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Purpose The purpose of the study was to find out if transpedicular decancellation osteotomy (TDO) is recommendable for neurological recovery in patients with myelopathy due to tubercular rigid kyphosis. We have analyzed the pattern of recovery seen after the surgery and also made an effort to correlate the neurological recovery with preoperative clinical and radiological features. Methods The clinical parameters used were (1) ASIA impairment scale for motor and sensory function, (2) sphincter dysfunction score, (3) time duration from the onset of myelopathy till the date of surgery, and (4) SRS 30 outcomes questionnaire. Radiological parameters used were (1) Cobb's angle in standing/sitting radiographs, (2) levels of gibbus, (3) cord changes in sagittal T2 MRI images, and (4) percentage of cord compression. Assessment was done preoperatively and at 1 month, 3 months, 6 months, 1 year and at 2 years postoperatively. Results Seventeen patients were included. The follow-up period was 2 years. We had one patient in ASIA A, nine patients in ASIA C and seven patients in ASIA D. Four patients with ASIA C presented with mild sphincter disturbance (score 2) and one presented with severe disturbance (score 1). The ASIA A patient had complete retention (score 0). The ASIA impairment scale improved after surgery, with maximum improvement at 3 months and improvement continuing up to 6 months. 16 (94 %) patients had improvement in lower limb function and 5 (83 %) patients had improvement of sphincter function. 94 % patients had neurological recovery after the operation. The neurological recovery reached a plateau at 6 months with no significant improvement in the further follow-up. Preoperative MRI changes, cord compression and duration from onset of myelopathy to day of surgery were not predictive of the final neurological outcome after surgery. Conclusion TDO gives good results in delayed onset neurological deficits in caries spine with rigid kyphosis. At least, one grade improvement in the neurological status of patients with ASIA C and ASIA D can be expected. Maximum improvement in the neurology is seen in the first 3 months and up to 6 months from the date of surgery, without much improvement thereafter. Level of evidence Level IV. © Springer-Verlag 2012.

Mandal C.,Council of Scientific and Industrial Research | Mandal C.,National Institute of Pharmaceutical Education and Research | Chandra S.,Park Clinic | Schauer R.,University of Kiel
Glycobiology | Year: 2012

Enhanced expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) and 9-O-acetylated disialoganglioside (9-OAcGD3) was observed on lymphoblasts of childhood acute lymphoblastic leukemia (ALL). Sialate-O-acetyltransferase (SOAT) and sialate-O-acetylesterase (SIAE) are the two main enzymes responsible for the quantity of the O-acetyl ester groups on sialic acids (Sias). We have earlier shown an enhanced level of SOAT activity, capable of transferring acetyl groups to Sias of glycoconjugates in the microsomes of lymphoblasts of these children. We further observed a decreased SIAE activity in both lysosomal and cytosolic fractions of ALL cell lines and primary cells from bone marrow of patients compared with peripheral blood mononuclear cells from healthy donors, which preferentially hydrolyze O-acetyl groups at C-9 of Sia. The level of O-acetylated Sias in the cytosolic and the lysosomal fractions showed a good correlation with SIAE activity in the corresponding fractions. The apparent KM values for SIAE in the lysosomal and the cytosolic fractions from lymphoblasts of ALL patients are 0.38 and 0.39 mM, respectively. These studies demonstrate that both SIAE and SOAT activities seem to be responsible for the enhanced level of Neu5,9Ac2 in lymphoblasts, which is a hallmark in ALL. This was subsequently confirmed by using an enzyme-linked immunosorbent assay that also demonstrated a steady decline in SOAT activities even in cell lysates of lymphoblasts during successful chemotherapy, like radioactive methods have shown earlier. © 2011 The Author.

