The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation.

Antibody-mediated rejection (AMR) is an increasingly recognized form of lung rejection. C4d deposition has been an inconsistent finding in previous reports and its role in the diagnosis has been controversial. We conducted a retrospective single-center study to characterize cases of C4d-negative probable AMR and to compare these to cases of definite (C4d-positive) AMR. We identified 73 cases of AMR: 28 (38%) were C4d-positive and 45 (62%) were C4d-negative. The two groups had a similar clinical presentation, and although more patients in the C4d-positive group had neutrophilic capillaritis (54% vs. 29%, P = .035), there was no significant difference in the presence of other histologic findings. Despite aggressive antibody-depleting therapy, 19 of 73 (26%) patients in the overall cohort died within 30 days, but there was no significant difference in freedom from chronic lung allograft dysfunction (CLAD) or survival between the two groups. We conclude that AMR may cause allograft failure, but that the diagnosis requires a multidisciplinary approach and a high index of suspicion. C4d deposition does not appear to be a necessary criterion for the diagnosis, and although some cases may respond initially to therapy, there is a high incidence of CLAD and poor survival after AMR.

Percutaneous embolization on hereditary hemorrhagic telangiectasia patients with severe epistaxis.

OBJECTIVES: To evaluate the results of embolization in patients with hereditary hemorrhagic telangiectasia (HHT) because of severe epistaxis. METHODS: All HHT patients who underwent an embolization (between 1992 and 2006) were asked to participate in this retrospective study. Twelve patients who had in total 19 embolization procedures were interviewed. A questionnaire was used assessing the frequency, severity, duration of epistaxis and their Impact on Lifestyle (IoL). Haemoglobin values were collected from the patients' records. Embolization of the pathologically enhancing lesions was performed using PVA particles. RESULTS: The direct effect of the embolization is very good in 95% of patients. The Impact factor (daily frequency x severity) of epistaxis improved in the first month (p = 0.000) and one year after embolization (p = 0.009). Eleven embolizations (61%) were still associated with significant improvement. There was a reduction in the duration of epistaxis by 16 minutes per day one month after embolization (p = 0.005). However, this reduction was not found one year after embolization. Mean haemoglobin rose significantly after 1 year by an average of 0.8 mmol/l (p = 0.045). Impact on Lifestyle improved in 68% of the procedures and was unchanged in 32%. CONCLUSION: Embolizations remain a therapeutic option in experienced hands. The indication should be made carefully, because of possible (major) complications.

5-Lipoxygenase metabolites of arachidonic acid regulate volume decrease by mudpuppy red blood cells.

We examined whether metabolites of arachidonic acid (AA) regulate K+ efflux during regulatory volume decrease (RVD) by mudpuppy red blood cells (RBCs). Volume regulation was inhibited by the phospholipase A2 antagonists mepacrine (10 microM) and ONO-RS-082 (10 microM); the inhibitory effect of ONO-RS-082 was reversed by gramicidin (5 microM). Eicosatetraynoic acid (ETYA, 100 microM), a general antagonist of AA metabolism, also blocked RVD. In addition, volume regulation was inhibited by the lipoxygenase pathway antagonist nordihydroguaiaretic acid (NDGA, 10 microM), the 5 lipoxygenase antagonists AA-861 (5 microM) and curcumin (20 microM), and by the 5-lipoxygenase activating protein inhibitor L-655,298 (5 microM). Inhibition by all four of these agents was reversed with gramicidin. In contrast, the 12- and 15-lipoxygenase pathway inhibitor ethyl-3,4-dihydroxy-benzylidene-cyanoacetate (EDBCA, 1 microM) and the cytochrome P-450 monooxygenase pathway blocker ketoconazole (20 microM) had no effect. On the other hand, the cyclooxygenase pathway inhibitor aspirin (100 microM) slightly enhanced RVD. Consistent with these findings, a K(+)-selective whole cell conductance responsible for K+ efflux during cell swelling was inhibited by ONO-RS-082 (10 microM), NDGA (10 microM), AA-861 (5 microM), curcumin (20 microM), and L-655,298 (5 microM). In contrast, EDBCA (1 microM), ketoconazole (20 microM), and indomethacin (10 microM) did not block this whole cell conductance. These results indicate that a channel mediating K+ loss during RVD is regulated by a 5-lipoxygenase metabolite of arachidonic acid.

A comprehensive survey of graduate education and training in hazardous waste management.

The United States Department of Health and Human Services through Wayne State University (WSU) has completed a study of hazardous waste education and training in the United States. The study documents university course work and degrees as well as non-degree continuing education short courses. Major portions of the study are based on a WSU sponsored survey in which 1469 four-year degree granting institutions were contacted. Of the 732 institutions responding, 113 were identified as offering course work of some kind in hazardous waste. Information on 499 distinct non-degree short courses was also gathered and evaluated. The purpose, methodology and results of the study are summarized in this article.

Identification and characterization of trypsin, chymotrypsin and elastase inhibitors in the hedgehog, Erinaceus europaeus, and their immunological relationships to those of other mammals (rat, pig and human).

1. Hedgehog plasma was separated by gel filtration on Sephacryl S-200, the fractions resolved by electrophoresis and the electrophoregrams characterized for trypsin, chymotrypsin and elastase inhibiting activities with both low and high molecular weight substrates. Approximate molecular weights were also determined. 2. At least ten protease inhibitors were characterized in hedgehog plasma including three macroglobulins. 3. The hedgehog protease inhibitors were identified by immunoelectrophoresis. Four protease inhibitors showed homologies with specific human, rat or swine antisera. These were alpha 2-and beta-macroglobulins, alpha 1-protease inhibitor, and alpha 2-antithrombin.