ABSTRACT
In the present work, orodispersible tablets of pheniramine maleate were designed with a view to enhance patient compliance by effervescent method. In the effervescent method, mixture of sodium bicarbonate and tartaric acid (each of 12% w/w concentration) were used along with super disintegrants, i.e., pregelatinized starch, sodium starch glycolate, croscarmellose sodium and crospovidone. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity and in vitro dispersion time. Based on in vitro dispersion time (approximately 60 s), three formulations were tested for in vitro drug release pattern (in pH 6.8 phosphate buffer), short-term stability (at 40+/-2 degrees /75+/-5% RH for 3 mo) and drug-excipient interaction (IR spectroscopy). Among three promising formulations, formulation ECP(4) containing 4% w/w crospovidone and mixture of sodium bicarbonate and tartaric acid (each of 12% w/w) emerged as the overall best formulation (t(70%) = 1.65 min) based on the in vitro drug release characteristics compared to commercial conventional tablet formulation. Short-term stability studies on the formulations indicated no significant changes in the drug content and in vitro dispersion time (P < 0.05).
ABSTRACT
BACKGROUND: Although cardiovascular disease (CVD) is recognized as a leading cause of death in patients with systemic lupus erythematosus (SLE) in western countries, there is hardly any data regarding Indian subjects with SLE. AIMS: To determine the incidence of cardiac abnormalities and vascular lesions at autopsy and to assess their contribution to the mortality in patients with SLE. SETTINGS AND DESIGN: Retrospective retrieval of reports of autopsies performed on 35 patients with SLE over a 11 year period and analysis of 27 cases with cardiac and/or vascular lesions. MATERIALS AND METHODS: Gross and microscopic features in 27 autopsies were analyzed with special attention to the heart and the vasculature of all organs. Findings were correlated with clinical features and ante-mortem investigations. Their contribution towards mortality was assessed. RESULTS: Valvar lesions were the commonest cardiac lesions noted with non-bacterial thrombotic endocarditis in nine (33.33%), valvar thickening in two (7.41%), Libman-Sacks endocarditis and infective endocarditis in one (3.70%) each. Myocarditis and myocardial scarring were seen in 10 (37.03%) and seven (25.92%) cases, respectively. Fibrinous pericarditis was noted in seven (25.92%). Thromboses/embolism, vasculitis and severe coronary atherosclerosis were seen in nine (33.33%), five (18.52%) and one (3.70%) subjects, respectively. Renal disease [13, 48.14%] and cardiovascular manifestations [8, 29.62%] were the leading causes of death in our patient population. CONCLUSION: CVD contributes significantly to the mortality in patients with SLE in India. It is second only to renal disease in this regard.
Subject(s)
Cardiovascular Diseases/pathology , Lupus Erythematosus, Systemic/pathology , Adolescent , Adult , Autopsy , Cardiovascular Diseases/mortality , Child , Female , Humans , Incidence , India/epidemiology , Lupus Erythematosus, Systemic/mortality , Male , Retrospective StudiesABSTRACT
BACKGROUND: Leptospirosis is an important sporadic zoonotic disease caused by the spirochete Leptospira icterohaemorrhagiae . The disease becomes a major public health problem, particularly during the monsoon months. MATERIALS AND METHODS: Analysis of autopsy findings of 62 cases of clinically suspected leptospirosis was carried out to identify the pathology and determine the cause of death. RESULTS: Most patients were young males who presented with fever, breathlessness, haemoptysis, bleeding, oliguria and icterus. They died after a brief stay in hospital. A post-mortem diagnosis of leptospirosis was made on the basis of characteristic organ findings, aided by results of serology, Levaditi's staining and / or immunohistochemistry (IHC) on kidney sections. Massive intra-alveolar haemorrhage (48 cases), acute interstitial nephritis and / or acute tubular necrosis (45 cases) and myocarditis (24 cases) were the main autopsy findings. Haemorrhage in various organs like the heart, gastrointestinal tract, brain, pancreas and adrenals were also seen. Thirty of 54 kidney sections were positive for leptospiral antigens by IHC. There was extensive haemorrhages in the lungs in 48 (77%) cases and that was the cause of death in most of these cases. CONCLUSION: Bleeding into various tissues and organs is the main finding noted in this study. The post-mortem examination of patients dying of leptospirosis revealed that pulmonary haemorrhage was the cause of death in most individuals.
