Involvement of neutrophil extracellular traps in the pathogenesis of glomerulonephritis in a case of systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome.

Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are autoimmune diseases that often cause rapidly progressive glomerulonephritis, with neutrophil extracellular traps (NETs) involved in their pathogenesis. However, the involvement of NETs in the renal damage caused by SLE/AAV overlap syndrome has not been clarified yet. In this study, we detected renal deposition of NETs in a patient with SLE/AAV overlap syndrome. In addition, a significantly increased level of NET-inducing activity was observed in the patient's serum, which improved with treatment. On the other hand, a markedly lower level of NET degradation was observed in the patient's serum as compared to healthy subjects' sera, without any posttreatment changes. These findings suggest that NETs may play a role in the pathogenesis of renal injury associated with SLE/AAV overlap syndrome.

[A Case of Liver Metastasis of Colorectal Cancer in a Hemodialysis Patient, Underwent Liver Resection and Chemotherapy after Colorectal Resection].

A 60 years old man has undergone hemodialysis due to chronic renal failure by diabetic nephropathy. A sigmoid colon cancer and multiple liver metastases(S2, S6)were found, and he had laparoscopic sigmoid colon resection first, it was local resection. The stage was pT3N2aH1, stage Ⅳ, and histopathological examination revealed that the tumor was well‒differentiated adenocarcinoma and RAS, BRAF mutation was negative. From the 4th week after surgery, mFOLFOX4 plus panitumumab( oxaliplatin 60 mg/m2[30% reduction]), continuous intravenous injection fluorouracil 600 mg/m2(regulated amount), rapid intravenous injection fluorouracil 400 mg/m2(regulated amount), Leucovorin 100 mg/m2(regulated amount), panitumumab 6 mg/kg(regulated amount)were given for 4 courses. Since partial response was obtained in both hepatic lesions, we underwent radiofrequency ablation for S6 lesion and laparoscopic partial hepatectomy for S2 lesion. Eight months have passed since the first visit, but no recurrence have been observed. The kidney is an organ that metabolizes many drugs, and it is necessary to adjust the drug volume and consider the timing of administration even in anticancer chemotherapy. We report that we experienced chemotherapy for colorectal cancer during hemodialysis with a review of the literature.

Why does activated partial thromboplastin time prolongation occur in severe fever with thrombocytopenia syndrome?

Severe fever with thrombocytopenia syndrome (SFTS) is caused by infection with SFTS virus and this mortality rate is 16.2% to 30%. An 85-year-old male patient presented to the emergency department of the hospital with primary complaints of fever and consciousness disturbance. Haemophagocytic syndrome and prolonged activated partial thromboplastin time (APTT) without associated prolonged prothrombin time were observed, suggesting SFTS, which was eventually diagnosed. APTT-only prolongation has been reported previously with SFTS, but the mechanism is unknown. The absence of coagulation factors was determined by a cross-mixing study. In addition, examination of intrinsic coagulation factors showed reduced factor XI activity. These results suggest that factor XI is causally related to APTT-only prolongation in SFTS.

IgM-mediated Warm Autoimmune Hemolytic Anemia: An Autopsy Report.

A 79-year-old man with Sjögren's syndrome and systemic lupus erythematosus developed acute impaired consciousness and hemolytic anemia. The patient's red blood cells agglutinated spontaneously at 25-37°C. The treatment of red blood cells with 2-mercaptoethanol resulted in the loss of spontaneous agglutination. A diagnosis of IgM-mediated warm autoimmune hemolytic anemia was made. The patient received steroid pulse and plasma exchange therapies. Rituximab was also administered. However, the patient died from multiple organ failure at six days from the symptom onset. The clinical progress of the patient and autopsy findings suggested that complement activation might have been associated with the pathology.

Comparative Effects of Direct Renin Inhibitor and Angiotensin Receptor Blocker on Albuminuria in Hypertensive Patients with Type 2 Diabetes. A Randomized Controlled Trial.

