Behçet's disease-induced massive small intestinal bleeding successfully treated with adalimumab.

We herein report a case of Behçet's disease in a 27-year-old female who suffered from generalized skin rashes for one week. After hospitalization, massive bloody stools accompanying hypovolemic shock occurred. Emergency abdominal computed tomography-angiography failed to detect the bleeding source. Esophagogastroduodenoscopy also demonstrated no definite bleeding points. Ileocolonoscopy showed multiple large and deep ulcers with some blood coating and mild oozing in the terminal ileum. We initially performed epinephrine injection and hemoclips for her intestinal bleeding. However, massive bloody stools still continued. Thus, we prescribed a loading dose of 160 mg adalimumab followed by weekly 80 mg adalimumab subcutaneous injections to the patient. Following this treatment, her gastrointestinal bleeding gradually subsided and completely stopped within a few days. After three-week therapy with adalimumab, capsule endoscopy showed several healing ulcers without bleeding in the distal to the terminal ileum. She continues to be treated with adalimumab, azathioprine, and mesalazine without recurrent bleeding.

A modified compression model of spinal cord injury in rats: functional assessment and the expression of nitric oxide synthases.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate a modified compression model of spinal cord injury (SCI) in adult rats by using a room-air- inflated Fogarty balloon catheter. SETTING: Kaohsiung, Taiwan. METHODS: The rats were divided into injury, sham-operated and control groups. A 2-French Fogarty catheter was passed from the lumbar spine (L3-L4) epidurally, with a mini-laminectomy under the microscope, to the level of thoracic spine (T6-T7). The actual site of the catheter tip was confirmed with X-ray. The balloon of Fogarty catheter then was inflated with room air, 0.2 ml, for 10 min. Mini-laminectomy was performed without inserting the catheter in the sham-operated group. Quantitative neurological outcomes were evaluated with the Basso, Beattie and Bresnahan (BBB) locomotor rating scale daily. The gene expression of nitric oxide synthases (NOSs) of the spinal cord was investigated at the end of the functional assessment. RESULTS: The mean BBB locomotor scores were 10±1.85 and 10±1.85, respectively, on days 1 and 3 in the injury group, and 21 and 20.29±0.69, respectively, in the sham-operated group. There was a significantly increased gene expression of inducible NOS in the SCI group compared with the sham-operated group and control group. Endothelial NOS gene expression was not significantly different among the groups. CONCLUSION: The functional and molecular assessments show that this modified balloon-compression technique is a reproducible, simple and inexpensive model of SCI in rats.

RNA is favourable for analysing EGFR mutations in malignant pleural effusion of lung cancer.

Malignant pleural effusion (MPE) is a useful specimen allowing for the evaluation of EGFR status in nonsmall cell lung cancer (NSCLC). However, direct sequencing of genomic DNA from MPE samples was found not to be sensitive for EGFR mutation detection. To test whether EGFR analysis from RNA is less prone to interference from nontumour cells that have no or lower EGFR expression, we compared three methods (sequencing from cell-derived RNA versus sequencing and mass-spectrometric analysis from genomic DNA), in parallel, for EGFR mutation detection from MPE samples in 150 lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors (TKIs). Among these MPE samples, EGFR mutations were much more frequently identified by sequencing using RNA than by sequencing and mass-spectrometric analysis from genomic DNA (for all mutations, 67.3 versus 44.7 and 46.7%; for L858R or exon 19 deletions, 61.3 versus 41.3 and 46.7%, respectively). The better mutation detection yield of sequencing from RNA was coupled with the superior prediction of clinical efficacy of first-line TKIs. In patients with acquired resistance, EGFR sequencing from RNA provided satisfactory detection of T790M (54.2%). These results demonstrated that EGFR sequencing using RNA as template greatly improves sensitivity for EGFR mutation detection from samples of MPE, highlighting RNA as the favourable source for analysing EGFR mutations from heterogeneous MPE specimens in NSCLC.

Catechin stimulates osteogenesis by enhancing PP2A activity in human mesenchymal stem cells.

