Osteoconductivity of Porous Titanium Structure on Implants in Osteoporosis.

In compromised bone conditions such as osteoporosis, developments of the implant surface are necessary to secure the stability of implants. This study investigated the effect of the surface porous titanium structure (PS) on the osseointegration of implants in osteoporotic bone. Bilateral ovariectomy (OVX) was performed in 4 female beagle dogs to induce osteoporosis for 32 wk. Success of induction was based on the evaluation of bone mineral density by Hounsfield units (HU) in computed tomography images. Posterior teeth in both mandibles were extracted 1 wk after OVX, and a total of 30 implants (15 implants in each group) were placed after 32 wk of osteoporosis induction. The control group implant underwent resorbable blast media (RBM) surface treatment, whereas the test group underwent RBM surface treatment in the coronal two-thirds and a PS added to the apical 3-mm portion. HU values in the mandibular trabecular bone, lumbar, and femoral head significantly decreased 32 wk after OVX, confirming osteoporotic condition after induction. Resonance frequency analysis and removal torque test showed comparable values between the 2 groups at 4 wk after implant placement. The surface topography of the implant after removal showed hard tissue integration at the PS in the test group. Bone-to-implant contact length was greater in the apical portion of the test group, although statistical significance was not found between the groups. Interthread bone area in the apical portion of the test group showed a significant increase compared to the control group (control: 0.059 ± 0.041 mm2, test: 0.121 ± 0.060 mm2, P = 0.028) with the histological feature of bone ingrowth at the PS. The findings of the study demonstrated that the surface PS could improve osteoconductivity in the osteoporotic trabecular bone by bone ingrowth at the pore space, thereby enhancing the osseointegration and stability of the implants.

Consensus statement from the international consensus meeting on post-traumatic cranioplasty.

BACKGROUND: Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. METHODS: The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. RESULTS: The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. CONCLUSIONS: This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

Demetylation of the sex-determining region Y gene promoter and incidence of disorder of sex development in cloned dog males.

Canine cloning is occasionally accompanied by abnormal sexual development. Some male donor cells produce cloned pups with female external genitalia and complete male gonadal dysgenesis, which is classified as an XY disorder of sex development (XY DSD). In this study, we examine the potential of 5-aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to reduce the phenotypic abnormality XY DSD in somatic cell nuclear transfer (SCNT)- derived pups. We used a 9-year-old normal male German Shepherd dog as a cell donor. Donor cells were treated with 10 nM 5-aza-dC for 4 days before being used for SCNT. At the same stage of cell development, significantly lower levels of DNA methylation of the sex-determining region Y (SRY) promoter was observed in the treated donor cells compared to that in the untreated cells (95.2% versus 53.3% on day 4 for the control and treated groups, respectively). No significant differences were observed in the control or treatment groups concerning fusion rate, pregnancy rate (30 days or entire period), the number of pups, or the incidence of XY DSD. However, more XY DSD dogs were observed in the control group (31.25%) than in the treatment group (14.29%). Hypermethylation of the SRY promoter was observed in the XY DSD cloned pups in both the treatment (84.8%) and control groups (91.1 ± 1.4%) compared to the methylation level in the phenotypically normal male pups of the treatment (23.2 ± 20.9%) and control groups (39.1 ± 20.1%). These results suggest that 5-aza-dC treatment of donor cells can reduce the methylation level of the SRY promoter in donor cells, and thus, 5-aza-dC is advantageous for reducing the incidence of XY DSD in canine cloning.

Soft Tissue Stability around Single Implants Inserted to Replace Maxillary Lateral Incisors: A 3D Evaluation.

