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Biomedical subjects

M J Brito

Publications and source records attributed to M J Brito.

At least 19 recordsLinked to original sources
PubMed2001

Shift work at a modern offshore drilling rig.

The oil and gas exploration and production offshore units are classified as hazardous installations. Work in these facilities is complex, confined and associated with a wide range of risks. The continuous operation is secured by various shift work patterns. The objective of this study was to evaluate how offshore drilling workers perceived shift work at high seas and its impacts on their life and working conditions. The main features of the studied offshore shift work schedules are: long time on board (14 to 28 days), extended shifts (12 hours or more per day), slow rotation (7 to 14 days in the same shift), long sequence of days on the night shift (7 to 14 days in a row) and the extra-long extended journey (18 hours) on shift change and landing days. Interviews revealed a wide range of stressors caused by the offshore shift work, as well as difficulties to conciliate work with family life. It was observed that changes of the family model, leading to role conflicts and social isolation, work in a hazardous environment, perceiving poor sleep when working at night shifts and the imbalance between the expected and actual rewards are the major stressors for the offshore drilling workers.

Adult↗
PubMed2000

Eleven novel APC mutations identified in Portuguese FAP families.

Germline mutations of the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to colorectal cancer. In the present study we screened all of the exons of the APC gene in individuals belonging to 85 Portuguese FAP families. We here report eleven novel mutations which are predominantly frameshifts or single base substitutions, resulting in premature stop codons. Hum Mutat 16:178, 2000.

Adenomatous Polyposis Coli↗
PubMed2000

Duodenal-content reflux esophagitis induces the development of glandular metaplasia and adenosquamous carcinoma in rats.

Recent studies have demonstrated that refluxed duodenal contents cause esophageal carcinoma in rats without exposure to carcinogens. The histopathological spectrum of these carcinomas includes squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma. Pure adenocarcinomas are thought to arise in areas of columnar metaplasia adjacent to the anastomosis, similar to Barrett's esophagus in humans. In contrast, the histogenesis of adenosquamous carcinomas is unclear. The purpose here was to investigate the pathogenesis of esophageal adenosquamous carcinomas in a time-course experiment of chronic duodenal-content reflux without carcinogen. Forty-two 8-week-old male Sprague-Dawley rats were divided into seven groups and exposed to duodenal-content esophageal reflux during 10, 15, 20, 25, 30, 35 and 40 weeks, respectively. All animals underwent an esophagojejunostomy with gastric preservation in order to produce chronic esophagitis. The rats received a standard diet without addition of carcinogens. An increasing incidence of glandular metaplasia and carcinoma was observed over the time course, starting at 20 weeks. After 40 weeks of reflux, multiple foci of glandular metaplasia and adenosquamous carcinoma were found in 83 and 50% of the animals, respectively. Most of the carcinomas occurred in the middle and proximal esophagus and had a dual pattern of differentiation, glandular and squamous. These findings confirm that duodenal content reflux alone has a carcinogenic effect. We propose that chronic duodenal reflux induces the development of metaplastic cells with glandular differentiation from the stem cells of squamous epithelium, and that glandular metaplastic foci are the morphological element from which tumors with a dual pattern of differentiation arise.

Anastomosis, Surgical↗
PubMed1999

Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer.

Raised serum levels of interleukin 6 (IL-6) have been described in cancer patients. This cytokine mediates the acute phase response and has been also involved in the pathogenesis of cancer cachexia. The objectives of the present study were: (1) to determine the relationships of IL-6 and other cytokines with neoplasia extension, acute phase response and nutritional status, in lung cancer patients; and (2) to establish the prognostic value of serum cytokine levels. A prospective study in which IL-1, IL-2, IL-6, tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have been determined in 66 newly diagnosed lung cancer patients. Nutritional status was assessed objectively. Serum levels of growth hormone (GH), insulin growth factor 1 (IGF-1) and acute phase reactants as C Reactive Protein, alpha1 antitrypsin and ferritine, were determined. Increased IL-6 levels were related to extensive disease, impaired performance status, enhanced acute phase response and malnutrition. Raised serum IL-6 levels, extensive disease, low Karnofsky index, malnutrition, acute phase response and low IFN-gamma were all related to a shorter survival. When assessed by a multivariate analysis, IL-6 kept its independent prognostic value together with age, disease extension, and decreased IFN-gamma serum levels.IL-6 is increased in lung cancer patients, enhances the acute phase response in them, and is correlated with poor nutritional status, impaired performance status and shorter survival.

Acute-Phase Reaction↗
PubMed1998

Acute colitis caused by caustic products.

We report two cases of acute proctocolitis caused by rectal application of caustic products of domestic use. One 61-yr-old woman applied an ammonia solution enema; the other patient, a 63-yr-old woman, accidentally applied an enema containing lye. Both patients presented with intense anal pain, but the first patient also had abdominal pain with guarding, hematochezia, and leucocytosis. An acute proctocolitis was found at sigmoidoscopy in both patients. Only conservative and symptomatic measures were prescribed in both cases, and a clinical and endoscopic recovery was seen. In spite of persistent fibrosis in the lamina propria, no signs of stenosis were found.

