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Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 181 records · Page 10Linked to original sources

Autologous transplantation with peripheral blood stem cells in children and young adults after myeloablative treatment: nonrandomized comparison between GM-CSF and G-CSF for mobilization.

Recombinant human granulocyte-monocyte colony-stimulating factor (rhGM-CSF) was compared with recombinant granulocyte colony-stimulating factor (rhG-CSF) in 34 patients for mobilization of peripheral blood stem cells (PBSC) and for posttransplantation use. Peripheral blood stem cell mobilization was initiated by a single 1 h infusion of cyclophosphamide (4 g/m2) in all patients, followed by either a continuous infusion of rhGM-CSF (250 micrograms/m2/day) in 17 patients (group A) or a daily subcutaneous injection of rhG-CSF (10 micrograms/kg/day) in 17 patients (group B). PBSC were collected using a Fenwal CS 3000 continuous flow blood cell separator in one to three sessions. All patients suffered from various childhood malignancies. No difference in the number of collected cells among both groups was found. A mean of 2.7 x 10(8)/kg mononuclear cells (MNC) and of 7.9 x 10(4)/kg CFU-GM (colony-forming unit-granulocyte-macrophage) were collected in group A. In group B, 2.3 x 10(8)/kg MNC and 11.8 x 10(4)/kg CFU-GM were collected. In 33 patients, PBSC were reinfused after myeloablative therapy. Patients of group A (n = 17) were treated with rhGM-CSF (250 micrograms/m2/day) starting day +1, and patients in group B (n = 16) were treated with rhG-CSF (10 micrograms/kg/day) i.v. All patients showed a rapid and complete hematopoietic recovery without significant differences in both groups. Time to achieve 0.5 x 10(9)/L granulocytes was 10.9 days in group A and 11 days in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Musculoskeletal neoplasm: perineoplastic edema versus tumor on dynamic postcontrast MR images with spatial mapping of instantaneous enhancement rates.

PURPOSE: To evaluate the utility of fast, contrast-enhanced, sequential magnetic resonance (MR) imaging in differentiating between extraosseous tumor and perineoplastic edema. MATERIALS AND METHODS: Fourteen patients underwent sequential MR imaging (3.5 seconds per image) after bolus administration of gadopentetate dimeglumine. Initial rates of enhancement (initial slope) were calculated on a pixel-by-pixel basis and displayed as a "slope image"' in which pixel intensity reflected the slope value. Close correlation with wedge biopsy specimens was performed. RESULTS: Mean initial slope values were viable extraosseous tumor, 9.33 (standard deviation, 2.23); infiltrated muscle, 9.07 (2.31); edematous muscle without tumor infiltration, 5.48 (1.27); normal muscle, 1.11 (0.65). Differences in initial slope between all neoplastic and nonneoplastic tissues were statistically significant. Within individual patients, initial slope of edematous muscle was always 20% or more lower than that of neoplastic tissue. Slope images highlighted areas of viable extraosseous tumor and infiltrated muscle against edematous and normal tissues. CONCLUSION: Computer-generated slope images derived from sequential postcontrast MR images allow differentiation between tumor and nonneoplastic edema and may thereby guide the surgeon in planning limb-sparing procedures.

Adolescent↗

Primary bone tumors: value of MR angiography for preoperative planning and monitoring response to chemotherapy.

OBJECTIVE: The purposes of our study were to investigate the use of MR angiography with two- (2D) and three-dimensional (3D) displays in evaluating vascular morphology of musculoskeletal neoplasms for preoperative planning of limb-salvage surgery and to assess the use of MR angiography for monitoring changes in neovascularity and evaluating response to chemotherapy. SUBJECTS AND METHODS: We used MR angiography (2D time-of-flight) to study 13 patients with primary bone tumors (nine osteogenic sarcomas, two Ewing's sarcomas, and two primary lymphomas of bone) at the time of initial presentation. Eight patients (all of whom had osteogenic sarcoma) also underwent MR angiography following chemotherapy before limb-salvage surgery. Two-dimensional maximum intensity projections were obtained. Three-dimensional reconstructions of vascular structures were created from the angiographic source images and were displayed simultaneously with 3D reconstructions of tumor and normal bone generated from conventional MR images. RESULTS: Two-dimensional maximum intensity projections were useful for evaluating small vessel neovascularity; 3D displays demonstrated spatial relationships of tumor, feeder vessels, and normal vascular structures. Tumor encroachment onto or encasement of normal vascular structures was shown in four patients on 2D maximum intensity projections and on 3D displays. The eight patients with osteogenic sarcoma who had follow-up imaging showed marked neovascularity prior to chemotherapy. Five patients responded to chemotherapy (> or = 90% tumor necrosis at histology); MR angiography showed marked reduction in tumor neovascularity in these patients. Three patients did not respond to chemotherapy; MR angiography showed unchanged neovascularity in one and increased neovascularity in two of these patients. CONCLUSION: MR angiography provides good visualization of peripheral vascular branches and tumor neovascularity in patients with primary bone tumors. MR angiography demonstrates encroachment onto and encasement of major vessels by the tumor mass and appears to be useful for assessing response to chemotherapy in osteogenic sarcoma and possibly other primary bone tumors by detecting treatment-induced changes in tumor neovascularity.

