Biomedical subjects

A Mancini

Publications and source records attributed to A Mancini.

At least 91 records · Page 5Linked to original sources

PubMed1995

A new approach in the treatment of stage IV neuroblastoma using a combination of [131I]meta-iodobenzylguanidine (MIBG) and cisplatin.

The outlook for disseminated neuroblastoma (NB) continues to be dismal. NB is a radiosensitive tumour. Owing to its high concentration in NB lesions, [131I]meta-iodobenzylguanidine [131I]MIBG has the potential for specifically delivering very large radiation doses to the malignant cells. Encouraging results have been reported with [131I]MIBG used alone in patients resistant to conventional therapy and at diagnosis. We report the first attempt to explore the integration of this new treatment modality with chemotherapy. Among the drugs effective in NB, cisplatin was chosen because of its high degree of activity against NB, its mild haematological toxicity and the known synergism between cisplatin and radiation. 4 patients, 3 with relapsed, heavily pre-treated, progressive stage IV NB, and 1 with stage IV NB at diagnosis, all with a good [131I]MIBG uptake, were investigated with combined therapy (CO-TH). Two complete remissions and one partial remission were observed in these patients 4-6 weeks following only a single course of both cisplatin and [131I]MIBG at "standard" dosage. The only toxicity was haematological, which was significant and relatively long-lasting, but was not associated with any serious infections or bleeding tendency. The general condition of these patients during the entire study period was excellent. The fourth patient, investigated at diagnosis with a modified less intensive treatment, obtained a partial remission with mild haematological toxicity. During the subsequent courses of intensive multidrug chemotherapy, this patient showed haematological toxicity comparable with that experienced by patients treated with an identical drug combination, but without previous treatment with CO-TH. The provisional conclusion of this ongoing study is that this new form of CO-TH appears most effective in obtaining a rapid and excellent response in heavily pretreated relapsed patients with progressive disease, and should be further investigated in earlier stages of the disease.

3-Iodobenzylguanidine↗

PubMed1995

Deferoxamine followed by cyclophosphamide, etoposide, carboplatin, thiotepa, induction regimen in advanced neuroblastoma: preliminary results. Italian Neuroblastoma Cooperative Group.

Based upon phase I and II studies of deferoxamine alone and in combination with cytotoxic agents cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT), we initiated a single arm multicentre trial in 1992 for advanced neuroblastoma. 57 of 65 patients who entered the trial were evaluable. Following 4 courses of the D-CECaT, almost all the patients underwent surgery. Toxicity was moderate and mainly reversible myelosuppression. The post-surgically defined responses in stage 3 high risk, stage 4 moderate risk and stage 4 high risk patients included 24 complete responses, 26 partial responses, and 3 minor responses, and 4 patients had progressive disease. These patients are being followed to determine the impact of this programme on their overall survival.

Adolescent↗

PubMed1995

GH response to oral and intravenous glucose load in acromegalic patients.

The lack of inhibition of Growth Hormone (GH) levels after glucose load is considered a marker of inappropriate GH secretion in acromegaly. In order to investigate the physiopathology of this phenomenon, we have studied the GH variations after an oral glucose load (0.75 g/kg BW per os, OGTT) or intravenous glucose bolus (25 g i.v., IVGTT), in a group of 12 acromegalic patients, aged 20 +/- 69 yr (mean 48), 5 males and 7 females, with basal GH levels ranging from 11 to 76.2 ng/ml. The results indicate that only a group of acromegalic patients (group 1) had a partial GH inhibition after OGTT (mean decrease: 56.4 +/- 4.2%), but in no patients GH levels were influenced by intravenous administration of glucose. It is possible that in group 1 patients, the gastroenteric response could partially influence the GH secretion by the pituitary tumor, probably due to an increased peripheral somatostatin release. The dissociation of the GH response to OGTT and IVTT could indicate a supersensitivity to peripheral somatostatin, related to a deficiency in central somatostatinergic tone and therefore represent a more unfavourable prognostic sign.

Acromegaly↗

PubMed1995

Pleural malignant mesothelioma and non-occupational exposure to asbestos in Casale Monferrato, Italy.

