ABSTRACT
Multiple myeloma (MM) can present with involvement of the central nervous system in the form of nerve palsy, plasma cell masses or, rarely, with endocrinological effects due to involvement of the pituitary gland. Usually, in such cases, the disease has a rapid progression and poor prognosis. We report a 52-year-old man who was admitted to the Kolkata Medical College, Kolkata, India, in 2016 with a prolonged low-grade fever and hypernatremia. Shortly afterwards, the patient began to complain of increased urinary frequency and drowsiness. The hypernatremia was treated with intranasal desmopressin and free water replacement. Serum protein electrophoresis and an immunofixation study revealed an immunoglobulin G-κ monoclonal band. Magnetic resonance imaging of the pituitary gland revealed the absence of a posterior bright spot and spotty infiltration of the pituitary fossa. A bone marrow biopsy confirmed a diagnosis of cranial diabetes insipidus due to posterior pituitary MM infiltration.
Subject(s)
Diabetes Insipidus, Neurogenic/etiology , Multiple Myeloma/complications , Pituitary Gland, Posterior/pathology , Fever/etiology , Humans , Hypernatremia/etiology , Hypernatremia/therapy , India , Male , Middle Aged , Multiple Myeloma/pathologySubject(s)
Ascites , CA-125 Antigen/blood , Ascites/diagnosis , Ascites/etiology , Female , Humans , Middle AgedSubject(s)
Bone Neoplasms/pathology , Cervical Vertebrae/diagnostic imaging , Plasmacytoma/pathology , Spinal Neoplasms/pathology , Biopsy , Bone Neoplasms/radiotherapy , Cervical Vertebrae/radiation effects , Dose Fractionation, Radiation , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Neck Pain/etiology , Neck Pain/radiotherapy , Plasmacytoma/complications , Plasmacytoma/radiotherapy , Radiotherapy , Spinal Neoplasms/complications , Spinal Neoplasms/radiotherapy , Tomography, X-Ray ComputedABSTRACT
Genetic variants are expected to play an important role in arsenic susceptibility. Our previous study revealed deficient DNA repair capacity to be a susceptibility factor for arsenicism. T241M polymorphism in XRCC3 (a homologous recombination repair pathway gene) is widely studied for its association with several cancers. We have investigated the association of XRCC3 T241M polymorphism with arsenic-induced precancerous and non-cancer disease outcomes. The present study evaluated the association of T241M polymorphism with arsenic-induced skin lesions, peripheral neuropathy (neurodegenerative changes), conjunctivitis and other ocular diseases. A case-control study was conducted in West Bengal, India, involving 206 cases with arsenic-induced skin lesions and 215 controls without arsenic-induced skin lesions having similar arsenic exposure. XRCC3 T241M polymorphism was determined using conventional PCR-sequencing method. Chromosomal aberration assay, arsenic-induced neuropathy and ocular diseases were also evaluated. The data revealed that presence of at least one Met allele (Met/Met or Thr/Met) was protective towards development of arsenic-induced skin lesions [OR=0.45, 95% CI: 0.30-0.67], peripheral neuropathy [OR=0.49; 95%CI: 0.30-0.82] and conjunctivitis [OR=0.60; 95%CI: 0.40-0.92]. A significant correlation was also observed between protective genotype and decreased frequency of chromosomal aberrations. Thus the results indicate the protective role of Met allele against the arsenic-induced skin lesions, chromosomal instability, peripheral neuropathy and conjunctivitis.
Subject(s)
Arsenic/toxicity , Carcinogens/toxicity , DNA-Binding Proteins/genetics , Mutagens/toxicity , Precancerous Conditions/chemically induced , Water Pollutants, Chemical/toxicity , Adult , Alleles , Amino Acid Substitution , Case-Control Studies , Chromosome Aberrations/chemically induced , Conjunctivitis/chemically induced , Conjunctivitis/genetics , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , India , Male , Methionine/genetics , Odds Ratio , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/genetics , Polymorphism, Genetic , Precancerous Conditions/genetics , Skin Diseases/chemically induced , Skin Diseases/genetics , Threonine/geneticsABSTRACT
Arsenic contamination in drinking water is one of the biggest natural calamities, which has become an imperative threat to human health throughout the world. Abbreviation of erythrocyte lifespan leading to the development of anemia is a common sequel in arsenic exposed population. This study was undertaken to explore the mechanism of cell death in human erythrocytes during chronic arsenic exposure. Results revealed transformation of smooth discoid red cells into evaginated echinocytic form in the exposed individuals. Further distortion converted reversible echinocytes to irreversible spheroechinocytes. Arsenic toxicity increased membrane microviscosity along with an elevation of cholesterol/phospholipid ratio, which hampered the flexibility of red cell membrane and made them less deformable. Significant increase in the binding of merocyanine 540 with erythrocyte membrane due to arsenic exposure indicated disruption of lipid packing in the outer leaflet of the cell membrane resulting from altered transbilayer phospholipid asymmetry. Arsenic induced eryptosis was characterized by cell shrinkage and exposure of phosphatidylserine at the cell surface. Furthermore, metabolic starvation with depletion of cellular ATP triggered apoptotic removal of erythrocytes from circulation. Significant decrease in reduced glutathione content indicating defective antioxidant capacity was coupled with enhancement of malondialdehyde and protein carbonyl levels, which pointed to oxidative damage to erythrocyte membrane. Arsenic toxicity intervened into red cell membrane integrity eventually leading to membrane destabilization and hemoglobin release. The study depicted the involvement of both erythrophagocytosis and hemolysis in the destruction of human erythrocytes during chronic arsenic exposure.
