Biomedical subjects
P Bernard
Publications and source records attributed to P Bernard.
[Pelagia noctiluca jellyfish poisoning on the Mediterranean coast].
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[Complicated colonic diverticulosis. Results of surgical treatment between 1981 and 1998 in 370 patients].
AIM OF THE STUDY: The aim of this retrospective study was to analyze case reports of all the patients with complicated diverticular disease of the colon admitted in the same surgical center during an 18-year period and to report the postoperative results in patients operated on in emergency and in patients operated on electively. PATIENTS AND METHOD: From 1981 to 1998, 501 patients were admitted for complicated diverticular disease. There were 233 men and 268 women. Mean age was 66 years (range: 27-96). One hundred and thirty-one patients were only treated medically and 370 patients were operated on, either as an emergency (n = 211) or electively (n = 159). The complicated diverticular disease was located on the left colon in 362 cases and in the right colon in 8 cases. RESULTS: In the emergency group, 103 patients were operated on for pelvic (n = 24) and generalized purulent (n = 67) or stercoral (n = 12) peritonitis, mainly with Hartmann procedure (n = 80) with 14 postoperative deaths; 67 were operated on for pericolic abscess with 6 deaths, 19 for colonic obstruction with two deaths and 22 for profuse hemorrhage with 4 deaths. The overall postoperative mortality rate was 12.3%, and morbidity rate 38.7%. Intestinal continuity was restored in 74% and eventrations were present in 10%. In the elective group, there were two postoperative deaths in patients with a colic fistula (n = 30), no mortality and a 10.8% morbidity rate in the other patients (n = 129). CONCLUSION: This series of an 18-year duration emphasizes the severity of surgery for acute complications in diverticular disease of the colon and the advantages of elective surgery. Large progress in the management of peritonitis and pericolic abscesses has made possible the improvement of their prognosis.
Validation of protein-based alignment in 3D quantitative structure-activity relationships with CoMFA models.
The predictive capabilities of protein-based alignment (PBA) and structure-based alignment (SBA) comparative molecular field analysis (CoMFA) models have been compared. 3D quantitative structure-activity relationship (3D QSAR) models have been derived for a series of N-benzylpiperidine derivatives which are potent acetylcholinesterase (AChE) inhibitors interesting for Alzheimer's disease. To establish a comparison with the classical SBA procedure, different assay models were derived by superposing ligand conformers that are docked to the AChE active site and by using the most active compound as the reference one. A Kohonen self organizing map (SOM) was applied to analyse the molecular diversity of the test set relative to that of the training set, in order to explain the influence of molecular diversity on the predictive power of the considered models. SBA 3D QSAR models have to be used to predict the inhibitory activity only for compounds belonging to subgroups included in the training set. The PBA 3D QSAR models appeared to have a higher predictability, even for compounds with a molecular diversity greater than that of the training set. This results from the fact that the protein helps to automatically select the active conformation which is fitting the 3D QSAR model.
[Olfactory esthesioneuroma manifesting as Schwartz-Bartter syndrome].
INTRODUCTION: Olfactory esthesioneuroblastoma is an uncommon neuroectodermal tumor originating from the olfactory epithelium, which is rarely associated with hormone excess syndrome. EXEGESIS: Asymptomatic olfactory esthesioneuroblastoma was diagnosed in a 22-year-old man who presented a syndrome of inappropriate antidiuretic hormone secretion. Following surgery, the immunohistochemical analysis demonstrated the existence of neurophysin hormone in tumoral cells. CONCLUSION: This case provides evidence that olfactory esthesioneuroblastoma can be uncovered by inappropriate antidiuretic hormone secretion.
[Secondary cutaneous effects of hydroxyurea: prospective study of 26 patients from a dermatologic consultation].
