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Biomedical subjects

P Bernard

Publications and source records attributed to P Bernard.

At least 73 records · Page 4Linked to original sources

Double common bile duct with ectopic drainage into the stomach. Case report and review of the literature.

A rare abnormal biliary tract consisting in a double common bile duct with an ectopic biliary tree draining into the stomach is described. This congenital anomaly, associated with lithiasis in the ectopic duct, was detected for the first time on MR-cholangiopancreatography. Only 23 cases of abnormal biliary drainage into the stomach have been reported in the literature. Embryogenesis and potential risks, such as lithiasis in the ectopic duct and the development of gastric carcinoma, are discussed.

Aged↗

[Accessory cystic duct discovered by intraoperative cholangiography during cholecystectomy].

The study aim was to report a rare biliary variation detected with an intraoperative cholangiography during a laparoscopic cholecystectomy. After the ligation of the cystic duct, the gallbladder was opacified via an accessory cystic duct flowing into a branch of the right hepatic duct. This accessory cystic duct was clipped and the postoperative course was uneventful.

Cholangiography↗

Ethnopharmacology and bioinformatic combination for leads discovery: application to phospholipase A(2) inhibitors.

A program combining ethnopharmacology and bioinformatic approaches has successfully been applied on anti-inflammatory activity. (i) An ethnobotanical study allowed the identification of several plants associated with putative anti-inflammatory properties as potential leads. (ii) On the other hand, it is well known that phospholipase A(2) is a target implicated in the pro-inflammatory process. Thus, (iii) some selected plant extracts were experimentally tested on phospholipase A(2). Finally, (iv) these experimental results combined with bioinformatic tools, such as database exploitation and molecular modeling, allowed to suggest that one compound, betulin and its oxidative form betulinic acid, might be responsible of the anti-PLA(2) activity. This suggestion was confirmed experimentally.

Chromatography, High Pressure Liquid↗

A molecular modeling and 3D QSAR study of a large series of indole inhibitors of human non-pancreatic secretory phospholipase A2.

Automated docking allowing protein-based alignment was performed for a series of 188 indole inhibitors of the human non-pancreatic secretory phospholipase A2 (hnps-PLA2). All the substituted indoles were docked to the crystal structure of hnps-PLA2 and a three-dimensional QSAR model was then established using the CoMFA method. The set of 188 compounds was divided into two subsets, the first one constituting the training set (126 compounds), while the second constituted the test set (62 compounds). The established CoMFA model derived from the training set was then applied to the test set. A good correlation between predicted and experimental activity data allows to validate the 3D QSAR model. A second and global 3D QSAR including all the compounds was established, allowing the creation of the hnps-PLA2 pharmacophore.

Anti-Inflammatory Agents↗

Protein-based alignment in 3D QSAR of 26 indole inhibitors of human pancreatic phospholipase A2.

An automated docking procedure was applied on a series of 26 reversible and competitive indole inhibitors of human pancreatic phospholipase A2 (hp-PLA2). X-ray data of this enzyme are not available and the structure was then reconstructed exploiting its protein sequence and the crystallographic data of a bovine pancreatic source. The docking data were used to build a three-dimensional quantitative structure-activity relationship (3D QSAR) model, established using the comparative molecular field analysis (CoMFA) method. This model, joined to the previous one developed for the indole inhibitors of human non-pancreatic secretory phospholipase A2 (hnps-PLA2), an enzyme involved in inflammation processes, will allow for the selection of new strong anti-inflammatory drugs with negligible side effects, at least at the level of hp-PLA2.

Animals↗

[Abnormal catheter mobility in a totally implantable venous access depending on the upright or supine position in an obese patient].

The authors advise on an exceptional complication in a totally implantable venous access and give recommendations on how to avoid this problem. In an obese person, one week after the implantation of a totally implantable venous access, a chest X-ray showed that the catheter was too short. In the operative room, at the time of the second intervention, the radioscopy did not find this anomaly. The subcutaneous injection port was positioned too low. When the patient was in a supine position, the subcutaneous injection port was in the correct position but when she was in an upright position, the breast descended and pulled down the subcutaneous injection port and the catheter.

Catheterization↗

Changes in cell proliferation and differentiation of adult rat small intestine epithelium after adrenalectomy: kinetic, biochemical, and morphological studies.

