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Biomedical subjects

A Johnstone

Publications and source records attributed to A Johnstone.

At least 19 recordsLinked to original sources
PubMed2006

Chronic benzylpiperazine (BZP) exposure produces behavioral sensitization and cross-sensitization to methamphetamine (MA).

BACKGROUND: Like other psychostimulant drugs, acute exposure to benzylpiperazine (BZP) increases dopaminergic neurotransmission, producing hyperactivity and stereotypy. The consequences of repeated BZP exposure have not however been investigated. The effects of acute and repeated BZP and methamphetamine (MA) exposure on locomotor activity and stereotypy were measured in order to determine whether there was sensitization and cross-sensitization between these two psychostimulant drugs. METHODS: The effects of acute treatment with MA (0.0, 0.5, 1.0 and 2.0 mg/kg, intraperitoneal (IP)) or BZP (0.0, 5.0, 10.0, 20.0 and 40.0 mg/kg, IP) on locomotor activity and stereotypy were determined. Effects of repeated exposure were determined in other groups that received five daily injections of 2.0 mg/kg MA, 20.0 mg/kg BZP or vehicle. Following a 2-day withdrawal period, rats from each treatment group received either a low dose MA (0.5 mg/kg) or BZP (10.0 mg/kg). RESULTS: MA and BZP produced dose-dependent hyperactivity and stereotypy. Repeated MA and BZP resulted in a potentiated locomotor but not stereotypy response. Following the withdrawal period, MA pretreated rats exhibited a sensitized locomotor and stereotypy response to the low dose MA and a conditioned response to saline. BZP pretreated rats also demonstrated a sensitized locomotor response to the low dose of BZP and MA. CONCLUSIONS: The present findings indicate that repeated exposure to BZP results in sensitization and cross-sensitization to MA.

Animals↗
PubMed2005

A new design concept for wrist arthroplasty.

The wrist joint is frequently affected by arthritis, which leads to pain, loss of function and ultimately deformity. Various designs of wrist arthroplasty have been introduced to attempt to relieve pain and provide a functional range of motion. The first generation of wrist implant was a one-piece silicone elastomer. Later generations have designs that have two parts that articulate against each other. However, wrist implants have not achieved the same clinical success to date, compared with hip and knee implants, and there is a high revision rate associated with them. This paper describes a new design concept for wrist arthroplasty, based around the idea of combining the principles of an articulating implant with that of a flexible elastomer implant. The design consists of assembling a radial, carpal/metacarpal, plate and flexible parts together. The radial and carpal/metacarpal parts are to be made from ultra high molecular weight polyethylene. The bearing surfaces of the radial and carpal/metacarpal parts articulate against the flat surfaces of the plate, made from cobalt chrome molybdenum alloy. The radius on the bearing surface of the radial part enables flexion/extension, while the radius on the carpal/metacarpal surface enables radial/ulnar deviation. The articulation of the carpal/metacarpal part against the plate also allows for rotation as well as flexion/extension. The flexible part, made from Elast-Eon, which is a silicone polyurethane elastomer, is inserted through the hole of the plate and into the holes of the radial and carpal/metacarpal parts.

Arthroplasty↗
PubMed1999

Beagle 2: a proposed exobiology lander for ESA's 2003 Mars Express mission.

The aim of the proposed Beagle 2 small lander for ESA's 2003 Mars Express mission is to search for organic material on and below the surface of Mars and to study the inorganic chemistry and mineralogy of the landing site. The lander will have a total mass of 60kg including entry, descent, and landing system. Experiments will be deployed on the surface using a robotic arm. It will use a mechanical mole and grinder to obtain samples from below the surface, under rocks, and inside rocks. Sample analysis by a mass spectrometer will include isotopic analysis. An optical microscope, an X-ray spectrometer and a Mossbauer spectrometer will conduct in-situ rock studies.

Equipment Design↗
PubMed1998

Preclinical and phase I clinical studies with the nonclassical antifolate thymidylate synthase inhibitor nolatrexed dihydrochloride given by prolonged administration in patients with solid tumors.

