Cutaneous lesions as a clue to severe combined immunodeficiency.

A 2-month-old boy experienced cutaneous lesions that revealed an underlying severe, combined immunodeficiency (SCID). It is important to recognize cutaneous manifestations of primary immunodeficiency disorders, as they may provide the earliest clue to a defect in immune function.

A novel syndrome of severe neutrophil dysfunction: unresponsiveness confined to chemotaxin-induced functions.

We have identified a patient with a number of neutrophil dysfunctions. The patient was a female baby who lived for 8 months. During her life, she developed severe bacterial infections and showed omphalitis, impaired wound healing, and a pronounced leukocytosis. She was not a patient with leukocyte adhesion deficiency, because all leukocyte CD18 complex proteins were expressed at normal levels. Yet, neutrophil polarization and chemotaxis to platelet-activating factor, leukotriene B4, or formyl-methionyl-leucyl-phenylalanine (FMLP) were completely absent. We found a strong defect in actin polymerization in response to chemotactic stimuli, but only a retarded or even normal reaction with other stimuli. This indicates that the cellular dysfunctions were not due to an intrinsic defect in actin metabolism. Instead, the regulation of actin polymerization with chemotactic stimuli seemed to be defective. We concentrated on FMLP-induced responses in the patient's neutrophils. Functions dependent on activation of complement receptor type 3, such as aggregation or adherence to endothelial cells, were normally induced. Binding to serum-coated coverslips was normal in cell number; however, spreading was not observed. Exocytosis from the specific granules was readily induced. In contrast, FMLP failed to induce a respiratory burst activity or degranulation of the azurophil granules. FMLP induced a normal increase in free intracellular Ca2+, but a decreased formation of diglycerides (especially the 1-O-alkyl,2-acyl compounds). Thus, we have described a patient whose neutrophils show a severe defect in functional activation via chemotaxin receptors, resulting in a selective absence of NADPH oxidase activity, exocytosis from the azurophil granules, and actin polymerization. Our findings show that actin polymerization for neutrophil spreading and locomotion is regulated differently from that for phagocytosis. Also, the release of azurophil and specific granule contents is clearly shown to be regulated in a different way.

Impact of tumor board recommendations on treatment outcome for locally advanced head and neck cancer

Background/Aims: To identify physician selection factors in the treatment of locally advanced head and neck cancer and how treatment outcome is affected by Tumor Board recommendations. Methods: A retrospective analysis of 213 patients treated for locally advanced head and neck cancer in a single institution was performed. All treatments followed Tumor Board recommendations: 115 patients had chemotherapy and radiation, and 98 patients received postoperative radiation. Patient characteristics, treatment toxicity, locoregional control and survival between these two treat- ment groups were compared. Patient survival was compared with survival data reported in randomized studies of locally advanced head and neck cancer. Results: There were no differences in comorbidity factors, and T or N stages between the two groups. A statistically significant number of patients with oropharyngeal and oral cavity tumors had chemoradiation and postoperative radiation, respectively (p < 0.0001). Grade 3-4 toxicities during treatment were 48 and 87% for the postoperative radiation and chemoradiation groups, respectively (p = 0.0001). There were no differences in survival, locoregional recurrences and distant metastases between the two groups. Patient survival was comparable to survival rates reported by randomized studies of locally advanced head and neck cancer. Conclusion: Disease sites remained the key determining factor for treatment selection. Multidisciplinary approaches provided optimal treatment outcome for locally advanced head and neck cancer, with overall survival in these patients being comparable to that reported in randomized clinical trials. Copyright © 2008 S. Karger AG.

An unusual case of severe combined immunodeficiency with hypereosinophilia

SCOPUS: ar.j