Role of colchicine to reduce NLRP3 marker in STEMI patients undergo primary PCI: A randomised controlled clinical trial.

INTRODUCTION: ST-segment elevation myocardial infarction (STEMI) is a fatal disease with significant burden worldwide. Despite advanced medical treatment performed, STEMIrelated morbidity and mortality remains high due to ischemia reperfusion injury after primary angioplasty mediated by NLRP3 inflammasome. Adding colchicine expected to reduce inflammation both in vitro and in vivo. We want to evaluate the effect of colchicine administration on the NLRP3 level of STEMI patient who undergo primary cutaneous intervention (PCI). MATERIALS AND METHODS: Randomised controlled trial was conducted on STEMI patients who undergo PCI in two hospitals in Jakarta, 104 patients enrolled to this study, and 77 patients completed the trial. 37 patients were randomly assigned to receive colchicines (2 mg loading dose; 0.5 mg thereafter every 12 hour for 48 hours) while 40 patients received placebo. NLRP3 level was measured from venous blood at baseline (BL), after procedure (AP), dan 24-hour post procedure (24H). RESULTS: No NLRP3 difference was observed initially between colchicine arm and placebo arm 38,69 and 39,0138, respectively (p >0.05). Measurement conducted at 24H, patients received colchicine demonstrate reduction in NLRP3 level (37.67), while placebo arm results increase in NLRP3 level (42.89) despite not statistically significant (p >0,05). CONCLUSION: Colchicine addition to standard treatment of STEMI patients undergo PCI reduce NLRP3 level despite statistically insignificant.

Comparative analysis of immune cell subsets in peripheral blood from patients with periodontal disease and healthy controls.

Periodontitis is a chronic inflammatory disease caused by the colonization of teeth by the bacterial plaque biofilm and the resultant host immune responses in adjacent periodontal tissues. Disease severity can vary dramatically between patients with periodontitis, with some subjects displaying inflammation without bony destruction (gingivitis), while others experience chronic progressive or rapidly aggressive gingival connective tissue damage and bone loss. To determine whether peripheral immune dysregulation is associated with periodontitis, we performed extensive analysis of immune cell subsets in peripheral blood from patients with chronic or aggressive periodontitis versus periodontally healthy control subjects. Peripheral blood mononuclear cells (PBMC) from patients with chronic periodontitis or aggressive periodontitis and from periodontally healthy controls were analysed by 8-10-colour flow cytometry for the frequencies of various lymphocyte subsets, including interleukin (IL)-17-, interferon (IFN)-γ-, tumour necrosis factor (TNF)-α- and IL-10-producing cells, and the frequencies and phenotype of monocytes. Cytokine levels in serum from the different groups were determined by Luminex assay. We found no significant differences in the frequencies of major immune cell populations [CD4+ T cells, CD8+ T cells, γδ T cells, CD4+ CD45RO+ CD25+ CD127low regulatory T cells (Tregs ), CD19+ B cells, CD14+ monocytes] or of cytokine-producing T cells, or in the phenotype of CD14+ monocytes in peripheral blood from these patient cohorts. Additionally, no significant differences were observed in serum levels of prototypical inflammatory cytokines. These results suggest that the local gingival inflammatory response is not reflected by obvious changes in major blood immune cell subset frequencies.

Characterization of Five Podoviridae Phages Infecting Citrobacter freundii.

