RESUMO
BACKGROUND: Reconstruction of the aorto-iliac segment with femoral vein (FV) as substitute for infected synthetic grafts or mycotic aneurysms constitutes the most sustainably convenient alternative. The aim of this study was to evaluate the long-term outcome of up to 16 years of follow-up, analysing the morphologic adaption of the FV with special emphasis on the distal and proximal anastomoses. METHODS: We conducted a retrospective study of 22 patients with 109 computed tomography angiograms (CTAs) treated between August 2001 and January 2020 in case of aortic infection/aortitis. Morphologic changes like anastomotic dilatation/stenosis as well as changes of FV wall thickness were retrospectively analysed in pre- and postoperative CTAs. RESULTS: Elective procedure was done in 17/22 (77%) cases, and 5/22 (23%) patients required emergent surgery. The median follow-up was 91.5 months (P25;P75 = 21;117). Cross-sectional diameter of proximal (20.38 ± 3.77 vs 22.04 ± 3.97 mm, p = 0.007) and distal anastomoses (13.05 ± 4.23 vs 14.61 ± 5.19 mm, p = 0.05) increased significantly, as well as the proximal and distal anastomotic areas (3.36 ± 1.29 vs 4.32 ± 1.63 mm2, p = 0.04 and 0.99 ± 0.48 vs 1.25 ± 0.72 mm2, p = 0.023, respectively). Venous wall thickness was significantly reduced at the anastomotic site (1.74 ± 0.46 vs 1.24 ± 0.31 mm, p = 0.001). The upper thigh diameter did not differ before and after harvesting of the FV (161.6 ± 29.1 vs. 178.2 ± 23.3 mm, p = 0.326, respectively). CONCLUSION: This long-term CTA follow-up study showed that the FV wall becomes thinner at the anastomotic site, and the anastomoses dilate with time without rupture. The FV is a durable conductor after replacement of the aorto-iliac segment due to aortic infection. Further CTA studies from more centres are warranted to evaluate the risk of vein rupture.
Assuntos
Aneurisma da Aorta Abdominal , Aortite , Implante de Prótese Vascular , Aorta/cirurgia , Aneurisma da Aorta Abdominal/cirurgia , Aortite/diagnóstico por imagem , Aortite/etiologia , Aortite/cirurgia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Veia Femoral/diagnóstico por imagem , Veia Femoral/cirurgia , Veia Femoral/transplante , Seguimentos , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. METHODS: Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. RESULTS: Serum NGAL [median 107.4 ng/ml (quartiles: 75.2-145.0) vs. 64.4 (50.4 -81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8-63.9) vs. 27.6 (16.0-42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8-195.6) vs. 64.8 (48.9-82.2] and [101.6 ng/ml (70.1-125.3) vs. 63.8 (51.0-81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. CONCLUSIONS: Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.
Assuntos
Estenose das Carótidas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Lipocalina-2/metabolismo , Metformina/uso terapêutico , Idoso , Biomarcadores/sangue , Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/metabolismo , Estenose das Carótidas/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/sangueRESUMO
OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL), a protein found in activated neutrophils, is expressed in kidney tubule cells in response to noxious stimuli, and is thus recognized as a marker of acute kidney injury. Recent studies have suggested that NGAL could also have pathophysiological importance in cardiovascular diseases. The aim of the present study was to examine NGAL expression in human carotid endarterectomy tissues ex vivo as well as the effects of NGAL in the main cell types involved in atherogenesis, namely in human macrophages, endothelial cells, and smooth muscle cells in vitro. METHODS: NGAL protein was analyzed in human endarterectomy samples from patients with asymptomatic and symptomatic carotid stenosis by immunofluorescence, and NGAL mRNA expression was detected using RealTime-PCR. Human monocyte derived macrophages (MDM), human coronary artery smooth muscle cells (HCASMC), and human umbilical vein endothelial cells (HUVEC) were treated with recombinant human (rh) NGAL at different concentrations. Interleukin (IL)-6, IL-8, and monocyte chemo-attractant protein-1 (MCP-1) were determined by specific enzyme linked immunosorbent assays (ELISAs) in culture supernatants of such treated cells. RESULTS: Expression of NGAL protein was demonstrated by macrophages, smooth muscle cells, and endothelial cells in human carotid atherosclerotic tissue. NGAL mRNA expression was detected at a higher rate in atherosclerotic tissue of patients with symptomatic carotid stenosis (in 70%; n = 19) compared with asymptomatic patients (in 37%; n = 20, p < .001). Treatment of MDM, HCASMC, and HUVEC with rhNGAL led to a significant (p < 0.05) and concentration dependent increase of pro-inflammatory cytokines IL-6, IL-8, and MCP-1 in all cell types analyzed. CONCLUSION: By induction of pro-inflammatory mediators in human macrophages, smooth muscle cells and endothelial cells, NGAL, which is predominantly expressed in atherosclerotic plaques of symptomatic patients, could be involved in creating the local and systemic pro-inflammatory environment characteristic for atherosclerosis.
