bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding a Place for Genomics in Health Disparities Research
Authors: Fullerton S.M. , Knerr S. , Burke W.
Published: April 2012

The existence of pronounced differences in health outcomes between US populations is a problem of moral significance and public health urgency. Pursuing research on genetic contributors to such disparities, despite striking data on the fundamental role of social factors, has been controversial. Still, advances in genomic science are providing an understanding of disease biology at a level of precision not previously possible. The potential for genomic strategies to help in addressing population-level disparities therefore needs to be carefully evaluated. Using 3 examples from current research, we argue that the best way to maximize the benefits of population-based genomic investigations, and mitigate potential harms, is to direct research away from the identification of genetic causes of disparities and instead focus on applying genomic methodologies to the development of clinical and public health tools with the potential to ameliorate healthcare inequities, direct population-level health interventions or inform public policy. Such a transformation will require close collaboration between transdisciplinary teams and community members as well as a reorientation of current research objectives to better align genomic discovery efforts with public health priorities and well-recognized barriers to fair health care delivery.
The Impact of Genomics on Public Health Practice: The Case for Change
Authors: Zimmern R.L. , Khoury M.J.
Published: April 2012

Public health practice will not be able in the 21st century to ignore the impact of genomics, cell and molecular biology. It will need to take into consideration issues that include, among others: the complementary nature of social and biological models of disease, genetic exceptionalism, the readiness of public and patient to respond to genomic information, the relationship between individuals and populations, and concepts of population stratification. Health systems will need to adapt their practice and organisation to include new sequencing technologies, bioinformatic expertise and proper evaluation of genetic and molecular tests. Links with the commercial sector will increase in importance. The impact on developing countries cannot be ignored and will require special attention.
The Role of Genomics in Health Behavior Change: Challenges and Opportunities
Authors: Bryan A.D. , Hutchison K.E.
Published: April 2012

The most common causes of morbidity and mortality in the western world can be accounted for by unhealthy patterns of behavior (e.g. smoking, sedentary lifestyle, unhealthy diet, and alcohol consumption). Interventions to improve health behavior are sorely needed. To fully realize the potential of health behavior change interventions, be they individual level, community level, social structural, or policy-based, a greater understanding of the extent to which genomics can inform efforts at health behavior change is warranted. In this commentary, we explore three relatively novel possible routes to the integration of genomics and health behavior: (1) genomics may influence health behavior indirectly through intermediate phenotypes, requiring well-defined theory-based and mechanistic models of health behavior, (2) genomics may moderate response to interventions to change health behavior, and (3) genomics, specifically epigenetic variation, may be influenced by health behavior. The integration of genomics into research on interventions to change health behavior is not without challenges and will certainly require transdisciplinary collaborative science to succeed. We provide specific action points for moving the science forward to explore the extent to which genomic information can be harnessed to ultimately decrease morbidity and mortality associated with unhealthy behavior.
Intracranial Stenosis in Young Patients: Unique Characteristics and Risk Factors
Authors: Siddiq Farhan , Chaudhry Saqib A. , Vazquez Gabriela , Suri Mohammad Fareed Khan , Qureshi Adnan I.
Published: April 2012

Background: Intracranial stenosis in young patients appears to have different characteristics from that observed in the older population. Objective: To study the differences in the pathogenesis of intracranial stenosis in younger patients as compared to the older population. Methods: The clinical characteristics of patients with angiographically confirmed intracranial stenosis were matched to a healthy population using the National Health and Nutrition Examination Study (NHANES). The study population was stratified into two age groups (≤45 and >45 years). The relative risk (odds ratios) and attributable risk of known cardiovascular risk factors were estimated. Results: A total of 17 (11%) patients from 153 patients with intracranial stenosis were aged ≤45 years. These patients were more likely to be women (53 vs. 28%, p < 0.05). The location of the lesion in the young patients was more likely to be in the internal carotid artery (65 vs. 29%, p < 0.05). When compared with the stroke risk factors from the NHANES control population, the attributable risk of hypertension, diabetes mellitus, and coronary artery disease for intracranial stenosis was lower among patients aged ≤45 years than that for patients aged >45 years (6.4 vs. 13.1%, 19.9 vs. 33.0% and 1.0 vs. 10.8%, respectively). Hyperlipidemia had a greater attributable risk of intracranial stenosis in patients ≤45 than in those >45 years of age (23.3 vs. 9.3%). Conclusions: Intracranial stenosis in young patients is predominantly located in the anterior circulation and more frequently occurs in young women. Even though the stroke risk factors appear to be strongly associated with intracranial stenosis in this age group, the impact of these risk factors is low due to the low prevalence.
Advancing the Post-Genomic Era Agenda: Contributions from Public Health
Authors: McGrath B.B.
Published: April 2012

As the science and practice of genomics increasingly turns attention to its role in common chronic illness prevention and treatment, contributions from public health become more visible. Integration of genomics into health care and public health is often framed by principles such as equity and utility, and the accompanying need to translate findings into interventions. This paper will discuss the ways the discipline of public health is in position to lead the way in promoting these principles. This can only occur with the support of an educated workforce and informed consumer base. Recommendations from the Secretary’s Advisory Committee on Genetics, Health, and Society address the issues of education and training these groups, and are summarized.
Why Is It So Difficult to Evaluate Nursing Interventions in Dementia
Authors: Schwarzbach Christoph , Förstl Hans , Nocon Marc , Mittendorf Thomas
Published: April 2012

