p27kip1 overexpression regulates IL-1ß in the microenvironment of stem cells and eutopic endometriosis co-cultures.

Endometriosis is a gynecological benign chronic disease defined as the growth of endometrial glands and stroma in extra-uterine sites, most commonly implanted over visceral and peritoneal surfaces within the female pelvis causing inflammatory lesions. It affects around 10% of the female population and is often accompanied by chronic pelvic pain, adhesion formation and infertility. Therefore, endometriosis could be considered a "social disease", since it affects the quality of life, reproductivity and also has a socio-economic impact. The expression of cell cycle and inflammatory proteins is modified in the endometriotic tissues. Immunostaining of glandular and stromal cells in endometrial biopsies obtained from patients with endometriosis compared with those of healthy control demonstrated that endometriotic tissues have lower levels of p27kip1 protein. Endometriosis endometrial cells cultures have also lower levels of p27kip1 compared to health endometrial cells cultures and restore the cell cycle balance when transduced with an adenoviral vector carring the p27kip1 coding gene (Adp27EGFP). The low levels of p27kip1 are related to the S phase in the cell cycle, whereas higher levels lead to a G1 cell cycle arrest. The inflammatory cytokine IL-1ß was recently identified as another key protein in the endometriosis proliferation. This cytokine has elevated levels during the proliferative and secretory phases of the menstrual cycle. In endometriosis endometrial cells cultures the IL-1ß stimulates the production of IL-6 and IL-8, increasing the cell proliferation and reducing the apoptosis and Bax expression in these cells. According to these remarks, this work aims to evaluate the inflammatory effects in vitro, but more next to what happens in a woman's body, associating endometrial cells with stem cells, thus mimicking the endometrial microenvironment, with gene therapy using Adp27, notoriously known as controller cell cycle, apoptosis and potent modulator of VEGF expression.

p27kip1 overexpression regulates VEGF expression, cell proliferation and apoptosis in cell culture from eutopic endometrium of women with endometriosis.

We hypothesized that p27(kip1) overexpression can regulate endometriosis cell proliferation, apoptosis and vascular endothelial growth factor (VEGF) expression in the endometrium. The overexpression of p27(kip1) was obtained by transduction of p27(kip1) in primary cultures of endometrium obtained from women with endometriosis tissue with gene therapy technology. First generation bicistronic adenovirus: AdCMVhp27IRESEGFP (Adp27) and AdCMVNull (AdNull) were engineered in order to induce p27(kip1) expression in endometrial cells primary culture. The effect of p27(kip1) overexpression was elucidated through the cell proliferation evaluation and the expression of the cell cycle-related proteins p16, p21, p27, and p53. Cell cycle and apoptosis in endometrial cells from women with and without endometriosis were also evaluated. The VEGF levels were evaluated 1 and 7 days after transduction. The experiments were performed using Immunofluorescence stainings and flow cytometry technique. The cell proliferation statistically diminished markedly following p27(kip1) overexpression in the endometriosis group. This process was accompanied, however, by a statistically significant modulation of the cell cycle-related proteins p16, p21, p27 and p53 markedly increase following p27(kip1) overexpression in the endometriosis group (p < 0.001) and an increase in apoptotic cells was observed. In the endometriosis group, significant downregulation of VEGF expression was observed 7 days after p27(kip1) overexpression, attaining levels strikingly similar to those observed in the control endometrial cells. The findings of this study showed a link between the cell cycle control protein (p27(kip1)) and angiogenesis (VEGF). Our results, also reinforces the background of endometrial dysfunction as part of the origin of endometriosis. We believe that better knowledge of endometrium milieu and the establishment of the link between different, previously describe, altered pathways in this tissue can facilitate future genetic cell therapy.

TP53 gene polymorphisms at codons 11, 72, and 248 and association with endometriosis in a Brazilian population.

