A one-year trial of lamivudine for chronic hepatitis B

Background and Methods: In preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score. Results: Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine, 49 percent of those receiving 25 mg of lamivudine, and 25 percent of those receiving placebo (P<0.001 and P=0.001, respectively, for the comparisons of lamivudine treatment with placebo). Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine, 8 percent of those receiving 25 mg, and 26 percent of those receiving placebo. The 100mg dose of lamivudine was associated with a reduced progression of fibrosis (P=0.01 for the comparison with placebo) and with the highest rate of hepatitis B e antigen (HBeAg) seroconversion (loss of HBeAg, development of antibody to HBeAg, and undetectable HBV DNA) (16 percent), the greatest suppression of HBV DNA (98 percent reduction at week 52 as compared with the base-line value), and the highest rate of sustained normalization of alanine aminotransferase levels (72 percent). Ninety-six percent of the patients completed the study. The incidence of adverse events was similar in all groups, and there were few serious events. Conclusions: In a one-year study, lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg.published_or_final_versio

Oynophagia in patients after dental extraction: surface electromyography study

OBJECTIVES: Surface electromyographic (sEMG) studies were performed on 40 adult patients following extraction of lower third and second molars to research the approach and limitations of sEMG evaluation of their odynophagia complaints. METHODS: Parameters evaluated during swallowing and drinking include the timing, number of swallows per 100 cc of water, and range (amplitude) of EMG activity of m. masseter, infrahyoid and submental-submandibular group. The above mentioned variables (mean + standard deviation) were measured for the group of dental patients (n = 40) and control group of healthy adults (n = 40). RESULTS: The duration of swallows and drinking in all tests showed increase in dental patients' group, in which this tendency is statistically significant. There was no statistically significant difference between male and female adults' duration and amplitude of muscle activity during continuous drinking in both groups (p = 0.05). The mean of electric activity (in μV) of m. masseter was significantly lower in the dental patients' group in comparison with control group. The electric activity of submental-submandimular and infrahyoid muscle groups was the same in both groups. CONCLUSION: Surface EMG of swallowing is a simple and reliable noninvasive method for evaluation of odynophagia/dysphagia complaints following dental extraction with low level of discomfort of the examination. The surface EMG studies prove that dysphagia following dental extraction and molar surgery has oral origin, does not affect pharingeal segment and submental-submandibular muscle group. This type of dysphagia has clear EMG signs: increased duration of single swallow, longer drinking time, low range of electric activity of m. masseter, normal range of activity of submental-submandibular muscle group, and the "dry swalow" aftereffect. The data can be used for evaluation of complaints and symptoms, as well as for comparison purposes in pre- and postoperative stages and in EMG monitoring during treatment of post-surgical oral cavity discomfort and dysphagia

Oral vs. pharyngeal dysphagia: surface electromyography randomized study

<p>Abstract</p> <p>Background</p> <p>A clear differential diagnosis between oral and pharyngeal dysphagia remains an unsolved problem. Disorders of the oral cavity are frequently overlooked when dysphagia/odybophagia complaints are assessed. Surface electromyographic (sEMG) studies were performed on randomly assigned patients with oral and pharyngeal pathology to evaluate their dysphagia complaints for the sake of differential diagnosis.</p> <p>Methods</p> <p>Parameters evaluated during swallowing for patients after dental surgery (1: n = 62), oral infections (2: n = 49), acute tonsillitis (3: n = 66) and healthy controls (4: n = 50) included timing and amplitude of sEMG activity of masseter, infrahyoid and submental muscles.</p> <p>Results</p> <p>The duration of swallows and drinking periods was significantly increased in dental patients and was normal in patients with tonsillitis. The electric activity of masseter was significantly lower in Groups 1 and 2 in comparison with the patients with tonsillitis and controls. The submental and infrahyoid activity was normal in dental patients but infrahyoid activity in patients with tonsillitis was high.</p> <p>Conclusion</p> <p>Dysphagia following dental surgery or oral infections does not affect pharynx and submental muscles and has clear sEMG signs: increased duration of a single swallow, longer drinking time, low activity of the masseter, and normal range of submental activity. Patients with tonsillitis present hyperactivity of infrahyoid muscles. These data could be used for evaluation of symptoms when differential dental/ENT diagnosis is needed.</p

Early Ahmed Glaucoma Valve Implantation after Penetrating Keratoplasty Leads to Better Outcomes in an Asian Population with Preexisting Glaucoma

To evaluate the efficacy of Ahmed Glaucoma Valve (AGV) surgery and the optimal interval between penetrating keratoplasty (PKP) and AGV implantation in a population of Asian patients with preexisting glaucoma who underwent PKP.In total, 45 eyes of 45 patients were included in this retrospective chart review. The final intraocular pressures (IOPs), graft survival rate, and changes in visual acuity were assessed to evaluate the outcomes of AGV implantations in eyes in which AGV implantation occurred within 1 month of post-PKP IOP elevation (Group 1) and in eyes in which AGV implantation took place more than 1 month after the post-PKP IOP evaluation (Group 2). Factors that were associated with graft failure were analyzed, and the overall patterns of complications were reviewed. By their final follow-up visits, 58% of the patients had been successfully treated for glaucoma. After the operation, there were no statistically significant differences between the groups with respect to graft survival (p = 0.98), but significant differences for IOP control (p = 0.049) and the maintenance of visual acuity (VA) (p<0.05) were observed. One year after surgery, the success rates of IOP control in Group 1 and Group 2 were 80% and 46.7%, respectively, and these rates fell to 70% and 37.3%, respectively, by 2 years. Factors that were associated with a high risk of AGV failure were a diagnosis of preexisting angle-closure glaucoma, a history of previous PKP, and a preoperative IOP that was >21 mm Hg. The most common surgical complication, aside from graft failure, was hyphema.Early AGV implantation results in a higher probability of AGV survival and a better VA outcome without increasing the risk of corneal graft failure as a result of post-PKP glaucoma drainage tube implantation

