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C Fenger

Publications and source records attributed to C Fenger.

At least 19 recordsLinked to original sources
PubMed2006

Microglia and macrophages express tumor necrosis factor receptor p75 following middle cerebral artery occlusion in mice.

The proinflammatory and potential neurotoxic cytokine tumor necrosis factor (TNF) is produced by activated CNS resident microglia and infiltrating blood-borne macrophages in infarct and peri-infarct areas following induction of focal cerebral ischemia. Here, we investigated the expression of the TNF receptors, TNF-p55R and TNF-p75R, from 1 to 10 days following permanent occlusion of the middle cerebral artery in mice. Using quantitative polymerase chain reaction (PCR), we observed that the relative level of TNF-p55R mRNA was significantly increased at 1-2 days and TNF-p75R mRNA was significantly increased at 1-10 days following arterial occlusion, reaching peak values at 5 days, when microglial-macrophage CD11b mRNA expression was also increased. In comparison, the relative level of TNF mRNA was significantly increased from 1 to 5 days, with peak levels 1 day after arterial occlusion. In situ hybridization revealed mRNA expression of both receptors in predominantly microglial- and macrophage-like cells in the peri-infarct and subsequently in the infarct, and being most marked from 1 to 5 days. Using green fluorescent protein-bone marrow chimeric mice, we confirmed that TNF-p75R was expressed in resident microglia and blood-borne macrophages located in the peri-infarct and infarct 1 and 5 days after arterial occlusion, which was supported by Western blotting. The data show that increased expression of the TNF-p75 receptor following induction of focal cerebral ischemia in mice can be attributed to expression in activated microglial cells and blood-borne macrophages.

Animals↗
PubMed2006

Eosinophilia in the upper gastrointestinal tract is not a characteristic feature in cow's milk sensitive gastro-oesophageal reflux disease. Measurement by two methodologies.

BACKGROUND: An association between cow's milk hypersensitivity (CMH) and gastro-oesophageal reflux disease (GERD) in childhood has been reported in the past decade. AIM: To assess whether biopsies from the upper gastrointestinal tract of children with cow's milk sensitive GERD have a specific allergic inflammatory pattern, and to compare two different techniques for measuring inflammatory cells in gastrointestinal biopsies. METHODS: GERD was diagnosed by means of endoscopy and oesophageal pH monitoring. Hypersensitivity to cow's milk was determined by an elimination diet and cow's milk challenge. Allergic inflammatory cells in upper gastrointestinal biopsies were identified by immunohistochemistry and their numbers were assessed by two different methods-counting the number of cells/high power field and using the computerised Cast-Grid system. RESULTS: Cow's milk sensitive GERD was identified in 10 of 17 children with severe GERD (median age, 7.8 years). Biopsies from children with endoscopic oesophagitis had significantly increased numbers of mast cells and T cells. No differences in the number of eosinophils, mast cells, or T cells were found between children with CMH and those with primary GERD. Several differences were found between the two different histological quantification methods. CONCLUSIONS: CMH was found not only in infants but also in school age children with GERD. Histology did not identify the cow's milk sensitive GERD subgroup. The computerised histological method provides a more complete evaluation based upon total biopsy area, and helped to limit the bias of uneven biopsy size.

Adolescent↗
PubMed2004

Colorectal adenoma characteristics as predictors of recurrence.

