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PubMed1999

Managed care organizations and mammography: opportunities to serve underserved women.

Breast cancer is one of the major causes of mortality and morbidity among women. Breast cancer screening (mammography) has been shown to be an effective preventive service. Significant proportions of women for whom mammography would be an appropriate intervention, especially older, low-income, and minority women, do not receive it. A large proportion of American women (including those in the workforce or who are Medicare and Medicaid beneficiaries) is now enrolled in managed care plans and that trend is likely to continue. Analysts have identified several concerns related to access and use of preventive services by low-income and other vulnerable populations. Research related to these concerns is summarized. Many research-based interventions have been identified that increase the likelihood of women receiving mammography. These are summarized and recommendations are made for managed care organizations to implement them.

Adult↗

PubMed1996

Cancer patients psychological adjustment and perception of illness: cultural differences between Belgium and Turkey.

Little is known about cultural differences in psychological adjustment and perception of illness (PI) during medical procedures in general and radiotherapy in particular. This study compares a Turkish (TP) and a French speaking Belgian (BP) population. A group of 296 consecutive patients attending the radiotherapy clinic of Institut Jules Bordet, Brussels, (n = 172) and Oncology Institute, Capa-Istanbul, (n = 124) were interviewed and assessed by a symptom checklist, the SCL-90-R, at the beginning and at the end of the radiotherapy. PI, derived from a semi-structured interview, was assessed at the beginning of radiotherapy by a five-point observer-rating scale derived from the Omega Vulnerability Rating Scale. Differences in SCL-90-R scores, taking into account country, age, gender, level of education and PI as potential explanatory variables, have been tested by a multivariate analysis of variance with a design of repeated measures using the SCL-90-R scores as dependent variables. Mainly a time effect and a country effect have been found. Some interactions between both effects have also been found. Globally, all the SCL-90-R scores decrease between the beginning and the end of the radiotherapy. The effect of country is noticeable for most of the SCL-90-R components, with higher scores in the BP, except for the positive symptom total score where the TP showed higher scores. The interaction between country and time is not significant, the scores of both the BP and TP decreasing over time, except for somatization scores (P < 0.001) where the scores of the BP were stable over time while the scores of the TP decreased considerably, and for paranoid ideation scores (P = 0.001) where the scores of the BP decreased while the scores of the TP increased. Results showed a higher rate of correct perception in the BP compared to the TP (P = 0.0001). A PI effect has been found for somatization (P = 0.02), anxiety (P = 0.01) and Global Severity Index scores (P = 0.05), with higher mean scores for the "correct perception" category. No interaction with time was found. A significant interaction effect between country and PI has been found for anxiety scores with higher scores in the correct perception category in the BP and in the "denial of implications" category in the TP (P < 0.001). Results highlight cultural differences in psychological adjustment and/or in the responses to self-report questionnaires: greater weight was given to items by the BP, more numerous items were scored by the TP, and greater weight was given to the somatization subscale compared to the psychological subscales by the TP. This study suggests that psychosocial distress is expressed differently in Belgium and Turkey, where patients express mostly somatic complaints. Finally PI, a culture-dependent factor, appears to influence psychological adjustment very differently, a correct perception of illness leading to more anxiety in the BP compared to the TP.

Adaptation, Psychological↗

PubMed1997

Epidemiology of ultraviolet-DNA repair capacity and human cancer.

The following conclusions are derived from an epidemiological study. Reduced repair of ultraviolet (UV)-induced DNA damage contributes directly to basal cell carcinoma (BCC) in individuals with prior sunlight overexposure. A family history of BCC is a predictor of low DNA repair. Repair of UV-damaged DNA declines at a fixed rate of approximately 1% per annum in noncancerous controls. The DNA repair differences between young BCC cases and their controls disappear as they age. Hence, BCC, in terms of DNA repair, is a premature aging disease. The persistence of photochemical damage because of reduced repair results in point mutations in the p53 gene and allelic loss of the nevoid BCC gene (Gorlin's syndrome) located on chromosome 9q. The fact that environmental vulnerability is gender oriented implicates hormones in regulating DNA repair. Xeroderma pigmentosum appears to be a valid paradigm for the role of DNA repair in BCC in the general population.

