Open and endovascular treatment by covered and multilayer stents in the therapy of renal artery aneurysms: mid and long term outcomes in a single center experience.

AIM: The purpose of this paper is to evaluate the mid and long terms outcomes of open and endovascular surgical treatment, as well as multilayer stent, in patients affected by Renal Artery Aneurysm (RAA). PATIENTS AND METHODS: Twenty five patients with RAA (24 monolateral and 1 bilateral aneurysm, 26 aneurysms) were observed between 2000 and 2015: 4 were not treated due to the small size of the aneurysm (< 2.5 cm); out of the remaining, 16 underwent endovascular treatment, 2 were treated by open surgery consisting in aneurysmectomy and graft reconstruction and 5 (in 1 patient bilateral) were treated by ex vivo repair and autotransplantation. RESULTS: Out of the 22 patients treated for RAA, one patient operated upon open surgery presented an early thrombosis of a PTFE graft, followed by nephrectomy (4.7%); one patient underwent autotransplantation showed an ureteral kinking without functional consequences. In a follow-up ranging from 1 and 11 years (mean 5 years), no deaths were observed; all the renal arteries repaired were patents and 16 out of 21 patients had a significative reduction of systemic blood pressure. DISCUSSION: The choice of the best treatment is based on aneurysm's morphology according to Rundback's classification. The type I, involving the main renal artery, is always treated by endovascular approach; type II, involving renal artery bifurcations may be treated by open surgery or multilayer stents; type III (hilar or intraparenchymal aneurysms) needs only an open surgical treatment as autotransplantation. CONCLUSION: Based on our experience it seems that most of RAAs may be treated by endovascular technique. The ex vivo autotransplantation represents the first-line treatment in hilar and intraparenchymal aneurysms. Multilayer stents seem to have good outcome in the treatment of aneurysms involving arterial bifurcations. Mid and long term results, related to kidney preservation and to normalization of blood pressure, seems satisfying.

Solid versus liquid phase assays in detection of insulin antibodies. Influence of iodination site on labelled insulin binding.

On type 1 newly diagnosed and on insulin treated diabetic patients, anti-insulin autoantibodies (IAA) and antibodies (IA) having the same specificity are respectively induced. Such immune response may be evaluated either by radiobinding assay (RBA) or enzyme-linked immunosorbent assay (ELISA). Both methodologies have been compared at previous International Workshops, which pointed out discrepancies in results. In this work, IAA/IA prevalence was assessed by displacement RBA and ELISA, in normal subjects, type 2 (treated with hypoglycaemic agents), insulin treated and newly diagnosed type 1 diabetic patients. Results showed a lack of RBA-ELISA agreement. An attempt was then made to determine whether such results were, at least in part, attributable to iodination site in Tyr-A14. For this purpose parallel RBA assays were carried out by using radiolabelled insulin at A14 and A19 Tyr residues. Control sera and samples from insulin treated and type 1 newly diagnosed diabetic patients were tested. Our results suggest that labelling position is not involved in artifactual binding of tracers, at least as a systematic phenomenon. In the majority of cases the variability in RBA-ELISA signal ratios are best explained in terms of differences in the basic principles operating in both methods instead of artifacts due to tracer preparation.

Lack of involvement of nitric oxide in NMDA-induced neuronal cell death in cortical culture.

In primary cultures of rat cerebral cortex, N-methyl-D-aspartate causes widespread neurotoxicity. Inhibitors of the nitric oxide generating the enzyme nitric oxide synthase has been shown to attenuate the effects of N-methyl-D-aspartate in a number of neuronal systems both in vivo and in vitro. In our experiments, the nitric oxide synthase inhibitor N-nitroarginine was ineffective at blocking neurotoxicity induced by N-methyl-D-aspartate. Cyclic guanine monophosphate, known to be synthesized in response to nitric oxide was demonstrably inhibited by identical treatments with N-nitroarginine in sister cultures. We conclude that although nitric oxide is produced in response to N-methyl-D-aspartate, it is neither necessary nor sufficient for neurotoxicity.

