bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Density Lipoprotein and the Risk of Recurrent Venous Thromboembolism
Authors: Eichinger Sabine , Pecheniuk Natalie M. , Hron Gregor , Deguchi Hiroshi , Schemper Michael , Kyrle Paul A. , Griffin John H.
Published: March 2007

Background—

High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is unknown whether it protects against recurrent venous thromboembolism.

Methods and Results—

We studied 772 patients after a first spontaneous venous thromboembolism (average follow-up 48 months) and recorded the end point of symptomatic recurrent venous thromboembolism, which developed in 100 of the 772 patients. The relationship between plasma lipoprotein parameters and recurrence was evaluated. Plasma apolipoproteins AI and B were measured by immunoassays for all subjects. Compared with those without recurrence, patients with recurrence had lower mean (±SD) levels of apolipoprotein AI (1.12±0.22 versus 1.23±0.27 mg/mL,
P
<0.001) but similar apolipoprotein B levels. The relative risk of recurrence was 0.87 (95% CI, 0.80 to 0.94) for each increase of 0.1 mg/mL in plasma apolipoprotein AI. Compared with patients with apolipoprotein AI levels in the lowest tertile (<1.07 mg/mL), the relative risk of recurrence was 0.46 (95% CI, 0.27 to 0.77) for the highest-tertile patients (apolipoprotein AI >1.30 mg/mL) and 0.78 (95% CI, 0.50 to 1.22) for midtertile patients (apolipoprotein AI of 1.07 to 1.30 mg/mL). Using nuclear magnetic resonance, we determined the levels of 10 major lipoprotein subclasses and HDL cholesterol for 71 patients with recurrence and 142 matched patients without recurrence. We found a strong trend for association between recurrence and low levels of HDL particles and HDL cholesterol.

Conclusions—

Patients with high levels of apolipoprotein AI and HDL have a decreased risk of recurrent venous thromboembolism.
Complementary and Incremental Mortality Risk Prediction by Cortisol and Aldosterone in Chronic Heart Failure
Authors: Güder Gülmisal , Bauersachs Johann , Frantz Stefan , Weismann Dirk , Allolio Bruno , Ertl Georg , Angermann Christiane E. , Störk Stefan
Published: March 2007

Background—

In patients with systolic heart failure, high levels of circulating aldosterone are associated with an adverse prognosis, and mineralocorticoid receptor blockade improves survival. The prognostic significance of cortisol that may also bind and activate the mineralocorticoid receptor in chronic heart failure is unknown.

Methods and Results—

Serum levels of cortisol and aldosterone were quantified in a prospective cohort study of 294 consecutive patients with chronic heart failure [48% were in New York Heart Association functional class III or IV; 58% had systolic heart failure]. During a median follow-up of 803 days (interquartile range, 314 to 1098), 79 patients died (27.3% mortality rate). Cortisol and aldosterone were independent predictors of increased mortality risk in Cox regression analyses adjusted for age, sex, New York Heart Association functional class, C-reactive protein, N-terminal pro-brain natriuretic peptide, sodium, and hypercholesterolemia. The hazard ratio for highest versus lowest tertile of cortisol was 2.72 [95% confidence interval [CI], 1.38 to 5.36;
P
=0.004], and the hazard ratio for aldosterone was 2.19 (95% CI, 1.23 to 3.93;
P
=0.008). Patients with both cortisol and aldosterone levels above the respective medians had a 3.4-fold higher mortality risk compared with subjects with both corticosteroids below the median (95% CI, 1.54 to 7.46;
P
=0.0001). Addition of cortisol and aldosterone levels to the fully adjusted model significantly improved the discriminatory power [increase in Harrell’s
C
-statistic from 0.80 (95% CI, 0.70 to 0.90) to 0.86 (95% CI, 0.79 to 0.94;
P
<0.001 for change].

Conclusions—

In patients with chronic heart failure, higher serum levels of both cortisol and aldosterone were independent predictors of increased mortality risk that conferred complementary and incremental prognostic value.
Clinical and Genetic Characterization of Families With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Provides Novel Insights Into Patterns of Disease Expression
Authors: Sen-Chowdhry Srijita , Syrris Petros , Ward Deirdre , Asimaki Angeliki , Sevdalis Elias , McKenna William J.
Published: March 2007

Background—

According to clinical-pathological correlation studies, the natural history of arrhythmogenic right ventricular dysplasia/cardiomyopathy is purported to progress from localized to global right ventricular dysfunction, followed by left ventricular (LV) involvement and biventricular pump failure. The inevitable focus on sudden death victims and transplant recipients may, however, have created a skewed perspective of a genetic disease. We hypothesized that unbiased representation of the spectrum of disease expression in arrhythmogenic right ventricular dysplasia/cardiomyopathy would require in vivo assessment of families in a genetically heterogeneous population.

