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Biomedical subjects

P Paoletti

Publications and source records attributed to P Paoletti.

At least 73 records · Page 4Linked to original sources
PubMed1990

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience.

In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours. In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.

Antineoplastic Agents↗
PubMed1990

Carbon monoxide diffusing capacity, other indices of lung function, and respiratory symptoms in a general population sample.

To assess the relationships among single-breath diffusing capacity for CO (DLCOsb) (13), respiratory symptoms, and cigarette smoking in a general population sample, the data of 718 men and 894 women 20 yr of age or older were analyzed, and comparisons were performed with flow-volume curve (MEFV) variables and the slope of the alveolar plateau (DN2%/L) as well. Percent predicted DLCOsb and its correction for alveolar volume (DL/VA) were significantly lower in smokers than in nonsmokers. The relationship of presence/absence of respiratory symptoms and cigarette smoking with DLCOsb and DL/VA was significant. DLCO indices were almost always selected as discriminant variables in multivariate analysis between asymptomatic and symptomatic subjects. Poor concordance among lung function tests was evident: in men, 30% with abnormal (i.e., lower than 97.5% percentile) and 21% with normal DLCO indices also had abnormal MEFV parameters and/or DN2%/L. In women, the corresponding figures were 24 and 10%, respectively. In men, when considering only DLCO indices, the percentage of symptomatic subjects with abnormal lung function tests ranged from 33% in those with at least one symptom to 45% in those complaining of dyspnea. When the proportion of symptomatic subjects with DN2%/L and MEFV abnormalities were added, it increased to 56 and 66%, respectively. However, in women the proportion of symptomatic subjects with abnormal lung function indices was very small. These results indicate the usefulness of including CO diffusing capacity in epidemiologic surveys in the detection of abnormalities.

Adolescent↗
PubMed1990

Natural course of treated pulmonary embolism. Evaluation by perfusion lung scintigraphy, gas exchange, and chest roentgenogram.

Perfusion lung scintigrams, pulmonary gas exchange data, and chest roentgenograms were obtained in 33 patients during acute embolism and over the following six months in order to assess their clinical usefulness in monitoring the effect of therapy. To this purpose, the measurement of pulmonary gas exchange and the presence of chest x-ray findings were compared with perfusion lung scintigraphic abnormalities both at diagnosis and after 7, 30, and 180 days during treatment. More than 50 percent of the pulmonary arterial tree was obstructed at diagnosis, and a large part of perfusion recovery was complete within the first month. All of the gas exchange parameters were abnormal at diagnosis, and the rate of their improvement was related to that of perfusion recovery. Interestingly, PaO2st (ie, PaO2 corrected for hyperventilation) and VE tended to return to normal during the first month as a consequence of the progressive recovery of perfusion, whereas oxygen and carbon dioxide gradients and physiologic dead space showed the persistence of some abnormalities six months after diagnosis. Significant correlations were observed between the number of ULSs evaluated on the perfusion lung scintigram (and considered an index of the severity of pulmonary embolization) and all of the gas exchange parameters at diagnosis (correlation coefficients averaged from 0.41 to 0.73) and after 7 and 30 days. The enlargement of the right descending pulmonary artery and particularly the "sausage" sign and the Westermark sign were significantly associated with a higher degree of gas exchange impairment and with a more severe embolization. In conclusion, this study demonstrates that perfusion lung scintigraphy has a primary role in monitoring the recovery of patients with pulmonary embolism under treatment. Moreover, the chest roentgenogram may help in this purpose. A second major result is that the simple measurement of some gas exchange parameters may allow the assessment of functional recovery of these patients, thus giving additional information about the effect of therapy.

Carbon Dioxide↗
PubMed1990

Bronchoalveolar lavage and morphology of the airways after cessation of exposure in asthmatic subjects sensitized to toluene diisocyanate.

