Angiographic progression of coronary artery disease and the development of myocardial infarction

AbstractThere are few data on angiographic coronary artery anatomy in patients whose coronary artery disease progresses to myocardial infarction. In this retrospective analysis, progression of coronary artery disease between two cardiac catheterization procedures is described in 38 patients: 23 patients (Group I) who had a myocardial infarction between the two studies and 15 patients (Group II) who presented with one or more new total occlusions at the second study without sustaining an intervening infarction.In Group I the median percent stenosis on the initial angiogram of the artery related to the infarct at restudy was significantly less than the median percent stenosis of lesions that subsequently were the site of a new total occlusion in Group II (48 versus 73.5%, p < 0.05). In the infarctrelated artery in Group I, only 5 (22%) of 23 lesions were initially >70%, whereas in Group II, 11 (61%) of 18 lesions that progressed to total occlusion were initially >70% (p < 0.01). In Group I, patients who developed a Q wave infarction had less severe narrowing at initial angiography in the subsequent infarct-related artery (34%) than did patients who developed a non-Q wave infarction (80%) (p < 0.05). Univariate and multivariate analysis of angiographic and clinical characteristics present at initial angiography in Group I revealed proximal lesion location as the only significant predictor of evolution of lesions ≥ 50% to infarction.This irrespective study suggests that myocardial infarction frequently develops from previously nonsevere lesions. In addition, it is often difficult to predict the location of a subsequent infarct from analysis of the first coronary angiogram. Non-Q wave infarction is usually preceded by a more severe pre-existing stenosis than is a Q wave infarction, perhaps indicating some degree of prior myocardial protection. A prospective evaluation will be necessary to confirm these findings

Coronary angiographic morphology in myocardial infarction: A link between the pathogenesis of unstable angina and myocardial infarction

It has previously been shown that analysis of coronary morphology can separate unstable from stable angina. An eccentric stenosis with a narrow neck or irregular borders, or both, is very common in patients who present with acute unstable angina, whereas it is rare in patients with stable angina. To extend these observations to myocardial infarction, the coronary morphology of 41 patients with acute or recent infarction and nontotally occluded infarct vessels was studied. For all patients, 27 (66%) of 41 infarct vessels contained this eccentric narrowing, whereas only 2 (11%) of 18 noninfarct vessels with narrowing of 50 to less than 100% had this lesion (p < 0.001). In addition, a separate group of patients with acute myocardial infarction who underwent intracoronary streptokinase infusion were also analyzed in similar fashion. Fourteen (61%) of 23 infarct vessels contained this lesion after streptokinase infusion compared with 1 (9%) of 11 noninfarct vessels with narrowing of 50 to less than 100% (p < 0.01).Therefore, an eccentric coronary stenosis with a narrow neck or irregular borders, or both, is the most common morphologic feature on angiography in both acute and recent infarction as well as unstable angina. This lesion probably represents either a disrupted atherosclerotic plaque or a partially occlusive or lysed thrombus, or both. The predominance of this morphology in both unstable angina and acute infarction suggests a possible link between these two conditions. Unstable angina and myocardial infarction may form a continuous spectrum with the clinical outcome dependent on the subsequent change in coronary supply relative to myocardial demand

Manganese oxide catalysts for secondary zinc air batteries: from

An efficient, durable and low cost air cathode with low polarization between the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is essential for a high performance and durable secondary zinc-air battery. Different valence states and morphologies of MnxOy catalysts were synthetized via thermal treatment of EMD (generating Mn2O3 and Mn3O4) and acid digestion of synthetized Mn2O3 (producing a-MnO2) in order to develop an efficient Bifunctional Air Electrode (BAE). Change in the ratio H+ to Mn2O3 during the acid digestion affects the sample microporosity, the crystallographic plane distribution, as well as the physical and chemical adsorbed water which was related to defects, i.e. cation vacancies (Mn4+) and Mn3+. These characteristics were discussed and linked to the electrocatalytic activity. The best ORR performing catalyst was that with the higher surface water content (associated to material BET surface area) and a (310) surface as the 2nd more contributing plane (after 211). On the other hand, the catalyst with the higher structural water and with (110) and (200) crystallographic planes being the most intensity contributors (after 211) was the most OER active material. In this work, it was able to find a relationship between catalyst structure and air-efficiency through a volcano-like relationship between air-efficiency and surface water content. Air-efficiency (also take as round-efficiency discharge/charge in battery context) can be taken as a good descriptor of potentially good materials for Zn-Air secondary batteries technology. In this term, we were able to prepare a Bifunctional Air Electrode based on the selected a-MnO2 sample which demonstrated a roundefficiency of 53%, a DV around 1 V and a neglected loss of the charge potential (about 2.1 V) over the entire lifecycle test (more 200 cycles over 30 hours) with a capacity retention superior to 95%.European Commission H2020: Proyecto ZAS “Zinc Air Secondary innovative nanotech based batteries for efficient energy storage” (Grant Agreement 646186

