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Biomedical subjects

A Agrawal

Publications and source records attributed to A Agrawal.

At least 73 records · Page 4Linked to original sources
PubMed2001

Long-term follow-up on an intensified treatment regimen for advanced resectable head and neck squamous cell carcinomas.

From February 1993 through July 1994, 37 patients with stage III-IV squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx (stage II-IV) were registered to a treatment regimen consisting of preoperative continuous infusion cisplatin (80 mg/m2/80 hours) with hyperfractionated external beam radiotherapy (9.1 Gy/7 fractions of 1.3 Gy BID), surgical resection, intraoperative radiotherapy (7.5 Gy), and postoperative radiotherapy (40 Gy) with concurrent cisplatin (100 mg/m2 x 2 courses). The objectives of the regimen were to improve patient compliance while also increasing treatment intensity. The purpose of this article is to report the local, regional (nodal), and distant disease control of these patients after an extended time at risk (median 40 months). Overall compliance (73%), local control at primary site (97%), and regional nodal control (95%) were excellent. The rate of distant metastasis was 19%. Absolute survival at 48 months was 45.9%.

Carcinoma, Squamous Cell↗
PubMed2001

Safety and efficacy of transcervical resection of parapharyngeal space neoplasms.

There are several surgical approaches for resection of parapharyngeal space (PPS) neoplasms. The purpose of this study was to evaluate local disease control, facial nerve injury, and need for mandibulotomy associated with resection of PPS neoplasms via the transcervical approach with submandibular gland excision. A retrospective chart review of 33 patients who underwent resection of a PPS neoplasm between October 1991 and July 2000 was performed. Of the 33 patients, 3 patients developed local recurrence after a median follow-up of 24 months. None of the patients experienced facial nerve paresis or paralysis. Three patients (9.1%) required a mandibulotomy for further exposure. This study demonstrated that the transcervical approach with submandibular gland excision for resection of PPS neoplasms provides excellent local disease control with minimal risk of facial nerve injury or need for mandibulotomy and/or tracheotomy.

Adenoma, Pleomorphic↗
PubMed2001

Squamous cell carcinoma of thyroid gland.

We present the clinical manifestation, management and outcome in two cases of squamous cell cancer arising in the thyroid gland which is a rare entity. Both cases had advanced disease invading adjacent structures. At the followup of three to six months, one patient developed recurrence and died.

Carcinoma, Squamous Cell↗
PubMed2001

Radiation induced peroxidative damage: mechanism and significance.

An interest has been generated in free radicals after the discovery of superoxide dismutase. These free radicals cause a number of diseases and are involved in the detrimental effect of ionizing radiation. Efforts have been made to understand their role in damage and death of the cell using lipid peroxidation process. Lipid peroxidation is an important effect of radiation on membranes, which apart from DNA, are critical targets of radiation action. This paper addresses the basic mechanism of radiation induced lipid peroxidation. Various factors, which determine the mode and magnitude of lipid peroxidation, are also discussed. Lipid peroxidation is shown to have importance in understanding the modifications of radiation effects. Efforts are made to show similarities between radiolytic and non-radiolytic lipid peroxidation. Recent findings related to the close link between radiation-induced lipid peroxidation and apoptosis are likely to open new avenues for future research and to develop new approaches for radiomodification of biological effects.

Animals↗
PubMed2001

An approach to guideline implementation with GEM.

Implementation of practice guidelines refers to the creation of strategies and systems to operationalize the knowledge and recommendations set forth by guideline developers. We describe an approach to guideline implementation that makes direct use of the guideline document as a knowledge base. The Guideline Elements Model (GEM) provides an XML-based guideline document model that facilitates implementation of guidelines. Knowledge extraction using GEM requires document markup rather than programming and can promote authenticity and consistent knowledge encoding. Knowledge customization for the local enterprise requires addition of meta-information to pertinent components of the GEM hierarchy in a design database. GEM provides an audit trail to track local adaptation. Knowledge integration with patient data can be promoted using information management services. A design goal is to devise a system that can be applied by local clinical domain experts, quality assurance experts, and information systems programmers without requiring trained informaticians and knowledge engineers to serve as intermediaries

Artificial Intelligence↗
PubMed2001

Evaluation of guideline quality using GEM-Q.

