Femoropopliteal In-stent Restenosis Repair: Midterm Outcomes After Paclitaxel Eluting Balloon Use (PLAISIR Trial).

OBJECTIVE: The aim was to assess 18 month outcomes of the paclitaxel eluting balloon (PEB) in patients with femoropopliteal (FP) in-stent restenosis (ISR). METHODS: In a national prospective and multicentre cohort study, symptomatic patients with femoropopliteal in-stent restenosis were included from January 2012 to June 2013. Patients were treated by paclitaxel eluting balloon angioplasty (In Pact Admiral, Medtronic, Santa Rosa, CA, USA). Clinical and duplex scan follow-up evaluations were performed at 1, 3, 6, 9, 12, and 18 months. The primary endpoint was freedom from target lesion revascularisation (TLR) at 12 months. Secondary endpoints were major adverse cardiovascular events (MACE), Target extremity revascularisation (TER), primary and secondary sustained clinical improvement, recurrent restenosis rate, primary and secondary patency, quality of life assessed by EQ-5D questionnaire, technical success, clinical success, and length of stay RESULTS: A total of 53 patients were enrolled. After a blinded review, 10 patients were defined as protocol violation because restenosis occurred more than 2 years after stent implantation. Procedures were performed in 55 limbs, 48 (87%) for claudication and 7 (13%) for critical limb ischaemia. The mean diameter and length of PEB were 6 ± 0.57 mm and 86 mm ± 32 mm, follow-up was 17 months (range 1-19). At 1 year, the survival rate was 96 ± 2.7% and freedom from TLR and TER were 90.2 ± 4.2% and 85 ± 5%, respectively. Sustained primary and secondary clinical improvements were 78.6 ± 5.7% and 92.0 ± 3.8%, respectively. At 1 year, the primary patency rate was 83.7 ± 5.0%. Prior to the procedure, the mean EQ-5D score was 66 ± 14 and 74 ± 16 at 1 year (p = .10). Two patients died during follow-up; one patient died 33 days after the procedure because of limb ischaemia. CONCLUSION: PEB for the treatment of FP ISR is associated with a low rate of re-interventions and restenosis. Clinical improvement is maintained at 18 months.

Identifying rare variants for genetic risk through a combined pedigree and phenotype approach: application to suicide and asthma.

Suicidal behavior is a complex disorder, with evidence for genetic risk independent of other genetic risk factors including psychiatric disorders. Since 1996, over 3000 DNA samples from Utah suicide decedents have been collected and banked for research use through the Utah Medical Examiner. In addition, over 12,000 Utah suicides were identified through examination of death certificates back to 1904. By linking this data with the Utah Population Database, we have identified multiple extended pedigrees with increased risk for suicide completion. A number of medical conditions co-occur with suicide, including asthma, and this study was undertaken to identify genetic risk common to asthma and suicide. This study tests the hypothesis that a particular comorbid condition may identify a more homogeneous genetic subgroup, facilitating the identification of specific genetic risk factors in that group. From pedigrees at increased risk for suicide, we identified three pedigrees also at significantly increased familial risk for asthma. Five suicide decedents from each of these pedigrees, plus an additional three decedents not from these pedigrees with diagnosed asthma, and 10 decedents with close relatives with asthma were genotyped. Results were compared with 183 publicly available unaffected control exomes from 1000 Genomes and CEPH (Centre d'etude du polymorphisme humain) samples genotyped on the same platform. A further 432 suicide decedents were also genotyped as non-asthma suicide controls. Genotyping was done using the Infinium HumanExome BeadChip. For analysis, we used the pedigree extension of Variant Annotation, Analysis and Search Tool (pVAAST) to calculate the disease burden of each gene. The Phenotype Driven Variant Ontological Re-ranking tool (Phevor) then re-ranked our pVAAST results in context of the phenotype. Using asthma as a seed phenotype, Phevor traversed biomedical ontologies and identified genes with similar biological properties to those known to result in asthma. Our top associated genes included those related to neurodevelopment or neural signaling (brain-derived neurotrophic factor (BDNF), neutral sphingomyelinase 2 (SMPD2), homeobox b2 (HOXB2), neural cell adhesion molecule (NCAM2), heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0)), inflammation (free fatty acid receptor 2 (FFAR2)) and inflammation with additional evidence of neuronal involvement (oxidized low density lipoprotein receptor 1 (OLR1), toll-like receptor 3 (TLR3)). Of particular interest, BDNF has been previously implicated in both psychiatric disorders and asthma. Our results demonstrate the utility of combining pedigree and co-occurring phenotypes to identify rare variants associated with suicide risk in conjunction with specific co-occurring conditions.