We evaluated the association between TP53 gene polymorphisms and endometriosis in Brazilian women. Genomic DNA was extracted from swabs of buccal cells collected from hospital patients. TP53 gene polymorphisms were investigated at three codons: TP53 11 Glu/Gln or Lys (GAG->CAG or AAG), TP53 72 Arg/Pro (CCG->CCC), and TP53 248 Arg/Thr (CGG->TCG) using the polymerase chain reaction-restriction fragment length polymorphism method. TP53 11 presented the following genotypic distribution: the control group was 98.28% homozygous wild-type (Glu) and 1.72% homozygous variant (Gln/Lys), and the heterozygous genotype was not identified. The genotypic distribution in the endometriosis group was 96% homozygous wild-type (Glu) and 4% heterozygous (Glu-Gln/Lys); the homozygous variant genotype was not identified (P = 0.02). TP53 72 showed the following genotypic distribution: the control group was 29.75% homozygous wild-type (Arg), 47.11% heterozygous (Arg-Pro), and 23.14% homozygous variant (Pro). The genotypic distribution in the endometriosis group was 16.15% homozygous wild-type (Arg), 51.54% heterozygous (Arg-Pro), and 32.31% homozygous variant (Pro) (odds ratio = 2.26; 95% confidence interval = 1.19-4.03; P = 0.02). Only one patient had the homozygous TP53 248 genotype (Arg-Trp/Gln); all other patients were homozygous wild-type in both the control and endometriosis groups (P = 0.51; NS). We found that TP53 72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold. Hence, this genetic variant is a potential candidate marker for endometriosis.

Reconstruction technique for umbilical endometriosis.

OBJECTIVE: To present a technique for immediate umbilical reconstruction in women undergoing resection of umbilical endometriosis. METHODS: Umbilical reconstruction using 2 semicircular defatted skin flaps was performed in 7 patients surgically treated for umbilical endometriosis from October 2000 to June 2004. The patients were followed up for at least 6 months. RESULTS: Anatomical aspect, depression, and abdominal wall scar were considered satisfactory, although hypertrophic umbilical scars developed in 2 patients. CONCLUSION: This technique using 2 semicircular defatted flaps is efficient in creating a new umbilicus with a natural appearance while leaving a minimal scar. Moreover, it allows for laparoscopic inspection of the abdominal cavity.

Assessing health system provision of well-child care: The Promoting Healthy Development Survey.

BACKGROUND: Preventive care guidelines for children include parent education and counseling, developmental assessment, and screening for psychosocial and safety risks. Health care providers are in a unique position to identify and follow up on potential problems and to influence parenting knowledge, attitudes, and behavior to ensure the healthy development of young children. Few quality measures are available to assess health care system performance in this important area. OBJECTIVE: To develop a feasible, valid, and reliable methodology for evaluating health care system performance in providing family-centered anticipatory guidance and child and family assessment services on behalf of children from birth through 48 months old. Methods. The Promoting Healthy Development Survey (PHDS) was developed and tested with a diverse group of families in 3 managed care organizations (n = 1478). A standard mail administration protocol was used, including an informed consent with a waiver of documentation, 2 mailings, a postcard reminder, and telephone reminders. The 36-item parent survey assesses whether health care providers(1) talk with parents about topics recommended in Bright Futures and the American Academy of Pediatrics Guidelines for Health Supervision,(2) provide follow-up for children who may be at risk for developmental problems,(3) and address psychosocial well-being and safety within the family. The PHDS also assesses the degree to which parent's interactions with providers are family-centered, helpful, and facilitate parental confidence. Psychometric, bivariate, and multivariate analyses were conducted to assess the reliability, validity, and patterns of variation in the seven quality measures derived from the PHDS. RESULTS: Psychometric analyses demonstrated that the PHDS quality measure scales have strong construct validity (mean factor loading: 0.69) and internal consistency (mean Cronbach's alpha: 0.80). Parents reporting positive parenting behaviors had significantly higher scores on the anticipatory guidance quality measure compared with parents not reporting positive behaviors. Parents who reported that their questions on specific anticipatory guidance topics were answered were more likely to report higher confidence in related parenting activities (odds ratio [OR]: 5.9, 95% confidence interval [CI]: 3.4-10.2; OR: 8.3, 95% CI: 5-13.8)and were less likely to report concerns about their child's development in related areas compared with parents who reported they wished they had talked more with their child's doctor about these topics (OR: 0.46, 95% CI: 0.29-0.72; OR: 0.58, 95% CI: 0.37-0.89). The 7 PHDS quality measure scores for health plans ranged from 17 to 67 (on a 0-100 scale; where 100 is the best score possible) and varied significantly across health plans. Performance was highest for provision of anticipatory guidance information from health plans and lowest for family psychosocial assessment. Scores for families with Medicaid coverage were significantly higher on 2 of the PHDS measures and significantly lower for 3 measures compared with scores for families with commercial insurance. Age of child, whether child is first- born, parental marital status, education, income, and race were significant predictors for 1 or more of the PHDS quality measures (average R(2) = 0.05). CONCLUSIONS: The PHDS provides a comprehensive, psychometrically valid and reliable assessment of how well health plans and the health care providers working within these plans promote the healthy development of young children. The PHDS seems to differentiate among health care plans and among the different aspects of preventive care provided within a health plan. For the population studied here, there is significant room for improvement in ensuring families and children receive appropriate and family-centered care to promote the healthy development of children between 3 and 48 months old. Because the PHDS is conceptually based on national recommendations for child health supervision, improved performance on the PHDS would indicate greater adherence to these national recommendations and progress toward the achievement of Healthy People 2010 goals. The generalizability of the findings presented in this report are being examined using data collected in 5 statewide Medicaid samples (N = 11 696) and data from the National Survey of Early Childhood Health, which has incorporated most of the PHDS items.