A variety of rating instruments that evaluate the quality of practice guidelines have been published. Application of these instruments can be difficult and time-consuming. In a literature review, we identified two evaluation instruments that are comprehensive, have clearly defined constructs, and have undergone validation/testing-the Guidelines Quality Assessment Questionnaire (GQAQ) and the Appraisal Instrument for Clinical Guidelines (AICG). Overall, the AICG is more comprehensive. The AICG addresses the implementability of a guideline, which is not evaluated by the GQAQ. However, the GQAQ is more amenable to computerization. GEM-Q is a Guideline Elements Model (GEM)-derived application intended to facilitate automated evaluation of guideline quality using one of the published instruments. To develop GEM-Q, various items in the GQAQ were mapped to corresponding elements in the GEM hierarchy and a customized XSL stylesheet was designed based on this mapping. GEM-Q selectively extracts text components of the guideline relevant to quality evaluation and displays the results in HTML format. GEM-Q was applied to a set of six guidelines to test its reliability. It ranked two guidelines as of "good" quality, two as "intermediate", and two as "poor". In all six instances, GEM-Q ranked guidelines in the same order of quality as the experts who validated the GQAQ. This work demonstrates the feasibility of developing an application to facilitate automated guideline quality evaluation.

Evaluation Studies as Topic↗
PubMed2001

Using GEM-encoded guidelines to generate medical logic modules.

Among the most effective strategies for changing the process and outcomes of clinical care are those that make use of computer-mediated decision support. A variety of representation models that facilitate computer-based implementation of medical knowledge have been published, including the Guideline Elements Model (GEM) and the Arden Syntax for Medical Logic Modules (MLMs). We describe an XML-based application that facilitates automated generation of partially populated MLMs from GEM-encoded guidelines. These MLMs can be further edited and shared among Arden-compliant information systems to provide decision support. Our work required three steps: (a) Knowledge extraction from published guideline documents using GEM, (b) Mapping GEM elements to the MLM slots, and (c) XSL transformation of the GEM-encoded guideline. Processing of a sample guideline generated 15 MLMs, each corresponding to a conditional or imperative element in the GEM structure. Mechanisms for linking various MLMs are necessary to represent the complexity of logic typical of a guideline.

Decision Making, Computer-Assisted↗
PubMed2001

A metadata framework for interoperating heterogeneous genome data using XML.

The rapid advances in the Human Genome Project and genomic technologies have produced massive amounts of data populated in a large number of network-accessible databases. These technological advances and the associated data can have a great impact on biomedicine and healthcare. To answer many of the biologically or medically important questions, researchers often need to integrate data from a number of independent but related genome databases. One common practice is to download data sets (text files) from various genome Web sites and process them by some local programs. One main problem with this approach is that these programs are written on a case-by-case basis because the data sets involved are heterogeneous in structure. To address this problem, we define metadata that maps these heterogeneously structured files into a common eXtensible Markup Language (XML) structure to facilitate data interoperation. We illustrate this approach by interoperating two sets of essential yeast genes that are stored in two yeast genome databases (MIPS and YPD).

Databases, Genetic↗
PubMed2000

Induction paclitaxel in previously untreated, resectable, advanced squamous cell carcinomas of head and neck.

