Pyridoxal phosphate prevents progression of diabetic nephropathy.

BACKGROUND: We have demonstrated that pyridoxal 5'-phosphate (PLP), an active form of vitamin B6, inhibits formation of advanced glycation end-products (AGEs) by trapping 3-deoxyglucosone. The present study aimed to clarify if PLP could exert beneficial effects on nephropathy in diabetic rats. METHODS: Streptozotocin (STZ)-induced diabetic rats were treated by oral administration of PLP or pyridoxamine (PM), another active form of vitamin B6, at a dose of 600 mg/kg/day for 16 weeks. AGEs [imidazolone, N(epsilon)-(carboxymethyl)lysine (CML) and N(2)-carboxyethyl-2'-deoxyguanosine (CEdG)], transforming growth factor-beta1 (TGF-beta1), type 1 collagen and fibronectin were detected in the kidneys using immunohistochemistry. Gene expression of TGF-beta1 and receptor for AGEs (RAGEs) in the kidneys was determined using real-time quantitative polymerase chain reaction. RESULTS: Administration of PLP significantly inhibited albuminuria, glomerular hypertrophy, mesangial expansion, and interstitial fibrosis as compared with diabetic rats. PLP markedly inhibited accumulation of AGEs such as imidazolone, CML and CEdG, a DNA-linked AGE, in glomeruli. PLP significantly inhibited expression of TGF-beta1, type 1 collagen, fibronectin and RAGE in the kidneys. PLP was superior to PM in inhibiting accumulation of AGEs, expression of TGF-beta1, type 1 collagen, and fibronectin, and the development of diabetic nephropathy. CONCLUSIONS: PLP prevented progression of nephropathy in STZ-induced diabetic rats by inhibiting formation of AGEs. PLP is considered a promising active form of vitamin B6 for the treatment of AGE-linked disorders such as diabetic nephropathy.     

Classification systems for tibial plateau fractures; Does computed tomography scanning improve their reliability?

Introduction

The purpose of this study was to evaluate the impact of computed tomography scanning on the inter- and intra-observer reliability of the OTA/AO, the Schatzker, and the Hohl classifications in the assessment of tibial plateau fractures.

Methods

Four independent observers classified 45 consecutive fractures of the tibial plateau according to the criteria of the OTA/AO system, the Schatzker classification, and the Hohl classification. Two sessions of readings were compared; first, the use of plain anterior-posterior and lateral X-rays alone was evaluated, then 4 weeks later the combination of plain X-rays and two-dimensional computed tomography scans were evaluated. The readings were repeated 8 weeks later to evaluate intra-observer reliability.

Results

The three classification systems showed “moderate” inter-observer reliability and “good” and “moderate” intra-observer reliability when classified solely on the basis of plain radiographs. After the addition of computed tomography scans inter-observer reliability significantly improved to “good” in all classifications. Likewise, intra-observer reliability improved to “good” in all classifications after the addition of CT-scans. Statistical analysis showed no significant difference regarding inter- and intra-observer agreement between the three classifications.

Conclusions

Computed tomography scanning improved the inter- and intra-observer reliability of the OTA/AO, the Schatzker, and the Hohl classification. Overall, all three classification systems showed “good” inter- and intra-observer reproducibility when classified with CT-scans.     

Transient demineralization of the hip--case report]

Transient osteoporosis of the hip is an uncommon disorder of unclear etiology. It is often confused with other diagnosis including osteonecrosis of the femoral head. Authors describe a case of transient osteoporosis of the hip of 32 years woman. The symptoms occurred in third trimester of pregnancy. The primary symptoms were right hip pain and decreased range of motion of the right hip. In diagnostic process helpful were clinical examination, X-ray, ultrasonography, MRI and microscopic examination. As a treatment authors used walking on crutches, calcitonin and calcium preparate. After a few months remission of symptoms and normalization in accessory investigations were obtained.     

Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer

PURPOSE: We assessed the relationship between GnRH agonists and the risk of clinical fractures in men with prostate cancer. MATERIALS AND METHODS: Using a database of medical claims from 16 large American companies we identified a study group of 3,779 men with prostate cancer who received treatment with a GnRH agonist and a control group of 8,341 with prostate cancer who were not treated with a GnRH agonist. Men with 1 or more medical claims for bone metastases were excluded. The rates of any clinical fracture, hip fracture and vertebral fracture were compared between the groups. RESULTS: The rate of any fracture was 7.91/100 vs 6.55/100 person-years at risk in men who received vs did not receive a GnRH agonist (relative risk 1.21, 95% CI 1.09 to 1.34). The rates of hip fracture (relative risk 1.76, 95% CI 1.33 to 2.33) and vertebral fracture (relative risk 1.18, 95% CI 0.94 to 1.48) were also higher in men who received a GnRH agonist. GnRH agonist treatment was independently associated with fracture risk on multivariate analyses. CONCLUSIONS: GnRH agonists increase the risk of clinical fracture in men with prostate cancer.     

