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Biomedical subjects

M Gosselin

Publications and source records attributed to M Gosselin.

At least 19 recordsLinked to original sources
PubMed2003

[Cutaneous metastatic Crohn's disease].

INTRODUCTION: Cutaneous metastatic Crohn's disease is a granulomatous inflammation of the skin that is noncontiguous to the gastrointestinal tract. CASE REPORT: A 42-year-old man with Crohn's disease is admitted for antibiotic resistant erysipela-like dermo-hypodermitis. The presence of granulomatous lesions on skin biopsy, the absence of any infectious agent identified despite extensive investigations and the dramatic improvement observed with corticosteroid eventually lead to the diagnosis of cutaneous metastatic Crohn's disease. CONCLUSION: During Crohn's disease, biopsy should be considered for every undiagnosed skin lesion as the characteristics of cutaneous metastatic Crohn's disease are not specific. The presence of a non caseous granulomatous dermal infiltration suggests the diagnosis and should make consider the initiation of corticosteroid and the discontinuation of others inappropriate therapeutics (i.e. surgical treatment, antibiotics).

Adult↗
PubMed2001

Novel C-terminus modifications of the Dmt-Tic motif: a new class of dipeptide analogues showing altered pharmacological profiles toward the opioid receptors.

The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic dipeptide analogues are described. These resulting analogues bearing different C-terminal functionalities were found to bind to the human delta receptor with high affinity. One specific class of dipeptides bearing urea/thiourea functionalities showed partial to full activation of the delta receptor. Several dipeptides also showed good binding affinities with full activation of the human kappa receptor, a novel property for those ligands.

Dipeptides↗
PubMed2001

Determination of equilibrium dissociation constants in fluorescence polarization.

A simple mathematical model (the FP K(d) model) is used to generate the dissociation equilibrium constant (K(d)) for G protein-coupled receptor-ligand binding measured using fluorescence polarization (FP) saturation curve analysis. The model generates data that may be analyzed by the method of Scatchard. The validity of the FP K(d) model is proven in six model systems in which the modeled K(d) values are within a factor of 5 of inhibitory equilibrium constant values obtained from radioligand competition assays.

Binding, Competitive↗
PubMed2001

[Crohn's disease complicated by multiple and recurrent aseptic splenic abscesses].

We report a case of multiple aseptic splenic abscesses occurring in a woman with Crohn's disease for three years. All microbiological samples were negative. The diagnosis was suspected on abdominal echography and CT scan and confirmed on histologic examination of the splenectomy specimen. The evolution was marked by recurrence of fever and inflammatory syndrome, associated to transitory morphological abnormalities of the accessory spleen. Aseptic splenic abscesses recurrence was suspected. This case allows us to consider aseptic splenic abscesses as an extra-intestinal manifestation and not as a splenic localisation of Crohn's disease.

Abscess↗
PubMed2000

A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9.

ACE2, the first known human homologue of angiotensin-converting enzyme (ACE), was identified from 5' sequencing of a human heart failure ventricle cDNA library. ACE2 has an apparent signal peptide, a single metalloprotease active site, and a transmembrane domain. The metalloprotease catalytic domains of ACE2 and ACE are 42% identical, and comparison of the genomic structures indicates that the two genes arose through duplication. In contrast to the more ubiquitous ACE, ACE2 transcripts are found only in heart, kidney, and testis of 23 human tissues examined. Immunohistochemistry shows ACE2 protein predominantly in the endothelium of coronary and intrarenal vessels and in renal tubular epithelium. Active ACE2 enzyme is secreted from transfected cells by cleavage N-terminal to the transmembrane domain. Recombinant ACE2 hydrolyzes the carboxy terminal leucine from angiotensin I to generate angiotensin 1-9, which is converted to smaller angiotensin peptides by ACE in vitro and by cardiomyocytes in culture. ACE2 can also cleave des-Arg bradykinin and neurotensin but not bradykinin or 15 other vasoactive and hormonal peptides tested. ACE2 is not inhibited by lisinopril or captopril. The organ- and cell-specific expression of ACE2 and its unique cleavage of key vasoactive peptides suggest an essential role for ACE2 in the local renin-angiotensin system of the heart and kidney. The full text of this article is available at http://www. circresaha.org.

Adult↗
PubMed2000

The CD28-related molecule ICOS is required for effective T cell-dependent immune responses.

While CD28 is critical for expansion of naive T cells, recent evidence suggests that the activation of effector T cells is largely independent of CD28/B7. We suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations. Our data indicate a critical function for the third member of the CD28 family in T cell-dependent immune responses.