BACKGROUND: Previous Phase II trials evaluating paclitaxel as a single agent have produced objective response rates of 38-40%. However, in these studies patients had recurrent disease and had received previous treatment with chemotherapy, radiation, surgery, or some combination of the same. To the authors' knowledge, the study reported here is the first to examine the role of paclitaxel in affecting objective antitumor response, as a single agent, in a previously untreated patient population. METHODS: Patients with untreated, resectable, advanced squamous cell carcinoma of the head and neck were eligible for this Phase II trial. The treatment plan included paclitaxel 250 mg/m(2) administered by 24-hour intravenous infusion every 21 days for a total of 3 courses and primary prophylaxis with colony stimulating factor during each course of chemotherapy. Surgical resection was performed after recovery from the final course of chemotherapy. After adequate wound healing, patients received external beam radiotherapy (median dose to primary site, 55.8 Gray [Gy]; median dose to neck sites, 50.4 Gy). RESULTS: Forty-five patients were registered. Thirty-eight patients completed the planned chemotherapy, 41 patients underwent surgical resection, and 37 patients completed the intended radiotherapy. The objective response rate was 50% (10% complete response; 40% partial response). Severe or life-threatening (Grade 3 or higher) granulocytopenia or thrombocytopenia occurred in 78% and 27% of patients, respectively. Two patients died of sepsis. Seventy-one percent, 67%, and 91% of patients were free of local, lymph node, and distant recurrence, respectively, with a median follow-up of 37 months. The 4-year overall survival and disease-related survival rates were 44.4% and 52.9%, respectively. CONCLUSION: The authors conclude that paclitaxel is an active agent in patients with advanced head and neck carcinoma. However, the overall disease control, achieved by using paclitaxel as induction therapy, did not appear to be better than that achieved with standard treatment methods. Combined modality regimens with concurrent chemotherapy and radiotherapy have demonstrated more promise.

Adult↗
PubMed2000

Amersham Pharmacia Biotech & Science Prize. Transposition and evolution of antigen-specific immunity.

Alka Agrawal grew up in Farmington Hills, near Detroit, Michigan, and earned her bachelor's degree in chemical engineering from the University of Michigan. Dr. Agrawal entered the pharmacology graduate school program at Yale University and began working in the laboratory of David Schatz, investigating the role of DNA repair proteins in V(D)J recombination. The development of an in vitro V(D)J cleavage system in the laboratory changed her focus and she began studying the cleavage mechanism as part of her doctoral research. Exposure to science policy at the National Academy of Sciences, and to science journalism through the AAAS Mass Media Science and Engineering Fellows Program, prompted Dr. Agrawal to pursue a career in science writing.

Allergens↗
PubMed2000

The Rel family member P50 mediates cytokine-induced C-reactive protein expression by a novel mechanism.

Transcription of C-reactive protein (CRP) in Hep 3B cells is induced by IL-6, acting through C/EBP isoforms and STAT3. IL-1beta, which alone has no effect, greatly enhances IL-6-induced transcription by unknown mechanisms. Because IL-1beta activates the NF-kappaB system, we explored the effects of overexpressed Rel family members on CRP expression. Unexpectedly, transactivation assays in transiently transfected Hep 3B cells showed p50 overexpression to markedly induce CRP transcription, acting in a region 3' to -86. In the presence of overexpressed p50, IL-1beta induced a 3-fold increase in CRP expression, and responses to IL-6 and to IL-6 plus IL-1beta were 4-fold greater than seen in cells without p50 overexpression. In contrast, overexpressed p65 abolished CRP induction by p50 and by cytokines. EMSA studies demonstrated that recombinant p50 bound to a nonconsensus kappaB site overlapping the proximal C/EBP binding site on the CRP promoter. Mutation of a polypyrimidine tract in the p50-binding site inhibited the transactivating effect of cytokines. P50- but not p65-containing dimers were found in nuclei of Hep 3B cells 18 h after stimulation with IL-1beta, when C/EBPbeta is greatly activated, in the presence or absence of IL-6. These findings suggest that IL-1beta induces nuclear translocation of p50-containing dimers and that p50 interacts with C/EBPbeta activated by both IL-6 and IL-1beta to induce CRP expression.

3' Untranslated Regions↗
PubMed2000

Gene structure and promoter function of murine Munc18-2, a nonneuronal exocytic Sec1 homolog.