Aging↗

PubMedDate not supplied

Planning a sexual health promotion intervention with homeless adolescents.

BACKGROUND: Homeless adolescents are at very high risk for sexually transmitted diseases (STDs), but few street-based interventions have been developed, tested, and made available to reduce risk and promote sexual health within this growing population. OBJECTIVES: This study, part of a larger study of the sexual health practices of homeless adolescents, explores participants' perceived need for more knowledge about sexual health and their ideas about developing a brief intervention to promote positive sexual health practices that would reflect their perspective. METHODS: Four focus groups with five to six participants each were conducted with 22 youth aged 16-20 years, randomly selected from the study sample of 425 homeless youth. Most participants (82%) were White, one was American Indian, two were Hispanic, and one did not indicate ethnicity. Local groups were audiotape recorded, transcribed, and analyzed for manifest and latent content. RESULTS: Participants were knowledgeable about symptoms, transmission, prevention, and treatment of STDs, but perceived the need for more knowledge about types of hepatitis, cancer, and long-term sequelae of untreated STDs. Participants identified barriers to seeking diagnosis and treatment for symptoms of STDs including cost, not knowing where to go, and lack of services specifically for females. They suggested developing a sexual health intervention based on respect that would provide concrete examples of how to promote their sexual health. CONCLUSIONS: Homeless adolescents were generally knowledgeable about symptoms and prevention of STDs and thought that street outreach interventions should be (a) brief, (b) gender-specific, (c) focused on the unique vulnerabilities and strengths of homeless youth, and (d) accessible.

Adolescent↗

PubMed2002

Ethical issues in including pediatric cancer patients in drug development trials.

Since the biology, pharmacology and toxicology of pediatric cancer is so different from cancer in adults, it is impossible to extrapolate from adult cancer experience; however, conducting studies in children with cancer is ethically and clinically very complex. This is especially so in phase 1 trials, aimed at dose finding for new modalities, where the chances to cure the child who failed standard therapy are marginal to non-existent. Hence, the child may be exposed to risks and discomfort which may be unbalanced by potential benefits. This situation, which is difficult for consenting adults, is much more complex when a parent gives proxy consent. This review addresses the ethical and clinical framework of such studies in the most vulnerable of children.

Antineoplastic Agents↗

PubMedDate not supplied

[DNA repair pathways and their involvement in human diseases].

Integrity maintenance of the genome is crucial. Human DNA is vulnerable to damage arising from both endogenous and exogenous sources. Different DNA repair pathways counteract these potentially mutagenic accidents: damage reversal by methylguanine methyl transferase (MGMT), base nucleotide repair (BER), nucleotide excision repair (NER), mismatch repair (MMR) and repair of strand breaks. In some cases, DNA damage is not repaired but is instead bypassed by specialized DNA polymerases. The existence of human diseases associated with defects in DNA repair illustrates the importance of this process of quality control. Many of these human diseases have an increased susceptibility to cancer.

DNA Damage↗

PubMed2004

Unequal access to breast-conserving surgery in Western Australia 1982-2000.

BACKGROUND: The purpose of the present study was to examine the effects of demographic, locational and social disadvantage and the possession of private health insurance in Western Australia on the likelihood of women with breast cancer receiving breast-conserving surgery rather than mastectomy. METHODS: The WA Record Linkage Project was used to extract all hospital morbidity, cancer and death records of women with breast cancer in Western Australia from 1982 to 2000 inclusive. Comparisons between those receiving breast-conserving surgery and mastectomy were made after adjustment for covariates in logistic regression. RESULTS: Younger women, especially those aged less than 60 years, and those with less comorbidity were more likely to receive breast-conserving surgery (BCS). In lower socio-economic groups, women were less likely to receive BCS (OR 0.73; 95% CI 0.60-0.90). Women resident in rural areas tended to receive less BCS than those from metropolitan areas (OR 0.84; 95% CI 0.55-1.29). Women treated in a rural hospital had a reduced likelihood of BCS (OR 0.74; 95% CI 0.61-0.89). Treatment in a private hospital reduced the likelihood of BCS (OR 0.70; 95% CI 0.54-0.90), while women with private health insurance were much more likely to receive BCS (OR 1.39; 95% CI 1.08-1.79). CONCLUSION: Several factors were found to affect the likelihood of women with breast cancer receiving breast-conserving surgery, in particular, women from disadvantaged backgrounds were significantly less likely to receive breast-conserving surgery than those from more privileged groups.

