Background & Aims: α4 integrins are important mediators of leukocyte migration across vascular endothelium.This pilot placebo-controlled study aimed to assess the safety and efficacy of natalizumab, ...a recombinant humanized monoclonal antibody to α4 integrin, in patients with mild to moderately active Crohn's disease.Methods: Thirty patients with active Crohn's disease (Crohn's Disease Activity Index CDAI ≥151 and ≤450) received a 3-mg/kg infusion of natalizumab (n = 18) or placebo (n = 12) by double-blind randomization.The study's primary endpoint was change in CDAI at week 2.Results: At week 2, the CDAI decreased significantly from baseline after infusion of natalizumab (mean 45 points) but not placebo (mean 11 points).Seven (39%) natalizumab-treated patients achieved remission at week 2, compared with 1 (8%) treated with placebo.In contrast, 4 (33%) of the placebo-treated patients required rescue medication by week 2, compared with 2 (11%) natalizumab-treated patients.Significant increases in circulating B and T lymphocytes were detected only after natalizumab administration.The frequency of commonly reported adverse events did not differ significantly between groups.Conclusions: A single 3-mg/kg natalizumab infusion was well tolerated by Crohn's disease patients, although the dose used may have been suboptimal.Elevated circulating lymphocyte levels after natalizumab suggest interrupted lymphocyte trafficking.Natalizumab therapy in active Crohn's disease merits further investigation.
GASTROENTEROLOGY 2001;121:268-274
Background:
Twin studies provide insight into the complex interaction between genetic and environmental factors in the development of inflammatory bowel disease (IBD). We assessed associations ...between childhood environmental factors and development of Crohn's disease (CD) and ulcerative colitis (UC) in twins.
Methods:
Questionnaires on clinical demographics and exposure to environmental factors were sent to twins with IBD, their healthy co‐twins, and their doctors. Kappa statistics were used to examine agreement between twin pairs and odds ratios were calculated by conditional logistic regression.
Results:
In all, 250 IBD twin pairs (122 CD; 125 UC; 3 CD/UC; 28 concordant pairs) were analyzed. Concordant monozygotic twins with CD showed good agreement for disease location (κ 0.88; 95% confidence interval CI: 0.45–1.00), disease behavior (κ 1.00; 95% CI: 0.43–1.00), and moderate agreement for age at diagnosis and need for medical and surgical therapy. Concordant monozygotic twins with UC showed good agreement for disease extent (κ 0.60; CI 0.13–1.00) and use of thiopurines (κ 0.73; CI 0.10–1.00). In discordant twins, symptomatic childhood mumps infection (odds ratio OR, 3.8; 95% CI, 1.2–11.3) and oral contraceptives (OR, 4.0; 1.1–14.2) were associated with CD. Smoking was associated with CD (OR, 4.3; 95% CI, 1.9–9.8) but inversely associated with UC (OR, 0.3; 95% CI, 0.1–0.9). Both CD and UC twins had suffered more “gastroenteritis” and spent more time with animals than their co‐twins.
Conclusions:
Disease phenotype in CD and disease extent in UC appeared to be genetically influenced. Smoking is a risk factor for CD but is protective for UC. Early exposure to “infections” during childhood may be associated with the development of IBD. (Inflamm Bowel Dis 2011;)
A Caucasian man aged 28 years with a history of pancreatitis presented with fatigue, intermittent melaena and severe anaemia. Symptomatic treatment for anaemia was coupled with thorough investigation ...to localise the source of gastrointestinal haemorrhage. Two oesophagogastroduodenoscopies and colonoscopies failed to identify a cause. CT abdomen revealed splenomegaly secondary to splenic vein thrombosis with evidence of portal hypertension and small collateral vessels. A CT mesenteric angiogram revealed a splenic artery pseudoaneurysm as the likely source of bleeding. This was embolised successfully via interventional radiology and the patient's haemoglobin levels stabilised. During admission, the patient also developed severe epigastric pain radiating to the back secondary to acute-on-chronic pancreatitis, as evidenced by MRCP. The acute pancreatitis resolved with medical management, but the pain from his chronic condition was extremely difficult to control, even with opioids. He consequently underwent a successful splenic nerve radiofrequency ablation.
The aim of our study was to audit dysphagia referrals received by a specialist gastroenterology unit during an entire year. We used a prospective audit carried out over a 12-month period at the ...District General Hospital gastroenterology unit. The audit included 396 consecutive patients who were referred with swallowing difficulties. We found that 60 referrals (15.2%) were inaccurate and the patients had no swallowing problem. Of the 336 patients with genuine dysphagia, only 29 (8.6%) were new cancer cases. The large majority of subjects had benign disease mostly related to acid reflux. Weight loss was significantly associated with malignancy but also occurred in one third of patients with reflux alone. The temporal pattern of dysphagia was not significantly predictive of cancer. All the cancer patients were above the age of 50 years. Although patients were in general assessed rapidly after hospital referral, the productivity, in terms of early tumor diagnosis, was extremely low. We conclude that there is a substantial rate of inaccurate referrals of dysphagia patients. Most true cases of swallowing difficulty relate to benign disease. Even the devotion of considerable resources to the early diagnosis of esophago gastric malignancy in an attempt to conform with best practice guidelines results in a very low success rate in terms of the detection of potentially curable tumors.
Alumina nanoparticles in the loading fraction of 3 wt% were incorporated in pure aluminum matrix to prepare nanocomposites for improved mechanical performance. Powder metallurgy route was adopted ...wherein nanoparticles were mixed with aluminium powder using dry mixing technique involving milling process, which was followed by the densification of composite mixture by uniaxial cold pressing and pressureless sintering. In order to increase the densification of nanocomposites, a batch of sintered nanocomposites was twice sintered at the same sintering parameters while another batch of specimens was cold pressed after initial sintering. The consolidated nanocomposites together with reference pure aluminum specimens were characterized microstructurally and mechanically by optical and electron microscopy, hardness and compressive strength tests. It was found that the hardness and compressive strength of nanocomposites after sintering increased up to ~ 29% and ~ 144% in comparison to pure aluminium specimens, respectively. Although the densification of nanocomposites increased after twice sintering, the hardness and compressive strength values decreased. However, the rise in consolidification along with improved mechanical performance was noted after cold pressing the specimens as secondary treatment after sintering; hardness increased up to ~ 36% while compressive strength rose to ~ 64%. In comparison to twice sintering, cold pressing after initial sintering significantly increased the hardness and compressive strength of nanocomposites up to ~ 76% and ~ 301% with reference to pure aluminum, respectively. It was found that both the incorporation of alumina nanoparticles and cold pressing after initial sintering improved the mechanical properties of nanocomposites.
PDF
