Single Nucleotide Polymorphisms in Cytokine Genes are Associated with the Susceptibility to Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of cancer among men in the Indian subcontinent. Cytokines regulate inflammation and angiogenesis in a variety of cancers. Genetic variability in the cytokine genes can potentially influence the predisposition to oral carcinogenesis. The aim of the current study was to investigate the associations of SNPs in cytokine genes with the susceptibility of oral squamous cell carcinoma. In the present study, we have analyzed the allelic frequency of 32 single nucleotide polymorphisms (SNPs) using MassArray-based iPLEX assay in 16 cytokine genes in 166 OSCC patients and 151 healthy subjects from central India. Out of 32 SNPs analyzed, five SNPs were significantly associated with the risk of OSCC. AA and GG genotypes of IL-1ß +3953 were associated with an increased and decreased risk of OSCC, respectively. In several genetic models, GG genotype and G allele in IL-12A 3'UTR G>A were found to be associated with an increased risk of OSCC. Similarly, the GG genotype of IL-12B +1188 T>G was associated with increased susceptibility to OSCC. We conclude that SNPs in the genes coding for IL-1ß, IL-12A and IL-12B are associated with increased genetic susceptibility to OSCC in the central Indian population.

Stem cells research prospects towards precision medicine.

The human body possesses an endogenous regeneration system based on stem cells, which may be found in practically every tissue type. They are classified as embryonic stem cells (ESCs) or nonembryonic stem cells (NESCs). Despite its enormous promise, the use of ESCs is presently limited because of ethical and scientific issues. Stem cells have the potential to improve healthcare by using and boosting the body's inherent regenerative capabilities. Although the stem cells offer an enormous promise for tissue regeneration and repair, much more about their biology, administration, and safety must be studied before they may be employed therapeutically. Stem cells and their derivatives will have enormous medical promise in the future. Current animal and laboratory investigations are looking into the viability of bringing stem cell therapy into clinical practice for regeneration in muscular dystrophy, intervertebral disc degeneration, cerebral infarctions, and transplantation medicine. This article delves into the many aspects at play, as well as current situation and possible issues with stem cell treatment in patient care and management (Fig. 1, Ref. 86). Keywords: stem cells, tissue engineering, regenerative medicine, stem cell application.

Prolonged asymptomatic venom induced consumption coagulopathy: Caused by hemotoxic snake bite.

Envenoming and deaths resulting from snake bite are a particularly important public health problem in the tropical world, with the highest burden in rural areas of South East Asia and Africa. Snake bite is one of the most severe "Neglected Tropical Diseases" in the world and more importantly in this part of India. We present a case of hemotoxic snake bite where the coagulation parameters remained deranged for a longer time without any active bleeding manifestations, despite treatment with Anti-Snake Venom (ASV) as per the National Treatment Guidelines. Indian Snake Bite Management Protocol emphasizes on the Role of Whole Blood Clotting Time (WBCT) as a bedside, accessible and feasible test for assessment of coagulopathy even in rural settings. Certain scenarios where the patients present late to our hospital with Snake Bite and Venom Induced Consumption Coagulopathy (VICC), the decision regarding ASV prescription in such patients is quite tricky, and needs to be individualized.

Epithelial TNF Receptor Signaling Promotes Mucosal Repair in Inflammatory Bowel Disease.

TNF plays an integral role in inflammatory bowel disease (IBD), as evidenced by the dramatic therapeutic responses in Crohn's disease (CD) patients induced by chimeric anti-TNF mAbs. However, treatment of CD patients with etanercept, a decoy receptor that binds soluble TNF, fails to improve disease. To explore this discrepancy, we investigated the role of TNF signaling in Wnt/ß-catenin-mediated intestinal stem cell and progenitor cell expansion in CD patients, human cells, and preclinical mouse models. We hypothesized that TNF exerts beneficial effects on intestinal epithelial cell (IEC) responses to injury. In CD patients, intestinal stem cell and progenitor cell Wnt/ß-catenin signaling correlates with inflammation status. TNF-deficient (Tnf-/-) mice exhibited increased apoptosis, less IEC proliferation, and less Wnt signaling when stimulated with anti-CD3 mAb. Bone marrow (BM) chimera mice revealed that mucosal repair depended on TNF production by BM-derived cells and TNFR expression by radioresistant IECs. Wild-type→Tnfr1/2-/- BM chimera mice with chronic dextran sodium sulfate colitis exhibited delayed ulcer healing, more mucosal inflammation, and impaired Wnt/ß-catenin signaling, consistent with the hypothesis that epithelial TNFR signaling participates in mucosal healing. The direct effect of TNF on stem cells was demonstrated by studies of TNF-induced Wnt/ß-catenin target gene expression in murine enteroids and colonoid cultures and TNF-induced ß-catenin activation in nontransformed human NCM460 cells (TOPFlash) and mice (TOP-GAL). Together, these data support the hypothesis that TNF plays a beneficial role in enhancing Wnt/ß-catenin signaling during ulcer healing in IBD. These novel findings will inform clinicians and therapeutic chemists alike as they strive to develop novel therapies for IBD patients.

