Torleiv Rognum | University of Oslo (original) (raw)
Papers by Torleiv Rognum
European Journal of Cancer and Clinical Oncology, 1986
Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent... more Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent DNA ploidy pattern and serial post-operative determinations performed in the 64 who had been operated for cure. The follow-up pen'od was $8 yr. All CEA measurements were performed consecutively with a RIA (Roche), and subsequently repeated in one batch with an EIA (Roche) based on a monoclonal antibody. Both assays showed a similar number of 'falsenegative' CEA levels pre-operatively-varying from 69% in aneuploid (AN) Dukes' A to 8% in AN Dukes' D turnours, andfrom 75% in near diploid (ND) Dukes' A to 40% in ND Dukes' D turnours. The sensitivity for detecting recurrence in patients with tumours of either ploi& pattern was slight& better with EIA than with RIA. A difference between the AN and ND group was shown somewhat better with RIA, the sensitivity in the AN group being 79% and the median lead time 7 months compared to 13% and 2 months in the ND group. The corresponding jigures with EIA were 71% and 7 months for the ANgroup and 63% and lfmonths for the ND group. However, all but one of the patients with ND DNA pattern who showed recurrenceassociated CEA elevation with EIA also had an elevated level pre-operatively. We conclude that all patients operated for cure should be followed by regular CEA measurements post-operatively if they had an elevated CEA level prior to operation. In addition, patients with AN tumour should be followed with serial GEA measurements even in the absence of pre-operative elevation.
The Lancet, 1990
There are genetic similarities between IDDM and RA. The former is seen in increased frequency in ... more There are genetic similarities between IDDM and RA. The former is seen in increased frequency in relatives of probands with RA6 and there is an excess of rheumatoid factor production in individuals with IDDM.' IDDM is also strongly associated with HLA, although the linkage is with DR3 and DR4.
Cancer Research
tract in the APC gene, resulting in substitution of lysine for isoleucine at codon 1307 (I1307K),... more tract in the APC gene, resulting in substitution of lysine for isoleucine at codon 1307 (I1307K), was found in a subset of Ashkenazi Jews. This sequence variant was most frequent in colorectal cancer patients with a positive family history of colorectal cancer. To determine whether the I1307K variant plays a role in colorectal or breast cancer predisposition in the Norwegian population, we have analyzed blood samples from 210 colorectal cancer patients and 183 breast cancer patients by PCR and direct sequencing. Thirty-seven of the colorectal cancer patients had a positive family history of cancer. Among the breast cancer patients, 24 had a family history of colorectal cancer and 75 a family history of breast and/or ovarian cancer. Only one colorectal cancer patient who belonged to a Jewish family was found to carry the A variant. Our data show that the I1307K variant is rare in the Norwegian population and should not be viewed as a candidate for susceptibility testing for colorectal cancer.
Tidsskrift for Den norske legeforening
Intracytoplasmic sperm injection (ICSI) is performed in a large number of fertility clinics; sinc... more Intracytoplasmic sperm injection (ICSI) is performed in a large number of fertility clinics; since 1991, several thousand children have been conceived by this method. Intracytoplasmic sperm injection is different than traditional in vitro-fertilization (IVF) in that a single spermatozoon is mechanically transferred into a mature oocyte using a glass pipette. Concern has been raised as to whether intracytoplasmic sperm injection damages the chromosomes and/or the spindle apparatus in the oocyte, leading to an increased risk of congenital abnormalities. We have reviewed the literature on congenital abnormalities in children conceived by intracytoplasmatic sperm injection. Although the reports are methodologically heterogeneous, most articles conclude that intracytoplasmatic sperm injection does not cause a statistically significant increased risk of congenital abnormalities compared to traditional in vitro fertilization or normally conceived children. However, some studies do report an increased risk. The issue cannot be finally settled until even larger studies on children conceived by intracytoplasmatic sperm injection are published.
