Genital prolapse with and without urinary incontinence

Procidentia, vaginal vault prolapse and severe cystocele may be associated with potential urinary incontinence, which becomes overt only after surgical repair of the genital prolapse. The normal support of the pelvic organs is provided by the pelvic diaphragm (levator ani and coccygeus muscles). The levator plate is a firm, muscular plate between the coccyx and anus formed by fusion of the levator ani muscles on each side. Recent investigators have indicated that the main mechanism for weakening the pelvic muscles occurs as a result of childbearing, when stretch injury of the pudendal nerve causes denervation of the muscles. This injury is aggravated with the changes of aging and has effects on anogenital prolapse and stress incontinence. There may be iatrogenic causes of both prolapse and stress incontinence when an operation produces a change in the direction of tissue forces or removes a prior barrier to incontinence. The evaluation of patients must include the actual and potential aspects of genital prolapse and incontinence. Testing for stress incontinence must be performed before and after reduction of the genital prolapse. Surgical repair should be planned carefully to correct all the significant and potential defects in the urogenital tract. Ideally a normal vaginal axis with adequate length will be restored, and urinary function will not be compromised.     

Cancer mortality study of employees at lead battery plants and lead smelters, 1947-1995

BACKGROUND: This study has examined cancer mortality of a cohort of male U.S. workers exposed to lead. METHODS: The cohort consisted of 4,518 workers at lead battery plants and 2,300 at lead smelters. Vital status was ascertained between 1947 and 1995. Site-specific cancer standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs), based on the mortality rates of the U.S. male population and adjusted for age and calendar time, were calculated for the total cohort as well as subcohorts stratified by various exposure parameters. In addition, a nested case-control study of stomach cancer (30 cases and 120 age-matched controls) was also conducted. RESULTS: Mortality from all cancers was as expected (897 observed deaths, SMR = 103.8, 95% CI: 97.1-110.8). Mortality was significantly raised for stomach cancer (SMR = 147.4, 95% CI: 112. 5-189.8), lung cancer (SMR = 116.4, 95% CI: 103.9-129.9), and cancer of the thyroid and other endocrine glands (SMR = 308.0, 95% CI: 133. 0-606.8). There was a nonsignificant mortality deficit from kidney cancer (SMR = 63.6, 95% CI: 33.9-108.7). For bladder cancer, mortality was significantly lower than expected (SMR = 55.5, 95% CI: 31.7-90.1). Nonsignificant mortality deficits were also reported for cancer of the central nervous system (SMR = 74.8, 95% CI: 41.9-123. 4) and lymphatic and hematopoietic cancer (SMR = 92.2, 95% CI: 72. 4-115.7). Additional analyses by type of facility (lead battery plants vs. lead smelters), length of employment, latency, and period of hire were also performed. In the nested case-control study of stomach cancer, odds ratios were calculated for various exposure indices, and none was found to be elevated. Furthermore, no exposure-response relationship between lead exposure and stomach cancer was found in the nested case-control study. CONCLUSIONS: A significant mortality increase from stomach cancer was found. However, based on the analyses in the cohort study and the nested case-control study, the increase did not appear to be related to lead exposure. A small, but statistically significant mortality increase from lung cancer was also observed. The small increase, in the absence of an exposure-response relationship, could be the result of confounding due to smoking, and was not likely causally related to lead exposure. Although the significant increase in cancer of the thyroid and other endocrine glands appeared to be consistent with an occupational interpretation, the small number of deaths (8), the lack of information on potential confounding factors, and the lack of reporting of a similar increase in other studies underscore the need to view this finding with caution. No increased mortality was found for kidney cancer, bladder cancer, cancer of the central nervous system, or lymphatic and hematopoietic cancer.     

