Biomedical subjects
Publications and source records attributed to R S Howard.
Two patients with sarcoidosis and glomerular mesangial proliferative lesions are described. Although a causative relationship between sarcoidosis and glomerulonephritis has been suggested, critical review of the literature fails to confirm this.
Histamine has been shown to mediate features of pulmonary allergic reactions including increased tracheobronchial blood flow. To determine whether the increase in blood flow was due to stimulation of H1- or H2-histamine receptors, we gave histamine base (0.1 micrograms/kg iv) or histamine dihydrochloride as an aerosol (10 breaths of 0.5% "low dose" or 5% "high dose") before and after H1- or H2-receptor antagonists. Blood velocity in the common bronchial branch of the bronchoesophageal artery (Vbr) was continuously measured using a chronically implanted Doppler flow probe. Pretreatment with H2-receptor antagonists cimetidine, ranitidine, or metiamide did not affect the increase in Vbr induced by intravenous histamine [106 +/- 45% (SD)]. Addition of the H1-receptor antagonists diphenhydramine or chlorpheniramine, however, reduced the Vbr response to 16 +/- 22, 21 +/- 28, 23 +/- 23, and 37 +/- 32% of the unblocked responses (P less than 0.05) when intravenous histamine was given at 3, 10, 20, and 30 min, respectively, after the H1 antagonist. At 40, 50, and 60 min the H1-receptor blockade appeared to attenuate, but subsequent continuous infusion of chlorpheniramine (2 mg.kg-1.min-1) then blocked the histamine response for 60 min. Low-dose histamine aerosol did not change mean arterial or pulmonary arterial pressures, cardiac output, or arterial blood gases but increased Vbr transiently from 15.2 +/- 3.4 to 37.6 +/- 8.4 (SE) cm/s. After chlorpheniramine, the Vbr response to histamine, 16.3 +/- 2.2 to 22.6 +/- 3.6 cm/s, was significantly reduced (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The thresholds used to define a positive result for bronchial provocation challenges (BPC) are arbitrary. Requiring smaller decrements in expired flow to define a positive study would capture more cases of reactive airways (increased sensitivity) but would include some "normal" responses (decreased specificity). To examine the relationship between threshold definition and the ability to correctly classify subjects as either normal or as having airways hyperresponsiveness (AHR), four different BPC tests were administered on different days to 20 patients with a clinical diagnosis of exercise-induced bronchospasm (EIB) and 20 control subjects. The four BPC tests were indoor exercise on a cycle ergometer, methacholine inhalation challenge (MIC), eucapnic voluntary hyperventilation (EVH) with dry gas, and EVH with cold gas. Our results indicate that the thresholds which best separate the two groups are different for each of the four BPC techniques. For methacholine inhalation (MIC), a fall in FEV1 (d%FEV1) of 15 percent or greater at 188 cumulative breath units was 100 percent specific for AHR but had a sensitivity of only 55 percent. Eucapnic voluntary hyperventilation (EVH) with room temperature dry gas was 100 percent specific at a d%FEV1 of 11 percent, but, at that threshold, sensitivity was only 50 percent. EVH with cold air was 100 percent specific at a d%FEV1 of 12 percent but sensitivity was only 35 percent. The bicycle ergometer challenge was far too insensitive to be of value in evaluating AHR. Based on their respective receiver operating characteristic curves, the best separation of the two subject groups occurred at a d%FEV1 of 5 percent and 12 percent for the two EVH techniques and MIC, respectively. An individual's response to one test was highly correlated with the response to either of the other two (r = 0.66, p less than 0.001 for dry vs cold gas EVH; r = 0.56, p less than 0.001 for dry gas EVH vs methacholine; and r = 0.69, p less than 0.001 for cold gas EVH vs methacholine). Thus, MIC and EVH techniques are equally useful in defining AHR and each has its optimal threshold for a positive test result.
We present a 10 to 20-year followup assessment of 191 patients with unexplained microhematuria (including persons with insignificant lesions). Genitourinary malignancies did not develop in any of the patients (128 alive and 27 dead) evaluated after the first diagnostic investigation. Patient and physician compliance with followup protocols was poor. We currently recommend renal ultrasound and cystoscopy for the first diagnostic survey, have abandoned routine periodic studies and advise diagnostic studies only for patients in whom symptoms develop.