Assuntos
Doenças das Artérias Carótidas/metabolismo , Inflamação/metabolismo , Lipocalina-2/metabolismo , Quimiocina CCL2/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Imunofluorescência , Humanos , Técnicas In Vitro , Inflamação/etiologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lipocalina-2/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVE/BACKGROUND: Matrix metalloproteinases (MMPs) play a pivotal role in the development and progression of abdominal aortic aneurysms (AAAs). The action of MMPs depends on a balance between tissue inhibitors of MMPs (TIMPs) and compounds that may prolong protease activity, such as neutrophil gelatinase-associated lipocalin (NGAL). METHODS: The study was designed to analyse gene expression and protein concentration of MMPs, TIMPs, and NGAL in AAA walls and intraluminal thrombi (ILTs) of patients on simvastatin (n = 10) and not on statins (n = 10). The patients were matched by age, sex, and AAA diameter. Expression of MMP2, MMP9, TIMP1, TIMP2, and NGAL was investigated by real time polymerase chain reaction, and MMP2, MMP9, MMP9/TIMP1, MMP9/TIMP2, and MMP9/NGAL protein levels by enzyme-linked immunosorbent assay. RESULTS: MMP2 and MMP9 protein and mRNA levels were comparable in the simvastatin and non-statin groups (p > .05); however, there was a significant decrease in TIMP1 mRNA in AAA tissue (p = .04). Moreover, a significant increase in MMP9/TIMP2 complex concentration in ILTs of patients on simvastatin was noted (median 94.71 ng/mL in the simvastatin group vs. 36.80 ng/mL in the non-statin group; p = .01). No significant difference was observed for NGAL mRNA or protein content in AAA and ILT. CONCLUSION: Simvastatin treatment in patients with AAAs may influence the concentration of proteases and their inhibitors (TIMPs) in aneurysmal wall tissue and ILTs. Thus, further studies should be undertaken to understand the different influence of statin therapy on the components of the MMP/TIMP system in AAAs and ILTs.
Assuntos
Proteínas de Fase Aguda/metabolismo , Aneurisma da Aorta Abdominal/tratamento farmacológico , Lipocalinas/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Sinvastatina/farmacologia , Trombose/tratamento farmacológico , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Idoso , Aneurisma da Aorta Abdominal/metabolismo , Feminino , Humanos , Lipocalina-2 , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Trombose/metabolismoRESUMO
BACKGROUND: The aim of this study was to evaluate long-term results, quality of life, satisfaction and compensatory sweating after endothoracic sympathetic block at T4 (ESB4). METHODS: Patients who underwent an ESB4 procedure for palmar or palmoaxillary hyperhidrosis between 2001 and 2008 were included in a prospective study at a university hospital. Questionnaires devised by Keller and Milanez de Campos were applied to evaluate disease-specific quality of life. RESULTS: A total of 189 patients underwent 374 ESB4 procedures. Of 174 evaluated patients, 54 (31·0 per cent) had palmar and 120 (69·0 per cent) had palmoaxillary hyperhidrosis. Median follow-up was 92 months. In both groups, treatment successfully reduced hyperhidrosis (P < 0·001) and quality of life increased significantly after ESB4 (P < 0·001), remaining stable after 5 years. Overall satisfaction rates decreased owing to the development of compensatory sweating and recurrence during follow-up. Compensatory sweating affected 41 patients (23·6 per cent), and was severe in 11 (6·7 per cent) of 163 patients at 5-year follow-up; eight of these 11 patients had been treated for palmoaxillary sweating. The severity of compensatory sweating did not deteriorate with time. The severe recurrence rate increased to 11·0 per cent during follow-up, and was twice as common in patients treated for palmoaxillary sweating as in those treated for palmar sweating (13·2 versus 6·1 per cent respectively). Nine reoperations (5·2 per cent) were performed for persistent sweating, recurrence or compensatory sweating. CONCLUSION: T4 endothoracic sympathetic clip application is safe and effective in patients with upper limb hyperhidrosis, with stable long-term improvements in quality of life.