PURPOSE: The identification of groups with a high risk of colorectal adenoma recurrence remains a controversial issue for clinicians. This study was designed to assess the predictive value of initial patient and adenoma characteristics of the three-year recurrence. METHODS: The study population was composed of 552 patients with resected colorectal adenomas who completed the European Fiber-Calcium Intervention trial. At both baseline and three-year examinations, the characteristics of adenomas were recorded according to a standardized protocol. The main outcomes measured were the three-year overall recurrence, recurrence of multiple adenomas, recurrence of advanced adenomas (size > or = 1 cm or tubulovillous/villous architecture or moderate/severe dysplasia), and proximal and distal recurrence. RESULTS: A three-year recurrence was observed in 122 patients (22.1 percent), and more than one-half of them had recurrent adenomas on the proximal colon. After adjustment for patient characteristics and treatment allocation, the number of adenomas and their proximal location at baseline were the main predictors of recurrence. In comparison with patients who had one or two adenomas on the distal colon, patients with three or more adenomas with at least one of them located on the proximal colon had a much higher risk of overall recurrence (5.3; 95 percent confidence interval, 2.7-10.3), proximal recurrence (8.5; 95 percent confidence interval, 4.1-18), and advanced adenoma recurrence (5.5; 95 percent confidence interval, 2.4-12.6). CONCLUSIONS: Follow-up colonoscopies in patients with adenomas should include careful examination of the proximal colon. The time interval between follow-up examinations could probably be extended beyond three years in patients who have only one or two distal adenomas.

Adenoma↗
PubMed2004

Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds.

BACKGROUND: Two large true population studies in Europe have shown a significant reduction in mortality from colorectal cancer (CRC) by screening with a faecal occult blood test. In one trial conducted in Funen County, 61,933 individuals (aged 45-75 years) were randomly allocated either to a control group or to receive a biennial Hemoccult-II test. METHODS: These individuals were followed from 1985 to 2002 and 9 screening rounds were performed. RESULTS: First screening was accepted by 67% (20,672). Positivity rates varied between 0.8% and 3.8%, and the cumulative proportion of the test group having colonoscopy was 5.3%. Screen-detected CRC was early (Dukes' A) in 36% compared to 11% among controls. Incidence of CRC was unchanged, but mortality was reduced by 11%. This figure increased to 43% in persons participating in all 9 rounds. No more than 8,558 were screened at the 9th round. Patients with CRC detected between screenings had better survival than controls. Death rates from causes other than CRC among participants never became higher than among controls. CONCLUSION: The lesser reduction in mortality from CRC of 11% compared to 18% after 5 screening rounds may be explained by the decrease in the number screened. Efficacy in those screened supports the introduction of countrywide screening in Denmark, but it must be ascertained that acceptability, proportion of early CRC and logistics all reach the same standard as in the randomized trial.

Adenoma↗
PubMed2003

Recurrence and survival after mesorectal excision for rectal cancer.

BACKGROUND: Mesorectal excision for rectal cancer has resulted in local recurrence rates of 3-11 per cent compared with up to 38 per cent after conventional methods. The results of a prospective Danish study with a historical control group are presented. METHODS: Three hundred and eleven patients with a mobile rectal cancer had mesorectal excision with curative intent performed by certified surgeons and were followed for 3 years. Demographic, perioperative and follow-up data were recorded prospectively. A series of patients who had conventional operations for rectal cancer served as a control group. RESULTS: The cumulative 3-year local recurrence rate was 11 per cent after mesorectal excision compared with 30 per cent after conventional surgery (hazard ratio (HR) 0.33 (95 per cent confidence interval (c.i.) 0.21 to 0.52); P < 0.001). Multivariate regression analysis showed that only advanced age (HR 0.97 (95 per cent c.i. 0.94 to 1.00); P = 0.048) and tumour in the lower third of the rectum (HR 0.21 (95 per cent c.i. 0.04 to 1.97); P = 0.075) were marginal independent predictors of local recurrence after mesorectal excision. The cumulative crude 3-year survival rate was 77 per cent after mesorectal excision and 62 per cent after conventional surgery (HR 0.58 (95 per cent c.i. 0.43 to 0.77); P < 0.001). Age was the only independent predictor of death after mesorectal excision (HR 1.04 (95 per cent c.i. 1.02 to 1.07); P = 0.001). CONCLUSION: Mesorectal excision is associated with a considerably lower risk of local recurrence and a better survival rate than conventional surgery, and is the optimum method for rectal cancer resection.

