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Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

Objectives To determine whether high perioperative inspired oxygen fraction (FiO2) compared with low FiO2 has more deleterious postoperative clinical outcomes in patients undergoing non-thoracic surgery under general anesthesia. Design Meta-analysis of randomized controlled trials. Setting Operating room, postoperative recovery room and surgical ward. Patients Surgical patients under general anesthesia. Intervention High perioperative FiO2 (≥0.8) vs. low FiO2 (≤0.5). Measurements The primary outcome was mortality within 30 days. Secondary outcomes were pulmonary outcomes (atelectasis, pneumonia, respiratory failure, postoperative pulmonary complications [PPCs], and postoperative oxygen parameters), intensive care unit (ICU) admissions, and length of hospital stay. A subgroup analysis was performed to explore the treatment effect by body mass index (BMI). Main results Twenty-six trials with a total 4991 patients were studied. The mortality in the high FiO2 group did not differ from that in the low FiO2 group (risk ratio [RR] 0.91, 95% confidence interval [CI] 0.42–1.97, P = 0.810). Nor were there any significant differences between the groups in such outcomes as pneumonia (RR 1.19, 95% CI 0.74–1.92, P = 0.470), respiratory failure (RR 1.29, 95% CI 0.82–2.04, P = 0.270), PPCs (RR 1.05, 95% CI 0.69–1.59, P = 0.830), ICU admission (RR 0.94, 95% CI 0.55–1.60, P = 0.810), and length of hospital stay (mean difference [MD] 0.27 d, 95% CI -0.28–0.81, P = 0.340). The high FiO2 was associated with postoperative atelectasis more often (risk ratio 1.27, 95% CI 1.00–1.62, P = 0.050), and lower postoperative arterial partial oxygen pressure (MD −5.03 mmHg, 95% CI -7.90– -2.16, P 30 kg/m2, these parameters were similarly affected between the groups. Conclusions The use of high FiO2 compared to low FiO2 did not affect the short-term mortality, although it may increase the incidence of atelectasis in adult, non-thoracic patients undergoing surgical procedures. Nor were there any significant differences in other secondary outcomes.

This study assessed the functional role of WNT genes and the association between WNT signalling cascades and fibrosis in interstitial cystitis/bladder pain syndrome (IC/BPS) patients. Twenty-five patients (3 males, 22 females; mean age 59.7 ± 10.9 years), included 7 non-Hunner-type IC (NHIC), 18 Hunner-type IC (HIC), and 5 non-IC (control) groups. The expression of sonic hedgehog, WNT gene family, and genes previously reported as biomarkers for IC/BPS were examined using RT-PCR in biopsy specimens from the mucosa and submucosa layer of the bladder. WNT2B, WNT5A, WNT10A, and WNT11 functions in the urothelium were evaluated by silencing in an HBlEpC cell line. Pelvic Pain and Urgency/Frequency Patient Symptom Scale scores, O’Leary-Sant Symptom and Problem Index scores, and Visual Analogue Scores did not differ between the NHIC and HIC groups. However, HIC patients had significantly shorter symptom duration (30.9 vs 70.8 months, p = 0.046), higher daily urinary frequency (16.1 versus 8.5 times, p = 0.006), and smaller bladder capacity (208.6 versus 361.4 ml, p = 0.006) than NHIC patients. Overall WNT gene expression was lower in NHIC than HIC patients. Bladder epithelial tissues from HIC patients were characterised by the downregulation of WNT11. Silencing of WNT11, WNT2B, WNT5A, and WNT10A in HBlEpCs resulted in fibrotic changes, indicated by fibrotic morphology, increased fibrosis-related gene expression, and nuclear localisation of phosphorylated SMAD2, and increased vimentin and fibronectin levels. Downregulation of WNT11 results in fibrotic changes of bladder epithelial cells and is associated with the pathogenesis and differential diagnosis of NHIC. Decreased expression of WNT11 is a potential biomarker for predicting NHIC.

Background: Metformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival. Methods: To identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated. Results: Six patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis. Conclusion: Renal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment.

