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Biomedical subjects

Anand Kumar

Publications and source records attributed to Anand Kumar.

At least 37 records · Page 2Linked to original sources
PubMed2005

The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels.

BACKGROUND: This study was designed to examine the relationship between the timing of antibiotic treatment and both survival rates and hemodynamic/inflammatory correlates of survival in a murine model of Escherichia coli septic shock. METHODS: Surgical implantation of an E. coli (O18:K1:H7)-laced, gelatin capsule-encased fibrinogen clot was used to generate a bacteremic model of murine septic shock. Survival duration, hemodynamic responses, and circulating serum tumor necrosis factor (TNF)-alpha , interleukin (IL)-6, and lactate levels were assessed in relation to increasing delays in or absence of antibiotic treatment. RESULTS: A critical inflection point with respect to survival occurred between 12 and 15 h after implantation. When initiated at or before 12 h, antibiotic treatment resulted in < or = 20% mortality, but, when initiated at or after 15 h, it resulted in >85% mortality. Physiologically relevant hypotension developed in untreated septic mice by 12 h after implantation. Values for heart rate differed between untreated septic mice and sham-infected control mice by 6 h after implantation, whereas values for cardiac output and stroke volume did not differ until at least 18-24 h after implantation. Antibiotic treatment initiated > or = 12 h after implantation was associated with persistence of increased circulating serum lactate, TNF- alpha , and IL-6 levels. CONCLUSIONS: The timing of antibiotic treatment relative to hypotension is closely associated with survival in this murine model of septic shock. Delay in antibiotic treatment results in the persistence of inflammatory/stress markers even after antibiotic treatment is initiated.

Animals↗
PubMed2005

Human serum from patients with septic shock activates transcription factors STAT1, IRF1, and NF-kappaB and induces apoptosis in human cardiac myocytes.

Proinflammatory cytokines have been linked to depression of myocardial contractility in vivo in patients with acute septic shock and in vitro models employing isolated myocytes exposed to serum from such patients. The key pathways involved in mediating this septic organ dysfunction (cell adhesion molecule expression, inducible nitric-oxide synthase induction, and apoptosis) are known to be regulated by transcription factors STAT1, IRF1, and NF-kappaB. Utilizing a model that mimics human disease, we have demonstrated activation of the transcription factors STAT1, IRF1, and NF-kappaB in human fetal myocytes exposed to human septic serum. Both reporter and electrophoretic mobility shift assays demonstrated a 5-19-fold increase in activation of transcription factors STAT1, IRF1, and NF-kappaB in response to incubation with human septic serum. The addition of human septic serum to human fetal myocytes induced apoptosis in human fetal myocytes and activation of the mitogen-activated protein kinase c-Jun NH -terminal kinase and caspase 1 as measured by Western blot. These data suggest that transcription factor activation and early myocyte apoptosis play a mechanistic role in septic myocardial depression and sepsis-induced organ dysfunction.

Adult↗
PubMed2005

Augmentation gastroplasty using a segment of transverse colon for corrosive gastric stricture.

BACKGROUND AND AIMS: Diffuse corrosive gastric stricture is a relatively rare entity, and gastric ablative procedures are traditionally recommended for it. We emphasize the importance of preservation of a cicatrized stomach and describe its augmentation using a segment of transverse colon. CASE REPORT AND PROCEDURE: A young female with a history of corrosive acid ingestion presented to our surgical unit with nonbilious vomiting following meals, consistent weight loss and features of gastric outlet obstruction. A barium study revealed a small-capacity stomach with pyloric stricture. We planned to augment the stomach capacity by using a segment of transverse colon. After documentation of a normal colon by barium examination, a 15-cm segment of transverse colon was harvested based on middle colic artery. This vascularized patch of bowel was united with the stomach that was opened up by a longitudinal incision made along the body. RESULT AND FINDING: A barium study on the tenth postoperative day revealed a good capacity and contour of the stomach and free entry of Barium into the small intestine. The patient is tolerating a normal meal and has no vomiting. At 3 months follow-up, the patient had a normal stomach radiologically and endoscopically, with a weight gain of 7 kg. CONCLUSIONS: Augmentation of corrosive gastric stricture by a segment of transverse colon is an innovative, practical, and useful procedure, although long-term results are awaited.

