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Biomedical subjects

G Bruno

Publications and source records attributed to G Bruno.

At least 37 records · Page 2Linked to original sources
PubMed2002

Management of spontaneous bleeding due to hepatocellular carcinoma.

BACKGROUND: Spontaneous rupture is a life-threatening complication of HCC, occurring in 4.8-26% of cases. Liver failure is the main cause of death. Debates still remain on the most appropriate treatment in such patients because of the high operative mortality of emergency surgery and the high risk of rebleeding and less satisfying mid- and long-term results of nonoperative procedures like angiographic embolization. Early and long-term results of a surgically oriented treatment, based on prompt evaluation of the functional liver reserve and tumor resectability was retrospectively review-ed. METHODS: From January 1994 to December 2000, 11 patients (7 males and 4 female, mean age 66.2 (11.86 years) were treated for ruptured HCC, in 10 cases involving a cirrhotic liver. Seven patients underwent emergency surgery and 4 patients transcutaneous arterial embolization (TAE). Liver resection was performed in patients with preserved liver function, after ultrasonography and/or CT scan demonstrated hemoperitoneum and a single resectable liver tumour (5 cases). In one patient with cirrhosis, ultrasonography showed only hemoperitoneum. A bleeding nodule was discovered intraoperatively and resected in a liver with a multinodular HCC. Another patient under-went emergency resection after referral at our Unit with a surgical packing. In 4 cases with poor liver function and/or unresectable tumour TAE of the neoplasm was performed, in one case after surgical packing. Mortality, morbidity and patients survival after treatment were analyzed. All patients had at least 1 year follow-up. RESULTS: All patients underwent minor resection; 2 left lobectomies, 1 segmentectomy (VII), 1 bisegmentectomy (VII-VIII), and 3 wedge resections. Postoperative course was complicated by ascites in 5 cases and subphrenic abscess in one case. Four patients died 3, 4, 6 and 62 months after surgery; 3 patients are actually alive 22, 25, and 89 months after surgery. Four patients were submitted to TAE: all patients died within 6 months. CONCLUSIONS: When ruptured HCC is suspected, preserved liver function (Child A-B7) and a resectable hepatic tumour are considered clear indications to surgery. Emergency liver resection achieved good early and long-term results. In cases of advanced liver disease or multinodular HCC a non-operative approach, like TAE, must be attempted. Surgical direct hemostasis or hepatic artery ligation must be reserved for patients with uncontrollable o recurrent bleeding after TAE.

Aged↗
PubMed2001

4,5-Dihydro-7,8-dimethoxy-1-phenyl-3H-2,3-benzodiazepin-4-one.

The title compound, C(17)H(16)N(2)O(3), is an antagonist for AMPA/kainate receptors. The molecule has its seven-membered oxadiazole ring in a boat conformation. Asymmetry of the two methoxy bond angles is evident, with (Me)O-C-C angles of 115.45 (12) and 124.78 (13) degrees, and 114.67 (12) and 125.31 (12) degrees. A centrosymmetric dimer involving the HN-CO moieties, with an N...O distance of 2.876 (2) A, graph set R(2)(2)(8), is further linked into chains through methoxy Csp(3)-H...N hydrogen bonds, with a C...N distance of 3.418 (2) A.

Azepines↗
PubMed2001

7-Chloro-1-(2,6-difluorophenyl)-1H,3H-thiazolo.

The title molecules, C(15)H(9)ClF(2)N(2)S and C(16)H(12)F(2)N(2)S, respectively, display the well known butterfly-like conformation with a flat thiazolobenzimidazole system. In both compounds, the mean plane through the tricyclic system is almost perpendicular to the 2,6-difluorophenyl ring. This arrangement of the aryl group is determined by two intramolecular hydrogen bonds and by an attractive F.S interaction.

Anti-HIV Agents↗
PubMed2001

Mast cell activation in acquired chronic urticaria-angioedema.

Mast cells play a central role in the pathogenesis of many allergic disorders. They can be activated in different ways. The present study was focused to evaluate the role of mast cells in acquired chronic urticaria-angioedema induced by gastroesophageal reflux. Tryptase, an important marker of mast cell activation, was detected with UniCap Tryptase Fluoroenzymeimmunoassay (Pharmacia & Upjohn AB, Uppsala, Sweden). Eight subjects were studied: four males and four females, aged between 29 and 71 years (mean age: 45 yrs.), suffering from acquired chronic urticaria-angioedema. Results were compared with the results of seven healthy control subjects. Moreover, data were compared with those of 13 subjects (10 males and 3 females, mean age: 24.7 years) suffering from allergic rhinitis. In acquired chronic urticaria-angioedema, serum tryptase levels (mean +/- S.D.: 9.6 +/- 4.3 microg/l) were significantly higher (P < 0.007) than those of the controls (mean +/- S.D.: 3.0 +/- 1.2 microg/l) and higher also than in allergic rhinitis (mean +/- S.D.: 6.1 +/- 2.4 microg/l, P < 0.03). The results underline the central role of mast cells in the inflammation of acquired chronic urticaria-angioedema.

