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Biomedical subjects

P M Warren

Publications and source records attributed to P M Warren.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effects on lung compliance, lung volume, and single-breath transfer factor for carbon monoxide in sheep with lentivirus-induced lymphoid interstitial pneumonia.

Static lung compliance, static lung volumes, and transfer factor for carbon monoxide were measured in 12 anesthetized adult Texel ewes seropositive for maedi-visna virus (MVV) and in 11 breed-, sex-, and age-matched seronegative controls. Median static lung compliance in MVV-infected sheep (1.24 L.kPa-1; range, 0.27 to 2.20 L.kPa-1) was not significantly different from that in controls (1.58 L.kPa-1; range, 0.82 to 2.08 L.kPa-1). Median body weight of MVV-infected sheep (56 kg; range, 40 to 75 kg) was significantly (P < 0.05) less than that of controls (65 kg; range, 53 to 87 kg). Median effective alveolar lung volume in MVV-infected sheep (3.36 L; range, 1.44 to 4.52 L) was significantly (P < 0.01) less than that in controls (4.12 L; range, 3.75 to 4.90 L). Median effective end expiratory lung volume in MVV-infected sheep (1.20 L; range, 0.56 to 1.99 L) was significantly (P < 0.001) less than that of controls (1.98 L; range: 1.76 to 2.78 L). Median lung volumes expressed per unit of body weight did not differ significantly between the groups. Median single-breath transfer factor for carbon monoxide in MVV-infected sheep (7.89 mmol.min-1.kPa-1; range, 3.45 to 12.74 mmol.min-1.kPa-1) was significantly (P < 0.001) less than that in controls (14.10 mmol.min-1.kPa-1; range, 10.02 to 18.30 mmol.min-1.kPa-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management.

BACKGROUND: On the basis of a retrospective survey by this unit it was suggested that patients with acute ventilatory failure should be given sufficient controlled oxygen treatment to raise the arterial oxygen tension (PaO2) to above 6.6 kPa, with the addition of a respiratory stimulant if the hydrogen ion concentration ([H+]) rose above 55 nmol/l and assisted ventilation if the patient remained acidotic despite these measures. This study was designed to verify the prognostic factors that determine survival in acute ventilatory failure and determine the outcome when our guidelines were implemented. METHODS: One hundred and thirty nine episodes of acute hypercapnic (type II) respiratory failure were studied prospectively in 95 patients admitted with acute exacerbations of chronic obstructive lung disease. Patients had to have a PaO2 below 6.6 kPa and an arterial carbon dioxide tension (PaCO2) above 6.6 kPa while breathing air. RESULTS: The mortality associated with episodes of acute ventilatory failure was 12%. Patients who died tended to be older and were significantly more acidotic, hypotensive, and uraemic on admission than those who survived, but they had similar degrees of hypoxaemia and hypercapnia. Death occurred in 10 of the 39 episodes in which arterial [H+] rose to 55 nmol/l or above, compared with seven of the 100 episodes in which it remained below 55 nmol/l. The respiratory stimulant doxapram was used in 37 episodes and was associated with a reduction in [H+] below 55 nmol/l within 24 hours in 23 episodes. Assisted ventilation was used in only four episodes. CONCLUSION: Arterial [H+] is an important prognostic factor for survival. Most patients treated according to the guidelines outlined above can be managed successfully without assisted ventilation.

Doxapram↗
PubMed1992

Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer.

