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Biomedical subjects

J S Milledge

Publications and source records attributed to J S Milledge.

At least 19 recordsLinked to original sources
PubMed1992

Salt and water control at altitude.

The physiological effect of altitude hypoxia, in the absence of exercise, is a sodium and water diuresis with decrease in plasma and extra-cellular volumes. Plasma aldosterone concentrations (PAC) are reduced but plasma atrial natriuretic peptide (ANP) levels are modestly increased. Day-long exercise at low altitude has almost opposite effects on fluid balance. There is an anti-diuresis, sodium retention, expansion of the plasma and extra-cellular compartments, elevation of PAC and ANP. Subjects who develop acute mountain sickness (AMS) show a pathological response to hypoxia even before the development of symptoms. There is an anti-diuresis, sodium retention, increased plasma and extra-cellular volumes and increased PAC compared with subjects resistant to AMS. Plasma ANP tends to be elevated compared with sea level values but the relation of ANP levels to AMS is variable. In general therefore, the pathological response to altitude hypoxia parallels that of exercise at low altitude and is opposite to the physiological response. Both exercise and the pathological response predispose the subject to edema and are probably important in the genesis of AMS.

Acute Disease↗
PubMed1992

Effect of captopril on functional, physiological and biochemical outcome criteria in aged heart failure patients.

1. Captopril was evaluated as an adjuvant to diuretic and digoxin therapy in heart failure in old age, using walking ability, minute ventilation and oxygen consumption and plasma atrial natriuretic factor (ANF) concentration as measures of outcome. 2. Twenty patients, mean (s.d.) age 81 (6) years, entered a double-blind, randomised, crossover study of three treatments, a twice daily regimen of captopril (AA), at a dosage established by titration against serum angiotensin converting enzyme (ACE) activity, the same dosage in the morning with placebo at night (AP), and twice daily placebo (PP). Each treatment lasted 3 weeks. A 2 week run-in period on triple therapy, with AA captopril, was used to assess stability and compliance. Seventeen completed all treatments: three completed two. 3. Any benefit of captopril was modest and there was deterioration in gait on the titrated dosage 3 months afterwards (P = 0.04). Efficacy in the old may be greatest when the titrated dose (25 or 50 mg) is given once daily: the multiple daily doses recommended may be unnecessarily demanding. 4. Walking performance was measured by gait analysis (GA) at free walking speed and by a simple walking test (SWT), in which patients stopped at the first relevant symptom. There was a consistent tendency for four measures of performance (GA: speed, stride length and double support time; SWT distance) to be best on the AP treatment, next best on AA, and worst on PP but for the fifth, SWT speed, AP and AA were similar. The trend appeared most marked for SWT distance, mean (s.e. mean) values for AP, AA and PP being 123 (15), 94 (16) and 75 (16) m, respectively. However, the treatment effect did not reach statistical significance at the 0.05 level. 5. There was no significant difference between treatments in minute ventilation, minute oxygen consumption, or their ratio, either at rest or on exercise. 6. Resting ANF concentrations were nearly four times higher (P = 0.0001) in the patients than those, mean (s.e. mean) 66 (5) pmol l-1, in eleven healthy volunteers of mean age 80 (6) years, and the increase on exercise, seen in the controls (P less than 0.01), was absent. In the patients the resting plasma ANF concentration was significantly affected by treatment (P = 0.03), being less on both AP, 245 (9), and AA, 214 (9) than on PP, 264 (10) pmol l-1 (P = 0.02 and 0.03, respectively). 7. Baseline serum ACE activity was induced on active treatment. The change in ACE activity at 3 h post an active dose was significantly greater on AP than AA (P = 0.005). The increased sensitivity to inhibition during once daily administration was reflected in mean arterial pressure. The pre-dose standing pressure was less on AP than on PP (P less than 0.05), and the change in postural fall (pre-dose minus 2 h post), was greater (P = 0.004), but AA and PP were similar in these respects.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1992

Lymphocyte macrophage interactions: peripolesis of human alveolar macrophages.

Peripolesis is a phenomenon in which a lymphocyte attaches itself to another cell, usually a macrophage or veiled cell, and proceeds to circle around it. In emperipolesis, a related phenomenon, the lymphocyte invaginates the target cell so deeply that it appears to be intracytoplasmic. Lung cells in bronchoalveolar lavage fluids from 20 patients were observed in the living state and filmed. Peripolesis of the alveolar macrophages was recorded in six cases. These patients included one case each of carcinoma of the bronchus, tuberculosis, sarcoidosis and asthma, while two patients had no detectable lung disease. Five out of the six positive cases were females. In every instance there was a high number of lymphocytes in the washing. The peripolesed macrophages were not injured, but temporary alteration of the cell membrane was noted in a minority of film sequences. The peripolesing cells were also examined by transmission and scanning electron microscopy. The lymphocyte was found to be closely attached to the surface of the macrophage, with no invagination and its ultrastructure was that of a small lymphocyte. Peripolesis is probably a physiological mechanism concerned with regulation of the immune response in the lung.

Adult↗
PubMed1991

Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response.

