Search

Chronic enteropathy associated with the solute carrier organic anion transporter family member 2A1 (SLCO2A1), or CEAS, causes anemia and hypoalbuminemia in young people. Dysfunction of the SLCO2A1 transporter protein is thought to involve genetic mutation, but mutant proteins have not been functionally characterized. We examined the prostaglandin EWild-type and mutant SLCO2A1 proteins were forcibly expressed in Xenopus laevis oocytes, and measurements of PGEThe extent of functional disruption of the 11 SLCO2A1 mutations identified in CEAS patients was variable, with 10 mutations (421GT, 547GA, 664GA, 770GA, 830dupT, 830delT, 940 + 1GA, 1372GT, 1647GT, and 1807CT) resulting in loss or reduction of PGEPGE

Background and Aim Vedolizumab is a humanized monoclonal antibody that selectively inhibits the migration of gut‐homing memory T cells into the intestinal submucosa by antagonizing the interaction of α4β7 integrin with MAdCAM‐1. Vedolizumab is employed for ulcerative colitis with moderate to severe activity; however, predictors of its clinical efficacy have not been established in real‐world clinical practice. We investigated the clinical characteristics predicting vedolizumab efficacy. Methods This was a single‐center, retrospective, observational study that enrolled patients with ulcerative colitis at Kyorin University Hospital. Fifty‐two consecutive patients who started vedolizumab induction therapy and were tracked for minimum 14 weeks between August 2018 and February 2021 were included. Clinical and endoscopic disease activities were scored at baseline and at weeks 2, 6, and 14 with the Lichtiger index and at baseline and week 24 with the Mayo endoscopic subscore, respectively. Clinical remission, clinical response, and endoscopic remission were defined as Lichtiger index of ≤3, Lichtiger index of ≤10 with a reduction of minimum 3 points from baseline, and Mayo endoscopic subscore of ≤1, respectively. Results In these cases, clinical response/remission rates at weeks 2, 6, and 14 were 26.9%/15.3%, 50.0%/46.3%, and 57.6%/50.0%, respectively. The endoscopic remission rate at week 24 was 60%. The clinical response at week 6 was significantly associated with endoscopic remission at week 24 after starting vedolizumab. Conclusions In vedolizumab treatment for ulcerative colitis, the clinical response at week 6 can be a predictor for endoscopic remission at week 24., Clinical response of vedolizumab at week 6 predicted endoscopic remission at week 24 in ulcerative colitis with moderate to severe activity.

Background Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. Methods Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. Results A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. Conclusions For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.

A 40-year-old woman (case 1) visited the hospital complaining of diarrhea and was diagnosed with ulcerative colitis (UC). She was administered 5-aminosalicylic acid (5-ASA), but developed intolerance. Prednisolone (PSL) was administered, and her symptoms improved. However, alopecia areata developed as the PSL was tapered, and her UC relapsed. Adalimumab, Infliximab (IFX), and golimumab were used, but all showed insufficient efficacy. Therefore, we started tofacitinib (TOF). Her bloody stools and diarrhea improved 3 days after TOF administration, and clinical remission occurred on day 14. Her alopecia areata improved 14 days after starting TOF and improved completely during TOF maintenance therapy. A 19-year-old man (case 2) had developed alopecia areata at 10 years old and was diagnosed with UC at 17 years old. He achieved sustained remission with IFX, but then stopped IFX to receive a live vaccination. His UC relapsed 4 months later, immediately after the live vaccine was administered. Vedolizumab was administered, but was ineffective, as was re-administration of IFX. TOF was administered, and his clinical symptoms improved 7 days later. He achieved clinical remission on day 20. In addition, his hair began to regrow 14 days after starting TOF.

Background and aims Small intestinal lesions in patients with Behcet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. Methods This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. Results Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 μg/g) and FL (cutoff value = 17 μg/g) were biomarkers for small intestinal lesions in patients with BD. Conclusion The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Background and Aims: Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations. Methods: MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed. Results: The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26–76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine. Conclusions: Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.

Background/aims Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. Methods UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. Results A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). Conclusions CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.

