Adverse effects of porcine small intestine submucosa (SIS) implants in experimental ventral hernia repair.
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Biomedical subjects
Publications and source records attributed to A Pinna.
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BACKGROUND: Since the incidence of myocardial infarction and other cardiovascular ischaemic events is highest in early morning, on account of a relative hypercoagulable state occurring in this time period, an attempt was made to test whether reperfusion of the hepatic artery at this time of the day, at liver transplantation, produces an increased risk of early thrombosis. METHODS: The records of 255 consecutive patients receiving a first transplant for chronic liver disease were retrospectively analysed. As possible risk factors, for early post-operative thrombosis (<30 days from transplantation), several medical and surgical parameters were taken into consideration. Arterial reperfusion was considered to have taken place at a time of high coagulability when occurred between 6.00 a.m. and 10.00 a.m. on the basis of previous reports. RESULTS: Logistic regression identified donor age (OR for age >60: P=0.017), bench reconstruction of the artery (OR: 5.06, P=0.013) and time of high coagulability at reperfusion (OR 2.93, P=0.087), as independently associated with early hepatic artery thrombosis. CONCLUSIONS: The present findings identified three independent predictors of early hepatic thrombosis, warranting stricter post-surgical follow-up of patients presenting such conditions. Interestingly, these factors are consistent with arterial reperfusion in the early morning being associated with an increased risk of early hepatic artery thrombosis, suggesting relative coagulative imbalances to provide a contribution in the pathogenesis of this severe complication of liver transplantation.
Caffeine, the most widely consumed psychostimulant drug, acutely stimulates motor behaviour and enhances dopamine agonists actions whilst chronically it induces tolerance to either caffeine- or dopamine agonist-induced motor activating effects. The present study examined whether subchronic caffeine administration (15 mg/kg, on alternate days for 14 days) induces enduring modifications in caffeine- and amphetamine-mediated motor activity. To this end, motor activation and rotational behaviour stimulated by either caffeine or D-amphetamine (0.5, 2 mg/kg), given 3 days after the last caffeine administration, were evaluated in neurologically intact and unilaterally 6-hydroxydopamine-lesioned rats respectively. Subchronic caffeine resulted in an increase in caffeine-induced motor and turning behaviour. Furthermore, caffeine pretreatment potentiated the motor effects of amphetamine in both intact and 6-hydroxydopamine-lesioned rats. These results suggest that subchronic caffeine treatment results in an enhancement of its motor stimulant effects, rather than in tolerance, and induces neuroadaptive facilitatory changes in dopamine transmission.
Lower eyelid involvement occurs in 6% of patients with discoid lupus erythematosus (DLE). Eyelid lesions are rarely the initial manifestation of DLE. We describe a 25-year-old woman presenting with discoid lesions of the lower eyelids, staphylococcal blepharitis and Meibomian gland dysfunction, who later developed a discoid lesion on the chin. Histopathological and immunofluorescence studies of a biopsy specimen from this lesion established the diagnosis of DLE. We are unaware of any previously reported cases of DLE presenting with discoid eyelid lesions associated with staphylococcal blepharitis and Meibomian gland dysfunction. DLE should be considered as a differential diagnosis in chronic blepharitis that persists despite usual medical management and eyelid hygiene. Misdiagnosis may lead to eyelid margin deformities, necessitate a complicated full-thickness biopsy, and delay diagnosis of systemic lupus.
AIMS: To compare the prognostic efficacy of the 5th and 6th edition of the TNM staging system for HCC. METHODS: We retrospectively applied the old and the new systems to 393 resected patients, comparing the efficacy of both in prognostic evaluation. RESULTS: The 1-, 3- and 5-year overall survival rates were 89.7, 71.1 and 56.3%, respectively. The 1-, 3- and 5-year disease-free survival rates were 79.4, 54.6 and 39.4%, respectively. Among the factors evaluated, Child's grade B and C (p=0.001) and presence of multiple nodules (p=0.01) were found to be related either to a worse long-term survival or to a worse disease-free survival. Stratifying patient survivals according to the old TNM system, we found significant differences only between stages II and IIIA (p=0.001); otherwise stages I and II (p=0.9) as well as stages IIIA and IVA (p=0.9) showed similar survival rates. Analysing the new TNM system, we found a more homogeneous staging stratification, with significant differences both between stage I and II (p=0.02) and between stage II and IIIA (p=0.05). CONCLUSIONS: In the present multicentric study, long term overall and disease-free survival after liver resection for HCC was strongly affected by the number of tumours and the underlying liver disease. Our results suggest that the new classification appears to achieve an accurate stratification of patients, simpler than the previous edition, as well as a more reliable comparative analysis of outcome after hepatic resection for HCC.
