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Biomedical subjects

P Benedetti

Publications and source records attributed to P Benedetti.

At least 37 records · Page 2Linked to original sources

Research project on the treatment of anorexia and bulimia: an integrative, multidimensional approach.

This research project tries to test a therapeutic strategy that could improve the prognosis of anorexic and bulimic syndrome, by reducing their tendency to chronicity. The hypothesis is that, whenever we deal with complex, multifactoral syndromes, such as anorexia and bulimia, a therapy based upon the association of different kinds of treatments (medical-biological-nutritional treatments plus family therapy) helps to obtain better results than one type of treatment only (medical-biological-nutritional alone). The selection of the samples (experimental and control samples), the materials and methods of the research project, and the follow-up series are described.

Anorexia Nervosa↗

H. pylori infection in HIV-positive patients. A serohistological study.

Sixty-seven consecutive patients infected with the human immunodeficiency virus (HIV-1), 72% of which with overt AIDS, were examinated by upper endoscopy due to various indications and evaluated for the prevalence of H. pylori infection. The infection was studied by performing both histological examination of gastric biopsies and serological testing for anti-H. pylori IgG antibodies. The H. pylori prevalence rate was 55% in histology; no significant differences were observed in HIV-infected subjects and those with overt AIDS (52% vs 63%, respectively; P = NS). Positive histological testing appeared to be directly related to the peripheral CD4+ lymphocyte count (minimum rates of 43% were detected in patients with CD4+ < 100 x 10(6)/liter and maximum rates of 78% in patients with CD4+ > 200 x 10(6)/liter, respectively; P < 0.05) and inversely related to the frequency of antibiotic treatments performed over the six months prior to endoscopy. Low CD4+ counts were also apparently associated with low-grade H. pylori infection. Serological testing was positive for anti-H. pylori IgG antibodies in 39% of patients; compared to histology, serology displayed a sensitivity of 57% and a specificity of 81%. The discrepancy between histological and serological positive results for H. pylori was noted to be higher in the more advanced phases of HIV infection. Based upon our results, the serological testing for anti-H. pylori IgG antibodies seems to require cautious interpretation in HIV-positive patients.

Acquired Immunodeficiency Syndrome↗

Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.

OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.

Adult↗

Molecular dissection of a protein SopB essential for Escherichia coli F plasmid partition.

Biochemical and genetic experiments were carried out to deduce the structural and functional domains of SopB protein involved in the equipartition of F plasmid. The protein is dimeric. Proteolytic and chemical footprinting studies support earlier genetic analyses that the binding of SopB to specific sites within the F plasmid sopC locus involves mainly the C-terminal region. In vivo, the expression of a high level of SopB protein is known to repress sopC-linked genes. This silencing activity is shown to be unaffected by the deletion of 35 N-terminal residues, but abolished when 71 or more were removed from the N terminus. An excess of SopB protein does not extend its in vitro binding outside sopC, implicating participation of a host factor(s) in SopB-mediated gene silencing. A data base search identified a number of SopB homologues, including both chromosomally encoded bacterial proteins and phage- and plasmid-encoded proteins known to be involved in partition. Sequence homology is limited to the N-terminal half, suggesting that the N-terminal regions of these proteins are conserved to interact with a conserved cellular structure(s), whereas the C-terminal regions have diverged to bind different nucleotide sequences.

Amino Acid Sequence↗

Effect of citicoline on visual acuity in amblyopia: preliminary results.

BACKGROUND: Citicoline has been used to improve consciousness levels in cerebral trauma and as a complement for levodopa in Parkinson's disease. It has also been shown that severe glaucomatous visual field deficits improve for at least 4 months with the use of citicoline. In this paper, preliminary results are presented of an open and a double-blind study on the effect of citicoline in amblyopia. METHODS: The open study was started in 1991. Fifty patients with amblyopia were treated with citicoline (1000 mg i.m. daily for 15 days). They were selected from an age group beyond the plastic period of the visual system. Occlusion or other types of anti-amblyopic treatment were never used at the same time as citicoline. A double-blind study was conducted on 10 more patients, randomly assigned to a treatment or placebo group and followed for 6 months. A statistical test for repeated measures was performed on all the results. RESULTS: A statistically significant improvement in visual acuity was found both for the amblyopic and the sound eye in 46 of the 50 patients (92%). The behaviour was different for normal and amblyopic eyes. The improvement remained stable for at least 4 months. These results have been substantiated by the double-blind study. No side effects were observed. CONCLUSION: Citicoline improves visual acuity, at least temporarily, in amblyopic patients beyond the plastic period of the visual system. Our results suggest that trials of citicoline as a medical treatment of amblyopia are warranted.

