Biomedical subjects
Publications and source records attributed to R K Sinha.
Two hundred and nineteen children treated with Ciprofloxacin were observed for drug related adverse reactions (ADR). ADR was observed in 35/219 (15.98%) children, arthropathy in 2/219 (0.9%) children only. All the ADR were reversible even on continuation of therapy except one child with arthropathy and no permanent sequele or death occurred as a drug related ADR.
Cell adhesion is dependent on many factors, including the repertoire of extracellular matrix (ECM) proteins and their receptors, e.g. integrins, synthesized by the cell, the composition of the ECM adsorbed to the surface, and the intrinsic chemistry of the surface. Factors that govern bone cell, i.e. osteoblast, adhesion and ECM elaboration significantly influence its re-modeling into mature bone, and ultimately its ability to integrate with biomaterials used for orthopedic prostheses. In this study, we have investigated how treatment with bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor-beta (TGF-beta) superfamily that promotes ectopic bone formation, modulates the organization and expression of osteoblastic cell proteins. Specifically, we analyzed how BMP-2 treatment affects cytoskeletal components, ECM, and alpha 5 and beta 1 integrin receptor subunits in osteoblastic cells plated on Ti6A14V, a titanium alloy widely used for orthopedic implants that interacts with bone cells in vitro and in vivo. Osteoblastic cells were pre-treated with BMP-2 for 12 h prior to plating; BMP-2 treatment stimulated adhesion and proliferation of osteoblastic cells and this adhesive advantage was reflected in enhanced long-term matrix mineralization in the BMP-2 pretreated cultures. Confocal laser scanning microscopic analysis of BMP-2 treated cells showed that enhanced cytoskeletal organization and focal contact formation occurred. These changes were accompanied by a concomitant increase in the spatial organization of fibronectin, whereas vitronectin, collagen type I, osteopontin, and osteocalcin showed little change. The changes in ECM organization correlated with increased fibronectin, alpha 5 and beta 1 integrin subunit, and focal adhesion kinase (p125FAK) expression, as well as increased p125FAK phosphorylation. By confocal microscopy, the alpha 5 integrin subunit was more concentrated in lamellipodia after BMP-2 treatment. These results demonstrate that BMP-2 significantly altered osteoblastic cytoskeletal and ECM organization and enhanced expression of fibronectin and of specific integrin receptor subunits, with concomitant changes in the levels and phosphorylation of p125FAK. These effects may contribute to downstream cellular responses important for bone cell function, and growth.
Understanding the cellular basis of osteoblastic cell-biomaterial interaction is crucial to the analysis of the mechanism of osseointegration, a requirement of long-term orthopedic implant stability. Clinically, the amount of bone ingrowth is variable, and cellular parameters that influence ingrowth have yet to be clearly determined. In this study, two clinically relevant orthopedic alloys, titanium Ti6A14V (Ti) and cobalt-chrome-molybdenum (CC), were used for a comparative analysis of primary human osteoblastic cell adhesion and spreading, where cell adhesion represents the initial interaction between cellular elements and the biomaterial surface. The kinetic profile of adhesion revealed enhanced cell attachment upon rough Ti surfaces relative to rough CC. Using confocal laser scanning microscopy (CLSM), we observed that, during the first 12 h of contact with the substratum, osteoblastic cells were relatively less spread on rough Ti, whereas cells appeared elongated with multiple cellular extensions on rough CC. Focal adhesion contacts, as indicated by vinculin immunostaining, were distributed throughout the cells adhering to Ti, but were relatively sparse and localized to cellular processes on CC. Furthermore, three-dimensional CLSM reconstruction analysis indicated the presence of vinculin at all membrane-to-surface contact points on both Ti and CC. On Ti, these contact points closely followed the surface contour, whereas, on CC, they were restricted to relative topographic peaks only. Actin cytoskeletal reorganization was prominent in cells cultured on Ti, with stress fibers arranged throughout the cell body, whereas, on CC, actin filaments were sparse and localized primarily to cellular extensions. Because cell attachment mechanisms are likely to influence signal transduction and regulation of gene expression, these early differential responses of osteoblastic cells on Ti and CC may have functional implications on subsequent extracellular matrix mineralization and bone ingrowth at the cell-biomaterial interface.
