Tumour necrosis factor alpha upregulates platelet CD40L in patients with heart failure

AIMS: Patients with heart failure (HF) have elevated values of the pro-inflammatory protein CD40L but the underlying mechanism is unclear. This study was performed to evaluate the interplay between tumour necrosis factor alpha (TNFalpha) and CD40L in HF. METHODS AND RESULTS: In patients with HF (n=86) and healthy subjects (HS, n=43), plasma levels of soluble CD40L (sCD40L), TNFalpha, soluble receptors of TNFalpha such as soluble TNF receptors I and II (sTNFR1 and sTNFR2), and 8OH-dG, a marker of oxidative stress, were determined. Also, an in vitro study was performed by determining platelet CD40L regulation upon platelet stimulation with TNFalpha. Compared with HS, HF patients had higher plasma values of sCD40L, TNFalpha, sTNFR1 and sTNFR2, and higher platelet expression of TNFR1 and TNFR2 with a progressive increase from NYHA I to NYHA IV classification. sCD40L significantly correlated with TNFalpha, sTNFR1, and sTNFR2; plasma levels of TNFalpha significantly correlated with sCD40L. Incubation of platelets from HF patients with a TNFalpha receptor inhibitor significantly decreased platelet CD40L expression. The in vitro study demonstrated that TNFalpha significantly increased CD40L expression, an effect weakly influenced by aspirin but significantly reduced by AACOCF3, an inhibitor of PLA(2), apocynin, an inhibitor of NADPH oxidase, or staurosporine, an inhibitor of PKC. CONCLUSION: The study shows that in HF patients, platelet CD40L is upregulated by TNFalpha via a cyclooxygenase-1-independent, arachidonic acid-mediated oxidative stress mechanism.     

Diagnosing Small Intestinal Bacterial Overgrowth: A Comparison of Lactulose Breath Tests to Small Bowel Aspirates

Background

Duodenal aspiration (DA) and lactulose breath tests (LBT) are commonly performed to diagnose small intestinal bacterial overgrowth (SIBO). There are no data directly comparing these tests.

Aims

To investigate the agreement between DA and LBT for the diagnosis of SIBO.

Methods

A retrospective cohort study of adult patients who underwent a LBT and a DA at a tertiary care center over 9 years was assembled. LBT was considered positive if the hydrogen baseline or peak change measurement was ≥?20 ppm, and/or if the methane baseline or peak change was ≥?10 ppm. DA was considered positive if >?100,000 cfu/mL of gram-negative flora was identified on culture, and contaminated if >?100,000 cfu/mL of gram-positive flora was identified.

Results

A total of 106 patients were evaluated; 81 (76.4%) were female; the mean age was 53.4?±?15.9 years. 21 patients (19.8%) had evidence of contamination on DA. 14 (16.5%) patients had a positive DA result. Patients with diabetes mellitus and those with PPI use were more likely to have a positive DA (94.4% vs. 71.4%, p?=?0.007; 62% vs. 28.6%, p?=?0.021, respectively). 33 (31.1%) patients had a positive LBT. Patients with a history of small bowel resection were more likely to have a positive LBT (12.1% vs. 1.4%, p?=?0.016). DA and LBT results agreed in 54 patients (63.5%; kappa?=???0.02), indicating poor agreement.

Conclusions

The agreement between LBT and DA in evaluation for SIBO was poor. LBT may be favorable to DA, as LBT is safer, cheaper, and less likely to yield a contaminant result.

     

Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis

The effect of proctocolectomy on the primary sclerosing cholangitis that frequently is associated with chronic ulcerative colitis in patients with both conditions is unknown. We have studied prospectively the progression of clinical, biochemical, cholangiographic, and hepatic histologic features in 45 patients with both primary sclerosing cholangitis and chronic ulcerative colitis to compare these variables in the 20 patients who had undergone proctocolectomy with the 25 who had not. The two groups were similar initially with regard to clinical, biochemical, cholangiographic, and hepatic histologic findings. All patients were followed for a minimum of 1 yr and overall duration of follow-up was similar in both groups (4.1 vs. 3.9 yr). Clinically, new onset of hepatomegaly, splenomegaly, esophageal varices, and ascites did not differ in patients with and without proctocolectomy. Biochemically, the serial changes in bilirubin, alkaline phosphatase, aspartate aminotransferase, prothrombin time, and albumin were similar. Histologic progression on liver biopsy did not differ between groups, nor did changes on serial cholangiograms. Proctocolectomy also had no effect on survival. We conclude that proctocolectomy for chronic ulcerative colitis has no beneficial effect on the primary sclerosing cholangitis in patients with both diseases.     

Conversational metrics,psychopathological dimensions and self-disturbances in patients with schizophrenia

European Archives of Psychiatry and Clinical Neuroscience - Difficulties in interpersonal communication, including conversational skill impairments, are core features of schizophrenia. However,...     

Early and long-term clinical outcomes of bilio-intestinal diversion in morbidly obese patients

Purpose

To evaluate the early and long-term postoperative results of malabsorptive surgery in morbidly obese patients.

Methods

Between 2000 and 2007, 102 morbidly obese patients were referred to the Department of Surgery “Pietro Valdoni”, “Sapienza” University of Rome, Policlinico “Umberto I°”, Rome, Italy for malabsorptive surgery. All patients underwent derivative biliodigestive surgery after they had been reviewed by a team of surgeons, physicians, dieticians, and psychologists.

Results

There were no intra-operative complications, but two patients suffered postoperative pulmonary embolisms, which resolved with medical treatment. The mean postoperative hospital stay was 7 days, with no early or late mortality. Maximum weight loss was reached 12–24 months after surgery, while the mean percentage excess weight loss at 3–5 years ranged from 45 to 64 %. Specific postoperative complications in the first 2 years after surgery were abdominal abscess (n = 2), gastroduodenal reflux (n = 4), and incisional hernia (n = 6). Diabetes resolved in 98 % of the diabetic patients within a few weeks after surgery and blood pressure normalised in 86.4 % of those who had had hypertension preoperatively. Obstructive sleep apnoea and obesity hypoventilation syndrome also improved significantly in 92 % of the patients.

Conclusions

Morbidly obese patients can undergo biliodigestive surgery safely with good long-term weight loss and quality of life expectancy.