Efficacy and safety of infliximab as rescue therapy for ulcerative colitis refractory to tacrolimus

Background and Aim: Little is known about the efficacy and safety of infliximab for ulcerative colitis refractory to tacrolimus. The aim of this study was to evaluate the efficacy and safety of infliximab in the induction of remission in ulcerative colitis patients with persistent symptoms despite tacrolimus therapy. Methods: We report a retrospective, observational, single‐center case series of 12 consecutively enrolled patients with ulcerative colitis refractory to tacrolimus that received infliximab therapy for the induction of remission. Eight patients received a single infusion of infliximab, and four received two or more infusions. Median follow‐up duration was 16.0 months (range, 1.6–41.4 months). The clinical response was evaluated based on a modified Truelove‐Witts severity index. Results: Six patients (50.0%) achieved clinical remission within 30 days. Overall cumulative colectomy‐free survival was estimated to be 58.3% at 41.4 months. Adverse events included an elevation of liver enzymes (1/12; 8.3%) and a mild infusion reaction (1/12; 8.3%). No mortality occurred. Conclusions: Infliximab can induce remission in patients with ulcerative colitis who do not tolerate or respond to tacrolimus therapy.     

Studies on percutaneous transvenous mitral commissurotomy using a modified transseptal approach

Summary A modified version of Brockenbrough's trans-septal catheterization technique was carried out in 11 patients indicated for percutaneous transvenous mitral commissurotomy (PTMC). In 8/11 (72.7%), a coiled guide-wire was successfully inserted through theforamen ovale without atrial septal puncture. The Brockenbrough needle was used merely to maintain stiffness and the orientation of the dilator. PTMC was performed with an Inoue single balloon without incident.Patent foramen ovale was found by transesophageal echocardiography prior to the operation in only 1/11 patients (9.0%); nonetheless, it proved not to be a critical factor for the success of the procedure. This procedure seems to have much potential to enable the treatment of mitral stenosis with a lowered risk to the patient, as long as it is performed with precision and caution.     

Intraductal papillary adenoma: Usefulness of magnetic resonance cholangiopancreatography in the diagnosis of cystic branch-duct dilatation of the pancreas

A 70-year-old woman with gastric cancer was referred to our hospital for further evaluation of a cystic mass in the head of the pancreas. Endoscopic ultrasonography (EUS) showed a mural nodule in the cystic mass. Endoscopic retrograde cholangio pancreatography (ERCP) revealed a cystic lesion with a filling defect caused by obstruction with mucus. Magnetic resonance cholangiopancreatography (MRCP) allowed visualization of the entire configuration of the cystic lesion despite the presence of mucus. Pancreatic juice was positive for K-ras point mutation. Pancreatoduodenectomy was performed, with a diagnosis of intraductal papillary adenoma or adenocarcinoma with gastric cancer. Pancreatography of the resected specimen showed a cystic lesion in the uncinate process, consistent with the MRCP findings. Histological examination revealed an intraductal papillary adenoma. MRCP is very useful for demonstrating the total configuration of cystic lesions and is not impeded by impacted mucin. Nevertheless, because of its lower spatial resolution, this noninvasive modality is of limited value in detecting mural nodules. At present, therefore, surgical indications for cystic lesion of the pancreas should be determined by comprehensively analyzing: size and sequential changes in size of the cyst; presence of mural nodules, cytologic examination for presence of malignant cells, and/or K-ras point mutation in pure pancreatic juice.     

Effects of HMGB1 on ischemia-reperfusion injury in the rat heart

BACKGROUND: Coronary ischemia-reperfusion (I/R) injury causes cardiomyocyte necrosis in a multi-step process that includes an inflammatory reaction. A recent study has suggested that high-mobility group box 1 (HMGB1) is a late mediator of lethal sepsis and an early mediator of inflammation and necrosis following I/R injury. In the present study a neutralizing monoclonal antibody (mAb) for HMGB1 was used to clarify the role of HMGB1 in cardiac I/R injury. METHODS AND RESULTS: Rats underwent 30 min of left coronary artery occlusion followed by 60 min reperfusion. An intravenous injection of anti-HMGB1 mAb or control IgG was administered just before reperfusion. The infarct size was enlarged in the anti-HMGB1 mAb group in comparison with the control group (p<0.05). The treatment of anti-HMGB1 mAb significantly increased the plasma troponin-T and norepinephrine (NE) content in the heart in comparison with the control (p<0.05). Moreover, the production of dihydroxyphenylglycol was reduced in the anti-HMGB1-treated group (p<0.05). CONCLUSION: This study shows for the first time the effects of treatment with neutralizing anti-HMGB1 mAb on I/R injury in the rat heart. The findings support the novel view that I/R-induced HMGB1 may be an important factor in the modulation of interstitial NE.     