The currently recommended protocol for treatment of kala-azar (KA) necessitates repeated bone marrow/splenic aspiration to monitor the response and duration of therapy as well as to detect resistance and change to alternative drugs. These procedures being invasive, there is a pressing need for less invasive diagnostic tools for this purpose. We have evaluated the role of C-reactive protein (CRP) in 201 children with visceral leishmaniasis at different stages of the disease to work out the relationship, if any, between CRP levels and disease activity, including response to therapy. The subjects belonged to the 2-12 year age group in whom CRP estimation was done on admission, every 5th day during treatment, and repeated on follow-up at 2 and 6 months. The levels were compared with those of 50 randomly chosen age-matched healthy children who served as controls. The mean serum CRP value in the study group before the commencement of treatment was 62.96 +/- 1.03 mg/l, which was significantly higher (p < 0.001) in comparison to the control group. Commencement of treatment resulted in a simultaneous decline in serum CRP. Parasitic clearance from the spleen was faster in patients with an initial low serum CRP level (< 60 mg/l) in comparison to patients with high levels (> 60 mg/l). During treatment, mean serum CRP levels were significantly higher in late responders than in early responders (p < 0.001). Correlation of CRP levels to indicate the presence or absence of parasites suggested a cut-off level of 12 mg/l by day 10, with a sensitivity of 82.5 per cent, specificity of 78.5 per cent, positive predictive value of 92 per cent, and negative predictive value of 60.2 per cent. Our observations suggest a promising role for CRP estimation every 5-10 days during therapy in visceral leishmaniasis for monitoring the response to therapy and to detect possible resistance.
Several reports concluded that free tissue transfer of the transverse rectus abdominis muscle (TRAM) flap for breast reconstruction is superior to pedicled transfer of the flap. In an effort to compare the various parameters of both techniques, the authors took advantage of a unique experience at one hospital where one surgeon (D.L.L.) used only the pedicled method and the other (N.J.Y.) used only free tissue transfer. Additionally, the authors compared the findings of the study with the experiences of other surgeons by surveying active members of the American Association of Plastic Surgeons. The records of 119 patients who underwent TRAM flap reconstruction between January of 1988 and July of 1997 were reviewed. Of these, 33 patients received free TRAM flaps, and 86 received pedicled TRAM flaps. To provide an adequate number of patients for statistical analysis, only those with unilateral, single-muscle reconstructions were considered (immediate or delayed). This provided 61 patients in the pedicled flap group and 26 in the free tissue group. Parameters examined included length of operation and of hospitalization, amount of pain medication used, amount of blood lost and received, and complications. A small subset of the patients had hospital records available to compare hospital charges; the comparison of 17 pedicled and 12 free TRAM flaps showed a mean difference of $15,637 (p < 0.001) in favor of the pedicled flap. On the basis of the findings from this study, it seems that the pedicled TRAM flap has significant economic and clinical advantages over the free TRAM flap. There is less need for blood, a shorter operating time and hospital stay, and a need for less pain medication. However, both methods of transfer have indications and contraindications in certain clinical settings. It will always remain the responsibility of the surgeon to evaluate all issues and select a method that is economically responsible and within the abilities of the surgeon, while producing a satisfactory outcome that best serves the patient. The information provided in this report should aid in accomplishing this goal.
Explore the source record for details and available documents.
Suppressor activity of buffalo intestinal intraepithelial leucocytes and lamina propria leucocytes was induced by Concanavalin A, and was assayed against the mitogenic response of autologous and allogenic leucocytes to mitogens. Appreciable suppression was observed with 25 micrograms ConA/ml on the proliferative activity of the responder cells cocultured at a ratio of < 2:1 (suppressor:responder cell). Mitomycin C treatment of intestinal leucocytes did not totally vanish the viability and functionality of leucocytes.
