bluuebunny/crossref_metadata_2025 huggingface dataset:
Work Out the Semantic Web Search: The Cooperative Way
Authors: Melo Dora , Rodrigues Irene Pimenta , Nogueira Vitor Beires
Published: August 2012

We propose a Cooperative Question Answering System that takes as input natural language queries and is able to return a cooperative answer based on semantic web resources, more specifically DBpedia represented in OWL/RDF as knowledge base and WordNet to build similar questions. Our system resorts to ontologies not only for reasoning but also to find answers and is independent of prior knowledge of the semantic resources by the user. The natural language question is translated into its semantic representation and then answered by consulting the semantics sources of information. The system is able to clarify the problems of ambiguity and helps finding the path to the correct answer. If there are multiple answers to the question posed (or to the similar questions for which DBpedia contains answers), they will be grouped according to their semantic meaning, providing a more cooperative and clarified answer to the user.
Acute Myeloid Leukemia Evolving from JAK 2-Positive Primary Myelofibrosis and Concomitant CD5-Negative Mantle Cell Lymphoma: A Case Report and Review of the Literature
Authors: Treaba Diana O. , Khedr Salwa , Mangray Shamlal , Jackson Cynthia , Castillo Jorge J. , Winer Eric S.
Published: August 2012

Primary myelofibrosis (formerly known as chronic idiopathic myelofibrosis), has the lowest incidence amongst the chronic myeloproliferative neoplasms and is characterized by a rather short median survival and a risk of progression to acute myeloid leukemia (AML) noted in a small subset of the cases, usually as a terminal event. As observed with other chronic myeloproliferative neoplasms, the bone marrow biopsy may harbor small lymphoid aggregates, often assumed reactive in nature. In our paper, we present a 70-year-old Caucasian male who was diagnosed with primary myelofibrosis, and after 8 years of followup and therapy developed an AML. The small lymphoid aggregates noted in his bone marrow were neoplastic in nature and represented bone marrow involvement by a CD5-negative mantle cell lymphoma (MCL) that presented without any associated lymphadenopathy. We reviewed the English medical literature to identify a single case report of simultaneous association of AML and a MCL in the bone marrow. The unusual association presented here suggests an increase in observer awareness to apparently benign lymphoid aggregates in chronic myeloproliferative neoplasms.
Elastic Modulus Determination of Al‐Cu Film Alloys Prepared by Thermal Diffusion
Authors: Huerta E. , Oliva A. I. , Avilés F. , González-Hernández J. , Corona J. E.
Published: August 2012

Elastic moduli of 50–250 nm thick Al‐50 at % Cu film alloys deposited by thermal evaporation on Kapton substrates and postformed by thermal diffusion are investigated. Formation of the Al2Cu alloy phase was confirmed by X‐ray photoelectron spectroscopy (XPS). Surface morphology was examined by atomic force microscopy (AFM) and scanning electron microscopy (SEM) before and after tensile mechanical testing. Force‐strain curves of the Al‐Cu alloy were obtained by subtracting the effect of the force‐strain Kapton curves from the corresponding curves of the Al‐Cu/Kapton system. A reduction in the elastic modulus of the Al‐Cu alloys from 106.1 to 77.8 GPa with the increase of alloy thickness was obtained. Measured elastic moduli were between the reported bulk modulus for Al and Cu. Reductions in the surface roughness and increments in the grain size were measured after tensile testing of the Al‐Cu alloys.
Histopathological Growth Pattern, Proteolysis and Angiogenesis in Chemonaive Patients Resected for Multiple Colorectal Liver Metastases
Authors: Eefsen Rikke Løvendahl , Van den Eynden Gert G. , Høyer-Hansen Gunilla , Brodt Pnina , Laerum Ole Didrik , Vermeulen Peter B. , Christensen Ib Jarle , Wettergren André , Federspiel Birgitte , Willemoe Gro L. , Vainer Ben , Østerlind Kell , Illemann Martin
Published: August 2012

The purpose of this study was to characterise growth patterns, proteolysis, and angiogenesis in colorectal liver metastases from chemonaive patients with multiple liver metastases. Twenty-four patients were included in the study, resected for a median of 2.6 metastases. The growth pattern distribution was 25.8% desmoplastic, 33.9% pushing, and 21% replacement. In 20 patients, identical growth patterns were detected in all metastases, but in 8 of these patients, a second growth pattern was also present in one or two of the metastases. In the remaining 4 patients, no general growth pattern was observed, although none of the liver metastases included more than two growth patterns. Overall, a mixed growth pattern was demonstrated in 19.3% of the liver metastases. Compared to metastases with pushing, those with desmoplastic growth pattern had a significantly up-regulated expression of urokinase-type plasminogen activator receptor (P=0.0008). Angiogenesis was most pronounced in metastases with a pushing growth pattern in comparison to those with desmoplastic (P=0.0007) and replacement growth pattern (P=0.021). Although a minor fraction of the patients harboured metastases with different growth patterns, we observed a tendency toward growth pattern uniformity in the liver metastases arising in the same patient. The result suggests that the growth pattern of liver metastases is not a random phenomenon.
On the Rational Approximation of Analytic Functions Having Generalized Types of Rate of Growth
Authors: Kumar Devendra
Published: August 2012

The present paper is concerned with the rational approximation of functions holomorphic on a domainG⊂C, having generalized types of rates of growth. Moreover, we obtain the characterization of the rate of decay of product of the best approximation errors for functionsfhaving fast and slow rates of growth of the maximum modulus.
Interspike Interval Based Filtering of Directional Selective Retinal Ganglion Cells Spike Trains
Authors: Martiniuc Aurel Vasile , Knoll Alois
Published: August 2012

