Primary sclerosing cholangitis in India

Six patients with PSC have been diagnosed and followed up at a centre in Northern India for periods upto 4 years. They all presented with cholestatic jaundice and cholangitis, but one of them subsequently presented with variceal haemorrhage. Cholangiographic features were the most characteristic and included irregular narrowing and segmental dilatation of the biliary radicles giving them a beaded appearance. Treating them was most frustrating. Two of them died of hepatic encephalopathy, others have also continued to be sick during the follow-up

Management of intra-articular fracture of distal femur with LCP and Lag screws in adults

Background: Accurate reconstruction of articular surface of distal femur by closed manipulation is not possible. The recent trend for displaced intra-articular fractures of the distal femur is open reduction and stable osteosynthesis with early rehabilitation. The best exposure is achieved through Swashbuckler approach with good results. Purpose of the study was to review the surgical management with LCP and lag screws of complex and most challenging intra-articular fracture of distal femur.Methods: 30 cases of intra-articular fractures of distal femur were treated with LCP and Lag screws in adults. Regular follow-up with all records was carried out for a period of 36 months. Most of patients were treated with Swashbuckler approach. Final outcome was carried based on Neer’s criteria.Results: Union was achieved in all the cases and mean time was 15 weeks. Patients have more range of motion in C1 and C2 types of fracture as compare to C3 Types. Mean range of motion was 1140. Early physiotherapy has big role to achieve good range of motion.Conclusions: LCP is better implant in comminuted I/A fractures of distal end of femur and in elderly patients with osteoporotic bone. In spite of the worst fracture anatomy of the comminuted fracture of distal femur and the poor quality of bone in elderly patients, this can provide better post-operative range of knee motion with overall better Knee score, achieving bony union in all the cases with early physiotherapy

Management of fracture upper end humerus with proximal humerus internal locking system

Background: Fracture of proximal humerus is the second most common fracture of the upper extremity, following distal forearm fractures. Aim of the present study was to evaluate the efficacy of proximal humerus internal locking system (PHILOS) plate fixation for proximal humerus fractures.Methods: Functional outcomes of 12 men and 18 women aged 22 to 78 (mean, 58) years who underwent PHILOS plate fixation for proximal humeral fractures were reviewed. Indications for surgery were 2 part (n=9), 3 part (n=14) or 4-part (n=7) closed proximal humeral fractures with angulation of more than 45 degrees or displacement of more than 1 cm. Functional outcomes and shoulder range of movement were assessed based on the Constant scoring system.Results: All patients will be followed up at monthly intervals for 6 months. During this period patient, will be motivated for physiotherapy and gradual normal use of the affected limb. Fracture union will be assessed clinically and radiologically. In our study of fracture proximal humerus union in most of the cases (24) occurring between 10-14 weeks. Range of union time was 8 to 18 weeks. one case of avascular necrosis of head occur in our case. In out of 30 cases excellent result in 7 cases, Good in16 cases Satisfactory in 5 cases and Poor in 2 cases were obtained.Conclusions: The PHILOS plate fixation is effective treatment for proximal humeral fractures particularly in osteoporotic bones

COMPUTATIONAL APPROACHES IN THE ESTIMATION AND ANALYSIS OF TRANSCRIPTS DIFFERENTIAL EXPRESSION AND SPLICING: APPLICATION TO SPINAL MUSCULAR ATROPHY

