Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequ...Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy.There is no single gold standard test that accurately reflects the presence of liver disease,or that can be used to monitor fibrosis progression,particularly in conditions such as cystic fibrosis.This has lead to controversy over how suspected liver disease in children is detected and diagnosed.This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease.In addition,the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.展开更多
Schistosomiasis,caused by parasitic bloodflukes of the genus Schistosoma,is a major source of human disease in developing tropical nations.This paper reviews the diagnostic various assays for schistosomiasis,with part...Schistosomiasis,caused by parasitic bloodflukes of the genus Schistosoma,is a major source of human disease in developing tropical nations.This paper reviews the diagnostic various assays for schistosomiasis,with particular reference to recent advances in assays incorporating direct parasitological examination,serology,antigen detection,and polymerase chain reaction detection of parasite genetic material.展开更多
BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)patients.AIM To assess the efficacy an...BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)patients.AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission.METHODS A retrospective review of Australian and Oxford,United Kingdom data for UC patients.Clinical response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were assessed.Cox regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing them.Safety outcomes were recorded.RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were included.The clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo respectively.Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%P<0.001,6 mo 73%vs 46%P<0.001,12 mo 66%vs 51%P=0.03).More Australian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 mo.CONCLUSION VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.展开更多
Human cerebral sparganosis is a rare but neglected parasitic disease. We present details of the diagnosis of two cases of migrating cerebral sparganosis from China based on computed tomography and magnetic resonance i...Human cerebral sparganosis is a rare but neglected parasitic disease. We present details of the diagnosis of two cases of migrating cerebral sparganosis from China based on computed tomography and magnetic resonance imaging combined with epidemiological information and serology. Its differentiatial diagnosis from other parasitic diseases, tuberculoma and brain tumor by neuroimaging is briefly discribed.展开更多
Splenic cysts are rare lesions and most of them are hydatid in origin. Hydatid disease is very rare in central Africa although it is cosmopolitan in North Africa. We are presenting a case of intracystic bleeding compl...Splenic cysts are rare lesions and most of them are hydatid in origin. Hydatid disease is very rare in central Africa although it is cosmopolitan in North Africa. We are presenting a case of intracystic bleeding complicated with shock in a rural based Cameroonian and owner of hunting dogs treated in our university teaching hospital.展开更多
AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarect...AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with S.mansoni proteins.Experiments were performed 5 d after TNBS injection.Inflammationwas quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo gastrointestinal motility.Peristaltic activity of distal colonic segments was studied in vitro using a modified Trendelenburg set-up.Cytokine profiles of T-lymphocytes isolated from the colon were determined by real time reverse transcriptase-polymerase chain reaction. RESULTS:Intracolonic injection of TNBS caused severe colitis.Treatment with S.mansoni proteins significantly ameliorated colonic inflammation after 5 d.TNBS did not affect gastric emptying but significantly decreased the geometric center and impaired colonic peristaltic activity 5 d after the induction of colitis.Treatment with S.mansoni proteins ameliorated these in vivo and in vitro motility disturbances.In addition,TNBS injection caused a downregulation of effector T cell cytokines after 5 d,whereas a S.mansoni protein effect was no longer observed at this time point. CONCLUSION:Treatment with S.mansoni proteins attenuated intestinal inflammation and ameliorated motility disturbances during murine experimental colitis.展开更多
There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their si...There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.展开更多
Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample wa...Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6% . This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2% .展开更多
Background To determine whether the introduction of pasteurized donor human milk and probiotics for infants born<32 weeks gestational age or<1500 g birthweight is associated with a reduction in mortality and the...Background To determine whether the introduction of pasteurized donor human milk and probiotics for infants born<32 weeks gestational age or<1500 g birthweight is associated with a reduction in mortality and the incidence of necrotising enterocolitis (NEC) and sepsis. Methods We performed a retrospective analysis of two cohorts: before and after the introduction of probiotics and pasteurised donor human milk. Univariate analysis of primary and secondary outcomes was performed;variables impacting outcomes were assessed using multivariate logistic regression. Results There were 1791 infants: 1334 in the pre-donor milk/probiotic cohort and 457 in the post-donor milk/probiotic cohort. On univariate analysis, mortality (7.6 vs. 2.4%, P<0.001) and incidence of sepsis (6.2 vs. 3.5%, P=0.028) were statistically significantly lower in the post-donor milk/probiotic group. NEC (2.8 vs. 1.5%, P=0.14) and non-NEC associ-ated gastrointestinal perforation (1.6 vs. 0.4%, P=0.052) were lower in the post-donor milk/probiotics cohort, but these were not statistically significant. The difference in mortality remained statistically significant on multivariate analysis in the post-donor milk/probiotic cohort compared to those in the pre-donor milk/probiotic cohort (odds ratio 0.31, 95% confidence interval 0.16–0.61). The decrease in the incidence of NEC was consistent with previous observational studies but the differ-ence was not statistically significant. Conclusion The availability of probiotics and pasteurised donor human milk is associated with a reduction in mortality in very preterm infants.展开更多
