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ABSTRACT: Long term ulcerative colitis (UC) increases the risk of colorectal cancer (CRC). DNA aneuploidy is a common feature of both dysplastic and non-dysplastic colonic epithelia from patients with longstanding UC, and is regarded as an early sign of possible malignant transformation. The spindle proteins Aurora A, BUB1B and Mad2 have been implicated as contributors to aneuploidy and carcinogenesis.
To investigate the role of these spindle proteins in relation to DNA aneuploidy and during the progressive morphological changes in ulcerative colitis associated colorectal cancer (UCCRC).
Tissue microarrays were made from 31 colectomy specimens from patients with longstanding UC. Expression of Aurora A, BUB1B and Mad2 was investigated by immunohistochemistry and their relation to ploidy status, mucosal morphology and Ki67 levels was explored.
Expression of Aurora A and BUB1B was significantly associated with the progressive morphological changes of UCCRC. In the progression from non-dysplastic to dysplastic mucosa, Aurora A expression decreased while BUB1B expression increased. There was an increasing incidence of aneuploidy with progression towards cancer; expression of all spindle proteins was associated with the level of Ki67 but not with aneuploidy.
Due to the significant differences in Aurora A and BUB1B expression in dysplastic compared non-dysplastic mucosa, these proteins may serve as putative biological markers for the progressive morphological changes in UC associated carcinogenesis. The close relationship to Ki67 levels reflect that spindle proteins are expressed in tissues with a high proliferative rate; a role for these proteins in the development of aneuploidy was not found.
Journal of clinical pathology 01/2008; 60(12):1403-8. · 2.43 Impact Factor
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ABSTRACT: Most patients with stage I and stage II colon adenocarcinomas do not have disseminated disease, and the group is not offered adjuvant therapy. However, more than 30% of stage II colon adenocarcinoma patients get metastases to remote organs. Thus, it is important to identify patients in this group at risk of disease relapse.
We have examined the prognostic value of isolated tumour cells (ITC) in mesenteric lymph nodes in a consecutive series of 156 colon carcinoma patients with stage II disease. Immunohistochemistry, using antibodies to cytokeratins, and morphology were used to identify presence of ITC.
ITC were detected in 59 (37.8%) patients. Presence of ITC in mesenteric lymph nodes was independently associated with reduced relative survival both in univariate (p=0.0199) and in a multivariate analysis (p=0.041).
The results strongly suggest that presence of ITC in mesenteric lymph nodes is associated with reduced relative survival in colon carcinoma patients stage II, and that detection of ITC may be important in treatment of these patients.
European Journal of Surgical Oncology 01/2004; 29(10):862-6. · 2.50 Impact Factor
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ABSTRACT: Progression of colorectal cancer may follow either of two main genetic routes: the chromosome- or microsatellite-instability pathways. Association between the patients' prognosis and microsatellite instability has been questioned. Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells. In this study, the expression of HLA-DR antigen was investigated by immunohistochemistry in 357 large bowel carcinomas stratified by microsatellite instability status. Sixteen per cent of the tumours showed strong HLA-DR expression and 35% had weak DR expression. We confirmed that patients with strong positive HLA-DR staining had improved survival (P<0.001) compared to patients with no HLA-DR expression. Strong epithelial HLA-DR staining was significantly associated with high level of microsatellite instability (P<0.001). In the subgroup of tumours with characteristics typical of the chromosomal instability phenotype, i.e. in microsatellite-stable tumours, the patients positive for the HLA-DR determinants showed better survival than those without HLA-DR expression. The protective effect of HLA-DR expression on survival was confirmed by multivariate analysis, both in the whole patient group and in the microsatellite-stable/microsatellite instability-low group. This might be explained by enhanced T-cell mediated anti-tumour immune responses against tumour cells in the HLA-DR positive tumours. The finding of better patient survival in the subgroup of strong HLA-DR positive microsatellite-stable tumours may have clinical implications for these patients.
British Journal of Cancer 09/2002; 87(7):756-62. · 5.04 Impact Factor
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H J Andreyev,
A R Norman,
D Cunningham,
J Oates,
B R Dix,
B J Iacopetta,
J Young,
T Walsh,
R Ward,
N Hawkins, [......],
J Costa,
V E Pricolo,
S D Finkelstein,
J S Thebo,
A J Senagore,
S A Halter,
S Wadler,
S Malik,
K Krtolica,
N Urosevic
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ABSTRACT: Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.
