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Biomedical subjects

M MacNeil

Publications and source records attributed to M MacNeil.

17 recordsLinked to original sources
PubMed1999

High-dose chemotherapy: is it standard management for any common solid tumor?

High-dose chemotherapy with stem-cell support had as its basis the observation of dose-response relationships for many chemotherapeutic agents in laboratory models. The rationale to explore high-dose treatment in the clinic was further enhanced by several retrospective reviews in the 1980s which suggested delivered dose intensity of treatment was an important determinant of patient outcome. The availability of hematopoietic growth factors and technologic advances in the efficiency of stem-cell collection and administration have made the evaluation of exploring high-dose therapy safe and feasible. However, real questions remain regarding the apparently superior results of this treatment in the management of solid tumors. This paper reviews the results of high-dose chemotherapy in breast, ovarian and small cell lung cancers. Firstly the evidence for a dose-response relationship to chemotherapeutic agents in the 'standard' dosage range is examined. Secondly results of non-randomized and, where available, randomized trials of high-dose chemotherapy (HDCT) with stem-cell support are summarized and finally conclusions regarding the weight of the evidence for use of HDCT as 'standard' treatment are given. In none of these tumors is there sufficient evidence from randomized trials to consider HDCT a standard to be offered to all patients with a given stage of disease. The apparent benefit of HDCT seen in phase II trials could well be explained by such phenomena as stage shifts and patient selection. Many randomized trials in ovary and breast cancer are either ongoing or presented only as abstracts so final results must be awaited to quantify the benefit, if any of HDCT. It is acknowledged, however, that some practitioners already utilize this treatment. We speculate about the differences in philosophical approaches to cancer treatment which might contribute to early acceptance of novel therapies in the absence of adequate randomized data.

Antineoplastic Agents↗
PubMed1997

Fever, lymphadenopathy, eosinophilia, lymphocytosis, hepatitis, and dermatitis: a severe adverse reaction to minocycline.

A 17-year-old female patient who had been taking oral minocycline (50 mg twice daily) for 3 weeks for acne developed an eruption that progressed to an exfoliative dermatitis. This illness was also characterized by fever, lymphadenopathy, pharyngitis, a leukemoid reaction, lymphocytosis, eosinophilia, hepatitis, and noncardiogenic pulmonary edema. Dramatic improvement followed institution of corticosteroid therapy. Studies for infectious and collagen vascular diseases were negative. This severe illness was likely caused by minocycline, and we speculate that minocycline may have acted as a superantigen, causing lymphocyte over-activation and massive cytokine release.

Acne Vulgaris↗
PubMed1997

From nurse to teacher: recognizing a status passage.

The purpose of this study is to examine the career trajectories of nurse teachers. The main focus of the study is the process of transition from nurse to teacher. The study looks at the anticipations, expectations, contrasts and changes encountered by nurse teachers when first embarking on the role. The interest lay in obtaining the teachers' view of their career trajectories and their experience of status transition. An ethnographic approach was adopted, and in-depth interviews were carried out with nurse teachers, to capture the breadth and depth of the teachers' experience. The teachers all volunteered to participate in the study, so are in no way statistically representative of their professional group. In analysing the data the mode of qualitative analysis called 'grounded theory' was modified and adopted. In this approach data collection, analysis and theory stand in reciprocal relationship to each other. The study operates at two levels. It relates to issues which appear to be meaningful only to the nurse education audience, but it also engages with the more anthropological concern of status passage. Finally, the results are discussed highlighting the many areas which were identified as causing concern and using the concept of 'identity' to offer an explanation for the 'troublesome-duality' experienced by nurse teachers.

Adaptation, Psychological↗
PubMed1995

Project 2000: a modular approach to course planning.

