Possible links between behavioral and physiological indices of tiredness, fatigue, and exhaustion in advanced cancer

Goals In this theoretical paper, we present the Edmonton Fatigue Framework (EFF), a new framework for the study of tiredness, fatigue, and exhaustion in advanced cancer. Materials and methods The Fatigue Adaptation Model (FAM), the starting point for the EFF, was drawn from a literature review pertaining to fatigue in depression, chronic fatigue syndrome, cancer, shift workers, and athletes published in the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed, PsychINFO, SPORTdiscus, and CancerLit between 1995 and 2004, and from seven qualitative studies conducted by our group. The EFF, an elaboration of the FAM, was constructed after an expansion of our literature review to 2006 and team discussion. The EFF provides new insights into possible links between behavioral and physiological indices of tiredness, fatigue, and exhaustion as they occur in both ill and non-ill states. In this paper, however, we consider only possible links in advanced cancer. Conclusions We propose that stressors associated with advanced cancer and its supportive treatment trigger declines in four systems—cognitive function, sleep quality, nutrition, and muscle endurance—and that these declines reduce one’s ability to adapt. While these systems each likely has its own effect on adaptation, we propose that the most important and serious effects arise from interactions among declines in cognitive function, sleep quality, nutrition, and muscle endurance. Conclusions Interventions for fatigue have been limited by a lack of understanding about its etiology. Hypotheses arising from the EFF` suggest a new direction for further study that focuses on interactions among cognitive function, sleep quality, nutrition, and muscle endurance.     

Retreatment of patients with chronic hepatitis C not responding to interferon/ribavirin combination therapy with daily interferon plus ribavirin plus amantadine

There is currently no accepted therapeutic regimen for patients with chronic hepatitis C who failed to respond to standard combination treatment with interferon-alpha plus ribavirin. We investigated triple combination treatment with induction dosing of interferon-alpha plus ribavirin plus amantadine in these difficult-to-treat patients. Nonresponders (n = 67), breakthroughs (n = 16) and relapsers (n = 19) to previous interferon/ribavirin combination treatment of at least 6 months were included. For the first 16 weeks, patients received interferon-alpha2a 6 MU daily, ribavirin 800-1200 mg/d, and amantadine 200 mg/d. In cases of undetectable HCV RNA at week 12, treatment was continued with interferon-alpha2a 6 MU every other day and the same doses of ribavirin and amantadine until week 48. In cases of HCV RNA positivity at week 12, treatment was stopped. A total of 102 patients were enrolled (80%: genotype 1, 19%: cirrhosis). HCV RNA was negative in 35/102 patients (34%) at week 12 and in 27/ 102 patients (26%) at the end of treatment. Virological response was sustained in 15/102 patients (15%). On-treatment virological response was higher in previous relapsers/breakthroughs than in previous nonresponders (week 12: 49% vs. 27%, p < 0.05; week 48: 46% vs. 16%, p < 0.01) but no such difference was found for sustained virological response (20% vs. 12%, NS). In conclusion, triple combination treatment with daily interferon-alpha plus ribavirin plus amantadine for 3 months can induce virological response in a considerable number of nonresponders/relapsers to previous dual combination treatment, but the sustained virological response rate remains low.     

Impaired renal Na(+) retention in the sgk1-knockout mouse

The serum- and glucocorticoid-regulated kinase (sgk1) is induced by mineralocorticoids and, in turn, upregulates heterologously expressed renal epithelial Na(+) channel (ENaC) activity in Xenopus oocytes. Accordingly, Sgk1 is considered to mediate the mineralocorticoid stimulation of renal ENaC activity and antinatriuresis. Here we show that at standard NaCl intake, renal water and electrolyte excretion is indistinguishable in sgk1-knockout (sgk1(-/-)) mice and wild-type (sgk1(+/+)) mice. In contrast, dietary NaCl restriction reveals an impaired ability of sgk1(-/-) mice to adequately decrease Na(+) excretion despite increases in plasma aldosterone levels and proximal-tubular Na(+) and fluid reabsorption, as well as decreases in blood pressure and glomerular filtration rate.     

A single nucleotide primer extension assay to detect the APC I1307K gene variant

Adenomatous polyposis coli (APC) is a tumor suppressor gene important in colorectal tumorigenesis. A genetic variant of APC, I1307K, results from a T-to-A transversion at nucleotide 3920 which converts the wild-type sequence to a homopolymer tract (A₈). The I1307K alteration is not itself oncogenic, but creates a hypermutable region (A₈) that is prone to frame-shift mutations. The APC I1307K variant occurs in approximately 6% of the Ashkenazi Jewish population and is reported to approximately double an individual’s risk for colorectal cancer. Here we describe a single nucleotide primer extension assay for the detection of the APC I1307K mutation. Following PCR amplification, nucleotide 3920 of the APC gene is directly sequenced using single nucleotide primer extension technology. The assay is in a multiplex format allowing simultaneous forward and reverse sequencing of the I1307K variant, which provides an internal, independent confirmation of each testing result. The assay was validated against 60 samples previously characterized by an allele-specific oligonucleotide (ASO) hybridization assay, with 100% concordance of results. Compared to the ASO assay, this single nucleotide primer extension assay requires significantly less technical time to perform, and has a greatly increased throughput capacity. The single nucleotide extension assay provides a highly sensitive and specific assay to identify individuals with the APC I1307K gene variant who may benefit from increased colorectal screening.     

