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Biomedical subjects

G Gobbi

Publications and source records attributed to G Gobbi.

At least 37 records · Page 2Linked to original sources

Antithrombotic therapy of unstable angina and non-Q-wave myocardial infarction.

Unstable angina and non-Q-wave myocardial infarction still represent an unsolved problem for clinicians, owing to their unpredictable evolution and high incidence of coronary events in the follow-up. Traditional antithrombotic agents, unfractionated heparin and aspirin, have been proved to be highly effective, but show some important limitations. New potent antithrombotic therapy have been studied to improve their efficacy, with encouraging results. Among these drugs, low molecular weight heparins (for subcutaneous administration) and inhibitors of platelet glycoprotein receptor IIb/IIIa (for intravenous, and possibly oral, administration) are the most promising and are now under extensive investigation.

Abciximab↗

Prospective study of first-line vigabatrin monotherapy in childhood partial epilepsies.

This was a prospective open comparative pilot study to assess the efficacy and tolerability of first-line vigabatrin monotherapy in childhood partial epilepsies. Two groups of patients were recruited over the same period. The vigabatrin monotherapy group comprised 40 patients (18 male, 22 female; mean age at last visit 7.5 years); the comparative carbamazepine monotherapy group comprised 40 consecutive clinic patients (22 male, 18 female; mean age at last visit 7.8 years). Seizures disappeared in 82% of vigabatrin patients and in all carbamazepine patients with idiopathic partial epilepsy, and in 50% of vigabatrin patients and 55% of carbamazepine patients with symptomatic partial epilepsy. Interictal EEG abnormalities decreased in vigabatrin patients more than in carbamazepine patients (P < 0.05). Tolerability was good in vigabatrin patients, but four out of 37 showed mild irritability by the end of the trial. Persistent sedation was observed in eight of the 40 patients receiving carbamazepine. No patient had drug therapy discontinued because of side-effects. During vigabatrin long-term monotherapy, efficacy and good clinical tolerability were maintained. These results suggest that vigabatrin may be an alternative first-line treatment for childhood partial epilepsies. Further blinded comparative randomized trials are needed.

Adolescent↗

Clozapine blocks dopamine, 5-HT2 and 5-HT3 responses in the medial prefrontal cortex: an in vivo microiontophoretic study.

Clozapine is an atypical antipsychotic drug active on both positive and negative symptoms of schizophrenia which has a unique serotonergic and dopaminergic profile. Given the putative role of the medial prefrontal cortex (mPFC) in negative symptoms of schizophrenia, the aim of this study was to assess the effects of clozapine on the dopamine- and serotonin-responsive neurons in that particular brain structure. D1 and D2 agonists (SKF 38393 and quinpirole) as well as 5-HT2 and 5-HT3 agonists (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, DOI, and phenylbiguanide) were applied by microiontophoresis alone and concurrently with clozapine while recording extracellularly mPFC neurons. Dopamine ejections inhibited firing activity while D1 and D2 agonists were ineffective. Clozapine did not change basal firing by itself, but was able to suppress the inhibition produced by dopamine and by the 5-HT2/5-HT3 receptor agonists. It is concluded that clozapine at the mPFC level exerts a complex modulatory activity on dopamine receptors, that is directly at the dopaminergic receptors and through 5-HT receptors on the same neurons.

Action Potentials↗

Absolute quantification of brain metabolites by proton magnetic resonance spectroscopy in normal-appearing white matter of multiple sclerosis patients.

The aim of this research was to obtain an absolute quantification of the N-acetyl-aspartate, choline, creatine and phosphocreatine levels in normal-appearing white matter by means of 1H magnetic resonance spectroscopy in a group of multiple sclerosis patients (27 with the relapsing-remitting form and 13 with the secondary progressive form). These values were compared with those of a group of 12 age-matched healthy control subjects. A significant decrease in the N-acetyl-aspartate concentration was found in normal-appearing white matter of frontal and parietal brain areas in multiple sclerosis patients compared with the same areas in control subjects. This reduction was more evident in progressive patients. The decrease in the N-acetyl-aspartate concentration in normal-appearing white matter significantly correlated with the Expanded Disability Status and the lesional load. No significant change was found in the concentration of creatine or choline. This finding concurs with previous evidence of heterogeneity in the multiple sclerosis pathological process which is not confined to the lesions and involves not only myelin, but also axons, even in white matter which appears normal on MRI.

Adult↗

Absolute metabolite quantification by in vivo NMR spectroscopy: II. A multicentre trial of protocols for in vivo localised proton studies of human brain.