Spinal Muscular Atrophy (SMA) is among the most common genetic neurological diseases that cause infant mortality. SMA is caused by deletion or mutations in the survival motor neuron 1 gene (SMN1), which are expected to generate alterations in RNA transcription, or splicing and most importantly reductions in mRNA transport within the axons of motor neurons (MNs). SMA ultimately results in the selective degeneration of MNs in spinal cord, but the underlying reason is still not clear entirely. The aim of this study is to investigate splicing abnormalities in SMA, and to identify genes presenting differential splicing possibly involved in the pathogenesis of SMA at genome-wide level. We performed RNA-Sequencing data analysis on 2 SMA patients and 2 controls, with 2 biological replicates each sample, derived from their induced Pluripotent Stem Cells-differentiated-MNs. Three types of analyses were executed. Firstly, differential expression analysis was performed to identify possibly mis-regulated genes using Cufflinks. Secondly, alternative splicing analysis was conducted to find differentially-used exons (DUEs; using DEXSeq) as splicing patterns are known to be altered in MNs by the suboptimal levels of SMN protein. Thirdly, we did RNA-binding protein (RBP) - motif discovery for the set of identified alternative cassette-DUEs, to pinpoint possible mechanisms of such alterations, specific to MNs. The gene ontology enrichment analysis of significant DEGs and alternative cassette-DUEs revealed various interesting terms including axon-guidance, muscle-contraction, microtubule-based transport, axon-cargo transport, synapse etc. which suggests their involvement in SMA. Further, promising results were obtained from motif analysis which has identified 22 RBPs out of which 7 RBPs namely, PABPC1, PABPC3, PABPC4, PABPC5, PABPN1, SART3 and KHDRBS1 are known for mRNAs stabilization and mRNA transport across MN-axon. Five RBPs from PABP family are known to interact directly with SMN protein that enhance mRNA transport in MNs. To validate our results specific wet-lab experiments are required, involving precise recognition of RNA-binding sites correspondent with our findings. Our work has provided a promising set of putative targets which might offer potential therapeutic role towards treating SMA. During the course of our study, we have observed that current methods for an effective understanding of differential splicing events within the transcriptomic landscape at high resolution are insufficient. To address this problem, we developed a computational model which has a potential to precisely estimate the \u201ctranscript expression levels\u201d within a given gene locus by disentangling mature and nascent transcription contributions for each transcript at per base resolution. We modeled exonic and intronic read coverages by applying a non-linear computational model and estimated expression for each transcript, which best approximated the observed expression in total RNA-Seq data. The performance of our model was good in terms of computational processing time and memory usage. The application of our model is in the detection of differential splicing events. At exon level, differences in the ratio of the sum of mature and the sum of nascent transcripts over all the transcripts in a gene locus gives an indication of differential splicing. We have implemented our model in R-statistical language

Management of Arbeitsgemeinschaft fur osteosynthesefragen type C fractures of distal humerus in adults with two column fixation

Background: Accurate reconstruction of articular surface of distal humerus by closed manipulation is not possible. The recent trend for displaced intra-articular fractures of the distal humerus is open reduction and stable osteosynthesis with early rehabilitation. The best exposure of both columns of the distal part of the humerus and articular surface is achieved through trans-olecranon approach. Objective of the study was to evaluate the management and outcome of two column fixation of intra-articular fracture of distal humerus in adults by posterior approach via olecanon osteotomy and to restore early elbow joint function.Methods: Twenty-five cases of intra-articular fractures of distal humerus were treated by open reduction and internal fixation. All the patients were of adult age group. Chevron type olecranon osteotomy was performed and fixed with tension band wiring in all cases and follow-up period was upto 36 months. Regular clinical examination and periodical radiological evaluation were done.Results: All fractures united within average duration of 3 months. Results were evaluated as per Mayo Elbow Performance Score. According to this criteria, excellent result was achieved in 8 patients (32%), good in 13 (52%), fair in 3 (12%) and poor in 1 (4%) patients. Thus satisfactory result was obtained in 96% cases.Conclusions: The critical factors for a successful outcome of intra-articular fractures of the distal humerus depend upon severity of fracture, meticulous surgical technique, stable internal fixation, surgical experimentation and early controlled postoperative mobilization

Role of closed intramedullary interlocking nailing in comminuted fractures of long bones in lower limbs

Background: Fractures are the most common form of skeletal injuries encountered in orthopaedic practice. Increase in mechanization and high-speed travel are accompanied by increase in the number and severity of the fracture. Our ultimate goal of femur and tibia fracture management is restoration of alignment, rotation and length, preservation of blood supply to aid union, prevention of infection and early rehabilitation of the patient.Methods: 30 adult patients of either sex with 30 comminuted fractures of long bones were treated with closed intramedullary interlocking nail. AO type B3 and C in femur and tibia are included. There were 25 males and 5 females, and average age of patients was 36.2 years. Out of 30 cases, 13 cases were of femur fracture while 17 cases were of tibia fracture. There were 21 closed and 9 patients had Grade I open fractures.Results: Closed intramedullary interlocking nailing was done in 13 cases of femur fracture and 17 cases of tibia fracture. The average duration of partial weight bearing in femur fractures was 4.85 weeks and in tibia fractures was 5.53 weeks. 20 fractures united without additional intervention. The average duration of radiological union in femur fractures was 18.65 weeks and for tibia fractures was 19.29 weeks.Conclusions: Closed intramedullary interlocking nailing is the treatment of choice of comminuted fractures of long bones in lower limbs which cause minimum damage to the blood supply of the fracture fragments which promotes the chances of bone union