SUMMARY: Using human mesenchymal stem cells, we identified catechin from a panel of herbal ingredients and Chinese traditional compounds with the strongest osteogenic effects. Catechin increased alkaline phosphatase activity, calcium deposition, and mRNA expression of Runx2 and osteocalcin. We further clarified the signaling pathway that catechin mediated to stimulate osteogenesis. INTRODUCTION: Human mesenchymal stem cells (hMSCs), useful as a species specific cell culture system for studying cell lineage differentiation, were examined as a tool to identify novel herbal ingredients and Chinese traditional compounds for enhancing osteogenesis. METHODS: Immortalized and primary hMSCs were induced in osteogenic induction medium in the presence of a variety of herbal ingredients and Chinese traditional compounds and osteogenic differentiation was evaluated by histochemical assays and quantitative RT-PCR. RESULTS: Using immortalized hMSCs, we first identified catechin, 18ß-glycyrrhetinic acid, baishao, and danggui with osteogenic properties, which enhanced calcium deposition at the dose without significant cytotoxic effects. Primary hMSCs were then applied for confirming the osteogenic effects of catechin, which increased alkaline phosphatase activity, calcium deposition, and mRNA expression of Runx2 and osteocalcin. We further found the extracellular signal-regulated kinase (ERK) pathway was downregulated upon stimulation with catechin. Catechin increased the level and activity of protein phosphatases 2A (PP2A) that dephosphorylates ERK kinase (MEK) and ERK. Further, PP2A inhibitor, okadaic acid, abolished the effect of catechin-mediated inactivation of ERK and stimulation of osteogenesis. The blocking effect of okadaic acid on osteogenesis was further reversed by PD98059, a specific inhibitor of MEK. Co-immunoprecipitation revealed the association of PP2A to both MEK and ERK. CONCLUSIONS: These studies propose catechin enhanced osteogenesis by increasing the PP2A level that inhibits the MEK and ERK signaling in hMSCs. These results prove the concept of using hMSCs as a convenient tool for rapid and consistent screening of the osteogenic herbal ingredients and traditional Chinese compounds.

Left atrial enlargement induced by pure mitral regurgitation: time frame in a new swine model.

BACKGROUND: Atrial enlargement occurs in patients with significant mitral regurgitation. However, the time frame of the development of atrial enlargement induced by mitral regurgitation remains unknown. METHODS: Fourteen Lanyu miniature pigs (age = 6.6 ± 0.9 months) were studied. Mitral regurgitation was created by placing a predefined hole on the middle scallop of the posterior mitral leaflet under cardiopulmonary bypass. The parasternal long-axis atrial dimension was measured by transthoracic echocardiographic examinations. RESULTS: All animals exhibited grade 3 mitral regurgitation immediately after surgery. Seven pigs expired within 2 weeks after the operation [technical complications (n = 1), acute cardiac tamponade (n = 1), and acute and subacute heart failure (n = 5)]. Seven pigs remained alive at a mean follow-up of 7.7 ± 2.1 months. The left atrial diameter indices of the 7 pigs increased significantly at 1 month (33.1 ± 8.6 mm, p = 0.018) and 3 months (41.3 ± 12.6 mm, p = 0.018) after surgery compared with baseline values (22.8 ± 5.2 mm), and the left atrial diameter index increased significantly at 3 months compared to 1 month (p = 0.018). CONCLUSIONS: Left atrial enlargement develops rapidly and progresses after the creation of significant pure mitral regurgitation.

Clinical outcomes of patients undergoing a cardiac implantable electronic device implantation following a recent non-device-related infection.

