bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease Severity Adversely Affects Delivery of Dialysis in Acute Renal Failure
Authors: Schiffl Helmut
Published: November 2007

Background/Aims: Methods of intermittent hemodialysis (IHD) dose quantification in acute renal failure (ARF) are not well defined. This observational study was designed to evaluate the impact of disease activity on delivered single pool Kt/Vurea in ARF patients. Methods: 100 patients with severe ARF (acute intrinsic renal disease in 18 patients, nephrotoxic acute tubular necrosis in 38 patients, and septic ARF in 44 patients) were analyzed during four consecutive sessions of IHD, performed for 3.5–5 h every other day or daily. Target IHD dose was a single pool Kt/Vurea of 1.2 or more per dialysis session for all patients. Prescribed Kt/Vurea was calculated from desired dialyzer clearance (K), desired treatment time (t) and anthropometric estimates for urea distribution volume (V). The desired clearance (K) was estimated from prescribed blood flow rate and manufacturer’s charts of in vivo data obtained in maintenance dialysis patients. Delivered single pool Kt/Vurea was calculated using the Daugirdas equation. Results: None of the patients had prescription failure of the target dose. The delivered IHD doses were substantially lower than the prescribed Kt/V values, particularly in ARF patients with sepsis/septic shock. Stratification according to disease severity revealed that all patients with isolated ARF, but none with 3 or more organ failures and none who needed vasopressive support received the target dose. Conclusion: Prescription of target IHD dose by single pool Kt/Vurea resulted in suboptimal dialysis dose delivery in critically ill patients. Numerous patient-related and treatment-immanent factors acting in concert reduced the delivered dose.
A Rare but Serious Complication of Ladd’s Procedure: Recurrent Midgut Volvulus
Authors: Alkan Murat , Oğuzkurt Pelin , Alkan Ozlem , Ezer Semire Serin , Hiçsönmez Akgün
Published: November 2007

An eighteen-month-old boy who had undergone a Ladd’s procedure for malrotation in the newborn period presented with acute onset of nausea, vomiting, rectal bleeding, and confusion. Laparotomy revealed midgut volvulus, mesenteric lymphadenopathy and massive chylous ascites. Recurrent midgut volvulus following Ladd’s procedure is extremely rare but should be borne in mind in cases of persistent or recurrent gastrointestinal symptoms. Timely surgery is necessary to avoid intestinal gangrene and decrease morbidity and mortality related to consequences of midgut volvulus.
Hyperprolactinemia and Delusion of Pregnancy
Authors: Ahuja Niraj , Vasudev Kamini , Lloyd Adrian
Published: November 2007

We describe the case of a 44-year-old woman admitted with mania with psychotic symptoms who presented with delusion of twin pregnancy a month after admission, which temporally correlated with hyperprolactinemia secondary to antipsychotic medication. Modification of antipsychotic medication was associated with fall in serum prolactin and disappearance of delusion of pregnancy. In light of this clinically striking temporal association between hyperprolactinemia and delusion of pregnancy, we review the literature to examine the hypothetical relationship. We highlight the clinical significance of examining the various factors, including antipsychotic-induced hyperprolactinemia, which could trigger the development of delusion of pregnancy.
Successful Conservative Management of Hereditary Hemorrhagic Telangiectasia in Pregnancy
Authors: Schwebel Marlene , Oyelese Yinka , Nath Carl , Ashkinadze Elena , Vintzileos Anthony M. , Smulian John C.
Published: November 2007

Background: Hereditary hemorrhagic telangiectasia (HHT) is a condition characterized by multiple telangiectases and arteriovenous malformations. Women with HHT may develop life-threatening complications in pregnancy. In particular, death from pulmonary hemorrhage has been reported. Consequently, these women are often advised not to conceive or to terminate their pregnancies. Case: We report a case of conservative management of HHT in pregnancy with a good outcome. Conclusion: This case demonstrates that in carefully selected cases, women with HHT who are managed conservatively may have good pregnancy outcomes. A diagnosis of HHT alone is not reason to advise women against pregnancy, nor should these women routinely be advised to undergo pregnancy termination.
A Continuous and Non-Invasive Arterial Pressure Monitoring System in Dialysis Patients
Authors: Mambelli Emanuele , Mancini Elena , Santoro Antonio
Published: November 2007

Background: As symptomatic intradialytic hypotension in the hemodialysis (HD) patient is often a sudden event whose onset cannot be predicted by means of extemporary measures, continuous blood pressure (BP) measurement would be far more useful. We tested a new continuous noninvasive BP monitoring system, Harmonized Alert Sensing Technology (HASTE), which, by means of the analysis of the finger pulse wave, obtained from an O2 sensor, estimates a beat-to-beat systolic pressure value (Esys) and supplies a continuous read-out. The study aim sought to verify the reliability of this non-invasive instrument in continuously providing systolic pressure values during HD. Methods: We studied 18 patients during HD treatment, initially comparing the Esys with the invasive blood pressure measurement (SYS). Subsequently, the Esys derived from the O2 sensor in the arm with the shunt (S) and the arm without (N), respectively, were both compared with the cuff measurement. Results: The mean difference between SYS and Esys was 0.7 ± 13.3 mm Hg (p < 0.01; r = 0.80). There was a mean difference of 0.2 ± 21.9 mm Hg (p = NS; r = 0.67) between Esys(N) and Esys(S). The correlation was not statistically significant even between Esys(N) or Esys(S) versus the cuff measurement, respectively. Patient movement compromised the accuracy of the estimations made using the O2 sensor in the non-fistula arm. Conclusions: A good correlation between the data estimated by HASTE compared with invasive BP suggests that the instrument may prove useful for continuously monitoring the blood pressure trends during the dynamic hemodialysis situation. However, its sensibility needs to be improved in order to be used indifferently in both arms with a view to achieving real intradialytic hypotension prevention.
Markers of Arterial Stiffness Are Risk Factors for Progression to End-Stage Renal Disease among Patients with Chronic Kidney Disease Stages 4 and 5
Authors: Taal Maarten W. , Sigrist Mhairi K. , Fakis Apostolos , Fluck Richard J. , McIntyre Christopher W.
Published: November 2007

