[Investigations on schizophrenia theory 1961-1965. II].
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Biomedical subjects
Publications and source records attributed to G Benedetti.
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Since some H2-receptor antagonists, like cimetidine or ranitidine, affect ethanol metabolism by interference with gastric and/or hepatic alcohol dehydrogenase (ADH) it was investigated whether omeprazole has a similar effect and its effects were compared with those of cimetidine, an inhibitor of gastric ADH. The first-pass metabolism (FPM), quantified by measuring the difference between areas under the curve (AUC) of ethanol blood concentrations after oral intake or intravenous administration of the same amount (0.3 g kg-1 b.w.) of ethanol (EtOH), was studied before and after 1 week of omeprazole (20 mg daily) or cimetidine (800 mg daily) administration in 10 normal male volunteers. ADH activity was determined in gastric mucosal samples, collected during endoscopy, before and after 1 month of omeprazole treatment. The effect of the drugs on gastric and hepatic ADHs was studied in vitro in both rat and man. No significant effect of omeprazole was found on AUCs of the blood EtOH concentrations. The ADH activity in antral mucosa before and after omeprazole therapy did not show significant differences. In vitro, omeprazole reduced the activity of the low Km gastric ADH with a Ki of 5.6 mM in rat and the hepatic ADH activity with a Ki of 2.4 mM in man, whereas the drug did not show any effect on hepatic ADH in rat and gastric ADH in man. On the contrary, cimetidine increased the AUCs of EtOH blood concentrations after both gastric and intravenous route and, in the in vitro assay, inhibited gastric and hepatic ADH in both man and rat. These results indicate that omeprazole does not affect EtOH metabolism in man and seems to be safer than cimetidine in subjects unable to reduce ethanol intake during the therapy for peptic ulcer or other hypersecretory conditions.
BACKGROUND: Dicarboxylic acids are water-soluble, contrary to monocarboxylic acids, and have a metabolic pathway intermediate between those of lipids and carbohydrates. Our goal was to investigate the plasma turnover and oxidation rate of dodecanedioic acid (C12) in eight healthy male volunteers. METHODS: A simultaneous infusion of both cold (0.24 mmol/min corresponding to 0.396 kcal/min) and radiolabeled (1.62 microCi/min) C12 free acid was performed. Blood specimens were sampled over a period of 360 minutes, and 24-hour urine samples were collected to measure the levels of C12 by high-performance liquid chromatography and liquid scintillation. Indirect calorimetry was continuously performed, and expired 14CO2 was collected. Binding of C12 in human plasma was determined in separate experiments using equilibrium dialysis. RESULTS: A linear one-compartment model was used to describe the kinetics of labeled C12. Its volume of distribution was 139.02 +/- 10.84 mL/kgbw (mean +/- SE), and its plasma elimination constant was 0.01 +/- 0.004 min-1. The 24-hour urinary excretion of C12 was 3.14 +/- 0.96 mmol, corresponding to about 7% of the administered dose. The amount of C12 oxidized, expressed as percent oxidation, was equal to 35.44 +/- 1.64%. The mean basal value of npRQ (0.80 +/- 0.006) significantly (p < .02) decreased during the infusion to 0.78 +/- 0.01, which is a value close to that theoretically calculated (0.77). The oxidation of free fatty acids was significantly increased at the end of the C12 infusion, whereas the glucose oxidation was reduced to about 50%. CONCLUSIONS: The experimental data suggest that C12 might represent a fuel substrate immediately available for tissue energy requirements, because a relevant amount of C12 is promptly oxidized. Its prompt oxidation and its conversion to succinic acid support the use of dodecanedioic acid in parenteral nutrition, especially in insulin-resistance conditions in which glucose uptake and oxidation is impaired.
BACKGROUND: Dicarboxylic acids (DA) are water-soluble substances with high-energy density proposed as an alternative lipid substrate for nutrition purposes. The aim of the present study was to investigate the interaction between glucose and DA or long-chain triglyceride (LCT) metabolism after oral administration. METHODS: Two test meals containing either dodecanedioic acid (C12, the 12-atom DA) or LCT, together with glucose and amino acids, were each administered to five healthy volunteers. Tracer amounts of 14C-dodecanedioic acid were added to the C12 meal to recover expired traced CO2 and estimate the minimum rate of C12 oxidation. Glucose, insulin, and C12 plasma levels were measured for 360 minutes after the test meal. Indirect calorimetry was performed for the duration of the study. RESULTS: LCTs proved ineffective in promoting their own oxidation after oral administration. On the contrary, C12 was promptly oxidized, a minimum of 21.9%+/-8.3% of the administered amount giving rise to the recovered expired CO2. This difference in metabolic fate was reflected in a sparing effect on glucose: suprabasal respiratory quotient and suprabasal carbohydrate oxidation were significantly (p < .05) lower under C12 administration than under LCT administration, with a difference of 0.024+/-0.015 in respiratory quotient (RQ) and a difference of 0.791+/-0.197 kJ/min in carbohydrate oxidation. In particular, carbohydrate oxidation increased by 54% over basal with LCT but only by 28% with C12 administration. RQ increased over basal by 5.8% with LCT but only by 3.0% with C12 administration. CONCLUSIONS: These results show a fundamental metabolic difference between conventional lipids and DAs, which is the basis for a possible role of DAs in clinical nutrition. The fate of spared glucose is likely to be storage in glycogen form when dodecanedioic acid is made available as an energy source.
