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Biomedical subjects

A Martelli

Publications and source records attributed to A Martelli.

At least 55 records · Page 3Linked to original sources
PubMed1997

Impact of positive end-expiratory pressure on chest wall and lung pressure-volume curve in acute respiratory failure.

To investigate whether chest-wall mechanics could affect the total respiratory system pressure-volume (P-V) curve in patients with acute respiratory failure (ARF), and particularly the lower inflection point (LIP) of the curve, we drew the total respiratory system, lung, and chest-wall P-V curves (P-Vrs, P-VL, and P-VW, respectively) for 13 patients with ARF, using the supersyringe method together with the esophageal balloon technique. Measurements were randomly repeated at four different levels of positive end-expiratory pressure (PEEP) (0, 5, 10, 15 cm H2O) and from each P-V curve we derived starting compliance (Cstart), inflation compliance (Cinf), and end compliance (Cend). With PEEP of 0 cm H2O (ZEEP), an LIP on the P-Vrs curve was observed in all patients (7.5 +/- 3.9 cm H2O); in two patients an LIP was detected only on the P-VL curve (8.6 and 8.7 cm H2O, respectively); whereas in seven patients an LIP was observed only on the P-VW curve (3.4 +/- 1.1 cm H2O). In four patients, an LIP was detected on both the P-VL and P-VW curves (8.5 +/- 3.4 and 2.2 +/- 1.0 cm H2O, respectively). The LIP was abolished by PEEP, suggesting that a volume-related mechanism was responsible for the observed LIP on both the P-VL and P-VW curves. At high levels of PEEP, an upper inflection point (UIP) appeared on the P-Vrs and P-VL curves (11.7 +/- 4.9 cm H2O and 8.9 +/- 4.2 cm H2O above PEEP, respectively) suggesting alveolar overdistension. In general, PaO2 increased with PEEP (from 81.7 +/- 35.5 mm Hg on ZEEP to 120 +/- 43.8 mm Hg on PEEP 15 cm H2O, p < 0.002); however, the increase in PaO2 with PEEP was significant only in patients with an LIP on the P-VL curve (from 70.5 +/- 16.2 mm Hg to 117.5 +/- 50.7 mm Hg, p < 0.002), the changes in PaO2 in patients without an LIP on the P-VL curve not being significant (from 91.3 +/- 45.4 mm Hg to 122.2 +/- 41.1 mm Hg). We conclude that in ventilator-dependent patients with ARF: (1) the chest-wall mechanics can contribute to the LIP observed on the P-Vrs curve; (2) the improvement in PaO2 with PEEP is significant only in patients in whom LIP is on the lung P-V curve and not on the chest wall curve; (3) high levels of PEEP may overdistend the lung, as reflected by the appearance of a UIP; (4) measurement of P-Vrs alone may be misleading as a guide for setting the level of PEEP in some mechanically ventilated patients, at least in the supine position, although it helps to prevent excessive alveolar overdistension by indicating the inflection volume above which UIP may appear.

Acute Disease↗
PubMed1997

Transsynaptic degeneration of lateral geniculate bodies in blind children: in vivo MR demonstration.

PURPOSE: To investigate signal alterations in the thalamic lateral geniculate bodies of blind patients compatible with transsynaptic degeneration of these nuclei caused by pregeniculate or postgeniculate interruption of the visual pathway. METHODS: Six patients were selected from a group of blind children in our care. Four had cerebral palsy caused by periventricular leukomalacia, one had infantile neuroaxonal dystrophy, and one had Chiari I malformation and hydrocephalus, which was worsened by bilateral ischemic lesions of the occipital lobes. MR examinations (obtained at 0.5 T) were reviewed retrospectively by two neuroradiologists, with particular attention to the visual pathway. RESULTS: Symmetric, focal areas of T2 prolongation were found at the precise site of the lateral geniculate bodies. CONCLUSION: Anterograde (pregeniculate) and retrograde (postgeniculate) transsynaptic degeneration of the second neurons of the visual pathway produce alterations in MR signal.

Arnold-Chiari Malformation↗
PubMed1996

A systemic "dumb-bell" haemangiopericytoma.

