Monoclonal Gammopathy of Renal Significance Triggered by Viral E Hepatitis.

Monoclonal gammopathy of undetermined significance does not have end organ damage, but a proportion of cases manifest with renal injury when it is called monoclonal gammopathy of renal significance (MGRS). Herein, we describe a case of acute hepatitis E infection, which precipitated the development of MGRS. The patient underwent kidney biopsy for elevated creatinine with clinical suspicion of drug-induced interstitial nephritis. On light microscopy, there were periodic acid-Schiff negative-fractured casts in tubules with giant cell reaction around them. The tubular epithelial cells showed intracytoplasmic bile pigment. On direct immunofluorescence, casts showed kappa restriction. A diagnosis of bilirubin proximal tubulopathy and light chain cast nephropathy was made, and possibility of myeloma was suggested. On further evaluation, κ:λ ratio was 27, ß2 microglobulin was 8036 ng/ml, and bone marrow examination showed 5% plasma cells. There were no bony lesions, and serum calcium was 8.6 mg/dl. The present case is unique in two aspects. First, the patient developed MGRS triggered by acute hepatitis E in less than a month. Second, the MGRS lesion was manifested in the form of light chain cast nephropathy.

DNA staining in agarose and polyacrylamide gels by methyl green.

Methyl green (MG) is an inexpensive, nonproprietary, traditional histological stain for cell nuclei. When bound to DNA and upon excitation with orange-red light, it fluoresces brightly in the far red region. We compared MG with ethidium bromide (EtBr), the conventional stain for DNA in gels, and Serva DNA stain G™ (SDsG), a proprietary stain marketed as a safer alternative to EtBr for staining of electrophoresed DNA bands in agarose and polyacrylamide gels. DNA-MG fluorescence was recorded and 2.4 µg/ml MG produced crisp images of electrophoresed DNA after incubation for 10 min. Stain solutions were stable and detection limits for faint bands as well as relative densitometric quantitation were equivalent to EtBr. MG, EtBr and SDsG cost 0.0192, 0.024 and 157.5 US cents/test, respectively. MG is an effective stain for visualizing DNA in agarose and polyacrylamide gels. Its major advantages including low cost, comparable quality of staining, storage at room temperature, photo-resistance and low mutagenic profile outweigh its disadvantages such as staining of tracking dye and requirement for a gel documentation system with a red filter.

Autologous Stem Cell Transplantation for Multiple Myeloma: Single Centre Experience from North India.

Autologous stem cell transplantation (ASCT) is considered as standard of care in patients with multiple myeloma (MM) patients aged 65 years or younger. We analyzed data of 94 patients of plasma cell dyscrasias who underwent 95 autologous transplants at our institute from October 2003 to Aug 2016. Other than 76 patients of newly diagnosed multiple myeloma, we also transplanted two patients of POEMS syndrome, two patients of plasma cell leukemia, three patients of concurrent light chain deposition disease, three patients of multifocal plasmacytomas, and eight patients of isolated light chain myeloma. One patient underwent transplant twice. The median age of patients was 53 years (range 21-65). The average interval between diagnosis and transplant was 10.51 ± 5.42 months. The predominant stage in the study cohort was ISS-III. IgG kappa was the commonest subtype of plasma cell dyscrasia (27.9%) followed by IgG lambda (16.27%). Renal involvement was seen in 25% patients at the time of transplantation. Following chemotherapy, 42% patients were in CR, 39% in VGPR, 5% had PR and 14% had progressive disease at the time of transplantation. All patients were conditioned with melphalan (dose 120-200 mg/m2) except for one who received an additional bortezomib for his second transplant. The mean time to neutrophil and platelet engraftment was 11.09 ± 1.82 and 12.69 ± 4.55 days respectively. Mucositis was noted in all patients (grade 3 in 37.5% patients). The median PFS (biochemical) was 55.8% and PFS (clinical) was 76.7% at 6.5 years. Thirteen percent of the transplanted patients succumbed to their illness of which three patients died within 30 days of transplant. Median OS was 76.7% at 6.5 years. ASCT is a feasible option for MM in India and the results are comparable.

A comparative evaluation of Eosin-5'-maleimide flow cytometry reveals a high diagnostic efficacy for hereditary spherocytosis.

