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Biomedical subjects

R Chiesa

Publications and source records attributed to R Chiesa.

At least 73 records · Page 4Linked to original sources
PubMed1998

Fresh and cryopreserved arterial homografts in the treatment of prosthetic graft infections: experience of the Italian Collaborative Vascular Homograft Group.

Following the experience of cardiac surgeons with homografts in the treatment of infective aortic valve endocarditis, cardiovascular surgeons have investigated in situ revascularization by means of homografts in the management of vascular prosthetic graft infections. Preliminary results are encouraging, but their late fate in long-term follow-up and the influence of preservation techniques are still under investigation. This article reports the experience of the Italian Collaborative Vascular Homograft Group, with the use of fresh and cryopreserved arterial homografts for the treatment of prosthetic graft infections. Between March 1994 and December 1996, 44 patients with prosthetic graft infection were treated with homografts (13 preserved at 4 degrees C, 31 cryopreserved). The mean age of the patients was 65 years. Emergency surgical procedures were performed in eight patients (18%). Sepsis was diagnosed in 11 patients, aortoenteric fistula in 13, and false aneurysms in 10. Staphylococcus was the main cause of infection. The types of vascular reconstruction with homograft were: 32 aortobifemoral, 3 aortoaortic, 2 iliofemoral, 4 peripheral, and 3 axillobifemoral. Human lymphocyte antigen (HLA) and antibody (ABO) blood group system compatibility between donors and recipients was not respected. The mean duration of follow-up was 15 months (range 1-33). Clinical and duplex scanning evaluations were routinely performed. Computed tomography (CT) or magnetic resonance (MR) scanning or arteriography were performed on the basis of duplex scanning results. There were six deaths during the early postoperative period (30 days) with a mortality rate of 13.6%. During the follow-up there were five late deaths with a mortality rate of 11.4%. Eight patients had graft occlusion. Three cases were successfully treated with thrombectomy. Two cases were successfully treated with femoropopliteal bypass with autologous vein. In three cases leg amputation was necessary. The results of fresh and cryopreserved homograft were compared. No significative differences of early postoperative mortality, late mortality, homograft related mortality, and graft occlusion were observed. We have evaluated the actuarial survival of the patients and the actuarial patency of the homografts on the aortoiliac reconstructions. Twelve months after the surgery the actuarial survival of the patients was 73% and the actuarial patency of the homografts was 56%. In our preliminary experience, we have not observed any significant difference in terms of clinical outcome by using fresh rather than cryopreserved homografts. In the near future it will be our policy to employ only cryopreserved homografts. Moreover, we will extend vessel harvesting to nonheart-beating donors, thus maximizing retrieval. The aforementioned solutions will supply the best graft availability to obtain dimensional and ABO compatibility between donors and recipients.

Adult↗
PubMed1998

A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.

PURPOSE: The EVEREST Trial was designed to determine whether the surgical technique influences the durability and complications of carotid endarterectomy (CEA). The current report focuses on the study design and preliminary results. METHODS: EVEREST is a randomized multicenter trial. A total of 1353 patients with carotid stenosis requiring surgical treatment were randomly assigned to received standard (n = 675) or eversion (n = 678) CEA. Primary end points included carotid occlusion, major stroke, death, and restenosis rate. RESULTS: The rate of perioperative major stroke and death (1.3 for each study group) and the incidence of early carotid occlusion (0.6% for eversion vs 0.4% for standard) were similar. No significant differences were found between eversion and standard CEA with respect to incidence of perioperative transient ischemic accident, minor stroke, cranial nerve injuries, neck hematoma, myocardial infarction, or surgical defects as detected with intraoperative quality controls. Clamping time was significantly shorter for eversion CEA compared with patch standard procedures (31.7 +/- 15.9 vs 34.5 +/- 14.4 minutes, p = 0.02). A shunt was inserted in 11% of patients undergoing eversion CEAs and in 16% of patients undergoing standard procedures. Overall 30-day events occurred in 13.3% of the eversion group and in 11.4% of the standard group (p = 0.3). At a mean follow-up of 14.9 months (range, 1 to 38 months), 16 (2.4%) restenoses occurred in the eversion group and 28 (4.1%) occurred in the standard group (odds ratio, 0.56; 95% confidence interval, 0.3 to 1.1; p = 0.08). CONCLUSION: The preliminary results of the EVEREST Trial suggest that eversion CEA is a safe and rapid procedure with low major complication rates. No significant differences in restenosis rates were observed between eversion and standard CEA at the available follow-up. Longer-term results are necessary to assess whether the eversion technique influences the durability of CEA.