PURPOSE: Hydroxyurea is a treatment of myeloproliferative syndromes. Its cutaneous side-effects are underestimated, because they are usually benign. We undertook a prospective study to evaluate their frequency. METHODS: During a 2-year period, all patients taking hydroxyurea for more than 6 months who had consultations at the dermatology department were systematically examined, regarding cutaneous side effects. RESULTS: Twenty-six patients were examined. All but one had cutaneous side-effects, including dryness (n = 16), moderate alopecia (n = 2), increased skin pigmentation (n = 5), melanonychia, single (n = 1) or multiple (n = 7), cutaneous atrophy (n = 4), leg ulcers (n = 8), plantar keratoderma (n = 3), pseudodermatomyositis (n = 1), lichen planus-like eruption on the dorsum of the hands (n = 2), actinic keratosis (n = 8), squamous cell carcinomas (n = 2), and mouth ulcerations (n = 1). CONCLUSION: This study shows that the frequency of hydroxyurea cutaneous side-effects diagnosed in 95% of studied patients is underestimated. They are usually benign, but some of them, in particular leg ulcers and squamous cell carcinomas, lead to modification of the treatment (39% of studied patients).
Twin-to-twin transfusion syndrome: treatment by amniodrainage and septostomy.
OBJECTIVE: Severe previable twin-to-twin transfusion syndrome (TTTS) is associated with a high fetal loss rate and is therefore usually treated. In this paper, serial amniodrainage and inter-twin septostomy are reviewed in terms of technical aspects and fetal outcome. STUDY DESIGN: A review of the literature using a MEDLINE DATA search between 1990 and 2000 was done in order to describe the mechanisms and technical aspects of both procedures with their physiopathological consequences. In addition, data from our experience with septostomy are given. RESULTS: Amniodrainage increases survival rate, with outcome ranging from 40 to 87% (mean: 56%). Inter-twin septostomy is associated with a mean fetal survival rate ranging from 57 to 83% (mean: 70%). CONCLUSION: In severe TTTS, amniodrainage and septostomy are simple therapeutic alternatives with a survival rate similar to what is currently reported for laser coagulation of placental vessels.
Early transitory rise in intracellular pH leads to Bax conformation change during ceramide-induced apoptosis.
Ceramide can induce apoptosis through a caspase independent pathway. Bax has been described as able to kill cells in the absence of caspase activity, therefore we measured Bax in situ during ceramide-induced apoptosis using anti-Bax antibodies and flow cytometry analysis. An early (<30 min) increase in Bax labeling was observed after the addition of several ceramide species to several hemopoietic-related cell types. On U937, this increase was not due to antigens synthesis or processing, but rather an increased accessibility or reactivity of Bax antigens for antibodies. This increased immuno-reactivity of Bax was not inhibited by Z-VAD-fmk nor leupeptin, and preceded nuclear fragmentation by several hours. Such an increase in immuno-reactivity was also observed after Fas ligation, but it occurred later (>2 h) accompanying nuclear apoptosis, and was inhibited by Z-VAD-fmk. Bax immuno-reactivity was found to be related to intracellular pH (pHi), and C2-Ceramide (C2-Cer) induced a very early (<10 min) transitory increase in pHi. Both Bax immunoreactivity and pHi increases were dependent on the mitochondrial permeability transition pore (PTP) status. It was concluded from these results that C2-Cer induced a transitory increase in pHi in relation to the PTP. This rise in pHi led to conformational changes in Bax which could be responsible for further apoptosis in the C2-Cer pathway while it was a consequence of caspase activation in the Fas pathway.
Implication of interleukin-4 in wound healing.
Interleukin-4 (IL-4) is a pleiotropic cytokine that is able to activate connective tissue cells and stimulate the accumulation of extracellular matrix macromolecules. In this report, the expression of IL-4 in normal wound healing was studied by immunohistochemistry. The effects of exogenous IL-4 or IL-4 antisense oligonucleotides administration were also studied in mouse experimental wounds. IL-4 expression was detected in the lower dermis below the wound as early as Day 1 after wounding. IL-4 expression was maximal by Day 4, then decreased progressively, and completely disappeared by Day 21 after wounding. Topical administration of IL-4 on experimental wounds in mice significantly accelerated the rate of healing, whereas IL-4 antisense oligonucleotides significantly inhibited healing. These results demonstrate that IL-4 may be implicated in normal wound healing.
