Microarray analysis reveals distinct immune signatures in BCR?ABL positive and negative myeloproliferative neoplasms

Background: BCR?ABL mutation on the Philadelphia chromosome is the key driver of chronic myeloid leukemia (CML) pathogenesis. However, there are certain cases of myeloproliferative neoplasms (MPN) wherein no inherent driver mutation is detected resulting in clinical phenotype. It is important to identify key genes and pathways in driving the disease. The aim of the study was to use a gene-based omics approach to molecularly characterize these mutation-positive and negative cases to further strengthen diagnostics and precision medicine. Methods: A microarray profiling was done on CD34 positive cells isolated from two BCR?ABL positive and five BCR?ABL negative samples. JAK2V617F mutation testing was also done to rule out the presence of any other mutation in the latter group. The fold change cut-off was taken as �5 with p?0.5 for significant genes. The gene network and pathway analysis were done using DAVID and STRING software. Results: The genes upregulated in BCR?ABL negative samples were shown to be involved in immune regulation, signal transduction and T- and B-cell signalling. The protein-protein interaction network of upregulated genes in these samples were enriched for various immunomodulatory genes such as HLADP, HLADQ , IL7R, CCR7, CD3 subtypes. These genes further formed a network with signal transduction genes such as LCK, FYN, RAG1, DOCK1, AKT3, SMAD3, LEF1. Conclusion: The results suggested a modulation of immune response genes and its subsequent effect on oncogenic signalling in BCR?ABL negative samples as compared to BCR?ABL positive samples. The protein network analysis was enriched for genes involved in Src, TGF-beta and PI3K-AKT pathway contributing to the proliferation of neoplastic clone.

Management of pseudo tumour in haemophilia patients

A hemophilic pseudotumor is one of the rare complications of hemophilia that results from repetitive bleeding, forming an expanding destructive encapsulated hematoma and necrosed tissue. It has a considerable amount of morbidity. These have become rare over the years with better treatment modalities like factor replacement. Presently, excision is the preferred treatment by many authors. There are instances where surgical excision is not feasible. In such situations, radiotherapy and arterial embolization should be considered either alone or as an adjunct to surgery. A 32 years old male patient, with severe hemophilia A diagnosed with an abdominal tumour 7 years ago during routine screening, that progressively grew to encompass the lower abdominal area. A 44 years old male patient with hemophilia A presented with slow growing swelling over the left gluteal region since, 10 years associated with ulceration and bleeding since, 3 days. The management of a patient with a haemophilic pseudo tumour is complex, with a high rate of potential complications. Surgical excision is the treatment of choice but can only be carried out by a multidisciplinary surgical team. The main postoperative complications are rebleed, infection, fistula and pathological fractures. Pelvic pseudo tumours can even become complicated by fistula formation to the large bowel and by obstruction of the ureters. Untreated pseudo tumours will ultimately destroy soft tissues, erode bone, and may produce neurovascular complications. The hemophilic pseudo tumour is a rare entity which is slow growing painless tumour, with few reports worldwide in the management of this rare complication.

Guidelines for screening, diagnosis and management of hemoglobinopathies.

The b‑thalassemias and sickle cell disorders are a major health burden in India. Diagnosis and management of these disorders both in adults and in newborns using appropriate approaches and uniform technology are important in different regions of a vast and diverse country as India. In view of a National Thalassemia Control Program to be launched soon, a need was felt for guidelines on whom to screen, cost‑effective technologies that are to be used as well as for establishing prenatal diagnosis programs in regional centers. Newborn screening for sickle cell disorders is in its infancy in India and uniform approaches need to be followed. Also, included are guidelines for monitoring and managing patients who are now growing older and need comprehensive care as well as management of complications of the disease.

ABO blood groups and malaria related clinical outcome.

