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Biomedical subjects

G Duncan

Publications and source records attributed to G Duncan.

At least 91 records · Page 5Linked to original sources
PubMed1994

Living wills: would sick people change their minds?

Patients admitted acutely to a geriatric medical unit were interviewed on admission about their opinions on cardiopulmonary resuscitation (CPR). They underwent a general examination and their mental health was documented by completing the geriatric depression scale. Those who did not wish CPR in the event of a cardiac arrest were questioned again on recovery. Of 216 patients admitted, only three objected to answering the questions and after the other exclusion criteria were applied, 100 patients were included in the study. A total of 92% of patients wished CPR in the event of a cardiac arrest. The 8% who did not wish CPR contained more people scoring high on the geriatric depression scale. After recovery, three of that eight had changed their minds and wished CPR if required. Patients who are acutely unwell may make decisions that are influenced by their condition at this point in time and it is important to recognize that these decisions may not be maintained. In this study, consultant geriatricians did not reflect their patients' desires in making decisions about who should receive CPR if required.

Acute Disease↗
PubMed1994

Validation of the doubly labeled water method in growing pigs.

The CO2 production (rCO2) of eight growing pigs was determined by continuous collection of CO2 over 21 days and simultaneously estimated using the doubly labeled water (DLW) method. The aim was to assess the accuracy of the method before and after correction for known sources of error and to test for any residual discrepancy arising from as yet unidentified sources of error. Mass spectrometer accuracy was verified by analyzing serial dilutions of the dose material in the form of an artificial decay curve; no significant bias was detected. The physiological errors were linearly dependent on weight gain. DLW-derived rCO2 (corrected only for fractionated water loss) underestimated the true value by 0.270 l CO2/g wt gain or -8% in the restricted (group R) and -16% in the ad libitum-fed (group AL) groups. Known sources of error accounted for -0.006 (methane), -0.032 (fecal 2H losses), -0.108 (fat synthesis), and -0.146 (changing pool size) l CO2/g wt gain. After correction for these sources of error the DLW-derived rCO2 differed from the true value by -2 +/- 3% in group R and 0 +/- 3% in group AL. Thus there was no significant bias in the DLW method after correction for known sources of error, even during rapid weight gain or at weight stability with or without correction. The precision estimates include both dose and background errors and uncertainty in the correction factors used. Strategies for optimizing precision are presented.

Animals↗
PubMed1994

Calmodulin antagonists induce changes in lens permeability and transparency.

Calmodulin has been shown to perform several important functions in the lens including regulation of the plasma membrane Ca(2+)-ATPase. This study investigated the effects of a variety of different CaM antagonists on rat lens membrane potential, membrane resistance, intracellular Na+ and Ca2+ content and transparency, in order to examine the role of CaM in control of lens membrane permeability. W7, calmidazolium and trifluoperazine caused biphasic changes in lens membrane electrical characteristics. Phase 1 consisted of a depolarization of the membrane potential and an increase in resistance, indicating that K+ channels were being blocked. This was confirmed by application of the K+ channel antagonist, quinine, which inhibited Phase 1 changes. Phase 2 was a further depolarization coupled with a decrease in resistance, indicating the activation of a cation conductance. Application of W7 in low Na+ medium slowed the Phase 2 depolarization and decrease in resistance indicating that Na+ is the main charge carrier through the activated conductance. The CaM inhibitors also led to a large increase in the Na+ and Ca2+ contents of the lens. W5, a less potent analogue of W7, caused a depolarization and increase in membrane resistance, but no Phase 2 changes were observed. Na+ and Ca2+ contents were similar to control lenses after 4 hours incubation in 200 microM W5. In addition, exposure to W7, TFP and calmidazolium resulted in a loss of transparency, while W5 treated lenses remained clear. It appears, therefore, that CaM is involved in control of lens membrane permeability. Loss of control of these channels leads to catastrophic changes in the intracellular ionic environment and hence opacification of the lens.

Animals↗
PubMed1993

Patterns of palliative radiotherapy in Canada.

A questionnaire study was performed to determine patterns of radiotherapy practice across Canada and the relationship of age, work-load, resources, intent and aims of therapy on departmental policy; 99 returns were analysed. Three case scenarios were given: Brain metastases were treated typically without a simulation as a parallel pair with palliative intent to 2000 cGy in 5 fractions; for locally advanced lung cancer most patients were simulated, but 40% we deemed 'radical' and there was a bimodal pattern of dose fractionation (the age of the radiation oncologist appeared to influence this and geographical differences were also notable); bony metastases from breast cancer were typically simulated as a single field using 2000-2500 cGy in 5 fractions and always considered palliative. Work-load and resources are likely to influence patterns of care. For example, over 20% felt that treatment choice was suboptimal, largely due to lack of radiation technologists and megavoltage equipment. The implications of these determinants on palliative care are discussed. Objective criteria and definitions are required to allow satisfactory workload measurements and comparisons to be made.