Systemic haemangiopericytoma is a rare soft tissue tumour originating from pericytes which are contractile pericapillary cells, and represents less than one percent of all vascular neoplasms. The most common site of involvement is the thigh followed by the retroperitoneum, while the paraspinal location is very rare. We report the first case of systemic "dumb-bell" haemangiopericytoma illustrated radiologically, which mimick, a dorsal "dumb-bell" neurinoma.

Child↗
PubMed1996

Induction of micronuclei and initiation of enzyme-altered foci in the liver of female rats treated with cyproterone acetate, chlormadinone acetate, or megestrol acetate.

The synthetic anti-androgen and progestin cyproterone acetate (CPA), recently found to be genotoxic for the liver, and two structurally similar progestins, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for clastogenic and tumor-initiating activities in female rats. In the micronucleus assay, carried out in rats given a single p.o. dose of 100 mg/kg, CPA induced the maximum increase in the frequency of micronucleated hepatocytes (6.6-fold as compared to controls) when treatment was performed 3 days before partial hepatectomy and cell sampling 2 days later. Under the same experimental conditions the clastogenic potencies of CMA and MGA were 69% and 36% of that of CPA respectively. In the liver foci assay, p.o. dosing with 100 mg/kg CPA once a week for 6 successive weeks induced, as compared to controls, a significant increase in the number and area of gamma-glutamyltranspeptidase-positive foci. At the same dosage schedule the tumor-initiating activity of CMA and MGA was 7- to 10-fold lower than that of CPA. These findings suggest that the 1,2 alpha-methylene group, present in CPA but absent in both CMA and MGA, favours the activation to a reactive species and/or hinders the biotransformation to non-toxic metabolites.

2-Acetylaminofluorene↗
PubMed1996

Comparative study of DNA repair induced by cyproterone acetate, chlormadinone acetate and megestrol acetate in primary cultures of human and rat hepatocytes.

Cyproterone acetate (CPA), a synthetic progestin recently found to induce genotoxic effects in hepatocytes from female rats and from humans of both genders, and two structural analogues, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for their capacity to induce DNA repair synthesis as measured by quantitative autoradiography. Exposure of primary human hepatocytes for 20 h to concentrations of CPA, CMA and MGA ranging from 2 to 50 microM induced positive responses in cultures from donors of both genders and the amounts of DNA repair elicited by the three progestins were similar. Under the same experimental conditions substantial differences were observed in the amounts of DNA repair elicited by the three progestins in primary hepatocytes from female rats, their potency decreasing in the following order CPA > CMA > MGA, and the three compounds failed to induce DNA repair in hepatocytes from male rats. These results, which agree with previous findings, suggest that for these sex steroids extrapolation to humans of results obtained in rats might be questionable.

Animals↗
PubMed1996

Genotoxic effects of alpha-hexachlorocyclohexane in primary cultures of rodent and human hepatocytes.

The genotoxicity of alpha-hexachlorocyclohexane (alpha-HCH) was evaluated in primary cultures of mouse, rat and human hepatocytes. DNA fragmentation was measured by the alkaline elution technique and DNA repair synthesis by quantitative autoradiography. A 20 h exposure to subtoxic concentrations ranging from 0.056 to 0.32 mM produced a dose-dependent frequency of DNA breaks in rat hepatocytes and in hepatocytes from four of five human donors, but not in mouse hepatocytes, DNA repair induction was absent in hepatocytes from all three species. The reduction in the frequency of DNA breaks observed in rat hepatocytes simultaneously exposed to metyrapone suggests that alpha-HCH is transformed into reactive species by a cytochrome P450-dependent reaction. The detection of DNA fragmentation but not of DNA repair synthesis may be tentatively explained by assuming that alpha-HCH behaves as a chemical eliciting short patch DNA repair, which is more easily revealed as genotoxic by the occurrence of DNA single-strand breaks.

Animals↗
PubMed1996

[Dynamic study of the distal radioulnar joint with computerized tomography].

