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Biomedical subjects

A Brocchieri

Publications and source records attributed to A Brocchieri.

12 recordsLinked to original sources

Hypophyseal non-Hodgkin's lymphoma presenting with diabetes insipidus: a case report.

We report the case of a 64 year old male patient with a history of ischemic heart disease who underwent surgery for an abdominal mass. The histological diagnosis was highly malignant non-Hodgkin's lymphoma. After surgery the patient was admitted to our Department and received 6 courses of chemotherapy according to the COP schedule, followed by radiotherapy to the left upper abdominal region and ipsilateral lung base. The patient achieved partial remission. One month later he began to complain of left axillary lymphadenomegaly, polydipsia and polyuria. A NMR brain scan showed a hypophyseal mass. The patient was treated with DDAVP and chemotherapy with the PRO-MACE protocol; the polyuria and lymphadenomegaly disappeared and the size of the hypophyseal mass reduced markedly. The clinical picture was, therefore, attributed to a hypophyseal localization of the non-Hodgkin's lymphoma, which is a very rare manifestation of lymphomatous spread to the central nervous system. Our case is also interesting because it shows that a favorable outcome can be obtained with chemotherapy, provided that the latter is sufficiently aggressive. This is not necessarily the case with radiotherapy which may also be followed by late and severe neurologic sequelae.

Antineoplastic Combined Chemotherapy Protocols↗

Bombesin, calcium homeostasis and tumour growth.

Bombesin and its analogues are a family of naturally occurring neuropeptides with potent mitogenic activity. The ability of this agent to induce Ca2+ transients is likely to be relevant in this context, but it is not yet clear whether the effect of bombesin on cell growth is directly and exclusively related to its capacity to increase cytoplasmic Ca2+ levels. The present study investigates the affect of bombesin on cytoplasmic Ca2+ concentrations in human tumour cells of different origin: lung adenocarcinoma, lung adenocarcinoma with properties of alveolar epithelial cells (A549 cell line), mesothelioma and uterine carcinoma (HeLa cell line). Furthermore, the ability of bombesin to promote the in vitro growth of the same cells has been analysed. This agent was able to induce a transient rise in cytoplasmic Ca2+ levels in tumour cells from all lines. In lung adenocarcinoma cells, but not in the other tumour cells, bombesin produced Ca2+ transients followed by a moderate but sustained elevation of Ca2+ levels. The effects of bombesin on tumour cell cytoplasmic Ca2+ levels were compared to those of other agents, i.e. adenosine diphosphate (ADP), collagen or thrombin, which have been reported to induce Ca2+ transients in tumour cells. Bombesin and ADP increased cytoplasmic Ca2+ levels in all cell lines, while collagen and thrombin gave rise to higher transients, but were effective only in some tumour cells and not in others. Furthermore, bombesin was able to stimulate in vitro growth of all the tumour cells, except for the A549 cells, in which this agent induced a slightly lower increase in cytoplasmic Ca2+ concentration. These data may aid a better understanding of the complex relationship between the Ca2+ mobilizing and mitogenic activities of bombesin and may be of general interest when considering the biological effects of growth-stimulating factors.

Bombesin↗

Platelet derived growth factor and subarachnoid haemorrhage: a study on cisternal cerebrospinal fluid.

