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Biomedical subjects

J H Winter

Publications and source records attributed to J H Winter.

At least 19 recordsLinked to original sources

Comparison of the relative airways and systemic potencies of inhaled fenoterol and salbutamol in asthmatic patients.

BACKGROUND: There is controversy as to the relative safety of fenoterol and salbutamol. No differences have been found in the relative cardiac beta 1/beta 2 receptor activity of inhaled fenoterol and salbutamol in normal subjects. These initial findings have been extended by comparing the respective potencies of equivalent doses by weight of fenoterol and salbutamol in asthmatic subjects, in terms of airways and systemic responses. METHODS: Eighteen asthmatic patients of mean (SD) age 40 (14) years and a forced expiratory volume in one second (FEV1)% predicted of 56 (14)% (1.97 (0.66)1) were randomised to inhale fenoterol (100 micrograms/puff or 200 micrograms/puff), salbutamol, or placebo (100 micrograms/puff or 200 micrograms/puff) on three separate days. Dose-response curves were constructed using cumulative doses of 100 micrograms, 200 micrograms, 400 micrograms, 1000 micrograms, 2000 micrograms, and 4000 micrograms, and airways and systemic responses were measured 20 minutes after each dose with 40 minute increments. Dose ratios for the relative potency of fenoterol versus salbutamol were calculated from the dose-response curves using regression analysis of parallel slopes. RESULTS: There was no difference in bronchodilator potency between fenoterol and salbutamol (as median dose ratio): FEV1 1.1 (95% CI 0.4 to 4.6). In contrast, dose ratios for systemic responses showed that fenoterol was more potent than salbutamol: serum potassium 3.7 (95% CI 2.0 to 6.0), tremor 5.7 (95% CI 1.4 to 10.2), heart rate 1.6 (95% CI 1.0 to 2.3). At a conventional dose of 200 micrograms the only difference in response between the two drugs was observed for tremor (as mean difference): 0.23 log units (95% CI 0.06 to 0.41 log units). CONCLUSIONS: There was no difference in the bronchodilator potency between fenoterol and salbutamol on a microgram equivalent basis. In contrast, systemic potency was greater with fenoterol, although this difference was not clinically relevant at conventional dosages up to 200 micrograms.

Administration, Inhalation

C-reactive protein. A clinical marker in community-acquired pneumonia.

STUDY OBJECTIVE: To assess the range of plasma C-reactive protein (CRP) in patients presenting with community-acquired pneumonia and to compare the serial changes of this acute-phase protein with clinical outcome. DESIGN: Prospective hospital-based study, including separate retrospective case series. PATIENTS: Twenty-eight consecutive patients (mean age, 60 years) admitted to our hospital with community-acquired pneumonia were studied. Serial daily plasma samples were taken and assayed for CRP, tumor necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6). Clinical parameters, laboratory data, and response to treatment were recorded. Four other patients considered to be antibiotic failures (three empyemas, one death) were studied separately. RESULTS: Two patients died. Of those who survived, mean (+/- SD) CRP values for days 1,2,3,4, and 5 were as follows: 136 +/- 43, 96 +/- 44, 53 +/- 36, 54 +/- 43, and 44 +/- 31 mg/L. CRP levels on day 1 in patients who had received antibiotics prior to hospital admission were significantly lower than those who had not, 107 +/- 42 and 152 +/- 44 mg/L (p < 0.05). CRP levels did not correlate with other laboratory parameters or with recognized predictors of mortality. A CRP value that continued to rise despite antibiotic treatment was associated with infective complications or death. Only 52% of patients had detectable TNF-alpha and 24% detectable IL-6 at some point during their hospital stay. CONCLUSIONS: CRP is a sensitive marker of pneumonia. A persistently high or rising CRP level suggests antibiotic treatment failure or the development of an infective complication. These results suggest that CRP, rather than TNF-alpha or IL-6, may have a role as a clinical marker in pneumonia.

Adult

Phagocyte function and cytokine production in community acquired pneumonia.