Role of drug exposure in aphthous ulcers: a case-control study.
BACKGROUND: Drug-induced aphthous ulcers have been the subject of several isolated and heterogeneous case reports for the last three decades. OBJECTIVES: To perform a case-control study to evaluate the risks linked to drug exposure in aphthous ulcers. METHODS: Eighty patients with typical clinical patterns of aphthous ulcers and 152 control patients who had had consultations for skin tumours were studied. A standardized questionnaire, concerning clinical features, life-style and medications taken during the last month, was completed for each patient. RESULTS: Case patients had a much higher intake of medications than control patients, respectively, 5.1 and 2. 8 medications per patient (P < 0.0001). Multivariate paired analysis showed an association between aphthous ulcers and two classes of drugs: non-steroidal anti-inflammatory drugs (P < 0.001) and beta-blockers (P = 0.002). Smoking could have a protective effect against aphthous ulcers (P < 0.001). CONCLUSIONS: Previous case reports and the results of this study suggest a real link between beta-blockers and aphthous ulcers. Our study did not confirm a role of other drugs but a few interesting case reports with positive reintroduction have to be considered. These results could be beneficial for patients, as healing may occur when the incriminated drug is discontinued.
Relationship between cell-associated matrix metalloproteinase 9 and psoriatic keratinocyte growth.
Primary cultures of psoriatic keratinocytes proliferated at a higher rate and produced lower amounts of matrix metalloproteinase 9 than normal keratinocytes cultured under similar conditions. Sup- plementation of psoriatic keratinocyte cell culture medium with batimastat or the use of a matrix metalloproteinase 9 blocking antibody further stimulated psoriatic keratinocyte growth. An increase in intracellular ceramide level enhanced matrix metalloproteinase 9 production and inhibited cell proliferation in parallel. Whether cells were treated with sphingomyelinase or not, however, conditioned media from psoriatic keratinocytes contained higher levels of tissue inhibitor of metalloproteinase-1 compared with matrix metalloproteinase 9 and secreted only the proenzyme form. Pro-matrix metalloproteinase 9, as well as active matrix metalloproteinase 9, was identified in membrane preparations of psoriatic keratinocytes, and enzyme amounts were greatly elevated following sphingomyelinase action. As (i) tissue inhibitor of metalloproteinase-1 antibody nearly totally abrogated keratinocyte growth and (ii) complexes of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase 9 were recovered in membrane extracts of sphingomyelinase-treated psoriatic keratinocytes, we postulate that an increased level of cell-associated matrix metalloproteinase 9 might compete for tissue inhibitor of metalloproteinase-1 binding to its receptor. As a consequence, the increased levels of matrix metalloproteinase 9 will decrease keratinocyte growth.
IgG autoantibodies from bullous pemphigoid patients recognize multiple antigenic reactive sites located predominantly within the B and C subdomains of the COOH-terminus of BP230.
