Using Southern blotting for the diagnosis of clonality in peripheral T‐cell lymphomas (PTCLs), analysis of the T‐cell receptor (TCR) γ gene rearrangement was shown to be more informative than that of ...the TCR β gene rearrangement. In order to amplify every VJγ rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC‐clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour‐specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged γ alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow‐up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T‐cell differentiation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
T-cell clones of unknown significance (TCUS), assessed by monoclonal or oligoclonal T-cell patterns in PCR–DGGE, were detected in blood of 7/9 patients with anti-Hu syndrome. Clonal patterns were ...also detected in 2/2 neoplastic lymph nodes, and in 2/2 inflamed dorsal root ganglia from three patients. Only some T-cell clones found in target tissues were also detected in blood or non-target tissues, and likely corresponded to TCUS. In one patient, an identical T-cell clone was found in both neoplastic lymph node tissue and dorsal root ganglia, but not in blood. Dorsal root-infiltrating lymphocytes were cytotoxic CD8
+ TIA-1
+ T-cells. They were often found in close contact to sensory neurons, most of which expressed MHC-1. Taken together, these data support a direct effector role of cytotoxic CD8
+ T-cells, the same clones being likely operative in sensory neuron damage and immune-mediated tumor growth control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In cutaneous T-cell infiltrates, the demonstration of a clonal T-cell receptor (TCR) gene rearrangement has been considered helpful to distinguish Cutaneous T-cell lymphomas from reactive ...lymphoproliferation. Hence, a polymerase chain reaction (PCR) method using GC-clamp primers and denaturing gradient gel electrophoresis has been developed in our laboratory to analyze the TCRγ locus configuration. Two hundred eleven cutaneous samples from 155 patients were analyzed. A detectable clonal TCRγ rearrangement was significantly associated with cutaneous T-cell lymphomas as defined by morphologic and immunologic criteria. A clonal TCRγ rearrangement was also detected frequently in lymphomatoid papulosis, never in reactive lymphocytic infiltrates and B-cell lymphomas, and rarely in parapsoriasis en plaque and cutaneous lymphoid hyperplasia. Forty five patients had both a cutaneous and a peripheral blood sample. Fifteen had a detectable clonal rearrangement in the two samples and 22 were negative. Six patients had a positive skin sample and a negative blood sample, whereas two patients had a positive blood sample and a negative skin sample. Four lymph node samples were analyzed and the PCR results were the same as in the skin. Finally, 21 patients had sequential samples of recurrent skin lesions. The PCR results were concordant in all and, when detectable, the clonal TCRγ rearrangement remained unchanged in a given patient. Because of its simplicity and accuracy, the newly designed PCR procedure improves the monitoring of diagnosis, staging, and follow-up in cutaneous T-cell infiltrates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
It is now widely accepted that polymerase chain reaction (PCR) analysis of cutaneous T-cell clonality is of diagnostic value in cutaneous T-cell lymphomas (CTCLs) and most helpful in the diagnosis of ...mycosis fungoides (MF). However, the diagnostic and prognostic value of circulating clonal T cells remains unclear. We studied T-cell clonality in the peripheral blood (PB) and the cutaneous lesion, sampled at the same time, in 363 consecutively seen patients with a clinical suspicion of cutaneous lymphoma. Using a PCR technique providing a specific imprint of T-cell clones (PCRγ–denaturing gradient gel electrophoresis), we found that detection of identical circulating and cutaneous T-cell clones was associated with the diagnosis of CTCL (P < .001). Detection of circulating tumor cells in patients with MF was infrequent (12.5%), except in those with erythrodermic MF (42%; P = .003). Moreover, among the 46 patients who had identical circulating and cutaneous T-cell clones, 25 (56%) had erythroderma. The finding of a dominant clone in the PB but not in the skin was frequent, regardless of the clinicohistologic classification; it occurred in 30% of patients with CTCL, 41% with non-CTCL malignant infiltrates, and 34% with benign infiltrates. This pattern was significantly more frequent in patients over 60 years of age (P < .002), even in the CTCL group (P < .01). In conclusion, dominant T-cell clones detected in the PB of patients with MF by using a routine PCR technique are rarely tumoral and are more often related to age. A multicenter prospective study is under way to establish the prognostic value of circulating tumor cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Résumé
Objectif
La simulation haute-fidélité est de plus en plus utilisée comme outil de formation. L’objectif de notre étude était d’évaluer l’intérêt de la simulation haute-fidélité comme aide aux ...médecins urgentistes pour mieux appliquer les procédures de soins.
Matériel et méthodes
Étude prospective évaluant la performance des médecins dans l’application correcte de procédures de soins standardisées sur la prise en charge d’une intubation difficile, d’un traumatisme crânien grave (TCG) et d’un arrêt cardiaque lors de deux séances de simulation (S1 et S2) à six mois d’intervalle par un évaluateur unique.
Résultats
Dix-sept médecins ont été évalués (durée moyenne d’expérience professionnelle de 9 ± 4 ans). La procédure d’intubation difficile était correctement appliquée par six (35 %) médecins lors de S1 et 13 (76 %) médecins lors de S2 (
p
= 0,02). La différence principale dans l’application de la procédure TCG résidait essentiellement au niveau de la prévention des agressions cérébrales secondaires d’origine systémique. Le nombre de médecins appliquant correctement la procédure TCG a augmenté de cinq (29 %) lors de S1 à 12 (71 %) lors de S2 (
p
= 0,03). Le nombre de médecins assurant une réanimation cardiopulmonaire d’un arrêt cardiaque selon les recommandations a augmenté de sept (41 %) lors de S1 à 14 (82 %) lors de S2 (
p
= 0,02).