Bhattacharya K.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology | Chandra S.,Park Clinic | Mandal C.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology
Immunology | Year: 2014

Summary: Regulatory T (Treg) cells act to suppress activation of the immune system and thereby maintain immunological homeostasis and tolerance to self-antigens. The frequency and suppressing activity of Treg cells in general are high in different malignancies. We wanted to identify the role and regulation of CD4+ CD25+ FoxP3+ Treg cells in B-cell acute lymphoblastic leukaemia (B-ALL). We have included patients at diagnosis (n = 54), patients in clinical remission (n = 32) and normal healthy individuals (n = 35). These diagnosed patients demonstrated a lower number of CD4+ CD25+ cells co-expressing a higher level of FoxP3, interleukin-10, transforming growth factor-β and CD152/CTLA-4 than the normal population. Treg cells from patients showed a higher suppressive capability on CD4+ CD25- responder T (Tresp) cells than normal. The frequency and immunosuppressive potential of CD4+ CD25+ FoxP3+ Treg cells became high with the progression of malignancy in B-ALL. Relative distribution of Tresp and Treg cells was only ~5: 1 in B-ALL but ~35: 1 in normal healthy individuals, further confirming the elevated immunosuppression in patients. A co-culture study at these definite ex vivo ratios, indicated that Treg cells from B-ALL patients exhibited higher immunosuppression than Treg cells from normal healthy individuals. After chemotherapy using the MCP841 protocol, the frequency of CD4+ CD25+ cells was gradually enhanced with the reduction of FoxP3, interleukin-10 positivity corresponded with disease presentation, indicating reduced immunosuppression. Taken together, our study indicated that the CD4+ CD25+ FoxP3+ Treg cells played an important role in immunosuppression, resulting in a positive disease-correlation in these patients. To the best of our knowledge, this is the first detailed report on the frequency, regulation and functionality of Treg cells in B-ALL. © 2013 John Wiley & Sons Ltd.

Mandal T.,CSIR - Central Electrochemical Research Institute | Bhowmik A.,CSIR - Central Electrochemical Research Institute | Chatterjee A.,CSIR - Central Electrochemical Research Institute | Chatterjee U.,Park Clinic | And 2 more authors.
Cellular Signalling | Year: 2014

Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival and proliferation and has been found to be persistently activated in most human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation in cancer cells have not been clearly evaluated. In our findings, correlation studies on the expression of CK2 and Stat3 Ser-727 phosphorylation levels in human glioma patient samples as well as rat orthotopic tumor model show a degree of negative correlation. Moreover, brain tumor cell lines were treated with various pharmacological inhibitors to inactivate the CK2 pathway. Here, increased Stat3 Ser-727 phosphorylation upon CK2 inhibition was observed. Overexpression of CK2 (α, α' or β subunits) by transient transfection resulted in decreased Stat3 Ser-727 phosphorylation. Stat3 Tyr-705 residue was conversely phosphorylated in similar situations. Interestingly, we found PP2A, a protein phosphatase, to be a mediator in the negative regulation of Stat3 Ser-727 phosphorylation by CK2. In vitro assays prove that Ser-727 phosphorylation of Stat3 affects the transcriptional activity of its downstream targets like SOCS3, bcl-xl and Cyclin D1. Stable cell lines constitutively expressing Stat3 S727A mutant showed increased survival, proliferation and invasion which are characteristics of a cancer cell. Rat tumor models generated with the Stat3 S727A mutant cell line formed more aggressive tumors when compared to the Stat3 WT expressing stable cell line. Thus, in glioma, reduced Stat3 Ser-727 phosphorylation enhances tumorigenicity which may be regulated in part by CK2-PP2A pathway. © 2014 The Authors.

Basu S.,Park Clinic
Frontiers in Neurology | Year: 2012

About 5% of spinal injuries occur in children - however the consequences to the society are devastating, all the more so because the cervical spine is more commonly affected. Anatomical differences with adults along with the inherent elasticity of the pediatric spine, makes these injuries a biomechanically separate entity. Hence clinical manifestations are unique, one of which is the Spinal Cord Injury Without Radiological Abnormality. With the advent of high quality MRI and CT scan along with digital X-ray, it is now possible to exactly delineate the anatomical location, geometrical configuration, and the pathological extent of the injury. This has improved the management strategies of these unfortunate children and the role of surgical stabilization in unstable injuries can be more sharply defined. However these patients should be followed up diligently because of the recognized long term complications of spinal deformity and syringomyelia. © 2012 Basu.

