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Biomedical subjects

M L James

Publications and source records attributed to M L James.

At least 19 recordsLinked to original sources
PubMed2006

Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate.

Recently, the pyrazolopyrimidine, [11C] N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide (DPA-713) has been reported as a new promising marker for the study of peripheral benzodiazepine receptors with positron emission tomography. In the present study, DPA-713 has been labelled from the corresponding nor-analogue using [11C]methyl triflate (CH3OTf). Conditions for HPLC were also modified to include physiological saline (aq. 0.9% NaCl)/ethanol:60/40 as mobile phase making it suitable for injection. The total time of radiosynthesis, including HPLC purification, was 18-20 min. This reported synthesis of [11C]DPA-713, using [11C]CH3OTf, resulted in an improved radiochemical yield (30-38%) compared to [11C]methyl iodide (CH3I) (9) with a simpler purification method. This ultimately enhances the potential of [11C]DPA-713 for further pharmacological and clinical evaluation. These improvements make this radioligand more suitable for automated synthesis which is of benefit where multi-dose preparations and repeated syntheses of radioligand are required.

Acetamides↗
PubMed1996

Antigenic and genetic analysis of equine influenza viruses from tropical Africa in 1991.

A detailed analysis of equine (H3N8) influenza viruses isolated in Nigeria during early 1991 has been undertaken. Antigenic analysis and the complete nucleotide sequence of the HA gene of three Nigerian equine influenza viruses A/eq/Ibadan/4/91, A/eq/Ibadan/6/91 and A/eq/Ibadan/9/91 are presented and limited sequence analysis of each of the genes encoding the internal polypeptides of the virus has been carried out. These results establish that, despite the geographical location from which these viruses were isolated, two were similar to the viruses which were concurrently causing disease in Europe in 1989 and 1991 and were related to viruses that have been predominating in horses since 1985. The third was more closely related to viruses isolated from 1991 onward in Europe but also in other parts of the globe. A comparison of the nucleotide sequence of two of the viruses isolated in Nigeria (A/eq/Ibadan/4/91 and A/eq/Ibadan/6/91) with a European strain (A/eq/Suffolk/89) showed limited variation in the haemagglutinin gene which caused amino acid substitutions in one of the antigenic sites: this mutation resulted in the potential production of a new glycosylation site in antigenic site A. The other Nigerian virus (A/eq/Ibadan/9/91) showed only a single one amino acid change from another European strain (A/eq/Arundel/12369/91). The two distinct Nigerian viruses had several amino acid substitutions in the antigenic sites of the haemagglutinin glycoprotein.

Animals↗
PubMed1992

Acidic fibroblast growth factor accelerates dermal wound healing.

Acidic fibroblast growth factor (aFGF) is a potent mitogen in vitro for many cells of ectodermal and mesodermal embryonic origin including skin-derived epidermal keratinocytes, dermal fibroblasts and vascular endothelial cells. Based on the mitogenic activity for these skin-derived cells, we tested the ability of topically applied aFGF to promote healing of full-thickness dermal wounds in healthy rodents. Low doses of aFGF can produce almost a two-fold maximum acceleration in the rate of closure of full-thickness dermal punch biopsy wounds in young healthy mice and rats. The mitogen also produces a 3 to 4 day acceleration in the time to complete closure in rats. Quantitative histomorphometric analysis of wound tissue shows that aFGF induces a marked stimulation of angiogenesis, granulation tissue formation and the growth of new epithelium, but does not promote dermal contraction. Application of aFGF to linear incisions in rat skin produces a transient increase in wound tensile strength accompanied by enhanced cellularity and deposition of collagen. Therefore, aFGF functions as a pharmacological agent that can accelerate dermal wound healing in rodents and could act therapeutically to promote dermal tissue repair in humans.

3T3 Cells↗
PubMed1990

Voluntary HIV antibody testing among STD clinic patients: a pilot study.