Sec1 family proteins are regulators of diverse exocytic processes, from yeast to man. Three mammalian homologues, Munc18-1, -2, and -3 have been described. We have studied the structure and expression of the mouse Munc18-2 gene. The Munc18-2 gene comprises 19 exons whose sizes range from 50 to 158 bp, with a total gene size of approximately 11 kb. A single transcript of 2.1 kb is expressed in multiple non-neuronal murine tissues. Munc18-2 has a striking resemblance to Munc18-1 in structure despite only 60% sequence identity, suggesting a recent gene duplication event. Analysis of the region upstream of the transcription start site shows that Munc18-2 has a TATA-less promoter, with a consensus initiator (Inr) sequence at the start of transcription, several Sp1 binding sites, and strong promoter activity in RBL-2H3 mast cells. The region from +5 to -430 is more active than +5 to -800, suggesting upstream repressor elements.

Animals↗
PubMed2000

The Arthus reaction in rodents: species-specific requirement of complement.

We induced reverse passive Arthus (RPA) reactions in the skin of rodents and found that the contribution of complement to immune complex-mediated inflammation is species specific. Complement was found to be necessary in rats and guinea pigs but not in C57BL/6J mice. In rats, within 4 h after initiation of an RPA reaction, serum alternative pathway hemolytic titers decreased significantly below basal levels, whereas classical pathway titers were unchanged. Thus the dermal reaction proceeds coincident with systemic activation of complement. The serine protease inhibitor BCX 1470, which blocks the esterolytic and hemolytic activities of the complement enzymes Cls and factor D in vitro, also blocked development of RPA-induced edema in the rat. These data support the proposal that complement-mediated processes are of major importance in the Arthus reaction in rats and guinea pigs, and suggest that BCX 1470 will be useful as an anti-inflammatory agent in diseases where complement activation is known to be detrimental.

Animals↗
PubMed2000

Clinical and sonographic findings in carcinoma of the penis.

PURPOSE: This study was performed to assess the accuracy of high-resolution sonography in measuring penile carcinoma. METHODS: Sonography was performed using a 7.5-MHz linear-array transducer in 59 patients with penile carcinoma. The sonographic measurement of tumor extent was compared with clinical and pathologic measurements. The tumor extent measured by gross pathologic evaluation on cut sections of the fresh penectomy specimen was used as the definitive standard. The echogenicity of the tumor was compared with that of the surrounding normal penile tissue to classify the tumor as hyperechoic, hypoechoic, or of mixed echogenicity (containing both hyperechoic and hypoechoic elements). We evaluated the relationship between the echogenicity of the tumor and both tumor morphology (exophytic or infiltrative) and tumor grade as determined on pathologic examination. RESULTS: The overall mean difference +/- standard deviation in the tumor extent between clinical and gross pathologic evaluation was 3.9 +/- 5.3 mm (range, 1-9 mm), whereas the overall mean difference between sonographic and gross pathologic evaluation was 1.2 +/- 1.7 mm (range, 1-7 mm). As determined with reference to the gross pathologic extent, the error in measuring the extent on clinical examination was significantly greater than the error on sonography (p < 0.001). Lesions involving the glans alone were more often underestimated by clinical examination than were lesions involving the shaft (with or without glanular involvement). The error in measuring the extent of tumor by sonography was not related to the site of the tumor. The tumor was hyperechoic in 21 cases (36%), hypoechoic in 28 cases (47%), and of mixed echogenicity in 10 cases (17%). There was no significant association between echogenicity and tumor morphology or grade. CONCLUSIONS: Sonography gives a more accurate estimate of penile tumor extent than does physical examination. Routine use of sonography for such measurements should enable preservation of more of the penis.

Adult↗
PubMed2000

The histological extent of the local spread of carcinoma of the penis and its therapeutic implications.

