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Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 163 records · Page 9Linked to original sources

Preliminary experience of infusional brachytherapy using colloidal 32P.

In the past, we have clinically evaluated radiolabelled antibodies in Hodgkin's disease and hepatocellular cancer. Increased tumour pressure, reduced vascularity and poor diffusion has limited significant radiolabelled antibody tumour dose deposition. Using intratumoural infusion of macroaggregated albumin to blockade exiting vasculature followed by colloidal chromic 32Phosphorous, we have been able to achieve 75% to 100% tumour dose deposition by interstitial tumour infusion under computerised tomographic guidance. Phase I studies in a variety of solid tumours indicate extremely high doses may be achieved without toxicity (i.e. non-resectable pancreas 900,000 cGy to 1.7 million cGy) with tumour control and remission. This is a review of those studies and how the technique was applied.

Astrocytoma↗

Experimental ablation of outflow tract muscle with a thermal balloon catheter.

BACKGROUND: Pulmonary balloon valvuloplasty has been performed in selected patients with tetralogy of Fallot as an alternative to surgical palliation; this technique is limited, however, by the fact that the balloon has little effect on the dynamic, muscular contribution to outflow tract obstruction. In an experimental model, we used a new thermal balloon catheter to ablate right ventricular outflow tract muscle. We evaluated the acute efficacy and muscle ablation parameters of this technology and its effects after myocardial healing. METHODS AND RESULTS: A prototype electrolyte-filled balloon catheter, heated by radiofrequency energy, was constructed. Studies were conducted to determine the optimum electrolyte solution needed to minimize balloon heating time with an unmodified, commercially available radiofrequency generator. In vivo ablations of right ventricular outflow tract muscle with the thermal balloon were performed in lambs that were divided into three groups (n = 5 each) according to the duration of thermal energy delivery (20, 40, and 60 seconds, respectively). Ablated lesion volume increased (460 +/- 63 to 1156 +/- 256 mm3) as the energy delivery time increased (20 to 60 seconds) and was correlated with delivered energy, temperature integral, and maximum epicardial surface temperature (r = .85, .82, and .72, respectively). All five lesions in the 60-second group showed an acute decrease of the wall thickness. Additional in vivo ablations were performed in 6 animals in which survival studies showed muscle thinning, healing by fibrosis, and no evidence of aneurysm formation. CONCLUSIONS: Thermal energy can be used with a balloon catheter delivery system to ablate myocardium. This study suggests that this energy delivery technology might be useful for relief of muscular outflow tract obstruction and that further studies are warranted.

Animals↗

[Blood transfusion before kidney transplantation, is it indicated?].

The beneficial effect of blood transfusions on the prognosis of renal transplantation has been recognized since 1972, and has led transplant centres to adopt a systematic transfusion policy in end-stage renal disease patients requiring a graft. By the end of the eighties, the dramatic improvement in the results of transplantation, the disappearance of transfusions prescribed in haemodialyzed patients after recombinant human erythropoietin became available and finally the evidence of the transfusion risk have raised questions both on transfusion policy, and even on the reality of the transfusion effect itself. The consequence has been great discrepancy in the current policies of different renal transplantation centres: some countries (USA, Great Britain, Scandinavia, Southern Europe) have nearly abandoned transfusion protocols, while others (Benelux, France) remain confident in their transfusion policy. The effect of transfusions on 1-year graft survival has not been detected since 1988 in multicentre international registry reports. However, recent studies have suggested that transfusions could still have a positive effect, especially on specific endpoints, such as the acute rejection incidence observed after transplantation. Moreover, clinical and biological data show that the transfusion effect and its mechanism could depend on the HLA compatibility between the blood donor and the recipient. This justifies current and further clinical and biological investigations on the topic, in order to evaluate the possible current persistent interest of the transfusion policy before transplantation, and to elucidate the biological mechanisms of this unique attempt at immunomanipulation.

Blood Transfusion↗

Integration vectors for antibody chimerization by homologous recombination in hybridoma cells.

Gene targeting in hybridoma cells provides a tool for generating chimeric antibodies with great ease and at high yield. We present an evaluation of integration vectors for the chimerization of the immunoglobulin heavy chain locus which are universally applicable to hybridomas of different isotypes and mouse strains. There are three problems arising with vector integration: (i) the frequent persistence of the parental isotype; (ii) an isotype-dependent aberrant replacement-like recombination giving rise to antibodies devoid of the CH1 domain; and (iii) secondary recombinations leading to excision of the integrated sequence. To overcome these problems, we have systematically evaluated the consequences of extending the vector flank. Although the homology length clearly determines the recombination frequency, this effect is counteracted by the secondary recombination, which also correlates to the homology length. In contrast, the truncating recombination events are not dependent on the homology length and never lead to re-excision of the construct. To take advantage of the increased genetic stability obtained with short flanks, we constructed an enrichment vector which yields high recombination efficiencies despite using a short flanking sequence. In addition, irradiation of the cells enhanced homologous recombination. The problem of the co-production of two isotypes was overcome by a two-step targeting reaction.

