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Biomedical subjects

A Tanguy

Publications and source records attributed to A Tanguy.

At least 19 recordsLinked to original sources

Cloning of a metallothionein gene and characterization of two other cDNA sequences in the Pacific oyster Crassostrea gigas (CgMT1).

Metallothionein (MT) genes encode essential metal-binding proteins involved in metallic homeostasis and detoxification in living organisms. Here, we describe the structure of the first Pacific oyster Crassostrea gigas metallothionein (CgMT1) gene and the sequences of two other MT cDNA. The CgMT1 gene sequence contains three coding exons plus a 5' entirely non-coding exon, and the predicted protein contains 21 cysteine residues organized in Cys-X-Cys motifs as classically described for MTs. The three cDNA sequences present few substitutions in either coding sequence or UTRs. Induction of these MT-mRNA in heavy metal-treated oysters (i.e. cadmium) was confirmed by Northern blot analysis and RT-PCR and suggests a potential specific tissue expression rate. Southern blot analysis suggested the presence of multiple CgMT genes, and allowed the detection of restriction fragment length polymorphisms (RFLPs). Although the CgMT1 coding sequence showed 30-73% nucleotide identities with known sequences in other mollusks, it included the specific motif Cys-X-Cys-X(3)-Cys-Thr-Gly-X-X-X-Cys-X-Cys-X(5)-Cys-X-Cys-Lys found in Mollusk family 2. Marine bivalves are commonly used as pollution bioindicators, thus the development of genetic markers based on CgMT1 polymorphism will allow a monitoring of heavy metal exposure in anthropogenically disturbed ecosystems.

Amino Acid Sequence↗

Cloning and characterization of a gene coding for a novel metallothionein in the Pacific oyster Crassostrea gigas (CgMT2): a case of adaptive response to metal-induced stress?

Cases of heavy metal resistance acquisition have already been demonstrated in eukaryotes, which involve metallothionein (MT) gene duplication or amplification mechanisms. We characterized in a marine bivalve, Crassostrea gigas, a gene coding for an unusual MT, which has never been described in other species. Our results illustrate a unique case of exon duplication and rearrangement in the MT gene family. The particular organization of the third exon of this gene allows the synthesis of a MT that presents a higher metal ion binding capacity compared to previously described MTs. The formation of a supplementary third structural beta-domain is proposed to explain results obtained in in vitro experiments. Differences in the metal responsive element (MRE) copy number and MRE core sequence observed in the promoter of CgMT2 also suggest differential regulation of CgMT2 transcription and possible implication in the detoxification processes.

Adaptation, Physiological↗

Clinical relevance of gallium-67 scintigraphy in lymphoma before and after therapy.

The clinical impact of gallium-67 scintigraphy before and after therapy for lymphoma remains controversial. The aims of this study were: (1) to compare the staging of lymphoma by 67Ga scintigraphy only with staging by clinical examination and conventional imaging (CI), and (2) to analyse the clinical relevance of both 67Ga imaging and CI after treatment. From March 1995 to November 1998, 86 67Ga scintigraphy studies were performed in 62 patients with Hodgkin's disease (n=52) or non-Hodgkin's lymphoma (n=10). 67Ga scintigraphy was performed at diagnosis (n=44) or after therapy (n=42) using 185-220 MBq 67Ga citrate and planar and single-photon emission tomography (SPET) studies. Treatment comprised radiotherapy, chemotherapy or combined modalities. CI included plain chest radiography, computed tomography (CT) of the chest and abdomen/pelvis, ultrasound of the abdomen, lymphography, bone marrow biopsy and, when necessary, magnetic resonance imaging (MRI) and bone scintigraphy. For individual suspected sites of disease before treatment, complete agreement between clinical examination and CI on the one hand and 67Ga scintigraphy on the other hand was observed in 25/44 patients (57%; 95% confidence interval 41%-72%). Clinical examination and CI showed more sites than did 67Ga scintigraphy in 12/44 patients (27%) and 67Ga imaging demonstrated more sites than CI in 6/44 patients (11%). The clinical stage of the disease as assessed using 67Ga scintigraphy only was in agreement with that using all diagnostic procedures in 34/44 patients (77%; 95% confidence interval 62%-89%). Compared with CI staging, 67Ga scintigraphy downstaged seven patients (16%) and upstaged three (7%). 67Ga scintigraphy downstaged mainly because of the limited value of the technique below the diaphragm and upstaged owing to the good sensitivity in the lung. After therapy, both CI and 67Ga scintigraphy were normal in 11 patients. All but one of these patients were in complete remission after a median follow-up of 31 months. In contrast, radiological residual mass was observed in 31/42 patients. 67Ga imaging was normal in 22/31 (71%); 17 of these 22 patients, including nine with a large residual mass (> or =2 cm), were in complete remission after a median follow-up of 32 months, while four suffered relapses 8-45 months later. The cause of death remained unknown in one patient. 67Ga scintigraphy showed abnormal uptake in 9 of the 31 patients with a large residual mass. Active disease was demonstrated in eight patients and one patient was in complete remission 30 months thereafter. Our data show that 67Ga imaging cannot replace CI in initial staging but can demonstrate additional individual sites of disease in more than 10% of patients and can lead to clinical upstaging with potential prognostic and therapeutic consequences. After therapy, 67Ga scintigraphy has a clinical impact when radiological abnormalities persist because it can either avoid unnecessary complementary treatment or confirm the need to change treatment modalities.