In a party of 17 subjects who travelled together to 4,500 m, hypoxic ventilatory response (HVR) and maximum oxygen consumption (VO2max) were measured before departure. HVR was measured under constant and varying alveolar carbon dioxide tension (PACO2) conditions. VO2max was measured by both standard expired gas collection technique on a treadmill and using the "shuttle run" technique. On arrival at altitude, symptoms of acute mountain sickness (AMS) were scored daily for three days. There were no cases of severe AMS but half of the party had mild to moderate degrees of AMS. There was no correlation between AMS scores and HVR by either method of measurement or with VO2max measured by either method of measurement or with VO2max measured by treadmill or shuttle run.

Acute Disease↗
PubMed1990

Peak expiratory flow at altitude.

The mini Wright peak flow meter is a useful, portable instrument for field studies but being sensitive to air density will under-read at altitude. True peak expiratory flow will increase at altitude, however, because of the decreased air density, given that dynamic resistance is unchanged. The effect of simulated altitude on peak expiratory flow (PEF) was determined in six subjects with both the mini Wright meter and a volumetric spirometer (which is unaffected by air density). With increasing altitude PEF as measured by the spirometer increased linearly with decreasing pressure, so that at a barometric pressure of 380 mm Hg* (half an atmosphere, corresponding to an altitude of 5455 m) there was a 20% increase over sea level values. The mini Wright flow meter gave readings 6% below sea level values for this altitude--that is, under-reading by 26%. Measurements of PEF made at altitude with the mini Wright meter should be corrected by adding 6.6% per 100 mm Hg drop in barometric pressure.

Altitude↗
PubMed1989

Atrial natriuretic peptide, altitude and acute mountain sickness.

1. To investigate the mechanisms of acute mountain sickness, 22 subjects travelled to 3100 m by road and the following day walked to 4300 m on Mount Kenya. Control measurements were made over 2 days at 1300 m before ascent and for 2 days after arrival at 4300 m. These included body weight, 24 h urine volume, 24 h sodium and potassium excretion, blood haemoglobin, packed cell volume, and symptom score for acute mountain sickness. In 15 subjects blood samples were taken for assay of plasma aldosterone and atrial natriuretic peptide. 2. Altitude and the exercise in ascent resulted in a marked decrease in 24 h urine volume and sodium excretion. Aldosterone levels were elevated on the first day and atrial natriuretic peptide levels were higher on both altitude days compared with control. 3. Acute mountain sickness symptom scores showed a significant negative correlation with 24 h urinary sodium excretion on the first altitude day. Aldosterone levels tended to be lowest in subjects with low symptom scores and higher sodium excretion. No correlation was found between changes in haemoglobin concentration, packed cell volume, 24 h urine volume or body weight and acute mountain sickness symptom score. 4. Atrial natriuretic peptide levels at low altitude showed a significant inverse correlation with acute mountain sickness symptom scores on ascent.

Acute Disease↗
PubMed1989

Respiratory function in the morbidly obese before and after weight loss.

The morbidly obese are known to have impaired respiratory function. A prospective study of the changes in lung volumes, carbon monoxide transfer, and arterial blood gas tensions was undertaken in 29 morbidly obese patients before and after surgery to induce weight loss. Before surgery the predominant abnormality in respiratory function was a reduction in lung volumes. These increased towards normal predicted values after weight loss, with significant increases in functional residual capacity, residual volume, total lung capacity, and expiratory reserve volume. The increases ranged from 14% for total lung capacity to 54% for expiratory reserve volume. After weight loss had been induced the smokers showed mild hyperinflation and air trapping. Resting arterial blood gas tensions improved, with a rise in arterial oxygen tension from 10.63 to 13.02 kPa and a fall in arterial carbon dioxide tension from 5.20 to 4.64 kPa. There was no correlation between weight loss and the changes in blood gas tensions or lung volumes. Loss of weight in the morbidly obese is thus associated with improved lung function. The effects of smoking on lung function could be detected after weight loss, but were masked before treatment by the opposing effects of obesity on residual volume and functional residual capacity.

Adolescent↗
PubMed1988

Respiratory criteria of fitness for surgery and anaesthesia.

A retrospective analysis has been undertaken of 53 operations in 42 patients with severe chronic obstructive airway disease. All patients had a forced expiratory volume in 1 second between 0.3 and 1 litre, but the outcome of surgery was successful after their first operations, all of which were elective; 38 of the 42 had uneventful anaesthesia and surgery together with a normal postoperative period, while four had artificial ventilation of the lungs. The best predictors of the use of postoperative ventilation were the arterial PO2 and whether the patient was dyspnoeic at rest.

Aged↗
PubMed1988

Hypoxic ventilatory response and acute mountain sickness.

The acute ventilatory response to hypoxia (HVR) and to hypercapnia (CO2VR) was measured in 32 members of two mountaineering expeditions prior to their departure. Both teams made rapid ascents to their base camps at 5200 m and 4300 m and remained there for at least four days. Symptom scores for acute mountain sickness (AMS) were collected daily for these four days. There was a range of AMS from the unaffected to severe sickness requiring evacuation, but there was no correlation between AMS scores and HVR or CO2VR. When ascent to altitude takes a day or more, HVR (measured at sea level) is probably not the major determinant of ventilation and from our studies does not predict susceptibility to AMS. The rate of respiratory acclimatization is probably more important.

