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Biomedical subjects

P Pelckmans

Publications and source records attributed to P Pelckmans.

At least 19 recordsLinked to original sources

Rapid improvement of bone metabolism after infliximab treatment in Crohn's disease.

BACKGROUND: Crohn's disease is associated with low bone mineral density and altered bone metabolism. AIM: To assess the evolution of bone metabolism in Crohn's disease patients treated with infliximab. METHODS: We studied 71 Crohn's disease patients treated for the first time with infliximab for refractory Crohn's disease. Biochemical markers of bone formation (type-I procollagen N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin) and of bone resorption (C-telopeptide of type-I collagen) were measured in the serum before and 8 weeks after infliximab therapy and compared with values in a matched healthy control group. RESULTS: Eight weeks after treatment with infliximab, a normalization of bone markers was observed with a median increase in formation markers of 14-51% according to marker and a lower but significant decrease in resorption marker (median 11%). A clinically relevant increase in bone formation markers was present in 30-61% of patients according to the marker. A clinically relevant decrease in C-telopeptide of type-I collagen was present in 38% of patients. No association was found with any tested demographic or clinical parameter. CONCLUSION: Infliximab therapy in Crohn's disease may rapidly influence bone metabolism by acting either on bone formation or bone resorption. This improvement seems to be independent of clinical response to infliximab.

Adolescent↗

Renal impairment in patients with inflammatory bowel disease: association with aminosalicylate therapy?

BACKGROUND: In recent years, several case reports have been published suggesting an association between the use of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) and the development of chronic tubulo-interstitial nephritis. Apart from lesions associated to 5-ASA treatment, however, it is clear that IBD itself may also induce renal impairment, albeit the frequency is unknown. METHODS: During 1 year, all IBD patients seen at the outpatient clinic of 27 European centres of gastro-enterology were registered and screened for renal impairment controlling for a possible association with 5-ASA therapy. Patients were questioned about their medical and drug history and their IBD disease activity. Renal screening (calculated creatinine clearance) was performed at baseline, after 6 and 12 months. RESULTS: Included patients (n = 1,529) had a mean age of 39 (range 14-98), 56% had Crohn's disease, 42% ulcerative colitis and 2% indeterminate colitis. Half of the patients used 5-ASA during the study period. Decreased creatinine clearance was observed in 34 patients, among them 13 with chronic renal impairment. Comparing patients with and without renal impairment, no difference could be observed in 5-ASA consumption. In contrast, patients with renal impairment were significantly older, had a lower body mass index and showed a higher frequency of male sex, bowel resection and stoma. CONCLUSION: Although the association between 5-ASA therapy and chronic tubulo-interstitial nephritis is clearly described in several case reports, this prospective study came to the reassuring conclusion that renal impairment in IBD patients is not frequently observed and is rarely associated with 5-ASA therapy.

Adolescent↗

Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease.

OBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNF have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CD patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease.

Adolescent↗

A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism.

BACKGROUND: Two-thirds to three-fourths of patients with either refractory luminal or fistulizing Crohn disease respond to infliximab treatment. The ability or inability to respond seems to persist over time. Biological characteristics and/or genetic background can influence the response to treatment. The aim was to assess the value of C-reactive protein and TNF-alpha serum levels before treatment as well as the TNF -308 gene polymorphism in the prediction of response to infliximab treatment in Crohn disease. METHODS: Two-hundred-and-twenty-six Crohn disease patients treated in the setting of an expanded access programme to infliximab in Belgium were studied. There were 136 refractory luminal diseases and 90 refractory fistulizing diseases. Luminal diseases were treated with one single infusion; fistulizing diseases with three infusions at weeks 0, 2 and 6. A clinical response to treatment was defined as either a Crohn disease activity index <150 (complete) or a drop of 70 points (partial) at week 4, for luminal disease, and as either complete fistula healing (complete) or a decrease of at least 50% of the number of draining fistulas on two consecutive visits between weeks 0 and 18, for fistulizing disease. CRP and serum TNF-alpha levels were measured at week 0 before treatment and were compared between responders and non-responders. Patients were genotyped for the -308 TNF gene polymorphism, and allelic as well as genotype frequencies were compared between responders and non-responders. RESULTS: There were 73.2% responders (46.4% complete and 26.8% partial) and 26.8% non-responders. Response rates were similar in luminal and fistulizing diseases. CRP level before treatment was significantly higher in responders than in non-responders (16.8 mg/l (5-160) versus 9.6 mg/l (5-143); P = 0.02). Furthermore, response rate was significantly higher in patients with elevated CRP (>5 mg/l) than in patients with a normal CRP value (<5 mg/l) before treatment (76% versus 46%; P=0.004; OR: 0.26 (0.11-0.63)). Allelic and genotype frequencies for -308 TNF gene polymorphism were not significantly different between responders and non-responders--with the exception of a slightly higher TNF2 frequency in non-responders in luminal disease (22.1 % versus 11.6%; P = 0.04). However, this was not associated with a significant difference in genotype frequencies. CONCLUSION: A positive clinical response to infliximab was associated with a higher CRP level before treatment in our population of Crohn disease patients, but there was no relevant association with -308 TNF gene polymorphism. We therefore suggest that CRP level may help to identify better candidates for infliximab treatment.

