[Assessment of preventive practices in primary care occurring in hospital]. / Évaluation des pratiques préventives d'une consultation de médecine générale hospitalière.

BACKGROUND: Preventive measures are available for most of the pathological conditions causing premature mortality in France. Moreover, there is a seven-year discrepancy in life expectancy figures between persons in the least favorable socio-occupational categories and the rest of the general population. The overall target of our study was to analyze preventive practices applied as part of routine primary care in the outpatient clinics of a general medicine hospital in Paris (Hotel-Dieu) where the majority of patients belong to unfavorable social categories. METHODS: We collected and analyzed the content of all outpatient visits conducted during a three-week period using a questionnaire designed to gather information about areas of preventive care requiring particular attention. RESULTS: Analysis of 211 outpatients visits shows that the population concerned was young (44±17-year-old) and that the visits lasted longer than commonly observed (21±8 min). Cancer screening was performed in 25 to 50% of the theoretical targeted population. Addictions were discussed during half of the visits, yet follow-up and advice on how to stop addictive behavior were insufficient. Blood pressure was measured during half of the visits. Vaccinations were checked for 60% of patients and STD status for 30%. Seventy percent of the patients stated they wanted to attend a preventive care consultation; the physician considered this type of consultation would be useful for 30% of patients; the opinions were in disagreement for half of the patients. Lack of time, heavy workload in terms of number of visits, and the current setup of charts prevented updating various precautionary measures, which would have been appropriate for each patient as a function of age, gender, past history and lifestyle. CONCLUSION: This inquiry highlights many weaknesses in our preventive practices. Delegating some medical acts, a more adapted medical file and the implementation of dedicated consultations could help improve prevention in this particularly vulnerable population. The key to success of such measures lies in physician and patient awareness.

TRAF4 overexpression is a common characteristic of human carcinomas.

Tumor necrosis factor receptor (TNFR) associated factor 4 (TRAF4) was initially identified as a gene amplified and overexpressed in breast carcinomas. Our aim was to evaluate whether TRAF4 protein overexpression exists in other cancer types. Immunohistochemistry analysis of tumor samples from 623 patients with 20 different tumor types showed that TRAF4 was overexpressed in 268 tumors (43%), including 82 of 137 lung adenocarcinomas (60%). Interestingly, 32 primary tumors and their matching metastases exhibited mostly similar TRAF4 expression pattern. TRAF4 protein overexpression was limited to cancer cells and the subcellular localization was consistently cytoplasmic in a large majority of cases. To investigate changes in TRAF4 gene copy number, 125 cases from six different types of carcinomas were also analysed by fluorescence in situ hybridization. Out of the 28 cases (22%) showing an increased TRAF4 gene copy number, 23 (82%) were overexpressing the protein. Thus, TRAF4 gene amplification is one of the mechanisms responsible for TRAF4 protein overexpression in human cancers. Considering that TRAF4 is located at 17q11.2 in a region of amplification devoid of known oncogenes and is commonly overexpressed in cancer, our data support an oncogenic role for TRAF4.

Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors.

ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is rare and generally presents as a sporadic disease. We describe a familial case of AIMAH with in vivo and in vitro demonstration of aberrant 5-HT4 and vasopressin adrenal receptors. Two sisters presented with clinical and biological features of mild Cushing's syndrome with bilateral macronodular adrenal enlargement on computerized tomography (CT)-scan evaluation. In vivo pharmacological tests showed a significant increase in plasma cortisol after terlipressin and metoclopramide administration. Unilateral adrenalectomy was performed in one of these patients. Reverse transcriptase-PCR analysis of the hyperplastic tissue revealed expression of 5-HT4 receptor isoforms (a), (b), (c), (i), and (n), and of vasopressin receptors, V1 and V2. Their father and brother were overweight, had easy bruisability and presented with biological features of subclinical Cushing's syndrome. CT scan showed moderate adrenal enlargement. In vivo pharmacological screening tests for the detection of adrenal aberrant receptors in the brother were negative. Finally, three out of the two sisters' children were evaluated. They had neither clinical nor biological features of Cushing's syndrome. Their adrenal glands were normal on CT-scan evaluation. In vivo evaluation for the detection of aberrant adrenocortical receptors performed in one of these subjects was negative. In conclusion, this study shows that (i) familial AIMAH could be an autosomal dominantly inherited disorder; (ii) aberrant 5-HT4 serotonin and vasopressin receptors can be expressed in familial AIMAH; and (iii) phenotypic expression of familial AIMAH could be varied in a same family and more pronounced in female than in male patients.

