Recruitment strategies and comparison of prostate cancer-specific clinical data on African-American and Caucasian males with and without family history.

Prostate cancer is the most common cancer in men in the United States. This is a complex disease with high heterogeneity and the exact causes are unknown in population-specific samples. Family history is a primary risk factor irrespective of race. Identifying prostate cancer families with multiple affected cancer cases is challenging. Herein we document recruitment techniques and present prostate cancer clinical factors described in a cohort of African Americans and Caucasians with or without a strong family history. A total of 521 prostate cancer patients (241 African Americans and 280 Caucasians) were identified using a novel cooperative methodology involving a combination of treating physicians and tumor registries. Higher prostate-specific antigen (PSA, P=0.0269) was found in familial cases as compared to sporadic cases in African-American men. In addition, PSA values for familial cases were higher (P=0.0093) in African-American as compared to Caucasian men. No differences were detected in Gleason score values in either race, regardless of family history. These findings remained the same after adjustment was made for age at diagnosis. In conclusion, methodologies for cohort acquisition, and clinical characteristics, are described for men with and without a family history of prostate cancer using both Caucasian and African-American populations.

Chemokine receptor expression in HIV-positive persons with oropharyngeal candidiasis.

OBJECTIVE: In HIV+ persons with reduced CD4+ T cells, oropharyngeal candidiasis (OPC) is often associated with the accumulation of CD8+ T cells at the epithelial/lamina propria interface within the lesion together with increased tissue-associated cytokines and chemokines. Despite this reactivity, a dysfunction in the ability of the CD8+ cells to reach the organism at the outer epithelium is postulated. The purpose of this study was to examine chemokine receptors present in the OPC lesions for a potential role in susceptibility to infection. METHODS: Biopsies taken from buccal mucosa of HIV- persons, healthy mucosa of HIV+ OPC- persons, and OPC lesions were processed for protein immunohistochemical staining or RNA analysis by real-time PCR and Superarray. RESULTS: There was little change in expression of chemokine receptors at the protein or RNA level between OPC+ and OPC- tissue. At the protein level, increases occurred in OPC+ persons only if associated with CD8 cells. In the Superarray, of the 22 chemokine receptor mRNAs expressed, c. 90% remained unchanged (< 1.0-fold change) between HIV- and HIV+ tissue and between HIV+ OPC- and HIV+ OPC+ tissue. CONCLUSION: Tissue-associated chemokine receptor expression does not appear to contribute to the dysfunction in cellular migration associated with susceptibility to OPC.

Effect of placement agitation and placement time on the shear bond strength of 3 self-etching adhesives.

This study measured the shear bond strength (SBS) of 3 self-etching bonding agents to enamel and dentin with and without agitation at 3 different application times. The null hypotheses tested were that agitation and application time have no effect on bond strength. Occlusal surfaces of 180 recently extracted caries-free human molars were wet ground with 600 grit wet-dry silica carbide abrasive paper to obtain a flat enamel surface. The teeth were divided into 18 groups of 10 teeth. Three self-etching bonding agents, Clearfil SE BOND (Kuraray America), Xeno III (Dentsply) and AdheSE (Ivoclar-Vivadent) were applied using application times of 10, 20 or 30 seconds with or without agitation, thinned with a gentle stream of air and cured for 10 seconds, according to manufacturers' directions. Z100 (3M ESPE) composite, A2 shade, was placed over the cured adhesive and cured for 40 seconds. The samples were stored in distilled water at room temperature until testing. The samples were tested in shear to failure with a 1-mm/minute crosshead speed. After enamel shear bond strength testing, the teeth were again ground with 400 and 600-grit wet-dry SiC paper to obtain a flat dentin surface. The protocol used for preparing the enamel bond test samples was repeated, and the teeth were stored until testing in distilled water at room temperature. The samples were again tested in shear at a 1-mm/minute crosshead speed. Values were converted to MPa and data analyzed for intergroup differences using ANOVA and Tukey post-hoc tests. Agitation did not improve enamel SBS for any of the materials tested, but there was a significant difference in enamel SBS among materials: Clearfil SE Bond shear bond strength was greater than Xeno III, which was greater than AdheSE. At 10 seconds application time on dentin, agitation improved the Clearfil SE Bond SBS and, at 20 seconds application time on dentin, agitation significantly improved SBS to dentin for all systems tested. Agitation had no affect when the adhesive was applied to dentin for 30 seconds. Clearfil SE Bond SBS to dentin was significantly higher than the other self-etching adhesives tested except at 10 seconds without agitation.