Two recent health technology assessment (HTA) reports published in Germany focused on non-pharmacological interventions for patients with dementia. One of the major results was the poor methodological quality of the studies in this field. This paper concisely presents the main quantitative and qualitative findings of the HTA report published by the German Agency for HTA at the Institute of Medical Information and Documentation (dahta@DIMDI), followed by a detailed discussion of the major methodological problems observed for the inclusion criteria, interventions, the setting, number of patients included, duration of observation, comparators, clinical endpoints, health economics, and, most obvious, the impossibility of blinding and eliminating placebo effects for future clinical studies. We conclude with several suggestions addressing these challenges for future research in this field.
Quantitative MRI and Cerebrospinal Fluid Inflammatory Mediators in Brazilian Patients with Relapsing-Remitting Multiple Sclerosis before and after Treatment with Immunomodulators: A Longitudinal Study
Authors: Ruocco Heloisa H. , Brandão Carlos Otavio , Farias Alessandro S. , Oliveira Celina , Oliveira Elaine C. , Cendes Fernando , Damasceno Benito P. , Santos Leonilda M.B.
Published: April 2012

Objective: The pathological hallmarks of multiple sclerosis (MS) lesions are inflammation, demyelination, axon loss and gliosis. The aim of this study was to verify the relation of brain lesion load and volume of the cerebral hemisphere determined by brain MRI with intrathecal antibody synthesis. Methods: A longitudinal study of 54 Brazilian patients with the relapsing-remitting form of MS was undertaken after an average of 6.3 ± 2.7 years of treatment. MRI scans were performed, and cerebrospinal fluid samples were collected both during the diagnostic process and after treatment with β-interferon or glatiramer acetate. Results: A positive correlation between the IgG index and total lesion volume was identified. Intrathecal IgG against Epstein-Barr virus (EBV) was observed in 21 patients. The number of contrast-enhanced lesions observed in these patients was correlated with intrathecal IgM synthesis. Brain atrophy was observed early in the disease, with the number of relapses inversely correlated with brain volume. Conclusion: The high intrathecal IgG synthesis observed in these relapsing-remitting MS patients is associated with the brain lesion burden and the presence of antibodies to EBV, whereas intrathecal IgM synthesis is associated with the activity of the disease, as revealed by MRI.
Reduced in vivo Ocular Surface Toxicity with Polyquad-Preserved Travoprost versus Benzalkonium-Preserved Travoprost or Latanoprost Ophthalmic Solutions
Authors: Liang Hong , Brignole-Baudouin Françoise , Riancho Luisa , Baudouin Christophe
Published: April 2012

The study used a validated acute in vivo model to compare a new formulation of travoprost 0.004% ophthalmic solution (travoprost PQ), preserved with polyquaternium-1 (PQ), with commercially available formulations of benzalkonium-chloride (BAK)-preserved travoprost 0.004% ophthalmic solution (travoprost BAK) and BAK-preserved latanoprost 0.005% ophthalmic solution (latanoprost BAK). Adult male New Zealand albino rabbits (n = 36) were randomly divided into 6 groups. Phosphate-buffered saline (PBS), 0.001% PQ, 0.015% BAK, travoprost PQ, travoprost BAK or latanoprost BAK were applied onto rabbit eyes as 1 drop, for 15 times at 5-min intervals. The ocular surface reactions were investigated at hour 4 and day 1 using slitlamp examination; in vivo confocal microscopy (IVCM) for cornea, limbus and conjunctiva/conjunctiva-associated lymphoid tissue, conjunctival impression cytology and standard immunohistology in cryosections for detecting CD45+ infiltrating cells and MUC-5AC-labeled cells. PBS, PQ and travoprost PQ did not induce obvious irritation by clinical observation, changes in microstructures of the whole ocular surface as measured by IVCM analysis, inflammatory infiltration or cell damage as measured by impression cytology, altered levels of goblet cell counts or numerous CD45+ cells in the cornea. In contrast, all BAK-containing products induced diffuse conjunctival hyperemia and chemosis, abnormal changes in the ocular surface microstructure, significant total ocular surface toxicity scores, damaged epithelial cells, inflammatory cell infiltration and decreased goblet cell density. Travoprost PQ did not elicit ocular surface toxicity when administered to rabbit eyes. These results suggest a greater safety advantage for the ocular surface of patients receiving chronic glaucoma treatment with PQ-preserved drugs.
Insights Gained from Symptom Evaluation of Esophageal Motility Disorders: A Review of 4,215 Patients
Authors: Tsuboi Kazuto , Hoshino Masato , Srinivasan Ananth , Yano Fumiaki , Hinder Ronald A. , DeMeester Tom R. , Filipi Charles J. , Mittal Sumeet K.
Published: April 2012

Background/Aims: Achalasia (Ach), diffuse esophageal spasm (DES), nutcracker esophagus (NE), and nonspecific motility disorder (NSMD) are described primary esophageal body motility disorders; however, their clinical symptom correlation is poorly understood. The aim of this study is to examine the association between a patient’s presenting symptoms and their manometric diagnosis. Methods: Manometric findings and reported symptoms of all patients undergoing esophageal manometry at the Creighton University Medical Center were prospectively entered in a database. Twenty-four-year data from 1984 through 2008 were accessed and analyzed. Results: Of the 4,215 patients, 130 (3.1%) had Ach, 192 (4.6%) had DES, 290 (6.9%) had NE, 508 (12.1%) had NSMD, and 3,095 (73.4%) had normal esophageal body motility. There was significant symptom overlap between the groups. Ach and DES had a similar symptom distribution, with dysphagia being the predominant symptom. Patients with NE, normal body motility, and NSMD presented predominantly with reflux symptoms. There was an increasing prevalence of esophageal dysmotility (DES and NSMD) with age, and women were found to be more likely to have NE than men. Conclusion: In an individual, reported symptoms do not correlate with their manometric diagnosis in a predictable fashion, and a thorough physiological assessment should be obtained to understand and diagnose the disease process. Esophageal motility deteriorates with age.
A Case Report of T Cell Prolymphocytic Leukemia and Kaposi Sarcoma and a Review of T Cell Prolymphocytic Leukemia
Authors: Paul R.N. , Alizadeh L. , Ajayi O.I. , Karpurapu H. , Ganesan C. , Taddesse-Heath L. , Aggarwal A.
Published: April 2012

