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91.
Prasenjit Das Tarun Puri Vaishali Suri M. C. Sharma B. S. Sharma Chitra Sarkar 《Child's nervous system》2009,25(7):825-835
Background Medulloblastoma (MB) is the most common pediatric brain tumor. It is however rare in adults. The genetic and protein expression
profile of medulloblastoma is complex, which is worthwhile in terms of prognostication and development or selection of targeted
therapy.
Aims and objectives The aims and objectives to correlate the MIB-1 proliferation index and protein expression profiles of c-Myc, ERBB2, and anti-apoptotic
proteins (Bcl2 and Bcl-xL) in tumor cells with histological subtypes and clinical outcome.
Methods and material In 50 cases, histopathological subtyping was done, and protein expression profiling by immunohistochemical technique was performed
by stains for MIB-1, Bcl2, Bcl-xL, c-Myc, and ERBB2 in 30 cases. The findings were correlated with histological types and
patient’s average follow-up data.
Results Histological subtypes were similar to that described in literatures. The average expression of Bcl2, Bcl-xL, MIB-1, c-Myc,
and ERBB2 were as follows: 50.38%, 38.18%, 59.03%, 46.16%, and 59.62%, respectively. Bcl2 expression showed statistically
significant correlation with progress-free survival (PFS) [p = 0.046], while ERBB2 and MIB-1 showed a trend of higher expression in progressive disease. The protein expression pattern
did not correlate with histological subtypes.
Conclusion Though Bcl-2, ERBB2, and MIB-1 LI came out to be potential markers of aggressive behavior, c-Myc did not correlate with PFS
in MB. 相似文献
92.
Nadeem Tanveer Mehar C. Sharma Chitra Sarkar Sheffali Gulati Veena Kalra Sumit Singh Rohit Bhatia 《Clinical neurology and neurosurgery》2009
Aims
Muscle biopsy is an important diagnostic modality and screening test for the diagnosis of dystrophinopathies. Sometimes muscle biopsies are needed for the diagnosis when genetic tests are inconclusive and are also useful for immunoblotting assay of the dystrophin protein. However, the procedure is painful, requires anesthesia and sometimes needs to be repeated. This study was undertaken to elucidate the role of skin biopsy in the diagnosis of dystrophinopathies and to validate if it can be utilized as a useful adjunct/replacement for the muscle biopsy.Methods
Paired skin and muscle biopsies were studied from 39 patients with Duchenne muscular dystrophy (DMD), 4 patients with Becker's muscular dystrophy (BMD) and 37 controls. Immunostaining for dystrophin and utrophin was done on frozen sections of the test group and controls and their staining pattern in skin biopsies was compared with corresponding muscle biopsies.Results
Immunostaining for dystrophin was negative in the skin biopsies of all patients (39/39, 100%) with DMD and was only weakly expressed in skin of BMD patients (4/4, 100%). Dystrophin was strongly expressed on arrector pili muscle cells of all control patients (94.6%) except two cases in whom it was weakly expressed. Utrophin was expressed on the arrector pili muscle cells of DMD patients (39/39, 100%) as well as controls (30/37, 81.1%).Conclusion
Our study suggests that skin biopsy is very useful for the diagnosis of dystrophinopathies and their differentiation from other muscle diseases. It has high degrees of sensitivity, specificity, and positive and negative predictive values. It can be a useful adjunct/replacement for the muscle biopsy especially when repeated biopsies are required for monitoring therapy or in patients with advanced DMD where extreme fibrosis, adipose tissue infiltration and inflammation make interpretation of the muscle biopsy difficult. Skin biopsy is a simple, cost effective, less invasive and less traumatic diagnostic procedure when compared with muscle biopsy. This is even more pertinent because patients with muscular dystrophies have a higher risk for any form of general anesthesia. A smaller scar and fewer chances of infection at the site of biopsy are other additional advantages of skin biopsy over muscle biopsy. 相似文献93.
