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M Braga

Publications and source records attributed to M Braga.

At least 145 records · Page 8Linked to original sources

Critical role of gonadal hormones on the genotoxic activity of the hepatocarcinogen DL-ZAMI 1305.

The DNA damaging capacity of the sex-dependent hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (DL-ZAMI 1305) was evaluated in different sex hormonal conditions. A single injection of DL-ZAMI 1305 causes DNA damage in the liver of the female but not the male Wistar rat. When the hormonal environment of the female rat is converted to 'male type' by ovariectomy and 1 week of treatment with testosterone, DNA damage by DL-ZAMI 1305 is completely abolished. On the contrary, in male rats orchiectomy coupled to 17 beta-estradiol administration increases the amount of hepatic DNA damage by DL-ZAMI 1305 to values similar to those observed in intact female rats. DL-ZAMI 1305 induces hepatic DNA damage also when administered to female Sprague-Dawley and Fisher 344 female rats. It is uneffective instead on the male rats of these strains. Moreover, in the female Fisher 344 rat phenobarbital pretreatment reduces the DNA damaging capacity of DL-ZAMI 1305. Our data indicate that the genotoxic activity of DL-ZAMI 1305 depends on the sex-hormonal status of the animal and that this is possibly due to a modulation of the microsomal mixed function oxidase system by sex hormones.

Animals↗

Associations between clinical disease, circulating antibodies and C1q-binding immune complexes in human onchocerciasis.

Onchocerciasis is a disease where often there are high levels of serum antibodies and high parasitic loads. The role of immune complexes in the development of the disease is investigated here by studying non-specific and Onchocerca volvulus specific immune complex levels, as well as the antibody concentrations, in the sera of 372 people living in either Southern (199) or Northern (173) Sudan; sera from Sudanese individuals (31) and Caucasians (21) living outside the onchocerciasis endemic area were also tested. The levels of non-specific immune complexes (NS-IC) in these sera were measured by a solid phase radio-immunoassay and those of O. volvulus-specific immune complexes (OV-IC) by an assay measuring antibody-excess complexes using C1q-coated plates. The concentrations of O. volvulus IgG antibodies were measured by ELISA. Immune complex and antibody levels of the serum donors were compared with regard to their clinical status due to onchocerciasis. These clinical changes were classified according to onchocercal lesions related to either the active destruction of microfilariae (acute changes), or the long term tissue alterations (chronic changes). Data was analysed using the Odds Ratio method. A negative association between microfilarial load and immune complex level was found, with the higher levels of OV-IC present in patients with the lower levels of dermal microfilariae (i.e., less than 10 mf/mg). Significant associations between immune complex levels and the severity of onchocercal disease were also found. Levels of OV-IC specific immune complexes were higher in infected individuals carrying dermal onchocercal lesions than in those without such clinical changes; there was no apparent relationship between these levels and the presence of ocular lesions. OV-IC levels varied considerably within each age group and from age to age. A weak positive association was detected between microfilarial load and parasite-specific IgG antibody concentration in the sera. On average younger individuals (less than 25 years) had the higher antibody levels with a gradual reduction in mean concentrations with age. The significance of these serological findings in terms of the pathogenesis of onchocerciasis is discussed.

Age Factors↗

Further studies on the tumor-initiating activity of the beta-blocker DL-ZAMI 1305.

The purpose of this study was to evaluate the initiating activity of the hepatocarcinogen beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylamino-propan-2-ol (DL-ZAMI 1305) by the initiation-promotion protocol of Pereira. Female Wistar rats were given a single dose 150 mg/kg of body weight of DL-ZAMI 1305 by gavage 24 hours before or 24 hours after partial hepatectomy. One week later rats were given phenobarbital (0.05%) in the diet for a period of 7 weeks. DL-ZAMI 1305-treatment resulted in the appearance of gamma-glutamyltranspeptidase foci and of other preneoplastic lesions in all animals. Preneoplastic lesions were also present in a fraction of DL-ZAMI 1305-treated animals not subjected to partial hepatectomy, whether given or not phenobarbital. Results obtained in a separate experiment demonstrated that DL-ZAMI 1305-treatment inhibits cell proliferation and induces DNA damage in the regenerating rat liver. The results of this study clearly demonstrated that the beta-blocker DL-ZAMI 1305 is an initiating carcinogen for the liver of female Wistar rats.