British Journal of Cancer 10/2001; 85(5):692-6. · 5.04 Impact Factor
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ABSTRACT: DNA aneuploidy has been shown to increase the risk of developing dysplasia in ulcerative colitis (UC) and is related to tumorigenesis in the colorectum. Therefore, it is of particular interest to study genetic aberrations behind DNA aneuploidization during colorectal carcinogenesis. We wanted to elucidate further the relationship between mucosal morphology and DNA aberrations in UC.
DNA flow cytometry was applied to multiple lesions including regenerative, dysplastic, and carcinomatous mucosa from the colectomy specimen of a male patient with long-standing UC. The lesions harbored multiple DNA aneuploid stemlines that were subjected to flow sorting. We analyzed gene alterations by degenerate oligonucleotide primer (DOP; universal primers) polymerase chain reaction (PCR)-based comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH) in diploid and aneuploid sorted cells.
DOP-PCR-based CGH shows gains and losses that can be verified by FISH. We show that with this approach one can study genetic evolution of distinct DNA diploid and aberrant subpopulations through defined stages of colorectal tumorigenesis. This includes getting information related to tumor heterogeneity that cannot be obtained by CGH with DNA extracted from nonsorted cell populations. Genetic imbalance was also detected in diploid nondysplastic flow-sorted mucosal cells from the same bowel.
Similar gains and losses were found in aneuploid dysplasias and carcinomas at widely separated locations in the same bowel, indicating a common selection pressure in different areas of the same bowel. The common aberrations may be of importance for progression from dysplasia to carcinoma.
Cytometry 02/2001; 43(1):46-54.
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ABSTRACT: K-ras mutation is one of the first genetic alterations in classical colorectal carcinogenesis.
To investigate the role of K-ras mutations in carcinogenesis, in long standing ulcerative colitis.
A total of 161 microdissected and 100 DNA samples from 13 patients were analysed for K-ras codons 12 and 13 mutations by means of a combination of enriched polymerase chain reaction amplification and temporal temperature gradient electrophoresis.
K-ras mutations were found in 21/161 (13%) microdissected samples in 7/13 large bowels (16 and five in codons 12 and 13, respectively), and in 10/100 (10%) mucosal DNA samples (six and four, respectively). One of four patients with six adenocarcinomas had a K-ras mutation in a carcinoma, as well as one of two patients with large dysplasia associated lesion or mass (DALM). Eight of 13 (61%) areas with villous architecture and large, distended goblet cells, had a K-ras mutation, which was significantly more frequent than in low grade dysplasia (one of 23, 4%) but did not reach significance versus high grade dysplasia (four of 14, 28.5%). K-ras mutations were found in one of 20 (5%) flat lesions indefinite for dysplasia, two of 14 (14%) in non-villous, hypermucinous mucosa, and in one of 57 flat areas negative for dysplasia.
The highest K-ras mutation frequency was found in villous, hypermucinous mucosa. We suggest that this entity should be investigated further as a potential risk lesion for cancer development. It may represent a pathway directly from non-classical dysplasia to cancer, not previously described.
Gut 12/1999; 45(5):686-92. · 10.11 Impact Factor
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ABSTRACT: The occurrence of pallidal lesions with or without other hypoxic/ischaemic brain injuries was evaluated in 100 intravenous (i.v.) heroin addicts. The brains were collected consecutively from forensic autopsies during the period from January 1995 to June 1996. The autopsies were required by the police and performed at The Institute of Forensic Medicine, The National Hospital, Oslo. There were 21 women and 79 men, median age 32 (range 21-47) and 34 (19-60) years, respectively. Of 38 brains with abnormalities, twenty-five cases showed isolated or combined lesions of hypoxic/ischaemic origin. Pallidal lesions were found in nine brains; six lesions were old, one was subacute (a couple of weeks), and two were part of recent, generalized hypoxia/ischaemia. Six persons had old infarcts in the hippocampal formation, and one of them in combination with old pallidal infarcts. In seven brains small and old infarcts were found in watershed areas in the cerebellum. Between five and ten percent of i.v. heroin addicts might have pallidal infarcts, either as the sole lesion, or combined with other manifestations of hypoxic/ischaemic brain injury. This might give severe mental disturbances in the affected persons.