Methods and Results—

A cohort of 200 probands and relatives satisfying task force or modified diagnostic criteria for arrhythmogenic right ventricular dysplasia/cardiomyopathy underwent comprehensive clinical evaluation. Desmosomal mutations were identified in 39 individuals from 20 different families. Indices of structural severity correlated with advancing age and were increased in long-term endurance athletes. Fulfillment of modified criteria indicated phenotypically mild disease, whereas asymptomatic status did not. In >80%, ECG, rhythm monitoring, and/or gadolinium-enhanced cardiovascular magnetic resonance were suggestive of LV involvement, the extent of which often was marked among individuals with chain-termination mutations and/or desmoplakin disease. Three patterns of disease expression were identified: (1)
classic
, with isolated right ventricular disease or LV involvement in association with significant right ventricular impairment; (2)
left dominant
, with early and prominent LV manifestations and relatively mild right-sided disease; and (3)
biventricular
, characterized by parallel involvement of both ventricles.

Conclusions—

LV involvement in arrhythmogenic right ventricular dysplasia/cardiomyopathy may precede the onset of significant right ventricular dysfunction. Recognition of disease variants with early and/or predominant LV involvement supports adoption of the broader term arrhythmogenic cardiomyopathy.
Elastin Stabilization for Treatment of Abdominal Aortic Aneurysms
Authors: Isenburg Jason C. , Simionescu Dan T. , Starcher Barry C. , Vyavahare Narendra R.
Published: March 2007

Background—Maintaining the integrity of arterial elastin is vital for the prevention of abdominal aortic aneurysm (AAA) development. We hypothesized that in vivo stabilization of aortic elastin with pentagalloyl glucose (PGG), an elastin-binding polyphenol, would interfere with AAA development.

Methods and Results—Safety and efficacy of PGG treatment were first tested in vitro using cytotoxicity, elastin stability, and PGG-elastin interaction assays. For in vivo studies, the efficacy of PGG was evaluated within a well-established AAA model in rats on the basis of CaCl2-mediated aortic injury. With this model, PGG was delivered periadventitially at 2 separate time points during the course of AAA development; aortic diameter, elastin integrity, and other pathological aspects were monitored and evaluated in PGG-treated aortas compared with saline-treated control aortas. Our results show that a one-time periadventitial delivery of noncytotoxic levels of PGG inhibits elastin degeneration, attenuates aneurysmal expansion, and hinders AAA development in rats without interfering with the pathogenic mechanisms typical of this model, namely inflammation, calcification, and high metalloproteinase activities. PGG binds specifically to arterial elastin and, in doing so, preserves the integrity of elastic lamellae despite the presence of high levels of proteinases derived from inflammatory cells.

Conclusions—Periadventitial administration of PGG hinders the development of AAA in a clinically relevant animal model. Stabilization of aortic elastin in aneurysm-prone arterial segments offers great potential toward the development of safe and effective therapies for AAAs.
Mutations in
FOXC2
Are Strongly Associated With Primary Valve Failure in Veins of the Lower Limb
Authors: Mellor Russell H. , Brice Glen , Stanton Anthony W.B. , French Jane , Smith Alberto , Jeffery Steve , Levick J. Rodney , Burnand Kevin G. , Mortimer Peter S.
Published: March 2007

Background—

Mutations in the
FOXC2
gene cause lymphedema distichiasis, an inherited primary lymphedema in which a significant number of patients have varicose veins. Because lymphedema distichiasis is believed to be caused by lymphatic valve failure (reflux), and FOXC2 is highly expressed on venous valves in mouse embryos, we tested the hypothesis that
FOXC2
mutations may be linked to venous valve failure and reflux.

