Smoking and use of mobile phones. Italian data don't show the same pattern.
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Biomedical subjects
Publications and source records attributed to G Invernizzi.
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Enlargement of cerebral ventricles is one of the most replicated biological features, and the one quantitatively most deviant in schizophrenia. It occurs in the early phases of the disease and may have pathogenetic relevance. Whether this abnormality is limited to a specific subgroup of patients or is a common feature to most or all patients affected by schizophrenia, however, is still a matter of debate. The answer to this question would improve our comprehension of the nature of this abnormality and contribute to the debate between the competing hypotheses of biological homogeneity vs heterogeneity of schizophrenia.We performed a distribution analysis of lateral ventricular dimensions of 340 schizophrenic patients and 162 non-psychiatric controls. All subjects underwent cerebral computerized tomographic scan, and ventricular dimensions were expressed as ventricular brain ratio (VBR). After removing the effect of confounding variables (age, sex and type of scanner) on individual VBR, data were power-transformed and different distribution hypotheses were tested by means of the maximum log-likelihood ratio method. Our findings indicate that, in the mixed sample of patients and controls, a mixture of two gaussian curves represents the distribution better than a single gaussian curve, but no evidence emerged leading to rejection of the normality hypothesis in the schizophrenic patients sample. Lateral ventricular enlargement in schizophrenia is not a marker of a discrete subgroup of schizophrenia, but occurs in most, if not all, schizophrenic patients. This supports the hypothesis of biological homogeneity of the disease, at least relative to its major brain morphological abnormality.
A variety of brain structural abnormalities, which can be identified only by qualitative methods, have been shown to correlate with clinical presentation and course of schizophrenia. In the present study, MRI scans of 122 patients with DSM-IV schizophrenia and 81 non-psychiatric controls were evaluated. Among males, the frequency of CNS developmental abnormalities (CDAs) was higher in patients than in controls. Lateral ventricular enlargement (LVE) was more frequent in patients than in controls; when subjects were grouped in three age classes, LVE was more frequent in patients than in controls in the youngest and the oldest age group. Patients with LVE or third VE were older than those without these abnormalities. Schizophrenic patients with LVE or cortical atrophy (CA) had a longer duration of illness than those without these abnormalities. Both patients with LVE and those with third VE had a poorer outcome than those without these abnormalities. CDA findings add to the evidence of a higher frequency of neurodevelopmental abnormalities in male schizophrenic patients. Results concerning LVE suggest that both developmental and degenerative processes underlie this abnormality. The association of LVE and third VE with a poor outcome indicates that qualitative MRI evaluation might be of clinical relevance.
PURPOSE: In diabetes, the interaction of glycated proteins with their cell-surface binding sites leads to oxidative stress and induction of the stress protein heme oxygenase (HO)-1. Considering that carbon monoxide (CO) is a product of HO activity, we studied the level of exhaled CO as a marker of oxidative stress in diabetes. METHODS: Eight patients with insulin-dependent diabetes mellitus (type 1) (4 men, 4 women; [mean +/- SEM] age, 50 +/- 8 years) were studied, of whom 2 had peripheral neuropathy and 1 had renal failure. Sixteen patients with non-insulin-dependent diabetes mellitus (type 2) (5 men, 11 women; age 63 +/- 8 years) were studied, of whom 2 had peripheral neuropathy. Glycosylated hemoglobin (HbA(1)c) levels were higher (7.4 +/- 0.3%) in patients with type 1 (mean duration of the disease, 20 +/- 5 years) than in type 2 (4.9 +/- 0.4%; p < 0.05; mean duration of the disease, 11 +/- 2 years). All of the patients were lifelong nonsmokers. RESULTS: Levels of exhaled CO were higher in patients with diabetes (type 1, 4.0 +/- 0.7 ppm; type 2, 5.0 +/- 0.4 ppm) when compared to 37 nonsmoking healthy subjects (20 men, 17 women; age, 33 +/- 3 years) (2.9 +/- 0.2 ppm; p < 0.05). There was a positive correlation between exhaled CO levels and the incidence of glycemia in all subjects (r = 0.52, p < 0.05) and the duration of diabetes (r = 0.48, p < 0.05), but there was not a strong correlation with concentrations of HbA(1)c (r = 0.06, p = 0.8). In addition, an oral glucose tolerance test was performed in five healthy nonsmoking volunteers (three men; age, 33 +/- 4 years). The maximal glucose increase (from 3.9 +/- 0.2 to 5.5 +/- 0.1 mmol/L at 15 min; p < 0.05) was associated with a significant increase in exhaled CO concentration (from 3.0 +/- 0.5 to 6.3 +/- 1.0 ppm; p < 0. 05). Both parameters returned to the baseline at 40 min after glucose administration. CONCLUSIONS: Elevated levels of exhaled CO in diabetes may reflect HO-1 induction and oxidative stress. The measurement of CO may be a new tool for disease monitoring.
