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Biomedical subjects

C Galli

Publications and source records attributed to C Galli.

At least 361 records · Page 20Linked to original sources
PubMedDate not supplied

Long-term observation of HCV-positive patients with normal ALT values: persistence of a clinically healthy state.

The purpose of our investigation was to ascertain the presence of viral replication in subjects positive for antibodies to hepatitis C virus (anti-HCV) with persistently normal values of liver tests, to define their natural history, and to determine whether the immunoglobulin M (IgM) response could be a useful parameter to distinguish viraemic from non-viraemic patients. Twenty-seven subjects were selected based on their anti-HCV positivity and sustained normality (for at least 18 months) of alanine-aminotransferase (ALT) values. They were enrolled into the study and observed for another 1-4 years (mean 2.6). Fifteen out of 27 subjects were positive for hepatitis C virus ribonucleic acid (HCV RNA) and 12/15 were also positive for IgM. The remaining 12/27 patients were negative for both assessments. ALT levels remained in the norm throughout the investigation for all 27 subjects studied; the 15 viraemic patients showed persistent positivity for HCV RNA and the 12 positive for IgM anti-core also maintained their positivity. Patients shown to be negative for HCV RNA and IgM sustained their negativity throughout the study. Our results indicates that some patients remain viraemic while not having and/or developing clinical and biochemical signs of liver damage. IgM anti-HCV seems to be a specific index of viraemia in HCV-positives and could be useful for monitoring these patients.

Adolescent↗
PubMedDate not supplied

Arachidonic and docosahexaenoic acids differentially affect the expression of fatty acyl-CoA oxidase, protein kinase C and lipid peroxidation in HepG2 cells.

Arachidonic (AA) and docosahexaenoic (DHA) acids (5-20 microM), when supplemented to human hepatoma HepG2 cells, which are depleted in these long-chain polyunsaturated fatty acids in conventional culture conditions, enhance the expression of acyl-CoA oxidase (ACOX), the first enzyme in the peroxisomal beta-oxidation cycle. DHA is effective at lower concentrations (at 5 microM) and to a greater extent (about 60% increment) than AA (about 40%) at 20 microM. Protein kinase C (PKC) appears to be involved in the activity of AA on ACOX, but not in that of DHA, since only the effect of AA is prevented by the PKC inhibitor Staurosporine, and since a remarkable elevation of the PKC activator diacylglycerol occurs only after AA supplementation. AA also induces elevation of lipoperoxides, favoured by the relative vitamin E deficiency occurring in cultured cells, and this effect, which is prevented by supplementation of the vitamin, may contribute to PKC activation.

Acyl-CoA Oxidase↗
PubMedDate not supplied

Temozolomide as first-line agent in treating high-grade gliomas: phase II study.

UNLABELLED: Temozolomide a recent, oral, second generation alkylating agent is a chemotherapeutic with demonstrated efficacy for the treatment of high-grade gliomas; its efficacy has been demonstrated in both pre-clinical and phase I and II studies. The goal of this study is to determine the activity and safety of temozolomide in improving overall survival (OS), progression-free survival (PFS) and health-related quality of life (HQL) in patient with malignant gliomas. Forty-two patients with newly diagnosed glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma were studied. The mean follow-up period was 12 months. The overall response rate (only responsive patient) for all histological groups was 40%, 10 patients (24%) showed a stabilization of disease. The median PFS and OS was respectively 8.35 and 14.1 months: time to progression was 34 week ranging from 21 to 47. In all patients, treatment with temozolomide was associated with improvement of performance status including the patient showing disease progression: Karnofski score improved in all patients by a minimum of 10, with a median of 20 at 6 months. No patient stopped the treatment due to side-effects, no major adverse events were recorded. CONCLUSION: Temozolomide appears to be an ideal, first-line, single-agent, with a safe profile and demonstrated HQL benefits in patients with high-grade gliomas.

Aged↗
PubMedDate not supplied

Polyunsaturated fatty acids in maternal plasma and in breast milk.