Citric Acid↗

Quantitative decrease of human cytochrome c oxidase during development: evidences for a post-transcriptional regulation.

In an earlier study, we showed that cytochrome c oxidase activity, measured in mitochondria isolated from human muscular biopsies, decreased steadily and substantially between the age of four years and adulthood (P < 0.05), whereas complexes I and III activity remained constant. The present study investigates a number of possible causes for this change in activity: although there is a drop in the apparent Vmax, neither the apparent enzyme Km, nor the cellular mtDNA concentration shows any variations over the studied period. Steady-state concentrations of mitochondrial gene transcripts (CO I. CO II, CO III, but also 12S, cytochrome b, or ND4) increase within this age group, indicating an overall increase in mitochondrial genome expression. Concentrations of transcripts of nuclear genes CO IV, CO Vb, and CO VIaH likewise show an increase, albeit less marked. On the other hand, heme aa3 levels and concentrations of mitochondrial (CO II) or nuclear (CO IV, CO VIIaH) subunits, estimated using specific antibodies, correlate closely with enzymatic activity and show a parallel decrease between 4 and 20 years. The observed decrease in complex IV activity is thus quantitative, and subject to post-transcriptional and/or post-translational regulation.

Adolescent↗

Late psychosocial sequelae in Hodgkin's disease survivors: a French population-based case-control study.

PURPOSE: To evaluate late psychosocial sequelae in long-term survivors of Hodgkin's disease (HD) in the population of Calvados, France. PATIENTS AND METHODS: Ninety-three patients issued from the Calvados General Tumor Registry, treated from 1978 to 1990, free of relapse and second malignancy since January 1991, were enrolled onto cross-sectional case-control study. One hundred eighty-six healthy controls, matched for sex, age, and residency, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in the spring of 1995. RESULTS: Compared with controls, HD patients reported (1) more physical (P < .001), role (P < .001), and cognitive (P = .015) functioning impairments, as well as dyspnea (P < .001) and chronic fatigue (P = .025), while no statistical difference was found in global health status; (2) to be more often childless (P = .04), fewer divorces or separations (P = .013), fewer changes in relationships with friends (P = .012), similar proportions at work but less ambitious professional plans (P < .001), and greater difficulties in borrowing from banks (P < .001); (3) a slight increase in the number of visits to a general practitioner (P = .05) and greater consumption of medical resources (mainly thyroid extracts, P = .05). CONCLUSION: The study demonstrated that French long-term HD survivors have good global health status and good psychologic, familial, and professional status, although difficulties in borrowing from banks remain a major limitation in daily life. Although physical, role, and cognitive functioning impairments persist that might limit their activities, HD survivors seem to have learned to cope with problems related to their disease and its treatment.

Activities of Daily Living↗

[Measurement of the torsion of the two bones of the forearm: evaluation of tomodensitometric reference points].

In order to evaluate the rotation following radial and ulnar fractures, the authors propose radial, ulnar and humeral landmarks for a CT scan measure of radial and ulnar torsion. In the ulna, the dorsal at the level of the proximal radio-ulnar articulation, as well as the bicondylar axis of the humerus seem to be fair landmarks. Distally, the styloid process is regularly identified and may serve as distal reference for the measure. In the radius, the ventral face of the distal epiphysis is always clearly visualized and seems to be a good landmark; the radial tuberosity, which was primarily chosen as proximal reference, is not consistently identified and cannot be used as landmark. The variation of position of the radial head with respect to the capitulum during pronation needs too know the amount of this movement before the measure if the bicondylar humeral axis is chosen as proximal reference.

