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Biomedical subjects

E Marchese

Publications and source records attributed to E Marchese.

At least 19 recordsLinked to original sources

Middle cerebral artery dolichoectasia in a young woman with a previous stroke.

We observed a 32-year-old female who had suffered from a left hemisphere ischemic stroke with right hemiparesis at the age of seven. At that time, a CT scan demonstrated a left ischemic lesion in nucleo-capsular region and a cerebral angiogram documented a complete occlusion of the supraclinoid segment of the internal carotid artery. When we observed the patient neurological examination demonstrated a moderate right brachio-crural hemiparesis. A brain MRI showed an old ischemic lesion involving the left nucleo-capsular and 'flow voids' suggestive for a vascular malformation in the left sylvian region. A cerebral rotational angiogram with 3-D reconstructions demonstrated a dolichoectatic left middle cerebral artery with an unusual 'corkscrew' aspect. Middle cerebral artery dolichoectasia is a rare pathological condition that may manifest with a stroke. The patients with intracranial arterial dolichoectasia (IADE) are most often hypertensive elderly men, and, to the best of our knowledge, an ischemic stroke associated with IADE has never been reported in children.

Adult↗

Chronic anaemia and adhesion molecules in patients with liver cirrhosis. A preliminary report.

AIM: The aim of our study was to investigate circulating levels of intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) in cirrhotic patients, with and without chronic anaemia, to establish whether there was a relationship between inflammatory activity and anaemia. METHODS: We investigated 14 anaemic (mean hemoglobin value 10.65+/-1.06 g/dL) and 14 non anaemic (mean hemoglobin value 13.8+/-0.89 g/dL) subjects affected by virus C-related liver cirrhosis comparable for sex, age and degree of liver dysfunction such as expressed by Child-Pugh classification. Circulating sICAM-1 and sVCAM-1 were measured by EIA commercial kit (R&D System Co, Abington, UK) and mean+/- standard deviation values in two groups were compared by t-test and Kruskall-Wallis test. RESULTS: Mean+/-standard deviation sICAM-1 was 35.06+/-4.06 ng/mL in anaemic and 23.39+/- 6.1 ng/mL in non anaemic cirrhotic patients. Mean+/-standard deviation sVCAM-1 was 47.66+/-8.18 ng/mL in anaemic 31.77+/-6.08 ng/mL in non anaemic patients, respectively. Statistical analysis showed a significant difference between the two groups both in sICAM-1 (p=0.01) and sVCAM-1 (p=0.03) values. CONCLUSIONS: Our study show that chronic anaemia, in liver cirrhosis, is associated to a greater increase of circulating adhesion molecules and suggests that inflammation may contribute to persistence of anaemic state, worsening the outcome of cirrhotic patients.

Aged↗

ICP and CBF regulation: effect of the decompressive craniectomy.

The view of the intracranial system as a rigid and closed box has been criticised by many authors who take into account the possibility of a certain degree of elastic bulk accommodation, mainly in the spinal sac. In nine patients, who underwent decompressive craniectomy for treatment of life-threatening intracranial hypertension, when the clinical conditions improved, just before cranioplasty, the blood flow velocities at middle cerebral artery (MCA) and at superior sagittal sinus (SSS) level were simultaneously recorded. The measurements were repeated after cranioplasty. The blood flow velocity recorded from SSS in craniectomized patients appeared flat, without evident pulsation; after cranioplasty a clear-cut pulsatile wave became again evident. The disappearance of a pulsatile shape in the blood flow velocity recorded from the SSS when the intracranial system was "open" and the reappearance of a pulsatile blood flow waveform after the "closure" of the skull confirm that the venous bed acts as a bulk compensatory system in order to maintain the intracranial volume absolutely constant.

Blood Flow Velocity↗

Pharmacogenomic analysis of rhIL-11 treatment in the HLA-B27 rat model of inflammatory bowel disease.