The complexity of a cancer, such as cell heterogeneity, and the existence of hypoxia, stromal cells and stem cells has present, the use of conventional therapies, such as chemo/radio therapy is limited, and only thera...The complexity of a cancer, such as cell heterogeneity, and the existence of hypoxia, stromal cells and stem cells has present, the use of conventional therapies, such as chemo/radio therapy is limited, and only therapies that are so far prevented successful development and treatment of patients suffering from the later stages of cancers. At focused on utilizing the patient's immune response to combat against the disease appear to be the most reliable and promising. Two decades ago, cytokines were discovered to be able to activate the imnune systems and mount an anti-tumour response. Then, dendritic cells were hailed as the most significant regulators of immunity and are employed in a variety of cancer management schemes. This review introduces current development in the field,focusing on combination of the components of the rapidly growing fields of immunotherapy and gene transfer/therapy, providing useful and significant detailed information for readers of cellular and molecular immunology. Cellular & Molecular Immunology.展开更多
基金Supported by a Project Grant from the National Health and Medical Research Council of Australia(NHMRC#496602 to GAR and PJL)Dr.Tamara Pereira is Supported by the Phillip Bushell Foundation Post-Doctoral Research Fellowship from the Gastroenterological Society of AustraliaAssociate Professor Grant A Ramm is Supported by a NHMRC Senior Research Fellowship(NHMRC#552409)
文摘Cholestatic liver disease causes significant morbidity and mortality in children.The diagnosis and management of these diseases can be complicated by an inability to detect early stages of fibrosis and a lack of adequate interventional therapy.There is no single gold standard test that accurately reflects the presence of liver disease,or that can be used to monitor fibrosis progression,particularly in conditions such as cystic fibrosis.This has lead to controversy over how suspected liver disease in children is detected and diagnosed.This review discusses the challenges in using commonly available methods to diagnose hepatic fibrosis and monitor disease progression in children with cholestatic liver disease.In addition,the review examines the mechanisms hypothesised to be involved in the development of hepatic fibrogenesis in paediatric cholestatic liver injury which may ultimately aid in identifying new modalities to assist in both disease detection and therapeutic intervention.
文摘Schistosomiasis,caused by parasitic bloodflukes of the genus Schistosoma,is a major source of human disease in developing tropical nations.This paper reviews the diagnostic various assays for schistosomiasis,with particular reference to recent advances in assays incorporating direct parasitological examination,serology,antigen detection,and polymerase chain reaction detection of parasite genetic material.
文摘BACKGROUND Vedolizumab(VDZ),a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis(UC)patients.AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission.METHODS A retrospective review of Australian and Oxford,United Kingdom data for UC patients.Clinical response at 3 mo,endoscopic remission at 6 mo and clinical remission at 3,6 and 12 mo were assessed.Cox regression models and Kaplan Meier curves were performed to assess the time to remission,time to failure and the covariates influencing them.Safety outcomes were recorded.RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom,[60%n=182,anti-TNF naïve]were included.The clinical response was 79%at 3 mo with more Australian patients achieving clinical response compared to Oxford(83%vs 70%P=0.01).Clinical remission for all patients was 56%,62%and 60%at 3,6 and 12 mo respectively.Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points(3 mo 66%vs 40%P<0.001,6 mo 73%vs 46%P<0.001,12 mo 66%vs 51%P=0.03).More Australian patients achieved endoscopic remission at 6 mo compared to Oxford(69%vs 43%P=0.01).On multi-variate analysis,anti-TNF naïve patients were 1.8(95%CI:1.3-2.3)times more likely to achieve remission than anti-TNF exposed(P<0.001).32 patients(11%)had colectomy by 12 mo.CONCLUSION VDZ was safe and effective with 60%of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.
文摘Human cerebral sparganosis is a rare but neglected parasitic disease. We present details of the diagnosis of two cases of migrating cerebral sparganosis from China based on computed tomography and magnetic resonance imaging combined with epidemiological information and serology. Its differentiatial diagnosis from other parasitic diseases, tuberculoma and brain tumor by neuroimaging is briefly discribed.
文摘Splenic cysts are rare lesions and most of them are hydatid in origin. Hydatid disease is very rare in central Africa although it is cosmopolitan in North Africa. We are presenting a case of intracystic bleeding complicated with shock in a rural based Cameroonian and owner of hunting dogs treated in our university teaching hospital.
