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Biomedical subjects

M Peeters

Publications and source records attributed to M Peeters.

At least 73 records · Page 4Linked to original sources
PubMed2000

The utility of positron emission tomography for the diagnosis and staging of recurrent esophageal cancer.

OBJECTIVE: To study the utility of whole-body positron emission tomography with (18)F-fluoro-deoxy-D -glucose (FDG-PET) for the evaluation of recurrence after curative resection of cancer of the esophagus or gastroesophageal junction. METHODS: Forty-one patients with a clinical or radiologic suspicion of recurrent disease underwent conventional diagnostic work-up, including a spiral computed tomographic scan, an endoscopic ultrasound, and a dedicated whole-body FDG-PET. PET lesions were classified as equivocal or suspicious recurrence. The conventional diagnostic work-up and PET findings were correlated with pathology or with radiologic and clinical follow-up. Equivocal lesions were classified as positive. RESULTS: Forty recurrences were found in 33 patients. The lesions were perianastomotic (n = 9), regional (n = 12), and at distant sites (n = 19). For the diagnosis of a perianastomotic recurrence, the sensitivity, specificity, and accuracy of FDG-PET were 100%, 57%, and 74%, versus 100%, 93%, and 96% for conventional diagnostic work-up, respectively (P = not significant). False-positive PET lesions were found in patients with a progressive anastomotic stenosis requiring repetitive endoscopic dilatation. For the diagnosis of regional and distant recurrences, the sensitivity, specificity, and accuracy of PET were 94%, 82%, and 87%, versus 81% (P = not significant), 82% (P = not significant), and 81% (P =.0771) for conventional diagnostic work-up. All false-positive PET lesions (n = 4) had been reported as equivocal. On a patient base, PET provided additional information in 11 of 41 (27%) patients. A major impact on diagnosis was found in 5 patients with equivocal or negative findings on complete diagnostic work-up in whom PET provided a true-positive diagnosis. In 5 other patients the diagnosis was staged upward from localized to extended recurrent disease, and in 1 patient with an equivocal complete diagnostic work-up, PET correctly excluded malignancy. CONCLUSION: FDG-PET allows a highly sensitive diagnosis and accurate whole-body staging of symptomatic recurrent esophageal cancer. Further studies in asymptomatic patients are needed to assess the potential benefit on survival.

Adenocarcinoma↗
PubMed2000

Histopathologic validation of lymph node staging with FDG-PET scan in cancer of the esophagus and gastroesophageal junction: A prospective study based on primary surgery with extensive lymphadenectomy.

OBJECTIVE: To assess the value of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) for preoperative lymph node staging of patients with primary cancer of the esophagus and gastroesophageal junction. SUMMARY BACKGROUND DATA: FDG-PET appears to be a promising tool in the preoperative staging of cancer of the esophagus and gastroesophageal junction. Recent reports indicate a higher sensitivity and specificity for detection of stage IV disease and a higher specificity for diagnosis of lymph node involvement compared with the standard use of computed tomography and endoscopic ultrasound. METHODS: Forty-two patients entered the prospective study. All underwent attenuation-corrected FDG-PET imaging of the neck, thorax, and upper abdomen, a spiral computed tomography scan, and an endoscopic ultrasound. The gold standard consisted exclusively of the histology of sampled nodes obtained by extensive two-field or three-field lymphadenectomies (n = 39) or from guided biopsies of suspicious distant nodes indicated by imaging (n = 3). RESULTS: The FDG-PET scan had lower accuracy for the diagnosis of locoregional nodes (N1-2) than combined computed tomography and endoscopic ultrasound (48% vs. 69%) because of a significant lack of sensitivity (22% vs. 83%). The accuracy for distant nodal metastasis (M+Ly), however, was significantly higher for FDG-PET than the combined use of computed tomography and endoscopic ultrasound (86% vs. 62%). Sensitivity was not significantly different, but specificity was greater (90% vs. 69%). The FDG-PET scan correctly upstaged five patients (12%) from N1-2 stage to M+Ly stage. One patient was falsely downstaged by FDG-PET scanning. CONCLUSIONS: FDG-PET scanning improves the clinical staging of lymph node involvement based on the increased detection of distant nodal metastases and on the superior specificity compared with conventional imaging modalities.