OBJECTIVES: To assess and quantify the occurrence of pleural malignant mesotheliomas in people who neither experienced occupational exposure to asbestos nor were married to (or known to live with) workers exposed to asbestos in the workplace. The study was conducted in the area of the local health authority of Casale Monferrato, in north western Italy, where a large factory that produced asbestos cement was active up to 1985. No other major activities related to asbestos have ever been present in the area. METHODS: A retrospective survey covering the period 1980 to 1991 identified 126 incident pleural malignant mesotheliomas histologically diagnosed among residents in the local health authority (population at the 1981 census 98,000). Submission of 83 of 95 cases diagnosed during 1980-9 for revision by a panel of five expert pathologists led to the exclusion of 21. The 31 cases diagnosed in 1990-1 were not submitted for revision. For 64 of the 105 retained cases, information derived from different sources (rosters of the employees in the asbestos cement factory dated back to 1907, list of their spouses, clinical records) did not suggest occupational or paraoccupational exposure to asbestos. RESULTS: Incidence excludes cases for which there was some suggestion of occupational or paraoccupational exposure to asbestos. Incidence of histologically confirmed malignant mesothelioma among residents in the local health authority (annual x 100,000; age adjusted) was 4.2 in men and 2.3 in women (based on 26 and 18 cases respectively). In both sexes, rates in 1985-9 were higher than in the previous quinquennium. Corresponding estimates for 1990-1 (based on unrevised diagnoses) suggest similar rates in men and women. CONCLUSION: Rate ratios which are four to six times those measured by conventional Italian cancer registries can hardly be totally explained by bias produced by lack of recognition of occupational or paraoccupational exposure. The problem of proving this type of negative data is common to other circumstances of alleged cancer clusters of environmental (non occupational) origin.

Adult↗

PubMed1995

Localized resectable neuroblastoma: results of the second study of the Italian Cooperative Group for Neuroblastoma.

PURPOSE: To optimize treatment for children with localized resectable neuroblastoma in 21 Italian institutions using a common protocol based on previous experience. PATIENTS AND METHODS: Between January 1985 and December 1992, 152 children aged 0 to 15 years with nondisseminated neuroblastoma were entered onto this study following complete resection of tumor without tumor rupture (TR) (stage 1), or resection with minimal tumor residue, and/or tumor infiltration of regional lymph nodes (LN+), and/or TR (stage 2). Of 144 assessable children, 69 were classified as having stage 1 disease and 75 as stage 2. Of stage 2 children, 49 had low-risk (LR) characteristics (age, 0 to 11 months or 1 to 15 years but negative lymph nodes and no TR). Stage 1 and stage 2 LR children did not receive adjuvant therapy. The remaining 26 stage 2 children had high-risk (HR) characteristics (age, 1 to 15 years with LN+ and/or TR) and received adjuvant chemotherapy for 6 months. RESULTS: Of 144 children, three died of therapy-related complications and 19 relapsed, of whom six died of disease. The estimated 5-year overall survival (OS) rate was 93% and the event-free survival (EFS) rate was 83%. Of 69 stage 1 children, one died postoperatively and five relapsed (one local and four disseminated, two of whom died), for 94% OS and 90% EFS rates. Of 49 stage 2 LR children, six relapsed (four local and two disseminated); relapses occurred in five of 20 infants with LN+, in one of four infants with TR, and in none of the remaining 25 children. One child died of disease and one of toxicity, for 96% OS and 85% EFS rates. Of 26 stage 2 HR children, eight relapsed (three of 20 with LN+, three of four with TR, and two of two with LN+ and TR), of whom three died of disease and one of toxicity, for 87% OS and 61% EFS rates. CONCLUSION: Our data confirm the overall good prognosis of children with localized resectable neuroblastoma. LN+ and TR predisposed to relapse at all ages, but infants tended to have a less aggressive course after relapse. Stage 1 and 2 LR children had 94% and 96% OS rates, respectively, which justifies a policy of no adjuvant chemotherapy. Eight of 26 children with stage 2 HR relapsed despite 6 months of chemotherapy; for these children, more intensive chemotherapy may be required.