The information regarding visual stimulus is encoded in spike trains at the output of retina by retinal ganglion cells (RGCs). Among these, the directional selective cells (DSRGC) are signaling the direction of stimulus motion. DSRGCs' spike trains show accentuated periods of short interspike intervals (ISIs) framed by periods of isolated spikes. Here we use two types of visual stimulus, white noise and drifting bars, and show that short ISI spikes of DSRGCs spike trains are more often correlated to their preferred stimulus feature (that is, the direction of stimulus motion) and carry more information than longer ISI spikes. Firstly, our results show that correlation between stimulus and recorded neuronal response is best at short ISI spiking activity and decrease as ISI becomes larger. We then used grating bars stimulus and found that as ISI becomes shorter the directional selectivity is better and information rates are higher. Interestingly, for the less encountered type of DSRGC, known as ON-DSRGC, short ISI distribution and information rates revealed consistent differences when compared with the other directional selective cell type, the ON-OFF DSRGC. However, these findings suggest that ISI-based temporal filtering integrates a mechanism for visual information processing at the output of retina toward higher stages within early visual system.
Complete Cervical Avulsion with Intravaginal Misoprostol for Second Trimester Pregnancy Termination
Authors: Sajjan G. R. , Patil Neelamma , Kaur Manpreet , Shirgur Shobha , Nandi Suvarna , Ashwini V.
Published: August 2012

Intravaginal misoprostol, a synthetic PGE1 analogue, has largely replaced all other techniques for pregnancy termination in II trimester, because of its successful results. Incidence of II trimester pregnancy termination has also increased in the present days, because of prenatal diagnosis of pregnancies with serious fetal abnormalities like cardiovascular and skeletal malformations. But there are serious and life threatening complications reported with the use of intravaginal misoprostol. Here we are reporting a case of complete avulsion of cervix from lower part of the uterus, with the use of intravaginal misoprostol, for II trimester termination of pregnancy. So, clinicians dealing with II trimester termination of pregnancy should be aware of such complications.
Nanofilled Composite Restorations with Different Adhesives Strategies: Clinical Cases
Authors: Carvalho Luana Dutra de , Machado Renata Gondo , Lopes Guilherme Carpena , Andrada Mauro Caldeira de
Published: August 2012

The esthetic procedures with composites are widely applied, both to posterior and anterior teeth to restore caries cavities, to replace failed restorations, or to make cosmetic procedures. The materials selected to each case may make the difference in the clinical result. This paper presents two clinical cases made with a nanofilled composite resin system used in different bond strategies. In the first, a wide posterior class I restoration, the self-etching strategy was used. The second, an esthetic anterior restoration, was made using the prior etching with phosphoric acid and a hydrophobic adhesive.
Strength Analysis Modelling of Flexible Umbilical Members for Marine Structures
Authors: Sævik S. , Gjøsteen J. K. Ø.
Published: August 2012

This paper presents a 3‐dimensional finite element formulation for predicting the behaviour of complex umbilical cross‐sections exposed to loading from tension, torque, internal and external pressure including bending. Helically wound armours and tubes are treated as thin and slender beams formulated within the framework of small strains but large displacements, applying the principle of virtual displacements to obtain finite element equations. Interaction between structural elements is handled by 2‐ and 3‐noded contact elements based on a penalty parameter formulation. The model takes into account a number of features, such as material nonlinearity, gap and friction between individual bodies, and contact with external structures and with a full 3‐dimensional description. Numerical studies are presented to validate the model against another model as well as test data.
Thalidomide in Total Therapy 2 Overcomes Inferior Prognosis of Myeloma with Low Expression of the Glucocorticoid Receptor GeneNR3C1
Authors: Heuck Christoph J. , Szymonifka Jackie , Hansen Emily , Shaughnessy John D. , Usmani Saad Z. , van Rhee Frits , Anaissie Elias , Nair Bijay , Waheed Sarah , Alsayed Yazan , Petty Nathan , Bailey Clyde , Epstein Joshua , Hoering Antje , Crowley John , Barlogie Bart
Published: August 2012

Purpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the impact of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 on survival outcomes in the context of treatment with or without thalidomide.

Experimental Design: We investigated the clinical impact of gene expression profiling (GEP)–derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to total therapy 2 (TT2).

Results: Low NR3C1 expression levels had a negative impact on progression-free survival (PFS; HR, 1.47; P = 0.030) and overall survival (OS; HR, 1.90; P = 0.002) in the no-thalidomide arm. Conversely, there was a significant clinical benefit of thalidomide for patients with low receptor levels (OS: HR, 0.54; P = 0.015; PFS: HR, 0.54; P = 0.004), mediated most likely by thalidomide's upregulation of NR3C1. In the context of both baseline and relapse parameters, post-relapse survival (PRS) was adversely affected by low NR3C1 levels at relapse in a multivariate analysis (HR, 2.61; P = 0.012).