A possible relationship between haematological adverse reactions and clozapine (CLZ) metabolism rate was studied. Sixteen chronic schizophrenic outpatients (mean age 34.62 years +/- 7.56 SD) were treated with CLZ, 75-600 mg/daily for 9 weeks. CLZ and norclozapine (NCLZ) plasma levels were determined weekly, contemporarily with blood cell counts. CLZ plasma levels ranged from 25 to 1270 ng/ml (mean 266.27 ng/ml +/- 197.44 SD), while NCLZ plasma levels ranged from 25 to 1280 ng/ml (mean 169.0 ng/ml +/- 127.94 SD). NCLZ/CLZ ratio ranged from 0.13 to 1.72 (mean 0.72 +/- 0.28 SD). Leukocyte count ranged from 5.2 to 18.8 10(9)/l (mean 9.37 10(9)/l +/- 2.94 SD) and neutrophil count ranged from 1.8 to 13.4 10(9)/l (mean 5.73 +/- 2.57 SD). No correlation was found between CLZ dosage and NCLZ plasma levels. Both CLZ and NCLZ plasma levels correlated positively with neutrophil count (CLZ: P = 0.001, r = 0.26; NCLZ: P = 0.01, r = 0.20). The correlation between NCLZ/CLZ plasma level ratio and neutrophil count was significantly negative (P = 0.002, r = 0.25). These preliminary data suggest that the NCLZ/CLZ ratio, as an index of CLZ metabolism, might be a possible risk factor associated with CLZ treatment.
Plasma and platelet levels of 18 amino acids were measured in 29 outpatients (mean age +/- SD 47.41 +/- 10.85 years; 14 F, 15 M) affected by major depression (DSM IV) and in 28 healthy volunteers (mean age 42.46 +/- 14.19 years; 12 F, 16 M). Plasma and platelet levels of amino acids tended to be higher in depressed patients than in healthy controls. In particular, glutamate, taurine and lysine plasma levels and aspartate, serine and lysine platelet levels were significantly higher. Tryptophan/large neutral amino acids ratio (trp/LNAAs) was significantly lower in depressed patients. Fluvoxamine treatment did not influence plasma and platelet levels of amino acids or trp/LNAAs ratio.
