Biomedical subjects
Publications and source records attributed to P Howard.
Oxygen therapy is given in three different ways in the home, long-term (LTOT), short burst and portable oxygen. Cost effective oxygen therapy depends upon appreciation of the indications for each form of administration, the nature of the disease causing oxygen deficiency, the most suitable oxygen source and careful monitoring of the therapeutic response. The many problems remaining in these areas are reviewed here.
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Short and long term administration of vasodilator drugs to patients with pulmonary artery hypertension (PAP) effects small falls of PAP and larger reductions of pulmonary vascular resistance due to increases of cardiac output. Side effects of systemic hypotension are sometimes troublesome. Improvement of survival has not yet been demonstrated. It is likely that any treatments capable of sustained clinical benefit in hypoxic cor pulmonale will have to arrest or reverse pathology in the airway and pulmonary vessel. There is no evidence that pulmonary vasodilator drugs will do this. Their clinical place is in doubt.
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Methyldopa (alpha-methyldopa) was given to patients with cor pulmonale secondary to chronic obstructive airways disease (COAD) to determine its effect on pulmonary haemodynamics. Twenty-five patients were randomly allocated to methyldopa (750 mg daily) or placebo. Pulmonary haemodynamics were measured twice, 12 months apart. Conventional therapies were continued unchanged. The effects of the drug on pulmonary haemodynamics were inconclusive when considered overall, but total pulmonary vascular resistance (TPVR) fell in all patients on active therapy in whom measurements were obtained both at rest and upon exercise. Only one patient in the placebo group achieved this. Over the trial period there was one death in the active but five in the placebo group. Survival was unrelated to abnormalities in pulmonary haemodynamics at the commencement of the trial in this study although the numbers of patients was small. Postural hypotension developed in patients receiving methyldopa and limited the dose that could be administered. The problems involved in long term trials of vasodilators in hypoxic cor pulmonale are discussed.
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Patients with hypoxaemia secondary to chronic obstructive pulmonary disease (COPD) are frequently prescribed oxygen therapy for short- and long-term domiciliary use. Oxygen administered via nasal cannulae incorporating a small collapsible reservoir ("Oxymizer", Chad Therapeutics Inc., CA, USA) improves transcutaneous oxygen tensions in the short-term when compared to standard nasal cannulae. The effects of this device on arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions was assessed over 60 min in twelve patients with severe hypoxaemia (6.2 +/- 0.9 kPa, mean +/- SD) and hypercapnia (7.5 +/- 1.2 kPa). Following baseline measurements, oxygen was administered using standard nasal cannulae, and further measurements were made at 15 min intervals for at least 45 min. Patients were then changed to the "Oxymizer" and measurements continued at 15 min intervals for a further 60 min. Mean PaO2 increased by 1.1 +/- 0.78 kPa (p less than 0.001), using the "Oxymizer", but PaO2 was significantly greater after 15 min on the device than after 60 min (p less than 0.05). There was no change in PaCO2 (p greater than 0.05). The "Oxymizer" increases PaO2 compared with standard cannulae, but the effect may not be sustained.
A pathophysiological study of the pulmonary vasculature in 10 patients with hypoxic cor pulmonale and severe airways obstruction (five treated and five untreated with long-term oxygen) is presented. The media of muscular pulmonary arteries was normal or atrophic but, in the intima, there was active deposition of longitudinal muscle, fibrosis and elastosis. In the arterioles a medical coat of circular smooth muscle bounded by a new internal elastic lamina had developed, while there was deposition of longitudinal muscle and fibrosis in the intima. In five cases the lumen was subdivided into parallel tubes, found by serial section to lead into alveolar capillaries. These features are distinctive of hypoxaemia and obstructive airways disease. Changes continued until death. The conspicuous longitudinal muscle may be attributable to stretching of vessels round distorted terminal airways; further exploration into mechanisms is required. The hypothesis that vascular changes follow hypoxic vasoconstriction is no longer tenable. No correlations were found between quantitative pathological findings and arterial blood gas tensions, pulmonary artery pressure or haematocrit. There were no differences between patients treated or not treated with oxygen which might suggest that it arrests pathological changes. Thus, once a patient is given oxygen, survival probably depends as much on progressive mechanical changes in the lung as on continuing hypoxaemia.
The prevalence of infection with Chlamydia psittaci, Toxoplasma gondii, Toxocara cati and Microsporum canis was examined in 51 cats on 22 sheep farms in the Bristol area. Serum antibody to C psittaci and T gondii was present in 45 per cent and 47 per cent of cats, respectively. At the time of sampling C psittaci was isolated from 6 per cent of the cats, T cati was identified in 63 per cent of faecal samples but neither T gondii nor M canis was isolated. When examined according to the farm of origin, 22.7 per cent of farms had cat populations with no evidence of infection with C psittaci or T gondii. Of the remainder, 45.5 per cent supported cat populations with evidence of both infections and 31.8 per cent had evidence of T gondii infection alone. None of the farms had cat populations with evidence of C psittaci infection alone. Two of the cats infected with C psittaci were excreting viable organisms in the faeces. The possible significance of this to the epidemiology of ovine enzootic abortion is discussed.
