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Biomedical subjects

T E Merchant

Publications and source records attributed to T E Merchant.

At least 55 records · Page 3Linked to original sources

Ex vivo phosphorus magnetic resonance spectroscopy on eye bank corneas and corneal metabolic health.

BACKGROUND: Since a potential exists for untoward effects on the cornea from the high magnetic fields and radio-frequency energies, and the further manipulation required for phosphorus-31 magnetic resonance spectroscopy (31P-MRS), we determined the effects of this technology on tissues using paired human corneas (n = 4) meeting criteria acceptable for transplantation. METHODS: Slit-lamp biomicroscopy, pachometry, specular microscopy, and redux fluorophotometry were performed on all corneas. One cornea of each pair was examined (< 30 min) by 31P-MRS. Following 31P-MRS, slit-lamp biomicroscopy, pachometry, and redox fluorophotometry were again performed. RESULTS: Data tabulated included the 31P energy modulus (1.37 +/- 0.28), the ATP/Pi (2.92 +/- 0.59) and SP/Pi (0.76 +/- 0.04) ratios, and the intracorneal pH (7.24 +/- 0.09). CONCLUSION: Since there were no significant differences in slit-lamp biomicroscopy, endothelial density and morphometry, cell counts, and pachometric and redox fluorophotometric measurements between corneas of each pair before and after 31P-MRS analysis, it was concluded that there was no detectable metabolic damage secondary to such analysis. This study suggests that MRS analysis of human eye-bank tissues does not damage the cornea metabolically and may provide a practical evaluation of the health of the cornea at the biochemical level.

Adenosine Triphosphate↗

Anaplastic ependymoma: treatment of pediatric patients with or without craniospinal radiation therapy.

The authors conducted a retrospective review of the clinical and treatment characteristics and outcomes in 28 pediatric patients with anaplastic ependymoma treated with radiation therapy since the advent of computerized tomography (CT) (1978-1994). Twelve patients received craniospinal irradiation followed by a boost to the primary site, two received whole-brain radiation therapy followed by a boost to the primary site, and the remaining 14 were treated with focal radiation therapy. The mean dose to the primary site was 5486 cGy. With a median follow-up period of 86 months for the 14 surviving patients (range 31-201 months), the median disease-free survival, measured from the date of diagnosis to the time of recurrence after radiation therapy, was 40 months. The median disease-free survival measured from the start of radiation therapy was 32 months. The median overall survival rate has not been reached and the actuarial estimates of overall survival rates at 5 and 10 years were 56% and 38%, respectively. According to univariate analysis, the disease-free survival rate was significantly improved (p < 0.01) in patients who underwent a gross-total resection at diagnosis. Overall survival rates were negatively influenced by treatment with craniospinal and whole-brain irradiation. As calculated by multivariate analysis, increasing dosage to the primary site (p < 0.05), infratentorial location (p < 0.01), and gross-total resections (p < 0.02) resulted in the longest disease-free survival times. All 19 patients in whom treatment failed after radiation therapy suffered a recurrence at the primary site. In addition, one of these patients experienced subarachnoid dissemination. Radiation treatment recommendations for patients with ependymoma have been based on the tumor's location, perceived risk for dissemination, and malignant propensity. The significance of anaplastic histological classification is controversial. Differences in the disease-free and overall survival rates have been demonstrated between ependymomas and anaplastic ependymomas treated in the pre-CT era. The results of this study show that there is no benefit from craniospinal irradiation in this group of patients.

Adolescent↗

Medulloblastoma: long-term results for patients treated with definitive radiation therapy during the computed tomography era.

