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PubMed2004

Parent-reported environmental tobacco smoke exposure among preadolescents and adolescents treated for cancer.

Exposure to environmental tobacco smoke (ETS) poses serious health risks for children with cancer. Parental smoke is a primary source of exposure for these children. Parent smoking behaviors and parent-reported ETS exposure among children treated for cancer were examined in this study. In addition, reports of ETS exposure among children with cancer who currently smoked or who had smoked in the past were compared to those of children with cancer who never smoked. Written questionnaires about smoking behaviors and ETS exposure were administered to 47 smoking parents of youngsters diagnosed with cancer, 10-18 years of age (57.4% male, 78.7% Caucasian). Child reports of smoking status were also obtained. Results indicated that children with cancer are exposed to ETS from a number of sources and settings, as reported by their parents. Current or previous child smokers had greater ETS exposure than non-smoking children. Older children and Caucasian children also had greater ETS exposure. Level of ETS exposure did not differ based on the child's treatment status. Interventions that teach parents to protect their youngster from ETS exposure have potential for reducing adverse health outcomes in this vulnerable population.

Adolescent↗
PubMed1995

Down-regulation of CD59 (protectin) expression on human colorectal adenocarcinoma cell lines by levamisole.

The vulnerability of tumour cells to complement-mediated immune attack is regulated by membrane associated molecules. Recently, we have shown that the expression of the membrane attack complex inhibitor CD59 is enhanced on colonic adenocarcinoma cells compared to normal colonic epithelial cells. CD59 was shown, in the same study, to protect the tumour cells from complement-mediated lysis. Levamisole (LMS), used in conjunction with 5-fluorouracil as adjuvant therapy, reduces the incidence of colon cancer relapse following surgical resection. This led to our investigation of the effect of LMS on CD59 expression and function on the human colorectal cell lines HT29 and Caco-2. When cultured in the presence of 10 microM LMS, the cells reduced their expression of CD59 in a time-dependent manner. LMS treated HT29 cells were more sensitive to lysis by complement than control cells, and the reduction in CD59 expression was shown to be partly responsible for this. A reduction in CD59 expression will augment complement-mediated immune surveillance and may contribute to LMSs anti-tumour activity in vivo.

Adenocarcinoma↗
PubMed1995

alpha-Ketoacids scavenge H2O2 in vitro and in vivo and reduce menadione-induced DNA injury and cytotoxicity.

We demonstrate that alpha-ketoacids reduce and, in some instances, abrogate menadione-induced DNA damage and cytotoxicity in the human breast cancer cell line, MCF7. We confirm that alpha-ketoacids quench the copious amounts of H2O2 generated by menadione while these alpha-ketoacids undergo nonenzymatic oxidative decarboxylation; our data thus support enhanced H2O2 production as an important pathway for menadione-induced DNA damage and cytotoxicity. We also demonstrate that alpha-ketoacids scavenge H2O2 generated by mitochondria and microsomes when these organelles are exposed to menadione; additionally, alpha-ketoacids protect oxidant-vulnerable enzymes against functional impairment induced by H2O2. Finally, we provide the first in vivo demonstration that acute elevations in concentrations of alpha-ketoacids in rat tissues and urine scavenge H2O2. We conclude that enhanced H2O2 production is a major pathway for menadione-induced DNA damage and cytotoxicity and that the diverse alpha-ketoacids present within the cell must be considered, along with glutathione peroxidase and catalase, as part of the intracellular antioxidant defense mechanisms that regulate the ambient levels of H2O2.

Animals↗
PubMed1990

[Families with hereditary cancer--a target group for prevention].

Although a large proportion of the population contract cancer, the risk is not uniform. In a small group (an estimated five per cent) with hereditary predisposition, the risk of cancer is high (often as high as 50 per cent) in every child of an affected parent. Another, considerably larger group consists of individuals at high risk (though how high is unknown), where a combination of hereditary and environmental factors is probably involved. In all likelihood, it is this group which would benefit most from general recommendations as to preventive measures. The study of such individuals will enhance our knowledge of the source of their vulnerability, thus facilitating the understanding of tumorigenic mechanisms in general, and on the basis of such knowledge improve the prospect of general and specific screening programmes, prevention and treatment.

