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PubMed1992

[Immunology and psychiatry].

This review of scientific literature comes within the interest arisen from ten years by psychoneuroimmunology, a field connecting several disciplines and illustrating in a new way the psychosomatic relationships. A first category of works has been dedicated to the study of psychiatric disorders associated with various diseases concerning immunity (systemic diseases, endocrine diseases, cancers, infectious diseases), but also to the possible effect of distressing life events on the upset activation of immune functions, or even to the discovery of predisposing personality profiles (type C profile, depressive vulnerability). A second category of works concerns the analysis of the immune disturbances associated with certain psychiatric diseases, such as depression or schizophrenia, but also with some distressing life conditions, like bereavement. Animal experimentation and human experimentation provide various informations on the factors conditioning the immunomodulating effects of stress, sometimes in the direction of an inhibition, sometimes in the direction of an activation of immune functions. Finally, several papers shed light on the immunomodulating effects of psychotropic drugs. All these works open new horizons to the scientific knowledge and let us glimpse an extension to the use of psychologic therapeutics, as well of pharmacological ones as of non pharmacological.

Autoimmune Diseases↗
PubMed2004

Music therapy's relevance in a cancer hospital researched through a constructivist lens.

The constructivist research paradigm informed a research investigation on the relevance of music therapy in a cancer hospital, that is, what did the music therapy do and did it help? Over 3 months, criterion sampling was used to elicit interpretations in 5 studies from 5 sources: 128 patients who participated, 27 patients who overheard or witnessed music therapy, 41 visitors, 61 staff, and the music therapist-researcher. Fifty-seven percent of the patients who participated had advanced or end stage cancer. The music therapist's interpretations were recorded in a reflexive clinical journal and the respondents' interpretations were written on anonymous open-ended questionnaires. Thematic and content analyses were performed on the 5 groups of data with the support of qualitative data management software. Findings from the 5 data groups were contrasted and compared. Many patients', visitors' and staff members' affective, contemplative, and imagined moments in music therapy affirmed their "aliveness," resonating with an expanded consciousness, in a context where life's vulnerability is constantly apparent. Philosophical depictions about the relevance of music in human life, including theories by Addis and Winnicott, substantiated the therapeutic reactions.

Aged↗
PubMed2004

Same old story? Do we need to modify our supportive care treatment of elderly cancer patients? Focus on antiemetics.

The incidence of cancer is highest among individuals > or =65 years of age. Physiological changes associated with aging, such as cognitive decline, renal and hepatic dysfunction, can often complicate treatment options, and the elderly represent a particular challenge to the oncologist because of the high incidence of comorbidity and polypharmacy. Effective supportive care is of particular importance in elderly cancer patients as they may recover less satisfactorily if adverse events are poorly controlled. Nevertheless, evidence suggests that supportive care agents, for example, antiemetics, are underutilised in this patient population. Chemotherapy and radiotherapy regimens are frequently associated with nausea and vomiting--symptoms that can have deleterious effects on vulnerable patients if not adequately managed. The serotonin 5-HT3-receptor antagonists represent a class of antiemetics that are currently regarded as the gold standard treatment for chemotherapy- and radiotherapy-induced nausea and vomiting. They are recommended as first-line treatment for patients at moderate-to-high risk of emesis. However, antiemetic guidelines do not differentiate between these agents and, more importantly, do not contain specific recommendations for the elderly. Pharmacological differences exist between the commonly available 5-HT3-receptor antagonists (dolasetron, granisetron, ondansetron, tropisetron and palonosetron), namely receptor sensitivity, duration of action, metabolism and tolerability profile. Of particular concern with prescriptions to elderly cancer patients is the convenience of once-daily administration, the low potential for drug-drug interactions and cardiovascular adverse effect profile. Moreover, the addition of the newly approved neurokinin NK1-receptor antagonist aprepitant to the choice of antiemetic regimen may complicate therapy and exacerbate the drug-drug interaction risk in elderly patients. Therefore, the use of antiemetics that are well tolerated and with the lowest risk of drug-drug interactions is imperative in this patient population and will enable even those patients with several comorbidities and a high level of polypharmacy to receive effective antiemetic therapy.

Aged↗
PubMed1985

Age-related changes in immunologic and hormonal activities.