Citrobacter freundii causes opportunistic infections in humans and animals, which are becoming difficult to treat due to increased antibiotic resistance. The aim of this study was to explore phages as potential antimicrobial agents against this opportunistic pathogen. We isolated and characterized five new virulent phages, SH1, SH2, SH3, SH4, and SH5 from sewage samples in Tunisia. Morphological and genomic analyses revealed that the five C. freundii phages belong to the Caudovirales order, Podoviridae family, and Autographivirinae subfamily. Their linear double-stranded DNA genomes range from 39,158 to 39,832 bp and are terminally redundant with direct repeats between 183 and 242 bp. The five genomes share the same organization as coliphage T7. Based on genomic comparisons and on the phylogeny of the DNA polymerases, we assigned the five phages to the T7virus genus but separated them into two different groups. Phages SH1 and SH2 are very similar to previously characterized phages phiYeO3-12 and phiSG-JL2, infecting, respectively, Yersinia enterocolitica and Salmonella enterica, as well as sharing more than 80% identity with most genes of coliphage T7. Phages SH3, SH4, and SH5 are very similar to phages K1F and Dev2, infecting, respectively, Escherichia coli and Cronobacter turicensis. Several structural proteins of phages SH1, SH3, and SH4 were detected by mass spectrometry. The five phages were also stable from pH 5 to 10. No genes coding for known virulence factors or integrases were found, suggesting that the five isolated phages could be good candidates for therapeutic applications to prevent or treat C. freundii infections. In addition, this study increases our knowledge about the evolutionary relationships within the T7virus genus.

Global avian influenza surveillance in wild birds: a strategy to capture viral diversity.

Wild birds play a major role in the evolution, maintenance, and spread of avian influenza viruses. However, surveillance for these viruses in wild birds is sporadic, geographically biased, and often limited to the last outbreak virus. To identify opportunities to optimize wild bird surveillance for understanding viral diversity, we reviewed responses to a World Organisation for Animal Health-administered survey, government reports to this organization, articles on Web of Knowledge, and the Influenza Research Database. At least 119 countries conducted avian influenza virus surveillance in wild birds during 2008-2013, but coordination and standardization was lacking among surveillance efforts, and most focused on limited subsets of influenza viruses. Given high financial and public health burdens of recent avian influenza outbreaks, we call for sustained, cost-effective investments in locations with high avian influenza diversity in wild birds and efforts to promote standardized sampling, testing, and reporting methods, including full-genome sequencing and sharing of isolates with the scientific community.

Evaluation of correlation between high serum-ascites albumin gradient and the upper gastrointestinal endoscopic parameters in children presenting with portal hypertension with ascites.

Portal hypertension which usually leads to bleeding from oesophageal varices in children remain a difficult medical problem. The upper gastrointestinal endoscopy is currently considered as the best reliable method to diagnose oesophageal varices in portal hypertension. But endoscopic screening is an invasive procedure and is not easily available even in tertiary health care facilities of Bangladesh till now. Therefore an alternative noninvasive indicator is being looked for the diagnosis of portal hypertension. Patients with serum ascites albumin gradient (SAAG) values ≥1.1gm/dl have recently found to have presence of portal hypertension. The study was carried out to set up a diagnostic value of SAAG for the prediction of portal hypertensive changes (oesophageal and gastric varices, gastropathy) of upper gastrointestinal endoscopy in children. This cross sectional study was conducted at the Department of Paediatric Gastroenterology and Nutrition of Bangabandhu Sheikh Mujib Medical University. A total of 30 cases of portal hypertension were studied from November 2008 to February 2010. Oesophageal varices were found in 86.7% of cases. Significant association was found between high SAAG values and presence of oesophageal varices. Frequencies of oesophageal varices increased as the SAAG values increased. The cut off point of SAAG value was found to be 1.55gm/dl for the presence of oesophageal varices where sensitivity and specificity were found 84.6% and 100 % respectively. From this study, it can be concluded that SAAG value 1.6gm/dl is an indicator of portal hypertensive changes especially oesophageal varices in children.

The efficacy of strontium and potassium toothpastes in treating dentine hypersensitivity: a systematic review.

