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Biomedical subjects

P Déchelotte

Publications and source records attributed to P Déchelotte.

At least 19 recordsLinked to original sources

[Idiopathic intrahepatic portosytemic shunts in 4 children].

Intrahepatic portosystemic anastomoses are macroscopic communications between the venous portal system and the systemic circulation and located partly in the liver. We report 4 new cases of type II shunts, which illustrate the circumstances of the diagnosis of these exceptional anomalies. For 2 children, the diagnosis was done antenataly by US and spontaneous involution in a few months was observed. In the third case the malformation was evidenced fortuitously at 3 weeks of life, and this 6-year-old child remains completely asymptomatic so far. Then, in the fourth case, a cerebral venous thrombosis was fortuitously and antenatally evidenced in an otherwise uneventful pregnancy and portosystemic shunt was demonstrated postnataly in the extensive work up of the neonate.

Follow-Up Studies↗

Guanylyl cyclase C as a reliable immunohistochemical marker and its ligand Escherichia coli heat-stable enterotoxin as a potential protein-delivering vehicle for colorectal cancer cells.

mRNA-based technologies and preclinical research in a variety of animal models have shown that guanylyl cyclase C (GCC) is a highly sensitive and specific molecular marker for the diagnosis of colorectal cancer (CRC). GCC is also a receptor for Escherichia coli (E. coli) heat-stable enterotoxin (STa) and can be used for STa-directed delivery of small-sized imaging agents to human CRC tumours. In this study, we have evaluated GCC as a new immunohistochemical (IHC) marker for CRC tissues and STa as a suitable vector for delivering high-sized protein molecules to CRC cells. Firstly, we have developed a highly sensitive EnVision(+)-based IHC staining method for detecting GCC in serial paraffin-embedded sections of primary and metastatic CRC (38 cases) or non-CRC (14 cases) adenocarcinomas. Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) were chosen as controls. Our results indicate that GCC staining was positive in 100% of CRC tumours and was comparable to CEA (95%) or CK20 (92%). In contrast to CEA and CK20, GCC was negative in all of the extra-intestinal non-CRC tumours examined. GCC appears to display higher specificity than either CEA or CK20 while retaining high sensitivity, suggesting that it is a better CRC marker than CEA or CK20. Secondly, STa was genetically coupled to green fluorescent protein (GFP) and the resulting GFP-tagged STa was characterized for expression in E. coli and enterotoxicity in mouse. The binding characteristics of GFP-STa in CRC Caco-2 cells were followed by immunofluorescence microscopy. In this work we show that GFP-tagged STa is biologically active and has retained its ability to internalise into Caco-2 cells making it a potential vehicle for the delivery of anticancer therapeutic protein agents.

Adult↗

[Solitary fibrous tumor of the orbit: an unusual cause of unilateral proptosis. Case report with a review of the literature].

BACKGROUND: The solitary fibrous tumor (SFT) is a spindle-cell tumor that very rarely involves the orbit. We report a new case that we compare to reports in the literature. CASE: A 72-year-old woman presented a conjunctival inflammation of the right eye developing over 5 months with progressive proptosis. Magnetic resonance imaging revealed an extraconal and homogeneous mass, which showed hypointensity on T1-weighted images and hyperintensity on T2-weighted images, without specificity. Histological examination of the lesion removed by anterior orbitotomy confirmed the diagnosis of the SFT of the orbit. The patient was doing well without recurrence after 9 months. DISCUSSION: The diagnosis of SFT is histological. It is a mesenchymal tumor. Immunohistochemically, the tumor cells are strongly positive for CD34 and vimentin. CONCLUSION: The SFT of the orbit is a very rare and generally benign tumor. It must be immunohistochemically differentiated from other spindle-cell tumors of the orbit. The treatment is a complete surgical excision, and long-term follow-up is necessary because recurrence may appear long after treatment.

Aged↗

In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases.