Background: Factors associated with chronic kidney disease (CKD) contribute to an increased risk of cardiovascular disease and death. The impact of vascular disease on CKD progression is, however, less well studied. Methods: We examined the effect of markers of vascular disease on the risk of progression to end-stage renal disease (ESRD) in 35 patients with CKD stages 4–5. Superficial femoral artery calcification was assessed by CT scan. Augmentation index (AI) and pulse wave velocity (PWV) were measured by applanation tonometry. Results: After 12.4 (5.5–28.4) months, 22/35 patients (63%) had commenced dialysis. Cox regression analysis identified baseline estimated glomerular filtration rate (hazard ratio, HR, 0.54; 95% CI 0.41–0.70; p < 0.0001), urinary protein (HR 1.84; 95% CI 1.32–2.58; p = 0.0005), PWV (HR 1.30; 95% CI 1.07–1.60; p = 0.01), AI (HR 1.08; 95% CI 1.04–1.14; p = 0.0001) and pack years of smoking (HR 1.01; 95% CI 1.00–1.03; p = 0.02) as independent risk factors for time to ESRD (–2 log likelihood = 86.7; χ2 = 30.9; p < 0.0001). Repeat analysis using AI as a categorical variable revealed an HR of 17.5 (95% CI 4.43–68.9; p < 0.0001) for time to ESRD in those with AI above versus below the median. Conclusions: We have identified two markers of arterial stiffness as independent risk factors for progression to ESRD suggesting that vascular disease may contribute to CKD progression.
New Records on Prey Capture and Meat Eating by Bonobos at Lui Kotale, Salonga National Park, Democratic Republic of Congo
Authors: Hohmann Gottfried , Fruth Barbara
Published: November 2007

Compared to data from chimpanzees, observations on prey capture and meat eating by bonobos(Pan paniscus)are still rare, fragmentary and anecdotal. Here we present new and unpublished information from wild bonobos at Lui Kotale, Salonga National Park, Democratic Republic of Congo. Our observations confirm that solitary and terrestrial ungulates are the major prey. However, bonobos at Lui Kotale also consumed other mammalian prey, including other primates. Evidence from direct observations is complemented with information obtained by macroscopic analyses of fresh faeces. Results suggest that bonobos consume meat with frequencies similar to some chimpanzee populations. The data emphasize differences between the twoPanspecies in terms of prey species selection and prey capture.
Does Phenotypic Plasticity Confound Attempts to Identify Hominin Fossil Species?
Authors: Collard Mark , Lycett Stephen J.
Published: November 2007

It has been hypothesised recently that masticatory strain-induced phenotypic plasticity complicates efforts to delineate species in the hominin fossil record. Here, we report a study that evaluated this hypothesis by subjecting craniodental data from 8 Old World monkey species to ANOVA and discriminant analysis. The study does not support the hypothesis. Characters associated with high masticatory strains were found to exhibit significantly higher levels of variability than low-to-moderately strained characters and dental characters, but the three sets of characters did not differ markedly in taxonomic utility. Moreover, the best discrimination was achieved when all variables were employed. These results suggest that phenotypic plasticity likely plays only a minor confounding role in hominin taxonomy, and that, rather than attempting to exclude phenotypically plastic characters, researchers should simply maximise the number of characters examined.
Sorl1 as an Alzheimer’s Disease Predisposition Gene?
Authors: Webster Jennifer A. , Myers Amanda J. , Pearson John V. , Craig David W. , Hu-Lince Diane , Coon Keith D. , Zismann Victoria L. , Beach Thomas , Leung Doris , Bryden Leslie , Halperin Rebecca F. , Marlowe Lauren , Kaleem Mona , Huentelman Matthew J. , Joshipura Keta , Walker Douglas , Heward Christopher B. , Ravid Rivka , Rogers Joseph , Papassotiropoulos Andreas , Hardy John , Reiman Eric M. , Stephan Dietrich A.
Published: November 2007

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressively disabling impairments in memory, cognition, and non-cognitive behavioural symptoms. Sporadic AD is multifactorial and genetically complex. While several monogenic mutations cause early-onset AD and gene alleles have been suggested as AD susceptibility factors, the only extensively validated susceptibility gene for late-onset AD is the apolipoprotein E (APOE) Ε4 allele. Alleles of the APOE gene do not account for all of the genetic load calculated to be responsible for AD predisposition. Recently, polymorphisms across the neuronal sortilin-related receptor (SORL1) gene were shown to be significantly associated with AD in several cohorts. Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval.
‘Dowel’ pinning for feline metacarpal and metatarsal fractures
Authors: Kornmayer M. , Matis U. , Zahn K.
Published: November 2007

