Development of an Artificial White Spot Lesion Creation Protocol: A Preliminary Study.

BACKGROUND AND OBJECTIVES: Protocols that determine the lesion depth of specific demineralization solutions are lacking. This in vitro study aimed to evaluate various lesion depths of artificial white spot lesions (WSLs) at different exposure times.  Materials and methods: Artificial WSLs were created by placing 30 extracted human premolar teeth into 0.05M acetate buffer solution with a controlled environment of pH 4.4 at 37ºC, which were then exposed in the solution for various durations of 4, 5, 6, 8, 10, and 12 days. The specimens were visually examined using the Ekstrand-Ricketts-Kidd (ERK) system to confirm the WSL, followed by buccolingual sectioning, and evaluated under a scanning electron microscope (SEM) to measure the lesion depth. RESULTS: The SEM showed that the mean lesion depths of representative specimens were 101.33 µm (day 4), 124 µm (day 5), 159 µm (day 6), 187 µm (day 8), 202 µm (day 10), and 212 µm (day 12). The artificial WSL was visually demonstrated in grades 1 and 2 of the ERK system. CONCLUSIONS: The depths of the lesions increased as the duration increased from day 4 to day 12, indicating that the lesion depths increased with the more prolonged exposure to the acetate buffer solution.

Insulin stimulated MCF7 breast cancer cells: Proteome dataset.

The proteome data provided in this article were acquired from MCF7 breast cancer cells stimulated with insulin, and were generated by using a 2D-SCX (strong cation exchange)/RPLC (reversed phase liquid chromatography) separation protocol followed by tandem mass spectrometry (MS) detection. To facilitate data re-processing by more advanced search engines and the extraction of additional information from already existing files, both raw and processed data are provided. The sample preparation, data acquisition and processing protocols are described in detail. The raw data relate to work published in "Proteome profile of the MCF7 cancer cell line: a mass spectrometric evaluation" (Sarvaiya et al., 2006) [1] and are made available through the PRIDE (PRoteomics IDEntifications)/ProteomeXchange public repository with identifier PRIDE: PXD004051 ("2016 update of the PRIDE database and tools" (Vizcaino et al., 2016) [2]).

Management of alcoholic hepatitis: Current concepts.

Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality. It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role. Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy. Primary therapy remains abstinence and supportive care, as continued alcohol abuse is the most important risk factor for disease progression. The cornerstone of supportive care remains aggressive nutritional support, and although acute alcoholic hepatitis has been extensively studied, few specific medical therapies have been successful. Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis; however, the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary. While liver transplantation for acute alcoholic hepatitis have demonstrated promising results, this practice remains controversial and has not been advocated universally, with most transplant centers requiring a prolonged period of abstinence before considering transplantation. Extracorporeal liver support devices, although still experimental, have been developed as a form of liver support to give additional time for liver regeneration. These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease.

Imaging of preoperative liver transplantation in adults: what radiologists should know.

Therapeutic strategies for treating patients with liver failure, particularly optimization of liver transplantation, are constantly being refined, with the goal of improving long-term survival with the lowest risk for toxicity in donors and recipients. Optimal planning for liver transplantation requires a multidisciplinary collaboration between the radiologist, hepatologist, clinical oncologist, and transplant surgeon. Radiologists play an essential role in identifying normal and abnormal variant anatomy and other conditions that may be present, a task that is critical for accurate surgical planning. Radiologists also must understand how their findings affect patient preparation. An awareness of the range of indications for liver transplantation, imaging modalities, and current surgical techniques is important to properly evaluate a patient who may undergo liver transplantation. Establishing a pretransplantation definition of the extent of liver disease and thoroughly evaluating the vascular and biliary anatomy are paramount for proper assessment of potential recipients and donors for liver transplantation.

Postoperative imaging in liver transplantation: what radiologists should know.