There is a growing body of evidence to support the efficacy of topical imiquimod in the treatment of primary skin carcinomas. Conflicting data exist concerning the use of imiquimod for the treatment of skin melanoma metastases. To date, only the impact of imiquimod on cytokines involved in immunological processes has been studied extensively. We report a woman successfully treated with imiquimod (once daily for 8 weeks) for skin melanoma metastases in whom we investigated the expression of molecules involved in metastasis and angiogenesis. Before and after treatment, a skin lesion was biopsied and the expression of the following molecules was investigated using real-time reverse transcription-polymerase chain reaction: matrix metalloproteinase (MMP)-1, 2 and 9 and their inhibitors KiSS-1 and tissue inhibitor of metalloproteinase (TIMP)-1, vascular endothelial growth factor (VEGF), fibroblast growth factor-2, and angiogenesis inhibitors (thrombospondin-1 and 2). Interferon (IFN)-alpha was also investigated as an in vivo marker of imiquimod activity. IFN-alpha was upregulated by the treatment. Under imiquimod, the following molecules were upregulated: TIMP-1, KiSS-1 and MMP-1. MMP-2 expression was not modified. MMP-9 expression was dramatically decreased. The expression of angiogenesis inhibitors was slightly increased but VEGF expression remained at a basal level. These results suggest that imiquimod could downregulate metastasis invasion and angiogenesis. However, these data were obtained at a transcriptional level and from a single case, and further investigations should include migration assays and additional cases in order to confirm that imiquimod may be safely used for treatment of melanoma metastases.

Administration, Topical↗

[Recurrence of multiple chorio-angiomas: a case-report].

Diffuse chorioangiomatosis is a rare placental pathology characterized by multiple chorioangiomas, inducing a high risk of fetal complications, especially cardiovascular, with a risk of fetal death. The physiopathology is not clearly established but seems to be related with an over-expression of vascular growth factors related to hypobaric-hypoxia. Here, we describe a case of recurrent chorioangiomatosis with fetal demise. No risk factors were identified (high altitude, genetic disease like Beckwith-Wiedemann, diabetes). Intra-amniotic, plasmatic values of alphafetoprotein and plasmatic beta gonadotrophin chorionic hormone remained low. Ultrasonographic assessment of placental thickness was in the normal range, at 22 and 32 weeks of gestation. In case of previous chorioangiomatosis, we recommend a weekly sonographic monitoring to diagnose fetal complications associated with an early inpatient hospitalization for daily surveillance at the age of previous accidents. Labor will be induced in case of fetal intolerance or systematically after 37-38 weeks of gestation.

Adult↗

Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut.

BACKGROUND & AIMS: Balance between pro-and anti-inflammatory mediators plays a key role in the pathogenesis and treatment of inflammatory bowel disease. Glutamine can modulate cytokine production by intestinal mucosa in healthy subjects, but studies in inflammatory states are still limited. The aim of this work was to evaluate the effects of glutamine on IL-1beta-induced cytokine production by human gut. METHODS: Duodenal biopsies from healthy volunteers were stimulated in vitro by IL-1beta in the presence of increasing glutamine concentrations. Cytokine production was assessed in culture media by ELISA and cytokine mRNA expression in biopsies by RT-PCR. Results, in pg/mg of tissue, (median [range]), were compared by non-parametric paired tests. RESULTS: IL-1beta stimulation increased IL-6 and IL-8, but did not affect IL-4 and IL-10 production. IL-8 and IL-6 production from stimulated biopsies significantly decreased with increasing glutamine concentration from 0.5 to 10mM, (2543 [828-3634] to 1499 [282-2617] for IL-8, 62 [22-117] to 24 [12-99] for IL-6, both P<0.05), whereas IL-10 production was increased (0.7 [0.2-1.6] to 1.2 [2.6-0.5],P<0.05). Glutamine also increased IL-10 mRNA level in biopsies (P<0.05). IL-4 production was not affected by glutamine. CONCLUSIONS: Glutamine was shown in human intestinal mucosa to reduce the production of the pro-inflammatory cytokines IL-6 and IL-8, and enhance the production of the anti-inflammatory cytokine, IL-10.

Adult↗

Cytokine-stimulated nitric oxide production and inducible NO-synthase mRNA level in human intestinal cells: lack of modulation by glutamine.

