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Objective: Photodynamic therapy (PDT) is a minimally invasive method with strong tissue selectivity and nonthermal effects. We aim to investigate the efficacy of an in-office method utilizing PDT with local application of 5-aminolevulinic acid (ALA) and 635 nm diode laser for treating laryngeal leukoplakia., Study Design: Retrospective cohort study., Setting: Outpatient clinic-tertiary medical center., Methods: This study reviewed 32 patients with laryngeal leukoplakia, including 11 recurrent cases after surgery. All the procedures were performed in an office setting under topical anesthesia. Fifteen percent ALA solution was locally applied to the lesion through a flexible laryngoscope. Light illumination was performed using a 635 nm diode laser through a 400 μm optic fiber. The power density was 165 mW/cm 2 to reach 100 J/cm 2 . Results of laryngostroboscopy and voice evaluation during follow-up were collected., Results: The mean follow-up was 7.91 ± 4.83 (3-18) months. Thirty-nine procedures were performed, including 1 session for 27 patients, 2 sessions for 3 patients, and 3 sessions for 2 patients. The total response rate was 96.875% (31/32), including complete responses in 26 (81.25%) patients, partial responses in 5 patients (15.625%), and no response in 1 patient (3.125%). It appeared that PDT selectively eliminated the leukoplakia without affecting lamina propria and the surrounding normal mucosa remained unharmed. Scores of Voice Handicap Index-10, jitter, shimmer, and harmonic-to-noise ratio were significantly improved after PDT., Conclusion: Office-based PDT is an effective, repeatable, and practical method for treating laryngeal leukoplakia. Local application of ALA is sufficient to achieve photodynamic reactions. PDT could eliminate laryngeal leukoplakia selectively while protecting the normal laryngeal structure., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Introduction: Inflammatory pseudotumor is an idiopathic, non-neoplastic mass lesion with few cases reported in the literature involving only the skull base and related structures. Imaging of skull-base pseudotumors shows characteristics similar to that of nasopharyngeal carcinoma and lymphoma, thereby requiring a biopsy to exclude malignancy. Surgical versus medical management relates to the location of the mass, the extent of bony invasion, and the involvement of corresponding anatomic structures., Methods: A retrospective chart review of patients diagnosed with inflammatory pseudotumor of the skull base from a single tertiary care institution over a five-year period., Results: Five cases of skull-base pseudotumor have been identified and followed from one to four years. In our clinical experience, maintenance oral corticosteroids have proven effective in improving symptoms and significantly reducing radiologic tumor dimensions., Conclusion: Inflammatory pseudotumor of the skull base is a challenging diagnosis due to its occult anatomic location, vague associated symptoms, and nonspecific histology. Low-dose oral corticosteroids are often very effective in management.

In 2006, the Centers for Disease Control and Prevention (CDC) released revised recommendations for performing human immunodeficiency virus (HIV) testing in health care settings, including implementing routine rapid HIV screening, the use of an integrated opt-out consent, and limited prevention counseling. Emergency departments (EDs) have been a primary focus of these efforts. These revised CDC recommendations were primarily based on feasibility studies and have not been evaluated through the application of rigorous research methods. This article describes the design and implementation of a large prospective controlled clinical trial to evaluate the CDC's recommendations in an ED setting. From April 15, 2007, through April 15, 2009, a prospective quasi-experimental equivalent time-samples clinical trial was performed to compare the clinical effectiveness and efficiency of routine (nontargeted) opt-out rapid HIV screening (intervention) to physician-directed diagnostic rapid HIV testing (control) in a high-volume urban ED. In addition, three nested observational studies were performed to evaluate the cost-effectiveness and patient and staff acceptance of the two rapid HIV testing methods. This article describes the rationale, methodologies, and study design features of this program evaluation clinical trial. It also provides details regarding the integration of the principal clinical trial and its nested observational studies. Such ED-based trials are rare, but serve to provide valid comparisons between testing approaches. Investigators should consider similar methodology when performing future ED-based health services research.

Hmunc13 is a cytosolic diacylglycerol (DAG)-binding protein, which is upregulated in renal cortical tubule and mesangial cells by hyperglycemia. In response to DAG activation, hmunc13 translocates to the Golgi. To investigate how this may relate to its function, we used a bacterial two-hybrid screen to look for hmunc13-interacting proteins. Full-length Rab34 was specifically isolated from a human kidney cDNA library. Co-expression of the two proteins confirmed Rab34 as a Golgi-associated protein, which was immunoprecipitated from cell lysates by hmunc13. Glutathione S-transferase fusion proteins of WT, Q111L (GTP bound), and T66N (GDP bound) mutants were created, and their GTP-binding activity verified by radioactive overlay assay. Binding of hmunc13 was observed with Q111L, barely detectable with T66N and enhanced with Rab34WT loaded with GTPgammaS compared with GDP loaded. Deletion of munc homolgy domain (MHD)-2, eliminated the hmunc13/Rab34 interaction. The Q111L mutant localized to the Golgi apparatus, but T66N was cytosolic. Localization of both mutants and Rab34WT was unchanged by DAG activation. The data suggest that DAG activation of hmunc13 causes it to be translocated to the Golgi, where it binds to GTP-bound Rab34 via MHD-2. Because Rab34 is known to regulate intracellular lysosome positioning, we propose that hmunc13 serves as an effector of Rab34, mediating lysosome-Golgi trafficking.