Conclusion: These findings justify the inclusion of NR3C1 expression data in the work-up of patients with myeloma as it can significantly influence the choice of therapy and, ultimately, OS. The identification of an interaction term between thalidomide and NR3C1 underscores the importance of pharmacogenomic studies in the systematic study of new drugs. Clin Cancer Res; 18(19); 5499–506. ©2012 AACR.
Contrasted Outcomes to Gefitinib on Tumoral IGF1R Expression in Head and Neck Cancer Patients Receiving Postoperative Chemoradiation (GORTEC Trial 2004-02)
Authors: Thariat Juliette , Bensadoun René-Jean , Etienne-Grimaldi Marie-Christine , Grall Dominique , Penault-Llorca Frédérique , Dassonville Olivier , Bertucci Francois , Cayre Anne , De Raucourt Dominique , Geoffrois Lionnel , Finetti Pascal , Giraud Philippe , Racadot Séverine , Morinière Sylvain , Sudaka Anne , Van Obberghen-Schilling Ellen , Milano Gérard
Published: August 2012

Purpose: Intermediate/high-risk operated patients with head and neck cancer may benefit from the addition of EGF receptor (EGFR) inhibitor gefitinib to chemoradiation. This study was designed to assess improved outcomes and identify predictive biomarkers.

Experimental Design: Patients provided informed consent for tumor biomarker analyses and, when eligible, were further enrolled in the therapeutic CARISSA multicenter randomized phase II trial of postoperative irradiation with cisplatin + gefitinib (GORTEC 2004-02-NCT00169221).

Results: Seventy-nine patients were included in the biomarker study, whereas 27 did not meet prerequisites for randomization between gefitinib and placebo. Two-year disease-free survival (DFS) rate was 65.0% and did not differ between randomized patients treated with gefitinib or placebo (P = 0.85). The similarity of DFS curves between nonrandomized patients (n = 27), randomized patients without gefitinib (n = 27), and randomized patients receiving gefitinib (n = 25), and similar histoclinical parameter distributions for all groups, allowed us to conduct statistical analyses on the entire population. On multivariate analysis, elevated expression of PAK1 by Western blotting, CD31 and membranous insulin-like growth factor 1 receptor (IGF1R) both by immunohistochemistry was significantly associated with shorter DFS. There was a significant interaction between IGF1R and gefitinib. Gefitinib abolished the prognostic discriminative power of high IGF1R expression; patients with elevated IGF1R expression benefited from gefitinib whereas those with low IGF1R fared worse.

Conclusion: Gefitinib treatment affords no significant clinical benefit on DFS in an unselected population of patients with head and neck cancer. Our results point to the potential advantage of personalizing treatment for gefitinib based on tumoral IGF1R expression. This should foster confirmatory analyses in trials involving EGFR-targeting agents. Clin Cancer Res; 18(18); 5123–33. ©2012 AACR.
Molecular Identification of a New Splicing Variant of the MLL-MLLT11 Fusion Transcript in an Adult with Acute Myeloid Leukemia and t(1;11)(q21;q23)
Authors: Lee Sang-Guk , Park Tae Sung , Yang John Jeongseok , Oh Seung Hwan , Cho Eun Hae , Lee Sanggyu , Oh Doyeun , Huh Ji Young , Marschalek Rolf , Meyer Claus
Published: August 2012

More than 70 different mixed lineage leukemia (MLL) rearrangements involving 11q23 have been molecularly characterized in acute leukemia. Among these, the MLLT11 gene is highly unique as MLL fusion partner because the entire open reading frame is usually fused in-frame to the N-terminal portion of the MLL gene. By using molecular genetic methods, we identified the chromosomal fusion site within MLL exon 10 sequences which were fused to the MLLT11 intron 1 sequences. This unusual break site results in the creation of two in-frame MLL-MLLT11 fusion transcripts in this acute myeloid leukemia patient with t(1;11)(q21;q23). One fusion transcript represents a normal splice product, while the other contains intronic sequences and a cryptic splice event in order to generate an intact fusion transcript. We also reviewed all published articles which have reported t(1;11)(q21;q23) in myeloid or lymphoid neoplasm and attempted to summarize these published data. Of interest, pediatric patients displayed a significant larger portion of unique balanced translocations (n = 40), while complex karyotypes were less often identified (n = 12). Vice versa, in adult leukemia patients, complex karyotypes (n = 5) were more frequent than unique balanced translocations (n = 2).
Role of Adherens Junction Proteins in Differential Herpes Simplex Virus Type 2 Infectivity in Communication-Competent and -Deficient Cell Lines
Authors: Miezeiewski Blair , McShane-Kay Kerry , Woodruff Richard I. , Mbuy Gustave K.N. , Knabb Maureen T.
Published: August 2012

Background: Gap junctional intercellular communication decreases with HSV-2 infection. To determine the importance of functional gap junctions for infectivity, we compared HSV-2 growth in communication-competent and -deficient cell lines. Methods: HSV-2 infectivity was tested in five cell lines: WB rat liver epithelial cells (communication-competent), WB-aB1 (communication-deficient), WB-a/32-10 (communication-rescued), HeLa (communication-deficient), and Cx43-transfected HeLa (communication-rescued) cells. HSV-2 growth curves and indirect immunofluorescence labeling of viral and cell proteins were performed in wild-type and mutant WB cells. Results: Although wild-type WB cells were highly permissive for HSV-2 infection, virus production was significantly attenuated in communication-deficient and -rescued mutant WB cells. HeLa exhibited no difference in infectivity between communication-competent and -deficient cell lines. Tight and adherens junction proteins, including zonula occludens-1 and nectin-1, were not different in the WB cell lines. However, E-cadherin levels were elevated and β-catenin was found to co-localize with glycoprotein E, a viral glycoprotein associated with cell-to-cell spread, in the mutant WB cells. Conclusions: These results suggest that attenuated viral production in mutant WB cells is due to viral protein co-localization with adherens junction proteins rather than the loss or restoration of functional gap junctions.
Wintering in Antarctica: Impact on Immune Response of Indian Expeditioners
Authors: Yadav Anand Prakash , Mishra Kamla Prasad , Ganju Lilly , Singh Shashi Bala
Published: August 2012