Adult↗
PubMed1998

Neurological illness in transgenic mice expressing a prion protein with an insertional mutation.

Familial prion diseases are caused by mutations in the gene encoding the prion protein (PrP). We have produced transgenic mice that express the mouse homolog of a mutant human PrP containing a nine octapeptide insertion associated with prion dementia. These mice exhibit a slowly progressive neurological disorder characterized clinically by ataxia and neuropathologically by cerebellar atrophy and granule cell loss, gliosis, and PrP deposition that is most prominent in the cerebellum and hippocampus. Mutant PrP molecules expressed in the brains of these mice are resistant to digestion by low concentrations of proteinase K and display several other biochemical properties reminiscent of PrP(Sc), the pathogenic isoform of PrP. These results establish a new transgenic animal model of an inherited human prion disorder.

Animals↗
PubMed1998

Biomechanics of abdominal aortic aneurysm in the presence of endoluminal thrombus: experimental characterisation and structural static computational analysis.

OBJECTIVES: To evaluate the role played by biomechanical and geometrical parameters of endoluminal thrombus and of aortic wall on abdominal aortic aneurysm (AAA) behaviour. MATERIALS AND METHODS: Tensile tests on 21 AAA thrombus specimens from six patients undergoing AAA repair and numerical evaluation of aneurysmal aortic wall stress and strain distribution. Parameters of the analysis were lumen eccentricity, thrombus Young's Modulus and the aortic wall constitutive equation. RESULTS: There was a linear stress/strain for all the thrombus specimens. The numerical analyses show the mechanical behaviour of AAA as a function of lumen eccentricity and biomechanical parameters. CONCLUSIONS: Well organised thrombus reduces the effect of the pressure load on the aneurysmal aortic wall.

Aged↗
PubMed1998

Extracellular calcium deprivation in astrocytes: regulation of mRNA expression and apoptosis.

Cell viability and gene expression were studied in primary astroglial cells cultured in a nominally calcium-free medium. Ca2+ deprivation reduced progressively the astrocytes' viability, starting from 12 h; the restoration of a normal Ca2+ concentration (1.8 mM) in the medium after 12-h deprivation reversed the degenerative effect within 24 h. Biochemical and morphological examinations indicated that cell death induced by Ca2+ deprivation was mediated by apoptosis. This was associated with the expression of c-fos, c-jun, and c-myc, which, with different time courses, were induced in astrocytes after Ca2+ deprivation. Furthermore, shifting to a Ca2+-free medium modified the expression of Ich-1S transcript and rapidly increased intracellular cyclic AMP, which has been implicated in the transcriptional activation of immediate-early genes. The absence of Ca2+ in the medium reduced the expression of constitutive proteins such as alpha-actin, clusterin, glial fibrillary acidic protein, amyloid precursor protein, and glucose-6-phosphate dehydrogenase. The expression of these mRNAs was reduced >50% after 8 h of Ca2+ deprivation, when the effect on cell viability was negligible. When Ca2+ deprivation was prolonged for 24 h the expression of mRNA dropped completely, and restoration of the Ca2+ ions in the medium for 48 h did not reverse this effect. In contrast with general assumption, the apoptotic machinery in astrocytes is activated similarly not only by increased Ca2+ influx but also with the extracellular Ca2+ deprivation.

Animals↗
PubMed1998

Recurrent Meesmann's corneal epithelial dystrophy after penetrating keratoplasty.