Bullous pemphigoid is a subepidermal bullous disorder characterized by an autoantibody response against the bullous pemphigoid antigen 230 (BP230) and the bullous pemphigoid antigen 180 (BP180), a cytoplasmic component and a transmembrane component, respectively, of hemidesmosomes. Although immunodominant sequences within the extracellular domain of BP180 have been identified, characterization of the antigenic sites on BP230 is still incomplete. To identify autoantibody-reactive sites on BP230 and to examine whether the targeted regions are contained within functionally important domains, recombinant fragments encompassing almost the entire BP230 were used to assess the reactivity of 25 bullous pemphigoid sera by immunoblotting. Our results demonstrate that (i) the region bearing the B and C subdomains of the COOH-terminus of BP230 contains immunodominant sequences recognized by the majority of bullous pemphigoid sera; (ii) additional autoantibody- reactive sites are present over extended regions of the NH2-terminal half of BP230 without evidence for antigenic cross-reactivity between the NH2- and COOH-termini of BP230; and, finally, (iii) autoantibodies reacting with the BP230 tail predominantly belong to the IgG4 and IgG1 subclasses, suggesting that both autoreactive TH2 and autoreactive TH1 cells regulate the autoantibody response to immunodominant sequences of BP230. As the COOH- terminus of BP230 mediates the attachment of keratin intermediate filaments to the hemidesmosomal plaque, whereas its NH2-terminus contains sequences important for its interaction with other constituents of hemidesmosomes, autoantibodies to BP230 might precipitate subepidermal blister formation and perpetuate the disease not only by eliciting an inflammatory reaction but also by interfering with the function of BP230 and thus the stability of hemidesmosomes.
Comparative methodologic study of NFkappaB activation in cultured endothelial cells.
The transcriptional regulatory protein nuclear factor kappaB (NFkappaB) participates in the control of gene expression of many modulators of the inflammatory and immune responses. Various activators trigger NFkappaB release and nuclear translocation after phosphorylation and proteolytic degradation of IkappaB. This study evaluated the abilities of fluorescence and confocal microscopies, laser scanning cytometry (LSC), electrophoretic mobility-shift assay (EMSA), and Western blotting to detect NFkappaB activation in endothelial cells (ECs) and to investigate the role of homocysteine (Hcy) in NFkappaB activation. ECs were treated with interleukin-1B (10 ng/mL) or Hcy thiolactone (1 and 5 mmol/L) as NFkappaB activators. Hcy, a thiol-containing amino acid, has been shown to directly damage ECs in vitro. Experimental evidence suggests that the atherogenic propensity associated with hyperhomocysteinemia results from EC dysfunction. When ECs were pretreated with an inhibitor (pyrrolidine dithiocarbamate, 100 micromol/L) or with staurosporine (5 microL/mL), no NFkappaB activation was observed. NFkappaB activation in ECs could be detected with all five techniques, clearly showing NFkappaB translocation from the cytoplasm to the nuclei. Confocal microscopy was more sensitive and less subjective than immunofluorescence microscopy. LSC was even more sensitive, specific, and reproducible. EMSA, the reference method, has the disadvantages of being radioactive, expensive, and time consuming. Western blot analysis detected the NFkappaB p50 subunit implicated in NFkappaB activation. The techniques usually used to detect NFkappaB activation in ECs are immunofluorescence microscopy and confocal microscopy, LSC, EMSA, and Western blot analysis, but none of them is ready for routine use.
Conservative management of triplet pregnancy after delivery of one foetus.
This paper intends to demonstrate that the conservative management of triplet pregnancy after delivery of one foetus is a feasible and reasonable approach. Three cases of triplet pregnancy with successful conservative management after miscarriage of one foetus, are presented and compared with cases in the literature. The route of delivery, as well as the role of tocolysis, cerclage, prophylactic antibiotic therapy and corticosteroids are discussed. Guidelines for conservative treatment are proposed. The deliveries of our three pregnancies were delayed by 63, 44 and 22 days respectively. Foetal and neonatal evolution are normal in five of the remaining foetuses. Only one intrauterine death is observed. No maternal complications with sequelae are reported. After abortion of the first triplet, contractions often persist and the birth of the two remaining foetuses may be unavoidable. Nevertheless, in our experience, confirmed by some reports in the literature, prolongation of the pregnancy after expulsion of the first foetus is possible. It can be achieved by cervical cerclage associated with tocolytic and antibiotic therapy. This management is not associated with significantly increased foetal-maternal morbidity.
Human papillomaviruses and DNA ploidy in anal condylomata acuminata.