Forensic Science International 06/1999; 102(1):51-9. · 2.30 Impact Factor
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ABSTRACT: Evaluation of dysplasia in long standing ulcerative colitis is a difficult and often subjective task. Therefore, the aim of this study was to search for a more objective parameter to help distinguish regenerative changes from epithelial dysplasia.
A total of 97 sections from colectomy specimens from 12 patients with ulcerative colitis of more than 10 years duration were stained immunohistochemically with MIB 1 to detect differences in the frequency and pattern of nuclei positive for the proliferation marker Ki-67. All patients had epithelial dysplasia in one or more areas (high grade dysplasia, n = 16; low grade dysplasia, n = 15; indefinite for dysplasia, n = 16), and three patients had additional adenocarcinoma (one Dukes's C multifocal, mucinous carcinoma; one Dukes's C adenocarcinoma in the sigmoid; and one Dukes's A adenocarcinoma in the caecum). Two patients had adenomas--one had an 8 cm villous adenoma with intramucosal carcinoma, and the other had a 4 cm tubulovillous adenoma with high grade dysplasia.
There were highly significant differences between the percentages of Ki-67 immunopositive cells in low grade and high grade dysplasia and carcinoma compared with regenerative epithelium. In high grade dysplasia and carcinoma, the distribution of Ki-67 positive cells was diffuse throughout the full length of the crypt, whereas low grade dysplasia and epithelium indefinite for dysplasia, as well as regenerative epithelium, showed an expanded basal zone.
Assessment of the number of Ki-67 immunostained cells is of additional value in deciding whether the mucosa is regenerative or dysplastic, and the MIB 1 staining pattern is characteristic for most lesions with high grade dysplasia and carcinoma. Therefore, this technique could be combined with routine histological evaluation of colorectal epithelium being examined for dysplasia.
Molecular Pathology 01/1999; 51(6):327-32.
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ABSTRACT: Faecal bile acids (FBA) have been implicated in colon carcinogenesis. The results of case-control studies of colorectal cancer and polyp patients are, however, conflicting. The aim of this study was to examine the influence of faecal bile acids on occurrence, growth and recurrence of colorectal polyps, and to see if a mixture of calcium and antioxidants might possibly act on cancer precursors through the effect on FBA. A total of 116 polyp-bearing patients were recruited from the outpatients department. Polyps < 10 mm in diameter were left in situ and measured by annual colonoscopy for 3 years. The patients received placebo or a mixture of antioxidants and calcium carbonate, 1.6 g calcium ion daily. Faecal samples were collected annually; the first, 1 month after start of intervention, freeze dried and subjected to bile acid profile analysis. Two age and sex matched control groups were recruited (n = 35), one from healthy volunteers (healthy controls) and one from the outpatients referred for colonoscopy, with no polyps (hospital controls). Twelve of 47 patients from the healthy volunteers had polyps (healthy polyp patients). One or more adenomas were found in 93 patients. The faeces of the hospital controls had significantly higher concentrations of total and secondary bile acids than did the healthy controls. There was no difference in FBA profile between the polyp group and the hospital controls, but significantly higher concentration of total and secondary faecal bile acids in the healthy polyp patients compared with the healthy control group (P < 0.05). No increased concentration of FBA were found in the polyp patients with multiple polyps (n = 21) or previous treatment for colorectal cancer (n = 7). No associations between FBA profile and growth or recurrence of colorectal polyps were found. The polyp patients receiving active medication had higher faecal concentrations of total and secondary bile acids in the beginning of the study than at the end, in spite of a good compliance. The present study does not support bile acids as being important markers of initiation or growth of small and medium sized colorectal adenomas. In the present study the calcium and antioxidants did not seem to affect the growth or recurrence of colorectal adenomas by increased TBA excretion in the faeces.
European Journal of Cancer Prevention 08/1998; 7(4):287-94. · 2.13 Impact Factor
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ABSTRACT: Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies.
In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 microg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of < 10 mm at enrollment or follow-up were left unresected until the end of the study.
87-91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3-2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of < 5 or 5-9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26-4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication.
The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.
Digestion 01/1998; 59(2):148-56. · 2.05 Impact Factor
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ABSTRACT: Colorectal carcinogenesis is regarded as a multistep process involving several genetic alterations, with mutation in the K-ras gene in about half of the tumours. We aimed at clarifying the role of this genetic alteration related to survival and clinicopathologic variables.
