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Biomedical subjects

J Millar

Publications and source records attributed to J Millar.

At least 55 records · Page 3Linked to original sources

Signal intensity on MRI of basal ganglia in multiple sclerosis.

It has been reported that a relative reduction in signal intensity on T2 weighted MRI may be seen in the basal ganglia of patients with multiple sclerosis and furthermore that this is due to excessive iron deposition. The basal ganglia are, however, rarely involved clinically or pathologically in multiple sclerosis, casting some doubt on this finding. Therefore MRI was carried out in 46 patients with definite multiple sclerosis and 42 age matched controls. Contiguous, 5 mm thick axial dual echo spin-echo images of the brain were obtained on a 1.5T imager. Visual rating scales were used to measure the lesion load as well as the signal intensity of the globus pallidus, putamen, caudate nucleus, substantia nigra, red nucleus, and thalamus. There was a mild degree of low signal intensity in the patient group in the thalamus only. The signal intensity of the thalamus and putamen was never lower than that of the globus pallidus. Low signal in the basal ganglia is rarely, if ever, found in multiple sclerosis and is not a useful radiological sign.

Adolescent↗

Prevention in practice. Ethnic groups.

This article focuses on people from India, Pakistan, Sri Lanka, Bangladesh, Laos, Cambodia, Vietnam, China, and the Pacific Islands. Health care providers must be aware of cultural differences, language obstacles, poverty, social isolation, and genetic conditions when treating these ethnic groups.

Black or African American↗

The neurodyne: a simple mains-powered constant-current stimulus isolator.

Electrical stimulation of neuronal tissue is a fundamental part of many experiments in neuroscience. It is now widely accepted that to minimise stimulus artefacts stimulators need to be both constant-current devices and also electrically isolated from ground. This difficult combination of parameters is usually only obtained with battery-powered devices. Here we describe a fully isolated and constant-current mains-powered stimulus interface ('Neurodyne') which is based around a toroidal transformer. It is simple to construct and has the ability to deliver analogue signals as stimuli as well as pulses. The signal amplitude can be up to 20 mA and has a voltage compliance of over 100 V. The device has been shown to perform satisfactorily when applied to a brain slice preparation in vitro.

Animals↗

Accounting for medical variation: the case of prescribing activity in a New Zealand general practice sample.

Medical practice variation is extensive and well documented, particularly for surgical interventions, and raises important questions for health policy. To date, however, little work has been carried out on interpractitioner variation in prescribing activity in the primary care setting. An analytical model of medical variation is derived from the literature and relevant indicators are identified from a study of New Zealand general practice. The data are based on nearly 9,500 completed patient encounter records drawn from over a hundred practitioners in the Waikato region of the North Island, New Zealand. The data set represents a 1% sample of all weekday general practice office encounters in the Hamilton Health District recorded over a 12-month period. Overall levels of prescribing, and the distribution of drug mentions across diagnostic groupings, are broadly comparable to results drawn from international benchmark data. A multivariate analysis is carried out on seven measures of activity in the areas of prescribing volume, script detail, and therapeutic choice. The analysis indicates that patient, practitioner and practice attributes exert little systematic influence on the prescribing task. The principal influences are diagnosis, followed by practitioner identity. The pattern of findings suggests also that the prescribing task cannot be viewed as an undifferentiated activity. It is more usefully considered as a process of decision-making in which 'core' judgements--such as the decision to prescribe and the choice of drug--are highly predictable and strongly influenced by diagnosis, while 'peripheral' features of the task--such as choosing a combination drug or prescribing generically--are less determinate and more subject to the exercise of clinical discretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Data Interpretation, Statistical↗

Mediastinal computed tomography in a British Asian population.

We describe a retrospective review of all the thoracic computed tomography (CT) scans performed on British Asian patients at New Cross Hospital, Wolverhampton between January 1989 and April 1992. 39 patients were studied. Of 15 patients with active tuberculosis (TB), 14 showed mediastinal lymphadenopathy. In nine of these 15 patients this adenopathy was the only positive imaging finding, as neither lung parenchymal nor pleural abnormalities were detected on CT or plain chest radiograph (CXR). The patterns of node distribution and enhancement following intravenous contrast are described. We conclude that thoracic CT is useful in Asian or other high risk patients in whom active TB is suspected, but who lack definitive microbiological or CXR proof of diagnosis.

Adolescent↗

Growth of primary human acute lymphoblastic and myeloblastic leukemia in SCID mice.