A sex chromosome locus for psychosis has been considered on the basis of some sex differences in genetic risk and expression of illness, and an association with X-chromosome anomalies. Previous molecular genetic studies produced weak evidence for linkage of schizophrenia to the proximal short arm of the X-chromosome, while some other regions were not ruled out. Here we report an attempt to expand the Xp findings in: (i) a multicenter collaboration focusing on 92 families with a maternal pattern of inheritance (Study I), and (ii) an independent sample of 34 families unselected for parental mode of transmission (Study II). In the multicenter study, a parametric analysis resulted in positive lod scores (highest of 1.97 for dominant and 1.19 for recessive inheritance at a theta of 0.20) for locus DXS7, with scores below 0.50 for other markers in this region (MAOB, DXS228, and ARAF1). Significant allele sharing among affected sibling pairs was present at DXS7. In the second study, positive lod scores were observed at MAOB (highest of 2.16 at a theta of 0.05 for dominant and 1.64 at a theta of 0.00 for recessive models) and ALAS2 (the highest of 1.36 at a theta of 0.05 for a recessive model), with significant allele sharing (P = 0.003 and 0.01, respectively) at these two loci. These five markers are mapped within a small region of Xp11. Thus, although substantial regions of the X-chromosome have been investigated without evidence for linkage being found, a locus predisposing to schizophrenia in the proximal short arm of the X-chromosome is not excluded.
Sixty-two schizophrenic patients and 26 healthy volunteers were administered the Wisconsin Card Sorting Test (WCST) a task putatively specific for frontal functions and the Wechsler Adult Intelligence Scale (WAIS). The purpose of this study was to evaluate the presence of specific frontal lobe deficits in the course of schizophrenia and the capacity of these tasks to discriminate between patients and controls. Schizophrenic patients showed a poorer performance than control subjects in both tests. No evidence emerged to support a higher discriminant power for the WCST in identifying schizophrenic subjects from healthy controls compared with the WAIS. Our data suggest that the deficit in WCST performance is not selective, but rather part of a more generalized neuropsychological impairment in schizophrenic patients.
In the absence of direct and conclusive data demonstrating the 'neurodevelopmental hypothesis' of schizophrenia, several neuromorphological findings provide relevant clues in support of it. In this paper, we review a number of results obtained by our group in this area of research. In particular, the demonstration of stability of cerebral ventricular dimensions both in chronic schizophrenia and around the onset of the disease, and that of an identical effect of ageing on this morphological feature in large samples of patients and controls, strongly support the neurodevelopmental nature of brain pathomorphology in schizophrenia.
Small cell lung cancer (SCLC) expresses somatostatin receptors that can be traced with 111In-DTPA-octreotide scintigraphy. Although this technique is currently employed for staging and follow-up of neuroendocrine tumors of the gastrointestinal tract, its role in the clinical work-up of SCLC is at present under discussion. A better imaging contrast is desirable and recent reports suggest that this aim could be achieved by pretreatment with cold octreotide. Here we report on the results of 111In-DTPA-octreotide scintigraphy in 12 SCLC patients carried out before and after octreotide treatment. The patients were treated for 7 days with octreotide 200 micrograms three times a day s.c. Uptake was studied at 5 h with whole body planar and SPET imagings. In all cases studied, pretreatment with octreotide was followed by enhancement of tumor imaging. In one patient a better contrast of the lesions was found at the parenchymal and mediastinal levels as well as at brain level, allowing a clear definition of otherwise questionable metastases. After octreotide treatment, a decrease in background uptake in the subdiaphragmatic area was observed in most cases, allowing a better imaging of liver metastases. The enhancement effect was confirmed by semiquantitative analysis of scintigraphic uptake. Taken together, our results seem to indicate that cold octreotide enhancement can improve 111In-DTPA-octreotide imaging and optimize its clinical role in SCLC.
Although the existence of chronic depression has been recognized for a long time, their definition was too inaccurate to enable reliable studies concerning their treatment. Among the numerous diagnostic classes that patients with chronic depression were assigned to, neurotic depression was the most common one, and was often considered to be unresponsive to antidepressant medication. Since DSM-III introduced 'Dysthymic Disorder', a new research was developed on the efficacy of tricyclic antidepressants, MAOIs or new antidepressants, whose results reversed previous opinion on its unresponsiveness. However the interpretation of those studies are hampered by methodological problems, yet unresolved, pertaining to the difficulty to differentiate dysthymia and major depression, to the frequency of 'double-depression', the usual mildness of symptoms in dysthymia, and the need of long-term trials.