BACKGROUND & AIMS: Excess NO production has been reported during intestinal inflammation. Modulation of the inflammatory response with nutrients in critically ill patients has gained increasing interest. Glutamine has beneficial effects on gut mucosa but its effects on human intestinal NO production during an inflammatory response are not known. METHODS: Caco-2/TC7 and HCT-8 cells were stimulated with a cytokine mixture (IL-1 beta, TNF alpha, IFN gamma) and duodenal biopsies from human healthy volunteers in organ culture were stimulated with IL-1 beta. All cultures were performed in the presence of 2-10 mmol/l glutamine. NO release in culture supernatant and iNOS mRNA level in cultured cells or biopsies were assessed by nitrate reduction and Griess assay and RT-PCR, respectively. RESULTS: In Caco-2, HCT-8 cells and duodenal biopsies, cytokine stimulation increased iNOS mRNA level 1.2-fold (ns), 3.8-fold (P=0.02), 4.7-fold (P=0.03) and NO production 1.4-fold (ns), 9.1 (P=0.01) and 1.7-fold (P=0.01), respectively. Increasing glutamine concentration had no significant effect on NO production and iNOS mRNA in any type of culture, stimulated or not by cytokines. In various models of human intestinal cells, glutamine does not further increase NO production induced by pro-inflammatory cytokines.

Adult↗

Epidemiological survey of melanoma in the Auvergne region (France): is there an increased incidence in Auvergne?

To assess the efficiency of melanoma screening and prevention campaigns in the Auvergne region (France), cases of melanoma have been recorded since 1st June 1998. The epidemiological follow-up of melanoma was carried out using two sentinel networks; one involving the pathologists, and the other, the dermatologists of the region. Incidence was calculated using the capture-recapture method, by cross-matching the data supplied by both dermatologists and pathologists. Between June 1st 1998 and December 31st 2000, 363 cases of melanoma were recorded. The crude incidence rate of melanoma per 100,000 person-years was 17.1 for all melanomas and 14.6 for invasive melanomas. These rates of incidence were higher than the estimated national rate of France, and were close to incidences found in countries of Northern Europe. This might be explained by an increase in screening for melanoma, by more precise estimation of the incidence due to the capture-recapture method, or by geographic factors (mountainous area). An answer may be provided by following the variation in time of incidence and thickness of melanomas; the increase in the number of thin (low Breslow index) melanomas corresponding with increased screening.

Adolescent↗

[Do bipolar scissors increase postoperative adhesions? An experimental double-blind randomized trial].

AIM: The use of bipolar scissors (PowerStar) which has been suggested to reduce bleeding during surgical dissection, involves the theoretical risk for increasing intraperitoneal adhesions because of burn damages to the peritoneum secondary to bipolar electrocautery. MATERIAL AND METHOD: Thirty-six white new-Zealand rabbits have been included in a double-blind randomised trial to undergo a laparotomy using either a sharp scissors with on-demand monopolar coagulation or a bipolar scissors. Operatives procedures were standardised: midline laparotomy (5 cm), mobilisation of the right colon, incision of the colonic serosa without suture, incision of the colonic serosa with running sutures, incision of the mesentery. All these steps were performed by the same device according to the randomisation. Ten days later, the rabbits were killed. Adhesions were measured and scored according to the Zühlke classification by a surgeon who was not aware of the type of scissors used. Finally a pathological examination of adhesion was randomly performed. RESULTS: The two groups were similar for weight and sex-ratio. Two rabbits died before the tenth postoperative day (1 unknown aetiology and 1 evisceration). 34 rabbits were available for the study (18 in the "PowerStar" group and 16 in the control group). The results showed no significant difference between the groups for all measured endpoints (length and score of intraperitoneal and parietal adhesions). Nevertheless, pathological examination showed the burn damages to be less pronounced after using PowerStar. CONCLUSION: Bipolar scissors do not increase postoperative adhesions in the rabbit and probably induce less burn damages than monopolar cautery. The additional advantage i.e. the decrease adhesions formation, because of a less intraperitoneal bleeding, has not been observed in this randomised trial.

Animals↗

[Sudden unexpected death in an infant due to a ruptured coronary aneurysm revealing Kawasaki disease].

