Search PubMed⌕ Search

Biomedical subjects

P Bernard

Publications and source records attributed to P Bernard.

At least 145 records · Page 8Linked to original sources
PubMed1999

[Ischemic colitic in the elderly: predictive factors of gangrenous outcome].

OBJECTIVE: To better characterize the presentation of gangrenous and non-gangrenous ischemic colitis in subjects older than 60 years, and to identify risk factors of gangrenous outcome. METHODS: Retrospective analysis of 80 cases of ischemic colitis (22 male, 58 female; mean age 76.9 +/- 8.7 years) with 64 and 16 non gangrenous and gangrenous forms, respectively. RESULTS: Hematochezia and diarrhea were significantly less prevalent in gangrenous colitis compared to the non-gangrenous group (31.2% vs 81.2%, P < 0.0001 and 6.2% vs 53.1%, P < 0.0001, respectively), whereas nausea and vomiting, and hyperleukcocytosis were significantly more frequent in the former group (50.0% vs 18.7%, P < 0.01 and 93.7% vs 62.5%, P < 0.02 respectively). Hypertension (P < 0.03), angina (P < 0.05), history of cancer (P < 0.03) and age older than 90 (P < 0.002) were risk factors for gangrenous outcome. After multivariate analysis, only two independent factors were identified, i.e.: hypertension and history of cancer. These factors predicted gangrenous course in 85% of cases. CONCLUSION: Patients older than 60 years suffering from ischemic colitis are at high risk of gangrenous course if they have hypertension or history of cancer.

Aged↗
PubMed1999

[Contribution of ultrasonography-guided microbiopsy in breast diseases].

OBJECTIVE: To assess the usefulness of core biopsy under ultrasonography (CBUS). MATERIALS AND METHODS: 165 US guided breast lesions biopsies were reviewed. Forty-eight underwent surgery and the 117 remaining cases were followed up for at least one year. Forty-four lesions were malignant and 89 were no palpable. Lesion size ranged from 3 to 35 mm (mean 14.8 mm). Core biopsy was performed with an automatic device with a 18 Gauge needle using a long-throw (2.2 cm excursion). Needle length was 10 cm. At least two passes were performed. RESULTS: Five false negatives were obtained which were all explained. All the infiltrative carcinomas without microcalcifications as mammographic sign were correctly diagnosed. A resolutive hematoma was the only complication to occur. None of the lesions with follow up showed any evolution. With CBUS, sensitivity for malignancy was 91% and specificity 100%. This is in agreement with previous studies. CONCLUSION: Methodology and indications of such core biopsies are peculiar. Actually, the lesion must be seen with ultrasonography and should not be superficial, be correlated with microcalcifications, or be a cyst even with a thick content. This method is safe and comfortable. It is not expensive when compared with surgery or stereotaxy. It should avoid useless surgical open biopsies as it allows histologic diagnosis with Scarff and Bloom grading and hormonal receptor status. So, US guided core-biopsy should contribute to increase the predictive positive value of surgical biopsy in senologic screening.

Adolescent↗
PubMed1999

[Oncogenic mucosal human papillomaviruses in Bowen's disease of the hands].

INTRODUCTION: The association between genital Bowen Disease (BD) and human papillomavirus (HPV) especially HPV-16 infection is well known, but it is more rarely related to extragenital BD. The aim of this study was to detect the presence of oncogenic HPV infection in the BD of the hands considering the histology and the presence of oncogenic HPV detected by in situ hybridization (ISH) and polymerase chain reaction (PCR). MATERIAL AND METHODS: Eleven formalin-fixed and paraffin-embedded samples of BD of the hands were selected. We looked for koilocytosis using standard histological procedure. ISH was performed using genomic HPV DNA probes types 16, 18 and 33 labeled with digoxigenin. Next, with a new amplification system using biotinyled tyramide (Kit Dako Gen Point K620) was used to detect hybrids. Otherwise, Baay's HPV type specific primers (type 16, 18, 31 et 33) were chosen for PCR. RESULTS: Koilocytosis were observed in all cutaneous samples. HPV 16 was detected in 9/11 cases (82 p. 100): 2/10 with ISH and 9/11 with PCR. DISCUSSION: We report here the largest series of BD of the hands, associated with HPV type 16 infection. This high rate (82 p. 100) compared to the other series is linked to the high sensitivity of PCR and is increased by the choice of Baay's oligonucleotide primers. Besides, the low HPV rate (2/10) by ISH, is similar to those obtained in the other series. Although ISH is less sensitive than PCR, the morphological study was useful to argue the pathogenicity of HPV. Finally, the high prevalence of genital oncogenic HPV on the hands, plaid in the scratching hypothesis resulting in autoinoculation from HPV lesions in the genital region.