Adolescent↗
PubMed1995

[Arguments against routine mumps vaccination].

Routine immunization against mumps was included in the MMR-elimination-programme of Switzerland despite the lack of any public health necessity. Seven years later, the theoretical presumptions of the mumps immunization campaign are challenged by practical experiences: An unnecessary vaccination proves to be of insufficient efficacy, yet associated with an unexpected high complication rate and bears thus the risk of discrediting also other immunizations in the general public. What could be considered a particular immunization failure reveals important inconsistencies of the entire MMR-mass-immunization-campaign. The project remains epidemiologically highly vulnerable and thus hazardous. Because of its constraining effects on the general population, compatibility with basic civil rights can be questioned. The reasons why some 20% of the Swiss population refuse mumps vaccination are little investigated so far. Nevertheless, research can provide important clues for further investigations in this field. As the maturation of the immune system follows learning principles, the question arises whether childhood diseases are not essential for the normal development of immunocompetence. In cancer therapy new attention is drawn to hyperthermia and thus to the healing potential of fever. And finally, there are concerns about the longterm effects of manipulations of the natural balance between man and microorganisms.

Adolescent↗
PubMed2006

Predictors of clinic satisfaction among adult survivors of childhood cancer.

Childhood cancer survivors experience a wide range of late-effects. As survival rates improve, follow-up in paediatric clinics becomes less feasible, and alternative models of care have been proposed. In this study, satisfaction among those attending a traditional paediatric late-effects clinic was compared with a multi-disciplinary clinic in an adult setting. Survivors (adult clinic n=93, paediatric clinic n=105, age 16-39 years) completed measures of symptoms, understanding of vulnerability to late-effects, purpose of follow-up, satisfaction and number of topics discussed. Predictors of satisfaction were: number of topics discussed, greater understanding of the purpose of follow-up and sex. Females, and those reporting longer waiting time were less satisfied. Aspects of clinic organisation, including shorter waiting times and opportunities to discuss health concerns, are more important in determining patient satisfaction than clinic type. Survivors' understanding of the purpose of follow-up is also integral in determining satisfaction.

Adolescent↗
PubMed2002

Preventive health care measures before and after start of renal replacement therapy.

OBJECTIVE: To describe utilization of preventive health care measures in patients with chronic kidney disease (CKD), both in the year prior to onset of renal replacement therapy (RRT), and in the first year of RRT. METHODS: We identified a large cohort of patients with CKD in the New Jersey Medicaid and Medicare programs with fixed enrollment into the cohort at 1 year prior to RRT. We applied commonly used quality assurance instruments (Health Plan Employer Data and Information Set measures) and defined levels and correlates of use of preventive care measures before and after RRT. These included mammography, Pap smear testing, prostate cancer screening, diabetic eye exams, and glycosylated hemoglobin testing (HbA1c). We employed logistic regression models with adjustment for age, race, gender, comorbidity, timing of first nephrologist contact, socioeconomic status, and calendar year of first RRT. RESULTS: Overall, screening rates were low with the exception of diabetic eye exams. Prostate cancer screening, diabetic eye exams, and HbA1c testing were performed less often after onset of RRT compared to the year before (P < .05). Although screening rates before RRT improved considerably over the period of observation for these measures (P < .05), this was not the case once patients were on RRT. CONCLUSIONS: Preventive health care interventions remain underutilized among RRT patients. Greater attention to such preventive measures could lead to significant improvements in the health status of such vulnerable patients. Thus, quality improvement of the general health care for patients on RRT should become a priority in renal health policy.

Cohort Studies↗
PubMedDate not supplied

Strategies to minimize risks and exploitation in phase one trials on healthy subjects.

Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors.

Adult↗
PubMed2026

Engagement and Retention in Precision Public Health: A Cascade Analysis of Two Cluster Randomized Trials.

