In-office laryngeal surgery with the 585nm pulsed dye laser (PDL).

OBJECTIVES: The 585nm pulsed dye laser (PDL) is a promising tool for in-office laryngeal surgery. Data with respect to the safety and efficacy of the PDL for office laryngeal use is sparse. The purpose of this study is to review our experience with unsedated office PDL surgery. METHODS: Records of individuals undergoing in-office PDL between September 1, 2004, and September 1, 2006 were abstracted from a clinical database. RESULTS: Forty-seven patients underwent 117 treatments. The most common indications were recurrent respiratory papillomatosis (RRP), Reinke's edema, and vocal fold polyps. One hundred and four of 117 procedures were felt to be a success ablating all disease. Thirteen treatments required early termination. The most common factor responsible for termination was an inability to achieve a comfortable level of anesthesia. One patient with Reinke's edema developed postprocedure stridor that required a 3-day hospital admission for observation and corticosteroids. There was no incidence of any vocal fold scarring, web formation, or other complications. CONCLUSIONS: The 585nm PDL is a promising tool for in-office treatment of various laryngeal disorders. Complications are rare.     

Minimal Acute Rejection after Lung Transplantation: A Risk for Bronchiolitis Obliterans Syndrome

Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft dysfunction. Although previous studies have identified mild to severe rejection (grade>or=A2) as a risk factor for BOS, the role of minimal rejection (grade A1) remains unclear. To determine if A1 rejection by itself is a risk factor for BOS, we performed a retrospective cohort study on 228 adult lung transplant recipients over a 7-year period. Cohorts were defined by their most severe rejection episode (none, A1 only, and >or=A2) and analyzed for the subsequent development and progression of BOS using univariate and multivariate time-dependent Cox regression analysis. In the univariate model, the occurrence of isolated minimal rejection was a risk factor for all stages of BOS. Similarly, multivariate models that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral infection, underlying disease and type of transplant demonstrated that A1 rejection was a distinct risk factor for BOS. Furthermore, the associated risk with A1 rejection was slightly greater than the risk from >or=A2 and treatment of A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that minimal rejection is associated with an increased risk for BOS development and progression that is comparable to A2 rejection.     

The exclusion among the Ustilago viruses — A dsRNA restriction modification system?

Summary Specific exclusion relations are know among the three Ustilago maydis viruses that are associated with the cytoplasmically transmitted killer phemomenon. Of the three viruses P1, P4 and P6, only P1, and P4 cancoexist in one host cell. Mutual exclusion occurs between P1 and P6 and P4 unilaterally excludes P6. The exclusion relations were originally defined among the wild-type viruses. Those relations can be modified by two specific segments that are a part of the P4 dsRNA genome and were also found in some sensitive strains that contained part of the viral genome. Also, deletion of the dsRNA segment that is assumed to encode the toxin information permits the formation of hybrid genomes that otherwise cannot be formed. The data is interpreted in terms of a dsRNA restriction modification system in which the killer toxin or a toxin-linked function acts as the restriction factor and segments H3 and H4 or H4 alone contain the necessary information for the modification of certain sites on the M and L segments of the P1 and P4 viruses but not on the P6 segments.     

Inhibition of ras by farnesylthiosalicylate significantly reduces the levels of autoantibodies in two animal models of the antiphospholipid syndrome

BACKGROUND: Stimulation and proliferation of lymphocytes require activation of Ras. S-farnesylthiosalicylic acid (FTS) is a synthetic substance that detaches Ras from the inner cell membrane and induces its rapid degradation. Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies detected in patients with antiphospholipid syndrome (APS), which is associated with thrombosis, pregnancy losses, and thrombocytopenia. OBJECTIVE: To examine the effect of FTS treatment on aPL levels in a genetic autoimmune model (the MRL/lpr mice) and in an induced model of APS. METHODS: Female Balb/C mice immunized once with beta2-glycoprotein I (beta2-GPI) in complete Freund's adjuvant (CFA) and female MRL/lpr mice were treated intraperitoneally with either FTS (5 mg/Kg/day) or saline 3-5 times a week. aPL and anti-beta2-GPI antibodies were measured by ELISA. RESULTS: FTS treatment 3 times a week resulted in significant decreases of aPL and anti-beta2-GPI antibodies in both animal models. In contrast, more frequent treatment (5 times a week) had no significant effect on autantibody levels in both animal models. We further compared 2 protocols in the induced APS model, one for alternate day treatment and the other for daily treatment on the first 3 days each week, and found a decrease in autoantibody levels only in the alternate day protocol. CONCLUSIONS: Inhibition of Ras activation by FTS is effective in decreasing autoantibody levels in models of APS. The differential modulation of immune function by alternate day compared to daily treatment may provide better understanding of the role of Ras activation in this system.     

Migrating anterior mesoderm cells and intercalating trunk mesoderm cells have distinct responses to Rho and Rac during Xenopus gastrulation.