PURPOSE: We performed a retrospective evaluation of the patterns of failure and outcome for medulloblastoma patients treated with craniospinal irradiation therapy during the computed tomography (CT) era. MATERIALS AND METHODS: The records of 100 patients treated at Memorial Sloan-Kettering Cancer Center between 1979 and 1994 were reviewed. CT scans or magnetic resonance imaging were used to guide surgical intervention and evaluate the extent of resection postoperatively. All patients were treated with conventional fractionation (1.8 Gy/day) and the majority received full-dose neuraxis radiation therapy and > 50 Gy to the primary site. RESULTS: With a median follow-up of 100 months, the median, 5-year, and 10-year actuarial overall survival for the entire group were 58 months, 50%, and 25%, respectively. The median, 5- and 10-year actuarial disease-free survivals were 37 months, 41%, and 27%, respectively. Patients with localized disease (no evidence of disease beyond the primary site) had significantly improved overall (p < 0.02) and disease-free (p < 0.02) survivals compared to those with nonlocalized disease. For patients with localized disease, the 5- and 10-year overall survival rates were 59% and 31%, whereas the disease-free survivals were 49% and 31%, respectively. Disease-free and overall survivals at similar intervals for patients with nonlocalized disease were 29% and 30% (5 years), and 29% and 20% (10 years), respectively. Sixty-four of 100 patients failed treatment. Local failure as any component of first failure occurred in 35% of patients or 55% (35 of 64) of all failures and as the only site of first failure in 14% or 22% (14 of 64) of all failures. For patients presenting with localized disease (n = 68), local failure as any component of first failure occurred in 32% (22 of 68) and in 18% (12 of 68) as the only site. A multivariate analysis showed that M stage was the only prognostic factor to influence overall survival. For disease-free survival, M stage and the extent of resection were prognostic factors. Ventriculoperitoneal shunting and the use of chemotherapy were associated with a poor outcome; however, these results were confounded by the positive impact of chemotherapy in decreasing the risk of extraneural metastases and the use of these therapies in the more advanced patients. CONCLUSION: These long-term follow-up data represent one of the largest series of patients with complete follow-up who were treated with a consistent radiation therapy treatment policy during the CT era. Local failure in patients with localized disease, the persistent risk of late failures, treatment-related toxicity, and the ever-present risk of secondary malignancies demonstrate the limitations of standard therapies. Strategies used to increase the total dose to the primary site should be pursued along with other adjuvant therapies such as intensive chemotherapy.

Adolescent↗

The influence of older age on breast cancer treatment decisions and outcome.

PURPOSE: Information concerning the differences between older and younger women with breast cancer, treated with standard therapy, is lacking from many prospective series. The purpose of this study is to identify factors that influence treatment decisions and determine if women age 65 and older are treated differently than younger women. The outcomes of older women would then be compared to younger to determine if treatment differences influence outcome. METHODS AND MATERIALS: The records of 558 women with early invasive breast cancer who were treated with breast conserving surgery and radiation therapy were retrospectively reviewed. Four hundred thirty-two women under the age of 65 (range: 24-64) and 126 women age 65 and older (range: 65-85) were assessed for treatment differences including breast reexcision, extent of axillary dissection, extent of breast and nodal irradiation, and the use of chemotherapy or hormonal therapy. Differences in the treatment of the two groups were determined and the end points of local control, disease-free survival, and overall survival were compared. Median follow-up was 5.5 years. RESULTS: The two treatment groups had identical pathologic TNM staging with the exception that 21% of the older age group and 5% of the younger group did not undergo axillary dissection. Women age 65 and older were less likely to have a reexcision, extensive axillary dissection, chemotherapy, or nodal irradiation. They were more likely to receive hormonal therapy. Reexcision in older women was positively influenced by a family history of breast cancer and negatively influenced by a history of previous malignancy. None of the patients who were treated without and axillary dissection suffered a regional recurrence. Although local control was better in older patients, there were no differences in disease-free or overall survival for the two groups. DISCUSSION: The findings of this study reveal that older patients have significant treatment differences as compared to younger patients; however, despite these differences, similar local control and survival were achieved at 5 to 10 years. With the expected survival of older women increasing, the prospective evaluation of treatment options for older women should be considered.

Adult↗

Desmoplastic small round-cell tumor: prolonged progression-free survival with aggressive multimodality therapy.