Methods and Results—

The venous system of the leg was investigated with Duplex ultrasound. Pathological reflux was recorded by color Duplex ultrasound in all 18 participants with a
FOXC2
mutation, including 3 without lymphedema. Every participant with a mutation in
FOXC2
showed reflux in the great saphenous vein (n=18), compared with only 1 of 12 referents (including 10 family members;
P
<0.0001, Fisher exact test). Deep vein reflux was recorded in 14 of 18 participants.

Conclusions—

FOXC2
is the first gene in which mutations have been strongly associated with primary venous valve failure in both the superficial and deep veins in the lower limb. This gene appears to be important for the normal development and maintenance of venous and lymphatic valves.
CD40 Ligand Mediates Inflammation Independently of CD40 by Interaction With Mac-1
Authors: Zirlik Andreas , Maier Christoph , Gerdes Norbert , MacFarlane Lindsey , Soosairajah Juliana , Bavendiek Udo , Ahrens Ingo , Ernst Sandra , Bassler Nicole , Missiou Anna , Patko Zsofia , Aikawa Masanori , Schönbeck Uwe , Bode Christoph , Libby Peter , Peter Karlheinz
Published: March 2007

Background—

Strong evidence supports a role for CD40 ligand (CD40L) as marker and mediator of inflammatory diseases such as atherosclerosis. Despite extensive characterization of CD40, the classic receptor of CD40L, its role in immune defense against inflammatory diseases remains uncertain. The present study aimed to characterize the contribution of CD40 signaling to atherogenesis.

Methods and Results—

Surprisingly, mice deficient in both CD40 and the low-density lipoprotein receptor did not develop smaller lesions in the aortic arch, root, and thoracoabdominal aorta compared with mice deficient only in the low-density lipoprotein receptor that consumed an atherogenic diet for 8 and 16 weeks. By flow cytometry, radioactive binding assays, and immunoprecipitation, we demonstrate that CD40L interacts with the integrin Mac-1, which results in Mac-1–dependent adhesion and migration of inflammatory cells as well as myeloperoxidase release in vitro. Furthermore, mice deficient in CD40L show significantly reduced thioglycolate-elicited invasion of inflammatory cells into the peritoneal cavity compared with mice deficient in CD40 and wild-type controls. Inhibition of Mac-1 in low-density lipoprotein receptor–deficient mice attenuates lesion development and reduces lesional macrophage accumulation.

Conclusions—

These observations identify the interaction of CD40L and Mac-1 as an alternative pathway for CD40L-mediated inflammation. This novel mechanism expands understanding of inflammatory signaling during atherogenesis.
Increased Connective Tissue Growth Factor Relative to Brain Natriuretic Peptide as a Determinant of Myocardial Fibrosis
Authors: Koitabashi Norimichi , Arai Masashi , Kogure Shinya , Niwano Kazuo , Watanabe Atai , Aoki Yasuhiro , Maeno Toshitaka , Nishida Takashi , Kubota Satoshi , Takigawa Masaharu , Kurabayashi Masahiko
Published: March 2007

Excessive fibrosis contributes to an increase in left ventricular stiffness. The goal of the present study was to investigate the role of connective tissue growth factor (CCN2/CTGF), a profibrotic cytokine of the CCN (
Cyr61
,
CTGF
, and
Nov
) family, and its functional interactions with brain natriuretic peptide (BNP), an antifibrotic peptide, in the development of myocardial fibrosis and diastolic heart failure. Histological examination on endomyocardial biopsy samples from patients without systolic dysfunction revealed that the abundance of CTGF-immunopositive cardiac myocytes was correlated with the excessive interstitial fibrosis and a clinical history of acute pulmonary congestion. In a rat pressure overload cardiac hypertrophy model,
CTGF
mRNA levels and
BNP
mRNA were increased in proportion to one another in the myocardium. Interestingly, relative abundance of mRNA for
CTGF
compared with
BNP
was positively correlated with diastolic dysfunction, myocardial fibrosis area, and procollagen type 1 mRNA expression. Investigation with conditioned medium and subsequent neutralization experiments using primary cultured cells demonstrated that CTGF secreted by cardiac myocytes induced collagen production in cardiac fibroblasts. Further, G protein-coupled receptor ligands induced expression of the
CTGF
and
BNP
genes in cardiac myocytes, whereas aldosterone and transforming growth factor-β preferentially induced expression of the
CTGF
gene. Finally, exogenous BNP prevented the production of CTGF in cardiac myocytes. These data suggest that a disproportionate increase in CTGF relative to BNP in cardiac myocytes plays a central role in the induction of excessive myocardial fibrosis and diastolic heart failure.
Immunoreactivity and Guanosine 3′,5′-Cyclic Monophosphate Activating Actions of Various Molecular Forms of Human B-Type Natriuretic Peptide
Authors: Heublein Denise M. , Huntley Brenda K. , Boerrigter Guido , Cataliotti Alessandro , Sandberg Sharon M. , Redfield Margaret M. , Burnett John C.
Published: March 2007