The immune system is one of the major thrust areas in understanding the effects of adverse climatic conditions on human health. Exposure to the Antarctic environment, such as isolation, cold, UV radiations, magnetic field, blizzards, circadian biorhythms, and fear of the unknown, modify various components of the immune system. Members of Antarctic expeditions suffer significant emotional strain as a result of physical isolation and social deprivation. The present study was performed on winter team members of the 28th Indian Scientific Expedition. In this study, different immunological parameters, which mainly include cytokines (TNF-α, IFN-γ, TGF-β, and IL-4), chemokine MIP-1α, immunoglobulins (IgA, IgM and IgG), cortisol and netrin-1, were assayed in sera by ELISA. Results showed that TNF-α and MIP-1α levels were significantly increased in March, May and August while IFN-γ levels were increased in March and May while TGF-β levels showed a significant decrease in March and May. Serum IgA levels were significantly increased during the entire period of the stressful expedition. Therefore, the present study suggests that serum IgA could be a potential biomarker for extreme environmental conditions.
Ambient Air Pollutants and Acute Case-Fatality of Cerebro-Cardiovascular Events: Takashima Stroke and AMI Registry, Japan (1988–2004)
Authors: Turin Tanvir Chowdhury , Kita Yoshikuni , Rumana Nahid , Nakamura Yasuyuki , Ueda Kayo , Takashima Naoyuki , Sugihara Hideki , Morita Yutaka , Ichikawa Masaharu , Hirose Kunihiko , Nitta Hiroshi , Okayama Akira , Miura Katsuyuki , Ueshima Hirotsugu
Published: August 2012

Background: Apart from the conventional risk factors, cerebro-cardiovascular disease (CVD) are also reported to be associated with air pollution, thus lowering the level of exposure might contribute in prevention activities to reduce the associated adverse outcomes. Though few studies conducted in Japan have reported on the CVD mortality but none have explored the effect of air pollutant exposure on the acute case-fatality of CVD. We investigated the effects of air pollution exposure on acute case-fatality of stroke and acute myocardial infarction (AMI) in a setting where pollutant levels are rather low. Methods: We leveraged the data from the Takashima Stroke and AMI Registry, which covers a population of approximately 55,000 in Takashima County located in central Japan. The study period of 6,210 days (16 years, leap years also taken into account) were divided into quartiles of daily average pollutant concentration; suspended particulate matter (SPM), sulfur dioxide (SO2), nitrogen dioxide (NO2), and photochemical oxidants (Ox). The stroke and AMI events were categorized to corresponding quartiles based on the pollution levels of the onset day. To study the effects of air pollutants, we estimated the fatality rate ratio across quartiles of the pollutants where the lowest quartile served as the reference. Results: There were 307 (men: 153 and women: 154) fatal stroke cases within 28 days of onset among the 2,038 first ever stroke during 1988–2004. In the same period, there were 142 (men: 94 and women: 54) fatal AMI cases within 28 days of onset among the 429 first ever AMI events. The mean of the measured pollutant levels were as follows: SPM 26.9 µg/m3, SO2 3.9 ppb, NO2 16.0 ppb, and Ox 28.4 ppb. Among the pollutants, higher levels of NO2 showed increased fatality risk. In multi-pollutant model, the highest quartile of NO2 was associated with 60% higher stroke case-fatality risk in comparison to lowest quartile of NO2. In the fully adjusted model the fatality-rate ratio was 1.65 (95% CI 1.06–2.57). This association was more prominent among stroke subtype of cerebral infarction. Other pollutant levels did not show any association with stroke or AMI case-fatality. Conclusion: We observed association between NO2 levels, an index of traffic related air pollution, with the acute case-fatality of stroke, especially cerebral infarction in our study population. Further studies are needed in different regions to determine the association between ambient air pollutants and acute cardiovascular fatalities.
Early Neurological Deterioration within 24 Hours after Intravenous rt-PA Therapy for Stroke Patients: The Stroke Acute Management with Urgent Risk Factor Assessment and Improvement rt-PA Registry
Authors: Mori Mayumi , Naganuma Masaki , Okada Yasushi , Hasegawa Yasuhiro , Shiokawa Yoshiaki , Nakagawara Jyoji , Furui Eisuke , Kimura Kazumi , Yamagami Hiroshi , Kario Kazuomi , Okuda Satoshi , Koga Masatoshi , Minematsu Kazuo , Toyoda Kazunori
Published: August 2012

