Radiology in the French health-care system.
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Biomedical subjects
Publications and source records attributed to J F Moreau.
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Venous tumor invasion in 42 renal cell carcinomas was evaluated by MRI. A correct diagnosis of renal vein and inferior vena cava (IVC) involvement was made in 14 of 17 tumors: 1 false negative diagnosis of right renal vein invasion was due to a double renal vein in which the inferior vein (identified by MRI) was not involved; 2 cases of IVC involvement were understaged (1 case of suprahepatic extension) or not identified (the false negative of renal vein invasion previously described). One false positive (among 31 tumors without venous invasion) was reported in a case of a large tumor in which the compressed but free right renal vein was overevaluated by MRI.
The results of extracorporeal shock wave lithotrity (Dornier lithotriptor) for 700 cases of urinary calculi have been reviewed and correlated with the radiological features of the calculi in order to define some predictive radiological criteria of effectiveness. The calculi were broken up in 74.5% of all cases, complete destruction (no residual fragment) was achieved in 34.5% and partial destruction in 40% of cases. The rate of failure (failure to break up or scatter the calculus) is 8.9%. Complications were observed in 2.6% of all cases, a second session of lithotrity or a surgical operation was required in 4.8% of cases (evolution lost to follow-up: 9.2%). The comparison of these results with the radiological data obtained before lithotrity allows distinguishing 2 categories of calculi: 1) Calculi with a favorable prognosis: single, smaller than 1 cm, pyelic, not very opaque and heterogeneous, located in normal-sized cavities; 2) calculi with a poor prognosis: multiple, larger than 2 cm, lower calyceal or ureteral, very opaque and homogeneous, located within dilated cavities.
Six human T lymphomas and an NK-like cell line were tested for their ability to produce HILDA, one of the two human growth promoting activities for the DA1.a cells. Among them, the HSB2 cell line turned out to be the only one secreting significant HILDA activity (200-400 units/ml) after activation with 50 nM phorbol myristate acetate. Subclones of the HSB2 cell line were obtained by limiting dilution experiments. One of them (2B3) was found to secrete 1,000-5,000 units/ml of HILDA after phorbol myristate acetate activation in the presence of 10% fetal calf serum and 200-500 units/ml in serum-free conditions. 2B3-HILDA was purified from serum-free conditioned medium by a four-step procedure including fast flow cationic exchange at pH 6, concanavalin A chromatography, reverse-phase high performance liquid chromatography and gel-filtration high performance liquid chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the purified radiolabeled cytokine revealed a single band of Mr 43,000, which co-electrophoresed with the biological activity. The NH2-terminal amino acid sequence of the first residues of the protein were determined and found to be similar to the equivalent residues deduced from the molecularly cloned cytokine. Isoelectric point determination revealed some charge heterogeneity of HILDA, which focused to pH 8.5-9 after neuraminidase treatment. Carbohydrate content of the cytokine was studied by deglycosylation experiments which showed that the O-linked oligosaccharides represented 2,000-3,000 and that the N-linked sugars account for half of the apparent molecular weight of HILDA.
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The accuracy of high-resolution real-time ultrasonic examination of the flexor tendons of the fingers was tested in a retrospective study of 27 patients treated surgically. In ruptured tendons (8 cases) the method proved sensitive and specific, except in cases of partial rupture. Ultrasound made it possible to distinguish between extrinsically developed palmar masses (8 cases) and masses involving the tendons (4 cases). A fluid collection inside the tendon sheath was detected in 5 cases of tenosynovitis, without false-positive results. The post-operative follow-up of surgically treated tendons (2 cases) was easier with ultrasound.
Human alloreactive T-cell clones derived from cells invading a rejected kidney allograft were found to be capable of proliferating upon specific antigenic stimulation in short term assays and in the absence of exogenous IL-2. In most culture supernatants there was no evidence of any activity capable of triggering proliferation of the murine IL-2-sensitive CTL-L2 line. The ability of these clones to produce IL-2 was investigated under several experimental conditions. A combination of phorbol ester plus calcium ionophore was very efficient in all clones tested (17/17) in inducing transcription of the IL-2 gene. Conversely, when cell activation took place through the CD3/Ti complex, we regularly failed to detect hu-IL-2 transcripts even when the number of stimulator cells was increased. However, a blockade of IL-2-R with a monoclonal antibody inhibiting ligand receptor interaction while decreasing proliferation induced by the antigen in dose-dependent fashion permitted the presence of IL-2 to be demonstrated in supernatants. These results strongly suggest that IL-2-driven proliferation is essential in this model and may represent a major, although not exclusive, pathway leading to proliferation of these clones.