Background: Invasive fungal infections (IFI) in immunocompromised patients are associated with significant morbidity and mortality, despite appropriate antifungal treatment and recovery from neutropenia. The outcome of these infections depends significantly on the overall state of immunosuppression, including mainly the phagocytic system (neutrophils and macrophages). Interferon-gamma (IFN-gamma), granulocyte-colony--stimulating factor (G-CSF) and granulocyte-macrophage-colony--stimulating factor (GM-CSF) are cytokines that enhance the activity of neutrophils and macrophages., Methods: The authors reported 4 patients with leukemia and refractory invasive candidiasis or trichosporonosis despite 1-13 months of appropriate antifungal treatment., Results: Cytokines were administered for 1.5-5 months without significant toxicity. For each patient, initiation of interferon-gamma plus a colony-stimulating factor resulted in a clinical response. The contribution of cytokines to control the fungal infection in these 4 patients was suggested by the strong inflammatory reaction observed in the 2 patients who had an immediate response (within 7 days of initiation of cytokine therapy) and by the good outcome in the 2 other patients in whom antifungal agents were discontinued at the start of cytokine therapy., Conclusions: These data suggested a potential role for immunomodulation in patients with leukemia with refractory invasive fungal infections.

Background: Mutations in fibroblast growth factor 3 receptor (FGFR3) are frequent events in low-grade bladder tumors. To assess the potential utility of the detection of FGFR3 mutations in a screening modality, the authors analyzed urine sediment DNA samples from 192 patients in a retrospective study., Methods: Urine sediment DNA samples from 192 patients were prepared. Seventy-two patients had undergone transurethral resection (TURBT group) of mainly Ta lesions and 120 patients had undergone cystectomy (cystectomy group). The majority of patients in the cystectomy group had more advanced tumors compared with patients in the TURBT group. DNA preparations were screened for FGFR3 mutations in exons 7, 10, and 15 using single-strand conformation polymorphism (SSCP) and DNA sequencing., Results: Using SSCP, 67% of patients in the TURBT group and 28% in the cystectomy group displayed FGFR3 mutations. Comparative analysis of cytology results and FGFR3 mutational analysis were performed in 122 cases. Within the TURBT group, FGFR3 mutation analysis outperformed cytology. FGFR3 mutation analysis identified change in 68% of urine sediment DNA samples whereas cytology recorded the presence of tumor cells in 32% of the DNA samples. In the cystectomy group, cytology outperformed FGFR3 mutation analysis. Cytology recorded tumor detection in 90% of patients, while SSCP identified mutational change in 24%., Conclusions: Combining FGFR3 mutation results with cytology in both groups correctly identified tumor presence in 105 of 122 (86%) of patients. The greater sensitivity of FGFR3 mutation detection over cytology in identifying the presence of low-grade, superficial bladder tumors represents a potential new tool to complement standard cytology in screening patients for bladder tumors and recurrent disease., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11536)

Background: The incidence of malignant melanoma is increasing rapidly. The risk for development of malignant melanoma has been reported to be higher in persons of higher socioeconomic status., Methods: This case-control study explores the relation between occupation and malignant melanoma relative risk through analysis of data collected by the American Cancer Society. A total of 1.2 million people were enrolled in a study of lifestyles and environmental factors in relation to mortality from cancer and other diseases. A total of 2780 persons had a history of malignant melanoma when the study began or developed malignant melanoma during the 6-year study follow-up period. The controls were matched for age, sex, race, and geographic location on an approximately 1:3 basis to persons selected from the remaining people enrolled., Results: In men, malignant melanoma risk was significantly higher in high-paying versus low-paying occupations (odds ratio [OR], = 1.58; P < 0.001) and in white-collar versus blue-collar occupations (OR = 1.33; P < 0.001). No significant conclusions could be drawn for women. No significant difference in risk was noted between those with indoor versus outdoor occupations. Among specific occupational exposures, only exposure to X-rays significantly raised malignant melanoma risk (OR = 1.37; P = 0.002)., Conclusion: Upper pay scale and white-collar occupations significantly increase the risk for development of malignant melanoma.

We consider simple lattice models for short peptide chains whose states can be exhaustively enumerated to find the lowest energy conformation. Using these exact results and numerical simulations, we compute the distributions for the mean time tN, required to find the global minimum energy state by simulated annealing (SA), as a function of N, the number of units in the chain. On the basis of scaling arguments, the time tN, to find the global minimum energy of longer chains, beyond the range covered by exhaustive enumeration, can be estimated. On the basis of the observed exponential increase in folding time of the standard SA algorithms, it is imperative that better algorithms be found for minimizing longer chains.