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Ceftriaxone (CTRX) is a third-generation cephalosporin widely used for the treatment of bacterial infections in patients with renal disease because of its excretion by both renal and hepatic mechanisms. Biliary pseudolithiasis is a known CTRX-associated complication; however, there have been no studies of this adverse event in adult patients receiving maintenance hemodialysis. Here we report the case of a 79-year-old Japanese woman with end-stage renal disease (ESRD) receiving maintenance hemodialysis who developed CTRX-induced pseudolithiasis. The patient received CTRX for bronchial pneumonia. Fifteen days following CTRX initiation, the patient presented with stomachache. Because of the presence of one gallstone and increased gallbladder wall thickness on computed tomography scans, not detected at the onset of pneumonia, the patient was diagnosed with CTRX-induced gallbladder pseudolithiasis. CTRX was discontinued immediately. At 48 days following CTRX withdrawal, the gallstone and thickening of the gallbladder wall had completely resolved. ESRD may be a risk factor for CTRX-induced pseudolithiasis as hepatic excretion of CTRX is the predominant clearance mechanism in patients with ESRD. More attention should be paid to CTRX-induced pseudolithiasis following the use of CTRX in ESRD patients.

Background Brain atrophy has been reported in patients with end-stage renal disease receiving hemodialysis, although its mechanism is unknown. However, little is known regarding brain atrophy in patients receiving peritoneal dialysis (PD). Therefore, we examined brain volume and its annual change over 2 years in PD patients compared with patients with non–dialysis-dependent chronic kidney disease (NDD-CKD). Study Design Cross-sectional and longitudinal cohort. Setting & Participants 62 PD patients and 69 patients with NDD-CKD with no history of cerebrovascular disease who underwent brain magnetic resonance imaging (MRI) were recruited in a cross-sectional study. Among them, 34 PD patients and 61 patients with NDD-CKD, who underwent a second brain MRI after 2 years, were recruited in a longitudinal study. Predictor PD therapy versus NDD-CKD. Outcomes & Measurements T1-weighted magnetic resonance images were analyzed. Total gray matter volume (GMV), total white matter volume (WMV), and cerebrospinal fluid space volume were segmented, and each volume was quantified using statistical parametric mapping software. Normalized GMV and WMV values were calculated by division of GMV and WMV by intracranial volume to adjust for variations in head size. We compared normalized GMV and normalized WMV between PD patients and patients with NDD-CKD in the cross-sectional study and the annual change in normalized GMV in the longitudinal study. Results In the cross-sectional study, normalized GMV, which was correlated inversely with age, was lower in PD patients than in patients with NDD-CKD. However, normalized WMV, which was not correlated with age, was comparable between the groups. Annual change in normalized GMV was significantly higher in PD patients than in patients with NDD-CKD. These differences remained significant even after adjustment for potential confounding factors. Limitations A short observation period and high dropout rate in the longitudinal study. Conclusions Decline in normalized GMV is faster in PD patients than in patients with NDD-CKD.

Background Accumulating evidence suggests that mineralocorticoid receptor (MR) blockade effectively reduces proteinuria in diabetic nephropathy although the renin-angiotensin-aldosterone system is generally suppressed in diabetes. The present study was designed to confirm the antiproteinuric effect of MR blockade in diabetic rats and elucidate its mechanism. Methods The present study investigated whether MR blockade inhibits hyperglycemia-induced podocyte injury, focusing on the involvement of reactive oxygen species (ROS) production, in diabetic rats and cultured podocytes. Sprague-Dawley rats were divided into three groups: control, streptozotocin (STZ; 75 mg/kg)-injected diabetic and STZ treated with spironolactone (SPL; 50 mg/kg/day) and sacrificed after 8, 16 and 24 weeks. Results Rats gradually developed proteinuria from 8 weeks after induction of diabetes. Immunostaining for Wilms' tumor-1 (WT1) and synaptopodin, markers of podocytes, was attenuated, whereas immunostaining for desmin, a marker of podocyte damage, and 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress, was up-regulated in the glomeruli of diabetic rats. Diabetic rats showed hypoaldosteronemia compared to the control, whereas SPL decreased proteinuria, ROS production and podocyte damage. To elucidate the paradox between hypoaldosteronemia and effect of SPL under hyperglycemia, the role of high glucose in MR activation and podocyte injury was explored. In cultured MR-expressing podocytes, high glucose significantly enhanced Sgk1 expression, activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and ROS production and induced podocyte apoptosis. All these effects were inhibited by SPL. Conclusion We conclude that hyperglycemia in diabetes, independent of plasma aldosterone concentration, induces podocyte injury through MR-mediated ROS production and leads to proteinuria. SPL inhibits hyperglycemia-induced podocyte injury by attenuating ROS production.