Adenocarcinoma↗
PubMed2003

Diagnostic yield in a biennial Hemoccult-II screening program compared to a once-only screening with flexible sigmoidoscopy and Hemoccult-II.

BACKGROUND: Flexible sigmoidoscopy (FS) has a higher degree of sensitivity for detecting colorectal neoplasia in the left side of the colon than Hemoccult (H-II). However, no randomized controlled trial has compared a single FS screening with a H-II screening program (annual or biennial) despite the well-documented mortality reduction from colorectal cancer (CRC) in the latter. The aim was to compare the diagnostic yield of colorectal neoplasia in two aged-matched groups from two different randomized screening trials; one group screened by a single FS+H-II, the other with biennial H-II over the course of 16 years. METHODS: 24,465 persons invited to participate in the Funen biennial H-II screening program were compared with 4,460 similar persons invited to another Funen trial using a single FS+H-II. RESULTS: Compliance in the biennial H-II program was 65.5% during the first screening round compared to 39.8% for FS+H-II. The cumulative number of persons with positive tests was 8.2% (positive H-II) in the biennial H-II program during 16 years and 20.3% (polyps > 3 mm in diameter seen at FS or positive H-II) for once-only FS+H-II. The diagnostic yield of CRC per 1,000 screened was 9.9 in the biennial H-II program and 6.6 after FS+H-II (6.5 and 2.7 per 1,000 invited). The yield of advanced adenomas (> or = 10 mm and/or villous structure and/or severe dysplasia) was 2.3% in the H-II program and 3.3% after FS+H-II among the screened persons, but this difference disappeared when persons invited, but not necessarily screened, were compared (1.5% versus 1.3%). CONCLUSION: Screening with H-II in a biennial screening program during 16 years detected more CRCs than a single screening with FS+H-II and a similar number of advanced adenomas.

Adenoma↗
PubMed2002

The scavenger receptor, cysteine-rich domain-containing molecule gp-340 is differentially regulated in epithelial cell lines by phorbol ester.

Gp-340 is a glycoprotein belonging to the scavenger receptor cysteine rich (SRCR) group B family. It binds to host immune components such as lung surfactant protein D (SP-D). Recent studies found that gp-340 interacts directly with pathogenic microorganisms and induces their aggregation, suggesting its involvement in innate immunity. In order to investigate further its potential immune functions in the appropriate cell lines, the expression of gp-340 in four conventional immune cell lines (U937, HL60, Jurkat, Raji), and two innate immune-related epithelial cell lines (A549 derived from lung and AGS from stomach), was examined by RT-PCR and immunohistochemistry. The resting immune cell lines showed weak or no gp-340 mRNA expression; while the two epithelial cell lines expressed gp-340 at much higher level, which was differentially regulated by phorbol myristate acetate (PMA) treatment. In the A549 cells, gp-340 was up-regulated along with the PMA-induced proinflammatory expression of both IL-6 and IL-8. In AGS cells, PMA down-regulation of gp-340 was seen in parallel with an up-regulation of the two mature gastric epithelial specific proteins TFF1 (trefoil factor 1) and TFF2, which are implicated as markers of terminal differentiation. Analysis of the distribution of gp-340, together with the TFFs and SP-D in normal lung and gastric mucosa, supported further our in vitro data. We conclude that the differential regulation of gp-340 in the two epithelial cell lines by PMA indicates that gp-340 s involvement in mucosal defence and growth of epithelial cells may vary at different body locations and during different stages of epithelial differentiation.

B-Lymphocytes↗
PubMed2002

A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds.