The goal of this retrospective study was to describe dowel pinning, and to compare the results of osteosynthesis and external coaptation of metacarpal and metatarsal fractures in cats. Evaluation of the medical records of 351 cats yielded 63 cats treated with dowel pinning, 35 cats treated with external coaptation and 14 cats treated with both methods within the same limb. All of the cats had been re-evaluated at an average of 2.8 years (six months – 15 years) postoperatively. Dowel pinning was superior to external coaptation when all fractured bones of a limb could be pinned. When internal fixation of multiple fractures was not feasible in all fractured bones due to comminution or fragments that were too short to pin, the outcome was not significantly different from cases treated with external coaptation alone. Malunion was seen in 16% of fractured bones in cats treated with external coaptation and occurred secondary to implant bending in 3% of fractured bones treated with dowel pinning. The latter refers to one operated cat, which had four metacarpal fractures in the same limb. Radiographs taken at re-evaluation showed implant migration within the medullary canal in two cats, although neither showed any signs of non-union or lameness. Non-union was seen in one operated cat, in which the fracture (MC IV) could not be completely reduced with a K-wire. Osteomyelitis did not occur. Dowel pinning is an easy, inexpensive and effective technique for repair of metacarpal and metatarsal fractures in cats.
What’s new in muscle and peripheral nerve diseases?
Authors: Shelton G. D.
Published: November 2007

It is likely that most neuromuscular diseases that are described in humans will have a counterpart in our companion animals. With the advent of molecular genetics and the completion of the canine and feline genomes, an ever expanding number of DNA-based tests should become available for the diagnosis of muscle and peripheral nerve diseases. Molecular testing procedures should enable us to continue to unravel the molecular basis of neuromuscular diseases for which the cause is still unknown. It is important that accurate clinical evaluations and diagnostic testing, including muscle and peripheral nerve biopsies, are performed in order to reach these goals. This review focuses on recently identified inherited neuromuscular diseases in companion animals.
Serum Total Bilirubin Level and Prevalent Lower-Extremity Peripheral Arterial Disease
Authors: Perlstein Todd S. , Pande Reena L. , Beckman Joshua A. , Creager Mark A.
Published: November 2007

Background—

Bilirubin, with recently recognized antioxidant and antiinflammatory activity, has emerged as a candidate for atheroprotection. We hypothesized that higher levels of bilirubin would reduce susceptibility to peripheral arterial disease (PAD).

Methods and Results—

We analyzed 7075 adults with data available on the ankle brachial index, serum total bilirubin level, and PAD risk factors in the National Health and Nutrition Examination Survey (1999 to 2004), a nationally representative cross-sectional examination of the United States population. A 0.1 mg/dL increase in bilirubin level was associated with a 6% reduction in the odds of PAD (OR 0.94 [95% CI 0.90 to 0.98]) after adjustment for age, gender, race/ethnicity, smoking status, diabetes, hypertension, hypercholesterolemia, chronic kidney disease, CRP, and homocysteine. This result was not dependent on bilirubin levels above the reference range, liver disease, or alcohol intake. The inverse association of bilirubin with PAD tended to be stronger among men (OR 0.90 [95% CI 0.85 to 0.96]) compared with women (OR 0.97 [95% CI 0.91 to 1.04];
P
interaction
=0.05), and was stronger among active smokers (OR 0.81 [95% CI 0.73 to 0.90]) compared with nonsmokers (OR 0.97 [95% CI 0.93 to 1.02];
P
interaction
<0.01).

Conclusions—

Increased serum total bilirubin level is associated with reduced PAD prevalence. This result is consistent with the hypothesis that bilirubin is protective from PAD.
Association of Gene Variants With Incident Myocardial Infarction in the Cardiovascular Health Study
Authors: Shiffman Dov , O’Meara Ellen S. , Bare Lance A. , Rowland Charles M. , Louie Judy Z. , Arellano Andre R. , Lumley Thomas , Rice Kenneth , Iakoubova Olga , Luke May M. , Young Bradford A. , Malloy Mary J. , Kane John P. , Ellis Stephen G. , Tracy Russell P. , Devlin James J. , Psaty Bruce M.
Published: November 2007

Objective—

We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older.

Methods and Results—

Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74 SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS). The prespecified risk alleles of 8 SNPs were nominally associated (1-sided
P
<0.05) with increased risk of MI in White CHS participants. The false discovery rate for these 8 was 0.43, suggesting that about 4 of these 8 are likely to be true positives. The 4 of these 8 SNPs that had the strongest evidence for association with cardiovascular disease before testing in CHS (association in 3 antecedent studies) were in
KIF6
(CHS HR=1.29; 90%CI 1.1 to 1.52),
VAMP8
(HR=1.2; 90%CI 1.02 to 1.41),
TAS2R50
(HR=1.13; 90%CI 1 to 1.27), and
LPA
(HR=1.62; 90%CI 1.09 to 2.42).

