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Biomedical subjects

M L Graham

Publications and source records attributed to M L Graham.

At least 37 records · Page 2Linked to original sources
PubMed1996

Resolution of Budd-Chiari syndrome following bone marrow transplantation for paroxysmal nocturnal haemoglobinuria.

Thrombosis of the hepatic veins (Budd-Chiari syndrome) is a life-threatening thrombotic complication which can occur in patients with paroxysmal nocturnal haemoglobinuria (PNH). Despite aggressive medical and surgical therapy, mortality from Budd-Chiari syndrome remains high. We report a boy with PNH who developed Budd-Chiari syndrome and underwent syngeneic bone marrow transplantation (BMT). Now, 3 years following BMT, he has had dramatic clinical and radiographic evidence of resolution of the thrombosis. We suggest that BMT for PNH can successfully correct life-threatening thrombosis in patients with PNH.

Bone Marrow Transplantation↗
PubMed1996

Ex vivo protocol for testing virus survival on human skin: experiments with herpesvirus 2.

We report an ex vivo method, which uses pieces of human skin excised during routine plastic surgery, for testing survival of hazardous pathogens. Using this procedure, we compared the survival of human herpesvirus 2 on human skin and on metal disks. At the physiological skin temperature of 32 degrees C, the half-life of the virus on skin was 1.44 h while on metal disks it was 0.36 h. Even at ambient temperature (22 degrees C), the virus lost infectivity faster (half-life = 0.96 h) on metal disks than on the skin at 32 degrees C. The method described could be used to assess the survival of other human pathogens on skin and to evaluate the germicidal activity of handwashing agents and other topicals.

Adult↗
PubMed1996

Medigap reform legislation of 1990: have the objectives been met?

The 1990 medigap reform legislation had multiple objectives: To simplify the insurance market in order to facilitate policy comparison, provide consumer choice, provide market stability, promote competition, and avoid adverse selection. Based on case study interviews with a cross-section of individuals and organizations, we report that most of these objectives have been achieved. Consumers of medigap plans are able to make more informed choices, largely because they can adequately compare policies based on standard benefits. Marketing abuses have apparently declined, as evidenced by a decrease in the number of consumer complaints. Finally, no major detrimental impact on the insurance industry was detected. Beneficiaries still face some confusion in this market, however, such as understanding the rating methodologies used to set premiums and how this may affect their choices. Confusion could increase with the growth of managed care options.

Aged↗
PubMed1996

Reversible leukoencephalopathy associated with graft-versus-host disease: MR findings.

Ten weeks after undergoing bone marrow transplantation for metastatic lymphoma of the parotid gland, a 9-year-old girl became disoriented and had tremor and myoclonus in the context of graft-versus-host disease (GVHD). MR images showed abnormal signal primarily within the brain stem and deep white matter, which resolved almost completely after treatment. The findings are consistent with brain involvement by GVHD.

Adrenal Cortex Hormones↗
PubMed1996

Changes in red blood cell methotrexate pharmacology and their impact on outcome when cytarabine is infused with methotrexate in the treatment of acute lymphocytic leukemia in children: a pediatric oncology group study.

Since it is unclear whether methotrexate and cytarabine are synergistic or antagonistic in the treatment of acute lymphoblastic leukemia, the Pediatric Oncology Group studied the prognostic significance of a potential interaction between these agents. RBC methotrexate concentrations were compared from 140 patients at lower risk of relapse randomized to two treatment groups: one receiving six methotrexate infusions with overlapping cytarabine; the other, six methotrexate infusions alone. Samples from 248 patients from all risk groups were studied to determine whether patients with extremely low RBC methotrexate concentrations had inferior outcomes. Among low-risk patients studied 3 weeks after the sixth infusion, median RBC methotrexate concentrations were 0.13 nmol/ml RBCs (n = 71) for the methotrexate-only group and 0.02 nmol/ml RBCs (n = 69) for the methotrexate/cytarabine-treated low-risk patients, P < 0.001 by the two-sided Wilcoxon test. For low- and high-risk patients receiving methotrexate/cytarabine infusions, event-free survival at 1 and 3 years after RBC sampling was 97 +/- 2% and 90 +/- 3% for patients with concentrations greater than the median, and 88 +/- 3% and 78 +/- 4% for those with concentrations at or below the median. Log rank comparisons of event-free survival in the first year and overall yielded P = 0.005 and P = 0.04, respectively. Cytarabine altered methotrexate pharmacology when the drugs were infused together. Patients whose levels were extremely low had an adverse prognosis. Although this study could not assess efficacy of the methotrexate/cytarabine combination, it appears that concurrent administration is not optimal.

