Hoarseness due to Mycobacterium kansasii.

OBJECTIVE: To present a case of unilateral vocal fold paralysis due to Mycobacterium kansasii induced pressure on the left recurrent laryngeal nerve, a specific aetiology not previously reported in the world literature. CASE REPORT: A 57-year-old Caucasian man presented with a short history of productive cough, fever, hoarseness and 14-kg weight loss. He was a smoker, had an abnormal chest X-ray and was human immunodeficiency virus negative. A sputum sample was positive on direct microscopy for acid fast bacilli. Initially, the patient was treated with Rifater (rifampicin, isoniazid and pyrazinamide) and ethambutol. Mycobacterium kansasii was isolated and proved sensitive to this antimycobacterial treatment. Nasoendoscopy revealed diminished movement of the left vocal fold, and a computed tomography scan showed enlarged mediastinal lymph nodes anterior to the aortic arch. After three months of antimycobacterial treatment, the vocal folds were fully mobile at repeat nasoendoscopy, and this coincided with gradual resolution of the patient's hoarseness and weight loss. CONCLUSIONS: There are many causes of unilateral vocal fold paralysis. This case illustrates the importance of anatomical knowledge in reaching a diagnosis, and also presents the first reported case of Mycobacterium kansasii creating this clinical picture.

Ulcerative colitis after statin treatment.

Statin treatment is widely used in both primary and secondary prevention of diseases in which hyperlipidaemia is a major risk factor, for example, ischaemic heart disease. The development of ulcerative colitis as an adverse reaction to simvastatin is reported, which, despite withdrawal of the drug, proved fatal. The adverse reaction profile of the statins is reviewed, which suggests that this is a class effect and not one limited to simvastatin.

Chronic respiratory symptoms, von Willebrand factor and longitudinal decline in FEV1.

Although some risk factors for accelerated decline in forced expiratory volume in 1 s (FEV1) such as cigarette smoking, are well defined, it is not possible to identify those individuals with the most rapid rates of decline. Von Willebrand factor (vWF) is a product of both the pulmonary and systemic endothelium, and serum levels are raised during episodes of acute bronchitis. We hypothesized that raised serum levels of vWF may indicate sub-clinical pulmonary injury and so may predict subsequent accelerated decline in FEV1. The aims of this study were 1. to define the prevalence of chronic respiratory symptoms and obstructive airway disease in an inner-city British population and 2. to determine whether elevated levels of von Willebrand factor (vWF) identify those individuals at risk for more rapid decline in FEV1 over time. In 1987, all 2013 individuals aged 45 to 74 years at an inner-city general practice were mailed a respiratory symptom questionnaire. One in six of the responders were asked to attend for spirometry and for assessment of serum vWF. In 1996, those individuals who had spirometry and vWF assessed in 1987 were traced, and repeat spirometry was performed. In 1987, 1527 of 2013 (75.8%) individuals completed the questionnaire. Forty-two point two percent of responders reported shortness of breath on hills, 34.7% reported wheeze and 31.6% reported mucus hypersecretion. Smokers were more likely to report these symptoms. Two hundred and ten of the 251 (84%) individuals approached had spirometry and vWF assessed. Eleven percent of these had both an FEV1 < 75% predicted and a forced expiratory ratio (FEV1 forced vital capacity (FVC)) < 70%. Sub-normal spirometry was associated with wheeze, mucus hypersecretion, cigarette smoking and increasing age. By 1996, 32 (15%) of the original group of 210 individuals had died, and 117 of the remaining 178 (66%) had spirometry repeated. FEV1 < 75% predicted was a strong predictor of interim mortality, independent of age, sex and smoking history. The average decline in FEV1 was 46.7 ml yr-1. There was no significant correlation between serum vWF levels and subsequent decline in FEV1. Chronic respiratory symptoms and spirometric evidence of airflow limitation are common in inner-city residents of the U.K., and are associated with smoking history. Much of this disease is unrecognised by health professionals. An FEV1 < 75% predicted is a strong independent predictor of subsequent mortality. The measurement of serum vWF levels is unhelpful in identifying those individuals at increased risk of accelerated decline in FEV1.