Objectives. The aim of the present paper was to review the published literature in order to identify all relevant studies for inclusion and to determine whether there was any evidence of the efficacy of strontium and potassium toothpastes in the treatment of dentine hypersensitivity (DH). Methods. Following a review of 94 relevant papers both from searching electronic databases (PUBMED) and hand searching of relevant written journals, 13 studies were identified, and 7 papers (1 for strontium-based toothpastes and 6 for potassium-based toothpastes) were finally accepted for inclusion. The main outcome measures were the methodology and assessment used by Investigators in studies designed to evaluate DH. Results. The results of the present paper would indicate that the reported efficacy of both strontium- and potassium-based toothpastes in relieving DH is questionable. Conclusions. The results from the present paper would appear to support the conclusions of previous investigators that there is only minimal evidence for the efficacy of both strontium- and potassium-based toothpastes in relieving symptoms of DH.

Necessity for long-term follow-up of patients with head and neck paraganglioma and mutation in the succinate dehydrogenase genes: an index case report and literature review.

OBJECTIVE: To describe a patient with hereditary head and neck paraganglioma (HNPGL) and to review the literature on these rare tumors. METHODS: We review the English-language literature regarding SDH mutations, HNPGL, hereditary paraganglioma-pheochromocytoma syndrome, and the role of functional imaging in the follow-up of these tumors. We also describe the clinical findings, imaging results, and follow-up of a man who initially presented with HNPGL and subsequently developed metastatic pheochromocytoma 20 years later. RESULTS: A 66-year-old man presented with a history of hypertension, palpitations, sweating, and elevated urinary norepinephrine. Iodine-123-metaiodobenzylguanidine (123I-MIBG) scan demonstrated a left suprarenal mass and multiple avid lesions in the abdomen, chest, and posterior cranial fossa. Histologic examination confirmed a metastatic pheochromocytoma, and molecular genetic testing revealed a mutation in the SDHD gene. The patient had had surgery 20 years earlier for HNPGL. Although most HNPGLs arise sporadically, susceptibility genes have been identified in approximately one-third of cases. Optimal follow-up remains controversial. We reiterate a need for long-term follow-up of patients with a mutation in an SDH gene. 123I-MIBG, highly specific for identifying ectopic neuroendocrine tissue, may have a role in long-term follow-up. CONCLUSIONS: Although HNPGLs rarely metastasize, their malignant potential is difficult to predict. Routine surveillance for at-risk patients is recommended. Patients with a mutation in an SDH gene should therefore undergo regular surveillance.

Loss of a single Hic1 allele accelerates polyp formation in Apc(Δ716) mice.

Adenomatous polyposis coli (APC) gene mutations have been implicated in familial and sporadic gastrointestinal (GI) cancers. APC mutations are associated with autosomal dominant inheritance of disease in humans. Similarly, mice that contain a single mutant APC gene encoding a protein truncated at residue 716 (Apc(Δ716)) develop multiple polyps throughout the GI tract as early as 4 weeks after birth. Inactivation of another tumor suppressor gene, Hypermethylated in Cancer 1 (HIC1), often occurs in human colon cancers, among others, via CpG island hypermethylation. Homozygous deletion of Hic1 in mice results in major developmental defects and embryonic lethality. Hic1 heterozygotes have previously been shown to develop tumors of a variety of tissue types. We now report that loss of a single Hic1 allele can promote crypt hyperplasia and neoplasia of the GI tract, and Hic1(+/-), Apc(+/Δ716) double heterozygotes (DH) develop increased numbers of polyps throughout the GI tract at 60 days. Hic1 expression is absent in polyps from DH mice, with concomitant increased expression of two transcriptional repression targets of Hic1, Sirt1 and Sox9. Together, our data suggest that loss of a gene frequently silenced via epigenetic mechanisms, Hic1, can cooperate with loss of a gene mutated in GI cancer, Apc, to promote tumorigenesis in an in vivo model of multiple intestinal neoplasia.

Langerhans cell histiocytosis revealed by painful hip: a case report.