Adolescent↗
PubMed1995

Dose escalation trial of cyclophosphamide with Sargramostim in the treatment of central nervous system (CNS) neoplasms.

We conducted a dose escalation trial of cyclophosphamide plus Sargramostim in the therapy of patients with newly diagnosed or recurrent central nervous system tumors. Cyclophosphamide was administered at doses ranging between 1.0 and 2.5 g/m2 daily for two doses. Sargramostim was administered at a fixed dose of 250 micrograms/m2 subcutaneously twice a day beginning 24 hours after the second cyclophosphamide dose and continuing through the leukocyte nadir until the absolute neutrophil count (ANC) was > 1,000 cells/microliters for two consecutive days. The MTD for patients who had not received any prior chemotherapy and who had received either no radiotherapy or radiotherapy confined to the cranium was 2.0 g/m2 daily for two doses. The MTD for patients previously treated with chemotherapy or neuraxis radiotherapy was also 2.0 g/m2 daily for two doses. Responses were seen in patients with medulloblastoma (8/9), glioblastoma multiforme (2/13), germinoma (1/1), and pineoblastoma (1/2).

Adolescent↗
PubMed1995

epsilon-Aminocaproic acid-associated myopathy in a child.

PURPOSE: A 12-year-old girl developed severe autoimmune thrombocytopenia after a bone marrow transplant for acute lymphoblastic leukemia. RESULTS: Although epsilon-aminocaproic acid helped to control her bleeding, it eventually caused a rare myopathy previously undescribed in a pediatric patient. CONCLUSION: The myopathy resolved when the drug was discontinued and a different antifibrinolytic agent was used.

Aminocaproic Acid↗
PubMed1994

Design of a fully integrated three-dimensional computed tomography simulator and preliminary clinical evaluation.

PURPOSE: We describe the conceptual structure and process of a fully integrated three-dimensional (3-D) computed tomography (CT) simulator and present a preliminary clinical and financial evaluation of our current system. METHODS AND MATERIALS: This is a preliminary report on 117 patients treated with external beam radiation therapy alone on whom a 3-D simulation and treatment plan and delivery were carried out from July 1, 1992, through June 30, 1993. The elements of a fully integrated 3-D CT simulator were identified: (a) volumetric definition of tumor volume and patient anatomy obtained with a CT scanner, (b) virtual simulation for beam setup and digitally reconstructed radiographs, (c) 3-D treatment planning for volumetric dose computation and plan evaluation, (d) patient-marking device to outline portal on patient's skin, and (e) verification (physical) simulation to verify portal placement on the patient. Actual time-motion (time and effort) recording was made by each professional involved in the various steps of the 3-D simulation and treatment planning on computer-compatible forms. Data were correlated with the anatomic site of the primary tumor being planned. Cost accounting of revenues and operation of the CT simulator and the 3-D planning was carried out, and projected costs per examination, depending on case load, were generated. RESULTS: Average time for CT volumetric simulation was 74 min without or 84 min with contrast material. Average times were 36 min for contouring of tumor/target volume and 44 min for normal anatomy, 78 min for treatment planning, 53 min for plan evaluation/optimization, and 58 min for verification simulation. There were significant variations in time and effort according to the specific anatomic location of the tumor. Portal marking of patient on the CT simulator was not consistently satisfactory, and this procedure was usually carried out on the physical simulator. Based on actual budgetary information, the cost of a volumetric CT simulation (separate from the 3-D treatment planning) showed that 1500 examinations per year (six per day in 250 working days) must be performed to make the operation of the device cost effective. The same financial projections for the entire 3-D planning process and verification yielded five plans per day. Some features were identified that will improve the use of the 3-D simulator, and solutions are offered to incorporate them in existing devices. CONCLUSIONS: Commercially available CT simulators lack some elements that we believe are critical in a fully integrated 3-D CT simulator. Sophisticated 3-D simulation and treatment planning can be carried out in a significant number of patients at a reasonable cost. Time and effort and therefore cost vary according to the anatomic site of the tumor being planned and the number of procedures performed. Further efforts are necessary, with collaboration of radiation oncologists, physicists, and manufacturers, to develop more versatile and efficient 3-D CT simulators, and additional clinical experience is required to make this technology cost effective in standard radiation therapy of patients with cancer.

