Biomedical subjects

A McGown

Publications and source records attributed to A McGown.

17 recordsLinked to original sources

PubMed2001

Vigilance on the civil flight deck: incidence of sleepiness and sleep during long-haul flights and associated changes in physiological parameters.

The study investigated sleepiness and sleep in aircrew during long-haul flights. The objectives were to identify loss of alertness and to recommend a practical approach to the design of an alerting system to be used by aircrew to prevent involuntary sleep. The flights were between London and Miami, covering both day- and night-time sectors, each with a duration of approximately 9 h. The subjects were 12 British Airways pilots. Various physiological variables were measured that could potentially be used to indicate the presence of drowsiness and involuntary sleep: brain electrical activity (electroencephalogram, EEG), eye movements via the electro-oculogram (EOG), wrist activity, head movements and galvanic skin resistance. The EEG and EOG identified sleepiness and sleep, as well as being potential measures on which to base an alarm system. Ten pilots either slept or showed evidence of sleepiness as assessed by the EEG and EOG. Many of the episodes of sleepiness lasted < 20 s, which could mean that the subjects were unaware of their occurrence and of the potential consequences on performance and vigilance. All physiological parameters showed changes during sleep, although only the EEG and EOG were modified by sleepiness. During sleep, skin resistance was increased, and wrist activity and head movements were absent for long periods. The study indicated that the measurement of eye movements (either alone or in combination with the EEG), wrist activity or head movement may be used as the basis of an alarm system to prevent involuntary sleep. Skin resistance is considered to be unsuitable, however, being related in a more general way to fatigue rather than to sleep episodes. The optimal way to monitor the onset of sleep would be to measure eye movements; however, this is not feasible in the flight deck environment at the present time due to the intrusive nature of the recording methodology. Wrist activity is therefore recommended as the basis of an alertness alarm. Such a device would alert the pilot after approximately 4-5 min of wrist inactivity, since this duration has been shown by the present study to be associated with sleep. The possibility that sleep inertia (reduced alertness immediately after awakening from sleep) could follow periods of sleep lasting 5 min needs to be considered. The findings reported here might be applicable to other occupational environments where fatigue and sleepiness are known to occur.

Adult↗

PubMed2001

Overexpression of NAD(P)H:quinone oxidoreductase 1 in human reproductive system.

NAD(P)H:quinone oxidoreductase 1 (NQO1; DT-diaphorase; DTD) is a two-electron reductase that efficiently bioactivates compounds of the quinone family, such as mitomycin C. The observation that DTD is overexpressed in many cancerous tissues compared to normal tissues has provided us with a potentially selective target that can be exploited in the design of novel anticancer agents. Because of the relative lack of information on the cell-specific expression of DTD, the purpose of this study was to perform a body mapping of its normal distribution. Tissue samples from various components of the human reproductive system were analyzed by immunohistochemistry. We found strong expression of this enzyme in testicular stromal cells (Leydig cells) and in the epithelium of epididymis, ductuli efferentes, and Fallopian tube. These results suggest that DTD-bioactivated quinones could be responsible for a selective toxicity on these components of the reproductive system and cause clinical problems due to testosterone deficiency and infertility. This observation needs to be investigated in preclinical evaluation of new anticancer quinones and in patients treated with these compounds. (J Histochem Cytochem 49:1187-1188, 2001)

Epididymis↗

PubMed2001

Influence of hypoglycaemia, with or without caffeine ingestion, on visual sensation and performance.

Full-field visual evoked potentials and visual information processing were measured in 16 normal, healthy subjects during a hyperinsulinaemic clamp. A randomized cross-over design was used across three conditions: hypoglycaemia and caffeine; hypoglycaemia and placebo; and euglycaemia and caffeine. The latency of the P100 component of the pattern-reversal visual evoked potential increased significantly from rest to hypoglycaemia, but no effect of caffeine was found. Subjects were subsequently divided into two median groups based on the increase in P100 latency in the placebo condition (Group 1, +0.5 ms; Group 2, +5.6 ms). In the absence of caffeine, an inverse correlation between the increase in P100 latency from rest and a deterioration in visual movement detection was found for Group 2, but not for Group 1. Caffeine ingestion resulted in a further increase in P100 latency, from rest to hypoglycaemia, for subjects in Group 2. Hypoglycaemia in the absence of caffeine produces changes in visual sensation from rest to hypoglycaemia. In those subjects most sensitive to the effects of hypoglycaemia (Group 2), the increase in P100 latency was associated with poorer performance in tests of visual information processing. Caffeine ingestion produced further increases in P100 latency in these subjects.

