Background: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases in the US, and little is understood about its pathogenesis. This study was conducted to characterize, retrospectively, the clinical, objective and immunological parameters that accompany recurrence of CRS during long-term follow-up after surgery. Methods: Fifty-six patients with CRS who had undergone endoscopic sinus surgery were followed up for 5 years after the surgery. The CRS parameters chosen were as follows: history of asthma and/or allergic rhinitis, peripheral eosinophilia of at least 520 cells/µl, peripheral eosinophil count, total IgE, presence of polyps, CT score, presence of fungi (positive fungal culture or stain), mucus or mucosal eosinophilia, mucosal eosinophil count, presence of acute infection after surgery, gender and age. Individual correlations and stepwise regression were performed. Results: Patients with a total peripheral eosinophil count of 520/µl or more and those with asthma were likely to experience recurrence of CRS within 5 years after surgery. Furthermore, patients with mucus or mucosal eosinophilia who were diagnosed as having eosinophilic CRS (ECRS) showed a high incidence of recurrence within 5 years. The parameter of mucus or mucosal eosinophilia (diagnosis of ECRS) had a positive predictive value of 85.7%. Conclusions: Surgeons should always examine the inflammatory infiltrate of nasal polyps or the paranasal mucosa, and patients with ECRS require anti-inflammatory medications, such as steroids, for a long time after surgery. Long-term follow-up is also essential.

Endoscopic surgery is particularly suitable for stapedial disease. Endoscopic stapes surgery can even be done in patients with a curved and narrow external auditory canal. Endoscopic surgery is also suitable for education: The surgical anatomy can be understood easily and both the surgeon and assistants can observe the procedure on the same monitor. However, it should only be performed by experienced surgeons because one-handed manipulation is required and stereoscopic vision is not available.

In murine ontogeny, macrophage precursor cells develop in the yolk sac and fetal liver. Primitive macrophages also appear in the yolk sac, migrate to various tissues, and differentiate into several fetal macrophage populations. Because the development of the monocytic cell lineage is incomplete in the early stage of fetal hematopoiesis, primitive/fetal macrophages are considered to originate from granulocyte-macrophage colony forming cells or earlier macrophage precursors, bypassing the early monocytic cell series. In adult mice rendered severely monocytopenic by administration of strontium-89, resident macrophages are maintained by self-renewal. In contrast, administration of liposome-encapsulated dichloromethylene diphosphonate (clodronate) results in the elimination of various tissue macrophage populations. The repopulation of affected macrophages is dependent on the increase of precursors in the liver and spleen during the period of macrophage depletion. Such precursors reconstitute heterogeneous macrophage subpopulations. In mice homozygous for the osteopetrosis (op) mutation, the absence of macrophage colony-stimulating factor (M-CSF) activity results in a deficiency of monocytes and monocyte-derived macrophages. However, immature macrophages are present in various tissues. Administration of M-CSF to op/op mice induces the increased proliferative capacity and the morphological maturation of macrophages. However, the responses of individual tissue macrophage subpopulations to M-CSF are different. These results indicate that macrophage development, differentiation, and proliferation are regulated by the tissue microenvironment including the in situ production of macrophage growth factors in both fetal and adult life.

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Dichloromethylene diphosphonate (MDPCl2) encapsulated in multilamellar liposomes was selectively incorporated by macrophages, immediately transferred to lysosomes, then released from liposomes into lysosomes by enzymatic digestion of the liposomal lipid layers. From 4 h after ingesting liposome-encapsulated MDPCL2 murine macrophages in vivo and in vitro acquired the ultrastructural features of apoptosis, such as condensed nuclear chromatic, nuclear fragmentation, cell shrinkage, and blebbing of the plasma membrane. Murine peritoneal macrophages and isolated rat Kupffer cells incubated in the medium containing liposome-encapsulated MDPCl2 increased DNA fragmentation in a dose-dependent manner. Electrophoretic analysis of extracted DNA from the isolated Kupffer cells showed DNA fragmentation. Another diphosphonate, Alendronate (4-amino-1-hydroxy-butylidene-1,1-diphosphonate) had less potent macrophage cytotoxicity. However, MDPCl2, Alendronate, and gadolinium chloride in solution were not cytotoxic to macrophages. These results implied that the intralysosomal accumulation of MDPCl2 generates signals to induce macrophage apoptosis.