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Biomedical subjects

G C Donaldson

Publications and source records attributed to G C Donaldson.

At least 37 records · Page 2Linked to original sources

Acute exacerbations of chronic obstructive pulmonary disease are accompanied by elevations of plasma fibrinogen and serum IL-6 levels.

BACKGROUND: Respiratory tract infections may acutely increase risk from coronary heart disease (CHD), though the mechanisms have not been defined. Patients with chronic obstructive pulmonary disease (COPD) are prone to repeated exacerbations that are often associated with respiratory infections. These patients also have increased cardiovascular morbidity and mortality. We hypothesized that transient acute increases in plasma fibrinogen, an independent risk factor for CHD, could occur at COPD exacerbation (mediated through a rise in IL6) and thereby provide a mechanism linking respiratory infection to risk of coronary heart disease. METHODS: 93 COPD patients [mean (SD) age 66.8 (8.1) years] were followed regularly over one year, with daily diary card monitoring of respiratory symptoms and peak expiratory flow rate (PEFR); 67 patients [mean FEV1 1.06 (0.44) l, FVC 2.43 (0.79) l] were seen during 120 exacerbations. At each visit spirometry was measured and blood samples taken for plasma fibrinogen and Interleukin-6 (IL-6) levels. RESULT: At baseline, the mean (SD) plasma fibrinogen was elevated at 3.9 (0.67) g/l in the 67 patients with exacerbations during the study and the median (IQR) IL-6 at 4.3 (2.4 to 6.8) pg/ml. Plasma fibrinogen increased by 0.36 (0.74) g/l at exacerbation (p <0.001). with IL-6 levels rising by 1.10 (-2.73 to 6.95) pg/ml (p = 0.008). There was a relation between the changes in fibrinogen at exacerbation and IL-6 levels (r = 0.348, p <0.001). Multiple regression revealed significantly greater rises in fibrinogen when exacerbations were associated with purulent sputum (b = 0.34 g/l; p = 0.03), increased cough (b = 0.31 g/l, p = 0.019) and symptomatic colds (b = 0.228; p = 0.024). CONCLUSIONS: Plasma fibrinogen levels were elevated in stable patients with COPD and may contribute to the increased cardiovascular morbidity and mortality in these patients. COPD exacerbations increased serum IL-6 levels, leading to a rise in plasma fibrinogen. Thus acute rather than chronic infection may have a role in predisposing to coronary heart disease or stroke.

Aged↗

Winter mortality in relation to climate.

We report further details of the Eurowinter survey of cold related mortalities and protective measures against cold in seven regions of Europe, and review these with other evidence on the relationship of winter mortality to climate. Data for the oldest subject group studied, aged 65-74, showed that in this vulnerable group, high levels of protection against indoor and outdoor cold at given outdoor temperatures were found mainly in countries with cold winters, and were associated with low levels of excess mortality at a given level of outdoor cold. Regions such as London that had poor protection against cold and/or high baseline mortalities had higher levels of winter excess mortality than expected for the coldness of their winters.

Aged↗

Effect of temperature on lung function and symptoms in chronic obstructive pulmonary disease.

The present study investigated whether falls in environmental temperature increase morbidity from chronic obstructive pulmonary disease (COPD). Daily lung function and symptom data were collected over 12 months from 76 COPD patients living in East London and related to outdoor and bedroom temperature. Questionnaires were administered which asked primarily about the nature of night-time heating. A fall in outdoor or bedroom temperature was associated with increased frequency of exacerbation, and decline in lung function, irrespective of whether periods of exacerbation were excluded. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) fell markedly by a median of 45 mL (95% percentile range: -113-229 mL) and 74 mL (-454-991 mL), respectively, between the warmest and coolest week of the study. The questionnaire revealed that 10% had bedrooms <13 degrees C for 25% of the year, possibly because only 21% heated their bedrooms and 48% kept their windows open in November. Temperature-related reduction in lung function, and increase in exacerbations may contribute to the high level of cold-related morbidity from chronic obstructive pulmonary disease.