A pilot study was conducted with the aim of measuring the acceptability of voluntary testing for human immunodeficiency virus (HIV) antibody among patients attending sexually transmissible disease (STD) clinics. Three STD clinics, two public and one private, participated in the study which was conducted over a three-month period beginning in November 1988. For each patient attending the clinics, sex, date of birth, HIV transmission category and previous HIV test result were recorded. Patients who did not request the HIV antibody test were offered testing. Of the 2356 patients who were included in the analyses, 784 (34%) requested testing. For almost all patients (97%) who requested testing, a serum sample was collected and testing completed. Approximately half (55%) of those patients who were offered the test accepted testing. Overall, 70% of patients completed HIV antibody testing. Of the major transmission categories, the acceptance rate for those offered the test was lowest among homosexual men (45%), who also had the highest rate of HIV antibody seropositivity (11%) among those tested. Of patients who reported themselves to be HIV antibody seronegative prior to the pilot study, 78% were retested during the study and seven had a positive test for HIV antibody. We conclude that voluntary HIV antibody testing is acceptable in both public and private STD clinic settings, although a substantial amount of additional resources would need to be allocated to counselling if voluntary testing is to be introduced on a routine basis.

Acquired Immunodeficiency Syndrome↗
PubMed1987

An evaluation of planned early postnatal transfer home with nursing support.

A community-based programme of planned early postnatal transfer home with the continuity of hospital nursing care was instituted in a defined geographic area of the western suburbs of Sydney in 1983. Mothers were offered the option of discharge in 24-48 hours after delivery, with home visits by a hospital midwife, subject to certain medical and social criteria. An evaluation of the programme in terms of morbidity, psychosocial impact on the family and costs was undertaken. For evaluation, a quasi-experimental study of parallel groups was designed in preference to randomized selection as it was believed that the personal choice would be fundamental to the success of the scheme. A contemporary control group was achieved with volunteer mothers who opted for the traditional five- to seven-day hospital stay. Studies of maternal response and the partner's response and adjustment were undertaken, including the administration of questionnaires that were designed to detect the presence of mild postnatal depression. No increased morbidity occurred in the early discharge group. The early discharge group performed more favourably on the questionnaire that was designed to measure their postpartum adjustment. Continued postnatal domiciliary surveillance reduces the risk that early neonatal pathological changes, especially jaundice, may be overlooked.

Adaptation, Psychological↗
PubMed1985

The need for palliative care services in a general hospital.

A population census in a major Sydney teaching hospital showed that, at any one time, between 5% and 10% of inpatients were in the terminal stages of their disease and, thus, were in need of palliative care. These needs challenge conventional patterns of practice in large hospitals and illustrate the magnitude of the problems arising from the generally observed trend towards hospitalization of the dying.

Hospitals, General↗
PubMed1984

Diflunisal-induced maternal anemia as a cause of teratogenicity in rabbits.

Diflunisal [5-(2,4-difluorophenyl)-salicylic acid] is a new analgesic antiinflammatory drug that, when administered orally to rabbits at 40 and 60 mg/kg/day, caused terata, most commonly axial skeletal defects. These same dosage levels also caused a severe maternal hemolytic anemia following a dramatic decrease in erythrocyte ATP levels. The teratogenicity, anemia, and depletion of ATP were unique to the rabbit among species examined. To test the possible causality between the teratogenic effects and anemia induced by diflunisal, a single dose of 180 mg/kg diflunisal was administered to rabbits on gestation day 5. This treatment produced an anemia that persisted through gestation day 15 in addition to causing the characteristic axial skeletal defects. Since diflunisal was cleared from maternal blood before gestation day 9, the critical day for induction of similar axial skeletal defects by hypoxia, the skeletal malformations probably resulted from maternal hypoxia secondary to anemia and not from a direct and specific effect of the drug on the embryo. In addition, we observed that the diflunisal level in the embryo was less than 5% of the peak maternal blood level probably as a result of high plasma protein binding of diflunisal in the maternal blood (greater than 98%). This relatively low placental transfer may explain the lack of diflunisal teratogenicity in rats and mice compared to aspirin which crosses the placenta more readily. These studies demonstrate that a species that exhibits unusually severe drug-specific maternotoxicity is probably an unsuitable model for the prediction of the teratogenic potential of that drug in humans.