[Disseminated tuberculosis and profound thrombopenia]. / Tuberculose disséminée et thrombopénie profonde.

Thrombocytopenia within the context of disseminated tuberculosis can lead to complications requiring rapid treatment. Although the origin is generally central, thrombocytopenia can arise from an immune disorder. We hereby report a case of disseminated tuberculosis associated with thrombocytopenia, which required, in addition to antituberculosis therapy initiated before bacteriological proof, corticosteroid treatment and multiple platelet transfusions. The discovery of anti-platelet antibodies along with the success of immunomodulator therapy confirmed the auto-immune origin of this thrombocytopenia.

Two distinct amplified regions at 17q11-q21 involved in human primary breast cancer.

Chromosomal segment 17q11-q21 is a commonly amplified region in human breast carcinomas. Several lines of evidence suggest that ERBB2 is the gene responsible for the emergence of this amplicon, but four novel genes (called MLN 50, MLN 51, MLN 62, and MLN 64) in 17q11-q21 have recently been found to be amplified and overexpressed in breast cancer cell lines. We investigated 98 primary breast tumors for amplification of these five loci. Twenty-five tumors (25.5%) showed amplification of at least one of these markers, but most amplifications did not encompass all of the tested loci. The genes most frequently amplified were ERBB2 and MLN 64 (22 of 25 amplified cases). MLN 64 was always coamplified with ERBB2, and to a similar level. Amplification of these five genes always leads to overexpression of their mRNA; we observed no cases of overexpression without amplification in any of these genes. Our results suggest that: (a) an independent, amplified region defined by MLN 62 (also called CART1 or TRAF4) is located in 17q11-q12; (b) in addition to ERBB2, MLN 64 is a major target for the 17q12-q21 amplicon; and (c) these MLN genes could be of pathogenetic significance in breast cancer.

Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells.

Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin. Unexpectedly the human growth hormone-releasing factor (GRF) gene promoter directs expression of SV40 Tag specifically in thymic epithelial (TE) cells. Expression starts in the neonate, in which GRF-Tag+ cells display strict numerical and spatial constraints. Tag supersedes mechanisms that constrain these features and GRF-Tag mice develop thymic hyperplasia. To characterize GRF-Tag+ TE cells and their putative normal counterparts we compared phenotypic and functional effects caused by transgenes encoding mutant large T antigens. This strategy is applicable to any situation in which T antigen is used to alter development. One large Tag mutant (K1 + 5080) does not cause thymic hyperplasia. GRF-Tag (K1 + 5080)+ TE cells display strict temporal and spatial constraints throughout life. TE cells expressing other mutant large T antigens that cause thymic hyperplasia do not obey these rules and reveal that phenotypically distinct GRF-Tag+ TE-cell stages exist in vivo. Analysis of conditional immortal GRF-Tag(tsA58)+ TE cells expressing a temperature-sensitive large Tag shows that large Tag blocks differentiation in these cells. Phenotype and functions in these cells are regulated by cellular differentiation and interleukin 4 (IL-4).

Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development.