Aged↗
PubMed1998

Fission yeast bub1 is a mitotic centromere protein essential for the spindle checkpoint and the preservation of correct ploidy through mitosis.

The spindle checkpoint ensures proper chromosome segregation by delaying anaphase until all chromosomes are correctly attached to the mitotic spindle. We investigated the role of the fission yeast bub1 gene in spindle checkpoint function and in unperturbed mitoses. We find that bub1(+) is essential for the fission yeast spindle checkpoint response to spindle damage and to defects in centromere function. Activation of the checkpoint results in the recruitment of Bub1 to centromeres and a delay in the completion of mitosis. We show that Bub1 also has a crucial role in normal, unperturbed mitoses. Loss of bub1 function causes chromosomes to lag on the anaphase spindle and an increased frequency of chromosome loss. Such genomic instability is even more dramatic in Deltabub1 diploids, leading to massive chromosome missegregation events and loss of the diploid state, demonstrating that bub1(+ )function is essential to maintain correct ploidy through mitosis. As in larger eukaryotes, Bub1 is recruited to kinetochores during the early stages of mitosis. However, unlike its vertebrate counterpart, a pool of Bub1 remains centromere-associated at metaphase and even until telophase. We discuss the possibility of a role for the Bub1 kinase after the metaphase-anaphase transition.

Amino Acid Sequence↗
PubMed1998

Response at three months is a good predictive factor for newly diagnosed chronic myeloid leukemia patients treated by recombinant interferon-alpha.

In a single institution, we have used recombinant interferon- (IFN-) to treat 116 newly diagnosed Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) patients and analyzed the predictive factors for response and survival. The patients whose median age was 50.3 years (range, 9 to 70) were administered IFN- (5 million units/m2/d) subcutaneously. The IFN- dose was subsequently adjusted to maintain the white blood cell and platelet counts between 1.5 and 5 x 10(9)/L, 50 and 100 x 10(9)/L, respectively. At diagnosis, the Sokal score was used to classify the patients into three groups: low (n = 57), intermediate (n = 42), and high risk (n = 16). A complete hematological response (CHR) was achieved in 93 cases (80.2%). Of the 116 patients, 113 were available for cytogenetic evaluation. Fifty patients (43%) achieved a major cytogenetic response (MCR) (=65% marrow Ph- cells), 37 of them having a complete cytogenetic response (CCR). The estimated 5-year survival of the 116 patients was 68% +/- 11% (95% confidence interval [CI]) with a median follow-up of 42 months (range, 3 to 114) and 85% +/- 11% (95% CI) with a median follow-up of 30.9 (range, 3 to 111) when patients were censored at the time of transplantation. Event-free survival at 5 years (adding death and transplant as event) was 46% +/- 11% (95% CI). Using proportional hazards regression to study time-dependent variables, we confirmed that the most significant factor associated with survival was the cytogenetic response (MCR or CCR) (P <.0001). This factor was independent compared with the Sokal score and baseline variables used to calculate the Sokal score. Moreover, using either univariate or multivariate analysis, the achievement of CHR within 3 months was strongly correlated with MCR (P <.0001). Minimum cytogenetic response (mCR, ie, at least 5% of Ph- metaphases) at 3 months was also a significant predictive factor for MCR (P <.0001). These results show that IFN- can induce a high rate of hematological and cytogenetic response when administered in doses leading to myelosuppression. Factors such as the achievement of CHR and mCR within 3 months could be useful to identify early those patients who will not respond to IFN- and who need alternative treatments such as stem cell transplantation.

