PubMed Health⌕ Search

Biomedical subjects

C Cuvelier

Publications and source records attributed to C Cuvelier.

At least 19 recordsLinked to original sources

Altered gut transcriptome in spondyloarthropathy.

BACKGROUND: Intestinal inflammation is a common feature of spondyloarthropathy (SpA) and Crohn's disease. Inflammation is manifested clinically in Crohn's disease and subclinically in SpA. However, a fraction of patients with SpA develops overt Crohn's disease. AIMS: To investigate whether subclinical gut lesions in patients with SpA are associated with transcriptome changes comparable to those seen in Crohn's disease and to examine global gene expression in non-inflamed colon biopsy specimens and screen patients for differentially expressed genes. METHODS: Macroarray analysis was used as an initial genomewide screen for selecting a comprehensive set of genes relevant to Crohn's disease and SpA. This led to the identification of 2625 expressed sequence tags that are differentially expressed in the colon of patients with Crohn's disease or SpA. These clones, with appropriate controls (6779 in total), were used to construct a glass-based microarray, which was then used to analyse colon biopsy specimens from 15 patients with SpA, 11 patients with Crohn's disease and 10 controls. RESULTS: 95 genes were identified as differentially expressed in patients with SpA having a history of subclinical chronic gut inflammation and also in patients with Crohn's disease. Principal component analysis of this filtered set of genes successfully distinguished colon biopsy specimens from the three groups studied. Patients with SpA having subclinical chronic gut inflammation cluster together and are more related to those with Crohn's disease. CONCLUSION: The transcriptome in the intestine of patients with SpA differs from that of controls. Moreover, these gene changes are comparable to those seen in patients with Crohn's disease, confirming initial clinical observations. On the basis of these findings, new (genetic) markers for detection of early Crohn's disease in patients with SpA can be considered.

Adult↗

Wound healing after paranasal sinus surgery: neutrophilic inflammation influences the outcome.

AIMS: After failure of medical treatment, functional endoscopic sinus surgery (FESS) remains the best treatment for chronic sinusitis (CS) and nasal polyposis (NP). The precise mechanisms involved in wound healing after sinus surgery remain unclear. The aim of this study was to explore systematically the different histomorphological processes and cell populations involved in the wound repair of the paranasal mucosa. METHODS AND RESULTS: Biopsy specimens from patients operated on for CS and NP were collected 1, 2 and 6 months after surgery and compared with baseline and control specimens. A pathologist blinded to biopsy status evaluated the haematoxylin/eosin-stained sections for oedema, fibrosis and inflammatory reaction, and the immunohistochemical preparations for epithelial replication, myofibroblasts, macrophages, neutrophils and eosinophils. Samples from NP showed significantly more oedema than those from CS. At baseline, oedema showed a significant correlation with macrophages, neutrophils and eosinophils, while fibrosis was inversely correlated with neutrophils. During healing, after a short increase at month 1, oedema decreased. Fibrosis and myofibroblasts showed an inverse relationship. Finally, during the postoperative period, both macrophages and neutrophils were increased when compared with controls. CONCLUSIONS: The severity of the neutrophilic inflammation appears to influence the formation of fibrosis during wound repair after sinus surgery.

Antigens, CD↗

Synthesis and evaluation of a 99mTechnetium labeled chitin-binding protein as potential specific radioligand for the detection of fungal infections in mice.