BACKGROUND There are no reports to prove the repeatability of gastric transit time (GTT) and small bowel transit time (SBTT) in capsule endoscopy (CE). OBJECTIVE To clarify the repeatability and factors that affect GTT/SBTT in CE. METHODS We analyzed the data of 150 healthy subjects from our previous randomized controlled trial that compared small intestinal injuries between two 14-day treatment groups: 1) celecoxib and 2) loxoprofen + lansoprazole. Correlation of GTT/SBTT with pre- and post-treatment CE was analyzed. In addition, the associations of pre-treatment CE SBTT with physical factors, post-treatment CE SBTT and the presence of small intestinal mucosal injuries were analyzed. RESULTS Analyses of 148 subjects pre-treatment CE and 146 subjects post-treatment CE were performed. There were no significant differences between mean GTT and SBTT before and after treatment. Both GTT (𝜌 = 0.22, p < 0.01) and SBTT (𝜌 = 0.47, p < 0.0001) showed positive correlations between pre- and post-treatment CE. In pre-treatment CE, physical factors and the presence of small intestinal mucosal injury had no associations with SBTT. CONCLUSIONS Moderate correlation in SBTT and slight correlation in GTT were shown on repeated CE. The factors affecting SBTT were not clarified in this analysis.

Background There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. Aim To identify the SNP that is most significantly involved with NSAID-induced enteropathy. Methods One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. Results After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10−7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p

We report the case of a 33-year-old Caucasian American man diagnosed with celiac disease in Japan. He presented to a community hospital because of chronic watery diarrhea and weight loss for 6 months. The laboratory data showed low serum albumin and serum cholesterol. A colonoscopy was normal. He was referred to our hospital for further work-up. Serum tissue transglutaminase immunoglobulin A (IgA) and endomysial antibody were positive. The HLA type was DQ2. Esophagogastroduodenoscopy (EGD) revealed nodular and mosaic-patterned mucosa from the bulb to the second part of the duodenum. The histopathological findings were consistent with Marsh type 3c of the modified Marsh classification for celiac disease. The patient was instructed to follow a gluten-free diet (GFD). Six months after the initiation of the GFD, his symptom and the levels of serum albumin and cholesterol were improved, and the serum tissue transglutaminase IgA and endomysial antibody became negative. However, EGD showed little improvement. Capsule endoscopy also revealed mosaic-patterned mucosa, nodular mucosa, and scalloping of the folds of the duodenum and proximal small intestine. There was no definite improvement in histopathological findings. Collectively, the GFD was effective in this patient with celiac disease, but it should be maintained to achieve endoscopic and histopathologic healing.

Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations.MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed.The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26-76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine.Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.

The aim of this study was to compare celecoxib with loxoprofen for protection of small intestine.RCT studies report that COX-2 selective inhibitor celecoxib induces fewer small intestinal injuries than nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Loxoprofen is a prodrug nonselective NSAID developed to protect upper gastrointestinal tract.A total of 150 healthy volunteers (40 to 70 y) were enrolled. After medical checkup including laboratory data, subjects were randomly assigned to celecoxib (200 mg daily) or loxoprofen (180 mg daily) plus lansoprazole (15 mg daily). All drugs were prepared using inactive capsules. After randomization, all subjects were first examined by baseline capsule endoscopy (CE). After 14 days, subjects underwent posttreatment CE. We compared baseline and posttreatment CE findings of the 2 groups. All CE data were evaluated blindly by 3 reviewers. Pretreatment and posttreatment laboratory variables were also compared.A total of 74 subjects (49±6 y, F/M: 36/38) were enrolled in celecoxib group and 76 subjects (49±7 y, F/M: 39/37)in loxoprofen group. Five in celecoxib group and 4 in loxoprofen group were excluded from CE analysis mainly due to incomplete CE. The percentage of subjects with at least 1 posttreatment mucosal break was lower in celecoxib group (10%) than in loxoprofen group (49%) (P0.0001). A total of 0.3±1.0 posttreatment small intestinal mucosal breaks were detected in the celecoxib group, and 6.8±21.5 in the loxoprofen group (P0.0001). Posttreatment hemoglobin concentration in loxoprofen group (5.1% reduction) was lower compared with celecoxib group (2.1% reduction) (P=0.006).In terms of protection of small intestine from NSAIDs toxicity, celecoxib monotherapy was superior to loxoprofen+lansoprazole combination therapy (UMIN: 000007936).