Recombinant human interleukin-11 (rhIL-11) reduces the clinical signs and histological lesions of inflammatory bowel disease (IBD) in transgenic rats expressing the human major histocompatability complex (MHC) class I allele, HLA-B27. To elucidate the pharmacogenomic effects of rhIL-11 in this model, we examined the global gene expression pattern in inflamed colonic tissue before and following rhIL-11 treatment using oligonucleotide microarrays. In total, 175 disease-related genes were identified. Increased expression of genes involved in antigen presentation, cell death and inflammation, and decreased expression of metabolic genes was associated with disease. A total of 27 disease-related genes returned to normal expression levels following rhIL-11 treatment including the MHC class II gene RT1-DMbeta. rhIL-11 induced the expression of four intestinal epithelial growth factors. These gene expression patterns indicate that treatment of inflammatory bowel disease with rhIL-11 affects class II antigen processing and colonic epithelial cell proliferation and metabolism.

Animals↗

Increased susceptibility of copper-deficient neuroblastoma cells to oxidative stress-mediated apoptosis.

Treatment of neuroblastoma cells with the copper chelator triethylene tetramine tetrahydrochloride induced intracellular decrease of copper content paralleled by diminished activity of the enzymes Cu, Zn superoxide dismutase, and cytochrome c oxidase. This effect appears to be specific for copper-enzymes and the treatment affects neither viability nor growth capability of cells. However, molecular markers of apoptosis Bcl-2, p53, and caspase-3 were slightly affected in these cells. When copper-deficient cells were challenged with oxidative stress generated by paraquat or puromycin, they underwent a higher degree of apoptosis with respect to copper-adequate control cells. The mechanism underlying paraquat-triggered apoptosis implies dramatic activation of caspase-3 and induction of the transcription factor p53. These results demonstrate that impairment of copper balance predisposes neuronal cells to apoptosis induced by oxidative stress. Overall findings represent a contribution to the comprehension of the link between copper-imbalance and neurodegeneration, which has recently been repeatedly suggested for the most invalidating pathologies of the central nervous system.

Apoptosis↗

Neurodegeneration in the animal model of Menkes' disease involves Bcl-2-linked apoptosis.

Copper plays a key role in brain development, function and survival. Alteration of its homeostasis is suggested to be an aetiological factor in several neurodegenerative diseases. However, the molecular mechanisms relating copper to neurodegeneration are still unknown. In the present report, using morphological analyses of brain sections of mottled/brindled mutant (Mo(br/y)) mice, the animal model of the human genetic copper deficiency associated with neurodegeneration (Menkes' disease), we demonstrated that a high degree of apoptotic cells is present in the neocortex and in the hippocampus. Biochemical characterisation revealed decreased levels of copper content and of the activity of the mitochondrial copper-dependent enzyme cytochrome c oxidase. Copper, zinc-superoxide dismutase activity also shows a slight decrease, while no change was observed for glutathione content. Lower levels of ATP were also found, indicative of a copper-dependent impairment of energy metabolism. Changes appear to be specific for the brain, since no alterations in the activity of liver enzymes were found, although the level of copper was strongly decreased. We also tested biochemical factors involved in cell commitment to apoptosis. The expression of the anti-apoptotic protein Bcl-2, which plays a fundamental role in brain development and morphogenesis, was dramatically decreased and the levels of cytochrome c released from mitochondria into the cytosol were significantly increased. On the basis of these findings, we propose that down-regulation of Bcl-2 can cause neurodegeneration triggered by mitochondrial damage due to copper depletion during brain development in Mo(br/y) mice.

Adenosine Triphosphate↗

Radial nerve palsy caused by spontaneously occurring nerve torsion. Case report.

An 18-year-old man presented with a spontaneously occurring radial nerve palsy that spared the triceps muscle. At surgery, the portion of the radial nerve located at the midarm level had an hourglass-like appearance. Under magnification, an external-internal neurolysis of the narrowed portion of the hourglass-shaped portion revealed nerve torsion. Straightening of the twisted nerve and fixation accomplished using epiperineurium-fascia stitches to avoid a new torsion resulted in complete functional recovery of the radial nerve.

Adolescent↗

Pathology of the peripheral nervous system.

