A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods

A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (>/=4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors.     

Lipid lowering in a multidisciplinary clinic compared with primary physician management

OBJECTIVE: This study analyzed questionnaire items that address complaints about sleep from the National Vietnam Veterans Readjustment Study, a nationally representative sample of the 3.1 million men and women who served in Vietnam. This study compared the frequency of nightmares and difficulties with sleep onset and sleep maintenance in male Vietnam theater veterans with male Vietnam era veteran and male civilian comparison subjects. It focused on the role of combat exposure, nonsleep posttraumatic stress disorder (PTSD) symptoms, comorbid psychiatric and medical disorder, and substance abuse in accounting for different domains of sleep disturbance. METHOD: The authors undertook an archival analysis of the National Vietnam Veterans Readjustment Study database using correlations and linear statistical models. RESULTS: Frequent nightmares were found exclusively in subjects diagnosed with current PTSD at the time of the survey (15.0%). In the sample of veterans who served in Vietnam (N = 1,167), combat exposure was strongly correlated with frequency of nightmares, moderately correlated with sleep onset insomnia, and weakly correlated with disrupted sleep maintenance. A hierarchical multiple regression analysis showed that in Vietnam theater veterans, 57% of the variance in the frequency of nightmares was accounted for by war zone exposure and non-sleep-related PTSD symptoms. Alcohol abuse, chronic medical illnesses, panic disorder, major depression, and mania did not predict the frequency of nightmares after control for nonsleep PTSD symptoms. CONCLUSIONS: Frequent nightmares appear to be virtually specific for PTSD. The nightmare is the domain of sleep disturbance most related to exposure to war zone traumatic stress.     

Factor structure of a measure of anxiety sensitivity in children

Anxiety sensitivity (i.e., the disposition to react to autonomic arousal with fear) has taken a central role in recent conceptualizations of anxiety. However, questions regarding the dimensional nature of anxiety sensitivity remain. In particular, the factor structure of anxiety sensitivity is unexplored in nonadult populations. The factor structure of the Anxiety Sensitivity Index for Children (ASIC) was examined in three studies. Study 1 (N = 95) used a sample of school children in Grades 4-8 to investigate the reliability of items and factor structure. Items with weak psychometric properties were eliminated, and subsequent analyses revealed that the ASIC was best viewed as a hierarchical scale with a higher order factor (Anxiety Sensitivity) and two first-order factors (Fear of Physiological Arousal and Fear of Mental Catastrophe). Study 2 (N = 112) and Study 3 (N = 144) used more distressed samples of youngsters, and they also found the ASIC to be a hierarchical scale. These findings add a developmental perspective to the Anxiety Sensitivity Index factor analytic discussion and are highly consistent with emergent thinking in the adult anxiety sensitivity literature.     

Spontaneous and induced mutagenesis in a culture of Chinese hamster cells

Spontaneous and nitrosoguanidine (NG)-induced rate of reversions to glutamine independence was studied in cultured temperature-sensitive glutamine auxotrophs of Chinese hamster cells. In 3 experiments the spontaneous rate of reversions varied from 0.8-10(-6) to 3.84-10(-6) per cell per generation. A dependence of the yield of NG-induced back mutations upon the time interval between the mutagenic treatment and the transfer to selective conditions (glutamine deficient medium, 40 degrees C) was established. No induced revertants were detected when cells were transferred to selective conditions immediately after the treatment with NG. After 2--3 days cultivation in glutamine containing medium at 36 degrees C and the sunsequent transfer to selective conditions the frequency of induced reversions varied from 0.56-10(-4) to 10.55-10(-4) in different experiments; after 6 days -- from 0.05-10(-4) to 4.0-10(-4). In all cases where induction was detected, the difference, between the frequency of glutamine prototrophs in treated and control plates was significant. Glutamine independence proved to be stable after prolonged cultivation under non-selective conditions, the degree of prototrophy being greatly unequal in different clones. No differnce in this respect was detected between spontaneous and NG-induced revertants. The proposed system of reverse mutations can be used for studying diverse problems of somatic cell genetics.