BACKGROUND: Studies of the relation between the severity of structural change in emphysema and physiological abnormality have been based on macroscopic assessments, which have not been truly quantitative or sensitive enough to detect early changes. With a highly reproducible method for measuring emphysema using histological sections and a semiautomatic image analysis system, this quantitative assessment of emphysema was compared with a semiquantitative macroscopic assessment of emphysema and measurements of carbon monoxide gas transfer. METHODS: Microscopic and macroscopic measurements of emphysema on 44 thoracotomy specimens were compared; only two were from non-smokers. Airspace wall surface area per unit volume was measured microscopically with an automatic image analyser and expressed as both the mean airspace wall surface area per unit volume and the mean value of the five fields with the lowest values. Macroscopic emphysema was measured directly on a tracing of the midsagittal slice using a digitising tablet attached to a microcomputer and expressed as a percentage of the total area of lung. In cases with centriacinar emphysema the number of discrete lesions was counted. RESULTS: The area of macroscopic emphysema ranged from 0 to 78% of the total area of lung examined, but most patients had less than 1% involvement so that the distribution was highly skewed. Both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume were normally distributed, with mean airspace areas ranging from 8.8 to 25.4 mm2/mm3 (mean 18.1 mm2/mm3). In lobes with centriacinar emphysema the number of discrete lesions correlated with airspace wall surface area per unit volume and with preoperative carbon monoxide transfer factor (TLCO) per unit lung volume. However, other measurements of macroscopic emphysema did not correlate with loss of alveolar wall surface area, and there was considerable overlap between subjects with no or minimal macroscopic emphysema and those with more severe disease. TLCO correlated with both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume but not with the severity of macroscopic emphysema. CONCLUSION: If emphysema is to be quantified it must be measured microscopically; macroscopic measurements do not, in general, reflect the microscopic loss of airspace wall.

Aged↗
PubMed1992

Should we judge a mask by its cover?

BACKGROUND: A table of the approximate ranges of inspired oxygen delivered at given oxygen flow rates is often given on the packaging of oxygen masks. A study was carried out to check the inspired oxygen concentration given by one of the new masks, which has been designed to be used with or without the Venturi attachment as a result of the proposal to use it without the Venturi attachment as a general purpose mask for emergency use. METHODS: Measurements were made at resting respiratory rate and 26 breaths/min in 12 normal subjects. Continuous oxygen and carbon dioxide concentrations were recorded at the lips with a mass spectrometer, and inspired oxygen concentrations were calculated from end tidal values by means of the alveolar gas equation. Measurements were made at oxygen flow rates of 2, 4, and 6 l/min for the mask alone and at 2 and 4 l/min with both the 24% and the 28% Venturi attachments. RESULTS: Without the Venturi attachment the mask gave average inspired oxygen concentrations 8-10% greater than are stated on the packaging at oxygen flow rates of 2, 4, and 6 l/min at resting respiratory rates of 8-20 breaths/min, some individuals receiving 30% more than expected. Addition of the interchangeable Venturi attachments designed to give 24% and 28% inspired oxygen delivered average concentrations within 2% of the expected concentrations, no individual receiving more than 5% above the expected concentrations. CONCLUSIONS: The labelling on the packaging of oxygen masks may lead to inappropriate use by those not expert in prescribing oxygen therapy. Caution is still needed when a single multipurpose mask is being selected for emergency use, where accurate delivery of low concentrations of oxygen is vital for some patients.

Adult↗
PubMed1991

Lung CT density correlates with measurements of airflow limitation and the diffusing capacity.

We studied 80 subjects (63 M, 17 F; 23-82 yrs) and related lung computerized tomography (CT) density with age, height, spirometry, lung volumes, diffusing capacity and arterial blood gas tensions. These subjects demonstrated a wide range of physiological impairment (forced expiratory volume in one second (FEV1) 8-116% predicted; diffusing capacity (Kco) 15-139% predicted; arterial oxygen tension (Pao2) 38-91 mmHg). They ranged from normal subjects to patients with chronic respiratory failure. Lung density was derived from CT density histograms measured as both mean Emergency Medical Information (EMI) number (EMI scale: 0 = water, -500 = air, EMI number of normal lung tissue range approximately -200 to -450) and the lowest 5th percentile EMI number, the latter value being more likely to represent the density of lung parenchyma. Lung CT density correlated most strongly with airflow obstruction (EMI 5th percentile versus FEV1/forced vital capacity (FVC) % predicted, r = 0.73, p less than 0.001) and diffusing capacity (EMI 5th percentile versus Kco, r = 0.77, p less than 0.001). This suggests that reduction in lung density, which reflects loss of the surface area of the distal airspaces, is a major index of respiratory function in patients with smoking related chronic obstructive pulmonary disease (COPD). These data provide no indication of other factors such as small and large airways disease, and loss of elastic recoil, which may contribute to airflow limitation, or disruption of the pulmonary vascular bed which may also affect CT lung density.

