Transverse rupture of ring-supported Dacron graft 10 years after axillobifemoral artery bypass: induced by graft deterioration and Fogarty thrombectomy

A 70-year-old woman underwent an axillobifemoral artery bypass using a bifurcated ring-supported Dacron graft in 2004 and then noticed a pulsatile mass in the left flank 10 years later. A Fogarty thrombectomy was performed for acute graft occlusion. Eight months later, computed tomography revealed pseudoaneurysm formation in the graft body and surgical graft interposition was performed. The operative findings showed a transverse rupture of the graft just above the bifurcation. Histological findings revealed graft deterioration with filaments broken off from the graft. Although the cause of pseudoaneurysm formation was not apparent, the combination of graft deterioration and additional damage from the Fogarty thrombectomy was highly suspicious.     

The diagnostic value of circulating microRNAs for middle-aged (40–60-year-old) coronary artery disease patients

OBJECTIVE:Circulating microRNAs have been recognized as promising biomarkers for various diseases. The present study aimed to explore the potential roles of circulating miR-149, miR-424 and miR-765 as non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged (40–60-year-old) patients.METHODS:Sixty-five stable coronary artery disease patients (49–57 years old), 30 unstable coronary artery disease patients (49–58 years old), and 32 non-coronary artery disease patients (49–-57 years old) who were matched for age, sex, smoking habits, hypertension and diabetes were enrolled in this study. Total RNA was isolated from plasma with TRIzol reagent. Circulating miRNA levels were measured by quantitative real-time polymerase chain reaction.RESULTS:Circulating miR-149 levels were decreased 4.49-fold in stable coronary artery disease patients (1.18 ± 0.84) and 5.09-fold in unstable coronary artery disease patients (1.04 ± 0.65) compared with non-coronary artery disease patients (5.30 ± 2.57) (p<0.001). Circulating miR-424 levels were reduced 3.6-fold in stable coronary artery disease patients (1.18 ± 0.60) and 5-fold in unstable coronary artery disease patients (0.86 ± 0.54) compared with non-coronary artery disease patients (4.35 ± 2.20) (p<0.001). In contrast, circulating miR-765 levels were elevated 3.98-fold in stable coronary artery disease patients (6.09 ± 2.27) and 5.33-fold in unstable coronary artery disease patients (8.17 ± 2.77) compared with non-coronary artery disease patients (1.53 ± 0.99) (p<0.001). Receiver operating characteristic curve analysis revealed that the respective areas under the curve for circulating miR-149, miR-424 and miR-765 were 0.938, 0.919 and 0.968 in stable CAD patients and 0.951, 0.960 and 0.977 in unstable coronary artery disease patients compared with non-coronary artery disease patients.CONCLUSION:Our results suggest that circulating miR-149, miR-424 and miR-765 might be novel, non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged patients. However, future prospective trials in large patient cohorts are necessary before reaching a solid conclusion.     

Anatomic basis for the treatment of aneurysms of the upper cervical segment of the internal carotid artery by extra- intracranial cervico-petrous bypass with inverted “in situ” saphenous vein graft

Summary In the surgical treatment of aneurysms of the upper cervical portion of the internal carotid a., exclusion of the affected vascular segment combined with an extra-anatomic cervico-petrous bypass using a vein graft (great saphenous v.) may be considered. One of the problems specific to these extra-anatomic bypasses is asociated with the sub-cutaneous positioning of the vein graft, exposing it to risks of angulation, torsion or extrinsic compression that may lead to early venous thrombosis. We suggest an alternative technique using the principle of telescoping and consisting of positioning the vein graft within the cervical portion of the artery (in situ bypass). The cervical portion of the ICA may be used as a tunnel for the vein graft since there are no collateral arterial branches at this level. The technical features of such a bypass are defined by means of an anatomo-surgical study in the cadaver: exposure of the petrous portion of the internal carotid a. in its horizontal segment by subtemporal access, exposure of the ICA in the neck, transverse arteriotomies of the ICA, angioplasty with a Fogarty balloon, intracarotid telescoping of a saphenous vein graft from the cervical to the petrous region, distal end-to-end anastomosis between the vein graft and the petrous portion of the ICA, and proximal end-to-end anastomosis between the vein graft and the cervical portion of the ICA.