Adolescent↗
PubMed2005

Relations in biomedical ontologies.

To enhance the treatment of relations in biomedical ontologies we advance a methodology for providing consistent and unambiguous formal definitions of the relational expressions used in such ontologies in a way designed to assist developers and users in avoiding errors in coding and annotation. The resulting Relation Ontology can promote interoperability of ontologies and support new types of automated reasoning about the spatial and temporal dimensions of biological and medical phenomena.

Biomedical Research↗
PubMed2005

Human endotoxemia and human sepsis: limits to the model.

Sepsis remains the most common cause of death in intensive care units of the developed world. Accurate models of this disease syndrome are crucial for to the understanding of the complex pathophysiology of this disorder. The administration of a small dose of lipopolysaccharide to healthy volunteers is one such model of spontaneous human sepsis. Although this human endotoxemia model appears to be reasonably effective in mimicking early biochemical, metabolic, hematologic and cardiovascular septic responses in septic shock, the ability to mimic other aspects of human sepsis is open to question. The current study demonstrates that human experimental endotoxemia fails to generate evidence of increased vascular permeability within the relatively short time frame of the study.

Capillary Permeability↗
PubMed2005

Adding another spectral dimension to 1H magnetic resonance spectroscopy of hepatic encephalopathy.

PURPOSE: To evaluate a localized two-dimensional correlated magnetic resonance spectroscopic (L-COSY) technique in patients with hepatic encephalopathy (HE) and healthy subjects, and to correlate the cerebral metabolite changes with neuropsychological (NP) test scores. MATERIALS AND METHODS: Eighteen minimal hepatic encephalopathy (MHE) patients and 21 healthy controls have been investigated. A GE 1.5-T magnetic resonance (MR) scanner was used in combination with a body MR coil for transmission and a 3-inch surface coil for reception. A 27-mL voxel was localized by three slice-selective radio frequency (RF) pulses (90 degrees-180 degrees-90 degrees) in the anterior cingulate region. The total duration of each two-dimensional L-COSY spectrum was approximately 25 minutes. The NP battery included a total of 15 tests, which were grouped into six domains. RESULTS: MR spectroscopic results showed a statistically significant decrease in myo-inositol (mI) and choline (Ch) and an increase in glutamate/glutamine (Glx) in patients when compared to healthy controls. There was also an increase in taurine (Tau) in patients. The NP results indicated a significant correlation between motor function assessed by NP tests and mI ratios recorded using two-dimensional L-COSY. CONCLUSION: The study demonstrated the feasibility of evaluating the two-dimensional L-COSY sequence in a clinical environment. The results showed additional cerebral metabolites that can be measured with the technique in comparison to one-dimensional study.

Brain↗
PubMed2005

Text mining and ontologies in biomedicine: making sense of raw text.

The volume of biomedical literature is increasing at such a rate that it is becoming difficult to locate, retrieve and manage the reported information without text mining, which aims to automatically distill information, extract facts, discover implicit links and generate hypotheses relevant to user needs. Ontologies, as conceptual models, provide the necessary framework for semantic representation of textual information. The principal link between text and an ontology is terminology, which maps terms to domain-specific concepts. This paper summarises different approaches in which ontologies have been used for text-mining applications in biomedicine.

Abstracting and Indexing↗
PubMed2005

Interleukin-10 blunts the human inflammatory response to lipopolysaccharide without affecting the cardiovascular response.