Adult↗
PubMed1990

The effect of steering on the physiological energy cost of wheelchair propulsion.

Previous studies of the energy cost of wheelchair propulsion have used ergometers or tracks requiring little steering. We have measured minute ventilation (VE), oxygen consumption (VO2), carbon dioxide output (VCO2) and heart rate (HR) during exercise in a two arm, hand-rim propulsion wheelchair on a treadmill, and on three tracks of increasing tortuosity in eight able-bodied subjects. During propulsion at 0.6 m/sec, VE, VO2, and VCO2 were significantly greater on the track with the maximal steering component than on that with the minimal steering component, or on the treadmill with no steering component. Heart rate was significantly higher on the maximal compared to minimal steering component track. Exercise at speeds varying from 0.2 to 1.0 m/sec showed that VO2 and VCO2 were significantly higher on the medium steering component track than on the treadmill at speeds of 0.6 m/sec and above. We conclude that the effort of steering contributes significantly to the energy cost of wheelchair propulsion particularly at higher speeds.

Adult↗
PubMed1989

Effect of almitrine on hypoxic ventilatory drive measured by transient and progressive isocapnic hypoxia in normal men.

1. In a double-blind placebo-controlled study, we have investigated the effect of the peripheral chemoreceptor stimulant drug almitrine bismesylate on hypoxic ventilatory drive (expressed as the slope of the minute ventilation/arterial oxygen saturation relationship in litres min-1+-1) as measured by both progressive isocapnic hypoxia at rest and transient hypoxia (three breaths of 100% N2) during moderate exercise, in seven normal men, to determine if the ventilatory response to the transient hypoxic stimulus is a more specific measure of peripheral chemoreceptor sensitivity to hypoxia. 2. Hypoxic ventilatory drive measured using progressive isocapnic hypoxia ranged from -0.13 to -2.65 litres min-1%-1 after placebo and from -0.20 to -6.48 litres min-1%-1 after almitrine. The response was greater after almitrine in six of the seven subjects, and the difference was significant for the whole group (P less than 0.05). 3. Hypoxic ventilatory drive measured using transient hypoxia ranged from -0.19 to -1.59 litres min-1%-1 after placebo and from -0.09 to -1.62 litres min-1%-1 after almitrine. The response was not consistently greater after almitrine, and the difference was not significant for the group. 4. Difficulties in accurately quantifying a brief rise in minute ventilation after transient hypoxia, particularly in subjects with a low hypoxic ventilatory drive, may have masked small changes in the slope of the minute ventilation/arterial oxygen saturation relationship with this method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

CT measurements of lung density in life can quantitate distal airspace enlargement--an essential defining feature of human emphysema.

