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M Peeters

Publications and source records attributed to M Peeters.

At least 37 records · Page 2Linked to original sources
PubMed2001

Full-length genome sequencing of HIV type 1 group O viruses isolated from a heterosexual transmission cluster in Senegal.

In a polygamous marriage in Senegal, the husband and his two spouses were infected with HIV-1 group O. This study provides new full-length genome sequences for the two spouses (99SE-MP1299 and 99SE-MP1300) and the 3'-end LTR-tat fragment (6084 bp) for the husband (98SE-42HALD). Phylogenetic tree and diversity plot analysis revealed that the new viruses belong to HIV-1 group O and that they are closely related to each other in a cluster around ANT-70. The intrafamilial transmission occurred at most 6 years ago. The interpatient variability was highest in the envelope region, and in some regions of the envelope the strains from the two spouses do not cluster together anymore. The source of infection was in Cameroon and confirms a slow but continuous spread of HIV-1 group O viruses.

Female↗
PubMed2001

Using human immunodeficiency virus type 1 sequences to infer historical features of the acquired immune deficiency syndrome epidemic and human immunodeficiency virus evolution.

In earlier work, human immunodeficiency virus type 1 (HIV-1) sequences were analysed to estimate the timing of the ancestral sequence of the main group of HIV-1, the virus that is responsible for the acquired immune deficiency syndrome pandemic, yielding a best estimate of 1931 (95% confidence interval of 1915-1941). That work will be briefly reviewed, outlining how phylogenetic tools were extended to incorporate improved evolutionary models, how the molecular clock model was adapted to incorporate variable periods of latency, and how the approach was validated by correctly estimating the timing of two historically documented dates. The advantages, limitations, and assumptions of the approach will be summarized, with particular consideration of the implications of branch length uncertainty and recombination. We have recently undertaken new phylogenetic analysis of an extremely diverse set of human immunodeficiency virus envelope sequences from the Democratic Republic of the Congo (the DRC, formerly Zaire). This analysis both corroborates and extends the conclusions of our original study. Coalescent methods were used to infer the demographic history of the HIV-1 epidemic in the DRC, and the results suggest an increase in the exponential growth rate of the infected population through time.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Evidence of two distinct subsubtypes within the HIV-1 subtype A radiation.

Members of HIV-1 group M are responsible for the vast majority of AIDS cases worldwide and have been classified on the basis of their phylogenetic relationships into nine roughly equidistant clades, termed subtypes. Although there are no known phenotypic correlates for these genotypes, the disproportionate spread of certain of these lineages has been taken to indicate that subtype-specific biological differences may exist. The subtype nomenclature thus remains an important molecular epidemiological tool with which to track the course of the group M pandemic. In this study, we have characterized HIV-1 strains described previously as unusual subtype A variants on the basis of partial sequence analysis. Six such strains from Cyprus (CY), South Korea (KR), and the Democratic Republic of Congo (CD) were PCR amplified from infected cell culture or patient PBMC DNA, cloned, and sequences in their entirety (94CY017, 97KR004, 97CDKTB48, and 97CDKP58) or as half genomes (97CDKS10 and 97CDKFE4). Distance and phylogenetic analyses showed that four of these viruses (94CY017, 97CDKTB48, 97CDKFE4, and 97CDKS10) were closely related to each other, but quite divergent from all other HIV-1 strains, except for subtype A viruses, which represented their closest relatives. In phylogenetic trees from gag, pol, env, and nef regions, the four newly characterized HIV-1 strains formed a distinct sister clade to subtype A, which was as closely related to subtype A as subsubtypes F1 and F2 are to each other. According to current nomenclature rules, this defines a subsubtype, which we have tentatively termed A2. The two other viruses, 97KR004 and 97CDKP58, as well as a full-length HIV-1 sequence from the sequence database (ZAM184), were found to represent complex A2/D, A2/G, and A2/C recombinants, respectively. These results indicate that HIV-1 subtype A is composed of two subsubtypes (A1 and A2), both of which appear to have a widespread geographic distribution. The A2 viruses described here represent the first reference reagents for this new group M lineage.

Cyprus↗
PubMed2001

High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.