Langerhans cell histiocytosis is a rare disease in childhood. It has a very polymorphous clinical expression, ranging from a single bony disease to a multisystemic disease involving vital organs. Prognosis has been improved by use of chemotherapy. We report a 2-year-old girl with multifocal Langerhans cell histiocytosis of bone and skin, revealed by a pain of the left hip and a limp trailing from 2 months. The diagnosis has been established by histological exam. The patient received chemotherapy and steroids. Outcome was favourable over 6-month follow-up. Trailing limp should evoke diagnosis of Langerhans cell histiocytosis. Skin biopsy should be preferred to a bone biopsy because of its safety.

Nonlinear mixed effects pharmacokinetic/pharmacodynamic analysis of the anticonvulsant ameltolide (LY201116) in a canine seizure model.

The anticonvulsant ameltolide (LY201116) is a novel potential therapy for the treatment of canine epilepsy. Eight dogs were administered five different oral doses of ameltolide and clinical scoring of the maximal electroshock (MES) induced seizures at 3 and 24 h postdosing were determined in two separate crossover design studies. Plasma ameltolide concentrations were determined at the time of seizures in all dogs and complete plasma concentration-time profiles were also determined in a separate study. A nonlinear mixed effects PK/PD model was fit to the resulting data. A one compartment open model with first order absorption was determined to best fit the ameltolide pharmacokinetics. An effect compartment with a cumulative logistic regression equation was used to establish the PK/PD relationship. The mean bioavailability normalized volume of distribution and the elimination half-life were estimated at 1.20 L/kg and 5.46 h, respectively. The fitted model estimated that from 2 to 15 h following a single 3 mg/kg oral ameltolide dose the mean probability of obtaining a 1 unit reduction in the seizure clinical score severity was greater than 0.80. The utilized PK/PD analysis combined with the canine MES model allowed for the rapid and efficient determination of the plasma ameltolide concentration-anticonvulsant relationship preclinically in dogs.

Single center, single operator comparative study of the effectiveness of electrohydraulic and electromagnetic lithotripters in the management of 10- to 20-mm single upper urinary tract calculi.

OBJECTIVES: This study compared the efficacy and safety profile of electrohydraulic (EH) and electromagnetic (EM) lithotriptors in the treatment of 10- to 20-mm renal and proximal ureteric stones at a single center and by a single operator. METHODS: Between January 2001 and December 2006, we sequentially treated patients meeting study inclusion criteria with MPL 9000 Dornier EH for the first 3 years, followed by the EM Siemens Modularis shockwave lithotripsy (SWL) unit. A single operator performed all SWL treatments under the supervision of an admitting urologist. We analyzed the demographic features and stone- and treatment-related parameters including complications for both groups. In each group, the stone-free rate and efficiency quotient was determined at 1-3 months. RESULTS: Of 274 patients, we sequentially treated 112 using the EH lithotriptor, and 162 the EM lithotriptor. The pre-SWL patients and stone-related parameters were similar in the two groups, except for diagnostic imaging modalities. The mean number of SWL sessions, need for ancillary procedure, retreatment rate, stone location, stone-free rate, and efficiency quotient were not significantly different between groups. The mean number of shockwaves required for complete fragmentation was 2977 and 6044 (P < .000) for the EH and EM groups, respectively. CONCLUSIONS: Single center, single operator experience with two types of lithotriptor indicated that both are equally efficacious, with similar safety profiles. The only significant difference was that the EH lithotriptor required fewer shockwaves for fragmentation.

Development and validation of the maximal electro-shock seizure model in dogs.