Platelet derived growth factor (PDGF) was identified as a powerful mitogenic growth factor which is released from activated platelets and has a marked activity as vasoconstrictor agent. In the present study we have measured cisternal cerebrospinal fluid (CSF) levels of PDGF in 72 patients operated on for intracranial aneurysm in order to verify whether it might be related to the clinical aspects of SAH with special regard to symptomatic vasospasm. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern the nearest to the aneurysm before aneurysm isolation and exclusion. The specimen were frozen in liquid nitrogen and stored at -80 degrees C until analysis. PDGF was measured using a commercially available reagent. Values are expressed as pg/ml of CSF. In 18 cases no radiological and clinical signs of SAH were detected and the mean cisternal CSF level of PDGF was 885.0 +/- 104.5 pg/ml; 20 patients were operated on between day 1 and 3 from the last SAH episode: mean cisternal CSF level of PDGF was 1917.5 +/- 459.4 pg/ml. In 34 patients treated with delayed surgery protocol, mean cisternal CSF level of PDGF was 995.3 +/- 73.8 pg/ml. Statistical analysis showed significant differences between groups (P: 0.011). In the subgroup of patients operated on within day 3 after SAH, 6 presented vasospasm and had mean cisternal CSF PDGF level which was significantly higher (P < 0.01) than in 14 patients without vasospasm. In the delayed "surgical" patients there was no significant difference in cisternal CSF levels of PDGF considering the occurrence of vasospasm. The results of the present study suggest that (a) after SAH there is a significant release of PDGF early after SAH and (b) higher levels of PDGF found in cisternal CSF of patients operated on within 72 hours after SAH may be predictive of symptomatic vasospasm.

Adult↗

[Levels of different metabolites of arachidonic acid in synovial fluid of patients with arthrosis or rheumatoid arthritis].

OBJECTIVE: Clinical and experimental evidence suggests that arachidonic acid metabolism through lipoxygenase and cyclooxygenase pathways may play an important role in the pathogenesis of both inflammatory and degenerative joint diseases. The aim of the present paper was to measure the levels of different arachidonate metabolites in arthrosis or rheumatoid joint effusions. MATERIALS AND METHODS: We studied synovial fluids from 22 patients with arthrosis and 8 patients with rheumatoid arthritis. The levels of TxB2, 6-keto-PGF1 alpha LTB4 and LTC4 were measured by radioimmunoassay. RESULTS: The levels of the different arachidonate metabolites were higher in patients with rheumatoid arthritis than in those with arthrosis and the differences were always statistically significant, except for TxB2 values. Furthermore, in patients with arthrosis the levels of such metabolites were not significantly correlated with one another, with the exception of LTB4 and LTC4 values, while in patients with rheumatoid arthritis these levels were directly and significantly correlated. CONCLUSIONS: In inflammatory joint disease levels of arachidonate metabolites are higher and more directly correlated with one another than in degenerative joint disease. Our data may explain the better efficacy of non-steroidal anti-inflammatory drugs in patients with arthrosis than in those with rheumatoid arthritis and the frequent necessity for steroidal treatment in this last condition.

6-Ketoprostaglandin F1 alpha↗

[Familial combined hyperlipidemia with particularly severe and premature arteriosclerotic lesions. Description of a case].

The case is reported of a 44 year old male patient admitted to our Department for left pyramidal hemisyndrome. Familial anamnesis was positive for premature cardiovascular complications and the patient, who was a heavy smoker, had suffered from arterial hypertension and claudicatio intermittens for 10 years. Laboratory investigations showed increased plasma levels of triglycerides, cholesterol and apolipoprotein B, with a sharp decrease in apo A/apo B ratio. Ultrasound and angiographic scans showed severe and diffuse atherosclerotic lesions. A diagnosis was made of familial combined hyperlipidemia and treatment was begun with simvastatin, which produced a progressive normalization of lipidic picture, without any effect of the symptoms related to lower limb occlusive arteriopathy. Two apparently healthy sisters of the patient have also been studied. The first was found to be affected by familial combined hyperlipidemia with isolated increase in cholesterol plasma levels, the second was perfectly normal. This case demonstrates that subjects with similar alterations in lipidic metabolism may present with completely different clinical pictures, even within the same inherited disorder. Different hypotheses are discussed to explain the particularly severe and precocious atherosclerotic lesions of our patient: sex, smoking habit and arterial hypertension, which would have been caused, at least in part, by the observed congenital malformation of renal circulation.

Adult↗

Verapamil inhibits to different extents agonist-induced Ca2+ transients in human tumor cells and in vitro tumor cell growth.