BACKGROUND: Clinical outcomes of patients undergoing a cardiac implantable electronic device (CIED) implantation following a recent non-device related infection are unknown. AIM: To evaluate the clinical outcomes of patients with recent infection before CIED implantation. METHODS: Consecutive patients (N = 1237) were classified as patients with recent infection (N = 72) and without recent infection (N = 1165). A recent infection was established by reviewing medical records, including symptoms and clinical manifestations, diagnosis of systemic inflammatory response syndrome, and quick Sequential Organ Failure Assessment (qSOFA) score. Multiple stepwise logistic regression analysis was used to identify independent predictors of in-hospital all-cause mortality. FINDINGS: During nearly three years of follow-up, 17 patients had CIED infection (1.4%), and the incidence of CIED infection did not significantly differ between patients with and without recent infection according to symptoms and clinical manifestations (2.8% vs 1.3%, respectively; not significant). However, patients with recent infection had a significantly higher in-hospital mortality rate compared to those without recent infection (22.2% vs 0.9%, respectively; P < 0.05). In multivariate analysis, predictors of in-hospital mortality were recent infection before CIED implantation (odds ratio: 20.3; 95% confidence interval: 8.4-49.3; P < 0.001) and end-stage renal disease (4.3; 1.4-12.8; P = 0.009). CONCLUSION: A CIED implantation is feasible in patients with recent infection if the patient is afebrile and has received an adequate duration of antibiotic therapy. Participants in shared decision-making before implant should be advised that recent infection increases in-hospital mortality risk, especially in patients with a qSOFA score of ≥2.

Circadian rhythm in uptake of tritiated thymidine by kidney, parotid, and duodenum of isoproterenol-treated mice.

The total uptake of [(3)H]thymidine by the mouse parotid gland, kidney, and duodenum exhibits a circadian rhythm. A single injection of isoproterenol changes the phasing and amplitude of these rhythms. Depending on the organ, there are certain points in the circadian time structure when isoproterenol stimulates or inhibits the uptake of thymidine; at other time points there is no difference between the responses to isoproterenol and to saline.

Three-dimensional optical coherence tomography of Barrett's esophagus and buried glands beneath neosquamous epithelium following radiofrequency ablation.

We report three-dimensional (3D) endoscopic microscopy findings in Barrett's esophagus, using an endoscopic optical coherence tomography (OCT) system in one patient before and in one patient after radiofrequency ablation (RFA). Findings were compared with those in a normal patient without Barrett's esophagus. In the normal patient,findings were of regular flat squamous mucosa with small subepithelial vessels and glands. In the Barrett's esophagus patient, findings were of large, densely packed glands with distortion of mucosal architecture. In the post-RFA case, findings were of a small number of isolated glands buried beneath 300-500 microm of neosquamous epithelium and lamina propria. Neosquamous epithelium is a marker of successful ablative therapy, while buried glands may have potential for dysplastic progression and are difficult to detect using conventional methods. These results indicate a potential role of 3D-OCT endoscopic microscopy for follow-up, including subsurface assessment, of ablative treatments for Barrett's esophagus.

Holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures: a single-centre experience.

PURPOSE: This study aimed to report the results of endoureterotomy for benign ureteral strictures using the holmium: yttrium-aluminum-garnet laser. MATERIAL AND METHODS: Nineteen patients (8 men and 11 women, mean age 51.47 years) underwent holmium: yttrium-aluminum-garnet laser endoureterotomy for benign ureteral strictures (8 proximal, 3 middle, and 8 distal) using semi-rigid ureteroscopy and 360-microm fibre at 1.2 J/pulse and 10 Hz. After completion of the incision, a 7-Fr double-J ureteral stent was left for 6 weeks. Thereafter, the patients were followed-up by ultrasound and/or intravenous urography at 3-6 monthly intervals. RESULTS: Success was defined as the absence of symptoms plus radiographic resolution of obstructions as assessed by diuretic renography and/or intravenous urography. With a mean follow-up of 40.2 months, success was achieved in 10 (52.6%) of the 19 patients. Nine patients developed recurrent strictures and were considered treatment failures. The stricture length and severity of hydronephrosis correlated with successful outcome, but gender, aetiology, side and location of strictures did not predict outcome. CONCLUSIONS: Although endoureterotomy using a holmium : yttrium-aluminum-garnet laser has an equivocal outcome, the procedure is recommended as a safe, less invasive therapeutic option for the initial management of benign ureteral strictures.

Bundled skin antiseptic preparation for complex cardiac implantable electronic device infection: a propensity-score matching cohort study.

