Platelet monoamine oxidase and serum dopamine-beta-hydroxylase activities in psychotic patients.
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Biomedical subjects
Publications and source records attributed to M Del Vecchio.
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Twenty-six, respectively twenty-three untrained Italian doctors participated in the rating of two patients with a preliminary Italian version of the CPRS. Despite an unfavourable setting, and some linguistic inaccuracies in the translation, a quite satisfactory degree of agreement was reached among the doctors. The Italian version of the CPRS has now been rewritten using a terminology more familiar to Italian psychiatrists.
In order to study the HL-A antigen turnover in vivo, the HL-A reactivities of the lymphocytes of eight blood donors were tested every week for six weeks with antisera HL-A1, 2, 3, 5, 7, 8 and 11. The analysis of variance showed that the "time" effect and the "time times donors" interaction were statistically significant for the HL-2, 3, 5 and 11 specificities. This supports the hypothesis that phenotypic expression of such antigens on the lymphocyte membrane of some of the blood donors examined varied with time. From a practical point of view, the HL-A antigenic fluctuation with time should be taken into consideration when lymphocyte typing is required for tissue transplantation.
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BACKGROUND: The association of 5-fluorouracil (5-FU) and leucovorin is currently the most used combination in the treatment of advanced gastrointestinal neoplasms. Doxifluridine (d-FUR) is a fluoropyrimidine derivative that is converted into 5-FU inside tumor cells, where it is selectively cytotoxic. The oral administration of dFUR has been extensively investigated in colorectal carcinoma, and has been proven to be active and well tolerated. The purpose of this study was to test the effectiveness of the oral combination with dFUR plus l-leucovorin in gastric and pancreatic cancer patients. METHODS: A total of 50 cases were treated with l-leucovorin 25 mg, followed 2 h later by d-FUR 1,200 mg/m2 for 5 days; the cycles were repeated every 10 days. The regimen was given for a maximum of 36 cycles or until disease progression. Twenty-six patients had gastric cancer (all of whom were pretreated with polychemotherapy) and 24 had advanced pancreatic carcinoma. RESULTS: Objective responses were obtained in 4 (15%; 95% Cl 1-29) patients with gastric cancer, and in 1 (4%) with pancreatic cancer. The median response duration was 4 months. All of the responses were seen in patients previously treated with 5-FU-containing regimens. The median survival in gastric cancer patients was 7 months. Toxicity was moderate: WHO grade III and IV diarrhea was observed in 14% of the cases. CONCLUSIONS: This study indicates the efficacy of oral d-FUR plus l-leucovorin as palliative treatment in gastric cancer patients. The results in pancreatic carcinoma are disappointing but are in line with the published data relating to fluoropyrimidines.
AIMS AND BACKGROUND: This trial evaluated the feasibility and tolerability of an immunochemotherapeutic approach that uses cisplatin, vindesine, and dacarbazine (DTIC), or only DTIC, in combination with interferon alpha-2a (IFN-alpha), in patients with metastatic melanoma, considering the significant toxicity of several different regimens used up to now. METHODS: Between May 1995 and September 1997, 51 melanoma patients (50 of whom were assessable) entered a multicentric trial and were randomized to receive cisplatin (30 mg/m2 daily for 3 days) + vindesine (2.5 mg/m2 only day 1) + DTIC (250 mg/m2 daily for 3 consecutive days) + IFN-alpha (3 MIU i.m. 3x/wk continuously) (CVD arm) versus DTIC (800 mg/m2 day 1) + IFN-alpha (3 MIU i.m. 3x/wk continuously) (DTIC arm). The chemotherapy was recycled every 21 days. Patient reevaluation was performed every two cycles, and the treatment was continued in case of objective response or stabilization of disease. RESULTS: We observed 3 complete responses, 2 partial responses and 5 stable diseases in the CVD arm, and 2 partial responses and 4 stabilizations of disease in the DTIC arm. CONCLUSIONS: We conclude that these chemotherapeutic regimens are well tolerated regimens with modest toxicity. Future trials will be conducted associating the CVD regimen with biological response modifiers (IFN, IL-2) in order to improve the results.