BACKGROUND: It is possible that many deaths from pneumonia may involve the generation of inflammatory mediators and tissue damage by activated phagocytes. To test this hypothesis phagocyte function, plasma levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha), and soluble interleukin 2 receptor (IL-2R), disease severity, and outcome have been examined in 46 patients with community acquired pneumonia. METHODS: Polymorphonuclear leucocyte (PMNL) and monocyte function were measured daily by chemiluminescence in these patients during the first week of admission, and cytokine levels were subsequently determined by ELISA. A series of 61 healthy individuals were used as a control group for the chemiluminescence results. RESULTS: There was evidence of phagocyte, particularly PMNL, activation on admission in 76% of the patients. Most patients (86%) also had raised IL-2R levels on admission. IL-6 and unbound TNF alpha were present in 23% and 41% of patients at varying times during the course of the disease. There was little correlation between measurements of cytokine or phagocyte levels and outcome or indicators of disease severity, although this may be because of the small number of patients included in this preliminary study. CONCLUSIONS: These results are consistent with the hypothesis that activated phagocyte function and raised levels of circulating cytokines may contribute to the pathogenesis of community acquired pneumonia. There are striking similarities in this respect between pneumonia, adult respiratory distress syndrome, and sepsis.

Adolescent

TNF and pneumonia.

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Community-Acquired Infections

Bronchodilator reversibility to low and high doses of terbutaline and ipratropium bromide in patients with chronic obstructive pulmonary disease.

BACKGROUND: There is uncertainty regarding the use of monotherapy or combination therapy with beta 2 agonists and anticholinergic drugs in patients with chronic obstructive pulmonary disease (COPD). The measurement of forced expiratory volume in one second (FEV1) or relaxed vital capacity (RVC) in the assessment of reversibility in these patients has also caused considerable debate. METHODS: Twenty seven patients with COPD were evaluated on two occasions. Patients received the following treatments in sequence: (sequence 1) low dose terbutaline 500 micrograms, high dose terbutaline 5000 micrograms, low dose ipratropium 40 micrograms, high dose ipratropium 200 micrograms; (sequence 2) low dose ipratropium 40 micrograms, high dose ipratropium 200 micrograms, low dose terbutaline 500 micrograms, high dose terbutaline 5000 micrograms. RVC, FEV1 and FVC were measured at baseline and 30 minutes after successive treatments. RESULTS: Values for FEV1 at baseline on the first and second study days were not significantly different: 0.90 (0.87-0.93) 1 v 0.90 (0.87-0.93) 1. Likewise, baseline values for RVC and FVC were not different. The number of patients showing a greater than 330 ml overall improvement in RVC was 20 of 27 for sequence 1 and 22 of 27 for sequence 2; similar trends were observed for FEV1 and FVC. For all three parameters there was a significant difference between mean responses to low and high doses of terbutaline when the latter was given as the first drug in sequence 1. When ipratropium was given first in sequence 2 there was, however, no significant improvement with high dose terbutaline over and above the response to low dose terbutaline. The latter effect was more noticeable with RVC than with either FEV1 or FVC. The total bronchodilator response at the end of each sequence was similar whether ipratropium was given first or second. CONCLUSIONS: The measurement of RVC, FEV1, and FVC were equally effective at picking up those patients who had a significant overall bronchodilator response to combined therapy with inhaled beta 2 agonist and anticholinergic medication. There was no significant benefit of adding a higher dose of terbutaline when ipratropium bromide had been given previously, particularly when using RVC as the parameter of response.

Administration, Inhalation

An audit of hospital discharge letters in patients admitted with acute asthma. Tayside Asthma Audit Group.