We report a case of community-acquired fulminant colitis caused by Clostridium difficile in Japan. A 46-year-old woman was diagnosed with severe infectious enterocolitis and was admitted at another hospital. The stool culture was positive for toxigenic C. difficile. Since the patient presented with fulminant C. difficile infection (CDI) with toxic megacolon, respiratory insufficiency, and circulatory failure, she was transferred to Kyorin University Hospital for intensive care. Intubation and antibiotic therapy were performed. The general condition improved with conservative treatment, and she was discharged without sequelae. While the recovered isolate was toxin A and B-positive and binary toxin-positive, it was identified as polymerase chain reaction (PCR) ribotype ts0592 and slpA sequence type ts0592. The isolate was different from PCR ribotype 027 epidemic in Europe and North America. In Japan, binary toxin-producing strains are rare and have not caused an epidemic to date. Furthermore, there are few data on community-acquired CDI in Japan. In this case, a non-elderly woman with no major risk factors such as antibiotic use, administration of proton pump inhibitor and history of gastrointestinal surgery developed community-acquired fulminant CDI caused by the binary toxin-positive strain, and ICU treatment was required. Further studies focusing on the role of binary toxin-positive C. difficile in the severity of community-acquired CDI are necessary.

Immunomodulator (thiopurines) and calcineurin inhibitors (cyclosporine, tacrolimus) have been used in IBD treatment. Thiopurines such as azathioprine and 6-mercaptopur- ine are used in steroid refractory and steroid dependent UC patients. They are also concomitant used both in CD and UC with other drugs including anti-TNFa monoclonal Ab mainly as maintenance therapy. Calcineurin inhibitors, cyclosporine and tacrolimus, are used in moderate to severe refractory UC patients. Adverse effects of thiopruine include bone marrow suppression, liver dysfunction, hair loss, and infectious disease. Recently, it was reported that the risk of acute onset leukopenia in thioprine use is associated with NUDT 15 gene variant, especially in Asian population. Renal dysfunction and infectious disease (e. g. pneumocystis) should be concerned in the patientg treated with calcineurin inhibitors.

We herein report a case of simultaneous amebic colitis and cytomegalovirus (CMV) enteritis in an HIV-infected patient. The patient was a 40-year-old man who developed bloody stool and diarrhea. We diagnosed him with severe amebic colitis associated with HIV infection and administered metronidazole. While his symptoms began to improve, the patient then developed CMV enteritis. We administered ganciclovir, and his symptoms improved. However, despite control of the infection, stenosis of the descending colon caused intestinal obstruction, and colostomy was performed. This case shows the importance of considering the possibility of simultaneous infection when gastrointestinal symptoms appear in people infected with HIV.

Background The usefulness of second-generation colon capsule endoscopy (CCE-2) for ulcerative colitis (UC) has not been fully demonstrated. This study aimed to develop an endoscopic severity score of UC for CCE-2. Methods Patients diagnosed with UC were enrolled prospectively and underwent colonoscopy and CCE-2 on the same day. The collected CCE-2 videos were adopted for the development of the score. These videos were scored by 4 blinded inflammatory bowel disease experts. The items validated with the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were used as the candidate items, some of which were automatically assessed using the workstation. Each item was divided into proximal and distal parts at the splenic flexure and then individually assessed. The image readers simultaneously evaluated the inflammation severity using the visual analog scale (VAS). The descriptors that contribute to this scale were evaluated, and a model to predict the VAS was constructed. The UCEIS was scored by other endoscopists using colonoscopy videos. The correlation coefficients with fecal calprotectin, blood tests, and Lichtiger index were calculated. Results The final scoring system was fixed as "vascular pattern sum (proximal + distal) + bleeding sum + erosions and ulcers sum (minimum-maximum, 0-14)" and was named Capsule Scoring of Ulcerative Colitis (CSUC). The correlation coefficient of CSUC with biomarkers and clinical score was similar to that of the UCEIS. Conclusions We developed a new simple score using the 3 descriptors of CCE-2.

