[Effect of iodinization on some properties of LATS and antithyroid antibodies].
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Antibodies↗
Biomedical subjects
S Mariotti
Publications and source records attributed to S Mariotti.
A new solid-phase immunoradiometric assay for anti-thyroglobulin autoantibody.
A newly developed sensitive and quantitative immunoradiometric assay (IRMA) for anti-thyroglobulin (anti-Tg) autoantibody is described. Serum samples to be tested are added to wells of polyvinyl microtiter plates coated with human thyroglobulin. After removal of the unbound material, anti-Tg antibody is determined by adding purified 125I-anti-human immunoglobulin G antibody. Using 1.0 microliter of serum anti-Tg antibody was detected in 81.2% of patients with Hashimoto's thyroiditis or idiopathic myxedema (n = 32), in 46.4% of those with Graves' disease (n = 28), in 11.9% of subjects with other thyroid disorders (n = 42) and in 4.2% of normal controls (n = 71). Similar percentages of positive tests were observed by passive hemagglutination (PH) and a good correlation was found between the antibody levels determined by the two techniques. Using larger amounts of serum (100 microliters) detectable anti-Tg antibody by IRMA was found in the majority of patients with thyroid autoimmune disorders who had negative PH tests. Quantitative measurements of anti-Tg antibody by IRMA could be obtained by using purified anti-Tg antibody as standard reference. The minimum detectable amount of anti-Tg antibody was 0.5 ng. The present method is proposed as a simple and convenient technique for quantitative measurement of any antibody, using wells coated with the appropriate antigen.
Antigen-Antibody Complex↗
Changes of circulating thyroid autoantibody levels during and after the therapy with methimazole in patients with Graves' disease.
The changes occurring in the levels of circulating thyroid microsomal antibody (M-Ab) and antithyroglobulin antibody (Tg-Ab) during antithyroid drug therapy were studied in 32 patients receiving methimazole for Graves' disease. M-Ab was determined by competitive binding radioassay and Tg-Ab by a sandwich radiometric method. Before treatment 25 subjects (78.1%) had abnormally elevated (greater than or equal to 75 U/ml) M-Ab levels. A more than 30% reduction of M-Ab concentration with respect to the pretreatment value was found in 16 (64.0%) of these patients within the first 3-5 months of therapy, in 23 (92.0%) within 8-11 months and in 21 (84.0%) at the end of treatment (16-18 months). No change was found in the 7 patients with initial M-Ab levels less than 75 U/ml. The reduction of M-Ab was more pronounced in the patients with good control of thyrotoxicosis than in those who were still hyperthyroid or were rendered hypothyroid during treatment. Twenty-three patients were followed after completion of the course of methimazole therapy, and 13 of them showed relapse of hyperthyroidism. A significant rise of M-Ab with respect to the values observed at the end of treatment occurred in all relapsing patients who had abnormally elevated M-Ab levels before therapy. With one exception, no M-Ab increase was found in the 10 nonrelapsing patients. However, no difference between relapsing and nonrelapsing patients was observed when the M-Ab changes occurring during treatment were considered. A similar trend during and after withdrawal of therapy was noted for Tg-Ab but, because of the relatively small percentage of positive subjects (25%), the results were less conclusive. The present data indicate that methimazole treatment induces a fall of thyroid antibodies in patients with Graves' disease, and that relapse of hyperthyroidism is associated with an increase of these antibodies. However, the antibody changes occurring during treatment showed no prognostic value in predicting the outcome of therapy.
Adolescent↗
Minimal sentinel node procedure for staging early breast cancer.