The inhibition of [125I]omega-conotoxin GVIA binding to neuronal membranes by neomycin may be mediated by a GTP-binding protein.

omega-Conotoxin GVIA (omega-CT) has been reported to block calcium currents at the L- and N-type calcium channels. In neuronal membranes omega-CT, and the aminoglycoside antibiotic neomycin, have been shown to inhibit [125I]omega-CT binding, presumably acting at the N-type calcium channel. We demonstrate here that the concentration curve for neomycin sulfate inhibition of [125I]omega-CT binding is shifted to the right by GTP analogues or fluoride, increasing the IC50 for neomycin. [125I]omega-CT binding is unaffected by these agents and in competition studies the potency of omega-CT, Ca2+, or La3+ is not modulated by GTP analogues or fluoride. These results indicate that the inhibition of [125I]omega-CT binding by neomycin may be mediated by a GTP binding protein.

Stereoselective enhancement by (R)-HA-966 of the binding of [3H]CPP to the NMDA receptor complex.

The enantiomers of the strychnine-insensitive glycine antagonist, HA-966 (1-hydroxy-3-amino-pyrrolidone-2), stereoselectively enhance binding of the N-methyl-D-aspartate (NMDA) competitive antagonist, [3H]CPP (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) to rat brain synaptosomal membranes. The enhancement by the more potent (R)-HA-966 is competitively inhibited by the glycine antagonist 7-chlorokynurenic acid and noncompetitively by the polyamine spermine. Thus, (R)-HA-966, apparently at the glycine site, enhances the binding of antagonist to the NMDA receptor, possibly through a mechanism partially in common with that of spermine.

HA-966 acts at a modulatory glycine site to inhibit N-methyl-D-aspartate-evoked neurotransmitter release.

The role of endogenous glycine in supporting N-methyl-D-aspartate (NMDA)-evoked neurotransmitter release was investigated. HA-966 (1-hydroxy-3-aminopyrrolidone-2) inhibited NMDA-evoked release of [3H]norepinephrine from rat hippocampal brain slices, but was much less effective in inhibiting [3H]norepinephrine release evoked by kainic acid (KA). Glycine (1 mM) reversed the HA-966 (1 mM) antagonism of NMDA-evoked release of [3H]norepinephrine. Strychnine (10 microM) had no effect on the ability of glycine to reverse HA-966 antagonism of NMDA-evoked neurotransmitter release. Other amino acids were also capable of reversing the HA-966 antagonism of NMDA-evoked [3H]norepinephrine release with a rank order of potency: D-serine greater than or equal to glycine much greater than L-serine approximately beta-alanine. These same compounds inhibited strychnine-insensitive [3H]glycine binding to rat cortical membrane fragments with a rank order of potency: glycine greater than D-serine much greater than L-serine greater than or equal to beta-alanine. In addition, HA-966 inhibited [3H]glycine binding (IC50 = 8.5 microM). The results suggest that HA-966 antagonism of NMDA-evoked neurotransmitter release is due to the inhibition of endogenous glycine acting at a strychnine-insensitive modulatory glycine site associated with the NMDA receptor/ionophore complex.

Rupture of Dacron aorto-femoral graft. Case report.

A 74-year-old patient was admitted to our department in a serious general condition due to massive bleeding. He had been treated 10 years previously in another hospital with an aorto-bifemoral bypass for obstructive disease using a knitted-Dacron graft. A large pulsating mass was present in the right iliac fossa as well as enormous pulsating enlargement of the scrotum. Echo color-Doppler investigation detected dilation up to 5 cm in diameter of the right branch of the graft and a large perigraft hematoma communicating with a similar mass in the scrotum. The patient was submitted to emergency surgery and a large rupture of the graft was found. The dilated segment was resected and replaced by a new 8 mm Dacron graft. Postoperative course was uneventful.

Carotid surgery without angiography is possible and safe.