We reviewed our experience with patients with primary squamous cell carcinoma of the vagina who received concurrent chemoradiation therapy (CCRT).We retrospectively analyzed six patients (median age, 60 years) with squamous cell carcinoma of the vagina who underwent CCRT between 2002 and 2005 at the University of the Ryukyus Hospital. Two patients were in International Federation of Obstetricians and Gynecologists (FIGO) stage II, one in stage III, and three in stage IVA. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Tumor size ranged from 3.2 to 7.7 cm. All patients were treated with true pelvic external-beam radiotherapy (EBRT) at 50 Gy. Then two of the six patients underwent intracavitary vaginal brachy-therapy. The remaining four patients received boost EBRT with shrinking fields. Total radiation dose to the vaginal tumor ranged from 60 to 66 Gy. All patients received two or three concomitant cycles of cisplatin during EBRT.All six patients completed their scheduled CCRT, and achieved a clinical complete response. One stage II patient died of disease 24 months after treatment, and the stage III patient had local failure at 12 months. The remaining four patients were free of their disease at 18, 23, 33, and 55 months, respectively. One patient with stage IVA developed a vesicovaginal fistula during CCRT. Nevertheless, CCRT was well tolerated by all six patients, and no grade 3 or 4 late toxicity was observed, as evaluated by the Radiation Therapy Oncology Group (RTOG) scoring system.CCRT is effective for primary squamous cell carcinoma of the vagina and should be considered for treatment in patients with high-risk disease having good performance status.

The question of whether patients with pure stage I squamous cell carcinoma in a mature cystic teratoma (MCT) should undergo conservative surgery, or postoperative adjuvant treatment remains unresolved.A 33-year-old woman with a left ovarian cyst underwent laparoscopic cystectomy at 16 weeks of gestation. Histological examination confirmed squamous cell carcinoma arising in an MCT. At 18 weeks of gestation, she underwent left salpingo-oophorectomy, and was diagnosed as having stage Ic malignant transformation of the MCT, and was observed closely without postoperative adjuvant chemotherapy. She delivered a healthy baby at 41 weeks of gestation. No evidence of recurrence was observed 14 months after the initial laparoscopic surgery.Although a thorough staging procedure , histopathologic evaluation, and long-term follow-up are indispensable, patients with early stage I squamous cell carcinoma in MCT may safely undergo conservative surgery.

The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure.We measured plasma endothelin-1 (ET) and the urinary excretion of endothelin-like immunoreactivity before and after infusion of radio contrast medium (CM) in patients with normal renal function (group N; n = 6; mean serum creatinine concentration, 0.8 +/- 0.1 (SEM) mg/dl), and in another group, with renal dysfunction (group R; n = 6; 2.7 +/- 0.5 mg/dl). Half-normal saline (0.45% NaCl solution) was continuously infused in all patients for 25 h, at a rate of 100 ml/h; starting from 5 h before the infusion of CM.Plasma ET in group R (5.2 +/- 1.4 pg/ml) was significantly higher than in group N (0.9 +/- 0.3; P0.01). Urinary endothelin excretion corrected by creatinine concentration (uET/Cr) in group R (7.9 +/- 2.4 mg/g Cr) was significantly higher than in group N (1.5 +/- 0.4 mg/g Cr; P0.05). Urinary excretion levels of N-acetyl-Beta- d-glucosaminidase (NAG) and Beta2-microglobulin (Beta2M) were also significantly higher in group R (0.8 +/- 0.2 mU/g Cr and 670 +/- 400 mg/g Cr, respectively) than in group N (0.3 +/- 0.1 and 7.5 +/- 2.2, respectively). After CM infusion, uET/Cr in group R significantly increased, to 10.7 +/- 2.6 mg/g Cr on the next day and returned to baseline level on the third day. NAG and Beta2M showed a similar pattern, but a significant change in NAG was observed on the second day in group R. In group N, uET/Cr, NAG, and Beta2M did not change after CM infusion. Plasma ET remained unchanged throughout the observation period of 4 days in both groups. No patient developed pulmonary edema or a significant rise in serum creatinine (more than 0.5 mg/dl), caused by infusion of the amount of half-normal saline used.In the present study, uET/Cr increased after the administration of CM only in the patients with renal impairment. This difference in endothelin reaction may be a causal one, in that patients with renal insufficiency readily develop RCN. The infusion of half-normal saline starting before CM infusion causes no side effects and is safe for the prevention of CM-induced acute renal failure. The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure.