Cooper DS Jacobs JP Moore L Stock A Gaynor JW Chancy T Parpard M Griffin DA Owens T Checchia PA Thiagarajan RR Spray TL Ravishankar C 《Cardiology in the young》2007,17(Z2):104-115
Mechanical circulatory support is an invaluable tool in the care of children with severe refractory cardiac and or pulmonary failure. Two forms of mechanical circulatory support are currently available to neonates, infants, and smaller children, namely extracorporeal membrane oxygenation and use of a ventricular assist device, with each technique having unique advantages and disadvantages. The intra-aortic balloon pump is a third form of mechanical support that has been successfully used in larger children, adolescents, and adults, but has limited applicability in smaller children. In this review, we discuss the current experiences with extracorporeal membrane oxygenation and ventricular assist devices in children with cardiac disease.A variety of forms of mechanical circulatory support are available for children with cardiopulmonary dysfunction refractory to conventional management. These devices require extensive resources, both human and economic. Extracorporeal membrane oxygenation can be effectively used in a variety of settings to provide support to critically-ill patients with cardiac disease. Careful selection of patients and timing of intervention remains challenging. Special consideration should be given to children with cardiac disease with regard to anatomy, physiology, cannulation, and circuit management. Even though exciting progress is being made in the development of ventricular assist devices for long-term mechanical support in children, extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation.As the familiarity and experience with extracorporeal membrane oxygenation has grown, new indications have evolved, including emergent resuscitation. This utilization has been termed extracorporeal cardiopulmonary resuscitation. The literature supporting emergent cardiopulmonary support is mounting. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Due to the limitations of conventional circuits for extracorporeal membrane oxygenation, some centres have developed novel systems for rapid cardiopulmonary support. Many centres previously considered a functionally univentricular circulation to be a contraindication to extracorporeal membrane oxygenation, but improved results have been achieved recently with this complex subset of patients. The registry of the Extracorporeal Life Support Organization recently reported the outcome of extracorporeal life support used in neonates for cardiac indications from 1996 to 2000. Of the 740 neonates who were placed on extracorporeal life support for cardiac indications, 118 had hypoplastic left heart syndrome. There was no significant difference in survival between these patients and those with other defects. It is now common to use extracorporeal membrane oxygenation to support patients with a functionally univentricular circulation, and reasonable survival rates are to be expected. Although extracorporeal membrane oxygenation has become a standard of care for many paediatric centres, its use is limited to those patients who require only short-term cardiopulmonary support. Mechanical ventricular assist devices have become standard therapy for adults with cardiac failure refractory to maximal medical management. Several devices are readily available in the United States of America for adults, but there are fewer options available to children. Over the last few years, substantial progress has been made in paediatric mechanical support. Ventricular assist devices are being used with increasing frequency in children with cardiac failure refractory to medical therapy for primary treatment as a long-term bridge to recovery or transplantation. The paracorporeal, pneumatic, pulsatile "Berlin Heart" ventricular assist device is being used with increasing frequency in Europe and North America to provide univentricular and biventricular support. With this device, a patient can be maintained on mechanical circulatory support while extubated, being mobilized, and feeding by mouth. Mechanical circulatory support should be anticipated, and every attempt must be made to initiate support "urgently" rather than "emergently", before the presence of dysfunction of end organs or circulatory collapse. In an emergency, these patients can be resuscitated with extracorporeal membrane oxygenation and subsequently transitioned to a long-term ventricular assist device after a period of stability. 相似文献
94.
Wernovsky G Kuijpers M Van Rossem MC Marino BS Ravishankar C Dominguez T Godinez RI Dodds KM Ittenbach RF Nicolson SC Bird GL Gaynor JW Spray TL Tabbutt S 《Cardiology in the young》2007,17(6):652-665
The medical records of all patients born between 1 September, 2000, and 31 August, 2002, and undergoing the first stage of Norwood reconstruction, were retrospectively reviewed for details of the perioperative course. We found 99 consecutive patients who met the criterions for inclusion. Hospital mortality for the entire cohort was 15.2%, but was 7.3%, with 4 of 55 dying, in the setting of a "standard" risk profile, as opposed to 25.0% for those with a "high" risk profile, 11 of 44 patients dying in this group. Extracorporeal membrane oxygenation was utilized in 7 patients, with 6 deaths. Median postoperative length of stay in the hospital was 14 days, with a range from 2 to 85 days, and stay in the cardiac intensive care unit was 11 days, with a range from 2 to 85 days. Delayed sternal closure was performed in 18.2%, with a median of 1 day until closure, with a range from zero to 5 days. Excluding isolated delayed sternal closure, and cannulation and decannulation for extracorporeal support, 24 patients underwent 33 cardiothoracic reoperations, including exploration for bleeding in 12, diaphragmatic plication in 4; shunt revision in 4, and other procedures in 13. The median duration of total mechanical ventilation was 4.0 days, with a range from 0.7 to 80.5 days. Excluding those who died, the median total duration of mechanical ventilation was 3.8 days, with a range from 0.9 to 46.3 days. Reintubation for cardiorespiratory failure or upper airway obstruction was performed in 31 patients. Postoperative electroencephalographic and/or clinical seizures occurred in 13 patients, with 7 discharged on anti-convulsant medications. Postoperative renal failure, defined as a level of creatinine greater than 1.5 mg/dl, was present in 13 patients. Eleven had significant thrombocytopenia, with fewer than 20,000 platelets per microl, and injury to the vocal cords was identified in eight patients. Risk factors for longer length of stay included lower Apgar scores, preoperative intubation, early reoperations, reintubation and sepsis, but not weight at birth, genetic syndromes, the specific surgeon, or the duration of surgery.Although mortality rates after the first stage of reconstruction continue to fall, the course in the intensive care unit is remarkable for significant morbidity, especially involving the cardiac, pulmonary and central nervous systems. These patients utilize significant resources during the first hospitalization. Further studies are necessary to stratify the risks faced by patients with hypoplasia of the left heart in whom the first stage of Norwood reconstruction is planned, to determine methods to reduce perioperative morbidity, and to determine the long-term implications of short-term complications, such as diaphragmatic paresis, injury to the vocal cords, prolonged mechanical ventilation, and postoperative seizures. 相似文献
95.