PURPOSE: To characterize the histopathology of recurrent Meesmann's corneal epithelial dystrophy after penetrating keratoplasty. METHODS: Postmortem examination by light and electron microscopy of the eyes of an 84-year-old patient with Meesmann's dystrophy who underwent a penetrating keratoplasty in the right eye at age 74 years and a lamellar keratoplasty in the left eye at age 51 years. RESULTS: In the right eye, the characteristic features of Meesmann's dystrophy were demonstrated in both the donor and recipient corneas. The pathologic findings were limited to the corneal epithelium and included increased thickness, architectural disorganization, loss of cell polarity, increased amounts of intracellular glycogen, presence of intraepithelial microcysts containing degenerated cells, and in some cells, the presence of an electron-dense fibrillogranular material associated with disrupted cytoplasmic filaments. In the left eye, the corneal findings were consistent with but not specific for Meesmann's dystrophy. These included architectural disorganization, loss of cell polarity, presence of intraepithelial microcysts, and irregular thickening of the basement membrane in the donor cornea. CONCLUSION: Meesmann's corneal epithelial dystrophy is demonstrated to recur after penetrating keratoplasty. This finding suggests that the abnormalities that lead to the disease are localized to the corneal epithelial cells and not in the stroma, as previously proposed.

Aged↗
PubMed1998

Successful surgical treatment of visceral artery aneurysms. After failure of percutaneous treatment.

We report 2 cases involving aneurysms of visceral arteries that needed surgical treatment after unsuccessful percutaneous treatment. In the 1st case, repeated embolizations with Gianturco coils and angiographic guidewires had failed to obliterate a large aneurysm of the hepatic artery. In the 2nd case, a peripancreatic pseudoaneurysm caused recurrent gastrointestinal bleeding despite embolization with Gianturco coils. In both patients, left medial rotation of the viscera provided access to the origin of the affected artery at the aorta, enabling the surgeon to control bleeding before opening the aneurysm. The advantages and limitations of the most commonly performed percutaneous procedures are discussed, as are the surgical options.

Aged↗
PubMed1998

Combined lung volume reduction surgery and thoracic aortic aneurysm resection.

Postoperative improvement of respiratory function has been reported with lung volume reduction surgery (LVRS) in patients with severe emphysema. Since smoking is an established risk factor for lung cancer, vascular diseases and emphysema, it is not infrequent to find these diseases associated in the same patient. Combined treatment of lung cancer and emphysema has already been reported. Surgical treatment of vascular diseases in emphysematous patients could also benefit from the application of LVRS techniques. We report resection of an aortic aneurysm combined with LVRS in a patient with concomitant thoracic aortic aneurysm and severe emphysema. Respiratory function improved in the postoperative period.

Aged↗
PubMed1997

Evidence for a six-transmembrane domain structure of presenilin 1.

Mutations in genes encoding presenilin 1 and presenilin 2 account for the majority of cases of early-onset familial Alzheimer's disease. The presenilins have been localized to the endoplasmic reticulum and Golgi, but which of the multiple hydrophobic segments of the polypeptide chain span the lipid bilayer is unclear. To address this question, we have constructed a series of chimeric molecules in which a topologically neutral reporter protein (a C-terminal fragment of prolactin) containing three artificial glycosylation sites is fused to presenilin 1 following each of the 10 potential transmembrane domains identified in hydrophobicity plots. We have expressed these chimeras by translation in reticulocyte lysate containing canine pancreatic microsomes and by synthesis in transfected COS cells. Based on utilization of the glycosylation sites and sensitivity of the reporter to protease digestion, we provide evidence that presenilin 1 has six transmembrane segments with the N and C termini in the cytoplasm. This model provides important clues to the potential functions of different parts of the presenilin molecule and how these might relate to the pathogenesis of Alzheimer's disease.

Alternative Splicing↗
PubMed1997

Hepatitis B and C virus infection, alcohol drinking, and hepatocellular carcinoma: a case-control study in Italy. Brescia HCC Study.