AIMS AND BACKGROUND: Sentinel lymph node dissection (SLND) has recently been evaluated as a new staging technique for early breast cancer. To minimize the extent of surgery, the feasibility of eradicating primary breast lesions and the relative sentinel lymph nodes (SLN) under regional anesthesia was evaluated in this study. METHODS AND STUDY DESIGN: A selected population of 76 patients with suspected operable breast cancer and no clinically palpable lymph nodes was enrolled in the study. Intra- and perilesional administration of a radiotracer was performed. Lymphoscintigraphy was carried out to confirm the drainage pathway and locate the SLN. The following day, after inducing a nervous block induction of the ipsilateral intercostal nerves, we performed the surgical procedure with the help of a hand-held gamma-detecting probe. In case the primary lesion was diagnosed as invasive carcinoma by frozen section, the SLN and the remaining axillary lymph nodes (non-SLNs) were removed. The status of SLN and non-SLNs was compared. RESULTS: The primary breast lesion was located and excised in all cases (identification rate: 100%). Lymphoscintigraphy positively identified SLNs in 40/45 (89%) patients; in five patients no lymphatic drainage was detected. In 38 cases an average of 1.5 SLNs and 14 non-SLNs per patient were removed and pathologically analyzed; the remaining two patients showed SLNs in the internal mammary chain, which were not excised. Twenty-nine percent of the patients showed metastatic disease in the lymph nodes examined. Of all patients with affected nodes, 55% had cancer cells only in the SLN. No false negatives (skip metastases) were found. No immediate or long-term anesthesia-related complications (e.g., pleural lesions, intravascular injection) were observed. CONCLUSIONS: Our data confirm the feasibility of single radiotracer administration for both occult lesion and SLN localization as well as the usefulness of SLND in staging early breast cancer. Regional anesthesia resulted in easy management and good patient compliance. This time-saving procedure allowed the completion of the whole surgical plan, reducing the recovery time without modifying the effectiveness of surgery.
Adult↗
Day-surgical management of ductal carcinoma in situ (DCIS) of the breast using wide local excision with sentinel node biopsy.
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Adult↗
Sentinel lymphadenectomy in cutaneous melanoma.
AIMS AND BACKGROUND: In the last ten years validation of the sentinel lymph node (SLN) concept has led to modification of the surgical approach for patients with intermediate-risk cutaneous melanoma. METHODS AND STUDY DESIGN: Forty-eight patients affected by cutaneous melanoma with a Breslow thickness between 0.65 and 4 mm were enrolled in the study. Approximately 2 mCi of radiotracer and 1 mL of vital blue dye were injected in each patient around the site of the primary lesion. Lymphoscintigraphy was performed until the lymphatic basin and the respective SLN were localized. The whole surgical procedure consisted of enlargement of the surgical margins followed by localization and excision of the SLN(s) by using both radiotracer and vital dye. Whenever the SLN proved to be histologically positive for metastasis, complete regional lymphadenectomy was performed. RESULTS: Within 15 minutes of radiotracer administration the lymphatic basin was localized in all 4 patients by lymphoscintigraphy. Vital dye and radiotracer successfully allowed SLN localization and excision in 46 of 48 patients (97%); in one case the SLN was detected by radiotracer alone. The SLN proved to be metastatic in six (13%) of 46 evaluable patients; interestingly, in three of them the presence of metastatic cells was revealed only by immunohistochemistry. All patients with tumor-positive SLNs had primary lesions with a Breslow thickness = 2 mm. CONCLUSIONS: Sentinel lymphadenectomy is able to identify lymph node involvement in patients with cutaneous melanoma with a Breslow thickness > 1 mm, thus avoiding the risks associated with radical regional lymphadenectomy. Lymphoscintigraphy proved to be an important tool to obtain correct preoperative localization of the drainage basin, especially for melanomas located on the face and trunk.
Adolescent↗
Prognostic value of serum and tumor tissue CA 72-4 content in gastric cancer.
To date no general agreement has been reached regarding the prognostic significance of CEA, CA 19-9 and CA 72-4 as serum markers in gastric cancer, and only scattered information is available on the predictive value of marker expression in tumor tissue. Therefore, a longitudinal study was designed to analyze the presurgical serum and tumor tissue content of CA 72-4, CEA and CA 19-9 in 166 patients at different stages of gastric cancer, and to evaluate the possible correlation with clinicopathological features in respect to prognostic information on relapse-free survival. The results obtained showed that 48.4% of patients with tumor recurrence had positive presurgical CA 72-4 levels compared to approximately 24% of patients who remained free of disease. Furthermore, the median presurgical serum CA 72-4 levels were significantly elevated in relapsing patients. Serosa and lymph node involvement as well as positive presurgical serum CA 72-4 levels had independent prognostic value in predicting recurrence. A significant association between disease-free survival and lymph node involvement, depth of invasion and tumor tissue content of CA 72-4 was also demonstrated. We may therefore conclude that CA 72-4 antigen can be considered the marker of choice in the follow-up of gastric cancer patients and may be used as a prognostic indicator of relapse.
Adult↗
Soluble selectin levels in patients with lung cancer.