[About two big buttocks: an erysipelas with lymphoedema after pelvis surgery]. / A propos de deux grosses fesses: un érysipèle sur lymphoedème après chirurgie du pelvis.

We report the case of a 58-year-old man with erysipelas of both buttocks secondary to lymphoedema after pelvis surgery for prostatic cancer and multiple vascular interventions for iliofemoral thrombosis. The diagnosis was based on clinical examination and lymphoscintigraphy. This location of lymphoedema, limited to the buttocks, is uncommon; lower limbs are usually affected. This location needs a specific curative and preventive treatment, including antibiotic therapy, lymphatic drainage and contention to abate the condition and prevent a relapse.

Asymmetric information in health insurance: evidence from the National Medical Expenditure Survey.

Adverse selection is perceived to be a major source of market failure in insurance markets. There is little empirical evidence on the extent of the problem. We estimate a structural model of health insurance and health care choices using data on single individuals from the NMES. A robust prediction of adverse-selection models is that riskier types buy more coverage and, on average, end up using more care. We test for unobservables linking health insurance status and health care consumption. We find no evidence of informational asymmetries.

An examination of flexible spending accounts.

This paper develops a framework for analyzing flexible spending account (FSA) participation and usage. We explore patterns of FSA usage using data from a benefits firm for 1996 including an examination of types of FSA expenditures and their timing. We estimate some simple econometric models of the participation decision and also the decision of how much to put into an FSA. Several pieces of evidence suggest that much of an FSA election amount is based on foreknowledge of expenditures. We also find that participants tend to spend their election amount early, thus obtaining an interest-free loan.

Percutaneous stenting of the internal carotid artery: the European CAST I Study. Carotid Artery Stent Trial.

PURPOSE: To report the results of a multicenter safety trial of percutaneous carotid stenting performed by vascular surgeons. METHODS: Symptomatic or asymptomatic patients > or = 65 years of age with internal carotid artery (ICA) stenoses > or = 70% and < or = 2-cm long were eligible for enrollment. The procedures were performed in an operating room with the choice of anesthesia and the percutaneous access site at the discretion of the surgeon. Only Palmaz stents were used. RESULTS: From January 1, 1996 to December 31, 1997, 99 patients (74 men, mean age 70 years, range 51 to 94) were enrolled in the study. More than half (57 of 99 patients) were asymptomatic. The direct cervical approach was used predominantly (97%). Three (3%) cases were converted to surgery for inability to access the artery or deploy the stent (technical success 97%). No perioperative death or myocardial infarction was reported. Six (6%) procedural complications included 1 reversible arterial spasm, 2 dissections, 1 cervical hematoma, and 2 residual stenoses. One neurological event reversed within 7 days (1% minor stroke rate) and 4 (4%) transient ischemic attacks resolved within 24 hours. One (1%) asymptomatic early occlusion occurred 2 days postoperatively. No neurological event was observed in the 1- to 24-month follow-up (mean 13 months). Two (2%) patients died of nonprocedurally related causes. No stent compression was seen, but 1 asymptomatic occlusion and 3 asymptomatic, non-flow-limiting restenoses (2 < 40%, 1 at 60%) were found within 1 year (3% restenosis rate on an intention-to-treat basis). Patency was 98% at 1 year. CONCLUSIONS: The results of this trial support the contention that carotid stenting of short ICA lesions can be performed with a low neurological complication rate.

Use of ipsilateral greater saphenous vein as a valved transplant in management of post-thrombotic deep venous insufficiency: long-term results.

