Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol

BACKGROUND: Between 1939 and the 1960s, the synthetic estrogen diethylstilbestrol (DES) was given to millions of pregnant women to prevent pregnancy complications and losses. The adverse effects of prenatal exposure on the genitourinary tract in men and the reproductive tract in women are well established, but the possible effects on psychosexual characteristics remain largely unknown. METHODS: We evaluated DES exposure in relation to psychosexual outcomes in a cohort of 2,684 men and 5,686 women with documented exposure status. RESULTS: In men, DES was unrelated to the likelihood of ever having been married, age at first intercourse, number of sexual partners, and having had a same-sex sexual partner in adulthood. DES-exposed women, compared with the unexposed, were slightly more likely to have ever married (odds ratio [OR] = 1.1; confidence interval [CI] = 1.0-1.4) and less likely to report having had a same-sex sexual partner (OR = 0.7; CI = 0.5-1.0). The DES-exposed women were less likely to have had first sexual intercourse before age 17 (OR = 0.7; CI = 0.6-0.9) or to have had more than one sexual partner (OR = 0.8; CI = 0.7-0.9). There was an excess of left-handedness in DES-exposed men (OR = 1.4; CI = 1.1-1.7) but not in DES-exposed women. DES exposure was unrelated to self-reported history of mental illness in women. CONCLUSIONS: Overall, our findings provide little support for the hypothesis that prenatal exposure to DES influences the psychosexual characteristics of adult men and women.     

Health-related needs of the displaced population due to armed conflict in Bogotá

BACKGROUND: The displacement of populations as the result of an armed conflict generally entails a worsening of the living and health conditions of those undergoing such a displacement. This paper is aimed at analyzing the health-related needs perceived by men and women displaced by the armed conflict and their main strategies to address those needs. METHODS: A qualitative study was carried out by means of semi-structured individual interviews to 31 displaced men and women in the transition stage. A narrative analysis of the contents was conducted, segmenting the information by age and sex. The area under study was made up of five localities in the city of Bogotá. RESULTS: The negative effects on their mental health and psychosocial stability, access to food and, to a lesser degree, gastrointestinal and respiratory disorders, are the main health problems reported by both groups of informants. The difficulty of accessing health care services comes up as an added problem. The precarious economic situation underlies the health care-related needs and problems. To solve their health problems, in addition to the health care services, they employ other strategies within their reach. Expressed needs are coherent with the problems perceived. Some differences between women and men and age groups were observed concerning the definition of the problems and employed strategies. CONCLUSION: In the health field, actions are required in order to improve their access to services in addition to specific strategies for the psychosocial rehabilitation of the displaced population which take into account the differences existing within this group.     

Susceptibility and exposure biomarkers in people exposed to PAHs from diesel exhaust

Xenobiotic metabolizing enzymes, especially CYP1A1 and GSTM1, are involved in the activation and conjugation of PAHs and are controlled by polymorphic genes. PAHs released from diesel emissions in many cities of the world, especially in developing countries, contribute significantly to the toxic effects of airborne inhalable particles. We have evaluated the gene-environment interaction in Santiago of Chile, studying the contribution of CYP1A1 and GSTM1 polymorphisms on 1-OH-P urinary levels used as the PAHs exposure biomarker. The study was performed on 59 diesel exposed (38 diesel revision workers and 21 subjects working in an urban area as established street vendors) and 44 non-exposed subjects living in a rural area. The 1-OH-P urinary levels of the urban (P=0.043) and rural (P=0.040) populations showed, without considering the genotypes, significant differences between smokers and non-smokers, but no significant differences were found between smokers and non-smokers among the diesel plant workers (P=0.33). Non-smoking subjects of the diesel plants and the urban area showed similar 1-OHP levels (P=0.466) which were significantly higher than those of the subjects living in the rural area (P<0.05). When 1-OH-P levels were related with genotypes, an association was observed for the CYP1A1*2A genotype, so that the diesel-exposed workers carrying the CYP1A1*2A allele showed significantly higher 1-OH-P levels than the subjects from the rural area with the same genotype (P=0.008). On the other hand, there was no significant correlation between urinary 1-OH-P levels and GSTM1 null genotype, although higher levels of the urinary metabolite were found in individuals carrying the combined CYP1A1*2A and GSTM1 null genotype (P=0.055). These results may suggest an association between levels of the exposure biomarker 1-OH-P and presence of the CYP1A1*2A genotype, a potential genetic susceptibility biomarker which might be useful in identifying individuals at higher risk among people exposed to high PAH levels in diesel exhaust.     