Adolescent↗

Applicability of the 1988 IHS criteria to headache patients under the age of 18 years attending 21 Italian headache clinics. Juvenile Headache Collaborative Study Group.

Seven hundred nineteen young patients attending 21 Italian headache care settings were evaluated by a diagnostic headache interview and a neurological examination. Headache disorders were classified according to the current 1988 criteria of the International Headache Society (IHS); 54.9% of the patients suffered from migraine, 33.9% from tension-type headache, 1.9% from secondary headache, and 3.4% had non-classifiable headache. A further 5.9% of the patients were not classified due to incomplete questionnaires. Of the 395 patients with migraine, 44.5% were affected by migraine without aura, 29.9% by migraine with aura, 1.3% from other migraine forms, and 24.3% by migrainous disorders which do not fulfill the 1988 IHS diagnostic criteria for headache. Among the 244 patients with tension-type headache, 51.6% had episodic tension-type headache, 15.2% chronic tension-type headache, and 33.2% headache of the tension-type which does not fulfill the 1988 IHS criteria for episodic and chronic tension-type headache. In young migraine patients, pain was of a pulsating type in 55.7%, severe in 57.8%, unilateral in 42.6%, and aggravated by routine physical activity in 38.9%. Tension-type headache was described as pressing in 73.8%, mild or moderate in 75.7%, bilateral in 87.4%, and not aggravated by routine physical activity in 85.5%. The duration of pain was less than 2 hours in 35% of the cases in migraine sufferers and less than 30 minutes in 26.7% of tension-type headache sufferers. Nausea, phonophobia, and photophobia were present in at least half of the migraine patients and in one third of tension-type headache patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Yeast Saccharomyces cerevisiae as a model system to study the cytotoxic activity of the antitumor drug camptothecin.

Eukaryotic DNA topoisomerase I catalyzes the relaxation of positively and negatively supercoiled DNA and plays a critical role in processes involving DNA, such as DNA replication, transcription and recombination. The enzyme is encoded by the TOP1 gene and is highly conserved in its amino acid sequence and sensitivity to the anti-neoplatic agent camptothecin. This plant alkaloid specifically targets DNA topoisomerase I by reversibly stabilizing the covalent enzyme-DNA intermediate. Presumably, it is the interaction of these drug-stabilized adducts with other cellular components, such as replication forks, that actually produces the DNA lesions leading to cell death. A conservation of the mechanism(s) of camptothecin-induced cell killing is also implicit in studies of the yeast Saccharomyces cerevisiae, where the camptothecin sensitivity of delta TOP1 yeast cells can be restored by plasmids expressing either yeast or human TOP1 sequences. This genetically tractable system is currently being exploited to describe the specific molecular interactions required for the cytotoxic action of camptothecin. The results of mutational analyses of yeast and human DNA topoisomerase I are presented, as well as a genetic screen designed to identify genes, other than TOP1, that are required for the cytotoxic activity of camptothecin.

Amino Acid Sequence↗

Topoisomerase II forms multimers in vitro: effects of metals, beta-glycerophosphate, and phosphorylation of its C-terminal domain.

We present a novel assay for the study of protein-protein interactions involving DNA topoisomerase II. Under various conditions of incubation we observe that topoisomerase II forms complexes at least tetrameric in size, which can be sedimented by centrifugation through glycerol. The multimers are enzymatically active and can be visualized by electron microscopy. Dephosphorylation of topoisomerase II inhibits its multimerization, which can be restored at least partially by rephosphorylation of multiple sites within its 200 C-terminal amino acids by casein kinase II. Truncation of topoisomerase II just upstream of the major phosphoacceptor sites reduces its aggregation, rendering the truncated enzyme insensitive to either kinase treatments or phosphatase treatments. This is consistent with a model in which interactions involving the phosphorylated C-terminal domain of topoisomerase II aid either in chromosome segregation or in chromosome condensation.

Calcium↗

Monoethylglicinexylidide test: a prognostic indicator of survival in cirrhosis.