T cell prolymphocytic leukemia (T-PLL) is a rare mature T cell lymphoproliferative disease. It has been associated with an aggressive course, a poor response to conventional chemotherapy and a short median survival. Here we present a rare case of concurrent T-PLL and Kaposi sarcoma who achieved a complete hematologic and cytogenetic remission after a very short course of treatment with alemtuzumab. A review of T-PLL was done. In this review, clinical features, laboratory features and current therapeutic strategies of T-PLL are presented.
Correlation between Imatinib Trough Concentration and Efficacy in Chinese Chronic Myelocytic Leukemia Patients
Authors: Zhong Jian-Sheng , Meng Fan-Yi , Xu Dan , Zhou Hong-Sheng , Dai Min
Published: April 2012

Background: Trough imatinib plasma concentration, intracellular drug levels and expression of drug transporters can be indicative of clinical responses in chronic myelocytic leukemia (CML) patients receiving imatinib. We aimed to determine plasma imatinib concentration, intracellular imatinib concentration, human organic cation transporter 1 (hOCT1) and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) mRNA expression in bone marrow cells of CML patients in order to evaluate the potential usefulness of these measures as markers of imatinib efficacy and understand their clinical relationships. Methods: Eighty-four CML patients receiving imatinib treatment were included in this study. Imatinib trough concentration was determined by high-performance liquid chromatography-tandem mass spectrometry. Real-time quantitative PCR with a TaqMan probe was used to assess hOCT1 and ABCB1 mRNA expression in bone marrow cells. All patients were divided into the major molecular response (MMR), complete cytogenetic response (CCyR), partial cytogenetic response (PCyR) or drug-resistant groups according to their response. Results: The plasma imatinib trough concentration was significantly higher in the MMR group than in the PCyR (p = 0.002) or drug-resistant groups (p = 0.011). The plasma imatinib trough concentration was also significantly higher in the CCyR group than in the PCyR group (p = 0.027). There were no significant differences between the CCyR and MMR groups with regard to the plasma imatinib trough concentration (p = 0.136). The intracellular imatinib concentration in bone marrow cells was significantly higher in the CCyR group compared to the drug-resistant or PCyR groups (p = 0.013). The hOCT1 mRNA expression in bone marrow cells was significantly higher in the CCyR group than in the drug-resistant or PCyR groups (p = 0.036). The ABCB1 mRNA expression in bone marrow cells was significantly higher in the drug-resistant group than in the CCyR or PCyR groups (p = 0.013). Plasma imatinib trough concentration was positively correlated with α1-acid glycoprotein (r = 0.443, p < 0.001) or dose (r = 0.422, p < 0.001). Conclusions: Clinical responses in CML patients are correlated with both the plasma trough concentrations and intracellular levels of imatinib.
The Triad of Pain, Fatigue and Depression in Ischemic Stroke Patients: The Bergen Stroke Study
Authors: Naess Halvor , Lunde Lene , Brogger Jan
Published: April 2012

Background: Many patients with cerebral infarction suffer from symptoms such as pain, fatigue and depression. Most studies focus on single symptoms, but these symptoms often occur together. Whereas symptom clusters have been studied in cancer patients, little is known about different symptom clusters in patients with cerebral infarction. The aim was to evaluate clusters of co-occurring symptoms in the long term. We hypothesized that patients with cerebral infarction display distinct symptom clusters. Furthermore, we hypothesized that multiple co-occurring symptoms have an adverse effect on patients. Methods: All consecutive patients with acute stroke (the index stroke) admitted to the Stroke Unit, Department of Neurology, Haukeland University Hospital, between February 2006 and July 2008, were prospectively registered in a database. Prior risk factors (including diabetes mellitus, hypertension, smoking, coronary heart disease, atrial fibrillation and prior stroke), prior depression and stroke severity (modified Rankin Scale (mRS) score on day 7) were registered. Patients with cerebral infarction were sent a questionnaire including a visual analogue pain scale (VAS), Fatigue Severity Scale (FSS), depression subscale of the Hospital Anxiety, Depression Scale (HADS-D) and Barthel Index at least 6 months after stroke onset. Results: The questionnaire was returned by 328 patients (response rate 60%). All three symptoms were reported by 10.1%. Pain and fatigue among nondepressed patients were reported by 19.6%. Pain and depression among nonfatigued patients were reported by 2.0%. Depression and fatigue, and no pain were reported by 4.4%. Single symptoms were reported by 31% whereas 33% reported no symptoms. VAS, FSS and HADS-D score severity increased with the number of co-occurring symptoms. Logistic regression analyses showed that two or three symptoms (versus no symptoms) was associated with high mRS score on day 7 (p = 0.02), prior stroke (p = 0.002), prior diabetes mellitus (p = 0.005) and prior depression (p < 0.001). Conclusions: Symptom clusters are frequent in patients with cerebral infarction. Fatigue was associated with pain and depression whereas there was little association between depression and pain in nonfatigue patients, indicating distinct symptom clusters. The severity of symptoms increased with the number of co-occurring symptoms.
Efficacy of Prophylactic Blood Pressure Lowering according to a Standardized Postoperative Management Protocol to Prevent Symptomatic Cerebral Hyperperfusion after Direct Revascularization Surgery for Moyamoya Disease
Authors: Fujimura Miki , Inoue Takashi , Shimizu Hiroaki , Saito Atsushi , Mugikura Shunji , Tominaga Teiji
Published: April 2012