Project 2000 has given nurse educators an opportunity to consider and plan educational programmes that will endure until the year 2000 and beyond. The United Kingdom Central Council for Nursing, Midwifery and Health Visiting (1986) highlighted the need for preparing practitioners for uncertainty by developing structures that adapt to rapid change. This includes planning smaller units of study, that are accessible and allow for credit transfers. This article describes the development of a semester based, modular programme of study, for Project 2000. The idea of modularity, both from the higher education and nurse education perspective is examined. An outline of the course is offered and for the benefit of colleagues who may be considering embarking on a similar remit, areas of difficulty encountered on implementation are highlighted with some resolutions.

Curriculum↗
PubMed1993

Duration of amyotrophic lateral sclerosis is age dependent.

Since 1985, we prospectively followed 246 patients with ALS. The relationship between the age of developing neurological impairment and disease duration was analyzed in 138 patients (86 men and 52 women) who died. Mean disease duration was 4.0 +/- 3.8 years for men and 3.2 +/- 2.5 years for women. There was an inverse, exponential, relationship between onset age and duration (goodness-of-fit P > 0.05). Mean duration at onset age < or = 40 years was 8.2 +/- 5.0 years compared with 2.6 +/- 1.4 years for patients aged 61 to 70 years (P > 0.001). The ratio of young (< or = 40 years) men to women was 3.6:1. When matched for age, disease duration was the same for patients with bulbar and nonbulbar onsets. We conclude that onset age, but not sex, is the most significant predictor determining disease duration in ALS. Longer survival in younger patients probably reflects their greater neuronal reserve.

Adult↗
PubMed1993

Receiver operating characteristic curve analysis in the prediction of carpal tunnel syndrome: a model for reporting electrophysiological data.

Receiver operating characteristic (ROC) curves were used to predict the risk of carpal tunnel syndrome (CTS). Patients were classified clinically as: (1) normal exam and no symptoms (169 hands); (2) having a motor and/or sensory deficit typical of CTS (115 hands); (3) having a history characteristic of CTS (156 hands); and (4) nondiagnostic symptomatology (122 hands). Electrophysiological studies consisted of median and ulnar motor, sensory, and palmar measurements. Group mean values for group 1 differed significantly from groups 2 and 3 (not 4) for all measurements, but values overlapped considerably. Median distal motor latency (DMML) combined with median-ulnar palmar latency differences (MUPLD) had significantly superior discriminant power than other measurements and correlated highly for all groups (r values = 0.71-0.73). These variables were used to construct ROC curves and prediction tables. The approach used allows one to assign a percentage risk of having a CTS and can be used in outcome studies.

Adult↗
PubMed1992

Quality control in nerve conduction studies with coupled knowledge-based system approach.

Contemporary equipment used for nerve conduction studies is usually capable of computerized measurement of latency, amplitude, duration, and area of nerve and muscle action potentials and resulting conduction velocities. Abnormalities can be due to technical error or disease. Identification of technical error is a major element of quality control in electromyography, and artificial intelligence could be useful for this purpose. We have developed a coupled knowledge-based prototype system (QUALICON) to assess the correctness of recording and stimulating characteristics in routine conduction studies. QUALICON extracts numeric features from CMAPs or SNAPs, which are translated into symbolic form to drive a Bayesian network. The network uses high-level knowledge to infer the quality of stimulating and recording electrode placement as well as polarity and stimulus strength making recommendations as to the likely technical error when abnormal potentials are detected. A preliminary assessment shows that QUALICON performs as well as manual assessment performed by professionals.

Action Potentials↗
PubMed1979

Evidence for a noncholinergic site for nicotine's action in brain: psychopharmacological, electrophysiological and receptor binding studies.

