Citations

ABSTRACTEosinophils are a hallmark of allergic diseases and helminth infection, yet direct evidence for killing of helminth parasites by their toxic granule products exists only in vitro. We investigated the in vivo roles of the eosinophil granule proteins eosinophil peroxidase (EPO) and major basic protein 1 (MBP) during infection with the rodent filariaLitomosoides sigmodontis. Mice deficient for either EPO or MBP on the 129/SvJ background developed significantly higher worm burdens than wild-type mice. Furthermore, the data indicate that EPO or MBP is involved in modulating the immune response leading to altered cytokine production during infection. Thus, in the absence of MBP, mice showed increased interleukin-10 (IL-10) production after stimulation of macrophages from the thoracic cavity where the worms reside. In addition to elevated IL-10 levels, EPO−/−mice displayed strongly increased amounts of the Th2 cytokine IL-5 by CD4 T cells as well as a significantly higher eosinophilia. Interestingly, a reduced ability to produce IL-4 in the knockout strains could even be seen in noninfected mice, arguing for different innate propensities to react with a Th2 response in the absence of either EPO or MBP. In conclusion, both of the eosinophil granule products MBP and EPO are part of the defense mechanism against filarial parasites. These data suggest a hitherto unknown interaction between eosinophil granule proteins, defense against filarial nematodes, and cytokine responses of macrophages and CD4 T cells.

Purpose Large rotator cuff tears present a challenge to orthopaedic surgeons. Because tissue may be insufficient or of inadequate quality to undergo repair, a variety of materials have been used as adjuncts. Human dermal tissue may be processed to render it acellular, and thus less immunogenic, but with the extracellular matrix left intact, creating a collagen scaffold with favorable characteristics. Because of these traits, use in rotator cuff repair was proposed. Methods A canine model for a full‐thickness infraspinatus tendon tear was used. Tendon was excised from the bony interface to the myotendinous junction, and a human acellular dermal matrix graft (experimental) or the autologous excised tendon (control) was used to bridge the defect. Animals were sacrificed, and shoulders were evaluated histologically and biomechanically. Results At time 0, strength of control and experimental repairs was similar. At 6 weeks, the strength of the experimental repair was half that of the control side. Strength of control specimens remained the same at 6 and 12 weeks, but by 12 weeks, the strength of the experimental repair was equal to that of the control. Histologically, cells infiltrated the control and experimental specimens by 6 weeks; chronic inflammation was consistent with surgery and repair. At 6 months, control and experimental specimens mimicked normal tendon structure grossly and histologically. Conclusions Use of human acellular dermal matrix as a patch is a viable option in this model of large rotator cuff defects. Within 6 weeks, histologic evidence of native cell infiltration and neotendon development was observed. Within 12 weeks, the strength of the dermal matrix graft repair was equivalent to that of autologous tendon. At 6 months, control and graft specimens mimicked normal tendon structure grossly and histologically. Clinical Relevance This study provides in vivo animal data to support the use of this acellular dermal matrix graft for repair of full‐thickness rotator cuff defects. Additional studies are indicated to determine the role of this material in the treatment of humans with rotator cuff tears.

Purpose Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. Patients and Methods Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. Results Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. Conclusion For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.