Search PubMed⌕ Search

Biomedical subjects

S Lele

Publications and source records attributed to S Lele.

32 records · Page 2Linked to original sources

A laboratory evaluation of the Kowa laser flare-cell meter for the study of uveitis.

The Kowa FC-1000 laser flare-cell meter (LFCM) has been described as an instrument which will objectively quantify inflammation of the anterior chamber of the eye. We evaluated the LFCM using the intravenous endotoxin-induced uveitis (EIU) rabbit model of ocular inflammation. In vitro flare and cell calibration measurements utilizing bovine serum albumin (BSA) and latex particles, respectively, were also performed. A linear relationship between the flare measurements and BSA concentrations was noted. In addition, the time course of the LFCM flare count in EIU was comparable to previously published fluorophotometric data. However, the LFCM reported cells in the anterior chamber of the EIU rabbits despite negative cytology and histology results. The LFCM also recorded cells in BSA solutions which contained neither cells nor latex particles. Our results suggest that although the LFCM may be useful for evaluating flare, its cell measurements are not accurate in cases of severe uveitis.

Animals↗

Some comments on coordinate-free and scale-invariant methods in morphometrics.

The unusual strategy for comparing biological shapes is to use some kind of superimposition of the two forms under study and then look at the "residuals" as the shape change. In this paper, I take a careful look at this general strategy and point out some subtle but inherent and important pitfalls. Additionally an alternative approach based on Euclidean Distance Matrix representation is presented. It is applicable to two- as well as three-dimensional objects.

Anatomy↗

Euclidean distance matrix analysis: a coordinate-free approach for comparing biological shapes using landmark data.

For problems of classification and comparison in biological research, the primary focus is on the similarity of forms. A biological form can be conveniently defined as consisting of size and shape. Several approaches for comparing biological shapes using landmark data are available. Lele (1991a) critically discusses these approaches and proposes a new method based on the Euclidean distance matrix representation of the form of an object. The purpose of this paper is to extend this new methodology to the comparison of groups of objects. We develop the statistical versions of various concepts introduced by Lele (1991a) and use them for developing statistical procedures for testing the hypothesis of shape difference between biological forms. We illustrate the use of this method by studying morphological differences between normal children and those affected with Crouzon and Apert syndromes and craniofacial sexual dimorphism in Cebus apella.

Acrocephalosyndactylia↗

Analysis of craniofacial growth in Crouzon syndrome using landmark data.

Finite-element scaling analysis (FESA), generalized procrustes analysis (GPA), and Euclidean distance matrix analysis (EDMA) are applied in a two-dimensional study of craniofacial growth in normal children and those affected with Crouzon syndrome. Longitudinal data are used and growth is measured as change local to 10 craniofacial landmarks. Although details of the results vary among the methods, all 3 methods determine Crouzon growth to be different from normal. Nuances of the methods, especially the use of superimposition in GPA and lack of superimposition in 2 others are partly responsible for the varying results. Although Crouzon craniofacial morphology is often obvious at birth, this study demonstrates that there are general differences between normal postnatal growth patterns and those of the Crouzon individual. These patterns of malgrowth are in part responsible for the adult morphology of the Crouzon craniofacial complex.

Adolescent↗

Weekly cis-diamminedichloroplatinum(II): active third-line chemotherapy in ovarian carcinoma--a preliminary report.

Ten evaluable patients with progressive ovarian adenocarcinoma received third-line chemotherapy consisting of weekly cisplatin (cis-diamminedichloroplatinum[II]) at a dose of 1 mg/kg weekly for a maximum of 6 weeks followed by 60 mg/m2 every 3 weeks. There was no life-threatening toxicity. Seven patients (70%) achieved an objective partial response. This is the highest response rate achieved, to date, by third-line chemotherapy in women with advanced ovarian adenocarcinoma. Weekly cisplatin therefore warrants a trial as first-line therapy.

Adenocarcinoma↗

Melphalan, 5-fluorouracil, and medroxyprogesterone acetate in metastatic or recurrent endometrial carcinoma. Preliminary report.