Adult↗
PubMed1994

Management of locally advanced carcinoma of the breast. I. Noninflammatory.

BACKGROUND: The treatment of patients with locally advanced noninflammatory breast cancer has evolved substantially over the past 30 years. From 1968 to 1989, 281 women were treated at Mallinckrodt Radiation Oncology Center with four different treatment methods. Median follow-up was 6.2 years (range 3-22 years); no patient was lost to follow-up. METHODS: Retrospective review of records and analysis of data on a computer file were carried out. Thirty-five patients were treated with irradiation alone, 33 with irradiation and adjuvant chemotherapy, 81 with mastectomy and irradiation, and 132 with mastectomy, irradiation, and chemotherapy (triple-modality). RESULTS: Actuarial 5- and 10-year disease free survival (DFS) rates were 45% and 36%, respectively, with triple-modality therapy, 31% and 10% with irradiation and chemotherapy, 32% and 19% with irradiation and mastectomy, and 19% and 11% with irradiation alone. Cause specific survival (CSS) paralleled DFS in the four groups. Locoregional tumor control at 5 years was 91% for irradiation, mastectomy, and chemotherapy, 80% for irradiation and mastectomy, 54% for irradiation and chemotherapy, and 31% for irradiation alone. Systemic therapy and/or irradiation given before mastectomy yielded better locoregional tumor control, DFS, and CSS (not statistically significant). No difference in results was noted with radical, modified radical, or total mastectomy. In the triple-modality group, no chest wall failures occurred with chest wall doses greater than 5040 cGy. Grade 2 or higher treatment sequelae were noted in 10-42% of patients, depending on treatment modality. CONCLUSIONS: Triple-modality therapy yielded improved locoregional tumor control, DFS, and CSS compared with other modalities. Patients treated with surgery had better locoregional tumor control than those who received irradiation alone or in combination with chemotherapy, but the impact on DFS and CSS was less impressive. Additional clinical trials are needed to define further the role and optimal use of the various therapeutic modalities in the management of locally advanced breast cancer.

Adult↗
PubMed1993

On-line image verification in radiation therapy: an early USA experience.

The intense effort in the past 5 to 10 years to develop on-line image verification (OLIV) systems is made partly in anticipation of the increased verification demands of complex 3-dimensional (3D) conformal radiation therapy, and partly to improve on the current practice of weekly treatment verification. These systems allow convenient acquisition of daily portal images or many images during one treatment session. Systems based on fluoroscopic and scanning approaches can now be purchased from various vendors and are being evaluated at several radiation therapy centers. The performances of these systems vary, but all appear to be adequate for clinical use. At the Mallinckrodt Institute of Radiology, we have been conducting clinical on-line imaging for the past 3 years using a fiber-optic fluoroscopic system. Daily operation of the system requires coordinated participation of the physics and radiation therapy technology staff. The major consideration is in the management and evaluation of the large amount of verification images about each individual patient. At present, it is not clear whether the technology would be cost-effective in the clinical setting. However, it is clear that OLIV provides a powerful tool in enhancing our knowledge of treatment variation. The information will be invaluable in the development of improved treatment techniques. It is also likely that these systems will play a important part in the verification of 3D conformal radiation therapy.

Calibration↗
PubMed1993

A human chimera for von Willebrand disease following bone marrow transplantation.

PURPOSE: von Willebrand disease (vWD) is a common bleeding disorder characterized by quantitative or qualitative defects in von Willebrand factor (vWF), a protein important for coagulation and platelet adhesion. There are two forms of vWF currently recognized: plasma vWF synthesized by endothelial cells and platelet vWF produced within megakaryocytes. Although both plasma and platelet vWF play important roles in overall hemostasis, the relative contribution of each form is not clear. PATIENTS AND METHODS: We report the results of bone marrow transplantation from a donor with Type I vWD into a hemostatically normal recipient. RESULTS: Following engraftment, the recipient appears to be a human chimera for vWD, with normal amounts of plasma vWF from endogenous endothelial cells, but low levels of platelet vWF derived from donor megakaryocytes. CONCLUSIONS: Although the vWD chimerism has not been associated with any clinical manifestations, the bleeding time has become prolonged, suggesting that platelet vWF is important for normalization of the bleeding time.

