Simplified risk stratification criteria for identification of patients with MRSA bacteremia at low risk of infective endocarditis: implications for avoiding routine transesophageal echocardiography in MRSA bacteremia.

The aim of this study was to identify patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with low risk of infective endocarditis (IE) who might not require routine trans-esophageal echocardiography (TEE). We retrospectively evaluated 398 patients presenting with MRSA bacteremia for the presence of the following clinical criteria: intravenous drug abuse (IVDA), long-term catheter, prolonged bacteremia, intra-cardiac device, prosthetic valve, hemodialysis dependency, vertebral/nonvertebral osteomyelitis, cardio-structural abnormality. IE was diagnosed using the modified Duke criteria. Of 398 patients with MRSA bacteremia, 26.4 % of cases were community-acquired, 56.3 % were health-care-associated, and 17.3 % were hospital-acquired. Of the group, 44 patients had definite IE, 119 had possible IE, and 235 had a rejected diagnosis. Out of 398 patients, 231 were evaluated with transthoracic echocardiography (TTE) or TEE. All 44 patients with definite IE fulfilled at least one criterion (sensitivity 100 %). Finally, a receiver operator characteristic (ROC) curve was obtained to evaluate the total risk score of our proposed criteria as a predictor of the presence of IE, and this was compared to the ROC curve of a previously proposed criteria. The area under the ROC curve for our criteria was 0.710, while the area under the ROC curve for the criteria previously proposed was 0.537 (p < 0.001). The p-value for comparing those 2 areas was less than 0.001, indicating statistical significance. Patients with MRSA bacteremia without any of our proposed clinical criteria have very low risk of developing IE and may not require routine TEE.

Evaluation of bupropion hydrochloride developmental cardiotoxic effects in chick cardiomyocyte micromass culture and stem cell derived cardiomyocyte systems.

The use of antidepressant drug bupropion hydrochloride (BPN) during pregnancy results in increased cardiovascular anomalies. In this study, BPN developmental cardiotoxic effects in in vitro system were evaluated using chick cardiomyocyte micromass (MM) culture system and mouse embryonic stem cell derived cardiomyocyte (ESDC) system. In MM system, the cardiomyocyte contractile activity significantly decreased only at BPN 200 µM, while in ESDC system BPN concentration above 75 µM resulted in decreased contractile activity. The increase in drug concentration also affected the cardiomyocyte viability and total cellular protein content in both systems, but in ESDC system the cell viability failed to attain significant difference. The drug failed to induce reactive oxygen species production in both systems, but has affected the cardiac connexin43 expression especially in MM system. We observed that BPN showed developmental cardiotoxic effects irrespective of the stage of cardiac development in both in vitro systems.

Congenital von Willebrand's disease and clinical hypothyroidism.

Data from case reports and systematic reviews suggest an association of Hypothyroidism and Acquired von Willebrand's syndrome. It is not known if congenital von Willebrand's disease is associated with hypothyroidism in a similar way. The aim of this study was to identify the association of congenital von Willebrand's disease (VWD) with clinical hypothyroidism. A total of 350 cases of congenital VWD were initially screened from our institution database from 1985 to 2010. A careful review of patient records was carried out to see if patients truly had congenital VWD and coexisting clinical hypothyroidism. Patients with uncertain diagnoses or other bleeding disorders were excluded, leading to 197 patients remaining in the final sample. A random age- and sex-matched parallel control group was also obtained from the hospital database. Of 197 patients (mean age 43.8 ± 17.5 years, women 72%) of congenital VWD, 32/197 (16%) were diagnosed with clinical hypothyroidism, while only 11/197 (5.6%) of the matched controls were clinically hypothyroid. Univariate and multivariate analysis demonstrated that VWD was an independent predictor of developing clinical hypothyroidism (OR 3.45; 95% CI 1.65-7.22, P = 0.001). The proportion of patients diagnosed with clinical hypothyroidism was more in the VWD group (P < 0.0001). Our analysis shows a strong association of clinical hypothyroidism in patients with congenital VWD, but future studies will be required to delineate a pathological mechanism. In our opinion, clinicians should consider checking thyroid function in the newly diagnosed and established cases of congenital VWD.

Antibiotic-resistant H. pylori infection and its treatment.

Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm that the infection has been cured 4 to 6 weeks later. Antimicrobial resistance is largely responsible for treatment failures. Resistance to metronidazole can frequently be overcome by increasing the dose and duration of treatment with acid suppression. Clarithromycin is the most effective antibiotic against H. pylori but, unfortunately, resistance to it is increasing and can not be overcome by increasing the dose or duration of therapy with clarithromycin. The choice of therapy should be based on local susceptibility patterns. Re-treatment regimens for treatment failure should exclude antibiotics where acquired resistance is expected (i.e., clarithromycin and possibly metronidazole). Where available, treatment failure should prompt endoscopy and culture and susceptibility testing. Overall, higher doses and longer durations of treatment result in the best cure rates. When multiple treatment regimens fail, salvage therapy regimens such as bismuth or furazolidone quadruple therapy (a bismuth and tetracycline HCl 4 times a day along with a proton pump inhibitor twice a day, and either metronidazole 400 or 500 mg three times daily or furazolidone 100 mg three times daily for 14 days) can be used. Newer agents are needed to cope with the increasing prevalence of antibiotic resistance among H. pylori.

Low-salt bowel cleansing preparation (LoSo Prep) as preparation for colonoscopy: a pilot study.

BACKGROUND: Currently available colon cleansing preparations are often poorly tolerated. AIM: To evaluate the efficacy of a low-volume, low-salt preparation for colonoscopy. METHODS: This was a pilot study in patients scheduled for colonoscopy. The preparation consisted of 34 g of magnesium citrate and four bisacodyl tablets the day before the procedure, and one bisacodyl suppository on the morning of the procedure. RESULTS: Twenty patients (age range, 49-81 years; all males) were entered into the study. There were no significant side-effects associated with the preparation. All rated the taste as 'tolerable or better'. The examination was considered to be adequate, with no limitations, in 17 patients (85%), and was scored as good to excellent (no solid stool) in 11 (55%), acceptable (small amounts of solid stool) in six (30%) and poor in three (15%: two in-patients and one out-patient). Importantly, two of the failures then received a standard polyethylene glycol preparation and again failed to show adequate colon preparation. CONCLUSIONS: This pilot study showed that the low-salt colon cleansing preparation was an effective alternative preparation for colonoscopy.

Ranitidine bismuth citrate, tetracycline, clarithromycin twice-a-day triple therapy for clarithromycin susceptible Helicobacter pylori infection.

BACKGROUND: Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success. AIM: To investigate the role of the new soluble form of bismuth, ranitidine bismuth citrate, in twice-a-day therapy for Helicobacter pylori infection. METHODS: Patients with histologically and culture proven H. pylori infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients). RESULTS: Sixty-three patients completed the therapy, 59 men and four women (average age 56.7 years; range 31-75 years). All patients had clarithromycin-susceptible strains prior to therapy. H. pylori infection was cured in 94% (95% CI: 85-98%). There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side-effects. Three of the isolates from treatment failures were available post-failure; two were clarithromycin-resistant and one was susceptible. Side-effects were severe in two patients (3%) and moderate in three (primarily diarrhoea). CONCLUSIONS: Twice-a-day ranitidine bismuth citrate, tetracycline, clarithromycin triple therapy was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin-susceptible H. pylori.

Long-term endoscopic management of variceal bleeding.

Recurrent hemorrhage from esophageal varices is a major source of morbidity and mortality in patients with portal hypertension. Esophageal sclerotherapy (EST) and more recently esophageal band ligation (EVL) can obliterate varices in 3-6 treatment sessions. Multiple band ligators make the use of overtubes unnecessary and make the procedure faster and more tolerable for the patient. EVL has several advantages, including fewer complications, fewer treatment sessions to obliteration, lower rebleeding rates, and lower mortality as compared to EST; the other advantages of EVL make it the treatment of choice for bleeding varices and long term management. The recommendations and rational for long term EST and EVL are presented and combination therapy and EUS guided EVL are discussed.

The role of endotoxin and cytokines in the pathogenesis of odontogenic cysts.