BACKGROUND: To evaluate the possibility to perform carotid surgery without angiography. METHODS: From January 1994 to June 1998, 514 patients with carotid obstructive disease were operated upon, 225 of them (43.8%) without previous angiography; 55 out of 68 (80.8%) during the last six months. Eighty-one (36.0%) had lateralizing symptoms, 50 aspecific ones (22.2%) and 94 were asymptomatic (41.8%). All patients were investigated by color-coded duplex sonography (CDS) of the arteries at the neck and by transcranial Doppler (TCD) and computed tomography (CT). One hundred eighty-eight patients were operated upon under local anaesthesia and 37 under general anesthesia; 204 had a carotid endartereotomy (90.7%) with patch angioplasty in 154 (75.5%), and 21 required a bypass graft (9.3%). In 26 patients (11.5%) an indwelling shunt was needed. RESULTS: Findings at surgery were consistent with CDS for plaque composition, ulcerations and degree of stenosis. There were no early deaths. Neurologic or ocular deficits occurred in 2 cases (0.9%). No strokes were observed in follow-up from 6 to 34 months. CONCLUSIONS: Carotid endarterectomy can be done without angiography in selected cases provided CDS plus TCD are of high quality. Under such conditions it can be considered a safer way to deal with carotid obstructive disease.

Efficacy of an intravenous low-molecular-weight dermatan sulphate (Desmin) in patients with acute proximal deep venous thrombosis and silent pulmonary embolism. A pilot study.

Ten patients affected by proximal deep venous thrombosis were treated in an open study with a low-molecular-weight dermatan sulphate (Desmin), administered at doses of 400 mg (intravenous bolus) followed by 1200 mg/day infused intravenously for 10 days, without activated partial thromboplastin adjustment. The evolution of the deep vein thrombosis and the presence of silent pulmonary embolism were evaluated by phleboscintigraphy and lung scan, performed before treatment and after 10 days of treatment, and by repeated echocolour-Doppler examination (every 2 days during treatment). The evolution of deep vein thrombosis showed a considerable improvement; similarly, lung scan showed a substantial reperfusion of lung, with regression of perfusional deficit. Repeated echocolour-Doppler examination of the deep venous system during treatment did not document further thrombus extension in any patient. Tolerance and safety were excellent. No adverse effects were observed. These preliminary results indicate that the tested dose of Desmin can be effective in treating deep vein thrombosis and silent pulmonary embolism.

[Considerations on the pathogenesis, diagnosis and therapy of renal venous aneurysm]. / Considerazioni di patogenesi, diagnosi e terapia degli aneurismi venosi renali.

An aneurysms of a renal vein is very uncommon an entity and even more so when a visceral vein is affected. The venous aneurysms are generally asymptomatic and are detected either at post-mortem examination or by Echography, CT scan or MR investigation. Occasionally they become symptomatic because of rupture, thrombosis and embolism, but even in those cases they are difficult to be diagnosed and can be life threatening particularly when bleeding occurs. Exceptionally an aneurysm of a visceral vein is an unexpected intraoperative finding and is detected during an abdominal procedure undertaken for other pathology. In our experience a true aneurysm of the main trunk of the left renal vein was detected during a procedure of aorto-bifemoral by-pass graft repair for chronic aorto-iliac occlusive disease. The aneurysm was resected and the vein repaired by direct suture. Congenital weakness of the vein wall was very likely the cause as suggested by the extreme thinness and media atrophy of the aneurysm and normal appearance of the wall of renal vein and inferior vena cava. Differences between varices and aneurysms of the renal veins are discussed as well as indications for surgical treatment.

[Carotid-carotid bypass. Indications and results]. / Bypass carotido-carotideo. Indicazioni e risultati.