The effects of 10-day bilateral adrenalectomy on morphometry, proliferation, and apoptosis were determined in the small intestine of 3-month-old Sprague-Dawley rats. The activities of sucrase, lactase, and its respective mRNA, aminopeptidase N, and intestinal alkaline phosphatase were also evaluated. Adrenalectomy lead to partial atrophy and disorganization of the epithelium, with an increased number of goblet and Paneth cells and a reduction of crypt cell proliferation paralleled by a marked increase in villus apoptosis. Biochemical assays revealed that aminopeptidase N and intestinal alkaline phosphatase activities were significantly decreased, whereas disaccharidases were increased by adrenalectomy. The corresponding induction of lactase mRNA suggests an active response of the epithelium. In conclusion, adrenalectomy modified maturation and the differentiation processes of the small intestinal mucosa, especially in the proximal part of the small intestine. This result points to an important role of adrenals and glucocorticoids in the trophic status of the adult small intestinal mucosa.

Adrenalectomy↗

Fission yeast Bub1 is essential in setting up the meiotic pattern of chromosome segregation.

In meiosis, sister-chromatids move to the same spindle pole during the first division (MI) and to opposite poles during the second division (MII). This requires that MI sister kinetochores are co-orientated and form an apparent single functional unit that only interacts with microtubules from one pole, and that sister-chromatids remain associated through their centromeres until anaphase II. Here we investigate the function of Bub1 and Mad2, which are components of the mitotic-spindle checkpoint, on chromosome segregation during meiosis. Both proteins are required to prevent the occurrence of non-disjunction events in MI, which is consistent with recent findings that components of the mitotic-spindle checkpoint also operate during meiosis. However, Bub1 has several functions that are not shared with Mad2. When the bub1 gene is deleted, sister chromatids often move to opposite spindle poles during MI, indicating that sister kinetochores are disunited. Furthermore, the cohesin Rec8 is never retained at centromeres at anaphase I and sister-chromatid cohesion is lost. Our results show that Bub1, besides its functions in monitoring chromosome attachment, is essential for two other significant aspects of MI - unification of sister kinetochores and retention of centromeric cohesion.

Anaphase↗

Respective contribution of neutrophil elastase and matrix metalloproteinase 9 in the degradation of BP180 (type XVII collagen) in human bullous pemphigoid.

Bullous pemphigoid is a blistering disorder associated with autoantibodies directed against two components of hemidesmosomes, BP180 and BP230. Autoantibodies to the extracellular collagenous domain of BP180 are thought to play a key role in the pathogenesis of the disease. In a murine model of bullous pemphigoid, neutrophil elastase and 92 kDa gelatinase (matrix metalloproteinase 9) have been implicated in subepidermal blister formation via proteolytic degradation of BP180. In this study we sought to elucidate the contribution of these two enzymes to subepidermal blister formation by assessing the expression, localization, and activity of the two proteases in lesional skin, serum samples, and blister fluids obtained from 17 patients with bullous pemphigoid. The results indicate that (i) neutrophil elastase is found in skin biopsy specimens from bullous pemphigoid lesions and is recovered as active enzyme in blister fluids, and (ii) although proform of matrix metalloproteinase 9 is present in lesional skin, it is present only as proenzyme in blister fluids, which also contain high levels of tissue inhibitor of metalloproteinase-1. Next, the capacity of matrix metalloproteinase 9 and neutrophil elastase to degrade a recombinant protein corresponding to the extracellular collagenous domain of the BP180 was studied. Our data illustrate that (i) recombinant matrix metalloproteinase 9, neutrophil elastase, and blister fluid from bullous pemphigoid patients are all able to hydrolyze recombinant BP180; (ii) the pattern of recombinant BP180 proteolysis with blister fluid was similar to that obtained with neutrophil elastase; and (iii) recombinant BP180 degradation by blister fluid could be inhibited by chloromethylketone, a specific elastase inhibitor, but not by batimastat, a wide spectrum matrix metalloproteinase inhibitor. Our results confirm the importance of neutrophil elastase but not matrix metalloproteinase 9 in the direct cleavage of BP180 autoantigen and subepidermal blister formation in human bullous pemphigoid.

Aged↗

Objectively assessing bioartificial organs.