Background: The initial 24 h after thrombolysis are critical for patients’ conditions, and continuous neurological assessment and blood pressure measurement are required during this time. The goal of this study was to identify the clinical factors associated with early neurological deterioration (END) within 24 h of stroke patients receiving intravenous recombinant tissue plasminogen activator (rt-PA) therapy and to clarify the effect of END on 3-month outcomes. Methods: A retrospective, multicenter, observational study was conducted in 10 stroke centers in Japan. A total of 566 consecutive stroke patients [211 women, 72 ± 12 years old, the median initial NIH Stroke Scale (NIHSS) score of 13] treated with intravenous rt-PA (0.6 mg/kg alteplase) was studied. END was defined as a 4-point or greater increase in the NIHSS score at 24 h from the NIHSS score just before thrombolysis. Results: END was present in 56 patients (9.9%, 18 women, 72 ± 10 years old) and was independently associated with higher blood glucose [odds ratio (OR) 1.17, 95% confidence intervals (CI) 1.07–1.28 per 1 mmol/l increase, p < 0.001], lower initial NIHSS score (OR 0.92, 95% CI 0.87–0.97 per 1-point increase, p = 0.002), and internal carotid artery (ICA) occlusion (OR 5.36, 95% CI 2.60–11.09, p < 0.001) on multivariate analysis. Symptomatic intracranial hemorrhage within the initial 36 h from thrombolysis was more common in patients with END than in the other patients (per NINDS/Cochrane protocol, OR 10.75, 95% CI 4.33–26.85, p < 0.001, and per SITS-MOST protocol, OR 12.90, 95% CI 2.76–67.41, p = 0.002). At 3 months, no patients with END had a modified Rankin Scale (mRS) score of 0–1. END was independently associated with death and dependency (mRS 3–6, OR 20.44, 95% CI 6.96–76.93, p < 0.001), as well as death (OR 19.43, 95% CI 7.75–51.44, p < 0.001), at 3 months. Conclusions: Hyperglycemia, lower baseline NIHSS score, and ICA occlusion were independently associated with END after rt-PA therapy. END was independently associated with poor 3-month stroke outcome after rt-PA therapy.
Can Roads Be Used as Transects for Primate Population Surveys?
Authors: Hilário Renato R. , Rodrigues Flávio H.G. , Chiarello Adriano G. , Mourthé Ítalo
Published: August 2012

Line transect distance sampling (LTDS) can be applied to either trails or roads. However, it is likely that sampling along roads might result in biased density estimates. In this paper, we compared the results obtained with LTDS applied on trails and roads for two primate species(Callithrix penicillataandCallicebus nigrifrons)to clarify whether roads are appropriate transects to estimate densities. We performed standard LTDS surveys in two nature reserves in south-eastern Brazil. Effective strip width and population density were different between trails and roads forC. penicillata, but not forC. nigrifrons. The results suggest that roads are not appropriate for use as transects in primate surveys, at least for some species. Further work is required to fully understand this issue, but in the meantime we recommend that researchers avoid using roads as transects or treat roads and trails as covariates when sampling on roads is unavoidable.
A de novo sSMC(22) Characterized by High-Resolution Arrays in a Girl with Cat-Eye Syndrome without Coloboma
Authors: Córdova-Fletes C. , Domínguez M.G. , Vázquez-Cárdenas A. , Figuera L.E. , Neira V.A. , Rojas-Martínez A. , Ortiz-López R.
Published: August 2012

Cat-eye syndrome (CES) results from trisomy or tetrasomy of proximal 22q originated by a small supernumerary marker chromosome (sSMC). Two critical regions for the major clinical features of CES (CESCRs) have been suggested; however, CES clinical presentation often does not correlate with the sSMC genetic content. We report here a CES girl without coloboma and carrier of a de novo type I sSMC(22) as determined by G- and C-banding, NOR staining and microarrays. This sSMC included 6 distal genes outside the original CESCR and led to a tetrasomy for 22q11.1–22q11.21. The patient’s final karyotype was 47,XX,+psu dic(22)(q11.21).arr 22q11.1q11.21(15,250,000–17,035,860)×4 dn. The amplified region outside of CESCR included some genes that may be related to neurologic, heart and renal abnormalities. Conversely, even though the amplification included the CECR2 gene, a major candidate for eye features, there was no coloboma in the patient. The genetic delineation of the present sSMC further strengthens that the CES clinical presentation does not fit completely with the duplicated genetic content and that CES is actually a genomic disorder. Furthermore, since we observed no mosaicism, we believe that other mechanisms might be behind the variability of CES phenotypes as well, mainly those related with functional interactions among amplified genes.
Restriction fragment length polymorphism of hsp70 gene, localized in the RT1 complex, is associated with hypertension in spontaneously hypertensive rats.
Authors: Hamet P , Kong D , Pravenec M , Kunes J , Kren V , Klir P , Sun Y L , Tremblay J
Published: August 2012

Previous studies from our laboratory have demonstrated that the intermediate phenotype of thermosensitivity is present in hypertensive mice and rats. Increased expression of hsp70 caused by increased transcription rate was demonstrated in vivo, in organs, and in cultured cells from spontaneously hypertensive rats and hypertensive mice. In this study, a polymorphism of this gene was revealed with BamHI enzyme by using a human hsp70 probe. A 4.4-kb fragment was visualized in normotensive rats (Brown-Norway BN.lx and Sprague-Dawley), and a 3.0-kb fragment was found in spontaneously hypertensive rats (SHR) of three different origins and in Wistar and Buffalo rats. Both fragments were present in the Wistar-Kyoto rat strain. The present study mapped the polymorphism of hsp70 into the RT1 complex in BN.1K and SHR.1N congenic strains. The hsp70 restriction fragment length polymorphism is associated with a blood pressure difference of 15 mm Hg in recombinant inbred strains. These results justify the search for a mechanism by which hsp70 could influence blood pressure.
Antihypertensive therapy in diabetic patients.
Authors: Trost B N , Weidmann P , Beretta-Piccoli C
Published: August 2012

