Low biological aggressiveness of screen-detected lung cancers may indicate over-diagnosis

All cases of lung cancer diagnosed in the Tampere University Hospital catchment area in 1983–1987 were identified, analyzed for DNA flow cytometry and followed up to 1992. The patients were classified into 3 groups: screen-detected, symptom-detected, and detected by chance. The biological aggressiveness as indicated by DNA flow cytometry was not related to the survival of the symptom-detected patients. Also the screen-detected patients with an aggressive tumour (aneuploid or high S-phase fraction, SPF) had the same survival as the symptom-detected patients. The survival of screen-detected patients with a diploid or low SPF tumour was significantly better than that in the other groups. It is concluded that some of the previously known discrepancy of no effect on mortality and effect on survival of lung-cancer screening may be due to over-diagnosis, i.e., detection of morphologically malignant but biologically indolent lesions by screening. © 1996 Wiley-Liss, Inc.     

Clinical characteristics and factors affecting growth in long-term survivors of cancer

We evaluated clinical characteristics and growth in 51 (24 males) long-term survivors of childhood cancer (median follow up 12.7 years). Patients were shorter, had a higher proportion of body fat and higher systolic blood pressure than their controls. The change in relative height during treatment was −0.83 standard deviation score (S.D.S.) in patients with cranial irradiation and −0.32 S.D.S. in patients without cranial irradiation; the figures after treatment were −0.56 and 0.20 S.D.S., respectively. Half (r² = 0.50) of the variation in growth retardation during therapy could be explained by the cumulative doses of 6-mercaptopurine (6-MP) and vincristine and relative height at diagnosis. Cranial irradiation, increased relative height at diagnosis and young age at diagnosis were significant predictors of growth failure over the total observation period, explaining 43% of the variation. We conclude that long-term survivors of childhood cancer have impaired linear growth, increased body fat mass and elevated systolic blood pressure. Young children who are tall for their age at diagnosis and treated with cranial irradiation have the highest risk of impaired growth after the diagnosis. High doses of 6-MP seem to contribute significantly to growth retardation during therapy. © 1996 Wiley-Liss, Inc.     

Cellular characteristics of non‐allergic eosinophilic conjunctivitis

Purpose: This study examines the histology of conjunctival biopsy samples from patients with persistent allergic eosinophilic conjunctivitis (AEC) or non‐allergic eosinophilic conjunctivitis (NAEC). Methods: Fourteen patients with conjunctivitis and eosinophilia in cytology samples were included in the study. Seven had positive skin‐prick tests (the AEC group) and seven had negative skin‐prick tests (the NAEC group). Eight asymptomatic subjects with negative skin‐prick tests served as a control group. In conjunctival biopsies eosinophils were identified with monoclonal antibodies. Mast cells were identified by specific immunostaining and tryptase‐positive granules were counted around them. The percentage of degranulated mast cells was used as a measure of cell activation. Eosinophil and goblet cell numbers were counted, epithelial thickness was measured, and the symptoms were characterized and graded. Results: The numbers of eosinophils in biopsies were higher in patients with AEC than in healthy controls (p = 0.010). The proportion of activated mast cells tended to be higher in AEC patients (65%) than in NAEC patients (48%) or control subjects (40%). Patients with AEC had more goblet cells than control subjects (p = 0.049) and their epithelial layer was thicker (p = 0.054). Patients with AEC had more severe symptoms than control subjects (p = 0.0005), whereas the symptoms of NAEC patients did not differ statistically from those of controls (p = 0.065). Conclusions: Patients with NAEC were characterized by mild eosinophilic inflammation and only minor structural conjunctival changes. The condition seems to run a relatively mild but persistent clinical course.     

Acute respiratory failure in intensive care units. FINNALI: a prospective cohort study

Objective  To evaluate the incidence, treatment and mortality of acute respiratory failure (ARF) in Finnish intensive care units (ICUs). Study design  Prospective multicentre cohort study. Methods  All adult patients in 25 ICUs were screened for use of invasive or non-invasive ventilatory support during an 8-week period. Patients needing ventilatory support for more than 6 h were included and defined as ARF patients. Risk factors for ARF and details of prior chronic health status were assessed. Ventilatory and concomitant treatments were evaluated and recorded daily throughout the ICU stay. ICU and 90-day mortalities were assessed. Results  A total of 958 (39%) from the 2,473 admitted patients were treated with ventilatory support for more than 6 h. Incidence of ARF, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) was 149.5, 10.6 and 5.0/100,000 per year, respectively. Ventilatory support was started with non-invasive interfaces in 183 of 958 (19%) patients. Ventilatory modes allowing triggering of spontaneous breaths were preferred (81%). Median tidal volume/predicted body weight was 8.7 (7.6–9.9) ml/kg and plateau pressure 19 (16–23) cmH₂O. The 90-day mortality of ARF was 31%. Conclusions  While the incidence of ARF requiring ventilatory support is higher, the incidence of ALI and ARDS seems to be lower in Finland than previously reported in other countries. Tidal volumes are higher than recommended in the concept of lung protective strategy. However, restriction of peak airway pressure was used in the majority of ARF patients. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. This article is discussed in the editorial available at: doi:.     