Tidsskrift for Den norske legeforening
Treatment with stem cells has given promising results in animal experiments and may be relevant i... more Treatment with stem cells has given promising results in animal experiments and may be relevant in a variety of diseases, including heart disease, cancer, diabetes, Parkinson's disease and Alzheimer's disease. However, the use of pluripotent stem cells grown from blastocysts available after in vitro fertilization or from fetuses raises difficult issues in medical ethics. The same goes for therapeutic cloning. Attitudes to this mode of treatment differ from country to country. In Britain, Parliament has accepted therapeutic cloning (February 2001), while the German Bundestag has banned the procedure. The EU Parliament has recommended European countries not to allow therapeutic cloning, and President George W. Bush takes a more critical stand than did the Clinton administration. The debate over embryonal cells and therapeutic cloning involves both scientists and politicians. In Norway, the Biotechnology Advisory Board wants to open up for research on fertilized eggs and for therapeutic cloning. The Storting, Norway's legislature, will have to reach a decision on these issues when the Biotechnology Act come up for revision, probably in 2002. In the debate in Norway, it has been claimed that accepting therapeutic cloning would be a violation of a traditional western norm: Man should always be an end onto himself, never be used as an instrument to other ends. Furthermore, some scientists think that one should use adult stem cells from adults--this also because the procedure seems less risky. Bone marrow transplantation with autologous bone marrow stem cells has been used for 30 years, and recent research has disclosed that such stem cells may be reprogrammed, for instance from bone marrow stem cells to nerve cells.
Ugeskrift for laeger
In the 15 years between 1975 and 1989 approximately 5,000 infants succumbed to SIDS in the Nordic... more In the 15 years between 1975 and 1989 approximately 5,000 infants succumbed to SIDS in the Nordic countries. Denmark and Norway were most seriously hit, with SIDS rates amounting to 2 and 2.5 per 1,000 live births in 1989. During the 1970's and 1980's especially Denmark and Norway experienced a significant increase in SIDS rates. In 1990 a co-operative study was initiated by Nordic Council of Ministers. Part of the study consisted of forensic pathologists examining SIDS victims. They showed that neither the increase during the 1980's nor the decrease during the 1990's was due to changes in the classification or diagnostic practise. A correlation between prone sleeping position and SIDS rates is now well recognised. However, neither an explanation for the great discrepancy in SIDS rates between the Nordic countries nor a possible explanation for the risk of prone sleeping position has been achieved.
Tidsskrift for den Norske laegeforening
European Journal of Cancer and Clinical Oncology, 1986
Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent... more Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent DNA ploidy pattern and serial post-operative determinations performed in the 64 who had been operated for cure. The follow-up pen'od was $8 yr. All CEA measurements were performed consecutively with a RIA (Roche), and subsequently repeated in one batch with an EIA (Roche) based on a monoclonal antibody. Both assays showed a similar number of 'falsenegative' CEA levels pre-operatively-varying from 69% in aneuploid (AN) Dukes' A to 8% in AN Dukes' D turnours, andfrom 75% in near diploid (ND) Dukes' A to 40% in ND Dukes' D turnours. The sensitivity for detecting recurrence in patients with tumours of either ploi& pattern was slight& better with EIA than with RIA. A difference between the AN and ND group was shown somewhat better with RIA, the sensitivity in the AN group being 79% and the median lead time 7 months compared to 13% and 2 months in the ND group. The corresponding jigures with EIA were 71% and 7 months for the ANgroup and 63% and lfmonths for the ND group. However, all but one of the patients with ND DNA pattern who showed recurrenceassociated CEA elevation with EIA also had an elevated level pre-operatively. We conclude that all patients operated for cure should be followed by regular CEA measurements post-operatively if they had an elevated CEA level prior to operation. In addition, patients with AN tumour should be followed with serial GEA measurements even in the absence of pre-operative elevation.
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1990
We present a case of fatal vascular destruction and granulomatosis of the lungs from intravenous ... more We present a case of fatal vascular destruction and granulomatosis of the lungs from intravenous injections of dissolved tablets containing microcrystalline cellulose as filler material. Numerous microcrystalline cellulose pulmonary emboli and foreign body granulomas were detected, and the pulmonary parenchyma showed signs of disturbed circulation with focal necrosis and oedema.
Pediatric Research, 1998
Elevated hypoxanthine (Hx) levels in the vitreous humor of victims of the sudden infant death syn... more Elevated hypoxanthine (Hx) levels in the vitreous humor of victims of the sudden infant death syndrome (SIDS) have been been claimed to indicate hypoxia before death. An important methodologic problem is the temperature-dependent Hx increase after death. Although most previous studies have corrected for expected postmortem Hx increase, the aim of the present study was to omit this problem by matching the subjects of the different groups studied for similar postmortem time. Thirteen cases of violent death, 11 cases of borderline SIDS, 22 cases of death from infectious disease, and 17 cases of death from heart/lung disease were compared with a 3-fold number of SIDS cases. To investigate the impact of environmental factors on the Hx levels of the SIDS cases, the following possible confounding factors were investigated: attempt to resuscitate, slight infections before death, sleeping position, and time of the day when found dead. To investigate whether the size of the eyeball would influence the Hx level, five cases of violent death in children were compared with 15 adults who died suddenly. The vitreous humor Hx level was significantly higher in SIDS victims than in cases of violent death (p < 0.01) and deaths due to heart/lung disease (p < 0.01), whereas no such difference was found either between SIDS and borderline SIDS or SIDS and infectious death. There were no differences between any of the subgroups of SIDS victims. The vitreous humor Hx level in small children and adults did not differ. The findings raise the question of possible similarities in death mechanism in SIDS and infectious death.