To investigate role of specific interactions in aiding formation and stabilization of amorphous state in ternary and binary dispersions of a weakly acidic drug. Indomethacin (IMC), meglumine (MU), and polyvinyl pyrollidone (PVP) were the model drug, base, and polymer, respectively. Dispersions were prepared using solvent evaporation. Physical mixtures were cryogenically coground. XRPD, PLM, DSC, TGA, and FTIR were used for characterization. MU has a high crystallization tendency and is characterized by a low T(g) (17 degrees C). IMC crystallization was inhibited in ternary dispersion with MU compared to IMC/PVP alone. An amorphous state formed readily even in coground mixtures. Spectroscopic data are indicative of an IMC-MU amorphous salt and supports solid-state proton transfer. IMC-MU salt displays a low T(g) approximately 50 degrees C, but is more physically stable than IMC, which in molecular mixtures with MU, resisted crystallization even when present in stoichiometric excess of base. This is likely due to a disrupted local structure of amorphous IMC due to specific interactions. IMC showed improved physical stability on incorporating MU in polymer, in spite of low T(g) of the base indicating that chemical interactions play a dominant role in physical stabilization. Salt formation could be induced thermally and mechanically. 相似文献
96.
97.
98.
Aggarwal BB Prasad S Reuter S Kannappan R Yadev VR Park B Kim JH Gupta SC Phromnoi K Sundaram C Prasad S Chaturvedi MM Sung B 《Current drug targets》2011,12(11):1595-1653
99.
Chitra Subramanian Jason A Jarzembowski Anthony W Opipari Jr Valerie P Castle Roland PS Kwok 《Neoplasia (New York, N.Y.)》2011,13(8):726-734
Ku70 was first characterized as a nuclear factor that binds DNA double-strand breaks in nonhomolog end-joining DNA repair. However, recent studies have shown that Ku70 is also found in the cytoplasm and binds Bax, preventing Bax-induced cell death. We have shown that, in neuroblastoma cells, the binding between Ku70 and Bax depends on the acetylation status of Ku70, such that, when Ku70 is acetylated, Bax is released from Ku70, triggering cell death. Thus, to survive, in neuroblastoma cells, cytoplasmic Ku70 acetylation status is carefully regulated such that Ku70 is maintained in a deacetylated state, keeping Bax complexed with Ku70. We have shown that overexpression of CREB-binding protein (CBP), a known acetyltransferase that acetylates Ku70, releases Bax from Ku70, triggering apoptosis. Although we have shown that blocking deacetylase activity using non-type-specific inhibitors also triggers Ku70 acetylation and Bax-dependent cell death, the targets of these deacetylase inhibitors in neuroblastoma cells remain unknown. Here, we demonstrate that, in neuroblastoma cells, histone deacetylase 6 (HDAC6) binds Ku70 and Bax in the cytoplasm and that knocking down HDAC6 or using an HDAC6-specific inhibitor triggers Bax-dependent cell death. Our results show that HDAC6 regulates the interaction between Ku70 and Bax in neuroblastoma cells and may be a therapeutic target in this pediatric solid tumor. 相似文献
100.
A highly porous silica and chitosan-based hemostatic dressing is superior in controlling hemorrhage in a severe groin injury model in swine 总被引:1,自引:0,他引:1
Chitra N. Sambasivan 《American journal of surgery》2009,197(5):576-580