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Biomedical subjects

Christian Folwaczny

Publications and source records attributed to Christian Folwaczny.

At least 19 recordsLinked to original sources
PubMed2006

Role of the NFKB1 -94ins/delATTG promoter polymorphism in IBD and potential interactions with polymorphisms in the CARD15/NOD2, IKBL, and IL-1RN genes.

BACKGROUND: Recently, an association of the NFKB1 polymorphism -94ins/delATTG with ulcerative colitis (UC) has been reported. This 4-bp insertion/deletion polymorphism is localized in the promoter region of the NFKB1 gene and appears to be functionally relevant. The aim of the present study was to confirm the association of the -94ins/delATTG (W/D) NFKB1 promoter polymorphism with UC in a population of German origin and to test for a potential association with Crohn's disease (CD). Furthermore, potential interactions of the -94ins/delATTG polymorphism with the IKBL and the IL-1RN genes should be determined. MATERIALS AND METHODS: The study population comprised 630 patients with CD, 365 patients with UC, and 974 healthy controls. Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism analysis. For statistical evaluation, the chi-square test and the Fisher exact test were used. RESULTS: No significant association of the W/D NFKB1 polymorphism with CD or UC was detected. In addition, no significant interactions between the -94ins/delATTG NFKB1 polymorphism and polymorphisms within the IKBL and the IL-1RN genes, respectively, were found in CD or UC. Also, no significant interactions of the NFKB1 polymorphism with mutations of the CARD15/NOD2 gene and with clinical phenotypes were detected in CD. Moreover, no associations of the NFKB1 polymorphism were found in UC depending on disease localization. CONCLUSIONS: The present study could not confirm the reported association of the -94ins/delATTG NFKB1 polymorphism with UC and also found no evidence for a role of this polymorphism in CD. The results do not give evidence for a role of this NFKB1 polymorphism in the pathogenesis of UC and CD.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Genetic variants and the risk of Crohn's disease: what does it mean for future disease management?

Genetic research in inflammatory bowel disease, especially in Crohn's disease, has made significant progress during recent years. There have been > 10 total genome scans that have been performed, and susceptibility loci on several chromosomes have been identified. Together with candidate gene studies, these scans have led to the identification of several susceptibility genes, with CARD15 being the most important. These genetic data have already provided important insights into the pathophysiology of inflammatory bowel disease and are stimulating future research. On the other hand, genotype-phenotype associations have illustrated the heterogenic nature of the disease. Although the clinical application of this knowledge is so far limited, there is significant optimism that an individual management of patients based on genetic data will be possible in the near future.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Recurrent severe gastrointestinal bleeding and malabsorption due to extensive habitual megacolon.

Dilatation of the colon and the rectum, which is not attributable to aganglionosis, is a rare finding and can be the result of intractable chronic constipation. We report a rare case of a 29-year-old male patient with impressive megacolon, in whom Hirschsprung's or Chagas disease was ruled out. In the present case, dilatation of the colon was most likely due to a behavioral disorder with habitual failure of defecation. Chronic stool retention led to a bizarre bulging of the large bowel with displacement of the other abdominal organs and severe occult blood loss. Because of two episodes of life-threatening gastrointestinal bleeding despite conventional treatment of constipation, a surgical approach for bowel restoration was necessary. Temporary loop ileostomy had to be performed for de-pressurization of the large bowel and the subsequent possibility for effective antegrade colonic lavage to remove impacted stools. Shortly after the operation, the patient was healthy and could easily manage the handling of the ileostomy. However, the course of the megacolon in this young adult cannot be predicted and the follow-up will have to reveal if regression of this extreme colonic distension with reestablishment of regular rectal perception will occur.

Adult↗
PubMed2005

The leukocyte count predicts the efficacy of treatment with azathioprine in inflammatory bowel disease.