This randomised trial was designed to compare two groups treated with different G-CSF administration schedules with a third group receiving no G-CSF, after autologous peripheral blood stem cell transplantation (APBSCT). Children and adults with haematological malignancies or solid tumours were randomly assigned to receive either 150 microg/m2/day of Lenograstim starting on day 1 (G1) or on day 5 (G5) post APBSCT, or no Lenograstim (G0). Randomisation was stratified according to the conditioning regimen (Busulfan vs TBI vs no Busulfan and no TBI) and the graft CD 34+ cell count. A total of 240 patients were randomised; 239 were evaluable. All three patient groups were comparable. Median duration of neutropenia was 9 days (4-40), and 10 days (5-15) in the G1 and G5 groups, respectively, significantly shorter than in the G0 group, 13 days (7-36) (P < 0.0001). No difference was observed in the duration of thrombocytopenia, transfusion support and extra-haematological complications. The duration of post transplant hospitalisation was significantly shorter in adults who received G-CSF. Clinical and cost arguments favour the initiation of G-CSF on day 5 in adults. The same policy could be applied in children given that clinical management is easier and costs are similar.
Early gene induction by L-DOPA in the striatum of dopamine denervated rats represents a useful way to study long-term modifications produced by this drug. The effects of acute and subchronic L-DOPA administration on zif-268 mRNA expression were compared in 6-hydroxydopamine-lesioned rats. Rats received a subchronic intermittent L-DOPA (6 mg/kg) treatment, which produces behavioural sensitization, a correlate of dyskinetic movements. Three days after interruption of subchronic treatment, zif-268 mRNA was evaluated after an L-DOPA challenge. Zif-268 mRNA levels increased in the lesioned dorsolateral striatum after either acute or subchronic L-DOPA administration. Double labelling of striatal cells with zif-268 and enkephalin or dynorphin mRNA probes was performed to assess neuronal activation in the indirect and direct output pathway. Single acute L-DOPA significantly increased zif-268 in all striatal neurons reflecting a hyperresponsiveness of dopamine-depleted striatum. After subchronic L-DOPA, zif-268 mRNA labelling was still increased in the striatonigral pathway, limited to dynorphin(+) neurons, whereas in all other neurons it was similar to the control value. Results suggest that striatal neurons responding to acute L-DOPA differ from those responding to subchronic L-DOPA. L-DOPA-induced behavioural sensitization was associated to a down-regulation in the responsiveness of striatopallidal and striatonigral dynorphin(-) neurons, whereas in striatonigral neurons containing dynorphin a hyperresponsiveness to L-DOPA was observed. High levels of zif-268, together with a persistent hyperresponsiveness of striatonigral dymorphinergic neurons and hyporesponsiveness of striatopallidal neurons, by creating an unbalanced state of striatal efferent neurons, may be implicated in dyskinetic movements observed in Parkinson's disease (PD).