Bone Neoplasms↗
PubMed1993

Calcium regulation in tissue-cultured human and bovine lens epithelial cells.

PURPOSE: To study calcium regulatory mechanisms in lens cells with particular reference to the relative contributions from the calcium adenosine triphosphatase of plasma and endoplasmic reticulum membranes, respectively. METHODS: The calcium-sensitive fluorescent dye, Fura 2, was incorporated into tissue-cultured human and bovine epithelial cells and internal calcium was calibrated using the ionomycin (1 microM) method. The dynamics of calcium release from the endoplasmic reticulum were also studied in digitonin-permeabilized bovine cells. RESULTS: Tissue-cultured bovine and human lens cells have very similar resting calcium levels (235 +/- 22 nM and 216 +/- 12 nM, respectively). Thapsigargin caused an increase in cytoplasmic calcium both in the presence and absence of external calcium, but the calmodulin antagonist W7 only initiated an increase in the presence of external Ca2+. The effects of thapsigargin and W7 were additive. Exposing lens cells to Na(+)-free perfusing solutions caused a transient increase in internal Ca2+. Bovine lens cells permeabilized by digitonin-released Ca2+ when exposed to inositol (1,4,5) triphosphate and the effect was maximal at 1 microM. CONCLUSIONS: Lens cytoplasmic calcium is controlled by calcium adenosine triphosphatases at the plasma and endoplasmic reticulum membranes. The former is inhibited by W7 and insensitive to thapsigargin whereas the latter is inhibited by thapsigargin, but insensitive to W7. The lens endoplasmic reticulum store is also controlled by an inositol (1,4,5) trisphosphate calcium-release mechanism. Na+/Ca2+ exchange plays a relatively minor role in calcium regulation, at least at resting calcium levels.

Aged↗
PubMed1993

pCMPS-induced changes in lens membrane permeability and transparency.

PURPOSE: To investigate the role of externally facing membrane protein sulfhydryl groups in controlling lens permeability and transparency using the impermeant sulfhydryl complexing agent p-chloromercuriphenyl sulfonate (pCMPS). METHODS: Membrane permeability changes were studied by measuring lens voltage and resistance. Ion movements were monitored by measuring 22Na+ and 45Ca2+ fluxes, and internal free calcium was monitored by ion-selective microelectrodes. Opacification was quantified by photographing and analyzing back-scattered light. RESULTS: pCMPS, at concentrations above 1 microM, produced a depolarization of membrane potential and decrease in membrane resistance. These changes were accompanied by a marked stimulation in 22Na+ and 45Ca2+ influxes into the lens. There was a concomitant loss of lens transparency, mainly in the bow region. The pCMPS-induced electrical changes could be prevented by substituting N-methyl-D-glucamine for Na+ in the external medium. Na(+)-free solution alone increased 45Ca2+ influx, and the addition of pCMPS further stimulated the influx. Quinine (300 microM) was found to reduce the pCMPS-induced stimulation of 22Na+ and 45Ca2+ influxes and also to reduce opacification. CONCLUSIONS: pCMPS at low concentrations induces many of the cation permeability changes previously found to occur with age and cataract in the lens. The fact that quinine can ameliorate pCMPS-induced changes in ion movements and opacification suggests a novel approach for membrane-based anticataract strategies.

4-Chloromercuribenzenesulfonate↗
PubMed1992

pH regulation in tissue-cultured bovine lens epithelial cells.

The intracellular pH (pHi) of tissue-cultured bovine lens epithelial cells was measured in small groups of 6 to 10 cells using the trapped fluorescent dye 2',7'-bis-(2-,carboxyethyl)-5 (and 6)carboxyfluorescein (BCECF). When perifused at 35 degrees C with artificial aqueous humour solution (AAH) containing 16 mM HCO3- and 5% CO2, pH 7.25, pH(i) was 7.19 +/- 0.02 (SEM, n = 95). On removing HCO3- and CO2 there was an initial transient alkalinization followed by a fall in pH to a steady value of 6.97 +/- 0.03 (SEM, n = 54). Addition of 0.25 mM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) to AAH containing HCO3- and CO2 led to a rapid and pronounced fall in pH. Exposure to Na(+)-free AAH again led to a marked fall in pH(i), but in this case the addition of DIDS did not produce a further fall. Substitution of the impermeant anion gluconate for Cl- in the presence of HCO3- led to a rise in pHi, while substitution in the absence of HCO3- led to a fall in pHi. The above data indicate a significant role for a sodium-dependent Cl(-)-HCO3- exchange mechanism in the regulation of pHi. Addition of 1 mM amiloride to control AAH in both the presence and absence of HCO3- led to a marked fall in pH(i), indicating that a Na+/H+ exchange mechanism also has a significant role in the regulation of pHi.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1992

Internal acidification modulates membrane and junctional resistance in the isolated lens of the frog Rana pipiens.