Background/aims Mesalazine is an effective drug for treating ulcerative colitis (UC), but causes allergic symptoms in a few cases. Therefore, the objective of this study was to evaluate the usefulness of the drug-induced lymphocyte stimulation test (DLST) for the diagnosis of mesalazine allergy. Methods Patients with UC treated with mesalazine with or without a history of associated adverse events (AEs) were enrolled at Kyorin University Hospital from July 2016 to April 2017. Results The DLST was performed in 104 patients with UC, of which 24 had a history of AEs due to mesalazine treatment. The control value of DLST was 337.4±296.3 counts per minute (cpm) in the AE+ group and 408.0±371.9 cpm in the AE- group. The measured value of DLST was 578.8±424.7 cpm in the AE+ group and 476.5±471.8 cpm in the AE- group. The stimulation index (SI) was 243.9%±291.1% in the AE+ group and 119.8%±53.0% in the AE- group. The SI value and DLST positivity were significantly higher in the AE+ group than in the AE- group (P=0.030 and P=0.029, respectively). The test sensitivity and specificity were 0.240 and 0.805, respectively, and the false-positive and false-negative rate was 0.195 and 0.760, respectively. Conclusions The DLST for mesalazine showed low sensitivity and high specificity, suggesting that it may be useful for the definitive diagnosis of allergy to mesalazine.

To investigate the effects of heat stress (hyperthermia) on muscle degeneration-regeneration, the soleus muscles of adult male Wistar rats were injected bilaterally with a single injection of bupivacaine. The rats were assigned to a sedentary control (Con), heat stress (Heat), bupivacaine-injected (BPVC), or bupivacaine-injected plus heat stress (BPVC+Heat) group. Heat stress was induced in the Heat and BPVC+Heat groups by immersion of the lower half of the body into water maintained at 42 ± 1°C for 30 min 48 h after the injection of bupivacaine and every other day during the following 1 or 2 wk. The soleus muscles in all groups were excised 24 h after the final bout of heat stress. Mean muscle weight, fiber cross-sectional area, myonuclear number, and heat shock protein 72 (Hsp72) and calcineurin protein levels were lower in the BPVC than in the Con or Heat groups at both time points. In contrast, several of these parameters in the BPVC+Heat group were not different or higher than in the Con or Heat groups at the 1- and/or 2-wk time points. The number of total and activated satellite cells, estimated by analyses of Pax7-negative, M-cadherin-negative, and MyoD-positive nuclei, was greater in BPVC+Heat than in all other groups. Combined, the results indicate that heat stress-related activation of satellite cells and upregulation of Hsp72 and calcineurin expression played important roles in the regeneration of the soleus fibers after bupivacaine injection.

Pneumatosis cystoides intestinalis (PCI) is a relatively rare disease in which multilocular or linear pneumatic cysts develop under the mucosa or serosa of the intestinal wall. We conducted a retrospective analysis to investigate the clinical characteristics of 68 patients with PCI. Hepatic portal venous gas (HPVG) was present in 9 patients, 8 of which had underlying intestinal tract necrosis. In most patients, PCI was mild and asymptomatic and resolved spontaneously. The main treatment strategy for PCI is conservative therapy. However, in cases complicated by HPVG, the presence of underlying intestinal tract necrosis must be considered in order to promptly determine whether emergency surgery is required.

We examined whether non-hematopoietic BM cells can migrate into the intestinal graft after fetal small intestinal transplantation (FSITx). Fetal small intestine from donor C57BL/6 mice was transplanted into the rectus abdominis of recipient C57BL/6 mice with only green fluorescent protein (GFP) BM cells (syngeneic FSITx). Intestinal grafts were harvested on days 5, 10, and 30 after FSITx and stained immunohistochemically using anti-CD45 antibody (a marker for hematopoietic BM cells). Although there were no GFP-positive cells identified in the epithelium of the graft intestinal villi, there were a few cells positive for both GFP and CD45 in the lamina propria on day 5 after FSITx, and many present on days 10 and 30. In some grafts there were only cells that were GFP positive/CD45 negative (i.e., non-hematopoietic BM cells) found in the lamina propria on days 10 and 30. These data indicate that non-hematopoietic BM cells as well as hematopoietic BM cells can migrate from the recipient's bone marrow, suggesting that recipient mesenchymal stem cells may be strongly implicated in graft regeneration and development after FSITx.

