Constipation in specialized palliative care: factors related to constipation when applying different definitions.

CONTEXT: For patients in palliative care, constipation is primarily a result of opioid treatment. Impacts from other factors related to constipation in palliative care are rarely studied. OBJECTIVES: The aim was to identify factors related to constipation in patients in palliative care, and then to compare these factors between patients with different types of constipation and patients without constipation. METHODS: Cross-sectional data on constipation was collected with a 26-item questionnaire from 485 patients in 38 specialist palliative care units in Sweden. Three different constipation groups were used; MC ONLY, PC ONLY, and MC & PC. Logistic regression analyses were used to calculate odds ratios. RESULTS: Patients with <3 defecations/week, MC ONLY, (n = 36) had higher odds of being hospitalized, bed-restricted, in need of personal assistance for toilet visits, and of having a poor fluid intake. Patients with the perception of being constipated, PC ONLY, (n = 93) had higher odds of having poor appetite, hemorrhoids, hard stool, more opioid treatment, less laxative treatment and of being more dissatisfied with constipation information. Patients with both <3 defecations/week and a perception of being constipated, MC & PC, (n = 78) had higher odds of having cancer- disease. CONCLUSION: There were several significant factors related to constipation with higher odds than opioid- treatment, for patients in palliative care, such as; hard stool, cancer diagnosis, dissatisfaction with information, low fluid intake, hemorrhoids, bed restriction, hospitalization, and need of personal assistance for toilet visits.

Hypertrophy of infected Peyer's patches arises from global, interferon-receptor, and CD69-independent shutdown of lymphocyte egress.

Lymphoid organ hypertrophy is a hallmark of localized infection. During the inflammatory response, massive changes in lymphocyte recirculation and turnover boost lymphoid organ cellularity. Intriguingly, the exact nature of these changes remains undefined to date. Here, we report that hypertrophy of Salmonella-infected Peyer's patches (PPs) ensues from a global "shutdown" of lymphocyte egress, which traps recirculating lymphocytes in PPs. Surprisingly, infection-induced lymphocyte sequestration did not require previously proposed mediators of lymphoid organ shutdown including type I interferon receptor and CD69. In contrast, following T-cell receptor-mediated priming, CD69 was essential to selectively block CD4(+) effector T-cell egress. Our findings segregate two distinct lymphocyte sequestration mechanisms, which differentially rely on intrinsic modulation of lymphocyte egress capacity and inflammation-induced changes in the lymphoid organ environment.

What is a 'secure base' when death is approaching? A study applying attachment theory to adult patients' and family members' experiences of palliative home care.

OBJECTIVE: Attachment theory has received much interest lately in relation to how adults cope with stress and severe illness. The aim of this study was using the experiences of patients and family members to explore palliative home care as a 'secure base' (a central concept within the theory). METHODS: Twelve patients and 14 family members were interviewed during ongoing palliative home care. The interviews were analysed with deductive qualitative content analysis. RESULTS: Informants expressed the relevance of sensing security during palliative home care because death and dying were threats that contributed to vulnerability. Palliative home care could foster a feeling of security and provide a secure base. This was facilitated when informants had trust in staff (e.g. due to availability and competence in providing symptom relief), felt recognised as individuals and welcomed to contact the team in times of needs. Being comfortable, informed and having an everyday life also contributed to a perception of palliative home care as a secure base. Family members stressed the importance of being relieved from responsibilities that were too heavy. The underlying meanings of experiencing palliative home care as a secure base involved gaining a sense of control and of inner peace, perceiving that despite a demanding and changed life situation, one could continue partially being oneself and having something to hope for, even if this no longer concerned cure for the ill person. CONCLUSIONS: Important aspects of palliative home care as providing a secure base were identified and these have implications for clinical practice.

Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men.

Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) gene. Subjects were reexamined after 4 wk of retraining. We found that bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after 4 wk of retraining. Pathway analyses revealed significant downregulation of 34 pathways, predominantly those of genes associated with mitochondrial function, including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity.

Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action.

AIMS/HYPOTHESIS: Insulin resistance in skeletal muscle is a key factor in the development of type 2 diabetes and although some studies indicate that this could be partly attributed to reduced content and activity of various proximal and distal insulin signalling molecules, consensus is lacking. We therefore aimed to investigate the regulation of proximal insulin signalling in skeletal muscle and its effect on glucose metabolism in a large non-diabetic population. METHODS: We examined 184 non-diabetic twins with gold-standard techniques including the euglycaemic-hyperinsulinaemic clamp. Insulin signalling was evaluated at three key levels, i.e. the insulin receptor, IRS-1 and V-akt murine thymoma viral oncogene (Akt) levels, employing kinase assays and phospho-specific western blotting. RESULTS: Proximal insulin signalling was not associated with obesity, age or sex. However, birthweight was positively associated with IRS-1-associated phosphoinositide 3-kinase (PI3K; IRS-1-PI3K) activity (p = 0.04); maximal aerobic capacity (VO2(max)), paradoxically, was negatively associated with IRS-1-PI3K (p = 0.02) and Akt2 activity (p = 0.01). Additionally, we found low heritability estimates for most measures of insulin signalling activity. Glucose disposal was positively associated with Akt-308 phosphorylation (p < 0.001) and Akt2 activity (p = 0.05), but not with insulin receptor tyrosine kinase or IRS-1-PI3K activity. CONCLUSIONS/INTERPRETATION: With the exception of birthweight, 'classical' modifiers of insulin action, including genetics, age, sex, obesity and VO2(max) do not seem to mediate their most central effects on whole-body insulin sensitivity through modulation of proximal insulin signalling in skeletal muscle. We also demonstrated an association between Akt activity and in vivo insulin sensitivity, suggesting a role of Akt in control of in vivo insulin resistance and potentially in type 2 diabetes.