Adult↗
PubMed2001

Virus-specific CD8(+) T cells with type 1 or type 2 cytokine profile are related to different disease activity in chronic hepatitis C virus infection.

The present study demonstrates that the quality of the virus-specific CD8(+) T cell responses, as detected by both enzyme-linked immunospot assay and specific MHC-peptide tetramers, changed in relation to the different disease activity in chronically hepatitis C virus-infected patients. Indeed, both the serum alanine transaminase and the hepatic flogosis levels were related directly to the frequencies of peripheral memory effector CD8(+) T cells producing IFN-gamma (Tc1), but inversely to the frequencies of those producing both IL-4 and IL-10 (Tc2). Longitudinal studies highlighted that Tc1 or Tc2 responses fluctuate in relation to the different phases of the disease in the same individual. Furthermore, the Tc1 or Tc2 phenotype correlates with tetramer-positive cells expressing either CXCR3 or CCR3, promoting differential tissue localization of these cells and the maintenance of T cell homeostasis. Finally, studies at the level of liver-infiltrating lymphocytes indicated that they produced both IFN-gamma and IL-4 with an evident bias towards the Tc1-like phenotype. Our studies suggest that the progressive fluctuation of Tc1 and Tc2 responses may play a fundamental role in maintaining a long-lasting low-level liver inflammation, and may constitute the basis for new therapeutic strategies of immune regulation.

Adult↗
PubMed2001

Increasing trend of type I diabetes in children and young adults in the province of Turin (Italy). Analysis of age, period and birth cohort effects from 1984 to 1996.

AIMS/HYPOTHESIS: This study aimed to determine if the incidence of Type I (insulin-dependent) diabetes mellitus increased over time and if the time trend is attributable to linear trend, calendar period or birth cohort effects. METHODS: This study was based on a cohort of subjects aged 0-29 years from 1984 to 1996, who resided in the province of Turin, Italy. Poisson regression models were used to estimate the effect of sex, age, calendar time and cohorts on incidence rates. RESULTS: The mean incidence rate in the age group of 0 to 29 years was 7.78 of 100,000 person-years (95% confidence interval: 7.26-8.32), with a lower risk in women than in men [rate ratio (RR): 0.76 (0.67-0.88)]. We found a trend of incidence increasing over time (annual increase of risk 2.25 % a year, 95 % CI 0.44-4.10). In Poisson regression analysis we found that the best model was the one with sex, age and a linear term attributable to either calendar period or cohort effects. The linear term corresponds to a RR of 1.12 (1.02-1.22,p = 0.015) for each 5-year age span. CONCLUSION/INTERPRETATION: We found that the time trend in this Mediterranean area was similar in magnitude to that reported in northern European countries. The increase was linear in pattern, each birth cohort and each calendar period showing a higher risk than the preceeding one with some evidence of two steep increases in the incidence of Type I diabetes centered on the years 1964 and 1984. We found that the incidence of diabetes increased in the 0 to 14 age group and also in the older age group of 15 to 29 years and that the age-period models were not statistically significantly better than the age-cohort models.

Adolescent↗
PubMed2001

Nickel(II) 2,6-diacetylpyridine bis(isonicotinoylhydrazonate) and bis(benzoylhydrazonate) complexes: structure and antimycobacterial evaluation. Part XI.

The reaction of 2,6-diacetylpyridine (dap) and isonicotinoyl- or benzoylhydrazide leads to bishydrazones H(2)dapin (1a) and H(2)dapb (1b), respectively. The condensation can either take place as a bimolecular kinetic process between the two reactants or as a monomolecular metal-templated synthesis in the presence of nickel(II) ions. In the latter case the reaction products are charged 2,6-diacetylpyridine bis(hydrazone) nickel(II) complexes, which can be easily deprotonated to neutral hydrazonates. Diffractometric analysis of one of these [Ni(dapb)](2) (8b) has shown a binuclear structure with two octahedral nickel(II) ions bridged by two helicoidal dap (bishydrazonates) in a spheroidal structure of C(2V) symmetry. The synthesized complexes 8 are promising as antimycobacterial agents against M. tuberculosis H37Rv. In particular, 8b displays significant activity (MIC=0.025 microg/mL) 10-fold higher than rifampin and equal to isoniazid, while its ligand is ineffective. Compound 8b is also capable of reducing HIV-induced cytopathogenic effect in human T(4 )lymphocytes.

