Functional domains of osteopontin stimulate renal crystal formation: analysis of OPN-transgenic mice

Osteopontin (OPN) has been described to play a nonredundant role in the formation of renal crystals. This biological activity of OPN may be attributed to its characteristic structure, which includes 2 calcium binding sites, Arg-Gly-Asp (RGD) sequences. To test this hypothesis, we evaluated wild-type mice (WT group), OPN-knockout mice (KO group), and two types of transgenic mice : (1) one type carrying a transgene in which the sequences coding for the 2 calcium-binding sites of the OPN were deleted (CaX group) and (2) the other type carrying a transgene in which the sequence that codes for the RGD sequence of the OPN was modified to one that codes for Arg-Gly-Glu (RGE ; RGE group). Changes occurring after intraperitoneal injection of glyoxylate for 9 d were analyzed. The amount of crystals deposited was the greatest in mice of the WT group and the least in those of the KO group. The number of crystal deposits in mice of the RGE and KO groups was approximately the same. Microscopic observations revealed that the crystal nuclei in mice in the CaX group were stratified and exhibited a disordered pattern ; this pattern was dissimilar to that observed in the mice in the WT and RGE groups, wherein the crystal nuclei exhibited a rosette petal-like radial pattern. The results indicate the possibility that each domain contributes to the mechanism by which OPN stimulates crystal formation.     

Safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin and low-dose metformin

Background: This study investigated the safety and efficacy of metformin up-titration in Japanese patients with type 2 diabetes mellitus treated with vildagliptin (100 mg/day) and low-dose metformin (500 or 750 mg/day).

Research design and methods: Fifty patients were randomly allocated to the control group (maintaining the initial low-dose of metformin) and the dose increase group (up-titrating of metformin to 1,500–2,250 mg/day) for 24 weeks. The primary outcome was change in HbA1c from baseline to 24 weeks.

Results: Among the 25 patients allocated to the dose increase group, four patients were not able to complete the study protocol because of gastrointestinal symptoms. HbA1c in the dose increase group was significantly but modestly lower than in the control group (change in HbA1c: 0.22 ± 0.57 vs. ?0.15 ± 0.58%, group comparison, P < 0.05). The dose increase group did not gain weight during the study period, and no hypoglycemic events were reported in both groups. The rate of gastrointestinal symptoms in the dose increase group was profoundly higher than in the control group (32 vs. 0%, P < 0.01).

Conclusions: In Japanese patients with type 2 diabetes treated with vildagliptin and low-dose metformin, metformin up-titration significantly but modestly improved glycemic control without hypoglycemia and weight gain.     

Initial experience of transnasal endoscopic biliary drainage without conscious sedation for the treatment of acute cholangitis (with video)

BACKGROUND: Endoscopic biliary drainage has been established as providing effective treatment for acute obstructive jaundice and cholangitis. A recently developed ultrathin transnasal videoendoscope is less invasive, even for patients who were critically ill, and can be performed without conscious sedation. OBJECTIVE: To evaluate the clinical efficacy and safety of biliary drainage (BD) by using transnasal videoendoscopy (TNE) without conscious sedation. DESIGN: Case series. SETTING: This procedure was performed at Tokyo Medical University Hospital. PATIENTS: Three patients with bile-duct stones and acute cholangitis and with a previous biliary endoscopic sphincterotomy (ES) were included in this study. INTERVENTION: All patients underwent BD by using a front-viewing TNE. Two 5F stents were placed into the bile duct across the major papilla. MAIN OUTCOME MEASUREMENT: The efficacy and safety of the TNE technique. RESULTS: Transnasal insertion of a TNE endoscope was feasible in all patients, without epistaxis. TNE BD was achieved in all patients. Abdominal pain, fever, and jaundice improved 24 hours after the procedure in all patients. Despite the absence of intravenous conscious sedation, all patients would agree to undergo the procedure again, if necessary. LIMITATIONS: Maneuverability of the TNE endoscope; limited to patients with a previous ES. CONCLUSIONS: In this small series, unsedated TNE can be used to successfully drain the biliary system in patients with a previous ES. Additional studies to validate this hypothesis are needed.     

