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.     

Long-term follow-up of patients from the 1989 Q fever outbreak: no evidence of excess cardiac disease in those with fatigue

BACKGROUND: In 1989, an outbreak of Q fever (C. burnetii infection) with 147 confirmed cases occurred in Solihull, West Midlands. Three patients developed cardiomyopathy in the subsequent 10 years. The cohort has been followed up with respect to the development of fatigue and, in this instance, cardiac effects after the original infection. AIM: To determine whether persisting fatigue after Q fever represented sub-clinical cardiomyopathy. DESIGN: Prospective follow-up study. METHODS: All traceable subjects from the original outbreak, and community age-, sex- and smoking-matched controls, were studied. Questionnaires for idiopathic fatigue, 12-lead ECG, echocardiography, spirometry and shuttle walk distance were undertaken, and a subset with CDC-defined chronic fatigue syndrome had gated cardiac scans. RESULTS: Of the original cohort, 19 had died, three had emigrated and 10 were untraceable. Of the remaining 115, 108 responded to a mailed questionnaire and 87 were investigated further, of whom 85 provided complete data. Two developed aortic valve vegetations, one of whom died. Chronic fatigue syndrome was found in 20% of cases and 5.3% of controls (including those with co-morbidities), falling to 8.2% and 0 when excluding those with co-morbidities. There were no significant differences in ECG and echocardiographic investigations or shuttle-walk distance between those with fatigue and those without. Six of the seven patients with CFS had gated cardiac scans: all were within normal limits. CONCLUSIONS: These findings do not support the existence of a sub-clinical cardiomyopathy in the patients in this cohort who suffer from fatigue after acute Q fever, although endocarditis can occur after acute infection.     

Triangulation in Qualitative Research: Evaluation of Completeness and Confirmation Purposes

The term triangulation has been applied to research strategies intended to serve two distinct purposes, confirmation and completeness. Many researchers who claim to have used a triangulated approach fail to provide evidence to show that their approach contributed to either confirmation or completeness of the data set. This paper reviews these distinct purposes and describes how triangulation of qualitative and quantitative methods was built into a study to achieve them. Analysis of data related to a single construct illustrates how data generated by qualitative and quantitative methods can provide both convergent validity and a broader understanding of one's subject matter.     

Immune response genes in the post-Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever

BACKGROUND: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear. AIM: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups. DESIGN: Genetic association study. METHODS: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population. RESULTS: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels. DISCUSSION: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.     

A simple clinical colitis activity index

Background—The appropriate medicaltreatment of patients with ulcerative colitis is determined largely bythe severity of symptoms. Hospital assessment of the severity ofdisease activity includes investigation of laboratory indices andsigmoidoscopic assessment of mucosal inflammation.
Aims—To develop a simplifiedclinical colitis activity index to aid in the initial evaluation ofexacerbations of colitis.
Methods—The information fordevelopment of the simple index was initially evaluated in 63 assessments of disease activity in patients with ulcerative colitiswhere disease activity was evaluated using the Powell-Tuck Index (whichincludes symptoms, physical signs, and sigmoidoscopic appearance). Thenew index was then further evaluated in 113 assessments in a differentgroup of patients, by comparison with a complex index utilisingclinical and laboratory data, as well as five haematological andbiochemical markers of disease severity.
Results—The newly devised SimpleClinical Colitis Activity Index, consisting of scores for five clinicalcriteria, showed a highly significant correlation with the Powell-TuckIndex (r=0.959, p<0.0001) as well as thecomplex index (r=0.924, p<0.0001) and alllaboratory markers (p=0.0003 to p<0.0001).
Conclusions—This new Simple ColitisActivity Index shows good correlation with existing more complexscoring systems and therefore could be useful in the initial assessmentof patients with ulcerative colitis.

Keywords:ulcerative colitis; disease activity

     

Lipoprotein (a) as a predictor of myocardial infarction in middle-aged men

PURPOSE: Whether serum lipoprotein (a) [Lp(a)] levels are an independent risk factor for coronary heart disease has been controversial. We have investigated its status in a prospective population survey, the Second Northwick Park Heart Study. METHODS: We recruited 2,616 men 50 to 61 years old from nine primary care practices in the United Kingdom. Baseline serum Lp(a) levels were measured by enzyme-linked immunosorbent assay (ELISA) and were analyzed in 3 groups (<25th percentile, 25th to 75th percentile, and >75th percentile) to overcome the problem of some measurements falling below the threshold of the assay. Coronary end points included sudden cardiac death, acute myocardial infarction, silent myocardial infarction on the electrocardiogram, and coronary artery bypass surgery. RESULTS: During a mean of 6 years of follow-up, 121 men had coronary events. In a multivariate analysis that also adjusted for fibrinogen, Apo-A1, Apo-B, and triglyceride levels, we identified several independent risk factors for coronary events, including cholesterol level (hazard ratio [HR] = 1.5 per SD 95% confidence interval [CI] 1.3 to 1.8), diabetes (HR = 4.1, 95% CI: 2. 0 to 8.4), current versus never smoking (HR = 2.5, 95% CI: 1.5 to 4.1), diastolic blood pressure (HR = 1.4 per SD, 95% CI: 1.1 to 1.7), Apo-A1 (HR = 0.8 per SD, 95% CI: 0.6 to 0.9), age (HR = 1.3 per SD, 95% CI: 1.1 to 1.6), and Lp(a) (>26.3 mg/dL [75th percentile] versus <2.9 mg/dL [25th percentile], HR = 1.9, 95% CI: 1.1 to 3.3]. There was a statistically significant (P = 0.01) difference in risk between the three levels of Lp(a). CONCLUSIONS: We found that a high Lp(a) level was an independent predictor of the development of coronary heart disease in middle-aged men.