1/8. Evidence for shutter-speed variation in CR bolus-tracking studies of human pathology.The standard pharmacokinetic model for the analysis of MRI contrast reagent (CR) bolus-tracking (B-T) data assumes that the mean intracellular water molecule lifetime (tau(i)) is effectively zero. This assertion is inconsistent with a considerable body of physiological measurements. Furthermore, theory and simulation show the B-T time-course shape to be very sensitive to the tau(i) magnitude in the physiological range (hundreds of milliseconds to several seconds). Consequently, this standard model aspect can cause significant underestimations (factors of 2 or 3) of the two parameters usually determined: K(trans), the vascular wall CR transfer rate constant, and v(e), the CR distribution volume (the extracellular, extravascular space fraction). Analyses of animal model data confirmed two predicted behaviors indicative of this standard model inadequacy: (1) a specific temporal pattern for the mismatch between the best-fitted curve and data; and (2) an inverse dependence of the curve's K(trans) and v(e) magnitudes on the CR dose. These parameters should be CR dose-independent. The most parsimonious analysis allowing for realistic tau(i) values is the 'shutter-speed' model. Its application to the experimental animal data essentially eliminated the two standard model signature inadequacies. This paper reports the first survey for the extent of this 'shutter-speed effect' in human data. Retrospective analyses are made of clinical data chosen from a range of pathology (the active multiple sclerosis lesion, the invasive ductal carcinoma breast tumor, and osteosarcoma in the leg) that provides a wide variation, particularly of K(trans). The signature temporal mismatch of the standard model is observed in all cases, and is essentially eliminated by use of the shutter-speed model. Pixel-by-pixel maps show that parameter values from the shutter-speed analysis are increased by more than a factor of 3 for some lesion regions. This endows the lesions with very high contrast, and reveals heterogeneities that are often not seen in the standard model maps. Normal muscle regions in the leg allow validation of the shutter-speed model K(trans), v(e), and tau(i) magnitudes, by comparison with results of previous careful rat leg studies not possible for human subjects.- - - - - - - - - - ranking = 1keywords = volume (Clic here for more details about this article) |
2/8. Acute cardiac toxicity associated with high-dose intravenous methotrexate therapy: case report and review of the literature.A 36-year-old woman was hospitalized for preoperative chemotherapy for osteosarcoma. She received intravenous fluids for 12 hours for volume expansion, then methotrexate 24 g (12 g/m2) over 6 hours. This was followed by intravenous leucovorin 200 mg over 1 hour. Two hours after the methotrexate infusion the patient developed chest pain and bradycardia. An electrocardiogram revealed sinus pauses, and telemetry recordings indicated a 4-beat run of ventricular tachycardia. A cardiac work-up consisting of cardiac enzyme level determination, two-dimensional echocardiography, and an adenosine technetium-99m tetrofosmin stress test was negative for structural and ischemic heart disease. The patient recovered without treatment and, approximately 2 weeks later, received a second course of methotrexate at half the dose without complication. One month later the patient received treatment with doxorubicin and cisplatin; 2 days later she died unexpectedly at home. Clinicians should be aware that high-dose methotrexate can cause cardiac symptoms and arrhythmias in previously healthy adults. This complication warrants attention and needs additional clinical investigation.- - - - - - - - - - ranking = 1keywords = volume (Clic here for more details about this article) |
3/8. Disposition of high-dose methotrexate in an obese cancer patient.The disposition of many drugs in obesity is altered, although little is known of the effect of obesity on the pharmacokinetics of anti-cancer drugs. In this report the authors describe the pharmacokinetics of high-dose methotrexate in an obese woman (184% ideal body weight) with osteosarcoma. For this patient, both the volume of distribution at steady-state (0.398 l/kg) and systemic clearance (0.0956 l/h/kg) of methotrexate were increased compared with values observed in adult patients with osteosarcoma. The terminal elimination half-life (9.29 hours) of methotrexate was similar to other reported values in adult patients, thus indicating that increases in methotrexate volume of distribution and clearance may offset each other in obesity. Based on the experience gained from this patient, the authors suggest that renal function and methotrexate serum concentrations should be monitored in obese patients receiving high-dose methotrexate with leucovorin rescue.- - - - - - - - - - ranking = 2keywords = volume (Clic here for more details about this article) |
4/8. cell proliferation rate and tumor volume in human osteosarcoma during exposure to methotrexate. A study on tissue transplants in nude mice.The growth inhibitory effect of methotrexate (MTX) on osteosarcoma cells was studied in dysthymic nude mice bearing tumor transplants obtained from a patient before (PRE-CHEM) and after (POST-CHEM) preoperative chemotherapy for osteosarcoma of the distal femur. cell proliferation was analyzed by autoradiographic evaluation of the fraction of labeled cells after continuous administration of 3H-thymidine for seven days. Histomorphometric analysis of the tissue distribution of cells in the partly ossified tumors was performed. The PRE-CHEM sarcoma transplants showed a significant reduction of labeled interphases from 52 to 1.7 percent upon daily MTX treatment of the mice as compared to controls. In contrast, MTX treatment did not inhibit cell proliferation in the POST-CHEM tumor transplants in which approximately 70 percent of the cells were labeled. Tumor volume increased by 65 and 54 percent in the MTX-treated PRE- and POST-CHEM groups, respectively. During the same eight-day period, control transplant volume increased by 30 percent (PRE-CHEM) and 20 percent (POST-CHEM). Tumor cell densities in the MTX-treated groups were reduced by a factor of approximately 11 in the PRE-CHEM transplants and by a factor of approximately 1.5 in the POST-CHEM transplants. The results show that in this patient the osteosarcoma cells had changed their responsiveness to MTX during the preoperative chemotherapy period. In both the MTX-sensitive and non-sensitive tumor lines, exposure to MTX induced increased tumor volume by increasing the extra cellular matrix volume, irrespective of the neoplastic cell proliferation rate. This effect of MTX was most pronounced in the MTX-sensitive tumor line. These results indicate that in the clinical situation it is difficult to judge the response to chemotherapy even from morphologic parameters.