Prognosis in the few patients with advanced-stage juvenile granulosa cell tumor (JGCT) of the ovary has traditionally been unfavorable. We report a recurrent JGCT patient managed by palliative radiotherapy. A 37-year-old woman with recurrent JGCT received a combination of paclitaxel–carboplatin chemotherapy and then single-agent docetaxel, but her disease progressed with multiple abdominal masses and ascites. We chose palliative radiation therapy to relieve her complaints. Whole-abdominal external beam radiotherapy with pelvic boost was delivered. She tolerated the treatment well. After the completion of radiotherapy, ultrasonography showed shrinkage of the tumor, and the ascites disappeared. We should consider using radiation therapy in a palliative setting for such patients with recurrent JGCT suffering from abdominal complaints

A 5-year-old girl and a 2-year-old boy presented with recurrent cerebral primitive neuroectodermal tumor (PNET) and were treated with intravenous administration of human fibroblast interferon (HuIFN-β) which was continued as outpatient maintenance therapy. Both patients showed a partial response and were still alive 14 months and 2 years after diagnosis. Our results suggest that HuIFN-β is an effective therapy for PNET, and can be used as long-term maintenance therapy without serious side effects.

To identify predictive factors for locoregional recurrence in patients with FIGO stage IB-IIB cervical cancer treated with concurrent chemoradiotherapy (CCRT).Data were analyzed for 123 patients with FIGO stage IB-IIB squamous cell carcinoma of the cervix between 1997 and 2007. Eligibility for CCRT included tumor size4 cm and/or lymph node enlargement over a minimum diameter of 1 cm.Tumor size (≥5.2 cm) and age (48 years) were independent predictive factors for locoregional recurrence by multivariate analysis. Based on these two factors, the patients were divided into low-risk (n=91) and high-risk (n=32) groups for locoregional recurrence. The 5-year disease-free survival for the low-risk group was 95.3%, which was significantly better than 65.5% for the high-risk group (p0.0001). Locoregional recurrence was noted in 10 out of the 32 patients in the high-risk group compared to only 3 out of the 91 patients in the low-risk group.To improve locoregional control in the high-risk group, it may be worthwhile to consider CCRT using new radiosensitizing agents, adjuvant hysterectomy or adjuvant chemotherapy.

To determine the clinical implications and prognostic value of the human papillomavirus (HPV) genotype, we evaluated the various HPV types in patients receiving radiotherapy for squamous cell carcinoma of the cervix. The study population included 113 invasive squamous cell carcinoma patients treated with radiation or chemoradiation between 1993 and 2002. The median age of the patients was 61 years. Tumors were classified by the International Federation of Gynecology and Obstetrics staging as stage IB in 11 patients, stage II in 39, stage III in 57 and stage IVA in 6 patients. To investigate HPV infection and its genotypes in the tumor specimens, L1 consensus PCR was performed followed by the direct nucleotide sequencing of the PCR products. Ninety-five samples (84.1%) were positive for HPV DNA. The most prevalent type was HPV-16 (34.7%). Poorer response to radiotherapy was observed in the patients with the HPV-16 genotype, in which 7 of the 33 patients had persistent disease. Only 1 of the 10 patients with HPV-58, 1 of the 5 with HPV-31 and 5 of the 10 patients with HPV-33 had a recurrence. The 5-year survival rate was 90, 80, 69.4 and 39% in the HPV-58, HPV-31, HPV-16 and HPV-33 type groups, respectively. Patients with HPV-31 and HPV-58 types were found to have better survival, whereas patients with the HPV-33 type experienced a higher risk of death. HPV genotyping may serve as a potential biomarker of response to radiation and prognosis in cervical carcinoma patients undergoing radio- or chemoradiotherapy.

