Biomedical subjects
Publications and source records attributed to A Perrotta.
A case of abscess of masseter muscle by Actinomyces spp. is described. Ultrasound-guided fine needle aspiration allowed diagnosis by cytology. Specific antibiotic treatment was started and US-follow-up showed complete healing of the lesion with restitution ad integrum of the muscle.
We have applied a new software program, based on graph theory and developed by our group, to predict mutagenicity in Salmonella. The software analyzes, as information in input, the structural formula and the biological activities of a relatively large database of chemicals to generate any possible molecular fragment with size ranging from two to ten nonhydrogen atoms, and detects (as predictors of biological activity) those fragments statistically associated with the biological property investigated. Our previous work used the program to predict carcinogenicity in small rodents. In the current work we applied a modified version of the program, which bases its predictions solely on the most important fragment present in a given molecule, considering as practically negligible the effects of additional less important fragments. For Salmonella mutagenicity we used a database of 551 compounds, and the program achieved a level of predictivity (73.9%) comparable to that obtained by other authors using the Computer Automated Structure Evaluation (CASE) program. We evaluated the relative contributions of biophores and biophobes to overall predictivity: biophores tended to be more important than biophobes, and chemicals containing both biophores and biophobes were more difficult to predict. Many of the molecular fragments identified by the program as being strongly associated with mutagenic activity were similar to the structural alerts identified by the human experts Ashby and Tennant. Our results tend to confirm that structural alerts useful to predict Salmonella mutagenicity are generally not very strong predictors of rodent carcinogenicity. Although the predictivity level achieved for oncogenic activity improved when the program was directly trained with carcinogenicity data, carcinogenicity as a biological endpoint was still more difficult to predict than Salmonella mutagenicity.
BACKGROUND: Both chemotherapy and tamoxifen are widely used either alone or in combination as adjuvant treatment following mastectomy. Despite the fact that both of them exhibit carcinogenic properties in experimental models, detailed reports on the incidence of new primaries following chemotherapy and/or tamoxifen in patients with early breast cancer are limited. PURPOSE: To investigate the incidence of new primaries (including opposite breast tumors and skin cancers) in untreated patients and in patients treated with either tamoxifen or chemotherapy or with both modalities. PATIENTS AND METHODS: A total of 1696 patients with early breast cancer, 1286 of whom were treated with either CMF-based adjuvant chemotherapy (n = 410), tamoxifen (n = 656) or with a combination of the two (n = 220) were considered for the present analysis. Patients were operated on between November 1983 and December 1991 and were followed up to June 1994. Detailed information about second malignancies were available for all patients. RESULTS: Overall, 53 new primaries, 19 of them opposite breast tumors, occurred in 53 patients. The actuarial cumulative incidence rates at 5 years were: 3.1% (95% CI: 1.4%-4.8%) in untreated patients; 1.7% (95% CI: 0.0%-3.5%) in tamoxifen-treated patients; 4.2% (95% CI: 1.3%-7.1%) in chemotherapy-treated patients and 2.6% (95% CI: 0.0%-5.2%) in the chemo-tamoxifen group (all groups: P = n.s.; chemotherapy-treated versus tamoxifen-treated: P = 0.01). The corresponding figures, after exclusion of the patients with opposite-breast and skin tumors, were: untreated patients: 2% (95% CI: 0.6%-3.4%); tamoxifen-treated patients: 0.95% (95% CI: 0.0%-2.4%); chemotherapy-treated patients: 2.6% (95% CI: 0.4%-4.8%); chemotherapy plus tamoxifen: 1.65% (95% CI: 0.4%-3.8%); (all groups: P = n.s.; CT versus TAM P = 0.05). Chemotherapy-treated patients showed a risk that was about two-fold that of the one to be expected in the general population. By contrast, a decrease in the total risk was observed in patients treated with tamoxifen. Patients who received chemotherapy and tamoxifen as well as those in the no-treatment group showed a risk which was comparable to that of the general population. CONCLUSIONS: Adjuvant chemotherapy appears to increase the risk of second malignancies. By contrast, tamoxifen seems to exert an overall protective effect in this regard, and it also appears to counteract, at least partially, the carcinogenic effect of chemotherapy. IMPLICATIONS: While there is plenty of evidence that the benefit achieved by adjuvant chemotherapy considerably exceeds the risk of second malignancies, the indiscriminate use of chemotherapy should be avoided, particularly in patients with a low risk of relapse. Moreover, it seems reasonable to prefer tamoxifen over chemotherapy for patients likely to obtain comparable therapeutic benefit from antiestrogenic treatment.
