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1.
J Vasc Surg ; 79(5): 1179-1186.e1, 2024 May.
Article in English | MEDLINE | ID: mdl-38145634

ABSTRACT

OBJECTIVE: Only 5% of patients with popliteal artery aneurysms (PAAs) are female. Evidence on PAA treatment and outcomes in women is therefore scarce. The POPART Registry provides one of Europe's largest data collections regarding PAA treatment. Data on clinical presentation, aneurysm morphology, and perioperative outcomes after open surgical PAA repair in women will be presented. METHODS: POPART is a multicenter, noninterventional registry for open and endovascular PAA repair, with 42 participating centers in Germany and Luxembourg. All patients aged >18 years who have been treated for PAA since 2010 are eligible for study inclusion. Data collection is based on an online electronic case report form. RESULTS: Of the 1236 PAAs, 58 (4.8%) were in women. There were no significant differences in age or cardiopulmonary comorbidities. However, female patients had a lower prevalence of contralateral PAAs and abdominal aortic aneurysms (P < .05). PAAs in women were more likely to be symptomatic before surgery (65.5% vs 49.4%; P = .017), with 19% of women presenting with acute limb ischemia (vs 11%; P = .067). Women had smaller aneurysm diameters than men (22.5 mm vs 27 mm; P = .004) and became symptomatic at smaller diameters (20 mm vs 26 mm; P = .002). Only 8.6% of women and 11.6% of men underwent endovascular aneurysm repair (P > .05); therefore, the perioperative outcome analysis focused on open surgical repair. In total, 23.5% of women and 16.9% of men developed perioperative complications (P > .05). There were no differences in major cardiovascular events (P > .05), but women showed a higher incidence of impaired wound healing (15.7% vs 7.2%; P = .05) and major amputation (5.9% vs 1.1%; P = .027). Female sex was significantly associated with the need for nonvascular reinterventions within 30 days after surgery (odds ratio: 2.48, 95% confidence interval: 1.26-4.88), whereas no significant differences in the odds for vascular reinterventions were observed (odds ratio: 1.98, 95% confidence interval: 0.68-5.77). In the multiple logistic regression model, female sex, symptomatic PAAs, poor quality of outflow vessels, and graft material other than vein graft were independently associated with perioperative reinterventions. CONCLUSIONS: Women have smaller PAAs, are more likely to be symptomatic before treatment, and are more often affected by nonvascular reinterventions in the perioperative course. As our understanding of aneurysmatic diseases in women continues to expand, sex-specific treatment strategies and screening options for women in well-selected cohorts with modified screening protocols should be continuously re-evaluated.


Subject(s)
Aortic Aneurysm, Abdominal , Arterial Occlusive Diseases , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Popliteal Artery Aneurysm , Male , Humans , Female , Aortic Aneurysm, Abdominal/surgery , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Blood Vessel Prosthesis Implantation/adverse effects , Arterial Occlusive Diseases/surgery , Popliteal Artery/diagnostic imaging , Popliteal Artery/surgery , Treatment Outcome , Retrospective Studies , Risk Factors
2.
J Enzyme Inhib Med Chem ; 28(5): 1061-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-22994585

ABSTRACT

Adenylyl cyclases, comprise of a large family of enzymes that catalyze synthesis of the cyclic AMP from ATP. The aim of our study was to determine the effect of monovalent ions on both basal, stimulated adenylate cyclase EC 4.6.1.1 (AC) activity and C unit of AC and on GTPase active G-protein in the synaptic membranes of rat brain cortex. The effect of ion concentration from 30 to 200 mM (1 mM MgCl2) showed dose-dependent and significant inhibition of the basal AC activity, stimulated and unstimulated C unit activity. Stimulation of AC with 5 µM GTPγS in the presence of 50-200 mM of tested salts showed inhibitory effect on the AC activity. From our results it could be postulated that the investigated monovalent ions exert inhibitory effect on the AC complex activity by affecting the intermolecular interaction of the activated α subunit of G/F protein and the C unit of AC complex an inhibitory influence of tested monovalent ions on these molecular interaction.


Subject(s)
Adenylyl Cyclase Inhibitors , Brain/enzymology , Cerebral Cortex/enzymology , Enzyme Inhibitors/pharmacology , Magnesium Chloride/pharmacology , Adenylyl Cyclases/metabolism , Animals , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Enzyme Inhibitors/chemistry , Ions/chemistry , Ions/pharmacology , Magnesium Chloride/chemistry , Male , Rats , Rats, Wistar , Structure-Activity Relationship
3.
J Vasc Surg ; 53(1): 61-70, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20875716

