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Biomedical subjects

E Jaramillo

Publications and source records attributed to E Jaramillo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Somatic mutations of the APC, KRAS, and TP53 genes in nonpolypoid colorectal adenomas.

Colorectal adenomas are macroscopically visible morphological changes of the mucosa that can develop focal carcinoma in the absence of surgical intervention. The successive molecular changes proposed to occur at different stages in the adenoma-carcinoma sequence were primarily based on DNA studies of exophytic, polypoid-type adenomas. Not all colorectal lesions, however, display an exophytic phenotype and a presumed distinct colorectal neoplasm, the nonpolypoid adenoma, was subsequently described as a precursor of colorectal cancer. The low incidence of KRAS mutations in nonpolypoid colorectal adenomas reported previously suggested a different genetic basis for the transformation process in these lesions. We have pursued the identification of genetic changes in benign sporadic nonpolypoid colorectal adenomas in a selected Swedish patient group with no family history of colorectal cancer. Mutation screening of the adenomatous polyposis coli (APC), KRAS, and TP53 genes was conducted using the protein truncation test, heteroduplex-single-strand conformation polymorphism analysis, and denaturing gradient gel electrophoresis on PCR-amplified fragments. Fourteen mutations in the APC gene were characterized in 10/20 samples. Mutations in the KRAS and TP53 genes were identified in 3/57 and 4/51 adenomas, respectively. The mutation frequencies and distribution of mutations in APC correlate with published data on exophytic adenomas. The low mutation frequency of the TP53 gene is consistent with the benign nature of the research material. KRAS activation (an early event in polypoid colorectal adenomas) apparently does not play a significant role in nonpolypoid adenoma development but may result in the development of a polypoid configuration. Genes Chromosomes Cancer 27:202-208, 2000.

Adenoma↗
PubMed1999

Cellular localization of a Hsp90 homologue in Porphyromonas gingivalis.

We previously reported an association between elevated serum antibody titers to the 90-kDa human heat shock protein (Hsp90), periodontal health and colonization by Porphyromonas gingivalis. In this study, we examined the cellular localization of the Hsp90 homologue of P. gingivalis. Cultures of P. gingivalis were heat-stressed (45 degrees C) and examined for localization of the Hsp90 homologue. Heat stress induced a 4-5-fold increase in anti-Hsp90 antibody reactivity over that of the unstressed controls. Western blot analysis revealed two bands (44 and 68 kDa) that reacted with anti-Hsp90 antibodies. The 68-kDa band was heat-inducible, while the 44-kDa band was not. Immunogold staining revealed that the Hsp90 homologue localized principally to the membrane and extracellular vesicles. Subcellular fractionation confirmed that the Hsp90 homologue was primarily membrane-associated.

Blotting, Western↗
PubMed1999

Encompassing treatment with prevention: the path for a lasting control of tuberculosis.

Tuberculosis is an important cause of death, mainly in the less developed countries. Thus far the strategy for its control had relied on the diagnosis of sick individuals and provision of chemotherapy. However, this strategy is problematic for several reasons: poor education about the disease and the low income of people with tuberculosis are important barriers for them to have access to early diagnosis and to keep adherence to treatment; provision of 'preventive therapy' to the enormous pool of people infected with tuberculosis is not feasible in less developed countries; and finally, long-term political commitment with the strategy is unlikely. Several facts indicate that tuberculosis patterns in different populations are shaped by biological, behavioral and socio-economic factors. This paper argues that a lasting control of tuberculosis requires a strategy based on a broader model of causality, which takes account of all these three causal factors.

Causality↗
PubMed1999

Multiple APC mutations in sporadic flat colorectal adenomas.