Administration, Cutaneous↗
PubMed1998

Fluorescent in situ hybridization on flow-sorted cells as a tool for evaluating minimal residual disease or chimerism after allogenic bone marrow transplantation.

We studied the feasibility and the sensitivity of fluorescent in situ hybridization (FISH) using leukemic or host/donor-specific probes on flow-sorted cells to assess minimal residual disease (MRD) or chimerism in transplanted patients in complete remission. We first performed experimental models of MRD and chimerism by mixing HL60 cells and normal lymphocytes in different proportions. Over 80% HL60 cells were obtained from mixtures of 5% HL60 cells in peripheral blood mononuclear cells (PBMC). We then evaluated MRD and mixed chimerism in a chronic myelogenous leukemia patient in relapse after allogeneic sex-mismatched bone marrow transplantation (BMT), who had received a donor lymphocyte infusion (DLI). Three months after DLI, mixed chimerism was observed in each bone marrow (BM)-sorted lineage (CD13+, CD14+, CD20+, and CD3+), with the highest level of recipient cells in the granulocytic lineage (CD13+). Five months after DLI, host cells were at a low level but remained detectable in the granulocytic lineage. In the same sample, the bcr-abl gene was detected in the granulocytic lineage and not in the lymphocytes. We also studied chimerism in an aplastic anemia sex-mismatched transplanted female patient. We determined the proportion of recipient total lymphocytes, CD4+ and CD8+ lymphocytes, and CD14+ monocytes under cyclosporin A therapy on five peripheral blood samples and one BM sample over 5 months. Results showed a regular decrease in recipient total lymphocytes (26.6% to 10.6%) and monocytes (20.7% to 8%). CD8(+)-recipient cells decreased rapidly, while CD4+ remained stable (17%). This work demonstrates the feasibility of FISH after cell sorting, combining the sensitivities of both flow cytometry and FISH and the specificities of both immunophenotyping and genotype analysis.

Anemia, Aplastic↗
PubMed1998

Construction of a human BcgI DNA fragment library.

A library made up of 36bp DNA fragments generated by digestion of human DNA with the restriction endonuclease Bcg I has been constructed. It contains 2.5x106 independent clones, representing several times the total human genome which should contain about 400000 such fragments. It is proposed to make use of these BcgI fragments to clone part of the coding sequences contained in the minor H3 isochore which represents 3% of the human genomic DNA and a quarter of all genes.

Cloning, Molecular↗
PubMed1998

Cytometric study of intracellular P-gp expression and reversal of drug resistance.

Expression of the multidrug resistance (MDR) phenotype is responsible for chemotherapy failure in numerous cancers. This phenotype is generally due to the expression of the mdr1 gene-encoded P-gp. Modulation of P-gp activity by chemotherapy has limited possibilities because of toxicity and poor specificity. In contrast, specific transcription blockage of the mdr1 gene can be obtained by oligonucleotides forming a triple helix structure at the DNA level. We used here immunofluorescence and both flow cytometry and image analysis to evaluate surface and total P-gp content in K562 MDR cells. The mdr1 mRNA content was measured by RT-PCR. We confirm the capacity of a 27-mer oligodeoxynucleotide, targeted to an mdr1 DNA fragment, to cause a 10-fold decrease in mdr1 mRNA level. However, this specific genetic inhibition was functionally limited because cellular growth was not modified in a cytotoxic environment. We found that total P-gp content was reduced in resistant cells treated with the mdr1-targeted oligonucleotide, while it remained in high levels on the cell surface, suggesting the existence of a large cytoplasmic pool of P-gp (approximately 50% of the total cellular P-gp). Moreover, when cycloheximide was used for 72 h to suppress protein synthesis, surface P-gp expression showed no decrease, whereas total P-gp was considerably lowered. A rapid 35% decrease in surface P-gp level was reached when resistant cells were treated for 24 h with brefeldin A, an inhibitor of intracellular protein trafficking. Simultaneously, the total P-gp level remained stable, thus indicating a probable accumulation of cytoplasmic P-gp, in agreement with the interruption of protein migration. We propose that the cytoplasmic P-gp pool could be a storage pool consumed for maintaining a steady-state level of surface P-gp. Cytometry could be a useful tool to study such a mechanism of P-gp trafficking and cellular distribution, which could explain the difficulties encountered in achieving stable and rapid effects of MDR reversal with oligonucleotides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Caspase activation is an early event in anthracycline-induced apoptosis and allows detection of apoptotic cells before they are ingested by phagocytes.