INTRODUCTION: When research fails to reach and engage all populations who might benefit from study findings, it can compromise scientific validity and ultimately health equity. Few studies have systematically examined factors driving study engagement through longitudinal intervention research. This project examined sociodemographic, geographic, and structural influences on engagement and attrition across the participation "cascade" (outreach, enrollment, retention) for two large-scale multilevel precision medicine and precision prevention trials for smoking and lung cancer screening. METHODS: Modified Poisson regression models were used to determine the factors associated with study engagement based on sociodemographic and geographical factors at each step in the cascade of participation, from initial outreach through retention at 12 months post-enrollment. Secondary analyses examined the cascade among the subset of patients who had active electronic patient portals and were approached via the portal. RESULTS: A total of 24,366 patients were approached for participation. Race, Social Vulnerability Index (SVI), insurance status, and distance from the study site were significantly associated with engagement at various points in the cascade. Black patients were more likely than White patients to be reached (48.9% vs 47.1%; p = 0.022) and to complete eligibility screening (52.8% vs. 38.4%; p < 0.001), but less likely to consent to participate (56.7% vs 69.8%; p < 0.001) and complete genetic testing (58.5% vs. 69.8%; p = 0.003). Patterns of engagement through electronic patient portal versus non-electronic recruitment channels also differed by race- and place-based factors, with Black patients being less likely than White patients to respond in the portal (8.8% vs 15.5%; p < 0.001), and patients who reside farther from the study site being more likely to respond in the portal compared to those who live closer (14.9% vs 12.5%; p < 0.001). CONCLUSIONS: These findings highlight the need for tailored, stage-specific engagement strategies to ensure representative participation in genomic and behavioral intervention research to advance the integration of genomics into public health practice.

Journal Article↗
PubMed1969

Mammary cancer induction by 7,12-dimethylbenz(a)anthracene: relation to age.

Mammary glands were transplanted from donors treated with 7,12-dimethylbenz(a)anthracene to untreated isologous recipients. Incidence of mammary tumors in mammary grafts from 56-day-old donors was significantly higher than that in grafts from 120-day-old donors, regardless of the age of the recipient hosts. Whent mammary glands were transplanted from untreated donors to isologous recipients that subsequently received 7,12-dimethyl-benz(a)anthracene, a similar difference in tumor incidence in the grafts was observed. In contrast to mammary glands of older females, mammary glands of young adult female rats are highly vulnerable to the carcinogenic effect of 7,12-dimethylbenz(a)anthracene.

Aging↗
PubMed2004

The influence of socio-economic and locational disadvantage on survival after a diagnosis of lung or breast cancer in Western Australia.

OBJECTIVE: The effects of demographic, locational and socio-economic disadvantage, and the influence of private health care on five-year mortality rates in patients with lung cancer or after breast cancer surgery in Western Australia were examined. METHODS: The Western Australian Record Linkage Project was used to extract all hospital morbidity, cancer and death records of all people with lung or breast cancer in Western Australia from 1982 to 1996. Mortality rate ratios after a diagnosis of lung cancer or breast cancer surgery were estimated using Cox regression. Two sets of analyses were carried out: demographically adjusted from 1982 to 1996; and demographically and disadvantage adjusted from 1992 to 1996. RESULTS: Overall, 87.7% of lung cancer and 17.8% of breast cancer patients were deceased by five years. Lung and breast cancer patients treated in rural hospitals had higher mortality rates (1992-1996: relative risk (RR) 1.24, 95% confidence interval (CI) 1.07-1.44, and RR 1.20, 95% CI 0.92-1.56, respectively; 1982-1996: RR 1.20, 95% CI 1.11-1.30, and RR 1.19, 95% CI 1.06-1.33, respectively), whereas location of residence had little effect. Lung and breast cancer patients treated in private hospitals had lower mortality (1992-1996: RR 0.85, 95% CI 0.76-0.95, and RR 0.90, 95% CI 0.77-1.05, respectively; 1982-1996: RR 0.91, 95% CI 0.84-0.97, and RR 0.92, 95% CI 0.85-0.99, respectively), although insurance status was not a factor. Women with breast cancer had significantly worse survival in the more socio-economically disadvantaged groups (1992-1996: RR 1.41 to 1.26; 1982-1996: RR 1.45 to 1.29). CONCLUSIONS: Survival was poorer in patients treated in the public hospital system, but the possession of private health insurance was not predictive of better outcomes. People treated in rural hospitals had worse survival, whereas location of residence was not an independent factor. Women in more socio-economically advantaged groups who underwent breast cancer surgery had improved survival.