Adult↗
PubMed2000

Exclusion of linkage of Crohn's disease to previously reported regions on chromosomes 12, 7, and 3 in the Belgian population indicates genetic heterogeneity.

Susceptibility to inflammatory bowel disease (IBD) is significantly determined by genetic factors. Linkage data from genome-wide searches have identified regions on chromosomes 16, 12, 7, and 3. Our goal was to replicate these four regions in a Belgian population of IBD families. Fifty-four IBD families were studied (47 with Crohn's disease [CD] and 7 with mixed CD and ulcerative colitis, containing 79 affected sibpairs (68 CD only, 11 mixed) for the regions previously implicated to chromosomes 16, 12, 7, and 3. In this study, no evidence for linkage was found on any of the four chromosomal regions studied for either the whole IBD dataset or the CD subgroup. The multipoint maximum logarithm of odds scores were less than 0.7 for all four regions. Exclusion mapping could significantly exclude chromosomes 3, 7, and 12. Despite earlier findings, we could significantly exclude linkage of CD with previously reported regions on chromosomes 12, 7, and 3, and could not find evidence for linkage to chromosome 16. It is important to report these findings in light of the genetic heterogeneity of IBD. A genome-wide search on a larger group of affected siblings is being analyzed to detect other possible susceptibility loci in the Belgian population.

Belgium↗
PubMed2000

Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B.

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.

Administration, Oral↗
PubMed2000

Genetic diversity of protease and reverse transcriptase sequences in non-subtype-B human immunodeficiency virus type 1 strains: evidence of many minor drug resistance mutations in treatment-naive patients.

Most human immunodeficiency virus (HIV) drug susceptibility studies have involved subtype B strains. Little information on the impact of viral diversity on natural susceptibility to antiretroviral drugs has been reported. However, the prevalence of non-subtype-B (non-B) HIV type 1 (HIV-1) strains continues to increase in industrialized countries, and antiretroviral treatments have recently become available in certain developing countries where non-B subtypes predominate. We sequenced the protease and reverse transcriptase (RT) genes of 142 HIV-1 isolates from antiretroviral-naive patients: 4 belonged to group O and 138 belonged to group M (9 subtype A, 13 subtype B, 2 subtype C, 5 subtype D, 2 subtype F1, 9 subtype F2, 4 subtype G, 5 subtype J, 2 subtype K, 3 subtype CRF01-AE, 67 subtype CRF02-AG, and 17 unclassified isolates). No major mutations associated with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors were detected. Major mutations linked to resistance to non-NRTI agents were detected in all group O isolates (A98G and Y181C) and in one subtype J virus (V108I). In contrast, many accessory mutations were found, especially in the protease gene. Only 5.6% of the 142 strains, all belonging to subtype B or D, had no mutations in the protease gene. Sixty percent had one mutation, 22.5% had two mutations, 9.8% had three mutations, and 2.1% (all group O strains) had four mutations. In order of decreasing frequency, the following mutations were identified in the protease gene: M36I (86.6%), L10I/V (26%), L63P (12.6%), K20M/R (11.2%), V77I (5.6%), A71V (2.8%), L33F (0.7%), and M46I (0.7%). R211K, an accessory mutation associated with NRTI resistance, was also observed in 43.6% of the samples. Phenotypic and clinical studies are now required to determine whether multidrug-resistant viruses emerge more rapidly during antiretroviral therapy when minor resistance-conferring mutations are present before treatment initiation.

Amino Acid Sequence↗
PubMed2000

Unprecedented degree of human immunodeficiency virus type 1 (HIV-1) group M genetic diversity in the Democratic Republic of Congo suggests that the HIV-1 pandemic originated in Central Africa.

