HCV Infection Alters Salivary Gland Histology and Saliva Composition.

Hepatitis C virus (HCV) infection is the most common blood-borne chronic infection in the United States. Chronic lymphocytic sialadenitis and sicca syndrome have been reported in chronic HCV infection. Up to 55% of these patients may have xerostomia; the mechanisms of the xerostomia and salivary gland (SG) hypofunction remain controversial. The objectives of this project are to establish if xerostomia associates with SG and HCV infection and to characterize the structural changes in SG and saliva composition. Eighteen HCV-infected patients with xerostomia were evaluated for SG dysfunction; 6 of these patients (patients 1-6) were further evaluated for SG histopathological changes and changes in saliva composition. The techniques used include clinical and laboratory assessment, SG ultrasonography, histological evaluation, sialochemical and proteomics analysis, and RNA in situ hybridization. All the HCV patients had low saliva flow, chronic sialadenitis, and SG fibrosis and lacked Sjögren syndrome (SS) characteristic autoantibodies. Further evaluation of a subgroup of 6 HCV patients (patients 1-6) demonstrated diffuse lymphocytic infiltrates that are predominantly CD8+ T cells with a significant increase in the number of inflammatory cells. Alcian Blue/periodic acid-Schiff staining showed significant changes in the ratio and intensity of the acinar secretory units of the HCV patients' minor SG. The submandibular glands showed significant ultrasonographic abnormalities in the parenchyma relative to the parotid glands. Significant changes were also observed in the concentration of sodium and mucin 5b. Although no significant correlation was observed between the lymphocytic infiltrates and the years of HCV chronic infection, a positive correlation was observed between HCV RNA-positive epithelial cells and the years of HCV infection. Consistent with the low saliva flow and xerostomia, patients showed changes in several markers of SG acinar and ductal function. Changes in the composition of the saliva suggest that HCV infection can cause xerostomia by mechanisms distinct from SS.

Lower brain-derived neurotrophic factor levels associated with worsening fatigue in prostate cancer patients during repeated stress from radiation therapy.

OBJECTIVES: Fatigue during cancer treatment is associated with depression. Neurotrophic factors play a major role in depression and stress and might provide insight into mechanisms of fatigue. This study investigated the association between plasma concentrations of three neurotrophic factors (BDNF, brain-derived neurotrophic factor; GDNF, glial-derived neurotrophic factor; and SNAPIN, soluble N-ethylmaleimide sensitive fusion attachment receptor-associated protein) and initial fatigue intensification during external beam radiation therapy (EBRT) in euthymic non-metastatic prostate cancer men. METHODS: Fatigue, as measured by the 13-item Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and plasma neurotrophic factors were collected at baseline (prior to EBRT) and mid-EBRT. Subjects were categorized into fatigue and no fatigue groups using a > 3-point change in FACT-F scores between the two time points. Multiple linear regressions analysed the associations between fatigue and neurotrophic factors. RESULTS: FACT-F scores of 47 subjects decreased from baseline (43.95 ± 1.3) to mid-EBRT (38.36 ± 1.5, P < 0.001), indicating worsening fatigue. SNAPIN levels were associated with fatigue scores (rs = 0.43, P = 0.005) at baseline. A significant decrease of BDNF concentration (P = 0.008) was found in fatigued subjects during EBRT (n = 39). CONCLUSIONS: Baseline SNAPIN and decreasing BDNF levels may influence worsening fatigue during EBRT. Further investigations are warranted to confirm their role in the pathophysiology and therapeutics of fatigue.

Longitudinal patterns of analgesic and central acting drug use and associated effectiveness in fibromyalgia.

BACKGROUND: We describe the changing pattern of analgesic and new central acting drug (NCAD) use (pregabalin, duloxetine, milnacipran) in fibromyalgia and measure NCAD effectiveness in clinical practice. METHODS: About 3123 US adult patients with fibromyalgia participated in an 11-year longitudinal study of fibromyalgia outcomes. We assessed severity-adjusted treatment prevalence and measured the effect of any use of NCAD on pain and fatigue, and functional status using the Health Assessment Questionnaire (HAQ) disability index. RESULTS: In 2010, 46.7% of patients used opioids, including 12.5% who used strong opioids. During the 11 years, severity-adjusted strong opioid use increased from 6.3% to 11.7% and any opioid use from 40.0% to 46.6%. Nonsteroidal anti-inflammatory drug (NSAID) use decreased from 74% to 44%. Tricyclic use dropped in half, from 27% to 15%, while NCAD use increased from less than 10% to 39%. The estimated 25th and 50th percentiles for NCAD discontinuation time were 1 and 2.5 years. Overall pain, fatigue and HAQ scores were unchanged over the 11 years. For patients treated with NCAD, pain scores were reduced significantly by 0.17 (0.03, 0.30) units following the start of NCAD, an improvement of 2.8%. Some sensitivity analyses showed improvements of up to 4.3%. There was no significant improvement in fatigue or functional status. CONCLUSIONS: There is a changing pattern of drug treatment in fibromyalgia, consisting mostly of decreased NSAID and amitriptyline use and an increase in NCAD. Drug costs are substantially higher because of NCAD use, but we found no evidence of clinical benefit for NCAD compared with prior therapy.

Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy.

The objective of this study was to assess the efficacy and safety of amitriptyline as a treatment of FM. A comprehensive computerized search in Medline (Pubmed), EMBASE and The Cochrane Library was performed. Randomized controlled trials (RCTs) comparing amitriptyline vs placebo in adult patients suffering from FM were identified, the methodological quality was assessed and the results of the main outcomes were evaluated. Ten RCTs were identified. Large clinical variability and statistical heterogeneity precluded quantitative meta-analysis. Overall, the study quality was moderate to high. Amitriptyline 25 mg/day (six RCTs) demonstrated a therapeutic response compared with placebo in the domains of pain, sleep, fatigue and overall patient and investigator impression. This benefit was generally seen at 6-8 weeks of treatment but no effect was noted at 12 weeks. Amitriptyline 50 mg/day (four RCTs) did not demonstrate a therapeutic effect compared with placebo. Neither dose of amitriptyline had an effect on tender points count. No clear statements on adverse events with amitriptyline can be made due to inconsistencies in data among the studies. A definitive clinical recommendation regarding the efficacy of amitriptyline for FM symptoms cannot be made. There is some evidence to support the short-term efficacy of amitriptyline 25 mg/day in FM. There is no evidence to support the efficacy of amitriptyline at higher doses or for periods >8 weeks. More stringent RCTs with longer follow-up periods are required to determine the long-term efficacy and safety of the amitriptyline and define its role in the multidisciplinary management of FM.