ABSTRACT

PURPOSE: Carotid angioplasty and stenting (CAS) is increasingly being used as a treatment alternative to endarterectomy (CEA) for patients with significant carotid stenosis. However, diffusion-weighted imaging (DWI) has indicated that CAS is associated with a significantly higher burden of microemboli. This study evaluated the potential effect on intellectual functions of new DWI lesions after CEA or CAS. METHODS: This prospective study analyzed the neuropsychologic outcomes after revascularization in 24 CAS and 31 CEA patients with severe carotid stenosis compared with a control group of 27 healthy individuals. All patients underwent clinical examinations, magnetic resonance imaging scans, and a neuropsychologic test battery that assessed six major cognitive domains performed immediately before CEA or CAS, ≤ 72 hours after, and at 3 months. RESULTS: New DWI lesions were detected among 15 of 21 (71%) of the CAS patients immediately after treatment but in only 1 of the 28 CEA patients (4%; P < .01). As a group, patients with new DWI lesions showed a decline in their performance in the cognitive domains, attention, and visuoconstructive functions within 72 hours of carotid revascularization. Individually, however, in none of the cognitive domains did the decreases reach a clinically relevant threshold of z < -1.5. Moreover, the cognitive performance was not significantly different between patients with and without new DWI lesions 3 months after treatment. The cognitive performance was similar between CEA and CAS patients at all points. CONCLUSIONS: The findings support the assumption that new brain lesions, as detected with DWI after CAS or CEA, do not affect cognitive performance in a manner that is long-lasting or clinically relevant. Despite the higher embolic load detected by DWI, CAS is not associated with a greater cognitive decline than CEA.


Subject(s)
Carotid Stenosis/therapy , Aged , Aged, 80 and over , Angioplasty, Balloon , Attention , Cognition , Diffusion Magnetic Resonance Imaging , Endarterectomy, Carotid , Female , Humans , Learning , Magnetic Resonance Imaging , Male , Memory , Middle Aged , Neuropsychological Tests , Prospective Studies , Stents
4.
World J Urol ; 28(4): 537-42, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20401660

ABSTRACT

PURPOSE: During rejection, leukocytes are recruited from the peripheral circulation into the graft leading to the damage of endothelial cells, capillary perfusion failure and graft loss. Chemokines play a pivotal role in the recruitment of leukocytes to the endothelium. Viral macrophage inflammatory protein-II (vMIP-II), a human herpes virus-8 DNA-encoded protein, is a broad-spectrum chemokine antagonist. The aim of the study was to prove the beneficial activity of vMIP-II treatment on acute rat kidney allograft damage. METHODS: Heterotopic rat kidney transplantation was performed in the Fischer 344 to Lewis transplantation model and animals were treated with vMIP-II (2 x 15 microg or 100 microg/day) for 7 days. Rejection-induced damage was analyzed by histology, and microcirculatory changes within the graft were analyzed by in vivo microscopy. RESULTS: Viral macrophage inflammatory protein-II significantly improved acute glomerular damage and tubulointerstitial inflammation and lowered the extent of vascular and tubulointerstitial damage of the treated allografts. Functional microcirculation of peritubular capillaries was significantly improved in vivo, and the firm adherence of leukocytes was significantly reduced by vMIP-II treatment. CONCLUSIONS: The administration of the broad-spectrum antagonist vMIP-II improved acute renal allograft damage, mainly by a reduction in leukocyte recruitment with a subsequently improved renal cortical microcirculation in vivo.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Chemokines/pharmacology , Graft Rejection/drug therapy , Graft Rejection/immunology , Kidney Transplantation , Acute Disease , Animals , Cell Adhesion/drug effects , Cell Adhesion/immunology , Cell Movement/drug effects , Cell Movement/immunology , Graft Rejection/pathology , Kidney Glomerulus/immunology , Kidney Glomerulus/pathology , Leukocytes/cytology , Leukocytes/drug effects , Leukocytes/immunology , Male , Microcirculation/drug effects , Rats , Rats, Inbred F344 , Rats, Inbred Lew , Renal Circulation/drug effects , Transplantation, Homologous
5.
Basic Res Cardiol ; 104(6): 719-29, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19352584

ABSTRACT

During acute rejection of cardiac transplants endothelial cell-leukocyte interaction fueled by co-stimulatory molecules like CD40/CD154 may ultimately lead to graft loss. One key player in up-regulating the expression of such pro-inflammatory gene products is the interferon-gamma-dependent transcription factor STAT-1. Hence down-regulating interferon-gamma-stimulated pro-inflammatory gene expression in the graft endothelial cells by employing a decoy oligodeoxynucleotide (dODN) neutralising STAT-1 may protect the graft. To verify this hypothesis, heterotopic mouse heart transplantation was performed in the allogeneic B10.A(2R) to C57BL/6 and syngeneic C57BL/6 to C57BL/6 strain combination without immunosuppression. Graft vessels were pre-treated with STAT-1 dODN, mutant control ODN (10 muM each) or vehicle (Ringer solution). Cellular rejection (vascular and interstitial component) was graded histologically and CD40, ICAM-1, VCAM-1, MCP-1, E-selectin and RANTES expression in the graft monitored by real time PCR 24 h and 9 days post-transplantation. Nine days after transplantation both rejection scores were significantly diminished by 85 and 70%, respectively, in STAT-1 dODN-treated allografts as compared to mutant control ODN-treated allografts. According to immunohistochemistry analysis, this was accompanied by a reduced infiltration of monocyte/macrophages and T cells into the graft myocardium. In addition, pro-inflammatory gene expression was strongly impaired by more than 80% in STAT-1 dODN-treated allografts 24 h post-transplantation but not in mutant control ODN or vehicle-treated allografts. This inhibitory effect on pro-inflammatory gene expression was no longer detectable 9 days post-transplantation. Single periprocedural treatment with a STAT-1 dODN thus effectively reduces cellular rejection in mouse heart allografts. This effect is associated both with an early decline in pro-inflammatory gene expression and a later drop in mononuclear cell infiltration.