International Journal of Cancer, 1997
Mutations in the k-ras and TP53 genes, as well as microsatellite instability (MIN), are frequent ... more Mutations in the k-ras and TP53 genes, as well as microsatellite instability (MIN), are frequent genetic alterations in colorectal carcinomas and represent 3 different mechanisms in the carcinogenic process. Both the incidence of colorectal cancer and the frequency of genetic alterations in such tumours have been related to different clinico-pathological variables, including age and gender of the patient and location of the tumour. A number of studies have also reported associations between different types of genetic alterations. We therefore wanted to explore the relationship between these genetic and clinico-pathological variables using multivariate analysis on material from 282 colorectal carcinomas. Three logistic regression models were constructed: 1) the presence of K-ras mutations was dependent on MIN and age and gender of patient, with an especially low frequency among younger males and in tumours with MIN (overall p ؍ 0.0003); 2) the presence of TP53 mutations was only dependent on tumour location, with a positive association to cancers occurring distally (p ؍ 0.002); and 3) the presence of MIN was dependent on age, gender and K-ras and TP53 mutations, as well as on tumour location. MIN was most frequent among younger male and older female patients, was rare in tumours with K-ras or TP53 mutations and was found almost exclusively in the proximal colon (overall p F 0.0001). Our data confirm that different genetic pathways to colorectal cancer dominate in the proximal and distal segments of the bowel and suggest that the K-ras-and MIN-dependent pathways are influenced by different sex-related factors. Int.
Gut, 1996
Background, Aims, and Patients-In a prospective follow up and intervention study of colorectal po... more Background, Aims, and Patients-In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis ofredetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. Results-Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net Medical Department,
Diagnostic Molecular Pathology, 1998
The aim of this study was to establish an experimentally based cutoff level for assessing p53 imm... more The aim of this study was to establish an experimentally based cutoff level for assessing p53 immunoreactivity in colorectal tumors. The accumulation of p53 protein in 273 colorectal tumors was correlated with previously obtained data on TP53 mutation and loss of heterozygosity at two 17p13 loci in the same tumors. The monoclonal antibody PAb 1801 was used for p53 staining, and the results obtained by immunohistochemistry and immunoblotting were similar. Mutation analyses of exons 5-8 were performed using constant denaturant gel electrophoresis followed by sequencing. There were no statistically significant differences for any measured TP53 gene alteration between the group of tumors without p53-positive nuclei (n = 83) and the group with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5% positive nuclei (n = 58). The majority of mutations within these groups were deletions/insertions and nonsense mutations without p53 accumulation. Therefore, we assume that 5% p53-positive nuclei is the relevant cutoff level to assess TP53 damage in colorectal tumors. A prerequisite for this recommendation is optimal conditions for p53 protein detection. The parameters for p53 dysfunction were correlated to DNA aneuploidy measured by flow cytometry. TP53 mutations were significantly associated with DNA aneuploidy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.00001), and a nonrandom distribution of TP53 gene alterations among diploid (DI = 1), hyperdiploid (1.0 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; DI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 1.3), and highly aneuploid (DI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 1.3) tumors indicates that DNA hyperdiploid tumors constitute a separate developmental entity different from tumors with gross aneuploidy.
Current Pediatric Reviews, 2010
Cancer, 1985
Tumor specimens were obtained from seven patients with large bowel carcinomas at operation of the... more Tumor specimens were obtained from seven patients with large bowel carcinomas at operation of the primary neoplasm and by resection of local recurrences or metastases 2% to 36 months later. All specimens were evaluated with regard to nuclear DNA distribution as mehsured by flow cytometry and expression of carcinwmbryonic antigen (CEA), secretory component, epithelial IgA, and HLA-DR antigens, as determined by immunofluorescence staining of tissue sections. Both the DNA distributions and the immunohistochemical staining patterns were similar in the primary and secondary tumors. These findings are in keeping with a monoclonal or oligoclonal tumor progression in advanced large bowel carcinoma.