An increasing number of methods are being described to detect apoptotic cells. However, attempts to detect apoptotic cells in clinical samples are rarely successful. A hypothesis is that apoptotic cells are cleared from the circulation by phagocytosis before they become detectable by conventional morphological or cytometric methods. Using LR73 adhering cells as phagocytes in a model of in vitro phagocytosis, we found that phagocytosis of daunorubicin (DNR)-treated U937, HL60, or K562 leukemia cell lines occurred prior to phosphatidylserine externalization, DNA hydrolysis, chromatin condensation, nuclear fragmentation, or mitochondrial potential alteration. Moreover DNR-treated K562 cells were eliminated by phagocytes while apoptosis was never observed by any of the above methods. By contrast, using a fluorometric batch analysis assay to detect caspase activity in ceramide- or DNR-treated cells (fluorogenic substrate for caspase), we found that caspase activity increased in apoptosis-committed cells before they were detected by flow cytometry or recognized by phagocytes. Similarly a caspase activity increase was detected in circulating mononuclear cells of luekemic patients 15 h after the beginning of anthracyclin treatment. We suggest that recent findings on enzymatic events (caspase activation) occurring in the early events of apoptosis must now allow the development of new markers for apoptosis, irrespective of the morphological features or internucleosomal fragmentation which are late events in apoptosis.

Animals↗
PubMed1998

High risk of death in elderly patients with extensive bullous pemphigoid.

OBJECTIVE: To evaluate survival and factors predicting death in bullous pemphigoid. DESIGN: Retrospective analysis of cohort. SETTING: Three referral centers (university hospitals). PATIENTS: Among 237 patients recruited between January 1, 1985, and December 31, 1992, 20 were excluded because of doubtful diagnosis. The 217 remaining patients were 79+/-11 years old (mean+/-SD); 120 were women and 97 were men; and 79% had been treated with oral corticosteroids, 40 to 90 mg/d. INTERVENTIONS: Missing information on follow-up was minimized by letters and/or telephone calls to patients, families, nursing homes, and physicians. MAIN OUTCOME MEASURES: Actuarial survival curve, compared with the expected curve as derived from census data, and evaluation of prognostic factors by comparing initial characteristics between patients alive at 6 months and these who died before that point. RESULTS: Survival curve demonstrated an early increased mortality: 17% at 3 months and 31% at 6 months, mainly from sepsis and cardiovascular diseases. Of the factors related to bullous pemphigoid activity (duration; pruritus; and number and extent of blisters, eosinophilia, and serum antibodies) only generalized pemphigoid was predictive of death in comparison with localized forms. In multivariate analysis, age of 86 years or more (relative risk, 7.1; 95% confidence interval [CI], 2.0-25.4; P < or = .01), poor general condition (relative risk, 8.2; 95% CI, 3.0-22.4; P < or = .001), female sex (relative risk, 2.4; 95% CI, 1.1-5.4; P < or = .05), and generalized disease (relative risk, 4.4; 95% CI, 1.4-13.7; P < or = .01) were associated with increased risks of death at 6 months. CONCLUSION: In this series, generalized bullous pemphigoid had a poor prognosis especially in older patients and those in poor general condition.

Aged↗
PubMed1998

Evaluation of clinical criteria for diagnosis of bullous pemphigoid. French Bullous Study Group.