We assembled 390 chemicals with a structure non-alerting to DNA-reactivity (145 carcinogens and 245 non-carcinogens) for which rodent carcinogenicity data were available. These non-alerting chemicals were defined by the absence in their molecules of DNA-reactive (directly or after metabolic activation) alerting structures, as described by Ashby and coworkers (Mutat. Res., 204 (1988) 17-115; Mutat. Res., 223 (1989) 73-103; Mutat. Res., 257 (1991) 209-227; Mutat. Res., 286 (1993) 3-74). Using our software program based on graph theory we analyzed the compounds in order to estimate the program's ability to predict nonalerting carcinogens. Our software fragmented the structural formula of the chemicals into all possible fragments of contiguous atoms with size between 2 and 8 (non-hydrogen) atoms and learned about statistically significant fragments from a training set of chemicals. These fragments were used to predict carcinogenicity or lack thereof in a verification set of compounds. For 390 runs of the software program we used (n - 1) of the chemicals as a training set, to predict the excluded chemical at each run (as a test set). Using two different probability thresholds to select significant fragments (P = 0.05 and P = 0.125 1-tailed according to binomial distribution), we performed two analyses: in the better one (P = 0.05) 19% of the molecules tested lacked significant fragments, for the remaining 81% the observed level of accuracy of the prediction was 66.0% against an expected level of accuracy of 51.7%. The difference was highly significant (P < 0.0001). We also examined the more significant activating fragments (biophores) and discussed at length both their biological plausibility and the working hypothesis that additional alerting structures for carcinogenicity (not only those related to genotoxicity) can be detected using this type of SAR approach. This new class of alerting structures could identify subfamilies of congeneric analogs active through mechanisms of receptor mediated carcinogenesis.
The pathogenesis and progression of breast cancer involve complex interactions between hormones and polypeptide growth factors such as insulin-like growth factor-I (IGF-I). IGF-I has been found in stromal fibroblasts derived from malignant and benign breast tissue and it is a mitogen for several breast cancer cell lines. It circulates bound to specific high-affinity binding proteins, which could act as either positive or negative modulators of tumorigenesis. This study has been addressed to characterize IGF-I and its binding proteins in the serum of 85 unselected patients with early breast cancer. The IGF-I concentration was assessed by radioimmunoassay of 69 out of 85 samples before and after dissociation of the IGF-I and IGF-binding protein (IGF-BP) complex whereas IGF-BP of all 85 sera were analyzed by Western ligand blotting; estradiol and progesterone were measured by radioimmunoassay in native serum samples. In our study no differences in IGF-I serum levels between pre- and post-menopausal patients were observed. Patients with higher estradiol and progesterone serum levels did not present different IGF-I concentrations compared to patients with lower serum levels. Furthermore, IGF-I median values were not found to depend on estrogen receptor (ER) status. A heterogeneous quali-quantitative molecular pattern of binding proteins was detected: IGF-BP3 and IGF-BP1 were the most and the least expressed respectively. No correlations between ER status, or parameters related to the hormonal status, and IGF-I or binding proteins expression were observed. No significant differences in IGF-I concentration and IGF-BP expression were observed between cancer patients and a control group matched for age and menopausal status. Finally, preliminary collection of 20 sera derived from patients with late breast cancer was analyzed for IGF-I and its binding proteins content.