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Preoperative differential diagnosis of a swelling in the neck is mandatory for a good therapeutic planning. Indiscriminate biopsy as first approach is to be disregarded, since it can compromise the result of a radical neck dissection in cases where a metastasis of epidermoid cancer is histologically recognized. A cervical biopsy is not to be performed until a complete HNT examination (including the thyroid and major salivary glands) has excluded the presence of a primary tumor in these regions. Since every localization of the head and neck malignancies shows rather fixed patterns in its lymphatic spreading, a correlation between site of T and particular localizations of N within the neck can be found. The knowledge of the probabilities that an adenopathy in a given region of the neck correlates with a primary tumor located in a given site of the body could strongly aid the physician in detecting the latter, following a rational statistically based approach. This study was performed applying Bayes theorem for probability calculus to the maps of distribution of metastases of tumors of different site in 3,700 patients who were taken into National Cancer Institute of Milan during 7 consecutive years. The results are gathered in tables and text-figures showing the great significance of some correlations, who become more evident when the adenopathies are multiple, but who usefully direct the physician also when the adenopathy is only one.
BACKGROUND: Fenretinide (4-HPR) is a synthetic retinoid being clinically tested in the chemoprevention of different tumors and precancerous lesions. Though safer than many other retinoids in experimental models, in humans 4-HPR may induce adverse effects that mainly affect the eye and visual function. Such effects are thought to be caused by the reduction of plasma retinol levels, which occurs after administration of the retinoid. METHODS: A series of 826 women treated with 4-HPR was studied to quantify the incidence and temporal pattern of occurrence of visual (dark adaptation) and ophthalmologic complaints (ocular dryness, lacrimation, conjunctivitis or photophobia) and to investigate the possible association between their occurrence and plasma retinol levels. RESULTS: The cumulative incidence of visual complaints reached nearly 20% at 5 years. The occurrence of these symptoms was more frequent at the start of treatment. The probability of developing visual complaints was significantly higher in patients with lower plasma retinol concentrations following 4-HPR treatment. The cumulative incidence of ophthalmologic complaints was 8% at 5 years. The occurrence of these complaints was evenly distributed during treatment. Ophthalmologic complaints were not associated with a greater degree of reduction of plasma retinol concentrations, but rather with the patient's age, since symptomatic patients were generally older than asymptomatic patients. CONCLUSIONS: Visual and ophthalmologic complaints are common during 4-HPR treatment; their estimated 5-year cumulative incidence is close to 20% and 8%, respectively. However, the pattern of occurrence over time and the underlying mechanisms of these two types of complaints seem different.
The Fenretinide (4-HPR) Breast Cancer Study is a randomized multicenter clinical trial originally designed and conducted by the investigators of the Istituto Nazionale Tumori of Milan. The study is sponsored by the National Cancer Institute of Bethesda and by the Italian National Research Council. The trial was designed to evaluate the effectiveness of the synthetic retinoid 4-HPR, at a dose of 200 mg per os every day for 5 years, in reducing the incidence of contralateral breast cancer in a population of patients previously operated on for breast cancer. Between 1987 and 1993, the Istituto Nazionale Tumori of Milan and 9 other collaborating Centers enrolled 2,972 women between the ages of 30 and 70 years who had been previously operated on for T1-T2 N- M0 breast cancer. This paper describes the rationale, design, methodology, organization, data management, statistics and accrual of the participating population.
AIMS AND BACKGROUND: The incidence of malignant melanoma is rapidly increasing in many countries, and when this disease has reached advanced stages, standard therapies have little impact. Dacarbazine (DTIC) is the most effective chemotherapeutic agent with an overall response rate of 20-25%, but durable responses are uncommon. Interesting results with the use of cisplatin (CDDP) have been reported in DTIC-resistant melanoma. Moreover, malignant melanoma is an immunogenic tumor and a potential target for biological response modifier (BRM) therapies. The aim of the present study was to evaluate the efficacy and tolerability of a chemo-immunotherapeutic regimen including high-dose CDDP combined with glutathione (GSH) to limit platinum-related toxicity, and natura interferon-alpha (IFN-alpha) in patients with DTIC-resistant metastatic melanoma. METHODS: The treatment schedule included GSH 1,500 mg/m2 i.v. and CDDP 40 mg/m2 i.v. for 4 consecutive days every 3 weeks, with a maximum of 6 courses, and IFN-alpha 3 MIU i.m. 3 times a week, continuative for a maximum of 12 months. RESULTS: Twelve patients were enrolled in this phase II trial. Accrual was stopped due to treatment-related toxicity. Ten patients were evaluable for response; there were 2 partial responses, lasting 5+ and 9+ months, respectively, and 2 cases of stable disease, lasting 3+ and 8+ months. None of these patients completed the therapeutic program due to treatment-related side effects. CONCLUSIONS: This regimen seems to be only partially active in DTIC-resistant metastatic melanoma. Hematologic and non-hematologic (nausea and vomiting, peripheral neurotoxicity, and asthenia) side effects are significant and GSH is not effective in limiting CDDP-related neurotoxicity in pretreated patients. Therefore, there is no indication to employ this regimen as second-line treatment in metastatic melanoma and these disappointing results highlight the urgent need for new therapeutic approaches.
