PubMed Health⌕ Search

Biomedical subjects

M Maclean

Publications and source records attributed to M Maclean.

12 recordsLinked to original sources
PubMed2006

A phase I, first in man study of OSI-7836 in patients with advanced refractory solid tumors: IND.147, a study of the Investigational New Drug Program of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, tolerability, toxicity profile, dose-limiting toxicities (DLTs), anti-tumor activity and pharmacokinetics of OSI-7836 given IV on day 1 and day 8 every 3 weeks in patients with advanced incurable cancer. METHODS: Twenty-seven previously treated patients with advanced or metastatic solid tumors were enrolled in this phase I study conducted by the National Cancer Institute of Canada Clinical Trial Group (NCIC CTG). OSI-7836 was administered IV on day 1 and day 8 every 3 weeks. The dose was initially escalated from 100 to 600 mg/m2 and finally de-escalated to 200 mg/m2 in seven cohorts of patients. Patients were evaluated every other cycle of treatment for radiological response. Pharmacokinetics were performed on day 1 and day 8 of cycle 1 for all patients. RESULTS: Twenty-six patients were evaluable for toxicity. All patients experienced reversible Grade 3 lymphopenia beginning at cycle 1. The maximal delivered dose was 600 mg/m2. MTD was reached at 400 mg/m2. DLTs included fever, fatigue, rash, herpes simplex infection, nausea and vomiting. The RP2D was 200 mg/m2. No objective responses were seen in 21 evaluable patients. Pharmacokinetics were dose proportional, with a mean half-life of 46.0 min and a clearance of 34 l/(h.m2). CONCLUSION: OSI-7836 given at 200 mg/m2 on day 1 and day 8 every 3 weekly is associated with manageable toxicity and is recommended for further study. While no objective responses were seen, the significant treatment related lymphopenia suggests that hematologic malignancies may warrant further investigation.

Adult↗
PubMed2005

Parenthood should not be regarded as a right.

In September 2004 the BBC broadcast a debate in the Straw Poll series about whether parenthood should be regarded as a right. The motion was carried by a large majority both among the audience present at the recording, and among listeners who were invited to telephone in with their votes, and views at a subsequent feedback programme. The arguments are presented here, in order to stimulate debate among readers.

Adult↗
PubMed1997

The dynamics of change: cancer patients' preferences for information, involvement and support.

BACKGROUND: While the importance of providing individualised communication to cancer patients is now well recognised, little is known about the stability and validity of patients' expressed preferences for information and involvement in decision-making. This study explored the stability and possible predictors of such preferences over time. PATIENTS AND METHODS: Cancer patients seeing two Medical Oncologists in an out-patient clinic at an Australian teaching hospital completed a questionnaire battery before and directly after one consultation, and before their next consultation. Eighty consecutive patients with heterogeneous cancers participated in the study. Preferences for general and specific information, involvement and support were elicited at each assessment. Locus of control and patient familiarity with the clinic were measured before the first consultation. Patient satisfaction with the consultation was assessed directly after the consultation. Demographic and disease data were recorded for each patient. RESULTS: General preferences for information and involvement were relatively stable, at least in the short term; however there was considerable variability in preferences for specific topics of information. Patients whose condition had recently worsened were more likely to want progressively less involvement in decision-making. Gender, the doctor seen and religion were also predictive of patient preferences. CONCLUSIONS: Situational factors, such as change in disease status, may alter a patient's preferences for information and involvement. If we wish to match the provision of information and support to the expressed needs of patients, we must ask patients at each consultation what those needs are.

Adolescent↗
PubMed1997

Survival during exposure to the electrophilic reagent N-ethylmaleimide in Escherichia coli: role of KefB and KefC potassium channels.

The role of the KefB and KefC potassium efflux systems in protecting Escherichia coli cells against the toxic effects of the electrophile N-ethylmaleimide has been investigated. Activation of KefB and KefC aids the survival of cells exposed to high concentrations (> 100 microM) of NEM. High potassium concentrations reduce the protection afforded by activation of KefB and KefC, but the possession of these systems is still important under these conditions. The Kdp system, which confers sensitivity to the electrophile methylglyoxal, did not affect the survival of cells exposed to NEM. Survival is correlated with the reduction of the cytoplasmic pH upon activation of the channels. In particular, the kinetics of the intracellular pH (pHi) change are crucial to the retention of viability of cells exposed to NEM; slow acidification does not protect cells as effectively as rapid lowering of pHi. Cells treated with low levels of NEM (10 microM) recover faster if they activate KefB and KefC, and this correlates with changes in pHi. The pHi does not significantly alter the rate of NEM metabolism. The possible mechanisms by which protection against the electrophile is mediated are discussed.

Antiporters↗
PubMed1995

Respiratory depression following morphine and morphine-6-glucuronide in normal subjects.

