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Biomedical subjects

M Hayes

Publications and source records attributed to M Hayes.

At least 73 records · Page 4Linked to original sources
PubMed1995

Quantitative determination and pharmacokinetics of a new antipsychotic (CGS 13429A) in human plasma using capillary gas chromatography/mass spectrometry.

A quantitative analytical method is described for the determination of a new antipsychotic (CGS 13429A) in human plasma. The method relies on capillary gas chromatography/mass spectrometry in the positive chemical ionization mode, utilizing ammonia reagent gas. The limit of quantification (LOQ) was 0.1 ng ml-1 and the method was validated over a concentration range of 0.1-50 ng ml-1. The method was used to measure CGS 13429A plasma concentrations following the administration of single oral ascending doses ranging from 0.1 to 10 mg in healthy male volunteers. The drug was rapidly absorbed (Tmax ranged from 1.1 to 3.7 h) and showed a mean terminal elimination half-life of 8.1 h, which was independent of dose. Area-under-the-curve (AUC) along with Cmax values were proportional to the administered dose.

Adult↗
PubMed1995

American National Standard for nonautomated sphygmomanometers. Summary report.

The Association for the Advancement of Medical Instrumentation develops voluntary standards for medical devices so that manufacturers might provide information on their product and basic safety and performance criteria that should be considered in qualifying the instrument for clinical use. American National Standards are generated through a consensus process by committees of experts in research, development, and design from user, industry, and government communities. Draft standards are made available for public review and become American National Standards after review by the American National Standards Institute. This report is a summary of the American National Standard that establishes both the safety and performance requirements of pneumatic and other nonautomated sphygmomanometers (especially mercury gravity and aneroid sphygmomanometers) used in the indirect measurement of blood pressure. This standard was developed by a consensus panel from academia, industry, and government; it updates the previous standard approved by the American National Standards Institute in 1986. This summary report does not cover all of the provisions of the revised 1994 American National Standard, thus users, researchers, and instrument designers should refer to the standard for detailed requirements.

Blood Pressure Determination↗
PubMed1995

Three cases of pulmonary aspergilloma in adult patients with cystic fibrosis.

Pulmonary aspergillomas usually occur when Aspergillus fungi colonise lung tissue previously damaged by disease. Pulmonary aspergillomas in three adult patients with cystic fibrosis are reported--an association not previously described. At the time of diagnosis all three patients had previous long term colonisation with Aspergillus fumigatus and severe advanced destructive lung disease with lung function less than 25% of the predicted normal values. It is likely that, with increasing survival in cystic fibrosis, more adult patients will develop aspergillomas during the protracted phase of end stage lung disease that characterises the terminal years of this condition.

Adult↗
PubMed1995

Native gel electrophoresis and isoelectric focusing of a 64-kilodalton eye muscle protein shows that it is an important target for serum autoantibodies in patients with thyroid-associated ophthalmopathy and not expressed in other skeletal muscle.

Although sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting are widely used to detect serum antibodies in patients with autoimmune disorders, this procedure unfolds and denatures proteins and may alter antibody-binding sites. We have used a gentle protocol for the preparation and purification of a 64-kilodalton (kDa) eye muscle (EM) membrane antigen associated with thyroid-associated ophthalmopathy (TAO) for use as antigen in immunoblotting. Pig EM membrane proteins were prepared from crude homogenates by high speed centrifugation and solubilized by hand homogenization. These native membrane proteins (NMprot) were then electrophoresed on an 8.5% polyacrylamide gel in the absence of SDS, reducing agents, or urea, and proteins from individual bands were eluted, applied to standard SDS-PAGE, and immunoblotted with selected TAO patient sera. A prominent 64-kDa protein, present in most of the bands, was recognized by autoantibodies in sera from 35% of the patients with TAO and 47% of those with Graves' hyperthyroidism without evident ophthalmopathy, but in only 4% of normal subjects. To further purify the 64-kDa protein and increase the sensitivity of immunoblotting, NMprot were separated by isoelectric focusing (IEF) in the absence of SDS, reducing agent, and urea. The 64-kDa protein appeared mainly in IEF fraction 7 and had an isoelectric point of 6.1-6.2. Similar results were found for a human EM protein of 64 kDa. Sera from groups of patients and normal subjects were tested in immunoblotting against a pig EM 64-kDa protein prepared from NMprot and purified in IEF. Tests were positive in 67% of patients with TAO, in 37.5% of those with Graves' hyperthyroidism without eye disease, in 11% of patients with Hashimoto's thyroiditis without eye disease, and in 9% of normal subjects. The 64-kDa protein was not found in other skeletal muscle. The demonstration that a native 64-kDa protein that is specifically targeted by autoantibodies in the serum of patients with TAO is expressed in EM, but not other skeletal muscle, greatly enhances its possible significance in the pathogenesis of this eye disorder.