AIMS/HYPOTHESIS: The neurotrophin nerve growth factor (NGF) is pro-angiogenic and facilitates wound repair. The present study was conducted to (i) assess the statement of NGF system components in diabetic wounds and (ii) evaluate whether NGF supplementation could prevent impairment of wound neoangiogenesis by diabetes. METHODS: Skin wounds were produced in the interscapular region of streptozotocin-induced diabetic mice. NGF (1 microg per day in PBS) or vehicle was applied onto the ulcers for 3 days after punching. Non-diabetic mice were used as controls. RESULTS: In wounds of untreated diabetic mice, endogenous levels of immunoreactive NGF were lower than those in wounds of non-diabetic mice ( p<0.01). Immunohistochemical analysis showed down-regulation of tyrosine kinase receptor-A (TrkA) and up-regulation of p75 receptor in granulation tissue microvasculature. Local NFG administration prevented diabetes-induced expressional alterations, enhanced reparative capillarisation ( p<0.01), and accelerated wound closure ( p<0.01). This was associated with a three-fold increase in endothelial cell proliferation ( p<0.01), while apoptosis was reduced by 50% ( p<0.05). Quantitative RT-PCR documented a 5.5-fold increase in the expression of vascular endothelial growth factor-A (VEGF-A) by exogenous NGF in diabetic tissues ( p<0.01). In in vitro preparations of human endothelial cells from derma, NGF increased the release of immunoreactive VEGF-A, and reduced high-glucose-induced apoptosis ( p<0.05), the latter effect being inhibited by a VEGF-A receptor-2 antagonist. CONCLUSIONS/INTERPRETATION: Diabetic ulcers display distinct alterations in reparative angiogenesis and in the expression of NGF and its receptors. NGF supplementation corrects endogenous liabilities, facilitates vascular regeneration, and suppresses endothelial apoptosis seemingly via VEGF-A. Our findings unravel new mechanisms responsible for NGF reparative action.
BACKGROUND: Celsior (CS) has recently been proposed as a cold storage solution for thoracic and abdominal organs. We compared University of Wisconsin (UW) and CS solutions for the preservation of livers from old donors, with regard to initial function as well as short- and long-term graft and patient survival. METHODS: A multicenter retrospective study from 1998 to 2002 includes 30 livers from octogenarian donors preserved in CS (n = 15) or UW (n = 15) solution prior to transplantation. Donor and recipient clinical and laboratory parameters as well as liver biopsy results were evaluated in all cases. RESULTS: The distribution of the main donor variables as well as recipient characteristics were comparable between groups. Mean cold ischemia time was 421 minutes in the CS group and 474 minutes in the UW group. Mild steatosis was present in 8 cases in the CS group and 7 cases in the UW group. No primary graft dysfunction or arterial or biliary complications were noted. There was 1 acute rejection episode in the CS group and 4 in the UW group. Late postoperative deaths were observed only in the UW group (ie, 7 of 15). Actuarial graft survival was 100% in the CS group vs 86.7% in the UW group (P = NS) at 3 months, and 100% in the CS group vs 52.5% in the UW group (P =.007) at 12 months. Patient survival was 100% in the CS group vs 93.3% in the UW group (P = NS) at 3 months, and 100% in the CS group vs 59.3% in the UW group (P =.01) at 12 months. CONCLUSIONS: Both CS and UW solutions effectively protect livers obtained from donors >80 years of age during the early postoperative course but the CS group had better long-term results.
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BACKGROUND: Enteroscopy plays a key role in the post-operative monitoring of patients with small bowel transplantation for the early detection of post-transplant complications and for the assessment of the graft's integrity. Routine surveillance enteroscopies (trans-stomal terminal ileoscopy or jejunoscopy) are invasive, may be unsafe in frail patients, and only allow incomplete exploration of the transplanted graft, which may be unsatisfactory. since the distribution of the lesions is often patchy or segmental. AIMS. To evaluate the potential of capsule enteroscopy, a new, minimally invasive technique which allows complete exploration of the small bowel. in small bowel transplant recipients. METHODS: Five small bowel transplanted patients underwent capsule enteroscopy with the GIVEN endoscopy system. The results of capsule enteroscopy were compared with those of trans-stomal ileoscopy. RESULTS: Capsule enteroscopy was better tolerated than ileoscopy and good quality images of the small bowel were obtained in four patients. The terminal ileum was normal both on ileoscopy and capsule enteroscopy. Mucosal changes in segments not reached by ileoscopy were detected by capsule enteroscopy in three of four patients. CONCLUSIONS: Capsule enteroscopy is better tolerated than ileoscopy, allows complete exploration of the transplanted graft and can detect mucosal changes in segments not reached by ileoscopy.
Classic lamellar ichthyosis is a rare, autosomal recessive, genetically heterogeneous skin disease caused by mutations in the transglutaminase 1 gene. Pseudoainhum is characterized by the appearance of a constricting band around a digit which may lead to spontaneous amputation. We describe a 41-year-old man with classic lamellar ichthyosis with unusual eye changes and pseudoainhum of both the fifth and the third right toes. Eye abnormalities included bilateral ectropion of the lower eyelids, chronic blepharitis, and nuclear cataract. A radiometric assay revealed greatly reduced skin transglutaminase activity. To the best of our knowledge, this report is unique as classic lamellar ichthyosis with deficient transglutaminase activity has never been associated with pseudoainhum of the toes and the early development of nuclear cataract.