The authors describe a CT technique which allows the dynamic study of the inferior radioulnar joint. The examination consists of 4 CT slices, three of them acquired at the same level-i.e., the radioulnar joint- in the prone, intermediate and supine positions, respectively. The last slice is acquired, with the patient in the prone position, at the base of the styloid process where the triangular fibrocartilage is demonstrated. The distal radioulnar ligaments are not directly visible. Nineteen patients complaining of painfully impaired pronation and supination because of previous trauma (11 Colles fractures, 7 distortions and 1 Galeazzi lesion) were examined with this technique. In all patients, both wrists were studied to obtain normal parameters. The radioulnar joint was evaluated superimposing a draft on the dynamic images, which demonstrated that, in healthy limbs, during movement the ulnar epiphysis is always contained between two parallel lines drawn on the volar and dorsal surfaces of the radial epiphysis, respectively. It was also confirmed that supination is possible up to 110-135 degrees from the support plane. CT demonstrated different causes of impaired movements in the affected joints: in 12 cases some fibrous density tissue was seen at the ulnar epiphysis on the volar aspect and considered to be the evolution of a traumatic hematoma; 6 patients presented dorsal subluxation of the ulna during movement; finally, volar subluxation was detected only in one case. In 6 patients the triangular fibrocartilage was detached; in 1 patient an intraarticular fluid collection was demonstrated. In 3 patients CT detected no abnormalities. The fibrous tissue is responsible for impaired movements and causes the detached triangular fibrocartilage to shrink. The authors believe that this simple CT technique can yield useful pieces of information for accurate surgical planning.

Female↗
PubMed1996

Cerebral visual impairment in periventricular leukomalacia: MR correlation.

PURPOSE: To evaluate the involvement of central visual pathways in cases of periventricular leukomalacia, and to correlate the neuroradiologic findings with the degree of visual acuity. METHODS: The MR brain examinations of 27 preterm children affected by cerebral palsy resulting from periventricular leukomalacia and without significant ophthalmologic lesions were reviewed retrospectively to search for possible involvement of the optic radiations and/or of the calcarine cortex. The data were compared with the degree of visual acuity estimated by means of the Teller Acuity Cards test. RESULTS: Seventeen (63%) of the 27 patients had cerebral visual impairment, which correlated strongly with MR lesions. Quantitative reduction and signal hyperintensity of the peritrigonal white matter and atrophy of the calcarine cortex were present in the more severe cases. In two blind patients, an altered MR signal was detected in the lateral geniculate bodies. CONCLUSION: This study clearly establishes a relationship between specific MR findings and visual impairment in children with periventricular leukomalacia. The finding of hyperintensity in the lateral geniculate bodies was interpreted as an axonal reaction. MR imaging is useful for detecting potential visual impairment and for improving clinical diagnosis.

Atrophy↗
PubMed1995

Testing of metoclopramide and procainamide for their ability to induce genotoxic effects in cultured mammalian cells.

Metoclopramide (MCA) and procainamide (PCA), two widely used benzamide drugs developed before the present regulatory climate but recently found to induce DNA breaks in human lymphocytes, were evaluated for their genotoxic effects in cultured rodent and human cells. In subtoxic concentrations neither MCA (from 0.10 to 0.32 mM) nor PCA (from 0.18 to 0.56 mM) induced DNA fragmentation and repair in primary cultures of metabolically competent rat and human hepatocytes. In the absence of metabolic activation a meaningful increase in the frequency of 6-thioguanine-resistant V79 cells was produced by the maximum tolerated concentration of MCA (3.2 mM), whereas PCA resulted nonmutagenic. Any clastogenic effect was absent in human lymphocytes exposed to MCA for 28 hr, but a statistically significant increase in the frequency of micronucleated cells was observed when the exposure was prolonged to 72 hr. In contrast, PCA was never clastogenic under the same experimental conditions. These results suggest that of the two benzamides tested only MCA should be considered potentially capable of producing mutagenic and clastogenic effects; it presumably behaves as an agent which is rapidly transformed by the liver into inactive metabolites, and the clinical relevance of its genotoxic activity remains to be ascertained.

Animals↗
PubMed1995

Evaluation of DNA-damaging, clastogenic, and promoting activities of metoclopramide and procainamide in rats.

The DNA-damaging and clastogenic activities of metoclopramide (MCA) and procainamide (PCA), two substituted benzamides not systematically tested for genotoxicity before clinical use, were investigated in rats given a single high oral dose (500 mg/kg) of these drugs. Neither MCA nor PCA induced DNA fragmentation in liver, kidney, gastric mucosa, spleen, and bone marrow, as detected by the alkaline elution technique. Moreover, neither drug increased the frequency of micronucleated hepatocytes and the frequency of micronucleated polychromatic erythrocytes in the bone marrow of partially hepatectomized rats. However, in rats initiated with N-nitrosodiethylamine and given water containing 0.125% MCA for 14 successive days a clear-cut and statistically significant increase in the number and size of liver gamma-glutamyltranspeptidase-positive foci and basophilic foci, which are consistent with potential promoting activity, was observed. Under the same experimental conditions the effect of PCA was markedly lower, only limited to a modest increase of the number and area of gamma-glutamyltranspeptidase-positive foci.