Increased expression of selectins has been found on endothelial cells of venules and capillaries in the tumor stroma of non-small cell lung cancer, suggesting their functional role in the process of chemotaxis for tumor cells. The present study was aimed at analyzing the role of both soluble (s)P-selectin and sE-selectin levels in association with clinico-pathological variables in 116 patients with lung cancer, 38 patients with benign diseases and 59 healthy donors. The results obtained showed that sP-selectin and sE-selectin levels were higher in patients with lung cancer compared to normal donors (p<0.02 and p<0.005, respectively). No differences were observed among patients with various benign diseases for both selectins. Increased levels of sP-selectin and sE-selectin were significantly associated with squamous lung cancer at late stages (p<0.05), but not adenocarcinoma. Both sP- and sE-selectin were independently related to the stage of squamous lung cancer by stepwise regression analysis (p<0.02 and p<0.03, respectively), while only sE-selectin was independently related to the presence of distant metastasis in the same histotype (p<0.02). These results suggest that measurement of plasma soluble selectins might represent a useful laboratory parameter in the management of patients with squamous lung cancer.
Adenocarcinoma↗
[Chemotherapy of advanced stage melanoma using cisplatin, epirubicin and alpha-interferon].
PURPOSE: To evaluate the activity and toxicity of cisplatin (DDP), epirubicin (EPI) and interferon alfa-2a (a-IFN) in patients (pts) with metastatic melanoma. PATIENTS AND METHODS: Thirty-seven pts with histologically-proven metastatic melanoma were treated with DDP 75 mg/m2 e.v. and EPI 90 mg/m2 e.v. on day 1 + alpha-IFN 9 MUI/die s.c. on days 4 to 8 and 18 to 22. Cycles were repeated every 4 weeks. RESULTS: Characteristics of the patients were the following: median age 55 years (range, 24-75), median WHO performance status 1 (range, 0-2), prior chemotherapy 9, prior immunotherapy 16 (adjuvant/advanced 11/5), sites of disease: soft tissue only 10, lung 22, liver 11, bone 1, brain 3. In 35 evaluable patients we have obtained 3 complete and 10 partial responses, for an overall response rate of 37%. Dose-limiting toxicity was myelosuppression with grade (G) 4 neutropenia in 59.5% of patients and G4 thrombocytopenia in 11% of patients. Other toxicities were generally mild to moderate with nausea and vomiting in 67.5% of patients, flu-like syndrome in 78.5% and fatigue in 48.5% of the patients. Median time to response, median time to progression and survival were 3 (range, 2-6), 7 (range, 2-45+) and 10 months (range, 4-45+), respectively. CONCLUSION: This combination is active and well tolerated in metastatic melanoma. Toxicity was manageable and has enabled us to conduct this trial on an outpatient basis.
Antineoplastic Combined Chemotherapy Protocols↗
Comparative analysis of CA 242 and CA 19-9 serum tumor markers in colorectal cancer patients. A longitudinal evaluation.
OBJECTIVE: Following the encouraging results obtained on CA 242 as an adjunctive marker for colorectal cancer this study was designed to compare the clinical behavior of CA 242 to that of its related marker CA 19-9. PATIENTS AND METHODS: Sera from 630 patients with benign (n = 201) or malignant (n = 429) colorectal diseases were evaluated. Moreover, 50 patients with colorectal cancer were longitudinally monitored during. post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Serum CEA, CA 19-9 and CA 242 levels were determined before treatment and at each scheduled follow-up. RESULTS: The distribution of CA 242 levels in colorectal cancer patients demonstrated a similar positivity rate (32.9%) compared to that of CA 19-9 (29.8%), although both sensitivities were lower than that of CEA (43.8%). Moreover, elevated CA 242 serum levels were found in metastatic disease (58.2%). A longitudinal evaluation demonstrated that serum CEA, CA 19-9 and CA 242 levels were elevated in 63.9%, 63.9% and 66.7% of recurrences. Combined evaluation of CEA, CA 19-9 and CA 242 serum levels in the overall population demonstrated a complementarity of CEA with the latter two markers. Conversely, a highly significant correlation was observed, suggesting that the two assays might recognize the same macromolecular complex. CONCLUSION: CA 242 determination does not seem to offer a particular advantage over CA 19-9, while CEA remains the marker of choice in monitoring colorectal cancer patients.
Adult↗
Radioguided-surgery of early breast lesions.