The immune system has been a focus of intensive gerontological research, because it appears to be involved in many deleterious diseases associated with ageing, including cancer, and because the likelihood of successful therapeutic strategies for altered immune functions in the elderly is high. Research efforts have been centred on two levels of biological complexity--the cell and the organism. At the cellular level, emphasis has been on the nature of the alteration in immune functions with age, and, at the level of the organism, whether the diseases associated with immunological dysfunction of elderly individuals can be controlled by immunomodulation. We discuss age-related changes at the cellular level with emphasis on qualitative changes in the antigen/mitogen responsive cells with respect to production of and response to hormones. We then consider whether ageing 'hot spots' exist along the differentiation vector of antigen/mitogen responsive cells; i.e., whether immune cells are vulnerable to ageing only at certain stages of their differentiation processes. We conclude by considering the use of tissue grafting and chemical treatment, the two most encouraging methods of immunopotentiation at the level of the organism, as an option in modulating resistance of old individuals to cancer.

Aging↗
PubMed1977

Clinical trials of adjuvant radiation therapy for breast cancer.

Years ago, radiation therapists conducted randomized clinical trials which showed that regional irradiation significantly reduces local recurrence of breast cancer but does not often affect life span. No new findings challenge these conclusions. Controlled trials in general have lost some credibility, however, as it has become more widely recognized that they are very vulnerable to fallacious reasoning and to simple human error. There is serious concern that some physicians may be unwisely abandoning well tested treatment methods because of the premature dissemination of early results of some trials. Still, many important questions remain that can only be answered by clinical trials, some including radiation therapy. This paper suggests that randomization schemes be incorporated into "routine" medical practice, although only after the most careful deliberation, in order to hasten fuller understanding of old therapeutic methods as well as new ones.

Breast Neoplasms↗
PubMed1989

A longitudinal analysis of psychological adaptation among survivors of cancer.

This longitudinal study examined the psychological adaptation of newly diagnosed cancer patients. Findings showed a decline in patient's mental health status over time. Initial psychological status and other psychosocial factors, and not illness-related factors, were predictive of subsequent adaptation. Two psychologically vulnerable patient groups were identified: those who remained distressed over time and those whose mental health status declined over time.

Adaptation, Psychological↗
PubMed1988

Postdischarge distress in surgically treated cancer patients and their spouses.

Temporal patterns of distress among two groups of nonterminally ill, surgically treated cancer patients (n = 40) and their spouses (n = 40) during the immediate pre- and postdischarge period were studied. Data about problems encountered and standardized measures of distress (State Anxiety Index, Brief Symptom Index, and Vulnerability Index) were obtained before hospital discharge and at 10, 30, 60, 90, and 180 days postdischarge. The intensity of distress experienced by patients and spouses was remarkably similar, although the temporal pattern of occurrence was significantly different. Prior to discharge, spouse anxiety was significantly higher than that of the patients and above the norm for hospitalized persons. Spouses were least distressed after 10 days at home, but thereafter experienced a rise in vulnerability culminating in observable clinical depression at 90 and 180 days. Peak distress for the patients occurred 10 days after discharge as a function of physical symptoms that were unexpected or more severe than anticipated. Patients with ostomies (n = 20) were slower to return to pre-illness functional levels and had somewhat more psychological distress than nonostomy patients.

Depression↗
PubMed1999

Community-based promotion of breast screening using small group education.

Small Group Education (SGE) to promote breast cancer screening was implemented in a community-wide program. Based on diffusion of innovations theory, SGE initially was directed toward women at higher occupation and education levels and then progressively shifted toward more vulnerable populations of women at risk of not getting screening. During the four-year intervention, 116 volunteers led SGE presentations, with 8,184 women participating in 740 groups at work sites, organizations, residences, and churches. High participation in SGE and positive participant responses suggest that delivery of SGE using a social diffusion model was an effective method for reaching women throughout the community.

Adult↗
PubMed1998

Why do dyspeptic patients over the age of 50 consult their general practitioner? A qualitative investigation of health beliefs relating to dyspepsia.

