Glutamate system,amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid β peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid β and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid β production, but also amyloid β can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness.     

Clinico-Pathological Spectrum of Primary Plasma Cell Leukemia Diagnosed at a Tertiary Care Centre in South India Over 5?Year Period

Plasma cell leukemia (PCL) represents a rare and aggressive form of plasma cell dyscrasia which can be primary (pPCL) or secondary (sPCL). It is diagnosed based on absolute plasma cell count of more than 2.0 × 10⁹/l or a relative proportion of greater than 20% of the peripheral blood leukocyte count. Although pPCL and sPCL share several clinical features, important differences exist. Patients with pPCL are younger; often have extra osseous organ involvement (liver, spleen and other extramedullary sites), increased frequency of renal failure, fast declining performance status and rapid progression to the terminal stage. Patients with sPCL have advanced bone disease. Presented in this article is India data of a short series of five cases of PCL diagnosed at a tertiary care centre from south India over last 5 years. All cases were de novo and had varied spectrum of presentation and so were not suspected to be plasma cell dyscrasia clinically. Detailed hemato-pathological evaluation clinched the diagnosis in all the cases.     

Anticoagulants for the treatment of acute coronary syndrome in the era of new oral agents

Acute coronary syndromes (ACS) cause cessation of myocardial blood flow leading to coronary ischemia. The standard medical treatment includes heparin or low molecular weight heparin in the hospital, antiplatelet agents in the hospital and long term, and occasionally warfarin long term. All of these therapies are associated with bleeding complications. Furthermore, warfarin, with its narrow therapeutic window and need for frequent laboratory monitoring, poses several disadvantages. The development of novel oral factor Xa inhibitors and oral direct thrombin inhibitors may provide an alternative to warfarin. In this review, we discuss the new agents, rivaroxaban, apixaban, and dabigatran, for the potential treatment of ACS. We also review the relevant clinical trials evaluating their effects in ACS. These novel anticoagulants allow convenience of use with no requirement for laboratory monitoring and limited drug interactions, which may provide multifaceted treatment options for ACS and anticoagulation in the future.     

A case of rhabdomyosarcoma masquerading as acute leukemia at presentation: a case report

Non-hematopoietic malignancies infiltrating bone marrow have always been a source of erroneous diagnosis. Among these, the small round cell tumors like neuroblastomas and rhabdomyosarcomas mimick the hematopoietic blasts. Several case reports of rhabdomyosarcoma mimicking acute leukemia, clinically and morphologically at presentation have been reported in the literature. To the best of our knowledge such an entity has not been reported in Indian literature. We report here one such case of alveolar rhabdomyosarcoma masquerading as acute leukemia. A thorough clinical examination with high degree of suspicion on bone marrow morphology and judicious use of appropriate immunohistochemistry markers will solve many of these cases.