We used a computerized microscopic image analysis system to directly measure the surface area of distal air spaces in methacrylate-embedded blocks randomly selected from inflation-fixed lobes that were resected from 45 patients as treatment of their peripheral lung tumors. In 28 of these patients, a preoperative computer tomography (CT) scan, at 6 and 10 cm below the sternal notch, was used to generate frequency histograms of CT numbers (measured as EMI units), a measure of lung density, in pixels from the lung or lobe that was subsequently resected. A similar CT number histogram was also derived from the lateral two fifths of the area of lobe/lung that was to be resected. The EMI unit that defined the lowest fifth percentile of this latter histogram correlated (n = 28, r = -0.77, p less than 0.001) with the mean value of the surface area of the walls of distal airspaces per unit lung volume (AWUV) in the five 1 mm x 1 mm microscopic fields with the lowest AWUV values, out of the 20 to 35 such fields examined in each patient. In the 34 of the 45 patients in whom we also measured volume-corrected diffusing capacity (DLCO/VA), this also correlated (n = 34, r = 0.84, p less than 0.001) with this value of AWUV, which measures the surface area of airspaces distal to the terminal bronchioles--reflecting an increase in airspace size, a defining characteristic of emphysema. However, a low DLCO/VA is nonspecific, whereas an abnormally low regional lung density is more likely to be specific for emphysema. In addition, highlighting those pixels of the CT display with low CT numbers (i.e., EMI units -500 [air] to -450, where zero = water) can locate areas of macroscopic emphysema, as shown by subsequent pathologic examination. Thus the quantitative CT scan can diagnose, quantitate, and locate mild to moderate emphysema, in humans, in life, noninvasively.

Aged↗
PubMed1985

Mechanism of transient nocturnal hypoxemia in hypoxic chronic bronchitis and emphysema.

In five patients with hypoxic chronic bronchitis and emphysema we measured ear O2 saturation (SaO2), chest movement, oronasal airflow, arterial and mixed venous gas tensions, and cardiac output during nine hypoxemic episodes (HE; SaO2 falls greater than 10%) in rapid-eye-movement (REM) sleep and during preceding periods of stable oxygenation in non-REM sleep. All nine HE occurred with recurrent short episodes of reduced chest movement, none with sleep apnea. The arterial PO2 (PaO2) fell by 6.0 +/- 1.9 (SD) Torr during the HE (P less than 0.01), but mean arterial PCO2 (PaCO2) rose by only 1.4 +/- 2.4 Torr (P greater than 0.4). The arteriovenous O2 content difference fell by 0.64 +/- 0.43 ml/100 ml of blood during the HE (P less than 0.05), but there was no significant change in cardiac output. Changes observed in PaO2 and PaCO2 during HE were similar to those in four normal subjects during 90 s of voluntary hypoventilation, when PaO2 fell by 12.3 +/- 5.6 Torr (P less than 0.05), but mean PaCO2 rose by only 2.8 +/- 2.1 Torr (P greater than 0.4). We suggest that the transient hypoxemia which occurs during REM sleep in patients with chronic bronchitis and emphysema could be explained by hypoventilation during REM sleep but that the importance of changes in distribution of ventilation-perfusion ratios cannot be assessed by presently available techniques.

Adult↗
PubMed1984

Fitness facilitates sleep.

Eight army recruits were studied at the start, middle, and end of their initial 18-week training programme. At each point the subjects were studied for four consecutive nights in the sleep laboratory. Their sleep was characterized by the means of the recordings on the last two nights. Within 2 days of the sleep recordings (but never on the same day) each subject spent 2 non-consecutive days in the exercise laboratory. On the 1st day a maximum oxygen consumption (VO2 max) measurement was performed on a treadmill and on the 2nd day a 24-min progressive exercise bicycle ergometer test was carried out with simultaneous venous sampling (for lactic acid measurements) and oxygen consumption recordings from which the lactate turn point (LTP) was calculated. LTP was used as a measure of fitness. Approximately 1 week after the above measures lean muscle mass as calculated by total body potassium estimation was obtained for each subject. Slow wave sleep (SWS) as a percentage of total sleep time increased significantly between the start and the measurements at 9 and 18 weeks, being 21.9%, 29.9%, and 28.5% respectively. Anaerobic threshold increased significantly (P less than 0.05) over the first 9 weeks and continued to increase to the end of the training period (P less than 0.001) using VO2 when lactate level was 2 mmol/l as a percentage of VO2 max. With increase in fitness, sleep onset latency and wake time during sleep decreased and sleep efficiency improved. The results suggest that as fitness increases sleep quality improves.