Dynamic condylar screws versus 95º angle blade plate fixation of subtrochantric fractures of femur

Background: The purpose of this prospective randomized study was to evaluate the results of dynamic condylar screw (DCS) system and 95º angle blade plate fixation in the management of sub-trochanteric femoral fractures, regarding stability, union time, complication rate and functional out come.Methods: Total 30 consecutive patients with sub-trochanteric fracture were studied. The inclusion criteria were closed sub-trochanteric fractures in adults of both gender aged 18 years or above. Pathological fractures and open fractures were excluded from the study. After fixation of fractures with dynamic condylar screw system and 95º angle blade plate patients were followed up in OPD at an interval of 2 weeks till full weight bearing was started and then after at an interval of 4 weeks. Results of treatment were assessed by the Harris hip score for clinical and radiological assessment at the end of 6 months.Results: Among 30 studied cases, males were 22 (73.30%) and female 8 (26.70%). Most common mode of injury was road traffic accidents that occurred in 17 patients (56.70%) and the rest 13 patients had a history of fall. Patients were divided into two random groups (A &B) of 15 cases each. Group A was treated with DCS and Group B was treated with Angle Blade Plate 95º implants. Radiological union in most of the patients (13 out of 15 cases) treated with 95°angle blade plate occurred between 14-18 weeks, while in cases treated with dynamic condylar screw radiological union in most of the patients (14 out of 15) occurred between 12-16 weeks. According to Harris hip score, good to excellent results were achieved in 10 cases (66.66%) of 95°angle blade plate group and 14 cases (93.33%) of dynamic condylar screw group.Conclusions: Patients with sub-trochanteric fractures treated with dynamic condylar screw had earlier radiological union, better functional outcome, less complications and earlier weight bearing

Osteosynthesis distal tibial metadiaphyseal fractures with intramedullary nailing versus plating

Background: The management of the tibial fracture remains controversial despite advances in both non-operative and operative care. Plates and intramedullary nails are two well-accepted and effective methods, but each has been historically related to complications. The present study was conducted to compare the results of displaced extra-articular distal tibia meta-diaphyseal fractures OTA/AO Type 42A- C (distal) and 43-A treated with intramedullary nailing versus plating with respect to union of fracture, early Restoration of function, the axial alignment and Complications, if any.Methods: In this study 30 patients of extra-articular distal tibia fracture AO type 42 A-C (distal) and 43 A were randomly selected and 15 were operated with intramedullary nailing and remaining 15 with plating. The patients were regularly followed up for a period of 9 months with radiological and clinical examination. Final assessment was done by Tenny and Wiss clinical assessment criteria.Results: In Interlocking group, average time for union was 20.33 weeks in Interlocking nail group compared to 23.21 weeks in plating group which was significant (p value 0.011). Also, the average time required for partial and full weight bearing in the nailing group was 7.2 weeks and 13.2 weeks respectively which was significantly less as compared to 9.33 weeks and 16.64 weeks in the plating group. Lesser complications in terms of implant irritation, ankle stiffness and infection (superficial and deep) were seen in Interlocking group as compared to plating group.Conclusions: In present study ILN showed better outcome as it offers advantage in terms of mean operating time, less invasive surgery, hospital stay, partial and full weight bearing time and union time

Chronic calcific pancreatitis: clinical profile in northern India

Twenty three patients with chronic calcific pancreatitis of the tropics in Northern India were prospectively studied. All had pancreatic calcification and ERCP changes typical of chronic pancreatitis, the most predominant being ductal dilatation which was detected in all patients by both ERCP and by ultrasonography. Pain was present in 19 (83%) patients and diabetes in 11 (48%) patients. Exocrine pancreatic dysfunction was uncommon, steatorrhoea being present in only 9% of patients. Ten of the 11 patients with diabetes required insulin for control and one case was able to be controlled by an oral antidiabetic agent. Two patients developed ketoacidosis during acute episodes of pancreatitis, 3 patients had peripheral neuropathy and one patient had visual changes. Recurrent severe pain was the reason for operation in 7 patients. All had a lateral pancreaticojejunostomy. In order to obtain an objective assessment of pain, a scoring system was developed to grade its severity according to its intensity, frequency and consequences. Six patients who preoperatively had a pain score of 15 or more (out of a maximum score of 24) attained significant relief after the surgery. We feel this scoring system may provide an easy objective assessment of pain in the subsequent follow-up of these patients