Previous studies have emphasized the usefulness of DNA ploidy measurement and Human Papillomavirus (HPV) detection as prognostic markers in low grade cervical lesions. We addressed the eventual relationship between HPV type, DNA profile, and p53 tumor suppressor protein expression in anal condylomata acuminata to eventually determine parameters which may be considered as predictive risk factors for the development of cancer. DNA ploidy was assessed by image cytometry after Feulgen staining of contiguous serial sections of 45 anal condylomata acuminata without atypia containing HPV detected by in situ hybridization and Polymerase Chain Reaction (PCR). p53 expression was detected by immunohistochemistry. DNA aneuploidy was found in 53.3% of these lesions, 48.9% containing non oncogenic HPV types 6 and/or 11 and 4.4% harbouring HPV types 11 and 18. The DNA diploid lesions were all associated with non oncogenic HPV types 6 and/or 11 and one case also contained HPV type 33. There was no significant correlation between the detection of DNA aneuploidy and the presence of immuno-detected p53. DNA aneuploidy was not related to the presence of oncogenic HPV in anal condylomata acuminata. The DNA aneuploid profile frequently observed, especially in lesions associated with non oncogenic HPV types, is not yet well explained and cannot be considered as a prognostic factor. In contrast, a more intensive clinical follow-up should be proposed in patients with oncogenic HPV associated to DNA aneuploidy.
[Early treatment of sexual exposure to human immunodeficiency virus].
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[Cryosurgery of basal cell carcinoma: a study of 358 patients].
INTRODUCTION: Cryosurgery is a well-established therapeutic modality for basal cell carcinoma. We report herein an important series of basal cell carcinoma treated by cryosurgery, with a five year cure rate evaluation. PATIENTS AND METHOD: Retrospective study with 395 basal cell carcinomas (over 358 patients - sex ratio H/F: 0.85) treated by cryosurgery between 1981 and 1992. For each patient the data were: age, sex, size of the lesion, location, clinical sub-type, tissue-temperature monitoring, recurrence date and esthetic outcome. RESULT: The lesions were located on the face (93 p. 100) and back (7 p. 100). Mean size was 17 mm. Clinical sub-types were known for 178 lesions; 11 p. 100 of BCC were morpheaform. Tissue-temperature monitoring was performed for 55 p. 100 of cases. 111 tumors were observed for more than 5 years. The 5-year actuarial failure rate was 9 p. 100. The 5-year cure rate was not significantly altered by sex, size of lesions, location and clinical sub-type. No frequent recurrences were observed when tissue-temperature monitoring had not been performed. Complications were rare and esthetic outcome was good. DISCUSSION: The 5-year actuarial recurrence rate with cryosurgery is similar to conventional surgery. It is not essential to control tissue-temperature for preventing recurrences. Cryosurgery is a reliable treatment and outcome depends on surgeon experience. Quickness and low cost of this procedure argue for choosing cryosurgery when treating elderly patients.
[Linear radiodermatitis following total body electron beam therapy].
BACKGROUND: We describe herein a peculiar clinical presentation of a linear overlapping radiodermatitis, localized on the internal side of the limbs, following a total body electron beam therapy. CASE REPORT: A 68-year-old-man was treated in April 1998 by a total body electron beam therapy, for a stage I mycosis fungoides. Few days after the last irradiation, the patient suffered from a linear eruption localized on the internal side of the limbs and the external side of the abdominal wall. DISCUSSION: Total body electron beam therapy can be proposed in early stage mycosis fungoides with localized or generalized cutaneous lesions. Because penetration depth of electron is well controlled and is limited to the skin, usual side effects of total body electron beam therapy do not concern internal organs (bone marrow,.). We report here a peculiar clinical presentation of a linear radiodermatitis in frontal plane which has not been reported to date, to our knowledge. This radiodermatitis corresponds to overlapping of posterior and anterior fields of irradiation.