UNLABELLED: The early mortality of Kawasaki disease is low, resulting from coronary complications, mainly aneurismal thrombosis with myocardial infarction. The aneurysmal rupture is an exceptional cause of death. CASE REPORT: We report on a six-month-old girl who died suddenly and unexpectedly. The autopsy showed a cardiac tamponade caused by an important ruptured aneurysm of the left coronary artery. Multiple aneurysms, with or without thrombosis, on the right coronary were also present. There was no ischaemic lesion. Three weeks before death, this infant demonstrated several clinical signs of Kawasaki disease whose diagnosis had not been done. CONCLUSION: Even if the rupture of coronary aneurysm is an exceptional initial complication of Kawasaki disease, a better knowledge of the atypical or incomplete forms, particularly below the age of one year, should allow an early diagnosis and treatment, decreasing the risks of coronary complications. This observation furthermore illustrates the interest of post-mortem examination in all sudden or unexpected infant deaths.

Coronary Aneurysm↗

First-trimester features of Fowler syndrome (hydrocephaly-hydranencephaly proliferative vasculopathy).

We describe the features of Fowler syndrome (proliferative vasculopathy and hydrocephaly-hydranencephaly) diagnosed in the first trimester. The pregnancy with no significant family history was referred for karyotyping and ultrasound examination after a cystic hygroma was seen at 12 weeks. At 13 weeks, ultrasound examination revealed hydrocephaly-hydranencephaly, fetal akinesia, and arthrogryposis associated with increased nuchal translucency. The parents opted for termination of pregnancy and the diagnosis of Fowler syndrome was confirmed by pathological examination of the fetus. Calcified necrotic lesions and proliferative vasculopathy were observed in the entire central nervous system including the brainstem and spinal cord. Cases previously reported in siblings suggest an autosomal recessive transmission but specific genetic antenatal diagnosis is not yet available. The diagnosis of proliferative vasculopathy and hydrocephaly-hydranencephaly (Fowler syndrome) should be considered whenever hydrocephaly-hydranencephaly associated with a fetal akinetic sequence are encountered at the end of the first trimester. Genetic counseling is recommended.

Adult↗

Influence of glutamine on cytokine production by human gut in vitro.

BACKGROUND: glutamine modulates cytokine production by immune cells in vitro and protects the gut from experimental enterocolitis, but data on the effect of glutamine on cytokine production in human gut are lacking. AIM: to assess the effect of glutamine pre-treatment in vivo and in vitro on cytokine production by intestinal mucosa. METHODS: nine fasted volunteers received either enteral glutamine or saline over 6 h in a cross-over design. Duodenal biopsies were cultured for 24 h with or without glutamine. Cytokine content of culture media was analysed by ELISA, and the expression of cytokine mRNA in biopsies was assessed by semi-quantitative RT-PCR. RESULTS: glutamine given in vivo and in vitro significantly decreased IL-6 [1.4 (0.8-8.5) vs 8.9 (1.0-43.9)] and IL-8 production [5.8 (0-51.4) vs. 53.0 (2.5-114.6), pg/mg wet tissue], median (range), both P< or =0.01, in comparison to no glutamine experiments. Glutamine did not influence IL-4 production. IL-1beta, IL-10 and TNF-alpha were not detectable in culture media. The expression of any cytokine mRNA was not influenced by glutamine. CONCLUSIONS: glutamine reduces pro-inflammatory cytokine production by human intestinal mucosa, probably by a post-transcriptional pathway. Glutamine could be useful to modulate inflammatory conditions with imbalanced cytokine production.

Adolescent↗

Cutaneous lymphoma associated with Epstein-Barr virus infection in 2 patients treated with methotrexate.

Whether patients with rheumatoid arthritis (RA) have an increased risk of developing non-Hodgkin lymphoma is controversial, and opinions differ on the possible role of methotrexate in the occurrence of lymphomas in patients with RA. We report 1 T-cell lymphoma and 1 B-cell lymphoma restricted to the skin associated with Epstein-Barr virus infection that healed completely and spontaneously after discontinuation of methotrexate in a man with RA and a woman with dermatomyositis. Cutaneous infiltrating cells were infected by a replicative form of Epstein-Barr virus. After discontinuation of methotrexate, the cutaneous lesions disappeared completely in 15 days without recurrence. Discontinuation of methotrexate is necessary in patients with RA or dermatomyositis who have a lymphoproliferative disorder, and a follow-up period of several weeks should be observed before specific therapy is initiated.