Aged↗
PubMed2002

The discursive properties of "hope": a qualitative analysis of cancer patients' speech.

The authors of this article question the usefulness of the empirico-realist search for a definitive definition of hope. Semistructured interviews on "do-not-resuscitate" issues with 23 oncology clinic outpatients were tape-recorded, transcribed, and analyzed following grounded-theory methodology and discursive analytical methodology. Twelve patients spontaneously spoke about hope as objective or subjective, a burden or a resource. Hope represented an evaluation of empirical states of affairs or the wish for desired outcomes and was a warrant for action or an excuse for inaction. It was attributed to both patient and caregiver, to individuals or situations. Hope was present or future oriented, both vulnerable and enduring. The variety of versions of hope has implications for interactions between health care workers and patients. Recognizing a taxonomy of hope might prove more useful than searching for definitions.

Adaptation, Psychological↗
PubMed1996

Fats for the food industry: implications for cholesterol-lowering.

The special needs of the food industry may not always coincide with what is healthiest for consumers. People always demand optimal taste, flavor and texture; they expect shelf-stability, convenience and novelty. The edible oils and fat industry has been particularly vulnerable in this regard but has tried, often very successfully, to modify its products to take into account the customer's preferences and their health. The following review illustrates some potential strategies in the retail and commercial sectors, especially in baking, frying and food service areas. Given the large increase in the consumption of convenient, small portion meals, the fat content and composition of such meals and products will critically influence further outcomes in areas related to cardiovascular disease, cancer, obesity and diabetes.

Animals↗
PubMed2004

A possible case of Werner syndrome presenting with multiple cancers.

The treatment of a man with six metachronous primary cancers is described. The primary lesions were in the soft palate, both edges of the tongue, the hard palate, the esophagus, and the right ureter. Pathologically, all of the first five tumors in the head and neck and esophagus were proven to be squamous cell carcinoma with various grades of differentiation, and the last one was transitional cell carcinoma. The cancers were found in the early clinical stage, and were completely controlled one by one except for the ureteral tumor under treatment. His characteristic medical history and physical findings, i.e. bilateral cataracts, short stature, baldness, diabetes mellitus, high-pitched voice, and multiple malignancies, met the clinical criteria for possible Werner syndrome, a genetic premature aging disorder, though the possibility of phenocopy of this syndrome has not been ruled out. We have followed him carefully because he might be vulnerable to malignant tumor formation.

Aged↗
PubMed2005

Aging: gene silencing or gene activation?

According to the author's theory of gene silencing, the key process in aging involves reduced expression of a number of genes. Silencing of genes has a complex mechanism, which involves methylation of DNA, histone modification and chromatin remodeling. In addition to deacetylation of the histones and methylation of DNA, recently described RNAi mechanism could initiate formation of silenced chromatin. Hypermethylation of the promoter will silence the gene. Genome-wide hypomethylation will induce genomic instability, amplification of oncogenes and also silencing of the genes through RNAi mechanism. Studies by different groups, conducted in yeast, worms, flies and mice, confirmed substantial changes in gene expression in aging. Among them, the most important was silencing of tumor suppressors and other genes involved in the control of cell cycle, apoptosis, detoxification, and cholesterol metabolism. There was also increased expression of the smaller group of oncogenes and other genes which are associated with typical diseases of old age. Caloric restriction normalizes expression of a substantial percentage of these genes. Animal studies confirmed importance of caloric restriction, which decreases signaling through the IGF-1/AKT pathway and expression of gene p53. These studies, however, cannot be directly applied to human aging. It is proposed that age management therapy should attempt to normalize gene expression in the older population to the level typical for young adults. This would require activation of silenced genes and normalization of overexpressed genes. Caloric restriction and exercise are helpful in decreasing the activity of important oncogenes and activation of silenced tumor suppressors, and may have a positive impact, not only on aging, but also on prevention of cancer. Dietary supplements containing phytochemicals should normalize increased expression of oncogenes. Examples are: genistein and EGCG, which effect signaling through the IGF-1/AKT pathway and resveratrol and limonen, which do so through the RAS pathway. A group of amino acid derivatives and organic acids of animal and human origin should activate silenced tumor suppressor genes (Aminocare A10, Aminocare Extra). Among them 3-phenylacetylamino-2, 6-piperidinedione intercalates specifically with DNA and protects sequences of tumor suppressor genes, which are vulnerable to the effects of carcinogens. Phenylacetate activates p53 and p21 through inhibition of methyltransferase and farnesylation of the RAS protein. Phenylbutyrate activates tumor suppressor genes through inhibition of histone deacetylation. Phenylacetylglutamine decreases genomic instability and expression of oncogenes and promotes apoptosis. The application of DNA microarray techniques to human studies should provide more information about differences in gene expression in different age groups and help design more effective age management regimens.

