Strain differences in anxiety-like behavior: association with corticotropin-releasing factor

The purpose of the current study was to relate basal corticotropin-releasing factor (CRF) mRNA level in the central nucleus of the amygdala (CeA) with anxiety-like behavior using three strains of rat reported to exhibit a range of behavioral and neuroendocrine responses to stress. Anxiety-like behavior was determined for Fischer (F344), Wistar, and Wistar-Kyoto (WKY) rats with an elevated plus-maze and CRF mRNA level was measured using in situ hybridization. WKY rats exhibited more anxiety-like behavior on the elevated plus-maze than both F344 (p's < 0.01) and Wistar rats (p's < 0.05). WKY rats had higher basal levels of CRF mRNA in the CeA than F344 rats (p < 0.05) with a trend toward higher levels than Wistar rats (p = 0.06). Wistar rats had similar indices of anxiety with F344 rats and comparable levels of CRF mRNA in the CeA. Basal plasma corticosterone was similar for all three strains and repeated experience with the plus-maze had no effect on basal corticosterone levels or CRF mRNA levels in the paraventricular nucleus of the hypothalamus (PVN) for Wistar or WKY rats. Consistent with reported hyperactivity of the hypothalamopituitary adrenal axis of F344 rats with repeated stress, we observed elevated corticosterone following repeated exposure to the elevated plus-maze in F344 rats (p < 0.01) with a trend toward increased CRF mRNA levels in the PVN (p = 0.09). Heightened expression of CRF in the CeA of WKY rats may be involved in anxiety-like behaviors observed in this strain.     

Neurolytic celiac plexus block for pain control in unresectable pancreatic cancer

BACKGROUND: A major focus of palliation in patients with unresectable pancreatic cancer is pain control. The aim of this systematic review was to examine the efficacy and safety of neurolytic celiac plexus blockade (NCPB) compared with standard treatment in randomized controlled trials (RCTs) involving patients with unresectable pancreatic cancer. METHODS: An electronic search was completed (1966 through August, 2005) for RCTs comparing NCPB versus control (standard treatment and/or sham NCPB) in patients with unresectable pancreatic cancer. The primary outcome was pain measured on a 10-point visual analogue scale (VAS). Secondary outcomes included opioid usage, adverse effects, quality of life (QOL), and survival. All outcomes were assessed at 2, 4, and 8 wk. RESULTS: Five RCTs involving 302 patients (NCPB, N = 147; control, N = 155) met the inclusion criteria. Mean age was 61.0 +/- 4.3 yr. Compared with control, NCPB was associated with lower VAS scores for pain at 2, 4, and 8 wk (weighted mean difference [WMD]-0.60, 95% CI -0.82 to -0.37). Opioid usage (in mg/d oral morphine) was also reduced at 2, 4, and 8 wk (WMD -85.9, 95% CI -144.0 to -27.9). NCPB was associated with a reduction in constipation (relative risk 0.67, 95% CI 0.49-0.91), but not other adverse events. No differences in survival were observed. QOL could not be adequately analyzed due to differences in outcome scales among studies. CONCLUSIONS: In patients with unresectable pancreatic cancer, NCPB is associated with improved pain control, and reduced narcotic usage and constipation compared with standard treatment, albeit with minimal clinical significance.     

After radical retropubic prostatectomy 'insignificant' prostate cancer has a risk of progression similar to low-risk 'significant' cancer

OBJECTIVE

To assess progression and survival among patients with small‐volume, well‐differentiated, organ‐confined prostate cancer found at radical retropubic prostatectomy (RRP), often defined as being ‘insignificant’, thus testing whether they are indeed ‘insignificant’.

PATIENTS AND METHODS

We identified 6496 men treated for prostate cancer by RRP between 1990 and 1999, and defined ‘insignificant’ tumours as those in men having a prostate‐specific antigen (PSA) level of <10 ng/mL before RRP, a cancer volume of ≤0.5 mL, a specimen Gleason of score ≤6 and stage ≤pT2. Survival was assessed using the Kaplan‐Meier method and compared using the two‐sided log‐rank test.

RESULTS

‘Insignificant’ tumours were found in 354 (5.5%) men, of whom only one had metastatic progression and none died from prostate cancer, with a median (range) follow‐up of 9.2 (0.8–15.6) years. Biochemical progression‐free survival (87% vs 85%, respectively, at 10 years, P = 0.5), systemic progression‐free survival (100% vs 99%, P = 0.3), overall survival (91% vs 88%, P = 0.16) and cancer‐specific survival (100% in each group, P = 0.32) were each similar among men with ‘insignificant’ prostate cancer and men with low‐risk (defined by Gleason score, preoperative PSA level, seminal vesicle and surgical margin status) ‘significant’ cancer. Clinical stage, biopsy Gleason score and preoperative PSA doubling time were multivariably predictive of ‘insignificant’ tumours at RRP.

CONCLUSIONS

‘Insignificant’ prostate cancer at RRP is associated with a comparable risk of biochemical progression as low‐risk ‘significant’ cancer. Although clinical predictors for ‘insignificant’ pathology can be identified, it remains to be established whether such patients can be safely managed conservatively.     

Associative learning in deficit and nondeficit schizophrenia

When two stimuli are associated and treated as equivalent, generalization occurs between them (acquired equivalence). The feedback-guided learning of associations is related to the basal ganglia, whereas the medial temporal lobe participates in acquired equivalence learning. In this study, we investigated feedback-guided associative learning and acquired equivalence in deficit and nondeficit schizophrenia. Results revealed that acquired equivalence learning was similarly impaired in deficit and nondeficit patients, whereas feedback-guided associative learning was impaired only in deficit patients. Associative learning and acquired equivalence were not related to frontal lobe tests. These results suggest that the enduring negative symptoms of deficit patients may be related to decreased response to cognitive feedback and deficient basal ganglia functioning.     

Body mass, fitness and survival in veteran patients: another obesity paradox?

Purpose

The paradox of obesity in patients with heart failure (HF) also has been observed in non-HF veteran patients. Veterans had to have met military fitness requirements at the time of their enlistment. Therefore, we assessed the relation of body mass index (BMI) to mortality in a clinical cohort of non-HF veterans, adjusting for fitness.

Methods

After excluding HF patients (n = 580), the study population comprised 6876 consecutive patients (mean age 58 [±11] years) referred for exercise testing. Patients were classified by BMI category: normal weight (BMI 18.5-24.9 kg/m²), overweight (BMI 25.0-29.9 kg/m²), or obese (BMI ≥30.0 kg/m²). The association between BMI, fitness, other clinical variables, and all-cause mortality was assessed by Cox proportional hazards analysis.

Results

During a mean (±SD) follow-up of 7.5 ± 4.5 years, a total of 1571 (23%) patients died. In a multivariate analysis including clinical, risk factor, and exercise test data, higher BMI was associated with better survival. Expressing the data by BMI category, obese patients were 22% less likely to die (relative risk [RR] = 0.78, 95% confidence interval [CI], 0.69-0.90, P <.001) than patients of normal weight. After further adjustment for cardiorespiratory fitness (CRF), this relationship strengthened such that mortality risk for the obese category was 35% lower (RR = 0.65, 95% CI, 0.57-0.76, P <.001), versus the normal weight category.

Conclusions

As has been observed in HF patients, obesity was associated with a substantially lower mortality risk in a clinical population of non-HF veterans. Higher CRF and obesity in later life may account for an obesity paradox in this population.