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PubMed2001

Pain in nursing home residents: management strategies.

Pain is prevalent and undertreated in nursing home residents, despite the existing wide array of effective pharmacological and nonpharmacological treatment modalities. In order to improve the quality of life of these vulnerable individuals, practitioners require education about the correct approach to assessment and management. Assessment should be comprehensive, taking into account the basic underlying pathology (e.g. osteoarthritis, osteoporosis, peripheral neuropathy, fibromyalgia, cancer) as well as other contributory pathology (e.g. muscle spasm, myofascial pain) and modifying comorbidities (e.g. depression, anxiety, fear, sleep disturbance). Pharmacological management should be guided by a stepped-care approach, modelled after that recommended by the World Health Organization for treatment of cancer pain. Nonopioid and opioid analgesics are the cornerstone of pharmacological pain management. Tricyclic antidepressants and anticonvulsants can be very effective for the treatment of certain types of neuropathic pain. In addition to treating the pain per se, attention should be given to prevention of disease progression and exacerbation, as maintaining function is of prime importance. Nursing home residents with severe dementia challenge the practitioner's pain assessment skills; an empirical approach to treatment may sometimes be warranted. The success of treatment should be measured by improvement in pain intensity as well as physical, psychosocial and cognitive function. Effective pain management may impact any or all of these functional domains and, therefore, substantially improve the nursing home resident's quality of life.

Aged↗
PubMed1987

Suicide in cancer patients.

Identifying the cancer patient who is at increased risk for suicide is the first step in prevention, and allows for appropriate psychosocial interventions to be initiated. The author presents a list of vulnerability factors that contribute to high suicide potential.

Aged↗
PubMed1994

Ethical issues in palliative care research.

During the last 10 years interest in palliative care research has grown. This interest has brought about an awareness of the unique ethical issues related to research in this special population. Issues related to the vulnerability of patients and families, consent protocols, unstable mental status, and the invasiveness of assessments have been discussed. Unfortunately, devastating physical and psychosocial distress continue to afflict the majority of cancer patients before death. Although our current knowledge of palliative care allows us to help a significant number of patients and families, there are a number of symptoms that are currently intractable. Further, a 50% increase in the number of cancer deaths in Canada is expected between 1990 and the year 2000 (11). Therefore, one of the major ethical issues we must confront during the coming decade is whether we can afford not to make a major commitment to research in palliative care. We are aware that maintaining the status quo of patient care is unacceptable. However, until now, administrators, governments, and clinicians have planned palliative care programs to have only service and some teaching components. And traditional research-sponsoring agencies have not allocated priority to palliative care in their funding strategies. The palliative care community must take the initiative in this debate.

Ethics, Medical↗
PubMed1991

Adolescent smoking and perceived vulnerability to smoking-related causes of death.

Tested adolescent smokers' perceptions of risk for smoking-related causes of death in comparison to nonsmoking peers. 408 high school Ss (11% regular smokers, 15% occasional smokers) estimated the likelihood of personal death from cancer, emphysema, and stroke. Smokers did not differ from nonsmokers on perceived risks for smoking-related deaths. Smokers and nonsmokers perceived the odds of dying from cancer as high but, unrealistically, smokers did not view it as higher than nonsmokers. Regular smokers who report high exposure to news appear to minimize the risks for cancer and stroke deaths. High sensation-seeking tendencies led to lower perceived risks for males but not for females. The "invulnerability syndrome" is discussed in relationship to adolescents' risk perceptions.

Adolescent↗
PubMed1990

How to kill cancer cells: membranes and cell signaling as targets in cancer chemotherapy.

Most approaches to cancer chemotherapy have centered around the idea that cytotoxic drugs can be used to eradicate proliferating neoplastic cells. Cytotoxicity is generally thought to evolve from the presence of drug-induced damage to the genetic material, and DNA has served admirably as a primary focus for drug development. Other cellular targets should also be vulnerable, however, and over the past decade the plasma membrane in particular has received considerable attention as a therapeutic locus. In the early stages of this work there were only vague notions as to how membrane disruption could lead to cell death, but recent thinking has coalesced around the idea that cell-surface signal transduction and growth control pathways represent an ideal target for the rational development of new cancer therapies. In this review, we discuss three aspects of signal transduction-phosphoinositide turnover, phosphorylation by protein kinase C, and phosphorylation by protein tyrosine kinases--and summarize the existing evidence that these vital processes can be specifically disrupted, and that such pharmacology offers rich prospects for future therapeutic design.