This is the first in situ hybridization analysis of expression of a tumor necrosis factor (TNF) receptor associated factor (TRAF) during development. TRAF4 is observed throughout mouse embryogenesis, most notably during ontogenesis of the central (CNS) and peripheral (PNS) nervous system, and of nervous tissues of sensory organs. TRAF4 is preferentially expressed by post-mitotic undifferentiated neurons. Interestingly, TRAF4 remains expressed in the adult hippocampus and olfactory bulb, known to contain multipotential cells responsible for neoneurogenesis.

Intraoperative testosterone assay for virilizing ovarian tumor topographic assessment: report of a Leydig cell tumor of the ovary in a premenopausal woman with an adrenal incidentaloma.

Ovarian virilizing tumors are rare and can lead to assessment difficulties because of their small size. A 41-yr-old female was referred for evaluation of hirsutism that had increased within the previous 3 yr. Menstrual cycle length was normal. Plasma testosterone was 3.9 ng/ml (normal range, 0.2-0.8 ng/ml), was not suppressible by 2 mg dexamethasone (4.3 ng/ml), and was increased (6.3 ng/ml) after three daily injections of hCG (5000 IU). Abdominal computed tomography scan showed an adrenal nodule (13 x 6 mm) that remained unchanged after 3 months. Ultrasound examination of the pelvis was normal. Ovarian and adrenal venous catheterization did not yield additional information. Topographic assessment was made by intraoperative measurement of testosterone in the samples taken from each ovarian vein (competitive chemiluminescent immunoassay ADVIA Centaur; right ovarian vein, 105 ng/ml; left ovarian vein, 5 ng/ml; peripheral blood, 7 ng/ml). Right annexectomy resulted in normalization of testosterone levels (0.22 ng/ml). Histopathological examination found a Leydig cell tumor of hilar type (1.5 cm). This observation illustrates the usefulness of intraoperative measurement of testosterone by a rapid automated technique for topographic assessment of ovarian virilizing tumor in premenopausal women.

Lasp-1 (MLN 50) defines a new LIM protein subfamily characterized by the association of LIM and SH3 domains.

MLN 50 was previously identified in a cDNA library of breast cancer metastasis. In this study, we show that MLN 50, which is expressed at a basal level in normal tissues, is overexpressed in 8% of human breast carcinomas most often together with c-erbB-2. MLN 50 cDNA encodes a putative protein of 261 residues, named Lasp-1 (LIM and SH3 protein) since it contains a LIM motif and a domain of Src homology region 3 (SH3) at the amino- and the C-terminal parts of the protein, respectively. Thus, Lasp-1 defines a new LIM protein subfamily.

Gene transcript assay by real-time RT-PCR in epithelial breast cancer cells selected by laser microdissection.

The cell type heterogeneity within clinical cancer tissue samples may affect the accuracy of gene expression analysis. In order to validate our laser microdissection (LMD) method using the Leica AS LMD system (LEICA Microsystems), we compared the mRNA levels of three major genes involved in breast cancer (ERalpha, PR, HER2), measured by means of real-time quantitative RT-PCR, in 5000 microdissected malignant epithelial cells and in corresponding bulk tumor homogenates from 14 patients. We also compared the mRNA level results to protein expression measured by immunohistochemistry (IHC) on the same tumors. For the three genes, significant correlations were found between mRNA results obtained on microdissected cells and IHC. Comparison between IHC and mRNA results obtained on microdissected cells and bulk tumors showed that in all cases microdissection enhanced the sensitivity of assessing target gene transcript levels and was essential for their accurate evaluation in heterogeneous tumors.

The elastic behavior of the urinary bladder for large deformations.

