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Biomedical subjects

M Lagrange

Publications and source records attributed to M Lagrange.

At least 19 recordsLinked to original sources

[The association of cardiac involvement and ischemic stroke in Churg Strauss syndrome].

In Churg and Strauss syndrome (CSS), three patterns of neurological involvement can be found, including mono or polyneuropathy, encephalopathy and stroke. We report two cases of stroke associated with major hypereosinophilia and cardiac involvement, leading to a diagnosis of CSS. Neurological and general outcome were good under treatment with steroids in combination with cyclophosphamide in one case. Churg and Strauss syndrome must be considered when a stroke is associated with a cardiac involvement and hypereosinophilia.

Adrenal Cortex Hormones↗

SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer.

The gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is located at the chromosomal region 18q21. In order to evaluate the clinical relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage using real-time quantitative PCR in 202 colorectal tumour biopsies from a previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4 diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy with a border line significance (overall survival: 3.23, P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with the previous observation that patients whose cancer had retention of the 18q21 region had a significantly higher benefit from 5-fluorouracil-based therapy. Moreover, these results may provide a refinement at the gene level of the clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive marker in colorectal cancer. This data also indicate that integrity of this component of the transforming growth factor-beta/bone morphogenetic protein signalling pathway may be a critical factor for benefit of chemotherapy in patients with colorectal cancer.

Antimetabolites, Antineoplastic↗

Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7.

Deletions of chromosome band 18q21 appear with very high frequency in a variety of carcinomas, especially in colorectal cancer. Potent tumor suppressor genes located in this region encode transforming growth factor beta (TGF-beta) signal transducers SMAD2 and SMAD4, and inactivation of either one leads to impaired TGF-beta-mediated cell growth/apoptosis. Following the assignment of SMAD7 to 18q21, we first refined the SMAD7 gene position within this region by genetically mapping SMAD7 between SMAD2 and SMAD4. Further, to compare the respective frequencies of genetic alterations of these three SMAD genes in colorectal cancer, we undertook a large-scale evaluation of the copy status of each of these genes on DNA samples from colorectal tumor biopsy material. Among a subset of 233 DNA samples for which data were available for all four genes, SMAD4, SMAD2, and the nearby gene DCC showed high deletion rates (66%, 64%, and 59%, respectively), whereas SMAD7 was deleted in only 48% of the tumors. Unexpectedly, we found some gene duplications; SMAD7 appears to be more frequently amplified (10%) than the three other genes (4-7%). Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7. Since SMAD7 normally counteracts SMAD2 and SMAD4 in TGF-beta signaling, we hypothesize that the tumor might not benefit from simultaneous SMAD7 inactivation, thereby exerting selective pressure to retain or even to duplicate the SMAD7 gene.

Chromosome Deletion↗

Indolent course as a relatively frequent presentation in T-prolymphocytic leukaemia. Groupe Français d'Hématologie Cellulaire.

T-prolymphocytic leukaemia (T-PLL) is a rare disorder with a poor outcome. Presentation features were studied in 78 T-PLL cases. Although 53 patients (group A) presented with typical progressive disease including rapidly increasing leucocytosis. 25 patients (group B) experienced an initial indolent clinical course with stable moderate leucocytosis. The morphology and antigenic profile of abnormal cells were similar in both groups, except for a lower incidence of CD45RO+ CD45RA- pattern in group B. A high incidence of inv(14)(q11;q32), t(14;14)(q11;q32) and i(8)(q10) chromosomal abnormalities were found in both groups. After an initial indolent phase (median 33 months; 6-103 months), 16 group B patients progressed to an aggressive stage with clinical and laboratory features similar to group A. Moreover, median survival after progression was short in both groups. In conclusion, T-PLL may start as an indolent disease similar to that reported in ataxia telangectasia. In this rare genetic disorder, some patients develop stable T-cell clones which progress toward T-PLL-like leukaemia. Moreover, ATM gene mutations have been reported in T-PLL. Thus, both diseases are likely to be closely related.

Adult↗

Non-specifically labelled cells that simulate bone marrow metastases in patients with non-metastatic breast cancer.

AIMS: To determine whether the presence of disseminated bone marrow tumour cells at diagnosis is a prognostic factor for breast cancer patients at high risk of recurrence or bone metastasis, and to assess their presence as a criterion for evaluation of the potential benefits of adjuvant chemotherapy. METHODS: Multiple bone marrow aspirates from 72 breast cancer patients free from metastasis were obtained during surgery at the time of diagnosis and were tested immunologically by alkaline phosphatase antialkaline phosphatase technique with a panel of three antiepithelial monoclonal antibodies (MoAb) KL1, EMA, and HMFG2. RESULTS: In nine of 72 patients, with each MoAb tested, numerous strongly positive cells always isolated were observed. However, it was demonstrated that these cells were non-specifically labelled and could be found in normal controls. CONCLUSIONS: There was no evidence of marrow tumour cells in 72 operable breast cancer patients. It is suggested that published results may be greatly overestimated and that non-specific labelling may be undetected. More specific MoAb should be found and a correlation with molecular biology should be performed if this criterion is to be considered as a prognostic factor.

Adult↗

["500 consecutive cases of laparoscopic cholecystectomy". Argument for the association to endoscopic sphincterotomy: analysis].

Our series of 500 consecutive laparoscopic cholecystectomies has drawn attention to several factors. Results would favor endoscopic sphincterotomy in cases with associated treatment of gall stones in the main bile duct. history taking should search for past history of laparoscopic surgery, especially in men with an extensive pillosity, work-up should include ultrasonography, liver function tests and intravenous cholangiography (in all patients excepting cases of allergy), it is important to use an identical material in a given hospital facility for identical procedures in order to avoid equipment-related conversions, an interesting alternative in emergency situations would be echo-guided transcutaneous transperietal cholecystotomy which allows time for safe opacification, safety is of prime importance and rapide conversion should be made when there is any doubt, especially concerning the main duct, morbidity and mortality in this series were nearly identical to those previously reported large series, for endoscopic sphincterotomy proposed as complementary therapy for cases with associated lithiasis in the main bile duct, 2/3 were performed peroperatively and 1/3 postoperatively. Considering all sphincterotomies, 2/3 were positive with extraction of a stone and demonstration of an enlarged bile duct evidencing recent migration (no failure or iatrogenic event), the relationship between the different elements should allow rapid indications in emergency situations and identify complications immediately (mean hospitalization less than 48 hours) or later. Finally, first intention laparoscopic cholecystectomy can be proposed for patients with signs of biliary distress with lithiasis depite other, sometimes contradictory, conclusions (ANDEM, CPAM, consensus conference). First intention laparoscopic cholecystectomy should eliminate in the future most of the major biliary-pancreatic abdominal syndromes.

Adolescent↗