Gastrointestinal amyloidosis: A focused review

Amyloidosis, a heterogenous group of disorders, is characterized by the extracellular deposition of autologous, insoluble, fibrillar misfolded proteins. These extracellular proteins deposit in tissues aggregated in ß-pleated sheets arranged in an antiparallel fashion and cause distortion to the tissue architecture and function. In the current literature, about 60 heterogeneous amyloidogenic proteins have been identified, out of which 27 have been associated with human disease. Classified as a rare disease, amyloidosis is known to have a wide range of possible etiologies and clinical manifestations. The exact incidence and prevalence of the disease is currently unknown. In both systemic and localized amyloidosis, there is infiltration of the abnormal proteins in the layers of the gastrointestinal (GI) tract or the liver parenchyma. The gold standard test for establishing a diagnosis is tissue biopsy followed by Congo Red staining and apple-green birefringence of the Congo Red-stained deposits under polarized light. However, not all patients may have a positive tissue confirmation of the disease. In these cases additional workup and referral to a gastroenterologist may be warranted. Along with symptomatic management, the treatment for GI amyloidosis consists of observation or localized surgical excision in patients with localized disease, and treatment of the underlying pathology in cases of systemic amyloidosis. In this review of the literature, we describe the subtypes of amyloidosis, with a primary focus on the epidemiology, pathogenesis, clinical features, diagnosis and treatment strategies available for GI amyloidosis.     

Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia.

OBJECTIVE: The authors assessed schizophrenia-associated changes in volume and neuronal number in the mediodorsal nucleus and the pulvinar regions of the thalamus. METHOD: Right-hemisphere thalami obtained at autopsy from 14 schizophrenic and eight comparison subjects were examined. Computer-assisted morphometric techniques were used to determine volumes for the mediodorsal nucleus, pulvinar, and the anterior and centromedian nuclei as well as the parvocellular, magnocellular, and caudodorsal subdivisions of the mediodorsal nucleus. Neurons in the mediodorsal nucleus and pulvinar were counted and measured by using a stereology-based sampling strategy. RESULTS: Four schizophrenic and three comparison subjects had Alzheimer's type pathology, leaving 10 schizophrenic and five comparison subjects without other documented neuropathological changes. In analyses that included either the full cohort or only the subjects without Alzheimer's type pathology, volumes of the mediodorsal nucleus and pulvinar, but not the anterior or centromedian nuclei, were significantly smaller in the schizophrenic subjects. For the schizophrenic subjects, neuronal number in the mediodorsal nucleus, parvocellular subdivision, and pulvinar was significantly lower, and neuronal size in the mediodorsal nucleus, caudodorsal subdivision, and pulvinar was significantly smaller. CONCLUSIONS: Schizophrenia is associated with volume and neuronal changes in the mediodorsal nucleus and pulvinar, the major association nuclei of the thalamus, whereas total thalamic volume and the volumes of anterior and centromedian nuclei were not significantly altered.     

Marjolin's ulcer of the scalp invading calvarial bone, dura and brain.

A Marjolin's ulcer arising in a chronic scalp scar is reported. Malignant transformation occurred after four decades. The tumour had invaded the skull, dura mater and underlying brain tissue. This case illustrates the importance of appropriate and expeditious initial wound management of scar ulcers with high malignant potential to prevent this devastating outcome and also the role of reconstructive surgical techniques in radical surgery for scalp cancers.     

Anxiogenic potential of ciprofloxacin and norfloxacin in rats

INTRODUCTION: The possible anxiogenic effects of fluoroquinolones, namely ciprofloxacin and norfloxacin, were investigated in adult Charles Foster albino rats of either sex, weighing 150-200 g. METHODS: The drugs were given orally, in doses of 50 mg/kg for five consecutive days and the experiments were performed on the fifth day. The tests included open-field exploratory behaviour, elevated plus maze and elevated zero maze, social interaction and novelty-suppressed feeding latency behaviour. RESULTS: The results indicate that ciprofloxacin- and norfloxacin-treated rats showed anxious behaviour in comparison to control rats in all the parameters studied. However, ciprofloxacin- and norfloxacin-treated rats did not differ significantly from each other in various behavioural parameters. CONCLUSION: The present experimental findings substantiate the clinically observed anxiogenic potential of ciprofloxacin and norfloxacin.     

Systemic adverse effects and toxicities associated with immunotherapy: A review

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use of immuno-therapeutic agents, it is vital for physicians to acquaint themselves with these adverse effects. The aim of this review is to investigate the common systemic adverse effects and toxicities associated with the use of different classes of immunotherapeutic agents. We provide an overview of potential adverse effects and toxicities associated with different classes of immunotherapeutic agents organized by organ systems, as well as an extensive discussion of the current recommendations for treatment and clinical trial data. As we continue to see increasing usage of these agents in clinical practice, it is vital for physicians to familiarize themselves with these effects.     

AID Biology: A pathological and clinical perspective

Activation-induced cytidine deaminase (AID), primarily expressed in activated mature B lymphocytes in germinal centers, is the key factor in adaptive immune response against foreign antigens. AID is responsible for producing high-affinity and high-specificity antibodies against an infectious agent, through the physiological DNA alteration processes of antibody genes by somatic hypermutation (SHM) and class-switch recombination (CSR) and functions by deaminating deoxycytidines (dC) to deoxyuridines (dU), thereby introducing point mutations and double-stranded chromosomal breaks (DSBs). The beneficial physiological role of AID in antibody diversification is outweighed by its detrimental role in the genesis of several chronic immune diseases, under non-physiological conditions. This review offers a comprehensive and better understanding of AID biology and its pathological aspects, as well as addresses the challenges involved in AID-related cancer therapeutics, based on various recent advances and evidence available in the literature till date. In this article, we discuss ways through which our interpretation of AID biology may reflect upon novel clinical insights, which could be successfully translated into designing clinical trials and improving patient prognosis and disease management.     

Bayesian algorithm using spatial priors for multiexponential T(2) relaxometry from multiecho spin echo MRI

Multiexponential T₂ relaxometry is a powerful research tool for detecting brain structural changes due to demyelinating diseases such as multiple sclerosis. However, because of unusually high signal‐to‐noise ratio requirement compared with other MR modalities and ill‐posedness of the underlying inverse problem, the T₂ distributions obtained with conventional approaches are frequently prone to noise effects. In this article, a novel multivoxel Bayesian algorithm using spatial prior information is proposed. This prior takes into account the expectation that volume fractions and T₂ relaxation times of tissue compartments change smoothly within coherent brain regions. Three‐dimensional multiecho spin echo MRI data were collected from five healthy volunteers at 1.5 T and myelin water fraction maps were obtained using the conventional and proposed algorithms. Compared with the conventional method, the proposed method provides myelin water fraction maps with improved depiction of brain structures and significantly lower coefficients of variance in white matter. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Imaging of chronic pancreatitis (including groove and autoimmune pancreatitis)

Multiple disorders may cause chronic pancreatitis (CP) through recurrent inflammation of the pancreatic parenchyma. Chronic calcifying pancreatitis caused by excessive alcohol intake accounts for most cases of CP. However, there are multiple other causes of CP, including obstructive chronic pancreatitis, autoimmune pancreatitis, groove pancreatitis, tropical, and hereditary pancreatitis. This article reviews the multiple imaging techniques, some of which are accepted as first-line modalities in patients with suspected CP, and the imaging features associated with the different causes of CP.