Plasma levels of von Willebrand factor antigen in acute bronchitis and in a normal population.

von Willebrand factor (vWF) is a large glycoprotein secreted predominantly by endothelial cells in both the systemic and pulmonary circulations and has a central role in the formation of the platelet plug. It has been put forward as a possible marker of endothelial cell injury, but is not ideal in that it is not specific for either the pulmonary or systemic circulation and may be released as part of the acute phase response from otherwise healthy endothelial cells. We undertook two studies (i) to assess within-subject to assess within-subject variation in plasma von Willebrand factor antigen (vWF:Ag) levels over time and to assess between-subject variation in a healthy patient population, and (ii) as part of a descriptive study of acute bronchitis, to assess whether plasma vWF:Ag levels altered in such a common and minor insult. A random sample of patients aged 45-74 years were taken from a local general practice. vWF:Ag levels were measured on three occasions, and spirometry was performed. The descriptive study was undertaken on patients in the general practice diagnosed with acute bronchitis without pre-existing pulmonary disease. Plasma vWF:Ag was measured on presentation and 14 and 42 days later. In 219 randomly selected patients the mean plasma vWF:Ag was similar at all three visits, the within-subject standard deviation being 0.09 U ml(-1) and 1.12 U ml(-1) respectively). There was no correlation between plasma vWF:Ag and C-reactive protein on presentation. We conclude that there is relatively little variation in an individual's plasma vWF:Ag level but that levels increase significantly with age. The observed elevation occurring with acute bronchitis is a true phenomenon; the absence of an associated acute phase response suggests that endothelial cell injury is the mechanism for the rise. These observations are important in the context of vWF as a marker of endothelial cell damage, as a common and supposedly minor insult such as acute bronchitis may markedly raise plasma levels.

Validation of British Thoracic Society guidelines for the diagnosis of the sleep apnoea/hypopnoea syndrome: can polysomnography be avoided?

BACKGROUND: The British Thoracic Society report on the diagnosis and treatment of the sleep apnoea/hypopnoea syndrome (SAHS) suggests that, if the pulse oximetry baseline oxygen saturation is above 90%, then 15 4% oxygen desaturation/hour in bed will diagnose SAHS requiring treatment. The diagnostic outcome of applying these guidelines has been studied. METHODS: One hundred patients referred to a district general hospital sleep clinic were recruited. After initial clinical assessment, overnight pulse oximetry measurements were performed, followed by full polysomnography at the regional laboratory. RESULTS: Sixty nine patients underwent both pulse oximetry and polysomnography. All 10 patients with more than 15 4% desaturations/hour on pulse oximetry had SAHS confirmed on polysomnography (specificity = 100%). Twenty two patients with SAHS were misdiagnosed using pulse oximetry alone (sensitivity = 31%). These patients had low apnoea scores but high hypopnoea scores. CONCLUSIONS: The BTS pulse oximetry criteria are highly specific when positive (specificity = 100%), but may miss patients with the SAHS who have hypopnoeic episodes which cause arousal but not significant oxygen desaturation (sensitivity = 31%). It should be emphasised that pulse oximetry alone does not always give sufficient information to discriminate between those patients with or without SAHS. Patients with "negative" pulse oximetry and symptoms of SAHS should undergo polysomnography or multi-channel recording.

Nedocromil sodium and sodium cromoglycate in patients aged over 50 years with asthma.

We conducted a double-blind parallel-group study to compare the efficacy of inhaled nedocromil sodium and inhaled sodium cromogylcate in patients aged 50 years or over with asthma. Seventy-seven patients were randomized, 38 to receive nedocromil sodium (4 mg q.d.s.) and 39 to receive sodium cromoglycate (10 mg q.d.s.) over a 16-week period. Eight patients withdrew from the study. Both patient groups showed a reduction in inhaled bronchodilator usage during the treatment period. No statistically significant differences were seen in diary card PEF recordings or symptom scores. Both clinic PEF and FEV1 were significantly greater (P < 0.05) in the sodium cromoglycate group at week 12. Patients considered the treatment to be very or moderately effective in 59% of the nedocromil sodium group and 50% of the sodium cromoglycate group. Thus, the study suggests that there is no difference in response to nedocromil sodium or sodium cromoglycate in this older group of patients with asthma who are already on moderate doses of inhaled steroids.

Deaths and necropsies in a thoracic unit.