To describe prevalence of antiretroviral (ARV) drug-resistant HIV-1 strains among patients with a history of earlier treatment with ARV drugs in Abidjan, Côte d'Ivoire, we determined mutations that confer HIV-1 ARV drug resistance by sequencing the viral reverse-transcriptase and protease genes derived from plasma viral RNA of 68 individuals consecutively enrolled in the Joint United Nations Program on AIDS Drug Access Initiative (UNAIDS-DAI) with a history of earlier ARV drug treatment in Abidjan between August 1998 and April 1999. Phenotypic ARV drug resistance was assessed using a recombinant virus assay. Primary mutations associated with ARV drug resistance to at least one of the reverse-transcriptase inhibitors or protease inhibitors were detected in 39 (57.4%) of the 68 patients. The prevalence of mutations associated with resistance to ARV drugs was: 29 (42.6%) to zidovudine, 10 (14.7%) to lamivudine, one (1.5%) to didanosine, one K103N mutation (associated with resistance to delavirdine, nevirapine, and efavirenz), one Y181C mutation (associated with resistance to delavirdine and nevirapine), two to both indinavir (M46I/L and V82A) and saquinavir (G48V and L90M), and one each to ritonavir (V82A) and nelfinavir (D30N). Phenotypic resistance to at least one nucleoside reverse transcriptase inhibitor (RTI) was seen in 25 (39.7%) patients, to nonnucleoside RTIs in 5 (8%) patients, and to protease inhibitors in 4 (6%) patients. The high prevalence we observed in this study may limit in future the effectiveness of ARV programs in the Côte d'Ivoire.

Anti-HIV Agents↗
PubMed2001

Role of the high affinity immunoglobulin E receptor in bacterial translocation and intestinal inflammation.

A role for immunoglobulin E and its high affinity receptor (Fc epsilon RI) in the control of bacterial pathogenicity and intestinal inflammation has been suggested, but relevant animal models are lacking. Here we compare transgenic mice expressing a humanized Fc epsilon RI (hFc epsilon RI), with a cell distribution similar to that in humans, to Fc epsilon RI-deficient animals. In hFc epsilon RI transgenic mice, levels of colonic interleukin 4 were higher, the composition of fecal flora was greatly modified, and bacterial translocation towards mesenteric lymph nodes was increased. In hFc epsilon RI transgenic mice, 2,4,6-tri-nitrobenzenesulfonic acid (TNBS)-induced colitis was also more pronounced, whereas Fc epsilon RI-deficient animals were protected from colitis, demonstrating that Fc epsilon RI can affect the onset of intestinal inflammation.

Animals↗
PubMed2001

Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy.

Resistance-mutation patterns in the reverse transcriptase (RT) and protease genes of HIV-1 were analyzed in 22 patients who had been extensively pretreated and who failed to respond to highly active antiretroviral therapy (HAART). The number of mutations ranged from 8 to 19 (median, 13): 4 to 12 (median, 6) mutations in the RT gene, and 4 to 8 (median, 7) mutations in the protease gene. In the RT gene, the most frequent resistance mutations were found at codons 215 (100%), 41 (95%), 67 (91%), and 210 (77%). Multidrug-resistant mutation patterns including Q151M and insertion mutations at codon 69, which confer cross-resistance to the different nucleoside analogue RT inhibitors were detected in 1 and 3 patients, respectively; 1 patient with insertion mutation displayed a NGQGV [corrected] sequence at codons 67 to 70. In the protease gene, the most frequent mutations were found at codons 63 (95%), 10 (86%), 90(86%), 71(77%), 46 (50%), 36 (45%), and 84 (45%). Genotypic resistance to zidovudine, saquinavir, and indinavir was found in 100% of the patients. All patients showed also resistance or possible resistance to stavudine, abacavir, ritonavir, and nelfinavir. Mutations conferring genotypic resistance to nonnucleoside analogue RT inhibitors (NNRTIs) were found in 12 (80%) of the NNRTI-experienced patients and 1 of 7 NNRTI-naive patients. Our results indicate that failure of HAART in the patients extensively pretreated results from the multiplicity of RT and protease mutations that confer genotypic resistance to almost all available antiretroviral drugs. In these patients, genotypic resistance tests confirm the lack of alternative salvage therapy strategies based on the currently available antiretroviral drugs.

Algorithms↗
PubMed2001

Detection of Chlamydia pneumoniae DNA in buffy-coat samples of patients with abdominal aortic aneurysm.