BACKGROUND: Cardiac implantable electronic device (CIED) infection, a major complication of a CIED implant procedure, can prolong hospitalization and cause mortality. AIM: To evaluate the efficacy of a bundled skin antiseptic preparation for preventing infection after implantation of a complex CIED. METHODS: This study analysed 1163 consecutive patients who had received a bundled skin antiseptic preparation before CIED implantation from July 2012 to December 2017. According to the complexity of the CIED implant procedure, the patients were divided into a complex CIED group (N = 370) and a non-complex CIED group (N = 793). A complex procedure was defined as a pacemaker replacement, implantation of implantable cardioverter defibrillator and cardiac resynchronization therapy, device upgrade, or lead revision. FINDINGS: During a mean follow-up of 2.9 ± 1.7 years, CIED infection developed in 15 patients (1.3%), and the incidence of minor and major infection was 1.1% and 0.2%, respectively. The incidence of CIED infection did not significantly differ between the complex CIED group and the non-complex CIED group (1.1% vs 1.4%, respectively; non-significant). Multivariate analysis indicated that procedural complexity was not an independent predictor of CIED infection. After 2:1 propensity score matching, the matched non-complex CIED group and the matched complex CIED group still showed no significant difference in the incidence of CIED infection. CONCLUSION: Bundled skin antiseptic preparation is an effective and widely applicable strategy for decreasing infection risk after a complex CIED implantation.

Isolation and characterization of mesenchymal stromal cells from human anterior cruciate ligament.

BACKGROUND: The anterior cruciate ligament (ACL) is one of the most commonly injured ligaments of the knee. Because the torn ACL is always discarded during ACL reconstruction, it may be a potential source for isolating mesenchymal stromal cells (MSC). METHODS: To characterize MSC from human ACL, cells were enzymatically released from the ACL of adult human donors and seeded in plastic dishes with serial passages at confluence. At different passages, ACL-derived cells were subjected to in vitro assays to investigate their multilineage potential. Upon treatment, the phenotypes of the cell cultures were analyzed by histo- and immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction for the expression of lineage-specific genes. RESULTS: Six independent cell lines from individual donors showed diversity in multilineage potential. Interestingly, five of the six lines displayed adipogenic potential, four had osteogenic and adipogenic potential, and only one cell line was tripotent. Both bone marrow (BM)- and ACL-derived MSC expressed marker genes for ligament fibroblasts, whereas the mRNA levels of collagen I and III were more abundant in ACL-derived MSC. DISCUSSION: Our study demonstrates that human MSC can be isolated from ACL with diversity in the potential to form bone, fat and cartilage and an increase as compared to BM MSC, in the potential to form ligament fibroblasts.

A randomized controlled trial of the efficacy and safety of a fixed triple combination (fluocinolone acetonide 0.01%, hydroquinone 4%, tretinoin 0.05%) compared with hydroquinone 4% cream in Asian patients with moderate to severe melasma.

BACKGROUND: Melasma is an acquired, chronic hypermelanosis for which therapy remains a challenge. OBJECTIVES: To compare the efficacy and safety of a triple combination [TC: fluocinolone acetonide 0.01%, hydroquinone (HQ) 4%, tretinoin 0.05%] vs. HQ 4% after 8 weeks of treatment of moderate to severe facial melasma in Asian patients. METHODS: This was a multicentre, randomized, controlled, investigator-blinded, parallel comparison study. East and South-East Asian patients aged 18 years or older, with a clinical diagnosis of moderate to severe melasma, were enrolled in this study. Patients were enrolled at baseline and treated daily for 8 weeks with TC cream (one application at bedtime) or HQ cream (twice daily). There were four study visits: at baseline and weeks 2, 4 and 8. The primary efficacy variable was the melasma global severity score (GSS). Other outcome measures included Melasma Area and Severity Index, global improvement and patient satisfaction. Safety was assessed through the reporting of adverse events. RESULTS: TC had superior efficacy to HQ for the primary variable: 77/120 patients (64.2%) on TC had GSS 'none' or 'mild' at week 8 vs. 48/122 patients (39.4%) on HQ (P < 0.001). The secondary efficacy variables confirmed these results. Patient satisfaction was in favour of TC (90/127, 70.8%, vs. 64/129, 49.6%; P = 0.005). More patients had related adverse events on TC (63/129, 48.8%) than on HQ (18/131, 13.7%) but most were mild and none was severe. CONCLUSIONS: Efficacy in Asians and patient satisfaction were superior with the fixed TC than with HQ 4%.

