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Sanjeev Aggarwal

Publications and source records attributed to Sanjeev Aggarwal.

4 recordsLinked to original sources

B-type natriuretic peptide as a marker for cardiac dysfunction in anthracycline-treated children.

BACKGROUND: Anthracyclines (AC) are useful antineoplastic agents, whose utility is limited by progressive cardiotoxicity. Our purpose was to evaluate plasma B-type natriuretic peptide (BNP), as a screening test for detecting late cardiac dysfunction in AC-treated children and to determine the prevalence of late cardiac dysfunction at low cumulative AC doses. MATERIALS AND METHODS: This was a prospective study in which patients who had completed AC therapy at least 1 year earlier, underwent a detailed echocardiogram and a simultaneous BNP level. Cardiac dysfunction was defined as any one of the following: shortening fraction (FS) <29%, rate corrected velocity of circumferential fiber shortening (VCFc) <0.9 c x sec(-1), end systolic wall stress (ESWS) >60 g x cm(-2), abnormal VCFc: ESWS ratio or decreased mitral inflow velocity (E/A) ratios, compared to age-specific norms. RESULTS: The cohort (n = 63) included 37 males with a median age of 13.1 years (range, 6.5-26.5 years). Cardiac dysfunction was found in 26 (41%) patients and in 40% of patients who received cumulative doses <150 mg x m(-2). ESWS was the most common abnormality. Mean BNP levels in the subset with abnormal function were significantly higher than the normal group (23.4 +/- 25.3 vs. 14.2 +/- 8.9 pg x ml(-1), P = 0.02). CONCLUSIONS: Plasma BNP was significantly elevated in AC-treated patients with late cardiac dysfunction, although there was considerable overlap of levels between groups with and without cardiac dysfunction. BNP may need further evaluation as a serial index of cardiac function in this population. Cardiac dysfunction was observed in a significant proportion of patients, even at low cumulative AC doses.

Adolescent↗

Amplification and overexpression of the dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2) gene in esophageal and lung adenocarcinomas.

Genomic amplification can lead to the activation of cellular proto-oncogenes during tumorigenesis, and is observed in most, if not all, human malignancies, including adenocarcinomas of lung and esophagus. Using a two-dimensional restriction landmark genomic scanning technique, we identified five NotI/HinfI fragments with increased genomic dosage in an adenocarcinoma of the gastroesophageal junction. Four of these amplified fragments were matched within three contigs of chromosome 12 using the bioinformatics tool, Virtual Genome Scan. All three of the contigs map to the 12q13-q14 region, and the regional amplification in the tumor was verified using comparative genomic hybridization analysis. The 12q14 amplicon was characterized using sequence tagged site-amplification mapping with DNA from paired normal-tumor tissues of 75 gastroesophageal and 37 lung adenocarcinomas. The amplicon spans a region of >12 Mb between genes DGKA and BLOV1. The core-amplified domain was determined to be <0.5 Mb between marker WI-12457 and gene IFNG. However, MDM2, a well-documented oncogene of the region, is outside the core-domain. Eleven genes and expressed sequence tags within the amplicon were selected for quantitative reverse transcription-PCR, and DYRK2, a member of the dual-specificity kinase family, was overexpressed in all of the tumors showing gene amplification. Among the sequence tagged site/expressed sequence tag/gene markers tested, DYRK2 demonstrated the highest DNA copy number and the highest level of mRNA overexpression in the tumors. Moreover, DYRK2 mRNA overexpression (>2.5-fold of normal mean) was found in 18.6% of additional 86 lung adenocarcinomas in an assay using oligonucleotide microarrays. DYRK2 mRNA overexpression occurs more frequently than gene amplification in both esophageal and lung adenocarcinomas. This is the first report of amplification and overexpression of DYRK2 in any tumor type.

Adenocarcinoma↗

Inhaled Nitric Oxide as a Preoperative Test (INOP Test I): the INOP Test Study Group.

BACKGROUND: This study was performed to determine whether a preoperative hemodynamic evaluation with oxygen and inhaled nitric oxide identifies patients with pulmonary hypertension who are appropriate candidates for corrective cardiac surgery or transplantation more accurately than an evaluation with oxygen alone. METHODS AND RESULTS: At 10 institutions, 124 patients with heart disease and severe pulmonary hypertension underwent cardiac catheterization to determine operability. The ratio of pulmonary and systemic vascular resistance (Rp:Rs) was determined at baseline while breathing approximately 21% to 30% oxygen, and in approximately 100% oxygen and approximately 100% oxygen with 10 to 80 parts per million nitric oxide to evaluate pulmonary vascular reactivity. Surgery was performed in 74 patients. Twelve patients died or developed right heart failure secondary to pulmonary hypertension following surgery. Rp:Rs<0.33 and a 20% decrease in Rp:Rs from baseline were chosen as 2 criteria for operability to determine, in retrospect, the efficacy of preoperative testing in patient selection. In comparison to an evaluation with oxygen alone, sensitivity (64% versus 97%) and accuracy (68% versus 90%) were increased by an evaluation with oxygen and nitric oxide when Rp:Rs<0.33 was used as the criterion for operability. Specificity was only 8% when a 20% decrease in Rp:Rs from baseline was used as the criterion for operability. CONCLUSION: By using a combination of oxygen and inhaled nitric oxide, a greater number of appropriate candidates for corrective cardiac surgery or transplantation can be identified during preoperative testing when a specific value of Rp:Rs is used as a criterion for operability.

Administration, Inhalation↗