Opposite effects of low-density and high-density lipoprotein on blood viscosity in fasting subjects.

Given the enlarging body of evidence implicating increased blood viscosity in atherogenesis, the authors hypothesize that lipoproteins modulate the atherogenic process by affecting blood viscosity. In order to define the magnitude of the effect of lipoproteins on blood viscosity, capillary viscometry was performed on blood from 16 healthy, fasting subjects, and results were correlated with lipoprotein-cholesterol levels. Low-density lipoprotein-cholesterol was positively associated with blood viscosity (r = 0.610, p = 0.01). High-density lipoprotein-cholesterol was negatively associated with blood viscosity (r = -0.479, p = 0.06). A multiple regression model was developed with these data, revealing that 54% of variation in blood viscosity was attributable to these lipoproteins. This model was validated on a second dataset, in which these lipoproteins accounted for 28% of variation in blood viscosity. A second model, including hematocrit, serum viscosity, and high-density lipoprotein-cholesterol levels, explained 73% of variation in blood viscosity. By modulating blood viscosity and flow, lipoproteins may affect the residence time of atherogenic particles and atherogenesis.

Analyzing multivariate data in crossover designs using permutation tests.

Studies using crossover designs typically involve observations on a large number of response variables made on each of a relatively small number of subjects. Moreover, investigators often observe the responses longitudinally over time. As the number of variates approaches the number of subjects traditional multivariate statistics based on the concept of statistical distance often are not very powerful, and when that number exceeds the total number of subjects in the study, these tests are not defined. In these situations, statisticians frequently analyze each variate separately and adjust for the multiple testing using a technique suitable for correlated data. In the case of a single variate measured repeatedly, we often make the assumption of a patterned covariance matrix and then conduct a univariate mixed-model analysis. We discuss an alternative approach using a variety of data structures in 2 x 2 crossover designs with (1) univariate response in each treatment period, (2) multivariate response in each treatment period, and (3) longitudinal repeated measures on a single variate in each treatment period.

Effect of granulocyte colony-stimulating factor on acute lung injury in the rat.

The effect of G-CSF pretreatment on experimental acute lung injury was studied in Sprague-Dawley rats receiving one of the following treatments: (1) G-CSF 50 micrograms/kg subcutaneously twice daily beginning 2 d prior to being killed; (2) ANTU 50 mg/kg intraperitoneally; (3) ANTU+G-CSF 50, 25, or 12.5 micrograms/kg; (4) HCl 0.6 ml of a 0.1 N solution intratracheally; (5) HCl+G-CSF 50 or 25 micrograms/kg; (6) control solutions. Lung injury was quantified by measurement of lung wet/dry weights, by histopathologic scoring, and by measurement of fluid flux during ex vivo perfusion. G-CSF pretreatment elevated the baseline blood neutrophil counts as much as 6-fold compared with Control, and it increased the numbers of lung neutrophils and caused a mild histologic lung injury, but it did not significantly alter wet/dry weight ratios or fluid flux. ANTU alone and HCl alone caused a moderate histologic lung injury, increased wet/dry weight ratio, and resulted in a small increase in flux. The combination injuries, ANTU+G-CSF and HCl+G-CSF, caused a more severe lung injury manifested by increased wet/dry weight ratios and increase in flux when compared with ANTU alone and HCl alone, respectively. We conclude that pretreatment with G-CSF potentiates ANTU- and HCl-induced lung injury in non-neutropenic rats. The potential for G-CSF to aggravate acute lung injury in patients remains speculative.

Long-term follow-up of generalized anxiety disorder.