Adolescent↗

Quantification of the volume of articular cartilage in the metacarpophalangeal joints of the hand: accuracy and precision of three-dimensional MR imaging.

OBJECTIVE: Cartilage loss is central to the development of joint failure in arthritis. However, radiographic assessment of cartilage loss is highly unreliable. This study examined the accuracy and reproducibility of a noninvasive technique for quantifying the volume of articular cartilage in the metacarpophalangeal joints of the hand by use of three-dimensional (3D) MR imaging. SUBJECTS AND METHODS: Eight metacarpophalangeal joints (four normal, one rheumatoid arthritic, and three normal cadaveric) each were imaged three times with a 1.5-T clinical MR imaging scanner with a small partial volume coil and a fat-saturated 3D spoiled gradient-echo sequence optimized for delineating articular cartilage. The volumes of cartilage over the metacarpal and phalangeal surfaces were quantified by summing the voxels within segmented 3D reconstructions of the images. Cartilage volumes in the three cadaver joints also were estimated by scraping cartilage off the articular surfaces and measuring water displacement in graduated cylinders. These values were used as the gold standard for assessing the accuracy of cartilage volume quantification by MR imaging. RESULTS: The fat-saturated sequence discriminated the articular cartilage from adjacent joint structures with high contrast and high spatial resolution. Cartilage volumes determined by MR imaging for the different subjects ranged from 115 microliters to 222 microliters for metacarpal cartilage and from 34 microliters to 86 microliters for proximal phalangeal cartilage. Accuracy errors for quantifying cartilage volume by MR imaging were -1.8% (95% confidence interval, -3.5% to -0.7%) for metacarpal cartilage and 9.1% (4.3% to 14.7%) for proximal phalangeal cartilage. Reproducibility errors were 5.2% (95% confidence interval, 2.9% to 7.6%) and 9.9% (5.4% to 15.1%), respectively. CONCLUSION: Fat-suppressed T1-weighted 3D MR imaging provides sufficient contrast and spatial resolution to allow accurate and reproducible quantification of articular cartilage volume in the metacarpophalangeal joints of the hand. This technique may be useful for monitoring cartilage loss in patients with arthritis.

Adult↗

Low-dose angiotensin-converting-enzyme inhibitor captopril to reduce proteinuria in adult idiopathic membranous nephropathy: a prospective study of long-term treatment.

The objective of this trial was to determine the long-term antiproteinuric effect of a low-dose of the angiotensin-converting-enzyme inhibitor (ACEI) captopril in patients with idiopathic membranous nephropathy (IMN), stable renal function, and no indicators of poor long-term prognosis. Fourteen adult IMN outpatients (median age 53 years) with a median duration of disease of 3 years received 12.5 mg of captopril twice a day for 12 months in a prospective trial. The effects of therapy were evaluated on the basis of plasma creatinine, 24-h proteinuria, the proteinuria selectivity index, albuminaemia, and serum IgG levels. Data were compared by means of the non-parametric paired Wilcoxon test. Three patients withdrew from the trial. Renal function remained stable in the 11 who completed the study. A clear decrease in proteinuria was observed after 1 month of therapy, which persisted with time and was associated with a trend towards a further long-term decrease. An increase in serum albumin was only observed after 6 months of therapy, again with a trend towards an increase over time. Serum IgG levels increased during therapy. This study together with data from the literature suggests a potential long-term benefit of angiotensin-converting-enzyme inhibitors in moderately proteinuric IMN. Prospective trials comparing low-dose and high-dose ACEI to no treatment or a placebo in non-severe IMN are now required.

Adult↗

Unaltered immunoglobulin expression in hybridoma cells modified by targeting of the heavy chain locus with an integration vector.

Chimeric antibodies against the murine T-cell antigen Thy-1.2 were generated in amounts sufficient for in vivo studies by substituting the constant gene segments via homologous recombination in the hybridoma cell. We show that an integration vector targets the heavy chain locus at high frequency even in a non-isogenic situation. Using this vector type, for the first time expression rates were obtained that were identical to the parental hybridoma. The use of the gpt selection marker seems to be crucial for efficient expression, and may overcome a recently claimed drawback of vector integration. A chimeric antibody produced by gene targeting was characterized in vitro and in vivo.