Background: Cerebral hyperperfusion is a potential complication of superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease, but the optimal postoperative management has not been determined. Aggressive blood pressure lowering is controversial because of the risk of ischemic complications. Objective: To establish the optimal postoperative management protocol to prevent symptomatic cerebral hyperperfusion in moyamoya disease. Methods: N-isopropyl-p-[123I]-iodoamphetamine single-photon emission computed tomography was performed 1 and 7 days after STA-MCA anastomosis on 152 hemispheres from 108 consecutive patients with moyamoya disease (2–69, mean 33.3 years). Between 2004 and 2007 (period 1), 65 patients were maintained under normotensive conditions after 93 operations, and only patients with cerebral hyperperfusion underwent blood pressure lowering. Between 2008 and 2010 (period 2), all 43 patients were prospectively subjected to intensive blood pressure lowering (<130 mm Hg of systolic blood pressure) immediately after 59 operations. Then the incidence of symptomatic cerebral hyperperfusion was compared between the two groups. Results: Systolic blood pressure the day after surgery was significantly lower in period 2 (mean, 120.9 mm Hg) than in period 1 (133.9 mm Hg) (p < 0.0001). Symptomatic cerebral hyperperfusion was seen in 22 patients during period 1 (23 hemispheres, 24.7%), but only in 4 patients during period 2 (6.7%, p = 0.0047). Multivariate analysis revealed that prophylactic blood pressure lowering was significantly associated with the prevention of symptomatic cerebral hyperperfusion (p = 0.015). Symptomatic cerebral hyperperfusion was relieved in all patients without developing a permanent neurological deficit due to cerebral hyperperfusion. Conclusion: Prophylactic blood pressure lowering prevents symptomatic cerebral hyperperfusion after STA-MCA anastomosis in patients with moyamoya disease. Accurate diagnosis of cerebral hyperperfusion and blood pressure lowering, and considering the severity of hemodynamic compromise in the contralateral and/or remote areas are essential for postoperative management of moyamoya disease.
Knowledge of Stroke among an Urban Population in Cotonou (Benin)
Authors: Cossi Marie-Joëlle , Preux Pierre-Marie , Chabriat Hugues , Gobron Claire , Houinato Dismand
Published: April 2012

Background: Studies on the knowledge of stroke, its related risk factors and warning symptoms in the populations of Sub-Saharan Africa are scarce. No study has been performed in Benin until now. Methods: A door-to-door survey was performed in two districts of Cotonou with a broad socioeconomic range. 15,155 individuals aged ≥15 years were interviewed using a semi-structured questionnaire adapted from previous reports. Results: 15,155 individuals consented to participate in the survey. 14.1% correctly identified the brain as the affected organ in stroke. The most commonly identified risk factor was hypertension (34.5%). The most often cited warning signs of stroke were paralysis and hemiplegia (34.4%). Relatives were the major source of information about stroke (25.1%). In multivariate analysis, age, education level, occupation, self-reported risk factors of stroke, overweight and obesity were associated with at least one correct response to the questionnaire about stroke risk factors or symptoms. Conclusion: The awareness of stroke, and its risk factors and symptoms is low in Cotonou. The results suggest that specific education programs may improve people’s knowledge of stroke and their awareness of related risk factors in Sub-Saharan African countries.
Tuning Characteristics of Ocular and Cervical Vestibular Evoked Myogenic Potentials in Intact and Dehiscent Ears
Authors: Taylor R.L. , Bradshaw A.P. , Halmagyi G.M. , Welgampola M.S.
Published: April 2012

Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) to air-conducted tone bursts (250–2000 Hz) were recorded in 14 patients with superior canal dehiscence (SCD) and 32 healthy controls. For cVEMPs, the most common ‘optimal frequency’ in control ears (48.2%) was 500 Hz; for oVEMPs, it was 1000 Hz (51.8%). We found a significant interaction between age and frequency, with a shift towards higher-frequency tuning in older subjects. cVEMP and oVEMP tuning in SCD was characterised by a broadening of amplitude and threshold tuning curves. The tendency of cVEMPs to tune to lower frequencies compared to oVEMP was enhanced in SCD. Differences in cVEMP and oVEMP ‘optimal frequencies’, demonstrated in 57.1% intact ears and 81.3% dehiscent ears, imply differences in the recruitment of hair cells generating these two reflexes. Age-matched oVEMP amplitudes provided excellent separation between SCD and control ears. Although cVEMP amplitudes overlapped between SCD and control ears, better separation was achieved by using a 2-kHz stimulus.
Dopaminergic Modulation of CD4+CD25high Regulatory T Lymphocytes in Multiple Sclerosis Patients during Interferon-β Therapy
Authors: Cosentino Marco , Zaffaroni Mauro , Trojano Maria , Giorelli Maurizio , Pica Carmela , Rasini Emanuela , Bombelli Raffaella , Ferrari Marco , Ghezzi Angelo , Comi Giancarlo , Livrea Paolo , Lecchini Sergio , Marino Franca
Published: April 2012