Adenomas are established pre-malignant lesions in colorectal carcinogenesis. To date the adenoma-carcinoma sequence for the development of colorectal carcinoma (CRC) has been based largely on molecular data of exophytic, polypoid-type adenomas. Subsequently, a different type of adenoma has been identified: the flat adenoma, so called for its flat, non-exophytic appearance, making it less likely to be detected during conventional endoscopy. However, due to technological advances in endoscopic methods, flat-type adenomas can now frequently be detected and are no longer considered rare colorectal lesions. The phenotype of flat colorectal adenomas differs macroscopically and histologically from exophytic adenomas. Flat colorectal adenomas, as a rule, are tubular structures often revealing high-grade dysplasia, irrespective of the size or villous component. Flat adenomas have also been recognised as pre-cancerous lesions in gastric cancer. Unlike the wealth of clinical and molecular information available for polypoid (exophytic) adenomas, molecular profiles of flat-type lesions have not yet been characterised systematically and the full clinical significance hereto realised. Previous molecular investigation of the K-ras gene in flat colorectal adenomas suggests a distinct pathway in their development. In this study, mutation analysis of the adenomatous polyposis coli (APC) gene using the protein truncation test (PTT) in 20 flat colorectal adenomas in a selected group of 16 patients without hereditary predisposition to colorectal cancer, revealed double truncations of the APC gene in four adenomas. In one of these adenomas a third mutation was detected by DNA sequence analysis.

Adenoma↗
PubMed1999

Non-polypoid adenomas of the colon are associated with subjacent lymphoid nodules. An experimental study in rats.

BACKGROUND: Subjacent lymphoid nodules (SLNs) have been found in 38% of non-polypoid colonic adenomas in humans. In the present work the presence of SLNs in experimentally induced colonic adenomas was investigated in rats. METHODS: 1,2-Dimethylhydrazine was injected subcutaneously in 290 Sprague-Dawley rats for 27 weeks. RESULTS: An SLN was present in 28.6% of the 84 adenomas, in 8.4% of the 119 adenocarcinomas, and in 9.7% of the 31 small carcinomas without remnant adenomatous tissue. An SLN was found in 35.6% of the 59 non-polypoid neoplasias but only in 9.1% of the 175 polypoid (that is, exophytic) neoplasias. When only adenomas were considered, SLNs were present in 50.0% of the 34 non-polypoid adenomas but only in 14.0% of the 50 polypoid adenomas. CONCLUSIONS: Non-polypoid colonic adenomas evolve preferentially from the minimal fraction of the colonic mucosa that overlays the few existing lymphoid nodules in rats.

Adenoma↗
PubMed1999

Clinical spectral characterisation of colonic mucosal lesions using autofluorescence and delta aminolevulinic acid sensitisation.

BACKGROUND AND AIMS: Laser induced fluorescence (LIF) from colonic mucosa was measured in vivo with and without delta aminolevulinic acid (ALA) in an attempt to differentiate between neoplasia and non-neoplasia in real time during colonoscopy. METHODS: Spectra from 32 adenomas, 68 normal sites, and 14 hyperplastic polyps in 41 patients were obtained with a point monitoring system. Twenty one of the patients had been given a low dose of ALA as a photosensitiser before the examination. Light of 337, 405, or 436 nm wavelength was used as excitation. Stepwise multivariate linear regression analysis was performed. RESULTS: With 337 nm excitation, 100% sensitivity and 96% specificity was obtained between normal mucosa and adenomas. Seventy seven per cent of the hyperplastic polyps were classified as non-neoplastic. When exciting with 405 and 436 nm, the possibility of distinguishing different types of tissue was considerably better in the ALA patients than in the non-ALA patients. CONCLUSIONS: The in vivo point measurements imply that a good discrimination between normal tissue and adenomatous polyps can be obtained using the LIF technique. Excitation at 337 nm and at 405 nm or 436 nm using ALA gives good results. LIF also shows potential for distinguishing adenomatous from hyperplastic polyps. The number of detection wavelengths could be reduced if chosen properly.

Adenoma↗
PubMed1998

Somatically acquired genetic alterations in flat colorectal neoplasias.

Somatically acquired mutations in several genes have been reported as playing an important role during colorectal tumorigenesis. Two alternative groups of carcinomas, termed LOH+ and RER+, have been defined on the basis of their genetic anomalies, a biallelic inactivation of the APC or the TGF-betaRII genes, occurring as an alternative, in LOH+ or RER+ tumors. It is a generally accepted hypothesis that most of colorectal cancers (CRC) develop from a pre-existing adenomatous polyp. Such benign lesions are usually exophytic polyps, a small proportion of adenomas having been described as flat lesions. The latter histological category has thus been proposed to bear specific genetic alterations. In order to examine this hypothesis, we have characterized a series of 44 flat colorectal neoplasias for their RER status and for somatic APC, KRAS and TGF-betaRII genes mutations. Flat colorectal neoplasias were found to be of the RER+ subtype in 22% of cases, all of them exhibiting a TGF-betaRII mutation. A mutation of the APC and KRAS genes has been found in 42% and 4% of tumors, respectively, none of these tumors being of the RER+ subtype. With the exception of a low KRAS mutation rate, flat adenomas appear to follow tumorigenesis pathways very similar to those identified in exophytic adenomas and carcinomas.