Subject(s)
Gene Expression/drug effects , Graft Rejection/prevention & control , Heart Transplantation , Oligonucleotides/pharmacology , STAT1 Transcription Factor/metabolism , Animals , Cell Adhesion Molecules/biosynthesis , Cell Adhesion Molecules/drug effects , Cell Adhesion Molecules/genetics , Down-Regulation , Gene Expression/genetics , Graft Rejection/genetics , Graft Rejection/pathology , Heart Transplantation/pathology , Immunohistochemistry , Inflammation/genetics , Inflammation/pathology , Mice , Mice, Inbred C57BL , Oligonucleotides/therapeutic use , Reverse Transcriptase Polymerase Chain Reaction
6.
Langenbecks Arch Surg ; 394(2): 357-62, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18509670

ABSTRACT

BACKGROUND AND AIMS: External support of vein grafts by fibrin glue possibly prevents overdistension, vascular remodeling, and neointimal hyperplasia. Previous animal models of neointimal hyperplasia showed conflicting results. Here, long-term effects of external fibrin glue support were studied in a new rat model of jugular vein to abdominal aorta transposition. MATERIALS AND METHODS AND METHODS: In male Wistar rats (250-300 g) right jugular vein (1.0-1.5 cm) was transposed to the infrarenal aorta. Fibrin glue (0.25 ml) covered the vein before releasing the vascular clamps (n = 6). Control vein grafts were exposed directly to blood pressure. After 16 weeks vein grafts were pressure-fixed for histology. Intima thickness, luminal and intimal area were measured by planimetry and elastic fibers demonstrated by Elastica van Giesson staining. RESULTS: Intimal thickness (74.04 +/- 6.7 microm vs 1245 +/- 187 microm, control vs fibrin treatment; p < 0.001), intimal area (2517.16 +/- 355 mm(2) vs 18424 +/- 4927 mm(2), control vs fibrin treatment; p < 0.05) and luminal area (2184.75 +/- 347 mm(2) vs 7231.85 +/- 1782 mm(2), control vs fibrin treatment; p < 0.05) were significantly increased, elastic fibers in the vessel wall were diminished and the vessel wall infiltrated by mononuclear cells in fibrin glue supported veins. CONCLUSION: External support of vein grafts by fibrin glue leads to aneurysmal degeneration and intimal hyperplasia, thereby possibly jeopardizing long-term graft patency.


Subject(s)
Aorta, Abdominal/surgery , Aortic Aneurysm, Abdominal/chemically induced , Fibrin Tissue Adhesive/adverse effects , Tunica Intima/drug effects , Tunica Intima/pathology , Veins/transplantation , Animals , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/pathology , Elastic Tissue/pathology , Graft Occlusion, Vascular/chemically induced , Graft Occlusion, Vascular/pathology , Hyperplasia , Male , Rats , Rats, Wistar , Veins/pathology
7.
J Allergy Clin Immunol ; 121(1): 158-165.e5, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17981315

ABSTRACT

BACKGROUND: Cytokines play a pivotal role in allergy development through activating signaling mechanisms, such as the Janus kinase/signal transducer and activator of transcription (STAT) pathway, which controls the expression of numerous proinflammatory genes. OBJECTIVE: In comparison with 2 different corticosteroids and a calcineurin inhibitor, the efficacy of a STAT1 decoy oligodeoxynucleotide (dODN)-containing ointment on hapten-induced contact hypersensitivity was examined in 3 different animal models. METHODS: After sensitization, the test compounds were administered before hapten challenge, after hapten challenge, or both to different sites of the animal skin. Subsequent erythema and edema formation was scored macroscopically, microscopically, or by a shift in ear weight. Biopsy specimens were taken and processed for histopathology, immunohistochemistry, and real-time PCR analyses. RESULTS: Treatment with the STAT1 dODN but not the corresponding control ODN markedly improved the clinical signs of inflammation in all 3 animal models in a dose-related manner. In guinea pig skin this was accompanied by a distinct decrease in leukocyte infiltration into the dermis after 24 hours. In addition, expression of CD40, IFN-gamma, IL-1beta, IL-8, IL-12, and TNF-alpha was strongly attenuated. The dODN was equally effective in the domestic pig model when administered therapeutically, and its preventive effect in the mouse model lasted for more than 48 hours. CONCLUSIONS: Altogether, treatment with the dODN proved to be at least as effective as treatment with the reference compounds.