Platelet agonists are known to contribute to the regulation of cytoplasmic Ca2+ levels in tumor cells and this property could be relevant in the stimulation of cell proliferation. In the present study we investigated the ability of ADP, collagen and thrombin to increase cytoplasmic Ca2+ levels in different human tumor cell lines (mesothelioma, DND-1A melanoma, HeLa uterine carcinoma) and we analyzed the effect of the calcium channel blocker verapamil on Ca2+ fluxes and on in vitro tumor cell growth. ADP was able to induce a transient increase in the cytoplasmic Ca2+ concentration in tumor cells from all lines; collagen showed this effect in mesothelioma cells and in HeLa cells, and thrombin was effective only in mesothelioma cells. Verapamil inhibited Ca2+ fluxes induced by the effective agonists in a dose-dependent manner. Values of IC50 for inhibition of ADP-induced Ca2+ transients were 63.5 microM in mesothelioma cells, 97.3 microM in DND-1A cells and 93.5 microM in HeLa cells, while those for inhibition of collagen-induced Ca2+ movements were slightly higher (170.2 microM in mesothelioma cells and 112.3 microM in HeLa cells) and the value of IC50 for inhibition of thrombin-induced Ca2+ fluxes (evaluated only in mesothelioma cells) was lower (22.5 microM). The drug dose-dependently also inhibited the in vitro growth of tumor cells; values of IC50 for growth inhibition were 21.8 microM in mesothelioma cells, 9.1 microM in DND-1A cells and 6.4 microM in HeLa cells, suggesting that the antiproliferative activity of verapamil was partly Ca(2+)-independent. These data may be of interest to elucidate the mechanisms of the two-way interactions of tumors with the hemostatic system and may help to identify new pharmacologic strategies for their control.

Adenosine Diphosphate↗

Effect of different platelet agonists on intracellular free Ca++ concentrations in human tumor cells: possible role in tumor growth.

Modulation of cytoplasmic Ca++ concentration is a mechanism common to signal transduction pathways regulating many cellular phenomena, including the interactions of tumors with the hemostatic system. We have investigated the pro-aggregating and pro-coagulant activities of human tumor cell lines cultured in vitro and the ability of different platelet agonists to induce Ca++ transients in these cells. Cells of a malignant mesothelioma line activated platelets by a thrombin-dependent mechanism; on the contrary, HeLa cells, derived from a uterine cervical cancer, possessed ADP-dependent pro-aggregating activity, and DND-IA melanoma cells did not stimulate platelet aggregation. All cell lines showed a tissue-factor-like procoagulant property, more pronounced in mesothelioma cells. Furthermore, ADP was able to induce a transient increase in cytoplasmic Ca++ concentration in tumor cells from all lines; collagen showed this effect in mesothelioma cells and in HeLa cells, and thrombin was effective only in mesothelioma cells. PAF never induced Ca++ fluxes in any of the cell lines investigated. Finally, the calcium-channel blocker verapamil inhibited agonist-induced Ca++ transients in tumor cells and in vitro tumor-cell growth. These data may help to identify new possible mechanisms of the 2-way interaction of tumors with the hemostatic system.

Adenosine Diphosphate↗

In vitro effect of bombesin-related peptides on the procoagulant activity of alveolar macrophages.