Recent studies have suggested that Chlamydia pneumoniae infection is a risk factor for abdominal aortic aneurysm. This study explores the presence of Chlamydia pneumoniae DNA in buffy-coat samples of control subjects and of patients with abdominal aortic aneurysm. The seroepidemiological association between abdominal aortic aneurysm and Chlamydia pneumoniae was also investigated. Buffy-coat samples and serum specimens were obtained from 88 patients and 88 control subjects. Detection of Chlamydia pneumoniae DNA in buffy-coat samples and measurement of IgG antibodies to Chlamydia pneumoniae in serum specimens were performed by polymerase chain reaction and microimmunofluorescence, respectively. Chlamydia pneumoniae DNA was detected in buffy-coat samples of 18 (20%) patients and 8 (9%) control subjects (adjusted odds ratio 2.9, 95% confidence interval 1-8.5). IgG antibodies to Chlamydia pneumoniae were detected in 85 (97%) patients and 71 (81%) control subjects (adjusted odds ratio 7.2, 95% confidence interval 1.7-31). The results show an association between abdominal aortic aneurysm and either the presence of Chlamydia pneumoniae DNA in buffy-coat samples or IgG antibodies to Chlamydia pneumoniae. These findings support the hypothesis that previous infection with Chlamydia pneumoniae might be a risk factor for abdominal aortic aneurysm.

Adult↗
PubMed2001

Correlation between detection methods of Chlamydia pneumoniae in atherosclerotic and non-atherosclerotic tissues.

Polymerase chain reaction (PCR) and immunohistochemistry (IHC) have been used to detect Chlamydia (C.) pneumoniae in vascular tissues. Discrepancies between the results of these two methods have frequently been reported. However, the correlation between PCR and IHC has not been analyzed yet. This study assesses the correlation between the detection of C. pneumoniae by PCR and IHC in 45 atherosclerotic and 50 non-atherosclerotic tissue specimens. Also, the presence of Mycoplasma (M.) pneumoniae in these 95 specimens was investigated. Correlation was found between the detection of C. pneumoniae by PCR and IHC in the atherosclerotic tissues. Both tests were positive in 10 specimens and negative in 17 specimens (p = 0.003). There was no significant correlation between PCR and IHC in non-atherosclerotic specimens (p = ns). M. pneumoniae was detected, by PCR, in one atherosclerotic specimen.The results show correlation between PCR and IHC in the detection of C. pneumoniae in atherosclerotic tissues, emphasize the association between C. pneumoniae and atherosclerosis, and support the specificity of the association between C. pneumoniae and atherosclerosis.

Adult↗
PubMed2001

Unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer: the utility of positron emission tomography (PET).

The aim of the study was to evaluate the use of positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) in patients with unexplained rising carcinoembryonic antigen (CEA) in the postoperative surveillance of colorectal cancer. 50 consecutive patients with elevated CEA levels and a completely normal (n=31) or equivocal (n=19) conventional diagnostic work-up (CDW) were retrospectively selected. All PET images were reviewed with full knowledge of the CDW. The gold standard consisted of histology, or clinical follow-up of more than 1 year. Recurrent disease was established in 56 lesions in 43 patients. On a patient-based analysis, the sensitivity of FDG-PET was 34/43 (79%), and the positive predictive value 34/38 (89%). In 14/50 patients (28%), the FDG-PET findings led to a surgical resection with curative intent. On a lesion-based analysis, FDG-PET detected 42/56 lesions (sensitivity: 75%), the positive predictive value was 79% (42/53). These results demonstrate that FDG-PET can have a clear impact on patient management in patients with an unexplained elevation in CEA levels.

Adult↗
PubMed2001

A randomized, double-blind, placebo-controlled study of itraconazole capsules for the prevention of deep fungal infections in immunodeficient patients with HIV infection.