Abatacept↗
PubMed2000

Fluorescence polarization assays for high throughput screening of G protein-coupled receptors.

Fluorescence polarization assays in 384-well microtiter plates have been demonstrated. The performance is suitable for high throughput drug screening applications with respect to speed of analysis, displaceable signal, precision, and sensitivity to various reagents. Rank order of potency was maintained relative to [(125)I]-ligand filtration assays, and the effects of the highly colored compounds, tartrazine and Chicago Sky Blue, were insignificant on the polarization signal up to a concentration of 1 microM. These attributes suggest that accurate assessment of drug binding can be obtained.

Fluorescence Polarization↗
PubMed2000

Impact of a red-shifted dye label for high throughput fluorescence polarization assays of G protein-coupled receptors.

High throughput screening fluorescence polarization assays using G protein-coupled receptors (GPCRs) as targets have been compared using fluorescein and BODIPY TMR-labeled peptides. The red-shifted BODIPY TMR dye exhibits improved assay performance relative to fluorescein due to improvement in both ligand affinity to the GPCRs and assay precision brought about by the higher intensity probe. Furthermore, the red-shifted dye demonstrates an insensitivity to the effects of the highly colored compound tartrazine, which can produce false-negative results for assays conducted with fluorescein as a label.

Binding, Competitive↗
PubMed2000

[Multicenter prospective study of prognostic factors of gastroduodenal ulcer hemorrhages. Reevaluation of clinical and endoscopic factors in the era of endoscopic hemostasis].

AIM: To evaluate in a prospective study the prognostic factors of recurrent bleeding and mortality in patients presenting with high risk peptic ulcer bleeding routinely treated by endoscopic hemostasis. PATIENTS AND METHODS: A multicenter study was carried out in 8 Western French hospitals in 144 patients with gastrointestinal bleeding peptic from ulcer type I or IIa, b as defined by Forrest classification. Thirty four and 38 parameters were studied respectively in order to predict recurrent bleeding and death. Significant predictive factors (P < 0.1) in univariate analysis were entered in a multivariate logistic regression analysis. RESULTS: Endoscopic hemostasis was performed in 108 of 144 cases (75%). Recurrent bleeding and death occurred in 39 (28%) and 22 cases (15%), respectively. By multivariate analysis, the only predictor of rebleeding was hypovolemia at admission. Predictors of death were ASA score, cardiovascular Goldman score and recurrent bleeding. In this study, prevalence of Helicobacter pylori infection was low (41%) but was not a predictive factor. CONCLUSIONS: In a selected population of peptic ulcer bleeding patients with high risk of rebleeding, prevalence of recurrent bleeding and death remains rather high, despite routine endoscopic hemostasis. In the era of endoscopic hemostasis, clinical parameters remain the best prognostic factors of peptic ulcer bleeding outcome.

Aged↗
PubMed1999

Fecal incontinence with normal anal canal pressures: where is the pitfall?

OBJECTIVE: One third of subjects who suffer from fecal incontinence are found to have values within the normal range when anal manometry is performed. For these patients, one hypothesis is that impaired rectal adaptation to distension may occur. The aim of our study was to analyze anorectal responses to rectal isobaric distension in this population. METHODS: This was a prospective study conducted in 51 consecutive incontinent patients (45 female, six male) divided into two groups according to their functional anal state: absence (19 patients aged 55 +/- 6 yr) or presence of manometric anal weakness (32 patients aged 59 +/- 2 yr). The subjects were submitted to two randomized modes of rectal isobaric distension (tonic, phasic) with an electronic barostat. Anal pressures, perception, and volumes of the rectum were recorded at six different preselected pressures. RESULTS: As compared with those having anal weakness, patients with no anal weakness retained higher mean pressures at both upper (36.9 +/- 2.2 vs 22.9 +/- 1.4 mm Hg; p = 0.01) and lower parts (41.0 +/- 2.0 vs 23.3 +/- 1.4 mm Hg; p = 0.002) of the anal canal, similar perception scores, but much lower rectal volumes (68.5 +/- 5.5 vs 121.8 +/- 7.0 ml; p = 0.008) in response to rectal isobaric distension. CONCLUSION: A decrease in rectal adaptation could be involved in fecal leakage in patients with no anal manometric weakness.

Adaptation, Physiological↗
PubMed1999

Perception of and adaptation to rectal isobaric distension in patients with faecal incontinence.

