Operation time and clinical outcomes for open infrarenal abdominal aortic aneurysms to remain stable in the endovascular era.

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. 225 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.

The Femoral Vein as a Long-Term Aorto-Iliac Graft for Aortic Infection and Aortitis.

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.

Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment.

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.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) is Associated with Symptomatic Carotid Atherosclerosis and Drives Pro-inflammatory State In Vitro.

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.

The Influence of Simvastatin on NGAL, Matrix Metalloproteinases and Their Tissue Inhibitors in Human Intraluminal Thrombus and Abdominal Aortic Aneurysm Tissue.

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.

Endovascular repair of thoracoabdominal aortic aneurysms with a novel multibranch stent-graft design: preliminary experience.

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.

Long-term outcomes after endothoracic sympathetic block at the T4 ganglion for upper limb hyperhidrosis.

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.

Decreased tissue levels of cyclophilin A, a cyclosporine a target and phospho-ERK1/2 in simvastatin patients with abdominal aortic aneurysm.

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.

Simvastatin decreases free radicals formation in the human abdominal aortic aneurysm wall via NF-κB.

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.

New epidemiological aspects of patients with severe hyperhidrosis presenting for sympathetic surgery.

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.

Novel SDHD germ-line mutations in pheochromocytoma patients.

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.

Improved quality of life after sympathetic block for upper limb hyperhidrosis.

BACKGROUND: The aim of the study was to assess two disease-specific quality of life (QoL) instruments after limited endoscopic thoracic sympathetic block (TS) at T4 for upper limb hyperhidrosis. METHODS: : Between 2001 and 2005, 112 patients underwent 223 TS procedures in a prospective study. Some 103 patients (92.0 per cent) had palmar, 87 (77.7 per cent) had axillary and 75 (67.0 per cent) had combined hyperhidrosis. QoL questionnaires devised by Keller et al. and Milanez de Campos et al. were employed before and after treatment. Mean(s.d.) follow-up was 21.9(10.1) months. RESULTS: A total of 106 patients (94.6 per cent) were evaluated. All patients with palmar hyperhidrosis were completely or almost dry after surgery. Side-effects of compensatory sweating and gustatory sweating were observed in 17.0 and 28.3 per cent of patients respectively. QoL improved after TS in 100 per cent (Keller) and 97.3 per cent (Milanez de Campos) of patients illustrated by ameliorated scores of 78.7 and 67.8 per cent, respectively (both P < 0.001). Both questionnaires showed that compensatory sweating resulted in reduced postoperative QoL (P = 0.011, Keller; P = 0.032, Milanez de Campos). CONCLUSION: Endoscopic sympathetic block at T4 leads to improved QoL. Both current questionnaires fulfilled validation criteria for disease-specific QoL instruments in upper limb hyperhidrosis.

Significant weight loss after laparoscopic Nissen fundoplication.

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.

Over-expression of anti-CD75 reactive proteins on distal and collecting renal tubular epithelial cells in calcium-oxalate stone-forming kidneys in Egypt.

OBJECTIVE: To assess the nature, distribution and expression pattern of CD75, a neuraminidase-sensitive lymphocyte cell surface differentiation antigen, in calcium oxalate (CaOx) stone disease, as cell-surface sialic acid might be involved CaOx crystal binding, and lectin-binding assays suggest that sialic acid in the alpha2,6 position is upregulated in stone-forming kidneys. MATERIALS AND METHODS: Human CaOx stone-forming and normal kidneys (13 each) and primary kidney epithelial cells (CAKI-1, three samples) were analysed. The protein pattern, distribution and expression of CD75 were analysed using Western blotting, immunohistology and semi-quantitative confocal laser scanning microscopy (cLSM). Production was investigated by alpha2,6-sialyltransferase specific reverse transcription-polymerase chain reaction. RESULTS: Western blotting showed one strong band at approximately 43 kDa that reacted with anti-CD75 when renal epithelial and CAKI-1 tumour cell extracts were analysed. However, in renal tissue extracts of CaOx stone formers there were additional bands at 120 and 205 kDa. Image processing after cLSM showed that anti-CD75 reactivity was significantly greater on E-cadherin-positive distal and collecting tubular cells from CaOx stone-forming kidneys, at a mean (sd) intensity of 87 (7), than on those from normal kidneys, at 41 (5) (P = 0.005). CONCLUSION: CD75 expression in human kidney was primarily on the luminal surface of distal tubules and collecting ducts. Whether increased epithelial CD75 expression in CaOx stone disease is a cause or result of the disease remains to be clarified.

Positive effect of treatment with synthetic steroid hormone tibolon on intimal hyperplasia and restenosis after experimental endothelial injury of rabbit carotid artery.

