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Biomedical subjects

S Shapiro

Publications and source records attributed to S Shapiro.

At least 145 records · Page 8Linked to original sources

Prevalence of antibodies to human papillomavirus (HPV) type 16 virus-like particles in relation to cervical HPV infection among college women.

A human papillomavirus type 16 (HPV-16) virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA) was used to measure serum antibody to capsid proteins in 376 sexually active college women who were also screened for the presence of genital HPVs by PCR and interviewed for demographic and behavioral risk factors for HPV infection. The seroprevalence was 46% in women with HPV-16 DNA in the genital tract. The corresponding values for women who harbored other HPV types or no HPV in the genital tract were 30 and 19%, respectively (HPV-16 group versus no-HPV group; odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5 to 8.9). The antibody response was significantly higher among women with a high viral load than among those with a low viral load (median optical density value, 0.838 versus 0.137, P = 0.009). Comparable levels of seroreactivity were observed among women infected with HPV types distantly or closely related genetically to HPV-16. Seroreactivity was significantly associated with an age of 25 to 30 years (OR, 2.3; 95% CI, 1.2 to 4.4), three or more lifetime sexual partners (OR, 2.9; 95% CI, 1.1 to 10), and history of a sexually transmitted disease other than HPV (OR, 3.1; 95% CI, 1.5 to 6.3). The percent seropositivity increased linearly with number of lifetime sexual partners until reaching a plateau at 35% for women with more than six partners (chi for linear trend, P < 0.001). The low sensitivity of HPV-16 VLP-based ELISA may limit the usefulness of the assay as a diagnostic test for HPV-16 infection. However, the assay appears to have adequate specificity and should be useful as an epidemiological marker of HPV-16 infection and sexual behavior.

Adolescent↗

Fear of fat, disregulated-restrained eating, and body-esteem: prevalence and gender differences among eight- to ten-year-old children.

Examined whether: (a) societal directives to be thin are perceived among children, (b) discontent with body and attitudes and behaviors associated with eating disorders begin before adolescence, and (c) these differ by sex. These issues were assessed in 239 Grade 3 students. Scales of eating and weight attitudes and behaviors for this under-studied population were either created or modified from existing instruments. These 8- to 10-year-old children expressed weight, dieting, and physique concerns that reflect Western sociocultural values and preoccupation with body weight and dieting. Sex differences were examined and revealed several but not very reliable distinctions at this young age. These findings appear to be consistent with research on adolescents. The components that may lead to the development of an eating disorder or disregulated-restrained eating in a vulnerable adolescent may be both internalized and expressed at a very early age.

Attitude to Health↗

gamma-Interferon-induced resistance to 1,25-(OH)2 D3 in human monocytes and macrophages: a mechanism for the hypercalcemia of various granulomatoses.

The hypercalcemia of various granulomatoses is caused by endogenous 1,25-dihydroxyvitamin D [1,25-(OH)2D3] overproduction by disease-activated macrophages. The inability of 1,25(OH)2D3 to suppress its synthesis in macrophages contrasts with the tight control of its production in macrophage precursors, peripheral blood monocytes (PBM). We examined whether 1,25(OH)2D3 resistance develops as PBM differentiate to macrophages or with macrophage activation. Normal human pulmonary alveolar macrophages (PAM) are less sensitive to 1,25(OH)2D3 than PBM, despite similar vitamin D receptor content; however, both PBM and PAM respond to exogenous 1,25-(OH)2D3 by inhibiting 1,25(OH)2D3 synthesis and inducing 1,25(OH)2D3 degradation through enhancement of 24-hydroxylase mRNA levels and activity. The human monocytic cell line THP-1 mimics PAM in 1,25(OH)2D3 synthesis and sensitivity to exogenous 1,25(OH)2D3. We utilized THP-1 cells to examine the response to 1,25(OH)2D3 with macrophage activation. Activation of THP-1 cells with gamma-interferon (gamma-IFN) enhances 1,25(OH)2D3 synthesis 30-fold, blocks 1,25-(OH)2D3 suppression of its synthesis, and reduces by 42.2% 1,25-(OH)2D3 induction of its degradation. The antagonistic effects of gamma-IFN are not merely restricted to enzymatic activities. In THP-1 cells and in normal PBM, gamma-IFN inhibits 1,25-(OH)2D3 induction of 24-hydroxylase mRNA levels without reducing mRNA stability, suggesting gamma-IFN inhibition of 1,25(OH)2D3 transactivating function. These results explain 1,25(OH)2D3 overproduction in granulomatoses and demonstrate potent inhibition by gamma-IFN of 1,25(OH)2D3 action in immune cells.

