Megalin contributes to the early injury of proximal tubule cells during nonselective proteinuria

Megalin, a member of the LDL receptor family, is expressed on the apical membrane of proximal tubules and serves as an endocytic scavenger of filtered proteins and hence might contribute to the tubule injury as a consequence of glomerular disease. To study its role, we crossed megalin knockout mosaic mice (lacking megalin expression in 60% of proximal tubule cells) with NEP25 mice (a transgenic line expressing human CD25 in the podocyte). Treatment of this transgenic mouse with the immunotoxin causes nephrotic syndrome, focal segmental glomerulosclerosis and tubule-interstitial injury. Following this treatment, the double transgenic mice had massive non-selective proteinuria and mild glomerular and tubular injury. Comparison of megalin-containing to megalin-deficient proximal tubule cells within each kidney showed that albumin, immunoglobulin light chain, IgA and IgG were preferentially accumulated in proximal tubule cells expressing megalin. Tubule injury markers such as heme-oxygenase-1, monocyte chemoattractant protein-1 and cellular apoptosis were also preferentially found in these megalin-expressing cells. These results show that megalin plays a pivotal role in the reabsorption of small to large molecular size proteins and provides direct in vivo evidence that reabsorption of filtered proteins triggers events leading to tubule injury.     

Relationship between serum pre-B cell colony-enhancing factor/visfatin and atherosclerotic parameters in chronic hemodialysis patients

Pre-B cell colony-enhancing factor (PBEF)/visfatin is produced by adipose tissue, skeletal muscle, bone marrow, the liver and lymphocytes. Although serum PBEF/visfatin is related to the pathogenesis of atherosclerosis, and its level is elevated in patients with chronic kidney disease, it remains unclear whether increased PBEF/visfatin is associated with atherosclerotic parameters in hemodialysis (HD) patients. In this study, we measured serum PBEF/visfatin in 68 chronic HD patients (age 66 +/- 14 years, time on HD 76 +/- 76 months, 41 males, 27 females) and examined the association of serum PBEF/visfatin with serum asymmetric dimethylarginine, arteriosclerotic parameters such as pulse wave velocity, ankle brachial pressure index and the percent of abdominal aortic wall calcification in a cross-sectional fashion. Serum PBEF/visfatin was significantly correlated with time on HD (r = 0.29, p = 0.02), but not with age, gender and diabetes. There was no association between PBEF/visfatin and body mass index, abdominal visceral and subcutaneous fat mass area, and total adiponectin. Serum PBEF/visfatin was significantly positively correlated with log-transformed highly sensitive C-reactive protein (r = 0.26, p < 0.05) but negatively with serum albumin (r = -0.33, p < 0.01). In contrast, there was no association between serum PBEF/visfatin and asymmetric dimethylarginine, aortic pulse wave velocity, brachial ankle pressure index and percent of abdominal aortic wall calcification. It follows from these findings that serum PBEF/visfatin may reflect the inflammatory status rather than atherosclerotic changes in chronic HD patients.     

Chondroblastic osteosarcoma arising from the pleura: Report of a case

Extraskeletal osteosarcoma is an uncommon malignant neoplasm. The origin of osteosarcoma in the pleura is extremely rare, with only four such cases so far documented in the literature to the best of our knowledge. We herein report the case of a 64-year-old Japanese man in whom a left pneumonectomy and pleurectomy were carried out to remove a huge tumor. The pathological examination confi rmed a diagnosis of chondroblastic osteosarcoma that had originally arisen from the pleura.     

Two-surgeon technique using saline-linked electric cautery and ultrasonic surgical aspirator in living donor hepatectomy: its safety and efficacy

Background

Saline-linked electric cautery (SLC) is introduced as an effective device to reduce blood loss in liver surgery. The aim of the current study was to evaluate the safety and efficacy of a 2-surgeon technique using SLC and the Cavitron Ultrasonic Surgical Aspirator (CUSA; Valleylab, Boulder, CO) in living donor hepatectomy.

Methods

Forty-three living donor right hepatectomy cases were enrolled in this study. The first 28 cases underwent liver transection with CUSA alone (CUSA group), while additional SLC was applied in the current 15 cases (2-surgeon technique, TS group).

