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Biomedical subjects

C Bonazzi

Publications and source records attributed to C Bonazzi.

At least 37 records · Page 2Linked to original sources

Thyroid gland size and function in patients with cirrhosis of the liver.

Thyroid dysfunction has long been reported in patients with liver disease, but limited information is available on thyroid gland size in cirrhosis. Most studies were carried out on small, selected series of patients, and no study has measured thyroid volume in relation to the etiology of liver disease. Thyroid volume was measured at ultrasound in 118 consecutive patients with cirrhosis of different etiology and 48 healthy subjects matched for age and sex. No subjects had evidence of overt thyroid disease. The mean volume was increased by 17% (from 16.0 [SD 5.2] ml in controls to 18.8 [7.6] in cirrhosis; P less than 0.025), and thyroid enlargement (antero-posterior diameter greater than 20 mm) was present in 38% of cases, in the presence of hormone values indicative of low-T3 syndrome. No significant differences in thyroid gland size were observed in relation to the extent of liver dysfunction or to the etiology of liver disease. The prevalence of thyroid nodules was similar in controls and in patients with cirrhosis. In only 8% of cases were laboratory values indicative of hypothyroidism, with low free triiodothyronine and raised thyroid-stimulating hormone levels; in these patients thyroid volume was decreased on average by 26%. This was mainly the case with patients with primary biliary and alcoholic cirrhosis. The largest mean thyroid volume was observed in patients with HBsAg + ve postnecrotic cirrhosis, whose thyroid volume was increased on average by 37%, and 53% of subjects had thyroid enlargement. This finding raises the question of a possible direct involvement of the thyroid in hepatitis B virus infection.

Female↗

Prognostic indicators in compensated cirrhosis.

In an attempt to identify variables predicting prognosis, 100 consecutive patients with compensated cirrhosis of the liver were followed for a mean of 4.9 (SD 0.7) yr. Fifty-one patients belonged to Child-Pugh class A, 49 to class B. At entry, five laboratory parameters were considered, together with sex, the grade of esophageal varices, and seven variables measured by ultrasonography (liver and spleen volume and the calibers of the splanchnic vessels). In a subgroup of 56 patients, the galactose elimination capacity also was determined. Forty-six patients were alive at the end of follow-up. Survival was analyzed according to Cox's model. Six parameters were able to predict survival (albumin, bilirubin, liver volume, prothrombin activity, cholesterol, varices). However, step-wise Cox regression analysis identified only four variables that independently correlated with survival: albumin, bilirubin, cholesterol, and liver volume. Galactose elimination failed to add any significance to routine liver function tests. This prospective study confirms the ability of routine liver function tests in predicting survival in compensated cirrhosis. The measurement of liver volume, easily obtained by ultrasonography, is also significant for prognosis, and may be introduced into clinical practice.

Actuarial Analysis↗

In vitro and in vivo effects of cisplatin on the generation of lymphokine-activated killer cells.

Pretreatment of human peripheral blood lymphocytes (PBL) with cisplatin (CDDP) before in vitro culture with interleukin-2 (IL-2) inhibited the generation of lymphokine-activated killer (LAK) cells and strongly inhibited proliferation. This inhibition was dose dependent, was significant only at concentrations greater than 6 microM, and it required exposure to the drug for more than 1 hour. This period of IL-2 unresponsiveness was maximum at 6 hours, but was spontaneously recovered within 24-48 hours and was more rapidly restored by increasing dosages of IL-2. Because inhibition of the generation of LAK cells by CDDP was observed only at relatively high levels of exposure to the drug (greater than 6 microM for greater than 1 hr), it was important that we explore the in vivo significance of these findings. The peripheral blood lymphocytes from patients bearing ovarian adenocarcinoma collected 1 hour after an iv infusion of 50 mg of CDDP/m2 were not inhibited, compared with those collected immediately before therapy. Relatively high levels of exposure to CDDP are required for inhibition of the generation of new cytotoxic effectors, most likely because of its antiproliferative effect. These results may bear relevance to approaches involving the combined use of CDDP and IL-2-LAK.

Adenocarcinoma↗

Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.

Age Factors↗

Association of serum IgA antibodies to milk antigens with severe atherosclerosis.