Cells, Cultured↗

Molecular changes in the offspring of liquidators who emigrated to Israel from the Chernobyl disaster area.

The primary goal of this research was to reveal de novo mutations in the liquidators (cleanup personnel) who emigrated to Israel from the Chernobyl disaster area. We used genome fingerprinting simple sequence repeat-anchored polymerase chain reaction (PCR) amplification and random amplified polymorphic DNA PCR (RAPD PCR). The methodology involved a combination of RAPD PCR, polyacrylamide gel electrophoresis, and silver staining, with arbitrarily primed PCR. Use of microsatellite markers appears to be the most promising technique for high sensitivity analysis. The analysis involved DNA isolated from the blood of experimental and control subjects (involving both offspring who were born before or after the disaster and their parents). Our studies have reproducibly detected new bands that appeared in the children born after the disaster. No such bands appeared in the children born in the same family before the accident or in the children of control families who had not been exposed to radiation.

Adult↗

Adolescent childbearing revisited: the age of inner-city mothers at delivery is a determinant of their children's self-sufficiency at age 27 to 33.

OBJECTIVES: Data from recent interviews with 1758 inner-city children, born between 1960 to 1965 and followed with their mothers in the Pathways to Adulthood Study to age 27 to 33 years, were used to address two related questions. 1) Is maternal age, across the reproductive age range, a determinant of child's adult outcome? and 2) Do covariates of maternal age at delivery reduce or eliminate the effect of maternal age on child's adult outcome? METHODS: An intergenerational life course model of development identified significant maternal and child characteristics at birth associated with the child's self-sufficient outcomes in adulthood: education (more than or equal to a high school diploma); financial independence of public support; and delay of first birth until age 20 or older. Bivariate and multiple logistic regression techniques were used to identify independent relationships between dependent and independent variables and to adjust the outcomes to compensate for the effect of possible confounding of maternal age at delivery by maternal education, parity, poverty status, and the child's race and gender. RESULTS: Each covariate was independently associated with maternal age at delivery. Adjustment for their effects reduced, but did not eliminate, the association between maternal age at birth and the child's outcome at age 27 to 33 years. As a group, children of the oldest mothers (>/=25 years of age) had the most favorable outcomes, and those of teenage mothers (<20 years of age) had the least favorable outcomes; 22% of daughters and 6% of sons of the oldest mothers versus 38% and 18%, respectively, of the youngest mothers became teenage parents. CONCLUSION: The mother's age at delivery is an independent determinant of the child's adult status.

Adolescent↗

Self-sufficiency at ages 27 to 33 years: factors present between birth and 18 years that predict educational attainment among children born to inner-city families.