Female↗

PubMedDate not supplied

A randomized controlled trial to increase cancer screening among attendees of community health centers.

BACKGROUND: We assessed the efficacy of the Cancer Screening Office Systems (Cancer SOS), an intervention designed to increase cancer screening in primary care settings serving disadvantaged populations. METHODS: Eight primary care clinics participating in a county-funded health insurance plan in Hillsborough County, Fla, agreed to take part in a cluster-randomized experimental trial. The Cancer SOS had 2 components: a cancer-screening checklist with chart stickers that indicated whether specific cancer-screening tests were due, ordered, or completed; and a division of office responsibilities to achieve high screening rates. Established patients were eligible if they were between the ages of 50 and 75 years and had no contraindication for screening. Data abstracted from charts of independent samples collected at baseline (n = 1,196) and at a 12-month follow-up (n = 1,237) was used to assess whether the patient was up-to-date on one or more of the following cancer-screening tests: mammogram, Papanicolaou (Pap) smear, or fecal occult blood testing (FOBT). RESULTS: In multivariate analysis that controlled for baseline screening rates, secular trends, and other patient and clinic characteristics, the intervention increased the odds of mammograms (odds ratio [OR] = 1.62, 95% confidence interval [CI], 1.07-9.78, P = .023) and fecal occult blood tests (OR = 2.5, 95% CI, 1.65-4.0, P <.0001) with a trend toward greater use of Pap smears (OR = 1.57, 95% CI, 0.92-2.64, P = .096). CONCLUSIONS: The Cancer SOS intervention significantly increased rates of cancer screening among primary care clinics serving disadvantaged populations. The Cancer SOS intervention is one option for providers or policy makers who wish to address cancer related health disparities.

Aged↗

PubMed2005

Systematic review of specialist palliative day-care for adults with cancer.

GOAL OF WORK: To inform future practice, research and policy in specialist palliative day-care by systematically reviewing the evidence for how the structure and process of this form of care relate to outcomes for adults with cancer. PATIENTS AND METHODS: Medical, nursing and social science computerized databases were searched up until December 2003 for studies of palliative day-care reporting information on service structure, care processes or outcomes including symptom control, quality of life, social and psychological support, and patient and relative satisfaction with care. Qualitative and quantitative studies were assessed for methodological quality and graded, and the findings synthesized into the review. MAIN RESULTS: Twelve observational studies were found that showed the difficulties of evaluating a service already operating and of recruiting a vulnerable population of patients as they deteriorated. Most services are nurse-led, but varied in the facilities, staff mix, care models, activities and places they offered. Patients attending seemed a selected group of those already receiving palliative care who were mostly white, aged over 60 years and retired, with needs for emotional and social support and pain control. There were insufficient studies to provide conclusive evidence of improved symptom control or health-related quality of life, but all qualitative studies found patients valued the social support and opportunity to take part in activities that day-care provided. CONCLUSIONS: There is evidence for high satisfaction among patients selected into day-care, but not yet sufficient to judge whether this improves symptom control or health-related quality of life. Further research should explore selection and access into care, the most effective models of care, its cost, and potential benefits for relatives and carers. Comparison with models of care for older adults and those with mental illness would also be informative.

Adult↗

PubMed2001

'What is it?': findings on preschoolers' responses to play with medical equipment.

