Higher levels of fatigue are associated with higher CRP levels in disease-free breast cancer survivors

Objective

To investigate the associations between level of fatigue and various potential inflammatory biomarkers for fatigue after multivariate adjustments for possible confounders in a sample of 299 disease-free survivors of breast cancer (BCSs) at a mean of 4 years post diagnosis.

Methods

Medical record data were used for cancer-related information, and a follow-up mailed survey collected data on fatigue, depression, anxiety and insomnia symptoms as well as information on demographics, physical health, medication and lifestyle. Blood samples drawn at an outpatient examination were analyzed for leukocyte count, high sensitivity C-reactive Protein (CRP), interleukin 1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type 1 (sTNF-R1) and neopterin.

Results

Fatigue levels were significantly and positively associated with hsCRP (p<.001) and leukocyte count (p=.018), but not with levels of IL-1ra, IL-6, sTNF-R1 or neopterin in unadjusted analyses. Only hsCRP remained significantly associated with fatigue levels in the fully adjusted models (p=.020). Depression and self-rated health also remained independently associated with fatigue; however these variables were not significantly associated with hsCRP in multivariate analyses.

Conclusion

In general, and after adjustment for potential confounders, our hypotheses of positive associations between fatigue and several inflammatory markers were not confirmed. However, a small but independent association between level of fatigue and hsCRP was observed and supports the hypothesis that low-grade inflammation could play a role in the pathogenesis of fatigue in BCSs.     

Estimates of harm associated with changes in Swedish alcohol policy: results from past and present estimates

AIMS: (i) To compare actual developments of alcohol-related harm in Sweden with estimates derived prior to major policy changes in 1995 and (ii) to estimate the effects on consumption and alcohol-related harm of reducing alcohol prices in Sweden. DESIGN: Alcohol effect parameters expressing the strength of the relationship between overall alcohol consumption and different alcohol-related harms were obtained from ARIMA (Auto Regressive Integrated Moving Average) time-series analyses. MEASUREMENTS: Measures of Swedish alcohol-related mortality (liver cirrhosis, alcoholic psychosis, alcoholism and alcohol poisoning), accident mortality, suicide, homicide, assaults and sickness absence from 1950 to 1995. FINDINGS: Previous estimates of alcohol-related harm based on changes in alcohol consumption for the period 1994-2002 for Sweden were, in some cases (e.g. violent assaults and accidents), relatively close to the actual harm levels, whereas in other cases (e.g. homicides, alcohol-related mortality and suicide) they diverged from observed harm levels. A tax cut by 40% on spirits and by 15% on wine is estimated to increase total per capita alcohol consumption by 0.35 litre. This increase is estimated to cause 289 additional deaths, 1627 additional assaults and 1.6 million additional sickness absence days. CONCLUSIONS: The estimates of future changes in harm based upon even relatively modest increases in alcohol consumption produce considerable negative effects, with large economic consequences for the Swedish economy. The additional alcohol-related deaths, for instance, amount to more than half the number of yearly traffic fatalities in Sweden.     

Mannose binding lectin and soluble Toll-like receptor 2 in heart failure following acute myocardial infarction

BackgroundTo determine the relationship between markers of innate immunity and clinical outcomes in patients with heart failure (HF) after acute myocardial infarction (AMI). Atherogenesis and HF is associated with the altered control of inflammation by innate immune defenses that include pattern-recognition molecules such as Toll-like receptors (TLRs) and mannose-binding lectin (MBL).Methods and ResultsWe assessed circulating levels, and relationships with adverse outcomes of MBL and sTLR2 levels in 234 patients with AMI complicated with HF. Blood was sampled at baseline (median 3 days after AMI), 1 month, 1 year, and 2 years. For comparison, we also measured MBL and sTLR2 levels in 20 age- and sex-matched healthy controls. Patients with post-MI HF had markedly decreased serum levels of sTLR2 at baseline that increased during follow-up, but did not reach the concentrations present in healthy controls. In contrast, serum MBL levels were initially normal in patients with post-MI HF, but decreased during follow-up, and MBL levels measured 1 month after the index infarct were inversely associated with a higher incidence of reinfarction.ConclusionThese findings suggest that circulating levels of MBL and sTLR2 may reflect different aspects of the innate immune response and further suggest the involvement of innate immunity responses in the pathogenesis of post-MI HF.     

The effects of adrenocorticotrophic hormone and an equivalent dose of cortisol on the serum concentrations of lipids, lipoproteins, and apolipoproteins

Previous studies have shown a strong lipid-lowering effect of adrenocorticotrophic hormone (ACTH) in healthy individuals and in patients with different kinds of dyslipoproteinemia. The mechanism behind this effect has not been established and its direct ACTH-specific nature has been questioned. Therefore, the present study was performed. Thirty healthy young males were randomized into 3 groups of equal size: one group received ACTH1-24 1 mg IM, daily for 4 days, another group was treated with cortisol 150 mg ID (50 mg tid) daily for 4 days, whereas a control group was observed for 4 days. Fasting blood samples were collected before and after treatment or observation. The serum concentrations of cholesterol (12%, P < .05), low-density lipoprotein cholesterol (24%, P < .01), and apolipoprotein (apo) B (31%, P < .01) decreased significantly in the ACTH group but not in the cortisol and control groups. The statistical workup confirmed that only ACTH had a lowering effect on the apo B-containing lipoproteins. In contrast, the results indicated conformity between the treatment groups with respect to increases in the serum apo E concentrations. There were inconsistent changes in the serum concentrations of the triglycerides, high-density lipoprotein cholesterol, apo A, and lipoprotein(a). The main results were clear: the lowering effect of ACTH on the serum concentration of apo B-containing lipoproteins could not be ascribed to cortisol. These, in combination with previous in vitro results, indicated an ACTH-specific effect.     