The purpose of this study was to document the genetic diversity of human immunodeficiency virus type 1 (HIV-1) in the Democratic Republic of Congo (DRC; formerly Zaire). A total of 247 HIV-1-positive samples, collected during an epidemiologic survey conducted in 1997 in three regions (Kinshasa [the capital], Bwamanda [in the north], and Mbuyi-Maya [in the south]), were genetically characterized in the env V3-V5 region. All known subtypes were found to cocirculate, and for 6% of the samples the subtype could not be identified. Subtype A is predominant, with prevalences decreasing from north to south (69% in the north, 53% in the capital city, and 46% in the south). Subtype C, D, G, and H prevalences range from 7 to 9%, whereas subtype F, J, K, and CRF01-AE strains represent 2 to 4% of the samples; only one subtype B strain was identified. The highest prevalence (25%) of subtype C was in the south, and CRF01-AE was seen mainly in the north. The high intersubtype variability among the V3-V5 sequences is the most probable reason for the low (45%) efficiency of subtype A-specific PCR and HMA (heteroduplex mobility assay). Eighteen (29%) of 62 samples had discordant subtype designations between env and gag. Sequence analysis of the entire envelope from 13 samples confirmed the high degree of diversity and complexity of HIV-1 strains in the DRC; 9 had a complex recombinant structure in gp160, involving fragments of known and unknown subtypes. Interestingly, the unknown fragments from the different strains did not cluster together. Overall, the high number of HIV-1 subtypes cocirculating, the high intrasubtype diversity, and the high numbers of possible recombinant viruses as well as different unclassified strains are all in agreement with an old and mature epidemic in the DRC, suggesting that this region is the epicenter of HIV-1 group M.

Africa, Central↗
PubMed1999

The identification of a complex A/G/I/J recombinant HIV type 1 virus in various West African countries.

In this sequence note we describe the full-length genome sequence of an HIV-1 isolate originating from the west African country of Mali. The phylogenetic tree analysis from the near full-length genome shows that the 95ML84 strain forms a separate cluster, supported by 100% of the bootstrap values, with the previously described A/G/J/? mosaic virus BFP90 from Burkina Faso. Additional analysis showed that throughout the genome the lowest diversity was seen between the 95ML84 and the BFP90 viruses, and bootscan analysis showed a similar complex genomic structure. In addition to the initial report describing the BFP90 virus as an A/G/J/? recombinant, our data show that for the BFP90 and 95ML84 strains the unclassified region corresponds to subtype I. The A/G/I/J BFP90 and 95ML84 strains represent the fifth and most complex circulating recombinant form of HIV-1 detected so far, and our data show its presence in various West African countries. Subtype I and J sequences, initially considered rare, seem to have broadened their geographical spread by way of these recombinant forms.

Burkina Faso↗
PubMed1999

Intrapatient variability of HIV type 1 group O ANT70 during a 10-year follow-up.

HIV-1 ANT70 is the first HIV-1 group O virus isolate obtained from a 25-year-old Cameroonian woman, who seroconverted in March 1987. This individual has remained asymptomatic and clinically healthy (clinical stage WHO 1, CDC II) even though she did not receive any antiretroviral therapy for HIV-1 before 97 months post-seroconversion. CD4+ T cell counts declined steadily to 200/microl at 70 months postseroconversion. The HIV-1 ANT70 nucleotide and amino acid sequence diversity of the V3C3-encoding env fragment within this individual was followed over a 10-year period. RT-PCR, cloning, sequencing, and genetic analyses were performed on eight plasma follow-up samples. Extensive increasing intra- and intersample variation was observed. This is the first long-term (>10 years) follow-up of the genetic variability of an HIV-1 group O-infected individual. As the course of the disease in the HIV-1 ANT70-infected woman was similar in many aspects to that of group M-infected individuals, it remains to be elucidated whether the changes observed in the V3 loop are critical for disease progression.

Adult↗
PubMed1999

High diversity of HIV-1 subtype F strains in Central Africa.