Aims To assess the distinct histopathological characteristics and their clinical significance between non-Hunner-type and Hunner-type interstitial cystitis (IC)/bladder pain syndrome (BPS). Methods and results We prospectively enrolled and classified IC/BPS patients, on the basis of cystoscopic findings, as having non-Hunner-type IC and Hunner-type IC. Specimens obtained from the posterior wall in non-Hunner-type IC cases during hydrodistension or from Hunner/non-Hunner lesions in Hunner-type IC cases during transurethral resection were evaluated. Stress urinary incontinence patients with microscopic haematuria were selected as controls. Biopsy specimens were obtained from 15 non-Hunner-type IC, 15 Hunner-type IC and 5 non-IC patients. Severe and moderate fibrosis was more frequently observed in non-Hunner-type IC than in Hunner-type IC and non-IC cases. However, severe and moderate inflammation was more frequently observed in Hunner-type IC than in non-Hunner-type IC cases. The remnant urothelium was significantly decreased in Hunner-type IC cases as compared with non-Hunner-type IC and non-IC cases (P

Aims To evaluate the associations between inflammatory cytokines and adiponectin and various vascular complications in type 2 diabetes mellitus (T2DM). Methods A total of 761 patients with T2DM were divided into a non-obese group and an obese group to enable the effects of obesity and T2DM on vascular complications to be differentiated. The serum levels of circulating inflammatory cytokines, that is, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, total adiponectin, and high molecular weight (HMW) adiponectin were measured, and carotid intima media thickness (IMT), the presence of carotid plaque, and the severities of retinopathy and nephropathy, were assessed. Results The obese group had significantly lower serum total and HMW adiponectin levels than the non-obese group. In the obese group, serum levels of total and HMW adiponectin, and TNF-α were significantly higher in patients with proliferative retinopathy than in those without retinopathy after adjusting for covariates. In the non-obese group, only IL-6 levels were significantly higher in patients with proliferative retinopathy than in those without. Serum levels of total and HMW adiponectin were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria. No significant difference of three cytokines levels were observed depending on the carotid IMT or the presence of plaque. Logistic regression analysis revealed that serum total adiponectin (OR=1.209, P =0.038), diabetes duration (OR=1.230, P =0.014), and HbA1c (OR=2.359, P =0.006) were significantly associated with proliferative retinopathy in the obese group. Conclusion The study shows total adiponectin may influence proliferative retinopathy in obese patient with T2DM.

Phlegmonous esophagogastritis is a rare bacterial infection that has been reported to result in mortality. The pathophysiology of phlegmonous gastrointestinal infection is unclear, but some predisposing factors are reported. Those include immunocompromised status, alcohol abuse, malignancy and uncontrolled diabetes mellitus. We report two cases of phlegmonous esophagogastritis with newly diagnosed diabetes mellitus. A 26-year-old woman and a 56-year-old woman individually visited our hospital for sore throat, neck pain and fever. The laboratory findings of both patients demonstrated leukocytosis, and elevated serum glucose levels. HbA1c of both patients was above 11%. Enhanced computed tomography of young woman showed submucosal edema with intramural abscess along the esophagus and stomach, and that of older woman showed the same defined to esophagus. In both cases, empirical antibiotic therapy with intravenous third generation cephalosporin and metronidazole were started. Later, we identified Klebsiella pneumonia through pus culture in both cases. The symptoms of case 1 improved with conservative management with antibiotics only. However, case 2 required surgical drainage and esophagectomy. Early radiologic diagnosis of this disease and accurate identification of pathogens are important factors for good prognosis. Therefore, we emphasize suspicion of such a rare disease is needed, especially when the patient has risk factors such as diabetes mellitus.

Cytomegalovirus (CMV) infection has been described in immunosuppressed individuals such as patients with AIDS, those receiving chemotherapy, and post-transplantation. CMV can cause severe disease either via reactivation of latent virus or via primary infection. In immunocompetent patients, CMV infection is usually transient and does not exhibit many symptoms. The colon is the site most frequently affected by severe CMV disease in immunocompetent patients. Clinically, CMV colitis commonly presents with diarrhea, fever, and abdominal pain. Although some patients recover spontaneously, others suffer from severe complications, such as bowel perforation, severe gastrointestinal bleeding and, rarely, stricture, and surgery is the choice of treatment in these patients. We report a case of stricture of the proximal transverse colon, presenting as a complication of CMV colitis, in an immunocompetent man with acute respiratory distress syndrome. We performed laparoscopic segmental resection of the proximal transverse colon. (Korean J Med 2013;84:284-289)