The diagnostic stability and long-term prognosis of generalized anxiety disorder (GAD) remain the subjects of considerable controversy. We report the results of an investigation of the long-term outcome of an original sample of 44 subjects who participated in a medication trial. Subjects were reinterviewed approximately 16 months after completion of the study, using structured interviews. Fifty percent continued to fulfill criteria for GAD. Other concurrent axis I diagnoses were as follows: dysthymia, 11%; major depression, 7%; and social phobia, 7%. Regarding axis II comorbidity, subjects with chronic GAD were more likely to fulfill criteria for one or more personality disorders, especially in clusters B and C. In addition, follow-up subjects with GAD and with remitted GAD reported a statistically equivalent number of recent life events, although subjects with chronic GAD were more likely to report significant dissatisfaction with life. The findings indicate that although many subjects with GAD do not follow a chronic course, many others remain symptomatic. The results also suggest that GAD symptoms are not simply the result of a subject's recent negative experiences, and that life satisfaction measures are an accurate reflection of GAD outcome.

The analysis of small-sample multivariate data with applications in clinical trials.

This article discusses statistical methods for the analysis of multivariate data arising in clinical trials involving a small number of subjects randomly assigned to one of several treatment groups. Possible violations of traditional assumptions such as variance homogeneity and normality of errors are often dealt with by carrying out the statistical analysis using strategies such as transforming the data or applying nonparametric procedures. Multivariate nonparametric tests provide a realistic alternative for analyzing such data. We present a permutation procedure for analyzing data arising in randomized experiments.

A computer package for the multivariate nonparametric rank test in completely randomized experimental designs.

When research data are measured on at least an ordinal scale and the assumptions required in the theory underlying parametric statistical methods are in question, nonparameteric procedures based on the ranks provide a sound approach to statistical analysis. Biomedical investigations, especially clinical trials, typically involve multivariate response and therefore multivariate statistical methods are called for in the interpretation of results. We discuss applications of the nonparametric multivariate rank test for completely randomized designs. Large sample theory can be used to support these statistical methods for assessing group differences in location. In small samples, randomization tests provide a basis for inferences. The execution of the procedure is facilitated by a computer program developed by the authors.

MULTPERM: a computer package for the analysis of multivariate data using permutation procedures.

MULTPERM is a user-friendly C program using an exact permutation test for comparing groups when the data involve one or more response variables. The program computes the average within group distance based on a generalized distance function. Statistical significance of group differences is assessed by comparing the average distance for the observed data to the distribution of distances generated by all permutations of subjects to groups. This procedure is nonparametric and is especially appropriate if the assumptions underlying more traditional methods are not satisfied. The program was developed for personal computers and compiled using Borland's Turbo C 2.0. It should be easily ported to other platforms. An approximate test based on the beta distribution is incorporated for large samples.

Quantitation of hypertensive nephrosclerosis on an objective rational scale of measure in adults and children.

The development of a precise, mathematical relationship between blood pressure and renal microvascular abnormalities would be highly desirable. Such a relationship would require that abnormalities be quantitative on a rational scale. The dominant abnormality in nephrosclerosis occurs in arcuate and cortical arteries of 50 to 400 micron outer diameter. This abnormality consists of acquired inner layers of fibroplastic tissue accompanied by variable fibrosis or withering of the preexisting vessel wall. It is this pathologic variable of interest, the amount of fibroplasia, that can be measured by its thickness in a direction perpendicular to the arterial axis. A method for quantitating the fibroplasia is described. Use of this method in a series of 93 autopsies suggests two tentative conclusions. The outer diameter of 141 micron marks the size of artery in which fibroplasia best correlates with blood pressure. The linear function, mean blood pressure = 1.60 X microvascular lesions +79.7, with correlation coefficient 0.698, governs a relationship similar at all ages. This relationship can be used to compute expected blood pressure from measurements of microvascular abnormalities in kidneys obtained at autopsy. Because all ages include ages 14 to 21 years, the observations imply that the initial tissue changes of hypertensive disease occur early in life.