Adrenergic beta-Antagonists↗

Nutritional status, function of the small intestine and jejunal morphology after total gastrectomy for carcinoma of the stomach.

We studied the nutritional status and the prevalence of malabsorption in 12 patients one to three years after total gastrectomy (TG) for gastric neoplasm. The Roux-en Y technique was used for reconstruction. A correct dietary regimen according to the recommended daily allowance was suggested and patients were seen quarterly on an out patient basis. The nutritional status was evaluated by measuring serum albumin levels, total iron binding capacity, cholinesterase, area muscular circumference, triceps skinfold and delayed hypersensitivity response. Work-up studies for the small intestine included: stool fat, D-xylose and glucose tolerance tests, Schilling test (phase II and III), serum iron levels, serum vitamin B12 levels and biopsy of the jejunum. Malnutrition, defined as the occurrence of two or more abnormal nutritional parameters, was observed in one patient; glucose and D-xylose tolerance tests were normal in all. A mild degree of steatorrhea was observed in four patients. The second phase of the Schilling test was abnormal in eight patients, but urinary excretion of vitamin B12 increased in three of four patients after use of antibiotics. Low serum vitamin B12 levels were common after the twentieth postoperative month. Serum iron levels were initially low and returned to normal six months after TG. All patients had normal jejunal histologic findings. These data indicate that malnutrition after TG is not common if an adequate dietary intake is maintained. Malabsorption, possibly due to bacterial overgrowth, is not a major clinical problem.

Aged↗

Causes of anergy in the surgical patient and its relationship to postoperative sepsis.

Between June 1981 and June 1983 the delayed hypersensitivity response (DHR) was studied in 401 patients considered for major surgical procedure: 320 of these patients underwent surgery. The incidence of sepsis and postoperative mortality was higher in anergic and relative anergic patients than in normal responders (p<0.001). To evaluate whether DHR depression in cancer patients was due to the direct effect of cancer or to tumour-linked malnutrition, the 401 patients were divided into 4 groups: 1) 140 malnourished cancer patients, 2) 51 malnourished non-cancer patients, 3) 120 well-nourished cancer patients and 4) 90 well-nourished non-cancer patients. The mean age was not significantly different for the 4 groups. The results showed a relationship between DHR and nutritional status (p<0.001). The tumour-related DHR impairment disappeared when the cancer and non-cancer patient groups were homogeneous with regard to their nutritional status. Therefore, the tumour was able to determine the DHR depression because of the cancer-linked malnutrition. We did not observe any relationship between local extension of the tumour and lymph node involvement and DHR depression. In 90 well-nourished non-cancer patients the relation between DHR and age was investigated. The incidence of anergy and relative anergy was higher in patients over 59 years than in patients under 60 years (p<0.001).

Journal Article↗

Thyroid and chemical hepatocarcinogenesis: further insights from the hepatocarcinogen ZAMI 1305.

The beta-blocker DL-1-(2-nitro-3-methyl-phenoxy)-3-tert-butylaminopropan-2-ol (ZAMI 1305), oncogenic to the liver of the female but not of the male Wistar rat, was used to investigate some aspects of the relationship between liver and thyroid during chemical hepatocarcinogenesis. Thyroidectomy (TDX) strongly reduces the amount of hepatic DNA damage induced by a single administration of ZAMI 1305 in the female Wistar rat. One week of treatment with triiodothyronine (T3) completely restores the susceptibility of the liver of thyroidectomized animals to the genotoxic activity of the molecule. The amount of hepatic DNA damage in intact females varies with the age of the animal, being maximal in rats of 4-8 weeks of age, when T3 serum concentration are also maximal. An increase of relative thyroid weight, coupled with histological hyperplasia of the gland, is observed in female Wistar rats treated for 6 months with ZAMI 1305. Minimal changes of the thyroid are observed in ZAMI 1305-treated male rats. The increase of relative thyroid weight in female rats appears to be related to the severity of preneoplastic and neoplastic liver changes. These findings and several suggestions from the literature lead us to propose a model for the interaction between liver and thyroid during chemical hepatocarcinogenesis.