Bombesin-related peptides (BRP) are present in the lung during foetal life and are mitogenic for normal bronchial epithelial cells, pulmonary fibroblasts, and small-cell lung carcinoma cell lines. Increased levels of BRP have been described in the adult lung of cigarette smokers and in smoking related lung diseases. BRP have also been involved in the network of neuroimmune interactions, having been shown to modulate the phagocytic function of monocytes and alveolar macrophages. BRP have recently been shown to modulate the release of procoagulant activity (PCA) by human monocytes and alveolar macrophages after a 24 h culture. The aim of this study was to evaluate the effect of bombesin on cell-associated PCA of alveolar macrophages (AMs) obtained from asymptomatic subjects. In basal conditions, AMs were found to possess a low procoagulant activity, that was not affected by their preincubation (4 h at 37 degrees C) with phorbol myristate acetate (1 microgram-mL-1). On the contrary, endotoxin (lipopolysaccharide (LPS)) induced a significant increase of procoagulant activity of macrophages when used at a concentration of 1 microgram.mL-1, in the same experimental conditions; whilst a lower (1 ng.mL-1) concentration of LPS nonsignificantly enhanced cell-associated PCA. Treatment of AMs with synthetic bombesin (BN) alone (10(-6) to 10(-10) M) did not enhance cell-associated PCA, whilst a significant effect was seen when BN was added to the lower concentration of LPS (BN 10(-6) M+LPS 1 ng.mL-1: 12.6 U.10(-6) cells; LPS alone 1 ng.mL-1: 7.8 U.10(-6) cells).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Factors↗

Current concepts in coronary thrombolysis.

Thrombolytic therapy has become standard care in treating acute myocardial infarction. Fibrinolytic drugs such as streptokinase, APSAC and urokinase are non fibrin specific, and induce systemic activation of the fibrinolytic process, while t-PA and prourokinase are fibrin specific since they are able to activate mainly fibrin bound plasminogen. Both groups of thrombolytics exert different and opposing effects on the hemostatic balance: indeed, they have antithrombotic as well as prothrombotic properties, and this may be important for explaining therapeutic failures or reocclusions. New strategies have been considered or are under investigation for further improving the already excellent efficacy of thrombolytic treatment in myocardial infarction: combined administration of fibrinolytic agents, thrombus-targeted thrombolytic drugs, association with other drugs both effective and ineffective on the hemostatic process. At present, however, the first priority still seems to be a continuing effort to increase the percentage of patients treated with thrombolytics, since the benefits of this therapy have already been clearly demonstrated.

Humans↗

[Neurocysticercosis and epilepsy. Description of a clinical case].

Since 1985 infection by suin tapeworm Taenia Solium seems to have disappeared in Italy, but patients may still exist which have contracted many years ago the disease that has followed its natural course. We report the case of an Italian, 50 year-old-man with neurocysticercosis presenting with generalized seizures. CT and MR showed typical calcific and cystic lesions in the brain. Rx scans of muscles revealed the presence of fusisorm calcific lesions suggestive for cysticercosis and the serum levels of specific antibodies confirmed the diagnosis. The patient was treated with albendazole with no regression of cerebral lesions after one month, but simultaneous treatment with antiepileptic drugs was able to control completely neurologic symptoms.

Brain Diseases↗

Effect of interferon alpha, interferon gamma and tumor necrosis factor on the procoagulant activity of human cancer cells.

BACKGROUND: It is not known whether the different cytokines may influence the procoagulant activity of cancer cells; the purpose of this study was to investigate the effect of interferon alpha, interferon gamma and tumor necrosis factor on the procoagulation capacity of human cancer cells cultured "in vitro" or isolated from tumor tissues. METHODS: "In vitro" cultured tumor cell lines were derived from a patient with malignant mesothelioma and a patient with lung adenocarcinoma. Cells isolated from 6 carcinomas of different origin were also investigated. The procoagulant activity of the cells before and after treatment with the cytokines was expressed as RBT U/10(5) cells or RVV U/10(5) cells. RESULTS: Short-term incubation of tumor cells cultured "in vitro" with cytokines did not modify their procoagulant activity; after longer incubation however, interferon alpha induced a significant increase in the procoagulant activity of mesothelioma cells, while interferon gamma induced and increase in the procoagulant activity of lung adenocarcinoma cells. Furthermore, short-term incubation of cells isolated from tumor tissues with interferon gamma or tumor necrosis factor resulted in a significant increase of procoagulant activity, while interferon alpha had no effect. CONCLUSIONS: Altogether, these data demonstrate that the cytokines may influence the expression of the different procoagulant activities of tumor cells.

Blood Coagulation↗