INTRODUCTION: Azathioprine has variable efficacy in inflammatory bowel disease. Previous studies suggested that either neutropenia, an increase in the mean corpuscular volume, the assessment of thiopurine methyl-transferase activity or erythrocyte 6-thioguanine values might predict the treatment response. However, due to the conflicting results of the preceding studies there are yet no established laboratory values which allow an estimation of the clinical response. PATIENTS AND METHODS: 45 patients with Crohn's disease and 39 patients with ulcerative colitis were enrolled in this retrospective evaluation. After a minimum of six months therapy with azathioprine patients in remission were compared with those who did not achieve a stable remission with respect to the number of leucocytes, lymphocytes, neutrophil granulocytes and the mean corpuscular volume. RESULTS: Patients who went into remission during treatment with azathioprine displayed significantly lower leukocyte counts if compared to patients who were not in remission (p = 0.004 in Crohn's disease and 0.003 in ulcerative colitis). A similar tendency was also observed with respect to the granulocyte count (p = 0.007 in Crohn's disease and 0.004 in ulcerative colitis). The mean corpuscular volume did not correlate with the response to purine analogues. DISCUSSION: The absolute leukocyte count and the percentage of granulocytes seem to predict the response to purine analogues in inflammatory bowel disease and possibly offers a feasible and cost effective diagnostic tool for the assessment of therapeutic efficacy. Subsequent preferably prospective studies should aim to define the optimal cut-off value for the leukocyte count.

Adult↗
PubMed2005

Preoperative serum levels of the carcinoembryonic antigen in hereditary non-polyposis colorectal cancer compared to levels in sporadic colorectal cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) serves as the most widely used and most cost-effective tumor marker in colorectal cancer for almost 30 years. Recent publications about serum CEA levels are based on patient groups without definite differentiation between hereditary and non-hereditary forms of colorectal cancer. PATIENTS AND METHODS: We compared preoperative CEA serum levels from 105 patients with hereditary non-polyposis colorectal cancer (HNPCC) and 107 patients with sporadic colorectal cancer including influences of age and Dukes stage. CEA values in cases of HNPCC were correlated to the findings of microsatellite analyses, mutation analyses of the MMR genes (MLH1, MSH2) and respective immunohistochemistries. RESULTS: Thirty-three HNPCC patients (31%) and 37 patients with sporadic CRC (34%) revealed elevated CEA levels higher than 5 ng/ml. The mean preoperative CEA level in all Dukes stages of HNPCC patients was lower with 31.7 +/- 180 ng/ml than in sporadic colorectal cancer with 68.3 +/- 424 ng/ml, but without significance (p = 0.72). HNPCC tumors with signs of de-differentiation (G3 and G4) revealed significantly higher CEA values with 62.2 +/- 262 ng/ml in comparison to well-differentiated tumors (G1 and G2) with 5.0 +/- 9.6 ng/ml (p = 0.02). HNPCC patients with "classical characteristics" (high microsatellite instability (MSI), MMR gene mutation, loss of MMR protein expression) had lower preoperative CEA serum levels than those without equivalent genetic alterations, but without reaching statistical significance. CEA levels of HNPCC tumors increased significantly under occurrence of metastases with mean values of 170.3 +/- 343 (p < 0.02). CONCLUSIONS: Normal preoperative serum CEA levels do not have the same validity for all colorectal cancer patients. Low CEA levels in HNPCC patients could occur due to well-differentiated tumors and should be considered more critically than in sporadic CRC patients. Further studies including comparison of postoperative CEA development are necessary to elucidate the importance of these results.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Prokinetic therapy: what can be measured by gastric scintigraphy?

OBJECTIVE: To evaluate whether gastric scintigraphy with quantitative analysis of gastric peristalsis may be a useful tool for documenting the effects of prokinetic therapy. METHODS: Gastric emptying was determined in eight patients with insulin dependent diabetes mellitus (IDDM) and nine patients with progressive systemic sclerosis (PSS) after ingestion of a semi-solid test meal. Fourier analysis of condensed images was used to evaluate contraction amplitudes of the entire stomach, as well as frequency and velocity of gastric contractions. Patients were studied twice, first under baseline conditions and then after 4 weeks of continuous oral prokinetic therapy with cisapride (10 mg t.i.d.). Findings were compared with data derived from 15 healthy controls. RESULTS: At baseline conditions IDDM and PSS patients exhibited reduced gastric peristalsis and delayed emptying compared to controls. After 4 weeks of prokinetic treatment, gastric contraction amplitudes increased significantly, especially in the gastric corpus and the proximal stomach, associated with a slight improvement of gastric emptying. Changes in frequency and velocity of gastric contractions during prokinetic treatment correlated with the improvement of gastric motility and emptying. CONCLUSIONS: Prokinetic therapy with cisapride stimulates gastric motility, and could be non-invasively monitored by scintigraphy. This radionuclide technique provides a number of relevant parameters of gastric function, such as gastric emptying, contraction amplitudes, frequency and velocity of gastric contractions, which give crucial insights into the mechanisms of action of prokinetic drugs.