Rearrangements of the T-cell Rearranging Gene (TRG) or T-cell-receptor gamma-chain genes were analyzed in 24 in vivo-sensitized alloreactive T-cell clones. This analysis represents the first complete assignment of TRG gene rearrangements to given variable and joining gene segments in nonleukemic T cells and provides some evidence for the hypothesis of sequential gamma genes rearrangements during T-lymphocyte differentiation. TRG gene rearrangements in our T-cell panel involved the known "active" V gamma genes, with a preferential use of V2 and V4 genes. In most clones, rearrangements occurred on both chromosomes and involved the J2 segment, but only 2 and 4 out of the 49 described rearrangements involved the additional J gamma segments JP1 and JP2, respectively. Two peculiar rearrangements were found. The first one was probably due to the creation of a new restriction enzyme site in the N-region at the V-J junction; the second can be explained by an aberrant rearrangement of a V gene to a sequence located between exons 2 and 3 of the TRGC1 gene.
Antihuman lymphocyte rabbit (or horse) gamma globulins used in recipients of organ transplantation are prepared against thymocytes or immortalized cell lines, the only two sources so far allowing enough antigen preparation. These cells lack, however, the surface determinants characteristic of alloreactive blasts involved in the rejection process. We have derived long-term cultures of a panel of alloreactive (untransformed) clones from a rejected kidney. Among them, clone 1E7 has been chosen as a cytotoxic CD4+ (CD2+ CD3+ TCR alpha beta+) clone proliferating against HLA-DR8 targets. This clone (clonality assessed on T cell receptor genomic rearrangements) has been grown using weekly stimulations with the kidney donor-derived EBV cell line and recombinant IL-2. Clone cultures have been adapted to mass production after optimization of culture conditions satisfying pharmaceutical requirements. This procedure warranted a reproducible source of antigen since the functional and phenotypic characteristics of the immunizing 1E7 cells remained identical through the life span of the culture. In addition, the study of the total growth capacity of 1E7 cells showed consistent expansion until the 40th cell cycle, ensuring a progeny that will satisfy the large-scale requirement for a clinical trial. Rabbits were injected with 100 x 10(6) 1E7 cells (21, 14, and 7 days before bleeding). Sera were depleted of agglutinin by red blood cell absorption and globulin antiblast (GAB) prepared by SO4Na precipitation and ion exchange chromatography; 50% complement-mediated target cell lysis and 50% inhibition of E rosette formation and alloproliferation were obtained at GAB dilutions of about 1:250-1:500. Prescreened on cynomolgus monkeys, GAB could significantly prolong skin grafts when given prophylactically. Finally GAB have been used in human recipients of kidney grafts for prophylaxis of early rejection. Results of this pilot study are given in a separate report in this issue. In conclusion we have, for the first time, set up a large-scale preparation of polyclonal globulin against a normal human alloreactive clone, and this new reagent should present several advantages over classic antilymphocyte or antithymocyte sera because it contains specificities against activation antigens and has less crossreactivity variation among batches.
Antiblast globulins (GAB) were prepared by immunization of rabbits with activated T lymphocytes (AT) derived from a rejected kidney allograft. AT consisted of a CD4+ (CD3+, CD2+ TCR alpha+ beta+) clone cytotoxic for HLA DR8-positive targets. The immunizing cells were adapted to industrial growth conditions by repetitive stimulations with an EBV-transformed line from the kidney donor and recombinant IL-2. In the pilot study, GAB (1.0-1.5 mg/kg/day) was given in 12-hr infusions, in association with prednisone (Pred) 1 mg/kg/day and azathioprine (Aza) 2 mg/kg/day, as prophylactic treatment of rejection in 12 kidney-transplanted patients during the first 2 weeks postgrafting. GAB dosage was further adapted according to the level of circulating E-rosette-forming T cells (ERFT). Cyclosporine A (8 mg/kg/day) was given at day 14 as a monotherapy after Pred and Aza were progressively tapered. No patient died, but one kidney was lost from surgical complication. No rejection occurred under GAB treatment; 41% of patients had at least one episode in the first 3 months and 16% from 3 to 9 months. GAB side effects were minor (skin rash: 2, low grade fever: 4) except for one acute serum sickness. Platelet and white blood cell counts were unchanged, but there was a significant decrease in hemoglobin during the 2 weeks of GAB infusions. Few infectious episodes occurred (3 bacterial, 2 viral). GAB monitoring showed a dramatic drop in T11+, T3+, T4+, and T8+ circulating T cells (less than 10% of normal values between days 3 and 14), whereas EFRT cells had a delayed and somewhat lower decrease (less than 10% after day 6 only). Consequently, mean GAB doses had to be raised to 1.3 mg/kg/day at day 4 and 1.6 at days 8 and 14. This pilot study suggests that this new bioreagent should be of major interest in the prophylaxis and treatment of rejection in allograft recipients. A controlled study is in progress.