Assuntos
Bloqueio Nervoso Autônomo/métodos , Hiperidrose/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Neuroendoscopia/métodos , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Qualidade de Vida , Recidiva , Reoperação/estatística & dados numéricos , Toracoscopia/métodos , Resultado do Tratamento , Extremidade Superior , Adulto JovemRESUMO
BACKGROUND: Cyclophilin A (CyPA), a cyclosporine A-binding protein, influences abdominal aortic aneurysm (AAA) formation and the ERK1/2 signalling pathway in animal and in vitro studies. Statins decrease CyPA in smooth muscle cells although their influence on CyPA in human AAA is unknown. MATERIAL AND METHODS: The study was performed on AAA wall-tissue samples obtained from 30 simvastatin-treated and 15 non-statin patients (2:1 case to control). The patients were matched by age, sex and AAA diameter. We investigated the gene expression of CyPA, its receptor extracellular matrix metalloproteinase inducer (EMMPRIN) by real-time RT-PCR. CyPA and EMMPRIN protein level and phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2) were measured by Western blot. RESULTS: The AAA wall tissue from simvastatin-treated patients had significantly lower CyPA gene expression and protein levels (P = 0.0018, P = 0.0083, respectively). Furthermore, phosphorylation of ERK1 and ERK2 was markedly suppressed in the simvastatin group (P = 0.0002, P = 0.0027, respectively). However, simvastatin did not influence EMMPRIN gene and protein expression. CONCLUSION: Simvastatin-treated patients with AAA exert lower CyPA messenger RNA (mRNA), as well as CyPA intracellular protein levels and a decreased amount of phospho-ERK1/2. Thus, the interference with signalling pathways leading to CyPA formation and ERK1/2 activation reveals a new anti-inflammatory role of statins in AAA.
Assuntos
Anti-Inflamatórios/uso terapêutico , Aorta Abdominal/efeitos dos fármacos , Aneurisma da Aorta Abdominal/tratamento farmacológico , Ciclofilina A/análise , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Proteína Quinase 1 Ativada por Mitógeno/análise , Proteína Quinase 3 Ativada por Mitógeno/análise , Sinvastatina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/enzimologia , Aneurisma da Aorta Abdominal/enzimologia , Aneurisma da Aorta Abdominal/genética , Basigina/análise , Basigina/genética , Western Blotting , Estudos de Casos e Controles , Ciclofilina A/genética , Regulação para Baixo , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fosforilação , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Objective: Endovascular aortic repair (EVAR) has become a routine procedure worldwide. Ultimately, the increasing number of EVAR cases entails changing conditions for open surgical repair (OSR) regarding patient selection, complexity, and surgical volume. This study aimed to assess the time trends of open abdominal aortic aneurysm (AAA) repair in a high-volume single center in Austria over a period of 20 years, focusing on the operation time and clinical outcomes. Materials and methods: A retrospective analysis of all patients treated for infrarenal AAAs with OSR or EVAR between January 2000 and December 2019 was performed. Infrarenal AAA was defined as the presence of a >10-mm aortic neck. Cases with ruptured or juxtarenal AAAs were excluded from the analysis. Two cohorts of patients treated with OSR at different time periods, namely, 2000-2009 and 2010-2019, were assessed regarding demographical and procedure details and clinical outcomes. The time periods were defined based on the increasing single-center trend toward the EVAR approach from 2010 onward. Results: A total of 743 OSR and 766 EVAR procedures were performed. Of OSR cases, 589 were infrarenal AAAs. Over time, the EVAR to OSR ratio was stable at around 50:50 (p = 0.488). After 2010, history of coronary arterial bypass (13.4% vs. 7.2%, p = 0.027), coronary artery disease (38.1% vs. 25.1%, p = 0.004), peripheral vascular disease (35.1% vs. 21.3%, p = 0.001), and smoking (61.6% vs. 34.3%, p < 0.001) decreased significantly. Age decreased from 68 to 66 years (p = 0.023). The operation time for OSR remained stable (215 vs. 225â min, first vs. second time period, respectively, p = 0.354). The intraoperative (5.8% vs. 7.2%, p = 0.502) and postoperative (18.3% vs. 20.8%, p = 0.479) complication rates also remained stable. The 30-day mortality rate did not change over both time periods (3.0% vs. 2.4%, p = 0.666). Conclusion: Balanced EVAR to OSR ratio, similar complexity of cases, and volume over the two decades in OSR showed stable OSR time without compromise in clinical outcomes.