Adult↗

PubMed2000

Phase I and pharmacologic study of CT-2584 HMS, a modulator of phosphatidic acid, in adult patients with solid tumours.

CT-2584 HMS, 1-(11-dodecylamino-10-hydroxyundecyl)-3, 7-dimethylxanthine-hydrogen methanesulphonate, is a modulator of intracellular phosphatidic acid. We treated 30 patients as part of a Phase I and pharmacokinetic study to determine the maximum-tolerated dose of CT-2584 HMS, toxicity profiles, pharmacokinetic profile and antitumour effects at escalating dose levels. CT-2584 HMS was given as a continuous infusion for 6 hours for 5 consecutive days every 3 weeks. Plasma samples for pharmacokinetic studies were analysed using a validated high-performance liquid chromatographic assay. Mean C(max)and AUC values for each dose group were similar on days 1 and 5 and increases in plasma concentration (C(max)and AUC) appeared proportional to the dose. CT-2584 HMS had a mean elimination half-life of 7.3 hours. Values of V(d)and clearance were independent of dose and duration of treatment. Dose escalation was halted at 585 mg/m(2)because of malaise and lethargy, which was sometimes accompanied by nausea and headache. 26 patients were evaluable for response, one patient with pleural mesothelioma achieved a partial response to treatment confirmed by CT scanning. A dose level of 520 mg/m(2)daily x 5 days would be suitable for Phase II testing. Alternative schedules of CT-2584 HMS to overcome the limiting toxicity of malaise would be worthy of examination.

Adult↗

PubMed1999

Development and validation of a sensitive solid-phase extraction and high-performance liquid chromatographic assay for the novel bio-reductive anti-tumor agent RH1 in human and mouse plasma.

A HPLC assay and solid-phase extraction technique from human plasma has been developed and validated for the experimental anticancer agent, RH1 (2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone) which is currently being evaluated by the CRC phase I/II committee. A 500 mg amino propyl solid-phase extraction cartridge was used to isolate RH1 from human plasma. Analysis was performed on a reversed-phase chromatography system using a 15 cm cyanopropyl column and isocratic elution with a 10% methanol-90% water (double distilled) solution. The lower limit of quantitation for RH1 was found to be 0.00375 microg/ml (3.75 ng/ml+/-8.3%) in water and following extraction from plasma. Recovery of >80%(+/-11.9%) was achieved over a five-day validation study. This method was used to carry out pre-clinical studies in BDF mice (standard strain of hybrid mice) at three dose levels (2, 5 and 10 mg/kg of RH1 in 0.9% (w/v) saline via an intraperotoneal injection). Standard Version of PC Winnonlin pharmacokinetic modelling software was used to model the data. A none-compartmental model was used to describe the disposition of RH1 in mice plasma. RH1 was rapidly eliminated from plasma with a mean plasma clearance of 23.4 ml/min, mean volume of distribution of 321.6 ml and mean t(1/2) alpha and beta decays of 4.8 and 9.6 min, respectively. RH1 in human and mouse whole blood and plasma was found to be stable up to 2 h.

Animals↗

PubMed1999

Development and validation of a high-performance liquid chromatographic assay using solid-phase extraction for the novel antitumor agent pancratistatin in human plasma.

The stability of the experimental anti-tumour agent pancratistatin in human plasma has been investigated. A solid-phase extraction technique and an HPLC assay with external standards have been developed and validated. Extraction was performed using C18 cartridges and HPLC, analysis was performed on a 15 cm Hypersil BDS column using isocratic elution with 13% acetonitrile and aqueous solution of 1% (w/v) acetic acid. The lower limit of quantification for pancratistatin in 5% DMF-95% water was found to be 0.58 ng/ml (+/-10.58%) and 2.3 ng/ml (+/-9.2%) following extraction from human plasma. Mean recovery of 89.4% (+/-4.73%) was obtained over the concentration range 0.0023-9.45 microg/ml for a five day validation study. Pancratistatin was stable at room temperature in light or dark for at least 15 days, in the refrigerator at 4 degrees C for at least 16 days and in the freezer at -20 degrees C or -80 degrees C for at least 28 days. Under all conditions monitored, % recovery of pancratistatin from human plasma was greater than 95% and no evidence of degradation had occurred. There also was no loss of pancratistatin after three cycles of freezing and thawing.

Amaryllidaceae Alkaloids↗

PubMed1997

Screening cognitive impairment in alcohol abusers.

1. Studies have reported various neuropsychological abnormalities in people with excessive drinking patterns and associated problems with the assessment and treatment of this group. 2. The aim of this study was to assess the potential of a screening instrument to help detect the presence of cognitive impairment in excessive alcohol users undergoing detoxification. 3. The Memory Screening Test has potential as a screening instrument to assess clients' cognitive ability to benefit from psychoeducational material.