Adaptation, Physiological↗
PubMed1975

5-Hydroxytryptamine and pain modulation in man: a clinical pharmacological approach with tryptophan and parachlorophenylalanine.

Monoamines are involved in the central nervous assimilation and modulation of the pain flow. According to a personal hypothesis, a disorder of this biochemical control (in particular a precariousness of brain 5-hydroxytryptamine turnover), is the basic mechanism of some painful conditions, such as migraine and other essential headaches. Acute (infusion) and chronic (ingestion) administration of tryptophan to migraine-headache sufferers improved the clinical course significantly in respect to placebo. Few patients with untractable pain from disseminated cancer received daily infusion of tryptophan and ingested a few gr of this amnioacid: improvement of pain and reduction of morphine necessity was observed. Parachlorophenylalanine chronic administration in migraine-headache sufferers lowered the pain threshold so far as to provoke (in 20% of cases) spontaneous pains in the trunk, legs and arms. This systemic pain syndrome was promptly reversible by discontinuing the treatment. Spontaneous pain syndrome was not reported by others in the healthy subject; this suggests an apparent vulnerability of 5HT turnover in essential headaches.

5-Hydroxytryptophan↗
PubMed1989

Cerebral shift after lateral craniofacial resection and flap reconstruction.

The biomechanical effects on the cranial contents after craniectomy and immediate soft-tissue flap reconstruction are substantial and potentially life threatening. Once the rigid protective covering of the skull is removed, the cerebral component of the cranial contents is vulnerable to rising extrinsic pressure. Intracranial pressure falls, brain compliance rises, and contralateral cerebral shift may occur by virtue of the craniectomy alone. However, if flaps filling the defect should compress by weight or swelling, even greater midline or craniocaudal shift of the brain may occur. We present three cases in which midline cerebral shift was documented by CT scan after flap reconstruction of lateral craniofacial/craniotemporal resection. Three other patients undergoing anterior craniofacial resection during the same time period for skin cancer (one patient) and esthesioneuroblastoma (two patients) had no shift in intracerebral contents. Symptomatic or asymptomatic intracranial shift may occur soon after substantial craniectomy and soft-tissue flap reconstruction. Midline shift from lateral resection and reconstruction is more likely than anteroposterior shift from anterior craniofacial resection. Strategies for minimizing this compression or shift are described.

Adolescent↗
PubMed2002

A brief assessment of concerns associated with genetic testing for cancer: the Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire.

The Multidimensional Impact of Cancer Risk Assessment (MICRA) is a new tool to measure the specific impact of result disclosure after genetic testing. The authors compared its performance with that of questionnaires measuring general and cancer-specific distress. Participants (158 women) responded 1 month after they received genetic test results. The women were divided into 4 standard clinical test result groups: BRCA1/2 positive, BRCA1/2 negative, panel negative, and true negative. Factor analysis supported the formation of 3 subscales: Distress (6 items, alpha = .86), Uncertainty (9 items, alpha = .77), and Positive Experiences (4 items, alpha = .75). All 3 MICRA subscales differentiated participants who were BRCA1/2 positive from the other 3 groups. MICRA thus helps identify subgroups of vulnerable genetic testing participants.

Adult↗