Effects of luseogliflozin, a sodium-glucose co-transporter 2 inhibitor, on 24-h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, crossover study.

The aim of the present study was to determine the effects of luseogliflozin on 24-h glucose levels, assessed by continuous glucose monitoring, and on pharmacodynamic variables measured throughout the day. In this double-blind, placebo-controlled, crossover study, 37 patients with type 2 diabetes mellitus inadequately controlled with diet and exercise were randomized into two groups. Patients in each group first received luseogliflozin then placebo for 7 days each, or vice versa. After 7 days of treatment, the mean 24-h glucose level was significantly lower with luseogliflozin than with placebo [mean (95% confidence interval) 145.9 (134.4-157.5) mg/dl vs 168.5 (156.9-180.0) mg/dl; p < 0.001]. The proportion of time spent with glucose levels ≥70 to ≤180 mg/dl was significantly greater with luseogliflozin than with placebo [median (interquartile range) 83.2 (67.7-96.5)% vs 71.9 (46.9-83.3)%; p < 0.001] without inducing hypoglycaemia. The decrease in glucose levels was accompanied by reductions in serum insulin levels throughout the day.

Twenty-year trends in neonatal surgery based on a nationwide Japanese surveillance program.

AIM: To discuss the chronological changes observed in a national survey of neonatal surgery in Japan performed every 5 years by the Committee in the Japanese Society of Pediatric Surgeons. METHODS: We analyzed the data obtained for 20 years from 1993 to 2013 and herein report the chronological changes. RESULTS: The number of summarized cases was least in 1993, with 2806 cases, and subsequently increased to 3753 cases in 2013. The mortality rate among the patients with maternal transport linearly decreased (p = 0.0386). Although the proportion of extremely low birth weight infants linearly increased (p = 0.0014), with an annual rate of +0.39 %, the mortality rate linearly decreased (p = 0.0010), with an annual rate of -1.68 %. Moreover, the overall mortality rate linearly decreased (p = 0.0002), with an annual rate of -0.26 %. Most diseases were observed to exhibit a decline in the mortality rate with the same trend as overall mortality. The decline in the mortality rate was most robust with respect to congenital diaphragmatic hernia (CDH). The mortality rates, except for that of CDH, omphalocele, esophageal atresia, and intestinal perforation, declined to 5 % or lower by 2013. CONCLUSIONS: The present findings may be the result of remarkable progress in perinatal management.

FcepsilonRIalpha gene (FCER1A) promoter polymorphisms and total serum IgE levels in Japanese atopic dermatitis patients.

Two promoter polymorphisms of the high-affinity IgE receptor alpha-subunit (FcepsilonRIalpha) gene (FCER1A), -66T>C (rs2251746) and -315C>T (rs2427827), were analysed in Japanese atopic dermatitis subjects. Patients with the -315CT/TT genotype tended to have higher total serum IgE levels, while the proportion of -315CT/TT genotype or the -315T allele was significantly higher in those with highly elevated total serum IgE concentrations.

Methyldopa: single daily dose versus multiple daily dose.

A single-blind, prospective, crossover study of 27 ambulatory hypertensive outpatients was conducted to compare the antihypertensive effects of single daily dose versus multiple daily dose methyldopa regimens. Patients were randomly assigned to the two treatment modalities for a four-week study period. After four weeks patients were crossed over to the other study regimen. Each patient's blood pressure was determined three times daily, once each week. At the end of the study both treatment modalities were equally effective in controlling blood pressure levels. No serious adverse reactions were detected. This study has shown that patients currently on divided daily doses of methyldopa can be effectively treated on a single total dose of the medication.

Effects of trimebutine on intestinal motility after massive small bowel resection.

Effects of trimebutine maleate (TM) on intestinal motility in short bowel syndrome (SBS) were studied in conscious canines in both acute and chronic phases following 80% massive distal small bowel resection (MSBR). TM was administered orally to beagles with MSBR or as controls in the postprandial and fasting states, and given simultaneously with meals. Intestinal motility was measured using bipolar electrodes for approximately 1 month after the electrodes were implanted in each beagle and the data compared between treatment groups. When TM was given with meals, the postprandial period without duodenal migrating myoelectric (or motor) complexes (MMCs) was shorter than in those given meals only. When TM was given in the postprandial state in short bowel beagles, the initial duodenal MMCs occurred earlier, i.e. the postprandial period was shorter. Diarrhea did not occur in these beagles. When TM was given in the fasting state, duodenal MMCs occurred and propagated to the distal intestine. In conclusion, oral TM administration can produce a more appropriate intestinal condition for the next food intake and make enteral nutrition possible even in the acute phase after MSBR. Such feeding can be carried out without overloading gut function as a result of the modulation of gastrointestinal motility by TM.

