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OBJECTIVES: To determine the prevalence of dyspnoea in older people at home, measure its impact on function and quality of life, and identify associated cardio-respiratory diseases. DESIGN: Cross-sectional population-based study. METHODS: We sent a modified Medical Research Council (MRC) dyspnoea questionnaire to identify breathlessness in 1404 randomly selected subjects from general practitioner lists of 5002 subjects aged 70 years and over living at home. We visited a further random sample of 500 of these subjects at home and at a study centre. SETTING: Community-based study in South Wales. MAIN OUTCOME MEASURES: Prevalence of dyspnoea (MRC grades 3-5) and its effect on psychological and functional status, and quality of life as measured by Hospital Anxiety and Depression, Nottingham Extended Activities of Daily Living and SF-36 questionnaires. RESULTS: The prevalence of dyspnoea as defined was 32.3% (95% confidence intervals: 30.3, 34.3). Breathless subjects had poorer functional status than non-breathless subjects. They also had poorer physical and mental health and were more likely to be anxious and depressed. The prevalence of left ventricular systolic dysfunction, reversible airways disease and obesity were all higher in those with dyspnoea. CONCLUSIONS: Dyspnoea is common in older people. Given its profound adverse effect on people's lives, dyspnoea is an important public health issue. [ABSTRACT FROM AUTHOR]

Investigates the intestinal humoral immunity of patients with dermatitis herpetiformis and normal jejunal histology to determine whether abnormal immunological reactivity, particularly to gliadin, occurs in the absence of enteropathy. Patients and methods; Results; Discussion.

Competing Interests: Conflicts of interest the authors declare they have no conflicts of interest.

Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest.

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

We reviewed haematological investigations for 43 patients treated at a single centre with alectinib, an inhibitor of anaplastic lymphoma kinase (ALK) which is considered standard first-line treatment for patients with ALK-rearranged advanced non-small cell lung cancer. Ninety-five percent of patients developed marked acanthocytosis, echinocytosis and/or spheroacanthocytosis, not observable with prior treatment with other ALK-inhibitors. Anaemia developed in 73% of patients (38% <100 g/L, 8% <80 g/L), though definite new haemolysis was present in only 11%. Eosin-5-maleimide binding was reduced in all assessed patients, and increased membrane cholesterol was identified in one patient assessed with lattice light sheet microscopy. We have identified a previously undescribed phenomenon whereby alectinib induces red cell membrane abnormalities in nearly all patients through an unclear, but likely ALK-independent, mechanism, resulting in mild anaemia without universal haemolysis., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Aims: To compare detection of Barrett's dysplasia and adenocarcinoma by systematic versus nonsystematic surveillance biopsy protocols., Methods: Upper GI consultation and open-access endoscopy are provided jointly at Glasgow Royal Infirmary by medical and surgical teams. The surgical team adopted annual systematic four-quadrant biopsy Barrett's surveillance in 1995. The medical team continued annual Barrett's surveillance with nonsystematic biopsy until 2004. We compare detection of Barrett's dysplasia and esophageal adenocarcinoma in unselected patients by these two biopsy strategies over 10 yr. All patients had > or = 3 cm Barrett's esophagus and histological proof of intestinal metaplasia. Patients referred for dysplasia management or with prevalent adenocarcinoma were excluded. Cohort A (N = 180) had four-quadrant biopsy every 2 cm while cohort B (N = 182) had nonsystematic biopsies., Results: Cohort A versus cohort B: Median number of biopsies per endoscopy: 16 versus 4. Prevalence of low-grade dysplasia (per patient): 18.9% versus 1.6% (P << 0.001). Prevalence of high-grade dysplasia: 2.8% versus 0% (P = 0.03). Incidence of low-grade dysplasia: 2.2% versus 6.6% (NS). Incidence of high-grade dysplasia: 2.8% versus 0% (P = 0.03). Nine cohort A patients (total 5%, 1.4% per patient-year) were treated for HGD (eight endoscopically, one by esophagectomy). Two had intramucosal adenocarcinoma. No cohort A patient developed advanced cancer but three cohort B patients developed and died of invasive Barrett's adenocarcinoma (0.6% per patient-year)., Conclusions: Patient age, gender, Barrett's segment length, and follow-up were similar (though not identical) in both cohorts, but confounding seems unlikely to account for a 13-fold difference in detection of prevalent dysplasia between the two groups. Our data support the hypothesis that systematic four-quadrant biopsy is considerably more effective than nonsystematic biopsy sampling in detecting Barrett's dysplasia and early adenocarcinoma. Greater biopsy numbers and the systematic pattern of biopsy taking may both contribute to this greater effectiveness.

The potential role of neutrophil elastase in exacerbating pulmonary infection and tissue damage in cystic fibrosis (CF) has led to proposals for treatment of lung disease in CF with the elastase inhibitor, alpha 1-proteinase inhibitor (alpha 1PI). Reports that alpha 1PI is inactivated in the CF lung suggest that the effectiveness of alpha 1PI therapy depends on the quantity of elastase present and the extent of alpha 1PI inactivation, both of which are expected to vary with disease severity. In this study we assessed the elastase-alpha 1PI profile in sputum and plasma from CF patients with various degrees of pulmonary involvement. Levels of active elastase in sputum samples increased with severity of pulmonary disease (F ratio = 5.63, p < 0.01), as did sputum levels of alpha 1PI (F ratio = 4.88, p < 0.01). A positive correlation was observed between sputum levels of active elastase and alpha 1PI (r = 0.68, p < 0.005). Plasma alpha 1PI levels were also elevated in CF patients compared with control subjects (p < 0.005), indicating a compensatory increase in plasma and sputum levels of alpha 1PI in response to increased elastase load. Molar levels of total immunogenic neutrophil elastase were, on average, 12 times higher than alpha 1PI in CF sputum. These results suggest that the major contributor to the elevated levels of active elastase observed in the CF lung is an increase in elastase release rather than inactivation of alpha 1PI.

A study of liver function in 108 adult cystic fibrosis patients showed that 20 had established liver disease, and that these had significantly better pulmonary function than the subgroup without liver disease. The relative risk of liver disease for homozygotes vs heterozygotes was 2:1 in our series. Four of the liver patients had a sibling with CF, but three of the sibships were discordant for liver disease. Environmental or genetic factors other than the deletion Delta F508 may influence the development of cystic fibrosis-related liver disease.