Recent studies support the speculation that different molecular forms of the cardiac hormone BNP with differential biological activity may circulate in heart failure and be detected by conventional assays. In the current study we determined the ability of 3 widely used conventional assays to detect these different forms thought to circulate in heart failure. We also evaluated the ability of pro-BNP (1-108), N-terminal peptide (NT)–pro-BNP (1-76), and BNP 3-32, the latter a cleavage product of BNP 1-32 by dipeptidyl peptidase IV, on an equimolar basis to activate cGMP in cultured cardiac fibroblasts and cardiomyocytes compared with the biologically active mature BNP 1-32. Specifically, we observed that the Roche NT–pro-BNP assay detected both NT–pro-BNP 1-76 and pro-BNP 1-108 and that Biosite Triage and Shionogi detected both mature BNP 1-32 and the shortened BNP 3-32. Moreover, in cultured cardiac fibroblasts and cardiomyocytes, BNP 1-32 (10
−6
mol/L) activated cGMP. BNP 3-32 demonstrated a similar cGMP activating property in both cardiac cell types. In contrast, the cGMP response to pro-BNP 1-108 and NT–pro-BNP 1-76 was not significantly greater than no treatment alone. We conclude that widely used commercial assays for NT–pro-BNP 1-76 and BNP 1-32 cannot differentiate among pro-, processed, or degraded forms and, thus, may not thoroughly identify circulating BNP forms in heart failure patients. These findings also demonstrate differential cGMP activating properties of BNP forms and, importantly, that pro-BNP 1-108 and NT–pro-BNP 1-76 have reduced cGMP activity in vitro that may have biological relevance to human heart failure.
Ambulatory Arterial Stiffness Index Is Not a Specific Marker of Reduced Arterial Compliance
Authors: Schillaci Giuseppe , Parati Gianfranco , Pirro Matteo , Pucci Giacomo , Mannarino Massimo R. , Sperandini Laura , Mannarino Elmo
Published: March 2007

Ambulatory arterial stiffness index (AASI), a measure based on the relative behavior of 24-hour systolic and diastolic blood pressure (BP), has been suggested as a marker of arterial stiffness and a predictor of cardiovascular mortality. However, a narrow range of diastolic BP values over the 24 hours tends to flatten the regression slope and to artificially increase AASI. We explored the possible influence of different ranges of 24-hour diastolic BP fluctuations, such as those related to nocturnal BP fall, on AASI, and on its relationship with target organ damage. In 515 untreated hypertensive patients, AASI was directly related to age (
r
=0.30) and 24-hour systolic BP (
r
=0.20), whereas it was inversely related with nocturnal systolic and diastolic BP reduction (
r
=−0.28 and −0.46, respectively; all
P
<0.001). A direct relationship was found between AASI and left ventricular mass index (
r
=0.17;
P
<0.001), but this relation was no longer significant after adjustment for age, sex, body mass index, daytime systolic BP, and day-night systolic BP reduction (all
P
<0.05). AASI was directly related to carotid-femoral pulse wave velocity, an intrinsic measure of aortic stiffness (
r
=0.28;
P
<0.001), but no independent relation was found in a multiple linear regression. Our conclusions are as follows: (1) AASI is strongly dependent on the degree of nocturnal BP fall in hypertensive patients; (2) there is no significant relation between AASI and left ventricular mass after proper adjustment for confounders; and (3) the relation between AASI and a widely accepted measure of aortic stiffness, such as pulse wave velocity, is weak and importantly affected by other factors.
Age-Related Changes in Echocardiographic Measurements
Authors: Peter Inga , Huggins Gordon S. , Shearman Amanda M. , Pollak Arthur , Schmid Christopher H. , Cupples L. Adrienne , Demissie Serkalem , Patten Richard D. , Karas Richard H. , Housman David E. , Mendelsohn Michael E. , Vasan Ramachandran S. , Benjamin Emelia J.
Published: March 2007