We have performed a multicentre trial to assess the performance of three techniques for absolute quantification of cerebral metabolites using in vivo proton nuclear magnetic resonance (NMR). The techniques included were 1) an internal water standard method, 2) an external standard method based on phantom replacement, and 3) a more sophisticated method incorporating elements of both the internal and external standard approaches, together with compartmental analysis of brain water. Only the internal water standard technique could be readily implemented at all participating sites and gave acceptable precision and interlaboratory reproducibility. This method was insensitive to many of the experimental factors affecting the performance of the alternative techniques, including effects related to loading, standing waves and B1 inhomogeneities; and practical issues of phantom positioning, user expertise and examination duration. However, the internal water standard method assumes a value for the concentration of NMR-visible water within the spectroscopic volume of interest. In general, it is necessary to modify this assumed concentration on the basis of the grey matter, white matter and cerebrospinal fluid (CSF) content of the volume, and the NMR-visible water content of the grey and white matter fractions. Combining data from 11 sites, the concentrations of the principal NMR-visible metabolites in the brains of healthy subjects (age range 20-35 years) determined using the internal water standard method were (mean+/-SD): [NAA]=10.0+/-3.4 mM (n=53), [tCho]=1.9+/-1.0 mM (n=51), [Cr + PCr]=6.5+/-3.7 mM (n=51). Evidence of system instability and other sources of error at some participating sites reinforces the need for rigorous quality assurance in quantitative spectroscopy.

Adult↗

Celiac disease, bilateral occipital calcifications and intractable epilepsy: mechanisms of seizure origin.

PURPOSE: To elucidate the mechanisms of seizure origin in patients with celiac disease and bilateral occipital calcifications (CEBOC). Individuals with CEBOC frequently present with occipital lobe seizures, but additional lesions and additional attack patterns may occur. METHODS: We studied two men and one woman who had CEBOC. Villous atrophy was revealed in the two patients who underwent duodenal biopsy. All had a comprehensive presurgical evaluation, including prolonged video-EEG recordings. Two had magnetic resonance imaging (MRI) with volumetric study of mesial temporal structures (MRIV). One patient had undergone stereotactic intracranial depth electrode studies (SEEG). RESULTS: All patients presented with intractable complex partial seizures. Two had partial simple seizures with visual aura. Neurologic examination was normal; one was of normal intelligence, and two were mildly retarded. Neuroimaging studies showed that each had bilateral occipital calcifications as well as epileptiform abnormalities over temporal lobes. In one, MRI showed an additional right frontal lesion, but SEEG demonstrated right occipital lobe seizure origin with anterior spread; this male patient later underwent a right occipital lobe resection. Another with a history of prolonged febrile convulsions had bilateral hippocampal and amygdalar atrophy demonstrated by MRIV. CONCLUSIONS: In one patient, SEEG confirmed that seizures originated in the occipital lobe. The presence of dual pathology was demonstrated in another, raising the possibility of both occipital and temporal seizure onset. The presence of extraoccipital lesions or of mesial temporal atrophy requires SEEG for clarification of seizure onset. In the absence of confounding factors and when laterality can be demonstrated, surgical treatment may be considered.

Adult↗

1H-MRS in patients with multiple sclerosis undergoing treatment with interferon beta-1a: results of a preliminary study.

BACKGROUND: In vivo magnetic resonance spectroscopy (MRS) has been widely used to assess biochemical changes which occur in demyelinating lesions in white matter of patients with multiple sclerosis. It has been suggested that metabolic variations evidenced by MRS are sensitive indicators of the effects of immunomodulatory treatments in this disease. Given the recent finding of an increase in the disease activity in patients with multiple sclerosis treated with interferon (IFN) beta-1a in the first period of treatment,1H MRS was used to investigate further the modification in brain metabolic indices, particularly in the first phase of IFN beta treatment. METHODS: A 1H MRS study was performed on five patients with relapsing-remitting multiple sclerosis who were being treated with intramuscular IFN beta-1a (6 million units/week) for six months and on five untreated patients. The mean age, duration of the disease, and expanded disability status scores (EDSS) of the two groups were similar. Patients were evaluated at the beginning of the study and in the first, third, and sixth months of treatment. RESULTS: In the multiple sclerosis white matter lesions, N-acetylaspartate (NAA), choline (Cho), inositol (Ins), and creatine (Cr) peaks did not vary significantly over the entire period of the study in the untreated group. In the treated group there was a significant increase in the Cho peak area at the first month compared with the pretreatment period, and this increase continued in the third and sixth months (p<0.001). A slight but not significant rise in the Cho peak was also found in normal appearing white matter in the patient group undergoing treatment with IFN beta-1a. The increase in Cho and the lack of significant changes in Cr and NAA peaks induced a significant rise in Cho/Cr and Cho/NAA ratios over the entire period of treatment compared with those at the beginning of the study (p<0.02 and p<0.005 respectively). In the treated group there was a slight but significant increase in the Ins peak in the first month (p<0.05) but in the third and sixth months of treatment the Ins values returned to the pretreatment range. CONCLUSIONS: IFN beta-1a has an impact on metabolite concentrations in multiple sclerosis lesions measured by proton MRS. The increase in Cho, Cho/NAA, and Cho/Cr ratios in multiple sclerosis lesions reinforces the view that they are an index of active or recent demyelination and could support the clinical, neuroradiological and immunological evidence showing an increase in disease activity during the first period of treatment with IFN beta-1a. On the other hand, the increase in the Cho peak could be indicative of a rise in membrane turnover in multiple sclerosis lesions or a remodelling of plaques which is not necessarily due to a de novo immune mediated demyelination.

