Platelet-rich plasma combined with hydroxyapatite for lumbar interbody fusion promoted bone formation and decreased an inflammatory pain neuropeptide in rats

STUDY DESIGN.: A prospective interventional trial, using a rat model of lumbar interbody fusion. OBJECTIVE.: To examine the potential efficacy of platelet-rich plasma (PRP) for lumbar interbody fusion, using hydroxyapatite (HA). SUMMARY OF BACKGROUND DATA.: PRP is an autologous product containing a high concentration of platelets in a small volume of plasma and has osteoinductive effects. HA has osteoconductive ability and has been used in combination with autogenous bone for spine fusion. However, reports using PRP with HA for spine fusion are very few. The purpose of this study was to examine the efficacy of PRP with HA for spinal interbody fusion and at the same time to estimate the change in immunoreactivity of the inflammatory neuropeptide, calcitonin gene-related peptide (CGRP), in dorsal root ganglion (DRG) neurons innervating spinal discs. METHODS.: A total of 35 Sprague-Dawley rats were used in this study. Twenty-one rats were used for conducting interbody fusion experiments, 7 rats were used as immunostaining controls, and 7 other rats were used as blood donors for making PRP. L5-L6 interbody fusion was performed on 21 rats using HA + PRP (n = 7), HA + platelet-poor plasma (n = 7), or HA + saline (n = 7). Simultaneously, Fluoro-Gold neurotracer was applied to the intervertebral space to detect DRG neurons innervating the discs. L5-L6 lumbar radiographs were obtained and lumbar DRGs were immunostained for CGRP. The rate of bone union and the change in CGRP immunoreactive DRG neurons innervating the discs were evaluated and compared among groups. RESULTS.: All L5-L6 lumbar discs were fused in the PRP + HA group (fused 7/total 7), whereas only 1 case was fused in the platelet-poor plasma group (1 of 7) and no cases in the HA-only group (0 of 7), which was a significant difference. Upon immunohistochemical analysis, CGRP-positive neurons innervated L5-L6 intervertebral discs in nonunion cases, and these were significantly increased compared with those in union cases. CONCLUSION.: Our study suggests that using PRP with HA was beneficial for spine fusion. This combination may promote bone union and also decrease inflammatory neuropeptide in sensory neurons innervating the discs.     

Effect of pulsatile left ventricular assist system implantation on Doppler measurements of renal hemodynamics in patients with advanced heart failure

The effects of left ventricular assist system (LVAS) implantation on renal hemodynamics remains to be fully elucidated. We evaluated renal function and intrarenal blood flow in five advanced heart failure patients who had been supported with a Toyobo LVAS for bridge to heart transplantation. Renal function expressed as estimated glomerular filtration rate (eGFR) was calculated using the modified formula of Modification of Diet in Renal Disease. Mean blood velocities in the bilateral segmental arteries during systolic and diastolic perfusion were measured using duplex Doppler sonography, and renal vascular resistance (resistive index [RI]) of the segmental arteries was defined as (peak systolic velocity [PSV]-end-diastolic velocity [EDV])/PSV. All studies were performed before and after implantation (mean duration of support, 15.6±10.9 months). LVAS implantation significantly improved eGFR (42.7±7.9 to 64.1±16.3mL/min, P<0.05). Beat-by-beat measurements of heart rate did not change significantly. Mean PSV decreased significantly (38.2±8.9 to 28.3±2.2cm/s, P<0.05), and mean EDV increased significantly (8.3±3.2 to 11.3±1.3cm/s, P<0.05), and thus, mean RI was significantly improved (0.79±0.06 to 0.60±0.04, P<0.01). In conclusion, in advanced heart failure patients, pulsatile LVAS implantation is associated with improved renal function, and this improvement may be mediated in part through an improvement of intrarenal hemodynamics.     

Surgical treatment of hip dislocation in Kabuki syndrome: use of incomplete periacetabular osteotomy for posterior acetabular wall deficiency

Purpose

Kabuki syndrome is characterized by distinctive facial features, skeletal anomalies, persisting fingertip pads with dermatoglyphic abnormalities, postnatal growth deficiency and mental retardation. This report reviews our results in the operative treatment of hip dislocations in patients with Kabuki syndrome.