Conclusions—

Although most of the SNPs investigated were not associated with MI in CHS, evidence from this investigation combined with previous studies suggests that 4 of these SNPs are likely associated with MI.
Association Between Plasma LDL Particle Size, Valvular Accumulation of Oxidized LDL, and Inflammation in Patients With Aortic Stenosis
Authors: Mohty Dania , Pibarot Philippe , Després Jean-Pierre , Côté Claude , Arsenault Benoit , Cartier Amélie , Cosnay Pierre , Couture Christian , Mathieu Patrick
Published: November 2007

Objective—

In patients with severe aortic stenosis (AS), we examine the association between: (1) the content of oxidized LDL (oxLDL) in the aortic valve and the degree of inflammation and remodeling; (2) The proportion of small dense LDL particles in the plasma and the presence of oxLDL in the valve along with hemodynamic progression of valve stenosis.

Methods and Results—

We have examined 102 explanted AS valves. Tissue remodeling, inflammation, and accumulation of oxLDL were determined. A complete plasma lipid profile including the measurement of the relative proportion of small low-density lipoprotein (%LDL
<255Å
) was obtained. Valves with higher oxLDL content had a significantly higher density of inflammatory cells, expression of tumor necrosis factor (TNF)-α, and increased tissue remodeling score. The %LDL
<255Å
was significantly associated with oxLDL score within the aortic valve. In a subset of 59 patients in whom stenosis progression was measured, the %LDL
<255Å
correlated with the annualized peak gradient (
r
=0.29;
P
=0.04).

Conclusion—

Increased proportion of circulating small dense LDL particles is associated with faster progression rate of stenosis and greater accumulation of oxLDL in the aortic valve. These findings suggest that therapeutic interventions aimed at lowering the production of small dense LDL particles in patients with AS might represent a potentially interesting therapeutic avenue.
Novel Mode for Neutrophil Protease Cathepsin G–Mediated Signaling
Authors: Rafiq Khadija , Hanscom Marie , Valerie Kristoffer , Steinberg Susan F. , Sabri Abdelkarim
Published: November 2007

Neutrophils are thought to orchestrate myocardial remodeling during the early progression to cardiac failure through the release of reactive oxygen species, antimicrobial peptides, and proteases. Although neutrophil activation may be beneficial at early stages of disease, excessive neutrophil infiltration can induce cardiomyocyte death and tissue damage. The neutrophil-derived serine protease cathepsin G (Cat.G) has been shown to induce neonatal rat cardiomyocyte detachment and apoptosis by anoikis. However, the involved signaling mechanisms for Cat.G are not well understood. This study identifies epidermal growth factor receptor (EGFR) transactivation as a mechanism whereby Cat.G induces signaling in cardiomyocytes. Cat.G induced a rapid and transient increase in EGFR tyrosine phosphorylation, and inhibition of EGFR kinase activity, either with AG1478 or by expression of kinase inactive EGFR mutants (EGFR-CD533), markedly attenuated EGFR downstream signaling and myocyte anoikis induced by Cat.G. Consistent with this effect of EGFR, high level expression of wild-type EGFR was sufficient to promote myocyte apoptosis. We also found that matrix metalloproteinase–dependent membrane shedding of heparin-binding EGF was involved in Cat.G signaling and that membrane type 1 matrix metalloproteinase activation may constitute a potential target that entails matrix metalloproteinase activation induced by Cat.G. The paradoxical proapoptotic effect of EGFR appeared to be dependent on protein tyrosine phosphatase SHP2 (Src homology domain 2–containing tyrosine phosphatase 2) activation and focal adhesion kinase downregulation. These results show that Cat.G-induced cardiomyocyte apoptosis involves an increase in EGFR-dependent activation of SHP2 that promotes focal adhesion kinase dephosphorylation and subsequent cardiomyocyte anoikis.
Altered Heart Rate and Sinoatrial Node Function in Mice Lacking the cAMP Regulator Phosphoinositide 3-Kinase-γ
Authors: Rose Robert A. , Kabir M. Golam , Backx Peter H.
Published: November 2007

Ablation of the enzyme phosphoinositide 3-kinase (PI3K)γ (PI3Kγ
−/−
) in mice increases cardiac contractility by elevating intracellular cAMP and enhancing sarcoplasmic reticulum Ca
2+
handling. Because cAMP is a critical determinant of heart rate, we investigated whether heart rate is altered in mice lacking PI3Kγ. Heart rate was similar in anesthetized PI3Kγ
−/−
and wild-type (PI3Kγ
+/+
) mice. However, IP injection of atropine (1 mg/kg), propranolol (1 mg/kg), or both drugs in combination unmasked elevated heart rates in PI3Kγ
−/−
mice, suggesting altered sinoatrial node (SAN) function. Indeed, spontaneous action potential frequency was ≈35% greater in SAN myocytes isolated from PI3Kγ
−/−
mice compared with PI3Kγ
+/+
mice. These differences in action potential frequency were abolished by intracellular dialysis with the cAMP/protein kinase A antagonist Rp-cAMP but were unaffected by treatment with ryanodine to inhibit sarcoplasmic reticulum Ca
2+
release. Voltage-clamp experiments demonstrated that elevated action potential frequencies in PI3Kγ
−/−
SAN myocytes were more strongly associated with cAMP-dependent increases in L-type Ca
2+
current (
I
Ca,L
) than elevated hyperpolarization-activated current (
I
f
). In contrast,
I
Ca,L
was not increased in working atrial myocytes, suggesting distinct subcellular regulation of L-type Ca
2+
channels by PI3Kγ in the SAN compared with the working myocardium. In summary, PI3Kγ regulates heart rate by the cAMP-dependent modulation of SAN function. The effects of PI3Kγ ablation in the SAN are unique from those in the working myocardium.
Hydrogen Peroxide Inhibits Cytochrome P450 Epoxygenases
Authors: Larsen Brandon T. , Gutterman David D. , Sato Atsushi , Toyama Kazuyoshi , Campbell William B. , Zeldin Darryl C. , Manthati Vijay L. , Falck John R. , Miura Hiroto
Published: November 2007