To evaluate the morphologic basis of the different outcomes of toluene diisocyanate (TDI) asthma after quitting occupational exposure, we examined ten patients with TDI asthma who showed, at diagnosis, a positive TDI challenge test and nonspecific bronchial hyperresponsiveness (NSBH) to methacholine. After diagnosis, all patients ceased work and a 4- to 40-month follow-up was obtained with three to eight determinations of the cumulative dose producing a 15 percent fall in FEV1 (PD15FEV1) methacholine in each patient. Bronchoalveolar lavage (BAL) and biopsy of bronchial muscosa were performed 3 to 39 months after cessation of work, in the absence of acute exacerbations of the disease. Total cell count in BAL fluid was moderately increased in four of ten patients, eosinophils were increased in five of ten patients, and neutrophils were increased in eight of ten patients. Mucosal biopsy specimens of main or lobar bronchi were available in eight of ten patients; epithelial damage and thickening of basement membrane was observed in almost all patients, as well as a mild-to-moderate inflammatory reaction in the submucosa, mainly represented by lymphocytes, eosinophils, and neutrophils. No relationship was observed between the cellularity of BAL and the degree of NSBH at the time of BAL; mean values of total cells and differential count were not different between patients with presence or absence of the different histologic findings. Mucosal biopsy and BAL were performed also in four subjects exposed to dusts without respiratory symptoms or NSBH; similar findings were obtained except for the absence of eosinophils in BAL and a lesser degree of basement membrane thickening and inflammatory reaction in the submucosa. The study of the changes in NSBH after quitting exposure showed that five of ten patients had a significant improvement in NSBH to methacholine, as evaluated by a positive significant linear regression between months of work cessation and PD15FEV1 methacholine; only one of these five patients had an increased number of eosinophils in BAL fluid. By contrast, four of the five patients with persistent NSBH after quitting exposure had an increased number of eosinophils in BAL. We suggest that persistent NSBH in TDI asthma after cessation of work may be related to an inflammatory reaction in which eosinophil infiltration seems to be a major determinant.

Adult↗
PubMed1990

Characteristics and biological role of steroid hormone receptors in neuroepithelial tumors.

Tissue samples from 57 patients with neuroepithelial tumors (25 glioblastomas, 18 anaplastic astrocytomas, and 14 astrocytomas) were analyzed in order to evaluate the presence of estrogen, progesterone, glucocorticoid, and androgen receptors. Glucocorticoid- and androgen-specific binding proteins were present in 38.6% and 21.6% of the cases, respectively. Only a few tumors showed estrogen or progesterone receptors. A correlation was found between grade of anaplasia, patient's sex and age, and presence of glucocorticoid and androgen receptors. The biological role of these two receptors was investigated in 10 primary cell cultures derived from neuroepithelial tumors. For this purpose, dexamethasone and testosterone were added to culture medium at different concentrations (from 50 to 0.016 micrograms/ml). A significant stimulation of the cell growth was observed in four of five glucocorticoid receptor-positive cultures when dexamethasone in doses ranging from 2 to 0.016 microgram/ml was added to the culture. No modulation of the growth was observed in glucocorticoid receptor-negative cultures at the same doses. Higher dexamethasone doses induced a significant decrease of the growth index independently from the glucocorticoid receptor status. All of the cultures tested for testosterone activity were negative for androgen receptors. This hormone induced an inhibition of the growth index at doses ranging from 50 to 0.4 micrograms/ml. The data suggest that neuroepithelial tumors contain specific glucocorticoid and androgen binding proteins. Glucocorticoid receptors modulate the growth of cultured neuroepithelial tumors in the presence of different concentrations of dexamethasone.

Adult↗
PubMed1989

Prostaglandin and thromboxane synthesis by human intracranial tumors.

Prostaglandin (PG) and thromboxane (TX) production by homogenates of human intracranial tumors (33 gliomas, 32 meningiomas, six brain metastases) and "normal" brain (n = 26) from tumor-bearing patients was studied. PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha (the hydrolysis product of PGI2) and TXB2 (the hydrolysis product of TXA2) were determined by high-resolution gas chromatography-mass spectrometry after ex vivo metabolism of endogenous arachidonic acid. Prostanoid profiles (relative abundance of each metabolite) were different for gliomas and meningiomas, but similar for gliomas and their nontumoral counterpart, i.e., "normal" brain. Mean overall prostanoid production was significantly higher in gliomas (539 +/- 95) and meningiomas (523 +/- 69) than in "normal" brain (198 +/- 23). Prostanoid synthesis significantly increased with anaplastic grade (glioblastomas greater than anaplastic astrocytomas greater than slow-growing astrocytomas greater than "normal" brain), while profiles did not substantially change (TXB2 was the most and 6-keto-PGF1 alpha the least abundant product). Meningioma profiles showed no marked prevalence of any particular metabolite and no major differences between histological subgroups. All brain metastases from different carcinomas (n = 5) showed a prevalence of TXB2 and PGE2 and very low PGD2 synthesis.

Arachidonic Acid↗
PubMed1989

Hormonal modulation of brain tumour growth: a cell culture study.

Tissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation. Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours. GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures. DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR. Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.

Aged↗
PubMed1989

Lung function in essential mixed cryoglobulinemia: a short-term follow-up.