Antitubercular Agents↗
PubMed2001

3-Phenyl-4H-furo[3,2-C]chromen-4-one.

The crystal structure of the title compound, C(17)H(10)O(3), is the first example of a furocoumarin containing three fused rings. The tricyclic furocoumarin fragment is perfectly planar. The phenyl substituent forms a dihedral angle of 39.52 (8) degrees with the plane of the tricyclic system. The crystal packing involves centrosymmetric dimers interconnected by strong pi-interactions between their furo[3,2-c]coumarin fragments [at distances of 3.42 (4) A].

Journal Article↗
PubMed2001

Retrospective analysis of the association of nodular goiter with primary and secondary hyperparathyroidism.

BACKGROUND: The association of hyperparathyroidism (HPT) with thyroid disease has long been known, but the mechanisms underlying such an association have not yet been clarified. OBJECTIVE: To elucidate the main factors determining this combination of endocrine diseases, in a retrospective multicenter study. METHODS: We retrospectively reviewed all patients referred for parathyroid scintigraphy in the period 1990-1999. A total of 487 patients in the age range 17-65 years were selected for the analysis (339 women and 148 men); group A included 241 patients with primary and group B 246 patients with secondary HPT. RESULTS: A total of 124/241 patients in group A (51.5%), but only 92/246 patients in group B (38.2%) had thyroid disorders (notably nodular goiter) associated with HPT (P=0.0035). Thyroid disorders were evenly distributed throughout the entire 17-65 years age range in group A, but 17-40-year-old patients in group B had significantly fewer thyroid disorders than the older patients of the same group (15.5% compared with 43.3%, P<0.002), as expected in a general population. In patients with primary HPT there was no difference in the prevalence of thyroid disease between women and men, whereas the ratio of women to men in secondary HPT patients with thyroid disease was about 3:1. CONCLUSIONS: These results demonstrate an increased prevalence of nodular goiter in patients with primary rather than secondary HPT, and are consistent with a possible role of increased endogenous calcium concentrations (a hallmark of primary, but not of secondary, HPT) as a goitrogenic factor in patients with HPT.

Adolescent↗
PubMed2000

Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer's disease.

Clinical and pathological evidence points to an involvement of dopamine in Alzheimer's disease (AD). The present study was designed to assay dopamine D1-like and D2-like receptors on peripheral blood lymphocytes (PBL) in 20 patients with AD and in 25 healthy controls by radioligand binding assay techniques with [3H][R]-(+)-(-)chloro-2,3,4,5 tetrahydro-5-phenyl-1H-3-benzazepin-al-hemimaleate (SCH 23390) and [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7OH-DPAT) as radioligands. The density of dopamine D1-like receptors and the affinity of [3H]SCH 23390 and [3H]7OH-DPAT binding to PBL were similar in both groups investigated. AD patients revealed a lower density of dopamine D2-like receptors on PBL than controls (P=0. 0016). The pharmacological profile of [3H]SCH 23390 and [3H]7OH-DPAT binding to PBL was consistent with the labeling of dopamine D5 and D3 receptor subtypes, respectively. The reduced density of dopamine D2-like receptors on PBL is consistent with the observation of changes in the expression of D2-like receptors in dopaminergic brain areas in AD. Our findings support the hypothesis of an involvement of dopamine in AD, even in those patients with no evidence of Parkinsonism, behavioral abnormalities or psychosis.

Aged↗
PubMed2000

Synthesis of new 2,6-prolylxylidide analogues of tocainide as stereoselective blockers of voltage-gated Na(+) channels with increased potency and improved use-dependent activity.