Bone loss with or without evidence of aseptic loosening is a long term complication after total hip arthroplasty (THA). It occurs with all materials and in all prosthetic systems in use or that have been used to date. Bone loss after THA can be a serious problem in revision surgery because bone deficiencies may limit reconstructive options, increase the difficulty of surgery, and necessitate autogenous or allogenic bone grafting. There are three factors adversely affecting maintenance of bone mass after THA: (1) bone loss secondary to particulate debris; (2) adaptive bone remodeling and stress shielding secondary to size, material properties, and surface characteristics of contemporary prostheses; and (3) bone loss as a consequence of natural aging. This chapter reviews the mechanisms of the primary causes of bone loss after THA.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Mechanism of immunoprotection and specificity of two highly immunoprotective mycobacterial proteins, viz. 71 and 30 kDa were investigated. The adoptive transfer studies indicated that immunoprotection was mainly mediated by cooperative effect of CD4+ and CD8+ (66.7-73.3% on the basis of percent survival) which was further enhanced marginally by supplementation of B cells, natural killer cells, dendritic cells, macrophages and other immune cells. The specificity studies indicated that both the proteins did not cross react with the unrelated intracellular pathogens i.e. Aspergillus fumigatus, Salmonella typhi and Leishmania donovani as seen by T cell proliferation assay. The protection imparted by these mycobacterial proteins was also specific as the 71 and 30 kDa primed mice did not exhibit any cross protection against sublethal challenge of S typhi. The results indicate 71 and 30 kDa mycobacterial proteins to contain T cell specific epitopes responsible for specific immunoprotection, thus indicating their potential role as antituberculous vaccine candidates.
The immunoprotective efficacy of the 30 kDa secretory protein isolated from mid-log phase culture filtrate of Mycobacterium tuberculosis H37Ra was investigated using liposomes as adjuvant. Immunization of animals with the 30 kDa protein entrapped in liposomes prepared by a freeze-thaw method and absorbed on alum induced both cellular (monitored by T cell proliferation assay and cytokine secretion, viz. IL-2, IFN-gamma) and humoral (evaluated by ELISA) responses which were comparable to those induced in the 30 kDa IFA-immunized group. The protection induced by liposome-encapsulated 30 kDa secretory protein was slightly lower than that induced in 30 kDa IFA-immunized animals on the basis of higher survival rates and decreased viable counts of M. tuberculosis H37Rv in various organs (spleen, lung and liver) after 30 days of infection compared to the controls. The results strongly indicate that liposomes are an ideal vaccine delivery system which can effectively replace IFA for the delivery of the immunoprotective 30 kDa secretory protein of M. tuberculosis H37Ra.
Integrins are transmembrane proteins that mediate attachment to extracellular matrix (ECM) proteins. Integrins act as ECM receptors and are believed to play a role in signal transduction and gene regulation, potentially influencing several cellular functions, including differentiation, growth, and migration. Several integrins have previously been found in bone cells in vivo and in vitro. Because the biologic fixation of orthopedic implants depends on optimal cell interactions at the interface, we examined whether integrins are involved in the attachment of osteoblasts to implant materials. In this study, we have used immunohistochemistry to examine the expression of integrins in primary human osteoblasts cultured on tissue culture polystyrene (PS), and rough and polished disks of the orthopedic alloys titanium-aluminum-vanadium (Ti) and cobalt-chrome-molybdenum (CC). The integrin subunits, alpha 2, alpha 3, alpha 4, alpha 5, alpha v, alpha 6, beta 1 and beta 3, were expressed by primary human osteoblasts cultured on PS coated with various ECM molecules. However, alpha 5 and alpha 6 were notably absent in cells attached to the alloys. Also, alpha 3 was not present on rough Ti, polished CC, or rough CC, and beta 3 was not expressed by cells on rough CC. Thus, the nature of the metal alloy appeared to influence the expression of particular integrins. As a result, the ability of cells to adhere to and receive messages from the extracellular matrix may also be influenced by the substratum. These differences may explain previously observed differences in degree of cell attachment to these metals.
Explore the source record for details and available documents.
OBJECTIVE: To determine the value of serum C-reactive protein (CRP) estimation in the follow-up of bacterial meningitis (BM). DESIGN: Longitudinal follow-up. SETTING: Urban hospital. METHODS: Sequential serum CRP estimation was done in 50 healthy children and in 100 children with BM. Serial serum CRP value was correlated with the clinical picture in BM. RESULTS: Serial serum CRP in 14 patients with complicated BM was significantly different than the 72 uncomplicated BM cases. CONCLUSIONS: Serial determination of serum CRP may be a cheap, simple and reliable prognostic indicator in BM.