In this review, the first four papers deal with an important chapter in peripheral nerve surgery: cranial nerve reconstruction after injury occurring during skull base surgery. The last paper discusses the problem of peripheral nerves affected by a ganglion cyst. Damage to a cranial nerve is no longer considered to be an absolutely irreparable event. The first two studies are related to facial nerve management during the surgical treatment of vestibular schwannomas. The most common mechanisms responsible for facial nerve injury during tumor removal and the technical means to avoid them are cited. The importance of intraoperative neurophysiologic monitoring to save the facial nerve is stressed. A comparison between microsurgery and radiosurgery results in the conclusion that for vestibular schwannomas, the first choice of treatment is microsurgery. These two large and exceptional series show that by using a refined technique it is possible to obtain both total tumor removal and preservation of the facial nerve in most of the vestibular schwannomas. In the minority of patients in whom the facial nerve is severed, there are several therapeutic options to re-establish facial nerve function. After facial nerve reconstruction, performed immediately during the same tumor operation, a satisfactory reinnervation was obtained in 74% of the cases. After facial nerve reanimation, using as donor nerve the hypoglossus and performed 1 week after the tumor operation, a satisfactory reinnervation was obtained in 96% of the cases. The other two papers deal with the intraoperative transection of the trochlear and abducens nerve during surgery for skull base tumors. These two cranial nerves, owing to their simply organized motor nerve system (they are purely motor nerves and supply one muscle each), show quite a good expectation of functional recovery. The behavior of ganglion cysts involving peripheral nerves is the topic of the last paper reviewed. These cysts are benign lesions that can cause permanent neurologic deficits of the involved nerve. The etiology, clinical presentation, surgical techniques, and recurrence rate are reported. In the present series, the outcomes after ganglion cyst excision are not as favorable as those reported in other series. Before surgery, patients must be informed about the possibility of residual motor deficits and recurrences.

Journal Article↗

Decrease of cytochrome c oxidase protein in heart mitochondria of copper-deficient rats.

Copper deficiency has been reported to be associated with decreased cytochrome c oxidase activity, which in turn may be responsible for the observed mitochondrial impairment and cardiac failure. We isolated mitochondria from hearts of copper-deficient rats: cytochrome c oxidase activity was found to be lower than in copper-adequate mitochondria. The residual activity paralleled copper content of mitochondria and also corresponded with the heme amount associated with cytochrome aa3. In fact, lower absorption in the alpha-band region of cytochrome aa3 was found for copper-deficient rat heart mitochondria. Gel electrophoresis of protein extracted from mitochondrial membranes allowed measurements of protein content of the complexes of oxidative phosphorylation, revealing a lower content of complex IV protein in copper-deficient rat heart mitochondria. The alterations caused by copper deficiency appear to be specific for cytochrome c oxidase. Changes were not observed for F0F1ATP synthase activity, for heme contents of cytochrome c and b, and for protein contents of complexes I, III and V. The present study demonstrates that the alteration of cytochrome c oxidase activity observed in copper deficiency is due to a diminished content of assembled protein and that shortness of copper impairs heme insertion into cytochrome c oxidase.

Animals↗

Purification of a fully metal-depleted Cu, Zn superoxide dismutase from copper-deficient rat liver.

A copper-deprived form of the enzyme Cu, Zn superoxide dismutase was identified in the liver of rats made copper-deficient by dietary restriction. In homogenates of such livers Cu, Zn superoxide dismutase presents a dis-homogeneous electrophoretic profile with respect to the native enzyme. When rat liver extracts were treated with exogenous copper an electrophoretic pattern resembling the native one was observed. Enzyme purified by chromatography on DE-52 resin shows two major components, one corresponding to genuine, native enzyme and another one, eluting at higher ionic strength. The latter protein (Fraction II) consists of several isoforms which show the same characteristics of the native superoxide dismutase as far as immunoreactivity and molecular weight are concerned, but with decreased contents of copper and zinc. Its catalytic constant, referring to copper content, was 15 times lower than that obtained for the native enzyme. Moreover, the catalytic power of purified Fraction II was not regained upon incubation with copper. The occurrence of a superoxide dismutase void of metals confirms the hypothesis that this protein plays a dual physiological role: in metal metabolism and in superoxide anion dismutation.