Perception of breast cancer risk and surveillance behaviours of women with family history of breast cancer: a brief report on a Spanish cohort

Women with a family history of breast cancer (FHBC) are at increased risk for developing this disease. In this study, we have investigated the differences between two groups of women; those with family history of breast cancer (N=42) and women at population risk (N=42) in a Spanish cohort. Questionnaires assessed distress, perception of breast cancer risk, screening behaviours, coping skills, personality and quality of life. Neither group received genetic counselling before or after this study. Women with FHBC overestimated their risk of developing breast cancer. They report a subjective risk of developing breast cancer of 50%, with their actual risk, using the risk tables elaborated by Claus et al., being only 15% (p<0.05). Discriminant function analysis revealed the patients' information about breast cancer, worries about breast cancer, perception of risk based on family history, perception of lifetime risk of breast cancer and quality of life were the five variables that distinguished between both groups. Only 34% of women in the FHBC group performed monthly breast self-examination, 24% (10 subjects) had never attended previously for clinical breast examination and 45% (19 subjects) had never undergone a mammogram. This group of women had a significantly lower level of general satisfaction (p<0.05), an indicator of Quality of Life. The results support the need for developing psychological intervention for women with family history of breast cancer in order to increase adherence to surveillance behaviours, reduce distress, improve quality of life, and assure the earliest detection of breast cancer.     

Local delivery of poxvirus vaccines for melanoma

The development of vaccines for melanoma has been accelerated by the identification of melanoma-associated antigens, a better understanding of basic immunologic principles, and the ability to construct complex vectors for immunization. The location and context in which T-cell priming occurs significantly influences the type and magnitude of immune response. Furthermore, there is a delicate balance between the generation of tumor-specific immunity and the emergence of tumor escape variants. We have focused on the direct intra-tumoral delivery of poxvirus vaccines expressing costimulatory molecules as a strategy for overcoming local immunosuppression in the treatment of established melanoma. Poxviruses provide potent danger signals and, in the presence of costimulation, local administration provides a mechanism to prime tumor-specific T-cell responses. The clinical application of this approach will likely depend on the ability to induce systemic anti-tumor immunity following local injection and we are evaluating this in current clinical trials. These studies may have important implications for the design of vaccine strategies for melanoma and other tumors.     

Death receptor 5 and Bcl-2 protein expression as predictors of tumor response to gemcitabine and cisplatin in patients with advanced non-small-cell lung cancer

The cytotoxic effects of gemcitabine (G) and cisplatin (C) seem to occur through induction of apoptosis. To examine whether the efficacy of GC chemotherapy might be influenced by the expression of death receptor 5 (DR5) and Bcl-2 of the tumor, we investigated the correlation between the tumor response rate and DR5 and Bcl-2 expression in a series of patients prospectively treated with GC. Thirty-four chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) received intravenously 1000 mg/m² gemcitabine on d 1 and 8 along with 80 mg/m² cisplatin on d 2, every 21 d. Tumor specimens were analyzed for DR5 and Bcl-2 expression by immunohistochemistry. The objective response rate was 56% (19 of 34 patients). With median follow-up of 10 mo, the predicted median survival time was 12 mo (95% confidence interval [CI], 9–15 mo). Eleven (32%) and 14 (41%) NSCLC cases were found positive for DR5 and Bcl-2, respectively. The response rate was significantly higher in patients with DR5 expression than those without DR5 expression (91% vs 39%; p=0.008). Patients with Bcl-2 expression were apparently less responsive than those without Bcl-2 expression (21% vs 80%; p=0.001). DR5 and Bcl-2 expression was significantly associated with response to GC chemotherapy. Therefore, DR5 and Bcl-2 status are useful factors for predicting the efficacy of GC.     