Effects of intestinal muscular wrapping on remnant intestinal motility after massive small bowel resection in conscious canines.

We searched the effect of the muscular valve on the management of short bowel syndrome. The motility of the remnant intestine with a special muscular valve after 80% massive distal small bowel resection (MSBR) was evaluated in conscious dogs. The valve (muscular ring) was made by the autointestinal muscle layer holding vascular pedicle. Interdigestive and postprandial bowel motility using bipolar electrodes and/or contractile strain gauge force transducers 2-4 weeks after the surgery, and data of this group (Group I) were compared to the motility in dogs after MSBR without valve construction (Group II) and in controls (Control). Results; Fasting duodenal migrating myoelectric (or motor) complexes (MMCs) in Group I occurred at longer intervals than in Control and almost similarly to those in Group II. MMCs arising from the duodenum were often interrupted before the jejunum above the valve and the anastomosis. The velocity of duodenal MMC propagation was slowed in every intestinal segment including that from the duodenum to the proximal jejunum, and to the jejunum above the anastomosis. Transit time in MSBR group (I and II) from the duodenum to the terminal ileum was extremely shorter than in Control, but there were no differences between in Groups I and II. The duration of the postprandial period without duodenal MMCs in Group I was significantly prolonged than in Control, but was shorter than that in Group II. The muscular valve was frequently activated, and the jejunum covered with the valve was contracted frequently which synchronized with the valve activity. It seemed the valve worked as sphincter. However, intestinal obstruction was not occurred through the jejunum covered by the valve. In conclusion, changes in gut motility after MSBR with the valve construction compensate for the shortened intestine and maintain the bowel content earlier postoperatively in comparison with the MSBR alone, and also contribute to the adaptive increase in the remnant intestinal absorption.

The role of endoscopic retrograde cholangiopancreatography in infants with cholestasis.

BACKGROUND/PURPOSE: Endoscopic retrograde cholangiopancreatography (ERCP) was assessed in the diagnosis of cholestatic liver disease in infants. METHODS: ERCP was performed in 50 infants who had prolonged cholestasis. Their ages ranged from 25 to 274 days (mean, 69 days), and their weight ranged from 2.6 to 6.7 kg (mean, 4.7 kg). Incomplete visualization of the biliary tree or visualization of only the pancreatic duct was followed by exploratory laparotomy. In those in whom the biliary tree was visualized completely, the caliber of the bile duct was compared with that of the pancreatic duct. RESULTS: ERCP was completed in 43 patients (success rate, 86%) without complications. In the 7 patients in whom ERCP failed, 6 had biliary atresia (BA) diagnosed by exploratory laparotomy. The other patient had congenital biliary dilatation (CBD). In 29 of the 43 patients, the biliary tree was seen partially or only the pancreatic duct was visualized. These patients had BA diagnosed by laparotomy. Complete visualization of the biliary tree was obtained in 14 patients. Of these, 9 had neonatal hepatitis (NH), 2 had a paucity of intrahepatic bile ducts (PIBLD), and 3 had CBD. In all of the patients with NH, cholestasis improved spontaneously. The 2 patients with PIBLD had biopsy-proven disease. The caliber of the bile duct was larger than that of the pancreatic duct in NH. This relationship was not observed in PIBLD. CONCLUSIONS: ERCP is safe in infants. It is useful in the diagnosis of prolonged cholestasis.

A study of therapy for pediatric hepatoblastoma: prevention and treatment of pulmonary metastasis.