Rho GTPases have been shown recently to be important for cell polarity and motility of the trunk mesoderm during gastrulation in Xenopus embryos. This work demonstrated that Rho and Rac have both distinct and overlapping roles in regulating cell shape, and the dynamic properties, polarity, and type of protrusive activity of these cells. Overexpression of activated or inhibitory versions of these GTPases also disrupts development of the head in Xenopus embryos. In this study, we have undertaken a detailed analysis of Rho and Rac function in migrating anterior mesendoderm cells. Scanning electron micrographs of these cells in situ revealed that their normal shingle arrangement is disrupted and both the cells and their lamellipodia are disoriented. Anterior mesendoderm explants plated on their natural blastocoel roof matrix, however, still migrated towards the animal pole, although the tendency to move in this direction is reduced compared to controls. Analysis of a number of parameters in time-lapse recordings of dissociated cells indicated that Rho and Rac also have both distinct and overlapping roles in the motility of the prospective head mesoderm; however, their effects differ to those previously seen in the trunk mesoderm. Both GTPases appear to modulate cell polarization, migration, and protrusive activity. Rho alone, however, regulates the retraction of the lagging edge of the cell. We propose that within the gastrulating Xenopus embryo, two types of mesoderm cells that undergo different motilities have distinct responses to Rho GTPases.     

Weight change adjusted equations for assessing resting metabolic rate in overweight and obese adults

BackgroundAlthough over one hundred equations have been developed to predict the energy expenditure of individuals, none are sensitive to weight change in assessment of resting metabolic rate (RMR) before and after weight loss.ObjectiveTo formulate adjusted equations for overweight and obese individuals and to compare their accuracy with existing prediction RMR equations before and after weight loss.Subjects/materialsThis is historical prospective study. Participants included 39 overweight and obese men and women before and after losing 10–20% from baseline weight on a diet and physical activity regimen for at least three months. Pre and post weight loss measured RMR results were compared to estimated RMR using several existing prediction equations: Harris and Benedict, Ravussin and Bogardus, and Mifflin et al. To improve the accuracy of these prediction equations, we suggest new equations adjusted for weight loss, based on measured RMR and evaluated their accuracy.ResultsPre and post weight loss data indicated: significant fat reduction in both genders; reduction in free-fat mass only in men, and a significant decrease in measured RMR only in women. Our suggested equations were the most accurate and closest to measured RMR in both genders, in comparison to the Harris and Benedict, Ravussin and Bogardus, and Mifflin et al equation results. Estimated RMR using the latter equations was significantly lower than measured RMR in both genders at pre and post weight loss (P < 0.01).ConclusionsThis study highlights the need for adjusting RMR equations before and after weight loss in overweight and obese individuals. Further research is needed to validate our suggested equations.     

Local anergy rather than systemic anti-tumour immunity to explain tumour growth in an animal model of oral squamous cell carcinoma

A chemically induced syngeneic hamster tumour model of human oral squamous cell carcinoma (OSCC) was used to investigate the possible influence of locally transplanted growing rumours on the immune system of the recipient. Cell activation and cell cytotoxicity assays were performed in vitro using the colorimetric MTT assay to measure any possible changes. The fast growing nature of the tumour model if grafted locally as a fragment was confirmed but not if injected as a single cell suspension (SCS). Stimulation (Concanavalin A) of spleen cells from normal and from tumour bearing animals showed that there was a minor though statistically significant decrease in the mitogenic response of the latter. Thus, the respective stimulatory indices (SI) were 4.06+/-1.61 and 2.06+/-0.87 (0.02

0.01). No significant difference was observed when spleen cells were stimulated with interleukin-2 (IL-2), although there was a similar trend. Pre-immunisation of animals with irradiated autologous SCS three weeks prior to grafting, resulted in a significant decrease in the tumour growth rate of subsequently grafted tumour. Thus, the mean If: SD (weight of takes in mg) for the successful takes of untreated (n=10) and treated (n=9) groups were 52.0+/-52.2 and 25.7+/-19.4 (0.02

0.05) respectively. The number of cases with no tumour takes were 2 of 10 (20%) and 6 of 9 (66%) respectively. In a separate experiment groups of 5 animals were immunized with an increasing number of cells as irradiated SCS, the results of which demonstrated an inverse correlation between the rate of tumour growth and the number of injected tumour cells. The addition of irradiated SCS to IL-2 activated normal spleen cells (LAK cells) in vitro led to a dose-related decrease in the efficiency of cytotoxicity of latter when tested against an xenogeneic super-sensitive surrogate tumour target cell line (Fen cells). Thus, the percent killing by IL-2-activated normal spleen cells was 56.4%. The corresponding mean values for IL-2 activated normal spleen cells in the presence of tumour SCS at 25/1 and 50/1 ratios were 35.9% (p<0.05) and 11.9% (p<0.001) respectively. Ln an attempt to establish the presence of T suppressor cells, spleen cells from tumour bearing animals were injected concomitantly with SCS into 5 recipients. After four weeks no tumour growth had occurred. In conclusion we demonstrated that the presence of injected or grafted tumour had only a minor effect on systemic immune function but induced a strong local anergic effect. This local anergic effect was demonstrable as blocking of LAK activity and thus perhaps allowed suppression of the functional activities of incoming immunocompetent cells.