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Biomedical subjects

E Joseph

Publications and source records attributed to E Joseph.

At least 19 recordsLinked to original sources
PubMed2004

Plasma pharmacokinetics and tissue distribution of the breast cancer resistance protein (BCRP/ABCG2) inhibitor fumitremorgin C in SCID mice bearing T8 tumors.

Multidrug resistance (MDR) remains a major obstacle in the treatment of human cancers. The recently discovered breast cancer resistance protein (BCRP/ABCG2) has been found to be an important mediator of chemotherapeutic MDR. Fumitremorgin C (FTC) is a selective and potent inhibitor of BCRP that completely inhibits and reverses BCRP-mediated resistance at micromolar concentrations. We report a study of the pharmacokinetics and tissue distribution of FTC when administered intravenously (IV) at a dose of 25 mg/kg to female SCID mice bearing the BCRP-overexpressing human ovarian xenograft Igrov1/T8 tumors. Plasma pharmacokinetics and tissue distribution of FTC in various organs and tissues were studied. In addition, the effect of FTC administration on the expression of BCRP in T8 tumors was also assessed by RT-PCR. Administration of a single FTC IV dose did not appear to cause any major toxicities. The resulting pharmacokinetic data were fit to a two-compartment model using NONMEM and the FTC clearance was determined to be 0.55 ml/min (25.0 ml/min/kg) with a 56% inter-animal variability. Area under the plasma concentration time curve was determined by Bailer's method and was calculated to be 1128+/-111 microg min/ml. FTC was widely distributed in all tissues assayed with highest concentrations found in lungs, liver and kidney in decreasing order, respectively. FTC did not appear to have any effect on the expression of BCRP in T8 tumors. Less than 2% of the administered dose was recovered in the urine and feces after 24 h, suggesting hepatic metabolism as a primary mechanism of elimination. The current study can be used as a basis for future animal or in vivo studies with FTC designed to further understand the impact of BCRP on drug resistance.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2000

Fibrous dysplasia of the orbit in an infant.

Fibrous dysplasia is an idiopathic fibro-osseous lesion of the skeletal bones. These uncommon osseous lesions usually manifest within the first two decades of life. Its occurrence during infancy is extremely uncommon, and we describe here a case of fibrous dysplasia involving the orbit in a 9-month-old male child.

Craniotomy↗
PubMed2000

Heat exposure study in the workplace in a glass manufacturing unit in India.

The heat exposure for working conditions in coastal areas of tropical and subtropical countries like India is a crucial factor in improved qualitative and quantitative production. The hot climate augments the heat exposure close to sources like furnaces. In the present work heat exposure to workers in glass manufacturing units in a coastal area of India has been assessed. The Wet Bulb Globe Temperature (WBGT), the Corrected Effective Temperature (CET) and Mean Radiant Temperature (MRT) were measured. The WBGT values much exceeded ACGIH TLVs. A revision of these standards to suit tropical and subtropical conditions is required. The recommended durations of work and rest have been estimated.

Environmental Monitoring↗
PubMed2000

Atypical meningioma: a clinicopathological analysis.

In this retrospective study, 382 operated cases of meningiomas were reviewed. 32 cases (8.3%) were histopathologically classified as atypical meningioma. The anatomical locations and histological features in all the thirty-two cases were correlated with their recurrence rates and biological behaviour. The overall recurrence rate for atypical meningioma within two years was 28% as compared to 9.3% in benign meningiomas. It is being emphasized that an accurate histopathological interpretation of atypical meningioma is essential for predicting the recurrence, biological behavior as well as post-operative management modalities.

Adult↗
PubMed1999

Lymphatic mapping for melanomas of the upper extremity.

Over a period of 4 years, 127 consecutive patients with upper extremity melanomas were identified from a prospectively accrued database. A protocol consisting of preoperative lymphoscintigraphy and intraoperative lymphatic mapping and with a vital blue dye and radiocolloid was used; the protocol had a 98% success rate of identifying the sentinel lymph node (SLN). Preoperative lymphoscintigraphy identified unpredictable cutaneous lymphatic flow in 15 (12%) of the patients. These discordant areas would not have been included in classic regional node dissection and possible sites of metastatic disease would not have been identified. Metastatic disease was identified within the SLNs in 12 (9%) of the patients. Of the 12 patients with a positive SLN, 2 (17%) were found on complete node dissection to have metastatic disease in higher nodes in the regional basin. The SLN was the only site of disease in 10 of these 12 patients with documented metastases in the regional basin. Patients with a negative SLN biopsy can be spared the morbidity and expense of a complete lymph node dissection.

