Biomedical subjects
Publications and source records attributed to D T McLeod.
A 55 year old woman with a conjunctival non-Hodgkin's lymphoma was found to have pulmonary nodules on a thoracic computed tomographic scan which were initially thought to be lymphomatous deposits. A subsequent biopsy specimen demonstrated granulomas consistent with sarcoidosis. The relationship between sarcoidosis and malignancy, in particular lymphoma, is discussed.
The British Thoracic Society (BTS) guidelines for the treatment of community-acquired pneumonia recommend initial therapy with a betalactam antibiotic, with the addition of erythromycin if there are features of an atypical pneumonia. To see if these guidelines were being followed, a prospective study was undertaken of all adult patients admitted to hospital over a 3-month period who were given erythromycin for a community-acquired lower respiratory tract infection. Erythromycin was given to 62 patients who could be fully assessed. Continued prescription of erythromycin was justified in 10 (16%)--two patients with penicillin allergy, two with M. catarrhalis infection and one patient with legionnaires disease. Five patients had infections severe enough on admission to warrant combined therapy in line with the BTS recommendations. Five patients had erythromycin stopped on day 2. Erythromycin was prescribed on admission and continued unnecessarily in 47/62 patients, showing that the BTS recommendations are not being followed correctly.
Over a period of 11 months, 37 patients infected with the Human Immunodeficiency Virus (HIV) presenting with symptoms of bronchopulmonary disease were investigated. Patients presented with cough, weight loss, fever and dyspnoea. Investigations included fibreoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. In eight patients (22%) Pneumocystis carinii was found. Pulmonary infiltrates were found on chest radiographs of six patients, while in the remaining two patients chest radiographs showed clear lung fields. P. carinii was found in two patients with pulmonary Kaposi's sarcoma. Infection with P. carinii often occurred with other pathogens: Streptococcus pneumoniae was found in four patients, Staphylococcus aureus in two and tuberculosis in two. P. carinii pneumonia does occur in patients with HIV infection in Africa and the diagnosis is relatively simple to make provided that transbronchial biopsy and bronchoalveolar lavage are carried out through a fibreoptic bronchoscope and specimens examined after appropriate staining. However, the prevalence of P. carinii in patients with HIV infection in Africa appears to be lower than that found in patients with HIV infection in Europe and North America.
In a prospective study pleural biopsy specimens obtained with a Tru-cut needle were compared with those obtained with an Abrams pleural biopsy punch from 36 patients in Zimbabwe judged to have an effusion of at least 1.5 litres; one patient had two biopsies. Both instruments were used on each patient, the Abrams punch being followed by the Tru-cut needle. There were no serious complications. The diagnoses determined by biopsy were: tuberculosis (11); carcinoma (12); chronic inflammation (9); and pleural fibrosis (4); one biopsy showed nothing abnormal. In 23 (62%) patients both biopsy needles produced adequate diagnostic material; in eight the Tru-cut needle alone produced diagnostic material and in six the Abrams punch alone. Thus diagnostic material was obtained in 31 patients from the Tru-cut needle and in 29 from the Abrams punch. The Tru-cut needle was useful and safe for pleural biopsy in this series and appeared to be particularly useful when the pleura was thickened.
A retrospective study of 596 case notes of 1195 patients notified for tuberculosis during a three year period, in one district, was conducted. Drug reactions occurred in 75 patients (12.6 percent) and required discontinuation of therapy in 59 (10 percent). In 69 patients the skin was involved. Thiacetazone was by far the commonest drug implicated: two patients died with the Stevens Johnson syndrome. This study suggests that in the all important first two months of anti-tuberculous chemotherapy, thiacetazone, a therapeutically unnecessary agent, should be omitted as its inclusion results in an unacceptably high rate of side effects.