One hundred large-bowel carcinomas operated on between 1978 and 1982 were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene, using enriched polymerase chain reaction amplification, restriction fragment length polymorphism analysis, and direct sequencing.
Forty mutations were found (40%): 31 in codon 12 and 9 in codon 13, 7 different types. There was no relationship between tumours with and without K-ras mutations with regard to Dukes' stages, age or sex of the patient, tumour localization, histologic grade, DNA ploidy pattern, HLA-DR staining pattern, or survival. Samples from 5 different localizations in 7 carcinomas showed identical K-ras mutation pattern, as did 19 recurrences/ metastases originating from 11 carcinomas.
When present, the primary tumour shows homogeneous distribution of K-ras mutation, and the mutation follows the carcinoma in the secondary deposit, regardless of lymphogenous or hematogenous spread. The presence of K-ras mutation does not seem to have prognostic significance for the patient, and the precise nucleotide change is furthermore not predictive of tumour behaviour.
Scandinavian Journal of Gastroenterology 02/1997; 32(1):62-9. · 2.02 Impact Factor
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ABSTRACT: 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 of redetection 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 regression in size, both for adenomas and hyperplastic polyps. This pattern was verified by computerised image analysis. Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients, and the same was true for those with multiple adenomas (four to five) compared with those with a single adenoma. The new adenomas were significantly smaller and 71% were located in the right side of the colon. Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma. One patient developed an invasive colorectal carcinoma, which may be evolved from a previously overlooked polyp. Two polyps, showing intramucosal carcinoma after follow up for three years, were completely removed, as judged by endoscopy and histological examination. CONCLUSIONS: The results show that follow up of unresected colorectal polyps up to 9 mm is safe. The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations, but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice. The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer.
Gut 10/1996; 39(3):449-56. · 10.11 Impact Factor
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ABSTRACT: Secretary component (SC) is expressed basolaterally as a transmembrane protein (pIg receptor) on secretory epithelial cells. As pIg receptor it plays a central role in humoral immunity by mediating the external translocation of dimeric IgA and pentameric IgM. A few case reports have suggested that reduced or absent SC protein expression is associated with diarrhoeal disease, but there is no convincing evidence that a primary pIg receptor deficiency can occur. In this study the relative presence of SC mRNA was determined by Northern blot analysis and related to immunohistochemically determined SC protein expression in 33 colorectal adenomas (31 patients) with increased risk of developing sporadic colorectal cancer, as well as in 19 colorectal carcinomas from 19 patients with such sporadic tumours. In the adenomas, SC mRNA levels were positively related to SC protein expression; both mRNA and SC protein were negatively related to histological grade. Similarly, SC mRNA levels tended to be related to the SC protein expression in the carcinomas. SC mRNA was detected in all adenomas, and only two of ten carcinomas (10.5%) deemed to be SC deficient by immunohistochemistry also lacked SC mRNA expression, suggesting diallelic alterations in the SC-encoding gene (locus PIGR). This possibility agreed with Southern blot analysis performed on a separate sample of 32 other colonic carcinomas in which the diallelic loss of D1S58 (which exhibits a close linkage centromerically to PIGR) was calculated to be 6.4%. Together these findings suggested that reduced SC protein expression in colorectal adenomas might be a transcriptional defect reflecting the degree of cellular dysplasia, whereas absent SC protein expression in colorectal carcinomas might also involve post-transcriptional defects and occasional diallelic gene deletions representing late events in carcinogenesis.