We performed a case-control study to assess the association of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol drinking. We recruited as cases 172 subjects with an initial diagnosis of HCC, who were admitted to the two major hospitals in the province of Brescia, northern Italy, and 332 subjects, sex-, age-, and hospital-matched, who were admitted to the Departments of Ophthalmology, Dermatology, Urology, Cardiology, and Internal Medicine, as controls. Of the HCC cases, 23.8% were positive for HBsAg and 37.8% for HCV RNA; among the controls, 5.4% were positive for HBsAg and 4.8% for HCV RNA. History of heavy alcohol intake (>80 g of ethanol per day for at least 5 years) was found among 58.1% of the cases and among 36.4% of the controls. The relative risks (RRs) for HBsAg, HCV RNA positivity, and heavy alcohol intake were, respectively: 11.4 (95% confidence interval: 5.7-22.8), 23.2 (95% confidence interval: 11.8-45.7), and 4.6 (95% confidence interval: 2.7-7.8). Positive interactions (synergisms) between both HBsAg positivity and HCV RNA positivity and heavy alcohol intake were found, suggesting more than additive effects of viral infections and alcohol drinking on the risk of HCC. Infection with HCV genotype 1b showed a higher risk than type 2 (RR = 2.9; 95% confidence interval: 0.9-10), suggesting a major role for the former type in causing HCC. On the basis of population attributable risks (AR), heavy alcohol intake seems to be the single most relevant cause of HCC in this area (AR: 45%), followed by HCV (AR: 36%), and HBV (AR: 22%) infection.

Adult↗
PubMed1997

A case-control study on GB virus C/hepatitis G virus infection and hepatocellular carcinoma. Brescia HCC Study.

A new hepatitis-associated RNA virus of the Flaviviridae family has been identified and named GB virus C/ hepatitis G virus (HGV). We carried out a case-control study to evaluate the association of HGV infection with hepatocellular carcinoma (HCC). We recruited 170 patients hospitalized for HCC (143 male and 27 female, mean age 64 years) and 306 patients hospitalized for nonliver diseases (controls) in Brescia, Italy. HGV RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) and antibodies against HGV E2 protein (anti-E2) by an immunoassay test. HGV RNA was found in 8 cases (4.7%) and 4 controls (1.3%). The relative risk (RR) for HGV RNA positivity adjusted for demographic variables and hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, and alcohol was 7.3 (95% confidence interval, 1.7-30.6; P = .009). No HGV RNA-positive subject was also positive for anti-E2. Anti-E2 prevalence did not differ significantly between cases (20%) and controls (15.3%), and no RR increase was found by this marker. Among subjects with HGV exposure (HGV RNA plus anti-E2 positive), a greater proportion of cases (40%) than controls (14%) had transfusion history. The possible role of HGV in HCC etiology seems modest because the population-attributable risk is lower (4%) than those for HBsAg (22%), HCV RNA (36%), and heavy alcohol intake (52%). This study supports the hypothesis of an association between HGV infection and HCC, although at present there are insufficient data on the causality of the association.

Aged↗
PubMed1997

Phosphorylation of HSP25 during lens cell differentiation.

Small heat shock proteins and alpha-crystallins are related proteins with several common structural and functional properties including homologous amino acid sequences and similar chaperone-like activity. Furthermore, small heat shock proteins and alpha-crystallins are phosphorylated in vivo at serine residues within homologous amino acid sequences. During the differentiation of lens epithelial cells to fiber cells, significant changes in the patterns of expression and phosphorylation of alpha-crystallins take place, leading to the accumulation of phosphorylated forms of these proteins in lens fiber cells. To determine whether the small heat shock protein HSP25 undergoes phosphorylation in lens cells and to ascertain whether its phosphorylation state changes during lens cell differentiation, a comparative analysis of the HSP25 phosphorylation pattern in epithelial and fiber cells was undertaken. Analysis of phosphorylated and non-phosphorylated forms of HSP25 was carried out in cell extracts from rat lens epithelium and cortex by isoelectric focusing and Western blot using an antibody specific for the recombinant murine protein. The phosphorylated forms were identified by their isoelectric points and the characteristic shift upon in vitro dephosphorylation with phosphoprotein phosphatase 2B. HSP25 accounted for up to 2.4% of the protein content of rat lens extracts where it was present predominantly in mono- and bi-phosphorylated forms. Compared to epithelial cells extracts, the fiber cells extracts contained 67% more total HSP25 and a significantly higher proportion of bi-phosphorylated form. Phosphorylated HSP25 was sensitive to dephosphorylation by phosphoprotein phosphatase 2B in both cell extracts but the apparent dephosphorylation rate was significantly slower in the fiber cell extracts. The results demonstrate that HSP25 is phosphorylated in the lens in vivo. Furthermore, synthesis and phosphorylation of HSP25 change with lens cell differentiation resulting in a significant accumulation of bi-phosphorylated form in the fiber cells. These findings indicate that HSP25 and its phosphorylation may have important roles in lens cell differentiation.