Aged↗

Cold related mortalities and protection against cold in Yakutsk, eastern Siberia: observation and interview study.

OBJECTIVE: To assess how effectively measures adopted in extreme cold in Yakutsk control winter mortality. DESIGN: Interviews to assess outdoor clothing and measure indoor temperatures; regressions of these and of delayed cause-specific mortalities on temperature. Setting Yakutsk, east Siberia, Russia. SUBJECTS: All people aged 50-59 and 65-74 years living within 400 km of Yakutsk during 1989-95 and sample of 1002 men and women who agreed to be interviewed. MAIN OUTCOME MEASURES: Daily mortality from all causes and from ischaemic heart, cerebrovascular, and respiratory disease. RESULTS: Mean temperature for October-March 1989-95 was -26.6 degreesC. At 10.2 degrees C people wore 3.30 (95% confidence interval 3.08 to 3.53) layers of clothing outdoors, increasing to 4.39 (4.13 to 4.66; P<0. 0001) layers at -20 degrees C. Thick coats, often of fur, replaced anoraks as temperature fell to -48.2 degrees C. 82% of people went out each day when temperatures were 10.2 degrees C to -20 degrees C, but below -20 degrees C the proportion fell steadily to 44% (35% to 53%) at -48.2 degrees C (P<0.001), and overall shivering outdoors did not increase. Living room temperature was 17.9 (17.2 to 18.5) degrees C at 10.2 degrees C outdoors, 19.6 (18.8 to 20.4) degrees C at -20 degrees C, and 19.1 (18.6 to 19.6) degrees C at -48.2 degrees C. Mortality from all causes and from ischaemic heart and respiratory disease was unaffected by the fall in temperature. Mortality from respiratory disease (daily deaths per million) rose from 4.7 (4.3 to 5.1) to 5.1 (4.4 to 5.7) (P=0.03), but this was offset by a fall in deaths from injury. CONCLUSIONS: People in Yakutsk wore very warm clothing, and in extremely cold weather stayed indoors in warm housing, preventing the increases in mortality seen in winter in milder regions of the world. Only respiratory mortality rose, perhaps because of breathing cold air.

Aged↗

Winter mortality and cold stress in Yekaterinburg, Russia: interview survey.

OBJECTIVES: To evaluate how mortality and protective measures against exposure to cold change as temperatures fall between October and March in a region of Russia with a mean winter temperature below -6 degrees C. DESIGN: Interview to assess factors associated with cold stress both indoors and outdoors, to measure temperatures in living room, and to survey unheated rooms. SETTING: Sverdlovsk Oblast (district), Yekaterinburg, Russia. SUBJECTS: Residents aged 50-59 and 65-74 living within approximately 140 km of Yekaterinburg in Sverdlovsk Oblast. Survey of sample of 1000 residents equally distributed by sex and age groups. MAIN OUTCOME MEASURES: Regression analysis was used to relate data on indoor heating and temperatures, the amount of clothing worn, the amount of physical activity, and shivering while outside, to outdoor temperature; results were compared with mortality patterns for ischaemic heart disease, cerebrovascular disease, respiratory disease, and mortality from all causes. RESULTS: As mean daily temperatures fell to 0 degree C the amount of clothing worn outdoors increased, physical activity while outdoors became more continuous, and only 11 (6.6%) of the 167 people surveyed who went outdoors at temperatures above 0 degree C reported shivering. The mean temperature in living rooms in the evening remained above 21.9 degrees C. Mortality from ischaemic heart disease, cerebrovascular disease, respiratory disease, and all causes did not change. As the temperature fell below 0 degree C the number of items of clothing worn plateaued at 16.0 and the number of layers at 3.7. With regression analysis, shivering outdoors was found to increase progressively to 34.6% (P < 0.001) of excursions at -25 degrees C, and mortality (after declining slightly) rose progressively (all cause mortality rose by 1.15% for each 1 degree C drop in temperature from 0 degree C to -29.6 degrees C, 95% confidence interval 0.97% to 1.32%). 94.2% of bedrooms were directly heated, and evening temperatures in the living room averaged 19.8 degrees C even when outside temperatures reached -25 degrees C. CONCLUSIONS: Outdoor cold stress and mortality in Yekaterinburg increased only when the mean daily temperature dropped below 0 degree C. At temperatures down to 0 degree C cold stress and excess mortality were prevented by increasing the number of items of clothing worn and the amount of physical activity outdoors in combination with maintaining warmth in houses.