Achalasia is a cause of chronic aspiration pneumonia that may be complicated by pulmonary infection with Mycobacterium fortuitum. In any patient with achalasia, the presence of a pulmonary infiltrate that does not respond to routine antibiotic therapy should suggest the possibility of M fortuitum pulmonary infection, and sputum should be cultured for these organisms.
1. Efferent discharges were recorded from inspiratory and expiratory intercostal nerve filaments (T2-T10) in artificially ventilated, anaesthetized or decerebrate rabbits with or without vagotomy. 2. Hypocapnic apnoea was used to study the fractional end-tidal CO2 (FET,CO2)-dependent tonic discharges of the expiratory motoneurones, the FET,CO2 threshold for rhythm generation and the FET,CO2 response curve of both inspiratory and expiratory burst activity. 3. Incremental doses of morphine (e.g. 1 mg kg-1 I.V.) produced slowing of the respiratory rhythm due to prolongation of the expiratory duration and an elevation of the FET,CO2 threshold for rhythm generation. Eventually apnoea supervened with associated tonic firing of the expiratory motoneurones. At the elevated levels of FET,CO2 bursts of inspiratory activity, with concomitant phasic inhibition of the tonic expiratory activity, could occur either spontaneously or following sensory stimulation. The peak integrated activities of these bursts were closely similar to the values obtained for corresponding levels of FET,CO2 before the administration of morphine. 4. Tonic expiratory activity responded to increased levels of FET,CO2, as it had during hypocapnic apnoea prior to morphine, by an increased discharge frequency of single units or recruitment of new units. 5. All of these effects of morphine were immediately reversed by naloxone (100 micrograms kg-1). 6. Naloxone (greater than 100 micrograms kg-1), without pre-treatment with morphine, led to an increase in respiratory frequency due to a shortening of the expiratory duration and a dose-dependent reduction in the FET,CO2 threshold for rhythm generation. There was little alteration either in the inspiratory response to FET,CO2 during rhythm or in the FET,CO2 response of the expiratory output whether expressed as tonic activity during hypocapnic apnoea or phasic activity following the onset of rhythm. 7. Thus opiates act upon the mechanisms of rhythm generation without depressing the FET,CO2 drive as expressed either as phasic or tonic activation of the motoneurones.
Mounier-Kuhn syndrome is a congenital abnormality of the trachea and main bronchi characterized by atrophy or absence of elastic fibers and thinning of muscle, which allows the trachea and main bronchi to become flaccid and markedly dilated on inspiration with narrowing or collapse on expiration or cough. The abnormal airway dynamics and pooling of secretions in broad outpouchings of redundant musculomembranous tissue between the cartilaginous rings predispose to the development of chronic pulmonary suppuration, bronchiectasis, emphysema, and pulmonary fibrosis. A broad spectrum of clinical abnormalities has been documented in Mounier-Kuhn syndrome, ranging from minimal disease with good preservation of pulmonary function to progressive disease leading to respiratory failure and death. In the appropriate clinical setting, Mounier-Kuhn syndrome is diagnosed in women from chest radiographs when the transverse and sagittal diameters of the trachea exceed 21 mm and 23 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 19.8 mm and 17.4 mm, respectively. In men it is diagnosed when the transverse and sagittal diameters of the trachea exceed 25 mm and 27 mm, respectively, and when the transverse diameters of the right and left main bronchi exceed 21.1 mm and 18.4 mm, respectively. The diagnosis can be confirmed easily by computed tomography.
A 16-year-old woman deliberately took a large, toxic overdose of carbamazepine and recovered despite a high plasma level. During the acute phase the EEG was dominated by occipital delta activity suggestive of a brainstem disorder. Following 24-h treatment with activated charcoal the plasma carbamazepine was cleared and the EEG returned to normal.