Animals↗

Assessment of the skeletal status by peripheral quantitative computed tomography of the forearm: short-term precision in vivo and comparison to dual X-ray absorptiometry.

In order to assess precision of peripheral quantitative computed tomography (pQCT), duplicate bone mineral density (BMD) measurements at the radius were performed in 20 healthy premenopausal, 20 healthy postmenopausal, and 20 osteoporotic postmenopausal women using a Stratec XCT-960 system. The short-term reproductibility in vivo for the total, trabecular, and cortical regions of interest (ROI) was expressed as the absolute precision error (standard deviation, SD) and as the relative precision error (SD/mean x 100, or coefficient of variation, CV, in %). Reproducibility in vivo was good in all volunteers but was influenced by the study group and the ROI. The precision error for trabecular BMD was 3 mg/cm3, or about 1.6%. This is large relative to the aging decrease of 0.22%/year, or to the difference (12 mg/cm3, or 7%) between osteoporotic women and postmenopausal controls. In order to compare pQCT to dual X-ray absorptiometry (DXA) at the forearm and at the lumbar spine (L1-L4), 40 premenopausal healthy controls, 40 postmenopausal healthy controls, and 35 postmenopausal osteoporotic women were assessed. DXA measurements performed at the ultradistal, middistal, 1/3, and total ROI of the radius showed only moderate correlations between r = 0.38--0.75, r = 0.27--0.64, and r = 0.38--0.53 for the comparison versus pQCT total BMD, versus pQCT trabecular BMD, and versus pQCT cortical BMD, respectively. Correlations of DXA at the lumbar spine and pQCT were between r = 0.18 and 0.44. DXA at radius and spine was able to discriminate between post- menopausal controls and osteoporotic women (p = 0.001--.004),but BMD measurements by pQCT did not show this ability (p = 0.15--0.52). However, two nonstandard pQCT parameters, namely the surface area of the cortical bone and the cortical BMC were factors that discriminated well between these two groups (p = 0.002, p = 0.005, respectively). These pQCT parameters also yielded the highest relative annual changes in pre- and post-menopausal control subjects. The measurement of cortical bone in the distal radius proved to be a good predictor of vertebral fracture status and was a good indicator of age-related skeletal change. Our data emphasize the importance of cortical measurements when using pQCT of the radius to assess osteoporosis.

Absorptiometry, Photon↗

MRI of bone marrow in the distal radius: in vivo precision of effective transverse relaxation times.

The effective transverse relaxation time T2* is influenced by the presence of trabecular bone, and can potentially provide a measure of bone density as well as bone structure. We determined the in vivo precision of T2* in repeated bone marrow measurements. The T2* measurements of the bone marrow of the distal radius were performed twice within 2 weeks in six healthy young volunteers using a modified water-presaturated 3D Gradient-Recalled Acquisition at Steady State (GRASS) sequence with TE 7, 10, 12, 20, and 30; TR 67; flip angle (FA) 90 degrees. An axial volume covering a length of 5.6 cm in the distal radius was measured. Regions of interest (ROIs) were determined manually and consisted of the entire trabecular bone cross-section extending proximally from the radial subchondral endplate. Reproducibility of T2* and area measurements was expressed as the absolute precision error (standard deviation [SD] in ms or mm2) or as the relative precision error (SD/mean x 100, or coefficient of variation [CV] in %) between the two-point measurements. Short-term precision of T2* and area measurements varied depending on section thickness and location of the ROI in the distal radius. Absolute precision errors for T2* times were between 1.3 and 2.9 ms (relative precision errors 3.8-9.5 %) and for area measurements between 20 and 55 mm2 (relative precision errors 5.1-16.4%). This MR technique for quantitative assessment of trabecular bone density showed reasonable reproducibility in vivo and is a promising future tool for the assessment of osteoporosis.

Adult↗

Which vertebrae should be assessed using lateral dual-energy X-ray absorptiometry of the lumbar spine.

The purpose of this study was to determine precision and diagnostic capability of bone mineral density measurements using lateral dual-energy X-ray absorptiometry (DXA) of the lumbar spine in supine position. Duplicate postero-anterior (PA) and lateral DXA measurements were performed in 60 women. Precision errors of the single vertebral levels using lateral DXA ranged from 3.3% to 4.9%. The combination of all levels improved the precision errors to 2.0%. Paired PA and lateral DXA measurements (Hologic QDR 2000) including the vertebral levels L2 to L4 were performed in 331 postmenopausal women. In 42 women an overlap of L4 by the pelvis was suspected on the lateral DXA images. Vertebral fractures were assessed as a fracture/non-fracture dichotomy. L4 and combinations of vertebrae including L4 showed the best discriminatory capabilities with respect to vertebral fractures in receiver operating characteristic (ROC) analyses, t-tests and Z-scores, with smaller variability of the results when multiple vertebral levels were used. The areas under the ROC curves were 0.662 and 0.639 for lateral and PA measurements of L2 to L4, respectively when all women were included. Excluding the women with pelvic overlap on lateral DXA scans improved the ROC area for lateral scans to 0.686 while that for PA scans remained almost constant (0.641). The differences between PA and lateral measurements were not statistically significant. In 162 women of our study cohort an additional quantitative computed tomography (QCT) measurement of the vertebral levels L2 to L4 was performed and overlapping bony structures at the three levels were studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