Liver transplantation is now frequently used in the treatment of end-stage liver disease. Therefore, it is important that radiologists be aware of common anastomotic techniques and expected postoperative imaging findings. Imaging is most useful in evaluating for posttransplantation complications, which are broadly classified into vascular, biliary, and other complications. Hepatic artery thrombosis is the most significant complication and is often associated with graft failure. Radiologists have multiple modalities at their disposal for optimal evaluation. Doppler ultrasonography (US) is the preliminary imaging modality for gross evaluation of the liver parenchyma, biliary tree, and vasculature for abnormalities. When US findings are indeterminate or there is persistent clinical suspicion for an abnormality, computed tomography (CT) is often performed. The major indications for CT are detection of bile leak, hemorrhage, and abscess, but CT is also useful in the assessment of the vasculature. T-tube cholangiography and magnetic resonance cholangiopancreatography are the best noninvasive imaging tools for evaluating for biliary stricture. Some investigators would argue that endoscopic retrograde cholangiopancreatography (ERCP) is a better diagnostic imaging modality; however, ERCP is invasive. Hepatobiliary scintigraphy is optimal for the evaluation of biliary leakage. Early detection of posttransplantation complications will help lower morbidity rates and will likely allow graft salvage in selected cases.

Effect of Metoprolol CR/XL on pulmonary artery pressure in chronic heart failure patients assessed by an implanted ultrasonic device with special emphasis on diurnal variation and exercise capacity.

OBJECTIVE: We evaluated the impact of Metoprolol CR/XL on the diurnal and exercise induced variation on Pulmonary Artery Pressure (PAP) in patients with Chronic Heart Failure (CHF) by implanted ultrasonic device. BACKGROUND: Metoprolol produces haemodynamic and clinical benefits in patients with chronic heart failure and improves survival rate. There is limited information about their effect on PAP, its diurnal and exercise induced variation in heart failure. This study evaluates the diurnal variation and effects of exercise capacity on PAP and impact of Metoprolol CR/XL (XL) on these variations on PAP in CHF patients. METHODS: In this first-in-man study, ten NYHA class III/IV patients were implanted with an ultrasonic pressure-monitoring device, followed a month later by loading with MXL 25 mg/day and uptitrated every two weeks to 200 mg/day. PAP was measured at each follow up. Diurnal variation was evaluated at baseline (no MXL), 100, and 200 mg/day MXL. Treadmill Test (TMT) was performed before and at each uptitration. Echocardiography was performed at one year. RESULTS: Uptitrating MXL caused a slight initial rise in PAP, followed by a subsequent decrease on reaching 200 mg/day dose. One patient showed repeated symptomatic rise in PAP indicating MXL intolerance and was discontinued from the uptitration. The nocturnal rise in PAP at baseline was reduced on reaching 200 mg/day MXL dose. Uptitrating MXL to 200mg7divide;day improved exercise time and metabolic equivalent tasks (METS) with no significant change in post TMT PAP. Ejection fraction also improved at one-year follow-up. CONCLUSIONS: PAP increases post exercise and diurnally in CHF patients. Slow and careful uptitration of MXL with simultaneous non-invasive monitoring of PAP may benefit in nocturnal rise and exercise capacity in CHF patients.

A case of Noonan syndrome and Whipple's disease in the same patient.

We report the first known case of both Noonan syndrome and Whipple's disease occurring in the same patient. A 36-year-old female with history of Noonan syndrome developed fatigue, anorexia, arthritis of the knees and hands with a diffuse hyperpigmented rash, night sweats, and an unintentional fifteen pound weight loss over 4 mo. Small bowel enteroscopy demonstrated mild edematous yellowish mucosa without friability. Random small bowel biopsies revealed extensive periodic acid-Schiff positive material within the foamy macrophages. She was treated with a 12 mo course of trimethoprim-sulfamethoxazole DS with clinical improvement to baseline status.

Efficacy of PercuSurge in acute myocardial infarction patients undergoing revascularization with a special emphasis on procedural time.

AIM: To evaluate the efficacy of the PercuSurge Guardwire(R) Plus Temporary Occlusion and Aspiration System, the actual procedural time involved and long-term follow-up in acute MI patients undergoing primary/rescue percutaneous coronary intervention (PCI). METHODS & RESULTS: It was a single centred, prospective study in 67 prospective AMI patients undergoing PCI. They were divided randomly into two groups depending on whether PercuSurge was used (n=30) or not used (control n=37) during PCI. Final TIMI flow, TMP grade and the time involved in or necessary for various steps of the PCI were recorded. PercuSurge showed significantly greater achievement of TIMI III flow and TMP III grade (p<0.01). Its use was associated with less total procedural time (p<0.05). The time required from guidewire crossing to stent placement; from guidewire crossing to TIMI III flow and from predilatation/stent placement to optimal TIMI flow was significantly reduced with its use (p<0.05 for all). Slow/no-reflow was significantly reduced (p<0.001), thus reducing intracoronary vasodilators and GP IIb/IIIa antagonists requirements. A 2 years' follow-up revealed four deaths in control and one death in PercuSurge group. CONCLUSION: PercuSurge reduced the total procedural time with better and faster optimal TIMI flow and TMP grade in primary/rescue PCI and was associated with less long term events.