Adult↗

Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging.

In order to evaluate the pattern of proton magnetic resonance spectroscopy (1H-MRS) in the gray and white matter of patients with Alzheimer's disease (AD) and healthy controls, a cross-sectional study was carried out on 13 consecutive AD patients and 7 healthy older subjects who were referred to the Day-Hospital for diagnostic assessment. All examinations were performed on a 1.5 Tesla whole-body scanner. Volumes of interest were selected in both the gray (temporal region) and the white (frontal region) matter. N-acetyl group, total creatine, total choline and myo-inositol were quantified referring the metabolite peak area to the unsuppressed water peak area acquired under the same conditions, and the ratio was expressed in arbitrary units. A significant decrease in N-acetyl-aspartate (NAA) in both gray and white matter and an increase in myo-inositol (mI) in gray matter of AD patients were observed. The gray matter NAA/mI ratio clearly separated the two groups. White matter mI was significantly associated with severity and duration of dementia. No association with age was documented. It can be concluded that in vivo 1H-MRS can contribute to the knowledge of pathophysiology of AD, giving neurochemical details of both gray and white matter. In particular, the gray matter NAA/ml ratio seems to be able to differentiate normal cerebral aging from Alzheimer's disease.

Aged↗

An experimental study in X-ray spectroscopy of the zirconium (Ca-PSZ) - bone interface. Microanalytic evaluation of the osteogenetic response.

Ultrastructural difractometric and chemical evaluations of calcium partially stabilized zirconium (Ca-PSZ) implants were performed in an in vivo study on animals in order to evaluate its biological behaviour. The chemical-morphological investigations demonstrated the presence of an osteogenetic activity at the bone-biomaterial interface. The new-osteogenesis was preceded by the formation of a loose connective tissue around the implants. This mesenchymal-type tissue without a capsular organization, allowing modulation of the mechanical forces to which the implant is subject, could be considered a positive event in the osteogenetic process and not a sign of future failure of the implant. Finally, microanalytical investigations carried out on non-implanted and implanted Ca-PSZ tools suggested that the surface of this ceramic material does not undergo modification once it has been inserted in the biological environment (12 months).

Journal Article↗

Familial Unverricht-Lundborg disease: a clinical, neurophysiologic, and genetic study.

PURPOSE: Progressive myoclonus epilepsies (PMEs) are a clinically and etiologically heterogeneous group of disorders. The authors report clinical, neurophysiological, and genetic findings of a family from Southern Italy with three members affected with PME. METHODS: All data about familial and personal antecedents, clinical history, neurologic examination, laboratory tests, neurophysiological findings, brain imaging studies, and DNA analysis were examined. RESULTS: All results were compatible with the features of Unverricht-Lundborg disease and patients were homozygous for the "Finnish" ancestral haplotype. CONCLUSIONS: Work is in progress to identify and characterize the common EPM1 mutation in the Finnish patients. Subsequently, it will be possible to verify the hypothesis on the existence of a common mutation in the Finnish patients and the Italian family under study, or even in other Mediterranean EPM1 families.

Adult↗

Clinical heterogeneity of adhalin deficiency.