In an effort to investigate the possibility of noncholinergic nicotine sites within the brain, psychopharmacological, biochemical and eletrophysiological studies were undertaken with nicotine and various newly synthesized derivatives of nicotine and piperidine. When 1-10 micrograms of (-)-nicotine was injected into the region of the lateral ventricle of rats through implanted cannulae, there resulted a characteristic prostration immobilization syndrome, which was accompanied by seizures and tremors at the higher dose range. The (+)-isomer possessed 1/100 the activity of the natural (-)-isomer. The syndrome could be prevented by pre-treatment, intraventricularly, with the N-benzyl and N-p-nitrophenylazido derivates of either nicotine or piperide. A variety of neurotransmitters and psychotropic agents, including acetylcholine and anticholinergic drugs, were without antagonistic action. After nicotine, recordings of spontaneous electrical activity from electrodes chronically implanted into the region of the dorsal hippocampus showed a marked decrease in the amplitude and number of 6-8 sec discharges, and the change was correlated with the behavioral syndrome. Receptor binding studies were performed with rat brain slices and various neural preparations using 3H-nicotine, 125I-alpha-bungarotoxin and 14C-d-tubocurarine as ligands; and only with 3H-nicotine was it possible to demostrate any competitive effect with the various nicotine and piperidine antagonists. It was possible to demonstrate stereospecific or specific nicotine binding to only glass fiber filters and, to a lesser extent, brain slices, but not to cell-free preparations. It was concluded that there existed specific noncholinergic sites for nicotine's action which have not been hitherto described.

Animals↗
PubMed1978

Phospholipid changes in synaptic membranes by lipolytic enzymes and subsequent restoration of opiate binding with phosphatidylserine.

A study has been made of the role of phosphatidylserine in stereospecific opiate binding to neural membranes, utilizing specific lipolytic enzymes to attack the lipid. At very low concentrations phospholipase A2 from bee venom will preferentially hydrolyze C22:6-fatty acid; and even after a few percent of the total phosphatidylserine is hydrolyzed, opiate binding is greatly inhibited. The addition of brain phosphatidylserine will restore opiate binding; however, when the inhibition approaches 50% restoration is only partial. Exposure of membranes to phosphatidylserine decarboxylase will partially inhibit opiate binding; and the binding returns to the control level after the addition of phosphatidylserine. The partial inhibition of opiate binding by low concentrations of Triton X-100, which presumably remove lipids, can be partially reversed by phosphatidylserine. The binding of 3H-naloxone, an opiate antagonist, is similar to agonists in its behavior towards phospholipases and phosphatidylserine; however, binding of naltrexone, also an antagonist, is far less responsive. It is concluded that the phosphatidylserine associated with the opiate receptor is the C18:0, 22:6-diacyl form, which is closely associated with protein.

Animals↗
PubMed1977

Enhancement of opiate binding by various molecular forms of phosphatidylserine and inhibition by other unsaturated lipids.

A study was undertaken on the possible involvement of phospholipids on stereospecific opiate binding to a rat brain membrane fraction comprised mainly of synaptic membranes. The addition of acidic phospholipids such as phosphatidylserine, phosphoinositides, and phosphatidic acid significantly enhanced opiate binding. With the exception of phosphatidylserine, when the acidic phospholipids contained a polyunsaturated acyl group, they were actually inhibitory, along with neutral phospholipids derived from brain. Both the C18:0, C18:1 form (derived from myelin) and the C18:0, C22:6 form of phosphatidylserine (derived from synaptic membranes) produced as much as a 45% enhancement in opiate binding. Unsaturated fatty acids were highly inhibitory, the degree of inhibition being related to the degree of unsaturation. Both phospholipase A and C were inhibitory; and the inhibitory effect of A could not be prevented by albumin or overcome with the addition of phosphatidylserine. With the use of the cross-linking agent, dinitrodifluorobenzene, it could be demonstrated that the phosphatidylserine of synaptic membranes appeared to be preferentially associated with membrane protein. The enhancement of opiate binding by phosphatidylserine diminished with increasing degree of cross-linking.

Animals↗
PubMed1976

Stereospecific opiate binding in human erythrocyte membranes and changes in heroin addicts.

Stereospecific opiate binding has been demonstrated in human erythrocyte membranes, having a Kd of 9-10(-9) M. In most respects the binding characteristics resemble those of synaptic membranes. These included the correlation of binding affinity and pharmacological potency of opiates; competition by naloxone; inhibition by Ca2+ and Na+; and sensitivity to phospholipases and trypsin. A comparison of stereospecific opiate binding in control human subjects and heroin addicts revealed a 43% increase in the addict group.

Adult↗