Acute Disease↗
PubMed1987

The ventilatory response to hypoxia: how much is good for a mountaineer?

Methods for measuring the ventilatory response to hypoxia (HVR) are reviewed. The criteria for success as a high altitude mountaineer are defined as freedom from acute mountain sickness (AMS) and ability to perform well at extreme altitude. The evidence for a brisk HVR being protective against AMS and associated with successful high altitude performance is reviewed. The contrary evidence of blunted HVR in high altitude residence and some elite climbers is discussed. The effect of a brisk HVR in producing periodic breathing when asleep at altitude is noted. It seems that there is an optimum HVR for different circumstances and peoples. A brisk HVR is a benefit in lowlanders going to altitude for the first time whereas a blunted HVR is appropriate for high altitude residents and possibly for very experienced elite climbers.

Acclimatization↗
PubMed1986

Contribution of ethanol and cigarette smoking to pulmonary dysfunction in chronic alcoholics.

Ethanol is claimed to have a specific damaging effect on the lung and to be at least partially responsible for pulmonary dysfunction in alcoholics. Adequate allowance for the damaging effects of cigarette smoking has not, however, been made hitherto. Pulmonary function studies were undertaken in 27 alcoholic subjects. Although there was a high prevalence of symptoms and abnormalities of pulmonary function, these were largely confined to current smokers: most of those who had never smoked and the ex-smokers who were symptom free and had normal pulmonary function. A case controlled study of alcoholics and matched controls showed no significant difference in pulmonary function between the two groups. It is concluded that the high prevalence of respiratory disease in alcoholics is largely attributable to their smoking habits: no evidence of a specific pulmonary toxic effect of ethanol was identified in the study.

Adult↗
PubMed1986

Nocturnal periodic breathing at altitudes of 6,300 and 8,050 m.

Nocturnal periodic breathing was studied in eight well-acclimatized subjects living at an altitude of 6,300 m [barometric pressure (PB) 350-352 Torr] for 3-5 wk and in four subjects during one night at 8,050 m altitude (PB 281-285 Torr). The measurements at 6,300 m included tidal volume by inductance plethysmography, arterial O2 saturation by ear oximetry (calibrated by arterial blood samples), electrocardiogram (ECG), and electrooculogram. At 8,050 m, periodic breathing was inferred from the cyclical variation in heart rate obtained from a night-long ECG record. All subjects at 6,300 m altitude showed well-marked periodic breathing with apneic periods. Cycle length averaged 20.5 s with 7.9 s apnea. Minimal arterial O2 saturation averaged 63.4% corresponding to a PO2 of approximately 33 Torr, i.e., approximately 6 Torr lower than the normal value at rest during daytime. This was probably the most severe hypoxemia of the 24-h period. At 8,050 m altitude, the cycle length averaged 15.4 s, much longer than predicted by a theoretical model. Cyclical variations in heart rate caused by periodic breathing occurred in all subjects, but abnormal cardiac rhythms such as ventricular premature contractions were uncommon. The severe arterial hypoxemia caused by periodic breathing may be an important determinant of tolerance to these great altitudes.

Adult↗
PubMed1985

Acute mountain sickness: pulmonary and cerebral oedema of high altitude.

Acute mountain sickness is a condition affecting otherwise healthy individuals on going rapidly to altitude. It is caused by sub-acute hypoxia in susceptible subjects. Its study may provide lessons for the more complicated situation of hypoxia in patients undergoing intensive care. This paper reviews the incidence and aetiology of acute mountain sickness, pulmonary and cerebral oedema of high altitude and possible mechanisms are discussed. Prophylaxis depends on an awareness of the condition in all those venturing to high altitude and guidelines are suggested. The treatment of the established condition is reviewed.

Altitude Sickness↗
PubMed1985

Serum erythropoietin in humans at high altitude and its relation to plasma renin.

Serum immunoreactive erythropoietin (siEp) was estimated in samples collected from members of two scientific and mountaineering expeditions, to Mount Kongur in Western China and to Mount Everest in Nepal. SiEp was increased above sea-level control values 1 and 2 days after arrival at 3,500 m and remained high on ascent to 4,500 m. Thereafter, while subjects remained at or above 4,500 m, siEp declined, and by 22 days after the ascent to 4,500 m was at control values but increased on ascent to higher altitude. Thus siEp was at a normal level during the maintenance of secondary polycythemia from high-altitude exposure. On descent, with removal of altitude hypoxia, siEp decreased, but despite secondary polycythemia levels remained measurable and in the range found in subjects normally resident at sea level. On Mount Everest, siEp was significantly (P less than 0.01) elevated above preexpedition sea-level controls after 2-4 wk at or above 6,300 m. There was no correlation between estimates of siEp and plasma renin activity in samples collected before and during both expeditions.

Adult↗