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Pontage extra-intracrânien cervicopétreux par greffon veineux saphène inversé in situ dans le traitement des anévrismes de la partie cervicale haute de l'artère carotide interne (bases anatomiques, applications chirurgicales)

Résumé Dans le traitement chirurgical des anévrismes de la partie cervicale haute de l'a. carotide interne, un trapping du segment vasculaire pathologique associé à un pontage extra-anatomique cervico-pétreux utilisant un greffon veineux (grande v. saphène) peut être proposé. Un des problèmes spécifiques de ces pontages extra-anatomiques est lié au positionnement sous-cutané du greffon veineux exposant aux risques de coudure, torsion ou compression extrinsèque du greffon pouvant conduire à une thrombose veineuse précoce. Nous proposons une alternative technique utilisant le principe du télescopage et consistant à positionner le greffon veineux dans l'a. carotide interne cervicale (pontage in situ). La partie cervicale de l'a. carotide interne peut être proposée comme tunnel au greffon veineux compte-tenu de l'absence de branches collatérales artérielles. Les modalités techniques de ce pontage cervico-pétreux in situ sont précisées à partir d'une étude anatomo-chirurgicale chez le cadavre : exposition de la partie pétreuse de l'a. carotide interne dans sa portion horizontale par voie sous-temporale, exposition de la partie cervicale de l'a. carotide interne par cervicotomie, artériotomie transversale de l'artère carotide interne aux niveaux cervical et pétreux, angioplastie par ballonnet de Fogarty, télescopage intra-carotidien d'un greffon veineux saphène de la région cervicale à la région pétreuse, anastomose termino-terminale distale entre le greffon veineux et la partie pétreuse de l'a. carotide interne, anastomose terminoterminale proximale entre le greffon veineux et la partie cervicale de l'a. carotide interne.

     

What role(s) for TGFalpha in the central nervous system?

Transforming growth factor alpha (TGFalpha) is a member of the epidermal growth factor (EGF) family with which it shares the same receptor, the EGF receptor (EGFR or erbB1). Identified since 1985 in the central nervous system (CNS), its functions in this organ have started to be determined during the past decade although numerous questions remain unanswered. TGFalpha is widely distributed in the nervous system, both glial and neuronal cells contributing to its synthesis. Although astrocytes appear as its main targets, mediating in part TGFalpha effects on different neuronal populations, results from different studies have raised the possibility for a direct action of this growth factor on neurons. A large array of experimental data have thus pointed to TGFalpha as a multifunctional factor in the CNS. This review is an attempt to present, in a comprehensive manner, the very diverse works performed in vitro and in vivo which have provided evidences for (i) an intervention of TGFalpha in the control of developmental events such as neural progenitors proliferation/cell fate choice, neuronal survival/differentiation, and neuronal control of female puberty onset, (ii) its role as a potent regulator of astroglial metabolism including astrocytic reactivity, (iii) its neuroprotective potential, and (iv) its participation to neuropathological processes as exemplified by astroglial neoplasia. In addition, informations regarding the complex modes of TGFalpha action at the molecular level are provided, and its place within the large EGF family is precised with regard to the potential interactions and substitutions which may take place between TGFalpha and its kindred.     

Coronary artery disease in Alström syndrome

Alström syndrome (ALMS) is a rare autosomal recessive condition, caused by mutations in the ALMS1 gene located on the short arm of chromosome 2. This gene codes for a protein linked with the centrosome, whose precise function is unknown. This condition was first described by Alström in 1959. ALMS is a multisystem condition that is characterised by childhood onset of blindness secondary to rod-cone retinal degeneration and dilated cardiomyopathy with heart failure, which often presents in infanthood and may recur later in life. Metabolic abnormalities including hypertriglyceridemia, liver steatosis, insulin resistance and type 2 diabetes mellitus are common, often occurring in association with obesity. Other abnormalities include endocrinological disturbances, such as thyroid disorder, growth hormone deficiency, hypogonadism and, in women, hyperandrogenism. This syndrome is also associated with sensorineural hearing loss, renal failure secondary to glomerulo-fibrosis, and fibrotic lung disease. Multiorgan fibrotic infiltration is the common feature in all cases. Considering the history of diabetes, hypertension, dyslipidemia, obesity and renal dysfunction in ALMS, it would be expected that this group of patients could develop coronary artery disease (CAD). But such cases have not been reported so far. We report a case of premature onset of CAD in one of the longest surviving patient with ALMS.     

Large artery and coronary compliance in health and disease

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Chitosan-poly(ε-caprolactone)-poly(ethylene glycol) graft copolymers: synthesis, self-assembly, and drug release behavior

B-type carbonated apatite (CAp) ceramics, nonstoichiometric hydroxyapatites (HAp) with carbonate ions (CO(3)(2-) substituting for phosphate ions, are the major inorganic components of vertebrate bones. Due to the carbonate substitution, CAp is more biodegradable than HAp and has been expected a next generation biomaterial. We have reported the electric polarization of HAp, and induced stored electric charges and electric fields in poling HAp could promote bone healing. Here, we applied electric polarization to CAp and showed the role of substituted CO(3)(2-) concentrations in CAp in its electric polarization and polarization mechanisms. We found that the electrical conductivities (σ) and stored charges (Q) of poling CAp dramatically increased with carbonate ion contents. We also found that CAp showed higher activation energy both for conduction and for depolarization than HAp, even though the values of σ and Q are much higher than those of HAp. These results suggested that the substitution of a small amount of CO(3)(2-) for PO(4)(3-) resulted in a change in the conduction and polarization mechanisms in CAp compared with HAp. Our study showed that the poling CAp has the potential to be a new functional biomaterial with biodegradation and large stored electric charges.     