A phase I study of human/mouse chimeric antiganglioside GD2 antibody ch14.18 in patients with neuroblastoma.

9 patients with stage IV neuroblastoma were treated with 19 courses of human/mouse chimeric monoclonal antiganglioside GD2 antibody ch14.18 at dose levels of 30, 40 and 50 mg/m2/day for 5 days per course. The maximum tolerated dose (MTD) per injection was 50 mg/m2/day. 7 patients received more than one course of treatment, and none revealed any human anti-mouse antibody (HAMA) response. Clinical side-effects of patients treated with ch14.18 were abdominal and joint pains, pruritus and urticaria. One patient presented with a transient pupillatonia, while 2 others showed a unilateral atrophy of the optical nerve that was probably attributable to prior therapies. A complete remission was seen in 2 patients, partial remission in 2 patients, a minor response in 1 patient and stable disease in 1 patient. 3 patients showed tumour progression. Thus, our results indicate that treatment with chimeric MAb ch14.18 can elicit some complete and partial tumour responses in neuroblastoma patients.

3-Iodobenzylguanidine↗

[Spontaneous osteonecrosis of the knee joint: MRT compared to CT, scintigraphy and histology].

PURPOSE: We compared MR imaging with scintigraphy and CT in eight patients with spontaneous osteonecrosis of the knee. The histological changes accounting for the MR signal abnormalities were evaluated. METHODS: Eight patients with spontaneous osteonecrosis of the knee joint underwent MR imaging before and after i.v. administration of Gd-DTPA. Nuclear scintigraphy was performed in all 8 patients, three patients also had CT scans of the knee area. Histologic correlation was available in three patients. RESULTS: Increased radionuclide uptake was observed in all patients. In one patient, however, scintigraphy showed increased radionuclide uptake consistent with osteonecrosis only in the medial femoral condyle, while MR imaging demonstrated osteonecrosis both in the medial as well as the lateral femoral condyles. MR demonstrated areas of low signal intensity on precontrast T1-weighted images in the femoral condyle in all patients. All these areas showed high signal intensity on T2-weighted images. On postcontrast T1-weighted images, signal intensity increase was either homogeneous throughout the lesion or it was seen at the periphery of the lesion in a band-like pattern. Histologically, the areas of high signal intensity on T2-weighted and on postcontrast T1-weighted images corresponded to granulation tissue. CONCLUSION: MR imaging detects granulation tissue adjacent to the necrotic zone. Using morphological and signal intensity criteria, MR imaging can be utilised to differentiate spontaneous osteonecrosis of the knee from osteochondritis dissecans, degenerative osteoarthritis, and other conditions affecting the knee joint.

Aged↗

[Distribution of hematopoietic and fatty bone marrow in the proximal humerus and scapula: magnetic resonance tomography and macroscopic anatomy].

PURPOSE: To establish the distribution pattern of haematopoietic and fatty bone marrow on MRI of the proximal humerus and the scapula in correlation with age, gender and nutritive factors. MATERIAL AND METHODS: 32 shoulder MR examinations (T1-weighted spin-echo and opposed-phase gradient-echo sequences) from 24 patients and 8 volunteers were analysed retrospectively. The amount of haematopoietic bone marrow within the proximal humerus and scapula was classified into four groups and was correlated with age (H-test), gender (chi 2-Test), and thickness of subcutaneous fat (H-test). The marrow distribution within 10 scapulae of cadavers over 60 years of age at death was studied. RESULTS: With increasing age, the amount of haematopoietic bone marrow in the proximal humeral metaphysis tends to decrease from lateral towards medial (H-test, p = 0.3). Diaphysis and epiphysis did not show haematopoietic marrow. The amount of haematopoietic bone marrow within the paraglenoid region of the scapula also revealed a decrease with increasing age (H-test, p = 0.003). Females had higher amounts of haematopoietic marrow than males (chi 2-test, p = 0.03). The thickness of subcutaneous fat was independent of the marrow distribution. CONCLUSION: The amount of haematopoietic bone-marrow of the shoulder girdle decreases with increasing age. The knowledge of marrow distribution patterns based upon these changes is important for shoulder MRI interpretation to prevent confusion with infiltrative disease.

Age Factors↗