Left ventricular (LV) mass and other LV measures have been shown to be heritable. In this study we hypothesized that functional variation in the gene coding for estrogen receptor-α (
ESR1
), known for mediating the effect of estrogens on myocardium, is associated with age-related changes in LV structure. Four genetic markers (
ESR1 TA
repeat;
rs2077647
, or +
30T
>
C
;
rs2234693
, or
Pvu
II; and
rs9340799
, or
Xba
I) were genotyped in 847 unrelated individuals (488 women) from the Framingham Offspring Study, who attended 2 examination cycles 16 years apart (mean ages at first examination: 43±9 years; at follow-up: 59±9 years). ANCOVA was used to assess the association of polymorphisms and their haplotypes with cross-sectional measurements and longitudinal changes in LV mass, wall thickness, end-diastolic and end-systolic internal diameter, and fractional shortening after adjustment for factors known to influence these variables. Changes over time were detected for all of the LV measurements (
P
ranging from <0.0001 to 0.02), except for fractional shortening in men. The
SS
genotype of the
ESR1 TA
repeat polymorphism in the promoter region was associated with longitudinal changes in LV mass and LV wall thickness (
P
ranging from 0.0006 to 0.01). Moreover, the
TA
[
S
]–
+30
[
T
]–
Pvu
II[
T
]–
Xba
I[
A
] haplotype (frequency: 47.5%) was associated with greater LV changes as compared with the
TA
[
L
]
–+30
[
C
]–
Pvu
II[
C
]–
Xba
I[
G
] haplotype (frequency: 31.8%). Our results are consistent with the hypothesis that common
ESR1
polymorphisms are significantly associated with age-related changes in LV structure. Understanding the mechanisms predisposing to unfavorable LV remodeling of the heart with advancing age may aid in the discovery of new therapeutic targets for the prevention of heart failure.
CYP3A5
and
ABCB1
Genes Influence Blood Pressure and Response to Treatment, and Their Effect Is Modified by Salt
Authors: Eap Chin B. , Bochud Murielle , Elston Robert C. , Bovet Pascal , Maillard Marc P. , Nussberger Juerg , Schild Laurent , Shamlaye Conrad , Burnier Michel
Published: March 2007

The permeability–glycoprotein efflux-transporter encoded by the multidrug resistance 1 (
ABCB1
) gene and the cytochromes P450 3A4/5 encoded by the
CYP3A4/5
genes are known to interact in the transport and metabolism of many drugs. Recent data have shown that the
CYP3A5
genotypes influence blood pressure and that permeability–glycoprotein activity might influence the activity of the renin–angiotensin system. Hence, these 2 genes may contribute to blood pressure regulation in humans. We analyzed the association of variants of the
ABCB1
and
CYP3A5
genes with ambulatory blood pressure, plasma renin activity, plasma aldosterone, endogenous lithium clearance, and blood pressure response to treatment in 72 families (373 individuals; 55% women; mean age: 46 years) of East African descent. The
ABCB1
and
CYP3A5
genes interact with urinary sodium excretion in their effect on ambulatory blood pressure (daytime systolic:
P
=0.05; nighttime systolic and diastolic:
P
<0.01), suggesting a gene–gene–environment interaction. The combined action of these genes is also associated with postproximal tubular sodium reabsorption, plasma renin activity, plasma aldosterone, and with an altered blood pressure response to the angiotensin-converting enzyme inhibitor lisinopril (
P
<0.05). This is the first reported association of the
ABCB1
gene with blood pressure in humans and demonstration that genes encoding for proteins metabolizing and transporting drugs and endogenous substrates contribute to blood pressure regulation.
What Initiates the Pressor Effect of Salt in Salt-Sensitive Humans?
Authors: Schmidlin Olga , Forman Anthony Sebastian Alex , Morris R. Curtis
Published: March 2007

