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91.
Involvement of the large intestine in a long standing case of dystrophic epidermolysis bullosa was characterized by recurrent episodes of diarrhoea synchronizing with exacerbation ofthe skin lesions. The radiological investigations revealed two narrow segments, one each in the descending and transverse colon, with ulcer craters in the lower part of the former. The haustra from the distal half of the transverse colon to the sigmoid colon were lost. 相似文献
92.
Background Although development of visceral pain is an important defensive mechanism, hypersensitivity results in a significant clinical problem and is likely to be one of the major factors involved in the pathogenesis of abdominal and chest pain in functional bowel disorders (FBDs). Understanding of the molecular mechanisms involved in peripheral sensitization of visceral nociceptors has advanced as a result of the experimental studies, especially in animal models, which have led to knowledge and identification of key mediators and receptors.
Aim To provide a comprehensive review focused on the peripheral mechanisms believed to be responsible for sensitization and potential molecular targets for a disorder which is common, distressing and has sub-optimal treatment options.
Methods Literature review using Ovid and Pubmed from 1966.
Results There is substantial interest in the development of new drugs for treatment of FBDs in the background of advances in understanding the molecular and physiological mechanisms of visceral hypersensitivity. The potential drug targets include TPRV1, ASICs, voltage-gated sodium channels, ATP, PAR-2, cannabinoid, prostaglandin, tachykinin and 5HT3 receptors.
Conclusion It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases. 相似文献
Aim To provide a comprehensive review focused on the peripheral mechanisms believed to be responsible for sensitization and potential molecular targets for a disorder which is common, distressing and has sub-optimal treatment options.
Methods Literature review using Ovid and Pubmed from 1966.
Results There is substantial interest in the development of new drugs for treatment of FBDs in the background of advances in understanding the molecular and physiological mechanisms of visceral hypersensitivity. The potential drug targets include TPRV1, ASICs, voltage-gated sodium channels, ATP, PAR-2, cannabinoid, prostaglandin, tachykinin and 5HT
Conclusion It is anticipated that with advancing molecular understanding of the basis of visceral hypersensitivity, the next decade will see accelerated development of new molecules for treatment of functional bowel diseases. 相似文献
93.
C. MA R. PANACCIONE S. J. HEITMAN S. M. DEVLIN S. GHOSH & G. G. KAPLAN † 《Alimentary pharmacology & therapeutics》2009,30(10):977-986
Background Therapy with adalimumab has been shown to be effective in Crohn's disease (CD) patients who have lost response or are intolerant to infliximab.
Aim To determine the efficacy of adalimumab in CD patients who discontinued infliximab through a systematic review.
Methods Electronic searches of EMBASE and MEDLINE databases up to May 1, 2009, as well as abstracts from the AGA (2006–2008), ACG (2006–2007), UEGW (2006–2008) and CDDW (2006–2009) identified randomized-controlled trials (RCT) or open-labelled cohorts (OLC) evaluating the short-term and/or long-term efficacy of adalimumab in infliximab failures. The response rates for short-term (clinical response and remission at 4 weeks) and long-term (remission at 6 and 12 months) efficacy were considered.
Results A total of 1810 CD patients were identified among the 15 studies (2 RCT and 13 OLC). The majority of studies evaluated CD patients who either lost response or were intolerable to infliximab, although five OLCs permitted patients refractory to infliximab. Short-term clinical response ( n = 9 articles) ranged from 41% to 83%. Long-term clinical remission at 12 months ( n = 8 articles) ranged from 19% to 68%. The occurrence of severe adverse events ranged from 0% to 19% and four patients died.
Conclusions Current RCT and OLC evidence suggest that adalimumab is an efficacious therapy for CD patients who discontinue infliximab. 相似文献
Aim To determine the efficacy of adalimumab in CD patients who discontinued infliximab through a systematic review.
Methods Electronic searches of EMBASE and MEDLINE databases up to May 1, 2009, as well as abstracts from the AGA (2006–2008), ACG (2006–2007), UEGW (2006–2008) and CDDW (2006–2009) identified randomized-controlled trials (RCT) or open-labelled cohorts (OLC) evaluating the short-term and/or long-term efficacy of adalimumab in infliximab failures. The response rates for short-term (clinical response and remission at 4 weeks) and long-term (remission at 6 and 12 months) efficacy were considered.
Results A total of 1810 CD patients were identified among the 15 studies (2 RCT and 13 OLC). The majority of studies evaluated CD patients who either lost response or were intolerable to infliximab, although five OLCs permitted patients refractory to infliximab. Short-term clinical response ( n = 9 articles) ranged from 41% to 83%. Long-term clinical remission at 12 months ( n = 8 articles) ranged from 19% to 68%. The occurrence of severe adverse events ranged from 0% to 19% and four patients died.
Conclusions Current RCT and OLC evidence suggest that adalimumab is an efficacious therapy for CD patients who discontinue infliximab. 相似文献
94.