Administration, Oral↗
PubMed1995

A silicon-based biosensor for real-time toxicity testing in normal versus cancer liver cells.

The potentiometric alternating biosensor (PAB) system has been utilized to monitor the effects on normal versus cancer cells of Mitoxantrone, a potent inhibitor of nucleic acid synthesis commonly utilized in the clinical treatment of hepatocarcinomas. In this first series of toxicity tests, we have utilized a primary culture of rat hepatocytes and a stabilized line named HepG2 from a human hepatoma. Primary cultures of hepatocytes represent a unique tool in toxicology/pharmacology as shown in previous works. A suitable microvolume flow chamber has been designed and produced. The chamber is equipped with inlet and outlet circuits and with a fixed transducer (Si/SiO2/Si3N4 chip) facing a cover slip on which cells grow. The PAB system is here utilized only in the pH-sensitive configuration with a single measuring spot, warranting an accurate determination of the change in the extracellular acidifcation rate resulting from drug administration. We have also observed the changes in the acidification rate of 3T6 mouse fibroblasts, induced by a treatment with Ara-C, a well-known DNA antimetabolite. New insights can be obtained from these studies into the drug response of normal versus cancer cells and into the feasibility of real-time PAB monitoring of drug toxicity and efficacy, towards effective human cancer treatment. The effect of increasing drug concentrations on cellular metabolism is here compared with the results obtained from conventional tests (optical microscopy, Neutral Red and Trypan Blue assays).

Animals↗
PubMed1995

Epilepsia partialis continua in a case of MELAS: clinical and neurophysiological study.

There are few reports in the literature dealing with the association between mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and epilepsia partialis continua (EPC) in children. We report the case of a child presenting with numerous stroke-like episodes associated with EPC which, despite therapy, were not controlled and aggravated the clinical condition of our patient. We present the neuroradiological, biochemical, genetic and muscle biopsy findings, and EEG characteristics, with attention to polygraphic recordings which were done during wake and sleep periods. We consider the correlation with other possible etiological factors relating to EPC and in particular coinvolvement of the basal ganglia as a cause of EPC in our patient.

Child, Preschool↗
PubMed1995

Nitrosation of propranolol under simulated gastric conditions.

Nitrosation of propranolol, a beta-adrenergic blocking drug previously found to react with nitrite in HCl solution yielding a genotoxic nitrosamine, was examined under simulated gastric conditions. In the presence of a low concentration of nitrite (2.9 mM) and a therapeutic gastric concentration of the drug (5.4 mM), the yield of N-nitrosopropranolol was higher in simulated gastric juice, which contained both pepsin and thiocyanate, than in distilled water, and at pH 3.5 than at pH 1.0. A 55 microM concentration of N-nitrosopropranolol was reached after 180 min. It is reasonable to assume that the extremely small amounts of N-nitrosopropranolol formed in the human stomach should not represent a significant carcinogenic risk, but co-formulation of propranolol with ascorbic acid, which has been found to minimize the nitrosation reaction, might be useful to avoid a further, even if minimal, contribution to the already existing exposure to genotoxic chemicals.

Gastric Juice↗
PubMed1995

DNA repair synthesis and DNA fragmentation in primary cultures of human and rat hepatocytes exposed to cyproterone acetate.

