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Biomedical subjects

R Chiesa

Publications and source records attributed to R Chiesa.

At least 37 records · Page 2Linked to original sources
PubMed2003

Traumatic rupture of the thoracic aorta.

Traumatic rupture of the thoracic aorta is a life threatening situation, and may be secondary to several mechanisms; mainly penetrating or iatrogenic lesions and blunt trauma. Although penetrating mechanisms predominate, the number of patients with aortic disruption due to blunt trauma has continued to increase. This paper shows an overview focusing on the pathogenesis, diagnosis, timing and type of treatment regarding traumatic injuries of the thoracic aorta; it also reports the experience of one single center that deals with these lesions. The major difficulty in the evaluation data on blunt aortic injury is that retrospective reviews often group together patients with all types of aortic lesions, comparing outcomes for injuries in different locations, with diverse methods of repair and different surgeons and/or institutions.

Adolescent↗
PubMed2002

Vascular prosthetic graft infection: epidemiology, bacteriology, pathogenesis and treatment.

UNLABELLED: Vascular prosthetic graft infection remains a major surgical challenge. Prevention of risk factors and antibiotic therapy can reduced but not eradicate it. Management of infected vascular grafts depends on several factors, including the location of the infected prosthesis, the extent of infection, and the underlying micro-organism. Classic treatment consists of extra-anatomic bypass grafting. The disappointing results due to the high mortality and amputation rate have kindled interest in alternative approaches, such as in situ reconstruction with antibiotic-bonded prostheses, autogenous veins or arterial allografts. PURPOSE: We focused on the treatment of aortic graft infection by means of both fresh and cryopreserved arterial allograft. Here, the experience of the Italian Collaborative Vascular Homograft Group is reported. METHODS: Between March 1994 and December 2000 seventy-nine patients with aortic graft infection were treated. The results of 68 patients are analysed. Eleven patients were treated with fresh, and 57 with cryopreserved homograft. Emergency surgical procedures were performed in 12 patients (17%). Aortoenteric fistula was diagnosed in 22 patients. The mean interval between the first procedure and the insertion of a homograft for patients with infected aortic graft was 3 years (range 1-15). The mean duration of follow-up was 30 months (range 1-68). Clinical and duplex scanning evaluation were routinely performed. Computer tomography (CT), magnetic resonance (MR), or arteriography were performed on the basis of duplex scanning results. RESULTS: The analysis was performed on 68 cases for which there were sufficient reliable data. Eleven deaths occurred during the early postoperative period (30 days), a mortality rate of 16%. There were also seventeen late deaths, a mortality rate of 25%. Eleven patients had graft occlusion; six cases were successfully treated with thrombectomy. In three cases leg amputation was necessary. The results of fresh and cryopreserved homografts were compared. No significant differences of early postoperative mortality, late mortality, homograft-related mortality, graft failure were observed. The presence of aortoenteric fistula is a negative predicting factor of perioperative early mortality, which causes a rapid decline in the survival curve. Thirty-six months after the surgery the actuarial survival of the patients was 57% and the actuarial patency of the allograft was 41%. CONCLUSION: No significant difference in terms of clinical outcome was observed when using fresh, rather than cryopreserved homografts. The only factor that significantly influenced the survival rate appeared to be the aorto-enteric fistula.

Anti-Bacterial Agents↗
PubMed2002

Osseointegration of sandblasted or anodised hydrothermally-treated titanium implants: mechanical, histomorphometric and bone hardness measurements.

The improvement of the implant-bone interface is still an open problem in the long-term mechanical stability of cementless fixed implants. Mechanical, histomorphometric and bone hardness measurements were performed in sheep femoral cortical bone implants at 8 and 12 weeks from surgery to compare in vivo the osseointegration of titanium screws (psi 3.5 mm x 7 mm length) with two different surface treatments: sandblasting with 70-100 microm HA followed by acid etching with HNO3 (Group A) and Ca-P anodization followed by a hydrothermal treatment (Group B). No significant differences were found for maximum push-out force and interfacial strength between groups at both experimental times. No significant difference was observed for Bone Ingrowth between groups at both experimental times, while the Affinity Index of Group B was significantly higher (7.5%, p<0.05) and lower (10.2%, p<0.05) than that of Group A at 8 and 12 weeks, respectively. Finally, a significant increase in bone microhardness measured within 200 microm from the interface and inside the thread depth of Group A was observed between the two experimental times (p<0.05). In conclusion, present findings show that osseointegration may be accelerated by adequate surface roughness and bioactive ceramic coating such as current tested treatments which enhance bone interlocking and mineralization.