Odontogenic cysts arise from tooth-forming epithelial residues. The stimulus for the formation of radicular cysts is thought to be endotoxin released from the infected necrotic tooth pulp. However, in keratocysts and follicular cysts, such a stimulus is not present. In order to investigate what drives the cyst epithelium to proliferate, explant media and fluids from 16 radicular cysts, eight keratocysts and seven follicular cysts and explant media from four specimens of non-inflamed gingival tissue were examined for the presence of endotoxin and cytokines. Cyst fluids were also cultured for 72 h in anaerobic and aerobic conditions to detect micro-organisms. Endotoxin from three different bacteria, cytokines [interleukin-(IL) 1 alpha, IL-1 beta and IL-6] as well as prostaglandin E2 (PGE2) were tested in an epithelial cell-proliferation assay. As the cyst epithelium is supported by a connective tissue capsule, the effect of fibroblast culture media on epithelial cell proliferation was also investigated. The results showed significantly higher concentrations of endotoxin in radicular cyst fluid than in the keratocyst or the follicular cyst. None of the cyst fluids contained micro-organisms. Immunoassays demonstrated the presence of IL-1 alpha and -6 in all fluids and explants tested; IL-1 beta was only found in the inflammatory radicular cysts. However, reverse transcriptase-polymerase chain reaction showed that mRNAs for IL-1 alpha, -1 beta and -6 were present in all cyst types. Proliferation studies indicated that endotoxin and the cytokines had a mitogenic effect on epithelia at low concentrations; PGE2 had very little effect at low concentrations, and had an inhibitory effect at high concentrations. Cyst fibroblast culture media had a mitogenic effect on the epithelia that was enhanced by the presence of endotoxin.

Diagnosis and management of Helicobacter pylori infection.

Helicobacter pylori infects more than half of the world's population, making it one of the most prevalent infections. H pylori is now accepted as the most common cause of histologic gastritis and is responsible for the majority of cases of peptic ulcer disease and gastric cancer. Approximately 1 in 6 (17%) persons with H pylori infection will develop peptic ulcer disease, and each year 1% to 2% of these will experience a major or life-threatening complication, such as bleeding, perforation, or gastric outlet obstruction. Peptic ulcer disease should no longer be regarded as a chronic, recurring, lifelong disease, but rather as a curable infectious disease. The diagnosis and therapy of this common infectious disorder have become increasingly straightforward. In this article, we discuss the possible outcomes of long-standing infection, the various diagnostic tests available, including whom and when to test, and the combination drug regimens approved for cure.

Zollinger-Ellison syndrome. Improved treatment options for this complex disorder.

Zollinger-Ellison syndrome is a rare disorder characterized by severe peptic ulcer disease, gastric acid hypersecretion, and non-beta islet cell tumors of the pancreas. Most gastrinomas are found within an anatomic area known as the gastrinoma triangle. However, they commonly occur in extrapancreatic sites in multiple endocrine neoplasia type 1 syndrome. In patients in whom Zollinger-Ellison syndrome is suspected, laboratory evidence of hypergastrinemia and hyperacidity establishes the diagnosis. Until the advent of proton pump inhibitors, total gastrectomy was the treatment of choice. Therapy with these agents (eg, omeprazole, lansoprazole) can prevent ulcer disease. However, surgical removal of gastrinomas offers a chance for cure and can improve longevity by preventing the malignant spread of the tumors.

Acute bleeding from peptic ulcers. How to restore hemostasis and prevent recurrence.

Prompt resuscitation is the cornerstone in management of acute upper gastrointestinal bleeding. Endoscopy has become the diagnostic procedure of choice because it offers the chance for hemostatic therapy. For patients in whom endoscopy reveals actively bleeding peptic ulcers or nonbleeding peptic ulcers or nonbleeding ulcers with visible vessels, endoscopic therapy decreases the likelihood that the patient will bleed further, require surgery, or die. Patients with critical illnesses requiring intensive care should receive prophylaxis against stress ulcers. Long-term management of bleeding peptic ulcer disease includes educating patients to quit smoking, avoid non-steroidal anti-inflammatory drugs, and comply with maintenance therapy with a histamine2 receptor antagonist.

Lithium carbonate teratogenic effects in chick cardiomyocyte micromass system and mouse embryonic stem cell derived cardiomyocyte--possible protective role of myo-inositol.

The drug lithium carbonate (Li2CO3) use during pregnancy increases the possibility of cardiovascular anomalies. The earlier studies confirm its phosphatidylinositol cycle (PI) inhibition and Wnt pathways mimicking properties, which might contribute to its teratogenic effects. In this study the toxic effects of Li2CO3 in chick embryonic cardiomyocyte micromass system (MM) and embryonic stem cell derived cardiomyocyte (ESDC) were evaluated, with possible protective role of myo-inositol. In MM system the Li2CO3 did not alter the toxicity estimation endpoints, whereas in ESDC system the cardiomyocytes contractile activity stopped at 1500 µM and above with significant increase in total cellular protein contents. In ESDC system when myo-inositol was added along with Li2CO3 to continue PI cycle, the contractile activity was recovered with decreased protein content. The lithium toxic effects depend on the role of PI cycle at particular stage of cardiogenesis, while relation between myo-inositol and reduced cellular protein contents remains unknown.

