In vitro monocyte maturation was studied in patients with squamous cell carcinoma of the lung--limited to the ipsilateral hemithorax in 30 and more extensive in 40. The patients were studied prospectively and initial monocyte maturation was correlated with survival. Monocyte maturation in patients with limited disease before treatment ranged from 3.1 to 57.6% with a median value of 21.4%. The survival of those patients in whom monocyte maturation was less than the normal range (less than 30.4%) was significantly shorter than the survival in those with normal maturation ( p less than 0.05). Four of the five patients whose initial maturation was less than 10% proved to be inoperable at surgery. Patients with extensive disease had monocyte maturation ranging from 2.4 to 52.9% with a median value of 13.2%, significantly lower than in those with limited disease (p less than 0.025). Patients with extensive disease and low monocyte maturation survived a significantly shorter time than those with normal maturation ( p less than 0.005). The depression of monocyte development may explain the finding of negative delayed hypersensitivity skin reactions in many patients with lung carcinoma and may prove useful as an index of prognosis.
The effects of pathologically relevant concentrations (0.38 to 12.5 microM) of the proinflammatory, Pseudomonas aeruginosa-derived pigment 1-hydroxyphenazine (1-hp) on Ca2+ metabolism and intracellular cyclic AMP (cAMP) in N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 1 microM)-activated human neutrophils, as well as on the release of myeloperoxidase (MPO) and elastase from these cells, have been investigated in vitro. Ca2+ fluxes were measured by the combination of a fura-2/AM-based spectrofluorimetric method and radiometric procedures, which together enable distinction between net efflux and influx of the cation, while radioimmunoassay and colorimetric methods were used to measure cAMP and granule enzymes, respectively. Coincubation of neutrophils with 1-hp did not affect intracellular cAMP levels or the FMLP-activated release of Ca2+ from intracellular stores but did retard the subsequent decline in the chemoattractant-induced increase in the concentration of cytosolic free Ca2+. These effects of 1-hp on the clearance of Ca2+ from the cytosol of activated neutrophils were associated with decreased efflux of the cation from the cells and increased release of MPO and elastase, while the delayed store-operated influx of the cation into the cells was unaffected by the pigment. The plasma membrane Ca2+-ATPase rather than a Na+-Ca2+ exchanger appeared to be the primary target of 1-hp. These observations suggest that the proinflammatory interactions of 1-hp with activated human neutrophils are a consequence of interference with the efflux of cytosolic Ca2+ from these cells.
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults.
There is no disease-specific instrument available for health status assessment in bronchiectasis. We examined the stability, validity and responsiveness of a measure designed for asthma and COPD, the St. George's Respiratory Questionnaire (SGRQ), in this condition. One hundred and eleven patients were studied on 2 separate d 6 mo apart. On both days each patient completed the SGRQ and measures of general and disease-specific health, mood, and fatigue. They also performed a shuttle walking test and comprehensive lung function tests. Repeatability was tested over 2 wk in 23 patients. The intraclass correlation (rI) for the SGRQ Total score was 0.97. The SGRQ component scores correlated well with relevant markers of disease activity. Examples include: SGRQ Symptoms score versus MRC Wheeze score, r = 0.634, p < 0.0001; Activity score versus shuttle walking test, r = − 0.659, p < 0.0001; and Impacts score versus physical fatigue, r = 0.610, p < 0.0001. Changes in the SGRQ Total score from entry to follow-up also correlated with changes in other measures of the patients' health. There were significant differences in the SGRQ total score between patients who improved and those who deteriorated over the 6 mo in respect to wheeze (F = 5.6, p < 0.01) and breathlessness (F = 6.05, p < 0.01). We conclude that the SGRQ reflects impaired health in bronchiectasis patients.
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