Adult↗
PubMed1995

Microbiology and immunology in patients with leg ulcers.

Aspects of the bacteriological and immunological status of patients with leg ulcers who also need podiatric treatment have been examined. Qualitative and quantitative bacteriological analyses of 52 patients have provided values for the numbers and types of bacteria present. A simple survey of the immunological status of 11 of the patients was also undertaken. The results of the bacteriological survey are consistent with those of other workers, while the results of the immunological studies are sufficiently heterogeneous to warrant a further dedicated study of a longitudinal nature. Because of the numbers of bacteria isolated, the range of bacterial species identified and uncertainties about the immunological status of the patients and others attending multi-clinic sites, it is suggested that in order to safeguard all patients, personnel and the immediate environment, clearly defined special procedures for infection control should be in place.

Adult↗
PubMed1994

The geographic variation of cancer incidence in Ontario.

OBJECTIVES: Our objectives were (1) to describe an analysis of the spatial pattern of cancer incidence in Ontario and (2) to discuss the quality of data in the Ontario Cancer Registry with respect to the accuracy of local cancer rates. METHODS: Cancer incidence rates were calculated for 22 cancer sites in 49 counties of Ontario during 1976 to 1986. Capture-recapture methods were used to estimate completeness of case registration, and completeness of residence information was also assessed. Spatial autocorrelation was used in measuring the geographic pattern of incidence rates. Comparisons were also made between sexes and with earlier data from 1966 to 1975. RESULTS: The quality of the geographic data in the registry appeared good, and corrections for incomplete or inaccurate registration had little impact. About one third of the sex-site combinations showed some evidence of spatial patterning in the cancer rate. Particularly strong regional variation was noted for cancers of the stomach, lung, uterus, and prostate. CONCLUSIONS: The analysis revealed a number of cancers with significant spatial patterning of risk. Further work is needed to relate the cancer data to other information on potential life-style and environmental factors.

Female↗
PubMed1993

Collagen-linked fluorescence in human atherosclerotic plaques.

Advanced glycosylation endproducts (AGE) are intraprotein crosslinks which form in the late stages of the Maillard (browning) reaction. It is unknown whether local changes in AGE-modified collagen occur within arteries. We measured AGE-modified collagen as collagen-linked fluorescence (CLF) in human arterial tissue and in various forms of atherosclerotic plaque. All tissues showed single fluorescence peak at excitation wavelength 340 nm and emission wavelength 420-440 nm. CLF in the aorta was 27.9 +/- 8.5 units/mg, in the coronary arteries 25.9 +/- 6.3 units/mg and in the tendon 47.8 +/- 11.5 units/mg. CLF in the skin correlated with CLF in the aorta (r = 0.467, P = 0.025) but not with CLF in coronary arteries (P = 0.935). In areas of aorta covered by superficial plaque, CLF was decreased compared with adjacent, atheroma-free segments (22.2 +/- 5.2 units/mg vs. 27.9 +/- 8.5 units/mg; P = 0.01). The CLF of collagenous plaques correlated with CLF of the atheroma-free regions. Individuals with low to moderate atheroma had lower (20.0 units/mg) CLF in superficial atherosclerotic plaques than patients with severe atheroma (22.5 units/mg; P = 0.0466). Our results indicate that local changes in vascular AGE-collagen concentration occur in atherosclerosis. This finding may have pathogenetic significance in atherosclerosis.

Aged↗
PubMed1993

Successful management of paraprotein-associated peripheral polyneuropathies by immunoadsorption of plasma with staphylococcal protein A.

Two patients with paraprotein-associated peripheral polyneuropathy were treated successfully using immunoadsorption of patient's plasma with staphylococcal protein A. Both had previously been treated with immunosuppressive agents or plasma exchange, and were rapidly relapsing at the time of their protein A immunoadsorption therapy. One patient was treated "on-line" with a blood cell separator, and one was treated "off-line." Both responded well to therapy with minimal toxicity. Serum levels of circulating immune complexes were elevated in one patient and remained so during and after therapy. Immunoadsorption with protein A should be investigated as a therapeutic option for patients with paraprotein-associated peripheral polyneuropathy. The therapy is relatively easy to administer, particularly "off-line," and was well tolerated by our patients. More experience, including formal clinical trials, will be required to properly define the indications for, and mechanism of response to, this therapy.

Aged↗
PubMed1992

Isolation and characterization of four CSF-1-dependent placental macrophage cell lines.