The fluoropyrimidine antimetabolites were employed in a wide range of neoplastic diseases. In particular, 5-fluorouracil in association with other chemotherapeutic agents, or biochemical modulators was successfully used in the treatment of colorectal, gastric, breast, head and neck cancers. With this type of chemotherapy, a response rate < or = 20% was obtained in gastrointestinal tumors, without a statistically significant impact on the overall survival. UFT is a combination of tegafur an uracil, which has the important advantage of an improved oral bioavailability, if we compare it with 5-fluorouracil. Uracil, avoiding the fluoropyrimidine degradation inside the tumor cells, increases the permanence of the metabolically active fluoropyrimidine into the target cell, so having an improvement in the therapeutic activity. A very large spectrum of cancers were treated with this molecule. In particular, a response rate in the range of 20-40% was observed in the treatment of patients with metastatic colorectal cancer. Phase III trials are ongoing to evaluate the advantage on 5-FU of this new fluoropyrimidine in terms of clinical efficacy, and quality of life, considering the possibility to administer it orally.
The possibility to administer chemo-hormone- and immunotherapy on an out-patient basis has greatly increased because of the progress reached in the management of the out-patient departments. The improved knowledges on tossicological, pharmacodynamic and therapeutic data as well as the advent of the cyclic schedules determined the feasibility of medical treatments even when they are combined with surgical and/or radiotherapeutic modalities. To the patient, the possibility to be carefully and effectively treated on out-patient clinic, renders more acceptable, both from a psychologic and economic point of view, even a prolonged combined treatment. On the same time, also the Institutions have some advantages both on their organization (a shorter median stay in hospital and consequently a reduced waiting list) and for their scientific program (increased number of patients who can be treated according to a therapeutic program, possibilities to obtain statistically valuable information on the treatment program of a given disease and on the knowledge of its natural history). The last five year increasing activity of the Out-Patient Clinic for Medical Oncology Treatment of the Istituto Nazionale Tumori of Milan is illustrated in Text-figure 1, while Text-figure 2 represents its actual organization; this is obviously of a multidisciplinary type, both on its diagnostic and therapeutic phase. Table 1 shows the activity carried out in 1975; it is noteworthy that 2,570 patients have been followed, thus accounting for a total of 20,164 medical examinations and/or intravenous drug administrations. Table 2 presents the incidence of the different types of neoplasia followed in the out-patient department: the large majority was represented by breast cancer (40%); followed by malignant lymphomas (31.5%) and pediatric tumors (7.5%). During 1975, 22 therapeutic protocols have been applied, 10 of which (table 4) required an initial hospitalization and 12 (table 5) could be entirely carried out in the out-patient department. As shown in Table 6 chest x-rays accounted for 52% and skeletal survey for 18% of the 11.906 radiological examinations. Table 7 shows the number of off-hand required radiological reports carried out for patients not geographically accessible who, in one signle day, could have their radiological, and medical examinations as well as their hemogram and treatment performed. A total 467 scintiscans have been required, 86% of which of the liver (table 8). The hemato-pathology unit counted out about 16,000 hemograms with platelets (table 9). The hemograms were always performed within 1-2 hours with immediate communication of the counts to the out-patient department. In order to modify clinical situations which were deteriorated because either of the disease or of the treatment 358 blood units were transfused.
The growth and progression of solid tumours is dependent on several biological factors, such as tumour angiogenesis, appearance of new genetic alterations and/or the failure of the immune defences of the host. Physicians have dreamed of treating cancer with vaccines since the first vaccines against infectious diseases were developed. The identification and availability of tumour-associated antigens now allows the possibility of eliciting humoral (antibody-mediated) and cell-mediated immunity to be tested, which may result in direct or indirect tumour destruction. Thus cancer vaccines have been constructed in order to activate and amplify the patient's immune reaction against tumour-associated antigens. Recent progress in defining the immunogenic epitopes of tumour antigens and in augmenting their immunogenicity (that is their ability to be recognised by and stimulate the immune system of the host), along with the new information on the mechanisms of tumour antigen presentation, has revolutionised the field of cancer vaccines, initially based on non-specific approaches. This review will briefly focus on the biological basis of the development and the clinical application of a wide spectrum of tumour vaccines.