Objective To identify prognostic factors in patients with locally advanced squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy (CCRT). Methods We analyzed 108 patients with FIGO stage Ib2–IVa carcinoma of the cervix treated with CCRT between 1996 and 2003 at the University of the Ryukyus Hospital. Patients with a local tumor size of 4cm or more in diameter or lymph node enlargement were treated with CCRT. Disease-free survival (DFS) was estimated by the Kaplan–Meier method. The log-rank test was used to test differences in survival. Fisher's exact test was used for univariate analysis. The Cox proportional hazard model was used for multivariate analysis. Results The median age and the median follow-up were 50 years (range: 25–70 years) and 48 months (range: 4–102 months), respectively. The 4-year distant DFS of all patients were 83%. Thirty-two of 108 patients were diagnosed with recurrence. Twenty patients had distant failure, of which 17 had only distant metastasis, three patients both distant and loco-regional recurrence, and the remaining 12 patients recurred loco-regionally. Positive serum squamous cell carcinoma antigen (SCC) immediately after CCRT was an independent predictive factor for distant recurrence on multivariate analysis. The 4-year distant DFS of these patients was 62.5%, which was significantly worse than 89.2% in patients with negative serum SCC level ( p =0.003). It should be noted that the distant metastasis occurred within 6 months in six of the nine patients. Conclusion Positive serum SCC immediately after the treatment was a predictive factor for distant recurrence. New strategies should be considered to control distant recurrence in this group of patients.

The crucial involvement of podocyte failure in the development of hereditary focal segmental glomerulosclerosis (FSGS) indicates that specific podocyte proteins are closely related to podocyte function and biology. We hypothesized that podocyte failure, reflected by alteration of these proteins, leads not only to FSGS but also to resistance to steroid therapy. We investigated the association between expression of synaptopodin and glomerular epithelial protein 1 (GLEPP1) and response to corticosteroid therapy in primary FSGS. The subjects of this retrospective study were 17 adult patients with primary FSGS with nephrotic syndrome (NS) seen at Fukuoka Red Cross Hospital between 1979 and 2001. They were divided into two groups according to the response to steroid therapy at 6 months: responders (n = 10) and non-responders (persistence of nephrotic-range proteinuria, n = 7). Expression levels of synaptopodin and GLEPP1 were examined immunohistochemically using image analysis software. Low expression levels of both proteins were associated with poor steroid responsiveness in FSGS. The average gray values for synaptopodin and GLEPP1 expression in responders vs. non-responders were 9.0 ± 0.7 (mean ± S.E.M.) vs. 6.3 ± 0.9 (P = 0.04) and 9.6 ± 1.2 vs. 6.0 ± 1.0 (P = 0.04), respectively. The percentages of glomerular area staining for synaptopodin and GLEPP1 in responders vs. non-responders were 15.4 ± 2.7% vs. 8.1 ± 1.2% (P = 0.045) and 11.9 ± 1.6% vs. 6.0 ± 1.3% (P = 0.02), respectively. Synaptopodin expression correlated with the severity of proteinuria and with GLEPP1 expression. Reduced expression of both synaptopodin and GLEPP1 is associated with poor response to steroid therapy in primary FSGS.

Multiple symptoms including reduced spontaneous activity, hemiparesis, and cognitive disturbance are frequently observed in the chronic phase of cerebral vascular diseases in humans. For investigating pathogenesis and drug therapy in the chronic phase of cerebral vascular diseases, it is important to observe the long-term functional consequences in a model of focal cerebral ischemia. Pathological and functional changes including neurological deficits, cognitive disturbances, brain edema, decreased cerebral blood flow and metabolism, and catecholamine levels after focal cerebral ischemia have been well documented in animals. However, most of these changes were observed only in the acute phase and few reports are available concerning the long-term functional consequences of focal cerebral ischemia [1].

16056 Background: The purpose of this study was to report the feasibility and efficacy of concurrent chemoradiotherapy (CCRT) for the locally advanced cervical cancer in our institute. Methods: We retrospectively reviewed 147 patients (stage Ib: 9, II: 82, III: 80, and IVa: 7) with squamous cell carcinoma of the cervix treated with CCRT. Cisplatin (20mg/m2/day) was administered for 5 days every 3 weeks for a median of three courses (range: 1–5 courses) during radiotherapy (RT). The patients with paraaortic and/or common iliac lymphadenopathy were excluded. RT consisted of pelvic external beam RT (EBRT) with 40Gy/20 fractions followed by high-dose rate brachytherapy (HDR-BT) with 18Gy/3 fractions and pelvic EBRT with 10Gy/5 fractions using a midline block. Late complications were graded by the RTOG/EORTC criteria. Results: The 5-year actuarial overall survival (OS), disease-free survival (DFS), and pelvic relapse-free survival were 78.5%, 70.7%, and 78.0%, respectively. The 5-year OS by the disease stage was as follows: stage Ib 100%, II 82.0%, III 62.3%, and IVa 35.7%. Multivariate analysis identified pelvic lymphadenopathy, tumor diameter > 7cm, and pretreatment hemoglobin < 9.0g/dl as an independent prognostic factor for both OS and DFS. Only one patient suffered from grade 3 enterocolitis, but no grade 4 complication developed. Conclusions: Our experience suggests that CCRT using HDR-BT for locally advanced cervical cancer could achieve favorable local control without suffering from severe late complications. No significant financial relationships to disclose.