Patients presenting with chronic obstructive airways disease and hypoxic cor pulmonale were assessed during a period of clinical stability. Seventy two patients (53 male) with a mean age of 60 years were selected for long term oxygen therapy. Mean FEV1 was 0.78 l and forced vital capacity 1.9 l. The mean arterial oxygen tension (PaO2) was 6.1 kPa (46 mm Hg) and the mean arterial carbon dioxide tension (PCO2) 6.9 kPa (52 mm Hg). All patients had a PaO2 of less than 8.0 kPa (60 mm Hg) and 57 patients had a PCO2 of more than 6.0 kPa (45 mm Hg). Pulmonary haemodynamics were measured in 45 patients yielding the following mean values: pulmonary artery pressure 28.3 mm Hg; cardiac output 5.9 l min-1; total pulmonary vascular resistance 59.2 kPa l-1 S. Oxygen delivery systems, including 23 oxygen concentrators, were installed in the patients' homes. Flow rates were adjusted to raise PaO2 to more than 8.0 kPa (60 mm Hg) for at least 15 hours each day and close supervision was maintained. Overall five year survival was 62%, which is better than previously reported for this type of patient; but the 10 year survival was only 26% owing to an observed acceleration in death rate at about this time. Progressive disturbances of the pulmonary circulation were arrested. Mortality was associated with the severity of airflow obstruction, reflecting a continuing pathological process affecting the airways.
There is a place in therapy for an orally active respiratory stimulant. Almitrine bismesylate is a respiratory agonist which: 1. Effectively increases PaO2 in a unique way, principally by stimulation of the peripheral chemoreceptors. 2. Appears to have an effect on blood gases through mechanisms other than stimulation of ventilation which could be on ventilation-perfusion relationships, or even metabolic, for which there is as yet no firm evidence. 3. After chronic administration has a plasma elimination half-life of 20-30 days. This could result in plasma accumulation of the drug, and means that drug intolerance problems are not readily resolved by stopping the tablets. Special dosing schedules may be required. 4. Has an action on the pulmonary vasculature which is mainly vasoconstrictor (and vasodilator in acute hypoxia in animal studies). Present evidence regarding the effect of long-term administration on pulmonary haemodynamics is conflicting. 5. May have an adverse, possibly dose-related effect on dyspnoea in some patients - more work is needed on patient characteristics associated with good drug tolerance. 6. Has an adverse effect on peripheral nerve function in some patients. Whether this is de novo, or aggravation of a preexisting lesion has yet to be established. Thus, although almitrine is effective in increasing PaO2 and as an experimental drug is fascinating, its clinical use remains to be clearly defined. The most powerful argument for the therapeutic use of almitrine would be the demonstration of a beneficial effect on mortality; either in acute exacerbations of respiratory failure, or in the same way as LTO2 exerts an effect in chronically hypoxaemic patients.
701 patients, age 61.9 +/- 8.3 yr (mean +/- SD), with hypoxaemic chronic obstructive airways disease (COAD) were entered into a one yr placebo-controlled double-blind study to determine the effect of oral almitrine bismesylate on arterial blood gas tensions and clinical condition. Initial arterial O2 tension (PaO2) was 7.6 +/- 0.8 kPa (57.0 +/- 6.2 mmHg) and arterial CO2 tension (PaCO2) was 6.0 +/- 0.9 kPa (45.2 +/- 6.7 mmHg). Forced expiratory volume in one second (FEV1) was 0.87 +/- 0.35 l and forced vital capacity (FVC) was 2.31 +/- 0.72 l. 163 patients, evenly distributed between treated and untreated groups, were receiving long-term O2 therapy; other conventional therapy was continued. In a stabilization period before treatment, excellent reproducibility of blood gas tensions and spirometry was achieved. In the placebo group (P; n = 357), little change in physiological measurements or clinical assessment was recorded, 90 patients (25%) were lost from the study, mostly due to deterioration of their respiratory disease or to death; 3.4% withdrew for adverse reactions. The almitrine group (A; n = 344), received 100-200 mg per day orally in two divided doses, depending on the improvement in PaO2 achieved. On entry to the study their blood gas tensions, lung function tests, clinical assessment, history of hospitalization and frequency of right heart failure were not significantly different from the placebo group. After one yr of treatment, PaO2 rose from 7.6 +/- 0.8 kPa (57.4 +/- 6.1 mmHg) to 8.5 +/- 1.3 kPa (63.7 +/- 9.7 mmHg), p less than 0.001 compared with the placebo group. Red cell count decreased p less than 0.001 compared with the placebo group and FEV1 increased from 0.92 l to 0.95 l, p less than 0.001 compared with the placebo group. Dyspnoea, assessed on a 100 mm analog scale was unchanged in the almitrine group as a whole, but some individual patients withdrew on account of breathlessness. A smaller proportion of patients in group A were hospitalized and had episodes of right heart failure during the study than in group P (p less than 0.05). Vital signs, biochemistry and ECG characteristics did not change. 139 patients (40%) in this group did not complete the study, 35 (10%) through deterioration of respiratory symptoms or death (4.9%); 43 (12.5%) withdrew because of adverse reactions, either drug-related or not. The most frequent adverse reactions were gastro-intestinal, central nervous system disturbances, increased dyspnoea and peripheral paraesthesiae.(ABSTRACT TRUNCATED AT 400 WORDS)
An overview of the various methods available for treatment of mandibular fractures is presented; these range from the application of arch bars and intermaxillary fixation alone to open reduction with compression plating. Whenever possible, particularly in young patients, mandibular fractures requiring open reduction are approached transorally.