Animals↗
PubMed1997

Safe and cost-effective approach to carotid surgery.

OBJECTIVE: To evaluate the safety and cost effectiveness of carotid surgery performed altering the perioperative protocol in an attempt to decrease resource utilisation. SETTING: Department of vascular surgery in a large metropolitan teaching hospital in northern Italy. DESIGN: Prospective, non-selective study. MATERIALS AND METHODS: Three hundred and eighty carotid procedures were performed in 1995 on 343 patients (274 males, 69 females, mean age 68.2 years, range 47-86 years). The most important cost containment measures, were: (i) limiting the use of contrast arteriography to cases of dubious ultrasonographic diagnosis; (ii) routine use of loco-regional anaesthesia; (iii) postoperative admission to an intensive care unit (ICU) only in selected cases; (iv) early postoperative discharge where possible. RESULTS: Mortality was 0.26% and neurological morbidity 1.58%. General anaesthesia was required in eight patients (2.1%), and only seven patients (1.8%) were admitted postoperatively to the ICU. Arteriography was performed in 56 cases (14.7%). The average hospital stay was 5 days with a global cost of 43,036 ECU, as compared with a cost of 6764 ECU for patients treated traditionally with routine arteriography, general anaesthesia and routine ICU admission. CONCLUSIONS: Selective use of arteriography and ICU, routine use of loco-regional anaesthesia and reduced hospital stay make it possible to lower the cost of carotid surgery without sacrificing quality.

Aged↗
PubMed1997

Neuroprotective effect of somatostatin on nonapoptotic NMDA-induced neuronal death: role of cyclic GMP.

Somatostatin (SRIF) exerts a modulatory function on neuronal transmission in the CNS. It has been proposed that a reduction of calcium currents is the major determinant of the inhibitory activity of this peptide on synaptic transmission. Because the neurotoxicity induced by activation of the NMDA subtype of glutamate receptor is mediated through excessive Ca2+ influx, we investigated whether SRIF counteracted NMDA-induced neuronal cell death. Neurons from embryonic rat cerebral cortex were cultured for 7-10 days and then exposed to 0.5 and 1 mM NMDA for 24 h. The neuronal viability, as assessed by the colorimetric method, decreased by 40 and 60%, respectively, compared with the control condition. Morphological and biochemical evidence indicated that cell death occurred by necrosis and not through an apoptotic mechanism. SRIF (0.5-10 microM), simultaneously applied with excitatory amino acid, significantly reduced in a dose-dependent manner the neurotoxic effect of NMDA but not that of KA (0.25-0.5 mM). GABA (10 microM) partially protected neurons to a similar extent from NMDA- or KA-induced toxicity. SRIF type 2 receptor agonists, octreotide (SMS 201-995; 10 microM) and vapreotide (RC 160; 10 microM), did not influence the NMDA-dependent neurotoxicity. The intracellular mechanism involved in SRIF neuroprotection was investigated. Pertussin toxin (300 ng/ml), a G protein blocker, antagonized the protective effect of SRIF on NMDA neurotoxicity. Furthermore, the neuroprotective effect of SRIF was mimicked by dibutyryl-cyclic GMP (10 microM), a cyclic GMP analogue, whereas 8-(4-chlorphenylthio)-cyclic AMP (10 microM), a cyclic AMP analogue, was ineffective. The cyclic GMP content was increased in a dose-dependent manner by SRIF (2.5-10 microM). Finally, both specific (Rp-8-bromoguanosine 3',5'-monophosphate, 10 microM) and nonspecific [1-(5 isoquinolinylsulfonyl)-2-methylpiperazine (H7), 10 microM] cyclic GMP-dependent protein kinase (cGMP-PK) inhibitors did not interfere with NMDA toxicity but substantially reduced SRIF neuroprotection. Our data suggest a selective neuroprotective role of SRIF versus NMDA-induced nonapoptotic neuronal death in cortical cells. This effect is likely mediated by cGMP-PK presumably by regulation of the intracellular Ca2+ level.