Arm↗
PubMed1999

Pathology of temporal lobe epilepsy: An analysis of 100 consecutive surgical specimens from patients with medically refractory epilepsy.

The neuropathological features of temporal lobe epilepsy were studied utilising 100 consecutive surgical specimens from patients with medically refractory complex partial seizures. A wide spectrum of neuropathological changes was recorded in 98 specimens. Fifty-eight specimens showed features of Ammon's horn sclerosis. Diffuse accumulation of corpora amylacea were demonstrated in the resected temporal lobes from 54 patients. Six patients had neoplastic lesions of temporal lobe. One unique case of dysembryoplastic neuroepithelial tumour showed a melanotic component within the tumour. The neuropathological features were regarded as nonspecific in 31% of cases. Our results indicate that a majority of patients with medically intractable epilepsy of temporal lobe origin reveal significant neuropathological features. Careful documentation of the neuropathological features and its correlation with radiological, electrophysiological and pre- and post-surgical clinical features will help in predicting the seizure outcome after temporal lobectomy for medically refractory epilepsy.

Brain Neoplasms↗
PubMed1999

Caries prevalence and its relation to socio-economic status and oral hygiene practices in 600 pre-school children of Kerala-India.

This Study was undertaken to determine the caries status of pre-school children in Ulloor Panchayat of Trivandrum, Kerala and to determine the relation if any, between their caries and socio-economic status and oral practices. 200 children each from the low, middle arid higher socio-economic group were visually examined for caries by the same examiner in natural daylight. Caries was recorded according to the WHO criteria. Information regarding the childrens' oral hygiene practices were obtained through structured questionnaires to the care takers of the children. Computer analysis of the data collected showed that 43% of the study sample were caries free. Socio-economic level was found to have a negative association with caries status. The mode of tooth brushing was found to be significantly related to caries severity while the frequency of tooth brushing was found to have no association with caries prevalence and severity.

Child, Preschool↗
PubMed1998

Molecular staging of malignant melanoma: correlation with clinical outcome.

CONTEXT: For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases. OBJECTIVE: To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma. DESIGN: A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months. SETTING: A major university-based melanoma referral center at a National Cancer Institute-designated cancer center. PATIENTS: A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases. MAIN OUTCOME MEASURE: Melanoma recurrence and overall survival. RESULTS: Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival. CONCLUSIONS: The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.

Adult↗
PubMed1998

Efficacy of hyperthermic isolated limb perfusion for extremity-confined recurrent melanoma.

BACKGROUND: Recurrent melanoma of the extremity has been treated by local excision, systemic chemotherapy, amputation, or a combination of these approaches. Hyperthermic isolated limb perfusion (HILP) provides a method of limb preservation through isolation, allowing the administration of chemotherapy in higher doses than is possible through systemic treatment. METHODS: An experimental group of 59 HILP patients with melanoma recurrences of the extremity was studied prospectively. A control group of 248 melanoma patients with similar recurrences was excluded from HILP because their recurrences were in non-extremity locations. The experimental group underwent HILP and excision; the control group had excision only. The experimental procedure consisted of vascular isolation of the affected extremity and a 1-hour perfusion with melphalan. Temperatures were maintained at 40 degrees C in the perfusion circuit. RESULTS: The HILP patients had a lower rate of locoregional recurrence (P=.028) and demonstrated increased survival (P=.026) compared to the control group. In multivariate regression analysis, which included age, ulceration and thickness of the primary, and the treatment variable of perfusion, age (P=.02) and perfusion for the treatment of recurrence (P=.006) were significant predictors of survival. CONCLUSIONS: HILP improves prognosis by sterilizing the treated extremity, controlling locoregional disease, and perhaps preventing metastasis, thus having a positive impact on overall survival.

Antineoplastic Agents↗
PubMed1998

Evaluation of an intensive strategy for follow-up and surveillance of primary breast cancer.