BACKGROUND: Radioguided-surgery has been recently proposed in patients with clinically occult breast lesions. This study aimed to evaluate the feasibility of correctly locating and eradicating, by a single intralesional injection of a radiotracer, any breast lesion and, in the case of malignancy, to perform simultaneous sentinel lymph node (SLN) biopsy procedure. PATIENTS AND METHODS: Sixty-three women with early breast lesions were enrolled: 42 were invasive carcinomas, 16 in situ ductal carcinomas (DCIS) and 5 fibroadenomas. RESULTS: Scintigraphic images clearly identified the lesions in all patients while SLN/s were evident in 88% of them. At surgery all the breast lesions were easily radiolocalized and eradicated with minimum surgical trauma and, for those patients with invasive carcinomas, the SLN technique was performed in 86% of them. No skip metastases were found. CONCLUSION: A single intralesional administration of radiotracer is an easy and reliable procedure to simultaneously locate and remove both the non-palpable breast lesion and the SLN when primary malignancy was intraoperatively confirmed.
Adult↗
Biological effects of a software-controlled voltage pulse generator (PhyBack PBK-2C) on the release of vascular endothelial growth factor (VEGF).
BACKGROUND: Electrical stimulation (ES) may induce vascular permeability and physiological angiogenesis. ES of rat muscles significantly increases the microvessel density and vascular endothelial growth factor (VEGF) protein levels. Thus, a pilot study was designed to analyze the effects of low-voltage electric impulses on VEGF levels in patients with dystrophic ulcers. MATERIALS AND METHODS: Circulating VEGF levels were analyzed in 9 patients undergoing an ES session with low voltage software-controlled impulses applied through topical transducers (1-9 micros width, 1-420-Hz frequency and 30-120 V strength-100 microA max). RESULTS: The session was accompanied by a peak of circulating VEGF (3-10 min from start) in all 9 patients, which was preceded by a rise of TNF-alpha (2-min) and was independently associated with soluble E-selectin levels. Nitric oxide generation was significantly improved on the day after treatment. No hemostatic activation or sustained inflammatory reaction were observed. CONCLUSION: ES may represent a safe method for augmenting VEGF-mediated vascular protection, either directly or by induction of NO.
Aged↗
Thyroiditis as a model of organ specific autoimmune disease.
In the last few years a great deal of information on the etiopathogenetic aspects of organ-specific autoimmune diseases has been obtained from the extensive study of both animal models of experimental or spontaneous thyroiditis and of human thyroid autoimmune diseases. It has been clearly shown that genetic factors play a fundamental etiologic role. They are responsible for the dysregulation of the immune system and for the target organ susceptibility which favor the onset of the disease. Environmental factors are presumed to act as initiating or precipitating events, leading genetically predisposed individuals to thyroid autoimmunity. A number of immune mechanisms able to trigger autoimmune responses, such as antigenic cross-reactions and the aberrant expression of HLA class II molecules, have been suggested, but the definition of why and how they become operative requires further investigation. Data obtained from experimental models and from human thyroid diseases clearly indicate that the ongoing expansion of autoreactive T cells with specificity for thyroid autoantigens represents the main immunological event responsible for induction and maintenance of thyroid damage. Such autoreactive T cells can induce tissue lesions through activation of different effector systems and secretion of different combinations of lymphokines. In overt thyroid autoimmune diseases autoantibodies directed against functional molecules or cellular receptors can also be involved in the pathogenesis of tissue lesions. However, the pathogenesis of inflammatory destructive lesions of the thyroid is more complex and not yet fully elucidated. It is worthy of note that a large proportion of T cells present in inflammatory human thyroid infiltrates are apparently not directed against the thyroid autoantigens recognized so far.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Case report on 2,4-dichlorophenoxyacetic acid poisoning].
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2,4-Dichlorophenoxyacetic Acid↗
High incidence of goiter in patients treated with lithium carbonate.
The effects of lithium carbonate on thyroid was evaluated in 40 consecutive psychiatric patients on long-term treatment with this drug. Five patients had clinical and/or biochemical hypothyroidism. Twenty four (60%) subjects showed goiter of different size, including very large glands. A very high prevalence of goiter (87%) was observed in the 15 patients coming from a moderate endemic area. A lower incidence of goiter (44%) was found in subjects coming from non endemic areas. Goiter was associated with significantly elevated serum thyroglobulin concentration similar to that reported in endemic or sporadic nontoxic goiter. None of 25 psychiatric patients not receiving lithium therapy was hypothyroid and only three (12.5%) of them showed a small size goiter. These data indicate a very high prevalence of thyroid enlargement in patients on lithium therapy and suggest the opportunity to institute a prophylactic thyroid hormone treatment at least in subjects coming from endemic areas.