The existential impact of starting corticosteroid treatment as symptom control in advanced metastatic cancer.

Treatment with corticosteroids often results in increased appetite, reduced nausea and improved well-being in patients with advanced metastatic cancer. Therefore, we have studied the existential impact of starting corticosteroid treatment as symptom control in this patient group using qualitative content analysis with both a descriptive and an interpretative focus. Ten patients were interviewed before and after 1 week of treatment with 4 mg betamethasone. Prior to treatment, patients reported distressing symptoms, deterioration and diminished autonomy, symbolising threat and death. Corticosteroid treatment produced symptom relief in the majority of the patients. They reported enhanced physical abilities and experienced feelings of a more normalized life and strengthened autonomy, symbolising health and hope. This transfer from threat to hope has important existential consequences in end-of-life care and should be addressed when communicating goals of treatment and care with the patient and family.

Receiving bad news: experiences of family members.

UNLABELLED: Little is known about how next-of-kin experience receiving bad news. The aim of this study was to explore the experiences of family members when receiving information about ending tumour treatment, with a focus on their role in this context. METHODS: Semi-structured interviews were performed and analyzed using a qualitative phenomenographic method. RESULTS: Twenty family members of patients with incurable progressive cancer admitted to hospital-based home care were included in the study. Data showed that family members want to protect, represent, or act on behalf of the patient. Some described themselves as assuming prominent roles: the demander-of-truth role, the secret-keeper role, and the controller role. Others assumed more passive roles: the surrendering role, the considerate listener role, and the excluded outsider role. CONCLUSION: This study has revealed possible-explanations as to why family members are dissatisfied with information. The results of this study may help doctors in clinical practice recognize the different types of behaviour family members exhibit when receiving bad news.

Breaking bad news in the transition from curative to palliative cancer care--patient's view of the doctor giving the information.

In the transition from curative to palliative cancer care, communication is of special importance. The aim of this study was to explore how patients with a disseminated cancer disease experienced the information about their incurable state, focusing on the physician. The persons taking part were 30 patients admitted to a hospital-based home care unit in Sweden. Semi-structured interviews were conducted and analysed using a qualitative method. All patients described their doctors as experts, despite different qualities. Six subcategories were identified: (1) the inexperienced messenger, (2) the emotionally burdened, (3) the rough and ready expert (4) the benevolent but tactless expert, (5) the "distanced" doctor and (6), the empathic professional. The relationship was described as very important to the patients' capacity to handle the information and was felt to have been built up during earlier meetings. The relationship was described in four subcategories: personal between well-acquainted individuals, impersonal between unacquainted individuals, personal between unacquainted individuals and impersonal between well-acquainted individuals. Both the character of the physician and his or her ability to create personal relationships influence patients' capacity to cope with this specific situation. Education and guidance are needed both in clinical practice and in medical schools.

Cancer patients' perceptions of their participation and own resources after receiving information about discontinuation of active tumour treatment.

The focus of most studies on informational needs has been on primary cancer diagnosis. The aim of this study was to explore how cancer patients in a palliative care setting perceived their own participation and resources after receiving information about the discontinuation of active tumour treatment. Thirty cancer patients admitted to a hospital-based home-care unit participated in the study. Semi-structured interviews were conducted and analysed using a phenomenographic method. The patients described their own participation as being either verbally passive or active, in order to receive more information or to avoid information. Furthermore, previous knowledge, at different levels, was described as important: 1) Unsuspecting naive, 2) apprehensive suspicious, 3) well prepared. Patients' own resources included a sense of wellbeing, a sense of security and individual strength. In conclusion, patients' previous knowledge and own resources are important components for their capacity to take part in the dialogue when receiving information.

Regulation of the human Gi alpha-2 gene promotor activity in embryonic chicken cardiomyocytes.

Increased expression of the inhibitory G protein Gi alpha-2 is assumed to contribute to desensitization of adenylyl cyclase in human heart failure. The mechanisms of upregulation involve increases in myocardial Gi alpha-2 protein, mRNA and gene transcriptional activity. To elucidate these mechanisms in more detail, the 5' flanking region of the human Gi alpha-2 gene (-1214/+115 bp) was cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and transfected in embryonic chick cardiomyocytes. CAT activity was measured 48 h after transfection. Unstimulated activity of the -1214/+115 bp construct was about 10-fold higher than activity of the basal CAT-construct (pGEMCAT). 5' deletion from -1214/+115 to -85/+115 bp upstream of the transcriptional start site increased, further stepwise deletions to 46/+115 gradually decreased promotor activity. Deletion from -46/+115 to -33/+115 bp completely abolished promotor activity. Stimulation of cardiomyocytes that had been transfected with the -1214/+115 CAT-construct with isoprenaline (10 microM), forskolin (10 microM), forskolin (10 microM) plus IBMX (10 microM) or dibutyryl-cAMP (1 mM) for 24 h induced an increase in CAT activity to 139 +/- 12% (n = 9), 211 +/- 18% (n = 12), 256 +/- 20% (n = 5) and 198 +/- 28% (n = 7) of unstimulated values, respectively. We conclude: 1) In chicken cardiomyocytes a sequence element of 52 bp between -85 and -33 bp is necessary to provide basal Gi alpha-2 promotor activity. 2) Elevation of cAMP has a stimulatory effect on the human Gi alpha-2 promotor, thereby offering a mechanism for beta-adrenoceptor-mediated increases in Gi alpha-2 in the heart.