Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease. Objectives: To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness. Methods: Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment. Measurements and Main Results: Lavage was performed in 201 individuals, including 141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P 5 0.04), more severe lung function, including a worse forced vital capacity (P 5 0.003), worse total lung capacity (P 5 0.005) and diffusing capacity of the lung for carbon monoxide (P 5 0.004), more extensive ground-glass opacity (P 5 0.005), and more extensive fibrosis in the right middle lobe (P 5 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P 5 not significant). Conclusions: The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registered with www.clinicaltrials.gov (NCT 000004563).

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Temporal and spatial measurements of the toxicity (EC50), chemical speciation, and complexation capacity (Cu-CC) of copper in waters from San Diego Bay suggest control of the Cu-CC over copper bioavailability. While spatial distributions of total copper (CuT) indicate an increase in concentration from the mouth toward the head of San Diego Bay, the distribution of aqueous free copper ion (Cu(II)aq) shows the opposite trend. This suggests that the bioavailability of copper to organisms decreases toward the head of the bay, and is corroborated by the increase in the amount of copper needed to reach an EC50, observed for larval stages of three marine invertebrates (Mediterranean mussel, Mytilus galloprovincialis, sand dollar, Dendraster excentricus, and purple sea urchin, Strongylocentrotus purpuratus), and by the increase in Cu-CC heading into the head of the bay. The amount of Cu(II)aq required to produce a 50% reduction in normal larval development (referred to here as pCuTox,) of the mussel, the most sensitive of the three marine invertebrates, was generally at or above approximately 1 x 10(-11) mol L(-1) equivalents of Cu (i.e., pCuTox approximately 11 = -(log [Cu(II)aq])). These results suggest that the copper complexation capacity in San Diego Bay controls copper toxicity by keeping the concentration of Cu(II)aq at nontoxic levels.

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In August 1985 and 1986, a senes of bathyphotometric measurements were made In icefree waters of Vestfjord, Norway, to quantify stimulable in situ bioluminescence. In 1986, we tested and identified the causative bioluminescent plankton. In all profiles, peak or maximum bioluminescence intensity was always within a zone of 15 to 30m below sea surface, with marked decreases below 50m. Maximum biolurninescence intensity from all profiles for both years ranged from 3 X 10' to 2 X 10' photons S-' cc-' of turbulently-flowing seawater. Testing some of the plankton on board ship revealed that the brightest flashes were produced by the copepods Metridia longa and M lucens and the ostracod Conchoecia sp. Dinoflagellates of the genus Protopendnium emitted light at an intermediate level. The total number of dinoflagellates ranged from 1300 to 3700 cells I-' at water depths of 10 to 30m, and sharply decreased at 80 to lOOm (2 to 11 cells I-'). It was estimated that dinoflagellates accounted for 96 % of the measured light from the surface to a depth of loon?. Several species of the luminous d~noflagellate Ceratium were found. However, their contribution to the overall light budget never exceeded 25 %. P. curtipescontributed at least 50 % of the measured light field at 30m and above. In general, luminous zooplankton (larval copepods and euphausiids) contributed less than 4 % of the light produced above 100 m. The number of bioluminescent dinoflagellates correlated with bioluminescent intensity at the 0.05 significance level. Correlation analysis of beam attenuation coefficient w t h biolun7inescent intensity yielded high r values resulting in an overall level of significance of less than 0.01, and, therefore, may be a useful indicator for bioluminescence.

This study compared the sensitivity of two rapid toxicity tests, QwikLite and Microtox, to seven metals and ammonia. Both of these tests measure a reduction in light production from bioluminescent microorganisms (dinoflagellates and marine bacteria, respectively) as a means of toxicity detection and are simple and inexpensive to conduct compared to many standardized acute toxicity tests. For QwikLite tests, three marine dinoflagellate species (Lingulodinium polyedrum, Ceratocorys horrida, and Pyrocystis noctiluca) were separately evaluated following a 24-h exposure period. The marine bacterium, Vibrio fischeri, was used in the Microtox tests, in 15-min exposures to the same metal preparations as those used for the QwikLite tests. The QwikLite tests were generally one to two orders of magnitude more sensitive than the Microtox tests, as indicated by lower median effects concentrations (EC(50)). Both QwikLite and Microtox, however, resulted in similar toxicity rankings for the metals tested. The dinoflagellate species used in the QwikLite tests responded similarly for most compounds tested, with L. polyedrum appearing to be somewhat more sensitive than the other two species for most metals evaluated. QwikLite was also more comparable in sensitivity to several commonly used standardized toxicity tests. As with all toxicity tests, species selection for QwikLite should take into account study-specific factors, including the potential for sensitivity to confounding factors, such as ammonia.

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