Barrett's esophagus and squamous cell carcinoma in a patient with psychogenic vomiting

We report the association of Barrett's esophagus and invasive squamous cell carcinoma of the distal esophagus in a young 31-yr-old woman with a history of self-induced psychogenic vomiting. The development of intestinalized columnar mucosa and esophageal cancer in this young patient illustrates the complicated associations between human behavior and pathogenetic mechanisms involved in esophageal carcinogenesis.     

Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Northern Italian patients

Abstract: Background/Aims: Hepatitis C virus (HCV) related disease follows a long, benign course and most affected patients have mild disease. Liver biopsy is mandatory to grade and stage the disease. Characteristic, though non-specific, HCV histological lesions such as bile duct damage and steatosis have been singled out but their association with non-histological parameters has not been completely defined. Our aim was to study the relationships among these histological lesions and clinical, biochemical, functional and virological characteristics in a group of Northern Italian patients with chronic hepatitis. Methods: We studied 172 patients with HCV-related chronic hepatitis. Patients were divided into groups on the basis of histology including bile duct damage and steatosis. Clinical, biochemical, functional and virological profiles were related to histological findings. Results: Histological grading and staging of disease increased as the age of patients increased. Steatosis was present in 70% of our patients and was related to a higher degree of fibrosis and to decreased functional activity. The prevalence of bile duct damage was 20%. This lesion was present in older patients with higher staging and impaired liver function. Biochemically it was associated with an increase in aspartate aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, and total bilirubin. Conclusions: In the population we studied, HCV chronic hepatitis was predominantly a mild disease. Moreover both steatosis and bile duct damage were also mild. Steatosis was associated with fibrosis and this might influence liver metabolic function. Bile duct lesions were found in older patients with advanced disease showing biochemical evidence of cholestasis. The molecular role HCV might play in the pathogenesis of these histological features should be addressed in further studies.     

Improved efficacy of 10-Day sequential treatment for Helicobacter pylori eradication in children: a randomized trial

BACKGROUND & AIMS: The currently recommended first-line eradication treatment of Helicobacter pylori in children is usually successful in about 75%. Recently, in adults, a novel 10-day sequential treatment has achieved an eradication rate of 95%. The aim of the study was to assess the H pylori eradication rate of the sequential treatment regimen compared with conventional triple therapy in children. METHODS: Seventy-eight consecutive children with H pylori infection were randomized to receive either sequential treatment (omeprazole plus amoxicillin for 5 days, followed by omeprazole plus clarithromycin plus tinidazole for another 5 days) (n = 38; 15 boys [39.5%]; median age, 11.0 years [range, 3.3-16 years]) or triple therapy (omeprazole, amoxicillin, and metronidazole) for 1 week (n = 37; 15 boys [40.5%]; median age, 9.9 years [range, 4.3-16 years]). H pylori infection was based on 2 out of 3 positive tests results: 13C-urea breath test, rapid urease test, and histologic analysis. Eradication was assessed by 13C-urea breath test 8 weeks after therapy. RESULTS: Seventy-four patients completed the study. H pylori eradication was achieved in 36 children receiving sequential treatment (97.3%; 95% confidence interval, 86.2-99.5) and 28 children receiving triple therapy (75.7%; 95% confidence interval, 59.8-86.7) (P < .02). Compliance with therapy was good (>95%) in all. CONCLUSIONS: Our study shows, for the first time in children, that 10-day sequential treatment achieves a higher eradication rate than standard triple therapy, which is consistent with the results of adult studies.     

Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes

OBJECTIVE: To assess whether there is a relationship between the effectiveness of alendronate treatment in postmenopausal women with osteoporosis and BsmI vitamin D receptor (VDR) genotypes. DESIGN: Prospective baseline-controlled clinical trial. PATIENTS: Sixty-eight Italian osteoporotic women were enrolled and treated with alendronate at a dose of 10 mg/day for 12 months. MEASUREMENTS: At entry and after treatment, lumbar bone mineral density (BMD) and serum osteocalcin (OC) and urinary deoxypyridinoline/creatinine ratio (DPD-Cr) levels were evaluated. DNA was extracted from blood and analysed for the BsmI polymorphism of the VDR gene. RESULTS: The mean percentage (% +/- SD) change from baseline in lumbar BMD was significantly higher (P < 0.01) in bb than in BB BsmI VDR genotypes (7.92 +/- 4.31 vs. 3.40 +/- 1.81). No significant difference in lumbar BMD was observed in Bb VDR patients (6.01 +/- 3.89) in comparison with other groups. The mean percentage of change in serum OC and urinary DPD-Cr levels was significantly (P < 0.01) lower in individuals with bb than in those with BB BsmI VDR genotypes (-14.34 +/- 2.87 vs.-10.39 +/- 1.43 and -9.61 +/- 5.56 vs.-4.61 +/- 2.31). No significant difference in serum OC and urinary DPD-Cr levels was observed in Bb VDR patients (-12.31 +/- 2.11 and -6.52 +/- 2.65) in comparison with other groups. CONCLUSION: The different BsmI vitamin D receptor genotypes modify the pharmacological response to alendronate treatment in postmenopausal women with osteoporosis.     

Radiofrequency ablation of hepatic tissue: a new experimental animal model

BACKGROUND/AIMS: Experimental radiofrequency ablation has already been performed in healthy livers of porcine models, but not in less expensive and easy-to-manage rats, with devices capable of delivering radiofrequency ablation in the 20-30 g liver of such small animals being so far unavailable. METHODOLOGY: We experimented with a modified system of radiofrequency ablation of liver tissue in rat models developing a custom-made needle-microelectrode of very small dimensions (0.3x2 mm) and an electrode-tip cooling technique, based on saline solution infusion. We adjusted duration (seconds) and power (watts) of radiofrequency ablation letting them range between 5-50 seconds and 5-25 W, respectively, to obtain the greatest lesions with the least side effects. After sacrificing the animals, an accurate histological examination of the liver was made. RESULTS: It is possible to establish beforehand the diameter of thermal liver lesion on the basis of joules of applied energy. The greatest increase of liver thermal lesion diameter (8 mm) is obtained with a 250-joule (10 W for 25 seconds) thermal energy cooling the electrode-tissue interface. CONCLUSIONS: Experimental radiofrequency ablation in rat liver is an effective and cheap way to study its effects on healthy hepatic tissues. It might be the first step to treat experimentally caused liver tumors.     

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.     

TSH/cAMP up-regulate sarco/endoplasmic reticulum Ca2+-ATPases expression and activity in PC Cl3 thyroid cells

OBJECTIVE: We recently reported that the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 2b is the SERCA form preferentially expressed in rat thyroid. Moreover, SERCA2b expression dramatically decreases in virally transformed, highly tumorigenic, PC Cl3 thyroid cells. These results suggest that, in the thyroid, SERCA2b, in addition to its housekeeping role, is linked to differentiation and is a regulated gene. We therefore sought to study the effect of TSH, the main regulator of thyroid function, on SERCA2b expression and activity. METHODS: PC Cl3 cells were hormone starved in low-serum medium and stimulated for long (48 h) or short (1, 2 and 4 h) times. SERCA2b expression and activity were evaluated by Northern and Western blots, Ca2+-ATPase activity and Ca2+ store content. RESULTS: In PC Cl3 cells, SERCA2b mRNA and protein were induced twofold by a 48-h long treatment with TSH. Long-term elevation (48 h) of intracellular cAMP levels, by forskolin or 8-Br-cAMP, had similar effects on SERCA2b mRNA and protein. We also measured Ca2+-ATPase activity and Ca2+ store content. Both long (48 h) and short (0.5-1 h) treatments with TSH, forskolin or 8-Br-cAMP induced a marked increase of SERCA2b activity. This effect was completely abolished by H89, a specific inhibitor of cAMP-dependent protein kinase A (PKA). TSH and 8-Br-cAMP increased Ca2+ store content after both long (48 h) and short (1-2 h) treatments. CONCLUSIONS: These data suggested that TSH/cAMP acts as an important regulator of both SERCA2b expression and activity in the thyroid system, through PKA activation.