Time-dependent sensory nerve ingrowth into a bone conduction chamber

We studied time-dependent ingrowth of sensory nerve fibers into a bone defect in a rat bone conduction chamber model. In 10 male Sprague Dawley rats, a titanium chamber was implanted bilaterally in the proximal tibiae, representing an experimental bone defect. To mimic a clinical situation, the chambers were filled with a fresh blood clot. After 1, 2, 4, 6 and 8 weeks, 2 rats were fixed in vivo at each time before removal of specimens, and histological and immunohistochemical analyses. We used antisera against protein gene product 9.5, neural growth-associated protein 43/B-50, calcitonin gene-related peptide, and substance P, to locate regenerating sensory nerve fibers in the chamber. During bone defect healing, hematoxylin/eosin sections showed that new bone grew in through the ingrowth openings in the chamber, gradually filling it and replacing the blood clot. At 1 and 2 weeks after implantation, no nerve fibers could be detected. At 4, 6 and 8 weeks, however, small numbers of nerve fibers were seen in 8 of 11 specimens. The nerve fibers were located mainly in the dense fibrous tissue in close proximity to the new bone, and in some cases within the new forming bone. In this chamber model, the periosteum is not in contact with the bone ingrowth openings, and all ingrowing nerve fibers thus originated from the cortical bone, endosteum or bone marrow. We speculated that these late ingrowing sensory nerve fibers may actively participate in bone repair.     

Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor).

CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.     

Arterial stiffness in predialysis patients with uremia

BACKGROUND: Hemodialysis patients have advanced arterial wall stiffening as shown by increased aortic pulse wave velocity (PWV), an independent predictor of cardiovascular mortality. We compared aortic PWV of uremic patients before starting hemodialysis treatment with that of patients on maintenance hemodialysis. METHODS: The subjects were 71 patients with end-stage renal disease (ESRD) before starting hemodialysis (predialysis group), 144 patients on maintenance hemodialysis, and 140 healthy control subjects. These three groups were all nondiabetic and comparable in age and gender. RESULTS: The hemodialysis group had greater aortic PWV than the healthy subjects, and the predialysis patients showed a still higher value than the hemodialysis group. Multiple regression analysis in the total subjects revealed that the presence of renal failure was significantly associated with increased aortic PWV independent of age, gender, blood pressure, body mass index, smoking, high-density lipoprotein (HDL) and nonhigh-density lipoprotein (non-HDL) cholesterol levels. In contrast, hemodialysis was associated with decreased aortic PWV independent of renal failure and the other factors. Further analyses in the combined uremic patients again indicated the favorable impact of hemodialysis on aortic PWV independent of the classical risk factors, use of antihypertensive medications, including angiotensin-converting enzyme inhibitors and calcium channel blockers, hematocrit, serum calcium, phosphorus, parathyroid hormone levels, and the use of calcium carbonate. Insulin resistance using homeostasis model assessment (HOMA-IR) was associated with increased aortic PWV. CONCLUSION: Aortic stiffening was present in uremic patients before starting hemodialysis treatment and no adverse effect of hemodialysis was observed, suggesting the important roles of renal failure and/or metabolic alterations secondary to renal failure in arterial stiffness in patients with uremia.     

Human mesenchymal stem cells in synovial fluid increase in the knee with degenerated cartilage and osteoarthritis

We investigated whether mesenchymal stem cells (MSCs) in synovial fluid (SF) increased in the knee with degenerated cartilage and osteoarthritis. SF was obtained from the knee joints of 22 patients with anterior cruciate ligament (ACL) injury during ACL reconstruction, and cartilage degeneration was evaluated arthroscopically. SF was also obtained from the knee joints of 6 healthy volunteers, 20 patients with mild osteoarthritis, and 26 patients with severe osteoarthritis, in which the grading was evaluated radiographically. The cell component in the SF was cultured for analyses. Synovium (SYN) and bone marrow (BM) were also harvested during total knee arthroplasties. The MSC number in SF was correlated with the cartilage degeneration score evaluated by arthroscopy. The MSC number in the SF was hardly noticed in normal volunteers, but it increased in accordance with the grading of osteoarthritis. Though no significant differences were observed regarding surface epitopes, or differentiation potentials, the morphology and gene profiles in SF MSCs were more similar to those in SYN MSCs than in BM MSCs. We listed 20 genes which were expressed higher in both SYN MSCs and SF MSCs than in BM MSCs, and 3 genes were confirmed by quantitative RT-PCR. MSCs in SF increased along with degenerated cartilage and osteoarthritis.     