Adult↗

Enzymatic activities of mitochondrial respiratory complexes from children muscular biopsies. Age-related evolutions.

Measurements were performed to determine maximum enzymatic activities of citrate synthetase and respiratory complexes I, III, and IV of mitochondria obtained from muscular biopsies in control children. The significant number of determinations carried out (43 different biopsies in controls aged 3.8 to 19.1 years) permits the formulation of a table of statistically validated reference values for these activities. These values are independent of sex of the controls, and of the studied muscles. Citrate synthetase activity, which remains stable in this age range, thus constitutes a good internal indicator of mitochondrial activity. Complexes I and III manifest activity which does not vary with age. On the other hand, cytochrome oxidase activity shows a highly significant decrease in this age group. This decrease may be correlated with qualitative changes (subunits VIa and VIIa) in composition of this complex.

Adolescent↗

Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group.

PURPOSE: To compare (1) clinical staging and irradiation alone versus staging laparotomy and treatment adaptation in patients with a favorable prognosis (H6F); (2) two combined modalities in patients with an unfavorable prognosis (H6U). PATIENTS AND METHODS: The H6F trial (n = 262) consisted of randomization to clinical staging plus subtotal nodal irradiation (STNI) or to staging laparotomy plus treatment adaptation (adjuvant chemotherapy [CT] only in the 33% with negative laparotomy). The H6U trial (n = 316) consisted of no laparotomy, randomization to mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and mantle irradiation. RESULTS: In the H6F trial, 6-year freedom from progression (FFP) rates (78% v 83%; P = .27) were similar in clinical and laparotomy stagings, respectively. Survival rates were 93% and 89%, due to laparotomy-related deaths. In the H6U trial, the ABVD arm had superior results (6-year FFP rate, 88% v 76%; P = .01), but they were not significant for survival (91% v 85%; P = .22). CT discontinuation due to hematologic intolerance occurred more often with MOPP (14.5% v 7.3%). Decrease of the pulmonary vital capacity ([VC] < 70% of the theoretic value) was observed more frequently after ABVD than after MOPP (12% v 2%; P = .08), with two lethal pulmonary insufficiencies occurring in the ABVD arm. No modification of the isotopic left ventricular ejection fraction (LVEF) occurred. Gonadal toxicity was less in the ABVD arm. CONCLUSION: Early-stage patients benefit from treatment adaptation to initial characteristics in terms of tumor control and late toxicities. Staging laparotomy before STNI may be deleted even in favorable patients at no cost to survival or FFP. In unfavorable patients, ABVD achieved better results than MOPP, at lower hematologic and gonadal cost. Therefore, despite its pulmonary toxicity, ABVD is the best choice to design improved CT regimens associated with mantle irradiation.

Adolescent↗

[Orthopedic aspects of Rett syndrome].

Rett syndrome is a degenerative neurological disorder with onset between 6 and 18 months of age. Severity of motor impairment is variable; some patients lose the ability to walk whereas others walk nearly normally. Orthopedic problems, which mainly involve the lower limbs and spine, can increase functional impairment and cause discomfort. Abnormal joint alignment in the lower limbs due to muscle contractures requires physiotherapy and orthopedic appliances. Surgery may be necessary, in particular to prevent dislocation of the hip or to correct talipes equinus. Scoliosis is common and unresponsive to conservative therapy and should be treated surgically if severe.

Child, Preschool↗

Severe farm machinery injuries to children--a report on 15 cases.

Fifteen children with 24 farm injuries were admitted to our institution during a 12 years period. Ten accidents occurred in boys and five in girls. They ranged in age from 1 to 15. The cause of fatal and non-fatal injury was farm machinery and especially tractor in 9/15. Fractures, lacerations and amputations were the most common injuries requiring multiple reconstructive surgical procedures. The magnitude of the problem requires emergency management in rural areas. However, educational programs with an emphasis on prevention by physicians, family members, educators and legislators is necessary to reduce the incidence of farm accidents.

Adolescent↗

[Plasmocytoma with asynchronous metastasis. Immunohistological and ultrastructural contribution].

The case of a 37-year-old male who developed multiple asynchronous extramedullary plasmocytoma localizations is reported. The first site involved was the cecum. Other tumors successively arose in the chest wall, testis, buttock, nasal cavity, skin, and mediastinum. The patient died 59 months after initial diagnosis. Light microscopy and ultrastructural studies disclosed a substantial proportion of immature plasmocytes in the different tumors, explaining in part the poor activity of radiotherapy and chemotherapy. Although in many cases this clinical pattern indicates multiple myeloma, investigations failed to detect this condition in the patient reported here. Shortly before the fatal outcome, a peak of IgA kappa globulin was detected in the serum. This immunoglobulin was also identified on tumor cells using immunoperoxidase labeling.