The purpose of this study was to evaluate therapy with melphalan, 5-fluorouracil (5-FU), and medroxyprogesterone acetate combination (MFP) in women with metastatic or recurrent endometrial carcinoma not amenable to surgery or radiation therapy, as compared to progesterone therapy alone. Previously, the authors have treated 114 women with progesterone therapy and achieved a 15.8% objective response rate; 7.0% were complete responders. Thirteen women with documented recurrent or metastatic endometrial carcinoma were entered into the MFP study. Thirteen were evaluable for toxicity and 11 for response (2 had no measureable parameter). Treatment consisted of melphalan 0.2 mg/kg/day for 4 days every 4 weeks; 5-FU 15 mg/kg/day for 4 days every 4 weeks; and medroxyprogesterone acetate 1.0 g intramuscularly weekly. Two of the first 3 patients who were treated with this regimen developed severe thrombocytopenia (platelets, 25,000 and 17,000/mm3). Therefore, the remaining 10 patients received 5-FU at a dose of 10 mg/kg/day for 4 days every 4 weeks. Except for 1 patient who devloped thrombophlebitis, there was no other significant toxicity in the 90 courses of therapy received by the 13 women. Of the 11 women evaluable for respone, 6 (54.5%) responded (2 complete responders, 4 partial responders), 2 for stationary disease, and 3 progressed after having had stationary disease for 3, 6, and 9 months, respectively. Of special interest was that the 2 women with adenosquamous carcinoma responded and 1 additional patient with adenocarcinoma maintained a complete response with 5-FU therapy alone.

Adenocarcinoma↗

Enterovaginal and enterocutaneous fistulae in women with gynecologic malignancies.

From 1957 to 1975, 43 women with gynecologic malignancies had associated enterocutaneous or enterovaginal fistula. Thirty-four of these women underwent surgical correction of the fistula. The etiology, diagnostic evaluation, preoperative complications, and surgical correction of such fistulae are discussed. In addition, a staged planned management of these fistulae is outlined.

Adult↗

Weekly paclitaxel in patients with recurrent or persistent advanced ovarian cancer.

The purpose of the study is to assess the role of palliative chemotherapy with weekly paclitaxel in patients with persistent or recurrent advanced ovarian cancer. Twenty-eight patients with predominantly paclitaxel- and platinum-resistant ovarian cancer disease were treated with weekly paclitaxel at 80 mg/m2 for 6-8 weeks. In 25 patients (89.2%), this combination represented at least a third line of therapy and for 14 patients (50%) it was more than the fifth line. A clinical response rate of 50% (14 partial responses) was obtained in the 28 patients with evaluable disease. Five patients (17.9%) had stable disease and nine patients (32.1%) had progression of disease. In patients with stable disease or a response, the median progression-free interval was 6 months and overall median survival is 8+ months. All the responses in paclitaxel-resistant tumors were seen in patients with a paclitaxel-free interval of more than 12 months. This regimen is well tolerated with acceptable toxicity. These data suggest that weekly paclitaxel has considerable antitumor activity in heavily pretreated patients with platinum- and paclitaxel-resistant advanced ovarian cancer.

Adult↗

Efficacy of adjuvant CYVADIC chemotherapy in early-stage uterine sarcomas: results of long-term follow-up.

Data on adjuvant chemotherapy in early-stage uterine sarcomas are conflicting and most often based on small patient groups with relatively short duration of follow-up. Approximately 60% of patients present with stage I disease with an overall 5-year survival of 30-50% when treated with surgery alone. This study examines the efficacy and results of long-term follow-up of a multiagent chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine sarcoma. Between 1982 and 1999, 24 evaluable patients with completely staged uterine sarcomas received adjuvant multiagent chemotherapy with vincristine sulfate (1mg /m(2)) on days 1 and 4, doxorubicin (40 mg /m(2)) and cyclophosphamide (400 mg /m(2)) on day 2, and dacarbazine (200 mg /m(2)) on days 1 through 4 for a total of nine monthly cycles or until recurrence of disease was documented. Survival distributions were calculated by the Kaplan-Meier method, and statistical significance was determined with the log-rank test. Factors significant on univariate analysis were analyzed in a multivariate fashion using Cox proportional hazards model. The histologic distribution of patients was 46% leiomyosarcoma, 33% mixed mullerian tumors, 13% stromal sarcomas, 4% adenosarcomas, and 4% hemangiosarcoma. The patients received 206 of a planned 216 cycles of chemotherapy. The median follow-up of the patient population was 93 months (range 11-213 months). Eight patients (33%) developed recurrent disease. The median time to recurrence was 19 months (range 7-184 months). The estimated survival for the entire group was 88, 75, and 69% at 2, 5, and 15 years, respectively. Factors that did not affect survival included age, histology, and tumor grade. Four patients required dose reductions secondary to grade 2-3 toxicities (hematologic). Grade 1 neurotoxicity was observed in six patients (25%) and grade 2 neurotoxicity in one patient (4%). Adjuvant CYVADIC chemotherapy appears to be safe and well tolerated in patients with stage I uterine sarcomas. Our data provide information on the longest duration of follow-up ever reported and suggests that CYVADIC may have a potential role in the adjuvant treatment of early-stage uterine sarcoma.

Adult↗

Pelvic exenterations for gynecological malignancies: twenty-year experience at Roswell Park Cancer Institute.