- - - - - - - - - - ranking = 8keywords = volume (Clic here for more details about this article) |
5/8. Multiple childhood osteosarcomas in an American Indian family with erythroid macrocytosis and skeletal anomalies.Three of nine children of possibly consanguineous American Indian parents developed typical osteosarcoma in a 2-year period. Etiologic investigations detected limb anomalies and elevated mean corpuscular volumes (98--109 micrometer3) in the surviving tumor patient, several of her sibs, and her father. Limb anomalies included simple clinodactyly with brachymesophalangy, absence of one digital ray of the foot, and bilateral radioulnar synostosis. The red cell macrocytosis was not accompanied by anemia or explained by the usual causes. No unusual environmental exposures were found and screening for possible oncogenic viruses by culture, electron microscopy, and serology was negative. All family members had elevated antibody titers to Epstein-Barr viral antigens. The proband and her father had excessive chromosomal breaks in the bone marrow. This unusual familial pattern of osseous malignancy and malformation and defective erythropoiesis, tentatively called OSLAM syndrome, may represent impaired regulation of bone development.- - - - - - - - - - ranking = 1keywords = volume (Clic here for more details about this article) |
6/8. Problems in resection of chest wall sarcomas.To illustrate the problems of reconstruction in major chest wall resection, five patients with a variety of soft tissue tumors of the chest wall, located at different sites, are presented. patients, who underwent a lateral or posterolateral chest wall resection required removal of two to five ribs sequentially as well as the adjacent soft tissue. Those who underwent an anterior chest wall resection required resection of the manubrium or the body of sternum as well as of adjacent costal cartilages. To prevent instability of the chest, herniation, and to minimize flailing, the chest defect was bridged with the use of Marlex mesh. Whenever possible, the omentum was brought into the chest cavity to increase the vascularity of the reconstruction. Since, in most instances, the tumors involved the skin because of previous damage from radiation therapy, extensive skin coverage was planned well in advance of resection. Pedicle skin flaps or rotation flaps were used to cover the skin defect. Ventilatory support by volume respirator, was required for three to four days. In all patients, the chest wall was completeley stable after three to six weeks.- - - - - - - - - - ranking = 1keywords = volume (Clic here for more details about this article) |
7/8. Structure, growth and cell proliferation of human osteosarcoma and malignant fibrous histiocytoma xenografts in serial transplantation in nude mice.Tumour specimens from one patient with osteosarcoma and one with malignant fibrous histiocytoma were transplanted in serial passages in nude mice. Structure, growth and cell kinetics of the xenografts were studied in order to assess the validity of the two tumour models. cell proliferation was analysed using in vivo labelling with the thymidine analogue iododeoxyuridine (IdUrd) and the IdUrd labelling index (LI) was determined by immunohistochemistry. The dna index (DI) was examined by flow cytometry. The c-myc oncoprotein expression was studied by immunohistochemistry. More intense proliferation was observed in the peripheral parts of the tumours. There was no correlation between tumour growth and cell proliferation in the two tumour groups. Stability of the tumour models was indicated by low intrapassage and interpassage variations of DI, LI, and volume doubling time, and also by retained histopathological characteristics and c-myc staining patterns of donor patients' tumours during serial transplantation.- - - - - - - - - - ranking = 1keywords = volume (Clic here for more details about this article) |
8/8. A new design of the iliac crest microsurgical free flap without including the "obligatory" muscle cuff.The iliac crest free flap has undergone a gradual evolution to provide more functional and cosmetic oromandibular reconstructions. The soft-tissue cutaneous component has largely resisted refinement and currently constitutes the flap's principal drawback. Conventionally, the cutaneous vessel's soft-tissue encasement and a protective cuff of abdominal muscle are harvested to ensure skin perfusion. These protective measures, however, produce a bulky flap that is tethered to the bone and difficult to inset into complex three-dimensional defects. A series of anatomic and clinical investigations has confirmed that in 30 percent of individuals, the skin island can be elevated on a dominant cutaneous branch from the deep circumflex iliac artery. Harvesting the skin as an axial pattern flap greatly increases its independence from the bone, improving maneuverability. A small collar of abdominal muscle is incised around the pedicle, obviating the need for the customary 2.5-cm protective muscle cuff. Exclusion of the abdominal muscular component reduces the flap's volume, decreases the need for secondary debulking, and reduces the donor site morbidity.- - - - - - - - - - ranking = 1keywords = volume (Clic here for more details about this article) |