beta2-integrin subunit (CD18) plays an essential role in leukocyte recruitment and adhesion in sites of endothelial injury. We analyzed the surface expression of CD18 on T lymphocytes and monocytes in a series of patients presenting acute coronary syndrome (ACS) who underwent primary percutaneous intervention (PCI) for coronary artery revascularization. We found that basal CD18 expression on peripheral blood-derived CD4+ (but not CD8+) T lymphocytes was significantly increased in ACS patients as compared with age-matched healthy volunteers. During primary PCI, a significant increase in CD18 molecule density was detected immediately after balloon deflation (reperfusion) on both CD4+ T cells and monocytes obtained from the right atrium (RT) as compared with basal values. These data suggest that upregulation of CD18 molecules plays an important role in local recruitment of CD4+ T cells and monocytes to the site of endothelial damage after ischemia/reperfusion, therefore being responsible, at least in part, for the inflammatory-mediated complications associated with primary PCI.
A symptomatic leiomyoma of the upper esophagus was successfully removed through a fiberoptic endoscope in an 84-year-old man. Endoscopic resection via flexible endoscope may be considered as an option in treating selected cases of esophageal leiomyoma and for high surgical risk patients.
Smoking habit has been evaluated in 108 patients with gastric or duodenal ulcer diagnosed by endoscopy and in a control group of 147 endoscopically normal subjects. We found a positive association for both the gastric and duodenal ulcer (relative risk of 3.5). Furthermore, an increasing risk was associated both with the duration of smoking and with the amount of cigarettes smoked daily. Conversely, no significant association was demonstrated between peptic ulcer and the more os less precocious age at starting smoking or with the nicotine and tar content of the cigarettes usually smoked. Among ex-smokers, an increasing risk (relative risk of 2.0) was observed for gastric ulcer only.
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Fifty individual psychotherapies of schizophrenic patients, supervised by a control group for fourteen years, are examined. 80 percent of the patients have shown important clinical progress and, in many cases, have been healed, especially those who continued therapy for more than two years and who had a deep and reciprocal emotional involvement with the therapist during and after treatment; there was a reduction by 70 percent of hospitalizations during this treatment and only one of these had a relapse. Other data confirm the efficacy of psychotherapy; however, to give a new instrument of scientific confirmation to this type of individual and subjective work, we tried to observe how the psychopathological and therapeutic mechanism of "symbiosis" induces personal dynamics in the therapist which are reflected in the control group. The psychopathological symbiotic disturbance of the patient, the therapeutic symbiotic relationship, and the way in which the group reacts to these permit the creation of a useful triangle, both for the therapist to understand his position toward the patient and to confirm or correct the subjective aspects of such a deep and emotional relationship.
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In psychosis the relationship between the patient and the world is deeply altered because the self-absorbment of the patient within the influence of his bad intrapsychic objects. The psychotherapy is possible through the establishment of a therapeutic symbiosis, where parts of the ill personality are introjected by the psychotherapist and parts of his personality are adopted by the patient, as shown by the fact that the dreams, the unconscious fantasies, and the efforts of the therapist reflect the anxieties of the patient, whereas the patient's dreams are structured by the inner movements of the psychotherapist, as if there were a partially shared identity between them both.
The author examines the genetic and the psychodynamic points of view of transexualism and transvestitism, on the basis of literature and of his clinical experience. While the genesis of the syndromes still remain obscure, in spite of new psychodynamic hypothesis, it is now possible to understand the inner world of the parents better than ever before. The author is able to show by means of his own cases that on the basis of the syndrome is a personality development which is centered in the struggle of self-identity and which does not correspond to our definitions of neurosis or of psychopathy but, rather can assume, at least in some patients, very realistic traits of solving an objective problem of sexual identity.