Aged↗

Co-localization of KLF6 and KLF4 with pregnancy-specific glycoproteins during human placenta development.

Pregnancy-specific glycoproteins (PSGs) are major placental proteins essential for the maintenance of normal gestation. However, little is known about their gene expression regulation during placentation. It was previously demonstrated that the human core promoter binding protein recently renamed Krüppel-like factor (KLF) 6 binds to a highly conserved sequence within the PSG promoters and is mainly expressed in human term placenta. Here, we determined the expression pattern of the 13 other KLFs during human placental development. We demonstrate that eight KLFs exhibit specific expression patterns in human placental tissues and membranes, in favor of a functional cooperation of specific KLFs during placentation. In addition, we demonstrate that KLF6, KLF4 and PSG proteins are co-expressed in same cell types of placental villi and membranes. This experimental evidence further strengthens the potential cross talk of both transcription factors for PSG gene regulation in vivo.

DNA-Binding Proteins↗

Low levels of gastric mucosal glutathione during upper gastric bleeding associated with the use of nonsteroidal anti-inflammatory drugs.

OBJECTIVES: To investigate the glutathione concentrations in gastric mucosa from patients with acute gastric bleeding related to nonsteroidal anti-inflammatory drugs (NSAIDs), and to test the influence of nutritional status on mucosal glutathione. Glutathione protects the gastrointestinal mucosa against reactive oxygen species, and glutathione content in various tissues may be depleted during malnutrition. METHODS: Endoscopic biopsies were obtained from 39 patients. Eighteen of these (9 well-nourished, 9 malnourished) presented with gastric bleeding ulcers related to NSAIDs. Twenty-one other patients (12 well-nourished, 9 malnourished) underwent normal routine diagnostic endoscopy and served as controls. Malnutrition was defined as a loss of over 10% of normal body weight and/or plasma albumin levels below 30 g/l. Gastric biopsies were taken from the fundus and antrum (controls) and from the region of the ulcer (patients with acute bleeding) and frozen quickly until glutathione analysis by high-performance liquid chromatography (HPLC) coulometric detection. Results were expressed as nmol/mg wet tissue. RESULTS: Gastric mucosal glutathione levels were significantly (P < 0.05) lower in both the antrum (0.81 +/- 0.34 v. 1.41 +/- 0.88 nmol/mg tissue) and the fundus (1.04 +/- 0.54 v. 1.43 +/- 0.92 nmol/mg tissue, P < 0.05) in malnourished than in well-nourished control patients. Glutathione mucosal concentrations were decreased significantly in patients with NSAID-induced gastric bleeding compared with control patients (0.38 +/- 0.36 v. 1.12 +/- 0.56 nmol/mg tissue, P < 0.001), and the lowest glutathione levels were observed in malnourished patients (0.28 +/- 0.20 v. 0.48 +/- 0.15 nmol/mg tissue in well-nourished patients, not significant). CONCLUSION: Malnutrition is associated with low levels of gastric glutathione. This may contribute to the severity and the onset of haemorrhage in NSAID-induced gastric ulcers.

Acute Disease↗

BRCA1 and BRCA2 protein expressions in an ovotestis of a 46, XX true hermaphrodite.

BRCA1 and BRCA2 breast cancer susceptibility genes encode proteins, the normal cellular functions of which are complex and multiple, and germ-line mutations in individuals predispose both to breast and to ovarian cancer. There is nevertheless substantial evidence linking BRCA1 and BRCA2 to homologous recombination and DNA repair, to transcriptional control and to tissue proliferation. There is controversy regarding the localization of BRCA1 and BRCA2 proteins to either nucleus or cytoplasm and whether the expression is present in premeiotic germ cells or can still be expressed in mitotic spermatogonia. We report herein an immunohistochemical study of BRCA1 and BRCA2 distribution in a rather unusual tissue (an ovotestis), which addresses this issue.

BRCA1 Protein↗