BACKGROUND: Perception of, and adaptation of the rectum to, distension probably play an important role in the maintenance of continence, but perception studies in faecal incontinence provide controversial conclusions possibly related to methodological biases. In order to better understand perception disorders, the aim of this study was to analyse anorectal adaptation to rectal isobaric distension in subjects with incontinence. PATIENTS/METHODS: Between June 95 and December 97, 97 consecutive patients (nine men and 88 women, mean (SEM) age 55 (1) years) suffering from incontinence were evaluated and compared with 15 healthy volunteers (four men and 11 women, mean age 48 (3) years). The patients were classified into three groups according to their perception status to rectal isobaric distensions (impaired, 22; normal, 61; enhanced, 14). Anal and rectal adaptations to increasing rectal pressure were analysed using a model of rectal isobaric distension. RESULTS: The four groups did not differ with respect to age, parity, or sex ratio. Magnitude of incontinence, prevalence of pelvic disorders, and sphincter defects were similar in the incontinent groups. When compared with healthy controls, anal pressure and rectal adaptation to distension were decreased in incontinent patients. When compared with incontinent patients with normal perception, patients with enhanced perception experienced similar rectal adaptation but had reduced anal pressure. In contrast, patients with impaired perception showed considerably decreased rectal adaptation but had similar anal pressure. CONCLUSION: Abnormal sensations during rectal distension are observed in one third of subjects suffering from incontinence. These abnormalities may reflect hyperreactivity or neuropathological damage of the rectal wall.

Adaptation, Physiological↗
PubMed1999

An immunomodulation strategy targeted towards immunocompetent cells or cytokines in inflammatory bowel diseases (IBD).

Many immunological abnormalities have been described in inflammatory bowel diseases (IBD). Even though, no clear cut primary defects have yet been described, some therapeutic trials have targeted either immunocompetent cells or overproduction of cytokines. Preliminary results have shown that antisense oligonucleotides (anti-ICAM), anti-cytokine antibodies (anti-TNF) or recombinant human cytokines (IL-10 or IL-11) are effective in some patients with Crohn's disease refractory to steroids. However, these data need to be confirmed and the potential side effects of these treatments must be further considered. These drugs need to be more precisely defined in particular compared to corticotherapy. Finally, data from immunomodulation strategies should help us understand the aetiology of abnormal immune responses in Crohn's disease (CD) and ulcerative colitis (UC).

Antibodies↗
PubMed1999

Gastric carcinoma in Sotos syndrome (cerebral gigantism).

We report the first case of the association of Sotos syndrome and gastric carcinoma (containing signet ring cells) in a twin patient. The other-probably monozygous-twin is also affected by the Sotos syndrome. The association of malign tumors in Sotos syndrome and other overgrowth syndromes is discussed.

Adult↗
PubMed1998

Octreotide acts on anorectal physiology: a dynamic study in healthy subjects.

BACKGROUND: Somatostatin is localized in the intestinal and pelvic nerves of the anorectum and it seems to act as an important neurotransmitter. However, previous analyses of octreotide (a somatostatin analog) effects on anal function showed conflicting results. By use of a dynamic model in healthy subjects, with comparison to the myogenic effect of glucagon, the aim of our study was to further investigate the pharmacologic targets of octreotide. METHODS: This was a placebo-controlled, randomized, double-blinded crossover study performed in 12 healthy volunteers who received octreotide, glucagon, or placebo intravenously on separate days. During each sequence, several pressure steps in 3 different protocols of rectal isobaric distension were applied with an electronic barostat. Manometric responses of the anal canal, adaptative volumes, and perception scores of the rectum were recorded. RESULTS: During both phasic and stepwise distensions, a significant drug effect was encountered at the anal level. Compared with placebo, octreotide significantly increased pressures at both upper and lower levels of the anal canal. In contrast, glucagon decreased pressures at the upper part of the anal canal. Octreotide significantly decreased rectal volumes to phasic distension, but glucagon did not induce any change on rectal adaptation. In addition, neither drug modified perception scores. CONCLUSION: This study suggests that octreotide acts on reflex arcs and rectal myenteric neurons rather than on anal myogenic targets that respond to glucagon.

Adult↗
PubMed1998

Effects of cholinergic agents on anorectal physiology.

BACKGROUND: Despite their potential therapeutic benefit, the effects of cholinergic agents on anal function have been poorly investigated. AIM: To analyse the effects of neostigmine and atropine on anorectal responses to rectal isobaric distension. METHODS: This was a placebo-controlled, randomized, double-blind crossover study, performed in 12 healthy volunteers who received intravenously, on 3 separate days, neostigmine, atropine or the placebo. During each day of the experiment, seven pressure steps (ranging from 1 to 31 mmHg) in three different protocols of rectal isobaric distension (phasic, stepwise and tonic) were applied using an electronic barostat. Manometric responses of the anal canal, adaptative volumes and perception scores of the rectum were recorded. RESULTS: During stepwise distension, a significant drug effect was encountered at the anal level. No drug effect was observed on the other investigated parameters (rectal volumes and rectal perception scores) or for the other modes of distension. Compared to placebo, neostigmine significantly decreased pressures at the upper level of the anal canal for both recto anal inhibitory reflex and mean resting pressures. In contrast, atropine significantly increased pressures at the lower part of the anal canal but did not modify upper anal pressures. CONCLUSION: The present study suggests that cholinergic effects result more from an indirect action on intermediate neurotransmitters and rectal myenteric neurons, than from a direct action on anal targets.