The presence of antibodies of the IgA class against dietary antigens (bovine IgG (BGG), beta-lactoglobulin, casein, alpha-lactalbumin and xanthine oxidase, chicken ovalbumin and crude gliadin) was checked in the sera of 23 severely atherosclerotic subjects (ATS) and 20 highly selected controls (C). In these subjects an association between serum IgA levels and atherosclerosis had previously been shown. Determinations were performed by a micro-ELISA method and results were expressed as absorbances at 405 nm x 1000. Higher levels of IgA antibodies were found in ATS with respect to C against beta-lactoglobulin (respectively, 113.4 +/- 152.4 (1 SD) vs. 40.0 +/- 34.2; P less than 0.005) and casein (69.8 +/- 35.5 vs. 52.4 +/- 27.5; P less than 0.05). There was no difference in IgG and IgM against these 2 proteins between the 2 groups. Significant differences of prevalence of IgA antibodies were found for the following antigens: beta-lactoglobulin (4 C and 16 ATS over the limit value of 51; P less than 0.002), xanthine oxidase (1 C and 9 ATS over 289; P less than 0.01), BGG (7 C and 17 ATS over 87; P less than 0.02) and casein (5 C and 14 ATS over 60; P less than 0.02). These data suggest an association between anti-milk IgA antibodies and atherosclerosis. Its relevance and significance deserves further investigation.

Aged↗

Analysis of 309 cases after hydatidiform mole: different follow-up program according to biologic behavior.

Between 1976 and 1985, at the Obstetrics and Gynecology Department of Milan University, a total of 309 cases of hydatidiform mole, 223 complete moles and 86 partial moles, were monitored with the assay of beta-human chorionic gonadotropin, following a postmolar biochemical surveillance program. Spontaneous remission of the disease occurred in 287 (92.9%) patients. Marker levels were undetectable in 80.4% of cases within 60 days after evacuation of the mole and in 19.6% between 61 and 140 days. There were 22 (7.1%) patients diagnosed as having gestational trophoblastic tumors (GTT) and treated with chemotherapy: 20 were complete moles and 2 partial moles. Considering these data, the authors suggest different follow-up times for partial and complete moles and confirm the necessity of selection criteria in a diagnosis of GTT.

Choriocarcinoma↗

EMA/CO regimen in high-risk gestational trophoblastic tumor (GTT).

From June 1980 through December 1985, 36 high-risk GTT patients received Bagshawe's EMA/CO regimen, 22 as first-line, and 14 as second-line treatment, after primary chemotherapy with CHAMOCA, or cyclic regimen, or MTX-CF. All treated patients were metastatic at the start of treatment with EMA/CO; three showed liver metastases and one brain metastasis. Seventeen patients had a high score, greater than 15. Nineteen patients had histologically confirmed diagnosis of choriocarcinoma. The overall response rate was 86% with 81% survival during a median observation time of 32 months. The median number of courses needed to achieve complete remission was 3 (range 3-7). Toxicity was acceptable, and was less than with CHAMOCA and MAC regimens. Only 1 out of 17 high-risk patients developed drug resistance, and 3 needed urgent surgery. The relapse rate of responders was 19% after a median of 5.5 months. The survival rate of high-risk patients was 88%, of which 76% are alive with no evidence of disease, while 12% have still detectable beta-chorionic gonadotrophin. The remission rate in the second-line treatment group was 64%, higher than using other regimens such as MAC or CHAMOCA. In conclusion, we consider EMA/CO to be the best choice for patients with high-risk GTT, because it is effective and well tolerated. In our opinion, the cure rate of high-risk GTT could perhaps be improved by starting trials to establish what salvage treatment to employ after EMA/CO failure and using more aggressive first-line chemotherapy in selected high-risk patients, on the basis of the scoring system.

Adult↗

Immunoglobulin A antigliadin antibodies in jejunal juice: markers of severe intestinal damage in coeliac children.

Antibodies to gliadin (AGA), detected in jejunal juice by immunofluorescence and enzyme-linked immunosorbent assay, have been found in 13 of 15 (87%) children with untreated coeliac disease. Jejunal AGA were also positive in 6 of the 9 (67%) coeliac children on gluten challenge, while they were consistently negative in coeliac children on a gluten-free diet and in controls. Jejunal AGA were always of immunoglobulin A (IgA) class, associated with IgM in some cases. Moreover, the presence of IgA AGA in jejunal juice was strictly related to the severity of intestinal damage. These data suggest that IgA AGA, detected in jejunal juice are synthesized from gut mucosa and are markers of its abnormal function. Like AGA, antibodies to milk and egg proteins were only found in jejunal juice of coeliac patients with flat intestinal mucosa, but their prevalence was significantly lower than that of AGA.

Celiac Disease↗

Cisplatin, vinblastine, and bleomycin combination chemotherapy in endodermal sinus tumor of the ovary.