Animals↗

Exploratory tools for disease mapping in geographical epidemiology.

In the present paper a new shrinkage estimator of relative risk, useful in disease mapping, is compared with the empirical and full Bayes estimators, using death certificate data for lung cancer (males and females) and breast cancer (females) 1982-1988 in the Emilia-Romagna region (Italy). The estimates are obtained averaging the relative risks obtained from recursive partitioning of the set of observed values. The number of partitions is fixed in advance and behaves as a smoothing parameter, the lower the number the higher the degree of shrinkage toward the overall mean of the observed values.

Algorithms↗

Pancreatoduodenectomy with occlusion of the residual stump by Neoprene injection.

Pancreatojejunal anastomosis disruption still represents the main postoperative complication after pancreatoduodenectomy. In this study, a technique of occlusion of the residual pancreatic stump instead of pancreatojejunal anastomosis is proposed. Between March, 1981 and August, 1987, we performed 51 pancreatoduodenectomies, using Neoprene injection in the Wirsung duct, for carcinoma of the pancreatic head (28 cases), ampullary carcinoma (12 cases), islet cell carcinoma (5 cases), and chronic pancreatitis (6 cases). We observed a 33.3% overall morbidity, with a 5.8% operative mortality. The complications observed seemed not to be related to the technique of pancreatic stump occlusion, except for 2 pancreatic fistulas which spontaneously resolved. Abdominal ultrasound and computed tomography scan performed during the follow-up did not show any significant morphological alteration of the residual stump. Pancreatic endocrine function was assessed in 10 patients by evaluating blood glucose, plasma insulin and plasma glucagon levels both fasting and after oral glucose, and intravenous arginine infusion. These tests were performed before surgery and 15 days, 6 months, 1, 2, and 3 years after surgery. The results showed that 60% of the patients had impaired glucose tolerance before surgery and the percentage did not significantly change up to 3 years later (75%). No patient developed diabetes mellitus, and only 1 patient progressed from a normal to an impaired glucose tolerance. In conclusion, intraductal injection of Neoprene after pancreatoduodenectomy seems to be a safer procedure compared to pancreatojejunal anastomosis and does not induce a post-surgical diabetes.

Adenoma, Islet Cell↗

Immunonutrition in gastric cancer surgical patients.

The aim of this study was to evaluate the potential advantages of perioperative versus postoperative administration of an enteral immune-enhancing diet on host defense and protein metabolism. Thirty subjects, candidates for gastrectomy for cancer, were randomly allocated into two groups. The first group (n = 15) received an enteral formula enriched with arginine, omega-3 fatty acids, and RNA 7 d before and 7 d after surgery; the second group (n = 15) received the same diet but only 7 d after surgery. Postoperative immune and inflammatory responses were investigated by phagocytosis ability of polymorphonuclear cells, interleukin-2 receptors (IL-2R), lymphocyte subsets, interleukin-6 (IL-6), and delayed hypersensitivity response (DHR). Prealbumin (PA), retinol binding protein, albumin, and transferrin were determined as protein synthesis indicators. Perioperative immunonutrition prevented the early postoperative impairment of phagocytosis, DHR, total number of lymphocytes, and CD4/CD8 ratio (P < 0.05 versus postoperative group). The IL-2R levels were significantly higher in the perioperative group (P < 0.05 versus postoperative on postoperative day [POD] 4 and 8). Perioperative group also showed lower levels of IL-6 (P < 0.05 versus postoperative on POD 1, 4, and 8) and higher levels of PA (P = 0.04 versus postoperative on POD 8). The perioperative administration of immunonutrition ameliorated the host defense mechanisms, controlled the inflammatory response, and improved the synthesis of short half-life constitutive proteins.

Adenocarcinoma↗

Increased psychiatric morbidity in female outpatients with skin lesions on visible parts of the body.