By selection and cloning in the presence of colony-stimulating factor 1 (CSF-1), we have obtained from separate explants of individual 12- or 13-day mouse placentas four clonal cell lines dependent on CSF-1 for survival and growth in culture. All four cell lines show characteristics consistent with their derivation from placental macrophages. We describe the effects of CSF-1 on growth, morphology, and CSF-1 receptor phosphorylation. One cell line, JPL2A, which shows relatively complete growth arrest in the absence of CSF-1, was characterized in detail with respect to the effects of CSF-1 on DNA synthesis and protein turnover and its response to the duration of CSF-1 stimulation. In contrast to previous studies, our results suggest that extended stimulation leads to continuous recruitment of cells competent to reenter the cell cycle. These findings are discussed in terms of growth factor effects on the cell cycle and the usefulness of these cell lines for further study of growth factor signal transduction in macrophages.

Animals↗
PubMed1992

The relationship between cardiac reserve and survival in critically ill patients receiving treatment aimed at achieving supranormal oxygen delivery and consumption.

The relationship between survival and cardiac responsiveness to therapy aimed at achieving supranormal values for cardiac index, oxygen delivery and oxygen consumption (cardiac index (CI) > 4.5 l/min/m2, oxygen delivery (DO2) > 600 ml/min/m2, and oxygen consumption (VO2) > 170 ml/min/m2), has been investigated in a heterogeneous group of critically ill patients. Thirty-two patients were prospectively studied and divided into survivors and non-survivors. Cardiac reserve was assessed by determining changes in CI, left ventricular stroke work index (LVSWI) and cardiac power output (CPO) in response to optimal fluid administration and inotropic stimulation with dobutamine. On admission LVSWI and CPO were significantly higher in survivors (P < 0.05), despite no significant differences in pulmonary artery occlusion pressure (PAOP). In response to fluid CI, CPO and LVSWI increased significantly in survivors (P < 0.01), but not in non-survivors. Following optimal fluid administration, survivors achieved significantly higher values for CI, LVSWI (P < 0.01), and CPO (P < 0.001) than non-survivors. At maximum resuscitation all three variables were significantly higher in survivors than in non-survivors (P < 0.001). The dose of dobutamine administered to non-survivors (median (range) 100 (5-200)) was significantly greater (P < 0.001) than that given to the survivors (median (range) 10 (0-25)). The dose of dobutamine was limited by complications in 12 of the non-survivors. These observations suggest that cardiac reserve is an important determinant of outcome following critical illness. In unresponsive patients attempts to achieve supranormal oxygen delivery and consumption with massive inotropic support may not only be ineffective but frequently precipitates tachydysrhythmias and myocardial ischaemia.

Adult↗
PubMed1991

Determination of CGS 16617 and stable isotope-labeled CGS 16617, an angiotensin-converting enzyme inhibitor, in human plasma by gas chromatography/mass spectrometry.

An analytical method has been developed for the simultaneous determination of a novel orally active angiotensin-converting enzyme inhibitor (CGS 16617) and a stable isotope-labeled analog. Both compounds are isolated from human plasma using an ion-exchange column, derivatized with pentafluoropropionic anhydride and pentafluoropropanol, and analyzed by gas chromatography/mass spectrometry. After splitless injection on a methyl-silicon column, the compound is detected using negative ion chemical ionization with nitrous oxide as a reagent gas. CGS 16617 labeled with four deuteriums and two 13C is used as an internal standard. The accuracy and precision of the method, expressed as the overall mean +/- SD recovery obtained from two sets of 36 quality-control samples used during a clinical study (concentration range 0.2-100 ng ml-1 plasma), was 96.1 +/- 16.2% for unlabeled drug and 97.6 +/- 14.4% for the D4-labeled drug (concentration range 0.2-100 ng ml-1 plasma). The limit of quantification using 1 ml plasma is 0.2 ng ml-1 for both labeled and unlabeled drug.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Antenatal prediction of mother-infant difficulties.

A prospective study of 143 "low risk" pregnant women expecting their first baby was conducted in Newcastle, Australia. The study was designed to examine the contribution of a woman's perception of her own childhood experiences, her trait anxiety level, socioeconomic status, and social support network to difficulties in her relationship with her baby during the baby's first year. The women were initially interviewed during pregnancy and followed up 3 and 12 months postpartum. Follow-up measures included the Dimensions of Perinatal Adjustment, the Neonatal Perception Inventory, the Ainsworth Strange Situation, and information from hospital records, family doctors, and baby health centre sisters. Women who perceived their social network as less supportive during pregnancy were likely to see their one-year-old babies (p less than .05) as more difficult. The other antenatal measures were not significantly predictive of outcome.

Adolescent↗