The combination of cisplatin, vinblastine, and bleomycin was administered to 13 previously untreated patients with pure endodermal sinus tumor of the ovary. Twelve had unilateral salpingo-oophorectomy as initial surgery. Among 11 women whose alpha-fetoprotein (AFP) levels returned to normal after cisplatin, vinblastine, and bleomycin therapy, nine are alive with no evidence of disease after periods of 20 months to six years and two months. In two patients, AFP levels returned to normal only after the introduction of different combination chemotherapies. Hematologic toxicity was moderate. Pulmonary toxicity due to bleomycin occurred in two cases. All menstruating patients resumed normal menstrual function after the interruption of chemotherapy. Two patients delivered normal term infants.

Adolescent↗

Lymphokine-activated killer activity of tumor-associated and peripheral blood lymphocytes isolated from patients with ascites ovarian tumors.

Peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) were isolated from 36 patients with advanced ovarian adenocarcinoma and peritoneal effusions for study of lymphokine-activated killer activity. PBLs and TALs cultured in vitro for 3-5 days in the presence of interleukin-2 (IL-2, supernatant of the MLA 144 gibbon cell line, or human recombinant IL-2) expressed higher levels of cytotoxicity as compared to cells cultured in medium alone, against natural killer (NK)-susceptible (K562) or NK-resistant targets (Daudi and the human ovarian carcinoma cell line SW626). When ovarian tumor cells, freshly isolated from carcinomatous ascites or surgical specimens, were used as target cells in the cytotoxicity assay, 8 of 14 PBLs and 5 of 7 TAL preparations lysed the autologous tumor after treatment with IL-2, while no spontaneous reactivity was observed in any of the 14 patients tested. Although levels of lysis were usually relatively low, these data demonstrate that PBLs and TALs from ovarian cancer patients (TALs usually exhibiting low NK activity) when stimulated in vitro by IL-2 acquire some cytotoxic potential against the autologous tumor.

Adenocarcinoma↗

Tumor-derived chemotactic factor(s) from human ovarian carcinoma: evidence for a role in the regulation of macrophage content of neoplastic tissues.

Supernatants from freshly disaggregated human ovarian carcinomas maintained in vitro for 24 hr, from primary ovarian carcinoma cultures (4-6 days in culture) and from established ovarian cancer cell lines were examined for chemotactic activity on blood monocytes in blind-well chemotaxis chambers. Tumor-cell culture supernatants induced migration of peripheral blood monocytes across polycarbonate filters with considerable heterogeneity among different tumors. Induction of migration occurred only in the presence of a gradient between the lower and upper compartments of the chamber. Chemotactic activity was characterized by means of supernatants from primary ovarian carcinoma cultures. Chemotactic factor(s) was (were) produced in serum-free conditions and the production was inhibited by emetine but not by mitomycin C. The activity was destroyed by exposure to proteolytic enzymes and by heating at 100 degrees C but was unaffected by RNase, DNase, lipase and exposure to extreme pH values or heating at 56 degrees C. Upon fractionation on Sephadex G 75, the activity eluted as a single peak in the cytochrome C region, corresponding to an apparent molecular weight of about 12 kd. The percentage of macrophages was assessed in 25 freshly disaggregated tumor specimens. Ovarian carcinomas were heterogeneous in their macrophage content with values ranging from 4 to 36%. A significant (r = 0.62; p = 0.00097), though far from absolute, correlation was found between chemotactic activity of culture supernatants and percentage of tumor-associated macrophages. Tumor-derived chemotactic factor(s) could be one of the mechanisms involved in the regulation of the macrophage content of human ovarian carcinomas.

Carcinoma↗

IgA antibodies to dietary antigens in liver cirrhosis.

Antibodies to dietary antigens (ovalbumin, beta-lactoglobulin, casein) have been detected by a micro-ELISA test in 47-50% of serum samples from patients with alcoholic liver cirrhosis, in 27-36% with non-alcoholic cirrhosis (HBV-related, autoimmune and primary biliary) and in 50-70% of cirrhotic patients with portacaval shunt. Dietary antibodies were mainly confined to the IgA class (90%). In patients with chronic active hepatitis dietary antibodies showed a low positivity (11%), similar to that of subjects with alcohol abuse without liver injury and of healthy subjects. Dietary antibodies were significantly associated with portal hypertension (evaluated on the presence of esophageal varices and/or ascites) both in alcoholic and non-alcoholic cirrhosis. The absence of dietary antibodies in the duodenal juice of cirrhotic patients positive for serum antibodies confirms that the intestinal mucosa is normal or slightly altered in liver cirrhosis. Unlike cirrhotics, untreated celiac patients showed a high prevalence of dietary antibodies also in the duodenal juice (55%).

Adult↗