When young people enter a hospital they are exposed to a foreign world of unfamiliar people, medical equipment and language. Children diagnosed with leukaemia are particularly vulnerable to repeated exposure to these distressing hospital visits. Assessing a child's understanding of the stresses associated with treatment during hospitalization is now seen as a key element of caring for the paediatric patient. A population particularly vulnerable to the effects of the stress of intensive treatments during hospitalization are preschool children. In order to understand the impact on leukaemia preschool children of intensive hospital treatment it is necessary to have comparative information on healthy peers who have not been exposed to such treatment experiences. This article presents findings from recent qualitative research that explored the beliefs held by healthy preschoolers about what happens in hospital, what it means to be sick, their reactions to and knowledge of medical equipment and their level of knowledge regarding cancer and leukaemia. It is the hope and expectation that the findings will be used comparatively to contribute to a deeper understanding of the world of the child coping with leukaemia and related disorders.

Adaptation, Psychological↗

PubMed2001

Community respiratory virus infections in bone marrow transplant recipients: the M.D. Anderson Cancer Center experience.

Community respiratory virus (CRV) infections are common among bone marrow transplant (BMT) recipients during community outbreaks. At M.D. Anderson Cancer Center (MDACC), experience with CRV infection in this population over the past decade suggests that BMT recipients in the preengraftment phase are at special risk of progression of upper respiratory tract infection (URTI) to pneumonia. After pneumonia is established, no currently available therapy substantially reduces mortality. For BMT recipients with respiratory syncytial virus URTIs, treatment with ribavirin and intravenous immunoglobulin may be helpful in preventing progression to pneumonia and thus in reducing mortality, but this approach requires confirmation in controlled clinical trials. Prevention of CRV infection in this vulnerable patient population is crucial to reducing morbidity and mortality. Aggressive infection control precautions, which have been in effect at MDACC since 1994, have reduced nosocomial transmission of these potentially lethal infections.

Antiviral Agents↗

PubMed2026

HRAS promotes mutant NRAS-driven transformation with codon and allele specificity.

Wild-type RAS family members determine the signaling and therapeutic response in cancers driven by mutant HRAS and KRAS because they activate alternate RAS effector pathways. Here, we found that the requirement for wild-type RAS to support mutant NRAS-driven transformation correlated with codon-specific differences in GTP hydrolysis. NRAS with mutations at either Gly12 (G12X) or Gly13 (G13X), which retained the GDP-GTP cycling function, had modest autonomous transforming potential. In contrast, NRAS with GTP-locking mutations at Gln61 (Q61X mutants) was uncoupled from receptor tyrosine kinase (RTK) input, rendering wild-type RAS an obligate partner for RTK-stimulated signaling and oncogenesis. In RASless cells expressing mutant NRAS, reintroduction of wild-type HRAS was sufficient to restore signaling and transformation. Global dependency mapping in human cancer cells revealed functional partitioning, wherein mutant NRAS promoted MAPK signaling and wild-type HRAS promoted PI3K-AKT survival signaling. Consequently, allele-specific or pan-RAS(ON) inhibitors synergized with inhibitors of proximal RTK signaling or of wild-type HRAS or KRAS to overcome this signaling plasticity. Pan-RAS(ON) and HRAS inhibition was synergistic for all NRAS mutants tested, with Q61X mutants showing greater sensitivity. These findings define the signaling partnership between mutant NRAS and wild-type HRAS as a targetable vulnerability and provide a biochemical blueprint for dual RAS inhibition in NRAS-mutated malignancies.

Humans↗

PubMed1993

Interleukin 2 and interferon-gamma augment anticolon antibody dependent cellular cytotoxicity in ulcerative colitis.