Purpose. To evaluate the soft tissue stability around single implants inserted to replace maxillary lateral incisors, using an innovative 3D method. Methods. We have used reverse-engineering software for the superimposition of 3D surface models of the dentogingival structures, obtained from intraoral scans of the same patients taken at the delivery of the final crown (S1) and 2 years later (S2). The assessment of soft tissues changes was performed via calculation of the Euclidean surface distances between the 3D models, after the superimposition of S2 on S1; colour maps were used for quantification of changes. Results. Twenty patients (8 males, 12 females) were selected, 10 with a failing/nonrestorable lateral incisor (test group: immediate placement in postextraction socket) and 10 with a missing lateral incisor (control group: conventional placement in healed ridge). Each patient received one immediately loaded implant (Anyridge®, Megagen, Gyeongbuk, South Korea). The superimposition of the 3D surface models taken at different times (S2 over S1) revealed a mean (±SD) reduction of 0.057 mm (±0.025) and 0.037 mm (±0.020) for test and control patients, respectively. This difference was not statistically significant (p = 0.069). Conclusions. The superimposition of the 3D surface models revealed an excellent peri-implant soft tissue stability in both groups of patients, with minimal changes registered along time.

Role of bursectomy for advanced gastric cancer: result of a case-control study from a large volume hospital.

AIMS: According to the recent Japanese Gastric Cancer Association's gastric cancer treatment guidelines, bursectomy is recommended for tumors penetrating the serosa of the posterior gastric wall. However, there is still little data to show whether bursectomy improves patient survival. The aim of this study is to evaluate the efficacy of bursectomy for subserosa or serosa-positive gastric cancer in terms of overall survival. METHOD: From April 2001 to December 2006, 470 patients underwent curative resection for macroscopically subserosa or serosa-positive gastric cancer. These patients were grouped according to whether bursectomy was performed or not (bursectomy+/bursectomy-). Clinicopathological characteristics and incidence of complications were compared between the groups. The overall survival rates were analyzed using a Cox proportional hazards model. RESULTS: There was no significant difference in morbidity and mortality between the bursectomy+ and bursectomy- groups. In the multivariable analysis for overall survival, bursectomy was not a significant independent factor (p = 0.978). In the subgroup analysis for clinical and pathological stage III and IV, and tumors penetrating the serosa of the posterior gastric wall, bursectomy did not have significant effect on overall survival as well (p = 0.582, 0.453, and 0.532, respectively). In the propensity score-matched patients, bursectomy still showed no significant effect on overall survival (p = 0.804). CONCLUSIONS: Bursectomy is unlikely to improve overall survival in patients with macroscopically subserosa or serosa-positive gastric cancer.

Analysis of etching mechanism and etched slope control of silicon for nanoimprinting lithography.

In the nanoimprint lithography (NIL) process, profile control of imprint masters is a very important task. Therefore, we attempted to control the etched slope of imprint masters as a function of adding O2 to CF4 plasma. Etched profile mechanisms and relationships between the etch kinetics and plasma chemistry were explored using zero-dimensional-based modeling. O2 flow rate increased to 24 sccm, the Si etch rate increased in the range of 186-393 nm/min, while the etch rate rapidly decreased as the O2 flow rate increases beyond 24 sccm. Meanwhile, change in the etch rate of SiO2 followed a similar tendency as the etch rate of Si as a function of O2 flow rate in the CF4/O2 mixing gases. The Si and SiO2 etch rate were expected to be closely dependent on the F radical intensity in CF4/O2 mixing gases. Moreover, the results of simulated normalized lateral etch critical dimension (NLECD) are in agreement with the measured NLECD as a function of O2 flow rate in the CF4/O2 mixing gases.

Clinical and angiographic follow-up of spontaneous isolated superior mesenteric artery dissection.

