The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and impro...The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.展开更多
Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is uncle...Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.展开更多
We developed and evaluated a multiplex PCR (m-PCR) for application in routine diagnostic laboratories to detect Campylobacter spp. in stool samples including C. concisus, C. jejuni, and C. coli. When this m-PCR was ap...We developed and evaluated a multiplex PCR (m-PCR) for application in routine diagnostic laboratories to detect Campylobacter spp. in stool samples including C. concisus, C. jejuni, and C. coli. When this m-PCR was applied on spiked faecal samples, C. concisus, C. jejuni, and C. coli were specifically identified at 105 cells/gm of faeces. To compare the sensitivity of the m-PCR with conventional culture techniques, the same spiked stool samples were cultured on an antibiotic free Columbia blood agar using the filtration technique. The detection limit of conventional culture method was 105 cells/gm of stool for C. concisus and 106 cells/gm of stool for C. jejuni and C. coli. The m-PCR was applied to test 127 faecal samples from children with gastroenteritis and the results were compared with the conventional bacterial cultures data. By this m-PCR technique, C. jejuni was detected in 7 samples, C. coli in 2 samples, and C. concisus in 7 samples. However, the conventional culture results for these samples were 6 for C. jejuni, 2 for C. coli and only one sample was positive for C. concisus. In total, 19 samples were positive for Campylobacter spp. by m-PCR while only 9 samples were positive for Campylobacter spp. by culture. In conclusion, m-PCR is more sensitive than the culture technique to detect C. concisus and other fastidious campylobacters in faeces.展开更多
Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mort...Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mortality.There was little information regarding the impact of adverse events on the postoperative recovery,especially the serious adverse events occurring immediately after surgery.We sought to evaluate the early postoperative serious adverse events and examine the impact of them on postoperative recovery.展开更多
Background: The mitochondrial DNA mutation A3302G in the tRNA Leu(UUR) gene causes respiratory chain complex I deficiency. The main clinical feature appears to be a progressive mitochondrial myopathy with proximal mus...Background: The mitochondrial DNA mutation A3302G in the tRNA Leu(UUR) gene causes respiratory chain complex I deficiency. The main clinical feature appears to be a progressive mitochondrial myopathy with proximal muscle weakness. Objective: To report on clinical and molecular features in 4 novel patients with the A3302G mutation. Design: Case reports. Patients: Four patients (3 of whom are from the same family) with a myopathy caused by the A3302G mitochondrial DNA mutation. Main Outcome Measure: Identification of the A3302G mutation by DNA sequencing. Results: All 4 patients had an adult-onset progressive mitochondrial myopathy with proximal muscle weakness, resulting in exercise intolerance. In 2 unrelated patients, upper limb reflexes were absent with preservation of at least some lower limb reflexes. Other features including hearing loss, recurrent headaches, ptosis, progressive external ophthalmoplegia, and depression were present. Conclusion: While the dominant clinical features of the A3302G mutation were exercise intolerance and proximal muscle weakness, other features of mitochondrial encephalomyopathies, previously not described for this mutation, were present.展开更多
文摘The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.
文摘Pruritis with abnormal liver function tests is the classical presentation of intrahepatic cholestasis of pregnancy(ICP),a condition associated with significant fetal complications.Although the etiology of ICP is unclear in many cases,certain features of the clinical presentation should alert the practitioner to the possibility of an underlying metabolic defect, which may not only affect subsequent pregnancies, but may be an indicator of more serious subsequent liver disease.We report a kindred of Anglo-Celtic descent,among whom many members present with ICP,gallstones or cholestasis related to use of oral contraception.Genetic studies revealed a novel mutation in the ABCB4 gene,which codes for a phospholipid transport protein.The clinical significance of this mutation and the importance of identifying such patients are discussed.
文摘We developed and evaluated a multiplex PCR (m-PCR) for application in routine diagnostic laboratories to detect Campylobacter spp. in stool samples including C. concisus, C. jejuni, and C. coli. When this m-PCR was applied on spiked faecal samples, C. concisus, C. jejuni, and C. coli were specifically identified at 105 cells/gm of faeces. To compare the sensitivity of the m-PCR with conventional culture techniques, the same spiked stool samples were cultured on an antibiotic free Columbia blood agar using the filtration technique. The detection limit of conventional culture method was 105 cells/gm of stool for C. concisus and 106 cells/gm of stool for C. jejuni and C. coli. The m-PCR was applied to test 127 faecal samples from children with gastroenteritis and the results were compared with the conventional bacterial cultures data. By this m-PCR technique, C. jejuni was detected in 7 samples, C. coli in 2 samples, and C. concisus in 7 samples. However, the conventional culture results for these samples were 6 for C. jejuni, 2 for C. coli and only one sample was positive for C. concisus. In total, 19 samples were positive for Campylobacter spp. by m-PCR while only 9 samples were positive for Campylobacter spp. by culture. In conclusion, m-PCR is more sensitive than the culture technique to detect C. concisus and other fastidious campylobacters in faeces.
文摘Objective Despite dramatic advances in surgical technique and perioperative care,some children still suffered serious adverse event in early postoperative period which were associated with increased morbidity and mortality.There was little information regarding the impact of adverse events on the postoperative recovery,especially the serious adverse events occurring immediately after surgery.We sought to evaluate the early postoperative serious adverse events and examine the impact of them on postoperative recovery.
文摘Background: The mitochondrial DNA mutation A3302G in the tRNA Leu(UUR) gene causes respiratory chain complex I deficiency. The main clinical feature appears to be a progressive mitochondrial myopathy with proximal muscle weakness. Objective: To report on clinical and molecular features in 4 novel patients with the A3302G mutation. Design: Case reports. Patients: Four patients (3 of whom are from the same family) with a myopathy caused by the A3302G mitochondrial DNA mutation. Main Outcome Measure: Identification of the A3302G mutation by DNA sequencing. Results: All 4 patients had an adult-onset progressive mitochondrial myopathy with proximal muscle weakness, resulting in exercise intolerance. In 2 unrelated patients, upper limb reflexes were absent with preservation of at least some lower limb reflexes. Other features including hearing loss, recurrent headaches, ptosis, progressive external ophthalmoplegia, and depression were present. Conclusion: While the dominant clinical features of the A3302G mutation were exercise intolerance and proximal muscle weakness, other features of mitochondrial encephalomyopathies, previously not described for this mutation, were present.