AIM: Radiopharmaceuticals can be used to exploit differences between microorganisms in order to distinguish fungal from bacterial infection. Chitin, abundant in the cell wall of fungi, is not present in mammalian or bacterial cells and therefore represents a highly specific target to localize fungal infection. In this study, we have examined the potential of chitin-binding protein (CBP21) from Serratia marcescens as a specific radiotracer for the detection of invasive fungal infections. METHODS: CBP21 was labeled with 99mTc via hydrazinonicotinamide (HYNIC) and its characteristics were analyzed. In vitro binding studies with polymorphic chitin forms and microorganisms (fungi as well as bacteria) were performed. In vivo biodistribution of the compound was studied in immunocompromised mice with bacterial and fungal infections in the left and right thigh muscle, respectively, using 99mTc-HYNIC-myoglobin as size-matched control and 67Ga-citrate as positive control. Scintigraphic images were acquired at 1 and 7 h postinjection of the tracer. RESULTS: 99mTc-HYNIC-CBP21 was labeled with a radiochemical yield of 61% and a specific activity of 22.3 MBq/nmol. Highest in vitro binding percentages were found with beta-chitin (86.8+/-2.4%). Binding interactions to fungi were higher than to bacteria (P<0.05). In vivo, best ratios of fungal infection versus bacterial infection were seen at 5 and 7 h (3.6+/-1.2 and 2.9+/-1.4, respectively) postinjection of the tracer. Maximum uptake of the tracer in fungal infections (0.63+/-0.11%ID/g) at 7 h was significantly (P<0.05) higher than uptake seen in bacterial infections (0.34+/-0.11%ID/g) or the uptake of 99mTc-HYNIC-myoglobin (P<0.05) in the same infections (0.35+/-0.11%ID/g, respectively, 0.3+/-0.01%ID/g). CONCLUSIONS: This study shows that 99mTc-HYNIC-CBP21 is able to specifically interact with chitin in vitro. Scintigraphy and postmortem in vivo data indicate that 99mTc-HYNIC-CBP21 is able to distinguish fungal infection from bacterial infection probably due to a specific interaction of the protein with the chitin in the fungal cell wall.

Animals↗

Neutrophil-derived metalloproteinase-9 predicts healing quality after sinus surgery.

BACKGROUND: In a recent study, we have shown that gelatinase-B (metalloproteinase [MMP]-9) in nasal secretions can have both monitoring and predictive value on the healing outcome after functional endoscopic sinus surgery (FESS) to treat chronic rhinosinusitis (CRS) and nasal polyposis (NP). In this work, we aimed to explore the source of MMP-9 and the influence of inflammation on MMP-9 expression and release in nasal tissue and secretions during airway remodelling after surgery. METHODS: Biopsies from 23 patients operated by FESS for CRS or NP were collected 1, 3, and 6 months after sinus surgery. MMP-9 expression in the paranasal mucosa was correlated with healing quality, with MMP-9 concentrations in nasal fluid, and with histomorphologic findings (edema, fibrosis, alphasmooth muscle actin, CD-68, myeloperoxidase, EG2, and transforming growth factor [TGF]-beta1 stainings). RESULTS: MMP-9 concentrations in nasal fluid were paralleled by MMP-9 expression inside the extracellular matrix (ECM) after sinus surgery. MMP-9 expression in ECM was significantly correlated with healing quality (r = 0.378, P = .0181), and poor healers presented significantly more edema (P < .05). The amounts of MMP-9 in nasal fluid were significantly and independently predicted by the number of neutrophils (P = .0224) and macrophages (P = .0497) in the tissue. In contrast, MMP-9 expression was not related to fibrosis, number of myofibroblasts, or TGF-beta1 expression in ECM. CONCLUSIONS: MMP-9 expression is increased in the ECM during wound healing and parallels concentrations of MMP-9 in nasal fluids. Inflammatory cells represent the major source of increased MMP-9 expression, which is linked to poor healing quality.

Adolescent↗

CARD15 polymorphisms are associated with anti-Saccharomyces cerevisiae antibodies in caucasian Crohn's disease patients.

Carriage of CARD15 gene polymorphisms and the serological marker anti-Saccharomyces cerevisiae antibodies (ASCA) are two markers for Crohn's disease (CD). Similar phenotypes have been associated with both markers. In the present study we analysed whether both markers were associated with each other and, if so, whether this association could be explained by a direct link or by an indirect association with those phenotypes. Therefore, we included 156 consecutive Caucasian CD patients and assessed the prevalence of the three common single nucleotide polymorphisms in the CARD15 gene. Serum samples were analysed for IgA and IgG ASCA by ELISA. CD patients with CARD15 polymorphisms were more frequently ASCA positive (OR 2.7 (1.4-5.2); P = 0.002) and had higher titres for ASCA IgA (P = 0.005) and ASCA IgG (P < 0.001) compared to patients carrying the wild type polymorphisms. Multivariate analysis demonstrated that this association was independent from ileal disease, penetrating disease and stricturing disease, the need for resective bowel surgery, familial cases, smoking habits and early age at onset. Homozygotes or compound heterozygotes for CARD15 polymorphisms had significantly more frequent ASCA positivity compared to single heterozygotes (OR 9.1 (1.1-74.2), P(c) (corrected P-value) = 0.030). These data indicate that there is a significant association between the carriage of CARD15 polymorphisms and ASCA, independent of the described phenotypes. Moreover, ASCA positivity is more frequent in CD patients carrying 2 CARD15 polymorphisms compared to single heterozygotes.