OBJECTIVE: To check the potential usefulness of clinical criteria for the diagnosis of bullous pemphigoid when state-of-the-art techniques such as Western immunoblotting, immunoprecipitation, and indirect immunofluorescence on salt-split skin or direct immunoelectron microscopy are not available. DESIGN: Comparison of the clinical criteria between 2 groups (with and without bullous pemphigoid) as defined by immunoelectron microscopy used as standard criterion, in a prospective study. Multivariate logistic regression analysis was carried out by including all items that were statistically significant (at P < .05 level) in univariate analysis. SETTING: Five dermatology departments in teaching hospitals. PATIENTS: The 231 patients studied had subepidermal autoimmune bullous diseases with linear IgG or C3 deposits in the basement membrane zone (157 with bullous pemphigoid, 33 with cicatricial pemphigoid, 30 with epidermolysis bullous acquisita, 5 with lupus erythematosus, and 6 others). A second set of patients was used to calculate predictive values. RESULTS: The multivariate logistic stepwise analysis resulted in a final set of predictors that included only 4 items: absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and age greater than 70 years. No additional variables met the .05 significance level to enter into the model. If 3 of these 4 characteristics were present, a diagnosis of bullous pemphigoid could be made with a sensitivity of 90% and a specificity of 83%; these predictive values were calculated on a sample of 70 new cases. CONCLUSIONS: With and estimated incidence of bullous pemphigoid among subepidermal autoimmune bullous diseases of 80%, the presence of 3 of the 4 significant criteria allows the diagnosis of bullous pemphigoid, with a positive predictive value of 95%. Our set of clinical criteria thus allows the diagnosis of bullous pemphigoid with good validity for both clinical practice and therapeutic trials.

Aged↗
PubMed1998

Prognostic significance of stromelysin 3, gelatinase A, and urokinase expression in breast cancer.

This study was aimed at testing the hypothesis that the expression of proteases essentially produced by reactive stromal cells (stromelysin-3 [ST3], gelatinase A [GELA], and urokinase [uPA]) is predictive of prognosis in patients with breast cancer. This was a study of patients with node-positive and node-negative breast cancer diagnosed from 1980 to 1986 and with an average of 10 years follow-up. ST3 (665 cases), GELA, and uPA (575 cases each) expression was obtained by in situ hybridization on formalin-fixed, paraffin-embedded material using mRNA antisense probes. ST3 was expressed by 86.6% of the cases; GELA, 77.7%; and uPA, 64.7%. A significant correlation (P < .05) was found between high (more than 10%) ST3 expression and a younger age, lymph node involvement, poor nuclear grade, ductal histology, aneuploidy, and HSP-27 expression. High GELA expression was significantly associated with c-erbB2, ductal histology, and HSP-27 expression. High uPA expression correlated with poor nuclear grade, ductal histology, lack of estrogen and progesterone receptors, and p53 protein accumulation. High level of expression of all three proteases correlated significantly with each other and with cathepsin D expression by reactive stromal cells. By univariate analysis, both ST3 and uPA expression significantly predicted a shorter recurrence-free survival (ST3, P = .0199; uPA, P = .0269). By multivariate analyses, the prognostic significance was lost, most particularly at longer term. This study adds support to the concept that protease expression by reactive stromal cells is related to cancer cell characteristics but that their contribution to cancer progression is marginal.

Adult↗
PubMed1998

[Familial autoimmune hepatitis and C4 deficiency].

INTRODUCTION: Familial auto-immune hepatitis is unusual. We report a case in which hepatitis was associated with a deficiency in the C4 component of the complement. EXEGESIS: Type 1 auto-immune hepatitis A was diagnosed in a 38-year-old woman presenting with systemic lupus erythematosus. Her daughter had to undergo a splenectomy for immunologic thrombocytopenic purpura when she was 9 years old. When she turned 13, she further developed type 1 autoimmune hepatitis. During follow-up (4 and 8 years, respectively), both patients had a mild deficiency in C4. CONCLUSION: C4 deficiency is not only frequently observed in relatives of patients with auto-immune hepatitis, but also in familial systemic lupus. This abnormality may have had a crucial pathogenic role in these two patients.

Adolescent↗
PubMed1998

[Nuclear transcription factor kappa B (NF-kappa B)].