We tested the traditional hypothesis that an abnormally enhanced renal reclamation of dietary NaCl alone initiates its pressor effect (“salt sensitivity”). Under metabolically controlled conditions, we grouped 23 normotensive blacks as either salt-sensitive (SS) or salt-resistant (SR), depending on whether or not dietary NaCl loading did or did not increase mean arterial blood pressure (MAP) by ≥5 mm Hg. We determined whether dietary NaCl loading induces greater increases in external Na
+
balance, plasma volume, and cardiac output in SS, compared with any in SR subjects, and differential changes in systemic vascular resistance (SVR) that could account for the pressor differences between SS and SR subjects. Using impedance cardiography, we measured cardiac output and SVR daily at 4-hour intervals throughout the last 3 days of a 7-day period of low NaCl intake (30 mmol per day) and throughout a subsequent 7-day period of NaCl loading (250 mmol per day). In the 11 SS subjects, compared with the 12 SR subjects, NaCl loading induced no greater increases in Na
+
balance, body weight, plasma volume, and cardiac output. Yet, from days 2 to 7 of NaCl loading, changes of MAP in SS diverged progressively from those in SR. From days 2 to 4, progressive increases of MAP in SS subjects reflected importantly impaired decreases of SVR, as judged from “normal” decreases of SVR in SR subjects. In SS and SR subjects combined, changes in both MAP and SVR on day 2 strongly predicted changes in MAP on day 7. In many normotensive blacks, vascular dysfunction is critical to the initiation of a pressor response to dietary NaCl.
Blood Pressure and Retinal Arteriolar Narrowing in Children
Authors: Mitchell Paul , Cheung Ning , de Haseth Kristin , Taylor Bronwen , Rochtchina Elena , Islam F. M. Amirul , Wang Jie Jin , Saw Seang Mei , Wong Tien Y.
Published: March 2007

Retinal arteriolar narrowing is a known response of hypertension and independently predicts cardiovascular mortality in adults. Whether elevated blood pressure leads to retinal arteriolar narrowing in young children is unknown. We examined the relationship of retinal vascular caliber and blood pressure levels in 2 population-based cohorts among children aged 6 to 8 years in Sydney, Australia (1572 children) and Singapore (380 children). Participants had digital retinal photographs and measurement of retinal arteriolar (or small artery) and venular (or small vein) caliber. Children with higher quartiles of blood pressure had significantly narrower retinal arterioles than those with lower blood pressure (retinal arteriolar caliber 162.8, 161.0, 157.8, and 157.1 μm (
P
for trend<0.001), comparing increasing quartiles of systolic blood pressure in Sydney, and 164.9.5, 164.0, 159.1, and 159.4 μm (
P
for trend=0.0024 in Singapore). After controlling for age, sex, race, body mass index, refraction, and birth parameters, each 10-mm Hg increase in systolic blood pressure was associated with narrowing of the retinal arterioles by 2.08 μm (95% confidence interval: 1.38 to 2.79;
P
<0.0001) in Sydney children and 1.43 μm (95% confidence interval: 0.27 to 2.59;
P
=0.016) in Singapore children. These associations were consistent across age, sex, body mass index, and birth parameters. Retinal venules were not affected by blood pressure. We conclude that higher childhood blood pressure is associated with retinal arteriolar narrowing. Our data provide evidence that the effects of elevated blood pressure may manifest early in life.
Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension
Authors: Forman John P. , Giovannucci Edward , Holmes Michelle D. , Bischoff-Ferrari Heike A. , Tworoger Shelley S. , Willett Walter C. , Curhan Gary C.
Published: March 2007

Hydroxylation of 25(OH)D to 1,25-dihydroxyvitamin D and signaling through the vitamin D receptor occur in various tissues not traditionally involved in calcium homeostasis. Laboratory studies indicate that 1,25-dihydroxyvitamin D suppresses renin expression and vascular smooth muscle cell proliferation; clinical studies demonstrate an inverse association between ultraviolet radiation, a surrogate marker for vitamin D synthesis, and blood pressure. We prospectively studied the independent association between measured plasma 25-hydroxyvitamin D [25(OH)D] levels and risk of incident hypertension and also the association between predicted plasma 25(OH)D levels and risk of incident hypertension. Two prospective cohort studies including 613 men from the Health Professionals’ Follow-Up Study and 1198 women from the Nurses’ Health Study with measured 25(OH)D levels were followed for 4 to 8 years. In addition, 2 prospective cohort studies including 38 388 men and 77 531 women with predicted 25(OH)D levels were followed for 16 to 18 years. During 4 years of follow-up, the multivariable relative risk of incident hypertension among men whose measured plasma 25(OH)D levels were <15 ng/mL (ie, vitamin D deficiency) compared with those whose levels were ≥30 ng/mL was 6.13 (95% confidence interval [CI]: 1.00 to 37.8). Among women, the same comparison yielded a relative risk of 2.67 (95% CI: 1.05 to 6.79). The pooled relative risk combining men and women with measured 25(OH)D levels using the random-effects model was 3.18 (95% CI: 1.39 to 7.29). Using predicted 25(OH)D levels in the larger cohorts, the multivariable relative risks comparing the lowest to highest deciles were 2.31 (95% CI: 2.03 to 2.63) in men and 1.57 (95% CI: 1.44 to 1.72) in women. Plasma 25(OH)D levels are inversely associated with risk of incident hypertension.
Inappropriate Left Ventricular Mass Changes During Treatment Adversely Affects Cardiovascular Prognosis in Hypertensive Patients
Authors: Muiesan Maria Lorenza , Salvetti Massimo , Paini Anna , Monteduro Cristina , Galbassini Gloria , Bonzi Bianca , Poisa Paolo , Belotti Eugenia , Agabiti Rosei Claudia , Rizzoni Damiano , Castellano Maurizio , Agabiti Rosei Enrico
Published: March 2007