Treatment of adjacent vertebral fractures following multiple-level spinal fusion.

BACKGROUND: Posterolateral fusion with cages and posterior instrumentation is an accepted method in the treatment of lumbar instability associated with spinal stenosis or scoliotic deformity, but with modest results. We propose hereby an alternative, simple method to treat kyphosis due to the vertebral fracture which has brought about comparable outcomes. METHODS: Three patients with documented adjacent segment compression fractures were treated. Vertebroplasty was performed with polymethylmethacrylate (PMMA), either using the transpedicular route at the adjacent level or via the route of the previous transpedicular screw at the top level of the long-segment fixation construct. Outcomes were measured by the visual analogue scale of pain and the kyphotic angle of the adjacent segment. RESULTS: The maximal kyphotic angle was 30.6 degrees preoperatively and the reduction rate averaged 69.6%. The pain scale improved from the mean of 9.3 to 1.7. No further progression of compression was noted in the follow-up of more than 6 months after the vertebroplasty in these cases. CONCLUSION: Vertebroplasty at either the adjacent level or the top level of the previous internal fixation construct may be a feasible alternative to treat the adjacent level fracture after long segment internal fixation of the spine.

Circadian peak dopaminergic activity response at the biological clock pacemaker (suprachiasmatic nucleus) area mediates the metabolic responsiveness to a high-fat diet.

Among vertebrate species of the major vertebrate classes in the wild, a seasonal rhythm of whole body fuel metabolism, oscillating from a lean to obese condition, is a common biological phenomenon. This annual cycle is driven in part by annual changes in the circadian dopaminergic signalling at the suprachiasmatic nuclei (SCN), with diminution of circadian peak dopaminergic activity at the SCN facilitating development of the seasonal obese insulin-resistant condition. The present study investigated whether such an ancient circadian dopamine-SCN activity system for expression of the seasonal obese, insulin-resistant phenotype may be operative in animals made obese amd insulin resistant by high-fat feeding and, if so, whether reinstatement of the circadian dopaminergic peak at the SCN would be sufficient to reverse the adverse metabolic impact of the high-fat diet without any alteration of caloric intake. First, we identified the supramammillary nucleus as a novel site providing the majority of dopaminergic neuronal input to the SCN. We further identified dopamine D2 receptors within the peri-SCN region as being functional in mediating SCN responsiveness to local dopamine. In lean, insulin-sensitive rats, the peak in the circadian rhythm of dopamine release at the peri-SCN coincided with the daily peak in SCN electrophysiological responsiveness to local dopamine administration. However, in rats made obese and insulin resistant by high-fat diet (HFD) feeding, these coincident circadian peak activities were both markedly attenuated or abolished. Reinstatement of the circadian peak in dopamine level at the peri-SCN by its appropriate circadian-timed daily microinjection to this area (but not outside this circadian time-interval) abrogated the obese, insulin-resistant condition without altering the consumption of the HFD. These findings suggest that the circadian peak of dopaminergic activity at the peri-SCN/SCN is a key modulator of metabolism and the responsiveness to adverse metabolic consequences of HFD consumption.

"Full house" proliferative glomerulonephritis: an unreported presentation of subacute infective endocarditis.

A severely ill 65-year-old man presented with symptoms of shortness of breath, edema and vasculitidic purpura over his lower extremities. He had severe mitral regurgitation which had not been surgically treated. Hematologic examination demonstrated leukocytosis with profound anemia. Other blood tests revealed impaired renal function, hypoalbuminemia, hypocomplementemia and mixed-type cryoglobulinemia. Urinalysis showed proteinuria, hematuria and pyuria, typical of a nephritic sediment. Renal biopsy indicated diffuse proliferative glomerulonephritis and a "full house" deposition in immunofluorescence study (positive for C3, C4, C1q, IgG, IgA and IgM), resembling the pathologic findings in class IV lupus nephritis. Although subacute bacterial endocarditis was initially suspected owing to a history of a predisposing valvular heart disease, probable vegetation shown by cardiac sonography and a clinical picture suggestive of a chronic infection, it was thought unlikely due to the entire afebrile course and initial sterile blood cultures. However, the blood cultures repeated 2 weeks after admission grew 3 sets of viridans streptococci. Following a course of penicillin and gentamicin treatment, his renal function, anemia and abnormal urine sediments improved gradually. Diffuse proliferative glomerulonephritis is well known to occur in infective endocarditis. However, the "full house" immunostaining in immunofluorescence study has never been reported. This case adds a new entity to the differential diagnosis of "full house" immune complex-related glomerulonephritis and exemplifies the need to maintain a high index of suspicion for underlying infectious disorders when facing glomerulonephritic or vasculitic syndrome.