Animals↗
PubMed2002

Screening of stabilized crosslinked polyethylene using a novel wear tester.

A novel pin-on-disk type wear tester is described allowing a rapid screening of different types of polyethylene under both unidirectional and multidirectional sliding motion. The wear of four polyethylene materials sliding against a roughened CoCrMo alloy was evaluated: a non-irradiated UHMWPE, a UHMWPE irradiated with a dose of 25 kGy in air, and two types of crosslinked UHMWPE (100 kGy, air), which were subjected to a stabilization heat treatment in nitrogen at 155 degrees C for 72 hours (XLPE I) and in water at 130 degrees C for 72 hours (XLPE II), respectively.Under multidirectional sliding conditions both types of XLPE exhibited significantly less wear with respect to the 25 kGy irradiated UHMWPE and the non-irradiated UHMWPE, even under the rough counterface conditions applied. Under unidirectional sliding motion both types of XLPE exhibited the highest wear of all materials tested, because the orientation hardening effect acting under linear lubricated condition is less pronounced for crosslinked polyethylene.

Dose-Response Relationship, Radiation↗
PubMed2001

Emergency stenting to treat neurological complications occurring after carotid endarterectomy.

OBJECTIVES: The purpose of this study was to assess the efficacy of emergency stent implantation for the treatment of perioperative stroke after carotid endarterectomy (CEA). BACKGROUND: Carotid endarterectomy has been proven safe and effective in reducing the risk of stroke in symptomatic and asymptomatic patients with >60% carotid artery stenosis. However, perioperative stroke has been reported in 1.5% to 9% of CEA cases. The management of such a complication is challenging. Recently, percutaneous transluminal carotid angioplasty with stent deployment has emerged as a valuable and alternative strategy for the treatment of carotid artery disease. METHODS: Between April 1998 and February 2000, 18 of the 995 patients (1.8%) who had CEA in our institution experienced perioperative major or minor neurological complications. Of these, 13 patients underwent emergency carotid angiogram and eventual stent implantation, whereas the remaining five had surgery re-exploration. RESULTS: Carotid angiogram was performed within 20+/-10 min and revealed vessel flow-limiting dissection (five cases) or thrombosis (eight cases). Percutaneous transluminal carotid angioplasty with direct stenting (self-expandable stent) was performed in all 13 cases. Angiographic success was 100%. Complete remission of neurological symptoms occurred in 11 of the 13 patients treated by stent implantation and in one of the five patients treated by surgical re-exploration (p = 0.024). CONCLUSIONS: Stent implantation seems to be a safe and effective strategy in the treatment of perioperative stroke complicating CEA, especially when carotid dissection represents the main anatomic problem.

Aged↗
PubMed2001

Copper converts the cellular prion protein into a protease-resistant species that is distinct from the scrapie isoform.

Several lines of evidence have suggested that copper ions play a role in the biology of both PrP(C) and PrP(Sc), the normal and pathologic forms of the prion protein. To further investigate this intriguing connection, we have analyzed how copper ions affect the biochemical properties of PrP(C) extracted from the brains of transgenic mice and from transfected cells. We report that the metal rapidly and reversibly induces PrP(C) to become protease-resistant and detergent-insoluble. Although these two properties are commonly associated with PrP(Sc), we demonstrate using a conformation-dependent immunoassay that copper-treated PrP is structurally distinct from PrP(Sc). The effect of copper requires the presence of at least one of the five octapeptide repeats normally present in the N-terminal half of the protein, consistent with the idea that the metal alters the biochemical properties of PrP by directly binding to this region. These results suggest potential roles for copper in prion diseases, as well as in the physiological function of PrP(C).