基金Supported by The Fund of Scientific Research(FWO),Flanders, Project G.0134.07the University of Antwerp,BOF Grant FA02/3/3257
文摘AIM:To investigate the therapeutic effect of Schistosoma mansoni(S.mansoni) soluble worm proteins on gastrointestinal motility disturbances during experimental colitis in mice. METHODS:Colitis was induced by intrarectal injection of trinitrobenzene sulphate(TNBS) and 6 h later,mice were treated ip with S.mansoni proteins.Experiments were performed 5 d after TNBS injection.Inflammationwas quantified using validated inflammation parameters. Gastric emptying and geometric center were measured to assess in vivo gastrointestinal motility.Peristaltic activity of distal colonic segments was studied in vitro using a modified Trendelenburg set-up.Cytokine profiles of T-lymphocytes isolated from the colon were determined by real time reverse transcriptase-polymerase chain reaction. RESULTS:Intracolonic injection of TNBS caused severe colitis.Treatment with S.mansoni proteins significantly ameliorated colonic inflammation after 5 d.TNBS did not affect gastric emptying but significantly decreased the geometric center and impaired colonic peristaltic activity 5 d after the induction of colitis.Treatment with S.mansoni proteins ameliorated these in vivo and in vitro motility disturbances.In addition,TNBS injection caused a downregulation of effector T cell cytokines after 5 d,whereas a S.mansoni protein effect was no longer observed at this time point. CONCLUSION:Treatment with S.mansoni proteins attenuated intestinal inflammation and ameliorated motility disturbances during murine experimental colitis.
文摘There have been multiple NOD2/CARD15 genotype- phenotype analyses undertaken in patients with Crohn’s disease since the gene’s discovery in 2001. This review focuses on the major published series based upon their size and on the presence of specific clinical and genetic information provided in the published material from 2001 to 2005. Twelve studies provided raw data to carry out comparisons of disease location while ten studies included analysis of NOD2/CARD15 genotypes. NOD2/CARD15 variant frequency in ileal disease did not differ significantly among studies, whereas a comparison of disease location demonstrated highly significant differences among studies. Meta-analysis confirmed significant associations between NOD2/CARD15 variants and both ileal and ileocolonic disease locations, and with both stricturing and penetrating forms of disease behavior. This review underlines the significant phenotypic differences that exist among populations, including similar ethnic groups, and has demonstrated the need for further studies of patients with long-term “inflammatory” Crohn’s disease.
基金Supported by the European Commission Fifth Framework Programme Grant No. QLK6-CT-1999-02237. GS was supported by a Clinical Fellowship from the European Commission (Leonardo da Vinci Grant I/99/2/09209/PL/II. 1.2.a/FPI)
文摘Somatic mutations of the BRAF gene are common in melanomas and nevi but the contribution of polymorphisms in this gene to melanoma or nevus susceptibility remains unclear. An Australian melanoma case-control sample was typed for 16 single nucleotide polymorphisms (SNP) within the BRAF gene, and five SNP in three neighboring genes. The sample comprised 755 melanoma cases from 740 families stratified by family history of melanoma and controls from 635 unselected twin families (2239 individuals). Ancestry of the cases and controls was recorded, and the twins had undergone skin examination to assess total body nevus count, degree of freckling, and pigmentation phenotype. Genotyping was carried out via primer extension followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry. SNP in the BRAF gene were found to be weakly associated with melanoma status but not with development of nevi or freckles. The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6% . This study shows that BRAF polymorphisms predispose to melanoma but the causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of 0.2% .
文摘Background To determine whether the introduction of pasteurized donor human milk and probiotics for infants born<32 weeks gestational age or<1500 g birthweight is associated with a reduction in mortality and the incidence of necrotising enterocolitis (NEC) and sepsis. Methods We performed a retrospective analysis of two cohorts: before and after the introduction of probiotics and pasteurised donor human milk. Univariate analysis of primary and secondary outcomes was performed;variables impacting outcomes were assessed using multivariate logistic regression. Results There were 1791 infants: 1334 in the pre-donor milk/probiotic cohort and 457 in the post-donor milk/probiotic cohort. On univariate analysis, mortality (7.6 vs. 2.4%, P<0.001) and incidence of sepsis (6.2 vs. 3.5%, P=0.028) were statistically significantly lower in the post-donor milk/probiotic group. NEC (2.8 vs. 1.5%, P=0.14) and non-NEC associ-ated gastrointestinal perforation (1.6 vs. 0.4%, P=0.052) were lower in the post-donor milk/probiotics cohort, but these were not statistically significant. The difference in mortality remained statistically significant on multivariate analysis in the post-donor milk/probiotic cohort compared to those in the pre-donor milk/probiotic cohort (odds ratio 0.31, 95% confidence interval 0.16–0.61). The decrease in the incidence of NEC was consistent with previous observational studies but the differ-ence was not statistically significant. Conclusion The availability of probiotics and pasteurised donor human milk is associated with a reduction in mortality in very preterm infants.
文摘The complexity of a cancer, such as cell heterogeneity, and the existence of hypoxia, stromal cells and stem cells has present, the use of conventional therapies, such as chemo/radio therapy is limited, and only therapies that are so far prevented successful development and treatment of patients suffering from the later stages of cancers. At focused on utilizing the patient's immune response to combat against the disease appear to be the most reliable and promising. Two decades ago, cytokines were discovered to be able to activate the imnune systems and mount an anti-tumour response. Then, dendritic cells were hailed as the most significant regulators of immunity and are employed in a variety of cancer management schemes. This review introduces current development in the field,focusing on combination of the components of the rapidly growing fields of immunotherapy and gene transfer/therapy, providing useful and significant detailed information for readers of cellular and molecular immunology. Cellular & Molecular Immunology.