Adolescent↗
PubMed1993

Is breast preservation possible in women with large, locally advanced breast cancers?

Breast conservation therapy is an accepted treatment option for early stage breast carcinoma, but is rarely considered appropriate for locally advanced nonmetastatic lesions. Mastectomy specimens of 46/50 patients treated at the Ochsner Clinic and the Mallinckrodt Institute of Radiology with neoadjuvant chemotherapy prior to mastectomy +/- irradiation were evaluated by a single pathologist to assess tumor response to chemotherapy. Forty percent of this group would potentially have been eligible for breast conservation therapy, using a residual tumor size of < or = 4 cm with negative surgical margins as the criteria. Patients most likely to qualify for breast conservation therapy were those with T3N0-1 lesions (67%). Least likely were patients with skin involvement at diagnosis 4/33 (12%). Tumors with an extensive intraductal component at biopsy often had residual islands of intraductal carcinoma occupying the original tumor volume, even when the invasive component was absent or much reduced. A prospective trial will be required to determine whether or not acceptable local control rates can be obtained after breast conservation therapy for that subset of patients with a favorable response to induction chemotherapy.

Adult↗
PubMed1992

Optimization of busulfan dosage in children undergoing bone marrow transplantation: a pharmacokinetic study of dose escalation.

Busulfan (BU) is a widely used myeloablative and antineoplastic agent in clinical bone marrow transplantation (BMT). The lower incidence of BU-associated toxicities and lower therapeutic effectiveness in young children given BU doses based on body weight (ie, 16 mg/kg) is associated with altered pharmacokinetics of BU; the area under the curve (AUC) of BU concentration versus time is significantly less in these patients than those observed in older children and adults. To optimize BU dosage in young BMT recipients, we developed a dosage regimen based on body surface area (BSA) and determined BU pharmacokinetics and BU-associated toxicities. Seven children (median age, 3.9 years, range, 1.1 to 5.7) undergoing allogeneic or autologous BMT for leukemia received 40 mg/m2/dose BU every 6 hours for 16 doses; BU concentrations were measured in the plasma, and AUCs were determined for each patient after the first and 13th doses. Expressed as a function of body weight, the median BU dosage was 26.4 mg/kg (range, 24.3 to 28.2), a 60% increase over the BU dosage based on body weight. Four patients developed mucositis, and one of them also developed nonfatal hepatic veno-occlusive disease (VOD). No patients receiving 40 mg/m2 BU developed neurotoxicity (eg, seizures) or interstitial pneumonitis. Prompt and sustained engraftment was observed in the allogeneic BMT recipients, and late graft failure was not seen. The mean BU AUCs were 1,105 mumol/L.min (range, 790 to 2,080) after the first dose and 1,022 mumol/L.min (range, 632 to 1,860) after the 13th dose of BU, comparable to the AUCs in adults given 16 mg/kg of BU. These studies suggest that, in young children, BSA-based dosing of BU (40 mg/m2) provides drug exposures (AUCs) closer to adult values with acceptable toxicities and may improve therapeutic effects.

Bone Marrow Transplantation↗
PubMed1992

Heterogeneity of progesterone receptor content and remodeling by tamoxifen characterize subpopulations of cultured human breast cancer cells: analysis by quantitative dual parameter flow cytometry.