Maiti A.,Park Clinic | Chatterjee S.,Park Clinic
Journal of Paediatrics and Child Health | Year: 2011

Aims: Data regarding the presentation and course of patients with congenital adrenal hyperplasia (CAH) is scarce in South Asia. We aimed to fill that gap by collating our experience with CAH and comparing it with findings from few other centres around the world for pertinent differences. Methods: We retrospectively analysed the records of 86 CAH patients seen at our tertiary care centre in Eastern-India from 1996 to 2010. Results: Forty-five patients (52.3%) had classic disease and 41 (47.7%) had non-classic disease (NC CAH). In the classic CAH group, 18 (20.9%) had salt wasting CAH (SW CAH) while 27 (31.4%) had simple virilising disease (SV CAH). Ten (11.6%) had a 46,XY karyotype. Patients with SW CAH were diagnosed earlier in infancy at a median age of 0.5 year, than those with SV type, who were diagnosed at 9 years (P < 0.05). The NC CAH patients were diagnosed still later, at 20.4 years. In patients with SW CAH, boys were diagnosed at an earlier median age of 0.1 year than girls who were diagnosed at 6.4 years (P < 0.05). Sixteen girls (21% of the girls) underwent vaginoplasty of whom four required additional clitoroplasty. One girl needed bilateral laparoscopic adrenalectomy. One NC CAH patient had a successful assisted pregnancy. Hypothyroidism, found in seven (8.1%) was the commonest coexisting abnormality. Conclusion: The skewed male: female ratio suggested that a substantial proportion of males were being missed and consequently may die. Majority of the diagnosed patients (n= 55, 64%) have been lost to follow-up. Remaining patients could be reasonably controlled with standard therapy. © 2011 The Authors.

Basu S.,Park Clinic | Sreeramalingam R.,Park Clinic
Indian Journal of Orthopaedics | Year: 2012

Postoperative spondylodiscitis after anterior cervical decompression and fusion (ACDF) is rare, but the same occurring at adjacent levels without disturbing the operated level is very rare. We report a case, with 5 year followup, who underwent ACDF from C5 to C7 for cervical spondylotic myelopathy. He showed neurological improvement after surgery but developed discharging sinus after 2 weeks, which healed with antibiotics. He improved on his preoperative symptoms well for the first 2 months. He started developing progressive neck pain and myelopathy after 3 months and investigations revealed spondylodiscitis at C3 and C4 with erosion, collapse, and kyphosis, without any evidence of implant failure or graft rejection at the operated level. He underwent reexploration and implant removal at the operated level (there was good fusion from C5 to C7) followed by debridement/decompression at C3, C4 along with iliac crest bone grafting and stabilization with plate and screws after maximum correction of kyphosis. The biopsy specimen grew Pseudomonas aeruginosa and appropriate sensitive antibiotics (gentamycin and ciprofloxacin) were given for 6 weeks. He was under regular followup for 5 years his myelopathy resolved completely and he is back to work. Complete decompression of the cord and fusion from C2 to C7 was demonstrable on postoperative imaging studies without any evidence of implant loosening or C1/C2 instability at the last followup.

Hall M.J.,Derriford Hospital | Connell D.A.,Imaging at Olympic Park | Morris H.G.,Park Clinic
Knee | Year: 2013

Introduction: We report the first non-designer study of the Unix uncemented unicompartmental knee prosthesis. Materials and methods: Eighty-five consecutive UKRs were carried out with sixty-five available for follow-up. Oxford Knee Scores, WOMAC questionnaire and radiological assessment were completed. Results: The mean Oxford Knee Score was thirty-eight and WOMAC Score was twenty. Overall Kaplan Meier survival estimate is 76% (95% confidence interval 60%-97%) at 12. years and 88% (95% confidence interval 76-100%) with aseptic loosening as the endpoint. Radiographic assessment showed lysis in the tibia in 6% of patients with no lysis evident around the central fin. Discussion: Survivorship is comparable to other published series of UKRs. We suggest the central fin design is key to dissipating large forces throughout the proximal tibia, resulting in low levels of tibial loosening.Level of evidence IV. © 2012 Elsevier B.V.

