Pietro Paoletti

Cerebral tumors induced by transplacental ENU: Study of the different tumoral stages, particularly of early proliferations

SummaryExperimental cerebral tumors have been induced by transplacental ENU. A systematic diachronic study of the brains has been performed starting from the 15th day of extrauterine life. The tumoral lesions firstly appear as “early stage proliferations” or oligodendroglial foci and develop as glial micro-and macrotumors or as isomorphic and polymorphic oligodendrogliomas respectively.Neurinomas appear later than glial tumors.The duration of the different lesions is sketched out. The usefulness of the model for chemotherapy studies is discussed.

Experimental brain tumors by transplacental ENU - Multifactorial study of the latency period

SummaryExperimental cerebral tumors have been induced by transplacental ENU. The morphologic study of the brains of treated rats revealed that cellular hyperplasias appear at the 30th day of extrauterine life in the paraventricular white matter, i.e., before the already known “early neoplastic proliferations”. Cytofluorimetric investigations failed to demonstrate differences between treated and control rats during the 1st month. On the contrary, adenylate cyclase activity is very high in that period. The duration of the latency period is discussed.

Multiple meningiomas: A clinical, surgical, and cytogenetic analysis

Eight cases of multiple meningiomas were found in our 13-year series of 148 operated meningiomas. The relative frequency, 5.4%, of multiple meningiomas observed is compared with that in the literature. The clinical presentation, surgical results, and diagnostic tools are discussed. Cytogenetic analysis was performed in five patients (eight neoplastic specimens). No specific abnormality for multiple meningiomas was found, but our results point out the different origin of each tumor and exclude cell migration through the subarachnoid space as a pathogenetic factor in multiple meningiomas.

Bioenergetics of different brain areas after experimental subarachnoid hemorrhage in rats.

We studied energy metabolism after experimental subarachnoid hemorrhage in rats. Four different cerebral areas were tested: frontal cortex, occipital cortex, hippocampus, and brainstem. Vmax of the following enzymatic activities was evaluated: in the homogenate: hexokinase, phosphofructokinase, and lactate dehydrogenase for the glycolytic pathway, and glucose-6-phosphate dehydrogenase for the hexose monophosphate shunt; in the purified nonsynaptic mitochondria: NAD+-isocitrate dehydrogenase, citrate synthase, and succinate dehydrogenase for the Krebs cycle, and cytochrome oxidase for the electron transfer chain. We also evaluated some parameters related to the respiration of nonsynaptic mitochondria (State 3, State 4, uncoupled state, respiratory control ratio, and ADP:O ratio). Subarachnoid hemorrhage did not significantly affect Vmax of the enzymatic activities related to anaerobic and aerobic metabolism; however, mitochondrial respiration was affected, particularly in the presence of NADH-producing substrates (glutamate + malate).

Decreased high density lipoprotein-cholesterol levels in male patients with transient ischemic attacks

Plasma lipid and lipoproteins levels were determined in a continuous series of 50 patients (36 males and 14 females), mean age around 50 years, with a clinical diagnosis of transient ischemic attacks (TIAs). TIA was defined as a sudden episode of focal cerebrovascular insufficiency, with complete resolution of the symptoms within 24 h. TIAs are considered an important prognostic symptom for ischemic cerebrovascular diseases, being manifest in approximately 45% of the patients later undergoing a complete stroke. Plasma total cholesterol levels did not differ in these patients, when compared with a similar series of patients of the same age and sex, free of cerebrovascular lesions. A slight elevation of mean triglyceride levels was detected in the patients of both sexes, as well as higher incidence of type IV hyperlipoproteinemia. The most significant finding, however, observed only in male TIA patients, was that of significantly reduced high density lipoprotein (HDL)-cholesterol levels. This reduction (-19.7% compared to the control group) is similar to that recently reported for patients with clear-cut ischemic cerebrovascular disease. The detection of decreased HDL-cholesterol levels in male TIA patients may be of considerable significance for a prognostic evaluation of this biochemical parameter.

