Osteomyelitis complicating Streptococcus milleri endocarditis

A patient with osteomyelitis of the spine complicating bacterial endocarditis due to Streptococcus milleri is discussed. To our knowledge, this is the first time this organism has been associated with this complication.     

Avoiding therapeutic pitfalls: the rational use of specifically targeted agents against hepatitis C infection

The development of specifically targeted antiviral agents against hepatitis C is a major therapeutic advance that promises to markedly improve treatment response rates in patients with chronic infection. However, rapid emergence of drug resistance has already been described, the consequences of which are not yet understood. Although there are important differences between hepatitis C (HCV) and human immunodeficiency virus (HIV) infection, the judicious use of candidate agents against HCV should be guided by principles that have been established in the HIV therapeutic arena. In this review, we attempt to draw useful parallels between the development of antiretroviral therapy for HIV and preliminary data on antiviral agents for hepatitis C virus infection. Applying concepts learned in HIV therapeutics will hopefully lead to a prudent and cautious path in HCV treatment paradigms, particularly with respect to drug resistance.     

Liquid chromatography-tandem mass spectrometry analysis of erythrocyte thiopurine nucleotides and effect of thiopurine methyltransferase gene variants on these metabolites in patients receiving azathioprine/6-mercaptopurine therapy

BACKGROUND: Polymorphic thiopurine S-methyltransferase (TPMT) is a major determinant of thiopurine toxicity. METHODS: We extracted 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) from erythrocytes with perchloric acid and converted them to 6-thioguanine (6-TG) and a 6-methylmercaptopurine (6-MMP) derivative during a 60-min acid hydrolysis step. The liquid chromatography system consisted of a C(18) column with an ammonium acetate-formic acid-acetonitrile buffer. 8-Bromoadenine was the internal standard. Analytes were measured with positive ionization and multiple reaction monitoring mode. With PCR-restriction fragment length polymorphism analysis and TaqMan allelic discrimination, common TPMT alleles (*1, *2, *3A, *3B, *3C) were determined in 31 792 individuals. We used perchloric acid extraction, acid hydrolysis, and HPLC with ultraviolet detection to measure erythrocyte 6-TG and 6-MMP nucleotide concentrations in 6189 patients with inflammatory bowel disease receiving azathioprine/6-mercaptopurine therapy. RESULTS: Intra- and interday imprecision were <10% at low and high analyte concentrations. The conversion of 6-TG and 6-MMP nucleoside mono-, di-, and triphosphates was complete after hydrolysis. Allelic frequency for TPMT variant alleles ranged from 0.0063% (*3B) to 3.61% (*3A). Compared with wild types, TPMT heterozygotes had an 8.3-fold higher risk for 6-TGNs >450 pmol/8 x 10(8) erythrocytes (concentration associated with increased risk for leukopenia), but an 8.2-fold lower risk for 6-MMPNs >5700 pmol/8 x 10(8) erythrocytes (concentration associated with increased risk for hepatotoxicity). CONCLUSIONS: The liquid chromatography-tandem mass spectrometry method can be applied to the routine monitoring of thiopurine therapy. The association between TPMT genotype and metabolite concentrations illustrates the utility of pharmacogenetics in the management of patients undergoing treatment with thiopurines.     

Dilated Cardiomyopathy and Role of Antithrombotic Therapy

BackgroundThere is no consensus as to whether anticoagulation has a favorable risk:benefit in reducing thromboembolic events in patients with heart failure (HF) secondary to dilated cardiomyopathy who do not suffer from atrial fibrillation or primary valvular disease.Methods and ResultsThe literature reviewed on this topic included most recent and ongoing studies that assessed the use of anticoagulation for this population. Several large retrospective studies showed an increased risk of thromboembolic events among patients with depressed left ventricular function. The relative risk of stroke in individuals with HF from all causes was found to be 4.1 for men and 2.8 for women, but confounding comorbidities (such as atrial fibrillation and coronary artery disease) were commonly present. Currently, there are no randomized prospective trials to guide the use of antithrombotics for these patients, and the risk of bleeding secondary to anticoagulation has limited the use of oral anticoagulants for prevention of thrombosis. Among patients with HF, increasing age directly correlates with both major bleeding and thromboembolic events, with a 46% relative risk of bleeding for each 10-year increase in age older than 40 years.ConclusionsTo date, there is no agreement on appropriate antithrombotic treatment (if any) for primary thromboembolism prophylaxis in patients with dilated cardiomyopathy with sinus rhythm. In recent years, several promising prospective trials were terminated prematurely due to inadequate enrollment. The Warfarin Aspirin-Reduced Cardiac Ejection Fraction trial may provide evidence regarding the use of anticoagulation for patients with decreased myocardial function.     