We report adhalin deficiency in 8 patients with clinically diagnosed muscular dystrophy, dystrophic histopathological features, high plasma creatine kinase levels, normal expression of dystrophin, and marked variability of symptoms. Although the distribution of hyposthenia was similar in all 8 patients and predominantly involved muscles in the pelvic girdle, age at onset and rate of disease progression were highly variable: In 2 patients onset, at ages 24 and 25, was later than has been previously observed. We found no apparent relation between disease severity and the quantity of adhalin expressed. Two kinds of myopathy with adhalin deficiency have been reported: one caused by a mutation in the adhalin gene on chromosome 17 (primary adhalinopathy) and the other linked to chromosome 13. The product of the gene on chromosome 13 is probably associated with adhalin and its deficiency results in secondary adhalinopathy. The severity of clinical phenotypes in these adhalinopathies seems to relate more to the kind and site of the mutations than to the residual amount of the protein. We also detected a variable reduction in the laminin beta 1 subunit by immunohistochemistry in most patients, confirming that this is commonly associated with adhalin deficiency.

Adolescent↗

1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging, age-associated memory impairment, and probable Alzheimer's disease.

OBJECTIVE: To better understand how to differentiate the "in vivo" normal aging brain from pathological conditions, namely dementia of the Alzheimer type (DAT), by means of magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and proton magnetic resonance spectroscopy (1H-MRS), to show neuroanatomical, perfusional and neurochemical details, respectively. DESIGN: 1H-MRS, MRI-based hippocampal volumetry and 99mTc-HMPAO SPECT were performed in healthy older subjects as well as patients suffering from age-associated memory impairment (AAMI) and dementia of Alzheimer type (DAT). SUBJECTS AND SETTING: Eighteen subjects were selected from those referred to an outpatient clinic for diagnostic evaluation of cognitive impairment entered the study. Six patients fulfilled NINCDS-ADRDA diagnostic criteria for DAT, six subjects were affected by AAMI, and six cognitively healthy subjects, selected from among relatives of the patients, were defined as controls. METHODS: The 1H-MRS and MRI studies were performed on a 1.5 Tesla NMR-imaging system equipped with a spectroscopy research package. SPECT scans were performed on a Gamma 11 computer system. FINDINGS: 1H-MRS showed significantly lower N-acetylasparatate concentration in DAT and AAMI compared with controls. Conversely, mean inositol concentration was significantly higher in DAT than in controls, whereas AAMI subjects registered intermediate values. MRI measurements showed significantly reduced volumes of hippocampal formations in DAT and AAMI groups compared with controls. Finally, 99mTc-HMPAO SPECT showed a significant frontal, temporo-parietal, and occipital hypoperfusion in DAT patients only. CONCLUSIONS: These findings support the hypothesis of a continuum among the three conditions studied, or at least between AAMI and DAT, where AAMI seems to be an early, monosymptomatic stage of Alzheimer disease. Accepting this view, it would be questionable to maintain the term "age-associated memory impairment" as a discrete entity.

Aged↗

Effects of fluoxetine at antidepressant doses on short-term outcome of detoxified alcoholics.

Compulsivity in alcohol-dependent patients is a frequent cause of early relapse in the post-detoxification period. The present study is a 2-month trial on detoxified alcoholics undergoing a double-blind placebo-controlled treatment with fluoxetine (20 mg/day). The rating instruments were the Hamilton Depression and Anxiety Scales, a visual analogue scale for alcohol craving and an original scale for evaluating alcohol withdrawal. The abstinence rate for fluoxetine-treated patients was significantly higher than in the placebo group, whereas no difference between treatments was found on the rating scales. Medical problems, additional psychiatric diagnoses, and family alcoholism were negatively correlated with abstinence. Two subgroups of patients having significantly different characteristics were identified as to the outcome, by means of cluster analysis. They are likely to represent two different stages in the evolution of alcoholism. Our results show that, independently from craving, fluoxetine at antidepressant doses is able to prevent relapses in weaned alcoholics. The anticompulsive therapy can positively influence the short-term outcome, while other factors are negatively associated with abstinence.

Adult↗

Alterations of the thalamo-cortical system in rats prenatally exposed to ethanol are prevented by concurrent administration of acetyl-L-carnitine.

We previously demonstrated that adult rats prenatally exposed to ethanol display permanent damages of thalamo-cortical connections [18,19,33]. Here the effect of simultaneous administration of ethanol and acetyl-L-carnitine has been investigated. Adult animals underwent cortical or thalamic injections of horseradish peroxidase and both anterograde and retrograde thalamic and cortical labeling have been analyzed. Ethanol-induced changes of thalamo-cortical circuits are prevented by concurrent administration of acetyl-L-carnitine. Possible mechanisms underlying this effect are discussed.

Acetylcarnitine↗