Methods

Between 2001 and 2009, seven dislocated hips (three unilateral and two bilateral hips) in five patients (all girls) were operatively treated at our institution. The operative treatment consists of open reduction, femoral derotation varus osteotomy, pelvic osteotomy (Salter in one and incomplete periacetabular osteotomy in six hips) and capsular plication. The age of the patients at the time of surgery ranged from 2.4 to 5.7 years, with an average of 3.6 years.

Results

The follow-up postoperative period ranged from 3.2 to 6.3 years, with an average of 5.0 years. At the final follow-up, all patients reported no click and no pain, and showed well-contained hips by radiographs. All seven hips were graded as Severin class I-II. One patient presented as having habitual dislocation of the hip 4.4 years after surgery. Computed tomographic (CT) scans revealed posterior acetabular wall deficiency, which was not corrected by the anterolaterally directed Salter osteotomy. The incomplete periacetabular osteotomy provided sufficient posterolateral coverage of the acetabulum.

Conclusion

Operative treatment combining open reduction, femoral derotation varus and incomplete periacetabular osteotomies, and capsular plication provided successful results in patients with Kabuki syndrome who had the characteristics of hip instability such as ligamentous laxity, muscular hypotonia and posterior acetabular wall deficiency.     

Efficacy of rhBMP-2 during distraction osteogenesis

Background Osteoinductive ability of bone morphogenetic protein-2 (BMP-2) has been studied in recent reports. In this study, we evaluated the efficacy of BMP-2 during distraction osteogenesis. Methods A group of 24 Japanese white rabbits were divided into four groups randomly and underwent lengthening of the right femur. Distraction was performed for 2 weeks (1.0 mm/day). Group A began distraction following a 7-day waiting period after surgery. For all other groups (B–D), distraction was started immediately after surgery. Groups A and B did not undergo any surgical intervention at the osteotomy site, as a control. The delivery system for rhBMP-2 used a polymer-coated gelatin sponge (PGS). Buffer/PGS was implanted into the osteotomy site in group C, and group D received rhBMP-2/PGS. Callus was evaluated radiographically at 1, 2, 4, and 6 weeks after the surgery, and all rabbits were killed at 6 weeks. One rabbit from each group was examined histologically; the remaining five rabbits underwent biomechanical testing. Results A significant increase in callus formation was evident in group D compared with that in other groups. In group D, regenerative changes were evident during the earlier phase. Formation of bone cortex and bone marrow cavity was almost complete in group D, and the cortex was thicker than that in the other groups. Torsional strength values (10⁻² Nm) of each group were as follows: A, 118.7 ± 52.4; B, 160.0 ± 40.7; C, 106.8 ± 8.1; D, 266.1 ± 93.1. Stiffness values (10⁻³ Nm/degree) were as follows: A, 390.2 ± 137.2; B, 391.8 ± 158.4; C, 183.1 ± 78.5; D, 624.4 ± 214.2. Group D exhibited the highest values for both torsional strength and stiffness. Conclusions Acceleration of the regenerative changes during the early phase occurred in the BMP-2-treated group. The efficacy of BMP-2 in distraction osteogenesis was recognized radiographically, histologically, and by biomechanical testing (torsional strength and stiffness).     

Vascular endothelial growth factor restores erectile function through inhibition of apoptosis in diabetic rat penile crura

PURPOSE: Vascular endothelial growth factor (VEGF) is known as a multifunctional protein with roles in angiogenesis stimulation and apoptosis inhibition. We hypothesized that intracavernous administration of VEGF would recover erectile dysfunction due to diabetes by protection from apoptosis in the penile cavernosum. MATERIALS AND METHODS: A total of 30, 6-month-old male Sprague-Dawley rats were divided into 2 large groups, namely 20 with diabetes and 10 healthy controls. The diabetic group received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Intracavernous injection of VEGF was administered to randomly selected STZ diabetic rats 6 weeks after STZ injections. Erectile functional studies were performed in 10 STZ and 10 STZ plus VEGF rats at 12 weeks. After completion of the functional study the penile crura were collected for molecular and immunohistochemical studies. RESULTS: Mean intracavernous pressure in the diabetic group was significantly lower than in controls and low pressure was significantly recovered by VEGF treatment. Gene expression of pro-apoptotic and anti-apoptotic factors were present in the control, diabetic and VEGF treated groups. However, anti-apoptotic protein expression was lacking in the diabetic group and it was recovered by VEGF treatment. The apoptotic index in the diabetic group was significantly higher than in controls and this index was significantly decreased in the VEGF treated group. CONCLUSIONS: The decrease in and recovery of intracavernous pressure correlated significantly with a variation in anti-apoptotic protein expression in the diabetic and VEGF treated groups. To our knowledge this is the first study to show that intracavernous injection of VEGF restores erectile dysfunction through the inhibition of apoptosis in diabetic rats.     