RESUMO
OBJECTIVES: Statins have been reported to suppress the progression of abdominal aortic aneurysm (AAA). However, the effects of statins on inflammatory processes and free radicals generation are poorly understood. METHODS: Wall samples from 51 patients (simvastatin patients, n = 34; non-statin patients, n = 17; matched by sex, age and aneurysm size) subjected to elective open AAA repair were analysed. We examined the effects of simvastatin on lipid peroxidation (4-hydroxy-trans-2-nonenal (4-HNE)), hydrogen peroxide (H(2)O(2)), tumour necrosis factor alpha (TNF-α) concentration, superoxide dismutase (SOD) and catalase (CAT) activity as well as nuclear factor kappa B (NF-κB) pathway activation in human AAA wall samples. RESULTS: Treatment with simvastatin resulted in a decrease in 4-HNE and TNF-α concentration (median 4.18 µg/mg protein vs. 4.75, p = 0.012; median 10.33 pg/ml vs. 11.81, p = 0.026, respectively). CAT activity was higher in the simvastatin group (median 3.98 U ml vs. 3.19, p = 0.023). NF-κB expression was lower (p = 0.018) in the simvastatin group. However, simvastatin had little effect on H(2)O(2) concentration (p = 0.832) and SOD activity (p = 0.401). CONCLUSION: Simvastatin inhibits free radicals and TNF-α generation and improves antioxidant capacity of human AAA wall tissue, possibly through the suppression of NF-κB activity. This may be one possible explanation how statins can inhibit AAA oxidative stress.
Assuntos
Antioxidantes/uso terapêutico , Aorta Abdominal/efeitos dos fármacos , Aneurisma da Aorta Abdominal/tratamento farmacológico , Radicais Livres/análise , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , NF-kappa B/análise , Estresse Oxidativo/efeitos dos fármacos , Sinvastatina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Aldeídos/análise , Aorta Abdominal/química , Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/cirurgia , Áustria , Estudos de Casos e Controles , Catalase/análise , Feminino , Humanos , Peróxido de Hidrogênio/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/análise , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: Epidemiological data on individuals suffering from severe primary hyperhidrosis are scarce. OBJECTIVE: This study aims to prospectively assess disease-specific characteristics of patients with severe, mostly therapy-resistant hyperhidrosis presenting for sympathetic surgery. METHODS: We evaluated a total of 227 patients (69.6% women) with a mean age of 30 years (standard deviation, 9.5 years) using a standardized questionnaire. Severity of disease was rated on a visual analogue scale (VAS) graded between 0 (no symptoms) and 10 (worst symptom). Age, sex, previous therapies, hormonal therapies and body mass index were analysed for their possible influence on severity of the disease and on hyperhidrosis sites. In addition, allergies were investigated for the first time in this patient population. RESULTS: There was a positive correlation between age of onset and sites of hyperhidrosis. The most commonly affected areas were palmar-axillary-plantar (51.1%) and palmar-plantar (15.0%), with sex-specific differences. Two hundred and twelve patients (93.4%) had previous conservative therapies; 219 patients (96.5%) reported VAS scores between 8 and 10. Female patients stated higher VAS scores for palmar (P = 0.009) and axillary (P = 0.012) sites. Type IV allergies were found to be much higher than in the general Austrian female population. Hormonal therapies and the body mass index had no influence on severity of hyperhidrosis after analysis of VAS scores. CONCLUSION: Sex-dependent aspects can be found in patients strongly affected by primary upper limb hyperhidrosis.
Assuntos
Hiperidrose/cirurgia , Sistema Nervoso Simpático/cirurgia , Adulto , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has evolved as a gold standard in antireflux surgery. However, the association between body weight and gastroesophageal reflux disease (GERD) is still unclear, and no data are available concerning the effect of fundoplication on body weight. We present the first report elucidating the impact of LNF on body weight in GERD patients with special emphasis on patients' quality of life. METHODS: From July 2000 to March 2003, LNF was carried out in 213 patients (85 women and 128 men) after thorough preoperative examination including clinical interview with standardized assessment of symptoms and quality of life (QoL), endosocopy, barium swallow, 24-h pH-metry, and manometry. Follow-up investigations were performed 3 and 12 months after LNF obtainable from 209 patients (98.1%) and 154 patients (72.3%), respectively. RESULTS: The mean body mass index (BMI) decreased significantly after LNF (27.6 +/- 5.6 kg/m(2) before LNF vs 26.0 +/- 3.8 kg/m(2) after LNF, p < 0.001). Twelve months after LNF, neither a tendency toward a renewed increase nor a further decrease in BMI was observable. The average body weight loss was 3.9 kg. BMI reduction was higher in women than in men (p < 0.002), and obese patients lost more weight than lean patients (p < 0.001). There was no association between BMI reduction and dysphagia. Plasma cholesterol and triglyceride levels did not change after LNF. The mean general score of the Gastrointestinal Quality of Life Index markedly improved (90.1 +/- 21.3 before LNF vs 118.0 +/- 16.2 after LNF, p < 0.01), as did the GERD-Health Related Quality of Life Index (21.9 +/- 6.4 before LNF vs 3.5 +/- 2.7 after LNF, p < 0.001). However, there was no association between changes in BMI and QoL. CONCLUSION: LNF leads to significant and persistent body weight loss.