Adolescent↗

PubMed1995

Prevention and treatment of complications after endoscopic prostheses placement in tumors of the upper gastrointestinal tract.

Endoscopic intubation is a popular palliative method to resolve immediately malignant dysphagia. However, the complication rate is still high. Between 1978 and 1993, at the Division of Diagnostic and Surgical Endoscopy of Istituto Nazionale Tumori in Milan, 305 patients suffering from malignant dysphagia, were endoscopically treated by insertion of an endoprosthesis. We report the analysis of data regarding our complication rate, compared with the literature, and our experience in preventing managing complications related to this endoscopic procedure.

Adult↗

PubMed1994

Opioid dysregulation in anorexia nervosa: naloxone effects on preprandial and postprandial growth hormone response to growth hormone-releasing hormone.

Previously, we have shown that in the opposite extremes of nutritional status, obesity and anorexia nervosa (AN), growth hormone (GH) response to growth hormone-releasing hormone (GH-RH) is not inhibited by the ingestion of a normal 800-cal meal consumed at lunch time (1 PM), which is at variance with results in normal subjects. However, in obese patients the postprandial increase in GH response to GH-RH is inhibited by an infusion of naloxone (NAL). In this study we have tested anorectic patients, performing the following tests at 1 PM: GH-RH test (50 micrograms IV) or, in a different day session, NAL (1.6 mg/h, starting 30 minutes before GH-RH) + GH-RH test (50 micrograms IV). The tests were performed in the following three different experimental conditions: (1) short-term fasting studies (lasting from breakfast), (2) long-term fasting studies (from midnight of the day before) and (3) postprandial studies (after a standard meal consumed 1 hour before the test). In AN, the GH response to GH-RH was not influenced by NAL infusion at 1 PM, in both short- and long-term fasting studies (short-term fasting: peak values after GH-RH alone, 26.5 +/- 6.5 ng/mL, during NAL, 28.0 +/- 3.3 ng/mL; long-term fasting: peak values after GH-RH alone, 32.2 +/- 6.8 ng/mL, during NAL, 30.6 +/- 4.0 ng/mL). A partial NAL-inhibitory effect was instead observed in postprandial studies, as evidenced by the calculation of areas under the curve ([AUCs] 1,662.1 +/- 90.0 after GH-RH alone v 1,090.5 +/- 245.4 ng/mL/h during NAL).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Coenzyme Q10 levels in human seminal fluid: diagnostic and clinical implications.

The levels of Coenzyme Q10 (CoQ10) were determined by HPLC in seminal fluid samples obtained from 77 patients who performed a standard semen analysis for infertility, previous phlogosis or varicocele. CoQ10 was determined in total seminal fluid (n = 60), in seminal plasma (n = 44) and in the cell pellet (n = 37). The molecule, in total fluid, showed a linear correlation with sperm count and motility. In the pellet of spermatozoa, a trend toward an inverse correlation between CoQ10 (expressed as ng/10(6) cells) and semen parameters could be observed. A different pattern was shown in varicocele patients, in whom, in total fluid, the correlation between CoQ10 and sperm count was preserved, but the one between CoQ10 and sperm motility was lacking; moreover, a higher proportion of CoQ10 was present in seminal plasma, and the inverse trend between cellular CoQ10 and sperm count and motility was not observed. These data suggest a pathophysiological role of ubiquinone in human seminal fluid and a molecular defect in the spermatozoa of varicocele patients.

Adult↗

PubMed1994

Role of immunosuppression in recurrence after liver transplantation for diethylnitrosamine-induced tumors in rats.