Subject(s)
Dermatitis, Contact/drug therapy , Ointments/administration & dosage , Ointments/therapeutic use , Oligodeoxyribonucleotides/therapeutic use , STAT1 Transcription Factor/antagonists & inhibitors , Animals , Aorta/cytology , Cells, Cultured , Cytokines/metabolism , Dermatitis, Contact/etiology , Dermatitis, Contact/immunology , Disease Models, Animal , Endothelium, Vascular/cytology , Female , Guinea Pigs , Hypersensitivity, Delayed/drug therapy , Hypersensitivity, Delayed/etiology , Hypersensitivity, Delayed/immunology , Inflammation/drug therapy , Inflammation/immunology , Male , Mice , Mice, Inbred BALB C , Ointments/pharmacokinetics , Oligodeoxyribonucleotides/administration & dosage , Oligodeoxyribonucleotides/genetics , Oligodeoxyribonucleotides/pharmacokinetics , STAT1 Transcription Factor/genetics , Skin/immunology , Skin/pathology , Swine , Treatment Outcome
8.
Int J Vasc Med ; 2018: 7205903, 2018.
Article in English | MEDLINE | ID: mdl-30186634

ABSTRACT

OBJECTIVE: Carotid artery stenosis in patients undergoing open-heart surgery may increase risk and deteriorate outcome. The aim of the study was the analysis of risks and outcome after simultaneous carotid and cardiac surgery. METHODS: We retrospectively reviewed the medical records of 100 consecutive patients who underwent simultaneous carotid surgery and open-heart surgery during a 5-year period (from 2006 to 2010). Seventy patients were male and 30 female; the mean age was 70.9±7.9 years (median: 71.8 years). Seventy-three patients underwent coronary bypass grafting (CABG), 18 patients combined CABG and valve procedures, 7 patients CABG combined with other procedures, and 3 patients isolated valve surgery. More than half of patients had had bilateral carotid artery pathology (n=51) including contralateral carotid artery occlusion in 12 cases. RESULTS: Carotid artery patch plasty was performed in 71 patients and eversion technique in 29. In 75 cases an intraluminal shunt was used. Thirty-day mortality rate was 7% due to cardiac complications (n=5), metabolic disturbance (n=1), and diffuse cerebral embolism (n=1). There were no carotid surgery-related deaths. Postoperatively, transient cerebral ischemia occurred in one patient and stroke with mild permanent neurological deficit (Rankin level 2) in another patient. CONCLUSION: Simultaneous carotid artery surgery and open-heart surgery have low risk. The underlying cardiac disease influences outcome.

9.
Transplantation ; 102(10): 1666-1673, 2018 10.
Article in English | MEDLINE | ID: mdl-29994982

ABSTRACT

BACKGROUND: The small bowel is prone to ischemic injury during transport before transplantation, an injury that endangers the recipient patient. The small-bowel mucosal microcirculation in particular appears to be highly sensitive to injury. Current preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution provide some protection to the graft. However, these were developed decades ago and do not address several critical processes, such as hypoxia-induced membrane pores and free radical-mediated hypothermic injury. METHODS: To protect the graft from cold ischemic injury, we implemented a modified HTK solution here, including glycine, alanine, and iron chelators in a heterotopic, syngeneic small-bowel transplantation model of the rat. The effects of the modified solution and its major components were compared against the conventional HTK solution using intravital microscopy in the early reperfusion period. RESULTS: The amino acid glycine, added to HTK solution, slightly improved mucosal perfusion. Both, the modified base solution (without iron chelators) and iron chelators increased functional capillary density of the mucosa during the early reperfusion period. The complete modified solution (with glycine, alanine, and iron chelators) significantly increased the perfusion index, functional capillary density of the mucosa, and red blood cell velocity in the grafts after reperfusion in comparison with the grafts preserved with HTK. CONCLUSIONS: The modified preservation solution improved the microcirculation of the transplants and needs detailed evaluation in further models of small-bowel transplantation.


Subject(s)
Cold Ischemia/adverse effects , Intestine, Small/transplantation , Organ Preservation Solutions/therapeutic use , Organ Preservation/methods , Reperfusion Injury/prevention & control , Alanine/pharmacology , Alanine/therapeutic use , Animals , Cell Hypoxia/drug effects , Disease Models, Animal , Glucose/chemistry , Glucose/pharmacology , Glucose/therapeutic use , Glycine/pharmacology , Glycine/therapeutic use , Humans , Intestine, Small/blood supply , Intestine, Small/drug effects , Intestine, Small/pathology , Iron Chelating Agents/pharmacology , Iron Chelating Agents/therapeutic use , Male , Mannitol/chemistry , Mannitol/pharmacology , Mannitol/therapeutic use , Microcirculation/drug effects , Organ Preservation Solutions/chemistry , Organ Preservation Solutions/pharmacology , Perfusion/methods , Potassium Chloride/chemistry , Potassium Chloride/pharmacology , Potassium Chloride/therapeutic use , Procaine/chemistry , Procaine/pharmacology , Procaine/therapeutic use , Rats , Rats, Inbred Lew , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Transplants/blood supply , Transplants/drug effects , Transplants/pathology
10.
J Invest Surg ; 31(2): 96-106, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28340319