Most patients with chronic obstructive lung disease prescribed oxygen at home by their family doctor use it for short periods when they feel breathless. Many patients are normoxic. Nineteen patients with advanced disease and variable hypoxaemia undertook exercise until they indicated severe breathlessness on a 100 mm visual analogue scale. Air, 67% oxygen, and air delivered from a cylinder in an identical manner to the oxygen were randomly administered during the recovery periods. Respiratory rate, heart rate and oxygen and carbon dioxide tensions, estimated by transcutaneous electrodes (tcPo2, tcPco2), were measured throughout the exercise and recovery periods. The mean recovery time for breathlessness as judged by visual analogue score was significantly shorter when oxygen was used than during placebo or air recovery (p less than 0.05). The rates of return to baseline levels of respiratory and heart rates were not significantly affected by the gas inhaled. No placebo effect was detectable. It was not possible to select good responders from the results of prior physiological tests. In seven patients the study was repeated after an interval of between one week and a year. The consistency of observed response to oxygen was poor. Although recovery judged by visual analogue scores showed some consistency within individual patients and greater overall consistency than heart rate or respiratory rate, the direction of change in recovery judged by visual analogue score after the breathing of oxygen was variable. The change during the breathing of oxygen was towards improvement in both studies in three patients and towards deterioration in both studies in one patient, and it showed no consistent direction of change in the remaining three patients. It is difficult to determine which patients will derive substantial and reproducible benefit from short burst oxygen but their numbers are probably small. The results cast doubt on the justification for the current widespread prescription of oxygen cylinders for occasional use.
The most common causes of hypoxic cor pulmonale are chronic bronchitis and emphysema. Although the clinical situation in some patients is characterized early by hypoxemia, oedema is rare in patients with an arterial pO2 above 60 mm Hg. The presence of oedema can be regarded as an unfavorable prognostic indicator. For many years, peripheral oedema had been considered an expression of congestive cardiac failure; it may be assumed, however, that neither right nor left ventricular failure is prerequisite to the development of oedema. Oedema formation can be attributed to excessive retention of salt and water or a redistribution of body water into the extracellular compartment. Hypercapnia and acidosis affect direct stimulation of renal hydrogen ion secretion. The resulting electrochemical imbalance is compensated by reabsorption of sodium. Hypercapnia and, in acute phases possibly, hypoxia lead to a fall in renal blood flow mediated by alpha-adrenergic stimulation through activation of the renin-angiotensin-aldosterone system. An increase in plasma ADH may also contribute to development of oedema. The development of cor pulmonale or respiratory insufficiency can be enhanced by nocturnal hypoventilation and hypoxia during sleep as well as by sleep apnoea. Nocturnal hypoxia, smoking and reduced oxygen tension in the relevant kidney cells responsible for erythropoietin release promote the occurrence of secondary polycythaemia. For treatment of acute exacerbations in cor pulmonale associated with infections bronchitis antibiotics such as amoxycillin and cotrimoxacol are drugs of first choice. While the use of digoxin is of doubtful value, the cautious administration of diuretics may bring symptomatic relief. In addition to physiotherapy, beta-2-selective bronchodilators and nebulized bronchodilator therapy can be useful; theophyllines dilate airways and increase cardiac output but they can cause arrhythmias and a deterioration of arterial blood gases in hypoxic patients. If the patient has been treated chronically with corticosteroids, the dosage will have to be incremented; if asthma is suspected, corticosteroid treatment is essential. Controlled oxygen therapy is the most important single therapy aimed at relief of severe arterial hypoxaemia. Oxygen should be titrated initially (for the first one or two days) to achieve an arterial tension of at least 48 mm Hg. Thereafter, the oxygen flow should be increased to yield an arterial tension in excess of 60 mm Hg during continued treatment for two to three weeks.(ABSTRACT TRUNCATED AT 400 WORDS)
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