The purpose of this paper is to investigate the theoretical basis for the pressure-distension behavior of the urinary bladder. A finite strain theory is developed for hollow spherical structures and it is shown that the Treloar model is a good prototype only for rubber balloons. The pressure-extension ratio relationship is inverted to lead a general form of strain energy function, and fitted by an empirical relation involving one exponential. The following form of strain energy function is derived: W(lambda, lambda, lambda -2) = C1 (P(1), a) + P(1)C2 (a, lambda)ea(lambda -1). Where C1(P(1), a) is a constant (N m-2), P(1) is the initial pressure, a is the rate of pressure increase and C2 (a, lambda) a third degree polynomial relation. P(1) and a are experimentally determined through volumetric pressure-distension data. It is verified that this type of energy function is also valid for uniaxial loading experiments by testing strips coming from the same bladder for which P(1) and a were computed. There is a good agreement between the experimental points and the theoretical stress-strain relation. Finally, the strain energy function is plotted as a function of the first strain invariant and appears to be of an exponential nature.

Mucopolysaccharides from psyllium involved in wound healing.

Mucopolysaccharides derived from the husk of psyllium (Plantago ovata) have properties beneficial for wound cleansing and wound healing. Recent studies indicate that these mucopolysaccharides also limit scar formation. Our in vitro and in vivo studies aimed to investigate the mechanisms involved, e.g., fluid absorption, bacterial adherence and in vitro stimulatory effects on macrophages, which are pivotal in wound healing. The mucopolysaccharides contained in a sachet (Askina Cavity) or in a hydrocolloid mixture (Askina Hydro) were found to have a gradual and sustained absorbency over a period of 7 days, amounting to 4-6 times their weight in water. The swelling index was 9 mm after 312 h. Adherence of wound bacteria to the mucopolysaccharides started after 2 h and was more pronounced after 3 h. Semiquantitative measurements of bacterial adherence used centrifugation and subsequent optical density determinations of supernatant. These confirmed the strong adherence potential of psyllium particles. Lactic acid dehydrogenase staining of pretreated cultured human skin explants did not reveal toxicity of the mucopolysaccharides derived from psyllium husk. Langerhans' cell migration from the epidermis was negligible and interleukin-1 beta expression in the explants was not significant, supporting the very low allergenic potential of psyllium. The characteristics of mucopolysaccharide granulate derived from psyllium husk in Askina Cavity and Askina Hydro related to fluid absorption, bacterial adherence, biocompatibility, stimulation of macrophages, irritancy response and allergenicity showed an optimal profile, supporting the good clinical performance of wound healing products containing psyllium husk.

Swelling of hydrocolloid dressings.

Wound healing is promoted by dressings that maintain a moist environment. Specifically, hydrocolloid dressings allow excess fluid to escape without permitting wound desiccation. However, the fluid handling capacity of hydrocolloid dressings depends on many factors such as the physicochemical properties of the gel formulation, and the design of the dressing. We measured the moisture uptake kinetics of different hydrocolloid dressings by placing the gel side of a sample in contact with water. The time evolution of the thickness was measured by means of a video camera linked to a computer. The theory of Tanaka and Fillmore (1979) was used to predict the kinetics of uniaxial swelling of a cylindrical gel sample. The model allows to associate to an experimental curve a total thickness increase hf-h0 (where hf and h0 are respectively the final and initial thickness) and a characteristic time tau. The model also relates hf-h0 and tau to the physiochemical composition of the dressing, and to the initial thickness h0. The influence of h0 is discussed by means of experiments performed on dressings with different initial thickness.

Doppler ultrasound study of the anterior cerebral artery in neonates.

In neonates doppler ultrasound of the anterior cerebral artery (ACA) enables cerebral haemodynamics to be studied in a non-invasive manner at the patient's bedside. The signal of the pericallosal artery is recorded through the fontanelle with a 7.5 mHz real-time probe. Two parameters are monitored: Pourcelot's resistance index and mean velocity which reflects blood flow rate. Having established normal values according to the gestational and post-natal ages, the authors describe the changes in cerebral circulation observed in such pathological situations as intraventricular haemorrhage, apnoea, patent ductus arteriosus, hydrocephalus and post-asphyxia syndrome.

[Acute hepatopathy compatible with Reye's syndrome in 3 children treated by chemotherapy]. / Hépatopathie aiguë compatible avec un syndrome de Reye chez trois enfants traités par chimiothérapie.