PURPOSE: To test intensive alkylator-based therapy in desmoplastic small round-cell tumor (DSRCT). PATIENTS AND METHODS: Patients received the P6 protocol, which has seven courses of chemotherapy. Courses 1, 2, 3, and 6 included cyclophosphamide 4,200 mg/m2, doxorubicin 75 mg/m2, and vincristine (HD-CAV). Courses 4, 5, and 7 consisted of ifosfamide 9 g/m2 and etoposide 500 mg/m2 for previously untreated patients, or ifosfamide 12 g/m2 and etoposide 1,000 mg/m2 for previously treated patients. Courses started after neutrophil counts reached 500/microL and platelet counts reached 100,000/microL. Tumor resection was attempted. Post-P6 treatment options included radiotherapy and a myeloablative regimen of thiotepa (900 mg/m2) plus carboplatin (1,500 mg/m2), with stem-cell rescue. RESULTS: Ten previously untreated and two previously treated patients have completed therapy. The male-to-female ratio was 11:1. Ages were 7 to 22 years (median, 14). The largest masses were infradiaphragmatic (n = 11) or intrathoracic (n = 1). Other findings included serosal implants (n = 11), regional lymph node invasion (n = 8), ascites or pleural effusion (n = 7), and metastases to liver (n = 5), lungs (n = 4), distant lymph nodes (n = 3), spleen (n = 2), and skeleton (n = 2). Tumors uniformly responded to HD-CAV, but there were no complete pathologic responses. One patient died at 1 month from tumor-related Budd-Chiari syndrome. Of seven patients who achieved a complete remission (CR), five remain in CR 9, 12, 13, 33, and 38 months from the start of P6, one patient died of infection at 12 months (autopsy-confirmed CR), and one patient relapsed 4 months off therapy. Of four patients who achieved a partial remission (PR), one remains progression-free at 34 months and three developed progressive disease. Five patients received local radiotherapy: three were not assessable for response, but in two patients, antitumor effect was evident. Four patients received thiotepa/carboplatin: two were in CR and remain so, and two patients had measurable disease that did not respond. CONCLUSION: For control of DSRCT, our experience supports intensive use of HD-CAV, aggressive surgery to resect visible disease, radiotherapy to high-risk sites, and myeloablative chemotherapy with stem-cell rescue in selected cases.

Abdominal Neoplasms↗

Characterization of malignant colon tumors with 31P nuclear magnetic resonance phospholipid and phosphatic metabolite profiles.

BACKGROUND: To further characterize selected pathologic features on a biochemical level, the authors analyzed the nuclear magnetic resonance metabolite and phospholipid spectra of 30 malignant colon tumors using 31P magnetic resonance spectroscopy. METHODS: Eleven individual generic phospholipids were identified in the spectra of 17 phospholipid extracts, and 31 individual phosphatic metabolites were identified in the spectra of 13 perchloric acid extracts. The metabolites and lipids were quantified for statistical intergroup comparisons based on tumor stage, lymph node status, differentiation, mucin production, blood vessel invasion (BVI), and lymphatic vessel invasion (LVI). RESULTS: Significant elevations in the relative concentration of alpha-glycerol phosphate were noted when comparing AJCC tumor classification (T3 vs. T2, 0.92 +/- 0.14 vs. 0.46 +/- 0.11, P < 0.009), tumor differentiation (moderately vs. well differentiated, 0.92 +/- 0.14 vs. 0.46 +/- 0.11, P < 0.009), and BVI (presence vs. absence, 1.03 +/- 0.04 vs. 0.68 +/- 0.10, P < 0.028) by elastic tissue stain. Among the tissue phospholipids analyzed, the relative concentration of a choline phospholipid was significantly different when comparing moderately and poorly differentiated tumors (6.26 +/- 0.56 vs. 3.29 +/- 0.30, P < 0.001), T2 and T3 tumors (3.90 +/- 0.45 vs. 6.31 +/- 0.56, P < 0.009), and mucin-positive vs. mucin-negative tumors (4.46 +/- 0.56 vs. 6.83 +/- 0.76, P < 0.028). Differences in lymph node status of the cases analyzed in this study (lymph node positive vs. lymph node negative) were noted for tumors with elevated levels of sphingomyelin (8.13 +/- 0.40 vs. 6.88 +/- 0.16, P < 0.02), diminished levels of phosphatidylinositol (5.25 +/- 0.27 vs. 6.38 +/- 0.34, P < 0.02), elevated levels of beta-glycerol phosphate (5.30 +/- 0.70 vs. 1.20 +/- 0.06, P < 0.05), and elevated levels of glycerol 3-phosphoserine (0.48 +/- 0.01 vs. 0.23 +/- 0.02, P < 0.002). CONCLUSIONS: The characteristic differences in the phospholipid and intermediate phosphate metabolite profiles identified through magnetic resonance spectroscopic and histopathologic analysis may provide important information regarding the nature of tumor and cell membrane metabolism. Differences in these profiles may identify markers useful for biologic behavior, provide prognostic information, and characterize the impact of the pathologic features of colon cancer.