Inappropriate left ventricular mass (LVM; ie, the value of LVM exceeding individual needs to compensate hemodynamic load) predicts the risk of cardiovascular (CV) events, independent of risk factors, either in the presence or in the absence of traditionally defined LV hypertrophy. The relation between changes in appropriateness of LVM during antihypertensive treatment and subsequent prognosis was evaluated in 436 prospectively identified uncomplicated hypertensive subjects, with a baseline and follow-up standard clinical evaluation, laboratory examinations, and echocardiogram (last examination: 6±3 years apart), followed for additional 4.5±2.5 years. The appropriateness of LVM to cardiac workload was calculated by the ratio of observed LVM to the value predicted for individual sex, height, and stroke work at rest. At baseline, low or appropriate LVM (≤128% of predicted) was found in 178 patients, and 258 had inappropriate LVM. A first CV event occurred in 82 patients. Event rate (×100 patient-years) was 3.18 among patients with inappropriate LVM persistence (n=152), 0.97 among patients with inappropriate LVM regression (n=104), 1.87 among patients with inappropriate LVM development (n=75), and 0.81 among patients with persistence of appropriate LVM from baseline to the follow-up (n=105; log-rank test:
P
=0.0001). Cox’s proportional hazard model, considering all of the known CV risk factors, indicated that age, male sex, persistence, or development of inappropriate LVM, in addition to persistence and development of LVH, were independently associated with the occurrence of CV events (
P
<0.001). The presence of inappropriate LVM during antihypertensive treatment may adversely influence subsequent CV prognosis.
"Great Command O'Ersways the Order": Purgatory, Revenge, and Maimed Rites in Hamlet
Authors: Beauregard David
Published: March 2007

Certain elements in Hamlet, together with historical and biographical events, suggest that Shakespeare's play can be better understood from a Catholic perspective. The representation of the Ghost from Purgatory contains obviously Catholic imagery and allusions. The notion of revenge or vengeance, understood in terms of a proper intention in appropriate circumstances, is considered a virtue in Thomistic theology rather than a vice, a notion applicable to the play particularly when the opposing vices of being excessive and being remiss in punishing (cruelty and negligence) are taken into account. And, finally, the Erastian measures taken by Claudius, whose "great command o'ersways the order" of Ophelia's funeral, deforms a traditional Catholic liturgy in producing "maimed rites."
The Siyar — An Islamic Law Of Nations?
Authors: Bouzenita Anke Iman
Published: March 2007

This article deals with an essential part of Islamic law usually referred to as siyar. It discusses the development of siyar in an Islamic context and in comparison to the development of the modern law of nations. It further follows up the evaluation of siyar in the Western literature and analyses recurring paradigms of categorisation used in this literature. The author discusses Kruse's (1979) approach to differentiate between an "Islamic" and a "Muslim" law of nations. As case studies of argumentative weaknesses and loopholes, the author scrutinizes the attempts to attribute siyar to a particular type of law of nations and to render it as a legal order of either personal or territorial validity. The article focuses on methodological aspects involved in presenting two independent legal systems as commensurable. The author concludes that a terminological transfer, be it with the intention of explaining Islamic legal concepts to a non-specialized reader, be it with the intention to reconcile between both systems, cannot do justice to either one of the legal systems.
Expressions of Religiosity and Blasphemy in Modern Societies
Authors: Hassan Riaz
Published: March 2007