SLEEVEPASS: A randomized prospective multicenter study comparing laparoscopic sleeve gastrectomy and gastric bypass in the treatment of morbid obesity: preliminary results

Background

The long-term efficacy of laparoscopic Roux-en-Y gastric bypass (RYGB) in the treatment of morbid obesity has been demonstrated. Laparoscopic sleeve gastrectomy (SG) as a single procedure has shown promising short-term results, but the long-term efficacy of SG has not yet been demonstrated. The aim of this study was to determine the preliminary 30-day morbidity and mortality of RYGB and SG in a prospective multicenter randomized setting.

Methods

A total of 240 morbidly obese (BMI?=?35–66?kg/m2) patients evaluated by a multidisciplinary team were randomized to undergo either RYGB or SG. There were 117 patients in the RYGB group and 121 in the SG group; two patients had to be excluded after randomization. Both study groups were comparable regarding age, gender, BMI, and comorbidities.

Results

There was no 30-day mortality. The median operating time was significantly shorter in the SG group (66?min vs. 94?min, p?p?=?0.292). Nine (7.4 %) SG patients and 20 (17.1 %) RYGB patients had minor complications (p?=?0.023). The overall morbidity was 13.2 % after SG and 26.5 % after RYGB (p?=?0.010). There were three (2.5 %) early reoperations after SG and four (3.3 %) after RYGB (p?=?0.719).

Conclusions

At 30-day analysis SG is associated with a shorter operating time and fewer early minor complications compared to RYGB. There were no significant differences in major complications or early reoperations. Long-term follow-up is required to determine the effect on weight loss, resolution of obesity-related comorbidities, and improvement of quality of life.     

Ruptured aneurysm of a posterior inferior cerebellar artery communicating artery. Case report and histological findings

A hypertensive 60-year-old man presented with a rare aneurysm arising from the posterior inferior cerebellar artery (PICA) communicating artery, manifesting as subarachnoid hemorrhage with intraventricular hemorrhage. Angiography showed a small aneurysm arising from a fine and tortuous artery interconnecting the bilateral vermian branches of distal PICAs. The right PICA was absent and its vermian territory was supplied by the left PICA through this communicating artery. The right anterior inferior cerebellar artery was also connected to the vermian branch of the right PICA. At surgery, a reddish and apparent fusiform aneurysm was noted at the top of the arterial loop under the cerebellar vermis. Microsurgical trapping and removal of the aneurysm was performed without complication. Histological examination demonstrated typical findings of a true aneurysm. Only four previous cases of aneurysm of the communicating artery between the bilateral distal PICAs have been reported. In all five reported cases including ours, the PICA communicating artery contributed to the collateral blood supply of the contralateral vermian territory based on vascular anomalies. Hemodynamic stress and congenital vulnerability may have caused this aneurysm. Trapping is suitable to treat this precarious aneurysm if other collateral vessels supply the contralateral vermian territory.     

Postoperative liver dysfunction in living donors after left-sided graft hepatectomy: portal venous occlusion of the medial segment after lateral segmentectomy and hepatic venous congestion after left lobe hepatectomy

Background

The aim of this study was to evaluate how sacrifice of the portal vein and/or hepatic vein affects remnant liver dysfunction after lateral segmentectomy or left lobe hepatectomy.

Materials and methods

Among 130 patients who underwent donor hepatectomy between March 2002 and July 2011, we enrolled lateral segment (n = 15) and left lobe donors (n = 40). We evaluated the postoperative courses and the territory of venous obstruction or congestion based on the sacrificed portal vein or hepatic vein after the donor operation: lateral segment grafts (P4a, P4b, LV4) and left lobe grafts (MV5, MV8) according to the results analyzed by MeVis Distant Service.

Results

Among lateral segment donors, the predicted sacrificed territory of portal vein and hepatic vein was 14.3% (7.3%-19.4%) in P4a + 4b: (P4a: 8.6%, P4b: 5.8%) and 2.9% (0%-8.4%) in LV4, respectively. On the other hand, in left lobe donors, the predicted congestive territory of the hepatic vein was 17.6% (2.8%-33.0%) in MV5 + 8 (7.8% in MV5 and 9.8% in MV8, respectively). The incidence of patients whose postoperative peak aspartate aminotransferase (AST) or alanine aminotransferase levels were higher than 500 IU/L was 20% in the lateral segment donors and 5% in the left lobe donors. The peak postoperative AST levels and territory of MV5 + 8 showed a significant positive correlation (R = 0.569, P < .05) among left lobe donors.