Dislocation Intermediate Cuneiform with Fracture Medial Cuneiform.

INTRODUCTION: Dislocation of intermediate cuneiform is a rare injury in English language literature. Dislocation of intermediate cuneiform with undisplaced medial cuneiform fracture has been reported only once. We report the first case of dislocation intermediate cuneiform with displaced medial cuneiform fracture. CASE REPORT: A 43-year-old male was diagnosed of dislocation of intermediate cuneiform with fracture medial cuneiform after a road traffic accident. This was treated by a method of distractor application that is only reported in navicular fracture dislocation. This treatment method avoids open reduction with minimal of complications and good outcome. CONCLUSION: Distractor technique was applied for the first time in cuneiform fracture dislocation in this case, and we recommend it to avoid open reduction. The previous reported injuries in this region were mostly treated by open reduction. Due to the rarity of this injury and technique, our case adds to the literature a novel reduction method.

Coronal shear fractures of distal humerus: Diagnostic and treatment protocols.

Coronal shear fractures of distal humerus involving the capitellum and the trochlea are rare injuries with articular complexity, and are technically challenging for management. With better understanding of the anatomy and imaging advancements, the complex nature of these fractures is well appreciated now. These fractures involve metaphysealcomminution of lateral column and associated intraarticular injuries are common. Previously, closed reduction and excision were the accepted treatment but now preference is for open reduction and internal fixation with an aim to provide stable and congruent joint with early range of motion of joint. Various approaches including extensile lateral, anterolateral and posterior approaches have been described depending on the fracture pattern and complexity. Good to excellent outcome have been reported with internal fixations and poor results are noted in articular comminution with associated articular injuries. Various implants including headleass compression screws, minifragment screws, bioabsorbable implants and column plating are advocated for reconstruction of these complex fractures. Inspite of articular fragments being free of soft tissue attachments the rate of osteonecrosis and osteoarthritis is reported very less after internal fixation. This article summarizes the diagnostic and treatment strategies for these rare fractures and recommendations for management.

Traumatic bilateral posterior hip dislocation in 10 year old male child.

Traumatic bilateral posterior hip dislocation in skeletally immature patient is reported very less in literature. We report a 10 yr old boy presented to us following farmyard injury with bilateral posterior hip dislocation, which was reduced manually under sedation with uneventful follow-up and complete hip range of motion at 2 year.

Periprosthetic subtrochanteric femoral fracture in a megaprosthesis of the knee.

We report a rare case of periprosthetic posttraumatic fracture of subtrochanteric region of femur after a megaprosthesis of the knee, done for resistant nonunion of distal femur with secondary osteoarthrosis in a 51 years old man. Treatment with a locking femoral plate was able to achieve primary union with a good result.

Correlation between severity of chronic kidney disease and thyroid dysfunction.

Kidneys play a significant role in thyroid hormone metabolism by conversion of thyroxine (T4) to triiodothyronine (T3) and abnormal thyroid function tests are frequently observed in patients of chronic kidney disease. The aim of present study was to analyse the thyroid function in patients of chronic kidney disease and its correlation with severity of kidney disease. Fifty patients of chronic kidney disease were included. All patients were on conservative management and were divided into 3 groups. Those with creatinine clearance < 7.5 ml/minute were placed in group A (n = 21), with creatinine clearance 7.5 - 15 ml/minute in group B (n = 21) and with creatinine clearance > 15 ml/minute in group C (n = 8). Thyroid profile was studied in all patients. The results were compared to age and sex matched healthy controls. Thirty-five patients (70%) of chronic kidney disease were found to be having abnormal thyroid functions. The mean values of serum total T3, free T3, total T4, free T4 were significantly reduced and that of thyroid stimulating hormone (TSH) were significantly higher in cases as compared to controls and these abnormities in thyroid function test increased as the creatinine clearance decreased (from group C to group A). It is concluded that thyroid dysfunction occurs in patients with chronic kidney disease. Mean values of TT3, FT3, TT4, FT4 reduced and that of TSH increased as severity of renal failure increased.

Outcome of surgical treatment of type IV capitellum fractures in adults.