BACKGROUND: Chemotherapy for malignant diseases sometimes leads to hepatic toxicity. Reye's syndrome has not been described in such a situation. CASE REPORTS: Three children, 4, 5 and 6 years-old, were treated for lymphoma or acute lymphoblastic leukemia. They were given polychemotherapy including drugs that were not potentially hepatotoxic. During remission, they suddenly developed manifestations such as neurologic disturbances, hepatomegaly, increased activity of liver enzymes, and microvesicular steatosis. These disturbances were consistent with the diagnostic criteria for Reye's syndrome recommended by the Centers for Disease Control. Factors such as viral infection, salicylate administration, primary metabolic disorder were not present. One child died and the other two recovered completely. CONCLUSION: Patients given chemotherapy, even though the relationship between them remains to be determined, may develop manifestations compatible with a diagnosis of Reye's syndrome.

[Testicular biopsy at the stopping of the treatment in acute lymphoblastic leukemia: value of the immunohistochemical detection of residual blasts]. / Biopsie testiculaire à l'arrêt du traitement des leucémies aiguës lymphoblastiques: intérêt de la détection immunohistochimique des blastes résiduels.

BACKGROUND: The prognostic value of clinical and histological detection of testicular leukemia after completion of therapy is still debated. Immunohistochemical study could improve the results of this detection. PATIENTS AND METHODS: Between 1982 and 1992, 70 consecutive boys with acute lymphoblastic leukemia (ALL) and treated with the same therapeutic regimen were included in the study. Testicular biopsy (TB) was surgical and bilateral. One piece of tissue was fixed and analysed by conventional microscopy. An immunohistochemical study was performed on the other sample with a panel of anti-T and anti-B Mc Ab, including JCB 117 (anti-CD79a) which stains early pre B lymphoblasts. RESULTS: Twenty-five children relapsed while on treatment and did not undergo TB. Among the 45 boys who underwent routine TB, one had a diffuse infiltration seen in conventional histology. Thirty-nine had normal morphological and immunohistochemical study: among them, six relapsed subsequently in bone marrow; in this group, event free survival (EFS) was 85 +/- 10% with a median follow-up of 80 months after the biopsy. In the five remaining boys, anti-CD79a was found positive on blasts in four cases and anti-CD3 in one case; four of those relapsed, including two in the testes during the year following the biopsy; EFS was 20 +/- 36% (P = 0.001). CONCLUSIONS: New Mc Ab such as JCB 117 (anti-CD79a) might detect a minimal residual disease in the testes of children treated for ALL, particularly on routine histological material. These results, if confirmed in larger series, might influence further therapeutic strategy.

[Prevention of peritoneal adhesions by local treatments. Experimental study in the rat]. / Prévention des adhérences péritonéales au moyen de traitements locaux. Etude expérimentale chez la rate.

Those local treatments that are most used clinically for the prevention of adhesions in the pelvis have been evaluated experimentally using peritoneal abrasion in the rat. In a first experiment these products, namely dexamethasone, high molecular weight dextran, and noxytioline, were compared with a saline solution on the one hand which confirmed the effect of these substances in preventing adhesions, and on the other hand showed that noxytioline was about as effective as dextran 70 and better than corticosteroids. The score for adhesions that were found were; in the control series an average of 9.25, in the dexamethasone series 6, in the dextran 70 series 4.1 and in the noxytioline series 4.00. This last substance, which has been for less broadly studied than dextran, was then made the subject of a second experiment carried out in the same way as the first, and showing that the anti-adhesion effect was not something that was added on to its anti-bacterial effect because noxytioline alone was more effective than a broad spectrum antibiotic by itself, and adding the two together gave a still better result. It would seem to us that using noxytioline and dextran 70 together does not improve the results achieved by using each substance by itself.

[Prevention of peritoneal adhesions. An experimental study using noxytiolin (author's transl)]. / Prévention de adhérences péritonéales. Etude expérimentale de la Noxytioline.