Thyroxine replacement therapy for 21 adult patients with primary hypothyroidism was adjusted to the dosage at which each patient had a normal thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH). Clinical assessment and measurement of TSH (by sensitive immunoradiometric assay), free thyroxine (FT4) and free tri-iodothyronine (FT3) were made at this dosage and at higher and lower doses of thyroxine. Clinical observations, FT3 and FT4 assays were relatively insensitive to small alterations of thyroxine dosage, in contrast to which basal TSH measurements correlated well with TRH responsiveness and were sensitive to fine adjustments of thyroxine dosage.
In 12 of 451 patients diagnosed as having pneumonia in a single hospital over 18 months the causative organism appeared to be Branhamella catarrhalis.
A patient is reported who presented with features of bronchial obstruction due to endobronchial tumour. Failure to recognise this as being due to choriocarcinoma led to a delay in diagnosis and effective treatment which, given earlier, may have proved lifesaving.
To distinguish Branhamella catarrhalis from Neisseria species a study of 140 strains was made on simple laboratory media, with particular reference to deoxyribonuclease (DNase) production, superoxol reaction, and growth characteristics. All 97 clinical isolates of B catarrhalis (58 of which were beta-lactamase positive) and eight strains of B catarrhalis from the National Collection of Type Cultures were DNase positive and superoxol positive. None grew on modified New York City medium, modified Thayer Martin medium, MacConkey agar, crystal violet blood agar, nor under anaerobic conditions. Of the 16 different non-pathogenic Neisseria species tested, all were DNase negative, eight (50%) were superoxol reaction negative, and 13 (81%) grew on crystal violet blood agar. Using simple laboratory media, DNase, and superoxol tests, it was possible to identify B catarrhalis and to distingish it from pathogenic and non-pathogenic Neisseria species.
During 1982-4 20 cases of Mycobacterium malmoense infection were identified in Scotland (13 male, seven female; age 34-82, median 62 years). Features of the disease were obtained from case notes and radiographs of 19 patients and were found to be indistinguishable from those of patients with pulmonary tuberculosis. Chronic chest disease, predominantly chronic airflow obstruction, was the most frequent associated disease. The organisms showed in vitro resistance in eight patients to rifampicin, in 19 patients to isoniazid, and in all patients to pyrazinamide and p-aminosalicylic acid. Nevertheless, all patients showed an early response to standard combination chemotherapy with rifampicin, isoniazid, and ethambutol, with or without pyrazinamide. Five have been cured and none had died of the infection, although four died of unrelated disease. Of nine patients still having treatment, five had relapsed after completing a course of antituberculosis drugs. All had received ethambutol for less than five months. The response to standard drugs was more satisfactory when the course included administration of ethambutol for at least nine months. Currently one new infection with M malmoense occurs in Scotland for every 40 with tuberculosis, and the incidence appears to be rising. In view of this, it is suggested that when tuberculosis is suspected the chemotherapeutic regimen should include ethambutol until the culture results are reported. If these then show M malmoense, ethambutol should be continued in the combination for at least nine months.
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We measured thyrotropin (TSH) with a sensitive immunoradiometric assay (IRMA) in 2329 consecutive serum samples received for thyroid-function tests from hospital and general practice. Of these, 185 (7.9%) had TSH values less than 0.2 milli-int. unit/L: 33 (1.4%) were hyperthyroid, 20 (0.9%) were being treated for hyperthyroidism, 115 (4.9%) were receiving L-thyroxin, and 17 (0.7%) were clinically euthyroid but had severe non-thyroidal illnesses. In the first 506 serum samples, we also measured free thyroxin, free triiodothyronine (FT3), and total thyroxin. Thyroliberin (thyrotropin-releasing hormone, TRH) tests performed on 84 patients showed that an undetectable initial TSH (usually ascribable to therapy with thyroxin) predicted a flat TRH response. All untreated thyrotoxic patients had undetectable TSH. Experience confirmed that this TSH assay, in conjunction with a supplementary assay of FT3 when the TSH concentration is less than twice the limit of detection, is efficient and economical for routine evaluation of thyroid function in an unselected population.