The normal internal pH (pHi) of the amphibian lens, measured using ion-sensitive microelectrodes, is 7.1 (pHo = 7.4) and the membranes appear to be relatively impermeable to hydrogen ions. Perifusing the lens with 100% CO2 appeared to be the most efficient way of decreasing pHi, which fell to 6.3 after an exposure lasting 30 min. Accompanying this acidification, there was a rapid depolarization of membrane potential (Em), a decrease in membrane resistance (Rm) and increase in internal or bulk resistance (Ri). These changes did not occur if the external pH alone was decreased. All changes were reversible, although the time course of Ri recovery was faster than the others. The decrease in membrane resistance could be prevented if the chloride concentration in the external solution was reduced, suggesting that internal acidification opens chloride channels in the amphibian lens. Since chloride ions are normally close to equilibrium across amphibian lens membranes, it is suggested that the pH-induced depolarization is due to a decrease in potassium conductance. The increase in internal resistance on perifusing with CO2 is most likely due to a closing of gap junctions between the fibre cells. The relationship between internal conductance and pHi was very similar to that obtained in other tissues and could be fitted by the Hill equation with n = 6 and pK = 6.9. Fibre junctional conductance seems sensitive to small changes in hydrogen ion concentration around the resting pH. Two agents, aspirin and cyanate, that are believed to influence cataract development, slowed the recovery of Em, Rm and Ri during recovery from an acid load.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Evidence for a Na(+)-Cl(-)-H(+)-HCO3- exchange system in the mammalian lens.

36Cl- efflux was studied in the isolated rat lens under two conditions that are known to decrease internal pH. The first follows exposure to a pulse of ammonium chloride (50 mM) and the second accompanies exposure to an acidified propionate (20 mM) solution. Under acidifying conditions, a stimulation in 36Cl- efflux was observed, that was abolished on removing external Na+ and also on removing external Cl- and HCO3-. In the absence of external Cl-, the presence of HCO3- (16 mM) resulted in an increase in 36Cl- efflux during internal acidification. In the absence of internal acidification, the addition of 0.1 mM dibutyrylcAMP or 0.5 mM IBMX to the external medium produced a rapid increase in 36Cl- efflux. This stimulation was reduced by 0.2 mM SITS. Neither cAMP or IBMX had any significant effect on the electrical resistance of the lens membranes. It is suggested that a coupled SITS-sensitive, Na(+)-Cl(-)-H(+)-HCO3- exchange mechanism is activated when the lens internal pH falls and further that cAMP may play a role in regulating this mechanism.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1992

Treatment strategies in advanced and metastatic cancer: differences in attitude between the USA, Canada and Europe.

Six-hundred and forty four radiation therapists from 21 European countries, Canada, and the USA responded to a questionnaire regarding the management of three cases of advanced cancer. The cases were a 64-year-old man with brain metastases from small cell carcinoma of the lung; a 64-year-old woman with bone metastases from carcinoma of the breast and a 59-year-old man with squamous cell carcinoma of the bronchus and mediastinal nodes. There was variation as to the perceived prognosis and appropriate aims of therapy, particularly for the case of squamous cell carcinoma of the bronchus. The total dose and number of fractions could be related to the perceived aims and expectations of treatment, for example, those aiming to extend life gave higher doses of radiotherapy and those aiming only to relieve symptoms gave lower. Similarly, those describing treatment as radical and estimating longer survival gave higher doses and more fractions than those treating palliatively. Variations in the role of the radiation oncologist in the management of advanced and metastatic cancer in the USA, Canada and Europe are discussed.

Attitude of Health Personnel↗
PubMed1992

The prognosis of adenosquamous carcinomas of the uterine cervix.

OBJECTIVES: Firstly, to identify a cohort of women with invasive adenosquamous carcinomas of the uterine cervix, including mucin-producing squamous cell carcinomas. Secondly, to compare the biological characteristics and behaviour of a cohort of adenosquamous carcinomas with a cohort of non-mucin-producing squamous cell carcinomas. DESIGN: Histological review, retrospective survival analysis. SETTING: Regional multidisciplinary gynaecological oncology service. SUBJECTS: 161 cases of stage 1B and above invasive cervical carcinoma presenting between 1 January 1980 and 31 July 1987. Thirty nine women with adenosquamous carcinomas were compared with 103 women with non-mucin-producing squamous cell tumours. RESULTS: Inclusion of routine stains for mucin in the assessment of histological material resulted in the reclassification of 38 (24%) of the cases, including the identification of 31 mucin-producing squamous cell carcinomas. The survival with adenosquamous tumours was significantly worse than with squamous cell cancers (P = 0.006), 5-year survival rates being 52% and 75% respectively. Multivariate analysis showed that this effect was explained by differences in clinical stage, pelvic lymph node metastasis and vascular invasion by tumour. CONCLUSIONS: The application of routine mucin stains to cervical tumours identifies a group of previously unrecognized adenosquamous cancers. Tumours so identified are likely to pursue a more aggressive clinical course associated with a poorer survival when compared to non-mucin-producing squamous carcinomas.