INTRODUCTION: The transcription factor NF-kappa B is a key regulator of genes involved in responses to infection, inflammation and stress. It was first identified as a protein with ADN-binding activity specific for the 10-base-pair kappa B site in the immunoglobulin k light-chain enhancer of B lymphocytes. CURRENT KNOWLEDGE AND KEY POINTS: NF-kappa B is normally present in the cell cytoplasm bound to an inhibitory I kappa B protein. The nuclear localization signal (NLS) in NF-kappa B is a short amino acid signal sequence involved in nuclear transport. Inducers of NF-kappa activation trigger dissociation and degradation of I kappa B from the NF-kappa B complex. This allows NF-kappa B to translocate to the nucleus and bind to kappa B DNA sites. Repression of NF-kappa B dependent gene expression is one of the major elements of immunosuppression by glucocorticoids. FUTURES PROSPECTS AND PROJECTS: Endothelial cells at sites of inflammatory responses express a variety of genes that are under the control of nuclear factor NF-kappa B. This transcriptional factor with its inhibitors may be linked in an autoregulatory system that can be activated by multiple signals relevant to vascular pathophysiology. NF-kappa B is therefore an obvious target for new types of anti-inflammatory treatment.

Endothelium↗
PubMed1998

Stable mixed chimerism without relapse after related allogeneic umbilical cord blood transplantation in a child with severe aplastic anemia.

Umbilical cord blood (UCB) cells from HLA-matched donors are used as an alternative to bone marrow for allogeneic transplantation and reports of successful UCB transplantation in patients with severe aplastic anemia (SAA) are scarce. SAA was discovered in a 4-year-old girl in February 1990. Transfusion support started in August 1990 and standard treatments were unsuccessful. The birth of an HLA-compatible brother in October 1993 permitted the cryopreservation of UCB. In December 1994 UCB transplantation was decided upon. No toxicity occurred. G-CSF was started at day 28. WBC and PMN reached 0.5 x 10(9)/l at days 33 and 37. RBC and platelet transfusion independence were reached at days 50 and 52. Mixed chimerism was demonstrated in blood cells at 1.5, 4 and 6 months after UCBT by molecular biology (VNTR). FISH studies yielded similar results at 15 and 18 months. Twenty months after UCBT, molecular biology showed full donor chimerism. Clinical follow-up (last follow-up: 32 months post transplant) is unremarkable. We suggest that CY and ATG may be a suitable regimen for related HLA-compatible UCBT in patients with SAA. Residual recipient cells can disappear even very late after UCBT, permitting the establishment of complete donor chimerism.

Anemia, Aplastic↗
PubMed1998

Factors influencing haemopoietic recovery following chemotherapy-mobilised autologous peripheral blood progenitor cell transplantation for haematological malignancies: a retrospective analysis of a 10-year single institution experience.

We retrospectively analysed the factors that influenced rate of haemopoietic recovery (HR) in 243 patients after transplantation with chemotherapy-mobilised autologous peripheral blood progenitor cells (PBPC). Approximately half the patients also received haemopoietic growth factors (HGF) for mobilisation. Conditioning for transplantation was with either chemotherapy alone or chemotherapy plus total body irradiation (TBI). Median time to recovery of granulocytes > or = 0.5 x 10(9)/l was 13 days (range 7-93 days) and of platelets > or = 50 x 10(9)/l 14 days (7-440). Speed of HR was greater, both for neutrophils and platelets for patients who received more rather than less CFU-GM than our median value of 18.9 x 10(4)/kg (P < 0.0001 in both instances) and more rather than less CD34-positive cells than our median value of 8.8 x 10(6)/kg (P < 0.0001 and P < 0.0005, respectively). For granulocyte recovery, in the multivariate analysis the dose of infused CFU-GM (P = 0.05) and the use of HGF for both mobilisation and post-transplantation (P < 0.0014) were significant positive factors. For platelet recovery in the multivariate analysis the dose of infused CFU-GM (P < 0.0016) was a positive factor. The use of busulphan and of TBI were significant adverse factors for rate of platelet recovery (P = 0.005 and 0.0004, respectively). When compared with non-HGF-mobilised PBPC, HGF-mobilised PBPC reduced the number of days of hospitalisation (28 vs 24, P = 0.0001) and of treatment with intravenous antibiotics (15 vs 11, P = 0.0004). These findings emphasise the importance of cell dose in accelerating haemopoietic recovery after autologous blood stem cell transplantation.

Adolescent↗