BACKGROUND: Controversies over the frequency and intensity of the follow-up care of breast cancer patients exist. Some physicians have adopted an intensive approach to follow-up care that consists of frequent laboratory tests and routine imaging studies, including chest radiographs, bone scans, and CT scans, whereas others have established a minimalist approach consisting of only history, physical examinations, and mammograms. OBJECTIVES: Our objective was to evaluate the role of intensive follow-up on detection of breast cancer recurrence and to examine the impact of follow-up on overall survival. METHODS: During a 10-year period (1986-1996), 129 patients with recurrent disease were identified from a prospective database of 1898 breast cancer patients. The patients with recurrent disease were divided into minimalist or intensive groups according to method of detection. RESULTS: Twenty-seven of 126 (21%) patients were assigned to the intensive method of detection group (LFT, CEA, CA 15-3, chest radiograph, CT scan, and bone scan); 99 of 126 (79%) patients were assigned to the minimal detection group (history, physical examination, and mammography). Distant disease to the bone was the most common initial tumor recurrence, at 27%. History, physical examination, and mammography detected recurrent cancer in approximately the same amount of time as LFTs, tumor markers, CT scans, and chest radiographs (P = .960). When the recurrent patients were divided into intensive and minimalist groups and analyzed by time to detection of recurrence, there was no significant difference between the time to detection in those recurrences detected by intensive methods and those recurrences detected by minimalist methods (P = .95). The independent variables age, tumor size, type of surgery, number of positive nodes, time to recurrence, method of detection, and site of recurrence (regional or distant) were subject to univariate and multivariate analysis by the Cox proportional hazards model. Only two variables had an impact on survival by multivariate analysis: early timing of the recurrence (P = .0011) and the site of the recurrence (P = .02). Timing was defined as early (< or =365 days from the time of diagnosis to recurrence) or late (> or =365 days from the time of diagnosis to recurrence). Early recurrence was the first variable found to be significant on stepwise forward regression analysis. The primary site of recurrence was significant at step two. The method of detection--intensive or minimal--did not significantly affect survival (P = .18). CONCLUSIONS: There is no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer. Expensive diagnostic tests such as bone scans, CT scans, and serial tumor markers are best used for detection of metastasis in symptomatic patients.

Breast Neoplasms↗
PubMed1998

Results of complete lymph node dissection in 83 melanoma patients with positive sentinel nodes.

BACKGROUND: The technique of sentinel lymph node (SLN) biopsy for melanoma provides accurate staging information because the histology of the SLN reflects the histology of the entire basin, particularly when the SLN is negative. METHODS: We combined two mapping techniques, one using vital blue dye and the other using radiolymphoscintigraphy with a hand-held gamma Neoprobe, to identify the SLN in 600 consecutive patients with stage I-II melanoma. The SLNs were examined using conventional histopathology and immunohistochemistry for S-100. RESULTS: Eighty-three (13.9%) patients had micrometastatic disease in the SLNs. Thirty percent of patients with primary melanomas greater than 4.0 mm in thickness had positive SLNs, followed by 48 of 267 (18%) of patients with tumors between 1.5 mm and 4 mm, and 12 of 169 (7%) of those with lesions between 1.0 mm and 1.5 mm. No patient with a tumor less than 0.76 mm in thickness had a positive SLN. Sixty-four of the 83 SLN-positive patients consented to undergo complete lymph node dissection (CLND), and five of 64 (7.8%) of the CLNDs were positive. All patients with positive CLNDs had tumor thicknesses greater than 3.0 mm. CONCLUSIONS: The rate of SLN-positive patients increases with increasing thickness of the melanoma. SLN-positive patients with primary lesions less than 1.5 mm in thickness may have disease confined to the SLN, thus rendering higher-level nodes free of disease, and may not require a CLND.

Adolescent↗
PubMed1998

Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer.

OBJECTIVE: To define preliminary guidelines for the use of lymphatic mapping techniques in patients with breast cancer. SUMMARY BACKGROUND DATA: Lymphatic mapping techniques have the potential of changing the standard of surgical care of patients with breast cancer. METHODS: Four hundred sixty-six consecutive patients with newly diagnosed breast cancer underwent a prospective trial of intraoperative lymphatic mapping using a combination of vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine hematoxylin and eosin (H&E) stains and immunohistochemical stains for cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined cluster of positive-staining cells that could be confirmed histologically on H&E sections. RESULTS: Fine-needle aspiration (FNA) or stereotactic core biopsy was used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422 patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients who failed lymphatic mappings, a complete axillary dissection was performed, and metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26 patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core biopsy. Of interest, there was only one skip metastasis (defined as a negative SLN with higher nodes in the chain being positive) in a patient with prior excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844 (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive SLNs was found in patients who had invasive tumors of increasing size: 18 of 112 patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs. However, a significantly greater percentage of patients (43 of 131 [32.8%] with tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and 5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a positive SLN (p < 0.001). CONCLUSIONS: This study demonstrates that accurate SLN identification was obtained when all blue and hot lymph nodes were harvested as SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a combination of vital blue dye and radiolabeled sulfur colloid is used. Furthermore, these data demonstrate that patients with ductal carcinoma in situ or small tumors exhibit a low but significant incidence of metastatic disease to the axillary lymph nodes and may benefit most from selective lymphadenectomy, avoiding the unnecessary complications of a complete axillary lymph node dissection.