Humans↗
PubMed2001

Safety aspects of acupuncture in palliative care.

Acupuncture can mask symptoms of cancer and tumour progression. It is not safe to use such a therapy without full knowledge of the clinical stage of the disease, and the current status of orthodox therapy. Contraindications to acupuncture needling include an unstable spine, severe clotting disorder, neutropenia and lymphoedema. Whilst semi-permanent needles are used increasingly in symptom control and pain management they should not be used in patients with valvular heart disease or in vulnerable neutropenic patients. Acupuncture has an increasing role in support for pain and symptom management, but patients should not be advised to abandon conventional treatments in favour of complementary or alternative therapies alone, and should not have their hopes raised inappropriately, or have any guilt projected on to them for the cause of their cancer.

Acupuncture Therapy↗
PubMed1987

Preliminary studies on a more effective phototoxic agent than hematoporphyrin.

Phototoxicity of benzoporphyrin derivative (BPD) has been tested in vitro and compared with that of hematoporphyrin (HP). After 1-hour activation with visible light, BPD was 10 times more cytotoxic than HP toward human adherent cell lines: A549 lung cancer, Calu-1 lung carcinoma, and CCD-19Lu normal lung, killing 100% of cells at the concentration of 70 ng/ml. Under the same conditions, BPD was 10-70 times more cytotoxic than HP toward nonadherent cells and cell lines. Tested were human leukemia cell lines HL60, K562, and KG1, normal human lymphocytes, and mouse mastocytoma cell line P815. The concentrations required to kill 100% of cells varied between 10 and 500 ng BPD/ml and between 0.2 and 10 micrograms HP/ml. The difference between the nonadherent cell lines in respect to their sensitivity to phototoxicity of both BPD and HP seemed to be related to the cell sizes, with the smallest cells being the most vulnerable. The most attractive characteristic of BPD in addition to its powerful phototoxicity is its maximum absorption around 700 nm, which is in the range of wavelengths penetrating tissues the best. This characteristic alone could make BPD a drug of choice in cancer photodynamic therapy when the safety of its use is ensured. Preliminary tests in vivo have shown that DBA/2J mice can tolerate a single ip injection of 20-60 micrograms BPD as well as the same dose of HP. The biodistribution and toxicity studies of BPD are under way in our laboratory.

Animals↗
PubMed2006

Increased health risk in Bangkok children exposed to polycyclic aromatic hydrocarbons from traffic-related sources.

The aim of this study is to assess potential health risk of exposure to particle-associated polycyclic aromatic hydrocarbons (PAHs) in children living in a megacity with traffic congestion such as Bangkok. The study population comprised 184 Thai schoolboys (aged 8-13 years) attending schools adjacent to high-density traffic areas in Bangkok and schools located in the provincial area of Chonburi. The ambient concentration of total PAHs at roadsides in proximity to the Bangkok schools was 30-fold greater than at roadsides in proximity to the provincial schools (30.39 +/- 5.80 versus 1.50 +/- 0.28 ng/m(3); P < 0.001). Benzo(g,h,i)perylene (BghiP), an indicator of automobile exhaust emission, was the predominant PAH. Personal exposure to total PAHs and the corresponding benzo(a)pyrene (BaP) equivalent concentrations in Bangkok schoolchildren were 3.5-fold higher than in provincial schoolchildren (4.13 +/- 0.21 versus 1.18 +/- 0.09 ng/m(3); P < 0.001 and 1.50 +/- 0.12 versus 0.43 +/- 0.05 ng/m(3); P < 0.001, respectively). The concentration of urinary 1-hydroxypyrene (1-HOP) was significantly higher in Bangkok schoolchildren. Bulky carcinogen-DNA adduct levels in peripheral lymphocytes were also significantly higher (0.45 +/- 0.03 versus 0.09 +/- 0.00 adducts/10(8) nt; P < 0.001). Finally, a significantly higher level of DNA strand breaks and a significantly lower level of DNA repair capacity were observed in Bangkok schoolchildren (P < 0.001). This study indicates that Bangkok schoolchildren exposed to a high level of genotoxic PAHs in ambient air may be more vulnerable to the health impacts associated with the exposure to genotoxic pollutants than children in provincial areas and may have increased health risks for the development of certain diseases such as cancer.

Adolescent↗
PubMed2005

Psychiatric disorders and mental health service use among caregivers of advanced cancer patients.