PURPOSE: A phase I, multicenter trial of the thymidylate synthase (TS) inhibitor THYMITAQ (nolatrexed dihydrochloride; Agouron Pharmaceuticals, Inc, San Diego, CA) given by 5-day continuous infusion was performed to establish the maximum-tolerated dose (MTD) and to investigate pharmacokinetics, pharmacodynamics, and antitumor effects. METHODS: In vitro and in vivo preclinical studies demonstrated increased activity with prolonged nolatrexed exposure. In 32 patients, nolatrexed was given as a 5-day infusion at 96 to 1,040 mg/m2/d for 5 days. Pharmacokinetics were determined from high-performance liquid chromatography (HPLC) analyses of plasma and urine. In addition to studying toxicity, plasma deoxyuridine (UdR) elevations were measured as a marker of TS inhibition. RESULTS: The MTD was 904 mg/m2/d for 5 days and the recommended phase II dose is 800 mg/m2/d for 5 days. The dose-limiting toxicity was neutropenia with clinically significant thrombocytopenia and mucositis. These antiproliferative toxicities of nolatrexed were predictable and reversible. A partial response that lasted 3 months occurred in a patient with metastatic colorectal cancer. Pharmacokinetics were nonlinear, with the median plasma clearance (CI) decreasing from 151 mL/min/m2 (range, 124 to 211) at 96 mg/m2/d for 5 days to 49 mL/min/m2 (range, 30 to 84) at 768 mg/ m2/d for 5 days. The half-life (t1/2) was 173 minutes (range, 43 to 784) and 18% (range, 9% to 35%) of the dose was excreted unchanged in the urine. Plasma UdR increased, but returned to pretreatment levels after the end of infusion. Hematologic toxicity was significantly related to nolatrexed plasma concentrations and dose. CONCLUSION: Nolatrexed can be safely administered to patients at a dose of 800 mg/m2/d over 5 days by continuous intravenous infusion and this schedule is associated with antitumor effects. The phase II evaluation of nolatrexed is ongoing.

Adult↗
PubMed1994

Unilateral anterior jugular phlebectasia.

We present a rare case of unilateral anterior jugular venous phlebectasia in an 82-year-old female patient presenting as a soft cystic lump in the anterior aspect of the neck increasing in size during straining and valsalva manoeuvre. Although cases of internal and external jugular phlebectasia have been reported, as far as we are aware no case of anterior jugular phlebectasia has been reported in the literature previously.

Aged↗
PubMed1994

Button battery in the nose--an unusual foreign body.

We present two rare, but similar, cases of button batteries in the nose in male children of Caucasian origin. The importance of early diagnosis, treatment and the long-term morbidity of such a foreign body in the nose are discussed.

Child↗
PubMed1989

Changes in mRNA levels of poly(ADP-ribose) polymerase during activation of human lymphocytes.

The level of mRNA encoding the nuclear enzyme poly(ADP-ribose) polymerase (ADP-ribosyltransferase, EC 2.4.2.30) was found to be very low in quiescent human lymphocytes and to increase at least 10-fold between 1 and 2 dyas after stimulation with the mitogen phytohaemagglutinin, staying high for several days thereafter. This increase was inhibited by 3-methoxybenzamide (a competitive inhibitor of poly(ADP-ribose) polymerase) but was not affected significantly by aphidicolin. Incubation of activated cells with cycloheximide for 2 h increased the expression slightly. These data demonstrate that, during lymphocyte activation, the level of mRNA of the poly(ADP-ribose) polymerase gene correlates with, and hence is presumably responsible for, the increase in poly(ADP-ribose) polymerase protein detectable by enzyme assay or immunochemistry.

Aphidicolin↗
PubMed1989

Phosphoinositide hydrolysis in mitogen-stimulated human peripheral-blood T lymphocytes.

Both phytohaemagglutinin and antibodies to the CD3 molecule induced proliferation and phosphoinositide hydrolysis in human peripheral-blood T lymphocytes, but the magnitude of the inositol phosphate response was small and the rate of accumulation slow [significant increases in Ins(1,4,5)P3 were observed only after 10 min]. Hence this response differs from the well-characterized Ins(1,4,5)P3 responses of many other systems. This slow response, its abrogation in Ca2+-depleted medium, the slow and maintained increase in Ca2+ as measured by Quin-2, and the ability of the Ca2+ ionophore A23187 to stimulate Ins(1,4,5)P3 accumulation all suggest that the increase in Ins(1,4,5)P3 occurs, at least in part, as a result of receptor-mediated Ca2+ influx in mitogen-stimulated T lymphocytes.

Antibodies, Monoclonal↗
PubMed1987

Differential control of proto-oncogene c-myc and c-fos expression in lymphocytes and fibroblasts.