Subject(s)
Leptospirosis/pathology , Adolescent , Adult , Aged , Autopsy , Cause of Death , Child , Female , Humans , India , Leptospirosis/metabolism , Leptospirosis/mortality , Male , Middle Aged , Retrospective Studies , Urban HealthABSTRACT
AIMS OF THE STUDY: To evaluate the advantages and reliability of screening for antinuclear antibodies (ANA) by enzyme immunoassay (ELISA). METHODOLOGY: Sera from 96 patients comprising 51 with systemic lupus erythematosus (SLE), 11 with other systemic rheumatological diseases (SRD) and 34 with various other diseases (non-SRD) were tested using a commercial ELISA kit (ANA-Ease, Genesis Biotechnology, U.K.). These sera consisted of 53 immunofluorescence assay (IF) ANA-positive and 43 IF ANA-negative samples RESULTS: We observed that when compared to the IF for ANA the sensitivity, specificity, predictive values for positives (PPV) and negatives (NPV) of ELISA were 90.7%, 85.7%, 89.1% and 87.8% respectively. Exclusion of borderline ELISA positive by slightly raising the cut-off optical density (OD) increased the specificity and PPV to 93.1%, and 94.1% respectively. Importantly, none of the non-SRD sera were positive when this higher cut-off was used. ELISA was noted to be strongly positive in three IF ANA-negative SLE patients. However there was no correlation between the ELISA ANA semi-quantitative index and the IF ANA titers. CONCLUSIONS: ELISA appears to be suitable as a preliminary screening test for ANA. An appropriate cut-off should be identified to segregate low positive samples that could be false-positives. Nevertheless, IF will need to be performed to estimate the titers, identify patterns of ANA positive samples and confirm results of low positive "gray-zone" samples and ELISA negative sera from patients with a high index of clinical suspicion of SLE.
Subject(s)
Antibodies, Antinuclear/blood , Enzyme-Linked Immunosorbent Assay , Lupus Erythematosus, Systemic/immunology , Biomarkers/blood , False Negative Reactions , False Positive Reactions , Humans , Lupus Erythematosus, Systemic/diagnosis , Mass Screening/methods , Predictive Value of Tests , Sensitivity and SpecificityABSTRACT
We present, herein, a case of venous thrombosis who was lupus anticoagulant negative and had low levels of anticardiolipin antibodies at the time of initial presentation. A definite diagnosis of antiphospholipid syndrome (APS) could be made only when repeat testing, six months later, revealed a dramatic rise of these antibodies.
Subject(s)
Antibodies, Anticardiolipin/blood , Antiphospholipid Syndrome/immunology , Venous Thrombosis/immunology , Adult , Antiphospholipid Syndrome/diagnosis , Female , Humans , Lupus Erythematosus, Systemic/diagnosis , Time FactorsSubject(s)
Hemorrhage/pathology , Leptospirosis/pathology , Pneumonia, Bacterial/pathology , Pulmonary Alveoli/pathology , Biopsy, Needle , Fatal Outcome , Hemorrhage/complications , Humans , Immunohistochemistry , India , Leptospirosis/complications , Male , Middle Aged , Photomicrography , Pneumonia, Bacterial/complications , Pulmonary Alveoli/microbiologyABSTRACT
AIM: To evaluate the utility of bronchoalveolar lavage (BAL) in immunocompromised patients. MATERIAL AND METHODS: We studied BAL cytology and microbiological culture in 16 kidney transplant recipients (Group A), 14 dialysis patients (Group B) and eight HIV positive patients (Group C) suspected of having pulmonary infections. A group of 21 individuals without pulmonary diseases were studied as controls. RESULTS: A comparison of the cytological profile in controls and study groups showed that percentages of lymphocytes and neutrophils were significantly increased in all three patient groups as compared to controls, BAL bacterial cultures were positive in 4, 3 and 4 cases of Group A, B and C, respectively. Direct examination of BAL cytosmears helped in detecting cytomegalovirus inclusions, acid fast bacilli and Pneumocystis carinii in 3, 2 and 5 cases of Group A, B and C, respectively though microbial cultures were negative. The sensitivity of BAL cytology was found to be 76.3%, whereas that of microbial culture was only 31.5%. The diagnostic yield of BAL was 68.75%, 71.42% and 100% in the Groups A, B and C, respectively, while it was 76% when all three groups were considered together. BAL cytology yielded the diagnosis in 47.36% of cases, a combination of BAL cytology and culture in 23.68% and culture alone in 5.3% of cases. CONCLUSIONS: BAL is useful relatively non-invasive investigative tool in the rapid diagnosis of infections in immunocompromised patients. BAL cytology was found to be more useful than microbial cultures.
Subject(s)
Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage , HIV Infections/immunology , HIV Infections/pathology , Immunocompromised Host/immunology , Kidney Transplantation/immunology , Kidney Transplantation/pathology , Renal Insufficiency/immunology , Renal Insufficiency/pathology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/pathology , Bronchoalveolar Lavage Fluid/immunology , Humans , Renal Dialysis , Renal Insufficiency/therapy , Respiratory Tract Infections/immunologyABSTRACT
The application of molecular biology tools to investigate the molecular basis of acute allograft rejection has unravelled many complex mechanisms and improved immunosuppressive therapies leading to significant improvements in graft survival. The "indirect" pathway of antigen presentation has emerged as more important, than the traditional "direct" pathway, for allorecognition by T cells. The recognition that CD28 costimulation is essential for allorecognition has provided novel targets for immunotherapy such as CTLA-Immunoglobulin. Understanding the role of Th1 and Th2 subsets of T helper cells, the cytokine network and cell adhesion molecules in the mediation or prevention of graft rejection has opened new avenues for research into therapeutic modalities. The ideal objective would be to identify the mechanisms of graft destruction and design specific inhibitors. This review highlights recent advances in the understanding of acute renal allograft rejection which may have future potential for rational design of new immunosuppressive strategies.