PURPOSE: Despite research demonstrating the psychological burden of caregiving for advanced cancer patients, limited information exists on the prevalence of psychiatric disorders and mental health service use among these informal caregivers. METHODS: Two hundred informal caregivers of advanced cancer patients were interviewed and administered the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition and an assessment of mental health service use. RESULTS: Thirteen percent of caregivers met criteria for a psychiatric disorder; 25% accessed treatment for mental health concerns since the patient's cancer diagnosis. The frequencies of current psychiatric disorders were as follows: panic disorder, 8.0% (95% CI, 4.6% to 12.7%), major depressive disorder, 4.5% (95% CI, 2.1% to 8.4%), post-traumatic stress disorder, 4.0% (95% CI, 1.7% to 7.7%), and generalized anxiety disorder, 3.5% (95% CI, 1.4% to 7.1%). Among caregivers with a current psychiatric disorder, 81% discussed mental health concerns with a health professional before the patient's cancer diagnosis compared with 46% after the diagnosis (McNemar test = 5.40; P = .02). Only 46% of caregivers with a current psychiatric disorder accessed mental health services. Caregivers who discussed mental health concerns with a clinician before the patient's cancer diagnosis (odds ratio [OR] = 3.51; 95% CI, 1.42 to 8.71) and after the diagnosis (OR = 21.23; 95% CI, 9.02 to 49.94) were more likely than caregivers not having these discussions to receive mental health services. CONCLUSION: Many caregivers of advanced cancer patients either meet criteria or are being treated for psychiatric problems. Discussing mental health issues positively influences the receipt of mental health services and should be actively pursued in this vulnerable population.

Adult↗
PubMed2003

IACM 2nd Conference on Cannabinoids in Medicine.

The International Association for Cannabis as Medicine 2nd Conference on Cannabinoids in Medicine focused on new clinical research with cannabis and single cannabinoids (Delta(9)-tetrahydrocannabinol, CT-3) and on animal research with possible therapeutic implications. The meeting brought together basic researchers, clinicians and physicians to facilitate an exchange of knowledge and experience in this field. Even a talk by a patient with multiple sclerosis was included in a workshop on neurology. Current clinical research with cannabinoids focuses mainly on chronic pain and neurological disorders adding to accepted indications such as anorexia in AIDS-wasting and antiemetic effects in cancer chemotherapy. First results are promising and larger studies are underway or have recently been completed and are awaiting publication. New basic research opens further areas of possible uses for modulators of the endogenous cannabinoid system, including osteoporosis, cancer and inflammation. A workshop on psychiatry focused on effects of cannabis use on onset, incidence and the course of schizophrenia. Basic and clinical research shows that adolescents might be more vulnerable than adults to possible psychiatric effects of cannabinoids. It was concluded that possible side effects of cannabinoids should be taken into account but do not preclude a legitimate medical use.

Cannabinoids↗
PubMed1998

Increased cell proliferation characterizes Crohn's disease.

Patients with long-standing Crohn's disease (CD), a chronic inflammatory intestinal disease, are at increased risk for intestinal cancer. The neoplasia likely results, in part, from deregulated cell proliferation, which allows mutations to become fixed in the crypt progenitor cells. We postulated that tissues derived from patients with CD would exhibit increased mucosal proliferation. Therefore, we examined specimens from 27 consecutive patients with chronic CD with a monoclonal antibody directed against the proliferation marker, Ki-67. The tissues were evaluated histologically, and the Ki-67 immunostaining patterns were recorded. The antibody to Ki-67 stained the bases of the crypts in both the small and large intestines. The mean number of Ki-67 immunoreactive cells in the normal crypt was 34.1 versus 95.1 in the regenerative mucosa and O in areas of pyloric metaplasia (P < .00001). Ki-67 staining of the mucosa of patients with CD confirmed that cell proliferation is markedly increased and that the replicating compartment of each crypt during regeneration is expanded. We concluded that the increased cell proliferation might predispose the mucosa to mutational events, thereby increasing the cancer risk in these patients. The lack of proliferation in areas of pyloric metaplasia might represent a mucosal adaptive response of the lower crypt that decreases the number of cycling cells vulnerable to genetic damage. Furthermore, growth factors produced by these cells might promote healing of the damaged mucosa.

Adult↗
PubMed2001

Differential expression of manganese superoxide dismutase and catalase in lung cancer.