Objective: We investigated dopaminergic inhibition of CD4+CD25high regulatory T lymphocytes (Treg) in relapsing-remitting multiple sclerosis (MS) patients treated with interferon (IFN)-β. Methods: MS patients were prospectively studied at baseline and during 1 year of IFN-β, and compared with healthy controls (HCs). Treg were separated by immunomagnetic sorting and the effect of dopamine (DA) on Treg was assessed in coculture experiments with homologous effector T lymphocytes (Teff). Tyrosine hydroxylase (TH), dopaminergic receptors (DR) D3 and D5, and forkhead box protein P3 (FoxP3) mRNA were assessed by real-time PCR. Circulating CD4+ T cell subsets were assessed by flow cytometry. Results: In coculture experiments, Treg inhibition of Teff proliferation was reduced by DA in HCs and completely abolished in MS patients at baseline. However, in patients after 12 months of IFN-β, Teff proliferation was impaired and DA had no more effect on Treg. In comparison to cells from HCs, Treg from MS patients at baseline had increased mRNA for DR D5 and TH (but not for DR D3). During treatment with IFN-β, both DR D5 and TH mRNA decreased down to values lower than those of cells from HCs. In comparison to HCs, MS patients had a higher frequency of circulating Treg, both at baseline and after IFN-β, while FoxP3 mRNA levels in Treg were similar in patients and HCs and did not show major changes during IFN-β. Conclusions: Dopaminergic inhibition of Treg in MS patients is suppressed during IFN-β treatment. Treg play a key role in the suppression of autoimmunity, thus the effect may have a therapeutic repercussion.
Familial Occurrence of Cervical Artery Dissection – Coincidence or Sign of Familial Predisposition?
Authors: Grond-Ginsbach Caspar , de Freitas Gabriel R. , Campos Cynthia R. , Thie Andreas , Caso Valeria , Machetanz Jochen , Kloss Manja
Published: April 2012

Backgroundand Purpose: The etiology of spontaneous cervical artery dissection (CeAD) is poorly understood in most patients. Mild cervical trauma preceding the dissection event is a common finding, but many CeAD occur spontaneously. It is likely that genetic factors may increase the risk for CeAD. However, familial cases are excedingly rare. Familial clustering of CeAD may be accidental or associated with genetic or environmental risk factors shared between affected relatives. In this explorative study, we aim to show that specific risk factors for familial CeAD exist. Methods: Age of onset, sex, affected artery and number of recurrent CeAD were documented for familial patients and compared with published findings from patients with sporadic CeAD. Concordance of age, sex and dissected artery within the families was analyzed by correlation analysis and by analysis of variance or Kruskal-Wallis testing. Results: The study sample consisted of 9 new patients with a family history of CeAD enrolled in the Neurology Department of the University of Heidelberg or referred to Heidelberg from other centers. The study sample also included published findings from another 23 patients, in total 32 patients. The mean age of the patients with familial CeAD at their first dissections was 38.4 ± 13.3 years. Twenty (62.5%) patients were female and 12 patients (37.5%) suffered multiple dissections. Four patients (12.5%) presented with recurrent dissections after >1 year. Patients with a familial history of CeAD were younger (p = 0.023) and presented more often with multiple dissections (p = 0.024) and recurrent dissections (p = 0.018). Age at the first event (correlation analysis p = 0.026; analysis of variance p = 0.029) and site of the dissection (correlation analysis p = 0.032; Kruskal-Wallis test p = 0.018) differed between the families, and there was no concordance of gender of affected family members (correlation analysis p = 0.500; Kruskal-Wallis test p = 0.211). Conclusions: The high prevalence of multiple dissection events and of long-term (>1 year) recurrent dissections in patients with a familial history of CeAD indicates that a specific predisposition for familial CeAD exists. Since age of onset and affected vessel differ between families, the risk profile for familial CeAD is heterogeneous. A large-scale (whole exome) sequencing analysis of 14 patients from 7 of the analyzed families is currently being performed in order to identify causative genetic variants.
Multiplex Ligation-Dependent Probe Amplification Improves the Detection Rate of NKX2.1 Mutations in Patients Affected by Brain-Lung-Thyroid Syndrome
Authors: Teissier Raphaël , Guillot Loïc , Carré Aurore , Morandini Melina , Stuckens Chantal , Ythier Hubert , Munnich Arnold , Szinnai Gabor , de Blic Jacques , Clement Annick , Leger Juliane , Castanet Mireille , Epaud Ralph , Polak Michel
Published: April 2012

Background: NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease. Aims and Methods: We evaluated the recently developed Multiplex Ligation-dependent Probe Amplification (MLPA) method to assess the relative copy number of genes. The goal was to determine if MLPA could improve, in addition to direct sequencing, the detection rate of NKX2.1 mutations in a phenotype-selected cohort of 24 patients affected by neurological, thyroid and/or pulmonary disorders. Results: Direct sequencing revealed two heterozygous mutations. Using MLPA, we identified two further heterozygous NKX2.1 gene deletions. MLPA increased the detection rate by 50%. All patients with gene deletions identified were affected by BHC and congenital hypothyroidism. Conclusion: MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. All patients with an NKX2.1 mutation had BHC and congenital hypothyroidism, emphasizing the high prevalence of these signs associated with defective NKX2.1 alleles.
Zoocin A and Lauricidin in Combination Reduce Streptococcus mutans Growth in a Multispecies Biofilm
Authors: Lester K. , Simmonds R.S.
Published: April 2012