Breast cancers treated with the antiestrogen tamoxifen invariably become resistant. To analyze the behavior of cell subpopulations within a tumor following tamoxifen treatment, we have used a new flow cytometry-based immunoassay and software that simultaneously quantitate PR levels and the DNA indices of ploidy and cell cycle stage in total cell populations or any subset thereof. The human breast cancer cell line T47D and its clonal derivatives were used as models of stage IV breast cancer, and growth and PR were measured as markers of antiestrogen responsiveness. We demonstrate and quantitate a remarkable heterogeneity in PR content and show the existence of distinct subpopulations with large differences in their PR levels and DNA indices, even among T47D sublines that are clonally derived. Following chronic tamoxifen treatment, an overall decrease in PR levels and growth masks an extensive heterogeneity in the response of cell subpopulations. PR levels decrease in some cells but increase in others; populations having a growth advantage expand while others contract. We find little evidence that cells, unaffected by the hormone, gain a growth advantage. Rather than exhibiting autonomy, we propose that under the influence of tamoxifen, tumors become remodeled as selected subpopulations emerge that are stimulated by the hormone, explaining the paradoxical recurrence of disease in patients undergoing endocrine therapy.

Breast Neoplasms↗
PubMed1992

Red blood cell methotrexate and folate levels in children with acute lymphoblastic leukemia undergoing therapy: a Pediatric Oncology Group pilot study.

We enrolled children with acute lymphoblastic leukemia (ALL) in a Pediatric Oncology Group (POG) pilot study to monitor erythrocyte (RBC) methotrexate (MTX) and folate (F) levels before and during treatment. The mean value for RBCF at diagnosis was 0.86 +/- 0.46 nmol/ml RBC in the 214 patients who achieved remission and 1.21 +/- 0.74 nmol/ml RBC in the 10 patients who did not (P = 0.020). Folate levels tended to increase during remission induction, but they dropped following an intensive consolidation with methotrexate to levels that were sustained throughout chemotherapy treatment. Methotrexate levels reached mean values of approximately 0.15 nmol/ml RBC at the end of an intensive methotrexate consolidation, then fell to levels that were sustained throughout maintenance therapy. There was a weak correlation between improved event-free survival and higher RBCMTX levels after consolidation, but no correlation was found between improved survival and the level of RBCMTX or RBCF during maintenance therapy. A larger study with more complete data is needed to determine whether RBCMTX or RBCF might be useful in predicting event-free survival in patients with ALL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Vitamin E in the treatment of chemotherapy-induced mucositis.

PURPOSE: To determine the efficacy of vitamin E in the treatment of chemotherapy-induced mucositis in patients with malignancy. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled study was performed to evaluate the efficacy of topical vitamin E in the treatment of oral mucositis in patients receiving chemotherapy for various types of malignancy. A total of 18 patients, 17 of whom had solid tumors and one with acute leukemia, were included in this study. Lesions were observed daily prior to and 5 days after topical application of either vitamin E or placebo oil. RESULTS: Six of nine patients receiving vitamin E had complete resolution of their oral lesions. In eight of nine patients who received placebo, complete resolution of their oral lesions was not observed. This difference is statistically significant (p = 0.025 by Fisher's exact test). No toxicity was observed in this study. CONCLUSION: These results suggest that vitamin E may be an effective therapy in patients with chemotherapy-induced mucositis.

Administration, Topical↗
PubMed1992

Treatment of recurrent and refractory pediatric solid tumors with high-dose busulfan and cyclophosphamide followed by autologous bone marrow rescue.

PURPOSE: The purpose of this study was to determine the toxicities of and responses to high-dose busulfan and cyclophosphamide with autologous bone marrow transplant (ABMT) in patients with recurrent or refractory pediatric solid tumors. PATIENTS AND METHODS: We treated 18 patients (ages, 2 to 38 years; median, 14) who had tumors that were resistant to conventional chemotherapy and radiotherapy with busulfan 16 mg/kg and cyclophosphamide 200 mg/kg. Seventeen patients received bone marrow purged with 4-hydroperoxycyclophosphamide; one received unpurged marrow. RESULTS: Despite extensive prior treatment, including radiotherapy in 16 patients, toxicity generally was acceptable. For seven patients with measurable disease, there were three partial responses of 2, 10, and 20 months' duration, three patients with stable disease (SD), and one early, toxic death. Of the 11 patients with no measurable disease at the time of transplantation, one patient with osteosarcoma continues in remission at 57+ months and one third of the patients survived for at least 16 months. Mucositis was the predominant nonhematopoietic toxicity. CONCLUSION: Although the high-dose busulfan and cyclophosphamide combination showed modest activity, changes in the preparative regimen should be considered to improve the response rate in refractory tumors.

Adolescent↗