Reactive oxygen species (ROS) are important in the initiation and promotion of cells to neoplastic growth. In this context, cigarette smoke exposure, the primary risk factor in lung cancer development, leads to high levels of ROS within the human airway. Although well-equipped with an integrated antioxidant defense system consisting of low-molecular weight antioxidants such as glutathione and intracellular enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, the lungs are vulnerable to increased endogenous and exogenous oxidative insults. Antioxidants increase in response to oxidative stress and minimize ROS-induced injury in experimental systems, indicating that antioxidant levels may determine whether ROS can initiate lung carcinogenesis. On this basis, we hypothesized that antioxidants would be decreased in lung carcinoma cells as compared with tumor-free adjacent lung tissues. Antioxidant expression was evaluated in 16 lung tumor and 21 tumor-free lung tissues collected between the years 1993 and 2001 from 24 individuals with surgically resectable non-small cell lung cancer, i.e., adenocarcinoma and squamous cell carcinoma. Total SOD activity was increased (P = 0.035), catalase activity decreased (P = 0.002), and glutathione and glutathione peroxidase were similar in tumors compared with tumor-free lung tissues. Alterations in antioxidant activities were attributable to increased manganese SOD and decreased catalase protein and mRNA expression in tumors. Immunohistochemical localization of catalase in the lung revealed decreased or no expression in the tumor cells, although healthy adjacent airway epithelial cells were strongly positive for catalase. Parallel changes in antioxidant activities, protein, and mRNA expression were noted in A549 lung carcinoma cell lines exposed to cytokines (tumor necrosis factor-alpha, interleukin 1beta, and IFN-gamma). Thus, inflammation in the lung may contribute to high levels of manganese SOD and decreased catalase, which together may lead to increased hydrogen peroxide intracellularly and create an intracellular environment favorable to DNA damage and the promotion of cancer.

Aged↗
PubMed2026

Development and characterization of triazole-based WDR5 inhibitors for the treatment of glioblastoma.

Glioblastoma (GBM) cancer stem cells (CSCs) contribute to tumor recurrence, treatment resistance, and dismal clinical outcomes. Genetic and pharmacological evidence suggests that the nuclear scaffolding protein WD-repeat containing protein 5 (WDR5) is a therapeutic vulnerability of the CSC population. However, previously reported WDR5 inhibitors display low permeability and are unable to penetrate the blood-brain barrier (BBB), limiting their utility in GBM. Herein, we report the structure-guided development of a series of triazole-based WDR5 WIN-site inhibitors designed to increase passive brain penetration. We identified triazole-based WDR5 inhibitors that are potent, passively permeable, and in some cases more brain penetrant than other scaffolds. We phenotypically assessed our WDR5 inhibitors in a panel of patient-derived CSC models and uncovered unique WDR5-regulated metabolic genes in GBM. We also evaluated their antiproliferative activity against CSCs both in vitro and in vivo. Finally, to identify potential combination opportunities, we screened a 2,100-compound chemical probe library and identified that the ATAD2 inhibitor BAY-850 synergizes with WDR5 inhibitors to enhance CSC killing. Our work diversifies the chemical matter targeting WDR5, clarifies the in vitro consequences of WIN-site inhibition in CSCs, and encourages the future development of next-generation WDR5 inhibitors with the potential to achieve in vivo efficacy in the brain.

Humans↗
PubMed2006

Model-driven approaches for in vitro combination therapy using ONYX-015 replicating oncolytic adenovirus.

Replicating genetically modified adenoviruses have shown promise as a new treatment approach against cancer. Recombinant adenoviruses replicate only in cancer cells which contain certain mutations, such as the loss of functional p53, as is the case in the virus ONYX-015. The successful entry of the viral particle into target cells is strongly dependent on the presence of the main receptor for adenovirus, the coxsackie- and adenovirus receptor (CAR). This receptor is frequently down-regulated in highly malignant cells, rendering this population less vulnerable to viral attack. It has been shown that the use of MEK inhibitors can up-regulate CAR expression, resulting in enhanced adenovirus entry into the cells. However, inhibition of MEK results in G1 cell cycle arrest, rendering infected cells temporarily unable to produce virus. This forces a tradeoff. While drug mediated up-regulation of CAR enhances virus entry into cancer cells, the consequent cell cycle arrest inhibits production of new virus particles and the replication of the virus. Optimal control-based schedules of MEK inhibitor application should increase the efficacy of this treatment, maximizing the overall tumor toxicity by exploiting the dynamics of CAR expression and viral production. We introduce a mathematical model of these dynamics and show simple optimal control based strategies which motivate this approach.