Animals↗

Callosotomy for drug resistant generalized seizures.

We report our series of drug resistant epileptic patients submitted to callosotomy. The 25 patients were affected by severe epilepsy with invalidating generalized seizures with fall, lacking of indication for ablative surgery. Nineteen patients, with at least 1 year of follow-up, were considered for this study. The surgical outcome was classified as: class A), seizure disappearance; class B) 80%, class C) 80-50%, class D) less than 50% seizure reduction; E) increase of seizure frequency. The follow-up analysis shows that the better results are obtained with the generalized seizures, in particular the GTA. Our surgical results are discussed considering the data of the literature: about the functional anatomy of the Corpus Callosum, the experimental studies and the clinical series published on callosotomized epileptic patients.

Adult↗

[Cancer of the gallbladder].

Carcinoma of the gallbladder is the most frequent neoplasia of the biliary tract with an incidence of 2.5-4.4 cases for every 100,000 inhabitants; it more often affects females and elderly patients (60-70 years). It is an extremely malignant tumour with an often fatal prognosis owing to both its site and the generally late diagnosis; the majority of patients in fact undergo surgery at an advanced stage of the disease when surgery is only palliative. At the Surgical Division of S. Massimo Hospital in Penne (PE) a total of 897 operations on the gallbladder and biliary tract were performed between 1988 and 1994, revealing 21 cases of carcinoma of the cholecyst (2.3%). Sixteen patients were female (male-female ratio 1:3.2) with a mean age of 67.8 years (range 58-83 years). These patients were divided into 5 stages according to the UICC-1992 classification: 80.9% of cases were stage 3-4. Diagnosis was performed intraoperatively in 2 patients, whereas in 3 cases cancer had been diagnosed by the anatomo-pathologist. A total of 3 simple cholecystectomies were performed, 4 were associated with hepatic resection and lymphadenectomy of the hilus and hepatoduodenal ligament; surgery was enlarged in 2 cases due to the involvement of adjacent organs. After exploratory laparotomy, palliative surgery was performed in the remaining 12 patients in the form of biliary and derivation. Four system were implanted for intra-arterial chemotherapy. The most frequently found histological type was adenocarcinoma (76.2%). The mean survival rate of patients who died was 7.6 months. Six of the operated patients are still alive, of whom only one with a follow-up of 4 years. In conclusion, the authors agree with those who consider carcinoma of the gallbladder generally fatal in view of the rarity of early diagnosis and the difficulties of performing radical therapy.

Adenocarcinoma↗

Age-related changes in the binding and uptake of Cu, Zn superoxide dismutase in rat liver cells.

The present paper reports the effect of aging on receptor mediated endocytosis of Cu, Zn superoxide dismutase in rat liver cells. The fate of bovine Cu, Zn superoxide dismutase conjugated to colloidal gold was followed by electron microscopy in young (2 months) and old (24 months) rats in situ, in vivo and in vitro experiments. The use of different models for the study of the binding and internalization of the enzyme allowed to discriminate the contribution of each different liver cell type. The data obtained demonstrate that aging of the liver affects binding and uptake of this enzyme. In particular both the number of binding sites and the rate of internalization were depressed in old rats. Therefore, the hypothesis of therapeutic application of superoxide dismutase for age-related diseases needs to be revalued in view of the fact that receptor-mediated endocytosis of this protein is a mechanism affected by senescence.

Age Factors↗

Metopic synostosis: in favour of a "simplified" surgical treatment.