Adolescent↗

Schistosoma mansoni infection causing diffuse enteric inflammation and damage of the enteric nervous system in the mouse small intestine.

Schistosomiasis mansoni is a major health problem, mainly occurring in developing countries. A large proportion of infected individuals suffers from motility-related gastrointestinal problems. In the present study, the diffuse inflammatory response in the small bowel wall, as compared to the egg-induced granulomatous inflammation, was investigated. For this purpose, OF1 mice infected with Schistosoma mansoni 8-16 weeks prior to the experiment, and uninfected control mice were studied. The ileum showed both a diffuse mucosal inflammation as well as a granulomatous reaction. The diffuse mucosal inflammation caused an increase in the thickness of the mucosa, with blunting of the villi. A significant, transient increase of thickness of the muscularis propria after 12 weeks of infection was noted. There was an infection-related mast cell infiltrate in the muscularis propria, consisting of formalin fixation-insensitive connective tissue mast cells. Ganglionitis of the myenteric plexus was noted. Rarely, ganglia of the myenteric plexus contained apoptotic cells. A general pharmacological set of experiments showed a significant increase in intestinal contractility, both to exogenously administered, as well as to endogenously released neurotransmitters. Our results demonstrate that S. mansoni infection in the mouse ileum leads to diffuse specific enteric inflammation that is associated with an enhanced response to contractile agents.

Animals↗

Intestinal stenosis from mesenteric injury after blunt abdominal trauma.

We report a case in which blunt abdominal trauma resulted in injury to the mesentery with subsequent ischemic stricture of the adjacent small bowel. We present CT images at the time of trauma and 5 weeks later when clinical signs of intestinal obstruction occurred. We include images of enteroclysis and angiography of this uncommon sequela of blunt abdominal trauma. At surgery, a stenotic small bowel loop was found adjacent to a healed defect in the mesentery. Histological examination of the resected segment showed mucosal and submucosal ischemia with mucosal ulceration, mural inflammation, and fibrosis. Posttraumatic intestinal stenosis subsequent to a mesenteric tear should be included in the differential diagnosis in a patient with a history of blunt abdominal trauma and signs of intestinal obstruction.

Abdominal Injuries↗

Diagnosis and nonsurgical management of bile leak complicated by biloma after blunt liver injury: report of two cases.

We report on two patients with biliary tract injury and associated biloma following blunt abdominal trauma. Both patients underwent emergency surgery because of hemodynamic instability and bloody peritoneal aspiration. Computed tomography in the postoperative days showed severe hepatic parenchymal injury and the presence of hypodense collections with intraparenchymal and subcapsular extension, suggestive for biloma, but otherwise failed to demonstrate the exact location of the bile duct injury. One of them underwent temporary percutaneous drainage. Bile duct injury was well demonstrated on endoscopic retrograde cholangiography (ERCP) and treated by endobiliary stent placement. This report advocates the use of ERCP and endobiliary stenting in the management of biliary injury resulting from liver trauma.

Abdominal Injuries↗

HBV-specific lymphoproliferative and cytokine responses in patients with chronic hepatitis B.

BACKGROUND/AIMS: Hepatitis B virus specific T cell responses are crucial for viral elimination but their nature is not fully understood. METHODS: We studied the regulation of proliferation and cytokine production after antigenic stimulation in peripheral blood mononuclear cells from chronically HBV-infected patients and subjects with natural immunity after recovery from an acute infection. Proliferation and production of interferon-gamma, IL-10 and tumor necrosis factor-alpha were determined after stimulation with HBcAg, HBeAg or HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12, interferon-gamma, IL-4, IL-10 or tumor necrosis factor-alpha. RESULTS: Upon stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic hepatitis B virus patients displayed a clear class-II restricted proliferative response (SI greater than 2.5). Both interferon-gamma (less than 50 IU/ml) and IL-10 levels up to 600 pg/ml were detected. Proliferative or cytokine responses to HBsAg were very weak or absent. Addition of IL-12 to HBeAg-stimulated cultures increased the production of interferon-gamma to more than 200 IU/ml in all patients and slightly increased the production of IL-10. Neutralization of IL-10 increased the HBeAg-induced interferon-gamma production but had no effect on tumor necrosis factor-alpha production. Addition of anti-IL-4 or anti-tumor necrosis factor-alpha had no significant influence on proliferation or cytokine release. Importantly, in both chronic hepatitis B virus patients and naturally immune subjects, IL-12 induced proliferative and interferon-gamma responses in peripheral blood mononuclear cells stimulated with HBsAg. CONCLUSIONS: Our data indicate that peripheral blood mononuclear cells from chronic hepatitis B virus patients proliferate and produce interferon-gamma and IL-10 upon HBeAg but not upon HBsAg stimulation. IL-12 augments the HBeAg-induced responses and, additionally, provokes proliferation and interferon-gamma production in HBsAg-stimulated cultures.