BACKGROUND: In patients with diabetes, albuminuria is a risk marker of end-stage renal disease and cardiovascular events. An increased renin-angiotensin system activity has been reported to play an important role in the pathological processes in these conditions. We compared the effect of aliskiren, a direct renin inhibitor (DRI), with that of angiotensin receptor blockers (ARBs) on albuminuria and urinary excretion of angiotensinogen, a marker of intrarenal renin-angiotensin system activity. METHODS: We randomly assigned 237 type 2 diabetic patients with high-normal albuminuria (10 to <30 mg/g of albumin-to-creatinine ratio) or microalbuminuria (30 to <300 mg/g) to the DRI group or ARB group (any ARB) with a target blood pressure of <130/80 mmHg. The primary endpoint was a reduction in albuminuria. RESULTS: Twelve patients dropped out during the observation period, and a total of 225 patients were analyzed. During the study period, the systolic and diastolic blood pressures were not different between the groups. The changes in the urinary albumin-to-creatinine ratio from baseline to the end of the treatment period in the DRI and ARB groups were similar (-5.5% and -6.7%, respectively). In contrast, a significant reduction in the urinary excretion of angiotensinogen was observed in the ARB group but not in the DRI group. In the subgroup analysis, a significant reduction in the albuminuria was observed in the ARB group but not in the DRI group among high-normal albuminuria patients. CONCLUSION: DRI and ARB reduced albuminuria in hypertensive patients with type 2 diabetes. In addition, ARB, but not DRI, reduced albuminuria even in patients with normal albuminuria. DRI is not superior to ARB in the reduction of urinary excretion of albumin and angiotensinogen.

Diagnosis of complex renal cystic masses and solid renal lesions using PET imaging: comparison of 11C-acetate and 18F-FDG PET imaging.

PURPOSE: The study aims to assess the usefulness of PET with C-acetate and F-FDG to differentiate renal cell carcinoma (RCC) from complicated renal cysts. METHODS: Thirty-one patients were enrolled, 14 patients with complicated renal cysts (12 with Bosniak III and 2 with Bosniak IV) and 17 patients with 19 solid renal tumors. The patients underwent both C-acetate PET and FDG PET. Nephrectomy or partial nephrectomy was performed after the PET scans. RESULTS: In 29 patients, 32 renal lesions were diagnosed as RCC. Twenty-three of the 32 RCCs (72%) had positive C-acetate PET findings, whereas only 7 FDG PET studies were positive (22%). Considering the relationship between tumor size measured by macroscopic appearance of resected tumors and PET results, 22 of 25 (88%) tumors more than 1.5 cm showed positive C-acetate PET findings. In 12 patients with Bosniak III renal cysts, 10 renal lesions were diagnosed as RCC. In this subgroup, 5 of the 10 RCCs (50%) had positive C-acetate PET findings, whereas 2 RCCs (20%) had positive FDG PET findings. None of the cases with benign findings had positive C-acetate PET or FDG PET scans. CONCLUSIONS: C-acetate PET demonstrates a pronounced increase in tracer uptake in RCC, especially in renal tumors more than 1.5 cm, and displays a higher sensitivity than FDG PET. These preliminary data show that C-acetate may be a useful PET tracer to exclude RCC in complex renal cysts.

Drugs interacting with organic anion transporter-1 affect uptake of Tc-99m-mercaptoacetyl-triglycine (MAG3) in the human kidney: therapeutic drug interaction in Tc-99m-MAG3 diagnosis of renal function and possible application of Tc-99m-MAG3 for drug development.

INTRODUCTION: Renal uptake of Tc-99m-MG3 involves organic anion transporter (OAT). Treatment with drugs showing OAT affinity might interfere with renal uptake of Tc-99m-MAG3, leading to misinterpretation in Tc-99m-MAG3. This study was conducted to discuss a possible drug interference with Tc-99m-MAG3 diagnosis on OAT sites. METHODS: Renal uptake and plasma clearance of Tc-99m-MAG3 were analyzed in healthy volunteers under control and OAT1 and OAT3 related drug treatment conditions. An in vitro uptake study using OAT1 or OAT3 expressing cells was also conducted. RESULTS: Both PAH and probenecid treatment induced delays in Tc-99m-MAG3 clearance from blood, and reductions in the renal uptake clearance. As a result, the normalized effective renal plasma flow estimated from Tc-99m-MAG3 clearance was significantly underestimated, whereas the glomerular filtration rate estimated from plasma creatinine levels was unchanged. The transport activity of Tc-99m-MAG3 was higher in OAT1-expressing cells than in OAT3-expressing cells. CONCLUSION: Drugs with OAT1 affinity affect the renal uptake of Tc-99m-MAG3 and blood clearance. This might cause misinterpretation of functional diagnosis of the kidney using Tc-99m-MAG3.