OBJECTIVES: To determine whether systemic or deep fungal infections can be prevented, a double-blind, placebo-controlled, phase III trial of itraconazole prophylaxis was undertaken in HIV-infected patients. METHODS: HIV-1 infected patients with CD4 counts < 300 cells/microL were treated with itraconazole (200 mg per day) or matching placebo and followed for 2 years. Development of deep fungal infections, episodes of mucocutaneous candidiasis, change in CD4 count, survival and safety data were collected at each study visit. RESULTS: Three hundred and seventy-four patients received study medication, 187 were given itraconazole and 187 matching placebo. Time to development of deep fungal infection did not differ between groups, in an intention to treat analysis. Low CD4 cell count and prior use of Pneumocystis carinii pneumonia (PCP) prophylaxis were significantly associated with a more rapid development of deep fungal infection (P = 0.044 and 0.017, respectively). Itraconazole treatment significantly reduced the incidence of oral candidosis (25% vs. 48% P < 0.001) and time to development of oral candidosis (508 vs. 413 days, P < 0.001) but not the number of deep fungal infections (11 vs. 13). Survival did not differ significantly between groups (nine vs. 14 deaths). CD4 counts decreased significantly over time in both study arms. Adverse events did not differ between groups; 20% vs. 23% stopped study medication due to an adverse experience. CONCLUSIONS: Although itraconazole prophylaxis significantly reduced the number and time to development of oral candidosis, too few episodes of deep fungal infection were noted to determine whether itraconazole prophylaxis was effective for this condition. Chronic itraconazole treatment is well tolerated in HIV-infected patients with marked immunodeficiency.

AIDS-Related Opportunistic Infections↗
PubMed2001

Modulation of the neuronal dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes.

There is considerable evidence that the activity of the neuronal dopamine transporter (DAT) is dynamically regulated and a putative implication of its phosphorylation in this process has been proposed. However, there is little information available regarding the nature of physiological stimuli that contribute to the endogenous control of the DAT function. Based on the close relationship between glutamatergic and dopaminergic systems in the striatum, we investigated the modulation of the DAT activity by metabotropic glutamate receptors (mGluRs). Short-term incubations of rat striatal synaptosomes with micromolar concentrations of the group I mGluR selective agonist (S)-3,5-dihydroxyphenylglycine were found to significantly decrease the DAT capacity and efficiency. This alteration was completely prevented by a highly selective mGluR5 antagonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). The effect of (S)-3,5-dihydroxyphenylglycine was also inhibited by staurosporine and by selective inhibitors of protein kinase C and calcium calmodulin-dependent protein kinase II. Co-application of okadaic acid prolonged the transient effect of the agonist, supporting a critical role for phosphorylation in the modulation of the DAT activity by mGluRs. In conclusion, we propose that striatal mGluR5 contribute to the control of the DAT activity through concomitant activation of both protein kinase C and calcium calmodulin-dependent protein kinase II.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2001

Evidence for inflammatory bowel disease of a susceptibility locus on the X chromosome.

BACKGROUND & AIMS: The technique of genomewide scanning has been applied successfully in inflammatory bowel disease (IBD). A number of putative susceptibility loci have been identified through genomewide searches including replicated regions of linkage on chromosomes 12, 16, 6 (the HLA region), and 14. We have investigated the contribution of the X chromosome in 145 Belgian affected relative pairs. METHODS: In the first stage of the study, 79 (68 CD, 11 mixed) sibling pairs were genotyped at 12 microsatellite markers covering the X chromosome. In the second stage, 10 additional markers in the X-pericentromeric region were studied in the families involved in stage 1 together with 62 additional families (52 sibling pairs, 14 second-degree relative pairs). RESULTS: In the first stage, evidence for linkage was found over a 30-cM pericentromeric region spanning dXs991, dXs990, and dXs8096 (multipoint maximum LOD score in the CD subgroup, 2.5; P = 0.0003). The remainder of the X chromosome was excluded (exclusion under LOD-2) for a locus with lambda(s) = 2. Fine mapping in the second stage confirmed linkage, and narrowed and shifted the linked region to Xq21.3 around dXs1203 (nonparametric linkage [NPL], 2.90; P = 0.0017). The NPL-1 interval around the linkage peak comprises 19.7 cM. CONCLUSIONS: These data provide suggestive evidence for the presence and chromosomal location of an X-linked susceptibility gene in IBD.

Chromosome Mapping↗
PubMed2001

Comparative study of ASCA (Anti-Saccharomyces cerevisiae antibody) assays in inflammatory bowel disease.