Activities of Daily Living↗

Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease.

Exacerbations occur commonly in patients with moderate or severe chronic obstructive pulmonary disease (COPD) but factors affecting their severity and frequency or effects on quality of life are unknown. We measured daily peak expiratory flow rate (PEFR) and daily respiratory symptoms for 1 yr in 70 COPD patients (52 male, 18 female, mean age [+/- SD] 67.5 +/- 8.3 yr, FEV1 1.06 +/- 0.45 L, FVC 2.48 +/- 0.82 L, FEV1/FVC 44 +/- 15%, FEV1 reversibility 6.7 +/- 9.1%, PaO2 8.8 +/- 1.1 kPa). Quality of life was measured by the St. George's Respiratory Questionnaire (SGRQ). Exacerbations (E) were assessed at acute visit (reported exacerbation) or from diary card data each month (unreported exacerbation). In 61 (87%) patients there were 190 exacerbations (median 3; range, 1 to 8) of which 93 (51%) were reported. There were no differences in major symptoms (increase in dyspnea, sputum volume, or purulence) or physiological parameters between reported and unreported exacerbations. At exacerbation, median peak flow fell by an average of 6.6 L/min (p = 0.0003). Using the median number of exacerbations as the cutoff point, patients were classified as infrequent exacerbators (E = 0 to 2) or frequent exacerbators (E = 3 to 8). The SGRQ Total and component scores were significantly worse in the group that had frequent exacerbations: SGRQ Total score (mean difference = 14.8, p < 0.001), Symptoms (23.1, p < 0.001), Activities (12.2, p = 0.003), Impacts (13.9, p = 0.002). However there was no difference between frequent and infrequent exacerbators in the fall in peak flow at exacerbation. Factors predictive of frequent exacerbations were daily cough (p = 0.018), daily wheeze (p = 0.011), and daily cough and sputum (p = 0.009) and frequent exacerbations in the previous year (p = 0.001). These findings suggest that patient quality of life is related to COPD exacerbation frequency.

Aged↗

An analysis of arterial disease mortality and BUPA health screening data in men, in relation to outdoor temperature.

1. Laboratory studies have shown that cold exposure causes an increase in blood pressure, cholesterol and erythrocyte count. However, whether the mild cold exposures received during everyday life are sufficient to cause such changes is unclear. 2. To test this, outdoor temperatures in central London between 1986 and 1992 were related to both haematological and blood pressure data on 50-69-year-old men attending BUPA health screening examinations in London, and to mortality in South-East England. Since any association with temperature may be an artifact due to common, temperature-independent, annual rhythms in the parameters, these data were also analysed after removal of these circannual components by digital filtering. 3. It was found that short-term falls in temperature produced significant increases in Hb, erythrocyte count, packed cell volume, mean corpuscular Hb concentration, serum albumin, systolic and diastolic blood pressure, and significant decreases in mean corpuscular volume and erythrocyte sedimentation rate. Mean corpuscular Hb, leucocyte count, platelet count and serum cholesterol concentrations were unchanged. Time-series analysis showed that these changes occurred almost immediately in response to a fall in temperature, but persisted for longer intervals of up to 1-2 days. 4. Mortalities from ischaemic heart disease and cerebrovascular disease were also significantly increased by short-term falls in temperature. 5. These finding indicate that in the general population the cold exposures of normal life are sufficient to induce significant and prolonged haemoconcentration and hypertension, which may explain why deaths from arterial disease are more prevalent in the winter.

Aged↗

Early increases in ischaemic heart disease mortality dissociated from and later changes associated with respiratory mortality after cold weather in south east England.