BACKGROUND: There is concern about the decrease in the number of requests for necropsies, so a study was undertaken to assess current clinical practice. METHOD: A prospective study was made of all deaths occurring under the care of five chest physicians and three thoracic surgeons at East Birmingham Hospital from 1 April to 30 June 1989. RESULTS: A necropsy was sought in 34 of 58 deaths (59%) and was performed in 22 instances (38%). Major unexpected findings which would have affected clinical management were noted in three patients (14%). The mean delay in reporting results of histological examinations was 146 days (range 41-260 days). As the result of an increase in pathology technical staff levels and alteration in the practice of processing histological data, there was a substantial improvement during the corresponding period in 1990 (mean reduction 58 days, 95% confidence limits 39-77 days). Apart from patients with histologically proved carcinoma, there was no consistent pattern for requests for necropsies. CONCLUSIONS: Necropsies continue to reveal diagnoses which were not suspected while the patient was alive. Although the number of requests made by clinical staff for necropsies is reasonable, the reasons for the requests are not consistent. Guidelines are suggested to improve the number of successful requests and to maximise the information obtained from them.

Penicillamine-induced changes in elastic tissue of the upper respiratory tract.

We describe a patient who developed upper respiratory tract symptoms following long-term treatment of Wilson's disease with penicillamine. These symptoms were attributed to areas of pharyngeal thickening and were treated with a laser. Histological examination of the lesions showed proliferations of abnormal elastic fibres similar to those previously described at other sites, especially the skin, in patients receiving penicillamine. This drug impairs the maturation and reduces the stability of elastic fibres and although elastic tissue throughout the body is affected, we are aware of no previous reports of penicillamine-induced changes presenting with upper respiratory tract symptoms.

Interphase nucleolar organiser regions and survival in squamous cell carcinoma of the bronchus: a 10 year follow up study of 138 cases.

BACKGROUND: Good prognostic indicators for patients with squamous cell carcinoma of the lung would help to determine the most appropriate treatment for individual patients. METHODS: A silver colloid technique that shows interphase nucleolar organiser regions (AgNORs) has been applied to representative paraffin sections from 138 cases of squamous cell carcinoma of the bronchus treated by surgical resection of the primary tumour at East Birmingham Hospital in 1977. Of the 138 patients, 23 (17%) were alive 10 years after their operation. RESULTS: The mean (SD) AgNOR count per cell was significantly higher for all grades of malignancy (well differentiated 10.5 (2.6), moderately differentiated 10.7 (3.2), and poorly differentiated 12.7 (4.5)) than for normal pseudostratified columnar epithelium from non-affected areas (2.3 (0.78)). There was a trend for AgNOR counts to be higher in poorly differentiated tumours, but a wide range of AgNOR counts was observed in all histological grades. AgNOR counts did not predict clinical outcome, irrespective of the stage of the disease, and did not relate to DNA ploidy or the percentage of cells in the proliferation phase of the cell cycle. Nine of 47 patients (19%) with tumours classified as DNA diploid and eight of 63 patients (13%) with DNA aneuploid tumours were alive 10 years after operation. Principal component analysis identified the clinicopathological stage of disease as the variable best related to survival. The percentage of patients surviving 10 years was 30% for stage I, 20% for stage II, 10% for stage IIIa, 9% for stage IIIb, and none for stage IV. CONCLUSION: The AgNOR technique is not of prognostic value in postoperative patients with squamous cell carcinoma of the bronchus.

Acute bronchitis in the community: clinical features, infective factors, changes in pulmonary function and bronchial reactivity to histamine.

A descriptive study of acute bronchitis in patients without pre-existing pulmonary disease was undertaken in the community during the winter months of 1986-87. Forty-two episodes were investigated in 40 individuals. The cardinal symptom was the acute onset of cough (100%), usually productive (90%). Wheezing was noted by 62% of patients, but heard on auscultation in only 31%. A potential pathogen was isolated in 29% of cases with a virus (eight cases) being identified more frequently than either Mycoplasma pneumoniae (three cases) or a bacterium (three cases). The acute illness was associated with significant reductions in forced expired volume in 1 second (P less than 0.02) and peak expiratory flow (P less than 0.001) but not forced vital capacity compared to 6 weeks later. Ten of the 27 (37%) patients who had a histamine challenge test performed at 6 weeks had a PD20 of less than 7.8 mumol histamine. Thirty-nine episodes (93%) were treated with antibiotics by the general practitioner, the clinical course being unremarkable apart from one patient who developed a lingular pneumonia despite antibiotic therapy. Further studies are required to assess whether acute bronchitis causes an acute increase in bronchial hyperresponsiveness and whether either antibiotics or inhaled bronchodilators or anti-inflammatory therapy has a useful role in the management of this predominantly viral illness.