The cytochrome P450 epoxygenase (CYP)-derived metabolites of arachidonic acid the epoxyeicosatrienoic acids (EETs) and hydrogen peroxide (H2O2) both function as endothelium-derived hyperpolarizing factors (EDHFs) in the human coronary microcirculation. However, the relative importance of and potential interactions between these 2 vasodilators remain unexplored. We identified a novel inhibitory interaction between CYPs and H2O2in human coronary arterioles, where EDHF-mediated vasodilatory mechanisms are prominent. Bradykinin induced vascular superoxide and H2O2production in an endothelium-dependent manner and elicited a concentration-dependent dilation that was reduced by catalase but not by 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE), 6-(2-propargyloxyphenyl)hexanoic acid, sulfaphenazole, or iberiotoxin. However, in the presence of catalase, an inhibitory effect of these compounds was unmasked. In a tandem-bioassay preparation, application of bradykinin to endothelium-intact donor vessels elicited dilation of downstream endothelium-denuded detectors that was partially inhibited by donor-applied catalase but not by detector-applied EEZE; however, EEZE significantly inhibited dilation in the presence of catalase. EET production by human recombinant CYP 2C9 and 2J2, 2 major epoxygenase isozymes expressed in human coronary arterioles, was directly inhibited in a concentration-dependent fashion by H2O2in vitro, as observed by high-performance liquid chromatography (HPLC); however, EETs were not directly sensitive to oxidative modification. H2O2inhibited dilation to arachidonic acid but not to 11,12-EET. These findings suggest that an inhibitory interaction exists between 2 EDHFs in the human coronary microcirculation. CYP epoxygenases are directly inhibited by H2O2, and this interaction may modulate vascular EET bioavailability.
Cardiac Troponin I Threonine 144
Authors: Tachampa Kittipong , Wang Helen , Farman Gerrie P. , de Tombe Pieter P.
Published: November 2007

Myofilament length–dependent activation is the main cellular mechanism responsible for the Frank–Starling law of the heart. All striated muscle display length-dependent activation properties, but it is most pronounced in cardiac muscle and least in slow skeletal muscle. Cardiac muscle expressing slow skeletal troponin (ssTn)I instead of cardiac troponin (cTn)I displays reduced myofilament length–dependent activation. The inhibitory region of troponin (Tn)I differs by a single residue, proline at position 112 in ssTnI versus threonine at position 144 in cTnI. Here we tested whether this substitution was important for myofilament length–dependent activation; using recombinant techniques, we prepared wild-type cTnI, ssTnI, and 2 mutants: cTnI
Thr>Pro
and ssTnI
Pro>Thr
. Purified proteins were complexed with recombinant cardiac TnT/TnC and exchanged into skinned rat cardiac trabeculae. Force–Ca
2+
relationships were determined to derive myofilament Ca
2+
sensitivity (EC
50
) at 2 sarcomere lengths: 2.0 and 2.2 μm (n=7). Myofilament length-dependent activation was indexed as ΔEC
50
, the difference in EC
50
between sarcomere lengths of 2.0 and 2.2 μm. Incorporation of ssTnI compared with cTnI into the cardiac sarcomere reduced ΔEC
50
from 1.26±0.30 to 0.19±0.04 μmol/L. A similar reduction also could be observed when Tn contained cTnI
Thr>Pro
(ΔEC
50
=0.24±0.04 μmol/L), whereas the presence of ssTnI
Pro>Thr
increased ΔEC
50
to 0.94±0.12 μmol/L. These results suggest that Thr144 in cardiac TnI modulates cardiac myofilament length–dependent activation.
Comparison of 10 Different Magnetic Resonance Perfusion Imaging Processing Methods in Acute Ischemic Stroke
Authors: Kane Ingrid , Carpenter Trevor , Chappell Francesca , Rivers Carly , Armitage Paul , Sandercock Peter , Wardlaw Joanna
Published: November 2007

Background and Purpose—

Several methods are available to assess the magnetic resonance perfusion lesion in acute ischemic stroke. We tested 10 of these to compare perfusion lesion sizes and to assess the relation to clinical scores and final infarct extent.

Methods—

We recruited patients with acute ischemic stroke, performed diffusion- and perfusion-weighted imaging, and recorded stroke severity at baseline, final infarct size on T2-weighted imaging at ≥1 month, and Rankin Scale score at 3 months. We calculated 10 perfusion parameters (6 of mean transit time, MTT; 3 of cerebral blood flow; 1 of cerebral blood volume; 7 relative and 3 quantitative), measured the perfusion-weighted imaging lesion and diffusion/perfusion mismatch volumes, and compared each with clinical and radiologic outcomes.