BACKGROUND & AIMS: Anti-Saccharomyces cerevisiae antibody (ASCA) is a serologic marker associated with Crohn's disease (CD). Although there is still discussion on its clinical value, several companies each promote their own ASCA assay to be used in the gastroenterologist's practice at considerable expense. The aim of this study was to determine whether different ASCA assays agree sufficiently well for the results to be used interchangeably. METHODS: Blood obtained from a large cohort of IBD patients with inflammatory bowel disease (IBD; 100 with CD, 100 with ulcerative colitis [UC]) and 178 controls (100 healthy blood donors and 78 patients with non-IBD diarrheal illnesses) was studied with 4 different ASCA assays. Sensitivity, specificity, and positive predictive value were compared. Agreement between assays was evaluated. RESULTS: Sensitivity of ASCA for CD ranged between 41% and 76%. Sensitivity was inversely related to specificity and positive predictive value. Results correlated well overall (range = 0.54-0.90) and the different ROC curves showed good agreement. When recalculated cutoff points were used, interchangeability increased. However, large differences were seen when absolute values were compared. CONCLUSIONS: A large range in sensitivities and specificities of ASCA for CD is seen with different ASCA assays, mainly as a consequence of the cutoff value chosen for each individual assay. Although agreement between and within assays is good, caution is important when absolute values are used. Standardization of ASCA measurements is greatly needed.

Adolescent↗
PubMed2001

Inflammatory bowel disease in spouses and their offspring.

BACKGROUND & AIMS: The rarity of inflammatory bowel disease (IBD) in both husband and wife is often given as an argument against an infectious origin. We registered conjugal instances of IBD in Northern France and in Belgium between 1989 and 2000. METHODS: Couples were assigned to group A if both partners had symptoms of IBD before cohabitation, to group B if one spouse had IBD before cohabitation and the other experienced first symptoms afterwards, and to group C if both partners got the disease after cohabitation. Risk of IBD was assessed in their offspring. RESULTS: Thirty conjugal instances were registered. Seventeen were concordant for Crohn's disease and 3 for ulcerative colitis; 10 were mixed. Two belonged to group A, 6 to group B, and 22 to group C. In group C, IBD occurred in the first affected spouse an average of 9 years after cohabitation and in the second spouse an average of 8.5 years later. Group C conjugal forms were more frequent than expected by chance (P < 0.02). Fifty-four children were born to 25 couples; among them 9, of whom 4 were siblings, developed Crohn's disease at a median age of 15 years. CONCLUSIONS: The frequency of conjugal forms of IBD suggests an etiologic role for environmental factors. Offspring of 2 affected parents have a high risk of developing IBD.

Adolescent↗
PubMed2001

Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis.

BACKGROUND & AIMS: Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids. METHODS: Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy. RESULTS: Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed. CONCLUSIONS: Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC.

Adult↗
PubMed2001

Tc-99m HMPAO white blood cell scintigraphy in the assessment of the extent and severity of an acute exacerbation of ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with frequent exacerbations, including the risk for toxic megacolon and severe complications. In very active disease, colonoscopy should not be performed to assess the severity and the extent of the disease. The aim of the current study was to determine whether Tc-99m HMPAO-labeled white blood cell (WBC) scintigraphy can be used as an alternative to colonoscopy to determine the extent and the severity of the disease in critically ill patients. METHODS: Twenty consecutive patients (7 women, 13 men; age 38.1 +/- 13.1 years) who had a severe attack of UC underwent scintigraphy on the day of admission. Leukocytes were labeled with 200 MBq (5.35 mCi) Tc-99m HMPAO. Planar anterior and posterior imaging of the abdomen was performed 45 and 120 minutes after WBC reinjection. The tracer uptake in the different colon segments was scored visually compared with bone marrow uptake. A symptom score was made and C-reactive protein was measured as a serologic marker of inflammation. Rectosigmoidoscopy with biopsy was performed within 24 hours of scintigraphy. Scintigraphic, endoscopic, and histologic results were compared for disease activity. RESULTS: The mean symptom score was 12.7 (+/-0.7) on a scale of 21, and mean the C-reactive protein level was 6.8 (+/-1.2) mg/l. No significant difference was found between the scintigraphic score of the rectum and the endoscopic or the histologic score. The best correlation was found with the latter (r = 0.66, P < 0.01). Based on the results of scintigraphy, disease involved the left side of the colon up to the splenic flexure in 10 patients. The other patients had pancolitis. CONCLUSIONS: Disease severity can be determined adequately by planar WBC scintigraphy in patients with severe attacks of UC. Because the presence and severity of disease correlates well with endoscopic and histologic findings, WBC scintigraphy can assess disease extent without the need for colonoscopy. This decreases the number and severity of complications that can occur in already critically ill patients.

Acute Disease↗