The aim of this study was to assess the value of the monoethylglicinexylidide assay, a dynamic liver function test based on the determination of the serum concentration of lidocaine major metabolite, as a predictor of survival in cirrhosis. For this purpose, the predictive value of monoethylglicinexylidide was evaluated in comparison with the Pugh score, ascites, encephalopathy and a number of different biochemical parameters as collected from the prospective follow-up of 118 patients with cirrhosis. A stepwise regression analysis was performed on the variables of prognostic value according to the Cox model and with respect to 1-yr survival; because Pugh score and monoethylglicinexylidide were the sole variables selected, they were proved to supply independent prognostic information. The most reliable cutoff values for discrimination between death and survival were 25 ng/ml or less for monoethylglicinexylidide and less than 9 for the Pugh score. In 74 patients without overt signs of liver failure (i.e., Pugh < or = 9), monoethylglicinexylidide provided a wide range of results (i.e., 4 to 77 ng/ml), namely values ranging from very low to elevated. Of the 38 patients with satisfactory Pugh scores (< or = 9) but poor monoethylglicinexylidide values (< or = 25), 11 died during follow-up and 3 underwent liver transplantation, despite having shown no clinical signs of liver failure at entry. On the bases of discriminant levels, the monoethylglicinexylidide test is suitable for adoption as a reliable and sensitive indicator of survival in patients with cirrhosis because it supplies more accurate prognostic information compared with the Pugh score.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Camptothecin resistance from a single mutation changing glycine 363 of human DNA topoisomerase I to cysteine.

A full-length human DNA topoisomerase I complementary DNA clone was mutagenized in vitro and the mutagenized DNA was used to replace wild-type human TOP1 complementary DNA in YCpGAL1-hTOP1, a plasmid constructed for the expression of the human enzyme in yeast. A yeast strain devoid of yeast DNA topoisomerase I and permeable to the anticancer drug camptothecin was transformed with the plasmid pool. Assays of DNA topoisomerase I in lysates of camptothecin-resistant transformants identified one with nearly the same level of the enzyme as transformants of unmutagenized YCpGAL1-hTOP1, and a single mutation changing Gly363 to a cysteine was found in this mutant. The G363C mutant enzyme was overexpressed in yeast and partially purified. It differed significantly from wild-type human DNA topoisomerase I similarly expressed and purified: camptothecin-stimulated cleavage of DNA was observed with the wild-type but not the G363C enzyme, and the DNA relaxation activity of the mutant enzyme, unlike that of the wild-type enzyme, was not significantly stimulated by Mg(II). The positions of the G363C and other previously reported camptothecin resistance mutations in eukaryotic DNA topoisomerase I were discussed in terms of a model in which the active site is an interdomainal cleft.

Amino Acid Sequence↗

Autologous stem cell transplantation: sequential production of hematopoietic cytokines underlying granulocyte recovery.

We investigated the serum concentrations of a variety of cytokines [granulocyte-macrophage-colony-stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin (IL) 1 alpha, IL-3, IL-6, IL-8, erythropoietin, tumor necrosis factor alpha, gamma-interferon in 10 patients with advanced ovarian cancer undergoing autologous peripheral blood stem cell (PBSC) harvesting followed by treatment with high-dose cisplatin, etoposide, and carboplatin and PBSC transplantation (chemotherapy was administered on days 1 through 3, PBSCT on day 6). Preliminary observations on cytokine serum levels were performed for 4 patients; on this basis, the kinetics of cytokines was then investigated in greater detail at closely sequential times in 6 further patients. We observed a consistent pattern of sequential GM-CSF, G-CSF, and IL-8 release after chemotherapy/PBSCT in all 10 cases, including the 6 patients monitored in detail: (a) at days 5-10 a GM-CSF peak; (b) at days 12-14 a pronounced release of both G-CSF and IL-8, which always preceded granulocyte recovery by approximately 7 days. At days 17-23, a second GM-CSF peak was monitored in 5 of the 6 patients analyzed in detail, as well as in the other 4 cases. Particularly relevant are the observations that: (a) the peak of G-CSF serum concentration and neutrophil number in the recovery phase are strikingly and directly correlated, thus indicating a key role for G-CSF in granulocyte rescue; (b) the time courses of G-CSF and IL-8 levels are strictly parallel, thereby suggesting a coordinate stimulus for production of granulocytes, mediated by G-CSF, and their activation/migration capacity, mediated by IL-8. Results were essentially negative for IL-3, tumor necrosis factor alpha, and gamma-interferon concentrations (except in one case for each cytokine). An early peak of IL-1 alpha was observed in all 3 analyzed patients, while an IL-6 peak was monitored at days 13-15 in all 4 patients analyzed in detail. The present results indicate a sequential coordinate pattern of cytokine release after ablative therapy and PBSCT and shed light on the mechanisms mediating the recovery of granulocytes, and more generally of hematopoiesis, after stem cell transplantation. Furthermore, these studies may contribute to the design of improved protocols for cytokine administration following myelosuppressive anticancer therapy, as well as to the prediction of granulocytic response.