Adenoviridae↗
PubMed2006

Multiple behavioral risk factors among adolescent survivors of childhood cancer in the Survivor Health and Resilience Education (SHARE) program.

BACKGROUND: Health-compromising behaviors among survivors of childhood cancer may increase their risks of cancer recurrence and the onset of chronic disease in adulthood. Regardless of whether such behaviors occur singly or in combination with one another, multiple behavioral risk factors must be identified and addressed early to promote better health outcomes within this special population. Adolescent survivors may be especially vulnerable, as reported rates of smoking and other risky behaviors are at or near levels of their healthy peers. The psychological literature suggests stress may play a role in risk behavior initiation and maintenance, including multiple behavioral risks, and that adolescent survivors are stress-prone. This report focuses on the prevalence and co-occurrence of three behavioral risk factors (cigarette use, insufficient physical activity, and non-adherence to sun protection recommendations) and describes stress-health behavior relationships in this special population. PROCEDURE: All patients in this study (n = 75) were adolescent survivors of childhood cancer and completed a baseline assessment of their health behaviors and stress as part of a randomized controlled trial of health promotion. RESULTS: Twenty-eight percent of the patients reported one of three risk factors, 12% reported two of three risk factors, and 7% reported all three risk factors. Non-adherence to sun protection was the single most common risk factor; physical inactivity and non-adherent sun protection were the most common co-occurring risk factors. Greater age and stress were significantly associated with the presence of more behavioral risk factors. CONCLUSIONS: The evidence suggests interventions to reduce multiple health-compromising behaviors in these patients are warranted, and that efforts to address these patients' personal and family stress levels are important as well.

Adolescent↗
PubMed1986

Psychological staging of pediatric cancer patients and their families.

Advances in the treatment of childhood cancer have required a shift in our approach to the patient and family. Previously parents were helped to cope with the inevitable decline of the child's health over a rather short period of time; the child was acutely ill and crisis-oriented intervention was utilized. Today, the family unit can be helped to maintain normal life amidst intensive medical treatment; the child is acutely ill at times, but also chronically ill, and even well. Crisis intervention is still appropriate, but so is education, ego-supportive counseling, and insight-oriented psychotherapy. Psychological staging of pediatrics cancer patients and their families is essential in order to properly anticipate psychological adjustment and plan appropriate interventions. Assessment and staging require a multi-dimensional perspective including stage of disease, socioeconomic vulnerability, degree of psychopathology, family cohesion, and personal/family history. This article discusses this multi-dimensional perspective and implications for intervention. Illustrative case material is utilized.

Adaptation, Psychological↗
PubMed2005

Survivors of childhood cancer and their guardians.

BACKGROUND: Survivors of childhood cancer are at increased risk for osteoporosis, cardiovascular disease, and second malignancies-conditions for which modifiable risk factors are recognized and lifestyle interventions have shown benefit. Although some data regarding health behaviors of this population exist, receptivity to health promotion is largely unknown. METHODS: A survey was mailed to 380 survivors (age range, 11-33 years) of childhood leukemia, lymphoma, or central nervous system carcinomas (and guardians of survivors < 18 years old) to elicit data on exercise, dietary intake of calcium, fat, and fruits and vegetables, smoking status, readiness to pursue lifestyle change, quality of life, and interest in various health interventions. RESULTS: Responses from 209 survivors (a 55% response rate) suggested that most did not meet guidelines for fruit and vegetable consumption (79%), calcium intake (68%), or exercise (52%), 42% were overweight/obese, and 84% consumed > 30% of calories from fat. Older (> 18 years) compared with younger (< 18 years) survivors were more likely to smoke (17% vs. 1%), to be obese (21.6% vs. 14.6%), and to have suboptimal calcium intakes (75.6% vs. 57.6%). No differences in lifestyle behaviors were observed between cancer groups. Compared with interventions aimed at weight control, improving self-esteem, or smoking cessation, the highest levels of interest were found consistently for interventions aimed at getting in shape and eating healthy. Survivors preferred mailed interventions to those delivered in-person, by telephone counselors, or via computers. CONCLUSIONS: Survivors of childhood cancer practiced several suboptimal health behaviors. Health promotion interventions aimed at areas of interest and delivered through acceptable channels have the potential to improve long-term health and function of this vulnerable population.

Adolescent↗