Pleural Effusion Secondary to Moraxella Catarrhalis Infection

A 43-year-old male with chronic kidney disease on maintenance hemodialysis presented with breathlessness, cough and right-sided abdominal pain. Examination revealed a large right-sided pleural effusion and subsequent thoracocentesis yielded an exudate. Although the fluid culture was sterile, sputum culture produced Moraxella catarrhalis. Tuberculosis was ruled out by pleural fluid analysis and pleural biopsy. Antibiotics were administered and subsequent radiograms indicated resolution of the effusion. This is a rare case of a large unilateral pleural effusion secondary to M. catarrhalis infection in a non-smoker with no pre-existing pulmonary pathology

Targeting of Histone Acetyltransferase p300 by Cyclopentenone Prostaglandin Δ12-PGJ2 through Covalent Binding to Cys1438

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx200383cInhibitors of histone acetyltransferases (HATs) are perceived to treat diseases like cancer, neurodegeneration, and AIDS. On the basis of previous studies, we hypothesized that Cys1438 in the substrate binding site could be targeted by Δ12-prostaglandin J2 (Δ12-PGJ2), a cyclopentenone prostaglandin (CyPG) derived from PGD2. We demonstrate here the ability of CyPGs to inhibit p300 HAT-dependent acetylation of histone H3. A cell-based assay system clearly showed that the α,β-unsaturation in the cyclopentenone ring of Δ12-PGJ2 was crucial for the inhibitory activity, while the 9,10-dihydro-15-deoxy- Δ12,14-PGJ2, which lacks the electrophilic carbon (at carbon 9), was ineffective. Molecular docking studies suggested that Δ12-PGJ2 places the electrophilic carbon in the cyclopentenone ring well within the vicinity of Cys1438 of p300 to form a covalent Michael adduct. Site-directed mutagenesis of the p300 HAT domain, peptide competition assay involving p300 wild type and mutant peptides, followed by mass spectrometric analysis confirmed the covalent interaction of Δ12-PGJ2 with Cys1438. Using biotinylated derivatives of Δ12-PGJ2 and 9,10-dihydro-15-deoxy- Δ12,14-PGJ2, we demonstrate the covalent interaction of Δ12-PGJ2 with the p300 HAT domain, but not the latter. In agreement with the in vitro filter binding assay, CyPGs were also found to inhibit H3 histone acetylation in cell-based assays. In addition, Δ12-PGJ2 also inhibited the acetylation of the HIV-1 Tat by recombinant p300 in in vitro assays. This study demonstrates, for the first time, that Δ12-PGJ2 inhibits p300 through Michael addition, where α,β-unsaturated carbonyl function is absolutely required for the inhibitory activity

Multiple intra-renal pathological injury patterns in resistant myeloma

Renal dysfunction in patients with multiple myeloma has a heterogeneous aetiology ranging from pre-renal, intra-renal to post-renal causes. Common pathological forms of paraproteinemic disease include cast nephropathy, amyloidosis and Immunoglobulin chain deposition disease. Infrequently cryoglobulinemic glomerulonephritis and light chain proximal tubulopathy have also been described. The presence of multiple intra-renal pathological injury patterns has been described only once previously with immunoglobulin light chains. We report a patient with long standing treatment resistant multiple myeloma and new onset progressive renal failure with heavy and light-chain amyloidosis, cast nephropathy and proximal tubulopathy on renal biopsy

Preparation, validation and user-testing of pictogram-based patient information leaflets for hemodialysis patients

AbstractBackground: Patient information leaflets are universally-accepted resources to educate the patients/users about their medications, disease and lifestyle modification. Objectives: The objective of the study was to prepare, validate and perform user-testing of pictogram-based patient information leaflets (P-PILs) among hemodialysis (HD) patients. Methods: The P-PILs are prepared by referring to the primary, secondary and tertiary resources. The content and pictograms of the leaflet have been validated by an expert committee consisting of three nephrologists and two academic pharmacists. The Baker Able Leaflet Design has been applied to develop the layout and design of the P-PILs. Results: Quasi-experimental pre- and post-test design without control group was conducted on 81 HD patients for user-testing of P-PILs. The mean Baker Able Leaflet Design assessment score for English version of the leaflet was 28, and 26 for Kannada version. The overall user-testing knowledge assessment mean scores were observed to have significantly improved from 44.25 to 69.62 with p value <0.001. Conclusion: The overall user opinion of content and legibility of the leaflets was good. Pictogram-based patient information leaflets can be considered an effective educational tool for HD patients

Spontaneous Tumor Lysis Syndrome in a Case of Multiple Myeloma

We describe a case of a 40-year-old male patient who was found to have multiple myeloma with spontaneous tumour lysis syndrome (TLS), following a compression fracture of the L–2 vertebrae. Multiple myeloma was confirmed by bone marrow analysis and the M–band on serum protein electrophoresis. Hyperuricaemia (26.2 mg/dL), hyperkalaemia (> 7.0 mEq/L), hyperphosphatemia (16.2 mg of phosphorus/dL), normocalcemia and acute kidney injury, prior to anticancer treatment suggested spontaneous TLS. Inciting events for tumour lysis, such as chemotherapy, dehydration and exposure to steroids were absent. Patient received hydration, hypourecemic drugs and haemodialysis. This case report highlights the rare presentation of multiple myeloma with spontaneous TLS