A series of tocainide chiral analogues were designed, synthesized, and evaluated in vitro, in pure enantiomeric form, as use-dependent blockers of skeletal muscle sodium channels to better understand the structural requirements responsible for the antimyotonic activity. The voltage clamp recordings showed a remarkable increase of both potency and use-dependent behavior with the analogue N-(2, 6-dimethylphenyl)-2-pyrrolidinecarboxamide (1a). In fact (R)-1a was 5-fold more potent than (R)-tocainide in producing the tonic block, i.e., the reduction of peak sodium current in resting conditions after application of the compound, but it was 21-fold more potent in condition of high frequency of stimulation (phasic block). Furthermore, as opposite to tocainide, this compound was also stereoselective, (S)-1a being 2-3-fold less potent than (R)-1a. The introduction in 1a of a methyl group in place of the hydrogen bonded to either the aminic nitrogen atom [N-(2, 6-dimethylphenyl)-1-methyl-2-pyrrolidinecarboxamide (2a)] or the amidic nitrogen atom [N-(2, 6-dimethylphenyl)-N-methyl-2-pyrrolidinecarboxamide (3a)] led unexpectedly to an inversion of stereoselectivity, the (S)-enantiomers being 3-fold more potent than the (R)-ones. The comparison between eutomers showed that (S)-2a and (S)-3a are almost equieffective to (R)-1a in producing a tonic block, the half-maximal concentrations being about 100 microM; however, the use-dependent behavior was remarkably decreased by the presence of the methyl group: i.e., the gain of potency observed at high frequency of stimulation amounted to 3 and 1.6 times for 2a and 3a, respectively. The replacement of both hydrogens bonded to the aminic and amidic nitrogen atoms resulted in N-(2,6-dimethylphenyl)-N, 1-dimethyl-2-pyrrolidinecarboxamide (4a) in which the (S)-isomer was still twice as potent as the (R)-one, but the absolute potency and mostly the use-dependent behavior were strongly reduced, showing therefore no clear advantages with respect to tocainide. The use-dependent behavior, which plays a pivotal role for antimyotonic activity, is strongly reduced by the presence of methyl groups on the nitrogen atoms, likely for modification of pK(a) and/or for constraint of molecular conformation.

Animals↗
PubMed2000

Differential anti-inflammatory effects of immunosuppressive drugs: cyclosporin, rapamycin and FK-506 on inducible nitric oxide synthase, nitric oxide, cyclooxygenase-2 and PGE2 production.

OBJECTIVE AND DESIGN: Cyclosporin, FK-506 and rapamycin have similar but distinct modes of interaction with cyclophilins, calcineurins and transcription factors. These immunosuppressive drugs have also been shown to inhibit cytotoxic and inflammatory responses in macrophage. Therefore, we evaluated the mechanism of action of these drugs on iNOS and COX-2 expression by macrophages, the products of which (NO and PGE2) have cytotoxic and proinflammatory activities. MATERIALS AND METHODS: The murine macrophage cell line RAW 264.7 was grown as monolayer cultures. The effects of pharmacologically relevant concentrations of cyclosporin, rapamycin and FK-506 were evaluated in the presence and absence of lipopolysaccharide (LPS) which is a known inducer of iNOS and COX-2. Subsequently the expression of iNOS and COX-2 were analyzed by Western and Northern analysis. The production of NO and PGE2 were assayed by Greiss and RIA respectively. RESULTS: Cyclosporin (1-5 microg/ml) and rapamycin (1.0-10 nM) but not FK-506 (5-10 nM) inhibited both iNOS and COX-2 expression at mRNA level which led to significant inhibition of NO and PGE2 production. CONCLUSION: These studies characterize differential mechanistic capacity of the immunophilin-binding immunosuppressive drugs (comparable to hydrocortisone) to inhibit both iNOS and COX-2 expression. Inhibition of iNOS and COX-2 mRNA accumulation by cyclosporin and rapamycin seem to be distinct. These studies also highlight potential anti-inflammatory properties of these drugs in addition to their known immunosuppressive activity.

Animals↗
PubMed2000

Detection of spirochaetes of Borrelia burgdorferi complexe in the skin of cervids by PCR and culture.

To determine whether deer may play a role in the cycle of the Lyme disease spirochete Borrelia burgdorferi, we sought evidence for the presence of the pathogen in skin of deer and roe deer. Biopsies of 2 mm3 were taken at four different levels from nail to tarsus. A total of 50 animals (200 biopsies) were shot in the Lyme disease foci of Rambouillet during the hunting season 1995-1996 and 1996-1997, from the beginning of November to the end of February. Borrelia burgdorferi s.l. DNA was detected by PCR in 18 biopsies from 14 animals (28%). Borrelia burgdorferi s.str. was predominant (50%), followed by B. garinii (30%) and B. afzelii (10%). Multiple infections were detected in four animals: same species at different levels or two different species from the same biopsy or from different biopsies from the same foot. A total of 125 biopsies were cultivated on BSKH medium. Cultures at 160 days revealed immobile spiralled forms in 10 cultures. One, from a deer killed at the end of December, was confirmed by PCR as B. burgdorferi s.str. These results, frequency of detection of spirochetes by PCR in the skin, multiple infections and alive spirochetes in biopsies taken out side the season of activity of ticks strongly suggest an affinity of Lyme disease spirochetes for skin of cervids.

Animals↗
PubMed2000

(E)-5-

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Journal Article↗