Citations

The purpose of this study was to establish treatment criteria for patients with early‐stage squamous cell carcinoma of the buccal mucosa. Thirty‐one patients were analyzed in a retrospective fashion. Distribution of patients according to tumor stage was relatively even. Within 5 years recurrent disease developed in nearly 80% of evaluable patients. There was a 100% overall incidence of local disease recurrence for patients with stage I and II tumors treated with wide local excision alone and followed up for more than 2 years. On the basis of these data, we conclude that wide local excision for early‐stage buccal carcinoma is associated with a high local failure rate. Possible causes for failure and alternative treatment approaches are discussed.

A transgenic mouse containing the complete human SLAM (hSLAM/CD150) gene, including its endogenous promoter for transcription, was generated by using human genomic DNA cloned into a bacterial artificial chromosome. hSLAM, the primary receptor for measles viruses (MV), was expressed on activated B, T, and dendritic cells with an expression profile equivalent to that of humans. We demonstrated that hSLAM + cells obtained from the transgenic mouse, including activated B, T, and dendritic cells, were susceptible to MV infection in a receptor-dependent manner. Evidence was provided for transient infection in the nasal lymph nodes of hSLAM + mice after intranasal inoculation. Virus was rapidly cleared without signs of secondary replication. To improve the efficiency of MV production, the hSLAM + mice were bred with mice having a Stat1 -deficient background. These mice were more susceptible to MV infection and produced more virus particles. After intranasal and intraperitoneal inoculation of these mice with MV, infections of the thymus, spleen, nasal, mesenteric, and leg lymph nodes were detected. Upon necropsy, enlarged lymph nodes and spleen were apparent. Flow cytometric analysis showed that abnormally large numbers of mature neutrophils and natural killer cells caused the splenomegaly. The hSLAM transgenic mouse constitutes an improved rodent model for studying the interaction of MV with immune cells that more accurately reflects the infection pattern found in humans.

Purpose A traditional end point for colon adjuvant clinical trials is overall survival (OS), with 5 years demonstrating adequate follow-up. A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice. Methods Individual patient data were pooled from 18 randomized phase III colon cancer adjuvant clinical trials. Trials included 43 arms, with a pooled sample size of 20,898 patients. The primary hypothesis was that disease-free survival (DFS), with 3 years of follow-up, is an appropriate primary end point to replace OS with 5 years of follow-up. Results The recurrence rates for years 1 through 5 were 12%, 14%, 8%, 5%, and 3%, respectively. Median time from recurrence to death was 12 months. Eighty percent of recurrences were in the first 3 years; 91% of patients with recurrence by 3 years died before 5 years. Correlation between 3-year DFS and 5-year OS was 0.89. Comparing control versus experimental arms within each trial, the correlation between hazard ratios for DFS and OS was 0.92. Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 (92%) of 25 cases. Formal measures of surrogacy were satisfied. Conclusion In patients treated on phase III adjuvant colon clinical trials, DFS and OS are highly correlated, both within patients and across trials. These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens, although marginally significant DFS improvements may not translate into significant OS benefits.

Background and Purpose— Mitral annular calcification (MAC) and aortic valve (AV) sclerosis have each been linked to cardiovascular disease. Whether MAC and AV sclerosis are risk factors for stroke independent of other echocardiographic or laboratory predictors has not been established. We evaluated the relationship between MAC, AV sclerosis, and first stroke events in a population-based cohort. Methods— Our study cohort consisted of 2723 American Indians participating in the Strong Heart Study who were free of prevalent cardiovascular disease. Participants underwent standardized clinical, echocardiographic, and laboratory evaluation, and incident stroke was ascertained using validated methods. Results— During a median follow-up of 7 years, 86 strokes occurred. Age- and sex-adjusted incidence rates of stroke were significantly increased for MAC (rate ratio [RR], 3.12; 95% CI, 1.77 to 5.25) but not for AV sclerosis (RR, 1.15; 95% CI, 0.45 to 2.49). MAC was also associated with a reduced time to first stroke events after adjustment for clinical variables and the inflammatory markers C-reactive protein and fibrinogen (hazard ratio [HR], 2.42; 95% CI, 1.39 to 4.21) or the echocardiographic covariates left ventricular hypertrophy and left atrial enlargement (HR, 1.89; 95% CI, 1.04 to 3.41). Individuals with and without AV sclerosis showed no significant difference in stroke-free survival in unadjusted analyses ( P =0.698). Crossing of the survival curves precluded multivariable analysis using Cox models. Conclusions— In this cohort of American Indians without clinical cardiovascular disease, the presence of MAC, but not AV sclerosis, proved to be a strong risk factor for incident stroke after extensive adjustment for other predictors. Individuals exhibiting MAC may benefit from aggressive risk factor modification, but this will require further investigation.