Adolescent↗

Organization of secondary lymphoid tissue and local IgE formation to Staphylococcus aureus enterotoxins in nasal polyp tissue.

BACKGROUND: Bilateral nasal polyposis (NP) is characterized by high concentrations of IgE in NP tissue, which show no relation to the atopic status. We aimed to study the relationship between systemic and local IgE formation, nasal carriage of Staphylococcus aureus and nasal polyposis. METHODS: In serum and nasal tissue homogenates from 24 NP patients and 12 controls, we determined concentrations of total IgE and IgE antibodies to inhalant allergens and S. aureus enterotoxins (SAEs; A,B,C,D,E,TSST) by ImmunoCAP. Tissue cryosections were stained for CD3, CD20, CD38, CD23, FcepsilonRI, IgE and SEA/SEB. RESULTS: We demonstrated a higher incidence of S. aureus colonization (17/24) and IgE antibodies to SAEs in NP tissue (12/24) compared with controls (3/12 and 0/12, respectively). Total IgE and IgE antibodies in serum and NP tissue were dissociated because of local polyclonal IgE formation in NP tissue. Staining of NP tissue revealed follicular structures characterized by B and T cells, and lymphoid accumulations with diffuse plasma cell infiltration. CONCLUSIONS: We demonstrated the organization of secondary lymphoid tissue in polyp tissue and a polyclonal hyper-immunoglobulinemia E associated with the presence of IgE antibodies to SAEs, colonization with S. aureus, and tissue eosinophilia in a relevant subgroup of polyp patients.

Adult↗

X linked agammaglobulinaemia and rheumatoid arthritis.

BACKGROUND: Much interest has been shown recently in the pathogenic role of B cells in rheumatoid arthritis (RA) owing to the marked clinical responses to anti-CD20 treatment in RA. CASE REPORT: A patient with X linked agammaglobulinaemia (XLA) presented with an erosive symmetric polyarthritis with histological features of RA, including formation of a destructive pannus. Furthermore, the patient developed subcutaneous nodules that were histologically indistinguishable from rheumatoid nodules. Surprisingly, lymphocytic infiltrates in both the synovium and nodule consisted almost exclusively of CD8+ T cells. DISCUSSION: Although some peculiar B cell subsets have been described in patients with XLA, no B cell subsets could be demonstrated in synovial tissue or the subcutaneous nodule. This case illustrates that classical RA can develop in the absence of mature B cells.

Agammaglobulinemia↗

CARD15 gene polymorphisms in patients with spondyloarthropathies identify a specific phenotype previously related to Crohn's disease.

BACKGROUND: The association between spondyloarthropathy and Crohn's disease is well known. A risk for evolution to Crohn's disease has already been shown in the subgroup of patients with spondyloarthropathy associated with chronic gut inflammation. OBJECTIVE: To investigate whether the reported polymorphisms in the CARD15 gene, a susceptibility gene for Crohn's disease, are associated with the presence of preclinical intestinal inflammation observed in spondyloarthropathies. METHODS: 104 patients with spondyloarthropathies were studied. All underwent ileocolonoscopy with biopsies between 1983 and 2004. The prevalence of three single nucleotide polymorphisms in the CARD15 gene (R702W, G908R, and 1007fs) was assessed using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR); the patients were compared with an ethnically matched Crohn's disease population and a control population. RESULTS: The carrier frequency of R702W, G908R, or 1007fs variants in the spondyloarthropathy populations (20%) was similar to the control population (17%), but increased to 38% in the spondyloarthropathy subgroup with chronic gut inflammation. This frequency was significantly higher than in the other spondyloarthropathy subgroups (p = 0.001) or the control group (p = 0.006), but not different from the Crohn's disease group (49%) (NS). This indicates that CARD15 polymorphisms are associated with a higher risk for development of chronic gut inflammation. CONCLUSIONS: CARD15 gene polymorphisms clearly identify a subgroup of patients with spondyloarthropathies associated with chronic intestinal inflammation.