Chatterjee A.,Indian Institute of Science | Chatterjee U.,Park Clinic | Ghosh M.K.,Indian Institute of Science
Cell Death and Disease | Year: 2013

Protein kinase CK2 (also known as Caseine Kinase II) is an ubiquitous Ser/Thr protein kinase present in both the nucleus and cytoplasm of cells, targeting several key enzymes, growth factor receptors, transcription factors and cytoskeletal proteins. It is not only a key player in regulating cellular growth and proliferation, but also behaves as a potent suppressor of apoptosis. CK2 has been frequently found to be deregulated (mostly hyperactivated) in all cancers, prostate cancer being prominent of them. In the recent past, tumor suppressor PML (promyelocytic leukemia) has been shown to be a target of phosphorylation by CK2. This phosphorylation promotes the ubiquitin-mediated proteasomal degradation of PML thereby effectively curbing its role as a tumor suppressor. Among many others, PML has also been established to mediate its tumor suppressive role by mitigating the inactivation of active AKT (pAKT) inside the nucleus by assembling a dephosphorylating platform for nuclear pAKT. One of the immediate consequences, of this inactivation is the stabilization of FOXO3a, another well-established tumor suppressor, inside the nucleus and its downstream activities. Here, we propose a novel signaling axis apexed by deregulated CK2, dismantling the association of PML and PHLPP2 (we also report PHLPP2 to be a novel interacting partner of PML inside the nucleus), ultimately leading to the inactivation and nuclear exclusion of FOXO3a, thereby downregulating p21/p27/Bim in which degradation of PML and the concomitant stabilization of pAKT plays a cardinal part. © 2013 Macmillan Publishers Limited.

Basu S.,Park Clinic
Journal of orthopaedic surgery (Hong Kong) | Year: 2011

To review treatment outcomes of 19 patients with delayed presentation of cervical facet dislocations. Records of 17 men and 2 women aged 21 to 63 (mean, 39) years who presented with unilateral (n=14) or bilateral (n=5) cervical facet dislocation after a delay of 7 to 21 (mean, 14) days were reviewed. The most common level of dislocation was C5-C6 (n=9), followed by C4-C5 (n=6), C3- C4 (n=2), and C6-C7 (n=2). The neurological status was graded according to the Frankel classification. One patient (with bilateral facet dislocation) had complete quadriplegia (grade A), 11 had incomplete spinal cord injury (grades C and D), and 7 had nerve root injury. Closed reduction using continuous skull traction for 2 days was attempted. In patients achieving closed reduction, only anterior discectomy and fusion was performed. Those who failed closed reduction underwent posterior partial/complete facetectomy and fixation. If there was traumatic disk prolapse, anterior decompression and fusion was then performed. The mean follow-up was 46 (range, 12- 108) months. 10 of 14 patients with unilateral facet dislocation were reduced with traction and then underwent anterior discectomy and fusion. The remaining 4 patients who failed closed reduction underwent posterior facetectomy and fixation; 3 of them had traumatic disk prolapse and thus also underwent anterior discectomy and fusion with cage and plate. Four of the 5 patients with bilateral facet dislocations failed closed reduction and underwent posterior facetectomy and lateral mass fixation, as well as anterior surgery. The remaining patient achieved reduction after traction and hence underwent only anterior discectomy and fusion. All patients achieved pain relief and sufficient neck movement for normal activities. All 7 patients with nerve root injury improved completely; 9 of the 11 patients with incomplete spinal cord injury improved by one Frankel grade, and the remaining 2 by 2 grades. The patient with complete quadriplegia showed no improvement. Preoperative traction is a safe and effective initial treatment for neglected cervical facet dislocation, as it reduces the need for extensive (anterior and posterior) surgery. If closed reduction is successful, anterior discectomy and fusion is the surgery of choice. If not, posterior facetectomy and fusion followed by anterior surgery is preferred.

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