The efficacy of four-slice helical CT in evaluating pancreatic trauma: a single institution experience

<p>Abstract</p> <p>Study objective</p> <p>To assess the efficacy of computed tomography (CT) in evaluating patients with pancreatic trauma.</p> <p>Methods</p> <p>We undertook a retrospective review of all blunt trauma patients admitted to the Chi-Mei Medical Center from January 2004 to June 2006. Every patients underwent abdominal CT scan in emergency department and the CT scans were obtained with a four-slice helical CT. Diagnosis of a pancreatic injury in these patients was by surgical observation or by CT findings. Radiographic pancreatic injuries were classified as deep or superficial lesions. Deep lesions were defined as the hematomas or lacerations >50% thickness of the pancreas. Superficial lesions were described as the hematomas or lacerations <50% thickness of the pancreas; pancreatic edema; and focal fluid accumulation around the pancreas</p> <p>Results</p> <p>Nineteen patients with pancreatic trauma, fourteen males and five females, average age 40.6 ± 21.4 years, were included. Most patients (73.7%) with pancreatic trauma had associated organ injuries. CT was performed in all patients and laparotomy in 14 patients. CT was 78.9% sensitive in detecting pancreatic trauma. All deep pancreatic lesions revealed on CT required surgical treatment, and complication was discovered in two patients undergoing delayed surgery. Superficial lesions were managed conservatively.</p> <p>Conclusion</p> <p>Four-slice helical CT can detect most pancreatic trauma and provide practical therapeutic guidance. Delayed operation might result in complications and is associated with prolonged hospital stays.</p

Transancestral fine-mapping of four type 2 diabetes susceptibility loci highlights potential causal regulatory mechanisms

To gain insight into potential regulatory mechanisms through which the effects of variants at four established type 2 diabetes (T2D) susceptibility loci (CDKAL1, CDKN2A-B, IGF2BP2 and KCNQ1) are mediated, we undertook transancestral fine-mapping in 22 086 cases and 42 539 controls of East Asian, European, South Asian, African American and Mexican American descent. Through high-density imputation and conditional analyses, we identified seven distinct association signals at these four loci, each with allelic effects on T2D susceptibility that were homogenous across ancestry groups. By leveraging differences in the structure of linkage disequilibrium between diverse populations, and increased sample size, we localised the variants most likely to drive each distinct association signal. We demonstrated that integration of these genetic fine-mapping data with genomic annotation can highlight potential causal regulatory elements in T2D-relevant tissues. These analyses provide insight into the mechanisms through which T2D association signals are mediated, and suggest future routes to understanding the biology of specific disease susceptibility loci

Gated Diffusion-controlled Reactions

The binding and active sites of proteins are often dynamically occluded by motion of the nearby polypeptide. A variety of theoretical and computational methods have been developed to predict rates of ligand binding and reactivity in such cases. Two general approaches exist, "protein centric" approaches that explicitly treat only the protein target, and more detailed dynamical simulation approaches in which target and ligand are both treated explicitly. This mini-review describes recent work in this area and some of the biological implications

A Comprehensive Association Analysis of Homocysteine Metabolic Pathway Genes in Singaporean Chinese with Ischemic Stroke

10.1371/journal.pone.0024757PLoS ONE69

Relational grounding facilitates development of scientifically useful multiscale models

We review grounding issues that influence the scientific usefulness of any biomedical multiscale model (MSM). Groundings are the collection of units, dimensions, and/or objects to which a variable or model constituent refers. To date, models that primarily use continuous mathematics rely heavily on absolute grounding, whereas those that primarily use discrete software paradigms (e.g., object-oriented, agent-based, actor) typically employ relational grounding. We review grounding issues and identify strategies to address them. We maintain that grounding issues should be addressed at the start of any MSM project and should be reevaluated throughout the model development process. We make the following points. Grounding decisions influence model flexibility, adaptability, and thus reusability. Grounding choices should be influenced by measures, uncertainty, system information, and the nature of available validation data. Absolute grounding complicates the process of combining models to form larger models unless all are grounded absolutely. Relational grounding facilitates referent knowledge embodiment within computational mechanisms but requires separate model-to-referent mappings. Absolute grounding can simplify integration by forcing common units and, hence, a common integration target, but context change may require model reengineering. Relational grounding enables synthesis of large, composite (multi-module) models that can be robust to context changes. Because biological components have varying degrees of autonomy, corresponding components in MSMs need to do the same. Relational grounding facilitates achieving such autonomy. Biomimetic analogues designed to facilitate translational research and development must have long lifecycles. Exploring mechanisms of normal-to-disease transition requires model components that are grounded relationally. Multi-paradigm modeling requires both hyperspatial and relational grounding