Hepatocellular carcinoma is one of the world's most common malignant diseases, with an increasing incidence related to liver cirrhosis. The purpose of the study was to evaluate the role of immunosuppression in recurrence in rats transplanted after liver tumor induction by diethylnitrosamine (DENA), which has proved to be a reliable carcinogen. In 14-week-old Lewis rats weighing 200 g, tumors were induced by the oral administration (5 mg/100 ml in drinking water ad libitum) of DENA for 13 weeks. Orthotopic liver transplantation (OLT) was performed after 4 weeks' latency. In the Lewis/Lewis rats weighing 200 g, tumors sporin A (CsA) treatment, median survival was 199-days with no recurrence or metastasis. In the BN/Lewis group with no CsA (5 ats) median survival was 144 days. All rats died due to rejection. In the other BN/Lewis group (10 rats), OLT was followed by CsA administration (7.5 mg/kg). Median survival was 161 days. In three rats (218 days), there was liver tumor recurrence; in two rats (137.5 days), kidney and lung metastases were found. The remaining rats died of septic complications. In the Lewis/Lewis + CsA group (10 rats), median survival was 131 days with 5 recurrencies and/or metastases. Two rats are still surviving at 84 and 88 days. Our results suggest that the DENA model is reliable; it proved to have a similar carcinologic pattern to HCC in man. Moreover, immunosuppression seems to play an important role in determining recurrence. Further studies are needed to investigate the efficacy of chemotherapy agents pre- and post-transplantation.

Animals↗

PubMed1994

[The current role of radiotherapy in immunogenic exophthalmos].

In this study, the value of radiation therapy was investigated in 41 patients with Graves' ophthalmopathy treated with orbital irradiation at the Radiotherapy Department of Mauriziano Hospital in Turin, 1986 through 1993. Our series consisted of 41 patients (32 women and 9 men), whose mean age was 53.6 years (range: 26-72 years). All patients had a high index of endocrine ophthalmopathy, based on the American Thyroid Association classification-NOSPECS classes III and IV. Irradiation was administered with two opposed convergent beams tilted posteriorly 5-10 degrees with 20 Gy/12 fractions/2 weeks. The total dose delivered to the lens was than 5%. The follow-up consisted of endocrinologic and ophthalmologic tests and, if possible, of pre/post-irradiation orbital US. A positive result was obtained in 31 patients, which was very good in 22 of them. Severe complications, i.e., 1 corneal ulceration and 3 cataracts, were observed in the patients with associated ocular conditions and were treated simultaneously with high-dose corticosteroids so that no direct and unquestionable correlation can be made between irradiation and complications. To conclude, our data show that radiation therapy can improve the signs and symptoms of Graves' disease, as many authors report.

Adult↗

PubMed1993

Endoscopic treatment of malignant dysphagia.

Palliative endoscopic treatment of dysphagia in patients with inoperable oesophageal cancer includes: dilation, Nd:YAG laser photocoagulation and intubation, used alone or in combination. Such procedures are usually performed on an outpatient basis and are associated with a low rate of morbidity and mortality. From 1978 to 1988, 476 patients (401 males, 75 females) were treated at the Endoscopy division of the National Cancer Institute of Milan for inoperable primary or recurrent malignancies of the oesophagus or cardia or for extra-oesophageal neoplasms causing dysphagia. Dilation was used in 172 cases, Nd:YAG laser photocoagulation in 90, prosthesis insertion in 72, dilation and laser in 97, and prosthesis and laser in 45. Functional improvement was reported in 75% of patients after dilation, in 89% after laser treatment, in 80% after intubation, in 80% after dilation and photocoagulation, and in 89% after laser and intubation. The median duration of dysphagia-free interval was 4 weeks in dilated patients, 6-8 weeks in photocoagulated patients and 20 weeks intubate patients. Overall median survival was 6.2 months. The complication rate was: 1.4% in dilation treatment, 1.4% in laser photocoagulation, and 8.8% in prosthesis intubation. Mortality related to endoscopic treatment was 2.1% (10/476 patients). Relief of dysphagia is one of the most important goals of palliative treatment in patients with inoperable oesophageal neoplasms. Moreover, endoscopic palliation improves the quality of life in the patients, with a low complication rate.

Aged↗

PubMed1993

Endoscopic treatment of postradiation strictures.