Incompetence of the deep venous valve is a common feature of post-thrombotic deep venous insufficiency. Various surgical techniques have been proposed to treat reflux. In this study we describe long-term results of a novel transposition technique using the ipsilateral greater saphenous vein. From 1984 to 1994 we used this procedure to treat 16 patients including 10 men and 6 women with a mean age of 56 years (range: 25 to 76 years). In all 16 cases the indication for surgery was incapacitating pain associated with recurring ulceration in 9 patients. From the results of using this technique we conclude that transposition using the ipsilateral greater saphenous vein is safe and effective with good mid-term results, especially for pain. For ulcers the primary success rate was 55% but this increased to 84% with proper surveillance and treatment of secondary insufficiency of the superficial venous system.

Endovascular repair of iliac artery aneurysm with Endoprosystem I: a multicentric French study.

Due to their position deep in the pelvis, the classical surgical treatment of iliac artery aneurysm leads to a high morbidity and mortality rate. The transfemoral percutaneous repair of these aneurysms is now possible thanks to a new device the endoprosystem I from "Mintech". We began in 1994 a study including radiological, cardiac and vascular centers all of them skilled in endovascular procedures. 27 patients entered the study: 1 patient died, 2 attempt failed and 2 presented leakage: the immediate failure rate was then 18.5%. For the late result (min 6, Max 19, mean 12 months) we had 1 thrombosis treated by surgery, 1 restenosis treated by PTA. We did not see any polyester dilatation or reactivation of aneurysm at the scan control at one year. We conclude that the percutaneous treatment of iliac aneurysm is possible and safe but we need long term result to validate the method.

Transluminal recanalization of occluded iliac arteries: a surgical experience.

The purpose of this study was to evaluate the feasibility of transluminal techniques in an unselected group of patients and to assess long-term outcome in successful procedures. All patients in whom iliac artery recanalization was attempted were included in this study. Patients with an occluded prosthesis or recent embolism were excluded. A total of 37 patients were studied. Assessment of the success or failure of the procedure was based on the results of control arteriography. Recanalization was deemed successful in 31 patients. This study demonstrates that transluminal recanalization of occluded iliac arteries by a surgeon is indeed feasible. Primary patency was 66% at 24 months. The potential risk, however, is long-term restenosis. Thus follow-up examination every 6 months is recommended including pressure index measurements after exercise and color Doppler ultrasonography of the recanalized zone.

Recanalization of occluded superficial femoral arteries using the rotational transluminal angioplasty catheter system (ROTACS).

A total of 85 occluded superficial femoral arteries were treated using the rotational transluminal angioplasty catheter system (ROTACS). The mean length of the occlusions was 7cm; 76% were uncalcified or only slightly calcified whereas 24% were calcified or highly calcified. The mean preoperative ankle:brachial index was 0.51. Primary success was achieved in 62 of 85 cases (73%). The mean length of reperfused occlusions was 6.2 cm: 26% of these lesions were calcified. The mean ankle:brachial index was 0.91. There were 23 primary failures (27%): reperfusion was impossible in 11 cases (including one complicated by perforation) and there were eight dissections, three cases where residual stenosis exceeded 50%, and one other unspecified failure. The mean length of these occlusions was 10.5 cm; 17% were calcified. Two patients developed a distal embolus and one died 10 days after reperfusion. The probability of primary patency of a reperfused artery was 44% at 1 year. Forty-two of the 62 patients who achieved primary success remained symptom free; the mean length of the original occlusion was 4.5 cm. Fifteen patients developed a new area of stenosis whereas five others exhibited new occlusion after a mean interval of 6 months. The mean length of these reperfused arteries was 9 cm. The probability of secondary patency at 1 year was 58%. Arterial calcification did not appear to influence the feasibility of reperfusion using the catheter. The main factor determining successful reperfusion was the length of the occlusal defect (P < 0.05). Reperfusion using the ROTACS did not improve the feasibility of reperfusion by conventional transluminal angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Naftidrofuryl in chronic arterial disease. Results of a six month controlled multicenter study using Naftidrofuryl tablets 200 mg.