We present a case of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis with diabetic nephrosclerosis, diagnosed by serial renal biopsies within a short period. A 78-year-old man with renal insufficiency, who had been diagnosed with diabetic nephrosclerosis by renal biopsy 9 months earlier, was admitted to the hospital for dyspnea and rapid deterioration of renal function. The titer of serum MPO-ANCA was high, and the second renal biopsy confirmed the presence of necrotizing glomerulonephritis with crescents. Methylprednisolone pulse therapy followed by oral administration of prednisolone led to resolution of respiratory symptoms and reversal of MPO-ANCA. Renal function did not improve, however, necessitating hemodialysis. A review of the literature showed several cases of necrotizing glomerulonephritis superimposed on diabetic nephropathy but only a few reported cases of MPO-ANCA glomerulonephritis associated with diabetic nephrosclerosis. Diabetic patients who show rapid deterioration of renal function should undergo renal biopsy to determine the concomitant presence, if any, of other glomerular diseases and to prevent life-threatening systemic involvement. © 2002 by the National Kidney Foundation, Inc.

Immunohistochemistry was used to localize brain natriuretic peptide in the porcine spinal cord and to compare it with that of atrial natriuretic peptide, substance P, calcitonin gene-related peptide and [Met]enkephalin. Brain natriuretic peptide-immunoreactive varicose fibers were observed in lamina I and the inner portion of lamina II of the dorsal horn. Semiquantitative analysis showed that the highest density of brain natriuretic peptide-immunoreactive varicosities was in the lumbosacral and coccygeal segments. The distributional pattern of brain natriuretic peptide-immunoreactive nerve fibers in the spinal cord was unique and quite distinct from that of the other neuropeptides studied. These neuroanatomical findings suggest that brain natriuretic peptide may play a role in the regulation of nociceptive processing in the spinal cord, either alone or with bioactive substances.

Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death. Background Tumor necrosis factor (TNF) receptor family members, such as Fas and TNF receptor 1 (TNFR1), are thought to induce apoptosis in a variety of cells and organs. Although a number of potential scenarios have been postulated for the involvement of these receptors in the pathogenesis of acute renal failure (ARF), direct evidence for their involvement in death of renal tubular cells (RTCs) and renal dysfunction is preliminary. Methods This study examined the roles of these receptors in RTC death in two systems: ( 1 ) in vivo murine and rat models of cisplatin-induced ARF, and ( 2 ) murine proximal tubular cells (PTCs), which were isolated from C57BL/6 (B6) mice, Fas -mutant B6 -lpr/lpr mice and TNFR1 -deficient mice, and normal rat kidney (NRK52E) cells in vitro. Results Reverse transcription-polymerase chain reaction indicated cisplatin-induced up-regulation of Fas, Fas ligand and TNF-α mRNAs in the kidney in vivo and in RTCs in vitro, both in mice and rats. In contrast, the level of TNFR1 mRNA was substantial but did not change in response to cisplatin. TNF-α production in cell culture medium determined by enzyme-linked immunosorbent assay (ELISA) and Fas expression determined by fluorescence-activated cell sorter (FACS) analysis increased following incubation with cisplatin in B6 PTCs. In order to examine whether Fas and TNFR1 are directly involved in RTC death and renal dysfunction, we compared cell resistance to cisplatin using a cell viability assay and FACS analysis with fluorescein isothiocyanate-conjugated annexin V and propidium iodide staining. The ratios of cell viability loss and cell death, both from apoptosis and necrosis, were higher in B6 PTCs than in other cells, while the ratios were comparable between Fas -mutant PTCs and TNFR1 -deficient PTCs. Caspase-8 activity was increased in B6 PTCs, but not in Fas -mutant PTCs and TNFR1 -deficient PTCs. Furthermore, the renal dysfunction and RTC death, both apoptosis and necrosis, induced by cisplatin were more severe in B6 mice in vivo. Conclusion Based on these data, we conclude that the Fas- and TNFR1-mediated apoptotic pathways are directly involved in the pathogenesis of cisplatin-induced RTC death process.