Our results of treatment for pediatric hepatoblastoma are presented with special emphasis on pulmonary metastasis. The pulmonary metastasis rate of hepatoblastoma was 44% (11/25). In 19 patients with resected hepatoblastomas, the 5-year survival rate without pulmonary metastasis was 90% (9/10); while with pulmonary metastasis it was 22% (2/9). Six patients with unresected hepatoblastomas all died within 4 months regardless of chemotherapy and/or metastasis. To improve survival in patients with hepatoblastoma, preoperative or postoperative chemotherapy was thought to be essential for tumors extending over 2 hepatic segments and having predictable factors for pulmonary metastasis (large size or histological evidence of capsular invasion). A long-term multidisciplinary approach including hepatic lobectomy, current multiagent chemotherapy (including CDDP, THP-ADR), and partial pulmonary resection for localized lung areas with metastases would ultimately be needed.

Sacrococcygeal teratoma: a series of 19 cases with long-term follow-up.

A series of 19 cases of sacrococcygeal teratoma (SCT) with follow-up of 5 to 25 years is presented. Twelve patients were neonates, age 0 to 26 days (5 immature teratomas and 7 mature teratomas, representing 3, 6, 2, and 1 Altman's type I, II, III, and IV tumors, respectively), four were infants, age 1 to 6 months (all mature teratomas, representing 1, 1, and 2 Altman's type I, II, and IV tumors), and 3 were children, age 1 to 4 years (all malignant teratomas, all Altman's IV tumors). Eight babies were delivered by elective caesarean section (CS). Though the mean gestational age at CS was 34.3 weeks in our series, we now believe that CS often must be performed earlier, depending on a tumor size or fetal condition. Eleven neonates and 4 infants were operated upon using a sacral approach in 10 and an abdominosacral approach in 5, and all survived. However, 4 patients had neurogenic bladder and were treated by urinary catheterization or vesicostomy for 2 to 5 years after surgery. Postoperative urogenital sequelae are seen in patients with a large tumor, urethral compression, urinary retention, or edema of the lower body. Malignant tumors usually had metastasized by the time of diagnosis, but the prognosis for outcome has been improved following surgery and combination chemotherapy.

Aspirin hepatotoxicity.

A case of aspirin hepatotoxicity in a 46-year-old male with rheumatoid arthritis is discussed, and this adverse reaction is reviewed. The patient was started on 900 mg aspirin four times daily; five days later the dose was increased to 1200 mg four times daily. After six days' therapy of 4.8 g aspirin daily, the serum salicylate level rose to 25 mg/100 ml and liver enzymes became elevated. Aspirin was discontinued and ibuprofen, 600 mg four times daily, begun. Eight days after cessation of aspirin therapy, the patient's liver enzyme values returned to normal. Previous case reports and studies of aspirin-induced hepatotoxicity are reviewed. It is concluded that aspirin-induced hepatotoxicity occurs much more frequently in patients with rheumatoid arthritis and other connective tissue disorders than previously recognized.

[Cold water immersion test for diagnosis of vibration diseases. Comparison between water at 5 degrees C and 10 degrees C].

5 degrees C-water 10-minute immersion test, generally used in Japan, is useful to diagnose vibration diseases. But severe pains during the immersion is troublesome. We studied the availability of 10 degrees C-water 10-minute immersion test to reduce the pain during the test. Subjects were forty-nine chainsaw operators, nineteen patients with vibration disease, and twelve controls. The same subject underwent both 5 degrees C and 10 degrees C immersion tests. The following results were obtained. 1) Skin temperatures in the highest score group after the immersion tests both at 5 degrees C and 10 degrees C was lower than that in the control group. Mean skin temperatures for the last five minutes during the immersion and the recovery activity in both the immersion tests showed a similar trend among subjects groups. Skin temperatures in patients under medical treatment (R'group) did not differ from those in the control group. 2) Hyperemia time by nail press test in the R'group and in the high score group after both immersion tests was longer than that in the control group. But this difference between chainsaw operators and the control group after 5 degrees C immersion test was more marked than that after 10 degrees C immersion test. 3) Vibratory sense as well as pain sense in the R'group and in the high score group after both immersion tests were less sharp than those in the control group. 4) Skin temperatures, nail press test, vibratory sense, and pain sense after 5 degrees C immersion test and those after 10 degrees C immersion test showed statistically significant positive correlation. 5) 10 degrees C immersion test is as effective as 5 degrees C immersion test in finding nervous disorders, but 5 degrees C immersion test is more effective than 10 degrees C immersion test in finding circulatory disorders. However patients with Raynaud's phenomena or moderate circulatory disorders can also be found even by 10 degrees C immersion test. 6) Cold water immersion test revealed disorders not only in skin temperature and by nail press test but revealed also disorders in vibratory sense and pain sense, therefore it is desirable that cold water immersion test should be done in the examination of vibration diseases.