AIM: The aim of this study is to evaluate the indications for a carotid-carotid bypass and its therapeutic efficacy. METHODS: Between January 1995 and December 2001, 42 out of 782 patients with obstructive lesions of carotid vessels were submitted to carotid-carotid bypass. Preoperative investigations included Duplex scanning, transcranial Doppler and cerebral CT in all the patients, angiography in 24, spiral CT in 8, MR angiography in 6. Carotid bypass was planned pre-operatively in 13 cases due to internal carotid occlusion in 4, to pseudo-occlusion in 8 and to restenosis in 1. In the remaining 29, due to a too thin residual wall or to the lack of a good clivage plane, a carotid bypass was planned intraoperatively. A PTFE graft was employed in 30 cases while the autologous saphenous vein in 12. Four patients were lost in a 12-80-month follow-up. No intra or postoperative mortality was recorded. RESULTS: Three patients died during the follow-up. In 1 patient the death followed an ischemic stroke due to bypass occlusion. Four bypasses became occluded, in 3 cases without clinical signs. Eight patients suffered by transient superior laryngeal nerve iniury. CONCLUSIONS: Carotid bypass, as an alternative to CEA, provides good results in the treatment of the patients with carotid stenosis, pseudo-occlusion or segmental occlusion. In most of the cases the surgical technique is planned intraoperatively but in selected cases angiographic findings, spiral CT and color flow duplex can suggest in the preoperative phase that carotid bypass is the best choice.

[Elective and emergency surgical treatment of popliteal aneurysms. Indications and results]. / Trattamento chirurgico degli aneurismi poplitei in elezione e in urgenza. Indicazioni e risultati.

BACKGROUND: The aim of this paper is to evaluate the long term results related to surgical technique and to prosthetic material in planned and emergency conditions. METHODS: From January 1990 to December 1999, fourty-five patients with popliteal aneurysms were observed. Eighteen patients (40%) were asymptomatic; eleven (24.4%) suffered from claudicatio; six had an acute ischemia (13.3%) and four presented (8.9%) clinical signs of rest pain; in four cases (8.9%) symptoms were related to venous compression and to rupture in two (4.4%). Diagnosis was obtained by ultrasounds, angiography and CT-scan. All patients were operated on and in four cases (8.9%) the procedure involved both legs. The prosthetic material was reversed autologous saphenous vein (ASV) in 30 patients (61.2%), PTFE-EXS-TW in 16 (32.6%), homologous vein in one (2%), composite graft in one (2%), and a Dacron in the last one (2%). RESULTS: Six patients died for causes not related to the operation and eight bypasses (18.2%) became occluded. Amputation was needed in two patient, in relation to late bypass occlusion. In one cases an amputation was carried out for acute thrombosis of the contralateral aneurysm which was not treated for patients refusal. The long term patency rate was 81.8%. CONCLUSIONS: Popliteal aneurysms must be considered for reconstructive surgery, also when asymptomatic and with a diameter over 2 cm. The routinely use of the ASV improves the long-term patency rate. Best long term results are obtained in elective surgery.

Immunologic and genetic markers in insulin-dependent diabetes mellitus (type 1) in an Argentine population.

The objective was to evaluate the prevalence and association of several markers (islet cell antibodies: ICA, insulin autoantibodies: IAA, glutamic acid decarboxylase antibodies: GADA and ICA512 antibodies: ICA512A) along with HLA DQB1 genotype in type 1 diabetes mellitus of recent onset, including siblings and individuals without any history of this disease, in an Argentine population. A total of 79 children with type 1 diabetes mellitus of recent onset were studied, as well as 79 control children, and 68 healthy siblings of type 1 diabetic cases. IAA, ICA, GADA, ICA512A and HLA DQB1 alleles were determined. Sensitivity was 67.1% for ICA, 36.7% for IAA, 74.6% for GADA and 63.4% for ICA512A. None of the control subjects was positive for the immunological markers. Combined sensitivity of ICA-IAA-GADA was 89.8%, similar to the ICA512A-GADA (87.3%) or ICA512A-GADA-IAA combination (91.1%). GADA correlated positively with ICA, but no such correlation was found between IAA, ICA512A and ICA. IAA correlated negatively and GADA positively with age. IAA was associated to DQB1*0201, whereas ICA and ICA512A associated to DQB1*0302. Among siblings, 3/68 (4.4%) were positive for IAA and a single case (1.5%) was positive for GADA and one for ICA512A. Our findings show that the combination of multiple tests increases the sensitivity for prediction, with the ICA512A-GADA combination proving highly sensitive and equivalent to other proposed combinations, such as ICA-IAA-GADA.

Alternative activation of macrophage by IL-10.