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In a six month prospective study during the winter Branhamella catarrhalis was isolated from the sputum of 63 patients with symptoms of bronchopulmonary infection: 49 isolates were in pure culture and 14 were with another pathogen, Haemophilus influenzae being the commonest (found with 10 of the 14 B catarrhalis isolates). Of 36 patients infected in the community, 26 required admission to hospital. The remaining 27 patients were infected while in hospital. Forty four of the 63 isolates produced beta lactamase; 26 of these had been acquired in the community. As a result 29 patients were treated inappropriately with ampicillin and did not respond to this treatment. beta Lactamase produced by B catarrhalis may also protect other pathogens normally susceptible to beta lactam antibiotics. Most patients had chronic lung diseases or lung cancer, but three otherwise healthy patients who did not smoke developed bronchitis. B catarrhalis contributed to the death of five patients. A survey of the antibiotic prescribing habits of the referring general practitioners together with the sensitivity results of B catarrhalis suggest that changes in antibiotic prescribing habits in the community may be responsible for the increase in B catarrhalis infection.
Clinical isolates of Branhamella catarrhalis from the sputum of 20 patients with acute bronchopulmonary infection were examined for synthesis of immunoglobulin A1 protease by immunoelectrophoresis. Ten strains produced beta-lactamase, and 10 were beta-lactamase negative. None of the strains demonstrated immunoglobulin A1 protease activity despite the fact that three different culture media were used.
The incidence of Branhamella catarrhalis in respiratory infections at City Hospital, Edinburgh from January 1981 to April 1984 is described. Beginning in January 1982 there was an increased incidence associated with a high proportion of beta-lactamase-producing strains. The number of these strains increased: from January 1981 to April 1983, 61% of strains produced beta-lactamase, and 83% produced beta-lactamase from January to April 1984. 53% of patients were infected in hospital. Environmental studies showed that 7% of staff and 8% of patients were carriers; there was also circumstantial evidence of ward and patient-to-patient infection. The antimicrobial susceptibility of 54 clinical strains was tested: all strains were resistant to trimethoprim but were susceptible to clavulanic acid plus amoxycillin, chloramphenicol, erythromycin, co-trimoxazole, cefotaxime and cefuroxime. beta-Lactamase-negative strains were uniformly susceptible to penicillin and ampicillin.
A study was made of the clinical features and therapeutic response of 144 patients from whose sputum Branhamella catarrhalis was isolated. Typically, features of bronchopulmonary infection with cough productive of moderate amounts of purulent sputum, fever and dyspnoea were present. Of 74 patients who were infected in the community, 50 required hospital admission. Nosocomial infection occurred in the remaining 70 patients. Most patients had chronic pulmonary diseases or carcinoma bronchus; pneumonia occurred in 12 patients. Acute tracheobronchitis developed in 4 healthy non-smokers after viral illnesses. B. catarrhalis contributed to the death of 8 patients. Overall, 59% of isolates produced beta-lactamase but the proportion had risen to 70% by the end of the study; half of these were community acquired. 41% of patients who were treated initially with ampicillin did not respond. Clavulanic acid plus amoxycillin, co-trimoxazole, erythromycin, tetracycline, cefuroxime and cefotaxime are useful alternative antibiotics. All strains of B. catarrhalis were resistant to trimethoprim.
The prevalence of environmental and nasopharyngeal carriage of Branhamella catarrhalis in hospital staff members and in-patients was higher than previous studies suggested. Pernasal swabs performed on 59 members of staff revealed four isolates of Branh. catarrhalis, two of which were beta-lactamase producers. Seven isolates, two beta-lactamase positive, were recovered from 89 in-patients none of whom had bronchopulmonary infection with Branh. catarrhalis. From 117 settle plates six isolates, one beta-lactamase positive, were recorded. Attempts to bacteriocine type the isolates failed. In the absence of a typing system for Branh. catarrhalis evidence of nosocomial spread remains circumstantial.