Symptoms and functional status of patients with disseminated cancer visiting outpatient departments

Considerable research has focused on pain and other symptoms in terminal cancer patients referred to hospices and palliative care services. These patients differ from Dutch cancer patients in the palliative stage of their disease because the latter are cared for by general practitioners at home and medical specialists in outpatient departments. To clarify the experience of these Dutch patients, a study was started to investigate the prevalence and severity of pain and other symptoms as well as the functional status of consecutive patients visiting oncology outpatient departments for follow-up. After randomization, one group (I) of patients was interviewed at home by a general practitioner using structured questionnaires. The other group (II) received the questionnaires by mail, and scored the symptoms independently. The results of the symptom assessment show that patients in groups I and II suffered 2.4 (SD = 1.7) and 2.8 (SD = 2.0) symptoms, respectively. Between 30% and 40% of all patients reported constipation, nausea, loss of appetite, coughing, and dyspnea. These percentages were 50% lower when only moderate, severe, or extremely distressing symptoms were included. Sixty percent of all patients had pain, and 20% indicated a daytime pain score of 5 or greater on a scale of 0 to 10. Functional status was measured by the COOPWONCA charts; the mean score for the charts "physical fitness" and "daily activities" was 1.5 points lower for cancer patients than a random sample from the community of the same age and gender. The findings of this study should motivate doctors to put more energy in symptom assessment and interventions in palliative care. Record 29 of 32 - SilverPlatter MEDLINE(R)

Phosporylation of androgen receptor isoforms

Phosphorylation of the human AR (androgen receptor) is directly correlated with the appearance of at least three AR isoforms on an SDS/polyacrylamide gel. However, it is still not clear to what extent phosphorylation is involved in the occurrence of isoforms, which sites are phosphorylated and what are the functions of these phosphosites. The human AR was expressed in COS-1 cells and AR phosphorylation was studied further by mutational analyses and by using reversed-phase HPLC and MS. The reversed-phase HPLC elution pattern of the three isoforms revealed that Ser-650 was phosphorylated constitutively. After de novo synthesis, only Ser-650 was phosphorylated in the smallest isoform of 110 kDa and both Ser-650 and Ser-94 were phosphorylated in the second isoform of 112 kDa. The hormone-induced 114 kDa isoform shows an overall increase in phosphorylation of all the isolated peptides. The activities of the Ser-Ala substitution mutant S650A (Ser-650-->Ala) was found to be identical with wild-type AR activation in four different cell lines and three different functional analyses, e.g. transactivation, N- and C-terminal-domain interaction and co-activation by transcriptional intermediary factor 2. This was also found for mutants S94A and S515A with respect to transactivation. However, the S515A mutation, which should eliminate phosphorylation of the potential mitogen-activated protein kinase site, Ser-515, resulted in an unphosphorylated form of the peptide containing Ser-650. This suggests that Ser-515 can modulate phosphorylation at another site. The present study shows that the AR isoform pattern from AR de novo synthesis is directly linked to differential phosphorylation of a distinct set of sites. After mutagenesis of these sites, no major change in functional activity of the AR was observed

The Prebiotic Inulin Aggravates Accelerated Atherosclerosis in Hypercholesterolemic APOE*3-Leiden Mice

Vascular Surger