Cryopreservation↗

Fine needle trucut biopsy of focal liver lesions: a new technique.

A series of 77 ultrasound guided biopsies were performed in 72 patients with an ultrasonographically diagnosed focal liver lesion using a new semiautomated biopsy gun (Temno Biopty Gun) with a 21 G trucut needle. The rate of insufficient sampling was very low (1.5%), and more precise identification of malignant as well as benign lesions was possible when compared with the results of other fine-needle techniques available in the literature. No higher complication rate was noted. Our results show a sensitivity of 88%, a specificity of 100%, and an overall accuracy of 91% in identifying malignancy. Therefore we conclude that fine-needle trucut biopsy is a safe and accurate procedure combining the safety of the fine needle with the better sample quality of a large-bore needle biopsy technique.

Adolescent↗

[Seroprevalence of HCV in the general population of Niger and in patients with chronic liver diseases: comparison of different second generation tests and PCR].

The aim of our study in Niger was to compare the seroprevalence of hepatitis C in a rural "normal" population and in a group of patients presenting at the hospital with signs of chronic liver disease: to estimate this seroprevalence, we used 4 second generation ELISA screening and 3 confirmatory tests (LIA, RIBA and PCR); genotyping was performed on PCR positive sera, using Inno-LIPA HCV. We could not find a statistically significant difference (Fisher's exact test) between the two groups of healthy and sick people (2.5 versus 5.4% for seroprevalence and 2.5 versus 3.2% for viremia). Our study didn't find any relationship between hepatitis C infection, blood transfusion or surgery; other major ways of transmission of hepatitis C have to be considered. The predominant genotype detected was 2a.

Chronic Disease↗

Endoscopic treatment of biliary ascariasis. Report of a case.

Ascaris lumbricoides is the most common intestinal parasite to infect humans. The incidence of ascariasis is increasing in our regions, due to world travel and population migration. In one third of cases, the worm can enter the bile duct and cause cholangitis or biliary colics. Diagnosis and treatment of ascariasis are discussed. Endoscopic retrograde cholangio-pancreaticography (ERCP) with endoscopic extraction of the worm, using a Dormia basket, is a safe and effective procedure for the diagnosis and treatment of biliary ascariasis. This technique serves as an effective alternative for surgery.

Animals↗

Postendoscopic sphincterotomy stenosis.

We report on two patients. The first patient is a 62-year-old female patient who had cholecystectomy in 1970, and in whom two small bile duct stones were removed after endoscopic sphincterotomy in 1987. Within two months of this procedure, she developed three episodes of documented acute pancreatitis. The other patient, a 58-year-old female, developed acute pancreatitis three months after an endoscopic sphincterotomy for stones in the common bile duct. In both patients, ERCP revealed a cicatricial stenosis of the common bile duct and the pancreatic duct. The condition was resolved by repeat sphincterotomy. The first patient needed repeated endoscopic insertion of bilioduodenal endoprostheses and an endoprosthesis in the pancreatic duct. It is interesting to note that, in contrast to surgical reports, very few postpapillotomy stenoses are reported by endoscopists.

Common Bile Duct Diseases↗

Prevention of duodenal ulcer recurrence by pirenzepine 50 mg twice daily.

Eighty-four patients with healed duodenal ulcers were treated for 1 year with pirenzepine, 50 mg twice daily, or placebo in this double-blind, randomized, multicenter trial. Clinical follow-up and endoscopy were performed before and after 3, 6, and 12 months of treatment. Endoscopy was also carried out whenever symptoms compatible with ulcer recurrence were present for more than 2 days. Both groups were well matched for age, sex, duration of peptic ulcer disease, and smoking habits. There were 21 drop-outs due to lack of compliance. Therefore, 32 patients treated with pirenzepine and 31 with placebo were included in the analysis. Expressed in cumulative percentage of recurrence, with pirenzepine, 28% of the patients had a relapse at 3 months, 41% at 6 months, and 53% at 12 months; with placebo, the recurrence rates were 58% at 3 months, 68% at 6 months, and 71% at 12 months. The mean success time at 1 year is also longer for pirenzepine (7.38 months) than for placebo (5.52 months). These differences are significantly in favor of pirenzepine (p less than 0.05). Both treatments were well tolerated. Dry mouth was more frequently observed with pirenzepine (14 versus 5 patients). We conclude that pirenzepine, 50 mg twice daily, significantly reduces the relapse rate of duodenal ulcers during a 1-year maintenance treatment.

Adult↗