Adult↗
PubMed1998

Rectal adaptation to distension in patients with overt rectal prolapse.

BACKGROUND: High recovery rates of continence are observed after surgical procedures for rectal prolapse. Increases in rectal compliance but no obvious rise in anal pressures have been reported. The authors' hypothesis was that decreased rectal adaptation to distension may contribute to incontinence in patients suffering from overt rectal prolapse. METHODS: This was a prospective study conducted in 20 consecutive incontinent patients suffering from overt rectal prolapse with no mucosal change (two men and 18 women; mean(s.e.m.) age 50(3) years). They were compared with 20 age- and sex-matched patients with incontinence without rectal prolapse and ten age- and sex-matched healthy volunteers observed during the same period. The subjects were submitted to phasic isobaric distension of the rectum with an electronic barostat. Anal pressures, perception scores and rectal volumes were recorded at six different preselected pressures. RESULTS: Compared with healthy subjects, maximum rectal volumes (mean(s.e.m) 98(6) versus 167(11) ml; P= 0.005), volumes related to compliance (56(5) versus 100(9) ml; P= 0.004) and tone (41(3) versus 67(4) ml; P = 0.003) were decreased significantly in the rectal prolapse group. Prolapse and incontinence groups did not differ significantly with respect to rectal adaptation for all three parameters and steps of distension considered. CONCLUSION: Patients suffering from overt rectal prolapse had markedly impaired rectal adaptation to distension which may contribute to incontinence.

Adaptation, Physiological↗
PubMed1998

Value of early blood Th-1 cytokine determination in predicting severity of acute pancreatitis.

BACKGROUND: Early evaluation of the severity of acute pancreatitis (AP) requires measurement of many variables within 48 h after admission. Septic complications (SC) are frequent, and preliminary studies have highlighted the value of prophylactic antibiotherapy; however, single and reliable predictive markers of sepsis are not yet available. The aim of this study was to assess the value of determining early blood Th-1 cytokines and their natural antagonists (interleukin-6 (IL-6), IL-1, IL-1ra, and the soluble form of tumor necrosis factor (sTNF) receptors RI and RII) to predict the severity and SC during AP. METHODS: Thirty-seven patients with AP were prospectively included; 25 of them had severe AP, including 8 with SC. Serum cytokines were measured 48 h and 72 h after the onset of AP with an enzyme-linked immunosorbent assay. The optimal severity or SC diagnostic thresholds was determined using receiver operative curves. RESULTS: Severe AP in accordance with the Atlanta criteria were better predicted by C-reactive protein and IL-6 serum determination, albeit these levels could not predict absolutely the death of two patients. In severe AP cases (n = 25) the IL-1 to IL-1-ra ratio was lower in cases further complicated by sepsis ((6+/-4) 10(-3) versus (34+/-13) 10(-3), P < 0.05); moreover, sTNF RI (2497+/-270 pg/ml versus 2133+/-611 pg/ml, P < 0.05) and RII (3751+/-400 pg/ml versus 3045+/-509 pg/ml, P < 0.05) were higher in AP characterized by further SC. The IL-1 to IL-1-ra ratio and IL-1 concentration were dramatically decreased within the first 48 h ((0.4+/-0.4) 10(-3) versus (30+/-11) 10(-3), P < 0.05, and 0.3+/-0.3 versus 15+/-3 ng/l, P < 0.05) in patients with further infection of the pancreatic necrosis (n = 3). The SC diagnosis was better anticipated by an IL-1 to IL-1-ra ratio lower than 5 x 10(-3) or by an sTNF RI higher than 1750 pg/ml and sTNF RII higher than 2750 pg/ml, and the infection of the pancreatic necrosis by an IL-1 concentration <2 ng/l or an IL-1 to IL-1-ra ratio <2 x 10(-3). CONCLUSION: Besides severity markers, IL-1, IL-1-ra, and sTNF RI and RII should be considered in base-line AP assays and, if confirmed by larger studies, could help to screen patients at risk for SC and candidates for prophylactic antibiotherapy with a good negative predictive value.

Acute Disease↗