Archives of Pediatrics & Adolescent Medicine, 2003
Cancer Detection and Prevention
In 100 patients with large bowel carcinomas, the tumors were divided into a distinctly aneuploid ... more In 100 patients with large bowel carcinomas, the tumors were divided into a distinctly aneuploid (AN) group (63) and a near diploid (ND) group (37) by flow cytometric (FCM) DNA quantitation of cell suspensions. Preoperative plasma CEA levels were determined in all patients. Thirty-eight patients with AN and 28 patients with ND tumors were operated on for cure and had normal plasma CEA levels postoperatively. These two groups had regular CEA plasma measurements as part of the clinical follow-up. In the AN group, 12 of 15 patients have had recurrence preceded by CEA elevation. In the ND group, however, only one of eight recurrences was preceded by a rise in CEA level; the one with elevation also had increased plasma CEA prior to operation. It thus seems that a low CEA output of ND tumors explains many of the "false-negative" CEA measurements in disseminated cases. It is concluded that, in addition to patients with an elevated preoperative plasma CEA level, all patients with aneuploid tumors should be subjected to repeated plasma CEA measurements as part of the follow-up program.
Scandinavian Journal of Gastroenterology
In sporadic colorectal adenomas mutations in the adenomatous polyposis gene (APC) are among the f... more In sporadic colorectal adenomas mutations in the adenomatous polyposis gene (APC) are among the first gene aberrations to appear. In familial adenomatous polyposis (FAP) the patients already have a germline mutation in the APC gene. To investigate the natural history of duodenal adenomas in FAP patients, we examined germline and somatic mutations of the APC gene and K-ras mutations in these lesions. Frozen sections from 54 duodenal polyps from 31 FAP patients were used to histologically verify the presence of adenomatous growth in the mucosa; the rest of each biopsy specimen was processed for DNA extraction. APC exon 15 was investigated with the protein truncation test (PTT), using four overlapping polymerase chain reaction (PCR) fragments, and samples showing an APC mutation were thereafter sequenced. The adenomas were examined for K-ras mutations by use of a combination of the 'enriched PCR method' and temporal temperature gradient electrophoresis. APC germline mutations in exon 15 were found in 19 of 31 (61%) patients, whereas somatic mutations were localized to 12 of 54 (22%) duodenal adenomas. In seven adenomas both the germline and the somatic mutations were found, whereas five small adenomas showed somatic mutations only. There was no tendency for more mutations to be detected in large and severely dysplastic adenomas compared with small and mildly dysplastic ones. K-ras mutations were found in four (7%) duodenal adenomas. The low rate of somatic APC and K-ras mutations in duodenal adenomas may indicate another neoplastic pathway than in FAP adenomas of the large bowel, or that a modifier gene is cosegregating with the disease.
Cellular oncology: the official journal of the International Society for Cellular Oncology
Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In... more Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In the present study, we aimed to identify and validate novel target genes inactivated through promoter hypermethylation in colorectal tumor development. With the use of microarrays, the gene expression profiles of colon cancer cell lines before and after treatment with the demethylating agent 5-aza-2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxycytidine were identified and compared. The expression of the responding genes was compared with microarray expression data of primary colorectal carcinomas. Four of these down-regulated genes were subjected to methylation-specific PCR, bisulphite sequencing, and quantitative gene expression analysis using tumors (n=198), normal tissues (n=44), and cell lines (n=30). Twenty-one genes with a CpG island in their promoter responded to treatment in cell lines, and were simultaneously down-regulated in primary colorectal carcinomas. Among 20 colon cancer cell lines, hypermethylation was subsequently identified for three of four analyzed genes, ADAMTS1 (85%), CRABP1 (90%), and NR3C1 (35%). For the latter two genes, hypermethylation was significantly associated with absence or reduced gene expression. The methylation status of ADAMTS1, CRABP1, and NR3C1 was further investigated in 116 colorectal carcinomas and adenomas. Twenty-three of 63 (37%), 7/60 (12%), and 2/63 (3%) adenomas, as well as 37/52 (71%), 25/51 (49%), and 13/51 (25%) carcinomas were hypermethylated for the respective genes. These genes were unmethylated in tumors (n=82) from three other organs, prostate, testis, and kidney. Finally, analysis of normal colorectal mucosa demonstrated that the observed promoter hypermethylation was cancer-specific. By using a refined microarray screening approach we present three genes with cancer-specific hypermethylation in colorectal tumors, ADAMTS1, CRABP1, and NR3C1.