Hypertension in diabetic patients is more common than in controls, contributes substantially to their increased cardiovascular morbidity and mortality, and should be treated as accurately as diabetes mellitus itself. After appropriate exclusion of secondary forms, the first therapeutic step consists of reduction of overweight, salt intake, and smoking; the omission of interfering drugs; and adequate instruction. Step 2 has usually been the prescription of a diuretic drug, in spite of its known side effects on carbohydrate and lipid metabolism. A new possible alternative may be a calcium antagonist. Results in 10 hypertensive diabetic persons suggest that at a dose that normalizes blood pressure, neither carbohydrate nor lipid metabolism is altered, uric acid decreases, the exaggerated cardiovascular reactivity toward norepinephrine becomes normal, and the pressor dose for angiotensin II tends to rise. Body weight, blood volume, exchangeable sodium, as well as plasma and urinary sodium, potassium, and creatinine levels were unchanged. The third therapeutic step is the addition of a cardioselective beta blocker in a moderate dose. This avoids the disadvantages of beta 2-adrenergic blockade such as decreased insulin output, prolonged hypoglycemia, diminished glucagon secretion, and increased vasospasticity during hypoglycemic states, as well as aggravation of peripheral vascular disease. Alternatives are other sympatholytics with their known tendency to cause or increase orthostatic and sexual problems or, again, a calcium antagonist. In step 4, a hydralazine-type drug or prazosine is added. The fifth step, which adds minoxidil or captopril to the previous drugs, should only be taken after a specialist reevaluates the overall situation.
Hypertension and cardiovascular risk factors in hemodialyzed diabetic patients.
Authors: Ritz E , Strumpf C , Katz F , Wing A J , Quellhorst E
Published: August 2012

In a retrospective study, the cause of death and the cardiovascular risk conferred by hypertension and other risk factors were analyzed in 200 diabetic and 200 nondiabetic patients who were matched for age, sex, year of admission, and center of treatment. Total and cardiovascular mortality were considerably higher in diabetics, cardiovascular mortality being 4.8 times higher in patients with type I and 3.0 times higher in those with type II diabetes compared to matched controls. Cardiovascular mortality progressively increased with age and had not improved in recent years. In both types I and II diabetes, the rate (58%) and proportion (38%) of deaths from cardiovascular causes were significantly higher in diabetics than in matched controls. Myocardial infarction (13%) and stroke (7%) accounted only for a minority of cardiovascular mortality, the majority (80%) being due to "sudden death of unknown cause." Autopsy was carried out in 33% of patients with sudden death. A documented history of long-standing hypertension increased cardiovascular death in diabetic more than in nondiabetic patients. Diabetic retinopathy (an index of microangiopathy) and absence of peripheral pulses, amputation, or history of myocardial infarction, stroke, or transient ischemic attacks (as evidence of macroangiopathy) caused surprisingly little increase in relative risk for cardiovascular death. In diabetics but not in nondiabetics, cardiomegaly, particularly in association with electrocardiographic abnormalities, was a strong predictor of cardiovascular death.
Continuous ambulatory peritoneal dialysis in diabetic patients. The relationship of hypertension to retinopathy and cardiovascular complications.
Authors: Rottembourg J , Remaoun M , Maiga K , Bellio P , Issad B , Boudjemaa A , Cossette P Y
Published: August 2012

From August 1978 to December 1983, 51 insulin-dependent diabetic patients with end-stage renal disease were selected for treatment by continuous ambulatory peritoneal dialysis. There were 27 male and 24 female patients, with a mean age of 52.3 +/- 13.5 years. Forty-five patients dialyzed themselves by continuous ambulatory peritoneal dialysis and six were treated by continuous cyclic peritoneal dialysis. All patients were treated at home. The cumulative duration of treatment was 65.6 patient-years; 14 patients were dialyzed for at least 24 months. Extrarenal complications were frequent at start of continuous ambulatory peritoneal dialysis, including hypertension in 48 patients, proliferative retinopathy in 50, and cardiovascular complications in 30. Age appeared to be the major risk factor, with success rates at 2 years of 78% in patients under age 50 years and only 50% in patients over age 50. The main cause of death was vascular and the main cause of transfer to other therapeutic modalities was abdominal complications or malnutrition or both. Excellent control of blood pressure, uremia, and blood glucose levels was obtained on a daily program of four exchanges. Improvement in visual status was frequently observed, mainly in the young population. In patients with juvenile diabetes, continuous ambulatory peritoneal dialysis should be part of an integrated program with transplantation, while in the elderly, the method offers a unique opportunity for them to treat themselves at home.
Adverse impact of hypertension on diabetic recipients of transplanted kidneys.
Authors: Friedman E A , Chou L M , Beyer M M , Butt K M , Manis T
Published: August 2012

The effect of hypertension on patient and allograft survival in 60 diabetic recipients of transplanted kidneys was assessed by retrospective chart analysis. Hypertension was present in 81% of recipients. Of eight of these patients who became normotensive after transplantation, all had functioning allografts and one died. By contrast, persistent hypertension after transplantation was associated with a higher mortality rate (25 of 54, 48%) and loss of kidney graft function (19 of 54, 35%). At a mean of 21 months after transplantation, living hypertensive diabetic recipients had worse renal function (mean serum creatinine of 3.1 mg/dl) than did nonhypertensive recipients (mean serum creatinine of 1.6 mg/dl). It is concluded that hypertension is a significant risk factor for diabetic patients and kidneys after transplantation.
Abnormalities of platelet function in hypertension and diabetes.
Authors: Hamet P , Skuherska R , Pang S C , Tremblay J
Published: August 2012