STUDY OBJECTIVE: To identify the time courses and magnitude of ischaemic heart (IHD), respiratory (RES), and all cause mortality associated with common 20-30 day patterns of cold weather in order to assess links between cold exposure and mortality. DESIGN: Daily temperatures and daily mortality on successive days before and after a reference day were regressed on the temperature of the reference day using high pass filtered data in which changes with a cycle length < 80 days were unaffected (< 2%), but slower cyclical changes and trends were partly or completely suppressed. This provided the short term patterns of both temperature and mortality associated with a one day displacement of temperature. The results were compared with simple regressions of unfiltered mortality on temperature at successive delays. STUDY POPULATION AND SETTING: Population of south east England, including London, over 50 years of age from 1976-92. MAIN RESULTS: Colder than average days in the linear range 15 to 0 degrees C were associated with a "run up" of cold weather for 10-15 days beforehand and a "run down" for 10-15 days afterwards. The increases in deaths were maximal at 3 days after the peak in cold for IHD, at 12 days for RES, and at 3 days for all cause mortality. The increase lasted approximately 40 days after the peak in cold. RES deaths were significantly delayed compared with IHD deaths. Excess deaths per million associated with these short term temperature displacements were 7.3 for IHD, 5.8 for RES, and 24.7 for all cause, per one day fall of 1 degree C. These were greater by 52% for IHD, 17% for RES, and 37% for all cause mortality than the overall increases in daily mortality per degree C fall, at optimal delays, indicated by regressions using unfiltered data. Similar analyses of data at 0 to -6.7 degrees C showed an immediate rise in IHD mortality after cold, followed by a fall in both IHD and RES mortality rates which peaked 17 and 20 days respectively after a peak in cold. CONCLUSION: Twenty to 30 day patterns of cold weather below 15 degrees C were followed:(1) rapidly by IHD deaths, consistent with known thrombogenic and reflex consequences of personal cold exposure; and (2) by delayed increases in RES and associated IHD deaths in the range 0 to 15 degrees C, which were reversed for a few degrees below 0 degree C, and were probably multifactorial in cause. These patterns provide evidence that personal exposure to cold has a large role in the excess mortality of winter.

Aged↗

Effect of posture on body temperature of young men in cold air.

We studied eight young adult men to see whether a supine posture caused a fall in body core temperature in the cold, as it does in thermoneutral conditions. In air at 31 degrees C (thermoneutral), a supine posture for 3 h reduced mean aural, gastric, oesophageal and rectal temperatures by 0.2-0.4 degree C, compared to upright and increased femoral artery blood flow from 278 (SEM 42)ml.min-1 whilst upright to 437 (SEM 42) ml.min-1 whilst supine. In cold air (8 degrees C) the supine posture failed to reduce these temperatures [corrected] significantly, or to increase femoral blood flow: it reduced heart rate, and increased arterial systolic and pulse pressures adjusted to carotid sinus level, less than in thermoneutral conditions. However, the behaviour of core temperature at the four sites was significantly nonuniform between the two postures in the cold, mainly because the supine posture tended to reduce rectal temperature. It may have done so by reducing heat production in the muscles of the pelvis, since it reduced overall metabolic rate from 105 (SEM 8) to 87 (SEM 4) W.m-2 in the cold. In other respects the results indicated that posture ceased to have an important effect on body core temperatures during cold stress.

Adult↗

Development of primer sets designed for use with the PCR to amplify conserved genes from filamentous ascomycetes.

We constructed nine sets of oligonucleotide primers on the basis of the results of DNA hybridization of cloned genes from Neurospora crassa and Aspergillus nidulans to the genomes of select filamentous ascomycetes and deuteromycetes (with filamentous ascomycete affiliations). Nine sets of primers were designed to amplify segments of DNA that span one or more introns in conserved genes. PCR DNA amplification with the nine primer sets with genomic DNA from ascomycetes, deuteromycetes, basidiomycetes, and plants revealed that five of the primer sets amplified a product only from DNA of the filamentous ascomycetes and deuteromycetes. The five primer sets were constructed from the N. crassa genes for histone 3, histone 4, beta-tubulin, and the plasma membrane ATPase. With these five primer sets, polymorphisms were observed in both the size of and restriction enzyme sites in the amplified products from the filamentous ascomycetes. The primer sets described here may provide useful tools for phylogenetic studies and genome analyses in filamentous ascomycetes and deuteromycetes (with ascomycete affiliations), as well as for the rapid differentiation of fungal species by PCR.