Microfluidic platform with mass spectrometry detection for the analysis of phosphoproteins.

The development of novel and reliable technologies for the analysis of proteins and their post-translational modifications, in particular, has recently received much attention and interest. The implementation of a fully integrated microfluidic device interfaced with MS detection for the analysis of phosphoproteins is presented in this paper. The microfluidic platform (3''x1.5'') comprises two individual sample processing systems: one for performing direct sample infusion and one for performing microfluidic LC separations. Various MS detection strategies, specific for the study of post-translational modifications, were conducted using alpha-casein as a model protein. Neutral loss ion mapping, data-dependent triple-play and neutral loss analysis, and in situ dephosphorylation followed by LC separation and MS detection were performed. Consistent results in identifying phosphopeptides with conventional and microfluidic instrumentation have been obtained. Unlike with conventional instrumentation, however, the microfluidic device enabled the completion of each analysis from only a few microliters of sample, in approximately 10-15 min, and on a bioanalytical platform that facilitates multiplexing and disposability, and thus high-throughput, contamination-free analysis.

Development and validation of a disease-targeted quality of life instrument in chronic hepatitis B: the hepatitis B quality of life instrument, version 1.0.

UNLABELLED: Despite the increasing realization that health-related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease-targeted instruments currently available. We sought to develop and validate the first disease-targeted HRQOL instrument in noncirrhotic HBV: the Hepatitis B Quality of Life instrument, version 1.0 (HBQOL v1.0). We established content validity for the HBQOL v1.0 by conducting a systematic literature review, an expert focus group, and cognitive interviews with HBV patients. We administered the resultant questionnaire to 138 HBV patients. We used factor analysis to test hypotheses regarding HRQOL domains and measured construct validity by comparing HBQOL v1.0 scores across several anchors, including viral response to treatment, SF-36 scores, and global health. Finally, we measured test-retest and internal consistency reliability. Content validation revealed that HBV affects multiple aspects of psychological, social, and physical health. The resultant questionnaire summarized this HRQOL impact with 31 items across six subscales: psychological well-being, anticipation anxiety, vitality, disease stigma, vulnerability, and transmissibility. Internal consistency and test-retest reliability were excellent. The HBQOL v1.0 discriminated between viral responders versus nonresponders and correlated highly with SF-36 scores and global health. CONCLUSION: Patients with chronic HBV infection attribute a wide range of negative psychological, social, and physical symptoms to their condition, even in the absence of cirrhosis or cancer. The HBQOL v1.0 is a valid and reliable measure that captures this HRQOL decrement. This instrument may be useful in everyday clinical practice and in future clinical trials.

Proteome profile of the MCF7 cancer cell line: a mass spectrometric evaluation.

The development of novel proteomic technologies that will enable the discovery of disease specific biomarkers is essential in the clinical setting to facilitate early diagnosis and increase survivability rates. We are reporting a shotgun two-dimensional (2D) strong cationic exchange/reversed-phase liquid chromatography/electrospray ionization tandem mass spectrometry (SCX/RPLC/ESI-MS/MS) protocol for the analysis of proteomic constituents in cancerous cells. The MCF7 breast cancer cell line was chosen as a model system. A series of optimization steps were performed to improve the LC/MS experimental setup, sample preparation, data acquisition and database search protocols, and a data filtering strategy was developed to enable confident identification of a large number of proteins and potential biomarkers. This research has resulted in the identification of >2000 proteins using multiple filtering and p-value sorting. Approximately 1600-1900 proteins had p < 0.001, and, of these, approximately 60% were matched by >or=2 unique peptides. Alternatively, >99% of the proteins identified by >or=2 unique peptides had p < 0.001. When searching the data against a reversed database of proteins, the rate of false positive identifications was 0.1% at the peptide level and 0.4% at the protein level. The typical reproducibility in detecting overlapping proteins across replicate runs exceeded 90% for proteins matched by >or=2 unique peptides. According to their biological function, approximately 200 proteins were involved in cancer-relevant cellular processes, and over 25 proteins were previously described in the literature as putative cancer biomarkers, as they were found to be differentially expressed between normal and cancerous cell states. Among these, biomarkers such PCNA, cathepsin D, E-cadherin, 14-3-3-sigma, antigen Ki-67, TP53RK, and calreticulin were identified. These data were generated by subjecting to MS analysis approximately 42 microg of sample, analyzing 16 SCX peptide fractions, and interpreting approximately 55,000 MS2 spectra. Total MS time required for analysis was 40 h.