In this paper, we studied the variability of HIV-1 subtype F strains in Africa. For 11 viruses, mainly of Central African origin, different parts of the genome were genetically characterized. For all strains the V3-V5 region of the envelope gene was sequenced, and for 7 strains, the entire envelope gene was studied. For 10 strains, the p24 region of the gag gene was also sequenced. For each region studied, three subgroups in the F subtype were identified, F1, F2, and F3. These three subgroups were supported by high bootstrap values and the intra- and inter-subgroup F distances were comparable to those obtained for the known subtypes A, B, C, D, E, G, and H. In subgroup F1, some African strains clustered with previously described strains from Brazil and Romania, suggesting an African origin of the HIV-1 epidemic in these countries. A more detailed analysis of the gag and the envelope sequences allowed the identification of four recombinant viruses. Our data show a high diversity among subtype F strains, suggesting the presence of new subtypes in the regions studied. If biological differences exist among subtypes, it is important that these subtypes be well defined. The data from our study show that there is a need to clearly identify the different subgroups within the F subtype.

Acquired Immunodeficiency Syndrome↗
PubMed1999

V3 serotyping of HIV-1 infection: correlation with genotyping and limitations.

HIV-1 V3 serotyping is a classification of immunodeficiency viruses based on antibody binding to V3 peptides that allows obtaining information on circulating subtypes that could be important for population-based epidemiologic studies. Recently, several laboratories have developed V3 enzyme-immunoassays (EIAs) using V3 peptides of subtypes A to E. In the present study, the utility of including additional peptides of subtypes F to H to the EIA was evaluated on a panel of 203 well-characterized serum samples from patients with diverse geographic origins (22 countries) and known HIV-1 genotype (79 A, 61 B, 21 C, 7 D, 7 E, 21 F, 6 G, 1 H). The results indicate a high predictive value (ppv) for serotypes B (> or =0.86), D (1) and E (0.88), and confirm the difficulty of predicting genotype A or C based on serotype A or C. Results also indicate that inclusion of the F peptide in the V3 EIAs may be useful (ppv = 0.61), but introduction of peptides G and H failed to demonstrate significant sensitivity or specificity for these subtypes. Correlation between serotyping and amino-acid sequences of the V3 region from 103 samples allowed the identification of key amino-acids that appear essential for subtype-specific seroreactivity.

Amino Acid Sequence↗
PubMed1999

Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes.

The human AIDS viruses human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) represent cross-species (zoonotic) infections. Although the primate reservoir of HIV-2 has been clearly identified as the sooty mangabey (Cercocebus atys), the origin of HIV-1 remains uncertain. Viruses related to HIV-1 have been isolated from the common chimpanzee (Pan troglodytes), but only three such SIVcpz infections have been documented, one of which involved a virus so divergent that it might represent a different primate lentiviral lineage. In a search for the HIV-1 reservoir, we have now sequenced the genome of a new SIVcpzstrain (SIVcpzUS) and have determined, by mitochondrial DNA analysis, the subspecies identity of all known SIVcpz-infected chimpanzees. We find that two chimpanzee subspecies in Africa, the central P. t. troglodytes and the eastern P. t. schweinfurthii, harbour SIVcpz and that their respective viruses form two highly divergent (but subspecies-specific) phylogenetic lineages. All HIV-1 strains known to infect man, including HIV-1 groups M, N and O, are closely related to just one of these SIVcpz lineages, that found in P. t. troglodytes. Moreover, we find that HIV-1 group N is a mosaic of SIVcpzUS- and HIV-1-related sequences, indicating an ancestral recombination event in a chimpanzee host. These results, together with the observation that the natural range of P. t. troglodytes coincides uniquely with areas of HIV-1 group M, N and O endemicity, indicate that P. t. troglodytes is the primary reservoir for HIV-1 and has been the source of at least three independent introductions of SIVcpz into the human population.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Evidence for differences in MT2 cell tropism according to genetic subtypes of HIV-1: syncytium-inducing variants seem rare among subtype C HIV-1 viruses.