Dental caries is the most prevalent human infection. It is a multifactorial disease in which the microbial composition of dental plaque plays a major role in the development of clinical symptoms. The bacteria most often implicated in the development of caries are that group of streptococci referred to as the mutans streptococci, in particular Streptococcus mutans and Streptococcus sobrinus. One approach to the prevention of caries is to reduce the numbers of mutans streptococci in plaque to a level insufficient to support demineralization of the tooth. In this study, zoocin A, a peptidoglycan hydrolase, combined with lauricidin, a cell membrane active lipid, was shown over a 72 h period to selectively suppress the growth of S. mutans in a triple species biofilm. Growth of the non-target species Streptococcus oralis and Actinomyces viscosus was not inhibited. In treated systems the amount of extracellular polysaccharide matrix produced was much reduced as determined by use of fluorescein isothiocyanate conjugated wheat germ agglutinin. The pH of treated biofilms remained above neutral as opposed to a value of 4.3 in untreated controls. We conclude that use of antimicrobial compounds that specifically target cariogenic bacteria should be further explored.
Myocardial Stunning with Hemodialysis: Clinical Challenges of the Cardiorenal Patient
Authors: Zuidema Mozow Y. , Dellsperger Kevin C.
Published: April 2012

We discuss the current state of knowledge related to the pathogenesis of myocardial stunning as well as the potential mechanisms responsible for the clinical presentation of myocardial stunning in hemodialysis patients. We suggest future research areas for this critical and clinically important condition in this high-risk patient population. In consideration of acute and chronic changes secondary to dialysis, especially in patients with risk for coronary artery disease, the prevalence of myocardial stunning and its role in the natural history of these patients’ disease progression is considered. We propose a paradigm: that the majority of the pathophysiologic mechanisms by which hemodialysis may induce myocardial stunning falls into two categories with (1) vascular and/or (2) metabolic contributions. In order to prevent eventual myocardial hibernation, myocardial remodeling, scarring, and loss of contractile function with aberrant electrical conductivity that could lead to sudden death, it is imperative to identify the risk factors associated with myocardial stunning during hemodialysis. Further understanding of these mechanisms may lead to novel clinical interventions and pharmacologic therapeutic agents.
The Role of Suboptimal Home-Measured Blood Pressure Control for Cognitive Decline
Authors: Yaneva-Sirakova Teodora , Tarnovska-Kadreva Rumiana , Traykov Latchezar
Published: April 2012

Aim: We aim to analyze if there is any correlation between suboptimal home-/self-measured blood pressure values and the results from neuropsychological screening tests for early cognitive impairment. Methods: We studied 325 patients with treated hypertension. Mean age was 66.12 (±10.1) years. There were 119 (36.6%) male and 206 (63.4%) female patients, among them 52 (16%) with atrial fibrillation. Neuropsychological tests performed were the Mini-Mental State Examination, Montreal Cognitive Assessment, and Hachinski Ischemic Score; additionally, home-measured blood pressure was used. Results: There is a nonlinear age- and risk factor-dependent correlation between early stages of cognitive impairment and suboptimal home-measured blood pressure. Conclusion: The use of specific and sensitive neuropsychological tests for early cognitive impairment in patients with suboptimal home-measured blood pressure is effective in the everyday practice.
Effects of Cinacalcet in Renal Transplant Patients with Hyperparathyroidism
Authors: Courbebaisse Marie , Diet Carine , Timsit Marc-Olivier , Mamzer Marie-France , Thervet Eric , Noel Laure-Hélène , Legendre Christophe , Friedlander Gérard , Martinez Frank , Prié Dominique
Published: April 2012

Background: Cinacalcet decreases serum parathyroid hormone (PTH) and calcium concentrations in kidney transplant recipients with autonomous hyperparathyroidism. Long-term treatment with cinacalcet may increase urinary calcium excretion and the risk of renal calcium deposits and may alter renal graft function. Methods: We studied 71 renal recipients with hypercalcemic hyperparathyroidism. Of these patients, 34 received cinacalcet between month 3 and month 12 after renal transplantation. We compared phosphate calcium balance, measured glomerular filtration rate (GFR) and renal biopsies in cinacalcet-treated and non-cinacalcet-treated patients. Measurements were performed before initiating cinacalcet treatment (month 3) and at month 12. Results: Patients treated with cinacalcet had more severe hyperparathyroidism. Serum PTH concentration decreased in both groups between months 3 and 12, but the decrease was much more important in cinacalcet-treated patients. Urinary calcium excretion significantly increased under cinacalcet treatment and was more than twice as high at month 12 as in patients who did not receive cinacalcet treatment. However, the hypercalciuria was not associated with an increase in calcium deposits on renal biopsies or an alteration of measured GFR. Conclusions: Despite sustained and marked hypercalciuria induced by cinacalcet treatment, cinacalcet does not have adverse effects on GFR or on renal graft calcium deposits in the first year following renal transplantation.
Comparative Safety and Efficiency of Five Percutaneous Kidney Biopsy Approaches of Native Kidneys: A Multicenter Study
Authors: Bataille Stanislas , Jourde Noémie , Daniel Laurent , Mondain Jean-René , Faure Magali , Gobert Pierre , Alcheikh-Hassan Zarih , Lankester Michel , Giaime Philippe , Gaudart Jean , Dussol Bertrand , Berland Yvon , Burtey Stéphane
Published: April 2012