The metrics used, thus far, to assess bioartificial organ function are shown to be subjective and requiring validation. Therefore, four categories of correlations are proposed based on, respectively, device, in vitro and in vivo evaluations, and clinical function. Examples are presented whereby the correlations among individual indicators are used as a means to expedite the development of immunoisolated cells. Specifically, a case study illustrating the validation of in vitro indicators of in vivo graft function for the bioartificial pancreas (microencapsulated islets) is summarized. This has revealed thresholds with respect to given metrics relating to in vivo device function, the necessity to couple bioartificial organ design with transplant site selection, as well as the lack of objectivity involved in the evaluation and establishment of hypotheses. Specific quantitative indicators illustrate the need for quality-controlled measures, for example, relating to the tolerance of microcapsule diameter and membrane thickness distributions. Qualitative indices representing fibrosis and device properties (e.g., sphericity) are also used to describe the need for in vitro experiments in the development of bioartificial organs.

Bioartificial Organs↗

[Paraneoplastic acquired ichthyosis revealing non-Hodgkin's lymphoma].

BACKGROUND: Paraneoplastic ichthyosis is a rare affection generally associated with malignant hemopathy. CASE REPORT: A 61 year-old man was seen with a generalized ichthyosis associated with a palmoplantar hyperkeratosis developed over the last 2 years, and an axillary lymph node. Histology of the lymph node revealed a large cell anaplastic lymphoma. Both ichthyosis and palmoplantar keratosis totally disappeared three weeks after adenectomy, without any other treatment. DISCUSSION: This rapid and complete regression of ichthyosis, after the sole ablation of the involved lymph node confirmed the paraneoplastic nature of the disorders of the keratinization (ichtyosis, palmoplantar keratodermia). The review of the literature showed only one case characterized by a rapid disappearance of ichthyosis after surgical treatment of the malignant lymphoma.

Humans↗

[Dealing with bacterial hypodermal infection in general practice: an inquiry and a prospective study].

OBJECTIVE: The author had for aim to collect data on how general practitioners deal with bacterial hypodermal inflammation. MATERIAL AND METHODS: An enquiry on practice and a prospective study were carried out over 3 months. RESULTS: The mean number of cases reached 0.54 per physician over the 3-month period, for a total of 103 cases of bacterial hypodermal infection. The patients'mean age was slightly superior to 60 years, with a high female predominance and a preferential site of infection located in the lower limbs (89.6 p. 100 of the cases). 20 p. 100 of the patients were immediately sent to hospital, mainly because of the importance of local and/or general symptoms, and of the underlying conditions. In home care, antibiotic therapy was almost always oral and consisted in courses of group A penicillin or pristinamycin in over half of the cases, for a mean duration of 12.4 days for erysipelas, and 9.1 days for cases classified as "other type of bacterial hypodermal infection". An anticoagulant treatment was associated in close to 30 p. 100 of the cases, and anti-inflammatory or corticoids agents were prescribed in 17.9 p. 100 of the cases. The cure rate among home care patients reached 89.3 p. 100 and only 3 patients were hospitalized after the initial treatment; these 3 patients had all been given non-steroidal anti-inflammatory agents.

Family Practice↗

[Primary and secondary hospitalization criteria].

The reference therapy for erysipelas is penicillin G given intravenously. Since I.V. injections are difficult to perform at home, hospitalization would seem mandatory. However, many cases of erysipelas are actually treated at home (cf. results of the 2 surveys concerning general practice). The lack of studies on non-hospitalized erysipelas patients makes it difficult to answer the following question: "What are the criteria for primary and secondary hospitalization?" The literature suggests, mostly indirectly, that the reasons of primary hospitalization are: the severity of general (fever, impairment of general condition, confusion) or local (blisters, purpura, skin necrosis, extent of the cellulitis, facial involvement) signs and symptoms, old age, associated diseases (diabetes, alcoholism, obesity, cardiovascular disease), the practical modalities of the treatment (penicillin given intravenously, bed rest), or the necessity to eliminate deep venous thrombosis. The reasons for secondary hospitalization are above all the (true or suspected) failure of oral antibiotherapy at home, or the occurrence of local complications. True criteria of primary or secondary hospitalization remain to be defined by adequate prospective studies performed in both in and outpatients. They will depend of the emerging possibilities of successfully treating erysipelas by oral antibiotics.