British Journal of Cancer 07/1996; 73(12):1503-10. · 5.04 Impact Factor
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ABSTRACT: Previous cytogenetic studies have indicated that a subset of large bowel adenomas have distal 1p deletions. We addressed this question by examining 70 sporadic polyps (63 adenomas, 5 hyperplastic polyps, and 2 polyps of undetermined histology) from 55 patients for alterations at eight loci on the short arm of chromosome 1 and found allelic imbalance (AI) or loss of one allele (LOH) in 14 (20%). The locus most frequently changed was MSI, which maps to 1p33-35. Fluorescence in situ hybridisation with centromeric and telomeric probes for chromosome 1, performed for 11 polyps, did not yield an abnormal number of signals, in accordance with the interpretation that the observed AI and LOH were the result of interstitial deletions in 1p. Whereas allelic imbalance at five other loci (mapping to 5q, 8p, 10p, 11p and 17q) was found less frequently, and then mainly in large (> 2 cm) tumours, the 1p alterations were equally distributed among small (< 1 cm) and large polyps. They were preferentially found in left-side tumours. Instability at microsatellite loci--the mutator phenotype--is demonstrated by shifts in the electrophoretic mobility of normal alleles. The mutator phenotype was first associated with hereditary nonpolyposis colorectal cancer but is also occasionally found in sporadic colorectal carcinomas; however, it is still uncertain when in the adenoma-carcinoma sequence in this type of genomic instability arises. We therefore looked for it at 12 dinucleotide repeat loci and found that seven tumours (six adenomas and one hyperplastic polyp) from seven patients had acquired new alleles not seen in the patients' corresponding normal DNA. Our results suggest that inactivation of a putative suppressor gene distally in chromosome arm 1p is an early event in colorectal tumourigenesis. They also show that microsatellite instability can be detected in large bowel polyps, indicating that this phenomenon, too, probably plays a pathogenic role for some colorectal tumours early in the adenoma-carcinoma sequence.
Genes Chromosomes and Cancer 11/1995; 14(3):182-8. · 3.31 Impact Factor
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ABSTRACT: One hundred large bowel carcinomas operated on between 1978 and 1982 were studied immunohistochemically with regard to expression of HLA-DR antigens. Three sections from each tumour were investigated by a semiquantitative scoring system, and a mean score for each patient established. Based on this scoring system, the tumours were divided into three groups: 0; 0.1-1.0; and > 1.0. All patients were followed until death (n = 68) or until June 1, 1992, and all cancer-specific deaths (n = 56) have been recorded. Analysis of survival in the whole patient group showed significant difference between the three levels of tumour HLA-DR expression (P = 0.006); patients who had tumours with strong HLA-DR expression showing the best survival. In a stratified analysis after Dukes' stages there was still a significant difference (P > 0.001) between the three levels of HLA-DR staining intensity. After a multiple regression analysis (Cox) with correction for different variables, the HLA-DR expression maintained its significance as a risk factor. To our knowledge this is the first time a relationship between intensity of tumour DR expression and survival has been shown in large bowel carcinoma.
British Journal of Cancer 07/1993; 68(1):80-5. · 5.04 Impact Factor
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ABSTRACT: Serum samples from 26 monozygotic twin pairs concordant or discordant with regard to inflammatory bowel disease, and rectal biopsies from 42 twins of the same subject group, were examined for IgG subclasses. They were all compared with normal controls. Almost all affected twins were in clinical remission. Paired immunofluorescence staining of the rectal mucosa showed that those with ulcerative colitis had a significantly higher (p < 0.01) proportion of IgG1 producing mucosal immunocytes than normal controls (78.1% v 55.9%). Conversely, the IgG2 cell fraction was significantly reduced (15.9% v 34.6%). Healthy twins from ulcerative colitis pairs tended to show a raised proportion of IgG1 cells and the IgG2 cell fraction was significantly reduced (p < 0.05). In discordant ulcerative colitis twin pairs, no difference appeared in the cellular IgG subclass pattern between healthy and affected twins. Furthermore, the proportion of IgG1 in these healthy and diseased twins showed good correlation (T = 0.867). The results in rectal mucosa of twins with Crohn's disease were widely scattered and affected twins did not differ significantly from normal controls. Healthy twins, however, showed a marginally raised IgG1 cell proportion, but no correlation was seen between the IgG subclass fractions in discordant Crohn's disease twin pairs. The serum concentrations of IgG1 and IgG2 did not differ from normal controls in twins of either category. These results suggested that in ulcerative colitis, the aberrant mucosal production of IgG1 and IgG2 does not depend on active disease, but is apparently at least partially explained by a genetic impact. Conversely, the mucosal IgG subclass pattern in Crohn's disease appears to be determined mainly by exogenous variables.