Adolescent↗
PubMed1981

Toxic megacolon in ulcerative colitis: a continuing challenge.

The incidence, predisposing factors, management and outcome of toxic megacolon (TM) has been reviewed in 65 cases of severe ulcerative colitis (UC) and compared in 2 successive 6-year periods before and after January, 1973. Nineteen episodes of TM occurred in 18 patients. Despite a conscious aim towards earlier surgery in recent years this was not achieved, and despite more intensive medical therapy the incidence of TM was unchanged. Emergency operative mortality in UC fell from 36% to 21% but the mortality of TM remained at 30%. The chief cause of death was colonic perforation. Mortality was associated with increased age, longer pre-operative hospital stay and lower levels of serum albumin. These findings reemphasize the need for earlier surgery if TM is to be prevented, but such a policy must result in some unnecessary emergency colectomies.

Adult↗
PubMed1980

Respiratory failure revisited: acute exacerbations of chronic bronchitis between 1961-68 and 1970-76.

Factors determining survival have been analysed retrospectively in 157 admissions of 135 patients with an acute exacerbation of chronic bronchitis and emphysema causing hypoxaemia and carbon dioxide retention. All were treated with controlled oxygen therapy. The death-rate increased with the age of the patient, but was not correlated with the age of the patient, but was not correlated with the severity of hypoxaemia on admission, when the patient was breathing air. The death-rate was significantly higher in those patients in whom arterial [H+] rose above 55 nmol/1 (pH = 7.26) during controlled oxygen therapy. The absence of a rise in the arterial PCO2 during controlled oxygen therapy was not necessarily indicative of a good prognosis, since 5 out of 18 patients showing this response subsequently died in that admission. Only 28% of the 111 patients who left hospital alive survived for five years.

Acidosis, Respiratory↗
PubMed1977

Methadone maintenance: effect of urinary pH on renal clearance in chronic high and low doses.

The subjects were 12 male patients stabilized on methadone for many months or years. A comparison was made of the plasma levels and renal clearance of methadone between patients on "high" doses (80 to 110 mg/day) and those on "low" doses (15 to 40 mg/day). A general trend to higher renal clearance was seen in the "high" -dose group, but on more detailed examination there was a direct correlation only when the patients were categorized by urinary pH. At low pHs, there was nearly a 3-fold increase in renal clearance which was associated with a decreased major metabolite to methadone ratio. No evidence for a difference in rate of metabolism between the two groups was found nor were there differences in hepatic function. It was concluded that urinary pH was a major factor in renal clearance of methadone.

Adult↗
PubMed1975

Reduced DNA repair capacity and increased cytotoxicity following split doses of the mutagen 4-nitroquinoline-1-oxide in cultured human cells.

Cultured human fibroblasts were exposed to single doses of 4-nitroquinoline-1-oxide(4NQO) and to two equimolar doses of 4NQO at intervals varying from 0.5 to 12 h. DNA repair synthesis as measured by an unscheduled uptake of tritium-labelled thymidine ([3-H]TdR), cell survival as estimated by the clone-forming capacity, and frequency of chromosome aberrations were used as endpoints. Cells respond with a reduced level of DNA repair synthesis when the second 4NQO dose (5 X 10 minus 7 or 1 X10-minus 7 M) is given within 3 h of the first 4NQO dose. If the interval between the two doses is 5 h or more, the level of DNA repair synthesis which is induced by the second 4NQO dose is comparable to that following a single 60-min 4NQO application. In this 3-h period the cultured cells show an increased sensitivity to the lethal effect and chromosome-damaging action of the second 4NQO dose. The reduced period of DNA repair capacity seems to increase the mutagenic effect of the chemical carcinogen.

4-Nitroquinoline-1-oxide↗