Results

Blood loss was significantly reduced by the 2-surgeon technique (1,115.2 ± 652.9 g in CUSA group vs 732.3 ± 363.6 g in TS group, P < .05). In the TS group, there was no bile leakage from the cut surface. The early graft function and postoperative recipient survival were not significantly different between the groups.

Conclusions

According to our single-center experience, blood loss and donor complications in living donor hepatectomies were significantly reduced using a 2-surgeon technique using CUSA and SLC, while maintaining the graft viability.     

Synthetic bioabsorbable stent material for duct-to-duct biliary reconstruction

Biliary stricture remains a significant cause of morbidity after liver transplantation. We performed duct-to-duct biliary anastomosis by using an absorbable stent tube with a diameter equal to that of pig common bile duct as an internal stent. The stent tube was constructed using a synthetic biodegradable material-a lactic glycolic acid and epsilon-caprolactone copolymer. Three pigs were alive without cholestasis for 180 d; however, 1 pig died on the 65th postoperative d, and autopsy revealed no cholestasis or biliary sledge in the biliary stent tube. The 3 pigs were euthanized for histological examinations 180 d after surgery; the biliary stent tube was completely absorbed by this time. These experimental results showed the good patency of the absorbable biliary stent tube. In the future, the absorbable biliary stent tube is expected to be clinically developed as a biliary stent for biliary anastomosis, which may protect the biliary anastomotic stricture.     

Successful repair for a giant coronary artery aneurysm with coronary arteriovenous fistula complicated by both right- and left-sided infective endocarditis

We report a rare case of a 65-year-old woman who underwent an emergent lifesaving heart operation for an undiagnosed right coronary artery aneurysm with a coronary arteriovenous fistula complicated by active infective endocarditis, which affected the aortic valve, mitral valve, and coronary sinus. We performed direct closure of the coronary arteriovenous fistula, ligation of the right coronary artery aneurysm, double coronary artery bypass grafting, and double valvular replacement. Five years after the operation, she had no sign of congestive heart failure or infection, and was not receiving antibiotics.     

Cardiac valvular surgery in dialysis patients: comparison of surgical outcome for mechanical versus bioprosthetic valves

Purpose  There has been a changing preference for bioprosthetic valves over mechanical valves in dialysis patients, but there is still much controversy. We reviewed our 17-year experience and assessed the influence of prosthesis choice. Methods  From 1990 to 2007, a total of 63 consecutive dialysis patients who underwent valvular surgery (64 operations including one reoperation) at our hospital were retrospectively reviewed. The mean age of the patients was 58.3 ± 9.0 years. The reasons for dialysis were glomerulonephritis (n = 32) and diabetes (n = 10). The major preoperative diagnosis was aortic stenosis (n = 44). The surgical procedures included aortic valve replacement (n = 44), mitral valve replacement (n = 7), double valvular replacement (n = 7), and mitral valve repair (n = 5). Prostheses for valve replacement were mechanical valves (n = 37) or bioprosthetic valves (n = 22). Follow-up was accomplished in 95.2%, and the mean follow-up period was 49 months. Results  Actuarial survivals at 1, 5, and 10 years were 85%, 64%, and 45% respectively. Freedom from cardiovascular events at 1 and 5 years was 61% and 41%, respectively. Mechanical valve patients had significantly higher early mortality than bioprosthetic valve patients (P = 0.03). However, both mechanical and bioprosthetic valve patients had similar survival and event-free rates (P = 0.87 and P = 0.27, respectively) in the midterm results. The mechanical group had a higher rate of bleeding events. There was no structural valve deterioration up to the 5-year follow-up. Conclusion  The choice of prosthesis did not influence the surgical outcome except for early mortality. Careful consideration of preventive measures against bleeding is important, and prosthesis selection should be based on the patient’s profile as well as the criteria for nondialysis patients.     

