The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study.

BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. METHODS: To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. CONCLUSION: The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.     

Two novel mutations at exon 8 of the Sequestosome 1 (SQSTM1) gene in an Italian series of patients affected by Paget's disease of bone (PDB).

PDB is genetically heterogeneous. Mutations of the sequestosome1 gene have been reported in sporadic and familial forms of Paget's in patients of French Canadian and British descent. Mutational analyses in different ethnic groups are needed to accurately investigate hereditary diseases. We describe two novel mutations of sequestosome1 in 62 Italian sporadic patients, confirming the role of the encoded protein in this disorder. INTRODUCTION: Paget's disease of bone (PDB) is a relatively common disease of bone metabolism reported to affect up to 3% of whites over 55 years of age. The disorder is genetically heterogeneous, and at present, there is scientific evidence that at least eight different human chromosomal loci are correlated with its pathogenesis. Mutations of the sequestosome1 (SQSTM1) gene were identified as responsible for most of the sporadic and familial forms of Paget in patients of French Canadian and British descent. Such mutations were located at exon 7 and 8 levels, encoding for the ubiquitin protein-binding domain (UBA) and representing a mutational hot spot area. MATERIALS AND METHODS: To verify the involvement of this gene in Italian subjects affected by PDB, we performed mutational analysis in 62 sporadic PDB cases. RESULTS: We described three different mutations at exon 8 level: P392L, already described in the French Canadian population and families predominantly of British descendent, and two novel mutations consisting of the amino acid substitutions M404V and G425R. No significant differences in the clinical history of PDB have been observed in patients with SQSTM1 mutations in respect to those without. CONCLUSIONS: Even though our findings suggest a minor involvement of the SQSTM1 gene in the pathogenesis of sporadic Italian Paget's cases, the identification of different significant mutations within the SQSTM1 gene in unrelated, but clinically similar individuals, offers extremely convincing evidence for a causal relationship between this gene and PDB. Longitudinal studies are needed to assess the penetrance of genotype/phenotype correlations. Our findings confirm the evidence of a clustered mutation area at this level in this disorder.     

Carbon dioxide laser salvage surgery after radiotherapy failure in T1 and T2 glottic carcinoma.

OBJECTIVES: Recurrent glottic carcinoma after radiotherapy (RT) may be managed by open neck or endoscopic surgery. The impact of endoscopic treatment with CO(2) laser for recurrent glottic carcinoma after RT is reported. METHODS: We present the oncologic and vocal outcomes of a retrospective study based on a series of 16 patients with rT1 and rT2 glottic carcinoma who were endoscopically managed between February 1995 and December 1999 after RT failure. All patients were males with a mean age of 68.7 years (range, 50 to 87 years). Before RT, the lesions had been staged as T1 N0 in 11 patients and T2 N0 in 5, and after RT as rT1 N0 in 12 and rT2 N0 in 4. According to the European Laryngological Society classification, a total of 9 transmuscular, 3 total, and 4 extended cordectomies were performed. Mean follow-up was 45 months (range, 9 to 79 months). RESULTS: Endoscopic salvage surgery was successful in 14 patients. One of them developed a second recurrence and was definitively cured with an additional endoscopic procedure. Two of the 16 patients had recurrent disease after salvage laser surgery and died due to progression of disease. Ultimate local control with laser alone at 3 years was 87.1%, according to the Kaplan-Meier method. Laryngeal preservation was obtained in all survivors after endoscopic rescue surgery. Voice analysis showed a clear correlation between the amount of vocal cord tissue resected and decrease of the vocal outcome. CONCLUSIONS: The present series indicates that selected recurrences after primary RT for T1 and T2 glottic carcinoma are eligible for endoscopic salvage surgery with oncologic results comparable to those with open neck procedures but with a lower complication rate and a favorable functional outcome.     

Dual Exposure to Sevoflurane Improves Anesthetic Preconditioning in Intact Hearts

Background: Anesthetic preconditioning (APC) with sevoflurane reduces myocardial ischemia-reperfusion injury. The authors tested whether two brief exposures to sevoflurane would lead to a better preconditioning state than would a single longer exposure and whether dual exposure to a lower (L) concentration of sevoflurane would achieve an outcome similar to that associated with a single exposure to a higher (H) concentration.

Methods: Langendorff-prepared guinea pig hearts were exposed to 0.4 mm sevoflurane once for 15 min (H1-15; n = 8) or 0.4 mm (H2-5; n = 8) or 0.2 mm sevoflurane (L2-5; n = 8) twice for 5 min, with a 5-min washout period interspersed. Sevoflurane was then washed out for 20 min before 30 min of global no-flow ischemia and 120 min of reperfusion. Control hearts (n = 8) were not subjected to APC. Left ventricular pressure was measured isovolumetrically. Ventricular infarct size was determined by tetrazolium staining and cumulative planimetry. Values are expressed as mean +/- SD.

Results: The authors found a better functional return and a lesser percentage of infarction on reperfusion in H2-5 (28 +/- 9%) than in H1-15 (36 +/- 8%; P < 0.05), L2-5 (43 +/- 6%; P < 0.05), or control hearts (52 +/- 7%; P < 0.05).     

Lymphocyte T helper-specific reactivity in sustained responders to interferon and ribavirin with negativation (seroreversion) of anti-hepatitis C virus.

BACKGROUND: Seroreversion, negativation of anti-hepatitis C virus previously positive, is sometimes found in some chronic hepatitis C-sustained responders (SRs) to antiviral therapy. AIMS: To determine the probability of seroreversion in SR treatment with Interferon and Ribavirin, and lymphocyte T helper (CD4+) reactivity to HCV antigens. METHODS: Thirty SR were followed on average for 54.8 months. Anti-HCV was tested by third generation test. Peripheral blood mononuclear cells (PBMCs) were isolated from venous blood and cultured to evaluate CD4+ proliferation in response to 2 microg/ml of eight HCV recombinant antigens from core, NS3, NS4, NS5 regions. RESULTS: Seroreversion was verified in 23% of patients (7/30), appearing at 47.5+/-24.0 months. The probability of anti-HCV loss in this group was 25% at 56 months after ending therapy. In 57% (4/7), anti-HCV returned to positive. These 7 SR patients with seroreversion also showed weaker CD4+ reactivity in 5% of tests (3/56) than the remaining 23 anti-HCV-positive SRs who showed stronger reactivity in 18% of tests (33/184), P=0.036. CONCLUSIONS: One-quarter of the SR showed seroreversion of anti-HCV and weaker CD4+ specific HCV proliferation than those who remained anti-HCV positive. The data suggest that complete viral eradication is a possible and achievable clinical objective.     

Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

Methodological issues in music interventions in oncology settings: A systematic literature review

This paper is part of a systematic literature review and presents methodological issues within studies, investigating therapeutic applications of music in cancer patients. This review focuses on published international research from the USA, Canada, Australia and European countries using four electronic databases: PSYCHINFO, WEB OF SCIENCE, MEDLINE and SCIENCEDIRECT. Thirty-two papers were identified and each paper was coded in terms of sample type, basic research question, research design and methodological details, results and implications for future research. This paper addresses questions related to study design and methodology. It explores and discusses the relative advantages and disadvantages of various approaches.     

An unusual association with Raynaud's phenomenon

A 36-yr-old lady with a year of typical Raynaud's and polyarthralgiahad a normal examination other than cold peripheries and bloodpressure of