Conclusion

Territories of P4 in lateral segment donors and MV5 + 8 in left lobe donors impacted postoperative liver dysfunction. It is important to recognize the precise territory of the portal vein and the hepatic vein before the donor operation.     

Living donor liver transplantation for the patients with portal vein thrombosis: use of an interpositional venous graft passed posteriorly to the pancreatic parenchyma without using jump graft

Background

It is difficult to reconstruct the portal vein (PV) using a long interpositional venous graft in living donor liver transplant (LDLT) patients with portal vein thrombosis (PVT), which involves the confluence of the superior mesenteric vein (SMV) and splenic vein (SV). We successfully performed LDLT for three patients with PVT using an interpositional vascular conduit passing posterior to the pancreas without a jump graft.

Methods

Three of 130 patients who underwent LDLT in our hospital between March 2002 and June 2011 required this technique. After indentifying the location of the SMV, SV and gastrocolic trunk, we ligated and cut the posterior superior pancreaticoduodenal vein and other short branches from the PV. The PV was drawn inferiorly to the pancreas and transected at the confluence of SMV and SV. The external iliac vein or internal jugular vein was sacrificed as a graft for anastomosis to the cut end of the SMV using 6-0 polypropylene running sutures. Then the venous graft was drawn superiorly to the pancreas by passing it posterior to the pancreas parenchyma for anastomosis to the liver graft PV. The interpositional vein was placed posterior to the pancreas where the PV used to be.

Results

All three patients displayed favorable postoperative courses with the Doppler ultrasound demonstrating good portal flow perioperatively. The postoperative portogram demonstrated patency of the vascular graft.

Conclusion

This method is easy and helpful to treat portal vein thrombosis, by providing the shortest route between the PV of the donor and the SMV of the recipient.     

Quadricuspid aortic valve associated with rapidly progressive aortic stenosis during chronic hemodialysis; report of a case

A 70-year-old man was referred to our department for surgical treatment for aortic valve stenosis. He was diagnosed with aortic regurgitation 30 years ago, but he was asymptomatic at that time. Ten years ago, chronic hemodialysis was instituted for diabetic nephropathy. In recent years, he became aware of nocturnal dyspnea and echocardiography revealed moderate aortic stenosis. After that, the symptom was getting worse and surgical treatment was indicated. We performed aortic valve replacement. Intraoperatively, we noticed his aortic valve was quadricuspid. The postoperative course was uneventful and he was discharged without complications. Quadricuspid aortic valve is rare congenital anomaly and patients are often operated on for aortic regurgitation. Our case is indicated for valve replacement because of aortic stenosis. In addition, there are a few reports of quadricuspid aortic valve associated with hemodialysis. We consider hemodialysis is one of the cause of rapid progression of aortic stenosis in this patient.     

Possible role of soluble erythropoietin receptors in renal anemia

Recombinant human erythropoietin(rHuEpo) is effective for the treatment of renal anemia associated with chronic renal failure(CRF). However, we have encountered some patients with CRF who have sometimes developed a resistance to rHuEpo. This resistance can be due to iron or folate deficiency, aluminum toxicity, hyperparathyroidism, or auto-antibodies for rHuEpo. In this study, we focused on the soluble erythropoietin receptor(sEpoR), which can bind to rHuEpo. To demonstrate the possibility that the sweeping of rHuEpo by sEpoR results in resistance to rHuEpo, we performed a bioassay using the rHuEpo-dependent cell line, UT7/EPO. The results showed that recombinant mouse sEpoR(rmsEpoR) can reduce the proliferation of UT7/EPO induced by rHuEpo in a dose-dependent manner. We consider that this cell line could be a useful tool in a bioassay to detect the inhibitory factor(s) against Epo. We selected sera from three groups of patients with renal anemia associated with CRF who were receiving hemodialysis three times a week: the first was a patient group that needed a high dose of rHuEpo(7,500-9,000 unit/dialysis), the second was a patient group that needed an intermediate dose of rHuEpo (4,500 unit/dialysis), the third was a patient group that needed a low dose of rHuEpo(below 1,500 unit/dialysis). Interestingly, the proliferation of UT7/EPO determined with [3H]-thymidine incorporation was reduced by the addition of sera from the first group, but not by the addition of sera from the third group. These results suggested that serum sEpoR may play an important role in signal transduction via EpoR on erythroid progenitor in CRF patients.