Non-syncytium-inducing (NSI) variants seem to be more readily transmitted than syncytium-inducing (SI) variants, and the switch from NSI to SI during HIV-1 infection seems to be a key determinant to the evolution of AIDS. We investigated eventual differences in the SI capacity on MT-2 cells according to genetic subtypes of HIV-1 and correlated this observations with CD4 counts and duration of HIV infection. In total, 86 patients, most with known date of HIV contamination and infected with different genetic subtypes, have been studied: 11 subtype A, 46 subtype B, 22 subtype C, and 7 subtype E. Multivariate analysis used a Cox's proportional hazards regression. The number and percentage of patients infected with an SI strain were as follows: 3 of 11 (27%) for subtype A, 15 of 46 (33%) for subtype B, 0 of 22 (0%) for subtype C, and 5 of 7 (71%) for subtype E. After adjustment for time after seroconversion and CD4 counts, significantly fewer SI variants were observed in patients infected with subtype C (p < .002) and it was found that subjects infected with subtype E had a higher risk of being infected with an SI strain (rate ratio [RR] = 12.39%; 95% confidence interval [CI] 1.55-98.67; p < .001). Most of the subtype E-infected patients from our study switched from an NSI to SI phenotype early after seroconversion (<4 years). To predict the in vitro presence of SI variants, we scanned V3-loop sequences for mutations at positions 11 and/or 25. Overall, 54 of 55 (98.2%) NSI strains in vitro were predicted NSI, and only 4 of 12 (33.3%) of SI viruses were predicted SI. For patients in whom a switch from an NSI to an SI virus was observed, the SI phenotype could be detected earlier in vitro than by the corresponding V3-loop sequence. No SI strains were observed among patients infected with subtype C; however, longer follow-up is needed to see whether the appearance of SI variants in subtype E or the absence of SI variants in subtype C-infected patients is also associated respectively with a faster or slower progression to AIDS as described for subtype B.

Amino Acid Sequence↗
PubMed1999

Interpatient genetic variability of HIV-1 group O.

OBJECTIVE: To analyse the genetic and phylogenetic characteristics of HIV-1 group O viruses. MATERIALS AND METHODS: The env gene, encoding the gp160 glycoprotein, and a partial p24-encoding gag gene fragment of a Cameroonian (CA9) and a Gabonese (VI686) HIV-1 group O virus, isolated from cultured peripheral blood mononuclear cells of symptomatic patients, were sequenced, aligned with other representatives of group O for which the same region has been documented, and genetically and phylogenetically analysed. RESULTS: Phylogenetic analysis of the env gene (gp160) revealed that CA9, VI686, ANT70, and four Ha strains formed a separate cluster, which was supported by 100% of all bootstrap trees. In addition, these seven isolates were part of the same clade in the p24 phylogeny. VAU and MVP5180 may represent two other subtypes. CONCLUSION: We have characterized two group O viruses, originating from Cameroon and Gabon, which show a close evolutionary relationship to ANT70 and four Ha strains based on the entire env gene, suggestive of a first group O subgroup, tentatively named the HIV-1 group O env ANT70 clade or subtype.

Amino Acid Sequence↗
PubMed1999

Genetic characterization of the nef gene from human immunodeficiency virus type 1 group M strains representing genetic subtypes A, B, C, E, F, G, and H.

Most efforts to characterize sequence variation of HIV isolates has been directed toward the structural envelope gene. Few studies have evaluated the sequence variability of auxiliary genes such as nef. In this study 41 new HIV-1 strains, representing the majority of the described envelope subtypes of HIV-1 (A to H), were genetically characterized in the nef region. Phylogenetic analysis showed that 34 strains could be classified in the same subtype in nef and env, and 7 (19%) of the 41 new viruses were recombinants. For two of the seven strains, recombination occurred upstream of the nef gene, whereas for five of the seven strains recombination occurred within the nef gene with a crossover close to the 5' end of the LTR (long terminal repeat). The low intersubtype distance between subtype B and D in the nef gene confirms previous observations in the pol, env, and gag genes, which suggest a common ancestor for these subtypes. The majority of all the previously described functional domains in the nef gene were relatively conserved among the different subtypes, with only minor differences being observed. The myristoylation signal among the different subtypes, with only minor differences being observed. The myristoylation signal was less conserved for subtype C, with one or more amino acid changes being observed at positions 3, 4, and 5. The highly conserved acidic region (positions 62 to 65), critical for the enhancement of viral synthesis with an increased virus growth rate, was less conserved among the subtype G strains from our study. At least three epitopic regions of the nef gene have been defined and each can be recognized by CTLs under a variety of HLA restrictions; all were also relatively well conserved between the different genetic subtypes. Despite the relatively important genetic variation in nef sequences obtained among the different genetic subtypes, functional domains and CTL epitopes were relatively well conserved. In vitro and/or in vivo studies are necessary to study the relevance of the observed differences.