95.
Prenatal diagnosis is the generally accepted option for genetic disorders including haemophilias and other bleeding disorders. Cord blood analysis between 17.4 and 20.6 weeks of gestation was performed in 172 confirmed carriers belonging to families of haemophilia A, haemophilia B, von Willebrand disease (VWD), factor VII and X deficiency; 133 were carriers for haemophilia A, 30 for haemophilia B, six for type 3 VWD, two for FX deficiency and one for FVII deficiency. The approach to the cord was either transabdominal or transamniotic. The volume of blood collected varied between 1 and 2 mL. In case of haemophilias, the diagnosis was offered by factor VIII/IX:C activity and antigen assays wherever required. In case of VWD, the diagnosis was based on von Willebrand factor antigen assays as detected by ELISA along with FVIII:C assay while in cases of FVII and FX deficiency, the diagnosis was based on FVII:C and FX:C respectively. The factor levels were compared with the normal range established in the laboratory for different coagulation factors between 18 and 21 weeks of gestation in women tested for other haematological disorders. Only in two cases, the procedure had to be repeated for reasons of extensive maternal contamination. All the deliveries have been followed up and the diagnoses reconfirmed by repeat clotting factor assays and DNA analysis whenever informative. Simple precautions like collection of fetal blood samples in smaller volumes in separate tubes, assaying multiple coagulation factors in the fetal blood samples helped us to offer diagnoses in all the women analysed. No fetal death or abortion was reported following the procedure. We suggest that accurate fetal blood sampling is a safe technique for the diagnosis of many of the bleeding disorders in places where genetic diagnostic services are not available. 相似文献
96.
B. GARDNER S. GHOSH D.M. BRAZIER A.M. HOLBURN 《International journal of laboratory hematology》1983,5(2):215-229
Summary Double antibody radioimmunoassays have been developed for the quantification of anti-IgG, anti-C3, anti-C3c, anti-C3d and anti-C4 antibodies and for the determination of their binding constants. Assays were undertaken on 53 polyspecific antiglobulin reagents obtained from a variety of commercial and public sources. Concentrations of anti-IgG varied from 1.2 to 12.8 μg/ml in commercial products and from 0.4 to 6.0 μg/ml in public products. Concentrations of anti-C3 and anti-C3c varied from 0.1 to 1.0 μg/ml in most commercial products but in public products concentrations varied by more than 100-fold from 0.02 to 6.5 μg/ml. Concentrations of anti-C3d varied from 0.05 to 0.7 μg/ml in most commercial products and from <0.01 to 1.3 μg/ml in public products. Concentrations of anti-C4 varied from <0.01 to 0.18 μg/ml in commercial products and from <0.01 to 0.08 μg/ml in public products. Mean binding constants for commercial products were: anti-IgG 6.6times109 1/mol, anti-C3 4.6 × 109 1/mol, anti-C3c 5.3 × 109 1/mol, anti-C3d 0.4 × 109 1/mol and anti-C4 4.9 × 109 1/mol. Relationships were found between results obtained in quantitative assays of specific antibodies and independently performed serological assessments of potency. Anti-IgG was present in suboptimal concentrations for agglutination in several public products and anti-C3 and anti-C3c were in suboptimal concentrations for agglutination in many public and commercial products. 相似文献
97.
Thromboelastography (TEG) assesses the global pattern of blood coagulation in the whole blood. Present day management of haemophilia is based on replacement therapy with lost factor by parenteral administration of factor concentrates. It is very well known that interaction of cellular components in the blood also affect the thrombin generation which in turn might produce varied TEG patterns that might reflect the clinical severity in haemophilia patients. We evaluated 66 severe haemophilia A and B patients (as assessed by one-stage assay) by TEG and correlated the varied TEG patterns with the clinical severity in the patients. Four distinct TEG patterns were observed; Group A consisted of eight patients with hypercoagulable patterns while group B consisted of two patients showing hyperfibrinolytic patterns. Group C comprised of 17 patients whose TEG tracings did not show the initiation of clot formation at all while group D comprising of 39 patients showed varied clot initiation times ranging from almost normal pattern to a highly prolonged split times. Groups A and D patients were relatively milder clinically while groups B and C were clinically severe as assessed by the number of bleeding episodes, the frequency of transfusion and joint deformity. Subsequently we also evaluated the in vitro efficacy of the antifibrinolytic drug, EACA in normalizing the TEG patterns in 12 patients (group C) who did not show the initiation of clot formation in the TEG tracings to see the contribution of fibrinolysis in producing such patterns. The use of EACA in vitro in this group improved the TEG profile of these patients. In conclusion, the classification of severe haemophilia patients based on TEG patterns correlated well with the clinical severity and the ex vivo use of antifibrinolytics like EACA are effective in improving the TEG profile of all patients who had an abnormal TEG pattern without any clot initiation. 相似文献
98.
99.
100.