Gut 11/1992; 33(10):1358-64. · 10.11 Impact Factor
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ABSTRACT: The dentate fascia of the hippocampus was studied in 25 infants with pontosubicular necrosis and in 21 control cases without hypoxic cerebral lesions. Of the control cases 19 were completely normal and 2 showed one single necrotic cell in the granule cell layer. In contrast 15 of the cases with pontosubicular necrosis showed varying degrees of neuronal karyorrhexis in the dentate fascia. The severity of these changes largely parallelled those in the subiculum but there were exceptions to this rule. It is concluded that the dentate fascia is frequently involved in pontosubicular necrosis.
Acta Neuropathologica 02/1992; 83(5):535-7. · 9.32 Impact Factor
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ABSTRACT: Autopsies on 195 male alcoholics aged 30-64 years who died outside hospitals and nursing homes in Oslo from 1984 to 1988, were carried out at the Institute of Forensic Medicine, Rikshospitalet. In 127 cases brain tissue was examined neuropathologically, 86 (67.7%) showed abnormalities and 28 contained lesions of more than one type. Lesions associated with alcoholism were found in 61 cases (48%), 18 (14.2%) showed Wernicke's encephalopathy, 47 (37%) cerebellar atrophy, 2 central pontine myelinolysis and 1 hepatic encephalopathy. Subdural haematoma and/or cortical contusions were found in 30 cases (23.6%) and cerebrovascular lesions in 19 (15%). Of the 195 cases, 22 had a history of recurrent convulsive attacks of which 19 were examined neuropathologically and 13 had focal damage that could have caused epileptic fits. Although cerebral damage was more frequent among vagrants and other persons dependent on social support, 50% of the alcoholics living in their own homes were also affected. Alcohol-related disease was considered the cause of death in 15 of 127 cases examined neuropathologically and 9 of these died from acute Wernicke's encephalopathy all of whom were sober at death. Although the post mortem analyses included neuropathological examination of the brain, the cause of death remained unknown in 27 (21%) of the 127 cases.
Deutsche Zeitschrift für die Gesamte Gerichtliche Medizin 02/1991; 104(4):209-13. · 2.59 Impact Factor
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ABSTRACT: The study comprised male citizens of Oslo, aged 30-64 years, who died outside hospital and were autopsied at the Institute of Forensic Medicine, Rikshopsitalet, from 1984 to 1988. Of the 636 cases, 195 (30.7%) were classified as alcoholics and 441 as non-alcoholics. The cause of death remained unknown after autopsy and toxicological analyses in 17.4% of the alcoholics and in 5.4% of the non-alcoholics. Suicide by other methods than medicamental poisoning was 6-7 times more frequent among non-alcoholics than among alcoholics, while death from poisoning was definitely more common among alcoholics. The frequency of lethal accidents other than intoxications was similar in both cases. Coronary heart disease was the cause of 72.7% of the natural deaths among the non-alcoholics. Among the alcoholics, however, infections (24.3%) and alcohol-related disorders (15.9%) caused nearly as many deaths as coronary heart disease (25.3%). There was a high rate of blood-alcohol concentration (greater than or equal to 0.5%) in men who died from accidents, suicides and homicides, irrespective of whether they were alcoholics or not. The findings give evidence that alcohol has a strong impact on the mortality statistics for Norwegian middle-aged men.
Tidsskrift for Den norske legeforening 05/1990; 110(11):1366-71.
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ABSTRACT: From 1984 to 1988, 195 male alcoholics aged 30-64 years who died outside hospitals and nursing homes in Oslo were autopsied at the Institute of Forensic Medicine, the National Hospital, Oslo. Of the 127 brains neuropathologically examined, 86 (67.7%) showed abnormalities, and 28 contained lesions of more than one type. One or two lesions associated with alcoholism were found in 61 cases (48%). Thus, 18 (14.2%) showed Wernicke's encephalopathy, 47 (37%) cerebellar atrophy, two central pontine myelinolysis, and one hepatic encephalopathy. Subdural haematoma and/or cortical contusions were found in 30 (23.6%), and cerebrovascular lesions in 19 (15%). Of the 195 cases, 22 had a history of repeated epileptic seizures. Nineteen of them were examined neuropathologically, and 13 had focal damage that might have been responsible for their fits. The results indicate that the frequency of Wernicke's encephalopathy and cerebellar atrophy in male alcoholics who die outside hospital is similar to that previously observed in cases who died in hospital. Although cerebral damage was even more frequent among vagrants and others dependent on social support, half the men living in their own homes were also affected.
Tidsskrift for Den norske legeforening 03/1989; 109(4):454-7.