European Journal of Cancer and Clinical Oncology, 1986
Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent... more Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent DNA ploidy pattern and serial post-operative determinations performed in the 64 who had been operated for cure. The follow-up pen'od was $8 yr. All CEA measurements were performed consecutively with a RIA (Roche), and subsequently repeated in one batch with an EIA (Roche) based on a monoclonal antibody. Both assays showed a similar number of 'falsenegative' CEA levels pre-operatively-varying from 69% in aneuploid (AN) Dukes' A to 8% in AN Dukes' D turnours, andfrom 75% in near diploid (ND) Dukes' A to 40% in ND Dukes' D turnours. The sensitivity for detecting recurrence in patients with tumours of either ploi& pattern was slight& better with EIA than with RIA. A difference between the AN and ND group was shown somewhat better with RIA, the sensitivity in the AN group being 79% and the median lead time 7 months compared to 13% and 2 months in the ND group. The corresponding jigures with EIA were 71% and 7 months for the ANgroup and 63% and lfmonths for the ND group. However, all but one of the patients with ND DNA pattern who showed recurrenceassociated CEA elevation with EIA also had an elevated level pre-operatively. We conclude that all patients operated for cure should be followed by regular CEA measurements post-operatively if they had an elevated CEA level prior to operation. In addition, patients with AN tumour should be followed with serial GEA measurements even in the absence of pre-operative elevation.
The Lancet, 1990
There are genetic similarities between IDDM and RA. The former is seen in increased frequency in ... more There are genetic similarities between IDDM and RA. The former is seen in increased frequency in relatives of probands with RA6 and there is an excess of rheumatoid factor production in individuals with IDDM.' IDDM is also strongly associated with HLA, although the linkage is with DR3 and DR4.
Cancer Research
tract in the APC gene, resulting in substitution of lysine for isoleucine at codon 1307 (I1307K),... more tract in the APC gene, resulting in substitution of lysine for isoleucine at codon 1307 (I1307K), was found in a subset of Ashkenazi Jews. This sequence variant was most frequent in colorectal cancer patients with a positive family history of colorectal cancer. To determine whether the I1307K variant plays a role in colorectal or breast cancer predisposition in the Norwegian population, we have analyzed blood samples from 210 colorectal cancer patients and 183 breast cancer patients by PCR and direct sequencing. Thirty-seven of the colorectal cancer patients had a positive family history of cancer. Among the breast cancer patients, 24 had a family history of colorectal cancer and 75 a family history of breast and/or ovarian cancer. Only one colorectal cancer patient who belonged to a Jewish family was found to carry the A variant. Our data show that the I1307K variant is rare in the Norwegian population and should not be viewed as a candidate for susceptibility testing for colorectal cancer.
Tidsskrift for Den norske legeforening
Intracytoplasmic sperm injection (ICSI) is performed in a large number of fertility clinics; sinc... more Intracytoplasmic sperm injection (ICSI) is performed in a large number of fertility clinics; since 1991, several thousand children have been conceived by this method. Intracytoplasmic sperm injection is different than traditional in vitro-fertilization (IVF) in that a single spermatozoon is mechanically transferred into a mature oocyte using a glass pipette. Concern has been raised as to whether intracytoplasmic sperm injection damages the chromosomes and/or the spindle apparatus in the oocyte, leading to an increased risk of congenital abnormalities. We have reviewed the literature on congenital abnormalities in children conceived by intracytoplasmatic sperm injection. Although the reports are methodologically heterogeneous, most articles conclude that intracytoplasmatic sperm injection does not cause a statistically significant increased risk of congenital abnormalities compared to traditional in vitro fertilization or normally conceived children. However, some studies do report an increased risk. The issue cannot be finally settled until even larger studies on children conceived by intracytoplasmatic sperm injection are published.
Tidsskrift for Den norske legeforening
Treatment with stem cells has given promising results in animal experiments and may be relevant i... more Treatment with stem cells has given promising results in animal experiments and may be relevant in a variety of diseases, including heart disease, cancer, diabetes, Parkinson's disease and Alzheimer's disease. However, the use of pluripotent stem cells grown from blastocysts available after in vitro fertilization or from fetuses raises difficult issues in medical ethics. The same goes for therapeutic cloning. Attitudes to this mode of treatment differ from country to country. In Britain, Parliament has accepted therapeutic cloning (February 2001), while the German Bundestag has banned the procedure. The EU Parliament has recommended European countries not to allow therapeutic cloning, and President George W. Bush takes a more critical stand than did the Clinton administration. The debate over embryonal cells and therapeutic cloning involves both scientists and politicians. In Norway, the Biotechnology Advisory Board wants to open up for research on fertilized eggs and for therapeutic cloning. The Storting, Norway's legislature, will have to reach a decision on these issues when the Biotechnology Act come up for revision, probably in 2002. In the debate in Norway, it has been claimed that accepting therapeutic cloning would be a violation of a traditional western norm: Man should always be an end onto himself, never be used as an instrument to other ends. Furthermore, some scientists think that one should use adult stem cells from adults--this also because the procedure seems less risky. Bone marrow transplantation with autologous bone marrow stem cells has been used for 30 years, and recent research has disclosed that such stem cells may be reprogrammed, for instance from bone marrow stem cells to nerve cells.