Accidents, Home↗
PubMed1998

[Nephrotic syndrome. What is new since the 1988 study?].

The authors make a retrospective review of 53 new cases of Nephrotic Syndrome followed up in the Nephrology Unit from November 1988 to March 1994, bearing in mind the evaluation of casual changes of the disease standard regarding a previous study of 1988. Epidemiological, clinical, therapeutical and evolutional aspects were studied. Forty-four cases of primary Nephrotic Syndrome (83%) were identified, 61.4% of which behaved as cortico-sensitive, 25% as cortico-dependent, and 13.6% as cortico-resistant; 8 cases (15%) of Nephrotic Syndrome secondary to infection, Systemic Lupus Erythematosus and Amyloidosis, and 1 case of congenital Nephrotic Syndrome (2%). The theory that the high number of cortico-dependent is, probably, related with a higher severity in the relapse diagnosis and/or changes in the children's standard of living is admissible. It was also observed that at present there is a lower number of hospital discharges, related to more careful attitudes adopted regarding the evolution of the disease.

Adolescent↗
PubMed1997

Charcoal deposits in the esophageal and gastric mucosa.

We report the case of a 75-yr-old woman referred for gastrointestinal endoscopy to investigate severe iron deficiency anemia. Black linear lesions were observed in the distal esophagus and stomach. Biopsies revealed aggregates of coarse black foreign material, which was later identified as charcoal. The patient's previous medical history included an antidepressant overdose 5 yr before the current admission. The patient had a gastric lavage, using a large bore orogastric tube, followed by the administration of activated charcoal. The patient had no other history of charcoal ingestion. We propose that the charcoal became entrapped in mucosal tears caused by the traumatic intubation 5 yr previously, causing the incidental mucosal tattooing seen at endoscopy.

Aged↗
PubMed1995

Association of transforming growth factor alpha (TGFA) and its precursors with malignant change in Barrett's epithelium: biological and clinical variables.

Adenocarcinomas of the gastro-esophageal junction (GEJ) and those arising in Barrett's esophagus (BE) are increasing in the West and have a poorer prognosis than distal stomach cancers. This has been attributed mainly to anatomical location, but biological factors such as growth-regulatory molecules have been implicated. We have investigated the expression of one of these factors, TGF alpha, and its precursor prepro TGF alpha in 82 adenocarcinomas of GEJ (32 resected specimens and 50 biopsies) as well as in 48 BE biopsies without tumor, by immunohistochemistry and by Western-blot analysis. TGF alpha staining was shown in the cytoplasm and membrane of cells. Western blot confirmed that most immunoreactivity was against mature TGF alpha (5.6 kDa), but higher-molecular-weight bands were also identifiable, suggesting some reactivity with prepro protein. TGF alpha expression was more extense and intense in intestinal metaplasia and cancer. The tubular histological type of adenocarcinoma was more often positive than the signet-ring type. Primary tumors with lymph-node metastases also had increased TGF alpha expression. We conclude, therefore, that there is differential regulation of the expression of TGF alpha and its precursors during esophageal tumorigenesis.

Adenocarcinoma↗
PubMed1995

Expression of transforming growth factor alpha, epidermal growth factor receptor and epidermal growth factor in precursor lesions to gastric carcinoma.

Epidermal growth factor (EGF), its related peptide transforming growth factor (TGF-alpha) and their common receptor (EGFR) have been implicated in the control of cell proliferation and differentiation in the gastrointestinal epithelium and may play an important role in gastric carcinogenesis. We compared the immunohistochemical expression and topographic distribution of these peptides using Western blot analysis in gastric carcinoma precursor lesions and in non-cancer tissue. We observed: (i) increased and extended expression of TGF-alpha in normal mucosa and hyperplasia in carcinoma fields compared with non-cancer controls; (ii) increased expression of EGFR in intestinal metaplasia (IM) from carcinoma fields compared with controls; (iii) EGF expression was not detected in normal mucosa and only weakly in IM; (iv) coexpression of TGF-alpha/EGFR and EGF/EGFR was higher in intestinal metaplasia in carcinoma fields than in non-cancer controls. We conclude that altered expression of TGF-alpha/EGFR is associated with morphological changes during gastric carcinogenesis. In this regard increased expression of TGF-alpha is a very early event which is subsequently followed by up-regulation of EGFR and this has important biological and clinical implications.

Epidermal Growth Factor↗
PubMed1994

p53 expression in Barrett's oesophagus, dysplasia, and adenocarcinoma using antibody DO-7.

Barrett's oesophagus has a well-recognized association with oesophageal adenocarcinoma, with phenotypic progression through dysplasia to malignancy. The nuclear phosphoprotein p53 is a putative tumour suppressor with mutations resulting in both loss of negative growth regulatory function and possible gain of oncogene function. Many mutant forms have a prolonged half-life and are demonstrable with immunohistochemical techniques. We examined 62 endoscopic oesophageal biopsies and 36 oesophageal resections for p53 overexpression using the monoclonal antibody DO-7 on paraffin-embedded tissue. The series included 40 cases of Barrett's metaplasia, 13 cases of dysplasia, and 81 cases of adenocarcinoma. None of the cases of metaplasia was p53-positive, compared with 4/13 cases of dysplasia and 52/81 cases of adenocarcinoma. There was no association between the degree of dysplasia and p53 expression, although a trend emerged of increasing p53 expression with higher tumour grade. We conclude that p53 overexpression is frequent in oesophageal adenocarcinoma and may be related to tumour grade. p53 overexpression is not restricted to neoplastic lesions and mutation of this tumour suppressor may occur early in the malignant progression of Barrett's oesophagus.