OBJECTIVES: To observe the clinical features and angiographic findings in patients with a spontaneous isolated superior mesenteric artery dissection (SISMAD) and to identify any correlation between them. METHODS: From a single institution, 32 patients (22 symptomatic patients at presentation; mean age 54years; men 97%) with SISMAD were retrospectively reviewed. All patients were available for clinical follow-up after treatment (conservative, n=28, 88%, open or endovascular superior mesenteric artery (SMA) reconstruction, n=4, 12%), and follow-up CT scans were available in 28 patients (mean 22months, range 1-80months). RESULTS: We found a positive correlation between pain severity and dissection length (p=0.03, rho=0.50, Spearman's partial correlation analysis). After conservative treatment, only one patient (3%) required bowel resection, and there was no difference in outcome between patients who were treated with anticoagulation or anti-platelet therapy and those who were not (p=1.00, Fisher's exact test). No patients had progression of their lesion on the follow-up CT angiography. CONCLUSIONS: In SISMAD patients, dissection length is positively associated with more severe clinical symptoms. After conservative treatment, we observed a benign clinical course and no CT progression of the dissection, even without anticoagulation or anti-platelet therapy. Based on our observation, patients with SISMAD can be treated conservatively without anticoagulation therapy.

Effect of proximal arterial occlusion on the progression of the distal arterial disease.

PURPOSE: To test the hypothesis that a proximal arterial occlusion has a protective effect on the progression of distal arterial disease, assessed by distal runoff resistance score (DRRS). MATERIALS AND METHODS: One hundred and nineteen patients (median age 64 y, male 96%) with a unilateral iliac and/or femoral arterial occlusion caused by atherosclerosis were analyzed retrospectively. DRRS was assessed on arteriograms of the test limb (with proximal arterial occlusion) and control limb (contralateral limb). Multivariate analysis was performed to determine if a proximal arterial occlusion was an independent risk factor for the development of a difference in the DRRS between the test and control limbs. RESULTS: The clinical features of the subjects were claudication in 85%, ankle brachial index 0.52 (median), diabetes in 30% and smoker in 76%. The upper leg DRRS of the test limb was significantly lower in the iliac occlusion group than in the control limb (1.87+/-1.69 vs 2.85+/-2.75, p=0.032). However, multivariate analysis failed to identify any risk factors associated with the difference in DRRS in both limbs. CONCLUSION: There was no evidence that a proximal arterial occlusion was associated with a slower progression of distal arterial disease.

The 'four-in-one' procedure for habitual dislocation of the patella in children: early results in patients with severe generalised ligamentous laxity and aplasis of the trochlear groove.

We describe our experience with the 'four-in-one' procedure for habitual dislocation of the patella in five children (six knees). All the patients presented with severe generalised ligamentous laxity and aplasia of the trochlear groove. All had a lateral release, proximal 'tube' realignment of the patella, semitendinosus tenodesis and transfer of the patellar tendon. The mean age at the time of the operation was 6.1 years (4.9 to 6.9), and the patients were followed up for a mean of 54.5 months (31 to 66). The clinical results were evaluated using the Kujala score. There has been no recurrence of dislocation. All the patients have returned to full activities and the parents and children were satisfied with the clinical results. The mean Kujala score was 95.3 (88 to 98). Two patients had marginal skin necrosis which healed after debridement and secondary closure. These early results in this small group have shown that the 'four-in-one' procedure is effective in the treatment of obligatory dislocation of the patella in children with severe ligamentous laxity and trochlear aplasia.

Preparation of 153Sm-chitosan complex for radiation synovectomy.

A samarium 153-chitosan complex was prepared by simply mixing acidic solutions of chitosan and (153)SmCl(3). When a solution of this complex was injected into the knee joints of rabbits, minimal extra-articular leakage was observed. This can be attributed to the rapid change in the pH of the complex solution from acidic to neutral, resulting in the formation of gel followed by the subsequent retention in the administered site. Thus, the complex solution represents a promising candidate for radiation synovectomy.

Structural and functional alterations of the peritoneum after prolonged exposure to dialysis solutions: role of aminoguanidine.