Cord serum cotinine as a biomarker of fetal exposure to cigarette smoke at the end of pregnancy

This study investigated the association between biomarkers of fetal exposure to cigarette smoke at the end of pregnancy, cotinine in cord serum and in maternal and newborn urine samples, and quantitative measurement of smoking intake and exposure evaluated by maternal self-reported questionnaire. Study subjects were 429 mothers and their newborns from a hospital in Barcelona, Spain. A questionnaire including smoking habits was completed in the third trimester of pregnancy and on the day of delivery. Cotinine concentration in cord serum was associated with daily exposure to nicotine in nonsmokers and with daily nicotine intake in smokers. The geometric mean of cotinine concentration in cord serum statistically discriminated between newborns from nonexposed and exposed nonsmoking mothers, and between these two classes and smokers, and furthermore was able to differentiate levels of exposure to tobacco smoke and levels of intake stratified in tertiles. Urinary cotinine levels in newborns from nonsmoking mothers exposed to more than 4 mg nicotine daily were statistically different from levels in two other categories of exposure. Cotinine concentration in urine from newborns and from mothers did not differentiate between exposure and nonexposure to environmental tobacco smoke (ETS) in nonsmoking mothers. Cord serum cotinine appeared to be the most adequate biomarker of fetal exposure to smoking at the end of pregnancy, distinguishing not only active smoking from passive smoking, but also exposure to ETS from nonexposure.     

Determination of the allelic frequencies of an L-myc and a p53 polymorphism in human lung cancer

The L-myc and p53 genes have been implicated in lung cancer.Both of these genes have restriction fragment length polymorphisms(RFLPs) that could account for differential expression or activityof variant forms. An EcoRI restriction site in the L-myc genewas previously reported to be a predictor of poor prognosisin Japanese lung cancer patients. There are several RFLPs inthe p53 gene. In exon 4 there is a polymorphism that codes foreither an arginine or proline residue at codon 72. We previouslyreported the frequency of DNA-RFLPs at these gene loci revealedby EcoRI and AccII respectively. Here we report results froma study comparing lung cancer cases (n = 31) with chronic obstructivepulmonary disease controls (n = 49). No association was foundbetween these RFLPs and disease status. Previous observationsthat the frequencies of these RFLPs varied by race were confirmed.The p53 arginine allele was found to be more common in Caucasians(0.71) than African Americans (0.50). The EcoRI restrictionsite present allele in L-myc was more frequent in African-Americans(0.71) than Caucasians (0.49). Thus, the allelic frequency forL-myc was similar in African Americans to that reported forJapanese, and the allelic frequency for p53 was similar in Caucasiansto that reported for Japanese.     

Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma,lung and breast carcinoma cell lines

Thrombospondin (TSP) is a member of a family of extracellular matrix glycoproteins that may participate in multiple aspects of the metastatic cascade. We report an inverse correlation of steady-state Thbs-1 mRNA and protein expression with malignant progression among murine melanoma and human lung and breast carcinoma cell lines. Murine K-1735 melanoma cell lines of low metastatic potential, including K-1735 lines transfected with the murine nm23-1 cDNA, expressed higher TSP levels than related highly metastatic lines. In a model system of lung carcinoma malignant progression, immortalized human bronchial epithelial cells expressed higher TSP levels than v-Ki-ras, v-Ha-ras or n-ras transfectants, which in turn expressed higher TSP levels than tumor-derived, more aggressive variants. Among 3 unrelated breast carcinoma cell lines, Thbs-1 steady-state mRNA levels were greater in the 2 nonmetastatic lines than the metastatic line. Our data show that malignant progression in some cell lines is associated with reduced TSP expression. The suppressive effects of nm23-1 transfection on metastatic potential are also associated with increased TSP expression; ras transfection, which results in increased tumorigenesis, is associated with decreased TSP expression.     

Comparison of immune-mediated models of acute and chronic otitis media

Summary The distribution of immunoglobulin-bearing cells and the pattern of histopathological changes in the middle ear (ME) mucosa, round window membrane (RWM), and inner ear were compared during acute and chronic immune-mediated otitis media with effusion (OME) in the guinea pig as an animal model. In both acute and chronic immune responses (IRs), mucosal hyperplasia, edema, neovascularization, and cellular infiltration were observed. IgG+ cells were predominant in both the acute and chronic IRs. The number of IgA+ cells, however, increased in the mucosa and RWM during chronic IRs. Only the chronic IR resulted in gland formation within the ME and inflammation within the cochlea. These results indicate that the chronic IR was more similar to reports of clinical OME than the acute IR, The cochlear inflammation associated with chronic OME can lead to sensorineural hearing loss, as reported in clinical studies.