In order to explain processes underlying the transfer of fatty acids from the maternal compartment into human milk, the lipid content and the fatty acid composition of maternal plasma and milk have been analyzed in breastfeeding mothers at 1 day and 3 months of lactation. The rise in milk lipids occurring during the study period was concomitant with a fall in plasma total fat content, mainly due to the decrease of triglycerides. Significant correlations between plasma and milk fatty acids at the two time points were observed only for linoleic (LA, 18:2 n-6) and (alpha;-linolenic acid (alpha LNA, 18:3 n-3), while for arachidonic (AA, 20:4 n-6) and docosahexaenoic acid (DHA, 22:6 n-3) correlations were found only at one day and 3 months, respectively. These data suggest that levels of the n-6 and n-3 18C polyunsaturated fatty acids in milk are closely dependent on their concentrations in maternal plasma, in turn related with the dietary intake, while the accumulation of AA and DHA in milk is the result of a sequence of transfer and metabolic processes.

Adult↗
PubMedDate not supplied

Regulation of PUFA metabolism: pharmacological and toxicological aspects.

Levels of the long-chain polyunsaturated fatty acids (LCP) of the n-6 and n-3 series in animal plasma and cells are directly or indirectly dependent upon the intakes of either their precursors, the short-chain polyunsaturated fatty acids (SCP), linoleic (LA, 18:2 n-6) and alpha linolenic acid (ALA, 18:3 n-3), respectively, and/or of the preformed products (arachidonic, 20:4 n-6) and eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3). We report here that pharmacological agents and cytotoxic compounds significantly affect the production of LCP from SCP in cultured cells. Using labelled substrates and radio HPLC separations, we observed that the potent hypocholesterolemic agent, simvastatin, activates the formation of AA from LA, mainly acting at the delta5 desaturation step, and increases also the mRNA levels, in cultured monocytic cells (THP-1). Elevation of AA occurs also in plasma lipids of hyperlipemic patients treated with statins (but not with fibrates). Conversely, oxysterols (mainly 7-beta-oxysterol), which are detected in circulating lipoproteins of rabbits on a hypercholesterolemic diet, potently inhibit the synthesis of AA from LA in hepatocytic cell lines (Hep-G2). At the same time plasma levels o AA are reduced vs controls, in spite of an identical intake of LA. Finally, on the basis of previous work showing reduced levels of LCP, mainly DHA, in the milk of cigarette-smoking mothers, we have observed that the incubation of human mammary gland cells with sera exposed to cigarette smoke results in marked inhibition of the production of DHA from ALA. The products in smoke responsible for this effect, are being identified through mass spectrometric techniques. In conclusion, pharmacological agents and toxic compounds, such as oxysterols and smoke products affect key steps in the synthesis of the LCP, major bioregulators in mammalian cells.

Animals↗
PubMedDate not supplied

Pulmonary vascular overreactivity in systemic hypertension. A pathophysiological link between the greater and the lesser circulation.

This study was undertaken to test whether the emphasized systemic vasomotion during sympathetic activation in hypertension is shared by the pulmonary circulation. To this end, 10 normotensive and 29 primary hypertensive subjects were investigated during adrenergic stimulation by mental arithmetic and cold pressor test. Both stimuli induced a systemic pressor reaction in both groups, which was mediated through an increase in cardiac output and a mild reduction in vascular resistance during arithmetic and through a predominant rise in systemic vascular resistance during cold. Each of these changes was emphasized in the hypertensive population as compared with the normotensive one. Pressure in the pulmonary artery remained unchanged during cold and was slightly raised (systolic) during arithmetic in normotensive subjects. On the contrary, in hypertensive subjects systolic and diastolic pulmonary pressures were consistently augmented by both stimuli, and pulmonary arteriolar resistance (dyn sec cm-5) rose from 92 in the baseline to 125 (p less than 0.01) during arithmetic and to 124 (p less than 0.01) during the cold test. This reaction is interpreted as reflecting a neurally mediated vasoconstriction and not as the consequence of mechanical or chemical changes, since no difference was observed in pulmonary wedge pressure, pleural pressure, arterial blood gas levels, and pH between controls and hypertensive subjects in the steady state and during either stressful stimulation. Baseline pulmonary arteriolar resistance was also found to correlate positively with systemic vascular resistance in the hypertensive group. When pressure changes occurred, the time course was similar in the two circuits; resistance increased to a proportionally similar degree in the two districts during the cold stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Decrease of polyunsaturated fatty acids and elevation of the oleic/stearic acid ratio in plasma and red blood cell lipids of malnourished cancer patients.