The promoting activity of benzene on rat liver carcinogenesis was investigated. The chemical was tested for its ability to enhance the growth of preneoplastic foci, as detected by gamma-glutamyl transpeptidase (GGT) staining in diethylnitrosamine (DENA) initiated hepatocytes. Two weeks after receiving a single ip dose of 200 mg/kg DENA, F344 rats were given daily oral doses of 400 mg/kg benzene (5 d/wk) for 6 wk. At wk 3 after the experiment began, all animals underwent partial hepatectomy, and at wk 8 were sacrificed. Following benzene treatment, no variation in the liver/body weight ratio was observed. After scoring of foci in liver slides, no significant difference in foci number and area could be observed between rats treated with DENA plus benzene and rats treated with DENA alone. Practically no foci were observed in the liver of rats treated only with benzene. The lack of benzene promoting activity in the liver model is discussed.
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BACKGROUND: Oophorectomy is one of the treatments of choice for premenopausal women with advanced breast cancer. However, in recent years LH-RH analogs have replaced surgical castration (or ovarian irradiation) on the basis of the comparable therapeutic activity shown by these drugs in phase II studies. Moreover, the combination of tamoxifen and LH-RH analogs has gained popularity among clinicians attempting to obtain a 'total estrogen blockade' according to the same rationale previously proposed for advanced prostatic cancer. However, it has thus far not been proven that medical castration is as effective as oophorectomy or ovarian irradiation, nor is there enough evidence that tamoxifen could improve the efficacy of ovarian ablation. PATIENTS AND METHODS: Eighty-five perimenopausal patients with estrogen receptor or unknown positive metastatic breast cancer were randomly allocated to receive one of the following treatments: surgical castration (or ovarian irradiation); goserelin; surgical castration (or ovarian irradiation) plus tamoxifen; goserelin plus tamoxifen. The study was performed according to a 2 x 2 factorial randomised design. RESULTS: While overall there was no significant difference in the response rates observed after two by two grouping, a trend did favour oophorectomy (or ovarian ablation) with respect to treatment activity. In fact, the best response rate was observed in patients allocated to this treatment (46.6% OR -95% CL: 21.2-72.9) while the lowest rate was observed in patients treated with oophorectomy plus tamoxifen (11.1% OR: CL: -3.4-25.6). Response to goserelin and goserelin plus tamoxifen was 27.2% (+/- 18.6) and 45% (+/- 21.8), respectively. Logistical regression analysis suggested that there might be a different interaction between tamoxifen and goserelin or oophorectomy (ovarian irradiation), respectively. Nevertheless, patient survivals were comparable, irrespective of allocated treatment. This indicates that two by two grouping has some value with respect to treatment efficacy and shows that oophorectomy (or ovarian irradiation) and goserelin have comparable efficacies. Tamoxifen did not improve the efficacy of gonadal ablation, although it did enhance the activity of goserelin treatment. CONCLUSIONS: The results of the present study confirm prospectively that the efficacy of chemical castration is comparable to that of oophorectomy (or ovarian irradiation). The concurrent use of tamoxifen can probably enhance the activity of goserelin, but it also induces more side effects. However, it doesn't appear that 'total estrogen blockade' is more effective than gonadal ablation alone. Indeed, the question of whether chemical and surgical castration have the same effect in breast cancer is still open as is the one concerning the interaction between tamoxifen and gonadal ablation. Both questions should be addressed by prospective studies.