Background: Renal biopsy (RB) is necessary for the diagnosis, prognosis, and therapy guidance of native kidney diseases. Few studies have compared outcomes of RB procedures. We retrospectively compared the safety and efficiency of five biopsy procedures. Methods: The number of glomeruli on light microscopy (LM) and on immunofluorescence (IF) and serious adverse events following RB performed in five nephrology units (C1–C5) were collected. C1 performed ultrasound (US) assessment before RB and used a 14-gauge core-cutting needle biopsy gun, C2 US guidance and a 14-gauge needle, C3 tomodensitometry guidance and a 14-gauge needle, C4 US guidance and a 16-gauge needle, and C5 tomodensitometry guidance and a 16-gauge needle. Results: RB was performed in 943 adults between January 2006 and July 2010. Serious adverse events occurred in 1.5% of biopsies. The complication rate was not different between nephrology units. The mean number of glomeruli on biopsy was 14.2 ± 8.6 with LM and 4.4 ± 3.3 on IF. It was different according to the nephrology unit for LM (p = 0.01) and for IF (p < 0.001). The number of failed biopsies was influenced by the nephrology unit and radiological guidance technique, favoring real-time US guidance. Failed biopsies using US or tomodensitometry assessment before RB was certainly due to kidney imprecise localization since it was often non-renal tissue sampling. At least 10 glomeruli were found in 69% of biopsies on LM. This rate varied according to the nephrology unit (p = 0.004) and was higher when 14-gauge needles were used in comparison with 16-gauge needles. Conclusion: RB is safe regardless of the technical procedure, but radiological guidance and needle size influence the efficiency of biopsies.
Diazoxide Maintains Human Myocyte Volume Homeostasis During Stress
Authors: Maffit Sara K. , Sellitto Angela D. , Al‐Dadah Ashraf S. , Schuessler Richard B. , Damiano Ralph J. , Lawton Jennifer S.
Published: April 2012

Background

Exposure to hypothermic hyperkalemic cardioplegia, hyposmotic stress, or metabolic inhibition results in significant animal myocyte swelling (6% to10%) and subsequent reduced contractility (10% to 20%). Both are eliminated by the adenosine triphosphate‐sensitive potassium channel opener diazoxide (DZX). The relationship between swelling and reduced contractility suggests that the structural change may represent one mechanism of postoperative myocardial stunning. This study evaluated human myocyte volume during stress to investigate if similar phenomena exist in human myocytes.

Methods and Results

Human atrial myocytes isolated from tissue obtained during cardiac surgery were perfused with Tyrode's physiological solution (20 minutes, 37°C), test solution (20 minutes), and Tyrode's (37°C, 20 minutes). Test solutions (
n
=6 to 12 myocytes each) included Tyrode's (37°C or 9°C), Tyrode's+DZX (9°C), hyperkalemic cardioplegia (9°C)±DZX, cardioplegia+DZX+HMR 1098 (sarcolemmal adenosine triphosphate‐sensitive potassium channel inhibitor, 9°C), cardioplegia+DZX+5‐hydroxydeconoate (mitochondrial adenosine triphosphate‐sensitive potassium channel inhibitor, 9°C), mild hyposmotic solution±DZX, metabolic inhibition±DZX, and metabolic inhibition+DZX+5‐hydroxydeconoate. Myocyte volume was recorded every 5 minutes. Exposure to hypothermic hyperkalemic cardioplegia, hyposmotic stress, or metabolic inhibition resulted in significant human myocyte swelling (8%, 7%, and 6%, respectively; all
P
<0.05 vs control). In all groups, the swelling was eliminated or lessened by DZX. The addition of channel inhibitors did not significantly alter results.

Conclusions

DZX maintains human myocyte volume homeostasis during stress via an unknown mechanism. DZX may prove to be clinically useful following the elucidation of its specific mechanism of action.

(
J Am Heart Assoc
. 2012;1:jah3‐e000778 doi

:
10.1161/JAHA.112.000778
.)
Individual Patient Data Subgroup Meta-Analysis of Surgery for Spontaneous Supratentorial Intracerebral Hemorrhage
Authors: Gregson Barbara A. , Broderick Joseph P. , Auer Ludwig M. , Batjer Hunt , Chen Xian-Cheng , Juvela Seppo , Morgenstern Lewis B. , Pantazis George C. , Teernstra Onno P.M. , Wang Wen-Zhi , Zuccarello Mario , Mendelow A. David
Published: April 2012

Background and Purpose—

By 2010 there had been 14 published trials of surgery for intracerebral hemorrhage reported in systematic reviews or to the authors, but the role and timing of operative intervention remain controversial and the practice continues to be haphazard. This study attempted to obtain individual patient data from each of the 13 studies published since 1985 to better define groups of patients that might benefit from surgery.

Methods—

Authors of identified published articles were approached by mail, e-mail, and at conferences and invited to take part in the study. Data were obtained from 8 studies (2186 cases). Individual patient data included patient's age, Glasgow Coma Score at presentation, volume and site of hematoma, presence of intraventricular hemorrhage, method of evacuation, time to randomization, and outcome.

Results—

Meta-analysis indicated that there was improved outcome with surgery if randomization was undertaken within 8 hours of ictus (
P
=0.003), or the volume of the hematoma was 20 to 50 mL (
P
=0.004), or the Glasgow Coma Score was between 9 and 12 (
P
=0.0009), or the patient was aged between 50 and 69 years (
P
=0.01). In addition, there was some evidence that more superficial hematomas with no intraventricular hemorrhage might also benefit (
P
=0.09).