Metopic synostosis is a relatively simple form of craniosynostosis, resulting from premature fusion of the metopic suture. In this pathology different degrees of dysmorphia of the anterior cranial fossa and the presence of associated anomalies of the skull might enable specific subgroups to be identified. Since most functional and cosmetic anomalies benefit from early surgical treatment, over the last few years neurosurgeons have been forced to elaborate less drastic, but nonetheless effective, surgical techniques. In the present report we analyze the surgical results obtained in a series of 62 infants with trigonocephaly operated on within their 1st year of life. Patients were subdivided into two groups (group I: 8 patients; group II: 54 patients) according to the specific dysmorphic characteristics of the frontal bone and anterior cranial fossa, and the presence of compensatory deformities affecting the anterior cranial base and temporo-parietal region. All the patients were treated using one of two relatively simple surgical techniques (procedure A: inversion of two hemifrontal bone flaps--48 cases; procedure B: the "shell" operation--14 cases). Both surgical procedures appeared to be effective, allowing adequate functional and cosmetic correction of the cranial deformity. In patients operated on following procedure B surgical time and blood loss were dramatically reduced. Long-term outcomes were satisfactory in all cases, irrespective of the surgical technique used. In the group II patients, however, progressive normalization of the interorbital distance was constantly observed, suggesting a different degree of stenotic involvement at the level of the anterior cranial base in these patients.

Adolescent↗

Callosotomy for severe epilepsies with generalized seizures: outcome and prognostic factors.

The purpose of the present study was to verify the effect of callosotomy on generalized seizures, to check the effect on other seizure types and to search for possible prognostic factors. Twenty patients with a minimum follow-up of one year (mean 3.5 years) were available for our analysis. In six of them the callosotomy was performed in two stages (total: 26 surgical procedures). Age ranged from 14 to 40 years (mean 23 years). Different aetiologies were known in 15 patients. Duration of epilepsy ranged from 6 to 23 years (mean 15 years). The frequency of seizures ranged between 19 and 750 per month. The most significant effect of surgery was the complete suppression of the generalized seizures associated with falling in 9/19 and their reduction of more than 80% in 7/19 patients (total "good results": 16/19). The generalized tonic-clonic seizures were less affected. The surgical effect on the partial seizures was very variable, the partial simple seizures being the most affected. A positive statistical association with the outcome of the generalized seizures with fall was found for a presurgical seizure frequency below 90 per month, a prevalent bilateral EEG epileptic activity and, to a less extent, the absence of cerebral structural lesions. The role of age, aetiology, duration of the disease, single or more seizure types, mental impairment and extent of callosotomy remains uncertain. Disconnection syndrome does not appear if the splenium is spared. The present findings confirm that the main indication for callosotomy is the occurrence of generalized seizures with fall. Surgery can be initially limited to the anterior 2/3 of the corpus callosum; further posterior section of the corpus, excluding the splenium, should be regarded as a second step, when necessary.

Adolescent↗

N-[5-nitro-2-furfurylidene]-3-amino-2-oxazolidinone activation by the human intestinal cell line Caco-2 monitored through noninvasive electron spin resonance spectroscopy.

The pathways participating in the metabolism of the nitrofuran antimicrobial drug N-[5-nitro-2-furfurylidene]-3-amino-2-oxazolidinone (furazolidone) in intact cells were investigated in the human intestinal cell line Caco-2. One-electron reduction of furazolidone led to the formation of a free radical intermediate that could be monitored in dense cell suspensions by noninvasive electron spin resonance spectroscopy. The effects of enzyme inhibitors on the kinetics of radical production and decay were used to estimate the relative contribution of different enzymes to the reductive activation of the drug. Although many enzymes are known to reduce nitrofurans in vitro (e.g., xanthine oxidase, aldehyde oxidase, DT-diaphorase, mitochondrial redox chain components), their contributions were insignificant in living Caco-2 cells. The first reducing equivalent required for the formation of the nitroanion derivative of furazolidone appeared to be provided essentially by the microsomal cytochrome P450 reductase. This was confirmed through studies of the NADPH-dependent radical formation by microsomes. Differentiated Caco-2 cells, an established enterocyte model, showed only modestly increased radical formation and the same enzyme-specificity pattern as undifferentiated cells. Consistently, only a small increase in P450 reductase activity was found in differentiated cells, in contrast to the 10-fold increase seen in typical differentiation marker enzymes. With the electron spin resonance method that we describe, it is possible to distinguish between sites of bioactivation of redox active drugs in intact cells.

Animals↗