ABSTRACT

PURPOSE: Lung ischemia-reperfusion injury (LIRI) can complicate lung transplantation or cardiac surgery with cardiopulmonary bypass, increasing morbidity and mortality. In LIRI, pro-inflammatory cytokines are activated, reactive oxygen species are generated and nuclear factor-κB (NF-κB) is up-regulated, altering lung mechanics. We tested the effect of the flavonoid apigenin on a rodent model of LIRI. METHODS: Thirty-seven Wistar rats were subjected to LIRI with or without a single or double dose of apigenin. Induction of LIRI involved sternotomy and clamping of either the left lung hilum or the pulmonary artery alone for 30 min, followed by 60 min of reperfusion. Control groups consisted of LIRI plus NaCl, a sham group and a baseline group. At the end of the experiments, both lungs were analyzed by RT-PCR, Western blot, and light microscopy. RESULTS: In placebos, the expression levels of pro-inflammatory markers were increased in both lungs significantly, whereas NF-κB was markedly up-regulated. Administration of apigenin reduced the activation of NF-κB and the expression of TNFα, iNOS, and IL-6. These effects were observed in total lung ischemia. Histology showed greater hemorrhage and exudation in the pulmonary periphery of all groups, whereby damage was practically absent in the central lung regions of the apigenin animals. A second dose of apigenin did not outclass a single one. CONCLUSIONS: We conclude that apigenin given intraperitoneally can reduce activation of NF-κB and also attenuate the expression of TNFα, IL-6, and iNOS in a surgical model of LIRI. The surgical procedure itself can induce significant damage to the lungs.


Subject(s)
Apigenin/therapeutic use , Inflammation Mediators/metabolism , Lung Injury/drug therapy , NF-kappa B/metabolism , Protective Agents/therapeutic use , Reperfusion Injury/drug therapy , Animals , Apigenin/pharmacology , Disease Models, Animal , Humans , Injections, Intraperitoneal , Lung/pathology , Lung/surgery , Lung Injury/etiology , Lung Injury/pathology , Male , Protective Agents/pharmacology , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Up-Regulation
11.
Medicine (Baltimore) ; 97(40): e12449, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30290602

ABSTRACT

The prosthetic surgical above-knee bypass (pAKB) is a standard therapy in superficial femoral artery (SFA) occlusive disease in absence of suitable vein. Viabahn graft has been established as a promising alternative. Since limited comparative data are available, we conducted a retrospective study to compare long-term outcomes of these 2 therapies in a real-world setting.Records of 52 patients (60 limbs), who were treated by pAKB (29 limbs) or Viabahn (31 limbs) were reviewed. Patients were followed up by clinical assessment, physical examination, and resting ankle brachial index (ABI) after 3, 6, 12 months and yearly thereafter. Long-term data were available for 97% in the Viabahn and 93% for pAKB after 73 ±â€Š3.7 months (mean ±â€Šstandard error [SE]).Long-term primary and secondary patencies in Viabahn group were 40% and 70%, respectively, after 63 ±â€Š2.8 months (mean ±â€ŠSE). Total lesion length was 19 ±â€Š11.06 cm (mean ±â€ŠSE), graft size was 6 ±â€Š0.72 mm (mean ±â€ŠSE). Hospital stay was 4.8 ±â€Š0.72 days (mean ±â€ŠSE). Limb salvage was achieved in 90%. Patients in the pAKB group showed a total lesion length of 24.39 ±â€Š1.97 cm (mean ±â€ŠSE), graft size was 7 ±â€Š0.99 mm (mean ±â€ŠSE). Long-term analysis after 83 ±â€Š6.8 months (mean ±â€ŠSE) revealed a primary patency of 78% with a secondary patency of 94%. Hospital stay was 10.4 ±â€Š1.27 days (mean ±â€ŠSE). Limb salvage was ensured in 97%. Long-term primary patency was lower for Viabahn (P = .044), secondary patency (P = .245), and leg salvage (P = .389) were not significantly different. However, hospital stay was shorter (P = .0002) for Viabahn.Long-term analysis of Viabahn revealed a significantly lower primary patency, a similar secondary patency, limb salvage, and significantly shorter hospital stay when compared with pAKB. Our data suggest that pAKB is still a valuable option in patients suitable for an open operation. However, Viabahn can be used as a less invasive treatment in high risk patients.