The 20-item Toronto Alexithymia Scale (TAS-20) has been shown in previous research to measure a general dimension of alexithymia with three intercorrelated factors. This study evaluated the reliability and factorial validity of an Italian translation of the TAS-20 in a group of normal adults (N = 206) and in a mixed group of medical and psychiatric outpatients (N = 642). Using confirmatory factor analyses, the previously established three-factor model of the TAS-20 was found to be replicable in both groups. In addition, the Italian TAS-20 demonstrated adequate estimates of internal reliability and test-retest reliability. Although evaluation of the convergent, discriminant, and concurrent validity of the TAS-20 is required in Italian populations, the present results support the use of the Italian translation of the scale for clinical and research purposes.
Sulpiride is a substituted benzamide with a selective action on receptors of the dopamine D2-like family, and clinical and pharmacological data suggest that it could be considered to be an atypical antipsychotic. Sulpiride penetrates the blood-brain barrier poorly because of its low lipid solubility. It is mainly excreted unchanged in the urine, and accumulation of the drug could occur in patients with renal dysfunction and possibly in elderly patients with declining glomerular filtration rate. At low dosages (50 to 150 mg/day), sulpiride produces a disinhibiting and antidepressant effect, which is probably related to its action on D2 presynaptic autoreceptors, thus facilitating dopaminergic neurotransmission. Data have confirmed the efficacy of sulpiride in patients with acute or chronic schizophrenia during both short and long term treatment, but long term, placebo-controlled trials are still lacking. It is still doubtful whether sulpiride is more effective than typical antipsychotics for the treatment of negative symptoms. Data from clinical studies are controversial; the majority of authors indicate that sulpiride produces a better recovery rate from negative than from positive symptoms at low doses, but it shows a similar efficacy either on negative and positive symptoms at higher doses. The safety profile of sulpiride is similar to that of typical antipsychotics, although the frequency of adverse effects seems to be globally lower. Extrapyramidal reactions appear generally to be mild. Autonomic effects occur less frequently with sulpiride than with typical antipsychotics, showing no clinically relevant influence on cardiovascular parameters and, on the whole, good tolerability in elderly patients. Sulpiride is known to induce prolactin elevation in both serum and CSF, which may be associated with impotence in men and diminished gonadal function in women; these effects appear to be dosage-dependent. Sulpiride can be considered to be an atypical antipsychotic, considering its action on negative, defective symptoms, its partial activity against positive symptoms, and its low incidence of extrapyramidal adverse effects. Sulpiride could find its specific therapeutic role in elderly patients with schizophrenia, as it shows a good margin of safety between therapeutic dosages and toxic concentrations.
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Somatostatin receptors have been described on the membrane of neoplastic cells derived from the APUD system and their expression has also been demonstrated on small cell lung cancer (SCLC) in vitro and in vivo. 21 patients with SCLC were studied using 111In-octreotide (111In-OCT) scintigraphy. Scintigraphic examinations were performed following intravenous (i.v.) injection of 111 MBq 111In-OCT with whole-body scintigraphy and planar scintigraphy of the thorax as well as the SPET technique. No short-term side effects were described following 111In-OCT administration. We studied the 111In-OCT biodistribution in 3 patients with serial scintigraphies at 1, 5 and 24 h. We used the 5 h as standard scanning time for the following 18 patients. The scintigraphic results were compared with those of other conventional diagnostic procedures. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy. It was positive in all 20 SCLC patients and negative in one lung adenocarcinoma. 111In-OCT showed high sensitivity for mediastinal metastases (94%) and good sensitivity for bone metastases (75%) and abdominal lymph node metastases (71%). 111In-OCT did not detect two liver metastases. 111In-OCT detected five unknown lesions which were confirmed by other diagnostic examinations. 111In-OCT was also effective in cancer patients with low levels of NSE. Our study shows that 111In-OCT scintigraphy is a reliable, non-invasive technique to detect primary SLCL and its locoregional or distant metastases. The clinical utility of receptor status characterisation obtained with 111In-OCT scintigraphy should be evaluated by means of an appropriate prospective study.