The objective of this study is to review the experience with pelvic exenterations for gynecological malignancies at our cancer institute. Charts of 48 women who underwent a pelvic exenteration between January 1980 and December 1999 were reviewed, and several outcomes were analyzed. Majority of patients had received prior radiation therapy. The median survival was 35 months, and the disease-free survival was 32 months. Mortality from the procedure was 4.2%. Early and late postoperative complication rates were 27% and 75%, respectively. Recurrence rate was 60%. Eight patients received intraoperative radiation. Median survival in this group was 11.3 vs 35 months (P = 0.003). Univariate analysis failed to show an association between type of pelvic exenteration, type of fecal and urinary diversion, outcome, need for reoperation, and recurrence. Contemporary pelvic exenterations are associated with a low mortality and a potential for long-term survival in a subset of patients who historically have been given a poor prognosis. In patients with recurrent gynecological cancer confined centrally to the pelvis, pelvic exenteration still remains the choice of therapy as response to chemotherapy to a centrally recurrent tumor in radiated area continues to be poor. Intraoperative radiation in select few patients needs to be further studied.

Adult↗

Methylation of death-associated protein kinase in ovarian carcinomas.

Death-associated protein (DAP) kinase is a serine/threonine kinase that plays an integral role in apoptosis and metastasis. The purpose of our study was to determine the methylation status of DAP kinase in ovarian carcinomas. Thirty-one patients with histologically confirmed epithelial ovarian cancers treated at Roswell Park Cancer Institute, Buffalo, New York, between 1987 and 1999 were studied. Sixty-two samples were examined for DAP kinase methylation status: 1 normal human genomic DNA sample from a healthy individual, 1 transformed normal surface ovarian epithelial cell line (IOSE, from Dr Nancy Auersperg, Vancouver, Canada), 2 ovarian carcinoma cell lines (OVCAR3 and A2780), 1 ovarian serous cystadenoma, and 30 ovarian carcinomas. Additionally, peripheral blood DNA was examined from the patients with the serous cystadenoma and ovarian carcinomas. Methylation-specific polymerase chain reaction was performed using primers designed for the unmethylated and methylated promoter regions. The DAP kinase gene was unmethylated in both the normal human genomic DNA sample and the transformed normal surface epithelial ovarian cell line. The two ovarian cancer cell lines were methylated. In the 30 patients with malignant disease, methylation of DAP kinase was observed in 20 (67%). Peripheral blood DNA was available in 26 (87%) of the 30 patients. Comparison of the paired samples indicated that 14 (54%) were methylated and 12 (46%) were unmethylated. There was no correlation between the DAP kinase methylation status and stage, grade, histology, or survival. Methylation of CpG islands in the promoter region of the DAP kinase gene is common in peripheral blood DNA and tissue samples of patients with ovarian carcinomas. This molecular aberration may represent a potential target for therapeutic intervention.

Adult↗

Cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin (CHAD) as second-line chemotherapy for ovarian adenocarcinoma.

Twenty women with recurrent ovarian adenocarcinoma received a monthly four-drug combination of cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin as second-line chemotherapy. There were no objective responses to this regimen. This is in contrast to the 49% response rate reported by Kane et al using these four drugs and the 63% response rate reported by Vogl et al using three of these drugs as second-line chemotherapy. The differences in the three regimens are reviewed; however, we could not identify reasons sufficient to account for the disparity in response rates.

Adenocarcinoma↗

Preoperative morphology and development in sagittal synostosis.

The goal of this study is to characterize the differences between normal cranial morphology and that of patients diagnosed with isolated sagittal synostosis, using three-dimensional (3D) landmark coordinate data collected from computed tomography (CT) scans. This retrospective study uses pre-operative CT images of a sample of children diagnosed with isolated sagittal synostosis (N = 23) and of dry skulls of unaffected children (N = 10). In order to be included in the study, patients had to have a confirmed diagnosis of sagittal synostosis and a pre-operative CT scan of acceptable quality available in digital format. Separation of normal and synostosed individuals on the basis of craniofacial morphology was achieved by applying a principal coordinates analysis to a dissimilarity matrix calculated from the landmark coordinate data. Direct comparison of age-graded samples of normal and synostosed individuals using Euclidean Distance Matrix Analysis enabled localization of the morphological differences between samples. This method was also used to characterize growth patterns of the two samples using cross-sectional data. The parietal bosses were found to be the features that were most influential in separating sagittal synostosis patients from their age-matched normal counterparts. A cross-sectional analysis of growth showed that the specifics of the growth differences between normal and sagittal synostosis individuals changed with the age interval considered. We present direct evidence that the parietal bosses are critical in the differentiation of normal and sagittal synostosis morphology, and indirect evidence of the possible role of the parietal tubers in the etiology of sagittal synostosis.

Child↗