Efficacy and safety of tenecteplase in pulmonary embolism

Pulmonary embolism (PE) is a relatively common life-threatening cardiovascular condition associated with significant morbidity and mortality. We present the efficacy and safety data of weight-adjusted tenecteplase in 30 consecutive patients of acute PE. 30 patients (22 male, 8 female) with acute PE were included in the study and divided into three groups: (1) Acute PE complicated by shock stage and/or persistent hypotension (12 patients). (2) RV dilatation and/or dysfunction without hypotension (14 patients). (3) Severe hypoxemia without hypotension and RV dysfunction (4 patients). Predominant symptoms were dyspnoea, cough, chest pain, syncope and haemoptysis, noted in 100 % (30), 40 % (12), 54 % (16), 32 % (9) and 10 % (3) of patients respectively. RV dilatation and dyskinesia were present in 86 %, septal paradoxical movement in 73 % and inferior venacava collapse absent in 53 % of patients respectively. 12 patients presented with acute PE and cardiogenic shock, 14 patients showed RV dilatation and dysfunction with systolic BP >90 mmHg and four patients were having RV dilation without dysfunction but severe hypoxemia. There was significant reduction in right ventricular systolic pressure and improvement in right ventricular dysfunction. Our study shows that tenecteplase is very effective and safe in the treatment of PE with minimal risk of bleeding in high risk group and intermediate risk and even in selective low risk category group of patients. However, in view of small number of patients in study group, a large multicentre randomized study would be required to draw a firm conclusion regarding the thrombolysis in low risk category patient.     

Role of Animal Danders as Inhalant Allergens in Bronchial Asthma in India

The etiological significance of animal danders in Indian patients with nasobronchial disorders has not yet been investigated. In the present study, the role of animal danders in the etiology of bronchial asthma was studied. Extracts of danders from 6 animals along with guinea pig whole pelt were prepared. Intradermal and bronchial provocation tests with these extracts were performed on (i) 68 asthmatics and (ii) 20 nonallergic healthy volunteers. In patients, significant positive skin reactions (2+ to 4+) ranged from 1.4% each with guinea pig whole pelt and ox dander to 8.8% with dog dander extracts. None of the healthy volunteers elicited such a response. On bronchial provocation, 20% and 53.8% of the tests were positive in asthmatics showing 1 +and 2+skin reactivity, respectively. All the patients as well as controls eliciting negative intradermal responses demonstrated uniformly negative bronchial provocation tests to different dander extracts. Analysis of various clinical features of asthmatics with respect to skin positivity to dander/pelt extract was also carried out. Radioallergosorbent tests (RASTs) were performed to estimate dander-specific IgE levels in the sera of patients showing different grades of skin response to dander extracts of dog, horse, and goat. Sixty percent of sera from the patients showing 2+ to 4+ skin reactivity to various animal dander extracts showed positive RASTs. RAST positivity as well as RAST ratio increased with increase in the intensity of skin response. All the patients with positive cutaneous as well as positive bronchial responses also showed positive RASTs. Similarly, all the patients with positive skin and positive RASTs showed positive bronchoprovocation tests. These results suggested that animal danders play an important role in the etiology of bronchial asthma. Some of the clinical characteristics of asthmatics, such as (i) early age at onset of asthma, (ii) positive family history, and (iii) asthma with associated allergies, have significant bearing on the cutaneous response to various dander extracts.     

High-hyperdiploidy in Philadelphia positive adult acute lymphoblastic leukaemia: case-series and review of literature

Patients with Philadelphia positive (Ph(+)) adult acute lymphoblastic leukaemia (ALL) have a poor prognosis. Stem cell transplantation (SCT) is increasingly being recognised as the treatment of choice in eligible patients with Ph(+)ALL, but disease-relapse remains a problem in a proportion of patients prior to and after SCT. Genetic abnormalities in addition to the Ph chromosome may influence the biology and clinical course of ALL, but there are not many studies on the potential genetic heterogeneity of adult Ph(+)ALL and clinical outcomes. Here, we report on five patients with ALL who were double Ph(+) and also had a high-hyperdiploid karyotype (Ph(+)/hyperdiploid) at diagnosis. In contrast to the presence of the Ph(+) chromosome, high-hyperdiploidy (>50 chromosomes) as the sole karyotypic abnormality in ALL is associated with a favourable clinical outcome. In our series, four patients with a Ph(+)/hyperdiploid karyotype achieved a cytogenetic remission after induction chemotherapy and proceeded to stem cell transplantation (SCT). The fifth had five subclones including Ph(+)/hyperdiploid, as well as those that were only Ph(+); the latter emerged as the dominant clone after induction therapy and the patient died of disease-relapse. Of the patients who underwent SCT, only one relapsed, but achieved a durable remission with donor lymphocyte infusions. Thus, it is conceivable that the presence of high-hyperdiploidy as an additional karyotypic abnormality may confer a better prognosis to Ph(+)ALL, presumably by altering the kinetics of Ph(+) neoplastic cells. We have discussed these results in the context of recent studies on the significance of high-hyperdiploidy in Ph(+) adult ALL.     

NMR based CSF metabolomics in tuberculous meningitis: correlation with clinical and MRI findings

Metabolic Brain Disease - We report the potential role of 1H Nuclear Magnetic Resonance (NMR) based metabolomics in tuberculous meningitis (TBM). We also correlate the significant metabolites with...     

Neurobehavioral alterations in a mouse model of chronic partial sleep deprivation

Metabolic Brain Disease - The night shift paradigm induces a state of chronic partial sleep deprivation (CPSD) and enhances the vulnerability to neuronal dysfunction. However, the specific neuronal...     

Association of Interleukin-1β-31C/T, -511T/C and -3954C/T Single Nucleotide Polymorphism and Their Blood Plasma Level in Acquired Aplastic Anemia

Aplastic anemia (AA) is an immune-mediated disorder in which hematopoietic stem and progenitor cells are targeted by a number of cellular and molecular pathways. This case control study aims to investigate the association of interleukin-1beta (IL-1β) gene polymorphisms, (IL-1β-31, IL-1β-511 and IL-1β-3954) and their plasma levels with acquired AA. Genotyping was done by Restricted Fragment Length Polymorphism (PCR–RFLP) method and IL-1β plasma levels were evaluated in peripheral blood using ELISA. Increased level of IL-1β was reported to be significant in cases as compared to controls. The susceptibility of developing AA was higher in the cases for IL-1β-3954 genotype. IL-1β-511 genotype showed significant association with the severity groups of AA. No significant association was noticed in responder versus non-responder group. Plasma level of IL-1β gene was found to be significantly higher in severe and very-severe group of AA versus control group. Our findings suggest that IL-1β gene and its genotypes might be involved in the pathophysiology of AA and play a central role in the etiopathogenesis of AA.     

Genes in one megabase of the HLA class I region.

To define the gene content of the HLA class I region, cDNA selection was applied to three overlapping yeast artificial chromosomes (YACs) that spanned 1 megabase (Mb) of this region of the human major histocompatibility complex. These YACs extended from the region centromeric to HLA-E to the region telomeric to HLA-F. In addition to the recognized class I genes and pseudogenes and the anonymous non-class-I genes described recently by us and others, 20 additional anonymous cDNA clones were identified from this 1-Mb region. We also identified a long repetitive DNA element in the region between HLA-B and HLA-E. Homologues of this element were located at several sites in the human genome outside of the HLA complex. The portion of the HLA class I region represented by these YACs shows an average gene density as high as the class II and class III regions. Thus, the high gene density portion of the HLA complex is extended to more than 3 Mb.