Results—

Among 32 patients, the median perfusion lesion volume varied from 0 to 14 882 voxels (
P
<0.0001); the proportion of patients with mismatch varied from 9% to 72% (
P
<0.05), depending on the perfusion parameter. Five measures of relative MTT were associated with baseline National Institutes of Health Stroke Scale score; 1 (arrival time fitted) was also associated with clinical outcome. Final infarct size was most strongly associated with MTT measures, including arrival time fitted. There was no advantage of quantitative perfusion measures and no relation between mismatch presence/absence and infarct expansion with any of the 10 perfusion measures.

Conclusions—

Perfusion lesion size differs markedly depending on the parameter calculated. Relative perfusion parameters performed as well as quantitative ones. Some parameters (mainly representing MTT measures) were correlated with clinical scores; others were correlated with final infarct size; and arrival time fitted was correlated with both. These findings should be validated in other datasets. A consensus is required on which perfusion measurement and processing methods should be used.
Protein Aggregation and Proteasome Dysfunction After Brain Ischemia
Authors: Ge Pengfei , Luo Yinan , Liu Cindy L. , Hu Bingren
Published: November 2007

Background and Purpose—

Protein unfolding and aggregation are dominant early pathogenic events in neurons after brain ischemia. This study used a transient cerebral ischemia model to investigate whether overproduction of unfolded proteins after brain ischemia is a consequence of proteasome dysfunction.

Methods—

Proteasome peptidase activity and proteasome subcellular redistribution and assembly were studied by peptidase activity assay, Western blot analysis, and size-exclusion chromatography.

Results—

Proteasome peptidase activity, as determined with the peptide substrate succinyl-LLVY-7-amino-4-methylcoumarin, was moderately decreased, and the 26S proteasome was disassembled during the early period of reperfusion after transient brain ischemia. Furthermore, the proteasome subunits, particularly the 19S components, were deposited into the protein aggregate-containing fraction after an episode of transient cerebral ischemia.

Conclusions—

These results clearly demonstrate that after an episode of brain ischemia, proteasomes are disassembled and aggregated and thus fail to function normally. Deposition of proteasomes into protein aggregates may also indicate that proteasomes attempt to degrade ubiquitin-conjugated proteins (ubiproteins) overproduced after brain ischemia. However, ubiproteins are too numerous to be degraded and trap some of the proteasomes into their aggregates after brain ischemia.
Shift Analysis Versus Dichotomization of the Modified Rankin Scale Outcome Scores in the NINDS and ECASS-II Trials
Authors: Savitz Sean I. , Lew Robert , Bluhmki Erich , Hacke Werner , Fisher Marc
Published: November 2007

Background and Purpose—

The SAINT I trial that showed a significant benefit of the neuroprotectant NXY-059 used a novel outcome for acute ischemic stroke trials: a shift toward good functional outcome on the 7-category modified Rankin scale (mRS).

Methods—

We used the Cochran-Mantel-Haenszel shift test to analyze the distribution of the 90-day mRS outcomes in the NINDS and ECASS-II databases and compared the results with a dichotomized mRS outcome by logistic regression (0 to 2 vs 3 to 6, or 0 to 1 vs 2 to 6). We also stratified each dataset based on National Institutes of Health Stroke Scale baseline severity.

Results—

Each dataset showed a statistically significant shift in the 90-day mRS distributions favoring tissue plasminogen activator (odds ratio, 1.6 for NINDS, 1.3 for ECASS-II). For ECASS-II, larger shift effects appeared in National Institutes of Health Stroke Scale 0 to 6 and 16 to 40 strata. Similarly, the mRS 0 to 2 analysis but not mRS 0 to 1 found similar treatment effects in both datasets (odds ratio, 1.6 for NINDS, 1.5 for ECASS-II) and similar variations in the low and high strata in the ECASS-II trial. NINDS found no significant treatment effects across the strata. After removing the strata at the fringes, the shift test lost significance in both datasets.

Conclusions—

Tissue plasminogen activator causes a beneficial shift toward wellness on the mRS in both the NINDS and ECASS-II trials, and ECASS-II would have been a positive trial according to the shift approach. However, the shift effect is not global for all treated patients and does not outperform the dichotomized 0 to 2 outcome. Patients with mild and severe deficits also shifted favorably on the mRS in the ECASS-II trial.
Novel Mouse Model of Monocular Amaurosis Fugax
Authors: Lelong Dominique Claude , Bieche Ivan , Perez Elodie , Bigot Karine , Leemput Julia , Laurendeau Ingrid , Vidaud Michel , Jais Jean-Philippe , Menasche Maurice , Abitbol Marc
Published: November 2007

Background and Purpose—

Retinal ischemia is a major cause of visual impairment and is associated with a high risk of subsequent ischemic stroke. The retina and its projections are easily accessible for experimental procedures and functional evaluation. We created and characterized a mouse model of global and transient retinal ischemia and provide a comprehensive chronologic profile of some genes that display altered expression during ischemia.

Methods—

Ischemia and reperfusion were assessed by observing flat-mounted retinas after systemic fluorescein injection. The temporal pattern of gene expression modulation was evaluated by quantitative reverse transcription–polymerase chain reaction from the occurrence of unilateral 30-minute pterygopalatine artery occlusion until 4 weeks after reperfusion. Electroretinograms evaluated functional sequelae 4 weeks after the ischemic episode and were correlated with histologic lesions.