Psychiatric disorders are frequent among patients with skin diseases. We aimed at identifying factors associated with psychiatric morbidity in dermatological outpatients. All adults attending the outpatient clinics of a dermatological hospital on predetermined days were given the 12-item General Health Questionnaire. The dermatologists indicated the diagnosis and location of skin lesions and rated the disease severity. A total of 1389 patients were asked to take part in the study. Of the 722 who accepted, 389 had a complete set of data and were included in the analysis. To verify the representativeness of our sample, we used the administrative registries to compare participants with the total population of patients who attended the clinics during the same period, and we examined the distribution of missing data. There was a tendency towards a younger age in the sample studied, but no evidence of substantial selection bias. The prevalence of psychiatric morbidity was 20.6%. We found higher probability of psychiatric disorders in women, controlling for age, clinical severity and localization of lesions. In women, but not in men, the prevalence of psychiatric morbidity was higher in patients with lesions on the face or hands. Given that the identification and appropriate management of psychiatric morbidity are important, it seems that the dermatologist should be particularly alert to the possibility of a concurrent psychiatric disorder in women with lesions on the face or hands.

Adult↗

Prognostic role of preoperative nutritional and immunological assessment in the surgical patient.

The utilization of delayed hypersensitivity response (DHR) for the identification of high-risk patients with regard to postoperative septic complications is still discussed. The aim of this study was to clarify how much DHR may improve the prognostic capacity of nutritional assessment (NA). Nutritional and immunological evaluations were performed at admission on 405 patients undergoing elective general surgical procedures. Subjects with serum albumin less than or equal to 3.0 g/dl or total iron-binding capacity less than or equal to 220 micrograms/dl or weight loss greater than or equal to 10% with respect to usual body weight were classified as malnourished. DHR was assessed by performing skin tests with four recall antigens: PPD, candida, trichophyton, sk-sd. The incidence of postoperative complications resulted higher among the 187 malnourished patients (31.0%) than in the 218 well-nourished ones (14.2%) (p less than 0.001), and among the 213 anergic patients (29.6%) than in the 192 normal responders (13.5%) (p less than 0.001). To determine how much skin tests may improve the prognostic ability of NA, the relationship between DHR and postoperative complications was also studied in the malnourished and in the well-nourished patients, separately. In the malnourished group, the patients with an impairment of DHR had a higher incidence of postoperative infections than normal responders (p less than 0.05). In the well-nourished group, no significant differences were found between anergic patients and normal responders. In our study, DHR slightly improved the prognostic capacity of NA. Therefore, the first approach to identify the high-risk patients seems to be the unexpensive, quick and available determination of nutritional status.

Antigens, Fungal↗

Evaluation of the predictive performance of nutritional indicators by receiver-operating characteristic curve analysis.

Four hundred twenty-two cancer patients who underwent major surgery were studied. At admission, nutritional status was evaluated in all patients by assessing serum albumin (SA), total iron-binding capacity (TIBC), total lymphocyte count (TLC), serum cholinesterase activity (CHE), and weight loss (WL). All patients received perioperative short-term antibiotic prophylaxis and postoperative total parenteral nutrition. Prognostic ability of nutritional indicators was assessed by receiver-operating characteristic (ROC) curve analysis. The area beneath the ROC curve (Az) is an index of predictor performance when its value ranges from 0.5 (chance performance) to 1 (perfect prediction). Specificity, sensitivity, Youden index, and predictive values were determined for each nutritional parameter within a wide range of potential threshold values. Postoperative septic complications were observed in 85 (20.14%) patients. The Az values for the considered nutritional parameters ranged from 0.52 to 0.57 and that showed the low predictive ability of the parameters. When sensitivity and specificity for each nutritional parameter were examined at different thresholds, a clearly more predictive cutpoint was not observed, but ranges of values with a similar predictivity were observed. Significant ranges of predictivity were found for SA (33 to 35 g/L), for TIBC (2200 to 2300 micrograms/L), for TLC (2100 to 2200 million/L), for CHE (1700 to 1900 U/L), and for WL (7% to 12%). The higher values of Youden index were as follows: 1.183 for WL (cutoff 11%), 1.150 for TLC (cutoff 2100 million/L), and 1.145 for SA (cutoff 35 g/L). In conclusion, ROC curve analysis showed that the nutritional parameters had a low predictive ability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A prospective, randomized clinical trial on perioperative feeding with an arginine-, omega-3 fatty acid-, and RNA-enriched enteral diet: effect on host response and nutritional status.