The management of patients following discharge with acute asthma is dependent on effective communication with general practitioners. A retrospective audit was therefore performed on copies kept of 81 typed discharge letters with a diagnosis of acute asthma between March and October 1991. A subset of 42 interim (handwritten) letters were also audited where case notes could be retrieved. Details on clinic follow up were also obtained from the case notes (n = 42). In the typed letter documentation of severity and treatment of the acute attack was accurate in most cases. Information concerning a precipitating factor was provided in 54% of cases and a smoking history in 57%. Deficiencies were found in specifying inhaler delivery devices (40% recorded), and whether inhaler technique had been formally assessed whilst in hospital (17%). Drug prescribing on discharge was as follows: oral steroid (69%), inhaled steroids (77%), inhaled B2-agonists (92%), theophylline slow release (38%), salbutamol controlled release (20%), and antibiotics (30%). The implementation of a self-management plan and domiciliary peak flow was mentioned in 66% of the letters. The interim letter was generally poor in particular for mention if discharge peak flow (2%), clinic follow-up (64%) and prednisolone regime (61%). Mean +/- s.d. time for clinic follow-up (n = 42) was 4.7 +/- 1.7 weeks (range 1-13 weeks) with 24% non-attendance. Thus, improvements in discharge letters are clearly required for optimum continuity of care in the community.

Acute Disease

Elevated levels of brain natriuretic peptide in acute hypoxaemic chronic obstructive pulmonary disease.

1. Studies in vitro have recently shown that both atrial natriuretic peptide and brain natriuretic peptide have pulmonary vasorelaxant activity. The purpose of the present study was to evaluate for the first time whether plasma levels of brain natriuretic peptide are elevated in chronic obstructive pulmonary disease. Plasma levels of brain natriuretic peptide and atrial natriuretic peptide were therefore measured in 12 patients admitted with acute hypoxaemic chronic obstructive pulmonary disease [arterial partial pressure of O2, 6.2 +/- 0.4 kPa; arterial partial pressure of CO2, 6.9 +/- 0.1 kPa; forced expiratory volume in 1 s, 0.6 +/- 0.07 litre (27 +/- 3% of predicted)]. All but three patients had oedema on admission. 2. Plasma levels of both brain natriuretic peptide and atrial natriuretic peptide were elevated in patients with chronic obstructive pulmonary disease (31.4 +/- 4.1 pmol/l and 45.0 +/- 8.1 pmol/l, respectively) compared with healthy control subjects (1.7 +/- 0.8 pmol/l and 8.0 +/- 3.5 pmol/l, respectively). Thus, plasma levels of brain natriuretic peptide and atrial natriuretic peptide in patients with chronic obstructive pulmonary disease were increased by 18.5- and 5.6-fold respectively compared with healthy control subjects. 3. There was a significant inverse correlation between the plasma level of brain natriuretic peptide and the arterial partial pressure of O2 (r = -0.65, r2 = 0.42, P = 0.03), but not between the plasma atrial natriuretic peptide level and the arterial partial pressure of O2 (r2 = 0.07, not significant). The arterial partial pressure of CO2 did not correlate with the plasma level of either brain natriuretic peptide or atrial natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

An audit of acute asthma admissions to a respiratory unit.

A criterion based audit was performed on 90 admissions with acute asthma to a specialist respiratory unit using the guidelines set by the British Thoracic Society. Three main areas were audited including: documentation of severity markers in the case notes on admission, acute treatment given on admission, and further investigations performed. Case notes were found to be deficient in documentation of objective severity markers such as peak expiratory flow rate (52% recorded) and blood gases (72% recorded), as well as subjective markers such as speech (27%), air entry (58%) and exhaustion (4%). Of the total 90 admissions, 78% were identified as having at least three out of five objective markers for acute severe asthma. Most of these severe cases (93%) were given corticosteroids but none were prescribed greater than 35% concentration of inspired oxygen. The majority of admissions had a chest radiograph (87%), and 56% had measurement of serum potassium. These results show that even in a specialised respiratory unit, guidelines such as those produced by the British Thoracic Society are not in general being adhered to. It also indicates that assessment of severity is inadequate, particularly for peak flow measurement, and that management is deficient in established treatments such as the use of high flow oxygen. As a result of the audit, a severity marker stamp for the case notes along with guidelines for treatment have been implemented in order to improve the quality of care delivered to patients admitted with acute asthma.

Acute Disease

The scope of lower respiratory tract infection.