Granulomatosis with polyangiitis presenting as an orbital inflammatory pseudotumor: a case report.

INTRODUCTION: Granulomatosis with polyangiitis is a systemic inflammatory disease that often presents with necrosis, granuloma formation and vasculitis of small- to medium-sized vessels. Affected patients usually present with disease of the upper respiratory tract, lungs and kidneys, but this disease has been reported to involve almost any organ. We report the case of a patient with ocular manifestations of granulomatosis with polyangiitis after the remission of renal and auditory manifestations. CASE PRESENTATION: An 81-year-old Japanese woman had a four-year history of biopsy-proven antineutrophil cytoplasmic antibody-related glomerulonephritis that had been treated with oral prednisolone and was in serological remission. She had also recovered from a one-year history of complete hearing loss immediately following the steroid treatment for glomerulonephritis. She gradually experienced right eye visual disturbance and exophthalmos over a two-month period. Radiographic and histopathological findings revealed an orbital inflammatory pseudotumor. The administration of prednisolone completely restored her right eye visual acuity and eye movement after two weeks. Considering this case retrospectively, our patient had an orbital inflammatory pseudotumor caused by granulomatosis with polyangiitis including a medical history of reversible hearing loss, although her glomerulonephritis had remitted with an undetectable level of specific antineutrophil cytoplasmic antibody. CONCLUSIONS: In this patient, hearing loss and visual loss occurred at different times during the course of treatment of granulomatosis with polyangiitis. Clinicians should consider a differential diagnosis of granulomatosis with polyangiitis in patients with treatable hearing and visual loss.

Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report.

INTRODUCTION: L-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia. CASE PRESENTATION: A 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient's ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7µmol/L (normal range, 45 to 91µmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily). CONCLUSION: This case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient's serum ammonium levels.

Improvement of intradialytic hypotension in diabetic hemodialysis patients using vitamin E-bonded polysulfone membrane dialyzers.

Currently, there are no detailed reports on the effects of vitamin E-bonded polysulfone (PS) membrane dialyzers on intradialytic hypotension (IDH) in diabetic hemodialysis (HD) patients. This study was designed to evaluate changes in intradialytic systolic blood pressure (SBP) using "VPS-HA" vitamin E-bonded super high-flux PS membrane dialyzers. The subjects were 62 diabetic HD patients whose intradialytic SBP fell by more than 20%. Group A comprised patients who required vasopressors to be able to continue treatment or who had to discontinue therapy due to their lowest intradialytic SBP being observed at 210 min (28 patients). Group B comprised patients who showed no symptoms and required no vasopressors but showed a gradual reduction in blood pressure, with the lowest intradialytic SBP seen at the end of dialysis (34 patients). The primary outcome was defined as the lowest intradialytic SBP after 3 months using VPS-HA. Secondary outcomes included changes in the following: lowest intradialytic diastolic blood pressure, pulse pressure, pulse rate, plasma nitric oxide and peroxynitrite, serum albumin, and hemoglobin A1c. Group A's lowest intradialytic SBP had significantly improved at 3 months (128.0 ± 25.1 mm Hg vs. 117.1 ± 29.2 mm Hg; P = 0.017). Group B's lowest intradialytic SBP had significantly improved at 1 month (134.4 ± 13.2 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.047) and 3 months (139.1 ± 20.9 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.011). We conclude that VPS-HA may improve IDH in diabetic HD patients.

Assessment of Therapeutic Effect of Sunitinib by (11)C-Acetate PET Compared with FDG PET Imaging in a Patient with Metastatic Renal Cell Carcinoma.

Although sunitinib shows a high response rate in patients with untreated metastatic renal cell carcinoma (mRCC), quite a few patients show no therapeutic effect. Therefore, it is crucial to distinguish the patients who respond to sunitinib from those who do not as early as possible after the administration of the therapy. We herein report a case of mRCC in which (11)C-acetate (AC) positron emission tomography (PET) showed an early therapeutic effect of sunitinib treatment 4 weeks after its administration.