OBJECTIVES: Some inner-city infants grow to be successful, self-sufficient adults. This study is designed to identify characteristics from early childhood that foster or impede favorable outcomes and are useful for formulation of public policy. METHODS POPULATION: 2694 children (G-2s), born 1960 through 1965, to 2307 inner-city women (G-1s) enrolled in the Johns Hopkins Collaborative Perinatal Study. DATA: 1) prospective observations (birth through 8 years) of neurologic and cognitive development, health, behavior, and family and neighborhood socioeconomic characteristics and 2) completed interviews with 1758 G-2s (age 27 to 33) and 1552 G-1s, bridging the period from age 9 to present status. An intergenerational, life course model of development identified significant characteristics and events associated with G-2 outcome (education, physical and mental health, healthy lifestyle, and financial independence of public support, emphasizing educational attainment of a high school diploma or a graduate equivalency degree). Multiple logistic regression equations identified independent, predictive variables during infancy, preschool and early school years, and adolescence. The probability of a good outcome was estimated in the presence of combinations of the six variables most strongly associated with that outcome. RESULTS: Among G-2s, 79% had a successful outcome for education, 60% health, 70% lifestyle, and 76% for financial independence. Black G-2s had more favorable outcomes than white G-2s in education and lifestyle, whites for financial outcome; health did not differ by race. The six variables most predictive of adult education were: G-1 education at G-2 birth and G-2 attainment of honor roll, average or better reading skills at 8 years, avoidance of regular smoking, and pregnancy before age 18, and not repeating a grade in school. CONCLUSIONS: Substantial proportions of inner-city children become successful adults. Attention to improving public education, particularly language and reading skills, and the prevention of smoking and adolescent pregnancy are clearly indicated.

Activities of Daily Living↗

A case control study of breast cancer risk and exposure to injectable progestogen contraceptives. Methods and patterns of use among controls.

OBJECTIVE: To describe the patterns of use of injectable progestogen contraceptives (IPCs) among coloured and black women in the Western Cape. These data are part of an ongoing study in the Western Cape, the main aim of which is to explore the relationship between IPCs and breast cancer. DESIGN: A population-based case-control study of breast cancer risk in relation to the use of IPCs among coloured and black women. SETTING: The Western Cape, including the Cape metropole and surrounding rural areas. STUDY SUBJECTS: All coloured and black women with newly diagnosed breast cancer, resident in the study area and below age 55 years, who present at either of the two tertiary care hospitals in the Western Cape are recruited. Controls are a sample of hospitalised patients representative of the populations from which the patients are drawn. Cases are frequency-matched to controls according to cross-tabulation of age, ethnic group and residential area in a ratio of approximately 1:3. MEASUREMENTS: Questionnaires are administered by trained nurse interviewers, information is elicited on a wide range of variables, including sociodemographic variables, medical history, family history of breast disease, lifetime history of all methods of contraception and use of non-contraceptive female steroids, reproductive variables, cigarette smoking, alcohol consumption and other potentially confounding variables. RESULTS: Between January and December 1994, 122 incident cases and 389 controls were enrolled. Ever-use of IPCs among the controls was 72% (N = 280) and use for 5 years or more was 30% (N = 117). Use of IPCs in the distant past was common, with 61% (N = 232) of all controls having initiated use 10 or more years previously. Current use was also high (19%). Other contraceptive methods were used far less commonly. CONCLUSION: Coloured and black women in South Africa have been using and continue to use IPCs for more commonly and for longer periods than women anywhere else in the world. It is therefore especially important to evaluate the risk of breast cancer and other health effects of IPCs. The rates of use identified in this study ensure that there will be adequate statistical power to evaluate long-term use, use in the distant past and current use of IPCs.

Adult↗

Severe vulvar vestibulitis. Relation to HPV infection.

OBJECTIVE: To determine whether patients with human papillomavirus (HPV)-associated vestibulitis present differently from patients with HPV-negative disease and whether the presence of HPV is a predictor of the outcome of surgical treatment by perineoplasty. STUDY DESIGN: Thirty-eight women with severe vulvar vestibulitis who underwent surgical perineoplasty were found to have HPV DNA in the vestibule by polymerase chain reaction. Thirty-six other women with severe vestibulitis had no HPV DNA in the surgical specimen. The two groups were compared with regard to demographic, social and medical variables as well as physical findings in the vestibule and response to operative treatment. RESULTS: Both groups were found to be similar in respect to age (mean 25.9 +/- 7.93 versus 25.47 +/- 5.8, respectively), parity, education, smoking habits, contraceptive use, presence of primary vestibulitis, presence of dysuria and involvement of the whole vestibule (both anterior and posterior). More unmarried than married women were infected with HPV (P < .002). There was no significant correlation between the presence of HPV and the outcome of surgical treatment (P < .6, relative risk = 0.9, 95% confidence interval = 0.5-1.5). CONCLUSION: Although HPV DNA was found in more than half of women with vestibulitis, it appears to play no role in the presentation or response to surgical therapy for vulvar vestibulitis.