BACKGROUND: The use of immune-enhancing enteral diets in the postoperative period has given contrasting results. The purpose of this prospective, randomized, double-blinded clinical study was to evaluate the effect of immunonutrition given perioperatively on cytokine release and nutritional parameters. METHODS: Patients with cancer of the stomach or colo-rectum were eligible. Subjects consumed 1 L/d of either a control enteral formula (n = 25; control group) or a formula supplemented with arginine, omega-3 fatty acids, and RNA (n = 25; verum group) for 1 week before surgery. Both formulas were given by mouth. Six hours after the operation, jejunal infusion with the same diets was started and maintained for 7 days. Blood was drawn at different time points to assess albumin, prealbumin (PA), transferrin, cholinesterase activity, retinol binding protein (RBP), interleukin-2 receptors alpha (IL-2Ralpha), IL-6, and IL-1 soluble receptors (IL-1RII). The composite score of delayed hypersensitivity response (DHR) to skin test also was determined (the higher the score, the lower the immune response). RESULTS: During the 7 days of presurgical feeding, none of the above parameters changed in either group. Eight days after operation, in the control group, the concentration of PA and RBP was lower than in the verum group (0.18 vs 0.26 g/L for PA and 30.5 vs 38.7 mg/L for RBP; p < .05). IL-2Ralpha concentration was 507 pg/mL in the verum group vs 238 pg/mL in the control group (p < .001), whereas IL-6 and IL-1RII were higher in the control group than in the verum group (104 vs 49 and 328 vs 183 pg/mL, respectively; p < .01). The DHR score was 0.68 in the control group vs 0.42 in the verum group (p < .05). CONCLUSIONS: Perioperative feeding with a supplemented enteral diet modulates cytokine production and enhances cell-mediated immunity and the synthesis of short half-life proteins.

Adolescent↗

Results of a mammographic and clinical screening in a health district (USSL) of Brescia, Italy.

AIMS AND BACKGROUND: Screening by mammography has been shown to be effective in reducing breast cancer mortality. We present the results of a mammographic and clinical screening program carried out in an Italian health district. METHODS: The first screening round started in June 1987 and ended in July 1990, and 25,100 women between the age of 50 and 60 years were invited. The second screening round invited 34,332 women between the age of 50 and 64 years and was carried out from September 1990 to September 1993. Women with positive or equivocal results at palpation or mammography were referred for immediate diagnostic assessment followed by surgery, when required. RESULTS: The attendance rate was 67.3% at the first and 62.1% at the repeat screening. At the first screening, 206 biopsies were advised and 197 were performed; 129 of the 197 were found to be malignant. At repeat screening, 248 biopsies were recommended, 208 were performed, and 125 were found to be malignant. The cancer detection rate was 7.7 per thousand at the first and 5.9 per thousand at repeat screening. Of 129 cancers, 107 (83.0%) were T1 at first screening; 6.2% were in situ carcinomas. Axillary lymph nodes were histologically positive in 24% of cases. At repeat screening, 77.6% (97/125) of cancers were T1; 11.2% were in situ carcinomas. Positive axillary lymph nodes were found in 16.8% of cases. CONCLUSIONS: The attendance to screening was satisfactory. A higher frequency of small tumors (83.0%) was found at first screening than before the introduction of screening (56.6%). A marked difference in lymph node positivity (24.0% vs 40.6% in the pre-screening era) was also observed. Such a difference was even more evident at repeat screening. Quality standards of the screening in our study proved to be higher than those currently recommended. The reported results are encouraging, also considering the greater chance for conservative treatment.

Axilla↗