Hepatic cerebrospinal fluid pseudocyst: a case report and review of the literature.

An abdominal pseudocyst is a rare, but important complication in patients with a ventriculo-peritoneal (VP) shunt insertion. Several predisposing factors for this complication have been suggested, including infection, obstruction or dislodgement, but the pathophysiology is still unknown. However, the abdominal inflammatory process is accepted widely as a hypothesis for the formation of an abdominal pseudocyst. In this study, we report the case of a 21-year-old male that presented with a high-grade fever, poor appetite, shortness of breath and unconsciousness 1 week after receiving a VP shunt insertion for obstructive hydrocephalus. Ultrasonography and computed tomographic scans of the abdomen revealed a well-defined large hepatic cyst surrounding the peritoneal tube of the VP shunt. A hepatic cerebrospinal fluid (CSF) cyst was diagnosed and Staphylococcus epidermis was cultured via CSF. After externalization of the VP shunt and adequate antibiotic treatment, the hepatic cyst was resolved. There was no recurrence observed in the regular follow up.

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the duodenum, jejunum, ileum, caecum, colon, and rectum of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular salivary glands of mice was injected ip at five different circadian phases into separate sub-groups of adult male CD2F1 mice that had been standardized to 12 h of light alternating with 12 h of darkness. Comparable control groups were injected only with the carrier substance. Four, 8, and 12 h after each of the five injection times, subgroups of five mice were killed. Thirty minutes before sacrifice, each mouse was injected ip with 24 mu Ci tritiated thymidine ([3H]-TdR). Incorporation of [3H]TdR into the DNA of the duodenum, jejunum, ileum, cecum, colon, and rectum was determined. The results demonstrate for the first time that EGF has a stimulatory effect on DNA synthesis in these tissues, particularly in the colon and rectum. Under the conditions of this study, the stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were more dramatic than those in the three regions of the small intestine; in fact, DNA synthesis in the latter was occasionally statistically significantly decreased, particularly for mice killed during the dark phase. Stimulatory effects of EGF on DNA synthesis in the cecum, colon, and rectum were noticed as early as 4 h after injection; however, maximal stimulation occurred 8 and 12 h post injection.

Circadian phase-dependent stimulatory effects of epidermal growth factor on deoxyribonucleic acid synthesis in the tongue, esophagus, and stomach of the adult male mouse.

Epidermal growth factor (EGF) previously isolated from the submandibular gland of mice was injected ip at different circadian phases into separate subgroups of adult male CD2F1 mice. Subsequent to each of the five time points of injection (0900, 1500, 1800, 2100, and 0300 h for animals standardized to 12 h of light alternating with 12 h of darkness), five animals were killed, 4, 8, and 12 h after the injection of EGF; comparable control groups were injected only with the carrier substance. Thirty minutes before sacrifice, each mouse was injected ip with 24 muCi [3H]thymidine. Incorporation of [3H]-thymidine into the DNA of the tongue, esophagus, and stomach was determined. The results demonstrate for the first time that EGF has a strong in vivo stimulatory effect on DNA synthesis in the tongue, esophagus, and stomach (studies on other areas of the gut have not yet been completed). Under the conditions of the study, stimulatory effects occurred as soon as 4 h subsequent to injection; however, maximal stimulation occurred for all three tissues 8 h after injection. Twelve hours after injection, the levels of DNA synthesis in all tissues were generally returning to normal levels found in the control animals. The results suggest circadian variation in susceptibility to EGF in the different tissues.