Adenocarcinoma↗
PubMed1994

Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa.

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.

Adenocarcinoma↗
PubMed1994

Quantitative measurement of DNA content in gastric carcinoma; flow cytometry and video image analysis.

The DNA content of 48 gastric carcinomas from archival material was analysed by static and flow cytometry. By image analysis 81.3% of the tumours were aneuploid and ploidy was related to stage (P = 0.024) and lymph node metastasis. A trend for better survival (> 12 months) was observed in patients with diploid tumours (P = 0.058). The mean 5c exceeding rate (5cER) was significantly related to tumour stage (P < 0.05) and patient's survival (P = 0.018). In contrast, by flow cytometry only 43.7% of these tumours were aneuploid and these were more often associated with lymph node metastasis (59.3%) but no relationship was observed with any other parameters or patient's survival. In this series, image analysis appears to be more sensitive than flow cytometry in detecting small aneuploid populations. It may give additional prognostic information. It is, however, a time-consuming technique.

Aneuploidy↗
PubMed1993

Patterns of immunohistochemical staining for proliferating cell nuclear antigen and p53 in benign and neoplastic human endometrium.

Immunohistochemical staining was carried out on a spectrum of normal, hyperplastic and malignant endometrial curettings, for proliferating cell nuclear antigen--PCNA (using the monoclonal antibody PC10) and for abnormally stabilized p53 (using the polyclonal antibody CM-1). The mean proportion of glandular epithelial cells showing PCNA immunoreactivity was significantly lower in atypical hyperplasia/intra-endometrial adenocarcinoma than in invasive adenocarcinoma, but the degree of overlap between the cases was such that this was not considered to be of diagnostic value. p53 immunoreactivity was detected in 47% of invasive adenocarcinomas and in a much smaller proportion of endometria showing simple hyperplasia and atypical hyperplasia, but staining was only focal in the last two conditions. The majority of p53-positive invasive adenocarcinomas had a large proportion of glandular epithelial cells expressing PCNA, but a significant number of p53-negative cases also had a high PC10 index. This suggests that, in endometrial neoplasia, there is not a simple relationship between abnormally stabilized p53 and PCNA expression.

Adenocarcinoma↗
PubMed1993

DNA ploidy in early gastric carcinoma (T1): a flow cytometric study of 100 European cases.

DNA ploidy of 100 early gastric carcinomas (T1) was analysed by flow cytometry on archival material from five European centres and was correlated to morphological features and clinical behaviour. Tumours were classified according to the macroscopic appearance, histological type, and growth pattern. Aneuploidy was observed in 39% of tumours. Aneuploidy was more frequent in submucosal than in mucosal tumours (p = 0.04), in raised than in flat or ulcerated lesions (p = 0.001), and in the intestinal histological than in the diffuse types (p = 0.016). The presence of lymph node metastasis in 10 cases had no obvious relation to DNA ploidy. Five related deaths occurred during the follow up (6 months--16 years) of 84 patients. These results are similar to those reported in a large Japanese series suggesting no major differences between the two populations. Although follow up data were insufficient to relate DNA ploidy to tumour behaviour in this study, the Japanese experience shows that particular attention should be paid to early direction and complete surgical excision of raised intestinal type T1 carcinomas that have a Pen A growth pattern and are aneuploid.

Adult↗
PubMed1992

Cell proliferation study on gastric carcinoma and non-involved gastric mucosa using a bromodeoxyuridine (BrdU) labelling technique.

Previous reports using [3H]thymidine have shown altered patterns of cell proliferation in gastric carcinogenesis. In this study we applied in vitro bromodeoxyuridine (BrdU) uptake and immunohistochemistry to tissue from carcinoma, its adjacent mucosa and distant mucosa (n = 16) cases and 10 normal control cases. The labelling index (LI) was calculated for the upper, neck/isthmus and lower gland compartments and in 10 random fields/carcinoma. The LI was greater in the carcinoma than in either the adjacent or far mucosa or the controls (p < 0.001). No difference was observed between the non-carcinoma areas. However, the LI varied significantly between the gland compartments within each area (p < 0.001). In the normal control cases, the location of the proliferating cells was limited to the neck/isthmus region and perhaps the most significant observation was the change of location and expansion of the proliferative zone towards the surface in the normal mucosa adjacent to carcinoma compared with distant mucosa and controls (p < 0.001). These altered patterns of cell proliferation may be an important aspect of the precancerous potential of field changes in gastric carcinoma patients and could help patient follow-up and serve as a marker in monitoring intervention studies.

Bromodeoxyuridine↗