The study was carried out on patients with intermittent claudication (Fontaine's stage II). The arterial and atheromatous origin of the disease was confirmed and localized by angiography or Doppler velocimetry examination. One hundred eighty-six patients were selected initially. Their pain-free walking distance on a treadmill (at a speed of 3 km/hour and an inclination of 10%) had to be 150-300 m. During the first month all patients received 3 placebo tablets daily. At the end of this run-in period (D-30; D 0) and after checking walking distance stability (allowed variation: +/- 20% between the two measurements) the patients were included in the study. One hundred fifty-four patients were selected and 118 remained during the whole study. The study was designed as a double-blind, using two parallel randomly selected groups. Sixty-four patients received for six months Naftidrofuryl (3 X 200 mg tablets daily with meals); 54 patients received placebo under the same conditions. During this period, clinical and paraclinical examinations were carried out every quarter (D 90 and D 180). After checking the initial homogeneity of the Naftidrofuryl and placebo-groups, the comparison between groups indicates a significant improvement in Naftidrofuryl group after 3 and 6 months of treatment. At the end of the study the observed differences in walking distance with Naftidrofuryl are approximately twice the difference in the reference group (D 90: p less than 0.05; D 180: p less than 0.02). The results of this study indicate that Naftidrofuryl is an efficient pharmacological tool for treatment of patients with chronic arterial disease (Fontaine's stage II).

Kinetic and structural investigation of acyl-binding sites on avian fatty acid synthase.

The acyl-binding sites of avian fatty acid synthase have been further characterized using the fluorescent acetyl-CoA analog, beta-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl]alanyl coenzyme A (NBDA-CoA). Binding to nonsulfhydryl sites has been studied by treatment with neutralized hydroxylamine to remove NBDA bound in a thioester linkage. The binding of NBDA to hydroxylamine-insensitive sites can be divided into two types: "loose" and "tight." The NBDA bound at the loose site can be removed by rapid gel filtration through a centrifuge column or by added CoA and is kinetically competent to be the loading site for acyl groups. The NBDA binds to the tight site apparently irreversibly and inhibits the overall enzyme activity completely at a stoichiometry of approximately 2 per enzyme molecule. Pyridoxal 5'-phosphate can modify a large number of enzyme amino groups (greater than or equal to 20) and totally inhibits the enoyl reductase activity. This inhibition appears to be correlated with the binding of approximately four molecules of pyridoxal 5'-phosphate per enzyme molecule. Although the beta-ketoacyl reductase activity is unimpaired, the binding of NADPH at the sites involved in this activity is weakened. The fluorescence resonance energy transfer efficiency from NADPH, bound to pyridoxal 5'-phosphate modified enzyme, to enzyme-bound NBDA, or from NADPH, bound to unmodified enzyme, to NBDA bound only at the tight hydroxylamine-insensitive sites is not significantly different from the overall efficiency previously reported. This suggests that all of the acyl-binding sites are located approximately the same distance from the enoyl reductase and beta-ketoacyl reductase catalytic sites.

[Should one operate on all asymptomatic carotid lesions?]. / Faut-il opérer toutes les lésions carotidiennes asymptomatiques?

Two subgroups in Natali and Thevenet's stage 0 class of asymptomatic diseases are defined. True asymptomatic affections occur in patients with neurologically asymptomatic carotid lesions. The natural history of these diseases when compared with results after surgery is in favor of preventive operative therapy. False asymptomatic affections are seen in patients who, after previous operations for symptomatic carotid lesions, present a lesion on the controlateral carotid which until then had been neurologically silent. The natural history of this group shows that immediate definitive cerebral accidents are rare and that life expectancy is low. In contrast, the course after repeat surgery, the present data being the first to be published, appears to be rather unfavorable. Careful selection of patients in this subgroup is therefore necessary when considering surgical treatment.

[Digestive endometriosis. Current concepts]. / L'endométriose digestive. Conceptions actuelles.

Endometriosis involving the digestive tract accounts for 1% of all cases of the disease. There is a marked predominance in the recto-sigmoid and terminal ileal loops. Symptomatology is dominated by disturbances in intestinal transit, sub-occlusion or acute obstruction, pain worsening at the time of menstruation and by a haemorrhagic rectal discharge again accompanying menstruation. Apart from classical aetiopathogenic theories such as grafting onto the digestive tract by tubal, lymph vessel or venous propagation, it would appear that prostaglandins and in particular a change in the (formula; see text) ratio may play a large role. Operative resection of localised stenosis combined with oophorectomy, if the latter is possible in view of the patient's age, or prolonged medical treatment with progestational agents or even better Danazol results in cure and avoids recurrences.