Numerous procedures have been used to try to prevent peritoneal adhesions following operations. Noxytiolin has been used experimentally in the rat in a double blind trial on 3 series of 30 rats. A reliable procedure for making adhesions is said to be always reproducible. Comparing two control groups this study shows that statistically significantly this product lessens the number and seriousness of adhesions that can form, although it does not totally stop them developing.

Ileal digestibility of amino acids of cassava, sweet potato, cocoyam and erythrina foliages fed to growing pigs.

Ileal digestibility in growing pigs fed starch-based diets with inclusion of four tropical leaves in a meal form was studied in a 5 × 5 Latin square design. Five diets were formulated with only casein as protein source in the basal diet (CAS), and casein plus dry cassava (CA) leaves, casein plus dry sweet potato (SP) leaves, casein plus dry cocoyam (CO) leaves and casein plus erythrina (ER) leaves in the other four diets. All diets contained the same amount of CP (14%), either provided by only CAS or a combination of casein and 250 g of leaf meal per kg of diet in the other diets. Leaves were separated manually from stems, and only the leaf part was used. A protein-free diet was fed during a sixth period in order to estimate the endogenous protein losses and calculate the CP- and amino-acid (AA)-standardized ileal digestibility (SID) values. The values for the foliages were calculated according to the difference method, assuming no interaction between the foliage and the casein. The ileal tract apparent digestibility of CP, organic matter and energy was higher in diet CAS than in the other diets (P < 0.05). The SID of CP and AA was close to 0.950 for casein, whereas the SID of AA was markedly lower in the foliages; the SID of indispensable and dispensable AA was highest in CO (0.500 and 0.352) and lowest in ER (0.170 and 0.195); intermediate values were obtained for SPs (0.367 and 0.349) and CA (0.232 and 0.242) leaves. Accordingly, the SID of lysine was highest (0.538) for CO leaves and lowest (0.126) in ER leaves; intermediate values were measured for CA and SP leaves. These low SID values in foliage meals must be related to the high levels of dietary fibre and the presence of secondary metabolites (tannins). These results suggest that it is only possible to replace a fraction of the conventional protein sources such as soyabean meal by tropical foliages in growing pig diets with a preference for CO leaves.

Quarterly individual outpatients lifestyle counseling after initial inpatients education on type 2 diabetes: the REDIA Prev-2 randomized controlled trial in Reunion Island.

AIMS: This study aimed to describe the 1-year evolution of type 2 diabetes (T2D) patients who attended inpatients education, and to assess whether quarterly outpatients counseling visits by nurses and dietitians can improve metabolic control and health-related behaviours. METHODS: Following in-hospital educational sessions, 398 adult T2D patients were randomized to either attend quarterly individual lifestyle counseling visits by a nurse and a dietitian (intervention group), or receive the usual care (control group). Primary (HbA(1c)) and secondary endpoints (fasting blood glucose, lipids, body mass index, waist circumference, fat mass, blood pressure, diet, physical activity) were assessed at baseline and at 12 months. RESULTS: HbA(1c) changes from baseline to 12 months were -1.74±2.64% (P<0.0001) for the intervention group and -2.02±2.57% (P<0.0001) for the control group. There was no statistically significant difference between the intervention group (n=153) and the controls (n=166) for any of the clinical and biological outcomes. In both groups, total energy and fat intakes decreased significantly from baseline levels. Also, no difference was found between the groups for any dietary outcome. A slight enhancement in sports activity was observed in the intervention group, but the difference between the two groups did not reach statistical significance, and no difference was found concerning any other physical activity scores. CONCLUSION: In this study of adults with T2D, patients significantly improved their metabolic control, and dietary and exercise habits, 1 year after receiving intensive inpatients education, whereas subsequent quarterly outpatients counseling visits with nurses and dietitians have not demonstrated any superiority compared with the usual care.