The fatty acids profiles of plasma and red blood cell lipids have been evaluated in 12 malnourished cancer patients in comparison with samples from eight healthy controls. In such patients, significantly lower levels of linoleic acid (LA) as percentage of total fatty acids were observed in plasma phospholipids (PL) and cholesterol esters (CE), and in red blood cells PL. The levels of arachidonic acid (AA) and the unsaturation index of the two lipid classes were also reduced in plasma CE but not in PL. In spite of the marked reduction of LA and, more generally, of total polyunsaturated fatty acids (PUFA), no elevation of eicosatrienoic acid (20:3 n-9) was observed, such acid being considered a typical index of essential fatty deficiency. Moreover, no modification of the parameters indicating impairment of the fatty acid desaturation activity was shown. In addition, the levels of palmitic and oleic acids were significantly higher in both plasma PL and CE and in red blood cells PL. The reported elevation of the oleic to stearic acid ratio in lipids of red blood cells from malnourished cancer patients, already observed by other authors, was confirmed in our study. This ratio was even more markedly elevated in plasma lipids of the patients. A very good correlation was found between the reduction of linoleic acid levels, especially in plasma CE, and weight loss, suggesting enhanced utilization of this fatty acid in association with extensive depletion of lipid stores, in this pathological state.

Erythrocytes↗
PubMedDate not supplied

Suramin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in metastatic colorectal cancer patients resistant to 5-FU+LV-based chemotherapy.

AIMS AND BACKGROUND: Suramin has been shown to be of interest as a potential new anticancer agent because of its capacity to inhibit the binding of several growth factors to their receptors and to inhibit the growth of cancer cells in vitro. Since multi-autocrine loops involving growth factors which are antagonized by suramin have been demonstrated in colorectal cancer, we previously evaluated the activity of suramin in patients with advanced colorectal cancer. Interestingly, in this study three patients who had received 5-FU+LV after suramin, although heavily pretreated with fluoropyrimidines, obtained an objective response. This observation was intriguing as it might have been that suramin had changed the biology of the tumor, making it sensitive to 5-FU+LV. We therefore conducted the present study to investigate the possibility that suramin might overcome the resistance to 5-FU+LV. METHODS AND STUDY DESIGN: Only colorectal cancer patients with metastatic and progressive disease during 5-FU+LV-based chemotherapy were eligible for this study. Suramin was administered for eight weeks at doses determined by means of a computer-assisted dosing algorithm that used Bayesian pharmacokinetics to maintain suramin plasma concentrations of 200-250 microg/ml. 5-FU was administered weekly at a dosis of 450 mg/m2 halfway through a two-hour infusion of I-LV 250 mg/m2 starting one week after the initiation of suramin for a maximum of 26 weeks. RESULTS: Treatment was relatively well tolerated, but no objective responses were observed after the accrual of 13 patients in the first stage of the trial. Consequently, the trial was interrupted according to the initial two-stage sampling design. CONCLUSIONS: The present study does not support the hypothesis that suramin might overcome resistance to 5-FU+LV and its use in colorectal cancer is not recommended.

Aged↗
PubMedDate not supplied

Pathophysiology, clinical manifestations and supportive care of metastatic brain cancer.

Brain metastases (BrM) are tumours that originate in tissues outside the central nervous system and spread secondarily to involve mainly the brain. The management of patients with cerebral metastases is complex, costly, and in some instances controversial. Furthermore, even in patients with widespread systemic cancer, the symptoms of the disease are often controllable while the symptoms of the BrM may be disabling. The treatment of BrM is one of the few areas of neuro-oncology where real progress has been made in the last twenty years. Moreover, the costs of managing this disease are rising, as therapies become more intensive and the number of patients with BrM increases. Modern neuroradiological imaging techniques, which are able to discover BrM earlier in the course of systemic cancer, and the greater efficacy of specific treatments, which lengthens survival, have increased the prevalence. The aggressive treatment of BrM may add some benefits to the patient, but its excessive cost leads to the necessity for accurate cost-effectiveness analysis. The latter begins with a complete understanding of the disease: its diagnosis, natural history and results of various modalities of treatment. While the development of BrM usually indicates a poor prognosis for the patient, advances in supportive care have made it possible to reverse most of the neurological symptoms and to give patients a meaningful extension of useful life.

Brain Neoplasms↗
PubMedDate not supplied

[Glial heterotopy of the nose ("nasal glioma"). Description of a case].