Results—

This model is the first to reproduce the features of transient monocular amaurosis fugax resulting from ophthalmic artery occlusion. The histologic structure was roughly conserved, but functional lesions affected ganglion cells, inner nuclear layer cells, and photoreceptor cells. We observed an early and strong upregulation of c
-fos
, c
-jun, Cox-2, Hsp70
, and
Gadd34
gene expression and a late decrease in
Hsp70
transcript levels.

Conclusions—

A murine model of transient retinal ischemia was successfully developed that exhibited the characteristic upregulation of immediate-early genes and persistent functional deficits. The model should prove useful for investigating mechanisms of injury in genetically altered mice and for testing novel neuroprotective drugs.
Impact of Scale and Aggregation on the Terrestrial Water Exchange: Integrating Land Surface Models and Rhône Catchment Observations
Authors: Stöckli Reto , Vidale Pier Luigi , Boone Aaron , Schär Christoph
Published: November 2007

Land surface models (LSMs) used in climate modeling include detailed above-ground biophysics but usually lack a good representation of runoff. Both processes are closely linked through soil moisture. Soil moisture however has a high spatial variability that is unresolved at climate model grid scales. Physically based vertical and horizontal aggregation methods exist to account for this scaling problem. Effects of scaling and aggregation have been evaluated in this study by performing catchment-scale LSM simulations for the Rhône catchment. It is found that evapotranspiration is not sensitive to soil moisture over the Rhône but it largely controls total runoff as a residual of the terrestrial water balance. Runoff magnitude is better simulated when the vertical soil moisture fluxes are resolved at a finer vertical resolution. The use of subgrid-scale topography significantly improves both the timing of runoff on the daily time scale (response to rainfall events) and the magnitude of summer baseflow (from seasonal groundwater recharge). Explicitly accounting for soil moisture as a subgrid-scale process in LSMs allows one to better resolve the seasonal course of the terrestrial water storage and makes runoff insensitive to the used grid scale. However, scale dependency of runoff to above-ground hydrology cannot be ignored: snowmelt runoff from the Alpine part of the Rhône is sensitive to the spatial resolution of the snow scheme, and autumnal runoff from the Mediterranean part of the Rhône is sensitive to the spatial resolution of precipitation.
Convective Planetary Boundary Layer Interactions with the Land Surface at Diurnal Time Scales: Diagnostics and Feedbacks
Authors: Santanello Joseph A. , Friedl Mark A. , Ek Michael B.
Published: November 2007

The convective planetary boundary layer (PBL) integrates surface fluxes and conditions over regional and diurnal scales. As a result, the structure and evolution of the PBL contains information directly related to land surface states. To examine the nature and magnitude of land–atmosphere coupling and the interactions and feedbacks controlling PBL development, the authors used a large sample of radiosonde observations collected at the southern Atmospheric Research Measurement Program–Great Plains Cloud and Radiation Testbed (ARM-CART) site in association with simulations of mixed-layer growth from a single-column PBL/land surface model. The model accurately predicts PBL evolution and realistically simulates thermodynamics associated with two key controls on PBL growth: atmospheric stability and soil moisture. The information content of these variables and their influence on PBL height and screen-level temperature can be characterized using statistical methods to describe PBL–land surface coupling over a wide range of conditions. Results also show that the first-order effects of land–atmosphere coupling are manifested in the control of soil moisture and stability on atmospheric demand for evapotranspiration and on the surface energy balance. Two principal land–atmosphere feedback regimes observed during soil moisture drydown periods are identified that complicate direct relationships between PBL and land surface properties, and, as a result, limit the accuracy of uncoupled land surface and traditional PBL growth models. In particular, treatments for entrainment and the role of the residual mixed layer are critical to quantifying diurnal land–atmosphere interactions.
An Alternative Mass Flux Profile in the Kain–Fritsch Convective Parameterization and Its Effects in Seasonal Precipitation
Authors: Anderson Christopher J. , Arritt Raymond W. , Kain John S.
Published: November 2007

The authors have altered the vertical profile of updraft mass flux detrainment in an implementation of the Kain–Fritsch2 (KF2) convective parameterization within the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (Penn State–NCAR) Mesoscale Model (MM5). The effect of this modification was to alter the vertical profile of convective parameterization cloud mass (including cloud water and ice) supplied to the host model for explicit simulation by the grid-resolved dynamical equations and parameterized microphysical processes. These modifications and their sensitivity to horizontal resolution in a matrix of experimental simulations of the June–July 1993 flood in the central United States were tested.

The KF2 modifications impacted the diurnal cycle of precipitation by reducing precipitation from the convective parameterization and increasing precipitation from more slowly evolving mesoscale processes. The modified KF2 reduced an afternoon bias of high precipitation rate in both low- and high-resolution simulations but affected mesoscale precipitation processes only in high-resolution simulations. The combination of high-resolution and modified KF2 resulted in more frequent and more realistically clustered propagating, nocturnal mesoscale precipitation events and agreed best with observations of the nocturnal precipitation rate.
Evaluation of the Hydrological Cycle over the Mississippi River Basin as Simulated by the Canadian Regional Climate Model (CRCM)
Authors: Music Biljana , Caya Daniel
Published: November 2007

The water cycle over a given region is governed by many complex multiscale interactions and feedbacks, and their representation in climate models can vary in complexity. To understand which of the key processes require better representation, evaluation and validation of all components of the simulated water cycle are required. Adequate assessing of the simulated hydrological cycle over a given region is not trivial because observations for various water cycle components are seldom available at the regional scale.