BACKGROUND: Esophageal stricture is a rare complication of radiotherapy: reports on its incidence and management are therefore anecdotal. METHODS: From January 1978 to September 1992, 44 patients presenting with an esophageal stricture related to a previous radiation treatment were endoscopically dilated at the Endoscopy Division of the Istituto Nazionale Tumori of Milan. RESULTS: Esophageal recanalization was obtained in 95% of the patients treated, and in 79% of these normal eating habits were restored. No strict correlation was observed between radiation dose and severity of the stricture, or time elapsed between first treatment and endoscopic dilation. CONCLUSIONS: In our experience, endoscopic dilation was a safe effective procedure and represented an effective palliative tool in dysphagic patients with esophageal strictures due to previous local radiotherapy.

Adult↗

PubMed1993

Growth hormone response to growth hormone-releasing hormone in early abstinent alcoholic patients.

The alpha-2-adrenoceptor agonist clonidine is able to stimulate GHRH secretion directly or via beta-endorphin and, therefore, induces a GH release in normal subjects. This effect has been shown to be blunted in alcoholism during early abstinence, due to central alterations of adrenergic mechanisms. To evaluate pituitary responsiveness to direct stimulation with GHRH, we have studied the GH and PRL response to GHRH in 10 alcoholics during early abstinence. Our data indicate that the pituitary response to GHRH is intact in abstinent alcoholics, except in obese patients, who displayed a blunted GH response. GHRH did not increase PRL. The dissociation between clonidine and GHRH in GH stimulation could reveal a different neuroendocrine mechanism, in comparison with other psychiatric disorders (anorexia nervosa), in which such a dissociation is accompanied by a PRL response to GHRH.

Adult↗

PubMed1993

Opioid-dopaminergic interactions in primary empty sella.

Previous studies have indicated different abnormalities of PRL secretion in patients with primary empty sella (PES). Since it is known that endogenous opiates and dopamine interact in modulating PRL secretion, we have studied the effect of an opiate receptor blockade (with Naloxone, NAL, 1.6 mg/h as a continuous infusion) on anterior pituitary hormones and on PRL responsiveness to metoclopramide (MCP), in 10 premenopausal normoprolactinemic patients with PES, studied in follicular phase, in order to investigate neurotransmitter abnormalities present in such a syndrome. NAL failed to significantly affect LH and FSH basal levels; on the contrary, slight but significant increases in PRL and GH secretion were observed. NAL partially blunted the PRL responsiveness to the dopaminergic blockade, which was very marked when tested after MCP alone. These data confirm that the modulation of anterior pituitary hormone secretion is different in PES patients, when compared with normal subjects. The infusion of NAL induced a "paradoxical" increase in hormones (PRL and GH) which are normally stimulated by endogenous opiates; but, on the other side, it blocked the marked PRL responsiveness to the dopaminergic blockade, which is characteristic of PES syndrome. This phenomenon seems to indicate that the relationships between dopaminergic and opiatergic neurons could be modified by the neuroanatomic alteration which is present in this complex syndrome.

Adult↗

PubMed1993

Pyridostigmine effects on TSH response to TRH in adult and children obese subjects.

Thyrotropin releasing hormone (TRH) administration is known to induce a greater TSH response in normal subjects than in obese subjects. In obesity even GH and PRL response to various stimuli are blunted, presumably because of an augmented somatostatinergic tone in obese subjects. Further studies have shown that pyridostigmine (Pyr), an acetylcholinesterase inhibitor, is capable of augmenting GH in obesity by means of somatostatin inhibition. In order to evaluate the possible interference of an increased somatostatinergic tone on TSH secretion, we studied the TSH response to a TRH bolus in 5 obese children with or without a pyr pretreatment. Similarly, we tested a group of 10 obese adult subjects, with TRH alone or TRH plus pyr administration, 30 min or 60 min before TRH. All subjects had a body weight of 30-50% greater than I.B.W. Our data show that a pretreatment with pyr, 60 min before TRH administration, significantly augments the TSH response in adult obese subjects but not in children; the modality of pyr administration seems to be crucial to evidenciate such an alteration since the pyr pretreatment is not effective when administered 30 min before TRH. The absence of this pyr effect in obese children induces to hypothesize that somatostatinergic tone is differentially modulated in children vs adult obese subjects.

Adolescent↗

PubMed1993

Endoscopic treatment of upper gastrointestinal tract malignancies.