The in vivo growth of 8 human primary acute lymphoblastic (ALL) and 17 primary acute myeloblastic (AML) cell populations was investigated in severe combined immunodeficient (SCID) mice. Bone marrow (BM) or peripheral blood (PB) samples, either fresh or cryopreserved, were implanted i.v. into irradiated SCID mice. The cells from 5/8 patients with ALL resulted in engraftment with systemic proliferation and dissemination leading to morbidity and mortality of the animals within 12-18 weeks from implantation. In contrast, none of the 17 AML samples resulted in sustained engraftment. Four of the 5 engrafted ALL populations have been successfully passaged into fresh recipients and phenotypic and karyotypic characteristics remain unaltered. The data presented indicate that the SCID mouse may be a useful model for studying the pathogenesis of ALL and may also enable the development and investigation of new therapies for this disease.

Adult↗

Day-case laparoscopy revisited: have post-operative morbidity and patient acceptance improved?

Previous studies of day-case laparoscopy have indicated considerable post-operative morbidity, with high incidences of nausea, vomiting and pain, often resulting in overnight admission. These studies also indicate that 30% of patients would have preferred an overnight stay. Changes in day surgery anaesthetic practice since then have included the wider use of non-steroidal analgesics and the specific use of propofol, a new short acting anaesthetic drug, with improved recovery and anti-emetic properties. We audited 74 patients who had day-case laparoscopy for diagnosis or sterilisation, and found that the incidence of nausea and vomiting was lower than any previously recorded, and mean pain scores were minimal. No patient was admitted for recovery problems, despite the inclusion of afternoon procedures; two patients only were admitted for surgical complications. Despite considerable morbidity after their return home, only 8% of patients said they would have preferred an overnight stay. Changes in anaesthetic practice would seem to make day-case laparoscopy a more acceptable procedure than previously reported.

Adult↗

When is the optimum time to harvest peripheral blood stem cells in children following standard dose chemotherapy?

The optimal time for peripheral stem cell harvest may be predicted by recovery of blood count following priming doses of chemotherapy. Bone marrow growth factors have also been used to enhance yield. Both these manoeuvres may necessitate alterations to standard treatment programmes. In order to determine whether adequate peripheral stem cell yields could be obtained without altering chemotherapy regimens, 18 children with either leukaemia or solid tumours were studied. Circulating bone marrow progenitor cells were estimated by CFU-GM cultures in soft agar. There were 8 males and 10 females, median age 5.6 years (range 2-13 years). Six out of 13 studies in leukaemia patients were done when the bone marrow contained significant leukaemic blasts, and in 2 of 9 studies in patients with solid tumours, there was active infiltration of the bone marrow. In 15 of 23 studies, a rise in CFU-GM levels to greater than 1,000 x 10(3)/l were observed following postchemotherapy aplasia. Maximum CFU-GM levels were maintained for only 1-2 days and could be predicted by the achievement of a total white cell count in the region of 2 x 10(9)/l and platelet count around 100 x 10(9)/l. Neutrophil recovery did not predict the rise in CFU-GM levels. A rapid rise in monocyte levels also preceded maximum CFU-GM levels. Predictably, the CFU-GM counts were lower in patients who were heavily pretreated, but in several children, the counts were sufficient to predict an adequate harvest to be used in conjunction with bone marrow autotransplantation. It is concluded that in children with active bone marrow recovery, chemotherapy priming or the use of bone marrow growth factors may not be necessary to achieve useful stem cell harvests.

Adolescent↗

Patch clamp studies on the kinetics and selectivity of N-methyl-D-aspartate receptor antagonism by memantine (1-amino-3,5-dimethyladamantan).

Memantine (1-amino-3,5-dimethyladamantan) was tested as an antagonist of N-methyl-D-aspartate (NMDA) receptors on cultured superior collicular and hippocampal neurones using the patch clamp technique and its actions were compared to those of Mg2+ ions, ketamine, dextrorphan, dextromethorphan, phencyclidine and dizocilpine (MK-801). Memantine (2-33 microM) concentration-dependently antagonized responses to NMDA 100 microM with an IC50 of 2.92 +/- 0.05 microM. In contrast, current responses to (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (L-AMPA 50-100 microM) and gamma-amino butyric acid (GABA 10 microM) were unaffected by Memantine 8 microM. Memantine 8 microM caused a non-parallel shift of the NMDA concentration-response curve to the right in a manner indicative of uncompetitive open channel block. The effects of memantine were similar to ketamine in that both antagonists were weakly use- and strongly voltage-dependent. In contrast, MK-801, phencyclidine and dextrorphan showed much slower kinetics that was reflected in their marked use- and weaker voltage-dependency. The antagonistic effects of memantine were not reversed by increasing concentrations of glycine (0.1-100 microM) ruling out the possibility of an interaction of memantine with the strychnine-insensitive glycine modulatory site associated with the NMDA receptor-channel complex. Memantine (1-100 microM) also selectively antagonized responses to NMDA (40 microM) in the cortical wedge preparation with IC50 of 12.9 +/- 1.5 microM.