OBJECTIVES: The association between asbestos exposure and risk of mesothelioma was studied among workers from two oil refineries located in the northern Italian cities of Genoa and La Spezia, given that previous cohort analyses revealed two clusters of mesotheliomas and that international cohort studies have so far not reported an excess of this neoplasm among oil refinery workers. METHODS: Men (N = 2300) who had been employed between 1914 and 1988 in two oil refineries located in northern Italy were studied. The follow-up covered the mortality of 639 white-collar and 1661 blue-collar from 1950 to 1991. RESULTS: Among the cases, the median duration of employment was 14.5 years, and the median time since first employment was 27.5 years. The job titles of the 10 men with pleural mesothelioma were maintenance worker (seven men), electrician (one man) and unspecified blue-collar worker (two men). Blue-collar workers experienced a significantly increased risk of pleural neoplasms, five deaths in each plant, in respect to both the provincial [standardized mortality ratio (SMR) 266] and national (SMR 1663) reference populations. The SMR, based on eight deaths, was 320 for workers with more than 10 years of employment and 20 years since first exposure. CONCLUSIONS: The results uphold the notion that exposure to asbestos in oil refineries causes pleural mesotheliomas. This is the first study to find an excess of pleural mesotheliomas among oil refinery workers exposed to asbestos.
This study was designed to assess whether the XbaI restriction fragment length polymorphism (RFLP) for apolipoprotein B (apo B) gene could be related with a genetic predisposition to develop hyperlipidemia and atherosclerosis. Relationships between XbaI RFLP and serum cholesterol were evaluated by comparing hyperlipidemic patients with healthy controls. Statistical analysis (chi-square test) showed no significant difference in either genotype distribution or allele frequencies. Hyperlipidemic patients were then divided according to triglycerides, either above or below 200 mg/dl and XbaI genotype frequencies were measured. No significant differences in genotype distribution or allele frequencies were found. The hyperlipidemic patients were tested for the presence of arterial disease by echo-Doppler and angina questionnaire. The XbaI genotype frequencies were determined in patients with arterial disease and compared to those without evidence of disease. No significant differences were found between the two groups.
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Hyperthyroidism and immune thrombocytopenia occurred concurrently in five patients; in a sixth, thyrotoxicosis developed after successful treatment of the thrombocytopenia. Correction of the hyperthyroidism was followed by a variable pattern of clinical response. In one case with mild asymptomatic thrombocytopenia spontaneous complete remission occurred. Two patients required adrenocorticosteroids to control severe thrombocytopenic purpura during the period of hyperthyroidism, after which complete remission occurred. Another patient with severe symptomatic thrombocytopenia remains with a partially compensated thrombocytolytic state but is without purpura and off all therapy. A fifth patient required splenectomy for drug-resistant thrombocytopenia and remains critically dependent on immunosuppressive therapy. The sixth patient had a relapse of immune thrombocytopenia with subsequent development of thyrotoxicosis but platelet count spontaneously returned to normal after correction of the hyperthyroidism. Pregnancy in two of these six patients was not associated with recurrence of either hyperthyroidism or thrombocytopenia. Management of symptomatic purpura in adults with co-existent hyperthyroidism may differ from that customarily employed since adrenocorticosteroid therapy may need to be extended until euthyroidism has been established before proceeding to splenectomy. When surgery is necessary, the risk of thyrotoxic storm should be anticipated, and the patient appropriately premedicated.
Five metabolites of actinomycete X-14881 were isolated from the fermentation broth and characterized. The major component was identified as [3R-(3 alpha,6a beta,7 beta,12 alpha,12a alpha)] or [3S-(3 beta,6a alpha, 7 alpha,12 beta,12a beta)]-6a, 7,12-trihydroxy-3,4,6a, 7,12, 12a-hexahydro-8-methoxy-3-methylbenz[a]-anthracen-1(2H)-one; the other four are closely related derivatives thereof.