Lung involvement in essential mixed cryoglobulinemia (EMC) has been recently described. In order to assess whether patients with EMC experience an accelerated deterioration of lung function, nineteen patients (17 females, 2 males; 49.6 +/- 6.6 years) underwent a short-term follow-up of lung function, chest X-ray and serologic investigations. Reduction of forced expiratory flows and presence of roentgenologic signs of interstitial involvement were confirmed in the baseline evaluation. In addition, a decrease of diffusing capacity was shown. After a mean interval of 15 months, no significant change in lung function was found, with the exception of decrease in maximal expiratory flow at 50% of forced vital capacity, total lung capacity, functional residual capacity, coefficient of transfer of CO. A slight decrease of hemolitic complement (CH50) and of complement fraction (C3) was also observed. This study suggests that patients with EMC tend to have an involvement of pulmonary interstitial space, possibly related to immune complex deposition, but they do not show a severe decline of lung function. Periodical assessment of lung function and chest X-ray is, however, worthwhile.

Adult↗
PubMed1989

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.

Adult↗
PubMed1989

Results of a randomized trial comparing BCNU plus radiotherapy, streptozotocin plus radiotherapy, BCNU plus hyperfractionated radiotherapy, and BCNU following misonidazole plus radiotherapy in the postoperative treatment of malignant glioma.

In Brain Tumor Cooperative Group Study 77-02, eleven institutions randomized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery: conventional radiotherapy (6000 cGy in 30-35 fractions) + BCNU, conventional radiotherapy + streptozotocin, hyperfractionated (twice daily) radiotherapy (6600 cGy in 60 fractions) + BCNU, and conventional radiotherapy with misonidazole followed by BCNU. Data were analyzed for the total randomized population and for the 557 patients (86% with glioblastoma multiforme) who met protocol eligibility specifications (including confirmed histopathology on central review). Median survival was approximately 10 months following randomization. Overall there was no statistically significant difference in survival among the four groups. Among non-glioblastoma patients, the misonidazole group appeared to have poor survival. Peripheral neuropathy was a dose-limiting toxicity with misonidazole. It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma.

Adolescent↗
PubMed1989

Effects of nicardipine on the ex vivo release of eicosanoids after experimental subarachnoid hemorrhage.

The activation of lipid peroxidation and the enhancement of arachidonic acid metabolism have been demonstrated as indicators of brain damage after subarachnoid hemorrhage (SAH). Meanwhile, the final common pathway of neuronal damage seems to be related to the impaired homeostasis of Ca++. The present study evaluated the effect of the calcium-antagonist nicardipine on arachidonate metabolism after experimental induction of SAH. The ex vivo release of four eicosanoids (prostaglandin (PG)D2, PGE2, 6-keto-PGF1 alpha, and leukotriene (LT)C4) was measured at different intervals after SAH induction. Rats were separated into the following three groups: a sham-operated group, an SAH group (rats were injected with 0.3 ml autologous arterial blood), and an SAH-treated group (after SAH induction, rats were treated with nicardipine 1.2 mg/kg intraperitoneally). Nicardipine significantly decreased the ex vivo release of PGD2 at 48 hours after SAH (p less than 0.01). The release of PGE2 was significantly enhanced at 6 hours after SAH, while in the nicardipine-treated group PGE2 release is significantly reduced. Nicardipine also affects the lipoxygenase pathway, reducing the release of LTC4 at 1, 6, and 48 hours after SAH induction. The results of the present study show that nicardipine treatment exerts an inhibitory effect on both biochemical pathways of arachidonic acid metabolism; aside from vascular effects, nicardipine could exert a protective role against the release of arachidonate metabolites, which could play a significant role in the pathogenesis of brain damage after SAH.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Estimates of mean alveolar gas in patients with chronic airways obstruction.

Alveolar to arterial differences (AaD) may be computed from representative alveolar gas pressures (PA). These are particularly difficult to obtain in patients with chronic airways obstruction (CAO) and severe inhomogeneity of the ventilation/perfusion (VA/Q) ratio. In 25 such patients, using a computerized mass spectrometer, representative values of alveolar gas were obtained: 1. as end-tidal concentrations (ET); 2. using the alveolar air equation with PACO2 derived from Bohr's equation (BE); 3. putting PACO2 = PACO2 into the alveolar air equation to compute ideal O2 alveolar pressure (ID); 4. applying Rahn's definition of "mean" alveolar gas (RD), i.e. taking within each jth breath, the alveolar pressures corresponding to the moment when the instantaneous gas exchange ratio R(t)j equals the overall exchange ratio for that breath Rj. During quiet breathing, the point where R(t)j equals Rj occurred at 71% of tidal volume (VT). Alveolar pressures by BE and RD resulted in similar values (115.5 +/- 6.9 and 115.5 +/- 6.6 mmHg for O2 and 30.3 +/- 5.7 and 30.8 +/- 5.7 mmHg for CO2, respectively), but they were significantly different from those by ET and ID (106.2 +/- 9.5 and 95.6 +/- 13.5 mmHg for O2 and 36.3 +/- 7.7 and 48.2 +/- 11.2 mmHg for CO2, respectively). These findings may be explained considering that PA(BE) and PA(RD) represent both high and low VA/Q units, whereas PA(ET) and PA(ID) represent mainly low VA/Q units. AaDCO2 by RD and BE appeared proportional to the severity of CAO as estimated from VT. Automated techniques make it possible to substitute end-tidal determinations with more accurate estimates either by measuring anatomical dead-space and using Bohr's equation or by applying Rahn's definition.