Adenoma↗
PubMed1998

Pulmonary tuberculosis and health-seeking behaviour: how to get a delayed diagnosis in Cali, Colombia.

Tuberculosis is a heavy burden in the developing countries. Early diagnosis and adherence to treatment are difficult to achieve by patients. Our qualitative research looked at the paths followed and the barriers experienced by patients at the health care services of Cali, Colombia, while seeking help for pulmonary tuberculosis symptoms. Results show that the cultural-based explanation patients give to the symptoms, the stigma attached to the disease, and the poor quality of health care services (communication skills, organizational structure, attitudes, and knowledge of the tuberculosis control strategy of health care workers) are strong barriers to early diagnosis.

Adolescent↗
PubMed1998

Tuberculosis control in less developed countries: can culture explain the whole picture?

Healthcare practices, adherence to treatment, and organizational behaviour of healthcare workers are the main issues concerning tuberculosis (TB) control influenced by culture. A review of research findings published in the English language literature concerning these issues, and the way in which they are affected by cultural and structural factors is presented and discussed. These findings suggest that structural rather than cultural factors may be the main explanation for the questionable behaviour of healthcare workers and patients suffering from TB in less developed countries.

Cultural Characteristics↗
PubMed1997

Small colorectal serrated adenomas: endoscopic findings.

BACKGROUND AND STUDY AIMS: Serrated adenomas are a distinct form of colorectal neoplasia. Several reports have indicated that serrated adenomas may give rise to invasive adenocarcinoma. The present study describes the endoscopic findings in 54 colorectal serrated adenomas detected in 35 patients. PATIENTS AND METHODS: Thirty-five of 1225 patients (2.9%) who underwent colonoscopy during 1993 in the gastrointestinal endoscopy section at Karolinska Hospital (22 men, 13 women; mean age 68 years, range 49-84 years) were found to have a total of 182 polyps, including 118 adenomas and 64 hyperplastic polyps at histopathology. Fifty-four of the 118 adenomas (46%) were of the serrated type. In two of the 35 patients, two large exophytic colorectal adenocarcinomas were also present. RESULTS: Twenty-nine of the serrated adenomas (53.5%) were flat, 23 were sessile (42.5%), and two were pedunculated (4%). The mean sizes of the flat and sessile lesions were 3.5 mm (range 2-10 mm) and 5.9 mm (range 2-20 mm), respectively. The endoscopic appearance of serrated adenomas of 5 mm or less (n = 39, 72%) was similar to that of hyperplastic polyps. Forty-two (78%) of the lesions were located in the sigmoid and rectum. Fifty-one lesions showed low-grade dysplasia (including one with microinvasive carcinoma), and the remaining three had high-grade dysplasia. CONCLUSIONS: The study suggests that small polyps with a hyperplastic appearance should not be regarded as innocuous, since they may represent serrated adenomas carrying a malignant potential.

Adenoma↗
PubMed1996

Small, flat colorectal neoplasias in long-standing ulcerative colitis detected by high-resolution electronic video endoscopy.

BACKGROUND: High-resolution video endoscopy complemented with chromoscopy allows for more detailed visualization of the colonic mucosal surface. METHODS: Using high-resolution video endoscopy and chromoscopy, we investigated 85 patients with extensive ulcerative colitis with a disease duration of at least 10 years who were taking part in a cancer surveillance program. RESULTS: In 38 of the 85 patients, 104 polyps were detected at endoscopy. Seventy-seven (74%) of the 104 polyps were endoscopically flat, 21 (20%) were sessile, 3 (3%) were pedunculated, and 3 (3%) had no recorded morphology. Twenty-three (22%) polyps were neoplastic (15 flat, 5 sessile, 2 pedunculated, 1 not recorded). Low-grade dysplasia was found in 21 of the 23 neoplastic polyps and high-grade dysplasia in the remaining 2 (1 flat tubular adenoma and 1 sessile villous adenoma with invasive growth). Flat polyps were small, with a diameter of 5 mm or less in 73% (n = 56) of cases. At histology flat polyps revealed either flat adenomas (n = 11; 14.3%), tubular or villous structures with dysplastic cells at the lower part of the crypts (n = 4; 5.2%), flat hyperplastic polyps (n = 26; 34%), inflammatory mucosa (n = 5; 6.5%), or mucosa in remission (n = 31; 40%). CONCLUSION: The use of high-resolution video endoscopy complemented with chromoscopy in ulcerative colitis enables the detection of flat neoplastic polyps. The existence of those hitherto undetected neoplasms in ulcerative colitis and their possible role in the histogenesis of colorectal cancer in ulcerative colitis deserve further investigation.