The development and validation of the maximal electro-shock (MES) model using phenobarbital (Pb) as the positive control is described. This approach builds on previous work in rodent model systems, and has been adapted to dogs as a tool for pharmaceutical dose selection. Dogs, like rodents, exhibit generalized convulsions which manifest as progressive clinical signs in a dose (electrical current) dependent fashion. At the limit (300 mA, 200 msec) animals underwent clonic-tonic convulsions consistent with complete generalized (Grand Mal) seizures with a grade 3 clinical score (CS) and a menace response time of 98.5 +/- 24.4 sec (n = 8). Pretreatment of animals with Pb at 3, 10, and 30 mg/kg, in a 4-by-4 complete block crossover design (Latin-Square), resulted in a dose-dependant reduction in CS and menace response time. Estimates of plasma Pb concentration taken prior to MES induction showed a similar dose-dependent reduction in CS and menace response time with concentration. Using a cumulative logistic regression model, a predicted 50% probability of a CS = 1 was approximately 11.4 mg/kg. In addition, plasma Pb concentrations predicted a 50% probability of a CS = 1 occurs at plasma Pb concentration of approximately 16.0 mug/mL. Combined these data suggest that MES is a useful model for evaluating generalized convulsions in canines and may provide a tool for dose selection of novel pharmaceutical compounds.

Intracerebellar granulocytic sarcoma. A case report.

Granulocytic sarcoma is a form of extramedullary leukaemia. The intraparenchymal localisation is extremely rare. We report a case of cerebellar granulocytic sarcoma occuring in a 43 years old woman without any precedent medical history. The diagnosis of granulocytic sarcoma was established by neoplastic cells findings through morphological and immunohistochemical studies. The patient died few days after surgery. There are still no conclusive treatment strategies for this entity; however, early antileukemic chemotherapy seems to lower the probability of developing systemic disease and thus prolong survival.

Cystic fibrosis in a Bangladeshi child.

Cystic fibrosis is one of the common lives limiting inherited diseases in Caucasians population. Recent reports suggest that the diagnosis of cystic fibrosis in this part of the world is missed or delayed due to low index of suspicion. A case of cystic fibrosis is reported here who is a Bangladeshi girl of nine-month-old who presented with the complaints of persistent cough, respiratory distress and failure to thrive. Diagnosis was made on the basis of sweat chloride estimation and mutation analysis, both of which were done, from abroad. She was put on pancreatic enzyme supplementation and nebulized bronchodilators. Cystic fibrosis though rare in Bangladesh its possibility is to be kept in mind in appropriate clinical circumstances

Epilepsy in children with cerebral palsy.

This was a prospective analytical study done from October'99 through December 2000 to observe the clinical profile of epilepsy in children with cerebral palsy. Sixty epileptic children with cerebral palsy were studied and their results were compared with the results of epilepsy in 30 developmentally normal children. Ages of all children studied were 1-15 years. Majority were below five years of age and male out numbered female. Spastic quadriplegia (60%) was the commonest type of cerebral palsy. Generalized tonic-clonic seizure (66%) was the commonest seizure type in both groups. Second most common type of seizure was partial (13%) and myoclonic (29%) in developmentally normal and cerebral palsy children respectively. Mental retardation (63%) and speech delay (58%) were the two common associated problems in cerebral palsy patients. Ventriculomegaly (55%) was the commonest computed tomographic findings in cerebral palsy patients. In electro encephalography generalized epileptiform activity was the commonest finding in both groups. Clinical pattern is different in many ways when epilepsy is associated with cerebral palsy.

Upper gastrointestinal endoscopy in children - an experience at a paediatric gastroenterology unit.

Upper gastrointestinal endoscopy has changed the management of upper gastrointestinal problems in children. The aim of this communication is to share our experience with 153 cases on whom upper gastrointestinal endoscopy was done over a period of 24 months at a paediatric gastroenterology unit of a tertiary care hospital of Dhaka, Bangladesh. Children who attended the department with various gastrointestinal problems are the subjects of this paper. Intravenous midazolam and 10% pharyngeal xylocain were used in majority of cases for sedating the children. The ages of the children were between 15 months to 15 years (9.41+/- 3.22 years). The positive diagnostic yield was 92 out of 153 cases (60.1%). The major indication for doing endoscopy in the present series was recurrent abdominal pain (51.6%), followed by upper gastrointestinal bleeding (28.8%). Combining histopathological findings and CLO/rapid urease tests the overall positive yield of recurrent abdominal pain was 45 out of 79 (57%). The sources of upper gastrointestinal bleeding could be identified in 79.5% cases. Esophageal varices indicating portal hypertension were found in 62.5% children who were endoscoped for unexplained splenomegaly with or without ascitis. Endoscopy has become a safe and valuable procedure in the management of upper gastrointestinal problems in children and gastric antral biopsy has increased the positive diagnostic yield of recurrent abdominal pain in the studied children.