Animals↗

Simultaneous "real-time" electrochemical and electrophysiological recording in brain slices with a single carbon-fibre microelectrode.

Many previous studies have demonstrated the value of carbon-fibre microelectrodes (CFMs) for single-unit activity recording and for fast cyclic voltammetry. In this report we show that these two independent methodologies can be combined at a single CFM and used to study simultaneous electrochemical and electrophysiological events in brain slices. In superfused slices of rat locus coeruleus, dorsal raphe and substantia nigra, we were able to record stable electrophysiological signals and stimulated monoamine efflux for periods of at least 2 h, thereby allowing quantitative pharmacological interventions. The simultaneous recording of amine efflux and unit activity at the same locus facilitates comparison of drug effects at pre- and post-synaptic sites. Furthermore, the system described here uses commercially available instrumentation. The circuitry is described and examples of its application are shown.

Animals↗

The effects of iontophoretic clonidine on neurones in the rat superficial dorsal horn.

Clonidine and glutamate were applied by iontophoresis to cells in the superficial 3 laminae of the spinal cord in the anaesthetised rat. Only cells that were excited by glutamate (up to 150 nA) were studied. Some spontaneously active cells could be excited by clonidine (up to 100 nA). However, when applied to non-spontaneous cells, clonidine had no effect at any dose level. When ejected in a cyclic pattern alternating with glutamate ejection, clonidine powerfully amplified the response of many cells to the glutamate stimulus. This effect was seen only on cells with small-amplitude spikes and low-threshold (LT) receptive fields. The amplification was often sustained and could outlast the clonidine ejection by several minutes. Clonidine had a long-lasting inhibitory effect on the responses to glutamate of cells with high-threshold (HT) or wide-dynamic-range (WDR) receptive fields. Clonidine appeared to selectively decrease the responsiveness of WDR cells to noxious stimulation. It is suggested that an amplification of the response of LT cells to other excitatory inputs could contribute to the analgesic action of clonidine.

Animals↗

Gut protection by cyclophosphamide "priming" in patients receiving high-dose melphalan--effect of drug scheduling.

A "priming" injection of cyclophosphamide (400 mg/m2 given i.v. on day -7) has been shown to reduce intestinal permeability and thus gut toxicity in patients receiving high-dose melphalan. To determine the optimal timing for this injection, patients receiving 200 mg/m2 melphalan with an autologous bone marrow transplant were randomly assigned to receive cyclophosphamide at 5, 7 or 9 days before the melphalan. The median percentage of [51Cr]-ethylenediaminetetraacetic acid excretion was similar (9.1% vs 7.1% vs 7.7%, respectively), with equivalent duration of WHO grade 2-4 mucositis and diarrhoea being recorded for each group. Thus, the timing of the cyclophosphamide prime is not critical, and the priming injection may be given between 5 and 9 days prior to high-dose melphalan.

Bone Marrow Transplantation↗

Continuous scan cyclic voltammetry (CSCV): a new high-speed electrochemical method for monitoring neuronal dopamine release.

This report describes a new form of fast cyclic voltammetry which samples electrochemical reactions of dopamine at one every 10 ms. We have called this technique 'continuous scan cyclic voltammetry' (CSCV). The technique uses a carbon fibre microelectrode which is connected to a continuously active sine-wave source. The applied voltage is a 100 Hz precision sine wave. Faradaic signals due to cycles of continuous oxidation and reduction of dopamine at the tip of the electrode can be observed superimposed on a fixed charging current. The technique is insensitive to moderate concentrations of ascorbate as a depletion zone for ascorbate is rapidly established around the electrode. In a brain slice preparation the technique can show the time course of dopamine release on a millisecond time scale. It should prove a valuable new tool for the investigation of dopamine transmission in the brain.

Animals↗

Vitamin C--the primate fertility factor?

The loss of the ability of primates and man to synthesise ascorbic acid (vitamin C) is usually seen as an evolutionary accident, with no benefit to the species. This paper argues that the loss of this biosynthetic ability has allowed vitamin C to act as a 'fertility factor' in primate societies. It is argued that the requirement for vitamin C increases with age, and so in times of food shortages the older members of society suffer higher mortality than the younger. This reduces the median age of the population towards the younger and most fertile members, and so enables the population to regrow rapidly when food resources are restored.

Aging↗