INTRODUCTION: Laboratory diagnosis of hereditary spherocytosis (HS) relies on increased incubated red cell osmotic fragility test for screening. We evaluated the diagnostic role of eosin-5'-maleimide (EMA) binding test by flow cytometry in spherocytic and microcytic hypochromic hematological disorders in North Indians. METHODS: EMA binding test using flow cytometry was performed on 55 HS (40 families), 26 iron deficiency anemia (IDA), 32 ß-thalassemia trait (ßTT), and 10 autoimmune hemolytic anemia (AIHA) cases and 121 normals. Mean channel fluorescence (MCF) and coefficient of variation (CV) were studied. Different MCF parameters (MCF, MCF ratio, percent decrease MCF) and percent increase in CV were analyzed. Receiver operating characteristics analysis was performed to determine best cutoff values, sensitivity, and specificity for discriminating HS from other red cell disorders. RESULTS: MCF ratio of HS group was significantly lower than normals (0.67 ± 0.07 vs. 1.01 ± 0.05, P < 0.001) and other cases. All patients with HS showed MCF ratio to be ≤0.79. Four postsplenectomy cases with near-normal hemograms also revealed low MCF ratio, showing the specificity of the test. CONCLUSIONS: EMA assay was efficient to diagnose cases of HS including postsplenectomy cases and shows no overlap with IDA, ßTT, and AIHA.

Vortex-dislodged cells from bone marrow trephine biopsy yield satisfactory results for flow cytometric immunophenotyping.

INTRODUCTION: A good bone marrow (BM) sample is essential in evaluating many hematologic disorders. An unsuccessful BM aspiration (BMA) procedure precludes a successful flow cytometric immunophenotyping (FCI) in most hematologic malignancies. Apart from FCI, most ancillary diagnostic techniques in hematology are less informative. We describe the feasibility of FCI in vortex-dislodged cell preparation obtained from unfixed trephine biopsy (TB) specimens. METHODS: In pancytopenic patients and dry tap cases, routine diagnostic BMA and TB samples were complemented by additional trephine biopsies. These supplementary cores were immediately transferred into sterile tubes filled with phosphate-buffered saline, vortexed, and centrifuged. The cell pellet obtained was used for flow cytometric immunophenotyping. RESULTS: Of 7955 BMAs performed in 42 months, 34 dry tap cases were eligible for the study. Vortexing rendered a cell pellet in 94% of the cases (32 of 34), and FCI rendered a rapid diagnosis in 100% of the cases (32 of 32) where cell pellets were available. CONCLUSION: We describe an efficient procedure which could be effectively utilized in resource-limited centers and reduce the frequency of repeat BMA procedures.

Macrophage activation syndrome in children with systemic onset juvenile idiopathic arthritis: clinical experience from northwest India.

The objective of this study is to describe the clinical and laboratory features of macrophage activation syndrome (MAS) in systemic onset juvenile idiopathic arthritis (SOJIA) at a tertiary care center in northwest India. Review of medical records of all children with SOJIA admitted during the period January 1995-December 2008 in Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, was done. Six patients (5 boys and 1 girl) with SOJIA and MAS were identified. Mean age at time of disease onset was 6.5 years. MAS was the presenting manifestation of SOJIA in 4 patients. Clinical manifestations included fever (6/6), clinical shock (6/6), encephalopathy (5/6), generalized lymphadenopathy (4/6), hepatosplenomegaly (3/6), jaundice and abdominal tenderness (3/6), cardiac involvement (3/6), and meningeal irritation (2/6). Laboratory findings at onset of MAS included decreasing total leukocyte and platelet counts, coagulopathy, elevated transaminases, hyponatremia, and lipid abnormalities. Hemophagocytosis was demonstrable in the bone marrow in 4 patients and in the lymph node in 1. For treatment, we used intravenous methylprednisolone (4/6), oral prednisolone (2/6), and intravenous immunoglobulin (2/6). Outcome was favorable in all patients except one who died of rapidly progressive disease. This paper describes the experience of JIA-related macrophage activation syndrome in a tertiary Indian center. We have shown that MAS can be the early presenting manifestation of evolving SOJIA. Early diagnosis and aggressive management can have a significant impact on the mortality associated with this syndrome. We stress on the role of glucocorticoids in the management of this condition and believe that glucocorticoids have a far more important role in the management of this condition than what has been previously reported.

Prothrombotic profile in children with peripheral gangrene: a single center experience.

Peripheral gangrene is rare in children. Protein C, protein S, and antithrombin deficiency, positivity for anticardiolipin antibodies or lupus anticoagulant and factor V Leiden mutation are important causes of thrombosis in the venous system. There is paucity of literature on the contribution of these factors in children with peripheral gangrene. We evaluated the role of aforementioned factors in children with peripheral gangrene. Protein S deficiency was seen in one case and another was transiently positive for lupus anticoagulant. None of the 11 age- and sex-matched normal controls had protein C, protein S, or antithrombin deficiency. Our results indicate that deficiency of protein C, protein S, and antithrombin, and positivity for anticardiolipin antibodies, lupus anticoagulant, and factor V Leiden are uncommon causes of peripheral gangrene in children in north-western India. Fibrinolytic and antiplatelet parameters were not tested. Testing for these may yield further clues to the etiology of this condition.