Transforming growth factor-β in graft vessels: histology and immunohistochemistry

OBJECTIVES:

The biological functions of transforming growth factor-β signaling that involves Smad proteins have not been previously investigated with respect to coronary artery bypass grafts. The aim of the present study was to observe the immunostaining of proteins that are related to this signaling pathway.

METHODS:

Fifteen remnants of coronary artery bypass grafts, including nine saphenous veins, three radial arteries and three mammary arteries, were collected from 12 patients who were undergoing coronary artery bypass. Hematoxylin and eosin, Masson''s trichrome, and immunohistochemical staining of transforming growth factor-β₁, type I receptor of transforming growth factor-β, Smad2/3, Smad4, and Smad7 were performed.

RESULTS:

The saphenous veins showed more severe intimal degeneration, more severe smooth muscle cell proliferation and more collagen deposition than the arterial grafts, as evidenced by hematoxylin and eosin and Masson''s trichrome stainings. Immunohistochemical assays demonstrated that the majority of the transforming growth factor -β₁ signaling cytokines were primarily localized in the cytoplasm in the medial layers of all three types of grafts, whereas ectopic transforming growth factor-β₁, type I receptor of transforming growth factor-β, and Smad7 overexpressions in the interstices were observed particularly in the saphenous vein and radial arterial grafts.

CONCLUSION:

Enhanced transforming growth factor-β₁ signal transduction with medial smooth muscle cell proliferation and ectopic transforming growth factor-β₁, the presence of the type I receptor of transforming growth factor-β, and Smad7 overexpressions in the extracellular matrix may provide primary evidence for early or late graft failure.     

Venous thromboembolism in Croatia – Croatian Cooperative Group for Hematologic Diseases (CROHEM) study

Aim

To analyze the incidence and characteristics of venous thromboembolism (VTE) in Croatia.

Methods

The Croatian Cooperative Group for Hematologic Diseases conducted an observational non-interventional study in 2011. Medical records of patients with newly diagnosed VTE hospitalized in general hospitals in 4 Croatian counties (Šibenik-Knin, Koprivnica-Križevci, Brod-Posavina, and Varaždin County) were reviewed. According to 2011 Census, the population of these counties comprises 13.1% of the Croatian population.

Results

There were 663 patients with VTE; 408 (61.54%) had deep vein thrombosis, 219 (33.03%) had pulmonary embolism, and 36 (5.43%) had both conditions. Median age was 71 years, 290 (43.7%) were men and 373 (56.3%) women. Secondary VTE was found in 57.3% of participants, idiopathic VTE in 42.7%, and recurrent VTE in 11.9%. There were no differences between patients with secondary VTE and patients with idiopathic VTE in disease recurrence and sex. The most frequent causes of secondary VTE were cancer (40.8%), and trauma, surgery, and immobilization (38.2%), while 42.9% patients with secondary VTE had ≥2 causes. There were 8.9% patients ≤45 years; 3.3% with idiopathic or recurrent VTE. Seventy patients (10.6%) died, more of whom had secondary (81.4%) than idiopathic (18.6%) VTE (P < 0.001), and in 50.0% VTE was the main cause of death. Estimated incidence of VTE in Croatia was 1.185 per 1000 people.