Assuntos
Fundoplicatura/métodos , Refluxo Gastroesofágico/cirurgia , Laparoscopia , Redução de Peso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de VidaRESUMO
To test the effects of prostaglandin E1 on 2.5 h of ischemia followed by 2 h of reperfusion, continuous nitric oxide measurements (electrochemical) were correlated with intermittent assays of superoxide and peroxynitrite levels (chemiluminescence) and ischemia/reperfusion injury in rabbit adductor magnus muscle. Administering prostaglandin E1 (1 microg/kg) before or during ischemia/reperfusion caused normalization of the release of nitric oxide, superoxide, and peroxynitrite to slightly above preischemic levels. This pattern was dramatically different from that observed during ischemia/reperfusion alone, where nitric oxide concentration increased three times above its basal level. Normalization of constitutive nitric oxide synthase activity in the presence of prostaglandin E1 was associated with a significant reduction of superoxide and peroxynitrite production and subsequent reduction of ischemia/reperfusion injury. At 2 h of reperfusion, vasoconstriction associated with ischemia/reperfusion injury was eliminated, and edema was significantly mollified but still apparent. Prostaglandin E1 treatment does not directly inhibit constitutive nitric oxide synthase, like the inhibitor N(omega)-monomethyl-L-arginine. Some phenomenon associated with ischemia turns on endothelial constitutive nitric oxide synthase to start transforming L-arginine and oxygen into nitric oxide, but prostaglandin E1 seems to inhibit this phenomenon. Thus, essential local L-arginine pools are not depleted, and normal basal levels of essential nitric oxide are maintained, whereas cytotoxic superoxide and peroxynitrite production by L-arginine-deficient constitutive nitric oxide synthase is prevented.
Assuntos
Alprostadil/uso terapêutico , Membro Posterior/irrigação sanguínea , Isquemia/tratamento farmacológico , Óxido Nítrico/biossíntese , Traumatismo por Reperfusão/prevenção & controle , Superóxidos/metabolismo , Acetilcolina/farmacologia , Alprostadil/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos , Masculino , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Nitratos/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Coelhos , Traumatismo por Reperfusão/tratamento farmacológico , Vasoconstrição/efeitos dos fármacosRESUMO
This study investigated the effect of a multivitamin preparation administered before ischemia or before reperfusion, on ischemia-reperfusion (I/R) injury of skeletal muscle. An in vivo hindlimb skeletal muscle I/R model (2.5 h/2 h) was carried out on adult New Zealand white rabbits. Animals used as I/R models were treated with a multivitamin preparation (0.4 ml/kg bw i.v. bolus), containing alpha-tocopherol, ascorbic acid, retinol, vitamin B complex, 30 min before starting ischemia (group MV(isc)) or 5 min before reperfusion (group MV(rep)) and compared to animals with I/R without treatment (group IR) and sham operated animals (group SHAM). Interstitial edema (muscle interfiber area, %MIFA) and changes in microvessel size (microvessel cross sectional area, MVCSA, microm(2)) were measured. Plasma malondialdehyde concentrations (MDA-TBA, nmol/ml) served as a measure of lipid peroxidation. After 2h of reperfusion, ischemia-reperfusion developed a significant microvascular constriction and an interstitial edema (IR, vs SHAM;P<< 0.01), but administration of antioxidative vitamins before the onset of ischemia reduced microvascular constriction and edema formation (P<< 0.05 vs IR group). In a similar manner, administration of vitamins before ischemia lowered plasma MDA-TBA levels as compared to the untreated group during reperfusion (p<< 0. 05). In animals treated with vitamins before reperfusion, the biochemical and morphological results showed no differences as compared to the untreated group. Antioxidative treatment with a multivitamin preparation exerted a beneficial effect on I/R injury of skeletal muscle when the aforementioned vitamins were administered before ischemia but not before the onset of reperfusion.