Biopsy↗
PubMed1997

The Role of Selective Lymphadenectomy in Breast Cancer.

BACKGROUND: Axillary node dissection is considered a standard staging procedure in patients with breast cancer. The procedure is associated with significant morbidity and provides pathologists with many lymph nodes to evaluate. METHODS: A total of 174 women participated in a trial that included preoperative lymphoscintigraphy and intraoperative lymphatic mapping using a combination of a vital blue dye and radiocolloid mapping. RESULTS: The intraoperative lymphatic mapping correctly identified a sentinel lymph node (SLN) in 160 (92%) of 174 patients. One skip metastasis (0.7%) occurred in 136 women who had a subsequent complete node dissection. CONCLUSIONS: Lymphatic mapping and SLN biopsy using a combination of mapping techniques provide accurate nodal staging for women with breast cancer. With this technique, approximately 70% to 80% of women with no axillary metastases could be spared the morbidity of a complete node dissection.

Journal Article↗
PubMed1997

Screening Childhood Cancer Survivors for Breast Cancer.

The development of second primary solid tumors, especially breast neoplasms, is increased among patients who have survived childhood or adolescent malignancies. With the increased long-term survival of patients with pediatric cancer, questions regarding breast cancer screening in this group have been raised. At this time, there are no established guidelines for breast cancer surveillance in this high-risk population. The objective of this review is to summarize the incidence, list additional risk factors for the development of breast cancer, and discuss the benefits of early detection of second primary breast cancers in pediatric cancer survivors. We have devised an algorithm for breast cancer screening in survivors of childhood malignancy. Implications of treatment with radiation and chemotherapy and the influence on prognosis of genetic abnormalities such as p53 mutations are debated.

Journal Article↗
PubMed1996

Maternal beta-catenin establishes a 'dorsal signal' in early Xenopus embryos.

In previous work, we demonstrated that maternally encoded beta-catenin, the vertebrate homolog of armadillo, is required for formation of dorsal axial structures in early Xenopus embryos (Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., Kintner, C., Yoshida-Noro, C. and Wylie, C. (1994). Cell 79, 791-803). Here we investigated, firstly, the role(s) of beta-catenin in spatial terms, in different regions of the embryo, by injecting beta-catenin mRNA into individual blastomeres of beta-catenin-depleted embryos at the 32 cell stage. The results indicate that beta-catenin can rescue the dorsal axial structures in a non-cell-autonomous way and without changing the fates of the injected cells. This suggests that cells overexpressing beta-catenin send a 'dorsal signal' to other cells. This was confirmed by showing that beta-catenin overexpressing animal caps did not cause wild-type caps to form mesoderm, but did cause isolated beta-catenin-deficient marginal zones to form dorsal mesoderm. Furthermore beta-catenin-deficient vegetal masses treated with overexpressing caps regained their ability to act as Nieuwkoop Centers. Secondly, we studied the temporal activity of beta-catenin. We showed that zygotic transcription of beta-catenin starts after the midblastula transition (MBT), but does not rescue dorsal axial structures. We further demonstrated that the vegetal mass does not release a dorsal signal until after the onset of transcription, at the midblastula stage, suggesting that maternal beta-catenin protein is required at or before this time. Thirdly we investigated where, in relationship to other gene products known to be active in axis formation, beta-catenin is placed. We find that BVg1, bFGF, tBR (the truncated form of BMP2/4R), siamois and noggin activities are all downstream of beta-catenin, as shown by the fact that injection of their mRNAs rescues the effect of depleting maternally encoded beta-catenin. Interference with the action of glycogen synthase kinase (GSK), a vertebrate homolog of the Drosophila gene product, zeste white 3 kinase, does not rescue the effect, suggesting that it is upstream.

Animals↗