OBJECTIVE: The objective of this study was to assess the efficacy of variations in dose and timing of administration of recombinant human IL-10 (rhIL-10) on inflammatory and cardiovascular responses in a human endotoxemia model of sepsis. DESIGN: The authors conducted a randomized, placebo-controlled, double-blind trial. SETTING: The study was conducted in a procedure room of an intensive-care unit. PARTICIPANTS: The study comprised 24 healthy male volunteers. INTERVENTIONS: Interventions consisted of intravenous administration of rhIL-10 at 1, 10, or 25 microg/kg either 2 mins or 2 hrs before Escherichia coli lipopolysaccharide (4 ng/kg) or placebo. MEASUREMENTS AND RESULTS: The placebo group receiving lipopolysaccharide alone demonstrated significant, time-dependent changes in vital signs, white blood cell counts, inflammatory cytokine/cortisol levels, and hemodynamic/cardiovascular (including echocardiographic) parameters over the duration of the study. rhIL-10, administered immediately before (concurrent) lipopolysaccharide resulted in decreased temperature and heart rate responses as well as decreased serum levels of proinflammatory cytokines (tumor necrosis factor-alpha, IL-6), IL-1 receptor antagonist, cortisol, and total leukocytes/neutrophils compared with lipopolysaccharide alone. Dose-dependent effects were absent. In contrast, rhIL-10 administration 2 hrs before endotoxin augmented the endotoxin-induced IL-beta and IL-1 receptor antagonist response. rhIL-10 failed to modulate major cardiovascular responses (cardiac output, stroke volume index, ejection fraction, peak systolic pressure/end-systolic volume ratio) to endotoxin in both study groups as assessed by echocardiography. CONCLUSION: Concurrent administration of rhIL-10 suppresses the human inflammatory/stress response but has no effect on the hemodynamic/cardiovascular response to endotoxin. Early administration of rhIL-10 can potentially augment elements of the cytokine inflammatory response to lipopolysaccharide. These findings suggest significant limitations of rhIL-10 as a potential immunomodulatory therapy for sepsis.

Adolescent↗
PubMed2005

The feasibility of nitric oxide delivery with high frequency jet ventilation.

A 27-year-old female with acute monocytic leukaemia (M5) developed acute respiratory distress syndrome (ARDS). Because of refractory hypoxaemia and severe barotrauma during conventional mechanical ventilation, the patient was switched to high frequency jet ventilation (HFJV) as a salvage therapy. Her refractory hypoxaemia improved temporarily but worsened again. Approval of the Institutional Review Board and the Food and Drug Administration was obtained to use nitric oxide (NO) with HFJV on a compassionate basis considering the grave situation. The NO delivery system was connected to the secondary flow circuit of the HFJV immediately after the humidifier. We measured the concentration of NO at least every hour by inserting a 7-Fr catheter connected to a McNeill analyzer into the endotracheal tube. Despite improvement of oxygenation, the patient's respiratory status deteriorated further and she died. In this case we were able to achieve reliable and constant levels of NO. The purpose of this report is to discuss the technical aspects and pitfalls of this method.

Adult↗
PubMed2005

Color Doppler ultrasound as an objective assessment tool for chemotherapeutic response in advanced breast cancer.

BACKGROUND: In our part of the world, the majority of the patients with breast cancer present with locally advanced disease and require neo-adjuvant chemotherapy as the primary treatment modality. It is essential to monitor the response to chemotherapy in these patients. Clinical examination as the sole criterion of response assessment is entirely subjective and fallacious. Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) are expensive. The role of Doppler ultrasonography as an imaging modality for this purpose is therefore being evaluated. METHODS: A prospective study was undertaken of 25 cases of locally advanced breast carcinoma (LABC) and Color Doppler sonography was used for the sequential assessment of chemotherapeutic response. The response assessed on the basis of clinical examination and Color Doppler was compared with the histological response. The parameters assessed on color Doppler were a change in the number of flow signals, maximum flow velocity (Vmax), pulsatility index (PI) and resistivity index (RI). Responses were analysed statistically using the Pearson correlation coefficient and Kappa statistics (kappa). The sensitivity, specificity, positive predictive & negative predictive values for predicting complete histological response were calculated. RESULTS: Color Doppler showed a sensitivity of 88.88 % for predicting complete histological response. The negative predictive value of color Doppler was 92.3 %. A significant correlation was obtained between color Doppler and histopathological response. CONCLUSIONS: Color Doppler was found to be an objective and effective tool or modality compared with clinical evaluation in sequential response assessment, especially for predicting complete histological response.