Assuntos
Músculo Esquelético/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Vitaminas/uso terapêutico , Animais , Edema/prevenção & controle , Isquemia/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/sangue , Músculo Esquelético/ultraestrutura , Coelhos , Traumatismo por Reperfusão/patologia , Vasoconstrição/efeitos dos fármacos , Vitaminas/administração & dosagemRESUMO
BACKGROUND: Endoscopic thoracic sympathicotomy of T2 to T4 (ETS 2-4) has evolved into an effective treatment for severe hyperhidrosis of the upper limb. Complications such as bleeding or Horner's syndrome are rare, but side effects such as compensatory and gustatory sweating occur in 30-50% of patients. Following the Lin-Telaranta classification, we aimed to reduce these side-effects by clipping T4 solely [endoscopic thoracic sympathetic block (ESB 4)]. We present our experience and clinical results using this method, with emphasis on patients' quality of life. METHODS: A total of 176 procedures (91 patients) were carried out in the ETS 2-4 group and 103 procedures (53 patients) in the ESB 4 group: 60.4 and 43.4% had palmar hyperhidrosis, 8.8 and 5.7% had isolated axillary, and 30.8 and 50.9% had combined manifestations, respectively. Follow-up was 22.1 months (obtained from 79.1% of patients) for the ETS 2-4 group and 7.5 months for the ESB 4 group (obtained from 88.7%). RESULTS: The success rate was similar for both groups: 87.9 and 64.5% had completely dry limbs, 9.9 and 35.5% ( p < 0.0002) were nearly dry, and 2.1 and 0% remained wet. (ETS 2-4 vs ESB 4). Although the armpits remained slightly humid in more patients in the ESB 4 group, 100% stated full satisfaction. Complications did not differ significantly. However, compensatory sweating (55.6 vs 8.5%, p = 0.0002) and gustatory sweating (33.3 vs 2.1%, p = 0.0019) were markedly reduced (ETS 2-4 vs ESB 4). Quality of life was assessed by a hyperhidrosis index, which significantly improved in most patients. CONCLUSIONS: ETS 2-4 and ESB 4 have similar success rates in the treatment of upper limb hyperhidrosis. The major side effects of compensatory and gustatory sweating were effectively reduced by the limited method of clipping T4, and patients' satisfaction and improvement in quality of life were remarkable.
Assuntos
Braço/inervação , Hiperidrose/cirurgia , Simpatectomia/métodos , Toracoscopia/métodos , Adulto , Axila , Feminino , Mãos , Humanos , Masculino , Satisfação do Paciente , Complicações Pós-Operatórias/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Instrumentos Cirúrgicos , Sudorese Gustativa/cirurgia , Cirurgia Torácica VídeoassistidaRESUMO
Delivery of DNA mixed with a degradable matrix carrier was supposed to improve transgene expression. Using a rabbit hind-limb ischemia model, we tested the angiogenic potency of plasmid encoding human vascular endothelial growth factor (pSG5-VEGF165) entrapped in fibrin sealant. Animals were injected intramuscularly with 500 microg of pSG5-VEGF165 or control plasmid, dissolved in saline (PBS) or fibrin glue. After 14 days, presence of delivered constructs and expression of transgene was confirmed in injected muscles of all animals. There were no significant differences in the levels of human VEGF mRNA and protein between VEGF-PBS and VEGF-fibrin groups (Mann-Whitney test). Accordingly, pSG5-VEGF165 regardless of the way of delivery, induced similar increases in capillary density within treated muscles (ANOVA). Control plasmid did not show any effects. In conclusion, injection of pSG5-VEGF165 into ischemic adductor muscle leads to synthesis of human VEGF and increases the number of capillaries. Fibrin carrier does not influence its angiogenic potential.
Assuntos
Fatores de Crescimento Endotelial/administração & dosagem , Fatores de Crescimento Endotelial/genética , Adesivo Tecidual de Fibrina/administração & dosagem , Expressão Gênica , Terapia Genética , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/genética , Isquemia/terapia , Linfocinas/administração & dosagem , Linfocinas/genética , Músculo Esquelético/irrigação sanguínea , Neovascularização Fisiológica/genética , Animais , Fatores de Crescimento Endotelial/imunologia , Feminino , Adesivo Tecidual de Fibrina/imunologia , Expressão Gênica/genética , Membro Posterior , Imunidade/efeitos dos fármacos , Imunidade/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Linfocinas/imunologia , Masculino , Modelos Animais , Neovascularização Fisiológica/fisiologia , Plasmídeos/administração & dosagem , Plasmídeos/genética , Plasmídeos/imunologia , Coelhos , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
The present study was undertaken to investigate whether the number of myelinated fibers in a sensory nerve used as an autograft influences the result of nerve fiber regeneration in the graft. In 30 rabbits, the left saphenous nerve was used as an autograft. It was coapted to the motor branch to the rectus femoris muscle. Biopsies from both ends of the graft were taken. Animals were separated into four investigation groups, which were reexamined 3, 6, 9 and 12 months after the grafting procedure. Biopsies for histological and morphometric examination were again taken from the proximal and the distal part of the grafts. Thus, the number of myelinated nerve fibers in the different specimens could be obtained by computer-assisted image analysis. At the proximal end of the original saphenous nerve, the number of fibers varied between 1032 and 3100 (mean 2145). Corresponding data obtained from the distal end ranged from 1044 to 3084 myelinated nerve fibers (mean 1724). Fiber numbers in the proximal and distal parts of the grafts before and after regeneration were correlated to each other. In the whole population of specimens (correlation coefficient +/-0) as well as in the experimental subgroups, the quantitative success of neurotization in the grafts did not depend to a high degree upon the fiber numbers in the original saphenous nerve. The correlation coefficient for the proximal part of the graft exceeded 0.5 to only three and twelve months after grafting, but did not reach a level of statistical significance. In the distal part of the graft, the coefficient for a linear correlation was always less than 0.45.