Long-Term Results of a Contemporary Metal-on-Metal Total Hip Arthroplasty : A 10-Year Follow-Up Study

The goal of the study was to evaluate the long-term results of a metal-on-metal articulation. We evaluated the results and histologic findings in patients who had undergone revision. One hundred total hip arthroplasties with a Lubrimet metal-on-metal articulation (Smith and Nephew, Rotkreuz, Switzerland) were implanted in 99 consecutive unselected patients in 1995 and 1996, and the results were prospectively analyzed up to a mean of 126 months postoperatively. Periprosthetic tissues of all 6 hips that had undergone revision because of aseptic loosening, mechanical failure, or periprosthetic fracture showed metallosis and extensive lymphocytic and plasma cell infiltration around the metal debris. With removal of the component because of aseptic loosening as the end point, survivorship was 98% for the stem and 96% for the cup.     

Immune response to perforated and partially demineralized bone allografts

Immune responses have been shown to be involved in the pathogenesis of clinical complications of cortical bone allografts. In an attempt to reduce the immunogenicity of these allografts, we evaluated cortical bone allografts modified by laser perforation and partial demineralization transplanted orthotopically into sheep tibiae. The recipient animals were divided into three groups, of eight animals each, according to the type of cortical allograft that was transplanted: group 1, no treatment (control); group 2, demineralization only; and group 3, laser perforation and partial demineralization. All animals were tissue-typed by biochemical definition of MHC class I molecules, using unidimensional isoelectric focusing and Western blotting. Mismatches of donors and recipients were assessed by testing samples of each donor and recipient pair in parallel and by comparing their individual bands. Donor-specific alloantibodies were detected by a similar technique, using an enzyme-linked immunosorbent assay (ELISA) format. Negative controls were included in all tests. All grafts were poorly immunogenic, whether they were untreated, processed by partial demineralization, or processed by both laser perforation and partial demineralization. Only two recipient animals showed a transient, antibody-mediated donor-specific immune response. One of these animals had received a control allograft, whereas the other animal had received a laser-perforated and partially demineralized bone allograft. All of the grafts in this study, including control grafts, were stripped of soft tissues and their bone marrow was removed; cellular sources of alloantibody stimulation may have been eliminated by these processes. The results of this study suggest that immune responses to bone allografts may be reduced by removing the bone marrow and adjacent soft tissues. The processing of cortical bone allografts by laser perforation and partial demineralization appeared to have little effect on immune responses.     

Clinical use of an epinephrine-reduced (1/400,000) articaine solution in short-time dental routine treatments--a multicenter study

The addition of epinephrine in dental local anaesthesia results in a longer and deeper anaesthesia under almost ischemic conditions. For short-time dental treatments, epinephrine-reduced anaesthetics may offer shorter and more individual anaesthesia with reduced potential side effects. The aim of this study was a clinical evaluation of anaesthetic potency and adverse effects of an epinephrine-reduced articaine formulation in dental patients undergoing short-time routine treatment. In a prospective clinical, not interventional, study between January 2008 and February 2009, 908 patients undergoing short-time dental treatment in five medical centers were anaesthetized with 4% articaine 1:400,000 epinephrine (Ubistesin, 3M/ESPE, Seefeld, Germany). Efficacy and safety in clinical use were evaluated. A follow-up after 1 day was conducted by telephone survey. A mean amount of 1.3-ml anaesthetic solution was needed to achieve a complete or sufficient anaesthesia in 97% (n = 876) of cases. A second injection had to be done in 3.7% (n = 34) before and in 11.9% (n = 108) during treatment. Here, the second injection had to be applied after a mean of 48.6 min. The mean duration of soft tissue anaesthesia after infiltration was 146.6 min, after nerve block 187.7 min. The painful treatment took a mean of 50.2 min and the total treatment time summed up to 68.8 min. In 1.7% cases (n = 15), unwanted side effects were observed. The results indicate that a lower concentration of epinephrine in combination with the 4% articaine solution leads to a high success rate of efficacy. The clinical use of a 4% articaine 1:400,000 epinephrine solution can be stated as safe and effective in short dental routine treatments. Reconsiderations concerning limitations of indication or additional contraindications are not necessary.