Abnormalities, Drug-Induced↗
PubMed1983

Characterization of a specific phorbol ester aporeceptor in mouse brain cytosol.

In the presence of phosphatidylserine, [20-3H]-phorbol 12,13-dibutyrate [( 3H]PBt2) bound specifically to a single class of binding sites in mouse brain cytosol (supernatant at 100,000 X g). The dissociation constant for binding was 3.1 X 10(-9) M, and at saturation 23.2 pmol of [3H]PBt2 was bound per mg of cytosolic protein. Less than 1 pmol of [3H]PBt2 per mg bound in the absence of phospholipids. Phosphatidic acid, sphingomyelin, and phosphatidylinositol also were able to reconstitute binding activity, whereas phosphatidylcholine and phosphatidylethanolamine were relatively ineffective. [3H]PBt2 binding was inhibited by phorbol 12-myristate 13-acetate (Ki = 4.4 X 10(-11) M), phorbol 12,13-didecanoate (Ki = 7.7 X 10(-9) M), phorbol 12,13-diacetate (Ki = 4.4 X 10(-7) M) and 4-O-methylphorbol 12-myristate 13-acetate (Ki = 5.1 X 10(-7) M). The apparent Ki values of the phorbol-related diterpenes for inhibiting binding agreed reasonably closely with the values previously determined for mouse brain membrane binding. The biologically inactive derivatives phorbol (30 microM) and 4 alpha-phorbol 12,13-didecanoate (30 microM) did not inhibit binding. The aporeceptor was eluted in one peak during Ultrogel 44 column chromatography, corresponding to a molecular weight of approximately equal to 77,000. Calcium phospholipid-dependent protein kinase C activity was eluted with a profile similar to that of the cytosolic aporeceptor-binding activity.

Animals↗
PubMed1981

Home-medication monitoring among older adults: the breach in services.

Available studies reveal alarming rates of substance and medication abuse among older adults. Professionals addressing the substance and medication abuse problems of seniors have argued for a move to medication monitoring in the home. At present, however, there has been only scattered evidence to support the contention that adequate medication monitoring actually occurs. The present study reports two surveys of all home care agencies in the state of Michigan. The first study reports the medication monitoring practices of home care staff. The second study examines possible medication monitoring interventions that might be implemented in home care agencies. Those medication monitoring interventions with the highest likelihood of successful implementation among home care staff are discussed.

Aged↗
PubMed1979

Methylmethacrylate metabolism in man. The hydrolysis of methylmethacrylate to methacrylic acid during total hip replacement.

Methylmethacrylate, the monomeric component of the polymethylmethacrylate cement used in orthopedic surgery, has been shown to undergo hydrolysis to methacrylic acid during hip replacement operations. Circulating levels of methacrylic acid were comparable with those of methylmethacrylate. Concentrations of both methylmethacrylate and methacrylic acid normally lay in the range 0--15 micrograms/cc. No correlation could be discerned between changes in the concentrations of methylmethacrylate and methacrylic acid, and changes in blood pressure.

Acetabulum↗
PubMed1976

Toxicology of methyl methacrylate: the rate of disappearance of methyl methacrylate in human blood in vitro.

1. The rate of disappearance of methyl methacrylate in blood has been determined using an isotope dilution technique. 2. At a concentration of 10(-4) mol dm(-3), methyl methacrylate disappears with pseudo first order kinetics. 3. The half-life of methyl methacrylate in blood at 37 degrees C lies in the range 20--40 min. 4. The half-life showed no dependence on the age or sex of the blood donor. 5. A major, possibly the only, pathway of metabolism is by hydrolysis to methacrylic acid.

Adult↗