Photothermal laser ablation of Barrett's oesophagus: endoscopic and histological evidence of squamous re-epithelialisation

Background—Barrett's oesophagus is acquired bysevere gastro-oesophageal reflux and is a premalignant condition. Acidsuppression or anti-reflux surgery alone do not cause significantregression of the metaplastic mucosa nor reduce the malignantpotential. Recent reports have suggested that the combination ofmucosal ablation with acid suppression may result in squamous regeneration.
Aims—To destroy Barrett's mucosa by thermalablation (in the setting of acid suppression) and so induce squamous regeneration.
Patients—Sixteen patients with non-dysplasticBarrett's oesophagus were recruited from a surveillance programme. Allhad been on a proton pump inhibitor.
Methods—At intervals, non-circumferentialareas of columnar mucosa were ablated using the KTP laser. Acidsuppression was obtained with 40 mg omeprazole daily. Multiple biopsyspecimens were obtained for histological examination from ablated areas.
Results—Ablation of all areas of glandular mucosaresulted in squamous regeneration. The number of treatments requireddepended on the length of the Barrett's segment. In 11 patients therewas evidence of squamous regeneration over remaining Barrett's glands (in some of the post-treatment biopsy specimens) whilst in nine patients squamous metaplasia was seen within Barrett's glands.
Conclusion—Mucosal ablation of Barrett'soesophagus by laser, in the setting of acid suppression, results insquamous regeneration (though some burying of Barrett's glands did occur).

Keywords:Barrett's oesophagus; laser; dysplasia; columnar-lined oesophagus; cancer

     

The effect of angiotensin‐blocking agents on liver fibrosis in patients with hepatitis C

Background: Multiple studies implicate the renin–angiotensin system in hepatic fibrogenesis. Few studies have examined the effects of angiotensin blockade on liver fibrosis via human histology. Aims: We studied the histological effect of angiotensin II blocking agents in chronic hepatitis C patients. Methods: This was a retrospective study of 284 chronic hepatitis C patients from 2001 to 2006 who underwent a liver biopsy. Group I was comprised of 143 hypertensive patients who received angiotensin‐blocking agents. Group II was comprised of 91 hypertensive subjects who received hypertensive agents other than angiotensin blockers. Group III was comprised of 50 non‐hypertensive subjects. Results: The groups were similar in age, sex, hepatitis C genotype, viral load and disease duration. They varied significantly in total diabetic patients (Group I, 43; Group II, 10; Group III, 1; P=0.0001), consistent with recommended use of angiotensin‐converting enzyme inhibitors in hypertensive diabetics. Non‐hypertensive patients had significantly less fibrosis than hypertensive patients, regardless of antihypertensive medications (Group I, 3.20; Group II, 3.73; Group III, 2.5; P=0.0002). Group I had significantly less fibrosis than Group II (P=0.02). This finding persisted in a non‐diabetic subgroup of Groups I and II (Group I, 3.07; Group II, 3.69; P=0.0129). Conclusion: Patients with hepatitis C and hypertension have increased fibrosis compared with non‐hypertensive patients. Hypertensive patients receiving angiotensin‐blocking agents had less fibrosis than hypertensive patients who did not receive angiotensin‐blocking agents. This suggests an association with hypertension, possibly via the renin–angiotensin system in the fibrosis development and suggests a beneficial role of angiotensin II blockade in hepatitis C virus‐related fibrosis.