Conclusions—

There is evidence that surgery is of benefit if undertaken early before the patient deteriorates. This work identifies areas for further research. Ongoing studies in subgroups of patients such as the Surgical Trial in Lobar Intracerebral Hemorrhage (STICH II) will confirm whether these interpretations can be replicated.
Carotid Artery Anatomy and Geometry as Risk Factors for Carotid Atherosclerotic Disease
Authors: Phan Thanh G. , Beare Richard J. , Jolley Damien , Das Gita , Ren Mandy , Wong Kitty , Chong Winston , Sinnott Matthew D. , Hilton James E. , Srikanth Velandai
Published: April 2012

Background and Purpose—

Traditional vascular risk factors do not completely explain the asymmetry, racial, and sex differences in carotid artery disease. Carotid anatomy and geometry may play a role in the pathogenesis of internal carotid artery (ICA) stenosis, but their effects are unknown. We hypothesized that carotid artery anatomy and geometry would be independently associated with ICA stenosis.

Method—

This is a retrospective study of patients with CT angiography at Monash Medical Centre, 2006 to 2007. Carotid arteries were segmented using semiautomated methods to estimate measures of carotid anatomy and geometry. Measurements of carotid artery geometry were performed according to the recent article by Thomas and colleagues. ICA stenosis was dichotomized as <30% or ≥30% stenosis. Cluster logistic regression was used to examine the associations of anatomy and geometry with stenosis accounting for the paired arteries within subjects, adjusting for age, sex, and vascular risk factors.

Results—

Mean age of the sample (n=178) was 68.4 years (SD, 14 years). The following were independently associated with ICA stenosis: ICA radius at the bifurcation (OR, 0.20; 95% CI, 0.14–0.29), ICA angle (OR, 1.05 per degree increment; 95% CI, 1.04–1.07), age (OR, 1.05 per year increment; 95% CI, 1.03–1.07), male sex (OR, 1.72; 95% CI, 1.08–2.8), and ever-smoker (OR, 1.85; 95% CI, 1.15–2.96).

Conclusions—

Carotid anatomy and geometry may enhance the risk of stenosis independent of traditional vascular risk factors and may be of help in very early identification of patients at high risk of developing carotid artery atherosclerosis for aggressive intervention.
Spatially Explicit Parameterization of a Terrestrial Ecosystem Model and Its Application to the Quantification of Carbon Dynamics of Forest Ecosystems in the Conterminous United States
Authors: Chen Min , Zhuang Qianlai
Published: April 2012

The authors use a spatially explicit parameterization method and the Terrestrial Ecosystem Model (TEM) to quantify the carbon dynamics of forest ecosystems in the conterminous United States. Six key parameters that govern the rates of carbon and nitrogen dynamics in TEM are selected for calibration. Spatially explicit data for carbon and nitrogen pools and fluxes are used to calibrate the six key parameters to more adequately account for the spatial heterogeneity of ecosystems in estimating regional carbon dynamics. The authors find that a spatially explicit parameterization results in vastly different carbon exchange rates relative to a parameterization conducted for representative ecosystem sites. The new parameterization method estimates that the net ecosystem production (NEP), the annual gross primary production (GPP), and the net primary production (NPP) of the regional forest ecosystems are 61% (0.02 Pg C; 1 Pg = 1015 g) higher and 2% (0.11 Pg C) and 19% (0.45 Pg C) lower, respectively, than the values obtained using the traditional parameterization method for the period 1948–2000. The estimated vegetation carbon and soil organic carbon pool sizes are 51% (18.73 Pg C) lower and 29% (7.40 Pg C) higher. This study suggests that, to more adequately quantify regional carbon dynamics, spatial data for carbon and nitrogen pools and fluxes should be developed and used with the spatially explicit parameterization method.
Transport of Stratospheric Air Masses to the Nepal Climate Observatory–Pyramid (Himalaya; 5079 m MSL): A Synoptic-Scale Investigation
Authors: Bracci A. , Cristofanelli P. , Sprenger M. , Bonafè U. , Calzolari F. , Duchi R. , Laj P. , Marinoni A. , Roccato F. , Vuillermoz E. , Bonasoni P.
Published: April 2012

This work analyzes and classifies stratospheric airmass transport events (ST) detected at the Nepal Climate Observatory–Pyramid (NCO-P; 27°57′N, 86°48′E, 5079 m MSL) Global Atmospheric Watch–World Meteorological Organization station from March 2006 to February 2008. For this purpose, in situ ozone (O3), meteorological parameters (atmospheric pressure and relative humidity), and black carbon (BC) are analyzed. The paper describes the synoptic-scale meteorological scenarios that are able to favor the development of ST over the southern Himalaya, by analyzing the meteorological fields provided by the ECMWF model (geopotential height, wind speed, and potential vorticity), satellite Ozone Monitoring Instrument data (total column ozone), and three-dimensional back trajectories calculated with the Lagrangian Analysis Tool (LAGRANTO) model. The study, which represents the first “continuous” classification of ST in the southern Himalaya, permitted classification of 94% of ST days within four synoptic-scale scenarios: stratospheric potential vorticity structures (PVS), subtropical jet stream (SJS), quasi-stationary ridges (QSR), and monsoon depressions (MD). SJS and PVS were the most frequent scenarios (48% and 30% of occurrences, respectively), QSR occurred for 12% of the ST days, and MD were detected only during the monsoon season (3%). SJS and PVS scenarios presented a peak frequency during the nonmonsoon seasons, when the jet stream and westerly disturbances influence atmospheric circulation over the southern Himalaya. During the identified ST, significant variations of O3 (+24%) and BC (−56%) were recorded relative to the averaged 2-yr mean values. On average, PVS and SJS were the most effective synoptic-scale scenarios in modifying the O3 and BC levels at NCO-P from postmonsoon to premonsoon seasons, and ST is one of the leading processes in defining the “background” BC variability at NCO-P.