Expression of multidrug resistance protein in metastatic colorectal carcinomas

To clarify the relationship between multidrug resistance protein (MRP) and clinicopathologic features, the influence of adjuvant chemotherapy, and prognosis of patients who underwent resection of metastatic liver carcinomas originating from colorectal carcinomas, we examined the expression of MRP in tumor tissues by immunostaining. Specimens of 38 primary colorectal tumors and 44 metastatic liver tumors of colorectal origin were examined (metastatic group). We also examined 28 nonmetastatic colorectal carcinomas. The percentages of nonmetastatic tumors and of primary and metastatic tumors of the metastasis group that expressed MRP were similar. MRP expression in primary and metastatic tumors did not correlate with any clinicopathologic features. The use of adjuvant chemotherapy after operation for primary colorectal carcinomas was associated with increased MRP expression among metastatic liver tumors. Expression of MRP in the tumor did not influence the prognosis or survival rate after resection of primary or metastatic tumors. Our data suggest that MRP expression in metachronous liver metastases from colorectal carcinomas may be induced by administration of anticancer drugs but is not associated with clinicopathologic features of the tumor, liver metastasis, or prognosis. Received: November 19, 1998 / Accepted: May 28, 1999     

Successful transvaginal repair of a rectovaginal fistula developing after double-stapled anastomosis in low anterior resection: Report of four cases

(Received for publication on Dec. 8, 1997; accepted on Sept. 11, 1998)     

Effect of a newly developed bisphosphonate,YH529, on osteolytic bone metastases in nude mice

YH529, [1-hydroxy-2-(imidazo [1,2-a] pyridin-3-yl) ethylidene]-bisphosphonic acid monohydrate, is a newly developed third-generation bisphosphonate with a potent inhibitory activity toward osteoclastic bone resorption. The primary cellular mechanism of osteolysis associated with metastatic cancer is osteoclast-mediated. It is likely that bisphosphonates would be efficacious in this situation. In the present study, we examined the effect of YH529 in a nude mice bone metastasis model, in which the intracardiac injection of a human breast cancer cell line, MDA-MB-231(MDA-231), leads to osteolytic bone metastases. To examine whether YH529 would prevent such bone metastasis, we administered YH529 s.c. to nude mice simultaneously with cancer cell inoculation through the entire experimental period (protocol 1) or performed short-term prophylactic administration before inoculation of the MDA-231 cells (protocol 2). In addition, to examine the possible therapeutic effects of the drug on established bone metastases, we injected YH529 after radiographically small but distinct osteolytic bone metastases had been detected (protocol 3). In all protocols, YH529 (2 μg/mouse/day) markedly inhibited bone metastases as well as the progression of established metastatic foci that were quantified on the radiographs. Histological examination and histomorphometrical analysis revealed that YH529 markedly reduced the number of osteoclasts and the size of the tumor at the metastatic bone sites. Our results suggest that YH529 may suppress metastasis formation and tumor growth in bone through inhibition of osteoclastic bone resorption. Int. J. Cancer 77:279–285, 1998.© 1998 Wiley-Liss, Inc.     

Changes with time in skin temperature of the shoulders in healthy controls and a patient with shoulder-hand syndrome

Background

Abnormal skin temperature in the shoulder is caused by various diseases. A thermography is unable to capture temperature changes over time. In contrast, a Thermocron is an effective measuring device to monitor temperature changes over time.

Purposes

The purposes of this study employing a Thermocron were to measure shoulder skin temperature over time in healthy subjects and to detect shoulder skin temperature abnormalities in a patient with shoulder-hand syndrome.

Subjects and methods

Subjects comprised 10 healthy volunteers (20 shoulders; 4 men and 6 women, mean age 54 years). For measurements, a Thermocron was attached on both shoulders. Measurements were made from 21.00 to 07.00 the following morning at 15-minute intervals.

Results

Gradual difference in right and left shoulder skin temperature was observed with the timing of measurements but no significant difference was apparent, i.e. dominant side 34.9 ± 0.8°C, non-dominant side 34.9 ± 0.9°C (P = 0.28).

Presentation of a case with shoulder-hand syndrome

A 54-year-old woman with the diagnosis of rotator cuff tear underwent surgical treatment of rotator cuff repair, but the pain of the operated shoulder persisted due to phase 1 shoulder-hand syndrome. In postoperative week 3, skin temperature measurement using Thermocrons demonstrated a significant decrease in temperature on the operated side (affected side 34.3 ± 0.4°C, healthy side 35.2 ± 0.3°C; P < 0.05).

Conclusion

The changing of the skin temperature during night-time was successfully recorded both in the healthy subjects and a case with shoulder-hand syndrome using a Thermocron.