Conclusion
Après deux séances de simulation à six mois d’intervalle, les performances des médecins urgentistes et leur application des procédures de soins se sont significativement améliorées. Cette étude a montré que les simulateurs hautefidélité peuvent être utilisés efficacement dans le cadre de la formation continue des médecins urgentistes confirmés.
Intravenous (IV) infusions of Ig concentrates are an effective but expensive treatment for patients with autoimmune thrombocytopenic purpura (AITP). The optimal treatment protocol and the long-term ...results are uncertain, and the precise mechanism by which the platelet count increases is poorly understood. Twenty adult patients with chronic AITP were enrolled in a prospective study to compare the respective efficacy of two high-dose IVIgG induction regimens (1 g v 2 g/kg body weight) and the long-term effect of six 1 g/kg body weight IVIgG reinfu-sions. An initial response was observed in all 18 evaluable patients: the platelet count increased to a mean value of 251 × 109/L (range 72 to 836 × 109/L) and the mean pretreatment platelet count was multiplied by 14.6. No difference in efficiency was observed between the two IVIgG dosages. The degree of the platelet count increment correlated in both groups with the increase in the clearance of antibody-coated red blood cells, measured by an isotopic method, but not with the serum IgG elevation. Treatment was considered to have failed in 11 patients, 90 days after the last IVIgG reinfusion (D90), because the platelet counts were comparable with pretreatment values. In contrast, a complete response was observed at D90 in five patients (mean platelet count: 184 × 109/L; range: 150 to 250 × 109/L) and a partial response at D90 was obtained in the remaining two patients (platelet counts: 70 and 104 × 109/L). Five of the 7 responders at D90 kept a platelet count above 50 × 109/L during the entire follow-up period (mean 33 months; range: 5 to 66) with no further treatment; unfortunately, no clinical or biologic criteria were found to be predictive of the long-term response. This study shows that an IVIgG infusion regimen of 1 g/kg body weight could safely replace the classical 2 g/kg body weight dosage, at least in patients who do not have life-threatening thrombocytopenia. Moreover, repeated IVIgG reinfusion could be an alternative for AITP patients in whom splenectomy is contraindicated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Background T‐cell receptor (TCR) gene rearrangement analysis, i.e. T‐cell clonality, using polymerase chain reaction (PCR) is a routine method used to assess the presence of a cutaneous ...dominant T‐cell clone in mycosis fungoides (MF).
Objectives To compare the outcome of cutaneous lesions of MF after treatment with the fate of the cutaneous T‐cell clonality, and to determine whether minimal residual disease can be detected in patients in clinical complete remission.
Methods Fifty‐one patients histologically diagnosed as having MF (17 stage IA, 21 stage IB and 13 stage III) were included in this retrospective study. T‐cell clonality was analysed by GC‐clamp multiplex PCRγ‐denaturing gradient gel electrophoresis. Every patient had two cutaneous biopsies at least 3 months apart. The second biopsy was performed at the site of a treated lesion.
Results The presence or absence of a dominant T‐cell clone in the skin remained identical in 26 of the 31 (84%) patients with persistent disease. Thirteen patients with a detectable dominant T‐cell clone at diagnosis went into complete clinical remission. In nine of these 13 (69%) patients, the T‐cell clone was no longer detectable after treatment. The remaining four (31%) patients had an unchanged T‐cell clonality.
Conclusions The TCR gene rearrangement imprint is a stable and reliable tumour marker of MF disease. One‐third of patients in complete clinical remission had a cutaneous molecular residual disease, the prognostic value of which will be analysed in an ongoing prospective study.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Fifty-seven cases of peripheral T-cell lymphoma were studied for cell expression of the T-cell receptor (TCR) chains, using monoclonal antibodies specific for the beta chain (beta F1) of the ...alpha/beta TCR, and for the delta chain (anti-TCR delta-1) of the gamma/delta TCR. Three different patterns were demonstrated: in 39 cases (69%), the phenotype (CD3+beta F1+TCR delta-1-) was that of most normal T cells. A second pattern was found on six cases (10%), which were of CD3+beta F1-TCR delta-1+ phenotype, and in which DNA analysis showed a clonal rearrangement of the delta locus in the five cases studied. It is suggested that these cases are the neoplastic counterpart of the small subpopulation of normal T cells that express gamma delta receptor. It is of considerable interest that these gamma delta lymphomas had unusual clinicopathologic presentations, as one case corresponded to a lethal midline granuloma and the five others to hepatosplenic lymphomas with a sinusal/sinusoidal infiltration in spleen, marrow, and liver. The fact that the distribution of the neoplastic gamma delta cells in the splenic red pulp resembles that of normal gamma delta cells reinforces the concept of a preferential homing of gamma delta T cells to this tissue. A third pattern (CD3 +/- beta F1-TCR delta-1-) was seen in 12 cases (21%), in which, by contrast to normal post-thymic T cells, no evidence of either alpha beta or gamma delta T cell receptor was found.
Patients with total hip arthroplasty were screened for the presence of proinflammatory cytokines in the systemic circulation. Only increased levels of interleukin-6 were detected in patients having ...had total hip arthroplasty more than 10 years ago. These increased levels of interleukin-6 were associated with a decrease in bone mineral density associated with polyethylene wear and with radiologic osteolysis in some patients. These abnormalities were not found in control subjects without total hip arthroplasty or in patients who had a prosthesis in place for less than 6 years. The elevation in interleukin-6 levels found in patients with the oldest prostheses could constitute a marker for periprosthetic osteolysis.
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