Palliative endoscopic treatment of the upper gastro-intestinal (UGI) tract includes: dilation, Nd:YAG laser photocoagulation and intubation, used alone or in combination. These procedures are usually performed on an outpatient basis and are associated with a low rate of morbidity and mortality. From 1978 to 1992, 836 patients were treated at the Endoscopy Division of the Istituto Nazionale Tumori, Milan, for inoperable primary or recurrent malignancies of the UGI-tract. Recanalization was obtained in 96% of patients treated; functional results have been computed according to the site and to the endoscopic method. Overall median survival was 6.2 months. The complication rate was 8%. Relief of dysphagia is the goal of palliative treatment in patients with inoperable neoplasms of the UGI-tract.

Aged↗

PubMed1993

Influence of adriamycin dose in the outcome of patients with osteosarcoma treated with multidrug neoadjuvant chemotherapy: results of two sequential studies.

The results of two sequential studies of neoadjuvant chemotherapy for osteosarcoma of the extremities performed at Rizzoli Institute between 1986 and 1991 in 228 patients are presented. In both studies preoperative chemotherapy consisted of two cycles of high dose methotrexate (HDMTX), cisplatinum (CDP) and adriamycin (ADM). Postoperatively the good responder patients were treated with the same drugs used before surgery while in the poor responder patients ifosfamide was added to these three drugs. The preoperative treatment was the same in both studies while after surgery in the second protocol either the cumulative dose of ADM (270 mg/m2 instead of 360 mg/m2) or the single dose per cycle of this drug (60 mg/m2 instead of 90 mg/m2) was reduced. These changes in the last protocol were done to reduce the cardiotoxicity of ADM that was high in the first study (2 deaths and 1 heart transplantation). Since in the last protocol--in comparison with the first protocol--after surgery chemotherapy was restarted earlier and ADM was administered not as a single drug but in combination with the CDP the dose intensity of ADM was unchanged while the dose intensity of MTX, CDP and ifosfamide was higher than in the first study. The preliminary results of the 84 patients treated in the second study show a 2-year disease free survival significantly lower than that achieved in the 144 patients treated in the first study (37/51--73% vs 123/144--85%: P < 0.008). In addition, even if in the last study there were no cases of clinical cardiotoxicity due to ADM, there was a significantly higher percentage of severe myelodepression that led to two deaths for infectious complications. These results suggest that in neoadjuvant treatment of osteosarcoma the total dose of ADM and/or the single dose per cycle of the same drug are an important determinant of outcome and that increasing the dose-intensity of less toxic but less active agents, MTX, CDP and ifosfamide, at the expense of the more active and more toxic agent, ADM, can lead to a poorer outcome without reducing toxicity.

Adolescent↗

PubMed1993

A cohort study on mortality among wives of workers in the asbestos cement industry in Casale Monferrato, Italy.

The study investigates mortality from cancer and other diseases in a cohort of wives of asbestos cement workers in Casale Monferrato (northwest Italy). After the exclusion of women with an occupational record in the asbestos cement industry, the cohort comprised 1964 women. Their domestic exposure was estimated according to their husbands' periods of employment in the plant: 1740 had a period of domestic exposure whereas the remaining 224 married an asbestos cement worker only after he definitely stopped his activity in the asbestos cement plant; these have, therefore, been considered as unexposed. The cohort of wives was constructed entirely through official records in the town offices and is both exhaustive and unaffected by recall bias. At the end of follow up (1988) 1669 women were alive, 270 were dead and 25 (1.2%) were untraced. Main mortality analyses were only up to age 79 to reduce the misclassification of causes of death. Expected mortality was based on local rates. Mortality analyses were limited to the period 1965-88 due to the availability of local rates: in that period 210 deaths occurred among women with domestic exposure v 229.1 expected. There were four deaths from pleural tumours (one diagnosed as mesothelioma at necropsis) and six from lung cancer v. 0.5 and 4.0 expected respectively. Two further cases of mesothelioma were diagnosed by histological examination after the end of follow up. None of the three wives with histologically diagnosed mesothelioma had been engaged in industrial activities. Corresponding information for the other three cases could not be traced.

Adult↗