Ugeskrift for laeger
In the 15 years between 1975 and 1989 approximately 5,000 infants succumbed to SIDS in the Nordic... more In the 15 years between 1975 and 1989 approximately 5,000 infants succumbed to SIDS in the Nordic countries. Denmark and Norway were most seriously hit, with SIDS rates amounting to 2 and 2.5 per 1,000 live births in 1989. During the 1970's and 1980's especially Denmark and Norway experienced a significant increase in SIDS rates. In 1990 a co-operative study was initiated by Nordic Council of Ministers. Part of the study consisted of forensic pathologists examining SIDS victims. They showed that neither the increase during the 1980's nor the decrease during the 1990's was due to changes in the classification or diagnostic practise. A correlation between prone sleeping position and SIDS rates is now well recognised. However, neither an explanation for the great discrepancy in SIDS rates between the Nordic countries nor a possible explanation for the risk of prone sleeping position has been achieved.
Tidsskrift for den Norske laegeforening
European Journal of Cancer and Clinical Oncology, 1986
Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent... more Pre-operative CEA levels were measured in 100 patients with large bowel carcinomas with dtflerent DNA ploidy pattern and serial post-operative determinations performed in the 64 who had been operated for cure. The follow-up pen'od was $8 yr. All CEA measurements were performed consecutively with a RIA (Roche), and subsequently repeated in one batch with an EIA (Roche) based on a monoclonal antibody. Both assays showed a similar number of 'falsenegative' CEA levels pre-operatively-varying from 69% in aneuploid (AN) Dukes' A to 8% in AN Dukes' D turnours, andfrom 75% in near diploid (ND) Dukes' A to 40% in ND Dukes' D turnours. The sensitivity for detecting recurrence in patients with tumours of either ploi& pattern was slight& better with EIA than with RIA. A difference between the AN and ND group was shown somewhat better with RIA, the sensitivity in the AN group being 79% and the median lead time 7 months compared to 13% and 2 months in the ND group. The corresponding jigures with EIA were 71% and 7 months for the ANgroup and 63% and lfmonths for the ND group. However, all but one of the patients with ND DNA pattern who showed recurrenceassociated CEA elevation with EIA also had an elevated level pre-operatively. We conclude that all patients operated for cure should be followed by regular CEA measurements post-operatively if they had an elevated CEA level prior to operation. In addition, patients with AN tumour should be followed with serial GEA measurements even in the absence of pre-operative elevation.
Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1990
We present a case of fatal vascular destruction and granulomatosis of the lungs from intravenous ... more We present a case of fatal vascular destruction and granulomatosis of the lungs from intravenous injections of dissolved tablets containing microcrystalline cellulose as filler material. Numerous microcrystalline cellulose pulmonary emboli and foreign body granulomas were detected, and the pulmonary parenchyma showed signs of disturbed circulation with focal necrosis and oedema.
Pediatric Research, 1998
Elevated hypoxanthine (Hx) levels in the vitreous humor of victims of the sudden infant death syn... more Elevated hypoxanthine (Hx) levels in the vitreous humor of victims of the sudden infant death syndrome (SIDS) have been been claimed to indicate hypoxia before death. An important methodologic problem is the temperature-dependent Hx increase after death. Although most previous studies have corrected for expected postmortem Hx increase, the aim of the present study was to omit this problem by matching the subjects of the different groups studied for similar postmortem time. Thirteen cases of violent death, 11 cases of borderline SIDS, 22 cases of death from infectious disease, and 17 cases of death from heart/lung disease were compared with a 3-fold number of SIDS cases. To investigate the impact of environmental factors on the Hx levels of the SIDS cases, the following possible confounding factors were investigated: attempt to resuscitate, slight infections before death, sleeping position, and time of the day when found dead. To investigate whether the size of the eyeball would influence the Hx level, five cases of violent death in children were compared with 15 adults who died suddenly. The vitreous humor Hx level was significantly higher in SIDS victims than in cases of violent death (p < 0.01) and deaths due to heart/lung disease (p < 0.01), whereas no such difference was found either between SIDS and borderline SIDS or SIDS and infectious death. There were no differences between any of the subgroups of SIDS victims. The vitreous humor Hx level in small children and adults did not differ. The findings raise the question of possible similarities in death mechanism in SIDS and infectious death.