PH monitoring in the distal and proximal esophagus in symptomatic infants

BACKGROUND: Standard distal esophageal pH monitoring data are sometimes within normal ranges in children with clinically suspected gastroesophageal reflux disease. Therefore, the authors hypothesized that the amount of acid reflux reaching the proximal esophagus may be greater in some subgroups of patients than in healthy controls or in other subgroups of patients. METHODS: The parameters of 24-hour pH monitoring in the proximal part of the esophagus were analyzed in 120 symptomatic infants in who the reflux parameters in the lower esophagus were clearly within normal ranges (reflux index < 5.0%). The infants were classified into four patient groups: excessive regurgitation (n = 41): inconsolable crying (n = 31), apparent life-threatening event (ALTE) (n = 18), and chronic respiratory disorders (n = 30). The control group consisted also of 120 infants. The following parameters were calculated: reflux index, the number of reflux episodes, the number of reflux episodes lasting longer than 5 minutes, the duration of the longest reflux episode, and the acid clearance time (ACT, duration of reflux episodes divided by number of reflux episodes). RESULTS: The patients with chronic respiratory disorders were significantly older than the patients in the other groups and the controls. In the distal esophagus, there was no statistically significant difference between the reflux parameters. As could be expected, every parameter was statistically (paired t test, Wilcoxon signed-rank test) significantly smaller in the proximal than in the distal esophagus, except for the ACT in infants who presented with inconsolable crying. In the proximal esophagus, there was no statistically significant difference between the different patient subgroups or controls, except for the number of reflux episodes in the group with chronic respiratory disorders and the group with inconsolable crying, applying one-way analysis of variance. As determined by applying the Mann-Whitney test, the number of reflux episodes in the upper esophagus was significantly higher in the group with chronic respiratory disorders than in the other patient groups and controls. Therefore, the authors' data do not support the hypothesis that reflux reaching the proximal esophagus is a frequent cause of ALTE. However, the data may suggest that the number of reflux episodes reaching the proximal esophagus in children with chronic respiratory disorders and with distal pH monitoring data within normal ranges may be increased. Whether this finding reflects reality or a statistical coincidence, or is influenced by the older age of this patient group, needs further evaluation. CONCLUSIONS: In theory, dual simultaneous esophageal pH monitoring in the distal and proximal esophagus may increase the diagnostic accuracy of pH monitoring in infants. Our results do not support a substantial advantage of a systematic application of this new technique, especially not in infants presenting with ALTE, excessive regurgitation, or inconsolable crying. In the subgroup of patients with chronic respiratory disorders, more data are needed before conclusions can be determined and recommendations can be made.     

Methods in preimplantation genetic diagnosis

Preimplantation genetic diagnosis (PGD) is a new strategy, orientated toward primary prevention of congenital anomalies in couples with reproductive risk, such as advanced maternal age, carriers of chromosomal abnormalities, and carriers of monogenic conditions. For these patients, PGD is an acceptable alternative to prenatal diagnosis, mainly in those countries where pregnancy interruption is forbidden by law. PGD effectively avoids the implications linked to traditional prenatal diagnosis. Centres that provide medical servicies on reproductive biomedicine are responsible for the development and improvement of this new prevention strategy. Thanks to advances in micromanipulation techniques, associated with recent progress in molecular genetics, PGD may be employed for any genetic condition in the future.     

Effect of interferon alpha-2b on endometrioma cells in vitro

OBJECTIVE: To examine the effect of interferon alpha-2b on the growth of endometrioma cells and its effect on the DNA synthesis. METHODS: Cells from four separate endometrioma cell lines were seeded into six-well plates in M199 medium containing increasing levels of interferon alpha-2b: 0 (control), 50, 100, 500, 1000, and 2000 U/mL. All cells were counted on days 0, 3, 6, and 9 in quadruplicate, and the counts were averaged for each condition. A second experiment was run to demonstrate the effect of short-term exposure of interferon alpha-2b on the growth of endometrioma cells in culture. In a separate experiment, cells from two endometriomas were plated in quadruplicate to evaluate the DNA synthesis. On day 3, 1000 and 4000 U/mL of interferon alpha-2b were added and run simultaneously with control (0 U/mL) wells. 3H-thymidine was added to each condition for 24 and 48 hours' incubation. Cells were then harvested and counted in a scintillation counter to study the 3H-thymidine uptake. RESULTS: Interferon alpha-2b suppressed endometrioma cell growth in vitro. This effect increased with increasing concentrations of interferon alpha-2b (50-2000 U/mL) compared with the control (0 U/mL). The suppression of cell growth was statistically significant, but when interferon alpha-2b was removed from the culture cell growth increased. 3H-thymidine uptake by endometrioma cells decreased compared with the control after 24 and 48 hours for interferon alpha-2b concentrations of 1000 and 4000 U/mL, respectively. CONCLUSION: Interferon alpha-2b inhibits the growth and DNA synthesis of endometrioma cells in culture. This finding may have prospects for the treatment of endometriosis.