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Leopard syndrome

LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4–5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable

Mutations in multidomain protein MEGF8 identify a Carpenter syndrome subtype associated with defective lateralization

Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutations of RAB23, encoding a small GTPase that regulates vesicular transport, are present in the majority of cases. Here, we describe a disorder caused by mutations in multiple epidermal-growth-factor-like-domains 8 (MEGF8), which exhibits substantial clinical overlap with Carpenter syndrome but is frequently associated with abnormal left-right patterning. We describe five affected individuals with similar dysmorphic facies, and three of them had either complete situs inversus, dextrocardia, or transposition of the great arteries; similar cardiac abnormalities were previously identified in a mouse mutant for the orthologous Megf8. The mutant alleles comprise one nonsense, three missense, and two splice-site mutations; we demonstrate in zebrafish that, in contrast to the wild-type protein, the proteins containing all three missense alterations provide only weak rescue of an early gastrulation phenotype induced by Megf8 knockdown. We conclude that mutations in MEGF8 cause a Carpenter syndrome subtype frequently associated with defective left-right patterning, probably through perturbation of signaling by hedgehog and nodal family members. We did not observe any subject with biallelic loss-of function mutations, suggesting that some residual MEGF8 function might be necessary for survival and might influence the phenotypes observed

Melanin-Based Coatings as Lead-Binding Agents

Interactions between metal ions and different forms of melanin play significant roles in melanin biochemistry. The binding properties of natural melanin and related synthetic materials can be exploited for nonbiological applications, potentially including water purification. A method for investigating metal ion-melanin interactions on solid support is described, with lead as the initial target. 2.5 cm discs of the hydrophobic polymer PVDF were coated with synthetic eumelanin from the tyrosinase-catalyzed polymerization of L-dopa, and with melanin extracted from human hair. Lead (Pb2+) binding was quantified by atomic absorption spectroscopy (flame mode), and the data was well fit by the Langmuir model. Langmuir affinities ranged from 3.4·103 to 2.2·104 M-1. At the maximum capacity observed, the synthetic eumelanin coating bound ~9% of its mass in lead. Binding of copper (Cu2+), zinc (Zn2+), and cadmium (Cd2+) to the synthetic-eumelanin-coated discs was also investigated. Under the conditions tested, the Langmuir affinities for Zn2+, Cd2+, and Cu2+ were 35%, 53%, and 77%, respectively, of the Langmuir affinity for Pb2+. The synthetic-eumelanin-coated discs have a slightly higher capacity for Cu2+ on a per mole basis than for Pb2+, and lower capacities for Cd2+ and Zn2+. The system described can be used to address biological questions and potentially be applied toward melanin-based water purification

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

Gorlin syndrome associated with small bowel carcinoma and mesenchymal proliferation of the gastrointestinal tract: case report and review of literature

<p>Abstract</p> <p>Background and Case Presentation</p> <p>A patient with nevoid basal cell carcinoma syndrome (Gorlin syndrome) presented with two unusual clinical features, i.e. adenocarcinoma of the small bowel and extensive mesenchymal proliferation of the lower gastrointestinal tract.</p> <p>Conclusions</p> <p>We discuss the possibility that these two features are pathogenetically linked to the formerly undescribed patient's <it>PTCH </it>germ line mutation.</p