Ascomycota↗

Primer sets developed to amplify conserved genes from filamentous ascomycetes are useful in differentiating fusarium species associated with conifers.

We examined the usefulness of primer sets designed to amplify introns within conserved genes in filamentous ascomycetes to differentiate 35 isolates representing six different species of Fusarium commonly found in association with conifer seedlings. We analyzed restriction fragment length polymorphisms (RFLP) in five amplified PCR products from each Fusarium isolate. The primers used in this study were constructed on the basis of sequence information from the H3, H4, and (beta)-tubulin genes in Neurospora crassa. Primers previously developed for the intergenic transcribed spacer region of the ribosomal DNA were also used. The degree of interspecific polymorphism observed in the PCR products from the six Fusarium species allowed differentiation by a limited number of amplifications and restriction endonuclease digestions. The level of intraspecific RFLP variation in the five PCR products was low in both Fusarium proliferatum and F. avenaceum but was high in a population sample of F. oxysporum isolates. Clustering of the 35 isolates by statistical analyses gave similar dendrograms for H3, H4, and (beta)-tubulin RFLP analysis, but a dendrogram produced by intergenic transcribed spacer analysis varied in the placement of some F. oxysporum isolates.

Journal Article↗

Do the competition rules of synchronized swimming encourage undesirable levels of hypoxia?

Recent anecdotal reports that some synchronized swimmers have become dizzy or disorientated towards the end of their performance, and in the worst cases fainted underwater, have caused concern. However, the rules of synchronized swimming encourage slow performance of compulsory figures, and an analysis of the competition placings and duration of underwater sequences showed that the highest rankings were gained by slowly performed compulsory figures and free programmes containing a long underwater sequence. The combination of breath-holding and the vigorous exercise involved suggests that some of the symptoms complained of by the swimmers might be due to hypoxia. We therefore studied the alveolar gas tensions in nine members of the Great Britain National Squad immediately following the performance of set figures and the initial underwater sequence of their free routine in a swimming-bath. All were cyanosed after the underwater sequences of the free routine and reported being mildly confused. The mean(s.d.) alveolar PO2 at this stage was 5.07(1.1) KPa, while three girls had an alveolar PO2 below 4 KPa, the lowest being 3.67 KPa. These gas tensions suggest that potentially dangerous levels of hypoxia may develop during competitive synchronized swimming and that prolonged underwent sequences should not be encouraged.

Adolescent↗

Cardiovascular mortality in winter.

Ischaemic heart disease is the biggest single cause of excess mortality in winter, accounting for approximately half of all the excess deaths. Most of these deaths take place hours or a day or two after exposure to cold suggesting that some result from thrombosis starting during or shortly after cold exposure, although some can result from immediate reflex effects of cold, and some can occur in association with respiratory deaths which are delayed many days after cold weather. Changes in blood composition observed in the cold that may explain the rapid thrombotic deaths include increased red cell count, plasma cholesterol, and plasma fibrinogen, which are all thrombogenic. The protective protein C does not increase significantly. British data suggests that cold housing particularly affects respiratory mortality in winter, and outdoor cold exposures mortality from arterial thrombosis. A Europe-wide survey is now being run as part of the EC- funded project "Eurowinter" to assess such factors.

Cardiovascular Diseases↗

Cold-induced increases in erythrocyte count, plasma cholesterol and plasma fibrinogen of elderly people without a comparable rise in protein C or factor X.