Animals↗
PubMed2001

Primary myopathy and accumulation of PrPSc-like molecules in peripheral tissues of transgenic mice expressing a prion protein insertional mutation.

A nine-octapeptide insertional mutation in the prion protein (PrP) gene is associated with an inherited variant of Creutzfeldt-Jakob disease in humans. Transgenic mice that express the mouse PrP homologue of this mutation (designated PG14) under control of a PrP promoter display a progressive neurological disorder characterized by ataxia, apoptosis of cerebellar granule cells, and accumulation in the brain of mutant PrP molecules that display the biochemical hallmarks of PrP(Sc), the pathogenic isoform of PrP. In this report, we have investigated the expression of PG14 PrP in the peripheral tissues of these mice. We found highest levels of mutant PrP in the brain and spinal cord, intermediate levels in skeletal muscle, heart, and testis and low levels in kidney, lung, spleen, intestine, and stomach. Up to 70% of the PG14 PrP expressed in peripheral tissues was detergent-insoluble, and digestion with low concentrations of proteinase K yielded a PrP 27-30 fragment. These results suggest that the mutant protein was converted to a physical state reminiscent of PrP(Sc), although its infectivity remains to be determined. Histological analysis of skeletal muscle, one of the peripheral tissues with the highest level of PG14 PrP, revealed features indicative of a progressive, primary myopathy, including central nuclei, necrotic and regenerating fibers, and variable fiber size. These results indicate that the PG14 mutation structurally alters the protein in a way that promotes conversion to a PrP(Sc)-like state, regardless of the tissue context, and suggest that accumulation of PrP(Sc) can have deleterious effects on skeletal muscle cells as well as on neurons.

Aging↗
PubMed2001

Prion diseases: what is the neurotoxic molecule?

A great deal of effort has been devoted during the past 20 years to defining the chemical nature of prions, the infectious agents responsible for transmissible spongiform encephalopathies. In contrast, much less attention has been paid to elucidating how prions actually damage the central nervous system. Although it is commonly assumed that PrP(Sc), the protein constituent of infectious prions, is the primary culprit, increasing evidence indicates that this may not be the case. Several alternative molecular forms of PrP are reasonable candidates for the neurotoxic species in prion diseases, although it is still too early to tell whether these or other ones will turn out to be the true instigating factors. The cellular pathways activated by neurotoxic forms of PrP that ultimately result in neuronal death are also being investigated, and several possible mechanisms have been uncovered, including the operation of quality control processes in the endoplasmic reticulum. Elucidating the distinction between the infectious and neurotoxic forms of PrP has important implications for designing therapy of prion diseases, as well as for understanding pathogenic mechanisms operative in other neurodegenerative disorders and the role of prion-like states in biology.

Adult↗
PubMed2001

Endovascular stenting for the nutcracker phenomenon.

PURPOSE: To present a case highlighting the efficacy of stent implantation for left renal vein (LRV) entrapment, otherwise known as the nutcracker phenomenon. CASE REPORT: A 17-year-old boy presented with a history of gross hematuria and left flank pain. Magnetic resonance angiography documented compression of the LRV between the superior mesenteric artery and aorta. A Memotherm stent was successfully placed across the LRV to restore adequate luminal flow after a Wallstent failed to adequately span the narrowed segment. Spiral CT angiography at 6 months confirmed LRV patency; the patient remains asymptomatic and free of hematuria at 12 months. CONCLUSIONS: Endovascular stenting for the nutcracker phenomenon is safe and effective and may represent a valuable approach for lessening the morbidity of surgical procedures.

Adolescent↗
PubMed2000

Enhanced wear performance of highly crosslinked UHMWPE for artificial joints.