Decreased survival in pancreatic cancer patients with high concentrations of organochlorines in adipose tissue

We analysed adipose tissue concentrations of persistent organic pollutants (POPs) in 21 cases with exocrine pancreatic cancer. The comparison group consisted of 59 subjects. Significantly increased concentrations of polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), sum of chlordanes and polybrominated diphenylethers (PBDEs) were found in the cases. For 1,1,-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) no significant difference was seen. For PCBs no odds ratio (OR) could be calculated since all cases had concentration>median in controls used as a cut-off. HCB yielded OR=53.0, 95% confidence interval (CI)=4.64-605 and sum of chlordanes OR=18.4, 95% CI=2.71-124 whereas OR was not significantly increased for p,p'-DDE or PBDEs. Body mass index (BMI) at the time of tissue sampling was significantly lower for the cases. This might have influenced the results. Using BMI one year previously or decreasing the concentrations of POPs with the same percentage as weight loss among the cases did not change the results. Survival of the cases was shorter in the group with the concentration of POPs>median among cases, significantly so for the sum of PCBs (147 vs. 294 days), p,p'-DDE (134 vs. 302 days), and sum of chlordanes (142 vs. 294 days) in the high and low group, respectively. The results were based on a low number of cases and should be interpreted with caution.     

Evaluation of cognitive behavioural training and physical activity for patients with stress-related illnesses: a randomized controlled study.

OBJECTIVE: To evaluate the effects of a cognitive behavioural training programme and a physical activity programme for patients with stress-related illnesses. DESIGN: In a randomized controlled study, patients were allocated randomly to 1 of 3 groups, where group 1 participated in a cognitive behavioural training programme, group 2 participated in a physical activity programme, and group 3, the control group, was offered usual care for the course of the study. SUBJECTS: A total of 75 patients participated in the study. They had been on sick leave for at least 50% of the time for between 1 month and 2 years due to stress-related illnesses. METHODS: Measurements of autonomic activity, pressure-pain thresholds and subjective ratings of health and behaviour were made before and after a 10-week intervention period, and at 6 and 12 months after the intervention. RESULTS: Minor differences in autonomic activity and pressure-pain thresholds were found between the groups immediately after the intervention. At the 6- and 12-month follow-up assessments, the differences were no longer present. Patients in the cognitive behavioural training group improved their ratings of general health compared with the physical activity group throughout the study. CONCLUSION: The study showed little difference in the effect of cognitive behavioural training and physical activity, compared with usual care, for patients with stress-related illnesses.     

Older people living in nursing homes or other community care facilities: Registered Nurses' views of their working situation and co-operation with family members

Background. Little attention has been paid to Registered Nurses’ working conditions and how they experience their working situation in community health care. The nurses’ vocational background is of interest, as well as their apprehension about communicating and co‐operating with the older persons’ family members. Aims and objectives. The aim of the study was to describe Registered Nurses’ views of their working situation in community health care and of co‐operation with family members of older people living in nursing homes or similar facilities. Design. The study was carried out in a geographically defined area in the south of Sweden. A questionnaire was sent to all the Registered Nurses (n = 314) working within community health care of whom 210 Registered Nurses replied to the questionnaires. Methods. Latent content analysis was used on the comments to six questions, in order to illuminate the statistical findings from the statements of the questions measured by the Likert scale. Results. The results showed that almost half of the Registered Nurses working in care of older people are not satisfied with their working situation. The nurses with less than 5 years working experience find their working situation most stimulating. All of them expressed that it is important that there is co‐operation between themselves and the family members and it was also considered important to develop models that could improve co‐operation. Male nurses believed, to a lesser extent, that family members were a resource in caring, compared with female nurses; however, all male nurses stressed the importance of facilitating informal caregivers. Nurses with more than 5 years of working experience expressed that it was important that family members show engagement in caring for older people. Furthermore, they expressed that it was necessary that the family members took care of the older persons’ interests. Relevance to clinical practice. The findings that half of the Registered Nurses are dissatisfied with their working situation have relevance in clinical practice because of the risk of losing competent nurses in this area.     

The heat/capsaicin sensitization model: a methodologic study.

The heat/capsaicin sensitization model induces cutaneous sensitization by using a combination of heat and topical capsaicin. It has been suggested that the stability and duration of the cutaneous sensitization are due to a synergistic effect between heat and capsaicin. The aim of this study was to evaluate a possible synergistic effect between heat and capsaicin in inducing cutaneous sensitization. Twenty healthy male volunteers completed this random order, 4-session study. Three different stimulation combinations were used to induce cutaneous sensitization: day A, heat and capsaicin; day B, heat alone; day C, capsaicin alone. Combination A was repeated on day D to determine between day reproducibility. Rekindling was performed 3 times at 40-minute intervals to maintain stable areas of secondary hyperalgesia. Brief thermal sensitization (45 degrees C for 3 minutes) was induced at each session. Within and between day reproducibility was calculated. There was no difference between the size of areas of secondary hyperalgesia after stimulation with heat/capsaicin compared to heat and capsaicin stimulation alone. The within day reproducibility was better with heat/capsaicin than with either stimulation alone. There was no synergistic or additive effect between heat and capsaicin in inducing cutaneous sensitization. Rekindling seems to be the important factor in maintaining stable and long-lasting cutaneous sensitization.     

Expression Pattern and Immunoregulatory Roles of Galectin-1 and Galectin-3 in Atopic Dermatitis and Psoriasis

Inflammation - The pathogenesis of atopic dermatitis (AD) and psoriasis (Ps) overlaps, particularly the activation of the immune response and tissue damage. Here, we evaluated galectin (Gal)-1 and...