Assuntos
Regeneração Nervosa/fisiologia , Transferência de Nervo/métodos , Nervos Periféricos/transplante , Animais , Membro Posterior/inervação , Microcirurgia/métodos , Músculos/inervação , Fibras Nervosas Mielinizadas/patologia , Nervos Periféricos/patologia , CoelhosRESUMO
In order to determine the value of a reconstructive procedure in the peripheral nerve, experimental studies often evaluate the number and the diameter of myelinated nerve fibers as a parameter for the quality of regeneration. This study addresses the correlation between the number of fibers in a peripheral motor nerve after microsurgical reconstruction and the functional result, expressed as the force of the reinnervated muscle. In a total number of 24 sheep, the motor branch to the rectus femoris muscle was severed. The muscle was reinnervated either by direct neurorrhaphy or by nerve grafting, performed in three different ways (free grafting to the ipsilateral muscle, free grafting to the contralateral muscle, vascularized grafting to the ipsilateral muscle). In the final experiments, the muscle force in the reinnervated muscle was determined by supramaximal electrical stimulation. Number and diameter of myelinated nerve fibers were evaluated by computer-assisted morphometric analysis. Regression analysis of morphometric data and the muscle forces was calculated. No correlation was found between fiber numbers in the nerve graft and the maximal force. However, a positive correlation between the number of myelinated fibers in the motor branch distal to the site of coaptation and the functional result was observed in some cases. The diameter of myelinated fibers had no influence on the functional outcome.
Assuntos
Microcirurgia/métodos , Neurônios Motores/fisiologia , Regeneração Nervosa/fisiologia , Transferência de Nervo/métodos , Nervos Periféricos/transplante , Animais , Lateralidade Funcional/fisiologia , Neurônios Motores/patologia , Músculo Esquelético/inervação , Fibras Nervosas Mielinizadas/patologia , Fibras Nervosas Mielinizadas/fisiologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , OvinosRESUMO
The technique of laser tissue welding with a low-output CO2 laser has become popular due to the minimal amount of nerve tissue damage caused. The purpose of this study was to ascertain the efficacy of nerve coaptation by laser tissue welding in comparison to micro-sutures. In a first series of 15 rats, peripheral nerves were transsected. 24 nerves were coaptated by laser welding (LW) with different parameters in order to evaluate the optimal laser settings. For comparison, six nerves were coapted (NS) with four 10/0 nylon sutures. Finally, the nerves were removed and the tensile strength of the different coaptations determined. The best results of the laser welds were obtained at laser settings of 40 to 60 mW in the continuous mode resulting in a tensile strength of 9.5 +/- 2.2 g. The tensile strength was 39.3 +/- 7.3 g for the sutured coaptation. In a second series, one sciatic nerve was coapted in thirteen rats by laser welding (LW) (60 mW, cont. mode) and in eleven rats using four 10/0 nylon sutures (NS). After six months, the Sciatic Function Index (SFI) was evaluated and the nerves were harvested for histological examination of transverse and longitudinal sections. All animals showed good regeneration and none of the 24 nerve coaptations showed dehiscence. The SFI was for the NS-group -94 +/- 23 and for the LW-group -77 +/- 20. The mean number of myelinated nerve fibres (NS 10,170 +/- 2512 vs. LW 11,902 +/- 1649) and the fibre diameter (NS 4.30 +/- 0.14 um vs. LW 4.02 +/- 0.59 microns) of the nerves distal to the coaptation were similar in both groups and showed no statistical difference. We conclude that nerve coaptation by CO2-laser welds are as successful as the 10/0 nylon sutures in the animal model. Improvements of welding techniques may in the future reduce nerve damage even further and so yield even better functional results.