BACKGROUND: The prognosis of late-diagnosed gastric cancer is poor, yet less than half of dyspeptic patients consult their general practitioner (GP). AIM: To construct an explanatory model of the decision to consult with dyspepsia in older patients. METHOD: A total of 75 patients over the age of 50 years who had consulted with dyspepsia at one of two inner city general practices were invited to an in-depth interview. The interviews were taped, transcribed, and analysed using the computer software NUD.IST, according to the principles of grounded theory. RESULTS: Altogether, 31 interviews were conducted. The perceived threat of cancer and the need for reassurance were key influences on the decision to consult. Cues such as a change in symptoms were important in prompting a re-evaluation of the likely cause. Personal vulnerability to serious illness was often mentioned in the context of family or friends' experience, but tempered by an individual's life expectations. CONCLUSION: Most patients who had delayed consultation put their symptoms down to 'old age' or 'spicy food'. However, a significant minority were fatalistic, suspecting the worst but fearing medical interventions.

Aged↗
PubMed1996

Lipid metabolism as a target for brain cancer therapy: synergistic activity of lovastatin and sodium phenylacetate against human glioma cells.

Malignant gliomas, the most common form of primary brain tumors, are highly dependent on the mevalonate (MVA) pathway for the synthesis of lipid moieties critical to cell replication. Human glioblastoma cells were found to be uniquely vulnerable to growth arrest by lovastatin, a competitive inhibitor of the enzyme regulating MVA synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase. The sodium salt of phenylacetic acid (NaPA), an inhibitor of MVA-pyrophosphate decarboxylase, the enzyme that controls MVA use, acted synergistically with lovastatin to suppress malignant growth. When used at pharmacologically attainable concentrations, the two compounds induced profound cytostasis and loss of malignant properties such as invasiveness and expression of the transforming growth factor-beta 2 gene, coding for a potent immunosuppressive cytokine. Supplementation with exogenous ubiquinone, an end product of the MVA pathway, failed to rescue the cells, suggesting that decreased synthesis of intermediary products are responsible for the antitumor effects observed. In addition to blocking the MVA pathway, lovastatin alone and in combination with NaPA increased the expression of the peroxisome proliferator-activated receptor, a transcription factor implicated in the control of lipid metabolism, cell growth, and differentiation. Our results indicate that targeting lipid metabolism with lovastatin, used alone or in combination with the aromatic fatty acid NaPA, may offer a novel approach to the treatment of malignant gliomas.

Antimetabolites, Antineoplastic↗
PubMed2006

Cryptobiosis, aging, and cancer: yin-yang balancing of signaling networks.

Some organisms adapt to persistent and severe stress by reversibly adjusting life-death balance to a new equilibrium, e.g., anhydrobiosis ("life without water") enables survival in a quiescent state on extreme desiccation. Aging is characterized by declining response and increasing vulnerability to stress, and the balance slowly, and irreversibly, tilts toward death. Although tumorigenesis tips the balance of cells to prolonged life, paradoxically it can cause organismal death. At the molecular level, all these phenomena involve complex signaling pathways, but it is highly likely that the overall balance of signaling outcomes, rather than individual signals themselves, plays the pivotal role in life-death decisions.

Aging↗
PubMed2002

Intersections between neurobiology and oncology: tumor origin, treatment and repair of treatment-associated damage.

The number of potentially intimate relationships between brain tumors and the precursor cells that contribute to normal central nervous system (CNS) development and repair now appears to be somewhat larger than would have been anticipated only a few years ago. It also appears that understanding the vulnerabilities of CNS precursor cells, and of the specific cells that they generate, might help us to reveal the biological basis for the cognitive impairment that is increasingly recognized as an adverse effect of systemic cancer therapies. Using neural stem cells as therapeutic vehicles in the treatment of brain tumors could be modified to allow repair of the damage caused by brain tumors themselves and of the neurological impairment that is frequently associated with traditional cancer treatment approaches.

Animals↗
PubMed2004

Decisions and outcomes of genetic testing for inherited breast cancer risk.

Since the discovery of breast cancer susceptibility genes and the availability of genetic testing, a substantial amount of research has been conducted to evaluate rates of genetic test acceptance and to understand the psychological and behavioral impact of BRCA1 and BRCA2 (BRCA1/2) genetic test results. This article explores findings related to genetic test acceptance for inherited breast cancer risk and the impact of genetic test results on psychological functioning, cancer prevention and control behaviors, and family communication about genetic testing. Overall, rates of genetic test acceptance were lower than anticipated based on interest in genetic testing reported in early research. While there is limited evidence that genetic testing generates adverse psychological effects, receiving positive BRCA1/2 test results may cause emotional reactions and concerns that are specific to such results. Although early reports suggested that receiving positive BRCA1/2 test results may have a limited impact on cancer screening or prevention behaviors, recent studies have shown that genetic testing for inherited breast cancer risk may increase screening behaviors among mutation carriers. However, utilization of some screening tests remains low among mutation carriers. Additional studies are needed to identify subgroups of participants in genetic testing who may be vulnerable to experiencing testing-specific concerns, and to evaluate the effects of interventions designed to promote behavioral change and address other concerns that may be generated by receiving positive BRCA1/2 test results.