Systolic dysfunction in heart failure with normal ejection fraction: speckle-tracking echocardiography

Left ventricular (LV) ejection fraction (EF) and LV end-systolic volumes are important measures of LV global function. However, in many patients with symptoms of heart failure, these measures are within normal limits. This condition is classified as heart failure with normal ejection fraction (HFNEF). Reduced EF and increased end-systolic volume, however, require impaired function in a number of LV segments. Therefore, apparently normal systolic function in HFNEF may reflect limited sensitivity of global EF, and assessment of regional systolic function may provide important diagnostic information. The recently introduced method, speckle-tracking echocardiography (STE), represents a simplified, objective, and angle-independent modality for quantification of regional myocardial deformation. The software uses conventional gray-scale B-mode recordings and tracks myocardial speckles, which serve as natural acoustic markers. Radial and longitudinal myocardial deformation can be measured simultaneously from long-axis recordings, radial and circumferential deformation from short-axis recordings, and LV torsion from assessment of apical and basal short-axis rotation. Experimental and clinical studies have demonstrated that the STE method can assess myocardial function accurately in healthy subjects in the settings of acute and chronic ischemia, dyssynchrony, and cardiomyopathy. So far, no STE studies have been performed regarding HFNEF. The purpose of this article is therefore to illustrate the potential of this novel method.     

Thalidomide attenuates the development of fibrosis during post-infarction myocardial remodelling in rats

BACKGROUND: Inflammation plays a pathogenic role in the development of heart failure (HF). The aim of this study was to examine the effect of treatment with the immunomodulating drug thalidomide in a rat model for post-myocardial infarction (MI) HF. METHODS: Rats were subjected to MI by left coronary artery ligation or sham-operated. Seven days after surgical intervention rats were randomised to treatment with thalidomide or vehicle for 8 weeks. RESULTS: Our main findings were: (i) thalidomide treatment did not affect cardiac function or the hypertrophic response, as determined by haemodynamic measurements and heart chamber weights, respectively. (ii) HF rats treated with thalidomide had a minor reduction in septum and relative wall thickness (p<0.05), indicating an anti-remodelling effect. (iii) Thalidomide appeared to have immunostimulatory effects on the myocardium as evident by increased MIP-1alpha gene expression (p<0.05). (iv) Treating HF rats with thalidomide reduced myocardial collagen content, as assessed by markedly decreased levels of hydroxyproline ( approximately 40% reduction; p<0.05), accompanied by lower TGF-beta(1) gene expression (p<0.05). CONCLUSION: Although thalidomide had no effect on cardiac function, our results suggest that intervention with thalidomide may have beneficial effects in post-MI HF by attenuating collagen accumulation and development of myocardial fibrosis.     

Genetic mapping of the cold-adapted phenotype of B/Ann Arbor/1/66, the master donor virus for live attenuated influenza vaccines (FluMist)

Cold adapted (ca) B/Ann Arbor/1/66 is the master donor virus for the influenza B (MDV-B) vaccine component of the live attenuated influenza vaccine (FluMist). The six internal genes contributed by MDV-B confer the characteristic cold-adapted (ca), temperature-sensitive (ts) and attenuated (att) phenotypes to the vaccine strains. Previously, it has been determined that the PA and NP segments of MDV-B control the ts phenotype while the att phenotype requires the M segment in addition to PA and NP. Here, we show that the PA, NP and PB2 segments are responsible for the ca phenotype of MDV-B when examined in chicken cell lines. Five loci in three RNA segments, R630 in PB2, M431 in PA and A114, H410 and T509 in NP, are sufficient to allow efficient virus growth at 25 degrees C. Substitution of these five amino acids with wt (wild type) residues completely reverted the MDV-B ca phenotype. Conversely, introduction of these five ca amino acids into B/Yamanashi/166/98 imparted the ca phenotype to this heterologous wt virus. In addition, we also found that the MDV-B M1 gene affected virus replication in chicken cells at 33 and 37 degrees C. Recombinant viruses containing the two MDV-B M1 residues (Q159, V183) replicated less efficiently than those containing wt M1 residues (H159, M183) at 33 and 37 degrees C, implicating the role of the MDV-B M segment to the att phenotype. The complexity of the multigenic signatures controlling the ca, ts and att phenotypes of MDV-B provides the molecular basis for the observed genetic stability of the FluMist vaccines.     

Testicular germ cell tumours in Iceland: a nationwide clinicopathological study

The purpose of this study was to examine the pathology of all germ cell tumours of the testis diagnosed in Iceland 1955-2002. A total of 214 patients were included in the study. The current age-standardized incidence was found to be 6.1 per 100,000 and had increased almost fourfold during the study period. Seminoma was diagnosed in 55% of cases. Non-seminomas were diagnosed in 45%, and these were further classified as mixed germ cell tumours (33%), embryonal carcinoma (8%), teratoma (3%), and yolk sac tumour (n=1). The mean age at diagnosis was significantly higher for the seminomas than the non-seminomas (38 years versus 29 years) (p<0.001) and the non-seminomas were diagnosed at a significantly higher stage than the seminomas (p<0.001). Thus, in seminoma patients the tumour was localized to the testis (stage I) in 81% of cases, in 17% of patients the tumour had spread to the lymph nodes (stage II or III), and only 2% had extranodal metastasis at diagnosis (stage IV). In contrast, in the non-seminoma patients, the tumours were found to be stage I in 56%, stage II or III in 24%, and stage IV in 20% of cases. No significant difference in staging was found between non-seminoma subtypes. Identification of necrosis or vascular invasion was significantly associated with metastatic disease at diagnosis (p=0.002). During the study period a significant increase in stage I tumours was found as well as a decrease in the size of the tumours.