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Griseofulvin was tested for its effects on the morphology, proliferation and metabolism of fibroblasts cultured from normal human skin and on established lines of mouse fibroblasts 3T3 and 3T6. In all cells treatment produced slight increases in the mitotic index compatible with transient mitotic arrest, but cultures of 3T3 and 3T6 cells also included high proportions (up to 25%) of abnormal multinucleate cells not present in human strains. The proliferation of all cell strains over a 2 or 4 day period was inhibited in proportion to dose (2--17 microgram/ml) with 50% inhibition of growth in the range of 5--11 microgram/ml. Acid mucopolysaccharide secretion was depressed by about 20% at 4--17 microgram/ml. Total protein synthesis was depressed in 3T6 and in human cells, but there was no specific effect on collagen synthesis or secretion.

Four corticosteroids were tested in vitro for effect on the proliferation of four strains of fibroblasts from scleroderma skin, four strains from normal adult skin and four strains of rheumatoid synovial cells. Significant effects on fibroblasts occurred only at the highest steroid concentration tested (10 microgram/ml) where the inhibitory ranking of the steriods was clobetasol propionate greater than clobetasone butyrate greater than betamethasone valerate greater than hydrocortisone. Hydrocortisone and betamethasone valerate stimulated proliferation of two normal strains, had no certain effect on the scleroderma group, and inhibited growth of synovial cells. Clobetasone butyrate and clobetasol propionate inhibited growth of all cells. All four steroids substantially reduced acid mucopolysaccharide secretion by scleroderma fibroblasts. These results suggest that fibroblasts from normal and abnormal skin show only small differences in their responses to corticosteroids in vitro, but contrast sharply with the mouse L-929 fibroblasts previously used in some assays of topical corticosteroid potency.

OBJECTIVES:Demonstrate the feasibility of weekly data collection and analysis of public health emergency (PHE) data. Assess fluctuations in, and challenges of, resource matching and potential effect on patient care for influenza in ICUs. DESIGN:Multicenter prospective noninterventional study testing effectiveness of leveraging the Discovery Critical Care Research Network Program for Resilience and Emergency Preparedness (Discovery-PREP) in performing PHE research. A 20-question internet survey was developed to prospectively assess ICU influenza-related resource stress. An informatics tool was designed to track responses; data were analyzed within 24 hours of weekly survey completion by the team biostatistician for timely reporting. PARTICIPANTS: Critical care and Emergency Medicine Discovery-PREP network investigators self-selected to participate in the voluntary query. SETTING: ICUs of 13 hospitals throughout the United States, 12 academic, and one community. INTERVENTIONS: ICU physicians were electronically surveyed weekly over 17 weeks during the influenza season (January 2018-April 2018). Responses were collected for 48 hours after each email query. MEASUREMENTS AND MAIN RESULTS:The average weekly response among the sites was 79% (range, 65-100%). Significant stress, defined as alterations in ICU staffing and/or resource allocation, occurred in up to 41% of sites during the national peak of influenza activity. These alterations included changes in staffing, not accepting external patient transfers, and canceling elective surgery. During this same period, up to 17% of the sites indicated that these changes might not have been sufficient to prevent potentially avoidable patient harm. CONCLUSIONS:This novel approach to querying ICU operational stress indicated that almost half of participating sites experienced critical care resource limitations during peak influenza season and required process and/or staffing changes to better balance resources with patient care demands. This weekly national reporting infrastructure could be adapted and expanded to better inform providers, hospital emergency management teams, and government leaders during PHEs.

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