Tear fluid concentration of mmp–8 is elevated in non—allergic eosinophilic conjunctivitis and correlates with conjunctival inflammatory cell infiltration

Background  To investigate tear fluid concentration of matrix metalloproteinase 8 (MMP–8) and its relation to conjunctival inflammatory cell infiltration in persistent non—allergic eosinophilic conjunctivitis (NAEC). Methods  Two groups were included: 26 consecutive adult patients with NAEC (conjunctival eosinophils at least 1+ [1-10 eosinophils/slide], skin prick test [SPT] to common allergens negative), and 26 asymptomatic adult persons (no conjunctival eosinophils, SPT negative). MMP–8 tear fluid concentrations were determined by immunofluorometric assay, and conjunctival brush cytology samples from NAEC patients were used for MMP–8 immunocytochemistry. Gelatin zymography was used to illustrate proteolytic activity within the tear fluid samples. Results  The mean MMP–8 concentration was significantly higher among NAEC patients (214.3 ± 327.7 μg/l) than among healthy persons (50.4 ± 62.3 μg/l, P < 0.0001). In the NAEC patients, tear fluid MMP–8 correlated with the numbers of conjunctival neutrophils (r = 0.66, P = 0.0002) as well as with goblet cells and columnar epithelial cells (r = 0.54 for both, P = 0.045), but not with the lymphocyte numbers (r = -0.36, P = 0.0741). By immunocytology, MMP–8 protein could also be detected in vivo in the inflammatory cell population within the conjunctiva. Zymography revealed that proteolysis was significantly higher in the NAEC group, and activated enzymes were practically found only in the NAEC group. Conclusions  The results showed that NAEC is an inflammatory condition characterized by increased tear fluid MMP–8 levels, probably derived from both inflammatory and structural conjunctival cells. The increased proteolytic activity in NAEC patients may indicate risk of conjunctival structural changes (remodeling).     

Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor–negative juvenile idiopathic arthritis in Finnish patients: Haplotype analysis in Finnish families

Objective

The SLC11A1 (formerly called NRAMP1) gene is important in natural resistance to a variety of intracellular infections mediated by macrophages and has been proposed as a candidate gene for autoimmune disease susceptibility. The aim of this study was to examine susceptibility in Finnish patients with persistent oligoarticular and polyarticular rheumatoid factor (RF)–negative juvenile idiopathic arthritis (JIA) due to the presence of the SLC11A1 locus on chromosome 2.

Methods

A total of 234 Finnish JIA nuclear families and 639 elderly Finnish controls without a history of JIA were evaluated for association with JIA at 3 intragenic single‐nucleotide polymorphisms: an intragenic insertion/deletion, a promoter microsatellite (NRAMP1), and a 3′ microsatellite (D2S1471).

Results

Analysis of marker haplotypes demonstrated a strong association of Finnish JIA with 6‐marker, 4‐marker, and 2‐marker haplotypes. Most impressively, 1 of the 6‐marker haplotypes showed an odds ratio (OR) of 4.0 (95% confidence interval [95% CI] 2.6–6.2) in all JIA patients, 3.5 (95% CI 1.9–6.5) in those with persistent oligoarticular JIA, and 4.1 (95% CI 2.5–6.7) in those with polyarticular RF‐negative JIA. Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well‐characterized strong susceptibility to DRB1*08 and *11 alleles. This SLC11A1 haplotype also had an additive effect with DRB1*JIASE in those with polyarticular, but not those with persistent oligoarticular, disease (P = 0.06, OR 2.9 [95% CI 0.9–9.2] versus P = 0.5, OR 1.6 [95% CI 0.4–6.0]).

Conclusion

Taken together, these data provide support for the existence of a locus at or near SLC11A1 that is a strong susceptibility factor for JIA in Finnish patients.

     

Early suppression of disease activity is essential for maintenance of work capacity in patients with recent‐onset rheumatoid arthritis: Five‐year experience from the FIN‐RACo trial

Objective

To explore the impact of an early treatment response on maintenance of work capacity in patients with early, active rheumatoid arthritis (RA).

Methods

In the Finnish Rheumatoid Arthritis Combination Therapy trial, 195 patients with recent‐onset RA were randomized to receive either a combination of disease‐modifying antirheumatic drugs (DMARDs) with prednisolone or a single DMARD with or without prednisolone for 2 years. Treatment responses were evaluated according to the American College of Rheumatology (ACR) criteria. After a 5‐year followup, the cumulative number of days of sick leave and RA‐related permanent work disability was calculated for each of the 162 patients who were available for the active work force at baseline.

Results

Of the 159 patients assessed at 6 months, 29 were in clinical remission, 66 achieved an ACR50 response but not remission, 29 achieved an ACR20 response but not an ACR50 response, and 35 failed to achieve an ACR20 response. In these 4 groups, the median numbers of work disability days per patient‐year from 6 months through 60 months of followup were 0 (interquartile range [IQR] 0–3), 4 (IQR 0–131), 16 (IQR 0–170), and 352 (16–365), respectively (P < 0.001). Pairwise multiple comparisons showed a statistically significant difference between all groups except the ACR50 and ACR20 groups. At 12 months, 30 patients were in remission. None of the 44 patients in remission at 6 or 12 months became permanently work disabled over the 5‐year followup, as compared with 15 patients in the ACR50 group (23%), 6 in the ACR20 group (21%), and 19 without an ACR20 response at 6 months (56%).

Conclusion

Prompt induction of remission translates into maintenance of work capacity. At 6 months, an ACR50 response is no better than an ACR20 response with regard to future productivity, while failure to achieve an ACR20 response carries a high risk for work disability.