It is well known that osteolysis induced by polyethylene wear debris is the main cause of long-term failure of hip and knee prostheses. We developed a treatment of medical-grade ultra-high molecular-weight polyethylene (UHMWPE) in order to improve its tribologic properties and reduce its wear. Medical-grade UHMWPE was irradiated with a 200 kGy dose of radiation, thermally stabilized at a temperature close to the melting point, and then sterilized with ethylene oxide. The irradiation treatment was performed to crosslink the UHMWPE. The thermal stabilization treatment, contributing to the reaction between the free radicals generated by the irradiation process, was chosen to enhance crosslinking and to prevent oxidation and the shortening of chains. The non-invasive sterilization process with ethylene oxide was chosen to prevent the re-formation of free radicals. The wear performance of this material was compared to UHMWPE, untreated or treated with different sterilization techniques, using gamma and beta irradiation. Insoluble crosslinked constituents were measured with an extraction method. Wear was evaluated using a flat-on-ring wear test machine. While small differences were found among the different sterilization processes, 200 kGy-irradiated UHMWPE followed by thermal treatment and sterilization with ethylene oxide had the least wear and the greatest amount of crosslinking.

Biocompatible Materials↗
PubMed2000

Accumulation of protease-resistant prion protein (PrP) and apoptosis of cerebellar granule cells in transgenic mice expressing a PrP insertional mutation.

We have generated lines of transgenic mice that express a mutant prion protein (PrP) containing 14 octapeptide repeats whose human homologue is associated with an inherited prion dementia. These mice develop a neurological illness with prominent ataxia at 65 or 240 days of age, depending on whether the transgene array is, respectively, homozygous or hemizygous. Starting from birth, mutant PrP is converted into a protease-resistant and detergent-insoluble form that resembles the scrapie isoform of PrP, and this form accumulates dramatically in many brain regions throughout the lifetime of the mice. As PrP accumulates, there is massive apoptosis of granule cells in the cerebellum. Our analysis provides important insights into the molecular pathogenesis of inherited prion disorders in humans.

Animals↗
PubMed2000

A transgenic model of a familial prion disease.

We have generated lines of transgenic mice that express a mutant prion protein containing 14 octapeptide repeats whose human homologue is associated with an inherited prion dementia. These mice develop an ataxic illness that begins at 65 days of age when the transgene array is homozygous, and results in death by 115-138 days. Starting from birth, mutant PrP is converted into a protease-resistant and detergent-insoluble form that resembles PrP(Sc), and this form accumulates dramatically in many brain regions throughout the lifetime of the mice. As PrP accumulates, there is massive apoptosis of cerebellar granule cells, as well as astrocytosis and deposition of PrP in a punctate pattern. These results establish a new transgenic animal model of an inherited human prion disease, and provide important insights into the molecular pathogenesis of these disorders.

Animals↗
PubMed2000

Eversion versus conventional carotid endarterectomy: late results of a prospective multicenter randomized trial.

OBJECTIVE: The durability of carotid endarterectomy (CEA) may be affected by carotid restenosis. The data from randomized trials show that the highest incidence of restenosis after CEA occurs from 12 to 18 months after surgery. The optimal CEA technique to reduce perioperative complications and restenosis rates is still undefined. This study examines the long-term clinical outcome and incidence of recurrent stenosis in patients who undergo eversion CEA. Previously published perioperative results of this study did not show statistically significant differences in study endpoints between the eversion and standard techniques. METHODS: From October 1994 to March 1997, 1353 patients with surgical indications for carotid stenosis were randomly assigned to undergo eversion (n = 678) or standard CEA (n = 675; primary closure, 419; patch, 256). Withdrawal from the assigned treatment occurred in 1.6% of the patients (in 13 assigned to eversion CEA, and in nine assigned to standard CEA). The clinical and duplex scan follow-up examination was 99% complete, and the mean follow-up interval was 33 months (range, 12 to 55 months). The primary outcomes were perioperative and late major stroke and death, carotid restenosis (stenosis >/= 50% of the lumen diameter detected at duplex scanning), and carotid occlusion. The primary evaluation of study outcomes was conducted on the basis of an intention-to-treat analysis. RESULTS: Restenosis was found at duplex scanning in 56 patients (19 in the eversion group, and 37 in the standard group). Within the standard group, the restenosis rates were 7.9% in the primary closure population and 1.5% in the patched population. Of the patients with restenosis, 36% underwent cerebral angiography that confirmed restenosis in all cases. The cumulative restenosis risk at 4 years was significantly lower in the group that underwent treatment with eversion CEA as compared with the standard group (3.6% vs 9.2%; P =.01), with an absolute risk reduction of 5. 6% and a relative risk reduction of 62%. Eighteen patients would have had to undergo treatment with eversion CEA to prevent one restenosis during the 4-year period. The incidence rate of ipsilateral stroke was 3.3% in the eversion population and 2.2% in the standard group. There were no significant differences in the cumulative risks of ipsilateral stroke (3.9% for eversion, and 2.2% for standard; P =.2) and death (13.1% for eversion, and 12.7% for standard; P =.7)) in the two groups. Of the 18 variables that were examined for their influence on restenosis, eversion CEA (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.6; P =.0004) and patch CEA (hazard ratio, 0.2; 95% confidence interval, 0.07 to 0.6; P =. 002) were negative independent predictors of restenosis with multivariate Cox proportional hazards regression analysis. CONCLUSION: The EVEREST (EVERsion carotid Endarterectomy versus Standard Trial) showed that eversion CEA is safe, effective, and durable. No statistically significant differences were found in late outcome between the eversion and standard techniques at the available follow-up examination.