Microfluidic liquid chromatography system for proteomic applications and biomarker screening.

A microfluidic liquid chromatography (LC) system for proteomic investigations that integrates all the necessary components for stand-alone operation, i.e., pump, valve, separation column, and electrospray interface, is described in this paper. The overall size of the LC device is small enough to enable the integration of two fully functional separation systems on a 3 in. x 1 in. glass microchip. A multichannel architecture that uses electroosmotic pumping principles provides the necessary functionality for eluent propulsion and sample valving. The flow rates generated within these chips are fully consistent with the requirements of nano-LC platforms that are routinely used in proteomic applications. The microfluidic device was evaluated for the analysis of a protein digest obtained from the MCF7 breast cancer cell line. The cytosolic protein extract was processed according to a shotgun protocol, and after tryptic digestion and prefractionation using strong cation exchange chromatography (SCX), selected sample subfractions were analyzed with conventional and microfluidic LC platforms. Using similar experimental conditions, the performance of the microchip LC was comparable to that obtained with benchtop instrumentation, providing an overlap of 75% in proteins that were identified by more than two unique peptides. The microfluidic LC analysis of a protein-rich SCX fraction enabled the confident identification of 77 proteins by using conventional data filtering parameters, of 39 proteins with p < 0.001, and of 5 proteins that are known to be cancer-specific biomarkers, demonstrating thus the potential applicability of these chips for future high-throughput biomarker screening applications.

Combination endoscopic band ligation and sclerotherapy compared with endoscopic band ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage: a meta-analysis.

Endoscopic band ligation (EBL) is the community-accepted standard therapy for the secondary prophylaxis of esophageal variceal hemorrhage. Recent data indicate that combination EBL and sclerotherapy may be a more effective therapy than EBL alone. Yet existing data are conflicting. We therefore performed a meta-analysis to compare the efficacy and safety of EBL and sclerotherapy versus EBL alone for the secondary prophylaxis of esophageal variceal hemorrhage. We performed a systematic review of two computerized databases (MEDLINE and EMBASE) along with manual-searching of published abstracts to identify relevant citations without language restrictions from 1990 to 2002. Eight studies met explicit inclusion criteria. We performed meta-analysis of these studies to pool the relative risk for the following outcomes: esophageal variceal rebleeding, death, number of endoscopic sessions to achieve variceal obliteration, and therapeutic complications. There were no significant differences between EBL and sclerotherapy versus EBL alone in the risk of esophageal variceal rebleeding (RR = 1.05; 95% CI = 0.67-1.64; P = 0.83), death (RR = 0.99; 95% CI = 0.68-1.44; P = 0.96), or number of endoscopic sessions to variceal obliteration (RR = 0.23; 95% CI = 0.055-0.51; P = 0.11). However, the incidence of esophageal stricture formation was significantly higher in the EBL group than in the sclerotherapy group. There is no evidence that the addition of sclerotherapy to endoscopic band ligation changes clinically relevant outcomes (variceal rebleeding, death, time to variceal obliteration) in the secondary prophylaxis of esophageal variceal hemorrhage. Moreover, combination EBL and sclerotherapy had more esophageal stricture formation than EBL alone.

The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal hemorrhage.