Adolescent↗
TAG-72 expression and its role in the biological evaluation of human colorectal cancer.
Immunohistochemical studies showed that TAG-72 is expressed in more than 80% of colorectal carcinomas, but is rarely expressed in normal epithelium and benign diseases. TAG-72 can also be found in the body fluids of patients with adenocarcinomas, and its direct measurement can be used in conjunction with immunocytochemical analysis to help in discriminating benign from malignant effusions. The evaluation of TAG-72 in serum of colorectal carcinoma patients showed a sensitivity of approximately 40%, comparable to that of the widely used CEA. TAG-72 serum levels correlate with the stage of disease, suggesting its utility in discriminating between early-stage versus late-stage colon carcinoma. Longitudinal studies demonstrated that TAG-72 serum levels may be used as a predictive marker of recurrences. Moreover, the simultaneous measurement of TAG-72 and CEA serum markers improves the monitoring of recurrent disease. Therefore, these data suggest that TAG-72 is a well suitable marker for colorectal cancer.
Antigens, Neoplasm↗
[Sequential therapy with methotrexate and 5-fluorouracil in patients with advanced colorectal cancer pretreated with 5-fluorouracil plus folinic acid].
PURPOSE: To evaluate the efficacy and toxicity of a sequential low-dose methotrexate (MTX) and 5-fluorouracil (5FU) regimen in the palliative treatment of patients with advanced colorectal cancer. PATIENTS AND METHODS: Enrolled in the study were patients with advanced colorectal cancer, refractory to 5FU + FA. Patients were treated with MTX 40 mg/m2 i.v. bolus d 1 and 8, 5FU 700 mg/m2 i.v. bolus d 2 and 9 (24 hours after MTX bolus). The cycle was repeated every 4 weeks. RESULTS: 48 patients entered the study, and 45 are evaluable. The overall response rate was 15% with 1 complete response and 6 partial responses. Eight patients obtained disease stabilization. Median time to progression was 9 months. Toxicity was mild. Grade 3 stomatitis was observed in 7 (15%) patients. CONCLUSIONS: Sequential MTX/5FU is a well tolerated regimen with mild antitumor activity in refractory advanced colorectal patients.
Antineoplastic Combined Chemotherapy Protocols↗
[Simultaneous infusion of vinorelbin and taxol as first-line chemotherapy in metastasized breast cancer].
PURPOSE: To evaluate the activity and toxicity of simultaneous infusion of vinorelbine (VNB) and paclitaxel (T) as first line chemotherapy in advanced breast cancer patients (pts). PATIENTS AND METHODS: 33 pts with histologically proven advanced breast cancer were treated with VNB 25 mg/m2 and T 150 mg/m2, both drugs given by i.v. infusion over 3 hours, with cycles repeated every 3 weeks. Granulocyte-colony-stimulating factor (G-CSF), 300 micrograms subcutaneously, was given on days 7 to 12 of each cycle in the first 10 patients. RESULTS: From October 1995 to July 1996, 33 untreated pts entered the study. Characteristics of the pts were the following: median age 53 years (29-71); median WHO performance status 1 (0-3); pre/postmenopausal 8/25; prior adjuvant chemotherapy 16; prior radiotherapy 8; dominant disease sites: soft tissue in 6; bone in 7, viscera in 19; number of metastatic sites: 1 in 18, 2 in 9, 3 in 6 pts. In 31 evaluable pts we observed: 1 CR (3%) and 14 PR (45%), for an overall response rate of 48%. Median time to response was 2 months; median time to progression and median survival were 7 and 22+ months, respectively. Median number of cycles was 6. Myelosuppression was the dose-limiting toxicity, with G 4 neutropenia occurring in 22% of the pts and neutropenic fever in 6% of the pts. Other toxicities were generally mild with nausea in 52% of the pts; mucositis in 15%; constipation in 12%; peripheral neuropathy in 46.5%. Alopecia was universal. CONCLUSIONS: Simultaneous infusion of VNB and T is well tolerated and active in untreated patients with advanced breast cancer. Median survival (22+ months) is similar to that reported with anthracycline-containing regimens, although response rate appears to be lower. It is likely that higher response rates may be achieved with a higher dose-intensity.
Adult↗