OBJECTIVE: The effect of long-term use of high glucose dialysate on peritoneal structure and function, and its relation with accumulation of advanced glycosylation end-product (AGE) in the peritoneum was investigated in this study. METHODS: Dialysates with 4.25% glucose were injected into the peritoneal cavity of normal rats for 12 weeks without (PD, n = 7) and with (1 g/L, PD+AG, n = 7) aminoguanidine in their drinking water. Rats not having intraperitoneal (IP) injection served as control (n = 9). After 12 weeks of IP injection, a 2-hour peritoneal equilibration test (PET) was performed using 30 mL 4.25% glucose dialysate. Intraperitoneal volume (IPV), dialysate-to-plasma urea ratio at 2 hours (D/P2), the ratio of dialysate glucose at 2 hours to initial dialysate glucose (D2/D0), and the peritoneal fluid absorption rate (Qa) were evaluated. After the PET, samples of the parietal peritoneum were taken for hematoxylin and eosin (H&E) staining and immunohistochemical staining for AGE. RESULTS: The IPV and D2/D0 glucose were significantly lower and Qa and D2/P2 urea significantly higher in the PD group than in the control group. Aminoguanidine reversed in part the changes in IPV and D2/P2 urea in the PD group; it had no effect on Qa and D2/D0 glucose. The H&E staining showed a linear mesothelial lining with negligible cells and capillaries in the narrow submesothelial space in the control group. Mesothelial denudation and submesothelial infiltration of monocytes and capillary formation were observed in the PD group. Mesothelial denudation was relatively intact in the PD+AG group compared with the PD group. Submesothelial monocyte infiltration and capillary formation in the PD+AG group were not as prominent as in the PD group. Positive AGE staining was found in the submesothelial space, vascular walls, and endomysium in the PD group, while it was markedly attenuated in PD+AG group and negligible in the control group. CONCLUSION: Long-term use of high glucose solutions induced peritoneal AGE accumulation and mesothelial denudation, and increased peritoneal permeability and peritoneal fluid absorption rate. Inhibition of peritoneal AGE accumulation prevented those functional and structural damages to the peritoneum.

Malignant esophagogastric junction obstruction: palliative treatment with an antireflux valve stent.

The authors assessed the efficacy of an antireflux valve stent in the palliation of malignant esophagogastric junction (EGJ) obstruction after in vitro testing of the stent. Seventeen patients with inoperable malignant EGJ obstruction were treated. Antireflux valves, made of three polyurethane leaflets, were attached to the distal part of the stent to prevent reflux. When the flow rate of normal saline was 100 mL/sec in the forward direction, the valve fully opened at a pressure of 10 mm Hg. When the flow rate of normal saline was 0.35 mL/sec in the backward direction, the valve nearly completely closed at a pressure of 10 mm Hg. Stent placement was successful in all patients without complications. The median dysphagia score decreased significantly, from 3.0 (dysphagia to liquids) to 1.0 (dysphagia to normal solid food) (P < .0005). No patients experienced reflux symptoms. There was one case of stent migration. A valve stent that can prevent major reflux is an effective device for the palliation of malignant EGJ obstruction.

Malignant obstruction of gastric outlet and duodenum: palliation with flexible covered metallic stents.

PURPOSE: To assess the usefulness of flexible covered metallic stents in the palliation of malignant obstruction of the gastric outlet and duodenum. MATERIALS AND METHODS: Twenty-four consecutive patients with malignant obstruction of the gastric outlet (n = 22) or duodenum (n = 2) underwent palliative treatment with self-expandable flexible covered metallic stents. Fourteen patients had advanced gastric carcinoma at the antrum and/or pylorus, and eight had obstruction at the anastomosis site of previous gastrojejunostomy. Complications and clinical status were investigated during the study period. RESULTS: The technical success rate was 75% (18 of 24 patients). Twenty-one stents were placed in 18 patients by using an introducer 6 (n = 7) or 8 mm (n = 14) in diameter. The mean follow-up period was 3.4 months (range, 1 week to 9 months). Symptoms improved in 12 (67%) patients after the procedure. There was no change in symptoms in five and a decrease in one. Twelve patients died during the follow-up period (mean survival, 4.3 months). The complication rate was 25% (six of 24 patients), including stent migration (n = 5) and fracture (n = 3). CONCLUSION: Flexible covered metallic stent placement can be useful for palliation in patients with malignant obstruction of the gastric outlet or duodenum.