Cell Differentiation↗

The effects of age on phosphatic metabolites of the human cornea.

Phosphatic metabolites from human corneas, pooled into 7 decades ranging from ages < 1 year through 79 years, were quantitated using phosphorus-31 magnetic resonance (31P MR) spectroscopy. Relative concentrations of phosphorus-containing compounds measured included the low-energy metabolites [phosphomonoesters (PME), inorganic orthophosphate (Pi), phosphodiesters (glycerol 3-phosphorylethanolamine and glycerol 3-phosphorylcholine)] and the high-energy metabolites [phosphocreatine (PCr), adenosine triphosphate (ATP), adenosine diphosphate (ADP), nucleosidediphosphosugars and the dinucleotides]. Significant linear changes attributable to age occur in the relative mole percentage decrease of phosphate concentrations of human corneal PME, PCr and ATP, and in the increase of Pi. Age-attributable rates of decrease in PME at -0.162 MPP/YR (mole percent phosphorus per year), PCr at -0.015 MPP/YR and ATP at -0.487 MPP/YR combined, approximate the rate of increase in Pi determined to be +0.729 MPP/YR. Of the indices computed from the human corneal spectral data, the ratios of ATP/Pi and PME/Pi and the tissue energy modulus were all found to decrease significantly with age. These changes in corneal phosphatic metabolites are indicative of an overall decline in high-energy metabolism with age.

Adolescent↗

Comparison of relative changes in phosphatic metabolites and phospholipids after irradiation.

Measurements of phosphatic metabolites and phospholipids using 31P NMR spectroscopy were performed on tumor extracts at specific times before and after a priming dose of radiation at 32 or 65 Gy. At both doses, statistically significant increases in the high-energy phosphates PCr and ATP, relative to their primary hydrolysis product Pi, were detected at 24 h after irradiation. These spectral changes are consistent with an increased capacity for aerobic metabolism and oxidative phosphorylation. The changes coincide with a significant reduction in the hypoxic cell fraction and 50% tumor control dose measurements reported previously for the same tumor model. A significant increase in the ratio of phosphorylethanolamine to phosphorylcholine was also detected at 24 h. The ratio of ethanolamine-containing to choline-containing phospholipids increased significantly between 48 and 96 h. The spectral changes measured in this study coincide with the changes in the hypoxic state of the tumor after irradiation and are consistent with spectral measurements performed in vivo. The high-resolution spectroscopic data also identify specific metabolites contributing to spectral changes measured in vivo.

Animals↗

Prone position breast irradiation.

PURPOSE: An alternative technique for irradiating the breast following breast conserving surgery is described. METHODS AND MATERIALS: The technique utilizes the prone position and has been developed to improve the dose distribution within the breast and reduce the volume of normal tissues irradiated during whole breast treatment. Improvements in the dosimetry of breast irradiation are obtained through the optimization of the shape of the breast and result in a reduction in the magnitude of high-dose regions and isodose gradients at the base of the breast. RESULTS: The high dose region at the base of the breast, without lung correction, generally ranges from 116-118% for large breasted women treated in the supine position. These high dose regions are reduced to 102-103% for the same women treated in the prone position. Irradiation of the heart, lungs, chest wall and contralateral breast are minimized with this technique. The improvements appear to benefit women with large breasts, pendulous breasts, large separations and/or irregularly shaped chest contours. CONCLUSION: The prone position technique takes advantage of the reproducibility characteristics of the supine position technique and combines them with the homogeneity and normal tissue-sparing characteristics of the lateral decubitus position technique. Prone position breast irradiation appears to be a simple and effective alternative to irradiation of the breast in the conventional supine position when the supine position is likely to result in unacceptable dose inhomogeneity or significant doses to normal tissues.

Breast↗

31P NMR phospholipid characterization of intracranial tumors.

