Relationship of interleukin-6 and C-reactive protein to the prothrombotic state in chronic atrial fibrillation

OBJECTIVES: We sought to test the hypothesis that there is a relationship between inflammation and the prothrombotic state in atrial fibrillation (AF). BACKGROUND: Atrial fibrillation is associated with a prothrombotic or hypercoagulable state, which may contribute to an increased risk of stroke and thromboembolism. Inflammation may be involved in the pathogenesis of AF, but the role of inflammation in the pathophysiology of the prothrombotic state of AF has not been studied in detail, despite evidence of a link between inflammation and arterial atherothrombotic disorders. METHODS: We measured plasma indexes of inflammation (C-reactive protein [CRP] and interleukin-6 [IL-6]) and the prothrombotic state, including markers of platelet activation (soluble P-selectin), endothelial damage/dysfunction (von Willebrand factor), the coagulation cascade (tissue factor [TF], fibrinogen), and indexes of blood rheology (plasma viscosity, plasma fibrinogen, and hematocrit) in 106 patients with chronic AF and 41 healthy control subjects included in a cross-sectional analysis. RESULTS: Compared with controls, AF patients had higher levels of IL-6 (p = 0.034), CRP (p = 0.003), TF (p = 0.019), and plasma viscosity (p = 0.045). Plasma IL-6 levels were higher among AF patients at "high" risk of stroke (p = 0.003). After adjusting for potential confounding clinical variables (e.g., vascular disease), AF remained significantly associated with a raised logarithmic transformation (log) of TF (p = 0.04), but the relationships between AF and log IL-6, log CRP, and plasma viscosity became nonsignificant. Among AF patients, log TF (p < 0.001) and high stroke risk (p = 0.003) were independent associates of log IL-6 (adjusted r(2) = 0.443), whereas log fibrinogen (p < 0.001) and plasma viscosity (p = 0.04) were independent associates of log CRP (adjusted r(2) = 0.259). CONCLUSIONS: Increased plasma IL-6, CRP, and plasma viscosity support the case for the existence of an inflammatory state among "typical" populations with chronic AF. These indexes of inflammation are related to indexes of the prothrombotic state and may be related to the clinical variables of the patients (underlying vascular disease and co-morbidities), rather than simply to the presence of AF itself.     

Mode of action of chlorothiazide in the reduction of blood pressure in hypertension

The possibility that chlorothiazide affects the hypertensive process is a very real one since the effect on the blood pressure of long term treatment is to reduce peripheral resistance.

The means by which this is achieved is unknown. It cannot be shown to be due to loss of sodium since the level of exchangeable sodium returns to normal on long term treatment. The only change we have been able to observe is a fall in total body water which is believed to be due to a loss of cellular water.     

Extrusion of testosterone pellets: a randomized controlled clinical study

BACKGROUND: It has previously been shown that testosterone implantation is an effective and well accepted form of androgen replacement therapy, but that pellet extrusion was the most frequent side-effect. The present study aimed to reduce the extrusion rate. OBJECTIVE: To determine whether the washing of testosterone pellets to remove potentially surface-adherent particles decreased the rate of extrusion of pellet implants. DESIGN: Prospective, randomized parallel group design in a single centre with consecutive procedures to be randomized (1 : 1) into a wash or control group. PATIENTS: The study included 251 testosterone implantation procedures in men with known androgen deficiency. MEASUREMENTS: The primary endpoint, extrusion rate per procedure, was evaluated prospectively by telephone contact at 1 week and then 3 and 6 month intervals. Secondary end-points included peri-procedure adverse events (bleeding, skin reaction, excessive discomfort) noted at the time of implant. Bruising, bleeding and infection were also evaluated as later adverse events by telephone and personal follow-up. Explanatory variables recorded as possible covariables included the number of implants used, production batch number of the implants, the operator, as well as other demographic and medical factors. RESULTS: In the wash group, the extrusion rate was 12% per procedure (19 pellets from 15 subjects) whereas in the control group, the extrusion rate was 11.1% per procedure (18 pellets from 14 subjects), indicating no evidence of any benefit of the wash procedure (OR = 1. 09 [95% CI 0.47-2.6] per procedure). There was no evidence of benefit in secondary endpoints including total adverse events (7.1%, OR 1.28 [0.44-3.9], bleeding/bruising (8.8%, 1.23 [0.47-3.3]) and infection (4.0%, 1.54 [0.35-7.6]) per procedure. Among men reporting an infection requiring antibiotic treatment according to their own general practitioners, six/ten (60%) subsequently experienced an extrusion. There were no significant differences in extrusion rate between four different operators (P = 0.24) nor among 12 different batches of pellets used during the course of the study (P = 0.77). CONCLUSIONS: The pellet washing procedure used during implantation does not reduce the subsequent extrusion rate. The higher rate of both primary and secondary adverse events in this prospective study compared with the previous retrospective survey may reflect either more rigorous follow-up or a secular trend.     

Questions to and answers from the International AIDS Society-USA Resistance Testing Guidelines Panel

In 1996 the International AIDS Society-USA convened an international panel of experts in HIV drug resistance and clinical management to develop guidelines for the clinical use and limitations of resistance testing. Since then the International AIDS Society-USA Resistance Testing Guidelines Panel has developed and regularly published its recommendations. The latest panel recommendations appear in the July 1 issue of Clinical Infectious Diseases. We periodically pose questions to the panel relating to clinical elements of resistance testing that have been collected from HIV practitioners across the nation. We are happy to feature the latest edition in this issue of Topics in HIV Medicine. It is our hope that addressing these issues will help guide your treatment strategy decisions regarding resistance testing.     

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota–heat shock proteins (HSPs)–probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota’s composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient’s microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.