Paraganglioma is a tumor originating from the extra-adrenal chromaffin cells, and functional paraganglioma causes paroxysmal hypertension, headache and tachycardia, due to excess excretion of catecholamine. However, rarely, ARDS, acute myocardial infarction, heart failure, arrhythmia, and pulmonary edema are also seen in patients with paraganglioma and clinical manifestations are depending on the patient’s intravascular volume status. Seventy one-years-old male was presented with hypotension and pulmonary edema after intravenous midazolam injection during colonoscopy under conscious sedation. The patient was initially suspected with anaphylactic shock, due to midazolam injection. However, later, he was diagnosed with paraganglioma, and blood pressure was successfully controlled with alpha adrenergic blockade. We suggest that when we encounter heart failure, pulmonary edema and shock of unknown origin, pheochromocytoma must be taken into consideration.

Although local anesthetics can cause adverse drug reactions (ADRs), most ADRs to local anesthetics are from vasovagal, toxic, or anxiety reactions, while immunoglobulin E (IgE)-mediated anaphylaxisis extremely rare. We report a case of IgE-mediated anaphylactic reaction to lidocaine. A 27-year-old male patient who had two episodes of anaphylactic reactions after local injection of lidocaine wasreferred to our clinic for the safe use of local anestheticsfor the subsequent dental procedure. Skin prick and intradermal tests were performed with amide local anesthetics; lidocaine, bupivacaine, mepivacaine, and ropivacaine. Lidocaine and mepivacaine showed positive response in prick test, and lidocaine, mepivacaine, and bupivacaine showed positive reactionsin intradermal test.Only ropivacaine showed negative response both in prick and in intradermal test, and the patient wassuccessfully treated with it. To detectserum-specific IgE, we prepared lidocaine-human serum albumin (HSA) conjugate. Enzyme-linked immunosorbent assay result showed high level of specific IgE to lidocaine-HSA conjugate in serum of the patient. This case suggests that local anesthetics can elicit specific IgE-mediated allergic reactions, and both skin prick and intradermal test should be performed in case of suspected IgE-mediated allergic response to local anesthetics.

Cushing's syndrome is characterized by central obesity, fatigability, weakness, amenorrhea, hirsutism, edema, hypertension, impaired glucose tolerance, and osteoporosis due to excessive production of steroids. Cushing's syndrome is an important cause of secondary osteoporosis. Patients with Cushing's syndrome have a high incidence of osteoporotic fractures. At least, 30-50% of patients with Cushing's syndrome experience fractures, particularly in the vertebral body. And it is consistent with the 50% prevalence of osteoporosis in patients with Cushing's syndrome. However, reports of multiple pathological fractures in young patients with Cushing's syndrome are rare. Thus, we describe the case of a 26-year-old woman with Cushing's syndrome accompanied with recurrent multiple osteoporotic fractures and being treated by parathyroid hormone. Careful consideration for the possibility of Cushing's syndrome will be necessary in case of young patients with a spontaneous multiple compression fractures in spine.

Day-to-day insulin requirements often change due to subtle variations in insulin metabolism in patients with type 2 diabetes undergoing hemodialysis. In such cases, intra-hemodialysis hypoglycemia frequently occurs and is a main factor interfering with the delivery of dialysis. As a result, it reduces the quality of life in patients undergoing hemodialysis. The long-acting insulin analogue glargine provides peakless, continuous release over 24 h that approximates a normal basal insulin pattern. Because it has no peak, its use in patients with diabetes undergoing hemodialysis would hypothetically be useful. Specifically, patients would be able to avoid intra-hemodialysis hypoglycemia without the necessity of skipping insulin administration on the day of hemodialysis and achieving adequate glucose control on other days. We recently experienced six cases that switched from treatment with intermediate-acting insulin to a long-acting insulin analogue, which provided better glycemic control by reducing hypoglycemia risk. Limited data are available in the literature concerning insulin analogue usage in patients with diabetes undergoing hemodialysis. Our experience suggests a large-scale prospective investigation is required on this issue. (Korean J Med 2012; 83:647-653)

We report a case of acute kidney injury following extracorporeal shock wave lithotripsy. A 41-year-old man with diabetes mellitus had suffered from urinary difficulty after several treatments of ESWL, bilaterally. It was suspected that fragments of renal stones had caused an obstructive nephropathy with bilateral hydronephrosis. Fortunately, even without renal replacement therapy, renal function gradually returned. (Korean J Med 2012;82:628-631)