Post-chemotherapy nerve-sparing retroperitoneal lymph node dissection for advanced germ cell tumor

Objective:   To report our experience with post-chemotherapy nerve-sparing retroperitoneal lymph node dissection (RPLND) for advanced germ cell tumor (GCT).
Methods:   Between 1994 and 2008, 92 patients with advanced GCT underwent RPLND after multiple treatments with systemic chemotherapy at our institution. A nerve-sparing RPLND was carried out in 78 patients (84.8%; median age 32 years). Of them, 19 had a seminoma and 59 had a non-seminoma.
Results:   Lumbar splanchnic nerves controlling ejaculatory function were macroscopically preserved during RPLND. Bilateral and unilateral lumbar splanchnic nerves were preserved in 40 patients and 38 patients, respectively. Sixty-five patients could be evaluated for ejaculation. Fifty-four patients (83.1%) achieved antegrade ejaculation with a median postoperative interval of 3 months (range: 1–10 months). Twenty-eight patients (28/30: 93.3%) and 26 patients (26/35: 74.3%) undergoing bilateral and unilateral nerve-sparing RPLND had antegrade ejaculation, respectively ( P  = 0.041). Only two patients (2.6%) had mediastinal and retroperitoneal recurrences during a median follow-up of 42 months (range: 1–138 months), respectively. However, these patients were cured by chemotherapy and surgery.
Conclusions:   Post-chemotherapy nerve-sparing RPLND preserves ejaculatory function in the majority of patients with advanced GCT without increasing the risk of local recurrence.     

Quantitative in vivo biocompatibility of new ultralow‐nickel cobalt–chromium–molybdenum alloys

Nickel (Ni) eluted from metallic biomaterials is widely accepted as a major cause of allergies and inflammation. To improve the safety of cobalt–chromium–molybdenum (Co–Cr–Mo) alloy implants, new ultralow‐Ni Co–Cr–Mo alloys with and without zirconium (Zr) have been developed, with Ni contents of less than 0.01%. In the present study, we investigated the biocompatibility of these new alloys in vivo by subcutaneously implanting pure Ni, conventional Co–Cr–Mo, ultralow‐Ni Co–Cr–Mo, and ultralow‐Ni Co–Cr–Mo with Zr wires into the dorsal sides of mice. After 3 and 7 days, tissues around the wire were excised, and inflammation; the expression of IL‐1β, IL‐6, and TNF‐α; and Ni, Co, Cr, and Mo ion release were analyzed using histological analyses, qRT‐PCR, and inductively coupled plasma mass spectrometry (ICP‐MS), respectively. Significantly larger amounts of Ni eluted from pure Ni wires than from the other wires, and the degree of inflammation depended on the amount of eluted Ni. Although no significant differences in inflammatory reactions were identified among new alloys and conventional Co–Cr–Mo alloys in histological and qRT‐PCR analyses, ICP‐MS analysis revealed that Ni ion elution from ultralow‐Ni Co–Cr–Mo alloys with and without Zr was significantly lower than from conventional Co–Cr–Mo alloys. Our study, suggests that the present ultralow‐Ni Co–Cr–Mo alloys with and without Zr have greater safety and utility than conventional Co–Cr–Mo alloys. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1505–1513, 2016.     

Effect of depression and neuropathic pain using questionnaires on quality of life in patients with low back pain; cross-sectional retrospective study

Purpose

The present study investigated the percentage of low back pain (LBP) patients who have depressive symptoms and neuropathic pain and analyzed the effects of these on the quality of life (QOL) in these patients.

Methods

Of the 650 new patients with LBP that visited the hospital between June 2012 and December 2013, 309 patients who completed questionnaires to assess LBP and QOL were included in the study. The questionnaire included demographic items, the self-rated depression scale (SDS)-Zung, the Japanese version of the PainDETECT questionnaire (PDQ-J), numerical pain rating scale (NRS), and QOL assessments. The patients were divided into two groups according to their SDS-Zung scores: a nondepressed group with SDS scores <40 and a depressed group with SDS-Zung scores ≥50.

Results

One hundred twenty-five patients (40.5 %) were classified as nondepressed and 63 (20.4 %) as depressed. The mean PDQ-J score was higher in depressed patients than in nondepressed patients. The frequency of neuropathic pain was greater in depressed patients, with neuropathic pain observed in 17 of the 63 (27 %) depressed LBP patients and 11 of the 125 (9 %) nondepressed LBP patients. The SDS-Zung and PDQ-J scores of LBP patients were correlated significantly (r = 0.261, p < 0.001). Depressed patients had higher pain NRS scores and lower QOL scores compared with nondepressed patients.

Conclusions

Both the depressed patients and those with neuropathic LBP had a higher level of pain, greater pain-related disability, and poorer QOL compared with nondepressed patients. This is the first study to use the SDS-Zung and PDQ-J screening questionnaires to estimate the presence of neuropathic pain associated with depressive symptoms in LBP patients and to evaluate the impact of these on QOL.