Assuntos
Terapia a Laser/métodos , Neurocirurgia/métodos , Animais , Dióxido de Carbono , Modelos Animais de Doenças , Microcirurgia/métodos , Neurocirurgia/instrumentação , Ratos , Ratos Sprague-Dawley , Resistência à TraçãoRESUMO
BACKGROUND: The present study was done in order to clarify whether the sometimes poor results after the use of long grafts for nerve reconstruction are due to the length of the graft itself or due to the concomitant big defect in the soft tissues necessitating the use of long grafts. METHODS: In 22 rabbits, the saphenous nerve was used as a nerve graft. Animals were separated into three groups with different lengths of the grafts, namely 3 cm (group 1), 5 cm (group 2) and 7 cm (group 3). In one hindlimb, the proximal end of the graft was coapted to the motor nerve branch of vastus medialis. In a second step, the distal end of the graft was coapted to the nerve branch of rectus femoris. After a total period of 15 months the maximum tetanic tensions in the reinnervated rectus femoris and in the contralateral untreated muscle were determined. Biopsies of the graft and the motor branch distal to the graft were taken in order to count the number of regenerated myelinated nerve fibers. RESULTS: The average maximum tetanic tension in the rectus femoris muscle reinnervated by the 3 cm long graft was 27.2 N; in group 2 the force amounted to 20.4 N. In group 3, the maximum force was 17.6 N, which meant an average loss of 29% compared to the contralateral untreated muscle. In accordance with the functional results, the mean number of regenerated myelinated fibres in the rectus femoris motor branch decreased from 1683 in group 1 to 1136 in group 3. CONCLUSIONS: The results show that the length of the graft influences the results after nerve grafting to a certain extent, but a combination of other factors like concomitant soft tissue injury and destroyed target organs may also be responsible for some of the poor results after the clinical use of long nerve grafts.
Assuntos
Microcirurgia/métodos , Regeneração Nervosa/fisiologia , Nervos Periféricos/transplante , Transmissão Sináptica/fisiologia , Animais , Membro Posterior/inervação , Contração Isométrica/fisiologia , Fibras Nervosas Mielinizadas/patologia , Nervos Periféricos/patologia , CoelhosRESUMO
AIM: The aim of this paper was to report our preliminary experience in outcome, safety and mid-term results in the treatment of thoracoabdominal aortic aneurysms (TAAA) with a novel multibranchstentgraft (E-xtra DESIGN ENGINEERING, JOTEC, Germany). METHODS: Eight patients (mean age 66 years, 2 female) with TAAA (Crawford type I: 2 cases, type III: 3 cases, type IV: 3 cases), mean aneurysm diameter 61 mm, growth over 5 mm per year were treated. Implantation was performed under general anesthesia and surgical exposition of the common femoral artery. Brachial access was percutaneous in 5/8 patients. Balloon-expandable (Advanta V12) bridging stent-grafts were employed and lined with self-expanding nitinol stents. All patients except type IV TAAA received a spinal drainage catheter. RESULTS: The device was successfully deployed in 8/8 patients. 29/32 visceral branches were engaged. One stenosed celiac trunk was left untreated without further consequences, two renal arteries which could not be cannulated were revascularized with iliorenal bypass. One patient needed surgical revision of groin hematoma, one patient suffered from permanent protopathic sensory deficit. No renal complications occurred. Since the primary implantation was deliberately kept short and amount of contrast agent was minimised, four patients needed a secondary percutaneous procedure (Palmaz stent implantation for type I endoleak, re-PTA or additional bridging stent-graft implantation for type III endoleak). The assisted primary success rate was 8/8. Mean follow-up was 18 months. Success was stable in 7/8 patients, one patient shows type V endoleak with 5mm sac expansion. No mortality or complication occurred during follow-up. CONCLUSION: The JOTEC E-xtra DESIGN ENGINEERING multibranch stent-graft is a promising new candidate for endovascular TAAA treatment with sufficient safety and efficacy. Its short delivery time suggests its use in patients with rapid aneurysm growth or high anxiety.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Desenho de Prótese , Stents , Idoso , Ligas , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/fisiopatologia , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
BACKGROUND: SDHD germ-line mutations predispose to pheochromocytoma (PCC) and paraganglioma (PGL). MATERIAL AND METHODS: The incidence and types of SDHD germ-line mutations are determined in 70 patients with apparently sporadic adrenal and extra-adrenal PCC. RESULTS: SDHD sequence variants were identified in the germ line of five patients. Two of three novel mutations were in exon 1 and one in exon 3. One patient had a codon 1 missense mutation (M1K) and a concurrent 3-bp deletion in intron 1. Three of 10 family members had only the exon 1 mutation, whereas one had only the intron 1 mutation. The other exon 1 mutation resulted from a deletion of nucleotides 28-33 with a 12-bp in-frame insertion (c.28_33 del ins TAGGAGGCCCTA). This mutation generated a premature stop codon after codon 9 and was also present in the brother who had a bilateral PCC. The third patient with a carotid body tumour, with an abdominal and a thoracic PGL had a 12-bp deletion in exon 3 (codons 91-94, c.271_282 del). Her father carried the same mutation and had bilateral carotid body tumours. Two further patients, one with six PGL, carried a previously described H50R polymorphism, whose disease-specific relevance is currently unclear. The three patients with bona fide SDHD mutations were younger than those without germ-line mutations. CONCLUSION: SDHD germ-line mutations are rare in patients with PCC, but their identification is an important prerequisite for the clinical care and appropriate management of affected individuals and their families.