Carbamazepine toxic effects in chick cardiomyocyte micromass culture and embryonic stem cell derived cardiomyocyte systems--possible protective role of antioxidants.

The use of carbamazepine (CBZ) during pregnancy increases cardiovascular anomalies. In this study CBZ developmental cardiotoxic effects were evaluated using chick cardiomyocyte micromass (MM) culture and mouse embryonic stem cells derived cardiomyocyte (ESDC) systems. In MM culture, CBZ only inhibited the cardiomyocyte contractile activity, while in ESDC it completely ceased the contractile activity at 200 µM with decreased cell viability and protein content. The antioxidant superoxide dismutase (SOD) supplement in MM and ascorbic acid (AA) in ESDC showed protective effects on CBZ toxicity, but elevated levels of reactive oxygen species (ROS) production were recorded with CBZ treatment only in ESDC. CBZ has also affected cardiac connexin 43 expression in both in vitro systems. Our results indicated CBZ induced ROS stress as mechanism of developmental cardiotoxicity at early stage of cardiogenesis in ESDC system compared to MM system's differentiated cells. These toxic effects can be negated by using antioxidant agent.

Frequency and predictors of venous thromboembolism in orthotopic liver transplant recipients: a single-center retrospective review.

BACKGROUND: Venous thromboembolism (VTE) is a potentially fatal complication of major abdominal operations. Liver transplantation is carried out as a treatment for end-stage liver disease (ESLD). It is not well studied whether this population is at increased or decreased risk of a VTE event after a liver transplantation. This study was to determine the frequency of VTE in this population and identify possible predictors. METHODS: Retrospective review of 917 patients over 15 years at a single tertiary center was conducted. Liver transplant recipients with symptomatic VTE occurring up to 1 year after liver transplantation were included. Upper and lower extremities deep vein thrombosis (DVT) was identified. The diagnosis of DVT and pulmonary embolism (PE) was made by appropriate diagnostic imaging. Data regarding known risk factors of VTE such as thrombophilia, recent hospitalization, malignancy, and other comorbid conditions were collected. RESULTS: Among 917 patients, a total of 45 events occurred in 42 (4.58%) patients. Twelve had PE and 33 had DVT events. On Cox regression analysis the absence of an alcoholism diagnosis (Hazard Ratio [HR], -0.33; 95% confidence interval [CI], 0.13-0.83), the presence of diabetes (HR, -3.36; 95% CI, 1.76-6.42), a history of VTE (HR, -8.06; 95% CI, 3.37-19.3), and the presence of end-stage renal disease (ESRD; HR, 3.68; 95% CI, 1.34-10.01) were significant predictors of a VTE outcome. No particular diagnosis, history of malignancy, or presence of thrombophilia were associated with increased risk of VTE. CONCLUSION: The 4.58 % incidence of VTE is comparable with the reported incidence after major abdominal procedures (5%-10%). This data also shows that there is increased risk of VTE in transplant recipients with comorbid conditions of diabetes, previous VTE, and ESRD. This study suggests that a more aggressive strategy for prophylaxis of VTE should be used in liver transplant recipients as with other major abdominal procedures.

CMOS Amperometric Instrumentation and Packaging for Biosensor Array Applications.

An integrated CMOS amperometric instrument with on-chip electrodes and packaging for biosensor arrays is presented. The mixed-signal integrated circuit supports a variety of electrochemical measurement techniques including linear sweep, constant potential, cyclic and pulse voltammetry. Implemented in 0.5 µm CMOS, the 3 × mm(2) chip dissipates 22.5 mW for a 200 kHz clock. The highly programmable chip provides a wide range of user-controlled stimulus rate and amplitude settings with a maximum scan range of 2 V and scan rates between 1 mV/sec and 400 V/sec. The amperometric readout circuit provides ±500 fA linear resolution and supports inputs up to ±47 µA. A 2 × 2 gold electrode array was fabricated on the surface of the CMOS instrumentation chip. An all-parylene packaging scheme was developed for compatibility with liquid test environments as well as a harsh piranha electrode cleaning process. The chip was tested using cyclic voltammetry of different concentrations of potassium ferricyanide at 100 mV/s and 200 mV/s, and results were identical to measurements using commercial instruments.