Lower respiratory tract infections (LRTI) are commonly classified as either bronchitis or pneumonia, and these infections are associated with an extremely high morbidity in the community, as well as a high mortality in those patients that require hospitalisation. Therefore, such infections place a huge burden, both economically and as a user of health services, on the entire health care system. The antibiotic treatment of community-acquired pneumonia caused by gram-negative organisms or staphylococci is controversial, and these organisms may cause one-third of the cases of community-acquired pneumonia. Nosocomial pneumonia is caused even more often by gram-negative bacteria, and as such the development of rational and effective antibiotic therapy to cover these organisms is very important.

Anti-Bacterial Agents

Treatment of pulmonary aspergilloma with itraconazole.

In a 12 month open study of itraconazole in pulmonary aspergilloma nine patients received oral itraconazole 200 mg daily for six months followed by further itraconazole or observation for a further six months. There was no change in the serum IgG specific for Aspergillus fumigatus (mean (SE) change -4% (10%)) or symptoms of chronic cough and haemoptysis. In two of the three patients who continued treatment beyond six months symptoms and radiographic appearances improved and a temporary reduction in A fumigatus specific IgG occurred in one patient. Further experience of the effects of longer treatment are needed before oral itraconazole can be recommended for aspergilloma.

Antibodies, Fungal

How to deal with a hospital outbreak of Legionnaires' disease.

The outbreak of Legionnaires' disease in Glasgow Royal Infirmary is discussed together with the problems such an outbreak poses to the microbiologist. The importance of early diagnosis is stressed. The outbreak was managed by a team drawn up from various disciplines within the hospital. Frank daily reports to the press, together with regular staff meetings with staff representatives helped to allay public anxiety. The subsequent maintenance and monitoring of the wet cooling tower required for the hospital ventilation system have resulted in considerable additional work for the microbiology department but especially for the hospital engineers.

Bacteriological Techniques

Evidence linking familial thrombosis with a defective antithrombin III gene in two British kindreds.

Using DNA probes in a structural study of the antithrombin III gene locus we found no evidence of gene deletion in two British kindreds with inherited antithrombin III deficiency. However, linkage analysis between a common DNA polymorphism and the antithrombin III deficiency trait showed that the defect lies at or close to the antithrombin III structural gene. The lod score for linkage within the larger Scottish kindred was 3.1 (theta = 0). These results are consistent with previously published data suggesting that mutation of the antithrombin III structural gene is the cause of inherited antithrombin III deficiency in some families.

Antithrombin III

Rapid diagnosis of an outbreak of Legionnaires' disease at Glasgow Royal Infirmary.

In the last three months of 1985 there was an outbreak of legionnaires' disease at Glasgow Royal Infirmary affecting 15 patients and one surgeon; five patients died. Legionnaires' disease was first suspected when a second case of severe nosocomial pneumonia occurred in a high dependency unit. The application of the direct fluorescent antibody test to specimens obtained at bronchoscopy was responsible for the rapid diagnosis of legionnaires' disease, which led to the prescription of appropriate antibiotic treatment and the shutting down of the contaminated cooling tower, thereby containing the outbreak. It also led to a search for further cases. It is suggested that these diagnostic techniques should be included in the investigation of affected patients in an outbreak of pneumonia.

Aged

Secondary amyloidosis in association with Aspergillus lung disease.

Three patients with amyloidosis secondary to bronchiectasis are described: in two patients bronchiectasis was secondary to allergic bronchopulmonary aspergillosis and in the third, post-tuberculous bronchiectasis was complicated by asthma and allergy to Aspergillus. We suggest that chronic Aspergillus allergy may cause amyloidosis and that some cases of amyloidosis ascribed to tuberculosis in the past may in fact have been secondary to Aspergillus allergy.

Amyloidosis

Life-threatening respiratory failure due to a previously undescribed myopathy.

The case of a young man with a previously undescribed myopathy associated with polydactyly is reported. Although both limb girdles were affected, the major effect of the disease was upon the respiratory muscles leading to his presentation with life-threatening respiratory failure. A further feature was pronounced stiffness of the vertebral column and limb girdles, similar in some respects to the 'rigid spine syndrome'. Muscle biopsy appearances were unique but showed some similarities to both nemaline myopathy and myotonic dystrophy. Ventilatory assistance at night using a rocking bed led to a marked improvement and has enabled the patient to return to full-time employment.

Adult