A six months female infant was admitted in our hospital for congenital dysmorphism of face: a subcutaneous nodule in left nose region was present. An x-ray study showed relevant scoliosis of the nasal septum. On surgery a white firm nodule was incompletely excised; a post-operatory CT-scan excluded any communication of neoplasia with brain. No bone lacunae were seen. Clinically there was neither rhinorrhea nor meningitis. The baby was discharged on 7th day. Grossly the mass presented white surface, firm consistency with small hemorrhages on cut surface. Microscopically the nodule, encircled by a fibrous pseudo-capsule, was mostly composed of gemistocytic astrocytes, occasionally binucleated, interspersed within fibrillary neuroglial tissue. Strands of fibrous tissue, in continuity with the pseudo-capsule, separated the glial tissue. No neuronal cells were seen. Necrosis, mitotic figures and vascular proliferations were absent. GFAP immunohistochemical stain confirmed the glial nature of the cells. Our diagnosis was one of "heterotopic glial tissue of nose" (nasal glioma). The absence of connection between the nodule and endocranial contents (CSF-filled spaces, leptomeningeal or dural tissue), excluded the diagnosis of encephalocele. In our case, the tissue was only of embryonic neuroectodermal derivation: on this basis the diagnosis of teratoma, which is classically composed of two or three embryonic layers could be excluded. The pathogenesis of nasal glioma is briefly discussed by authors.

Biomarkers, Tumor↗
PubMedDate not supplied

[Evaluation of the efficacy and tolerability of quinapril monotherapy in mild and moderate arterial hypertension].

The aim of this single blind, placebo controlled study is to evaluate the efficacy and safety of quinapril in mild to moderate hypertension. Thirty-six patients (from 32 to 64 years old, mean 54.8 +/- 8.84) with diastolic blood pressure (DP) greater than or equal to 96 mmHg and less than or equal to 114 mmHg were enrolled. After a two week wash-out, a placebo was administered for two weeks and than for 12 weeks 20 mg of quinapril u.i.d. At the eighth week if DP was not less than less than or equal to 94 mmHg 40 mg of quinapril was administered. Blood pressure was evaluated at the onset of the study, at the beginning of every step and every 4 weeks. Mean DP and systolic pressure were respectively 159.17 +/- 11.43 and 101.14 +/- 4.39 at the enrolling time, 159.72 +/- 9.41 and 101.86 +/- 3.45 after the wash-out period, 152.78 +/- 9.22 and 98.33 +/- 2.9 after the placebo period, 150 +/- 9.34 and 95.28 +/- 3.52, 144.72 +/- 8.89 and 92.22 +/- 4.32, 140.25 +/- 8.21 and 88.24 +/- 5.27 after 4, 8, 12 weeks of treatment.

Adult↗
PubMedDate not supplied

Co-culture: the future for embryo development in vitro.

Important interactions occur between the somatic cells of the oviduct and the developing embryo, during the later stages of pre-attachment development. In these stages secretions from the oviduct are very important in conferring viability on the embryos, especially plasmatic proteins and proteins secreted by the oviduct cells. The oviduct secretions obtained at various stages of the oestrus cycle have now been tested for potential growth factors. If an active fraction of the oviduct secretion is identified, the potential embryotrophic factor(s) will be characterized and produced on a large scale so that culture medium can be supplemented.

Animals↗
PubMedDate not supplied

Hypoxia-induced pulmonary hypertension: nifedipine only temporarily reduces pulmonary artery pressure and vascular tone.

Fifteen patients affected by hypoxia-induced pulmonary hypertension were studied before and during (1st and 8th week) nifedipine (180 mg/die) treatment. Nifedipine reduced pulmonary pressure (33 +/- 4 vs 26 +/- 3 mmHg, p less than 0.02) after 1 week of treatment; this pulmonary hypotensive effect was due to a reduction of pulmonary vascular tone as assessed by a reduction of Y-intercept on the pulmonary pressure/flow plot drawn from invasive recordings of pulmonary pressure/cardiac output obtained during exercise. Oxygen breathing effects on pulmonary pressure were also measured with and without nifedipine. Oxygen significantly reduced pulmonary pressure only in the absence of nifedipine regardless of the severity of pulmonary hypertension. Therefore nifedipine is not suitable for long-term treatment of hypoxia-induced pulmonary hypertension and inhibits O2 capability to reduce pulmonary pressure.

Adult↗