Faculty Bibliography

Tissue irritation, as evidenced by phlebitis, associated with Optiva (Johnson & Johnson Medical) and Insyte (Becton Dickinson) polyurethane cannulae was studied. The integrity of the cannulae on removal, the incidence of infection at the cannula site and the factors which influence phlebitis were also examined. One thousand and eight patients had a polyurethane cannula placed for induction of anaesthesia for cardiac surgery. After surgery, the cannula was examined every 24 hours. If evidence of phlebitis occurred, the cannula was removed and sent for culture. All remaining cannulae were removed at 72 hours and the site examined daily for a further three days. There were 503 Optiva and 505 Insyte cannulae studied. The distributions between the two cannulae with respect to patient characteristics, gauge of cannula, number of attempts and difficulty of insertion, cannula site and anaesthetist inserting were similar. The early removal rate for both groups was 47%. Overall phlebitis rate with Optiva was 31% and Insyte 33%. This difference is not statistically significant. The cumulative phlebitis rate increased with time but did not differ between the two types of cannulae. Minor tip distortion or shaft kinking of the cannulae occurred in 16.2% of Optiva and 23.5% of Insyte. This difference is statistically significant and may relate to the slightly more acute taper at the Optiva cannula tip. Both cannulae were similar in clinical performance.

The Alger Hiss case continues to raise questions about liberalism's romance with Communism and conservatism's assault on civil liberties. The latest evidence is not kind to Hiss, who died just last month at the age of 92

Oshinsky reviews "Radical Son: A Generational Odyssey" by David Horowitz

PURPOSE: We evaluated in patients with prostate cancer whether treatment is associated with in decreased mortality and whether the association of treatment with mortality varies with calendar time. MATERIALS AND METHODS: Using the 146,979 prostate cancer patients from the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program, we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of disease specific and overall mortality. RESULTS: In men with prostate cancer, advanced age, black race, high tumor stage and not having treatment were independently associated with disease specific and overall mortality. The relative risk of mortality in treated patients decreased significantly from 1973 to 1990. CONCLUSIONS: The fact that advanced age and black race are associated with disease specific mortality (even when treatment and stage are controlled) is a new observation, which suggests that tumor biology and/or response to treatment is worse in elderly and black men. Overall, the data are consistent with the hypothesis that treatment of prostate cancer is associated with lower disease specific and overall mortality rates. The decreases in relative mortality in treated patients from 1973 to 1990 indirectly support the theory that changes in patterns of care from 1973 to 1990 had a beneficial effect on mortality. This observation implies that future studies should account for calendar time when interpreting outcomes data.

Sensitive responses of monocytes, macrophages, and neutrophils to bacterial LPS require membrane-bound CD14 (mCD14) and a plasma protein called LPS-binding protein (LBP). Cells lacking mCD14 respond to complexes of LPS and soluble CD14 (sCD14); these responses do not require LBP. To determine whether LBP is necessary for responses of mCD14-bearing cells to LPS, we measured responses of macrophages and neutrophils to complexes of LPS and sCD14 formed in the absence of LBP. We found that the amount of LPS needed to induce adhesive responses of neutrophils or cytokine production by macrophages was the same whether LPS was added with LBP or as LPS-sCD14 complexes, and was >100-fold less than when LPS was added alone. This result supports the view that LBP transfers LPS to CD14, but is not directly involved in responses of CD14-bearing cells to LPS. Responses of neutrophils to LPS-sCD14 complexes could be inhibited partially by blocking mCD14, suggesting that LPS may move rapidly from sCD14 to mCD14. Additionally, we found that responses of neutrophils to LBP and smooth LPS were made 30 to 100 times more sensitive when sCD14 was added. Our findings show that LBP is not necessary for the activation of CD14-bearing cells with LPS, and suggest that LPS-sCD14 complexes are an important intermediate in the inflammatory responses of leukocytes to LPS.

Human polymorphonuclear leukocytes (PMN) respond to LPS with strongly increased integrin-mediated adhesion. While the first step of this process has been identified as the interaction of LPS with CD14 on the cell surface, subsequent steps remain to be elucidated. The experiments presented here suggest that monomeric LPS is internalized in vesicles, and uptake may be required for signaling. Fluorescently labeled LPS presented as monomeric complexes with soluble CD14 appeared in the plasma membrane of PMN by 5 min and was concentrated in cytoplasmic vesicles by 20 min. Adhesion in response to LPS/soluble CD14 occurred only after a 15- to 20-min lag period, consistent with endocytosis occurring before signal generation. In contrast, there was no time lag for adhesion in response to the formyl peptide formyl-norleucyl-leucyl-phenylalanine (fNLLP). Adhesion in response to LPS, but not fNLLP, was completely blocked by lowering the temperature to 19 degrees C, a procedure that prevents vesicle fusion. These studies indicated that an event with the time and temperature dependence of endocytosis precedes signaling by LPS. Cytochalasin D, an inhibitor of phagocytosis, and wortmannin, an inhibitor of phosphatidylinositol 3-kinase that blocks vesicle fusion and phagocytosis, both completely blocked adhesion in response to LPS but not in response to fNLLP. These results support the idea that LPS internalization and early endosomal fusion may be required for signal transduction. Parallel studies showed that the adhesion response to TNF had time, temperature, and inhibitor sensitivities nearly identical with those of LPS, suggesting that responses to TNF may also include an obligate vesicle fusion step.