Adolescent↗

Alcohol-containing mouthwashes and oropharyngeal cancer: a spurious association due to underascertainment of confounders?

Recently it has been suggested that the use of alcohol-containing mouthwashes may increase the risk of oropharyngeal cancer. Heavy alcohol intake and tobacco use are established causes of oropharyngeal cancer. Their use is associated with mouthwash use. In addition, alcohol and tobacco use both tend to be underreported. Here the authors show that, under the hypothesis that mouthwash does not increase the risk of oropharyngeal cancer, confounding due to underascertained exposure to alcohol and tobacco would result in a spuriously elevated odds ratio for mouthwash use. As a general principle, a null association becomes apparently positive if a confounding variable is incompletely ascertained: a spurious association may be produced even in the absence of a difference in the extent of the underascertainment of the confounder among the comparison groups.

Confounding Factors, Epidemiologic↗

Family history and prostate cancer risk.

The authors examined the relation between family history of prostate cancer and the risk of this cancer in a population-based case-control study conducted in Massachusetts between December 1992 and October 1994. Cases were all incident cases of prostate cancer in men younger than 70 years (n = 563); controls were men with no history of the disease matched to the cases on age and town of residence (n = 703). Prostate cancer risk was increased among men who reported a history of this cancer in either their fathers or brothers (odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.7-3.3). Risk varied with the number of relatives affected and their relationship to the case. For a history of prostate cancer in one relative, the OR was 2.2 (95% CI 1.5-3.2); if two or more relatives were affected, it was 3.9 (95% CI 1.7-5.2). For prostate cancer in the father, the OR was 1.9 (95% CI 1.2-3.0); for prostate cancer in a brother, it was 3.0 (95% CI 1.8-4.9). Risk was inversely related to the subject's age and to age at diagnosis of prostate cancer in his affected relative. Among probands younger than 60 years, the OR was 5.3 (95% CI 2.5-12); for those 60-64 years of age, the OR was 2.7 (95% CI 1.3-5.5); and for those 65 years of age and older, the OR was 1.6 (95% CI 1.0-2.5). For prostate cancer diagnosed in a relative before age 65, the OR was 4.1 (95% CI 2.3-7.3); for detection of the disease after age 74, the OR was 0.76 (95% CI 0.38-1.5). The association was present both among men with local and advanced stage disease and among men whose prostate cancer was detected either by screening or because of symptoms. These data provide evidence that after controlling for diet and other potential confounders, familial factors are significantly associated with the risk of prostate cancer.

Aged↗

Risk of aspirin-associated major upper-gastrointestinal bleeding with enteric-coated or buffered product.

BACKGROUND: Aspirin products are known to cause irritation and injury to the gastric mucosa. The belief that enteric-coated and buffered varieties are less likely to occasion major upper-gastrointestinal bleeding (UGIB) than plain aspirin was tested in data from a multicentre case-control study. METHODS: 550 incident cases of UGIB admitted to hospital with melaena or haematemesis and confirmed by endoscopy, and 1202 controls identified from population census lists, were interviewed about use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) during the 7 days before the onset of bleeding (cases) or interview (controls). Relative risks of UGIB for each type of aspirin used regularly (at least every other day) were calculated overall, and according to dose, by multiple logistic regression, with control for age, sex, marital status, date, education, cigarette smoking, alcohol use, and use of NSAIDs. FINDINGS: The relative risks of UGIB for plain, enteric-coated, and buffered aspirin at average daily doses of 325 mg or less were 2.6, 2.7, and 3.1, respectively. At doses greater than 325 mg, the relative risk was 5.8 for plain and 7.0 for buffered aspirin; there were insufficient data to evaluate enteric-coated aspirin at this dose level. There were no important differences in risk attributable to the three aspirin forms according to bleeding site (gastric vs duodenal), or when users of NSAIDs were excluded. INTERPRETATION: Use of low doses of enteric-coated or buffered aspirin carries a three-fold increase in the risk of major UGIB. The assumption that these formulations are less harmful than plain aspirin may be mistaken.