Animals↗
PubMed1997

Prion protein fragment 106-126 differentially induces heme oxygenase-1 mRNA in cultured neurons and astroglial cells.

Heme oxygenase (HO), which catalyzes the degradation of heme, has two isozymes (HO-1 and HO-2). In brain the noninducible HO-2 isoform is predominant, whereas the inducible HO-1 is a marker of oxidative stress. Because brain oxidative stress might be present in prion-related encephalopathies (PREs), as in other neurodegenerative diseases, we investigated whether HO-1 mRNA was induced in neuronal and astroglial cell cultures by a peptide corresponding to residue 106-126 of human prion protein (PrP). This peptide is amyloidogenic, and when added in vitro to cultured cells it reproduces the neuronal death and astroglial proliferation and hypertrophy occurring in PREs. HO-1 mRNA did not accumulate in rat cultured neurons from hippocampus or cortex exposed to PrP 106-126 (50 microM for 5 days). PrP 106-126 induced HO-1 mRNA accumulation in rat astroglial cultures depending on the exposure time and concentration, being maximal (33-fold) after 7 days of exposure at 50 microM. The nonamyloidogenic amidated or amidated-acetylated PrP 106-126 was ineffective, as was a scrambled peptide used as control. N-Acetylcysteine reduced (50%) the accumulation of HO-1 mRNA in astroglial cells after PrP 106-126 (25 microM) given for 5 days. Thus, oxidative stress is apparently a feature of the toxicity of PrP 106-126, and it might also occur in PREs; induction of HO-1 could contribute to the greater resistance of astrocytes compared with neurons to PrP 106-126 toxicity.

Acetylcysteine↗
PubMed1997

Interferon-gamma potentiates interleukin (IL)-6 and tumor necrosis factor-alpha but not IL-1beta induced by endotoxin in the brain.

Because interferon-gamma (IFN gamma) is present in the central nervous system during neurologic diseases associated with inflammation, its effect on endotoxin-induced cytokines was studied. Cerebrospinal fluid (CSF) and serum levels of interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF alpha), their messenger RNA expression in brain areas (hypothalamus, hippocampus, and striatum) and in spleen were evaluated 2 and 8 h after endotoxin [lipopolysaccharide (LPS), 25 microg/rat i.c.v.], IFN gamma (2.5 microg/rat i.c.v.) or after their coadministration in rats. CSF and serum IL-1beta levels were increased by LPS alone and IFN gamma coadministration did not furtherly increase them. IFN gamma potentiated LPS effect on IL-6 and TNF alpha levels in both CSF and serum. LPS and IFN-gamma coadministration did not alter IL-1beta messenger RNA expression induced by LPS in brain areas and in spleen, but it potentiated that of IL-6 and TNF alpha. The present in vivo data show that i.c.v. coadministration of LPS and IFN gamma results in a potentiation of cytokine production (IL-6 and TNF alpha) which may trigger a cascade of events relevant to neurodegenerative processes. This action is independent of IL-1beta because the production of this cytokine is not altered by IFN gamma treatment.

Animals↗
PubMed1997

Cigarette smoking and sports participation in adolescents: a cross-sectional survey among high school students in Italy.

All the male students in a high school in Brescia, North Italy (about 195,000 inhabitants) in Grades 9 through 13 were given a self-administered anonymous questionnaire during school time. Among the 1,462 students who filled in a valid questionnaire, 29.1% claimed to practice one or more sports regularly (at least 4 hours/week for 9 months/year or more), 30.2% practice sports occasionally, and 40.7% no sports at all. The percentage of current smokers (at least one cigarette a month) increased from 9th grade (11.1%) to 10th (13.2%), 11th (15.2%), 12th (27.7%), and 13th (23.7%) grade. The percentage of smokers showed a steady linear increase from the lowest to the highest grade in students practicing no or occasional activity but no increase in those who regularly practice sports. Students' smoking was negatively associated with the regular practice of sports among 12th-13th grade students.

Adolescent↗