Fungal contamination of mini peak flow meters.

Sixteen peak expiratory flow meters from the Outpatient Department of Solihull Hospital were dismantled for inspection and washing. Fungal contamination was found in all 16 machines with visible contamination in four.

Sequential demonstration of antigens and AgNORs in frozen and paraffin sections.

A technique has been designed which enables the sequential demonstration of nucleolar organizer regions (NORs) and various antigens, in both frozen and paraffin wax-embedded sections. The NORs were demonstrated by the standard argyrophil (AgNOR) method and the antigens were shown by either immunoperoxidase (PAP) or immunoalkaline phosphatase (alkaline phosphatase-anti-alkaline phosphatase or avidin-biotin-alkaline phosphatase) methodology. Clear, reproducible results were obtained and AgNOR sites were enumerated with ease. It is suggested that the sequential method may be of great use in the evaluation of AgNOR numbers in neoplasms, where cell populations are heterogeneous. Cell populations may be demarcated with accuracy prior to the counting the AgNORs.

How should we count AgNORS? Proposals for a standardized approach.

There is interest currently in the AgNOR technique, for NOR-associated proteins. In some cases, this technique enables the distinction to be made between certain grades of malignancy and may enable prognostic assessment. This paper attempts to suggest a standardized means for the enumeration of NORs in histological sections. Attention should be paid to rigorous technique and careful resolution of intranucleolar AgNOR dots. The timing of the reaction and fixation methods are also most important.

Application of the AgNOR method to cell imprints of lymphoid tissue.

The argyrophil (AgNOR) staining technique for nucleolar organizer regions was applied to both cell imprint preparations and 3 microns sections of 40 specimens of lymphoid tissue (10 normal tonsil, 10 reactive follicular hyperplasia, and 10 low-grade and 10 high-grade non-Hodgkin's lymphomas). The mean AgNOR count per nucleus was higher for imprint preparations than for 3 microns sections for each group of specimens (P less than 0.01). The difference was particularly evident for specimens with high AgNOR counts, that is, the high-grade non-Hodgkin's lymphomas (pooled mean AgNOR count/cell 16.3 for imprints as opposed to 6.0 for 3 microns sections, P less than 0.0001). Furthermore, individual AgNOR dots were much more readily discerned in cell imprints than in sections, and this appears to be the method of choice if pathologists wish to at least approach absolute rather than relative AgNOR counts.

Sedation for endoscopy: midazolam or diazepam and pethidine?

One hundred patients received either diazepam given with pethidine, antagonized with naloxone, or midazolam alone in a double-blind randomized study of sedation for upper gastrointestinal endoscopy. Midazolam produced better amnesia for the procedure (P less than 0.0001) but diazepam and pethidine resulted in less retching during the procedure (P less than 0.01) and less sedation after the procedure, as judged by a simple performance test (P less than 0.02) and patient recall of results (P less than 0.02).

Treatment of phenobarbitone poisoning with repeated oral administration of activated charcoal.

Six patients with moderate to severe phenobarbitone intoxication were treated with repeated oral doses (50 g) of activated charcoal following an initial dose of 50 to 100 g. All recovered more rapidly than would otherwise be expected with supportive care alone. The mean maximum rate of fall in plasma phenobarbitone concentrations corresponded to a half-life of only 6.2 +/- 2.5 h (normally three to five days); 62 to 93 per cent of the absorbed dose was eliminated within 24 h and the mean total body clearance of the drug during and for up to 12 h after administration of charcoal was 84 +/- 34 ml/min. Treatment with repeated oral doses of activated charcoal is simple and safe. It seems to be as effective as forced alkaline diuresis, haemodialysis and haemoperfusion for the removal of phenobarbitone following overdosage.