Adult↗

PubMed1997

Fatigue, depression, and quality of life in HIV-positive men.

1. Fatigue is a real symptom of HIV infection, and up to two thirds of clients with HIV report symptoms of depression. 2. Depression and fatigue, besides being closely related in HIV cases, have an adverse effect on quality of life. 3. Treating depression and underlying causes of fatigue will improve the quality of life for patients with HIV, who now have an extended life span.

Activities of Daily Living↗

PubMed1996

Out of control! the most effective way to help the binge-eating patient.

This article assessed the effectiveness of different treatments for bulimia nervosa by screening 400 studies published from 1987 through July 1933. Nineteen independent studies with a total of 1,015 subjects with 11 treatment types, and 316 subjects in 11 control groups fulfilled these criteria. Therapy outcome across studies was assessed meta-analytically, producing effect sizes that represent pretreatment to posttreatment changes in bulimic symptoms.

Antidepressive Agents, Second-Generation↗

PubMed1994

Drug-resistance associated alterations of cell surface antigen expression in a human anthracycline-resistant ovarian carcinoma cell line.

The anthracycline uptake and cell surface expression of plasma membrane antigens (HLA class I, c-erbB-2, protectin-CD59, integrin beta 1-chain-CD29, etc.) were compared on a parental anthracycline sensitive and an anthracycline-resistant subline of the human ovarian carcinoma cell line A2780. The anthracycline-resistant (A2780/ADR) subline incubated for 30 min in the presence of daunomycin displayed two subpopulations with different anthracycline cell content as determined by flow cytometry. The subpopulation with lower daunomycin cell content was absent in the parental anthracycline sensitive cell line. The most predominant antigenic changes on the resistant subline as compared with the sensitive one were as follow: Loss of HLA class I and a twofold increase in the expression of CD59 antigen and a slight decrease of integrin beta 1-chain on the cell surface of the resistant subline.

Antibiotics, Antineoplastic↗

PubMed1993

Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours.

The cellular expression of O6-alkylguanine-DNA-alkyltransferase (ATase) may be an important factor in determining tumour sensitivity to certain alkylating agents. In a comparative study, we have examined the inter- and intracellular distribution of ATase in tumour biopsies of a series of patients with Hodgkin's disease and ovarian cancer using a rabbit antihuman ATase antiserum. The antibody recognises the ATase protein on western blots of cell-free extracts of a number of ovarian tumours with ATase activities varying from 20 to 420 fmol/mg protein as determined by in vitro assay and there was a linear correlation between ATase activity and the intensity of the band on western blots (r = 0.993). Immunohistochemical staining was seen in all of the ovarian tumours examined and was confined to the nucleus. This is in contrast to the Hodgkin's tissue, where staining was much reduced and present in both nuclei and cytoplasm. The results suggest that in ovarian tumours the general resistance to nitrosourea chemotherapy may be related to the high cellular expression of ATase protein: this is in contrast to the more chemosensitive Hodgkin's disease. This raises the possibility that it might be feasible to predict sensitivity or resistance to these alkylating agents by immunohistochemical staining of tumour or tissue specimens.

Adult↗

PubMed1993

A phase I study of intravenous bryostatin 1 in patients with advanced cancer.

Bryostatin 1 is a novel antitumour agent derived from Bugula neritina of the marine phylum Ectoprocta. Nineteen patients with advanced solid tumours were entered into a phase I study to evaluate the toxicity and biological effects of bryostatin 1. Bryostatin 1 was given as a one hour intravenous infusion at the beginning of each 2 week treatment cycle. A maximum of three treatment cycles were given. Doses were escalated in steps from 5 to 65 micrograms m-2 in successive patient groups. The maximum tolerated dose was 50 micrograms m-2. Myalgia was the dose limiting toxicity and was of WHO grade 3 in all three patients treated at 65 micrograms m-2. Flu-like symptoms were common but were of maximum WHO grade 2. Hypotension, of maximum WHO grade 1, occurred in six patients treated at doses up to and including 20 micrograms m-2 and may not have been attributable to treatment with bryostatin 1. Cellulitis and thrombophlebitis occurred at the bryostatin 1 infusion site of patients treated at all dose levels up to 50 micrograms m-2, attributable to the 60% ethanol diluent in the bryostatin 1 infusion. Subsequent patients treated at 50 and 65 micrograms m-2 received treatment with an intravenous normal saline flush and they did not develop these complications. Significant decreases of the platelet count and total leucocyte, neutrophil and lymphocyte counts were seen in the first 24 h after treatment at the dose of 65 micrograms m-2. Immediate decreases in haemoglobin of up to 1.9g dl-1 were also noted in patients treated with 65 micrograms m-2, in the absence of clinical evidence of bleeding or haemodynamic compromise. No effect was observed on the incidence of haemopoietic progenitor cells in the marrow. Some patients' neutrophils demonstrated enhanced superoxide radical formation in response to in vitro stimulation with opsonised zymosan (a bacterial polysaccharide) but in the absence of this additional stimulus, no bryostatin 1 effect was observed. Lymphocyte natural killing activity was decreased 2 h after treatment with bryostatin 1, but the effect was not consistently seen 24 h or 7 days later. With the dose schedule examined no antitumour effects were observed. We recommend that bryostatin 1 is used at a dose of 35 to 50 micrograms m-2 two weekly in phase II studies in patients with malignancies including lymphoma, leukaemia, melanoma or hypernephroma, for which pre-clinical investigations suggest antitumour activity.