BACKGROUND: Arterial intimal hyperplasia and following restenosis may be inhibited by estrogens. We investigated the effect of a synthetic steroid hormone, Tibolon: (a) on intima hyperplasia and restenosis in vivo, and (b) on production of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), endothelial cell proliferation and apoptosis in vitro. METHODS: Influence of Tibolon treatment (0.1 mg/kg body weight, during 3 days before and 3 weeks after the operation as a drinking solution once daily) on neointimal formation (measured by morphometry) and arterial wall damage (by qualitative histology) were investigated in vivo using an animal model of balloon injury of carotid artery. In human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1), the effect of Tibolon (0.1 microg/ml) on eNOS and VEGF was assessed by ELISA. Cell proliferation was induced by VEGF(165) and measured by BrdU incorporation assay, cell apoptosis was detected colorimetrically measuring DNA fragmentation. RESULTS: Balloon injury resulted in neointima formation and prominent damage of the carotid artery wall. Treatment with Tibolon increased luminal area, decreased intimal area and intima to media ratio, and promoted better reparation of damaged vessel wall. In vitro, Tibolon treatment did not influence the expression of eNOS protein in HUVEC as well as cell proliferation rate but reduced apoptosis of endothelial cells by about 40%. Additionally, this treatment suppressed basal and IL-1beta-stimulated synthesis of VEGF in HMEC-1. CONCLUSIONS: Tibolon treatment suppressed neointimal formation and promoted better reparation of damaged vessel wall in carotid artery after balloon injury. This positive effect seems to be associated with improved endothelial cell survival resulting possibly in increased NO production. It might be also related to the decrease of VEGF generation.

Limited endoscopic thoracic sympathetic block for hyperhidrosis of the upper limb: reduction of compensatory sweating by clipping T4.

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.

Development of 'no-reflow' phenomenon in ischemia/reperfusion injury: failure of active vasomotility and not simply passive vasoconstriction.

BACKGROUND/AIM: Local blood flow failure (no-reflow phenomenon) during ischemia/reperfusion (I/R) injury may be mediated by interstitial edema formation (passive vasoconstriction) and/or microvascular spasm (active vasoconstriction). The development of the no-reflow phenomenon in the rabbit hind limb I/R model and the influence of treatment with L-arginine and/or antioxidative vitamins were investigated. METHODS: Untreated rabbits were compared with those treated with L-arginine (4 mg/kg/min) or antioxidative vitamins (0.4 ml/kg) alone or in combination during hind limb I/R (2.5/2 h). Interstitial edema formation and microvessel diameter alterations were measured morphometrically. Capillary blood perfusion was measured continuously with laser Doppler flowmetry. RESULTS: I/R injury was expressed by interstitial edema formation (interstitial space increase by 80%), microvascular constriction (microvessel cross-sectional area decrease by 30%), and development of no-reflow phenomenon (blood flow reduction by 60%). Treatment with antioxidative vitamins alone or L-arginine alone reduced interstitial edema by 22 and 31%, consequently, while combined L-arginine/antioxidative vitamin treatment showed a more pronounced edema reduction by 40%. Treatment with only antioxidative vitamins failed to influence the development of no-reflow, although interstitial edema formation was reduced. L-Arginine treatment alone or in combination with antioxidative vitamins prevented microvascular constriction and preserved blood flow after reperfusion without development of no-reflow despite still apparent interstitial edema. CONCLUSIONS: Affections of active vasomotility and not merely passive changes of external pressure (i.e., interstitial edema formation) should be considered important in the development of microvascular constriction during 'no-reflow' phenomenon.

Delivery of high dose VEGF plasmid using fibrin carrier does not influence its angiogenic potency.

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.

Efficacy and safety of thoracoscopic sympathicotomy for hyperhidrosis of the upper limb. Results of 734 sympathicotomies.

BACKGROUND: Thoracoscopic sympathicotomy (TS) evolved as treatment of choice in severe hyperhidrosis. The aim of this study was to assess the role of video-assistance in TS (VATS) versus conventional TS (CTS) for primary hyperhidrosis of the upper limb with regard to safety, side-effects and long-term outcome. METHODS: 734 TS were performed from below T1 to T4 in 406 patients. In the CTS and in the VATS group 558 and 176 procedures were performed, respectively. Follow-up was completed in 82% of all patients after a median observation period of 16 years. RESULTS: Dry limbs were immediately achieved in 92% (CTS) and 97% (VATS, p = 0.98). Only one patient (CTS) underwent conversion due to bleeding. In the CTS group Horner's syndrome occurred in 2.2% and rhinitis in 9.9% of procedures. No patient of the VATS group experienced Horner's syndrome (p = 0.025), 3 patients developed rhinitis (p = 0.11). At follow-up compensatory sweating was observed in 67.6% vs. 55.6% (p = 0.051) and gustatory sweating in 50.4% and 33.3% (p = 0.01). There were 5 failures or recurrences (1.9%) in the CTS group and 2 (2.8; p > 0.05) in the VATS group at reevaluation. Overall 6.5% (CTS) and 5.6% (VATS) of patients regret the operation (p = 0.7). CONCLUSIONS: We observed a significant decrease of the incidence of complete or incomplete Horner's syndrome and gustatory sweating when the procedure was guided by video-imaging while success rate was similar when compared with CTS.

Prostaglandin E1 reduces ischemia/reperfusion injury by normalizing nitric oxide and superoxide release.

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.