Effects of conjugated estrogens and progestogen in surgically induced endometriosis in oophorectomized rats.

This study aimed to verify whether estrogen replacement alone or associated with progesterone promotes the recurrence of experimental endometriosis in oophorectomized rats. The procedure utilized for endometriosis induction was adapted from the one described by Jones (1984). The rats were castrated three weeks after the induction. Hormonal replacement was started 14 days after the castration and was given for 24 days. One group received estrogen alone, another received estrogen associated with medroxiprogesterone acetate, and a last one received placebo. At the end of this study, the animals who received hormonal medication showed recurrence of the disease. This fact was more evident in the group that received estrogen alone. We concluded that estrogen alone leads to recurrence of endometriosis in oophorectomized rats with surgically induced endometriosis. The association of medroxiprogesterone promotes involutional changes in the implants, and should be added upon the existence of a past history of endometriosis.

The health of children.

OBJECTIVE: To summarize the concept of child health and the measurement of child health status in order to help guide the evaluation of the effectiveness of medical, social, and policy programs. CONCLUSIONS: Opportunities for research on children's health status and quality of care abound. Comprehensive and functional definitions create problems of measurement, but investigators are making progress in measuring children's health status both generically and for specific chronic health conditions. RECOMMENDATIONS: Measures of child health need to be developed, improved, tested, and made user-friendly for clinical and policy research. The relationship between health status and a variety of social programs for children and families needs study. The impact of changes in healthcare organization and financing must be investigated, especially for children from vulnerable subgroups. Determining the value and effectiveness of preventive services is a pressing issue. It is crucial to understand better the link among quality of care; other factors biological, family, and social; and children's health status.

Adolescent alcohol use: social determinants and the case for early family-centered prevention. Family-focused prevention of adolescent drinking.

The family plays a central role in the use of alcohol by children and adolescents, yet preventive interventions rarely focus on the family. Early drinking and much subsequent use of alcohol by children and adolescents is sanctioned and sometimes encouraged by their families. Unlike experimentation with alcohol, problem drinking is associated with low levels of family social support and with dysfunctional coping strategies of families that may lead children to use drinking as an adaptive behavior. While risk-factor research has advanced understanding of alcohol use by children and youth, the poor predictive power of individual risks has limited its contribution to successful interventions. On the other hand, protective factors, provided by relationships within and outside the family, can be preventive and health promoting. Parents influence their children's drinking through family interactions, modeling and reinforcing standards, and attitudes that children learn and use to guide their behavior in new situations. Thus, parental influences endure. This article argues that interventions to prevent alcohol abuse should be designed to help parents to carry out their parental functions. This can be accomplished by providing social support, resources, and education for parents, as well as developing extra-familial sources of social support and socialization for children and adolescents.

Behavioral correlates of differences between a child's assessment and the parents' assessment of the child's self-esteem.

When, as commonly occurs, a parent's and child's reports about the child differ, the lack of agreement usually leads to consideration of which information is objective and valid. Little attention has been given to understanding what meaning these differences might have in the context of parent-child relationships or to whether the existence or absence of these differences might be causally related to the child's psychosocial status and functioning. Third- through fifth-grade children (N = 178) in behavior disorder and regular classrooms were asked to complete a self-concept measure; parents were asked to independently complete the same instrument as they thought their child would. Parents of children without behavior disorders were significantly more accurate in their descriptions of their children's perceptions than were parents of children with behavior problems. They also tended to expect their children to have more positive self-concepts than the children actually reported. Parents who are able to accurately report their children's feelings and who err toward more positive assessments may be preventing behavior problems.