Cyproterone acetate (CPA), a synthetic steroid used in human therapy, has recently been shown to cause DNA damage in cultured rat hepatocytes and in rat liver. In the present study we have investigated whether CPA also induces genotoxic effects in human hepatocytes. Genotoxicity of CPA was determined by measuring the capability of the compound for inducing DNA repair synthesis and for causing the formation of DNA single-strand breaks. Autoradiography and alkaline elution were used to quantitate DNA repair and DNA fragmentation, respectively. Exposure of hepatocytes to CPA for 20 h induced DNA repair synthesis in two hepatocyte preparations derived from males and in four of the five preparations derived from females. In cultures from some donors, induction of repair was detected at 1 microM CPA, the lowest concentration tested. The maximum effect generally occurred at 10-20 microM. Only a very slight increase in the frequency of DNA single-strand breaks was found following exposure of the hepatocytes to 50 microM CPA for 20 h. For comparative purposes, the effects of CPA on DNA repair and DNA fragmentation were also determined in cultured rat hepatocytes. A strong induction of DNA repair synthesis, but only a slight enhancement in DNA fragmentation was observed in CPA-treated hepatocytes derived from female rats. These results indicate that the measurement of repair is a more sensitive indicator for the genotoxicity of CPA than the measurement of DNA fragmentation. No genotoxic effects of CPA were detectable in hepatocyte cultures derived from male rats. The present findings show that CPA is genotoxic in human hepatocytes and that the striking sex difference in the genotoxicity of CPA in rat cells is not observed with human cells.

Aged↗
PubMed1995

Ganglioneuroblastoma of the spinal cord.

We report a case of ganglioneuroblastoma of the spinal cord in a 42-year-old man. MR examination was nonspecific, and the diagnosis was made from histologic findings. The MR picture was that of an intramedullary, mainly solid tumor with a central necrotic or cystic portion. The clinical picture and course were also nonspecific.

Adult↗
PubMed1995

In vitro and in vivo testing of hydralazine genotoxicity.

Hydralazine (HDZ), a p.o. effective antihypertensive drug, was evaluated for its genotoxic effects in both rodent and human cultured cells and in the intact rat. Dose-dependent amounts of DNA fragmentation, as measured by the alkaline elution technique, and of DNA repair synthesis, as revealed by autoradiography, were produced in primary cultures of metabolically competent rat hepatocytes by subtoxic HDZ concentrations ranging from 0.32 to 1.0 mM. A similar potency in inducing DNA repair synthesis was displayed by HDZ in primary cultures of hepatocytes from four human donors. A modest reduction of both DNA fragmentation (-13%) and DNA repair (approximately -50%) was observed in hepatocytes obtained from rats pretreated with indomethacin in order to reduce prostaglandin synthetase activity. In contrast, neither in rat nor in human hepatocytes, differences in N-acetyltransferase activity resulted in meaningful changes of the same end points. V79 cells, which are essentially deficient of monooxygenases catalyzing the biotransformation of xenobiotics, were as sensitive as hepatocytes to the DNA-damaging activity of HDZ. Moreover, after exposure to 0.1 to 0.3 mM HDZ, a modest (2.1- to 2.8-fold), but significant, increase in the frequency of mutation to 6-thioguanine resistance was observed in V79 cells in the absence of a metabolic activation system. In rats, a single p.o. dose of 80 mg/kg produced a clastogenic effect in the liver, but not in the bone marrow, and the p.o. administration for 14 successive days of approximately 46 mg/kg/day increased the average diameter of liver basophilic foci initiated by diethylnitrosamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hepatitis B in children in Italy: incidence and risk factors: SEIEVA Collaborating Group. Sistema Epidemiologico Integrato dell'Epatite virale Acuta.

The objectives of the present report were to give a baseline picture of hepatitis B notification incidence rates in children before the campaign of mass vaccination for newborns and adolescents (12-13 years old), and to study the role of different risk factors. Data from a specific national surveillance system of acute viral hepatitis (SEIEVA, Sistema Epidemiologico Integrato dell'Epatite Virale Acuta) were used and acute hepatitis B cases were compared to acute hepatitis A patients with the case-control study method to estimate the associations with the considered risk factors. Since the system began, one hundred and sixty-three local health departments have joined SEIEVA covering 30% of the Italian population. The incidence of acute hepatitis B notifications among 0-14 aged children was 9 per 100,000 in 1985 and 1 per 100,000 in 1990. Such decline in incidence was observed in both the North and the South of Italy. Surgical interventions, dental therapy and household contacts with a HBsAg chronic carrier were found to be associated with acute hepatitis B. The point estimate of the odds ratio was 10 for the latter risk factor. Other preventive measures in addition to vaccination are needed to control the risk of hepatitis B infection and other parenteral diseases due to surgical intervention and dental therapy.

Acute Disease↗