[Current problems posed by arterial injuries in hospital practice]. / Problèmes actuels posés par les traumatismes artériels en pratique hospitalière.

The authors analyse a series of 100 arterial lesions in respect to the localization, the time elapsed between the accident and reconstructive surgery, and the number of associated lesions (two or more). The results confirm the prognostic importance of the factor time: 83% of the good results are obtained in the first twelve hours, and only 67.5% after twelve hours. The results seen with popliteal and tibial lesions show a steady improvement from a 50% amputation rate twenty years ago to a 21.6% rate at the present time. The presence of associated lesions is equally important in the outcome: isolated arterial lesions (or accompanied by no more than two other anomalies) are successfully treated in 91% of the patients, opposed to 50% when loco-regional lesions are found (bone, skin, veins, nerves, muscles). The optional treatment of these complex traumatisms should be by means of a multidisciplinary approach.

Subunit interaction in catalysis. Some experimental and theoretical approaches with glyceraldehyde-3-phosphate dehydrogenase.

The evidence for equivalent catalytic sites in tetrameric glyceraldehyde-3-phosphate dehydrogenase from rabbit muscle has been re-examined and found to be insufficient to exclude alternating or reciprocating sites models. Using a column centrifugation technique, lower limits have been set on the rates of binding and release of coenzyme, and on the ratio of the affinities of NAD+ and NADH. The binding to acyl enzyme has also been examined. The tightly bound NAD+ has been found to be reduced preferentially and kinetically competently when glyceraldehyde 3-phosphate is added, demonstrating the nonequivalence of the sites in the transient reduction of NAD+. The rate of release of the NADH formed rapidly from tightly bound NAD+ was monitored directly by using lactate dehydrogenase and pyruvate to regenerate NAD+. This rate was sufficiently rapid for the NADH formed from tightly bound NAD+ to be a catalytic intermediate. Although these and other results are consistent with a simple alternating sites model, additional approaches appear necessary to find if subunit catalytic cooperativity occurs with this enzyme.

Investigation of reduced nicotinamide adenine dinucleotide phosphate and acyl-binding sites on avian fatty acid synthase.

The binding of reduced nicotinamide adenine dinucleotide phosphate (NADPH) to chicken liver fatty acid synthase has been studied by using both fluorescence titrations and the direct binding method of forced dialysis. Four apparently identical sites are found per enzyme molecule, with an intrinsic dissociation constant of 0.6 microM at pH 7.0, 23 degrees C. The acyl-binding sites on the enzyme have been studied with a fluorescent analogue of acetyl-CoA, beta-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl)]alanyl coenzyme A (NBDA-CoA). The enzyme slowly transfers NBDA to acyl-binding sites. Analysis of the kinetics of binding and of the stability and hydroxylamine sensitivity of the acyl-enzyme at pH 7.5 suggests that binding occurs predominantly at two classes of sulfhydryl sites, with two sites of each class per enzyme molecule. Up to one NBDA per enzyme molecule is bound to a nonsulfhydryl site after overnight incubation of enzyme with NBDA-CoA. The acyl linkage at one class of sulfhydryl sites appears to be hydrolyzed by the thioesterase activity of the enzyme. This hydrolysis can be prevented by modifying the enzyme with tosyl fluoride. The binding of NBDA is inhibited by acetyl-CoA, malonyl-CoA, and NADPH. The NBDA-enzyme adduct is inactive, although activity can be partially restored by incubation at 35 degrees C. The binding of NADPH to the enzyme is not significantly altered by the binding of NBDA. Fluorescence resonance energy transfer between enzyme-bound NADPH and enzyme-bound NBDA suggests that the acyl-binding sites are 30-40 A from NADPH-binding sites. This distance can only be defined approximately because of the presence of multiple energy donors and acceptors and the uncertainty in the dipole-dipole orientations of the energy acceptors and donors.