Phospholipid extracts from 48 intracranial tumors were analyzed using 31P NMR. Phospholipids commonly identified in the tumor spectra included phosphatidylglycerol (PG), phosphatidic acid (PA), diphosphatidylglycerol (DPG), uncharacterized phospholipid (U), ethanolamine plasmalogen (EPLAS), phosphatidylethanolamine (PE), phosphatidylserine (PS), sphingomyelin (SM), lysophosphatidylcholine (LPC), phosphatidylinositol (PI), a choline phospholipid (CPLIP), and phosphatidylcholine (PC). Differences in the mean relative mole-percentage of phosphorus concentrations of individual phospholipids were used to differentiate among tumors. Neural sheath tumors (neurilemmoma, neurofibroma and fibrosarcoma) were noted to contain significantly elevated levels of SM relative to tumors of neural glial origin and individually, glioblastoma multiforme was noted to contain depressed levels of SM relative to neurilemmoma, neurofibroma and meningioma. Significantly decreased levels of PA were noted for glioblastoma relative to neurilemmoma along with significantly decreased levels of PE relative to meningioma. Elevated levels of LPC and CPLIP were seen in glioblastoma multiforme relative to meningioma. Additional findings included elevated levels of PC for glioblastoma multiforme relative to neurofibroma, and neurilemmoma was differentiated from neurofibroma with elevated levels of PA and depressed levels of PI. 31P NMR phospholipid analysis provides supplemental biochemical information which may be used to improve the interpretation of spectra acquired in vivo, and reveals important tumor-specific biochemical information which may further improve the understanding of the biological behavior of intracranial tumors.

Brain Chemistry↗

Meningioma phospholipid profiles measured by 31P nuclear magnetic resonance spectroscopy.

Fourteen cases of intracranial meningioma were characterized after chloroform/methanol extraction by 31P nuclear magnetic resonance (NMR) spectroscopy at 202.4 MHz. Each phospholipid class detected in the extracts was identified and quantitated in terms of its molar percentage relative to the total phospholipids measured. The following phospholipids were assayed by 31P NMR: phosphatidylglycerol, phosphatidic acid, diphosphatidylglycerol, ethanolamine plasmalogen, phosphatidylethanolamine (PE), lysophosphatidylinositol, phosphatidylserine, sphingomyelin, lysophosphatidylcholine (LPC), phosphatidylinositol (PI), sphingosylphosphorylcholine and phosphatidylcholine. In addition, two unidentified phospholipids were detected with resonances at 0.13 and -0.78 ppm, respectively. Three distinct types of spectra were obtained on the extracts and grouped accordingly for comparison purposes. Type 1 tumors showed unusual 31P NMR profiles with low levels of PE and PI and elevated levels of LPC; type 2 tumors were characterized by low levels of the ethanolamine phospholipids and near equivalent levels of PI and LPC. The spectra of type 1 and type 2 tumors were characteristic of degenerative cells that lacked membrane permeability associated with loss of ethanolamine plasmalogen in the presence of significant phospholipid turnover. Meningiomas belonging to the third spectral type showed characteristics similar to those of normal tissues with normal levels of PE and ethanolamine plasmalogen, as well as very low levels of LPC relative to PI. Type 3 tumors lacked the characteristic signs of degeneration noted in type 1 and type 2 tumors. The data corroborate and augment in vivo spectroscopic findings reported earlier and demonstrate the value of 31P NMR spectroscopic phospholipid analysis on lipid extracts for the characterization of meningiomas.

Humans↗

Sarcoidosis following chemotherapy for Hodgkin's disease.

A case report describing persistent paratracheal lymphadenopathy after doxorubicin, bleomycin, vinblastin, and dacarbazine (ABVD) chemotherapy for a patient with Hodgkin's disease (HD) is presented. Mediastinoscopy and biopsy of the paratracheal lymph nodes showed non-caseating granulomas characteristic of sarcoidosis. The authors discuss the relationship between sarcoidosis and HD and hypothesize that the development or progression of sarcoidosis in a patient with HD is a potential consequence of chemotherapy. Two possible mechanisms are proposed. The first includes the immunosuppressive effect of chemotherapy and the second implicates the influence of a specific chemotherapy agent, bleomycin, which is known to have relatively higher lymph node, skin and lung tissue concentrations than other agents included in the ABVD regimen, and a predilection for those tissues that are prone for the development of sarcoidosis. With the incidence of sarcoidosis exceeding that of HD for the general population, the authors emphasize the importance of considering the presence of sarcoidosis in the differential diagnosis of patients who do not respond radiographically to HD chemotherapy.