Adult↗

Superiority of second over first generation chemotherapy in a randomized trial for stage III-IV intermediate and high-grade non-Hodgkin's lymphoma (NHL): the 1980-1985 EORTC trial. The EORTC Lymphoma Group.

A first-generation CHOP-like cyclic combination chemotherapy (CT) regimen using cyclophosphamide 600 mg/m2 IV d1, hydroxorubicin (doxorubicin) 50 mg/m2 IV d1, VM26 60 mg/m2 IV d1, and prednisone 40 mg/m2 PO d1-5 (CHVmP) was compared to a second-generation combination wherein vincristine 1.4 mg/m2 IV and bleomycin 6 mg/m2 IM/IV were added at mid-interval (d15) to the former drugs (CHVmP + VB) in the treatment of intermediate- and high-grade malignant NHL. From April 1980 to January 1986, 141 eligible patients with stage III-IV unfavorable histologies (except T lymphoblastic NHL) entered this EORTC randomized trial. In both arms adjuvant radiotherapy (30 Gy) was given in instances of bulky or residual disease. In all patient subsets the outcome favored the second-generation regimen. The difference was even greater in patients with Diffuse Large Cell Lymphoma (DLCL). At 5 years, overall survival was 53% with CHVmP + VB versus 29% (p = 0.002). The advantage was due to a higher complete remission (CR) rate (80% versus 50%, p = 0.01). Indeed, once CR was achieved the relapse-free survival (RFS) was not significantly influenced (59% versus 49%). No significant additional toxicity could be attributed to vincristine and bleomycin. This study demonstrates a clear benefit for intermediate- and high-risk malignant NHL and particularly DLCL from intercalating non-myelotoxic drugs at mid-cycle intervals, without adverse effects.

Adolescent↗

[Prothrombin time, activated partial thromboplastin time, plasma fibrinogen determination. Comparison of two automated coagulation systems: Koagulab 40-A and ACL-100].

In this study the authors compare two automated coagulation instruments: the koagulab-40A (Orthodiagnostics Systems) and l'ACL-100 (Instrumentation Laboratory) using two different methods of detection, photo-optical and nephelemetric respectively. The three parameters studied are: prothrombin time (PT) (82 samples), activated partial thromboplastin time (APTT) (86 samples) and fibrinogenemia (FIB) (109 samples). For each test, they use two reagents of different origins. Samples come from people without any haemostatic disorder and from patients showing abnormal levels of these parameters (heparins or antivitamins K treatments, hypo or hyperfibrinogenemias). For the tree parameters examined, they obtain coefficients of correlation: 0.94 to 0.99 between the two instruments. These values are not noticeably modified by reagent substitution. For fibrinogenemia, the coefficient of variation (CV) is about 4%. Finally, in comparison with the photooptical classical method, the ACL-100 is more rapid, more economical (reduced volumes of reagents) and more feasible (dilutions of plasmas and tubulure changing are not necessary for fibrinogen).

Autoanalysis↗

Sciatic nerve blocks in children: comparison of the posterior, anterior, and lateral approaches in 180 pediatric patients.

Three techniques for blocking the sciatic nerve, differing in approach (posterior in group P; lateral in group L; and anterior in group A), were prospectively evaluated in 180 children who were also given light general anesthesia for surgery below the knee. Four anesthetic solutions with epinephrine (1% lidocaine, 0.5% bupivacaine, and two mixtures of 0.5% bupivacaine with either 1% lidocaine or 1% etidocaine) were administered to 15 patients in each group. The sciatic nerve was located by electrical stimulation or, when muscle twitches were not elicited, using a loss-of-resistance technique. Twitches were "typical" in 154 patients of whom 153 developed sciatic nerve block. In 26 patients twitches were atypical (eight patients) or absent (18 patients) and a sciatic block developed in only 13 patients (50%). The depth to which the needle was inserted was measured in each procedure; it varied according to patient's age and weight and was significantly less with the posterior approach than with either the lateral or anterior routes. The overall success rate exceeded 90% in the three groups but significantly fewer difficulties were encountered in group P than in group A. Although the spread of the anesthetic was different in the three groups, the distribution of anesthesia in the lower extremity was similar, including not only dermatomes supplied by the sciatic nerve, but also those supplied by the posterior femoral cutaneous nerve. No neurological sequelae were observed. It is concluded that the posterior and lateral approaches are the most suitable in children for blocking the sciatic nerve proximally.