OBJECTIVE: Recurrent variceal hemorrhage is common following an initial bleed in patients with cirrhosis. The current standard of care for secondary prophylaxis is endoscopic band ligation (EBL). Combination of beta-blocker and nitrate therapy, guided by hepatic venous pressure gradient (HVPG) monitoring, is a novel alternative strategy. We sought to determine the cost-effectiveness of these competing strategies. METHODS: Decision analysis with Markov modeling was used to calculate the cost-effectiveness of three competing strategies: (1) EBL; (2) beta-blocker and nitrate therapy without HVPG monitoring (HVPG-); and (3) beta-blocker and nitrate therapy with HVPG monitoring (HVPG+). Patients in the HVPG+ strategy who failed to achieve an HVPG decline from medical therapy were offered EBL. Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per recurrent variceal hemorrhage prevented. RESULTS: Under base-case conditions, the HVPG+ strategy was the most effective yet most expensive approach, followed by EBL and HVPG-. Compared to the EBL strategy, the HVPG+ strategy cost an incremental 5,974 dollars per recurrent bleed prevented. In a population with 100% compliance with all therapies, the incremental cost of HVPG-versus EBL fell to 5,270 dollars per recurrent bleed prevented. The model results were sensitive to the cost of EBL, the cost of HVPG monitoring, and the probability of medical therapy producing an adequate HVPG decline. CONCLUSIONS: Compared to EBL for the secondary prophylaxis of variceal rebleeding, combination medical therapy guided by HVPG monitoring is more effective and only marginally more expensive.

Primary prevention of cirrhosis. Public health strategies that can make a difference.

Cirrhosis is associated with high morbidity and mortality and often affects persons during the most productive years of life. In the United States, alcoholic liver disease is the leading contributor to the overall prevalence of cirrhosis, followed by infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). In this article, Drs Karsan, Rojter, and Saab examine lifestyle behaviors that can lead to cirrhosis and enumerate public health strategies aimed at primary prevention.

Endoscopic screening for esophageal varices in cirrhosis: Is it ever cost effective?

Current guidelines for the management of patients with compensated cirrhosis recommend universal screening endoscopy followed by prophylactic beta-blocker therapy to prevent initial hemorrhage in those found to have esophageal varices. However, the cost-effectiveness of this recommendation has not been established. Our objective was to determine whether screening endoscopy is cost-effective compared with empiric medical management in patients with compensated cirrhosis. Decision analysis with Markov modeling was used to calculate the cost-effectiveness of 6 competing strategies: (1) universal screening endoscopy (EGD) followed by beta-blocker (BB) therapy (EGD-->BB) if varices are present, (2) EGD followed by endoscopic band ligation (EBL) (EGD-->EBL) if varices are present, (3) selective screening endoscopy (sEGD) in high risk patients followed by BB therapy if varices are present (sEGD-->BB), (4) selective screening endoscopy followed by EBL (sEGD-->EBL) if varices are present, (5) empiric beta-blocker therapy in all patients, and (6) no prophylactic therapy ("Do Nothing"). Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per initial variceal hemorrhage prevented. The "Do Nothing" strategy was the least expensive yet least effective approach. Compared with the "Do Nothing" strategy, the empiric beta-blocker strategy cost an incremental $12,408 per additional variceal bleed prevented. Compared with the empiric beta-blocker strategy, in turn, both the EGD-->BB and the EGD-->EBL strategies cost over $175,000 more per additional bleed prevented. The sEGD-->BB and sEGD-->EBL strategies were more expensive and less effective than the empiric beta-blocker strategy. In conclusion, empiric beta-blocker therapy for the primary prophylaxis of variceal hemorrhage is a cost-effective measure, as the use of screening endoscopy to guide therapy adds significant cost with only marginal increase in effectiveness.

Classification of Transient Synovitis with Magnetic Resonance Imaging / 대한정형외과학회잡지

PURPOSE: To classify the type of transient synovitis and determine a treatment plan using MRI. MATERIALS AND METHODS: From March 1985 to October 1998, 37 hips in 33 children with clinical symptoms of transient synovitis were evaluated with MRI. The average age of the patients was 7.5 years (range, 3.5-15 years) . The mean follow-up period was 18 months (range, 12-36 months) . The 37 hips were classified as grade l, ll, lll, or lV according to the amount of accumulated joint fluid on MRI. RESULTS: Of 37 hips with transient synovitis, 36 hips had no involvement of epiphysis and metaphysis and one hip had a cyst and bone marrow edema in the metaphysis on MRI scans. The amount of joint fluid was classified as seen on MRI scans: grade 1 in 2 hips, grade 2 in 14 hips, grade 3 in 5 hips, and grade 4 in 16 hips. CONCLUSION: MRI is a very useful diagnostic tool to classify and determine the treatment plan for transient synovitis. In patients with grade 3 and 4 joint fluid, the risk of vascular compromise of the femoral epiphysis could be higher. These patients should be hospitalized and immobilized in flexed position of the hip. Patients with grade 1 and 2 joint fluid can be treated at home with immobilization.