BACKGROUND: Three randomised trials have demonstrated reduction in mortality from colorectal cancer (CRC) by repeated screening with faecal occult blood tests, including the trial presented here, which is the only one still in progress. AIMS: To evaluate reduction in mortality after seven screening rounds and the possible influence of compliance on mortality from CRC. METHODS: At Funen in Denmark, random allocation to biennial screening with Hemoccult-II in 30 967 subjects aged 45-75 years and 30,966 controls was performed in 1985 from a population of 137,485 of the same age. Only participants who completed the first screening round were invited for further screening. Colonoscopy was offered if the test was positive. The primary end point was death from CRC, and the 10 year results were published in 1996. RESULTS: From the beginning of the first screening to the seventh round, mean age increased from 59.8 to 70.0 years in the screening and control groups, and the male/female ratio decreased from 0.92 to 0.81. Those who accepted screening were younger than non-responders. Positivity rates varied from 0.8% to 3.8%, the cumulative ratio of a positive test was 5.1% after seven rounds, and 4.8% of patients had at least one colonoscopy. Mortality from CRC was significantly less in the screening group (relative risk (RR) 0.82 (0.69-0.97)), and the reduction in mortality was most pronounced above the sigmoid colon. After seven rounds, RR was reduced to less than 0.70 compared with controls. Mortality rates from causes other than CRC did not differ. Non-responders had a significantly increased risk of death from CRC compared with those who accepted the full programme. Subjects who accepted the first screening, but not subsequent ones, demonstrated a tendency towards increased risk. CONCLUSIONS: The persistent reduction in mortality from CRC in a biennial screening program with Hemoccult-II, and a reduction in RR to less than 0.70 in those adhering to the programme, support attempts to introduce larger scale population screening programmes. The smaller effect on mortality from CRC in the rectum and sigmoid colon suggests evaluation by additional flexible sigmoidoscopy with longer intervals.

Aged↗
PubMed2001

The pathology and molecular biology of anal intraepithelial neoplasia: comparisons with cervical and vulvar intraepithelial carcinoma.

BACKGROUND: Anal intraepithelial neoplasia (AIN) is a well-described pathological precursor of invasive squamous cell carcinoma which has recently been detected with increasing frequency in immunocompromised patients, particularly those with seropositivity for human immunodeficiency virus (HIV). The epidemiology and natural history of this entity is somewhat unclear, since the overall prevalence in the HIV seronegative population is unknown. DISCUSSION: There is a clear etiological association between AIN and high-risk human papillomavirus (HPV) subtype infection although there is great variability in HPV DNA detection of cytological and histological material in these patients. It appears that there is an antigen-specific hyporesponsiveness by cytotoxic lymphocytes against HPV peptide sequences or recombinant proteins encoded by oncogenic HPV subtypes in these patients, which is dependent upon the stage of their HIV-associated disease. Although the molecular biology of AIN and cervical or vulvar intraepithelial neoplasia are comparable, in AIN there is less significance of tumor suppressor gene mutations, proto-oncogenic growth factor activation, and genomic instability. CONCLUSION: Current concepts in the epidemiology and etiology of AIN are discussed, as well as its immunological response in the HIV-positive population, drawing parallels where possible between other HPV-related preinvasive disorders, and concluding with a suggested management protocol

Anus Neoplasms↗
PubMed2001

Assessments of clonal composition of colorectal adenomas by FISH analysis of chromosomes 1, 7, 13 and 20.