Objectives: The study was undertaken to correlate the blood groups and clinical presentations in malaria patients and to understand the differential host susceptibility in malaria. Methods: From October 2007 to September 2008, malaria positive patients’ samples were evaluated in this study. Hemoglobin, total leukocyte count, and platelet count of each patient were done on an automated cell counter. After determining the blood groups, malarial species and the severity of clinical course were correlated. Results: A total of 100 patients were included in the study, of which 63 cases were positive for Plasmodium falciparum and 37 cases were positive for P. vivax infection and 11 patients had mixed infection. The results of the blood groups showed 22 – ‘A’ group, 42 – ‘B’ group, 35 – ‘O’ group and 1 was ‘AB’ group. When the clinical courses between different groups were compared using the following parameters for severe infection—a parasitic load of >10/1000 RBCs, severe anemia with hemoglobin < 6 g%, platelet count of <10,000/mm3, hepato or splenomegaly or clinical signs of severe malaria such as fever >101oF and other organ involvement, it was observed that ‘O’ group had an advantage over other the groups. The difference in rosetting ability between red blood cells of different ‘ABO’ blood groups with a diminished rosetting potential in blood group ‘O’ red blood cells was due to the differential host susceptibility. Conclusion: ‘O’ group had an advantage over the other three blood groups. Based on literature and the results of this study, the diminished rosetting potential in blood group ‘O’ red blood cells is suggested as the basis for the differential host susceptibility.

The teacher and the taught: Medical education in India at the crossroads.

In a good medical teacher we would like to see a good doctor, a good teacher, a good orator and, overall, a good human being. Many teachers of yesteryears may not have had all these qualities but they had the ability to instil in the student’s mind a sense of respect and a desire to learn. We now have more of the science and less of the art of teaching. We have failed to live by example. Modern-day consumerism and a single-minded approach to money, coaching classes, destruction of proper medical training by effectively removing internship and housemanship have made students apathetic with no desire to learn. We suggest that there are several ways by which the situation can be remedied including a system of mentoring, incentives and feedback.

Melioidosis.

Melioidosis is an emerging infectious disease in India acquired through percutaneous inoculation or contaminated water. Known risk factors include diabetes mellitus, renal failure, cirrhosis, and malignancy. Melioidosis presents with a febrile illness, with protean manifestations ranging from septicemia to localized abscess formation. We present the case of a 42-year-old male from a non-endemic region who presented with fever of 2 months duration, sepsis, persistent pneumonia, right hip joint pain and hepatic and splenic abscesses. Aspiration of the joint and soft tissue fluid collection and subsequent culture yielded gram negative bacilli identified as Burkholderia pseudomallei. The epidemiology, clinical features, and laboratory diagnosis of this rare infection and its treatment is reviewed.

Reviparin sodium clivarine: a review of its therapeutic use.

Reviparin sodium (clivarine) is a second generation LMWH, developed with the aim of maximising the antithrombotic action while minimising the risk of haemorrhage. Clivarine has been extensively studied in acute coronary syndrome. Various clinical studies in unstable angina and acute coronary syndrome have proved that clivarine in a dosage of 3436anti-Xa units twice daily is an effective antithrombotic agent. Clivarine has been shown to be as effective as unfractionated heparin (UFH) in thromboprophylaxis and it has less incidence of local haematoma at injection site. At a daily dose of 1432 IU anti-Xa it was found to be as effective as UFH in preventing deep vein thrombosis (DVT) in moderate risk surgery (general and abdominal) and reducing to a significant extent DVT in patients with brace immobilisation of the legs. At a daily dose of 3436 IU anti-Xa reviparin was as effective as UFH or enoxaparin in preventing DVT in high risk orthopaedic surgery and as effective as UFH in prevention of DVT and/or pulmonary embolism (PE) and/or mortality in high risk orthopaedic surgery. In patients with acute venous thrombo-embolism (VTE), reviparin was more effective than UFH in thrombus reduction and at least as effective as UFH in the prevention of clinical recurrence of DVT and/or PE. The use of reviparin is associated with a similar or lower incidence of bleeding complications than UFH. The benefits of reviparin sodium have been demonstrated in a number of clinical trials.