Subject(s)
Blood Vessel Prosthesis Implantation/methods , Blood Vessel Prosthesis , Femoral Artery/surgery , Peripheral Arterial Disease/surgery , Stents , Aged , Aged, 80 and over , Female , Humans , Knee , Limb Salvage/methods , Male , Middle Aged , Postoperative Period , Retrospective Studies , Treatment Outcome , Vascular Patency
13.
Transplantation ; 77(11): 1683-92, 2004 Jun 15.
Article in English | MEDLINE | ID: mdl-15201667

ABSTRACT

BACKGROUND: Increased oxygen radical production may not only contribute to posttransplant ischemia-reperfusion injury but also to acute rejection of renal allografts. Xanthine oxidoreductase (XOR) may constitute a relevant reactive oxygen species (ROS) source. The study was conducted (1). to determine ROS production as well as oxidant and antioxidant enzyme activities in renal grafts and (2). to modulate acute rejection by tungsten administration, a specific inhibitor of XOR. METHODS: Syngraft (Lewis to Lewis, Fisher344 to Fisher344) and allograft (Fisher344 to Lewis) kidney transplantations were performed with or without tungsten administration. Analysis was performed at day 1, 3, or 9 posttransplantation. RESULTS: Generation of ROS was enhanced, being 10-fold higher in renal allografts versus control kidneys at day 9 (P <0.01); this was associated with histologic signs of acute rejection. Oxygen radicals were generated to a significant degree by enhanced XOR activity, which increased more than 10-fold in renal allografts at day 9 posttransplantation; XOR protein in glomeruli and tubulointerstitium was also elevated in allo-grafts. In addition, NADPH oxidase activity increased significantly in allografts. The activity of antioxidant enzymes tended to decrease. Tungsten treatment resulted in a pronounced reduction of XOR activity and ROS production, without any effect on NADPH-oxidase activity; mononuclear cell infiltration and rejection signs were significantly ameliorated at day 9 post-transplantation by selective inhibition of XOR. CONCLUSIONS: A major part of ROS generation in acute rejection was contributed by XOR. ROS are not only associated with but also contribute to acute allograft rejection because inhibition of XOR alleviated rejection phenomena.


Subject(s)
Graft Rejection/physiopathology , Kidney Transplantation , Xanthine Dehydrogenase/metabolism , Acute Disease , Animals , Catalase/metabolism , Kidney/enzymology , Kidney/pathology , Kidney/physiopathology , Kidney Glomerulus/metabolism , Kidney Glomerulus/pathology , Kidney Tubules/metabolism , Kidney Tubules/pathology , Multienzyme Complexes/metabolism , NADH, NADPH Oxidoreductases/metabolism , NADPH Oxidases/metabolism , Nephritis/pathology , Oxidoreductases/metabolism , Postoperative Period , Rats , Rats, Inbred F344 , Rats, Inbred Lew , Reactive Oxygen Species/metabolism , Transplantation, Homologous , Transplantation, Isogeneic , Tungsten/pharmacology
14.
Transplantation ; 75(1): 3-9, 2003 Jan 15.
Article in English | MEDLINE | ID: mdl-12544863

ABSTRACT

BACKGROUND: Chronic rejection with development of transplant arteriosclerosis is the major culprit involved in loss of kidney allografts. The allografts' fate was thought to depend on the intensity of the host immune responses and the potency of immunosuppressive regimens. Recent data suggests that grafts contribute to their own survival by way of up-regulation of "cytoprotective" genes. METHODS: We analyzed the expression of four cytoprotective genes, A20, Bcl-2, Bcl-x(L) and heme oxygenase (HO)-1, in three rat renal allograft models of chronic rejection: Fisher 344-Lewis (F344/Lew), Dark Agouti-Brown Norway (DA/BN), and DA-Wistar-Furth (WF). We chose these genes for their known anti-inflammatory and anti-apoptotic function in endothelial cells (EC) and the atheroprotective function of A20 in smooth muscle cells (SMC). RESULTS: Twenty-eight and 9 weeks following transplantation, F344/Lew and DA/BN transplants had stable graft function. Histopathologic analysis showed moderate tissue damage, minimal cellular infiltrates, and preserved vascular integrity correlating with high expression of A20 in SMC. Conversely, impaired allograft function in the DA/WF combination with substantial transplant arteriosclerosis was noted in 60% of the grafts correlating with absent or decreased A20 expression in EC and SMC. In all combinations, expression of HO-1, Bcl-2, and Bcl-x(L) colocalized with infiltrating cells and was not informative on the graft status. CONCLUSIONS: We demonstrate for the first time a strict correlation between A20 expression in the vessel and the absence of transplant arteriosclerosis in rat kidney-allograft models. This data is similar to data obtained in human kidney allografts and suggests that A20 may represent a novel therapeutic target for the prevention of chronic allograft rejection.