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AIM: Since living donor liver transplantation (LDLT) can offer a viable response to the lack of transplantable cadaveric organs, our center instituted an LDLT program in 2001. METHODS: The authors report their experience with the first 35 LDLT procedures successfully completed at the Liver and Multiorgan Transplant Center of the University of Modena between 9 May 2001 and 21 May 2003. The case series comprised 35 patients, 7 of which received a left-half liver and 1 a left lobe. RESULTS: The global survival rate was 77.2% (27 out of 35 patients), with a mean follow-up period of 295 days; the survival rate at 1 year was 81%. In 4 cases (11%) retransplantation was performed. The donor demographics are described; all donors returned to their normal activities before transplantation, after a mean follow-up period of 373 days. No intraoperative complications were experienced by the donors, whereas during the postoperative period, 2 donors (5.7%) developed major complications (1 biliary fistula on the cut surface, 1 stenosis of the main bile duct). CONCLUSION: Our study shows that LDLT can be safely completed in the donor, with good results achieved in the recipient as well. Underlying these results is the accurate pretransplant assessment that continued into the operation itself. Even more important was the demonstrated ability and experience of the surgical team to attain results in the donor which we believe are necessary for carrying forth a LDLT program.
To evaluate the short and long term outcome of liver resections for hepatocellular carcinoma in cirrhotic patients. A retrospective analysis was performed on 106 consecutive cirrhotic patients with hepatocellular carcinoma resected between June 1974 and September 2002 at the Department of Surgery "Pietro Valdoni" - University of Rome "La Sapienza" and at the Liver and Multivisceral Transplant Unit of the University of Modena. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. Overall mortality and morbidity were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumour recurrence appeared in 25 patients (23,5%). The 1-, 3-, and 5-year overall survival rates were 86,6%, 70,3%, and 60,6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86,3%, 58,1%, and 40,7%. On univariate analysis, viral ethiology of cirrhosis (p=0.03), presence of multiple nodules (p=0.02) and vascular invasion (p=0.05) were found to be related to a worse long-term survival. At the multivariate analysis only the viral ethiology of cirrhosis and the presence of multiple nodules were confirmed as indipendent prognostic factors. Early results after hepatic resection for HCC can be improved by using a limited surgical approach. The viral ethiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.
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Several evidences indicate that the selective blockade of adenosine A(2A) receptors counteracts the motor activity impairment in experimental models of Parkinson's disease. In the present study, the effects of the adenosine A(2A) receptor antagonist, SCH 58261 (5-amino-7-(beta-phenylethyl)-2-(8-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine, were assessed following a repeated treatment schedule in the contralateral turning behavior rat model of Parkinson's disease. Unilateral lesions of the nigrostriatal pathway were induced by injecting 6-hydroxydopamine (6-OHDA) in medial forebrain bundle. Repeated administration of SCH 58261 was performed either alone (7 and 14 days repeated SCH 58261) or together with L-dopa (19 days repeated SCH 58261 plus L-dopa or L-dopa alone). After a 7- and 14-day repeated administration schedule, SCH 58261 (5 mg/kg) maintained its ability to potentiate the contralateral turning behavior induced by a subthreshold dose of L-dopa (2 mg/kg i.p.), showing no tolerance to its stimulant effects. SCH 58261 (5 mg/kg) plus L-dopa (3 mg/kg) or L-dopa (6 mg/kg) alone induced, at these dosages, the same number of contralateral turnings after the first administration. While chronic intermittent SCH 58261 plus L-dopa did not lead to a modified turning behavior during treatment, L-dopa alone produced a progressive increase in turning behavior intensity and duration. These results provide evidence that SCH 58261 retains its ability to potentiate L-dopa effects in a validated rat model of Parkinson's disease even after repeated treatments. Moreover, these results suggest that adenosine A(2A) blockade prevents the appearance of motor response alterations in L-dopa-treated rats, supporting the concept that A(2A) receptor antagonists have a therapeutic potential for the treatment of Parkinson's disease. Copyright 2001 Wiley-Liss, Inc.