Although respiratory insufficiency is common in the advanced stages of motor neuron disease, some patients may develop distressing respiratory symptoms early in the course of the disease or even present with respiratory failure or arrest. We describe 14 patients with motor neuron disease who were considered for respiratory support; 11 received such support and all derived significant symptomatic improvement without distressing prolongation of life. Of the 8 patients with typical features of amyotrophic lateral sclerosis, 7 had predominant diaphragm weakness and 1 generalized respiratory muscle weakness; 7 received negative pressure ventilation by cuirass which improved both the quality of sleep and exercise tolerance. Three patients with predominantly bulbar disease had nocturnal apnoea or hypoventilation. Two received no support. One, who also developed diaphragm weakness, was treated by a cuirass, continuous positive airway pressure (CPAP), and later nocturnal intermittent positive pressure ventilation (IPPV). Three patients with progressive muscular atrophy had predominant diaphragm weakness or nocturnal apnoea. These patients received nocturnal CPAP, cuirass or IPPV with symptomatic benefit. This series shows that some patients with motor neuron disease, mainly those with symptoms due to respiratory muscle weakness in the absence of severe bulbar impairment, derive symptomatic benefit from supported ventilation.
Two adult patients are described with cerebellar ectopia whose presentation at diagnosis was respiratory arrest. Following surgical decompression both patients become self ventilating and now lead independent lives. Cerebellar ectopia is a potentially remediable condition and should be considered in patients with unexplained respiratory arrest.
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Progressive functional deterioration following poliomyelitis has been reported after a prolonged period of stability. We present follow up data on 209 patients; the period from the original illness to December 1985 or death was between two and 73 years (mean 33.9). One hundred and sixty-three (78 per cent) patients developed late functional deterioration. This was due to purely respiratory factors in 99 cases, new neurological signs in 20 cases, and orthopaedic problems in 17 cases; 31 patients deteriorated due to a combination of factors. The commonest cause of respiratory deterioration was the development of nocturnal alveolar hypoventilation, sometimes associated with late progressive scoliosis. Eighty-six patients needed respiratory support beginning between one year and 66 years (mean 28.5) after the acute illness. New neurological signs had a clearly defined cause in each of 20 patients. No cases of motor neurone disease or post-poliomyelitis muscular atrophy (PPMA) were identified. This series shows that late sequelae following poliomyelitis are common. There were no patients with functional deterioration after poliomyelitis in whom a clear underlying cause could not be shown. The major causes of deterioration may be treatable or avoidable, and in particular, those who develop chest infections or new respiratory symptoms should be treated with caution as respiratory failure may rapidly supervene.
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Four patients are described with an encephalitic illness identical to that described by von Economo. Electroencephalographic, evoked potential and autopsy data suggest that involvement of the cerebral cortex is more extensive than has been generally recognized. Serological tests and viral cultures failed to reveal the infectious agent but the presence of oligoclonal IgG banding in the cerebrospinal fluid in 3 of the patients during the acute phase of the illness would be in keeping with a viral aetiology.
Eighty-five patients with retinal emboli, visible ophthalmoscopically, were studied retrospectively. All the patients had presented with transient or permanent visual loss. Follow up from the time of presentation was one year to 12 years with a mean of 4.5 years. Life expectancy in the 58 medically treated patients who presented with cholesterol emboli was significantly reduced (p = 0.028). Stroke was the commonest cause of death and was significantly more frequent than in the general population (p less than 0.001); there was also an increased total incidence of cerebrovascular disease (fatal and non-fatal) compared with the Oxfordshire Stroke Project (p less than 0.001). The mortality from ischaemic heart disease was not significantly increased. We report a series of 85 patients with retinal emboli, 69 of whom had cholesterol emboli (70 fundi), 15 calcific emboli and one platelet-fibrin embolus. The natural history of medically treated patients with cholesterol emboli is compared both with an age and sex matched population and with patients with amaurosis fugax but no visible retinal emboli.
A patient is described who presented with visual loss due to infiltration of the optic chiasm by chronic lymphocytic leukaemia. This case demonstrates intracranial infiltration as a primary presentation of chronic lymphocytic leukaemia without lymphoreticular involvement and, to our knowledge, is the first report of a chiasmal syndrome due to this lymphoproliferative disorder.
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A mother presented at 28 weeks with epileptiform convulsions which were due to a malignant cerebral tumour. Labour and delivery at 34 weeks were managed under epidural analgesia. The infant was healthy, but the mother died several days later following cerebral decompression.