Subject(s)
Arteriosclerosis/prevention & control , Kidney Transplantation/adverse effects , Muscle, Smooth, Vascular/metabolism , Proteins/physiology , Renal Artery/metabolism , Animals , Cytoprotection , Genes, bcl-2 , Immunohistochemistry , Kidney/pathology , Muscle, Smooth, Vascular/chemistry , Proteins/analysis , Proteins/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Rats , Rats, Inbred Strains , Renal Artery/chemistry , Transplantation, Homologous , bcl-X Protein
15.
Vasc Endovascular Surg ; 47(7): 502-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23867203

ABSTRACT

OBJECTIVE: We conducted a retrospective study to compare short- and mid-term patencies of Viabahn with surgical above-knee prosthetic bypass (pAKB). METHODS: The records of 52 patients with either pAKB (n = 25) or Viabahn (n = 27) were reviewed. The majority had Rutherford clinical grade 3. Patients were followed after 3, 6, and 12 months and yearly thereafter. RESULTS: For Viabahn, the short-term (1-16 months) primary patency rate was 60% with a secondary patency rate of 90%, and mid-term (1-68 months) patencies of 47% and 83.3%, respectively. In pAKB, the short-term results revealed a primary patency rate of 78% with a secondary patency of 91% and mid-term results of 65% and 90%, respectively. No statistical difference was found concerning short-term patencies. Mid-term primary patency was lower for Viabahn (P < .05) and secondary patency proved no significant difference. CONCLUSION: Viabahn revealed similar short-term primary and secondary patencies but lower mid-term primary patency. It provides a good alternative therapy to pAKB.


Subject(s)
Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Endovascular Procedures/instrumentation , Femoral Artery/surgery , Peripheral Arterial Disease/surgery , Stents , Aged , Aged, 80 and over , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Female , Femoral Artery/physiopathology , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/physiopathology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Peripheral Arterial Disease/diagnosis , Prosthesis Design , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Vascular Patency
16.
Vojnosanit Pregl ; 69(5): 389-93, 2012 May.
Article in English | MEDLINE | ID: mdl-22764539

ABSTRACT

BACKGROUND/AIM: Saliva is a body fluid which, like serum, can be used for determination of concentrations of certain drugs, both in pharmacotherapy as well as in acute poisonings. The aim of this study was to determine carbamazepine concentrations in both saliva and serum in acute poisoning in order to show if there is a correlation between the obtained values, as well as to monitor toxicokinetics of carbamazepine in body fluides. METHODS: Saliva and serum samples were obtained from 26 patients treated with carbamazepine and 20 patients acutely poisoned by the drug immediately after their admission in the Emergency Toxicology Unit. Determination of salivary and serum carbamazepine concentrations was performed by the validated high pressure liquid chromatography-ultraviolet (HPLC-UV) method. RESULTS: A significant correlation of salivary and serum carbamazepine concentrations in both therapeutic application and acute poisoning (r = 0.9481 and 0.9117, respectively) was confirmed. In acute poisonings the mean ratio between salivary and serum concentrations of carbamazepine (0.43) was similar to the mean ratio after its administration in therapeutic doses (0.39), but there were high inter-individual variations in carbamazepine concentrations in the acutely poisoned patients, as a consequence of different ingested doses of the drug. In acute poisoning the halftime of carbamazepine in saliva and serum was 12.57 h and 6.76 h, respectively. CONCLUSION: Our results suggest a possible use of saliva as an alternative biological material for determination of carbamazepine concentrations in therapeutic application and acute poisoning as well, and a possible extrapolation of the results obtained in saliva to serum concentrations of carbamazepine.


Subject(s)
Anticonvulsants/poisoning , Carbamazepine/pharmacokinetics , Carbamazepine/poisoning , Saliva/chemistry , Acute Disease , Anticonvulsants/pharmacokinetics , Anticonvulsants/therapeutic use , Carbamazepine/therapeutic use , Drug Monitoring , Humans
17.
J Neurol ; 259(11): 2309-18, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22527231

ABSTRACT

Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (<68 years and ≥68 years); 27 healthy subjects served as a control group. In all patients clinical examinations, MRI scans and a neuropsychological test battery that assessed four major cognitive domains were performed immediately before, within 72 h, and 3 months after CEA or CAS. While patients <68 years of age showed no significant cognitive alteration after either CEA or CAS, a significant cognitive decline was observed in patients ≥68 years in both treatment groups (p = 0.001). Notably, this cognitive deterioration persisted in patients after CEA, whereas it was only transient in patients treated with CAS. These results demonstrate an age-dependent effect of CEA and CAS on cognitive functions. In contrast to the recently observed increased clinical complication rates in older subjects after CAS compared with CEA, CEA appears to be associated with a greater, persistent decline in cognitive performance than CAS in this subgroup of patients.


Subject(s)
Angioplasty, Balloon/adverse effects , Carotid Stenosis/psychology , Carotid Stenosis/surgery , Cognition Disorders/psychology , Endarterectomy, Carotid/adverse effects , Stents/adverse effects , Age Factors , Aged , Angioplasty, Balloon/psychology , Carotid Stenosis/epidemiology , Cognition Disorders/epidemiology , Endarterectomy, Carotid/psychology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Retrospective Studies , Treatment Outcome
18.
Anticancer Res ; 30(4): 1347-51, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20530451

ABSTRACT

BACKGROUND: Lactate formation is up-regulated in tumorous cells by lactate dehydrogenase (LDH). High serum LDH level is linked to many malignancies with poorer survival, but tumour LDH-5 has not been well investigated in non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In 89 patients operated on for NSCLC stage I-III, the serum LDH level was assayed and immunohistochemistry for tumour LDH-5 was performed. Impact on long-term survival and correlation was analysed. RESULTS: High serum LDH was associated with poorer survival (p<0.001). No correlation was revealed between serum LDH and the tumour LDH-5. Only in tumours greater than 3 cm were high tumour LDH-5 values associated with higher serum LDH values (p=0.04) and in this subgroup, high tumor LDH-5 was associated with poorer long-term survival (p=0.024). CONCLUSION: High serum LDH has a negative impact on long-term survival in NSCLC, whereas for tumour LDH-5, this was seen only in a subgroup of patients with larger tumours.