Erysipelas↗

[Skin cancer diagnosis by dermatologists in the region of Champagne-Ardenne: a prospective study].

INTRODUCTION: The exact incidence of skin cancers is not well established in France as in other european countries, except for cutaneous melanoma. It is the same for the part taken by dermatologists in the screening of skin malignancies. We have therefore planned a prospective study in the Champagne-Ardenne region to determine the incidence of the various types of skin cancers diagnosed by dermatologists. PATIENTS AND METHOD: A prospective study was performed within a 4-month period at the end of 1998 with the participation of the dermatologists of the Champagne-Ardenne and the south of Aisne. The new incident cases of skin cancers confirmed histologically were recorded using a questionnaire including the type of tumour, demographic data of the patient and type of practice of the dermatologist. Parallely, the pathology laboratories of the same region were asked about the number of squamous and basal cell carcinomas and melanomas diagnosed histologically during the same period of time. RESULTS: The rate of participation of dermatologists was 86 p. 100. During the study period, 898 skin cancers were diagnosed in 794 patients (408 women and 386 men; mean age 70.1 years) including 643 basal cell carcinomas, 123 squamous cell carcinomas, 48 Bowen diseases, 53 melanomas, 7 lymphomas and 24 other tumours. More than 80 p. 100 of patients were primarily seen in private practice. Ten of 13 pathology laboratories of the region replied to the inquiry. From these pathological data, 585 basal cell carcinomas, 125 squamous cell carcinomas and 44 melanomas were recorded during the same period of time. DISCUSSION: This study shows that the oncologic clinical practice of dermatologists in our region is considerable. Taking into account both participation and exhaustivity rates, one can estimate at more than 3,500 the annual number of skin cancers diagnosed by dermatologists in our region, with an expected distribution of the various types of cancers. The essential role of the dermatologists in screening skin malignancies is confirmed by data provided by pathology laboratories. This role is a french characteristic and cannot by applied to other industrialized countries.

Adolescent↗

[Hemodynamic tolerance and rapid hypertrophy of a hepatic graft corresponding to less than 30% of the ideal mass in pigs].

BACKGROUND AND OBJECTIVE: Evaluation of a new pig liver transplantation technique for survival and hypertrophy of a small-sized graft by providing adapted and controlled venous portal flow. MATERIAL AND METHODS: [corrected] Twenty Large-White pigs underwent heterotopic liver transplantation after a mesocaval shunt and ligation of the superior mesenteric vein downstream from the shunt. The donor-to-recipient weight ratio was below 30%. Furthermore, recipient's biliary duct and portal vein into the hilum were tied. In a control group, no mesocaval shunt was performed and the graft received the entire splanchnic venous flow. RESULTS: The mesocaval shunt provided diversion of 60% of the splanchnic blood flow. The median survival of study pigs was 39 days (range: 8-98). Median serum bilirubin levels at 1 week were 12 micromol/L (range: 4-59). At autopsy, graft weight was increased to 2.7 times the initial weight and histological findings were normal. In the control group, all pigs died quickly from acute splanchnic congestion. CONCLUSION: In a model of heterotopic liver transplantation using small-sized grafts, complete diversion of mesenteric blood flow through a mesocaval shunt resulted in hemodynamic tolerance and hypertrophy of a graft corresponding to less than 30% of the ideal mass.

Anastomosis, Surgical↗

A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells.

Renewed interest in cancer immunotherapy has been raised by the availability of a variety of tumor-associated antigens and animal models. We have recently described the presence of a new antigen, TLP, in sera and cancer tissue from lung and colorectal cancer patients. In order to develop an experimental model suitable for preclinical studies on cancer vaccines, we investigated the presence of TLP antigen in vitro, in the DHD-K12 cell line and in vivo, in metastases induced in syngeneic BDIX rats by DHD-K12 cell injection. TLP was not detected in any tissue of healthy rats nor in normal tissues of tumor-bearing rats. This is in agreement with our previous studies, in which we had demonstrated that TLP is expressed in human colorectal cancer and adenomas but not in normal colonic mucosa. Our results indicate TLP as a possible human tumor-specific antigen naturally expressed in DHD-K12 tumor syngeneic to immunocompetent BDIX rats.

Animals↗