In this paper, a comprehensive validation method of the water budget components over a river basin is presented. In addition, the sensitivity of the hydrological cycle in the Canadian Regional Climate Model (CRCM) to a more realistic representation of the land surface processes, as well as radiation, cloud cover, and atmospheric boundary layer mixing is investigated. The changes to the physical parameterizations are assessed by evaluating the CRCM hydrological cycle over the Mississippi River basin. The first part of the evaluation looks at the basin annual means. The second part consists of the analysis and validation of the annual cycle of all water budget components. Finally, the third part is directed toward the spatial distribution of the annual mean precipitation, evapotranspiration, and runoff.

Results indicate a strong response of the CRCM evapotranspiration and precipitation biases to the physical parameterization changes. Noticeable improvement was obtained in the simulated annual cycles of precipitation, evapotranspiration, moisture flux convergence, and terrestrial water storage tendency when more sophisticated physical parameterizations were used. Some improvements are also observed for the simulated spatial distribution of precipitation and evapotranspiration. The simulated runoff is less sensitive to changes in the CRCM physical parameterizations.
Systematic Bias in Land Surface Models
Authors: Abramowitz Gab , Pitman Andy , Gupta Hoshin , Kowalczyk Eva , Wang Yingping
Published: November 2007

A neural network–based flux correction technique is applied to three land surface models. It is then used to show that the nature of systematic model error in simulations of latent heat, sensible heat, and the net ecosystem exchange of CO2 is shared between different vegetation types and indeed different models. By manipulating the relationship between the dataset used to train the correction technique and that used to test it, it is shown that as much as 45% of per-time-step model root-mean-square error in these flux outputs is due to systematic problems in those model processes insensitive to changes in vegetation parameters. This is shown in the three land surface models using flux tower measurements from 13 sites spanning 2 vegetation types. These results suggest that efforts to improve the representation of fundamental processes in land surface models, rather than parameter optimization, are the key to the development of land surface model ability.
The Impact of Different Physical Parameterizations and Their Interactions on Cold Season QPF in the American River Basin
Authors: Jankov Isidora , Schultz Paul J. , Anderson Christopher J. , Koch Steven E.
Published: November 2007

The most significant precipitation events in California occur during the winter and are often related to synoptic-scale storms from the Pacific Ocean. Because of the terrain characteristics and the fact that the urban and infrastructural expansion is concentrated in lower elevation areas of the California Central Valley, a high risk of flooding is usually associated with these events. In the present study, the area of interest was the American River basin (ARB). The main focus of the present study was to investigate methods for Quantitative Precipitation Forecast (QPF) improvement by estimating the impact that various microphysical schemes, planetary boundary layer (PBL) schemes, and initialization methods have on cold season precipitation, primarily orographically induced. For this purpose, 3-km grid spacing Weather Research and Forecasting (WRF) model simulations of four Hydrometeorological Test bed (HMT) events were used. For each event, four different microphysical schemes and two different PBL schemes were used. All runs were initialized with both a diabatic Local Analysis and Prediction System (LAPS) “hot” start and 40-km eta analyses.

To quantify the impact of physical schemes, their interactions, and initial conditions upon simulated rain volume, the factor separation methodology was used. The results showed that simulated rain volume was particularly affected by changes in microphysical schemes for both initializations. When the initialization was changed from the LAPS to the eta analysis, the change in the PBL scheme and corresponding synergistic terms (which corresponded to the interactions between different microphysical and PBL schemes) resulted in a statistically significant impact on rain volume. In addition, by combining model runs based on the knowledge about their impact on simulated rain volume obtained through the factor separation methodology, the bias in simulated rain volume was reduced.
El Niño Effects and Upwelling off South Australia
Authors: Middleton John F. , Arthur Craig , Van Ruth Paul , Ward Tim M. , McClean Julie L. , Maltrud Mathew E. , Gill Peter , Levings Andrew , Middleton Sue
Published: November 2007

To determine the possible importance of ENSO events along the coast of South Australia, an exploratory analysis is made of meteorological and oceanographic data and output from a global ocean model. Long time series of coastal sea level and wind stress are used to show that while upwelling favorable winds have been more persistent since 1982, ENSO events (i) are largely driven by signals from the west Pacific Ocean shelf/slope waveguide and not local meteorological conditions, (ii) can account for 10-cm changes in sea level, and (iii) together with wind stress, explain 62% of the variance of annual-averaged sea level. Thus, both local winds and remote forcing from the west Pacific are likely important to the low-frequency shelf edge circulation. Evidence also suggests that, since 1983, wintertime downwelling during the onset of an El Niño is reduced and the following summertime upwelling is enhanced. In situ data show that during the 1998 and 2003 El Niño events anomalously cold (10.5°–11.5°C) water is found at depths of 60–120 m and is more than two standard deviations cooler than the mean. A regression showed that averaged sea level can provide a statistically significant proxy for these subsurface temperature changes and indicates a 2.2°C decrease in temperature for the 10-cm decrease in sea level that was driven by the 1998 El Niño event. Limited current- meter observations, long sea level records, and output from a global ocean model were also examined and provide support for the hypothesis that El Niño events substantially reduce wintertime (but not summertime) shelf-edge currents. Further research to confirm this asymmetric response and its cause is required.