1. Morphine 6-glucuronide (M6G) is a metabolite of morphine with analgesic activity. A double-blind, randomised comparison of the effects of morphine and M6G on respiratory function was carried out in 10 normal subjects after i.v. morphine (10 mg 70 kg-1) or M6G (1, 3.3 and 5 mg 70 kg-1). Analgesic potency was also assessed using an ischaemic pain test and other toxic effects were monitored. 2. Following morphine there was a significant increase in arterial PCO2, as measured by blood gases 45 min post dose (0.54 +/- 0.24 (s.d.) kPa, P < 0.001), and in transcutaneous PCO2 from 15 min post dose until the end of the study period (4 h), whereas blood gas and transcutaneous PCO2 were unchanged after M6G at 1.0, 3.3 and 5.0 mg 70 kg-1. This increased PCO2 following morphine was associated with an increase in expired CO2 concentration (FECO2) (0.20 +/- 0.14% expired air at 15 min post dose, P = 0.002), compared with small but significant reductions in FECO2 following morphine 6-glucuronide (-0.15 +/- 0.17% at 1 mg 70 kg-1 P = 0.030, -0.14 +/- 0.15% at 3.3 mg 70 kg-1 P = 0.017, -0.18 +/- 0.11% at 5 mg 70 kg-1 P = 0.024). Maximum transcutaneous PCO2 was significantly increased after morphine (0.63 +/- 0.28 kPa P = 0.009), but was not changed after M6G at 1 mg (0.10 +/- 0.34 kPa P = 0.11) 3.3 mg (0.06 +/- 0.37 kPa P = 0.34) or 5 mg (0.26 +/- 0.07 kPa P = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cell phenotypes in the efferent lymph of sheep persistently infected with Border disease virus.

The prefemoral efferent lymphatics of sheep persistently infected (PI) with Border disease virus (BDV) were cannulated in order to study the effects of the virus on cells of the immune system. Efferent lymphocytes recovered from PI sheep were phenotyped using a panel of monoclonal antibodies (MoAb) specific for ovine cell-surface markers and compared to lymphocytes recovered from normal, healthy controls. PI sheep had an increased percentage of cells expressing the T cell-associated molecules CD5, CD4, CD8 and T19, also an increase in cells expressing CD1 and a population of cells expressing low levels of the T19 molecule which was not present in control sheep. The lymphocytes were examined for the presence of BDV using virus-specific MoAb. On average 8.5% of the efferent lymphocytes from PI sheep carried virus antigen. BDV antigen was also found in the mononuclear cells and connective tissue of lymph nodes indicating widespread virus dissemination within the lymphoid system of PI sheep.

Animals↗
PubMed1990

Women's childhood experience of parental separation and their subsequent health and socioeconomic status in adulthood.

The long term consequences for women of parental divorce and separation in childhood are explored using data from a national, prospective, longitudinal survey. In comparison with women who suffered no parental loss, parental divorce is associated with lower educational attainment and occupational status, poorer mental health, higher alcohol consumption and higher rates of remarriage. Links with earlier signs of emotional disturbance and current levels of stress are explored.

Adolescent↗
PubMed1990

Children of divorced and separated parents: summary and review of findings from a long-term follow-up study in the UK.

As divorce and separation rates continue to rise it is likely that problems among the children of such parents will also continue to increase. The nature of short term problems for the children of separating parents are well known. There is now evidence of a risk of longer term difficulties which may be the result of a chain of circumstances which begins close in time to the separation and divorce. Long term as well as short term risks should therefore be considered in planning care strategies for the children of divorcing parents.

Adolescent↗
PubMed1989

A fodder mycotoxicosis of ruminants caused by contamination of a distillery by-product with Aspergillus clavatus.

Cattle and sheep, grazed successively on the same pasture and given the same supplementary feeding, developed ataxia and several animals became recumbent. Three cattle died within two weeks and the worst affected sheep were killed for laboratory examination. The supplementary diet which consisted largely of a distillery by-product, malt culms, was submitted for mycological examination and fed to two housed lambs. Aspergillus clavatus was cultured from the culms, and both the affected sheep and the housed lambs showed cerebrospinal degenerative changes. The clinical signs and neuropathology were closely similar to a mycotoxicosis, attributed to A clavatus, which is seen infrequently in cattle in France, Bulgaria, South Africa and China.

Animal Feed↗
PubMed1989

Nursery rhymes, phonological skills and reading.

Nursery rhymes are an almost universal part of young English-speaking children's lives. We have already established that there are strong links between children's early knowledge of nursery rhymes at 3;3 and their developing phonological skills over the next year and a quarter. Since such skills are known to be related to children's success in learning to read, this result suggests the hypothesis that acquaintance with nursery rhymes might also affect children's reading. We now report longitudinal data from a group of 64 children from the age of 3;4 to 6;3 which support this hypothesis. There is a strong relation between early knowledge of nursery rhymes and success in reading and spelling over the next three years even after differences in social background, I.Q and the children's phonological skills at the start of the project are taken into account. This raises the question of how nursery rhymes have such an effect. Our answer is that knowledge of nursery rhymes enhances children's phonological sensitivity which in turn helps them to learn to read. This paper presents further analyses which support the idea of this path from nursery rhymes to reading. Nursery rhymes are related to the child's subsequent sensitivity to rhyme and phonemes. Moreover the connection between knowledge of nursery rhymes and reading and spelling ability disappears when controls are made for differences in these subsequent phonological skills.

Achievement↗