Aged↗
PubMed1989

Effects of childhood and adolescence-adulthood respiratory infections in a general population.

The role of childhood respiratory infections before 12 yrs of age (CRI) and during adolescence-adulthood (ARI) was studied in a general population sample (n = 3,289), living in an unpolluted area of Northern Italy. The presence of respiratory symptoms and diseases, as well as risk factors for obstructive airways disease (OAD), was assessed by a standardized questionnaire. Forced vital capacity and derived expiratory flows, and single-breath diffusing capacity were measured using computerized instrumentation. There were 1,185 (36.2%) subjects who reported pertussis (PT), 374 (11.4%) recurrent chest colds, pneumonia and croup, singly or in combination, with or without pertussis (CRI), and 1,718 (52.4%) reported no respiratory infections in childhood (NOCRI). Prevalence rates of respiratory symptoms and diseases were significantly higher in subjects of the CRI group in all ages, and in older smokers. Wheeze and attacks of shortness of breath with wheeze were significantly higher in younger nonsmoking subjects with a history of CRI. Respiratory symptoms and diseases were not more prevalent in subjects of the PT group. Prevalence rates of respiratory symptoms and diseases were significantly higher in subjects with a history of ARI, both in smokers and nonsmokers. Lung function parameters adjusted for sex, age and smoking were significantly lower in CRI subjects; PT subjects showed lower values than NOCRI subjects. A significantly higher prevalence rate of ARI was present in subjects who reported CRI, both in smokers and nonsmokers. Subjects with both CRI and ARI showed the highest prevalence of respiratory symptoms and diseases. In addition, they had the lowest lung function values regardless of smoking habit.

Adolescent↗
PubMed1989

Prevalence of asthma and asthma symptoms in a general population sample of north Italy.

The prevalence rates of asthma and asthma symptoms were investigated in a general population sample (n = 3,289) living in a rural area of northern Italy. The subjects received a standard questionnaire and performed lung function tests with automated equipment. The overall prevalence rate of reported diagnosis of asthma was 5%. In young nonsmokers of both sexes the prevalence rates of reported diagnoses were higher than those of symptoms whilst the reverse occurred in older age groups. The prevalence rates decreased from childhood to young adults and increased again in older age groups. In smokers, reported diagnoses and symptoms increased with age and the prevalence rates of symptoms were always higher than those of diagnoses. Smokers with symptoms and reported diagnoses had lower lung function parameters than those with only symptoms. The distribution of asthma symptoms in our population indicates the importance of cigarette smoke and other environmental factors in the expression of the disease.

Adolescent↗
PubMed1988

Presence of epoxide hydrolase and glutathione S-transferase in human pulmonary alveolar macrophages.

Pulmonary alveolar macrophages (PAMs) were obtained from 11 patients by bronchoalveolar lavage. Epoxide hydrolase and glutathione S-transferase in sonicated PAMs were measured using benzo(a)pyrene-4,5-oxide as the substrate. The activity of epoxide hydrolase was 0.24 +/- 0.10 nmol/min/mg protein (mean +/- SD), and of glutathione S-transferase 0.22 +/- 0.12 nmol/min/mg protein. There was a significant difference in enzyme activities in the PAMs from smokers and non-smokers. Epoxides may be metabolized in PAMs.

Epoxide Hydrolases↗
PubMed1988

A computer-based method for on-line acquisition and analysis of bronchial challenge test.

We developed a computer program for the optimization and management of data collection in order to compute the change of forced expiratory volume in the first second (delta FEV1), provocative doses and to plot the dose-response curve for bronchial challenge test. Doses of methacholine are entered via the keyboard and forced vital capacity (FVC) with the highest FEV1 value obtained in each step is selected. When the imposed threshold of response has been reached, doses of administered methacholine and corresponding spirometric parameters are displayed and printed. Dose-response relationships are analysed: the increase of delta FEV1 for each unit of metacholine is computed in the interval between the two doses where delta FEV1 reached one of the imposed values (i.e. 15% or 20% or 30%). Finally spirometric values, dose-response curve and provocative doses are shown in a print-out. Computer values of provocative doses are higher than those obtained manually. This difference may be ascribed to the incorrect manual linear extrapolation. In conclusion the computer program is able to reduce consistently the time spent to analyze data from bronchial challenge test and allows a more precise determination of provocative doses by avoiding also inter-intra individual errors.

Asthma↗