In vitro effects of cytokines and therapeutic drugs on antibody dependent cellular cytotoxicity (ADCC) mediated by anticolon antibody were investigated in serum samples from patients with ulcerative colitis. A 51Cr release assay was used to examine ADCC activity with the colon cancer cell line, colo 205, as the target and peripheral blood mononuclear cells as the effector. High ADCC activity was shown in 13 of 32 (41%) patients with ulcerative colitis. This ADCC activity was inhibited by protein A treatment of the serum samples. Interleukin 2 (IL2) activated effector cells could enhance ADCC activity, but interferon-gamma (IFN-gamma) or tumour necrosis factor-alpha (TNF-alpha) had no effect on the cytotoxic activity of effector cells. Treatment of target cells with IFN-gamma increased the vulnerability of these cells to ADCC with a large increase of intercellular adhesion molecule-1 (ICAM-1) expression on their surface. Monoclonal antibodies to ICAM-1 inhibited this IFN-gamma enhanced ADCC activity. Interestingly, prednisolone (PSL) reduced ADCC activity, but sulphasalazine (SASP) or 5-aminosalicylic acid (5-ASA) did not. These results suggest that IL2 and IFN-gamma could enhance colonic epithelial cell injury mediated by the ADCC mechanism in ulcerative colitis and that ADCC enhanced by cytokines is restored by PSL treatment.

Adolescent↗

PubMed2005

The protective role of DL-alpha-lipoic acid in the oxidative vulnerability triggered by Abeta-amyloid vaccination in mice.

Recent reports indicate that beta-amyloid peptide (Abeta) vaccine based therapy for Alzheimer's disease (AD) may be on the horizon. There are however, concerns about the safety of this approach. Immunization with Abeta has several disadvantages, because it crosses the blood brain barrier and cause inflammation and neurotoxicity. The present work is aimed to study the protective effective of alpha-lipoic acid (LA) in the oxidative vulnerability of beta-amyloid in plasma, liver, spleen and brain, when Abeta fibrils are given intraperitoneally in inflammation induced mice. Result shows that reactive oxygen species (ROS) in the astrocytes of inflammation induced mice along with Abeta (IA) has shown 2.5-fold increase when compared with LA treated mice. The increased level of lipid peroxidase (LPO) (p < 0.05) and decreased antioxidant status (p < 0.05) were observed in the plasma, liver, spleen and brain of LA induced mice when compared with LA treated mice. Data shows that there were no significant changes observed between the control and LA treated mice. Our biochemical and histological results highlight that significant oxidative vulnerability was observed in IA treated mice, which was prevented by LA therapy. Our findings suggest that the antioxidant effect of LA when induced with Abeta may serve as a potent therapeutic tool for inflammatory AD models.

Adenosine Triphosphatases↗

PubMed2005

Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes.

Aging is associated with a reduced ability to cope with physiological challenges. Although the mechanisms underlying age-related alterations in stress tolerance are not well defined, many studies support the validity of the oxidative stress hypothesis, which suggests that lowered functional capacity in aged organisms is the result of an increased generation of reactive oxygen and nitrogen species. Increased production of oxidants in vivo can cause damage to intracellular macromolecules, which can translate into oxidative injury, impaired function and cell death in vulnerable tissues such as the brain. To survive different types of injuries, brain cells have evolved networks of responses, which detect and control diverse forms of stress. This is accomplished by a complex network of the so-called longevity assurance processes, which are composed of several genes termed vitagenes. Among these, heat shock proteins form a highly conserved system responsible for the preservation and repair of the correct protein conformation. The heat shock response contributes to establishing a cytoprotective state in a wide variety of human diseases, including inflammation, cancer, aging and neurodegenerative disorders. Given the broad cytoprotective properties of the heat shock response, there is now a strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. Acetylcarnitine is proposed as a therapeutic agent for several neurodegenerative disorders, and there is now evidence that it may play a critical role as modulator of cellular stress response in health and disease states. In the present review, we first discuss the role of nutrition in carnitine metabolism, followed by a discussion of carnitine and acetyl-l-carnitine in mitochondrial dysfunction, in aging, and in age-related disorders. We then review the evidence for the role of acetylcarnitine in modulating redox-dependent mechanisms leading to up-regulation of vitagenes in brain, and we also discuss new approaches for investigating the mechanisms of lifetime survival and longevity.