Adult↗
PubMed2005

A polymorphism of the bactericidal/permeability increasing protein (BPI) gene is associated with Crohn's disease.

BACKGROUND: The bactericidal/permeability increasing protein (BPI) is involved in the elimination of gram-negative bacteria. A functionally relevant single nucleotide polymorphism of the BPI gene causes an amino acid exchange (Glu216Lys). STUDY: To evaluate whether this single nucleotide polymorphism contributes to the predisposition to inflammatory bowel disease, we compared the allele frequencies of 265 patients with Crohn's disease, 207 patients with ulcerative colitis, and 608 healthy controls. RESULTS: The Glu/Glu genotype frequency was decreased significantly in Crohn's disease patients as compared with controls (P < 0.027). No differences were obvious in patients with ulcerative colitis. CONCLUSIONS: Failure of the innate intestinal immune system could be involved in the pathogenesis of Crohn's disease via reduced/impaired defense against gram-negative bacteria.

Alleles↗
PubMed2005

Association of polymorphisms in the interleukin-18 gene in patients with Crohn's disease depending on the CARD15/NOD2 genotype.

UNLABELLED: An increased expression of interleukin-18 (IL-18), a proinflammatory cytokine inducing interferon-gamma, has been found in Crohn's disease (CD). In the IL-18 gene, several partly functional relevant polymorphisms are known. This study sought to investigate associations of IL-18 polymorphisms in inflammatory bowel disease and CD according to CARD15/NOD2 mutation status and clinical phenotypes. METHODS: The IL-18 polymorphisms -607, -137, and the third position of codon 35 (c35/3) were genotyped in 210 patients with CD, 140 patients with ulcerative colitis, and 265 healthy controls using polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: Frequencies of alleles and genotypes of the 3 polymorphisms and of the respective haplotypes and diplotypes displayed no significant differences between the whole groups of patients with CD and ulcerative colitis, respectively, compared with the controls. After stratification of patients with CD for CARD15/NOD2 status, significant associations of genotypes -137 CC (P = 0.018) and c35/3 CC (P = 0.010) and of the diplotype 2-2 (P = 0.018) were found in cases carrying CARD15/NOD2 mutations. Associations of genotypes -137 GG (P = 0.015) and c35/3 AA (P = 0.030) with colonic disease only in cases positive for CARD15/NOD2 mutations and of the genotype -607 AA (P = 0.007) with fistulas in cases negative for CARD15/NOD2 mutations were observed. CONCLUSIONS: In this study, significant differences of several genotypes and diplotypes within the IL-18 gene in CD depending on CARD15/NOD2 status have been found. In context with an increased expression of IL-18 in CD, it remains to be shown whether the expression of IL-18 is influenced by CARD15/NOD2 mutation status.

Adult↗
PubMed2005

Polymorphisms of the interleukin-18 gene in periodontitis patients.

BACKGROUND: Interleukin (IL)-18 regulates the expression of the proinflammatory cytokine interferon (IFN)-gamma. The present study sought to test the putative involvement of six different IL-18 gene polymorphisms in pre-disposition to destructive periodontal disease. METHODS: A total of 123 patients with periodontitis and 121 healthy controls were genotyped for six IL-18 polymorphisms at position -656, -607, -137, +113, +127 and codon 35/3. Genotyping has been performed by PCR and restriction fragment length polymorphism analysis. The frequencies of alleles and genotypes as well of haplotypes within both study groups were compared using the Pearson Chi-square test at a level of significance of 5% (p<0.05). RESULTS: Coseggregation was found to be 100% for the two polymorphisms at position -656 and -607 as well as for the polymorphisms at position -137, +113, and +127. The distribution of genotypes for the IL-18 gene polymorphism at position -656/-607 (p=0.854), at position -137/+113/+127 (p=0.320), and at codon 35/3 (p=0.481) was not significantly different among periodontitis patients if compared with healthy control subjects. The distribution of haplotype combinations for the -607 and -137 polymorphism also showed not significant difference between the both study groups (p=0.545). CONCLUSION: Herein the six different IL-18 gene polymorphisms were not associated with destructive periodontal disease.