Amino Acid Sequence↗
PubMed1999

Evaluation of small-bowel transit for solid and liquid test meal in healthy men and women.

Evaluation of severe functional gastrointestinal motility disorders requires an investigation of the entire gastrointestinal tract. This should be possible with a single radionuclide imaging study. The purpose of this study was (1) to define normal values of small-bowel transit in men and women and (2) to assess a possible difference between gender or test meal, since it has been shown that women have slower gastric emptying than men, and gastric emptying of solids is slower than liquids. A standard gastric-emptying test for a solid (technetium-99m sulphur colloid, 230 Kcal) and liquid (indium-111 DTPA water) test meal was performed in 12 healthy male and 12 healthy female volunteers. After 135 min, the volunteer was placed in the supine position for static imaging of the abdomen every 15 min for 6 h. Decay and crossover-corrected geometric mean gastric-emptying data were fit to a modified power exponential function to determine the 10% stomach emptying time for solids and liquids separately. An ROI was drawn around the caecum and ascending colon to determine the arrival time of at least 10% of the solid and liquid test meal. Ten percent small-bowel transit time (10% SBTT) and orocaecal transit time (OCTT) were calculated. The OCTT for males and females, respectively for solids and liquids, are 294.6 +/- 18.8; 301.3 +/- 24.5; 294.6 +/- 18.8 and 301.3 +/- 24.5 min. The 10% SBTT for males and females, respectively for solids and liquids, are 280.3 +/- 18.4; 280.6 +/- 24.0; 288.2 +/- 18.9 and 297.4 +/- 24.4 (mean +/- SEM) min. We observed a simultaneous transfer of solids and liquids from the terminal ileum to caecum (correlation coefficient 0.90). There is no statistically significant difference in SBTT between gender or solids and liquids. In contrast to the gastric-emptying time, the SBTT of solids and liquids were not significantly different nor was a gender difference found. Determination of the OCTT seems to be the simplest and most accurate approach to measure SBTT. Since ileocaecal transfer occurs as a bolus phenomenon, a 111In-labelled test meal can also be used for the determination of colon transit in a single imaging study protocol.

Adult↗
PubMed1999

Tumor necrosis factor alpha antibody (infliximab) therapy profoundly down-regulates the inflammation in Crohn's ileocolitis.

BACKGROUND & AIMS: Anti-tumor necrosis factor alpha monoclonal antibody treatment (infliximab) reduces clinical signs and symptoms in patients with Crohn's disease. The effects of infliximab on mucosal histopathologic abnormalities in Crohn's ileocolitis were studied. METHODS: Thirteen patients with steroid-refractory Crohn's disease were treated with a single infusion of infliximab (5-20 mg/kg), and 5 were treated with placebo. Ileal and colonic biopsy specimens of all patients were collected before and 4 weeks after therapy. Severity of inflammation was assessed by a histological score. Immunohistochemical stainings with antibodies against HLA-DR, CD68, tumor necrosis factor alpha, intercellular adhesion molecule 1, lymphocyte function-associated antigen, CD4, CD8, and interleukin 4 were performed. RESULTS: Total histological activity score was reduced significantly in both ileitis and colitis after infliximab. This is caused by a virtual disappearance of the neutrophils and a reduction of mononuclear cells. Mucosal architecture returned to normal in 4 patients at 4 weeks. The number of lamina propria mononuclear cells decreased because of a global reduction of CD4(+) and CD8(+) T lymphocytes and CD68(+) monocytes. Aberrant colonic epithelial HLA-DR expression completely disappeared. The percentage of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 1-expressing and interleukin 4- and tumor necrosis factor-positive lamina propria mononuclear cells sharply decreased. CONCLUSIONS: Infliximab dramatically decreases histological disease activity in Crohn's ileocolitis. Signs of active inflammation nearly disappear accompanied by a profound down-regulation of mucosal inflammatory mediators.

Adult↗