Macrophage activation by proinflammatory stimuli is suppressed by IL-10. We tested the hypothesis that IL-10 induces an alternative state of macrophage activation rather than solely mediating suppression. We therefore searched for genes the expression of which might be up-rather than downregulated in response to IL-10. Total RNA was obtained from mouse macrophages J774 A.1 before or after stimulation with IL-10 (20 ng/ml). Poly(A)+RNA was isolated in both cases in order to obtain driver and tester mRNA. Subtraction suppression hybridization was performed using the PCR-select cDNA subtraction procedure. After evaluation of the subtraction efficiency the subtracted cDNA library was cloned into pCRII.1. A total of 1,300 clones were obtained. Southern blot hybridization analysis was performed as the first screening step of this total number of clones. 140 (10.7%) were identified as upregulated in response to IL-10. Sequence analyses so far showed perfect or near perfect matches with already known genes for the majority of clones. Our results clearly indicate that IL-10 stimulates the expression of a large number of genes in macrophages. We conclude that IL-10 induces in macrophages a noninflammatory state of reactivity which may serve to contain proinflammatory conditions.

The polyamine spermine affects omega-conotoxin binding and function at N-type voltage-sensitive calcium channels.

1. The effects of the polyamines, spermine and spermidine on neuronal N-type voltage-sensitive calcium channels were investigated using the binding and function of the ligand omega-conotoxin GVIA (omega-CT). 2. Spermine and spermidine enhanced (EC50 approximately 0.16 and 0.45 microM) and, at higher concentrations, inhibited (IC50 of 9 and 240 microM) the binding of [125I]omega-CT to rat hippocampal synaptosomes. 3. Spermine and, less potently, spermidine inhibited the neurotransmitter-mediated, omega-CT-sensitive, electrical-field-stimulated contractile responses of the rat vas deferens. 4. The polyamines also inhibited the phenylephrine-evoked contractile responses of the vas deferens with the same rank order, consistent with a postsynaptic mechanism of inhibition. 5. However, pre-exposure to spermine prevented the irreversible inhibition of vas deferens twitch responses by omega-CT (previously found to be presynaptic). The prevention of inhibition by omega-CT demonstrates that the neuronal binding of spermine and omega-CT is mutually exclusive. Thus spermine (and presumably spermidine at higher concentrations) appears to modulate the actions of omega-CT at N-type voltage-sensitive calcium channels.

Neomycin is an agonist at a polyamine site on the N-methyl-D-aspartate receptor.

Neomycin appears as a full agonist and spermidine as a partial agonist at the site where polyamines enhance 1-[1-(2-thienyl)cyclohexyl][3H]piperidine ([3H]TCP) binding on the N-methyl-D-aspartate (NMDA) receptor. Other aminoglycosides also enhance [3H]TCP binding with efficacies roughly proportional to the number of primary amine groups. The polyamine antagonists ifenprodil and arcaine inhibit enhancement of [3H]TCP binding by spermidine or neomycin. The inhibition of [3H]TCP binding by arcaine is apparently competitively reduced by neomycin and spermidine, supporting a common site. Diethylenetriamine (previously described as a polyamine antagonist) may be a partial agonist. Enhancement by neomycin or spermidine is not additive to that of Mg2+, consistent with competition of Mg2+ and spermidine or neomycin at the site where these compounds enhance [3H]TCP binding. Polyamines also enhance the binding of the competitive antagonist 2-(2-carboxypiperazin-4-yl)[3H]propyl-1-phosphonic acid ([3H]CPP). Neomycin, which does not enhance [3H]CPP binding, inhibits the enhancement by spermidine. That this site is distinct from the site where spermidine and neomycin increase [3H]TCP binding is supported by different pharmacology. Arcaine and diethylenetriamine do not inhibit spermidine enhancement of [3H]CPP binding. Mg2+ also does not compete with the spermidine enhancement of [3H]CPP binding. Ifenprodil inhibits the spermidine enhancement of [3H]CPP binding. The data suggest two or more polyamine sites, with arcaine selective for the site that enhances [3H]TCP binding. Neomycin is an agonist at one polyamine site and antagonist to the second.