Adult↗
PubMed2005

The angiotensin I-converting enzyme gene insertion/deletion polymorphism is linked to early gastric cancer.

The insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been linked to the pathogenesis and progression of human cancers. Using genomic DNA from 88 patients with early gastric cancer confined either to mucosa (pT(1a)) or submucosa (pT(1b)), we assessed the insertion (I) and deletion (D) polymorphism by PCR analysis and compared it with a large noncancer control population (n = 145). In the noncancer control group, the II genotype was observed in 33 (23%) individuals, whereas the ID and DD genotypes were found in 72 (50%) and 40 (27%) individuals, respectively. Interestingly, in the cancer group, we found the II genotype in six (7%) patients and the ID genotype in 46 (52%) individuals, whereas the DD genotype was observed in 36 (41%) individuals (P = 0.0034). Accordingly, the odds ratio for the II genotype was 0.20 [95% confidence interval (95% CI), 0.08-0.54; P = 0.009] and 0.55 for the ID/II genotype (95% CI, 0.31-0.96; P = 0.044) using the high-activity genotype DD as the reference category. No correlation was found among tumor type, tumor stage, the presence of Helicobacter pylori, and the ACE genotype. Our study provides further evidence that the ACE insertion/deletion gene polymorphism may be linked to the development of early gastric cancer.

Adult↗
PubMed2004

Allele 2 of the interleukin-1 receptor antagonist gene is associated with early gastric cancer.

PURPOSE: In advanced gastric cancer (tumor stages T2-T4), associations with polymorphisms of the interleukin-1 (IL-1) gene cluster have been made. In early-stage gastric cancer, which we defined as adenocarcinoma confined to the mucosa or submucosa (stage T1), the role of host genetic susceptibility remains to be determined. PATIENTS AND METHODS: Eighty-eight patients with early-stage gastric cancer (stage T1, 77 positive for Helicobacter pylori) and 145 controls were genotyped for polymorphisms in the IL-1 gene cluster and the tumor necrosis factor alpha (TNF-A) gene. Statistical analysis was performed using the chi2 test and the Fisher's exact test, respectively. RESULTS: The homozygous genotype IL-1RN*2/2 of the IL-RN gene was strongly associated with early-stage gastric cancer (P < .0001), whereas further associations with the IL-1 gene cluster were not observed. A weak association of the TNF-A-308A allele with the diffuse type of early-stage gastric cancer, and an association with a composite of two or three proinflammatory polymorphisms, which predispose to increased production of the proinflammatory cytokines IL-1beta and TNF-alpha, could also be demonstrated. CONCLUSION: The genotype IL-1RN*2/2 seems to be associated with early-stage gastric cancer. As opposed to advanced-stage gastric cancer, further proinflammatory cytokine polymorphisms were not associated independently, but might act in combination and mirror early steps of gastric carcinogenesis in hosts colonized by Helicobacter pylori. However, these findings await confirmation in future trials and should be underscored by gene expression studies.

Adenocarcinoma↗
PubMed2004

Polymorphisms of the lipopolysaccharide-signaling complex in inflammatory bowel disease: association of a mutation in the Toll-like receptor 4 gene with ulcerative colitis.

Genes encoding for receptors of the innate immune system are potential candidates for susceptibility to inflammatory bowel disease, e.g., mutations in the cytosolic receptor NOD2/CARD15 were associated with Crohn's disease. Herein, two mutations of the Toll-like receptor (TLR)-4 gene (Asp299Gly and Thr399Ile) resulting in impaired lipopolysaccharide signaling, the -159C/T promotor polymorphism of the CD14 gene, polymorphisms of the lipopolysaccharide binding protein gene and the bactericidal permeability increasing protein gene were evaluated in 102 patients with Crohn's disease, 98 patients with ulcerative colitis and 145 healthy controls. The allele and carrier frequencies for the Thr399Ile mutation in TLR4 gene were significantly increased in ulcerative colitis when compared to the controls (P = 0.014 and P = 0.018, respectively). None of the other five polymorphisms was associated with inflammatory bowel disease. In conclusion, a novel association between a functional polymorphism in TLR4 and ulcerative colitis is reported. This observation underscores the importance of impaired innate immunity in inflammatory bowel disease.

Acute-Phase Proteins↗