International Journal of Cancer, 1997
Mutations in the k-ras and TP53 genes, as well as microsatellite instability (MIN), are frequent ... more Mutations in the k-ras and TP53 genes, as well as microsatellite instability (MIN), are frequent genetic alterations in colorectal carcinomas and represent 3 different mechanisms in the carcinogenic process. Both the incidence of colorectal cancer and the frequency of genetic alterations in such tumours have been related to different clinico-pathological variables, including age and gender of the patient and location of the tumour. A number of studies have also reported associations between different types of genetic alterations. We therefore wanted to explore the relationship between these genetic and clinico-pathological variables using multivariate analysis on material from 282 colorectal carcinomas. Three logistic regression models were constructed: 1) the presence of K-ras mutations was dependent on MIN and age and gender of patient, with an especially low frequency among younger males and in tumours with MIN (overall p ؍ 0.0003); 2) the presence of TP53 mutations was only dependent on tumour location, with a positive association to cancers occurring distally (p ؍ 0.002); and 3) the presence of MIN was dependent on age, gender and K-ras and TP53 mutations, as well as on tumour location. MIN was most frequent among younger male and older female patients, was rare in tumours with K-ras or TP53 mutations and was found almost exclusively in the proximal colon (overall p F 0.0001). Our data confirm that different genetic pathways to colorectal cancer dominate in the proximal and distal segments of the bowel and suggest that the K-ras-and MIN-dependent pathways are influenced by different sex-related factors. Int.
Gut, 1996
Background, Aims, and Patients-In a prospective follow up and intervention study of colorectal po... more Background, Aims, and Patients-In a prospective follow up and intervention study of colorectal polyps, leaving all polyps less than 10 mm in situ for three years, analysis ofredetection rate, growth, and new polyp formation was carried out in 116 patients undergoing annual colonoscopy. The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo. Results-Redetection rate varied from 75-90% for each year, and was highest in the rectum and sigmoid colon. There was no net change in size of all polyps in the placebo group, however, polyps less than 5 mm showed a tendency to net growth, and polyps 5-9 mm a tendency to net Medical Department,
Diagnostic Molecular Pathology, 1998
The aim of this study was to establish an experimentally based cutoff level for assessing p53 imm... more The aim of this study was to establish an experimentally based cutoff level for assessing p53 immunoreactivity in colorectal tumors. The accumulation of p53 protein in 273 colorectal tumors was correlated with previously obtained data on TP53 mutation and loss of heterozygosity at two 17p13 loci in the same tumors. The monoclonal antibody PAb 1801 was used for p53 staining, and the results obtained by immunohistochemistry and immunoblotting were similar. Mutation analyses of exons 5-8 were performed using constant denaturant gel electrophoresis followed by sequencing. There were no statistically significant differences for any measured TP53 gene alteration between the group of tumors without p53-positive nuclei (n = 83) and the group with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;5% positive nuclei (n = 58). The majority of mutations within these groups were deletions/insertions and nonsense mutations without p53 accumulation. Therefore, we assume that 5% p53-positive nuclei is the relevant cutoff level to assess TP53 damage in colorectal tumors. A prerequisite for this recommendation is optimal conditions for p53 protein detection. The parameters for p53 dysfunction were correlated to DNA aneuploidy measured by flow cytometry. TP53 mutations were significantly associated with DNA aneuploidy (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.00001), and a nonrandom distribution of TP53 gene alterations among diploid (DI = 1), hyperdiploid (1.0 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; DI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 1.3), and highly aneuploid (DI &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 1.3) tumors indicates that DNA hyperdiploid tumors constitute a separate developmental entity different from tumors with gross aneuploidy.
Current Pediatric Reviews, 2010
Cancer, 1985
Tumor specimens were obtained from seven patients with large bowel carcinomas at operation of the... more Tumor specimens were obtained from seven patients with large bowel carcinomas at operation of the primary neoplasm and by resection of local recurrences or metastases 2% to 36 months later. All specimens were evaluated with regard to nuclear DNA distribution as mehsured by flow cytometry and expression of carcinwmbryonic antigen (CEA), secretory component, epithelial IgA, and HLA-DR antigens, as determined by immunofluorescence staining of tissue sections. Both the DNA distributions and the immunohistochemical staining patterns were similar in the primary and secondary tumors. These findings are in keeping with a monoclonal or oligoclonal tumor progression in advanced large bowel carcinoma.