Adolescent↗

Adult height and risk of breast cancer among white women in a case-control study.

Data from a hospital-based case-control study were analyzed to evaluate the relation of adult height to the risk of breast cancer among white women. The authors compared 5,358 newly diagnosed breast cancer cases and 4,555 controls interviewed from 1976 to 1992 in hospitals located mainly in the United States. Overall, there was no association between stature and risk of breast cancer. In comparison with women whose heights were less than 62 inches (< 158 cm), the adjusted odds ratios were 1.1 (95% confidence interval (Cl) 0.9-1.2), 1.0 (95% Cl 0.9-1.2), 1.0 (95% Cl 0.9-1.1), and 1.0 (95% Cl 0.8-1.2) for women with heights of 62-63, 64-65, 66-67, and > or = 68 inches (equivalent to 158-160, 163-165, 168-170, and > or =173 cm), respectively. There was no consistent evidence of modification of the effect of height by other risk factors. The results suggest that adult stature in white women is not related to the risk of breast cancer.

Adult↗

Prepregnant weight in relation to risk of neural tube defects.

OBJECTIVE: To examine the relation between prepregnant weight and the risk of neural tube defects (NTDs). DESIGN: Data were collected from 1988 to 1994 in a case-control surveillance program of birth defects. SETTING: Study subjects were ascertained at tertiary care centers and birth hospitals in the greater metropolitan areas of Boston, Mass, and Philadelphia, Pa, and in southeastern Ontario. PARTICIPANTS: Cases were 604 fetuses or infants with an NTD identified within 6 months of delivery. Controls were 1658 fetuses or infants with other major malformations identified within 6 months of delivery. For 1992 to 1994, there were 93 control infants without major malformations. MAIN OUTCOME MEASURE: Relative risk of NTDs in infants or fetuses for different maternal weights. RESULTS: Relative to women who weighed 50 to 59 kg, risk of NTDs increased from 1.9 (95% confidence interval [CI], 1.2 to 2.9) for women weighing 80 to 89 kg to 4.0 (95% CI, 1.6 to 9.9) for women weighing 110 kg or more. When women were classified according to daily intake above or below the recommended level of 400 micrograms of folate, approximate threefold increases in risk were estimated for the heaviest weights in both groups. Intakes of 400 micrograms of folate or more reduced risk of NTDs by 40% among women weighing less than 70 kg, but no risk reduction was observed among heavier women. CONCLUSION: The risk of NTDs increased with increasing prepregnant weight, independent of the effects of folate intake.

Adult↗

Case-control study of oral contraceptive use and risk of breast cancer.

The relation of oral contraceptive use to the risk of breast cancer in white women aged 25-59 years was assessed with data collected during 1977-1992 in a case-control surveillance system in hospitals in Boston, New York, and Philadelphia. A total of 3,540 cases with breast cancer were compared with 4,488 controls with nonmalignant nongynecologic conditions unrelated to oral contraceptive use. Relative risk estimates were obtained by unconditional logistic regression with control for major risk factors. For at least 1 year of use relative to less than 1 year, the multivariate relative risk estimate was 1.7 (95% confidence interval (CI) 1.3-2.3) in women aged 25-34 years, 0.9 (95% CI 0.7-1.0) in women aged 35-44 years, and 1.2 (95% CI 1.0-1.4) in women aged 45-59 years (p < 0.01 for the difference across age). Among women aged 25-34 years, the relative risk estimates were greatest for use of long duration, but the trend was not statistically significant (p = 0.17); in addition, the duration of use was correlated with the recency of use, and it was not possible to distinguish their effects. Among women aged 35-44 years, the relative risk estimate decreased with increasing duration of use (p = 0.01). Among women aged 45-59 years, some relative risk estimates were increased, but there was no consistent pattern. The results add to the evidence of an association between oral contraceptive use and an increased risk of breast cancer at young ages.