BRCA1 Protein↗
PubMed1992

Epidemiology of cervical cancer--overview.

Numerous studies of the epidemiology of cervical cancer have shown strong associations with religious, marital and sexual patterns. Although it is well established that women with multiple partners and early ages at first intercourse are at high risk, less is known about how these factors interact or how risk is affected by specific sexual characteristics. Recent studies indicate that number of steady partners and frequent intercourse at early ages may further enhance risk, supporting hypotheses regarding a vulnerable period of the cervix and a need for repeated exposure to an infectious agent. It is now widely accepted that HPV is the major infectious etiological agent, but whether other infectious agents play supportive or interactive roles is unclear. Of specific interest is the independent effect of HSV 2 on risk, especially given some evidence that this viral agent may interact with HPV. Other speculative risk factors for cervical cancer include cigarette smoking, oral contraceptive usage and certain nutritional deficiencies, but again it is not clear whether these factors operate independently from HPV. Although cervical cancer incidence trends correlate with the population prevalence of various venereally transmitted agents, it is not certain how disease rates are affected by other potential risk factors which have changed during recent time (e.g., exposure to HPV, sexual behaviour, cigarette smoking). In addition, a number of recent studies highlight the need for considering not only female influences on risk of cervical cancer, but also male factors, since the sexual behaviour of the male consort appears to play an important role.

Europe↗
PubMed2003

Stimulation of CD40 inhibits Fas- or chemotherapy-mediated apoptosis and increases cell motility in human gastric carcinoma cells.

The widespread expression of CD40, a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, is likely to account for the central role of CD40 in the regulation of humoral immunity and host defense. Interestingly, the expression of the CD40 in various types of carcinoma cells was often observed and conveys signals regulating diverse cellular responses, ranging from proliferation to growth suppression. Thus, the biologic role of the CD40-CD40L interaction in solid tumors is still controversial. In this study, we investigated the expression and function of the CD40 in gastric carcinoma cells. In 3-4,5 dimethylthiozol-2-yl-2,5-diphenyl tetrazolium bromide (MTT) assay and Annexin V/propidium iodide staining, CD40 stimulation using a soluble form of CD40 ligand did not affect cell viability, but significantly inhibited Fas-mediated or chemotherapy-mediated apoptosis in three CD40-positive gastric cancer cell lines. Moreover, in migration assay, CD40 stimulation induced an elevation of cell motility in CD40-positive gastric carcinoma cells. Our results show that the CD40 expression on gastric carcinoma makes cells less vulnerable to apoptosis induced by Fas or chemotherapy. These results suggest that the CD40 expression on gastric carcinoma may be associated with cell survival and elevation of cell motility.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Effects of environmental exposures on the cardiovascular system: prenatal period through adolescence.

Exposures to drugs, chemical and biological agents, therapeutic radiation, and other factors before and after birth can lead to pediatric or adult cardiovascular anomalies. Furthermore, nutritional deficiencies in the perinatal period can cause cardiovascular anomalies. These anomalies may affect heart structure, the conduction system, the myocardium, blood pressure, or cholesterol metabolism. Developmental periods before and after birth are associated with different types of risks. The embryonic period is the critical window of vulnerability for congenital malformations. The fetal period seems to have lifelong effects on coronary heart disease and its precursors. During the weeks immediately after birth, susceptibility to myocardial damage seems to be high. Exposure to cancer chemotherapy or radiotherapy in childhood raises the risk of long-term progressive left ventricular dysfunction and other cardiovascular problems. In childhood and adolescence, use of recreational drugs such as cocaine and tobacco poses cardiovascular dangers as well. Where evidence about environmental exposures is limited, we have included models of disease and other exposures that are suggestive of the potential impact of environmental exposures.

Adolescent↗