Adult↗

MR spectroscopy of the breast.

Breast cancer results from perturbations in normal cellular biochemistry that lead to alterations in the flux of intermediary metabolites and in the function of cell membranes. Alterations in cellular biochemistry can be measured and monitored noninvasively by MR spectroscopy, and the data so derived are complementary to MR imaging and portray interactions of biomolecules in metabolic pathways and membranes. The biochemical information obtained from MR spectra can be used to characterize and distinguish disease and nondisease states for diagnostic and therapeutic purposes. This information may be used to expand our knowledge of tumor biology and to determine the extent of disease and prognosis. MR spectroscopy, which was once the sole province of the physical chemist, is now an instrument of the physician.

Biochemical Phenomena↗

Advantages of magnetic resonance imaging in breast surgery treatment planning.

Preoperative magnetic resonance imaging (MRI) was performed in 40 patients with malignant and benign breast tumors. Images were qualitatively evaluated to determine features of MRI that would benefit breast surgery treatment planning. MRI was found to be exceptional in demonstrating the relationship of tumors with respect to structures such as the chest wall, nipple, and skin. Tumor size was estimated by MRI, mammography, and gross pathological measurement in the 32 patients confirmed to have a malignant tumor of the breast. MRI estimated the tumor size to be larger than mammography in 71% of the cases and larger than pathological measurement in 84% of the cases. Compared with the standard method for determining tumor size (pathological measurement), MRI would have upstaged 22% of the evaluated cases from T1 to T2 and 10% of the cases from T2 to T3. MRI may prove useful in selecting patients for breast conserving therapy.

Adult↗

Magnetic resonance image appearance of hamartoma of the breast.

The magnetic resonance imaging (MRI) features of a breast hamartoma are presented. The hamartoma was evaluated using several imaging techniques with and without gadolinium-DTPA. This case demonstrates that, in selected cases, MRI is of value as an adjunct to mammography and sonography.

Adult↗

A birdcage resonator for intracavitary MR imaging.

An intracavitary probe for magnetic resonance imaging of the pelvis has been developed that takes advantage of the "inside-out" spatial characteristics of a birdcage resonator. The probe consists of an eight-leg, birdcage resonator in a low-pass configuration operating in receive-only mode. The resonator circuit is mounted on a solid rod, is encased in Teflon, and has been used to obtain detailed images of pelvic anatomy in a male canine. The approximate cylindrical symmetry of the external sensitivity profile of this type of circuit, employed in an intracavitary application, demonstrates the potential superiority of this type of probe design over single-loop intracavitary coils. Axial, coronal, and sagittal MR images, obtained with 8 and 16 cm fields of view, are presented to illustrate the advantages of this type of intracavitary probe compared with conventional body-coil images. The prototype described in this report has been designed for clinical use in human subjects and is currently undergoing testing to determine its efficacy in the evaluation of rectal, prostate, and gynecologic pathology.

Animals↗

Application of a mixed imaging sequence for MR imaging characterization of human breast disease.

Single slice MR images were obtained from 9 normal breasts, 17 breasts with benign tumors, and 11 breasts with malignant tumors using an interleaved (mixed) spin echo (SE) inversion-recovery (IR) imaging sequence. SE and IR MR images were synthesized with variable repetition, echo and inversion times from the mixed sequence data. These images were used to qualitatively evaluate the contrast possibilities available when imaging the breast with MR imaging. Proton T1 and T2 relaxation times were determined for normal breast tissues and malignant and benign breast tumors from pure T1 and T2 images calculated using the mixed sequence data. The mean T1 value in benign tumors of 1,049.02 +/- 40.31 was found to be significantly longer (p < 0.0001) than the mean value of malignant tumors (876.09 +/- 27.83) and normal tissues (795.64 +/- 21.12). The value of T2 in benign tumors (89.15 +/- 8.33) was significantly longer (p < 0.01) than the value of T2 in normal tissues (62.82 +/- 4.06). The mixed sequence can be applied to improve image contrast between malignant tumors, benign tumors, and normal tissues of the breast and can potentially differentiate between these tissues in vivo.

Breast Diseases↗