Conclusion

Characteristics of VTE in Croatia are similar to those reported in large international studies. Improved thromboprophylaxis during the presence of risk factors for secondary VTE might substantially lower the VTE burden.Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major health problem in the world, associated with significant morbidity and mortality (1-9). Incidence rates for VTE mostly vary from 1 to 2 in 1000 individuals per year (1-5,7,9). PE, the most serious manifestation of VTE, has a mortality rate of more than 15% in the first 3 months after diagnosis, with short-term survival of less than 60% (10,11). Cohen et al estimated that the number of VTE-related deaths across the European Union (EU) was 543 454 per year, which was more than double the number of combined deaths in EU due to AIDS, breast and prostate cancer, and traffic accidents (8).VTE in survivors is associated with several chronic consequences of the disease that can severely impair the patients’ quality of life, including post-thrombotic syndrome (PTS) and pulmonary hypertension (PH), as well as recurrent VTE. PTS affects at least one-third of patients after DVT (8,12-15) and PH affects 4%-5% of patients after PE (8,16,17). VTE has significant incidence of recurrence: 10.1% at 6 months, 12.9% after 1 year, and 30.4% after 10 years (18).Total VTE-related costs to health care system are enormous. For example, the total cost of VTE to the UK National Health Service in 1993 was £235-£257 million (€349-€382 million), and the combined direct and indirect costs in 2004/2005 were approximately £640 million (€950 million), and are even higher when PTS is taken into account (8,19,20).VTE is a multifactorial disease, resulting from a complex interaction of genetic and acquired factors. Although some studies estimated that genetics was related to up to 60% of the risk of VTE (including FV Leiden and prothrombin G20210A mutations, deficiencies of protein C, S and antithrombin, and elevations of some procoagulant factors) (21), there is also a large number of acquired risk factors for VTE such as immobilization, surgery, trauma, cancer, pregnancy and puerperium, oral contraceptives, autoimmune diseases, and other disorders (1-8,21).In spite of the importance of VTE, there is not enough data on its incidence and characteristics in transitional countries. Also, although several studies analyzed the epidemiology of VTE in different study settings (1-9), there is still not much information on conditions present at the diagnosis of thrombosis, comparing idiopathic and secondary (provoked) VTE. Therefore, the Croatian Cooperative Group for Hematologic Diseases (CROHEM) analyzed the incidence and characteristics of idiopathic and secondary newly diagnosed VTE in Croatia in 2011, the year of the most recent national population census.     

Poly-α,β-(N-(2-hydroxyethyl)-L-aspartamide)-g-poly(1,3-trimethylene carbonate) amphiphilic graft co-polymer as a potential drug carrier

A biodegradable amphiphilic graft polymer was successfully synthesized by grafting hydrophobic poly(1,3-trimethylene carbonate) (PTMC) sequences onto a hydrophilic poly-α,β-(N-(2-hydroxyethyl)-L-aspartamide) (PHEA) backbone. The graft polymer, PHEA-g-PTMC, was synthesized by ring-opening polymerization initiated by the macroinitiator PHEA bearing hydroxyl groups without adding any catalyst. The graft polymer was characterized by Fourier transform infrared spectroscopy, ¹H-nuclear magnetic resonance spectroscopy, combined size-exclusion chromatography and multiangle laser light scattering analysis. Two drugs with distinct water solubility, prednisone acetate and tegafur, were encapsulated in the PHEA-g-PTMC nanoparticles. The in vitro release of two drugs from PHEA-g-PTMC nanoparticle drug-delivery systems was investigated.     

The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age ≤50 years)

Adiponectin, an adipocyte-derived protein, is an essential modulator of insulin sensitivity and several studies suggest an important role of adiponectin in the processes leading to atherosclerosis, thus indicating the adiponectin gene as a potential candidate for coronary artery disease (CAD). In the present study we have studied the association between two single nucleotide polymorphisms (SNPs) (+45T>G and +276 G>T) of the adiponectin gene and CAD, looking also into the possible influence of these SNPs on adiponectin plasma levels. The SNPs were analysed in a first cohort of 595 subjects, 325 with CAD and 270 matched controls. We observed a significant association (p<0.001) between the SNP +276G>T in the adiponectin gene and CAD. In multivariate analysis, carriers of the +276G>T SNP had an odds ratio (OR) for CAD of 4.99 (p<0.0007). A strong interaction between the +276G>T SNP and age was also present (OR, 1.03; p<0.0001). The increase in CAD risk was most evident among individuals with early-onset CAD (age 50 years), whereas in older CAD subjects other factors, and not the adiponectin SNP, were the major determinants. Furthermore, in CAD subjects with early-onset disease this SNP was also a significant determinant of lower levels of serum adiponectin levels. This association resulted independent from the other variables known to be associated with CAD in our population, including sex, body mass index, high-density lipoprotein and Homeostasis Model Assessment for insulin resistance. To confirm the results the +276G>T SNP was analysed in a second cohort of CAD and controls. The difference between CAD and controls in the +276G>T SNP frequencies showed a similar trend as before, although not significant. The combination of the two cohorts (1,046 subjects: 580 CAD and 466 controls) showed a statistically significant association, particularly in CAD subjects with early-onset of disease. In addition, we confirmed that in younger CAD subjects the SNP was a significant determinant of lower levels of adiponectin. In view of these results, it could be speculated that the adiponectin gene variant, or a mutation in linkage with it, determines lower adiponectin gene expression, causing in turn an increased risk to develop insulin resistance, atherosclerosis and cardiovascular disease. The significant association of the adiponectin gene in subjects with early-onset CAD also suggests that that genetic factors for late-onset diseases may exert a greater influence in younger persons, when other risk factors are not as prevalent as in older age groups.