Background: Nearly 30% of childhood cases of chronic renal failure in Japan are attributed to congenital anomalies of the kidney and urinary tract (CAKUT), and the number is increasing. Urine screening at school facilitates early diagnosis and treatment of glomerulonephritis, but early screening for anomalies is currently not in practice. The authors evaluated the value of early abdominal ultrasonography screening in 1-month-old infants. Methods: The following characteristics of kidneys were assessed: presence versus absence, size, symmetry of size, position, separation of the central echo complex (CEC), abnormal echogenicity, and other abnormal findings. The bladder and ureter were checked for abnormalities in bladder shape and wall, as well as retrovesical ureteral dilation. Criteria for abnormalities included kidney length of ≤35 mm, or ≥60 mm; a difference in length of left and right kidneys of 10 mm or more; and CEC separation of Society for Fetal Urology (SFU) grade 2 or higher. Results: Beginning in April 1994 and continuing until September 2001, screening of 5700 1-month-old infants yielded 198 positive cases (3.5%) of CAKUT. Most frequent was abnormal CEC separation (approximately 60% of all abnormalities), followed by abnormal renal size or size asymmetry (30%). Further investigation yielded a specific diagnosis in 32 cases (0.6%) of all subjects. Most prevalent was obstructive uropathy (15 cases); 8 children underwent surgery. Small kidneys and vesicoureteral reflux were next in frequency. Conclusions: Ultrasonograpy was effective for early detection of renal and urinary tract anomalies. Ultrasound screening in early infancy may permit early treatment, that can prevent renal dysfunction.

We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for GFP-positive cells confirmed reconstitution of transplanted bone marrow. Bone marrow transplant mice subsequently underwent left coronary artery ligation (myocardial infarction) or sham-operation, and were killed at 1 mo or 3 mo after operation. Infarct size was similar in bone marrow transplant mice at 1 mo (47.1 +/- 5.9%) and at 3 mo (45.3 +/- 7.8%), and echocardiography at 2 and 8 wk revealed decreasing left ventricular function. In infarcted heart, GFP-positive cells that expressed desmin and troponin T-C were identified by confocal microscopy. GFP and troponin T-C double-positive cells were predominantly in the peri-infarcted region (1 mo, 365 +/- 45 cells/50 sections; 3 mo: 458 +/- 100 cells/50 sections; p0.05 versus noninfarct, infarct, and sham-operated regions). Furthermore, BMC mobilization and differentiation into cardiomyocytes was found to be complete within 1 mo after myocardial infarction. These results demonstrate that circulating BMC undergo mobilization and differentiation in cardiac cells after myocardial infarction. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.

A characteristic prenatal ultrasonographic finding of patent urachus is described. Routine obstetrical ultrasonography first revealed a cystic mass in the umbilical cord at 16 weeks of gestation. The mass spontaneously decreased in size and was undetectable at full term on serial ultrasound examination. The male newborn infant was delivered uneventfully at 38 weeks of gestation, weighing 2,774 g. He was noted to void urine from the umbilicus soon after birth, and the diagnosis of patent urachus was confirmed. On the 8th day of life, complete surgical removal of the urachus was performed, and the postoperative course was uneventful. An umbilical cystic mass which diminishes in size over the course of pregnancy is a sugesstive prenatal sonographic finding for urachal anomalies.

We report a case of Epstein-Barr virus-associated aggressive natural killer cell leukemia/lymphoma with giant splenomegaly in which splenectomy resulted in progression of apoptosis and hemophagocytosis. The serum level of ferritin, triglycerides, interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and soluble Fas ligand (sFasL) increased markedly, and liver damage progressed after splenectomy. The number of apoptotic cells in peripheral blood smears increased following splenectomy. In the present case, splenectomy caused disruption of the cytokine network, resulting in apoptosis of blood cells and hepatocytes, as well as phagocytosis.