Adult↗

PubMed1993

Caregivers' emotional well-being and their capacity to learn about stroke.

This study examines the effects of distress on the capacity of informal caregivers of stroke patients to absorb information about stroke and caregiving. Thirty-seven caregivers took part in a stroke seminar. Minor psychiatric symptoms were related to caregivers' knowledge prior to the seminar, with the more emotionally distressed being the least knowledgeable. The emotional state of the caregivers, however, did not affect how much they learnt. Knowledge after the seminar was best predicted from pre-seminar knowledge and age. Older caregivers were less well-informed afterwards, although they did not differ significantly from younger caregivers in their scores initially. These findings do not discount the possibility that emotional carers are too shocked to take in information from hospital staff at the time of admission. The data do demonstrate that, given time to accept the caregiving role, emotional carers are receptive to learning about stroke and the stroke patient's needs.

Adult↗

PubMed1992

Stereotypes of emotional caregivers and their capacity to absorb information: the views of nurses, stroke carers and the general public.

This study examines the phenomenon of stereotyping informal caregivers' capacity to learn about the condition of stroke victims. Forty-nine nurses, 55 carers and 39 members of the general public gave their opinions on how emotional they considered six hypothetical wives of stroke patients to be and how much information they thought each wife would be able to absorb. Results indicated that nurses were more pessimistic than caregivers in their assessment of how much information could be absorbed, even though these two groups did not differ in their assessment of the emotionality of the wives. Nurses and the general public responded in accordance with the expected stereotype: those rated as being high in emotionality were less likely to absorb information. No such association emerged from the ratings of caregivers. The existence of the stereotype, particularly among health professionals, has serious implications for rehabilitation programmes and caregiver well-being, and provides an explanation for why caregivers sometimes feel neglected in medical settings.

Adult↗

PubMed1987

Comparison of daunorubicin and anthrapyrazolone sensitivity and transport in resistant cell lines.

Two P388 cell lines with acquired resistance to daunorubicin have been shown to exhibit cross-resistance to anthrapyrazolone (NSC 357885). The degree of cross-resistance observed in these cell lines (58 and 150 fold) is similar to those observed towards daunorubicin (34 and 142 fold). However the decreased drug accumulation observed for daunorubicin in the resistant cell lines (4-6 fold) is not observed for anthrapyrazolone. Similarly, verapamil can increase daunorubicin accumulation in resistant cells but has no effect on anthrapyrazolone accumulation. It is concluded that in contrast to daunorubicin, decreased anthrapyrazolone accumulation is not the resistance mechanism operative in daunorubicin resistant cell lines towards anthrapyrazolone.

Animals↗

PubMed1986

Oestrogen receptor status of breast cancers from related patients.

Breast tumours from nine pairs of related women have been studied with respect to their oestrogen receptor (ER) concentrations and histological appearance and grade. 72% of these tumours were oestrogen receptor positive in both soluble and nuclear fractions. in eight of the nine pairs, the tumours were of the same ER status. Apart from a suggestion of a similar host response to the tumours in two related pairs, the histological appearance of the tumours showed no striking similarities. This small study suggests that familial breast cancers are more likely to be hormone dependent.

Breast Neoplasms↗

PubMedDate not supplied

Bereavement: theoretical perspectives and adaptation: Canberra, Australia.

This article presents an integrative model for understanding the range of individual differences arising from the bereavement process which occurs through the loss of a significant person, such as a spouse, parent or child. It is suggested that cognitive behavioral models are useful in determining stress reactions to bereavement; however, such models have certain limitations for adaptation purposes. Finally, to enhance well-being, reactions to loss are examined from a clinical perspective by using a five-phase model which outlines holistic adaptation processes, intervention strategies, and time span indicators.

Adaptation, Psychological↗