Adult↗

The fiberoptic intraparenchymal cerebral pressure monitor in 244 patients.

BACKGROUND: The fiberoptic intraparenchymal pressure monitor has been shown to provide reliable data in patients monitored for a short period of time. An analysis of a large population, including patients monitored for a prolonged period such as weeks, has never been performed. METHODS: We conducted a retrospective study in which we evaluated the fiberoptic intraparenchymal cerebral pressure monitor for complications and accuracy. RESULTS: The fiberoptic intraparenchymal cerebral pressure (ICP) monitor was used in 244 patients since 1988. Pathology included trauma in 180, intracerebral hemorrhage (ICH) in 19, aneurysmal subarachnoid hemorrhage in 16, arteriovenous malformations in 10, cerebral edema in 12, and tumor in 7. The mean length of monitoring was 7 days with 49 patients (20%) monitored 1-2 days, 105 (43%) monitored 3-6 days, 48 monitored for 7-10 days (20%), and 42 (17%) monitored from 10-24 days. Seventy-four patients also had ventriculostomies and there was strong correlation with the ICP monitor (p < 0.001). Complications from insertion were 2 patients (0.8%) with ICH, both with hepatic dysfunction. In the group monitored greater than 6 days, 34 patients (38%) required at least one catheter change due to upward drift of the ICP. Fiberoptic breakage requiring replacement was documented in 41 patients (16%). An insertion-site infection occurred in one case monitored for 23 days. Two infected bone flaps occurred that had a monitor placed in the flap. There were no cases of bacterial meningitis or cerebral abscess. CONCLUSIONS: The monitor is easy, safe, and reliable to use with a very low rate of infection. Coagulopathic patients may best be monitored by an alternative method.

Brain Edema↗

Immunoregulatory effects of interferon-beta and interacting cytokines on human vascular endothelial cells. Implications for multiple sclerosis autoimmune diseases.

The mechanism(s) of action responsible for the anti-inflammatory effects mediated by interferon (IFN)-beta are still elusive although suggestions include anti-viral effects, the enhancement of natural killer (NK) or suppressor T cell activity and opposition to the effects of inflammatory cytokines. As vascular endothelial cells are active participants in inflammatory and demyelinating processes, we decided to examine the effects of IFN-beta on the expression of major histocompatibility complex (MHC) gene products and intercellular adhesion molecule (ICAM)-1 on human vascular endothelial cells (ECs). Human umbilical ECs demonstrated constitutive expression of ICAM-1 and MHC class I molecules but did not express MHC class II molecules. Basal expression of ICAM-1 molecules was enhanced by TNF alpha and to a lesser extent by IFN-beta, but was not affected by IFN-gamma. MHC class I expression on ECs was enhanced by IFN-beta, IFN-gamma, and tumor necrosis factor (TNF)-alpha. Furthermore, a synergistic effect was observed to combinations of these interacting cytokines. Incubation of ECs with IFN-gamma, but not IFN-beta, induced class II expression in a dose dependent manner. Moreover, co-incubation of ECs with IFN-beta and IFN-gamma resulted in significant down-regulation of class II molecules expression which was directly dependent on IFN-beta concentration. Northern blot analysis of DR alpha and Beta 2-microglobulin mRNA expression suggested that cytokine-mediated regulation of MHC molecules is at the transcriptional level, while modulation of ICAM-1 expression appears to be at the transcriptional as well as post-transcriptional level. Thus, our study demonstrated that IFN-beta and interacting cytokines exert complex immunoregulatory effects on endothelial cells with differential modulatory effects on various cell surface markers. Understanding the biological significance of these immunomodulatory effects mediated by IFN-beta may have important implications for cytokine-based strategies in the treatment of inflammatory and autoimmune diseases.

Autoimmune Diseases↗