The increased frequency of hypertension in diabetes and of abnormalities of carbohydrate metabolism in hypertension are now well established. It is conceivable that the high coincidence of the two diseases is based on a common metabolic defect. Studies of platelets permit the evaluation of the stimulatory, phosphoinositol-linked and the inhibitory, cyclic adenosine 3',5'-monophosphate-dependent pathways of cell activation. Furthermore, platelets may be relevant for the development of angiopathy through their contents of growth factors. Abnormalities of platelet aggregation have been demonstrated in hypertension and diabetes. They are accompanied by exaggerated stimulation of adenylate cyclase in hypertension and abnormal activity of cyclic guanosine 3',5'-monophosphate phosphodiesterase in diabetes. Defective function of platelets is also observed in patients and animals when the two diseases are present at the same time. Both increased and decreased aggregation have been described in these two diseases in the literature. The apparent discrepancies may be due to different types of platelet preparation, evaluation of aggregation, evolution of defect with age, and form of the disease. Integrated studies of biochemical mechanisms responsible for cell activation are needed to characterize the exact defect present in diabetes and hypertension in platelets.
A review of 10 years of experience with indapamide as an antihypertensive agent.
Authors: Thomas J R
Published: August 2012

Indapamide is an effective antihypertensive agent for which a dual mechanism of action has been put forward: a limited diuretic activity combined with antivasoconstrictive effects, resulting in decreased peripheral vascular resistance. Results from clinical trials show that 2.5 mg indapamide once daily effectively reduces arterial blood pressure in about two-thirds of patients with mild to moderate hypertension and that this reduction is related to the severity of the hypertension. As a rule, indapamide's blood pressure-reducing effect is rapid in onset (within 1 or 2 weeks) and by 1 month reaches 65% of its maximum, which occurs after 3 to 4 months of treatment. No tachyphylaxis has been observed during long-term treatment, nor has withdrawal syndrome at discontinuation of therapy. Indapamide has been successfully combined with beta blockers, methyldopa, and other antihypertensive agents, adding considerable effectiveness without noticeable increase in adverse reactions. In general, the drug is well tolerated and side effects are mild and rare. Possibly in relation to its limited diuretic activity at 2.5 mg daily, long-term treatment seldom elicits significant changes in electrolyte balance. In addition, indapamide does not induce deleterious effects on carbohydrate and lipid metabolism. Indapamide is an effective, well-tolerated, first-line antihypertensive agent. The fact that long-term administration does not induce biochemical abnormalities that constitute cardiovascular risk factors indicates another advantage of the drug.
Indapamide in the treatment of hypertension in non-insulin-dependent diabetes.
Authors: Raggi U , Palumbo P , Moro B , Bevilacqua M , Norbiato G
Published: August 2012

The antihypertensive effect of indapamide, a new thiazide derivative, has a low diuretic effect and a primary action on vascular smooth muscle. It was evaluated in a series of 20 patients with non-insulin-dependent diabetes (age range 47-75 years) who had arterial hypertension of mild to moderate degree treated with hypoglycemic agents and/or diet. Indapamide, 2.5 mg, was given as a single daily dose for 6 months. A statistically significant reduction of systolic and diastolic pressures was observed in both supine and upright positions. This decrease was significant beginning in the first month of therapy (p less than 0.001). No significant modifications of fasting glycemia, postprandial glycemia, and glycosylated hemoglobin were noted. No significant changes were observed in serum sodium, potassium, chloride, calcium, and uric acid. Indapamide is an effective and practical treatment of hypertension of mild to moderate degree in patients with diabetes. The absence of effect on glucose metabolism makes it an especially interesting drug.
Serum lipoproteins during treatment with the antihypertensive agent indapamide.
Authors: Gerber A , Weidmann P , Bianchetti M G , Ferrier C , Laederach K , Mordasini R , Riesen W , Bachmann C
Published: August 2012

Considering the documented, potentially undesirable influence of various thiazide-type or loop diuretics on serum lipoproteins, we prospectively investigated in 69 men (mean age +/- SEM, 32 +/- 1 years) the metabolic effects of the new diuretic-antihypertensive compound indapamide. Compared to placebo, indapamide (2.5 mg/day) given for 6 to 8 weeks lowered (p less than 0.02 to less than 0.001) blood pressure (supine values from 148/98 +/- 3/2 to 137/93 +/- 3/2) in 29 men with mild to moderate essential hypertension, but not in 40 healthy men. In both groups, significant (p less than 0.05 to less than 0.001) decreases in body weight (-0.8 kg) and plasma potassium (-0.6 mmol/L), and increases in plasma uric acid (+20%), renin activity (+200%), and aldosterone documented good compliance. There were no significant changes in total cholesterol (in all subjects, from 208 +/- 6 to 213 +/- 6 mg/dl), low- or very low-density lipoprotein (VLDL) cholesterol (127 +/- 6 to 129 +/- 6 and 21 +/- 1 to 21 +/- 2 respectively), high-density lipoprotein cholesterol (50 +/- 1 to 51 +/- 1 mg/dl), total triglycerides (Tg) (108 +/- 5 to 112 +/- 6 mg/dl), VLDL-Tg, apoproteins A1 and A2, plasma glucose, epinephrine, norepinephrine, sodium, calcium, magnesium, and creatinine; apoprotein B (84 +/- 2 to 88 +/- 3 mg/dl) and plasma insulin after glucose loading dose tended to be increased minimally. The absence of distinct lipoprotein alterations after short-term indapamide treatment may be of clinical and epidemiological interest.
Serum lipoprotein levels during long-term treatment of hypertension with indapamide.
Authors: Meyer-Sabellek W , Gotzen R , Heitz J , Arntz H R , Schulte K L
Published: August 2012

