Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma

Background

Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC.

Methods

Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium.

Results

Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS.

Conclusions

Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.     

Risk factors for citation errors in peer-reviewed nursing journals

BACKGROUND: Citation errors are common among nursing journals. But, there are no data regarding the factors that predispose to these errors. OBJECTIVE: To determine the risk factors that predispose to citation error in peer-reviewed nursing journals. METHODS: Five hundred and fifty references were selected randomly from articles published in eleven nursing journals for the year 1998. The incidences of major and minor citation errors were determined by comparing with the original articles. The relative odds of citation errors for the number of authors, collaborating institutions and the length of the reference list were calculated. The correlation between the scientific quality of the journal (by means of journal impact factor and immediacy index) and the incidence of citation error were also determined. RESULTS: The incidence of citation errors is comparable to those reported previously. Long reference lists in articles written by a single author predicted strongly the occurrence of minor citation errors. Journals with a high impact factor and immediacy index tend to contain fewer minor mistakes. None of these factors affect the incidence of major errors. CONCLUSION: Contributors to journals should be aware of the various risk factors for citation errors. Citation accuracy may be improved by modifying these factors.     

Epidemiology and demographic aspects of treated end-stage renal disease in the elderly

Over the last 10 years an increasing number of patients worldwide have started dialysis or had transplantation. Many are elderly with complex comorbid conditions. Registries across the world all show a rapid and dramatic increase in the number of older patients accepted for renal replacement therapy. In addition, the number of patients who grow old on dialysis is increasing, leading to a marked change in the demographics of the renal population. Changes over time and across registries are discussed with reference to patient characteristics, survival statistics, and the trends seen with transplantation in the elderly.     

One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study

BACKGROUND AND AIM: In individuals with biopsy-proven non-alcoholic steatohepatitis (NASH), short-term weight loss has been shown to improve biochemical abnormalities; however, its effect on liver histology is largely unknown. The aim of the article is to determine if dietary intervention is effective in improving histological features of steatohepatitis in patients with biopsy-proven NASH. METHODS: Twenty-three patients (11M/12F) with BMI >25 kg/m(2) and biopsy-proven NASH received standardized nutritional counseling aimed at reducing insulin resistance (IR) and weight. Blood tests were checked at baseline and every 1-4 months, and liver biopsy was repeated at month 12. IR was assessed by the homeostasis model assessment (HOMA). Liver biopsies were scored according to modified Brunt criteria for NASH. "Histologic response" was defined as a reduction in total NASH score of >/=2 points with at least one point being in the non-steatosis component. RESULTS: Sixteen patients (8M/8F) completed 12 months of dietary intervention, and 15 underwent repeat liver biopsies. At month 12, mean weight decreased from 98.3 to 95.4 kg. Mean waist circumference, visceral fat, fasting glucose, IR, triglycerides, AST, ALT, and histologic score were all reduced but the difference was not significant. Nine patients had a histologic response, six had stable scores, and none had a worsened score. Compared to patients with unchanged histologic scores, patients with improved scores had significantly greater reduction in weight, waist circumference, AST, ALT, steatosis grade, and total NASH score. CONCLUSION: Among patients who successfully completed 1 yr of intense dietary intervention, nine of 15 patients with NASH displayed histologic improvement. This pilot study suggests that dietary intervention can be effective in improving histology in patients with biopsy-proven NASH.     

Maintenance therapy for duodenal ulcer: a randomized controlled comparison of seven forms of treatment.

PURPOSE: We performed a randomized controlled trial to compare the efficacy of seven forms of maintenance treatment of duodenal ulcer, including a mealtime regimen of antacids. PATIENTS AND METHODS: We randomized 785 patients with healed duodenal ulcer to receive: (1) no treatment; (2) mealtime antacids with an acid-neutralizing capacity of 80 mmol/day; (3) an antidepressant, trimipramine 25 mg; (4) an anticholinergic, pirenzepine 50 mg; (5) cimetidine 200 mg; (6) cimetidine 400 mg; (7) ranitidine 150 mg; or (8) sucralfate 1 g twice a day. Symptomatology and side effects were assessed every 2 months and endoscopy was performed every 4 months up to 1 year. RESULTS: The patients were comparable in the majority of clinical characteristics before entry. The cumulative percentages of patients with relapse of ulcers at 12 months by life-table analysis were 61% with no treatment, 38% with mealtime antacids, 60% with trimipramine, 52% with pirenzepine, 46% with cimetidine 200 mg, 44% with cimetidine 400 mg, 30% with ranitidine 150 mg, and 40% with sucralfate. Cimetidine 400 mg, antacids, ranitidine 150 mg, and sucralfate were significantly better than no treatment and the other forms of treatment. Ranitidine was significantly better than antacids, cimetidine, and sucralfate in preventing endoscopically documented duodenal ulcer relapse by multiple comparison at 12 months, but not by life-table analysis nor when symptomatic relapses were compared. No significant difference was detected among antacids, cimetidine, and sucralfate. No major side effects occurred with the seven forms of treatment, but those receiving antacids had the highest incidence of minor adverse events (26%). CONCLUSION: This study suggests that mealtime antacids are as effective as H2-receptor antagonists and sucralfate in the maintenance treatment of duodenal ulcer disease, but have to be taken three times a day and had the highest incidence of reported minor adverse events. The relapse rate was lower with ranitidine than with cimetidine, sucralfate, and antacids, but the difference was small and may not be clinically important.