Socioeconomic status and preventive health-care use by children in Spain.

National health systems are intended to provide equal access to health-care services to whole populations. However, they do not seem to address successfully the problem of social class differentials in access to health care, in particular access to preventive care. This study examines the relationship between the socioeconomic status (SES) of families and the use of preventive health care by children under a national health system in Spain. The study is based on weighted multivariate ordinal logistic regression analyses of data from the 1987 Spanish National Health Survey for a sample of 5,622 children, one to 10 years of age. A positive relationship was found between preventive health-care use by children and the SES of their families. Adult respondents' level of education and total family income were the most influential variables in this relationship. As these increased, children were more likely to receive visual, hearing, and dental exams. In addition, there was a gradient effect between family income and rate at which children received these preventive health-care services. Universal access to care, like that available in Spain, does not guarantee that social inequalities in children's receipt of preventive health care will not persist. In order to succeed, health-care reform must deal with social issues beyond financial access to care.

The influence of families on child health. Family behaviors and child outcomes.

The family is the most central and enduring influence on children. Families, regardless of their composition, are themselves subject to a variety of social forces that influence how well they are able to meet children's needs. Pediatricians who understand the functions families serve and the factors that constrain them will be better able to assist parents in promoting their children's health and well-being.

Physicians' assessment of functional health status and well-being. The patient's perspective.

BACKGROUND: Ascribing quality to medical care rests in part on the expectation of physician behavior and the content of care. The adoption of functional outcomes of care as legitimate measures of quality will require greater attention to patient-provided assessments of health and add new dimensions to medical practice and quality assessment. METHODS: We conducted a cross-sectional, national population survey of adults to obtain estimates of the frequency with which physicians reportedly inquire about patients' functional health status and emotional well-being, patients' attitudes about such assessments, and the perceived use of data thus obtained in the therapeutic process. RESULTS: The majority of physicians rarely or never ask about the extent to which patients' health limits their ability to perform everyday activities (64.7% to 78.7%); neither do they inquire about limitations imposed by emotional problems (71.4% to 84.4%). Physicians are more likely to make such inquiries in the presence of chronic illness or diminished health status, or with older patients, although such assessments remain the exception to usual practice and a large portion of functional impairment is undiscovered. More than 60% of respondents want their physicians to assess their functional health status and well-being. CONCLUSIONS: While individuals want their physicians to assess their functional performance and emotional well-being as a part of medical care, by their reports this occurs infrequently. The content of care may be less comprehensive than physicians believe to be the case.

Developing communality: family-centered programs to improve children's health and well-being.

Despite decades of enormous investment in research and public programs, the United States continues to face pandemics of preventable health problems such as low birth weight, teenage pregnancy, drug abuse, and interpersonal violence. With some justification, these problems have been blamed on the failings of families. The reasons why families may function poorly in their child-rearing roles have not been coherently or vigorously addressed by our social policies; sometimes these policies have aggravated the problems. This paper provides background to allow a better understanding of families' role in the social determination of children's health, and argues for programs and policies that assist families through the creation of social supports embedded in communities that are characterized by trust and mutual obligation.

Families, family roles, and psychological diagnoses in primary care.

This study examined the effect of belonging to a specific family on rates and occurrence of psychological diagnoses among the family members. Data were obtained from 693 families totaling 2907 parents and children during ambulatory care visits to a prepaid health care center. Families tended to have the majority of their members either with or conversely without a psychological diagnosis. The likelihood of having a psychological diagnosis was increased by 35% if another family member had been so diagnosed. Consequently, a small (3%) proportion of families accounted for a large (25%) proportion of these diagnoses. Children whose fathers were high utilizers of general health care services, or whose parents, particularly mothers, had a psychological diagnosis, were significantly more likely to have a diagnosis in this category as well. Families in which both parents had such a diagnosis were twice as likely to have an affected child. Siblings appeared not to exert any effect on one another in this regard. Family size and birth order had no effect on the incidence of psychological diagnoses.

Foster care.

The placement of children in foster care is a signal that families are in trouble and that our social system is struggling. Foster care, designed to provide remedial services to the child and family and thus to facilitate family reconstitution, often fails. Health care of children in foster care cannot be separated from the circumstances that led to their placement or from the structure and operation of the foster care system itself. Physicians caring for children in foster care should be aware of the challenges presented by these children's high rate of chronic illness and emotional problems and by the barriers imposed by the foster care system.