Adult↗
PubMed2005

Antidepressant exposure may protect against decrement in frontal gray matter volumes in geriatric depression.

OBJECTIVES: Depressed elderly patients with and without antidepressant exposure were compared to normal controls to examine the effects of prior antidepressant exposure on regional brain gray matter volumes using magnetic resonance imaging (MRI). METHOD: The study was conducted from October 1999 to January 2003. Patients and controls were closely matched by age and education. They underwent comprehensive neuropsychiatric and physical examinations. Measures of the total frontal lobe and the frontal gray and white matter volumes corrected by the intracranial volume were obtained using MRI, together with clinical measures of medical burden. Historical information about prior exposure to antidepressant drugs was collected using multiple information sources. The groups were compared using multivariate analyses of covariance, controlling for age, sex, and medical burden. RESULTS: The study sample comprised 41 patients who met the DSM-IV criteria for major depressive disorder (32 women; 11 antidepressant exposure and 30 drug-naive; mean age 70.5 years) and 41 controls (20 women; mean age 72.2 years). In the multivariate analysis, the depressed group had smaller corrected orbitofrontal cortex (OFC) total and gray matter volumes compared to the controls (p < .01). However, depressed patients with prior antidepressant exposure had larger OFC gray matter volumes compared to drug-naive depressed patients, but smaller than those in normal controls (p = .005). This effect was not explained by the group differences in sex ratio, age at onset of depression, or the number or duration of depressive episodes. CONCLUSIONS: We observed larger OFC regional volumes in depressed patients exposed to antidepressants compared to the drug-naive depressed subjects, but smaller than those in age-matched controls. Antidepressant exposure may protect against gray matter loss in geriatric depression.

Age Factors↗
PubMed2005

Recurrent stupor due to lysinuric protein intolerance.

Recurrent stupor in children is an uncommon clinical problem with a wide differential diagnosis; inherited metabolic disorders account for a vast majority. We report a 9-year-old girl with recurrent episodes of stupor. Initial episode was treated as viral encephalitis and the second episode was managed as non-convulsive status epilepticus. Hyperammonemia was detected in the last episode. Metabolic work-up after dietary protein challenge revealed classical biochemical features of lysinuric protein intolerance. She was managed with protein-restricted diet, which resulted in marked neurological improvement. LPI is a rare inherited metabolic disorder due to membrane transport defect of cationic amino acids.

Amino Acid Metabolism, Inborn Errors↗
PubMed2005

An ontology for carcinoma classification for clinical bioinformatics.

There are a plenty of existing classifications and staging schemes for carcinomas, one of the most frequently used being the TNM classification. Such classifications involve entities which exist at various anatomical levels of granularity and in order to apply such classifications to the Electronic Health Care Records, one needs to build ontologies which are not only based on the formal principles but also take into consideration the diversity of the domains which are involved in clinical bioinformatics. Here we outline a formal theory for addressing these issues in a way that inferences drawn upon the ontologies would be helpful in interpreting and inferring on the entities which exist at different anatomical levels of granularity. Our case study is on the colon carcinoma, one of the commonest carcinomas prevalent within the European population.

Computational Biology↗
PubMed2005

A strategy for improving and integrating biomedical ontologies.