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We analyzed the proliferative response of DA1, DA1-a, NFS 60, 32DC1, Ea 3-17 and FDCP2 murine interleukin 3 (mIL3)-sensitive cell lines to human recombinant IL1 alpha, IL1 beta, IL2, IL4, IL5, IL6, granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), granulocyte-macrophage-CSF (GM-CSF), interferon gamma (IFN gamma), tumor necrosis factor (TNF) alpha, gibbon IL3, purified HILDA and mouse recombinant IL3, IL4, GM-CSF. All cell lines responded to mIL3 and IL4. Various response patterns were observed with human IL2, G-CSF and murine GM-CSF. Human IL4 and GM-CSF were absolutely inefficient in triggering proliferation of lines sensitive to their murine counterparts, confirming the species specificity of these two cytokines. Among the cell lines responding to G-CSF, some variations in sensitivities were observed. Thus the 32DC1 cell line needed 10 to 30 times more G-CSF to reach the same level of proliferation as the NFS60 cell line. DA1-a was the only factor-dependent cell line responding to purified HILDA, and IL6 was found to trigger proliferation of the NFS60 cell line, with a half-maximum effect observed for 0.1 pM of hormone.
Bone status, calcium and phosphate metabolism were prospectively evaluated in 98 renal transplant recipients with stable renal function. Aseptic necrosis of bone was found in 30 patients, leading to arthroplasty in 12 patients. Plasma parathyroid hormone and nephrogenic cyclic adenosine monophosphate (cAMP) values were greater and the duration of pre-transplant chronic renal failure longer in patients with aseptic necrosis of bone than in those who were not affected. Cumulative oral corticosteroid doses and the number of acute rejection episodes treated by intravenous methylprednisolone pulses were similar in patients with or without aseptic necrosis of bone. Hyperparathyroidism was confirmed histologically in 14 patients, comprising 4 cases of adenoma and 10 of diffuse hyperplasia. Serum parathyroid hormone correlated positively with serum creatinine (r = 0.47; P less than 0.001) and with cumulative corticosteroid dose (r = 0.30; P less than 0.003). This study suggests that hyperparathyroidism is a factor in the pathogenesis of aseptic bone necrosis. The frequency and severity of bone necrosis may be decreased by early detection and treatment of post-transplant hyperparathyroidism.
Repeated analysis of peripheral blood lymphocytes (PBLs) from a patient with large granular lymphocytosis, neutropenia, and rheumatoid arthritis revealed that approximately 45% of PBLs displayed the following phenotype: CD3+, CD4-, CD8-, CD16+, HNK-1-, WT31-. This population was purified for further analysis by depletion with anti-CD4 and anti-CD8 monoclonal antibodies (MoAbs). Southern blot analysis showed preferential rearrangements of the V gamma 9 genes. Northern blot demonstrated the presence of V gamma 9 mRNA transcripts. With MoAbs directed against either the V gamma 9 peptide (Ti gamma A) or the delta chain of the gamma delta T-cell receptor (TCR delta 1), we further demonstrated that those cell surfaces expressed both V gamma 9 and a delta gene product. In addition, analysis of the gamma gene rearrangements on six clones derived from this population demonstrated a unique rearrangement on a single chromosome, strongly suggesting the monoclonality of this T-cell population. Significant cytotoxic activity against K562, U937 was observed only after an in vitro culture period with interleukin-2 (IL-2), whereas no specific inhibitory effect on autologous bone marrow (BM) CFU-G was noted.
26 urothelial carcinomas studied with MRI and CT have been reviewed. The results are connected with surgical and histological data. The assessment of the size and number of tumoral sites is more accurate with MRI, which allows a correct assessment of bladder wall infiltration in 20 of the 22 tumors studied with T2-weighted sequences. The sensitivity of both techniques is the same for the invasion of fat (92%) and the involvement of neighboring organs (67%), although MRI seems to be more specific (85% and 95% for 77% and 89%). The results are similar for the study of lymph node invasion (71% sensitivity). The performances of MRI for the assessment of bladder cancer extension are therefore comparable to those of CT. The advantages of the former technique include the clearer visualization of the tumor itself, especially for cancers of the neck and dome of the bladder owing to exploration in several planes. In addition, it allows a reliable assessment of the degree bladder wall infiltration and differentiates tumors that are not or not very infiltrating from highly infiltrating tumors.
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Invasion of the hyothyroepiglottic (HTE) space, or pre-epiglottic space, constitutes an important element in selecting the type of therapy in cancer of the larynx (functional surgery, radiotherapy), the oropharynx and the hypopharynx. Clinical examination and standard X-ray films provide insufficient information. High frequency real time ultrasonography offers a reliable means for exploring the pre-epiglottic space, as evidenced by this study carried on 34 histologically-confirmed cases taken among 77 cases of carcinoma of the upper digestive and respiratory tracts. Advantages presented by this method over CT-scanning and MR imaging in this particular pathological are simplicity, rapidity and low cost, combined with good performance.