Adolescent↗

Ad libitum feeding following ovariectomy in female Beagle dogs: effect on maintenance energy requirement and on blood metabolites.

The aim of this study was (i) to evaluate the effect of ovariectomy on daily energy requirement in Beagle dogs, and (ii) to evaluate the effects of ad libitum feeding with a high energy diet on energy consumption, body weight gain and blood metabolites in these spayed dogs. Four young adult female Beagle dogs were used. Ovariectomy induced a significant decrease of daily energy requirement in dogs. Ad libitum feeding, initiated 6 months after spaying, induced a significant increase in consumption in spayed dogs. This overconsumption was greatest during the first month of ad libitum feeding but continued for the entire 4 months of this period. When fed ad libitum, dogs gained excess body weight without significant effect on plasma cholesterol, triglycerides, glucose and insulin, at short term. These data suggest that energy intake should be strictly controlled to avoid excess weight gain in spayed dogs.

Animal Feed↗

Hypercholesterolaemia in a family of rough collie dogs.

A family of five privately owned rough collie dogs was referred for corneal lipidosis and also suffered from hypercholesterolaemia. The hypercholesterolaemia was characterised by an increase in the alpha-2 high density lipoprotein-1 band and was due to an increase in the cholesterol content of the very low density lipoprotein, low density lipoprotein and possibly the high density lipoprotein-1 fractions. A low-fat and energy-restricted diet did not reduce either total cholesterol or the corneal lipidosis. Corneal lipidosis regressed with short-chain fructo-oligosaccharide supplementation. However, the effects of short-chain fructo-oligosaccharides on total cholesterol were transient and variable.

Animals↗

Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease.

BACKGROUND: Sacroiliitis is a common extraintestinal manifestation of Crohn's disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn's disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases. OBJECTIVES: To investigate whether the presence of sacroiliitis in patients with Crohn's disease is linked to the carriage of CARD15 polymorphisms. METHODS: 102 consecutive patients with Crohn's disease were clinically evaluated by a rheumatologist. Radiographs of the sacroiliac joints were taken and assessed blindly by two investigators. The RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms (SNP) in the CARD15 gene. Every SNP was verified by direct sequencing. The HLA-B27 phenotype was determined. RESULTS: Radiological evidence of sacroiliitis with or without ankylosing spondylitis was found in 23 patients (23%), of whom only three were HLA-B27 positive. In contrast, 78% of patients with sacroiliitis carried a CARD15 variant v 48% of those without sacroiliitis (p = 0.01; odds ratio 3.8 (95% confidence interval, 1.3 to 11.5)). Multivariate analysis (logistic regression) showed that the association between sacroiliitis and CARD15 polymorphisms was independent of other CARD15 related phenotypes (ileal and fibrostenosing disease, young age at onset of disease, familial Crohn's disease) (p = 0.039). CONCLUSIONS: CARD15 variants were identified as genetic predictors of Crohn's disease related sacroiliitis. An association was demonstrated between these polymorphisms and an extraintestinal manifestation of Crohn's disease.

Adolescent↗

Cervical smears and human papillomavirus typing in sex workers.

OBJECTIVES: Sex workers are at increased risk for sexually transmitted infections (STI), human papillomavirus (HPV) and hence cervical cancer. In Belgium screening for cervical cancer starts at the age of 25, and is at 3 yearly intervals. The aim of this study is to assess risks for abnormal cervical smears and HPV in sex workers and decide whether the current screening policy is sufficient for them. METHODS: In an outreach programme for sex workers results of 653 smears sampled between 1992 and 2001 were analysed, and compared to a control group matched for age from the general population in 2001. Separately, 99 consecutive samples were typed for HPV and compared to an equal control group, matched for age. Smears and typing were performed according to current techniques. RESULTS: In the sex worker group 2.6% were diagnosed with atypical glandular cells of undetermined significance (AGUS)/atypical squamous cells of undetermined significance (ASCUS), 15.6% with low grade squamous intraepithelial lesion (LSIL), and 2.9% with high grade squamous intraepithelial lesion (HSIL), and in the control group results were 1.4%, 2.9% (p<0.001) and 0.6% (p<0.001) respectively. When considering only those under 25 years, 24.4% should have further follow up. Of the sex workers, 77.4% were positive for one or more types of HPV (55.9% for high risk HPV), in comparison with 27.6% of the control group (14.3% for high risk HPV) (p<0.001). In high risk HPV samples more LSIL and HSIL were found. CONCLUSION: Abnormal smears and high risk HPV were significantly more prevalent in sex workers than in controls. Current screening policy would miss many sex workers with an abnormal smear who should be referred for further follow up. It is proposed to screen sex workers when they enter prostitution regardless of their age.