Chromosome banding analysis has shown that numerical aberrations, in particular gains of chromosomes 7, 13 and 20, are common in colorectal adenomas but cannot provide reliable information on the size of the abnormal clones in vivo. We examined interphase nuclei from 70 colorectal adenomas, of which 64 had been previously karyotyped, using fluorescence in situ hybridization (FISH) with probes for the pericentromeric regions of chromosomes 1, 7, 13 and 20. Gain of chromosome 7 was seen in 34% of the analyzed adenomas, +13 was seen in 44% and trisomy 20 was found in 32% of the adenomas, verifying that the trisomies are in vivo phenomena. The median proportion of cells with trisomy was larger than 50%. A comparison with the G-banding analysis showed a good correlation between the results yielded by the 2 methods. Based on the clonal size and karyotypic findings, a likely order of events during clonal evolution could be ascribed to each case. More than 1 numerical aberration was detected by FISH analysis in 16 adenomas. In 6 adenomas, a clone with only trisomy 7 was present alongside a clone with additional gain(s) of chromosomes 13 and/or 20. Seven cases had gain of chromosome 13 and/or gain of chromosome 20 in the largest clone, suggesting that a clone with either of these changes was present before the changes in chromosome 7 copy number took place. On the basis of the results of this combined meta- and interphase cytogenetic study, we conclude that gains of chromosomes 7, 13 and 20 are common in colorectal adenomas and that the trisomies usually are present in a large proportion of the cells. They seem to be primary chromosome aberrations in some adenomas, whereas in others they arise secondarily as part of the clonal evolution. Although the first gain usually is of chromosome 7, it is evident that it is the end result of the chromosomal aberrations, not the exact sequence in which they occur, that determines the pathogenetic consequences.

Adenoma↗
PubMed2001

[Diagnostic benefit of gastrointestinal endoscopy in infants under one year of age--a two-year survey].

INTRODUCTION: Gastrointestinal endoscopy in children is a well-established procedure. We reviewed our experience of endoscopy in infants below one year of age to evaluate indications, endoscopic findings, histology, and complications. MATERIAL AND METHODS: Twenty-eight infants were studied over a two-year period. Of these, 18 underwent upper endoscopy, six recto/sigmoidoscopy or colonoscopy, and four both procedures. RESULTS: The most common indication (10/22) for upper endoscopy was vomiting and suspicion of gastrooesophageal reflux disease. In these infants, 24-hour continuous monitoring of the oesophageal pH followed the procedure. Indications for lower endoscopy were rectal bleeding (n = 6) and intractable diarrhoea (n = 4). There were no complications to anaesthesia, endoscopy, or biopsy. Overall, there were endoscopic abnormalities in 82% and histological abnormalities in 75% of the infants. The diagnostic findings included rare disorders, such as eosinophilic gastroenteritis, microvillous inclusion disease, and chylomicron retention disease. Diagnosis of these diseases requires gastrointestinal biopsy. DISCUSSION: Gastrointestinal endoscopy is a safe procedure, which is a valuable part of the diagnostic work-up in a selected group of infants with long-lasting or severe gastrointestinal symptoms.

Colonoscopy↗
PubMed2000

[Celiac disease with subepithelial deposition of collagen].

In 1970 a case of malabsorption with flat small intestinal mucosa with subepithelial collagen deposition was described. There was no response to a gluten-free diet, and the condition was termed collagenous sprue. We report a case of coeliac disease with subepithelial deposition of collagen in duodenal biopsy, which responded to a gluten-free diet.

Celiac Disease↗
PubMed2000

Anal cancer subtype reproducibility study.

For histological subtyping of anal squamous carcinomas the WHO advocates a six-way subdivision, but it has been suspected that the six types cannot be reliably discriminated in practice. We conducted a blinded study involving slides from 103 consecutive cases, each slide being examined by three experts (from Denmark, Australia and UK) on two occasions at least 8 months apart. Agreement on subtypes was low: 72% between rounds within pathologist, 61% between pathologists. Even for the commonest, and most stably diagnosed, type, viz. large-cell keratinising squamous carcinoma, the intra- and interpathologist frequencies of confirmation were only 81% and 71%, respectively. The pathologist marked the picture as typical and his subtype diagnosis as certain 41% of times: even then confirmation frequencies were only 88% and 74%, respectively. Calculations, including kappa analyses, suggest that 26% of the typing variation was noise. The WHO scheme must be even more unreliable in everyday practice. We finally mention a recently demonstrated link between human papilloma virus (HPV) and certain types of anal cancer, which may well provide an additional argument for revising existing subtyping schemes.

