No abstract

This study was undertaken to determine whether defects in leukocyte function or in genes at the MHC play a role in the etiology of either localized (LJP) or generalized (GJP) juvenile periodontitis. Thirteen LJP and five GJP patients (ranging in age from 13 to 22 years) and their matched controls were compared with respect to selected leukocyte functions and HLA phenotypic frequencies. The results of these studies indicated that there were significant decreases in the phagocytic and chemotactic abilities of polymorphonuclear leukocytes (PMN) in both LJP and GJP. All JP patients displayed intrinsic cell defects in chemotaxis compared with controls; in addition, some patients displayed multiple defects, including those which were serum-associated. Also, there appeared to be a significant association between JP and HLA-DR2 and HLA-A33 phenotypes. Fifty percent of the JP patients were HLA-DR2-positive, whereas only six percent of the matched controls were positive. Thirty-six percent of JP patients were HLA-A33-positive, whereas none of the controls was positive. The association seen with DR2 may be due to sampling, since there were no significant differences between the JP cases and a larger unmatched control sample which was not evaluated for periodontal disease. We conclude from these data that increased susceptibility of some patients to a very aggressive and destructive form of periodontal disease (JP) is based on defects in PMN responsiveness. Further investigations are necessary to determine whether these defects are under genetic control.

The in vitro activity of nonoxynol-9 against four serotypes (C, D, H, and K) of Chlamydwa trachomatis was investigated. A constant inoculum of each serotype was exposed to serial twofold dilutions (1:100 to 1:800) of Koromex, Conceptrol, or reference preparations (not containing nonoxynol-9) for 4 and 24 h at 37°C. The mixtures of nonoxynal-9 or nonnonoxynol preparations and control inocula were dispensed into triplicate wells containing McCoy cell monolayers. After incubation at 37C, the monolayers were fixed and stained with idoine and examined for evidence of infection with C. trachomatis. All nonoxynol-9-containing preparations showed marked antichlamydial activity as judged by percent reduction of glycogen-containing intracytoplasmic inclusions. The reference preparations, which did not contain nonoxynol-9, were markedly less active when tested in this in vitro system. Nonoxynol-9 (N-9), a membrane-active detergent, is the active ingredient in numerous commercially available intravaginal contraceptive foams, inserts, and jellies. Previous studies have shown that this compound is active in vitro against many pathogens causing sexually transmitted diseases. However, the activity of N-9 against Chlamydia trachomatis has not been well studied. In this study, we investigated the in vitro activity of N-9 against C. trachomatis by using two commercially available spermicides, both containing N-9, and reference preparations not containing N-9.MATERIALS AND METHODS Microorganisms. Four strains of C. trachomatis, serotypes C, D, H, and K, were tested. All strains were provided by E. R. Alexander, Atlanta, Ga., and were selected because they are representative of the strains commonly associated with urethritis in men and cervicitis in women.Contraceptives. The contraceptive products used in this study were the commercial preparations Conceptrol (Ortho Pharmaceutical Laboratories, Raritan, N.J.), containing 4% N-9, and Koromex (Youngs Drug Products, Piscataway, N.J.), containing 2% N-9. Although each contained N-9 as the spermicidal agent, the contraceptives differed slightly with regard to other constituents. Reference formulations of each product were provided by the manufacturers and were identical to the commercial formulations except for the absence of N-9. (1:10 to 1:2,560) were prepared in cell culture media. These dilutions were then dispensed into 96-well microtiter plates that contained McCoy cell monolayers and were incubated for 48 h at 37°C. Cellular toxicity was assessed by two methods: (i) visual determination of the condition of the monolayer under x100 magnification and (ii) the ability of the cells to exclude trypan blue.The antichlamydial activity of N-9 was assayed by the inoculation of serial twofold dilutions (1:100 to 1:800) of spermicide (N-9) or reference (non-N-9) preparations, mixed with a constant inoculum of each of four strains of C. trachomatis, into McCoy cell monolayers. Each of these mixtures and controls of cell culture media and inocula of the four strains had been incubated at 37°C ...

According to the Food and Drug Administration's Guidelines for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, approval of a new drug "should be supported by more than one well-controlled trial and carried out by independent investigators. This interpretation is consistent with the general scientific demand for replicability." Nevius has described a four-point proposal for assessing statistical evidence in a single multicenter trial. Briefly, these four points are: (1) combined analysis shows significant results, (2) consistency over centers in terms of direction, (3) consistency over centers in terms of producing nominally significant results in centers with sufficient power, and (4) evidence of efficacy after adjustment for multiple comparisons. What is not clear from Nevius' proposal is how to quantify whether the amount of evidence in a single multicenter trial is equivalent to that from two separate trials. It is proposed that the post hoc subdivision of a multicenter trial may address this issue if the inherent multiple testing problem is accommodated. A minimax statistic is developed to test the hypothesis that the effect of the drug has been reproduced in a single multicenter trial. Monte Carlo simulation is used to generate the distribution of the minimax statistic under the null and several alternative hypotheses. Data from a multicenter trial are used to demonstrate the technique. Bootstrapping is used to determine the null distribution of the minimax statistic.

Six methods of combining k independent binomial test statistics are compared with respect to their median significance levels, asymptotic relative efficiencies, and accuracy of null distribution approximations. The test statistics considered are the minimum significance level, Fisher's omnibus test, the likelihood ratio, an approximate likelihood ratio, the Mantel-Haenszel statistic, and the sum of chis. Fisher's test and the likelihood ratio perform relatively well for all alternative hypotheses. The Mantel-Haenszel procedure performs well when departures from the null hypotheses are similar for all tests. The minimum is sensitive to the situation in which most of the parameters assume the null value. The sum-of-chis procedure tends to assign too much weight to individual binomial statistics with large standard errors, whereas the approximate likelihood ratio assigns too much weight to statistics with small standard errors.