Subject(s)
Carcinoma, Non-Small-Cell Lung/enzymology , L-Lactate Dehydrogenase/blood , Lung Neoplasms/enzymology , Adult , Aged , Carcinoma, Non-Small-Cell Lung/pathology , Female , Follow-Up Studies , Humans , Immunohistochemistry , Isoenzymes/biosynthesis , Isoenzymes/metabolism , L-Lactate Dehydrogenase/biosynthesis , L-Lactate Dehydrogenase/metabolism , Lactate Dehydrogenase 5 , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Survivors
19.
Vojnosanit Pregl ; 66(5): 347-52, 2009 May.
Article in English | MEDLINE | ID: mdl-19489468

ABSTRACT

BACKGROUND/AIM: Carbamazepine is antiepileptic drug widely used for the treatment of epilepsy. Due to low therapeutic index of carbamazepine there is a need for routine measuring its concentrations in biological fluids. The aim of the study was to describe a method for concomitant determination of carbamazepine in the serum and saliva. METHODS: Separation of the drug from matrix is achieved by reversed-phase chromatography on a C18 column, with a mobile phase of methanol-water-acetic acid (65:34:1) at a flow-rate of 1.0 ml/min. Detection was effected by ultra-violet absorption at 285 nm. The total run time was 5 min. Samples were prepared by alkaline extraction (pH 10) using chlorophorm. RESULTS: Calibration curves were in the range 0.1-5 microg/mL for serum and saliva samples. Mean recoveries of spiked serum and saliva were 97.59 and 92.30%, respectively. Limits of detection (LOD) of carbamazepine in serum and saliva were 0.166 and 0.178 microg/mL, respectively. Limits of quantification (LOQ) in the serum and saliva were 0.237 and 0.226 microg/mL, respectively. The method precision was carried out with coefficient of variation of 2.10% and 4.03% for the serum and saliva, respectively. The obtained data showed that there was a strong correlation between saliva and serum concentrations (r = 0.9481, p < 0.001). CONCLUSION: The method described here is rapid, precise, accurate and simple, and can be used for quantitative determination of carbamazepine in human serum and saliva after therapy applying. Saliva samples could be used as an alternative matrix for therapeutic drug monitoring of this antiepileptic drug.


Subject(s)
Anticonvulsants/analysis , Carbamazepine/analysis , Chromatography, High Pressure Liquid/methods , Saliva/chemistry , Anticonvulsants/blood , Carbamazepine/blood , Humans
20.
Ann Thorac Surg ; 88(5): 1433-9, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19853087

ABSTRACT

BACKGROUND: Emergent coronary artery bypass graft surgery (CABG) for acute myocardial infarction is associated with an increased operative risk. For estimation of mortality risk, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) is appropriate up to a medium risk score (<6 points). To predict mortality risk more accurately in cases of higher EuroSCORE, additional cardiac data can be helpful. METHODS: Over a 3-year period, patient data including acute myocardial infarction and emergent CABG were retrospectively reviewed. Univariate and multivariate analysis for in-hospital mortality was performed. The EuroSCORE analysis and follow-up was investigated. RESULTS: Overall in-hospital mortality was 18.3%. Preoperative cardiac related predictors for in-hospital mortality were cardiogenic shock (p < 0.001), very poor left ventricular function (p = 0.001), and ST-segment elevation (p = 0.012). In multivariate regression analysis, age, cardiogenic shock, and pulmonary hypertension were independent preoperative risk factors. According to the EuroSCORE, we could define three statistically different groups: intermediate-risk, high-risk, and very high risk, with an observed mortality of 3.3%, 20.0%, and 63.2%, respectively. The EuroSCORE correlates with but overestimates the mortality risk. In subgroup analysis, the creatine kinase-myocardial band/hour ratio for the intermediate-risk group and ST-segment elevation for the high-risk group were additional cardiac risk factors. CONCLUSIONS: Patients with an acute myocardial infarction and emergency aortocoronary CABG have an elevated operative risk. Logistic EuroSCORE overestimates the mortality rate. Three different risk groups can be defined, in which creatine kinase-MB/h-ratio and ST-segment elevation can more accurately predict operative risk.


Subject(s)
Coronary Artery Bypass/mortality , Models, Statistical , Myocardial Infarction/mortality , Myocardial Infarction/surgery , Risk Assessment , Adult , Aged , Humans , Prognosis , Retrospective Studies
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