Adult↗

Hypertension in newly diagnosed non-insulin-dependent diabetic subjects.

Medical records of newly diagnosed non-insulin-dependent diabetic patients attending a Diabetic Centre in Modena, northern Italy, during the period 1985-88 were reviewed to analyze the prevalence of hypertension at age of diagnosis of diabetes and its association with selected risk factors. The prevalence of hypertension was also determined in a representative sample of control subjects. In the multivariate analysis, greater body mass index and older age, but not smoking, were strongly associated with increased rates of hypertension both in control and in diabetic subjects. In diabetic patients, family history of diabetes, defined as presence of diabetes in close relatives, was not significantly associated with hypertension, while rates of hypertension were significantly lower in patients who reported at least one parent affected by diabetes. After adjustment for age and body mass index, newly diagnosed non-insulin-dependent diabetes was not an independent risk factor for hypertension. These findings seem to be consistent with the hypothesis that diabetes and hypertension are not linked by a common genetic background.

Adult↗

Severe outcome of brain perfusion failure: a pre-hydranencephalic state?

Four children surviving severe hypoxic-ischemic brain damage showed subtotal destruction of the cerebral hemispheres, with partial preservation of some infratentorial and supratentorial brain structures. True multicystic encephalopathy features were identified in two cases on CT scanning. The other patients showed more pronounced brain tissue destruction, with overall malacia of the hemispheres. An echographic study demonstrated that the brain damage occurred progressively, within about one month, and was preceded by oedema, white matter malacia and cavitation. The role of the compensatory mechanisms responsible for preservation of structures supplied by the vertebral-basilar circle is discussed. The authors suggest that the observed outcome could be considered a stage immediately preceding the most severe damage represented by hydranencephaly.

Brain↗

Cathepsin D assay in ovarian cancer: correlation with pathological features and receptors for oestrogen, progesterone and epidermal growth factor.

Using an immunoradiometric assay, Cathepsin-D (Cath-D) concentrations were measured in the cytosol of 68 normal and neoplastic human ovarian tissues. Cath-D levels were higher in malignant tumours than in normal tissue samples (P less than 0.01) and benign tumours (P less than 0.01). In six out of seven cases, metastatic deposits showed Cath-D concentrations higher than the respective primary tumours. Using 12 of 17 pmols.mg-1 protein as cut-off levels, the Cath-D status (high or low) was not related to any pathological parameter. Moreover, no correlation was found between Cath-D levels and receptors for oestrogen, progesterone and epidermal growth factor. Our results indicate that ovarian tumours produce Cath-D. Further studies are needed to evaluate whether this protein could represent a prognostic factor for this neoplasia.

Biomarkers, Tumor↗

[10 years of legionellosis in Italy (June 1980-June 1990)].

Legionella infection was recognized as a cause of human disease in 1976, following the occurrence of an epidemic at Bellevue Stratford Hotel, Philadelphia, USA. In the subsequent years, various cases, both sporadic and epidemical, have been reported worldwide. In Italy, the first reports date from 1980. The compulsory notification of the disease was established in February 1983, and a few months later a National Surveillance Programme started operating at the Istituto Superiore di Sanità, Rome. Up to June 30, 1990, 542 confirmed cases of legionellosis were reported. For 249 of them, data of clinical and epidemiological significance are available. The incidence of the disease is higher in males (76% of total cases) and 51.5% of the patients are aged more than 50 years. During the clinical course, the occurrence of hepatic and/or renal dysfunction, cough, dyspnoea, diarrhoea and confusion was documented in a significant proportion of patients. The fatality rate was 12.4%. The disease occurred both sporadically and epidemically. Namely, clusters and outbreaks were detected all over the country, accounting for a total of 97 cases. Hospital patients should be regarded as an important category at risk for infection. The occurrence is also frequent among travellers and tourists, because of the stressing factors that may increase individual susceptibility, as well as the more frequent contact with infective sources. In Italy, the major risk of infection appears connected with water plumbing systems of hotels, residential houses and hospitals, where oxygen bubble-humidifiers have been found to represent an important source of infection. On the contrary, the association of human infection with air conditioning systems has not been evidenced up-to-now.

Adult↗