Cell kinetics of human brain tumors: in vivo study with bromodeoxyuridine and flow cytometry

Bromodeoxyuridine (BUDR) is a thymidine analog which is incorporated into the DNA of proliferating cells. Since the dose of BUDR needed to label cells is not toxic, cell labelling can be accomplished in vivo, by infusing the substance in patients. A monoclonal antibody against BUDR is then used to identify BUDR-labelled cells. The same cell population can also be stained for DNA content with propidium iodide (PI). Using bivariate flow cytometry (FCM) for measurements, both the percentage of BUDR-labelled cells and their total DNA content can be evaluated. This technique allows one to obtain the labelling index (LI) and the DNA synthesis time (TS). The potential doubling time (Tpot) and the fractional turnover rate (FTR) can be mathematically derived, so that a complete picture of tumor growth can be obtained. Our aim was to ascertain whether this method is clinically applicable and whether the kinetic values obtained are reliable. We studied 22 patients with benign and malignant brain tumors, and observed no immediate toxicity from BUDR administration. The BUDRLI obtained ranged from 0.9% to 3.9% (median: 2.0%) in meningiomas and from 3.8% to 7.6% (median: 6.3%) in malignant gliomas (P less than 0.01). The fraction of S-phase cells determined with the BUDR FCM technique was statistically similar to that found by single DNA flow cytometric analysis performed on duplicate samples of both benign and malignant brain tumors. The TS obtained in malignant gliomas ranged from 10.5 to 227 h (median: 12.8). The calculated Tpot ranged from 7.6 to 26.8 days (median: 11.6), and the calculated FTR ranged from 3.7 to 13.1 cells/100 cells/day (median: 8.8). These data suggest that in vivo BUDR infusion coupled with FCM can be performed in clinical settings, and it is reliable and can easily be used for kinetic studies in clinical trials aimed at evaluating the prognostic relevance of proliferative parameters and in planning tumor treatment.

Multiple primary intracranial tumors of different cell types: Association of anaplastic astrocytoma and acoustic neurinoma — with review of the literature

Abstract We describe the case of a patient who had a right acoustic neurinoma and a right temporal anaplastic astrocytoma that were diagnosed and operated on 7 months apart. Reports of 2 other cases of neurinomas associated with a glioma appear in the literature; neither of these 2 patients underwent surgical intervention for either of their tumors. In a careful survey of the literature, we encountered 86 cases of multiple primary intracranial tumors of different cell types. Clinical presentations and locations and types of tumors are discussed.

Arachidonic acid metabolic profiles in human meningiomas and gliomas

We determined arachidonic acid (AA) cyclooxygenase metabolic profiles in specimens of human intracranial tumors (gliomas and meningiomas) and, when available, normal brain tissue. Samples were collected at surgery and immediately frozen in liquid nitrogen. The five stable metabolites of AA (PGE2, PGD2, PGF2α, 6-keto-PGF1α and TXB2) were measured by high-resolution gas chromatography-mass spectrometry after ex vivo metabolism of endogenous AA by tissue homogenates. The absolute amounts of AA metabolites varied widely between samples, though meningiomas and gliomas showed characteristic profiles. Compared to the slow-growing benign meningiomas, the rapidly-growing infiltrating gliomas had higher synthesis of TXA2 (reported as a procancer metabolite) and lower synthesis of PGD2 and PGI2 (reported as anticancer metabolites). A higher overall synthesis capacity, preferentially toward TXA2, was found in glioblastomas than in nonpathological brain tissue.

Meningiomas of meckel's cave

Meningiomas of Meckels cave are unusual. Forty-six cases of this tumor are described in the literature and two others are reported in this paper. Symptomatology frequently begins with typical or atypical trigeminal neuralgia; when no other signs are associated, diagnosis of the tumor is difficult. Total removal of the tumor results in a complete relief of symptoms, and no other therapy for pain is necessary.

Radio- and chemotherapy of malignant gliomas. Pathological changes in the normal nervous tissue

SummaryThe pathological effects of radio- and chemotherapy on the normal nervous tissue have been studied in 42 brains with malignant gliomas. The brains have been examined by means of the complete study technique. In seven cases the picture of delayed radionecrosis has been found. Apart from this, many histological features have been related to post-operative survival, radiation dose, interval between radiation and death, chemotherapy, steroids, size and activity of the tumour. Some alterations, such as peritumoural necroses, macrophage areas, vessel wall degenerations etc. result from radiotherapy. The relations and pathogenesis are discussed.