Influence of reduced glutathione on the proliferative response of sulfamethoxazole-specific and sulfamethoxazole-metabolite-specific human CD4+ T-cells.

1. Hypersensitivity to the drug sulfamethoxazole (SMX) is thought to be a consequence of bioactivation to the hydroxylamine metabolite (SMX-NHOH) and further oxidation to the ultimate reactive metabolite, nitroso-sulfamethoxazole (SMX-NO). SMX-NO covalently modifies self proteins which in turn might be recognized as neo-antigens by T-cells. The antioxidant glutathione (GSH) is known to protect cells from reactive metabolites by conjugation and subsequent dissociation to SMX-NHOH and/or SMX. 2. To study the reactivity of T-cells to SMX metabolites and their respective role in the generation of drug-specific T-cells, we analysed the effect of GSH on the response of PBMC to SMX and its metabolites SMX-NHOH and SMX-NO. Furthermore, we monitored the proliferative response of drug-specific T-cell clones in the presence or absence of GSH. 3. We found that addition of GSH to peripheral blood mononuclear cells had no effect on the SMX-specific response but enhanced the proliferation to SMX-metabolites. The response of SMX-NO-specific T-cell clones was abrogated when GSH was present during the covalent haptenation of antigen presenting cells (APC). Conversely, SMX-specific T-cell clones gained reactivity through the conversion of SMX-NO to the parent drug by GSH. While GSH had no effect on the initial activation of T-cell clones, it prevented covalent binding to APCs, reduced toxicity and thereby led to proliferation of drug-specific T-cells to non-reactive drug metabolites. 4. Our data support the concept that in allergic individuals T-cells recognize the non-covalently bound parent drug rather than APC covalently modified by SMX-NO.

Diagnostic pitfalls in the cholangiographic diagnosis of choledochoceles: cholangiographic quality and its effect on visualization.

BACKGROUND: We wanted to establish reasonable cholangiographic diagnostic criteria by determining the sensitivity of cholangiography in detecting choledochoceles and those factors that could compromise visualization of choledochoceles. METHODS: Over 4 years, 21 patients (seven male, 14 female; mean age = 67 years) were confirmed as having choledochoceles on endoscopic retrograde cholangiopancreatography (ERCP). Cholangiographic diagnosis was made by following three criteria: a radiolucent halo around the distal common bile duct (CBD), bulbous dilatation of the distal CBD, and the presence of sequential morphologic changes on serial cholangiography. Any two or more combinations of these three criteria were considered enough to diagnose a choledochocele on cholangiography. We compared cholangiographic imaging findings with the ERCP results. RESULTS: Of 21 patients with choledochoceles, nine (43%) were correctly diagnosed on cholangiography. A radiolucent halo was present in six (28%) patients; four of these cases showed optimal duodenal filling, one showed faint duodenal filling, and one showed poor duodenal filling. The shapes of the distal CBD were bulbous, conelike, and blunt. Morphologic changes such as collapsing and bulging of the choledochocele could be seen in 12 (57%) patients on serial cholangiography. Waists were seen in 11 (52%), pseudowebs in four (19%), and wrinkling of the distal CBD in seven (33%). CONCLUSION: Cholangiography should be obtained with optimal timing and adequate conditions to diagnose choledochocele correctly.

Measurement of radiation absorbed dose in endovascular Ho-166 brachytherapy using a balloon angio-catheter.