The number of metastatic lymph nodes: a promising prognostic determinant for gastric carcinoma in the latest edition of the TNM classification

Background: The number of metastatic regional lymph nodes determines the new pN categories in the 5th edition of the TNM classification.

Study Design: Our retrospective study was conducted to compare the new method of defining lymph node status with the conventional classification, consisting of the anatomic extent of lymph node metastases, a well-established prognostic factor. The study was based on clinical data for 493 patients with gastric carcinomas who underwent potentially curative operations and had histologically confirmed nodal metastases. These patients were stratified into 1) n categories according to the Japanese Classification of Gastric Carcinoma, 2) the new pN categories, and 3) the pN categories determined by the number of metastatic perigastric nodes resected by standard D1 gastrectomy. Survival data were analyzed for each group.

Results: The number of metastatic nodes after D2 lymphadenectomy reflected prognosis well and was shown by multivariate analysis to be a strong independent prognostic factor. When the classification was performed limited to the metastatic perigastric nodes, stage migration was evident, but the variable remained competent as a prognostic indicator.

Conclusions: The number of metastatic nodes is a promising determinant in the new international stage classification.     

Traumatic dislocation of the hamate and pisiform: a case report and review of the literature

Isolated dislocation of the hamate bone and pisiform bone is rare. We describe the simultaneous complete dislocation of both the hamate and pisiform bones in a 27-year-old man who crushed his right hand in a rolling press. An open reduction and internal fixation with Kirschner wires was performed. Four weeks later, the Kirschner wires were removed and rehabilitation was started. At 6 months follow-up, the patient had minimal pain and full range of motion in the affected wrist joint and fingers. However, grip strength was 50% compared to his unaffected left hand, and sensation of the ulnar nerve area was reduced to almost 30% of that of his left hand. It appears that the ulnar nerve injury was the largest contributing factor to the poor outcome of our patient. Evaluation of soft-tissue injuries, especially nerve injury, is important in the treatment of complex carpal dislocations.     

Herbert screw fixation of capitellar fractures

From 1993 to 2003, 6 patients with displaced fractures of the humeral capitellum were treated by open reduction and internal fixation of the capitellar fragments with Herbert bone screws. By use of the criteria of Grantham et al, there were 2 type II-A fractures, 1 type II-B fracture, 1 type II-C fracture, and 2 type III-A fractures. A lateral approach was used in 4 patients and a posterior approach with olecranon osteotomy in 2. The elbows were immobilized postoperatively for 4 to 28 days (mean, 13.5 days). We evaluated the range of motion, stability, and pain using the criteria of Grantham et al. The follow-up period ranged from 2.5 to 9.3 years (mean, 5.6 years). All patients had a stable, pain-free elbow with good range of motion at follow-up. All fractures healed, and there was no evidence of avascular necrosis or degenerative change.     

Attenuation of cartilage degeneration by calcitonin gene‐related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice

Osteoarthritis (OA) is a progressive joint disorder which affects cartilage and subchondral bone. Calcitonin gene‐related peptide (CGRP) plays a role in bone metabolism. The purpose of this study is to examine the therapeutic effect of the blocking CGRP on OA progression in mice by inhibition of subchondral bone sclerosis. OA was induced by the resection of the medial meniscotibial ligament of the knee in C57/BL6 mice. An intraperitoneal injection of the CGRP receptor antagonist (BIBN4096) was administered after OA surgery. At 1, 4, and 8 weeks after injection, histological analysis were performed. In vitro, the effect of CGRP and BIBN4096 on osteogenesis and osteoclastogenesis was analyzed. BIBN4096 could prevent cartilage degeneration and subchondral bone sclerosis. The OARSI score in the BIBN4096 group was significantly lower than that in the control. In vitro, CGRP up regulated osteocalcin expression, but its expression was down regulated by BIBN4096. CGRP inhibited osteoclastogenesis of raw 267.4 cells, but its effect was reduced by the addition of BIBN4096.The current study showed that subchondral bone sclerosis and increasing expression of CGRP occurs in the early phase of OA in relation to cartilage degeneration, and that BIBN4096 could effectively attenuate OA progression. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1177–1184, 2016.