lungs from untreated animals, indicating that acute silicosis had been produced. In lungs from silica-treated animals, the concentration of microsomal tissue, expressed as milligrams of microsomal protein per gram of lung, was increased by more than 2-fold, and total microsomal protein content was increased by almost 5-fold relative to untreated animals. When expressed as activity or amount per milligram of protein, the microsomal concentrations of NADPH cytochrome P-450 reductase, total cytochromes P-450, 7-ethoxycoumarin (EC)-0-deethylase, and cytochrome P-4502B1 are reduced by approximately 50% in silica-treated rats. However, when expressed as total activity or amount in the lungs, all are increased by approximately 1.5- to 2.5-fold in silica-treated lungs. On the other hand, total lung 7-ethoxyresorufin (ER)-0-deethylase activity and cytochrome P-4501A1 are increased by 4- to 5-fold in silica-treated lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Expired air temperature at the mouth during a maximal forced expiratory manoeuvre.

We have studied the temperature of expired air during a maximal forced expiratory manoeuvre, because this has not previously been fully investigated and it will influence how flow and volume recording devices should be calibrated and used. Temperature was recorded with a fine thermocouple, the response time of which was determined at various gas velocities and for which a correction was made. Recordings during maximal forced expiratory manoeuvres were made on 12 normal subjects and 12 subjects with chronic airflow limitation. The thermocouple was placed in the mouthpiece, so that it was at the level of the lips during a blow. In the normal subjects, the effect of differing inhalation protocols was also determined. In the normal subjects, the mean temperature was 33.6 degrees C at peak expiratory flow (PEF), and 34.4 degrees C at 75% forced vital capacity (FVC), but fell to 33.4 degrees C at FVC. In the subjects with chronic airflow limitation, the temperature was constant at 35.0 degrees C from PEF up to 50% FVC, being significantly higher than in the normals, and fell to 33.5 degrees C at FVC. Expired air temperature up to 50% FVC was significantly negatively correlated with absolute PEF, forced expiratory volume in one second (FEV1) and FVC. In the normals, a slow inhalation through the nose raised the expired temperature by almost 1 degree C throughout the blow, whereas inhaling air at 6 degrees C did not affect expired air temperature. The expired air temperature can vary by up to 3 degrees C between individual subjects, and it is influenced by the route of inhalation and the inspired volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