Urethral Sensations are Related to the Development of Detrusor Overactivity.

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C-fiber afferent nerves. α1A -adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A -adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.

[Present state of female urology].

This chapter critically reviews the literature on surgery for stress urinary incontinence (SUI) and pelvic organ prolapse (POP), and medical treatment for overactive bladder in women. The midurethral polypropylene sling was reported to provide a durable option with significant improvement. The tension-free vaginal tape (TVT) procedure is based on a theory of pathophysiology of stress incontinence presented by Petros and Ulmsten. In their "integral theory" impairment of the pubourethral ligament is one of the primary cause of SUI. The transobturator sling was found to be effective in SUI patients with less incidence of perioperative complications and voiding difficulties. Prolapse of the uterus/vaginal apex and posterior vaginal wall may also be found in women with stress incontinence. There are many procedures for the correction of POP. Transvaginal repair of anterior and posterior compartment prolapse with polypropylene mesh has been developed in recent years. It is necessary to assess and compare the current quality of outcomes.

Activation of vascular protein kinase C-beta inhibits Akt-dependent endothelial nitric oxide synthase function in obesity-associated insulin resistance.

Activation of protein kinase C (PKC) in vascular tissue is associated with endothelial dysfunction and insulin resistance. However, the effect of vascular PKC activation on insulin-stimulated endothelial nitric oxide (NO) synthase (eNOS) regulation has not been characterized in obesity-associated insulin resistance. Diacylglycerol (DAG) concentration and PKC activity were increased in the aorta of Zucker fatty compared with Zucker lean rats. Insulin-stimulated increases in Akt phosphorylation and cGMP concentration (a measure of NO bioavailability) after euglycemic-hyperinsulinemic clamp were blunted in the aorta of fatty compared with lean rats but were partly normalized after 2 weeks of treatment with the PKCbeta inhibitor ruboxistaurin (LY333531). In endothelial cell culture, overexpression of PKCbeta1 and -beta2, but not PKCalpha, -delta, or -zeta, decreased insulin-stimulated Akt phosphorylation and eNOS expression. Overexpression of PKCbeta1 and -beta2, but not PKCalpha or -delta, also decreased Akt phosphorylation stimulated by vascular endothelial growth factor (VEGF). In microvessels isolated from transgenic mice overexpressing PKCbeta2 only in vascular cells, Akt phosphorylation stimulated by insulin was decreased compared with wild-type mice. Thus, activation of PKCbeta in endothelial cells and vascular tissue inhibits Akt activation by insulin and VEGF, inhibits Akt-dependent eNOS regulation by insulin, and causes endothelial dysfunction in obesity-associated insulin resistance.

Characterization of protein kinase C beta isoform's action on retinoblastoma protein phosphorylation, vascular endothelial growth factor-induced endothelial cell proliferation, and retinal neovascularization.

Retinal neovascularization is a major cause of blindness and requires the activities of several signaling pathways and multiple cytokines. Activation of protein kinase C (PKC) enhances the angiogenic process and is involved in the signaling of vascular endothelial growth factor (VEGF). We have demonstrated a dramatic increase in the angiogenic response to oxygen-induced retinal ischemia in transgenic mice overexpressing PKC beta 2 isoform and a significant decrease in retinal neovascularization in PKC beta isoform null mice. The mitogenic action of VEGF, a potent hypoxia-induced angiogenic factor, was increased by 2-fold in retinal endothelial cells by the overexpression of PKC beta 1 or beta 2 isoforms and inhibited significantly by the overexpression of a dominant-negative PKC beta 2 isoform but not by the expression of PKC alpha, delta, and zeta isoforms. Association of PKC beta 2 isoform with retinoblastoma protein was discovered in retinal endothelial cells, and PKC beta 2 isoform increased retinoblastoma phosphorylation under basal and VEGF-stimulated conditions. The potential functional consequences of PKC beta-induced retinoblastoma phosphorylation could include enhanced E2 promoter binding factor transcriptional activity and increased VEGF-induced endothelial cell proliferation.