OBJECTIVE: Fractures of the capitellum and trochlea constitute less than 1% of all elbow fractures and a shear fracture involving the capitellum and extending medially into most of the trochlea is rarely reported. Type IV capitellum fracture is still controversial in regard to its radiographic appearance, surgical approach and osteosynthesis. We report 10 cases of type IV capitellum fracture with a view to elucidating its clinical features and treatment outcome. METHODS: We treated 10 patients of type IV capitellum fracture with a mean age of 32 years. A uniform surgical approach and postoperative rehabilitation were followed. RESULTS: Nine patients presented to us after a mean of 4 days of injury and one patient was nonunion after 6 months of injury who had been treated conservatively by a bone setter. Double arc sign was absent in 6 cases. Intraoperatively 6 capitellotrochlear fragments were devoid of soft tissue attachments. By Mayo Elbow Performance Score evaluation, 7 patients got excellent, 2 good and 1 fair results. One patient with associated elbow dislocation developed heterotopic ossification. There was no case of avascular necrosis, osteoarthrosis or fixation failures. CONCLUSIONS: Type IV capitellum fractures are rare and belong to complex articular injuries. A good functional outcome can only be achieved with open reduction and stable internal fixation followed by early mobilization. Preoperative radiographic assessment and computed tomography help surgeons in choosing the right surgical approach and implants. Good surgical technique and stable internal fixation are the keys to early mobilization and good functional outcome.

In vitro antioxidant and free radical scavenging activity of Nardostachys jatamansi DC.

In this study, the antioxidative potential of a hydroalcoholic extract of Nardostachys jatamansi (NJE) rhizomes was evaluated by various antioxidant assays, including antioxidant capacity by the phosphomolybdenum method, total antioxidant activity in linoleic acid emulsion systems, 1,1-diphenyl-2-picrylhydrazyl (DPPH), superoxide, hydroxyl radicals, nitric oxide (NO) scavenging, metal chelating and reducing power activity. These various antioxidant activities were compared with standard antioxidants such as butylated hydroxytoluene, tocopherol, catechin, and L-ascorbic acid. Total phenolic and flavonoid content of NJE was also determined by a colorimetric method. The extract exhibited high reduction capability and powerful free radical scavenging, especially against DPPH and superoxide anions as well as a moderate effect on NO. Moreover, the peroxidation inhibiting activity of NJE was demonstrated in the linoleic acid emulsion system. The results obtained in the present study clearly established the antioxidative potency of NJE, which may account for some of the medical claims attributed to this plant.

Neglected floating fifth metacarpal: a case report.

Simultaneous dislocation of the metacarpophalangeal and carpometacarpal joint has been previously reported. Floating metacarpals occur when the metacarpal head displaces volarly and the base displaces towards the dorsal side. A closed dislocation at both ends of the fifth ray is unusual. In this study, we report a neglected case of floating fifth ray and its management along with a review of the literature.

Monteggia fracture dislocation equivalents--analysis of eighteen cases treated by open reduction and internal fixation.

OBJECTIVE: Monteggia fracture dislocation equivalent, though already described by Bado, is still an unclassified entity. We aimed to retrospectively analyze 18 cases of Monteggia variants and discuss the injury mechanisms, management, and outcome along with a review of the literature. METHODS: A retrospective record of Monteggia fracture dislocation (2003-2008) was reviewed from medical record department of our institute. Classic Monteggia fracture dislocation, children below 12 years or adults over 50 years, as well as open grade II and III cases were excluded from this study. Monteggia variant inclusion criteria included fracture of the proximal ulna together with a fracture of the radial head or neck and skeletal maturity. Totally 26 patients were identified with Monteggia variants and 18 were available for follow-up, including 11 males and 7 females with the mean age of 35 years. The ulna fracture was treated by compression plating along with tension band wiring. Radial head/neck was reconstructed in 12 patients while excised in 6 patients. RESULTS: Follow-up ranged from 1-4 years, mean 2.6 years. Patients were assessed clinicoradiologically. Mayo Elbow Performance Score was employed to assess the outcomes. At final follow-up, the results were excellent in 10 patients, good in 4, fair in 2 and poor in 2. Mean range of motion of the elbow was 20 degree 116 degree, 50 degree and 55 degree for extension, flexion, pronation and supination, respectively. Two patients had complications in the form of heterotopic ossification and stiffness of the elbow. One nonunion ulna, primarily treated by tension band wiring, was managed by refixation with locking reconstruction plate and bone grafting. Bone grafting was only required in this patient for nonunion. Another patient had implants removed on his request. The results in our series closely correlated with extent of intraarticular damage, coronoid fracture and comminuted fractures. CONCLUSIONS: Monteggia fracture dislocation equivalents are rare injuries and pre-surgery recognition by radiographs and 3-D CT helps make optimal plan. The poor results usually relate to intraarticular damage, coronoid fractures and comminution of the ulna and radial head fractures.

Nonunion of coronal shear fracture of femoral condyle.

Isolated coronal fractures of femoral condyle are rare in adults and nonunion of Hoffa fracture is reported only a few times in the literature. We analyzed six cases of nonunion of Hoffa fractures over a period of three years. Three patients were treated conservatively and three patients had fixation failures. Delay of presentation was 2 months to one year. Treatment protocol consisted of open reduction, excision of pseudoarthrosis, bone grafting and internal fixation along with knee arthrolysis. Union was achieved in all patients at mean 16 weeks. The treatment of nonunion of Hoffa fractures requires careful preoperative planning and meticulous surgical technique. The literature regarding the controversies in fracture management and surgical technique are reviewed.