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BACKGROUND: We evaluated the efficacy of abdominal ultrasound (US) and fine-needle aspiration biopsy (FNAB) in the diagnosis of disseminated mycobacteriosis (DM) in acquired immunodeficiency syndrome (AIDS). METHODS: Twelve AIDS patients (nine male, three female; age range, 22-43 years) with DM underwent abdominal US within 2 days after admission with 3.5- to 5-MHz convex probes and a 7.5-MHz linear probe. All patients underwent FNAB of one or two enlarged abdominal lymph nodes. Eight patients underwent FNAB of the spleen. The aspirated specimens were stained with acid fast for quick examination and cultured for isolation of mycobacteria. RESULTS: Abdominal US showed enlarged, hypoechoic, round or oval, abdominal lymph nodes (diameter, 10-35 mm; mean, 18 mm) in all patients; splenomegaly (spleen diameter, 14-22 cm; mean, 16.8 mm) in all patients; numerous splenic abscesses (diameter, 3-20 mm) in nine patients; hepatomegaly (right hepatic lobe thickness, 14.5-17 cm) in all patients; small intestinal wall thickening in five patients (maximum bowel wall thickness, 7-15 mm); mild to moderate ascites in six patients; pleural effusion in four patients; bilateral enlargement of the kidneys with hyperechogenicity of the cortex in three patients; and a retroperitoneal tubercular abscess in one patient. No complication occurred after FNAB of lymph nodes and spleens. Fast-acid stain of spleen and/or lymph node FNAB specimens allowed early diagnosis of mycobacteriosis in 12 of 12 cases (100%). Cultures of lymph node aspirates grew mycobacteria in six of 12 patients (50%). Spleen aspirates grew mycobacteria in nine of nine patients (100%). Blood cultures were positive in four of 12 patients (33%). Mycobacterium tuberculosis was diagnosed in six patients and M. avium in five. CONCLUSION: Abdominal US features can suggest DM in AIDS patients. Spleen and/or lymph node FNAB indicated the specific diagnosis in 100% of patients.
This study examined the results obtained with a modern apparatus for laser hair removal (neodymium: yttrium-aluminum-garnet [Nd:YAG] laser at long impulses with a wave-length of 1,064 nm; Q-switched laser) over a follow-up period of 3 years. A large heterogeneous group of 480 patients was taken into consideration. These patients were treated according to a standard protocol with monthly checkups and a personalized protocol at deferred appointments. The results, discovered by means of the most objective procedure possible, were retrieved and put into a graph showing two different curves for the repopulation of hair. In their clinical travels, the authors observed an average variable regrowth of 40% to 65%, allowing them to affirm that laser hair removal using Nd:YAG at long impulses is decisively efficient in obtaining long-term results. The use of a protocol (denominated "prolonged monthly checkup") with laser sessions at ever-decreasing periods permits, among other things, more outstanding and advantageous results for the patient. Thanks to more efficiently synchronized phases of the biologic hair cycle, this shortens and moves the telegenic phases closer and also renders the anagenic phases (those in which the selective photoermolysis on the pilipheric follicle proves to be efficient) more efficient. Personalization of the treatment relative to the monthly health checkup sessions is of fundamental importance to the scope of obtaining the best results in terms of cost-benefit rate, provided submassimal fluxes are (i.e., those well-tolerated by the patient) used. All this allows hair removal that is not definitive, but which becomes progressively permanent (i.e., characterized by ever-growing periods of lack of hair sustained by sporadic maintenance laser sessions based on the individual's necessity).
Three different methods of sedation or sedoanalgesia using remifentanil, Propofol, or midazolam to increase intra- and postoperative comfort and to reduce neuroendocrine stress in patients who had undergone typical ambulatory cosmetic surgery under local anesthesia were studied. A sample of 90 patients who underwent upper and lower eyelid blepharoplasty to correct baggy eyelids or otoplasty to correct protruding ears was selected according to standard criteria for the study. Remifentanil provided the best tolerability profile and the most effective perioperative pain control among the substances studied, demonstrating it to be a valid drug for modern sedoanalgesia aimed at increasing the well-being of patients undergoing ambulatory cosmetic surgery.