The purpose of this study was to estimate the absorbed dose distribution of Ho-166 endovascular beta irradiation using an angio-catheter. The liquid form of Ho-166 was produced at the Korea Atomic Energy Research Institute (KAERI) by an (n,gamma) reaction. Ho-166 has a half-life of 26.8 h and emits a high-energy beta particle with a maximum energy of 1.85 MeV. GafChromic film was used for the estimation of the absorbed dose of beta particles. A Co-60 teletherapy source and a 6 MV photon beam from a linear accelerator were used to generate dose-optical density calibration curves. The exposed films were read using a videodensitometer. With a modified micrometer, the film was positioned accurately on the surface of the balloon in water. The balloon was filled with Ho-166 solution to a pressure of 4 atm. Several film exposures were made with varying irradiation times and activities. The radiation absorbed dose rates were 1.02, 0.51 and 0.35 Gy x min(-1) x GBq(-1) x ml(-1) at the balloon surface, 0.5 and 1 mm from the balloon surface, respectively. The absorbed dose distribution revealed that Ho-166 is a good source for endovascular irradiation as the beta range is very short, avoiding unnecessary irradiation of normal tissue. A clinically applicable irradiation and duration of exposure were achievable utilizing our system.

Effect of transcatheter endovascular radiation with holmium-166 on neointimal formation after balloon injury in porcine coronary artery.

BACKGROUND: Neointimal formation in response to arterial injury is a major contributing element in restenosis after coronary balloon angioplasty and stenting. Endovascular irradiation has been reported to be effective in reducing restenosis. The purpose of this study was to investigate the effect of beta-emitting holmium-166 for the inhibition of neointimal formation in porcine coronary artery. METHODS AND RESULTS: A total of 34 pigs weighing 25 to 30 kg underwent oversized balloon injury (balloon/artery ratio, 1.3:1.4) at the proximal portion of the left anterior descending and circumflex arteries. One artery was randomly assigned to receive radiation after injury. Ho-166 was left in the balloon within the delivery catheter for a period sufficient to deliver 9 Gy and 18 Gy to a depth of 1 mm from the surface of the balloon. Four weeks later, pigs were sacrificed and hearts were perfusion-fixed, followed by histopathologic analysis and planimetry for measurement of maximal intimal thickness, intimal area, and fracture length. The coronary segment of the pigs in the control group had neointimal area of 1.18+/-0.55 mm2; the pigs in the 9-Gy group had neointimal area of 0.68+/-0.40 mm2 (P<.05 vs. control); and the pigs in the 18-Gy group had neointimal area of 0.29+/-0.12 mm2 (P<.01 vs. control). The maximal intimal thickness in the 18-Gy group (0.14+/-0.11 mm) was significantly reduced compared with the maximal intimal thickness in the control group (0.48+/-0.13 mm) (P<.01). CONCLUSIONS: Intracoronary radiation with liquid Ho-166 contained in a perfusion balloon catheter is feasible and effective in reducing neointimal formation after coronary overstretch injury in pigs. Therefore intracoronary irradiation on the injured segment may further reduce restenosis after balloon injury.

Treatment of Bowen's disease with a specially designed radioactive skin patch.

Bowen's disease can be treated by various methods, including surgical excision, cryosurgery, laser ablation, curettage, Mohs' microsurgery and ionizing radiation. Radiotherapy has been a useful therapeutic modality in the treatment of Bowen's disease and other skin cancers in areas which are difficult to excise, especially the central areas of the face, including eyelids, nose and lips. To overcome some of the disadvantages of external radiotherapy, a specially designed skin patch coated with high-energy beta-emitter holmium-166 was made for topical application at our institute. Twenty-nine sites of Bowen's disease in eight patients, confirmed by skin biopsy, were treated with 166Ho patches. The patches were applied to the surface of skin cancers for 30-60 min for a total radiation dose of 35 Gy (3500 rads). One to two weeks after application of the 166Ho patch, desquamation, erythema or erosion developed in treated sites, but these acute radiation reactions healed gradually with epithelial regeneration, and they showed good functional and cosmetic results without any complications. Follow-up biopsies were performed 1-5 months after 166Ho patch therapy, and they did not show any signs of Bowen's disease. One to two years after treatment with 166Ho skin patches, there were no recurrences of Bowen's diseases and no late complications. The 166Ho patch is an effective and convenient alternative method for the treatment of Bowen's disease that yields good cosmetic and functional results.