Animals↗

[CT and MRI in elastofibroma. A rare, benign soft tissue tumor].

Elastofibroma is a rare, benign soft-tissue tumor that occurs along the chest wall in the periscapular region. We identified five patients with a surgical diagnosis of elastofibroma who had had CT and/or MR scans. CT and MR imaging were compared to histologic findings in two patients. CT was available in three patients and demonstrated periscapular soft-tissue tumor with an attenuation similar to that of adjacent muscle. In one patient, the tumors appeared homogeneous. In two patients, the tumor showed strands of low density similar to that of adjacent subcutaneous fat on CT. On MR imaging, all five tumors showed predominantly low-signal intensity on both T1 and T2-weighted images. The tumors contained focal areas with high-signal intensity on T1-weighted scans that showed intermediate to high-signal intensity with T2-weighting. The areas of low-signal intensity on both T1 and T2-weighted images corresponded histologically to fibroelastic tissue. The areas of high signal intensity on T1-weighting and intermediate to high-signal intensity on T2-weighting reflected focal areas of fat within the tumor. Although CT and MR imaging findings are not specific, the presence of a soft-tissue tumor along the chest wall in a periscapular location that shows predominantly low intensity on all sequences reflecting fibrous tissue with interspersed focal areas of fatty tissue is highly suggestive of elastofibroma.

Aged↗

A new method for delivering radioactive cytotoxic agents in solid cancers.

PURPOSE: Therapeutic agents such as monoclonal antibodies, radiopharmaceuticals, and radioactive growth factors are limited in effectiveness due to the inability to deposit significant quantities of the agents and for limited periods of time in solid cancer. A new technique based on knowledge of the pathophysiology of solid tumors allows for significant concentration of these agents to accumulate and for a prolonged period of time, thus allowing interaction with the tumor for potentially increased effectiveness. METHODS AND MATERIALS: Three agents have been studied: 131I antiferritin monoclonal antibody, colloidal 32P chromic phosphate, and 131I transferrin. The time required for maximal tumor uptake was determined in vitro in tissue culture and was 10 min, 25 min, and 40 min, respectively. The new method of in vivo tumor infusion consisted of a direct intratumoral injection of macroaggregated albumin (MAA) 10,000 particles, followed by the radioactive agents under study. Tumors were infused in vivo using the new technique and compared to intratumoral infused controls. In the instance of radiolabeled antiferritin antibody, intraperitoneal administration and intratumoral infusion were compared to the new technique. In the other two instances, intratumoral infusion was compared to the new method. RESULTS: In all instances the direct vascular blockade caused by MAA led to greater deposition of the agent under study for at least 24 h. These results were clinically applied with MAA followed by 32P colloidal chromic phosphate and were consistent with the experimental findings. CONCLUSION: A new technique is described that may be carried out in the experimental laboratory and clinic by direct tumor infusion of macroaggregated albumin (MAA), followed by other radioactive agents that will remain localized in solid cancers and will allow for high tumor dose deposition for potentially increased therapeutic efficacy.

Animals↗

Tissue-specific variations in the expression and regulation of the small GTP-binding protein Rho.

Rho proteins are involved in the regulation of the assembly of the microfilamental cellular network and are known to be specific substrates for the ADP-ribosyltransferase C3 from Clostridium botulinum. Here, we studied the distribution of Rho and Rho-regulating proteins in extracts from various rabbit tissues. The highest amounts of [32P]ADP-ribosylated proteins were detected in cell extracts from lung and kidney. Compared to these tissues, 50-95% reduced labeling of Rho proteins was observed in extracts from liver, spleen, brain, heart and muscle. The level of the C3-mediated [32P]ADP-ribosylation of Rho did not correlate with the amount of RhoA proteins detected by Western analysis. The relative amounts of [32P]ADP-ribosylated proteins located in cytosolic or membrane fractions, respectively, depended on the type of tissue investigated, indicating a tissue-specific variation in the subcellular distribution of Rho proteins. The same was true for the complexation of Rho with other factors and the expression of diverse Rho species. In respect to Rho-regulating proteins, extracts from lung and brain contained the highest amounts of guanine nucleotide dissociation-inhibitor proteins (Rho-GDI). The association of Rho with Rho-GDI however showed tissue specificity and did not correlate with Rho-GDI amounts. The highest Rho-GAP (GAP = GTPase-activating protein) activities were observed in extracts from lung, kidney and spleen, the lowest ones in extracts from muscle and heart. In total, our data demonstrate tissue-specific differences in the expression of RhoA, [32P]ADP-ribosylated proteins and Rho-regulating factors, indicating a tissue-specific variation in the activity and regulation of Rho proteins.

Animals↗