The integration of biomedical terminologies is indispensable to the process of information integration. When terminologies are linked merely through the alignment of their leaf terms, however, differences in context and ontological structure are ignored. Making use of the SNAP and SPAN ontologies, we show how three reference domain ontologies can be integrated at a higher level, through what we shall call the OBR framework (for: Ontology of Biomedical Reality). OBR is designed to facilitate inference across the boundaries of domain ontologies in anatomy, physiology and pathology.

Anatomy↗
PubMed2004

Effect of large volume infusion on left ventricular volumes, performance and contractility parameters in normal volunteers.

OBJECTIVE: Characterize the normal human cardiovascular response to large volume infusion of normal saline. DESIGN: Prospective, interventional trial. SETTING: ICU procedure room. PARTICIPANTS: Healthy male volunteers ( n=32). INTERVENTIONS. Volumetric echocardiography during 4-L saline infusion (3 L over 3 h followed by 1 L over 2 h). MEASUREMENTS AND RESULTS: Following 3-L saline infusion, stroke volume and cardiac output increased approximately 10% without a significant change in heart rate or blood pressure. A decrease in end-systolic volume contributed to the increase in stroke volume to an extent similar to that provided by the increase in end-diastolic volume. All contractility indices except end-systolic wall stress/end-systolic volume index were increased at 3 h post-initiation of saline infusion. Stroke volume but not cardiac output remained elevated at 5 h with persistence of ventricular volume responses; only ejection fraction was significantly elevated among the contractility indices. Afterload measures including total peripheral resistance and end-systolic wall stress were significantly decreased after 3-L infusion but were unchanged compared to baseline following infusion of an additional 1 L over 2 h. Modeled blood viscosity studies demonstrate that changes in apparent contractility after 3-L saline infusion can be explained solely by viscosity reduction associated with hypervolemic hemodilution. CONCLUSION: The initial increase in stroke volume associated with high volume saline infusion in normal volunteers is associated with increases of most load-dependent and ostensibly load-independent parameters of left ventricular contractility. This phenomenon is unlikely to represent a true increase in contractility and appears to be caused by reduced afterload as a consequence of decreased blood viscosity. This decrease in blood viscosity may complicate analysis of some previous in vivo studies examining the effect of volume loading on cardiac function using low-viscosity solutions.

Adult↗
PubMed2004

Preload-independent mechanisms contribute to increased stroke volume following large volume saline infusion in normal volunteers: a prospective interventional study.

INTRODUCTION: Resuscitation with saline is a standard initial response to hypotension or shock of almost any cause. Saline resuscitation is thought to generate an increase in cardiac output through a preload-dependent (increased end-diastolic volume) augmentation of stroke volume. We sought to confirm this to be the mechanism by which high-volume saline administration (comparable to that used in resuscitation of shock) results in improved cardiac output in normal healthy volunteers. METHODS: Using a standardized protocol, 24 healthy male (group 1) and 12 healthy mixed sex (group 2) volunteers were infused with 3 l normal (0.9%) saline over 3 hours in a prospective interventional study. Individuals were studied at baseline and following volume infusion using volumetric echocardiography (group 1) or a combination of pulmonary artery catheterization and radionuclide cineangiography (group 2). RESULTS: Saline infusion resulted in minor effects on heart rate and arterial pressures. Stroke volume index increased significantly (by approximately 15-25%; P < 0.0001). Biventricular end-diastolic volumes were only inconsistently increased, whereas end-systolic volumes decreased almost uniformly. Decreased end-systolic volume contributed as much as 40-90% to the stroke volume index response. Indices of ventricular contractility including ejection fraction, ventricular stroke work and peak systolic pressure/end-systolic volume index ratio all increased significantly (minimum P < 0.01). CONCLUSION: The increase in stroke volume associated with high-volume saline infusion into normal individuals is not only mediated by an increase in end-diastolic volume, as standard teaching suggests, but also involves a consistent and substantial decrease in end-systolic volumes and increases in basic indices of cardiac contractility. This phenomenon may be consistent with either an increase in biventricular contractility or a decrease in afterload.

Adolescent↗