Adenoma↗
PubMed1996

Flat serrated adenomas of the colorectal mucosa.

A total of 47 flat serrated neoplasias of the colorectal mucosa are presented: 44 were flat serrated adenomas and the remaining 3 flat serrated adenocarcinomas arising in flat serrated adenomas. These lesions were found among 600 flat mucosal lesions removed at colonoscopy during a 3-year period (1992 and 1994) at the Karolinska Hospital. Thirty-five of the 47 patients (74%) were males and the remaining 12 (26%), females. Depending upon the degree of cellular dysplasia within the epithelium, serrated adenomas were divided into those with low-grade dysplasia (LGD), when the dysplastic nuclei were present in the deeper half of the epithelium, and those with high-grade dysplasia (HGD), when the dysplastic nuclei were found even in the upper half of the epithelium. LGD was present in 37 (84.1%) of the 44 serrated adenomas and HGD in the remaining 7 (15.9%). Depending upon the topographic distribution of the dysplastic epithelium within the crypts, flat serrated adenomas were divided into type I, when the dysplastic epithelium was limited to the lower half of the serrated crypts, and type II, when the dysplastic epithelium was even present in the superficial half of the serrated crypts. Of the 44 serrated adenomas, 38 (86.1%) were type I and the remaining 6 (13.9%) type II. The dysplastic epithelium seemed to originate at the base of the crypts and to progress upwards, replacing the scalloped, serrated epithelium of the sides of the crypts. Invasive adenocarcinomas (i.e., with submucosal extension) were seen to arise from flat serrated adenomas with LGD type I (n = 2) or with HGD type II (n = 1). This preliminary survey suggests that flat serrated adenomas of the colorectal mucosa may be lesions with a propensity to evolve into invasive adenocarcinoma, irrespective of the degree of the epithelial dysplasia or of their extension along the crypts.

Adenocarcinoma↗
PubMed1995

Flat neoplastic lesions of the colon and rectum detected by high-resolution video endoscopy and chromoscopy.

Because small flat colorectal neoplastic lesions (i.e., flat adenomas and flat adenocarcinomas) may be as translucent as the surrounding mucosa, they can remain undetected at conventional endoscopy. By combining high-resolution video endoscopy and chromoscopy, we detected 109 colorectal flat neoplastic lesions in 55 of 232 patients studied. Forty-three (78%) of the 55 patients with flat neoplastic lesions were over 60 years of age. No flat neoplastic lesions were seen in patients under 40 years of age. Flat neoplastic lesions were more frequent in men (35%) than in women (15%). Seventy-seven (71%) of the 109 flat neoplastic lesions measured 0.5 cm or less, 23 (21%) between 0.6 and 1.0 cm, and 9 (8%) more than 1.0 cm. Low-grade dysplasia and high-grade dysplasia were found in 94 (86%) and 13 (12%) of the flat neoplastic lesions, respectively. Adenocarcinoma was diagnosed in 3 (3%) flat lesions: 1 (1%) carcinoma originating in a flat adenoma and 2 (2%) adenocarcinomas without recognizable adenomatous elements. No adenocarcinomas were seen in lesions measuring 1.0 cm or less. Fourteen flat neoplastic lesions had a central depression at endoscopy. Flat neoplastic lesions with central depression more frequently showed high-grade dysplasia (43%) than did flat neoplastic lesions without central depression (7%). Central depression in flat neoplastic lesions should be considered a possible endoscopic marker for severe dysplasia. Our results suggest that flat neoplastic lesions occur more frequently than previously reported in Scandinavia. Flat adenomas may play an important role in the histogenesis of colorectal cancer.

