Robinow syndrome

Robinow syndrome is a rare congenital abnormality. It is characterized by mesomelic brachymelia, hemivertebrae, dysmorphic facies, genital hypoplasia, micropenis, clinodactyly, camptodactly, hypoplastic nails and moderate short stature. We are documenting the case on the account of its rarity and additional features.     

Effects of diabetes mellitus on the biomechanical properties of human ankle cartilage

Metabolic changes attributable to diabetes mellitus affect numerous organ systems in the body. For example, patients with diabetes have an increased number of musculoskeletal injuries and afflictions compared with patients without diabetes and experience more morbidity associated with injury and treatment. Although diabetes also may afflict articular cartilage, no studies have shown a conclusive link between diabetes and cartilage structural integrity. The objective of this study was to obtain and compare the intrinsic material properties of human ankle articular cartilage from patients with diabetes and those without diabetes. These biomechanical properties (aggregate modulus, Poisson's ratio, shear modulus, and permeability) were found to differ significantly between specimens from patients with diabetes and patients without diabetes. Specifically, cartilage from patients with diabetes was significantly softer and more permeable than cartilage from control subjects. For example, in the central portion of the talus, cartilage from patients with diabetes had a 38% smaller aggregate modulus, 37% smaller shear modulus, and 111% larger permeability than did tissue from patients without diabetes. These results provide evidence that joint pathologic processes in patients with diabetes may be associated with compromised structural integrity of articular cartilage.     

The effect of ultra-high molecular weight polyethylene wear debris on MG63 osteosarcoma cells in vitro

BACKGROUND: Focal osteolysis due to ultra-high molecular weight polyethylene wear debris involves effects on both bone resorption and bone formation. METHODS: The response of MG63 osteoblast-like osteosarcoma cells to ultra-high molecular weight polyethylene wear debris isolated by enzymatic digestion of granulomatous tissue obtained from the sites of failed total hip arthroplasties was examined. Scanning electron microscopy, particle-size analysis, and Fourier transform infrared spectroscopy were used to characterize the number, morphology, size distribution, and chemical composition of the particles. Cell response was assessed by adding particles at varying dilutions to confluent cultures and measuring changes in cell proliferation (number of cells and [3H]-thymidine incorporation), osteoblast function (alkaline-phosphatase-specific activity and osteocalcin production), matrix production (collagen production and proteoglycan sulfation), and local cytokine production (prostaglandin-E2 production). RESULTS: The mean size of the particles was 0.60 micrometer, and 95 percent of the particles had a size of less than 1.5 micrometers. The number of particles per gram of tissue ranged from 1.39 to 3.38x10(9). Three of the four batches of particles were endotoxin-free. Exposure of the cells to particles of wear debris significantly increased the number of cells (p<0.05) and the [3H]-thymidine incorporation (p<0.05) in a dose-dependent manner. In contrast, the addition of particles decreased alkaline-phosphatase-specific activity and osteocalcin production. Collagen production and proteoglycan sulfation were also decreased, while prostaglandin-E2 synthesis was increased by the addition of particles. CONCLUSIONS: Ultra-high molecular weight polyethylene particles isolated from human tissue stimulated osteoblast proliferation and prostaglandin-E2 production and inhibited cell differentiation and matrix production. These results indicate that particles of wear debris inhibit cell functions associated with bone formation and that osteoblasts may produce factors in response to wear debris that influence neighboring cells, such as osteoclasts and macrophages. CLINICAL RELEVANCE: Particles of wear debris, especially ultra-high molecular weight polyethylene, have been implicated in the loosening of implants and the development of osteolysis. The present study shows that particles of ultra-high molecular weight polyethylene isolated from human tissue inhibit osteoblast functions associated with bone formation. In addition, particles of wear debris induced osteoblasts to secrete factors capable of influencing neighboring cells, such as osteoclasts and macrophages. These results suggest that osteoblasts may play a role in the cascade of events leading to granuloma formation, osteolysis, and failure of orthopaedic implants.     

Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days.

PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting.     

MUC 1 core protein as a marker of gallbladder malignancy.

AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.