1. Six elderly (66-71 years) and six young (20-23 years) subjects (half of each group women) were cooled for 2 h in moving air at 18 degrees C to investigate possible causes of increased mortality from arterial thrombosis among elderly people in cold weather. Compared with thermoneutral control experiments, skin temperature (trunk) fell from 35.5 to 29.5 degrees C, with little change in core temperature. 2. Erythrocyte count rose in the cold from 4.29 to 4.69 x 10(12)/l, without a change in mean corpuscular volume, indicating a 14% or 438 ml decline in plasma volume; increased excretion of water, Na+ and K+ accounted for loss of only 179 ml of extracellular water. 3. Plasma cholesterol and fibrinogen concentrations rose in the elderly subjects from 4.90 mmol/l and 2.97 g/l (control) to 5.45 mmol/l and 3.39 g/l in the cold, and in the young subjects from 3.33 mmol/l and 1.84 g/l (control) to 3.77 mmol/l and 2.07 g/l in the cold. Increases were significant for the elderly subjects, the young subjects and the group as a whole, except for cholesterol in the young subjects, and all were close to those expected from the fall in plasma volume. 4. Plasma levels of Protein C and factor X did not increase significantly in the cold in the elderly subjects, young subjects, or the group as a whole. 5. The results suggest that loss of plasma fluid in the cold concentrates major risk factors for arterial thrombosis, while small molecules, including protective Protein C, redistribute to interstitial fluid.

Adult↗

The chaotic behaviour of resting human respiration.

The study of non-linear mathematics has led to the concept of an attractor that can confine to within certain boundaries the path traced out in multidimensional space when a variable is plotted against itself delayed by various lag times. The type of attractor present can be determined by monitoring the exponential rate (called a Lyapunov exponent) at which almost identical values within a time series become dissimilar. Lyapunov exponents estimated from data collected during the normal resting breathing of eight adults were all positive, end-tidal PCO2 had the lowest Lyapunov exponent (0.06 +/- 0.01 bits/s; Mean +/- SE), breath and expiratory duration had the highest exponents (0.23 bits/s). The results indicate that resting respiration is chaotic. This chaotic behaviour may allow fast and flexible responses to sudden changes, allow if necessary complete readjustment of the control parameters, and may be involved in the phase locking of respiration to external stimuli.

Adolescent↗

Potassium as a respiratory signal in humans.

Six renal transplant recipients underwent a series of incremental exercise experiments. Minute ventilation (VE), carbon dioxide production rate (VCO2), and arterial blood chemistry were measured at rest and while subjects exercised on a stationary bicycle. Four of the subjects performed a similar experiment while exercising on a static rowing machine. Within each subject, arterial potassium concentration ([K+]a) was linearly related to VCO2 and VE during exercise. The slope of the relationship between [K+]a and VCO2 was similar in the cycling and rowing experiments. This implies that the absorption of potassium by resting muscle does not significantly limit the arterial hyperkalemia seen during exercise. When VE, VCO2, and [K+]a were measured 1 and 5 min after the end of cycling there was no correlation, whereas VE continued to be closely correlated with VCO2. The relationship demonstrated between change in [K+]a and VCO2 in these experiments is compatible with change of [K+]a acting as a respiratory signal during exercise but not during recovery from exercise in humans.

Adult↗

A method to determine significant levels of immunoglobulin G to Aspergillus fumigatus antigens in an ELISA system and a comparison with counterimmunoelectrophoresis and double diffusion techniques.

A method is described which assesses results obtained from an ELISA system for the determination of human serum levels of IgG class antibodies to Aspergillus fumigatus. The method is used to discriminate positive from negative samples, and significant antibody activity may be reported to the clinician, relative to a reference positive control serum monitored simultaneously under the same test conditions. Antibody content is expressed as the absorbance of a certain dilution of serum. Duplicate samples were analysed at a single serum dilution and their absorbtion values obtained from a semi-automated ELISA microplate reader. These were entered into a computer programmed to convert the data into units on a logarithmic scale. In parallel experiments, ELISA results were compared with those obtained by the techniques of counterimmunoelectrophoresis and double diffusion which measure precipitating antibody of all classes. A relatively good degree of correlation between tests was found only among sera with a high level of antibody.

Antibodies, Fungal↗