Adenocarcinoma↗
PubMed1994

Histogenesis of small colonic adenocarcinomas.

It has been claimed that in order to identify the type of mucosal lesion which precedes colonic adenocarcinoma only those tumours measuring < or = 1 mm in diameter should be considered. The review of the English literature indicates that only 35 colorectal adenocarcinomas measuring < or = 1 cm in diameter have been so far reported. From the three cases of colonic adenocarcinoma measuring 8 mm or less in diameter presented here, one adenocarcinoma originated in a flat adenoma, the second in an exophytic tubular adenoma, and the third showed no adenomatous component. It would thus appear that colonic adenocarcinomas can originate not only from exophytic adenomas or from flat adenomas but also from apparently nonadenomatous flat mucosa.

Adenocarcinoma↗
PubMed1994

DNA aneuploidy and histologic dysplasia in long-standing ulcerative colitis. A 10-year follow-up study.

PURPOSE: This study was designed to assess the presence of DNA aneuploidy and mucosal dysplasia, respectively, in 63 patients with long-standing ulcerative colitis. METHODS: The DNA content in colonic biopsies was investigated, using a flow cytometry method, and compared with conventional histology. Patients were subsequently followed each or every second year with colonoscopy and histology. A second flow cytometry examination to monitor the DNA pattern was performed after 10 years. RESULTS: Initially, abnormal DNA pattern (i.e., aneuploidy) was found in 13/63 (21 percent) patients. The colonic mucosa was flat in 10, polypoid in 1, and tumor infiltrated in 2. Eight of the 10 aneuploid cases with a flat mucosa showed no signs of histologic dysplasia. In one of two cases with simultaneous aneuploidy and low-grade dysplasia, a carcinoma Dukes B was found at subsequent colectomy. On the other hand, dysplasia (one low grade and one high grade) without aneuploidy was found in two patients at the initial investigation. After 10 years, 13 had been colectomized, 11 had died (7 noncolitis related), and 3 were lost to follow-up. In the remaining 36 living patients with intact colorectum, no case of histologic dysplasia, but 6 cases of DNA aneuploidy were discovered at the initial investigation. Of the six aneuploid cases, one was later reclassified as diploid and one consisted of an aneuploid adenomatous polyp (removed by polypectomy). At follow-up 10 years later, 3/4 of the other aneuploid cases showed repeated abnormal DNA pattern, now together with histologic low-grade dysplasia (in flat colon mucosa). The 30 patients with initially normal DNA patterns were all still diploid at re-examination 10 years later, but 2 now revealed low-grade dysplasia histologically. CONCLUSIONS: DNA aneuploidy in chronic ulcerative colitis seems to be stable and it may precede histologic dysplasia by many years. It appears to be an additional marker for detecting neoplastic transformation in ulcerative colitis.

Adenocarcinoma↗
PubMed1992

Comparison between double-contrast barium enema and colonoscopy to investigate lower gastrointestinal bleeding.

A retrospective study was performed to compare the diagnostic accuracy of high-quality double-contrast barium enema (DCBE) against gold standard colonoscopy in 288 patients with suspected lower gastrointestinal bleeding who went through both examinations. Colonoscopy detected the potential cause of bleeding in 99 patients (100%); in order of frequency: polyps greater than or equal to 1 cm (N = 47; 48%), carcinoma (N = 21; 21%), inflammatory bowel disease (IBD) (N = 15; 15%), solitary ulcers (N = 6; 6%), other types of colitis (N = 5; 5%), angiodysplasia (N = 3; 3%), and stenosis (N = 2; 2%). DCBE diagnosed 88 cases (89%) and missed 11 consisting of IBD (N = 4), angiodysplasia (N = 3), solitary ulcers (N = 3), and polyps (N = 1). The overall sensitivity and specificity of DCBE was 0.89 and 0.97, respectively. The sensitivity for carcinoma, polyps, and IBD was 1.00, 0.98, and 0.73, respectively. We conclude that DCBE is very effective to diagnose carcinoma and polyps greater than or equal to 1 cm, the most frequent causes of bleeding, but less effective to diagnose IBD and other nonfrequent causes. If a high-quality DCBE does not reveal the cause of bleeding, the contribution of a following colonoscopy will be to diagnose causes of bleeding other than carcinoma and polyps less than 1 cm and to offer therapeutic possibilities.

Adolescent↗