Cerebellar liponeurocytoma: a case report and review of the literature.

Cerebellar liponeurocytoma has recently been recognised by the 2000 World Health Organisation classification of tumours of the central nervous system as a distinct clinicopathologic entity. To our knowledge, 18 cases have been reported so far, under different names, such as "lipomatous medulloblastoma, lipidized medulloblastoma, neurolipocytoma, medullocytoma and lipomatous glioneurocytoma". The new classification included cerebellar liponeurocytoma in the category of glioneuronal tumours grade I or II because of its favourable clinical behaviour. The origin and nature of the lipomatous component have been matter of debate and make this tumour entity puzzling. We describe a new case of liponeurocytoma removed from the left cerebellar hemisphere of a 38-year-old-woman. The patient showed unspecific signs of intracranial hypertension and symptoms suggesting a posterior fossa lesion.

Hepatitis C infection in children: a Melbourne perspective.

OBJECTIVE: To examine the clinical spectrum of hepatitis C virus (HCV) infected children in our care by determining presentation, mode of acquisition, degree of co-infection, biochemical evidence of persisting hepatitis and treatment outcome. METHODOLOGY: A retrospective review of the medical records of all children attending the Royal Children's Hospital, Melbourne, between 1990 and 1998, who had antibodies to HCV infection detected. Detailed clinical information, investigations and the results of treatment were extracted from the clinical notes. RESULTS: A total of 94 children (age range 2 weeks to 19.7 years) were identified, of whom nine had passive transfer of maternal antibodies from HCV-positive mothers and were excluded from analysis. Sixty-seven children (79%) were infected by transfusion of blood or blood products. Perinatal transmission occurred in 11 children (13%), and six children (7%) had a history of i.v. drug abuse. The majority of children were asymptomatic at presentation. Of the 65 patients tested for HCV-ribonucleic acid, 43 (66%) were positive. Fifty-seven cases had serial alanine aminotransaminase (ALT) measurements over a mean of 28 months. Of these, 38 (67%) had an abnormal ALT. Ten cases (12%) were co-infected with hepatitis B virus, HIV or both. Of 12 patients treated with interferon, four responded with normalisation of ALT from 3 to 12 months post-commencement of therapy. CONCLUSIONS: Although HCV was largely an asymptomatic condition in our clinic population, more than half the patients had biochemical evidence of ongoing liver damage. Given the chronicity of this infection in the majority of patients and the long-term risks of cirrhosis and hepatocellular carcinoma, children with HCV infection represent a high-risk group worthy of regular follow up.

Four epitopes on tumor necrosis factor-alpha defined by murine anti-tumor necrosis factor-alpha monoclonal antibodies.

Eight murine anti-TNF alpha monoclonal antibodies (mAb) were produced after immunization of BALB/c mice with rhTNF alpha. Six of these mAbs were able to neutralize cytotoxic activity of TNF alpha against L929 cells. Two other mAbs had no neutralizing effect. Epitope mapping studies were performed by ELISA and by using a BIAcore system (Pharmacia). The described mAbs were allowed to define 4 different epitopes on TNF alpha. Three of them were involved in the binding of TNF alpha with its receptor (cytotoxic neutralization of TNF alpha). Another epitope was defined by non-neutralizing mAbs.