Adenocarcinoma↗
PubMed1992

Clinical correlates of sway in elderly people living at home.

Postural sway has been noted to increase with advancing age and to correlate with a wide variety of clinical features. The relationships between sway and various clinical features were explored in a group of elderly subjects living at home and free from neurological illness and severe incapacity. Each subject underwent a thorough physical examination and sway was measured in the anteroposterior and lateral planes with eyes open and closed using a modified Wright's ataxiameter. Vibration sense was the only clinical feature to show a consistent relationship with all 4 measurements of sway in men. Age showed only a weak and inconsistent relationship to sway in both men and women. Weak but inconsistent relationships were noted between sway and mental function, tone, passive joint movement, antidepressant and tranquilliser therapy. This suggests that dorsal column function is of prime importance in the maintenance of balance and that the previously noted increase in postural sway with advancing age may have been exaggerated by the presence of disease processes.

Aged↗
PubMed1992

Evaluation of DNA probe removal from nylon membrane.

Genetic fingerprinting is one of the most challenging applications of any hybridization membranes. Forensic DNA fingerprinting typically uses samples in the range of 100-400 ng of genomic DNA. To ensure the ability to successfully reprobe the samples, it is imperative that repeated stripping of sample DNA be minimized while stripping of the probe DNA be maximized. By using standard dilutions of K562 cell line, we compared the following three stripping techniques: NaOH at 25 degrees C, formamide (HCONH2) at 65 degrees C and 0.1 x standard saline citrate and 0.1% sodium dodecyl sulfate at 95 degrees C (high-temperature stripping). The largest amount of genomic DNA was stripped from the membrane with NaOH, with the other two techniques removing less. Formamide and high-temperature procedures resulted in a loss of approximately 5-10 ng of DNA per strip. In contrast, the NaOH resulted in a loss of approximately 10-20 ng per strip.

Autoradiography↗
PubMed1992

Collaboration between geriatricians and general surgeons.

The operation over ten years of a simple and practical method of collaboration between general surgeons and geriatricians is described. This was designed, by means of a weekly ward round by geriatricians and consultant surgeons on general surgical wards (120 beds), to give geriatric medical advice and, when appropriate, to arrange transfer for geriatric assessment, medical treatment and rehabilitation, long-term care, or terminal care. Some 240 such transfers are described, comprising approximately 2% of all patients over the age of 65 admitted to the surgical units. The commonest single surgical diagnosis was of malignant disease. A total of 43% had had no operation and 18% had no medical diagnosis. 64% of those transferred for assessment etc. went home, half of them within two weeks, but nearly a third of them after more than four weeks. The system was effective, and benefited both surgeons and geriatricians, at no cost to the former and little to the latter in terms of time or increase in work load.

Aged↗
PubMed1991

Analysis of rat lens 45Ca2+ fluxes: evidence for Na(+)-Ca2+ exchange.

The influx and efflux kinetics of 45Ca2+ were studied in the rat lens in vitro. Both data sets could be fitted by a multi-compartment mathematical model and were interpreted in terms of extracellular, cytosolic and slowly-exchanging (bound) components. At the end of a 16-hr influx period, when uptake into the extracellular and cytosolic compartments is complete, the 45Ca2+ exchanged fraction is less than 20% of the total calcium determined by atomic absorption. The bound compartment is therefore by far the largest in the lens. The efflux rate constant determined from the model for the cytosolic compartment was approximately 8 x 10(-3) min-1 and its origin was confirmed by its sensitivity to temperature, absence of external sodium and presence of the amiloride-analogue, dichlorobenzamil. A 55% reduction in efflux was obtained in sodium-free solution, indicating that Na(+)-Ca2+ exchange is responsible for a large proportion of calcium movement from the lens against its electrochemical gradient. This was confirmed in influx studies where, reduction of the lens sodium gradient by either exposure to sodium-free medium or 0.1 mM ouabain significantly elevated the 45Ca2+ content of the lens relative to the control level. Exposure to sodium-free conditions also rendered the lens opaque, which did not occur in the absence of external calcium. These experiments suggest a critical role for Na(+)-Ca2+ exchange in maintaining a low internal Ca2+ and hence transparency.

Amiloride↗