The beneficial effect of antihypertensive pharmacotherapy in decreasing morbidity and mortality in hypertensive patients may be counteracted by metabolic and biochemical disturbances, such as hypokalemia, hyperglycemia, hyperuricemia, and hyperlipoproteinemia, that occur with the administration of thiazides and related diuretics. Antiatherogenic high-density lipoprotein cholesterol may be unchanged, whereas the potentially atherogenic low-density lipoprotein cholesterol may be increased by long-term therapy with thiazide diuretics. Indapamide is a methylindoline antihypertensive diuretic with a considerable peripheral vasodilatory effect. At a low dose of 2.5 mg daily, it did not alter total circulating cholesterol, in contrast to chlorthalidone. High-density lipoprotein cholesterol levels increased significantly in 20 hypertensive men after 6 months of therapy with indapamide, resulting in a significant fall of the low-density lipoprotein/high-density lipoprotein ratio, an atherogenic risk factor, regardless of preexisting lipid disorders.
Hypertension in diabetes as related to nephropathy. Early blood pressure changes.
Authors: Feldt-Rasmussen B , Borch-Johnsen K , Mathiesen E R
Published: August 2012

We measured the blood pressure under standardized conditions in three groups of patients with type I (insulin-dependent) diabetes: group 1, patients with Albustix-negative urine and normal urinary albumin excretion rate below 20 micrograms/min; group 2, patients with Albustix-negative urine and elevated urinary albumin excretion rate 20 to 200 micrograms/min; and group 3, patients with Albustix-positive urine at the time of diagnosis of diabetic nephropathy, that is, proteinuria greater than 0.5 g/24 hr on four consecutive visits with an interval of more than 1 month. We also studied blood pressure data at the time of diagnosis of diabetes in patients with type I diabetes who later died with severe nephropathy (n = 84), and in those who survived their disease for more than 40 years (n = 256). Patients subsequently developing diabetic nephropathy could not be identified on the basis of systolic and/or diastolic blood pressure during the first 2 to 10 years of diabetes. Our study also demonstrated that the blood pressure in group 3 (147/93 mm Hg) was significantly higher than that in group 2 (135/86 mm Hg), which again was higher than that in group 1 (128/79 mm Hg). We concluded that arterial hypertension is an early feature in the developing of diabetic nephropathy, with blood pressure rising before the presence of clinical proteinuria.
Renal histopathology in hypertensive diabetic patients.
Authors: Ditscherlein G
Published: August 2012

A total of 250 renal biopsy specimens from diabetic patients and from the kidneys of 400 autopsy cases were examined histologically and compared to kidneys from 160 autopsied nondiabetics. The morphological findings were assessed in relation to hypertension. There was a high prevalence of arteriolosclerosis, glomerulosclerosis, and pyelonephritis; in addition, early diabetic glomerulopathy and glomerulonephritis, particularly of the membranous type, were noted in a remarkably high percentage of diabetic patients. Ninety-three percent of patients with hypertension had arteriolosclerosis, and a good correlation existed between the extent of this lesion and the level of blood pressure. Even in 66% of normotensive patients, however, arteriolosclerosis was found. This fact and the involvement of the vas efferens argue against the notion of arteriolosclerosis being exclusively a sequela of hypertension. More than 70% of patients with glomerulosclerosis suffered from hypertension, compared to less than 50% of patients without either that condition or early diabetic lesions. The majority of diabetic patients with pyelonephritis and glomerulonephritis were hypertensive. We conclude that hypertension in diabetic patients with renal involvement may result from different renal lesions that can be differentiated only by histological examination.
Exchangeable sodium and renin in hypertensive diabetic patients with and without nephropathy.
Authors: O'Hare J A , Ferriss J B , Brady D , Twomey B , O'Sullivan D J
Published: August 2012

The objective of this study was to examine total exchangeable sodium, plasma-blood volume, and the status of the renin-angiotensin system in hypertensive diabetic patients with established nephropathy. We also evaluated hypertensive patients with diabetes who were free of clinically apparent nephropathy or other diabetic complications. Total exchangeable sodium (by 24Na dilution) was expressed as percentage predicted. Subjects were studied as inpatients receiving unrestricted sodium intake and in stable metabolic control. Total exchangeable sodium was 100 +/- 2% in controls (n = 42), higher (p less than 0.01) at 108 +/- 2% in normotensive patients with diabetes (n = 30), and higher still (p less than 0.005) in hypertensive patients with diabetic nephropathy (n = 16) 118 +/- 4% (p less than 0.05 vs normotensive diabetics). The value correlated with blood pressure only in diabetics with nephropathy (r = 0.61, p less than 0.01). Plasma renin activity, and blood and plasma volumes were similar in nephropathic diabetics and controls. Hypertensive patients with maturity-onset (type II) diabetes free of nephropathy (n = 18) were compared with nondiabetic controls (n = 16) and normotensive patients with type II diabetes (n = 18) of similar age. Total exchangeable sodium in the controls was 100 +/- 3%, higher (p less than 0.01) in normotensive diabetics at 109 +/- 2%, but not significantly elevated in hypertensive diabetics at 106 +/- 2%. Again, blood and plasma volumes did not differ among the groups. Plasma renin activity was suppressed (p less than 0.01) to a comparable degree in both normotensive and hypertensive patients with type II diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)