Sadik A. Khuder

Streptococcus pneumoniae is a serious worldwide pathogen and the focus of numerous vaccine development projects. Currently the most widely accepted surrogate marker for evaluating the efficacy of a given vaccine is to utilize ELISA. Measurement of antibody concentration by ELISA without reduction in cross-reactive antibodies causes an overestimation of antibody concentration and therefore protection, this is most notable in the aged, an at risk group for this infection. We compared the immune response to the pneumococcal polysaccharides (PPS) 4 and 14 of 20 young to 20 elderly adults. Pre-and post-vaccination IgG antibody concentrations and antibody avidity against PPS4 and PPS14 were measured using two different enzyme-linked immunosorbant assay (ELISA) absorption protocols. All sera were pre-absorbed with either cell-wall polysaccharide (CPS), or CPS and serotype 22F polysaccharide. Pre- and post-vaccination IgG antibody concentrations for serotype 4, but not 14, were significantly lowered with the additional absorption with serotype 22F polysaccharide in both age groups. Young and elderly demonstrated a significant increase from pre- to post-immunization antibody concentration, using either absorption method; and opsonophagocytic antibody titers in response to both PPS4 and PPS14. The correlation coefficients between ELISA and opsonophagocytic assays were improved by additional absorption with serotype 22F in response to serotype 4, but not serotype 14 in all age groups. Opsonophagocytic antibody titers in a sub-group of elderly (>77 years of age) were significantly lower than the opsonophagocytic antibody concentrations in young adults. These results suggest the importance of eliminating cross-reactive antibodies from ELISA measurements by absorption of serum and an age-related impairment in the antibody response to pneumococcal polysaccharides.

Although 40–50% of non-small cell lung cancer (NSCLC) tumors respond to cisplatin chemotherapy, there currently is no way to prospectively identify potential responders. The purpose of this study was to determine whether transcript abundance (TA) levels of twelve selected DNA repair or multi-drug resistance genes (LIG1, ERCC2, ERCC3, DDIT3, ABCC1, ABCC4, ABCC5, ABCC10, GTF2H2, XPA, XPC and XRCC1) were associated with cisplatin chemoresistance and could therefore contribute to the development of a predictive marker. Standardized RT (StaRT)-PCR, was employed to assess these genes in a set of NSCLC cell lines with a previously published range of sensitivity to cisplatin. Data were obtained in the form of target gene molecules relative to 106 β-actin (ACTB) molecules. To cancel the effect of ACTB variation among the different cell lines individual gene expression values were incorporated into ratios of one gene to another. Each two-gene ratio was compared as a single variable to chemoresistance for each of eight NSCLC cell lines using multiple regression. In an effort to validate these results, six additional lines then were evaluated.

In this review we examine the association between rheumatoid arthritis (RA) and exposure to silica and other environmental toxicants. We performed a series of meta-analyses of peer-reviewed studies, using 10 studies for silica, and 5 studies for other exposures published between 1986 and 2001. Before the meta-analyses, all studies were reviewed and evaluated for heterogeneity and publication bias. We detected a significant heterogeneity among studies on silica and calculated a combined estimator of relative risk (RR), using the random effect model. Most studies reported consistent elevation in the risk of RA with exposure to silica. The combined RR for silica exposure was 3.43 195% confidence interval (95% CI) 2.25-5.22] for all studies, and 4.45 (95% CI 2.24-8.86) for male cohorts. The combined RR for male farmers was 1.40 [95% CI 1.18-1.66] and was 1.29 [95% CI 0.84-1.97] for pesticide exposure. The combined RR for hair dressers was 1.52 [95% CI 1.04-2.20]. The findings of this study suggest a significant elevation in the risk of RA from exposure to silica. Further studies assessing the dose-response effect would greatly aid in determining whether the observed association is causal.

Background: Although systemic sclerosis is a rare disease, incidence rates have increased recently in the United States. This study investigated the association between systemic sclerosis and exposure to solvents.Methods: A Medline search of articles published between 1966 and 2000 dealing with solvent exposure and systemic sclerosis identified eight studies that met inclusion criteria of the meta‐analysis. The studies included seven case‐control studies and one cohort study published between 1989 and 1998. A series of meta‐analyses of studies on systemic sclerosis and solvent exposure were performed for all studies and for case‐control studies. A random effect model was used to calculate a combined estimator of relative risk.Results: The combined estimator of relative risk for all studies was 2.91, with a 95% confidence interval (CI) of 1.60 to 5.30. The combined estimator of relative risk for the seven case‐control studies was 3.14 (95% CI, 1.56–6.33).Conclusions: A statistically significant increased relative risk for all studies and for case‐control studies suggests that exposure to organic solvent may be a risk factor for developing systemic sclerosis. Further studies using other study designs and better control of confounders are needed. Am. J. Ind. Med. 40:271–274, 2001.

Epidemiological studies have implicated smoking as a possible risk factor in the etiology of breast cancer, yet the evidence is not conclusive. We conducted meta-analyses of peer-reviewed studies published between 1984 and 2001 to assess the relation between smoking and breast cancer. The studies were located by searching the MEDLINE (1966 to 2001) and Cancer Abstracts (1980 to 2001) databases. Combined estimators of relative risk (RR) were calculated using fixed and random effect models. The combined RR for ever smokers was 1.10 (95% CI = 1.02-1.18). The association was stronger in premenopausal cases (RR = 1.21, CI = 1.08-1.36). The dose-response trend was significant but weak for the number of cigarettes smoked per day and for the duration of smoking. Early age at the start of smoking was associated with elevated risk (RR = 1.14, CI = 1.06-1.23). Our results suggest that smoking is a weak risk factor for breast cancer and the risk is higher in the premenopausal period and in those who started smoking at an early age.

Recent epidemiological studies have suggested passive smoking as possible risk factors in breast cancer etiology. However, the evidence is not conclusive. We conducted a meta-analysis of the risk of...

This study examined the association between Hodgkin's disease and farming. A series of meta-analyses of peer-reviewed studies was performed, using 30 studies published between 1981 and 1998. Prior to the meta-analyses, all the studies were reviewed and evaluated for heterogeneity and publication bias. Combined relative risks (RR) were calculated using the random effect model. The combined RR was 1.25 [95% confidence interval (95% CI) 1.11-1.42] for all the studies, and 1.08 (95% CI 0.91-1.29) for the studies involving female farmers. Significant heterogeneity among the studies was detected, and a stratified analysis was carried out by study design, country of study, and time of publication. Significantly elevated RR values were obtained for the case-referent studies (odds ratio 1.53, 95% CI 1.18-1.98) and proportionate mortality studies (PMR)(PMR 1.18, 95% CI 1.02-1.36). A decrease in risk was eminent in the more recent studies. The findings suggest that male farmers have a slightly elevated risk of developing Hodgkin's disease. No specific etiologic exposure was identified, but exposures commonly experienced by farmers (infectious microorganisms, herbicides and insecticides) may contribute to the occurrence of the disease.