Angina-like syndrome with diazoxide therapy for hypertensive crisis.

In 14 patients with hypertensive crisis treated with diazoxide, close monitoring of blood pressure, heart rate, and symptoms was performed. Standard 12-lead electrocardiograms were recorded before and after diazoxide. All patients showed a significant fall in blood pressure after drug administration. Seven patients (50%) showed significant ST-T changes after diazoxide. Six patients (43%) developed substernal discomfort demonstrated by substernal pain of tightness. Five patients (35%) had both chest discomfort and ST-T changes. One of these patients with substernal pain and ST elevation had evidence of acute myocardial infarction with serial enzyme studies. In the patients with significant ST-T changes, the average fall in blood pressure was significantly greater than the average fall in blood pressure in the patients without significant ST-T changes. These findings suggest that both ST-T changes and substernal discomfort were due to myocardial ischemia secondary to a sudden severe drop in blood pressure.

The herbal medicine Rikkunshi-to stimulates and coordinates the gastric myoelectric activity in post-operative dyspeptic children after gastrointestinal surgery.

Rikkunshi-to (TJ-43), a gastroprotective herbal medicine, has been used for the symptomatic relief of adult patients with dyspepsia. However, its mechanism has yet to be fully elucidated. The aim of this study is to evaluate the effect of TJ-43 on the gastric myoelectric activity in post-operative dyspeptic patients, whose symptoms persisted for over 1 year after gastrointestinal surgery. Electrogastrography (EGG) recordings were performed to calculate the biomechanical parameters on the dominant peak frequency (DPF). Eight pediatric patients with dyspeptic symptoms after gastrointestinal surgery were examined and six age-matched children without any dyspeptic symptoms were used as controls, and they were compared with nine age-matched children without any dyspeptic symptoms after gastrointestinal surgery as subcontrols. All patients exhibited symptomatic relief after the administration of TJ-43, and the mean symptom score decreased significantly after the treatment of TJ-43 over a 1-month period ( P<0.0001). The variability index (VI) and the percentage of normal waves (PNW) were calculated as irregularity parameters of DPF. The power ratio (PR) was calculated as a parameter of the gastric contractile activity. There were no significant differences in the VI and PNW between the controls and patients during the postprandial state after therapy, even though significant differences existed regarding those parameters between the controls and patients before the therapy. There were no significant differences in the DPF, VI, and PNW between the controls and subcontrols. Furthermore, PR exhibited a significant increase after therapy ( P<0.05). However, there was a significant difference in the PR between the controls and subcontrols ( P<0.05). Postprandial dip was observed in all control subjects, eight patients in the subcontrols, and two patients after administration of TJ-43, respectively. An abnormal gastric electrical activity therefore seems to be an important factor in the pathophysiology of post-operative dyspeptic children. The coordinating and stimulating effect of TJ-43 on the gastric myoelectric activity therefore seems to play an important role in the reduction of dyspeptic symptoms.

Treatment of ruptured undifferentiated sarcoma of the liver in children: a report of two cases and review of the literature.

Undifferentiated (embryonal) sarcoma of the liver (USL) is a highly malignant tumor of early life. Treatment choices for USL, especially with intraperitoneal rupture, are uncertain. Outcomes have been almost uniformly poor until recently. We describe two 7-year-old girls treated for ruptured USL. In the more recent patient, operative biopsy was followed by three cycles of cisplatin (CDDP), adriamycin (ADR), and cyclophosphamide (CPM). A fluid-filled cavity in the tumor showed enlargement and was drained. Two cycles of CDDP, ADR, vincristine (VCR), and ifosfamide were accompanied by reduction in tumor size, and trisegmentectomy was performed. She has no evidence of disease 3.5 years after surgery. In the other patient, left lobectomy was followed by a less intensive regimen, including CPM, VCR, and fluorouracil. This patient died of dissemination within 5 months. In 170 reported pediatric patients with USL, the 2-year disease-free survival was 17%. For the 96 such patients reported since 1980, 2-year disease-free survival had improved to 27%. More aggressive chemotherapy has been associated with this change. Of 8 patients with tumor rupture whose details have been reported (including the 2 present patients) after resection of the tumor, 4 died, 1 was alive with disease, and 3 were free of disease at 8, 49, and 58 months, respectively, after diagnosis. Ruptured USL should be treated with combination chemotherapy including CDDP and ADR, as well as with curative resection.