Anus Neoplasms↗
PubMed2000

Review of colorectal cancer and its metastases in rodent models: comparative aspects with those in humans.

BACKGROUND AND PURPOSE: Colorectal cancer (CRC) remains one of the most common cancer forms developing in industrialized countries, and its incidence appears to be rising. Studies of human population groups provide insufficient information about carcinogenesis, pathogenesis, and treatment of CRC. To study these phenomena in detail, a number of animal models of human CRC have been developed. The hypothetical ideal animal model should mimic the human disease in terms of morphology, biochemical alterations, and biological behavior. No existing model replicates the disease as an entity, but available models approximate many of the characteristics of human colonic carcinogenesis and metastasis. So far few comparative evaluations of the various animal models of CRC have been made. CONCLUSION: Animal studies cannot replace human clinical trials, but they can be used as a pre-screening tool, so that human trials become more directed, with greater chances of success. The orthotopic transplantation of colon cancer cells into the cecum of syngeneic animals or intraportal inoculation appears to resemble the human metastatic disease most closely, providing a model for study of the treatment of metastases. Which model(s) to choose depends on the goal(s) of the experiment(s). The review published here can provide help in selecting the most optimal CRC model(s) for a certain purpose and in preventing unnecessary duplication of animal experimentation.

Adenocarcinoma↗
PubMed1999

Variants of squamous cell carcinoma of the anal canal and perianal skin and their relation to human papillomaviruses.

High-risk types of human papillomaviruses (hrHPVs) may be a necessary cause in cervical cancer and in some subtype of anal, vulvar, and penile cancers. Large studies aimed at characterizing hrHPV-associated and non-hrHPV-associated subtypes of anal carcinomas are, however, lacking. We searched for human papillomavirus type 16 and 13 other hrHPVs in tumor tissue by PCR and performed a systematic histological evaluation of specimens from 386 patients with anal cancer (86% invasive; 302 women and 84 men). Cancers in women and homosexual men were more often hrHPV positive (P < 0.01) and located in the anal canal (P < or = 0.01) than were cancers in heterosexual men. In both women and men, anal canal cancers contained hrHPV clearly more often than did perianal skin cancers, and increasing hrHPV positivity was seen with higher localization in the anal canal. Indeed, 95 and 83% of cancers involving the anal canal in women and men, respectively, were hrHPV positive versus 80 and 28% of perianal skin cancers (P-trend < 0.001). Basaloid feature, adjacent anal intraepithelial neoplasia, poor or absent keratinization, and a predominance of small or medium neoplastic cells were all strongly positively associated with hrHPV status. Like cancer of the uterine cervix, the development of cancer of the anal canal may require infection with hrHPV, whereas a dual etiology of perianal skin cancers bears parallels to vulvar and penile cancers.

Age Factors↗
PubMed1999

Possible advantages and drawbacks of adding flexible sigmoidoscopy to hemoccult-II in screening for colorectal cancer. A randomized study.

BACKGROUND: Flexible sigmoidoscopy (FS) has been recommended as a screening method to reduce mortality from colorectal cancer (CRC). The present study evaluates the effect of adding FS to the fecal occult blood test Hemoccult-II (H-II) on diagnostic yield of colorectal neoplasia. METHODS: A total of 10,978 normal persons aged 50-75 years were invited to participate, 5495 persons being allocated at random to H-II and FS and 5483 to H-II alone. RESULTS: In spite of a lower compliance (40% versus 56%) for the combined procedure, the diagnostic yield of colorectal neoplasia was higher than for H-II alone (12 CRC versus 4 CRC, and 72 large adenomas versus 14). Within 24-62 months after screening there were fewer CRCs detected after H-II + FS than after H-II alone. The stage distribution was less favorable than in screen-detected cases. CONCLUSION: One FS may not be an optimal way of screening, but FS deserves to be evaluated in randomized population studies including repeated H-II tests in the control arm.

Aged↗