Acetylcarnitine↗

PubMed1989

Differences in biologic maturation, sexual behavior, and sexually transmitted disease between adolescents with and without cervical intraepithelial neoplasia.

Because several cofactors may influence the development of cervical intraepithelial neoplasia (CIN) in young women, we compared differences in behaviors (sexual activity, contraception, and cigarette use), sexually transmitted disease (STD) infection rates (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and herpes simplex virus), and cervical maturation (age of menarche and percentage of cervical ectopy) in groups of sexually active female adolescents with and without CIN. Those with CIN were compared with three non-CIN groups: (1) teenagers who were referred to a teen colposcopy clinic but had no evidence of CIN (high-risk group), (2) teenagers seen at a gynecology clinic without STD symptoms (asymptomatic group), and (3) teenagers seen at the gynecology clinic with STD symptoms (symptomatic group). The percentage of cervical ectopy was measured by colpophotography. Subjects with CIN had more lifetime sexual partners than the asymptomatic group (p less than 0.001) and were more likely to smoke cigarettes than either gynecology clinic group (p less than 0.01). No differences in behaviors existed between the CIN and high-risk groups. The mean age of menarche in those with CIN was 1 year older than all three non-CIN groups (p less than 0.05), and those with CIN had a greater area of ectopy than those without CIN (p less than 0.02). Those with CIN were more likely to have a past or present history of C. trachomatis infection than the two gynecology clinic groups; no difference was found between the CIN and high-risk groups. We conclude that cofactors such as smoking, sexual promiscuity, and C. trachomatis infection may influence cervical vulnerability. However, cervical biologic immaturity is an important risk factor for development of CIN in adolescent girls.

Adolescent↗

PubMed1994

The role of the NIH's Office of Research on Women's Health.

The Office of Research on Women's Health (ORWH) at the National Institutes of Health (NIH) was created in 1990 to carry out three major mandates: (1) to strengthen, develop, and increase research into diseases, disorders, and conditions that are unique to, more prevalent among, or more serious in women, or for which there are different risk factors for women than for men; (2) to ensure that women are appropriately represented in biomedical and biobehavioral research studies, especially clinical trials, that are supported by the NIH; and (3) to direct initiatives to increase the number of women in biomedical careers. One of the ORWH's first accomplishments was a 1992 report that serves as a basis for the ORWH's research agenda; its recommendations focus on scientific issues affecting women's health from birth to old age. To implement these recommendations, the ORWH does not fund studies directly but instead provides funds through NIH institutes and centers to augment new research initiatives, to expand ongoing studies to address high-priority areas concerning women's health (14 of which were identified for special consideration in FY 93), and to increase the participation of women in clinical studies. In addition, the ORWH is playing a key advisory role in the NIH's Women's Health Initiative, a long-term study of over 100,000 women to examine the major causes of death, disability, and frailty--heart disease and stroke, breast and colorectal cancers, and osteoporosis--in older women of all races and from all socioeconomic strata.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral Research↗

PubMed1992

Therapeutic adherence to oral medication regimens by adolescents with cancer. II. Clinical and psychologic correlates.

The focus of our study was to identify specific demographic, treatment, and psychologic factors that may differentiate patients who complied with cancer therapy from those who did not. In a companion study, bioassay techniques revealed frequent nonadherence to oral medication regimens among 50 adolescents and young adults with acute lymphoblastic leukemia or Hodgkin disease. In this sample, compliers and noncompliers did not differ with respect to either demographic variables (age, gender) or treatment variables (treatment duration, continuity, complexity, or parental involvement). Psychologic variables were assessed in 34 patients. Patients who adhered poorly to the therapeutic regimen had significantly less developed concepts of the illness (specifically, concepts of causality and prognosis), less perceived vulnerability (especially as related to subclinical disease), higher levels of denial as a psychologic defense, and less cohesive future orientation. The perceived health locus of control was not a significant factor. The results suggest that patients construct their own subjective view of the illness and its treatment, which then has implications for adherence to medication regimens.

Administration, Oral↗