Adolescent↗

[Mechanics of the characteristic geometry of the human spine undergoing vertical pressure].

Since MAGENDIE in 1816, it has been a common assertion in books of Anatomie that curves of the spine increase its strength. This increase in strength has been estimated by a formula attributed to EULER: R = nc2 + 1 in which R is the strength and nc2 stands for the square of the number of curves. Applying the actual law of Euler on the strength of beams submitted to a vertical effort, the authors conclude that strength is increased by about 30% and not multiplied by 10, 16 or even 17 as is often falsely written.

Biomechanical Phenomena↗

Prognostic factors in soft tissue sarcomas. A multivariate analysis of 109 cases.

Prognostic factors were evaluated in 109 soft tissue sarcomas of the extremities, walls of the trunk, head, and neck. All lesions were graded according to the systems proposed by the National Cancer Institute (NCI) and the French Federation of Cancer Centers (FNCLCC), and a correlation was found between tumor grade and prognosis. Univariate analysis selected the following variables as unfavorable prognostic factors: invasive tumor margins, extra-compartmental status, deep tumors, tumor diameters over 5 cm, inadequate excision, presence of necrosis, high mitotic count, histologically undifferentiated tumors, and blood vessel invasion. These variables were found to be interdependent. Multivariate analysis selected quality of surgery as the most important variable for predicting local recurrences. The factors selected with regard to overall and metastasis-free survival were tumor size, tumor margins, necrosis, and adequacy of excision. These results permitted classification of patients into four prognostic groups: two with good and two with bad prognosis. Five-year survival for the four groups was 100%, 83%, 53%, and 0%; 5-year metastatic rates were 0%, 12%, 67%, and 100%. Similar groups were obtained when the variables of tumor margins and size were combined with an adaptation of the NCI grading (low-grade tumors/high-grade tumors without necrosis/high-grade tumors with necrosis). Comparative analysis showed that patients with tumors of the same histologic grade or type were not necessarily classed in the same prognostic groups. A better clinicopathologic correlation was obtained using a combination of prognostic factors than with histologic grading or typing alone.

Adolescent↗

Toward comprehensive management tailored to prognostic factors of patients with clinical stages I and II in Hodgkin's disease. The EORTC Lymphoma Group controlled clinical trials: 1964-1987.

From 1964 to 1987, the EORTC Lymphoma Group conducted four consecutive controlled clinical trials on clinical stages I and II Hodgkin's disease in which 1,579 patients were entered. From the onset the main aim of these trials was to identify the subsets of patients who could be treated safely by regional radiotherapy (RT). Therefore, several prognostic indicators were prospectively registered and progressively used in the trial protocols for the delineation of the favorable and unfavorable subgroups as soon as they were recognized of high predictive value. In the H2 trial (1972 to 1976), the histologic subtype was the only variable taken into account for the therapeutic strategy and the staging laparotomy findings were found to be of prognostic value only in patients with favorable prognostic indicators. In the H5 trial (1977 to 1982), patients were subdivided into two subgroups according to six prognostic indicators. Patients with favorable features were submitted to a staging laparotomy (lap); lap negative patients were randomized between mantle field RT and mantle field plus paraaortic RT. Disease free survival (DFS) and total survival (S) were similar in the two arms. Among patients with unfavorable features, DFS and S were significantly higher in the arm treated by combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) chemotherapy (CT) and RT than in the arm treated by total nodal irradiation. Nevertheless, in patients below the age of 40, the overall survival rates were equivalent in the two arms. In the H6 trial, the delineation of the favorable subgroup was based on (a) absence of systemic symptoms and elevated ESR, (b) no more than one or two lymph node areas involved. The aim of the study was to assess the impact on survival of a therapeutic strategy including staging laparotomy. At a 4-year follow-up, no difference in survival was evidenced. In patients with unfavorable prognostic indicators, 3 MOPP-RT-3 MOPP were compared with 3 ABVD-RT-3 ABVD. From H1 to H5 trials, the proportion of patients having received CT during the course of the disease gradually decreased; the data suggest that a further reduction in the proportion of patients aggressively treated is conceptually possible. On the basis of the prognostic factors identified, one can delineate three subsets of patients and modulate toxic cost of the initial treatment according to the characteristics of these subsets. In the most favorable subgroup, RT alone produces high survival and CT is not justified.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