Actuarial Analysis↗
PubMed2000

Extensible expanded polytetrafluoroethylene vascular grafts for aortoiliac and aortofemoral reconstruction.

The operative experience and medium-term outcome achieved with longitudinally extensible ('stretch') expanded polytetrafluoroethylene (ePTFE) bifurcated grafts in patients undergoing aortoiliac or aortofemoral reconstruction for occlusive disease at our institution was reviewed. Between 1991 and 1998, 242 patients received a bifurcated stretch graft. Forty-one patients (17%) required an aortic endarterectomy, and 63 (26%) underwent femoral artery endarterectomy. 228 patients were followed for a mean of 32 months. One patient (0.4%) died perioperatively. The perioperative morbidity included cardiac (3.7%), respiratory (2.5%), and renal (3.3%) complications. Three patients required early reoperation for bleeding. Four (1.7%) grafts thrombosed within 24h of surgery; eight additional grafts (3.3%) thrombosed 5-8 months later. There were three postoperative aortic graft infections, one inguinal infection, three inguinal pseudoaneurysms, and one aortic pseudoaneurysm. Ultrasonography during follow-up showed no periprosthetic fluid collections or graft dilatations. The bifurcated ePTFE stretch graft is suitable for aortoiliac and aortofemoral reconstruction, and its physical characteristics may help to reduce graft-related complications.

Aged↗
PubMed2000

Nerve growth factor-induced differentiation does not alter the biochemical properties of a mutant prion protein expressed in PC12 cells.

Insertional and point mutations in the gene encoding the prion protein (PrP) are responsible for familial prion diseases. We have previously generated lines of Chinese hamster ovary cells that express PrP molecules carrying pathogenic mutations, and found that the mutant proteins display several biochemical properties reminiscent of PrP(Sc), the infectious isoform of PrP. To analyze the properties and effects of mutant PrP molecules expressed in cells with a neuronal phenotype, we have constructed stably transfected lines of PC12 cells that synthesize a PrP molecule carrying a nine-octapeptide insertion. We report here that this mutant PrP acquires scrapie-like properties, including detergent insolubility, protease resistance, and resistance to phospholipase cleavage of its glycolipid anchor. A detergent-insoluble and phospholipase-resistant form of the mutant protein is also released spontaneously into conditioned medium. These scrapie-like biochemical properties are quantitatively similar to those seen in Chinese hamster ovary cells and are not affected by differentiation of the PC12 cells into sympathetic neurons by nerve growth factor. Moreover, there is no detectable effect of mutant PrP expression on the morphology or viability of the cells in either the differentiated or undifferentiated state. These results indicate that conversion of mutant PrP into a PrP(Sc)-like form does not depend critically on the cellular context, and they suggest that mutant PrP expressed in cultured cells, even those having the phenotype of differentiated neurons, is not neurotoxic.

Animals↗