OBJECTIVE: The purpose of the study was to compare regional cerebral blood flow (CBF) in schizophrenic patients never treated with psychotropic drugs (drug-naive) and in schizophrenic patients free from drugs for various amounts of time. METHOD: Seventeen schizophrenic patients (nine who were drug naive and eight who had been drug free for at least 3 weeks) and 12 healthy volunteers were included in the study. Regional cerebral perfusion was studied with the use of a head-dedicated, high-resolution single photon emission computed tomography (SPECT) system. Cerebral SPECT scans were performed with technetium-99m-hexamethyl-propyleneamine oxime as a tracer. Regional CBF was measured as a ratio of regional tracer uptake to either cerebellar or whole brain tracer uptake. RESULTS: When the cerebellum was taken as the reference region, the drug-naive patients showed a significant bilateral reduction of perfusion in the mesial, dorsolateral, and basal prefrontal cortex, in the temporal cortex, and in the subcortical gray structures: thalamus, caudate nucleus, and putamen/pallidum complex. No significant differences emerged in the comparison between the drug-free patients and the healthy subjects. With correction for whole brain activity, some of the differences that had been found disappeared, but a significant hypoperfusion persisted in the basal ganglia and thalamus of the drug-naive, but not the drug-free, patients. Few correlations between symptom presentation and regional CBF perfusion were observed in the schizophrenic patients. CONCLUSIONS: These results suggest a pattern of cerebral hypoperfusion in schizophrenic patients never treated with neuroleptics that was not detectable in patients who had undergone various periods of pharmacological washout.
A particular importance can assume, especially during the onset of Alzheimer's disease, the psychiatric symptomatology characterized by depressive mood, auto and hetero-aggressive behaviour, psychomotor agitation, anxiety disorders, sleep disorders, delusions and hallucinations, these pictures showing a prevalence of 30%. 13 patients affected by Alzheimer's disease at the onset, of both sexes, age ranging from 45 to 80 years, were included in the study. The clinical picture was assessed by BDS, GDS, ICS, IADL, BIMC, MMSE, ADAS, a neuropsychological test battery such as Token Test, verbal fluency test for semantic categories, prose memory test, scribble discrimination test, numeric matrix test, Raven test, judgement of line orientation. A computerized test battery by NYU Computerized Test Battery have been also administered. The psychiatric clinical picture has been evaluated by HRS-D and the non cognitive session of ADAS. There was a positive significant (r = 0.85, p = 0.0004) correlation between depressive symptomatology evaluated at HRS-D and deterioration of daily living activities evaluated at the Blessed Dementia Scale (BDS). On the other hand the deterioration of cognitive capacities was not significantly correlated with a worsening of behavioural aspects. In conclusion seems to have a particular importance, at the onset of Alzheimer's disease, the psychopathological component that often seems to be the principal component in the determination of the early deterioration of daily living and behaviour or patients.
AIMS AND BACKGROUND: The somatostatin analog octreotide has an antiproliferative effect on small cell lung cancer lines in vitro and in experimental xenograft transplantation systems in vivo. Thus it is worth investigating octreotide activity in the clinical setting. METHODS: We studied the effect of octreotide (200 micrograms three times a day subcutaneously for seven days) on serum levels of the tumor marker neuroenolase in 13 patients with small cell lung cancer. RESULTS: A decrease in neuroenolase levels was observed at day 7 during octreotide treatment, with a mean +/- SD of 32.6 +/- 42.0 ng/ml compared to basal values of 44.4 +/- 57.7 ng/ml and to washout values of 50.3 +/- 65.7 ng/ml (P < 0.03). CONCLUSIONS: Our results indicate that octreotide is effective in reducing neuroenolase levels in small cell lung cancer patients. These data suggest a possible role for octreotide in the treatment of this kind of tumor.