A case of immotile-dyskinetic cilia syndrome responding to clenbuterol hydrochloride and azithromycin]

In this case, a 30-year-old man had been treated for chronic sinusitis and bronchiectasis since 2000, and presented at our outpatient clinic in May 2001 with chief complaints of massive yellow sputum expectoration and dyspnea. After he was admitted by our hospital, Pseudomonas aeruginosa bacteria were isolated at the rate of 10(8)/ml from his sputum culture. In electron-microscopic observation, the cilia of the bronchial epithelium were found to lack dynein arms. Semen examination revealed decreased sperm motility. Thus, the following diagnosis was made: diffuse bronchiectasis associated with the immotile-dyskinetic cilia syndrome, complicated with a P. aeruginosa infection. After the airway infection was ameliorated, 40 mg/day of clenbuterol hydrochloride was administered in combination with 250 mg of azithromycin, which was given twice a week, and which led to a markedly decreased frequency of exacerbation of airway infection. Moreover, chest CT scanning and respiratory function testing also indicated improvements. It was hypothesized that the decreased cilia motility due to P. aeruginosa-produced pyocyanin would be ameliorated with a b2 stimulant, and the inhibitory effect of a macrolide on the P. aeruginosa biofilm and production of pyocyanin would also be involved in the improvement of this case.     

Primary non-Hodgkin’s lymphoma of the gallbladder diagnosed by laparoscopic cholecystectomy

Primary lymphoma of the gallbladder is an exceedingly rare disease. We experienced an asymptomatic case of primary non-Hodgkin’s lymphoma of the gallbladder in a 55-year-old woman in whom laparoscopic cholecystectomy made a definite diagnosis. Abdominal computed tomography revealed a 4-cm gallbladder tumor with markedly enlarged lymph nodes in the retropancreatic area. Despite the marked involvement of lymph nodes, serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were not elevated. The discrepancy between the imaging findings and the patient’s mild clinical presentation led us to suspect that the tumor was a lymphoma. We examined serum markers of lymphoma, revealing slight elevations of interleukin (IL)-2 receptor and thymidine kinase. Laparoscopic cholecystectomy for a total biopsy was performed successfully, and the results of intraoperative frozen-section examination led us to have a high suspicion of malignant lymphoma. The final diagnosis was large diffuse B-cell lymphoma of the gallbladder with a positive CD20 antibody reaction. The patient received postoperative chemotherapy with R-CHOP (rituximab, 500 mg; cyclophosphamide, 1000 mg; adriamycin, 68 mg; vincristine, 1.9 mg; and prednisone, 80 mg) starting on postoperative day 12. She achieved complete remission and is still in complete remission 3 years and 2 months after the cholecystectomy. In conclusion, gallbladder lymphoma should be added to the differential diagnosis of gallbladder tumors, especially when the imaging findings and clinical presentation are not consistent with typical signs of gallbladder carcinoma, and laparoscopic cholecystectomy is helpful for the confirmation of suspicious cases.     

Septic pulmonary embolism associated with periodontal disease: reports of two cases and review of the literature

We report two cases of septic pulmonary embolism associated with periodontitis. Chest CT revealed multiple nodular shadows with features characteristic of septic pulmonary embolism in both patients. Both patients had toothache, fever, and chest pain, and showed findings of periodontitis at initial presentation. Antimicrobial agents combined with dental surgery were successful in treatment. While septic pulmonary embolism from the lesions of periodontitis appears to be rare, periodontitis remains important in the differential diagnosis of septic pulmonary embolism.     

Ability of myeloma cells to secrete macrophage inflammatory protein (MIP)-1alpha and MIP-1beta correlates with lytic bone lesions in patients with multiple myeloma

Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta have been identified as candidates for multiple myeloma (MM)-derived bone-resorbing factors. To validate the clinical relevance of these observations, we investigated correlations between the ability of MM cells to secrete these chemokines and the extent of MM bone lesions as well as levels of biochemical bone markers in patients with MM. Patients with multiple bone lesions exhibited higher MIP-1alpha and MIP-1beta secretion from MM cells along with elevated urinary deoxypyridinoline (Dpd), without significant elevation of serum bone-specific alkaline phosphatase (BALP) or osteocalcin compared with those with minimal bone lesions. MIP-1alpha and MIP-1beta levels correlated positively with urinary Dpd and serum BALP but not with serum osteocalcin. These results provide further evidence for a causal role of MIP-1alpha and MIP-1beta in the development of lytic bone lesions, and suggest that MM cells suppress osteoblastic bone formation to cause an imbalance of bone turnover and development of destructive bone lesions.