Archives of Pediatrics & Adolescent Medicine, 2003
Cancer Detection and Prevention
In 100 patients with large bowel carcinomas, the tumors were divided into a distinctly aneuploid ... more In 100 patients with large bowel carcinomas, the tumors were divided into a distinctly aneuploid (AN) group (63) and a near diploid (ND) group (37) by flow cytometric (FCM) DNA quantitation of cell suspensions. Preoperative plasma CEA levels were determined in all patients. Thirty-eight patients with AN and 28 patients with ND tumors were operated on for cure and had normal plasma CEA levels postoperatively. These two groups had regular CEA plasma measurements as part of the clinical follow-up. In the AN group, 12 of 15 patients have had recurrence preceded by CEA elevation. In the ND group, however, only one of eight recurrences was preceded by a rise in CEA level; the one with elevation also had increased plasma CEA prior to operation. It thus seems that a low CEA output of ND tumors explains many of the "false-negative" CEA measurements in disseminated cases. It is concluded that, in addition to patients with an elevated preoperative plasma CEA level, all patients with aneuploid tumors should be subjected to repeated plasma CEA measurements as part of the follow-up program.
Scandinavian Journal of Gastroenterology
In sporadic colorectal adenomas mutations in the adenomatous polyposis gene (APC) are among the f... more In sporadic colorectal adenomas mutations in the adenomatous polyposis gene (APC) are among the first gene aberrations to appear. In familial adenomatous polyposis (FAP) the patients already have a germline mutation in the APC gene. To investigate the natural history of duodenal adenomas in FAP patients, we examined germline and somatic mutations of the APC gene and K-ras mutations in these lesions. Frozen sections from 54 duodenal polyps from 31 FAP patients were used to histologically verify the presence of adenomatous growth in the mucosa; the rest of each biopsy specimen was processed for DNA extraction. APC exon 15 was investigated with the protein truncation test (PTT), using four overlapping polymerase chain reaction (PCR) fragments, and samples showing an APC mutation were thereafter sequenced. The adenomas were examined for K-ras mutations by use of a combination of the 'enriched PCR method' and temporal temperature gradient electrophoresis. APC germline mutations in exon 15 were found in 19 of 31 (61%) patients, whereas somatic mutations were localized to 12 of 54 (22%) duodenal adenomas. In seven adenomas both the germline and the somatic mutations were found, whereas five small adenomas showed somatic mutations only. There was no tendency for more mutations to be detected in large and severely dysplastic adenomas compared with small and mildly dysplastic ones. K-ras mutations were found in four (7%) duodenal adenomas. The low rate of somatic APC and K-ras mutations in duodenal adenomas may indicate another neoplastic pathway than in FAP adenomas of the large bowel, or that a modifier gene is cosegregating with the disease.
Cellular oncology: the official journal of the International Society for Cellular Oncology
Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In... more Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In the present study, we aimed to identify and validate novel target genes inactivated through promoter hypermethylation in colorectal tumor development. With the use of microarrays, the gene expression profiles of colon cancer cell lines before and after treatment with the demethylating agent 5-aza-2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-deoxycytidine were identified and compared. The expression of the responding genes was compared with microarray expression data of primary colorectal carcinomas. Four of these down-regulated genes were subjected to methylation-specific PCR, bisulphite sequencing, and quantitative gene expression analysis using tumors (n=198), normal tissues (n=44), and cell lines (n=30). Twenty-one genes with a CpG island in their promoter responded to treatment in cell lines, and were simultaneously down-regulated in primary colorectal carcinomas. Among 20 colon cancer cell lines, hypermethylation was subsequently identified for three of four analyzed genes, ADAMTS1 (85%), CRABP1 (90%), and NR3C1 (35%). For the latter two genes, hypermethylation was significantly associated with absence or reduced gene expression. The methylation status of ADAMTS1, CRABP1, and NR3C1 was further investigated in 116 colorectal carcinomas and adenomas. Twenty-three of 63 (37%), 7/60 (12%), and 2/63 (3%) adenomas, as well as 37/52 (71%), 25/51 (49%), and 13/51 (25%) carcinomas were hypermethylated for the respective genes. These genes were unmethylated in tumors (n=82) from three other organs, prostate, testis, and kidney. Finally, analysis of normal colorectal mucosa demonstrated that the observed promoter hypermethylation was cancer-specific. By using a refined microarray screening approach we present three genes with cancer-specific hypermethylation in colorectal tumors, ADAMTS1, CRABP1, and NR3C1.