Postoperative fecoflowmetric analysis in patients with anorectal malformation.

Because conventional methods of evaluating anorectal function do not necessarily provide good correlations between investigative results and symptoms in patients who have undergone surgery for an anorectal malformation (ARM), we recently introduced feco-flowmetry (FFM) to simulate natural anorectal evacuation. The purpose of this study was to embody significant parameters to elucidate the dynamics of anorectal activity on FFM. The parameters of FFM were compared with those of manometry and Kelly's clinical score (KCS) in 24 patients who underwent surgery for an ARM. There were three fecoflow patterns, namely, block (B) type, segmental (S) type, and flat (F) type. The B-type or S-type patterns were seen in patients classified as "clinically good." There were close relationships between the fecoflow pattern and both the operative procedure and the KCS (P = 0.01 and 0.001, respectively). Maximum fecal stream flow rate (Fmax) precisely reflected the tolerance rate of intended normal saline solution in the colorectum (TR), the evacuative rate (ER), and KCS. Fmax > 45 ml/s or TR > 70% or ER > 50% was statistically regarded as the borderline of fecal continence. Thus, the fecoflow pattern might reflect the motor activity of the pelvic floor muscle. FFM provided quantiative and qualitative evaluations concerning anorectal motor activity in patients who had undergone surgery for an ARM.

Fiberoptic colonoscopic polypectomy in childhood: report and review of cases.

BACKGROUND: Fiberoptic colonoscopy has been a routine therapeutic modality for colorectal polyps in pediatric patients. Methods of bowel preparation, anesthesia, area of investigation and treatment depending on histopathology are still controversial. In order to clarify the rationale of pediatric colonoscopy the present study was performed. METHODS AND RESULTS: We analyzed the results of colonoscopic examination in 21 patients with colorectal polyps. Mean patient age was 3.7 years, with a range of 1--7 years. Rectal polyps were seen in 10 cases: seven had a solitary polyp (juvenile in six and adenoma in one) and three had multiple polyps (juvenile, lymphoid and Peutz--Jeghers coexisting with hyperplastic polyps). Sigmoid colon polyps were seen in 10 cases: all were solitary juvenile polyps, but one had adenomatous change. Another had multiple Peutz-- Jeghers polyps located in the entire colon. Flexible colonoscopic polypectomy was performed in 16 patients and transanal polypectomy was performed in four patients. Autoamputation was seen in two cases of juvenile polyp (resection was ultimately performed in a case having repeated autoamputation). After removing the polyps, all patients have had no recurrence for a period ranging from 6 months to 15 years, except for one case with Peutz--Jeghers syndrome. CONCLUSIONS: Most polyps are located in the rectum or the sigmoid colon. Although the majority are solitary or juvenile polyps, because histopathologic variety is seen in pediatric colon polyps, histopathologic examination of each polyp is important to detect any dysplastic or adenomatous element with malignant potential and to make a suitable follow-up schedule. Symptomatic polyps should be removed by fiberoptic colonoscopy or transanal resection with total colon endoscopic examination under general anesthesia. Polypectomy using the electrocautery snare and clip is effective and safe and bowel preparation using polyethylene glycol electrolyte solution is sufficient for the procedure.

A case of Currarino triad with familial sacral bony deformities.

We describe a male patient presenting with Currarino triad: a recto-urethral fistula, sacral bony deformity, and a presacral teratoma. Clinical screening of his family revealed three additional cases with incomplete forms of this association. Cytogenetic findings in the patient and his mother were normal. This case suggests that the occurrence of an anorectal malformation together with a sacral bony deformity should raise a physician's index of suspicion for associated presacral tumors, and that screening of the patient's family members with sacral radiographs is necessary.