Adolescent↗

Healing of experimental colonic anastomoses: effects of combined preoperative high-dose radiotherapy and intraperitoneal 5-fluorouracil.

To study the effects of preoperative radiochemotherapy (RCT) on the healing of colonic anastomosis, the rectosigmoid colon in male Wistar rats was irradiated up to an end dose of 41.6 Gy (RT) or sham-irradiated (SR). During the last 5 days of the irradiation schedule, 5-fluorouracil (5-FU) was administered intraperitoneally in either a high dose (20 mg/kg, chemotherapy-high dose [CH]) or a low dose (10 mg/kg, chemotherapy-low dose [CL]). Animals were randomly arranged into six groups: group I, control (SR + saline intraperitoneally); group II, RT only; group III, SR + CL; group IV, RT + CL; group V, SR + CH; group VI, RT + CH. Four days after RCT, a side-to-side anastomosis was constructed between the irradiated rectosigmoid and the nonirradiated caecum. Animals were killed 10 days postoperatively. No significant differences were found in the anastomotic bursting pressure or the bursting wall tension. In group VI, mitoses were less (P < 0.01) and mucosal ulceration was more (P = 0.03) pronounced compared to group I. Sclerotic arteries were seen in all irradiated groups and in animals that received high-dose 5-FU alone. 5-FU administration in high or low dose, with or without RT, induced more inflammation in the submucosa compared to controls (P < 0.05). Conclusively, RCT has no detrimental effect on the mechanical strength of colonic anastomosis in this rat model. However, RCT with high-dose 5-FU induces more histological alterations at the anastomotic site.

Anastomosis, Surgical↗

Immunomodulatory effects of anti-tumor necrosis factor alpha therapy on synovium in spondylarthropathy: histologic findings in eight patients from an open-label pilot study.

OBJECTIVE: To assess the effects of treatment with anti-tumor necrosis factor alpha (anti-TNFalpha) on synovial histology in patients with spondylarthropathy (SpA) in order to confirm the effect on peripheral synovitis and to investigate the immunologic mechanisms involved in anti-TNFalpha therapy. METHODS: Patients with treatment-resistant SpA were treated with infliximab (5 mg/kg) at weeks 0, 2, and 6 in an open-label pilot study. In 8 patients, synovial biopsy tissues obtained at baseline, week 2, and week 12 were used for histologic and immunohistochemical evaluation. RESULTS: In all 8 patients (3 with ankylosing spondylitis, 1 with undifferentiated SpA, and 4 with psoriatic arthritis), there was a clear clinical improvement in the peripheral arthritis after anti-TNFalpha therapy. Histologic analysis of the synovial biopsy tissues indicated that the synovial lining layer thickness tended to decrease, with a significant reduction of CD55+ synoviocytes, at week 12. In the sublining layer, vascularity was reduced at week 12, with a decreased endothelial expression of vascular cell adhesion molecule 1 but not intercellular adhesion molecule 1, platelet endothelial cell adhesion molecule 1, and E-selectin. Although at week 2 and week 12, the number of neutrophils and CD68+ macrophages in the sublining layer was decreased, the overall degree of inflammatory infiltration remained unchanged. This could be related to the lymphocyte infiltration since at week 12, only CD4+ cells (but not CD3+, CD45RO+, and CD8+ cells) tended to decrease, while CD20+ lymphocytes and plasma cells were clearly increased. CONCLUSION: The reduction in lining layer thickness, vascularity, and infiltration with neutrophils and macrophages paralleled the beneficial effect of anti-TNFalpha therapy on peripheral synovitis in 8 patients with different subtypes of SpA. The adhesion molecule expression, T cell infiltration, and, most important, B cell infiltration seemed to contrast with previous observations in RA. Although these preliminary data need to be confirmed in a larger cohort, they suggest distinct immunomodulatory mechanisms of anti-TNFalpha in SpA.

Adjuvants, Immunologic↗