In lymphocytes stimulated with the mitogen phytohaemagglutinin, an inhibitor of the enzyme ADP-ribosyltransferase (ADPRT) completely blocks the proliferative response and the increase in expression of the proto-oncogene c-myc without affecting c-fos significantly. Conversely, in fibroblasts the serum-induced growth is not affected by the ADPRT inhibitor, and both oncogenes are dramatically super-induced. Hence there are differences between lymphocyte and fibroblast early responses to mitogenic stimulation and also between regulation of c-fos and c-myc gene expression.

Benzamides↗
PubMed1986

The outcome of hidden neurotic illness treated in general practice.

One thousand patients attending a general practice surgery were asked to complete the general health questionnaire as the first stage of screening for hidden minor psychiatric disorders. Those who had an unexpectedly high score of 20 or more were randomly allocated to doctors or health visitors for treatment. After one year, these two groups were reinterviewed by the doctors and health visitors respectively and comparable rates of recovery were found. After five years, they were interviewed again and a second general health questionnaire completed. It was found that both groups had improved significantly, and that there was no significant difference between them.Poor outcome was associated with problems with children, household or neighbours and with a previous history of psychiatric illness. Improvement was associated with physical treatment of the original disorder, resolution of the original problem and job satisfaction.The implication of these findings for the comparative management of minor psychiatric disorders by general practitioners and non-medical health workers in primary care are discussed.

Allied Health Personnel↗
PubMed1978

The evaluation of a model speech training program for deaf children.

Systematic speech training procedures were employed with a group of 20 hearing-impaired children ranging in age from 7 to 10 years. Using a primarily auditory-oral approach, the speech training program employed a hierarchical sequence in order to teach the suprasegmental patterns of English to the children. The children's performance on the speech training hierarchy was monitored on a daily basis using a checklist system. Based on their rate of progress in the development of speech skills, the children were divided into three groups post hoc: rapid, slow but steady, inordinately slow. Although the system worked well, on the average, approximately one-third of the children encountered serious difficulites at one or more levels of the hierarchy. Examination of the children's background information and audiological data revealed that those children who encountered difficulty had an extremely limited amount of residual hearing and/or problems other than a hearing handicap.

Child↗
PubMed1977

Dominant lethal assays in male mice: evaluation of experimental design, statistical methods and the sensitivity of Charles River (CD1) mice.

Male CD1 mice were dosed by intraperitoneal injection of 20, 40 or 80 mg of methyl methanesulphonate (MMS) per kg body weight or with the solvent, water. After dosing, each male was caged with (a) 2 or (b) 3 females per week for 8 consecutive weeks and 13 days after mating the females were killed and examined for evidence of dominant lethal mutations. Results were analysed to determine (1) the sensitivity of CD1 mice to the mutagenic effect of MMS. (2) the influence of the number of females mated with each male. (3) the adequacy of the experimental design and (4) the adequacy of the statistical methods. A dose-related increase in early foetal deaths was induced in females mated to male mice in the first week after dosing with 20, 40 and 80 mg/kg MMS. A reduction in foetal implants was demonstrated in females in the 40 and 80 mg/kg MMS groups but not after dosing males with 20 mg/kg. Thus dominant lethal mutations were induced in male CD1 mice dosed IP with 20, 40 and 80 mg/kg giving a degree of sensitivity which compares favourably with that obtained with other strains of mice in other laboratories. For a given number of male mice, the greater precision obtained with 3 rather than 2 females arose directly from the numbers used. For a given number of female mice, the allocation of 2 per male (rather than 3 per male) is a more efficient design in that 50% more treated animals are available for estimation of the relevant error. Also more information would be available as a result of the probable increase in pregnancy rate. The experiment did not suggest the need for any modification in the statistical approach.

Animals↗
PubMed1976

Psychiatric screening in general practice. A controlled trial.

This study reports the efficacy of the General Health Questionnaire (G.H.Q.) in the secondary prevention of minor psychiatric illness in a primary-care setting. 1093 consecutive attenders at a general practitioner's surgery were screened for minor psychiatric disorder using the G.H.Q. 32% were found to have a conspicuous psychiatric disorder and a further 11% had a hidden psychiatric disorder. The group with hidden disorders were randomly assigned to a treated index group and an untreated control group. The effects of case detection and treatment were beneficial and immediate, with the duration of episode of the disorder being much shorter for patients whose disorder was recognised by the general practitioner. For patients with more severe disorders there are significant differences still demonstrable between the groups one year later; but patients with mild disorders do equally well, some recovering spontaneously but others becoming manifest to the general practitioner over the next year and so receiving treatment. The "detected" group of patients increased their consultations for emotional complaints over the next year, but their total consultation-rate was not increased.

Clinical Trials as Topic↗