OBJECTIVE: To explore the possibility of reducing the margin of clearance at surgery for carcinoma of the penis without causing an increase in the incidence of local tumour recurrence, so that the functional and cosmetic compromise associated with penectomy might be minimized. PATIENTS AND METHODS: Sixty-four patients underwent partial or total penectomy based on the extent of tumour. The specimens were evaluated histologically for grade and for proximal microscopic extensions beyond the grossly visible tumour margin, by examining serial proximal 5 mm sections. The histological grade of the lesion was correlated with its clinical site, morphology and proximal microscopic spread. Differences were assessed using the chi-squared test. RESULTS: Of 64 tumours, 31% were grade 1, 50% grade 2 and the remaining 19% grade 3. Higher grade lesions were more likely to involve the penile shaft. The maximum proximal histological extent was 5 mm for grades 1 and 2, and 10 mm for grade 3 tumours; there was no discontinuous spread. CONCLUSIONS: Histological grading is mandatory in the management of carcinoma of the penis. A 10-mm clearance is adequate for grade 1 and 2 lesions, and 15 mm for grade 3 tumours. This approach would qualify more patients for partial rather than total amputation; the residual length of the penis would then be cosmetically and functionally more acceptable.

Humans↗
PubMed2000

Resection of cancer of the tongue base and tonsil via the transhyoid approach.

OBJECTIVE: To assess whether transhyoid resection of the tongue base and tonsil lesions is an effective approach to tumors involving this region compared with more traditional anterior surgical approaches that arbitrarily involve either segmental resection or division of the mandible. STUDY DESIGN: Retrospective review. METHODS: Since 1988, we have used a combined transhyoid and transoral approach to resect lesions involving the tongue base, tonsil, or both. Forty-one patients were identified who underwent surgical resection of lesions involving this region via this combined approach during this period. A stage-matched group of 41 patients was also identified in which patients underwent resection via traditional composite or mandibulotomy approaches and was used as a basis for comparison. Factors assessed included status of surgical margins, postoperative complications, degree of postoperative dysphagia, and long-term outcome. RESULTS: Comparison between the two groups revealed similar rates of negative surgical margins. Levels of postoperative dysphagia, notably severe primarily in patients with either T4 or recurrent disease, were also similar between groups. Complication rates, especially with regard to fistula occurrence and mandible-healing problems, were significantly lower in the transhyoid group. Analysis of long-term outcome revealed similar patterns with regard to disease status in both groups. CONCLUSIONS: The combined transhyoid and transoral approach is an effective surgical option for a number of lesions affecting the tongue base, tonsil, or both. Although similar to other approaches with regard to postoperative function and disease outcome, the transhyoid approach is associated with decreased postoperative morbidity. However, tumors that extend to involve the mandible or pterygoid musculature or skull base are probably best suited for traditional approaches that involve division of the mandible.

Carcinoma, Squamous Cell↗
PubMed2000

An evaluation of fibrin tissue adhesive concentration and application thickness on skin graft survival.

OBJECTIVES: To examine the effects of fibrinogen concentration and application thickness of fibrin tissue adhesive on skin graft survival. STUDY DESIGN: Prospective controlled study. METHODS: Ten domestic pigs were included in the study. A 20 x 5-cm area of skin was harvested bilaterally along the flanks of the animals using a Padgett dermatome. The harvested grafts were trimmed into four 4 x 4-cm squares. Donor sites were treated according to group assignment and the non-meshed grafts were placed on the side opposite their initial orientation and secured with staples. Both single- and multiple-donor human fibrin tissue adhesive preparations, with low and high average fibrinogen concentrations of 30 mg/mL and 60 mg/ mL, were used. Adhesive preparations were applied in either a thin layer (0.015 mL/cm2) or a thick layer (0.06 mL/cm2) using a spray applicator. A constant thrombin concentration of 10 U/mL was used in the study. No adhesive was used in the control group and grafts were stabilized with staples. No topical dressings were applied to any of the treatment sites. Animals were sacrificed 4 weeks after graft application. RESULTS: Based on statistical analysis, thickness of adhesive application had a significant effect on skin graft survival. Percent mean graft survival in the control and thin application groups was found to be 92% and 97.8% respectively; the mean survival rate in the thick application group was 63.1%. Fibrinogen concentration, when evaluated independently within the thin and thick application groups, was found to have no significant effect on graft survival. CONCLUSION: Independent of fibrinogen concentration, a thin layer of fibrin tissue adhesive, when applied between two opposing surfaces, does not interfere with and may support the healing process, whereas a thick layer of adhesive inhibits skin graft healing.

Animals↗