In Abrahamic religions blasphemy exists to prevent challenge to the notions of the sacred. Its existence is a litmus test of the standards a society feels it must enforce to preserve its religious beliefs and morality in order to prevent mockery of the Divine. Its commission has invariably evoked severe punishment. This paper examines the debates around these issues in Christianity and Islam. It examines the struggle against blasphemy laws in Christian and Muslim countries. It concludes by arguing that modernity plays a significant role in shaping attitudes towards blasphemy in modern societies. Using empirical evidence it explores the relationship between modernity, religiosity and blasphemy in seven contemporary Muslim countries.
Institutional Transformations in the Regime of Knowledge Production: The University as a catalyst for the Science-Based Knowledge Economy
Authors: Dzisah James
Published: March 2007

Although, the process of the capitalization of academic scientific knowledge is not benign across university campuses, recent acceleration of the process have sparked debates in many circles. This debate mirrors two sets of issues-public versus private interests. While the discourse has shed some light on the socio-economic and political forces at work, it is not devoid of problems. The paper argues that the understanding of the university as a catalyst for the science-based knowledge economy should be built around the framework that the university like industry and government is responding to a wide range of socio-economic and political demands that cannot be delinked from each other. It contends that, in a period of an ever-increasing demand for science and technology, universities' as citadels of knowledge have through the capitalization of academic scientific knowledge become a catalyst for the science-based knowledge economy.
Septic Arthrt anitis after Arthroscopic Anterior Cruciate Ligament Reconstruction
Authors: Van Tongel Alexander , Stuyck Jos , Bellemans Johan , Vandenneucker Hilde
Published: March 2007

Background

Septic arthritis after arthroscopic anterior cruciate ligament reconstruction is a rare complication. In the literature, several different managements are proposed.

Hypothesis

The graft can be retained during treatment of a septic arthritis after anterior cruciate ligament reconstruction.

Study Design

Case series; Level of evidence, 4.

Methods

A retrospective analysis of knee joint infections occurring after arthroscopically assisted anterior cruciate ligament reconstructions was conducted. Fifteen patients were treated for postoperative septic arthritis of the knee after anterior cruciate ligament reconstruction between 1996 and 2005. All patients underwent an urgent extensive arthroscopic debridement (washout and synovectomy) and parenteral antibiotics and oral antibiotics subsequently. Repetitive wash-outs were performed if necessary. The average time at follow-up for our series was 58 months (range, 9-99 months).

Results

Only 1 graft was removed during debridement because it was nonfunctional. All other patients retained their anterior cruciate ligament reconstruction. There was no reinfection. There were 2 traumatic reruptures. We evaluated 11 patients: in 6 patients the Lachman test showed a translation of more than 3 mm, but all patients had a firm endpoint and there was no subjective instability. Early signs of radiological degeneration were seen in 3 patients. The value for the Lysholm knee scoring scale was 83, on average, ranging from 57 to 100. Regarding the International Knee Documentation Committee score, 2 patients had a final evaluation of normal, 7 patients nearly normal, and 2 patients abnormal.

Conclusion

The graft can be retained during treatment of septic arthritis after anterior cruciate ligament reconstruction.
The Relationship between Neurocognitive Function and Noncontact Anterior Cruciate Ligament Injuries
Authors: Swanik Charles Buz , Covassin Tracey , Stearne David J. , Schatz Philip
Published: March 2007

Background

Biomechanical analyses suggest that the loss of neuromuscular control is associated with noncontact anterior cruciate ligament sprains; however, previous research has not explored the link between neurocognitive function and unintentional knee injuries.

Purpose

To determine if athletes who suffer a noncontact anterior cruciate ligament injury demonstrate decreased baseline neurocognitive performance when compared with matched controls.

Study Design

Case control study; Level of evidence, 3.

Methods

The baseline scores from a computerized neurocognitive test battery (ImPACT) were analyzed to compare verbal memory, visual memory, processing speed, and reaction time. Eighty intercollegiate athletes who, subsequent to testing, experienced noncontact anterior cruciate ligament injuries, were matched with 80 controls based on height, weight, age, gender, sport, position, and years of experience at the collegiate level.

Results

Statistical differences were found between the noncontact anterior cruciate ligament injury group and the matched controls on all 4 neurocognitive subtests. Noncontact anterior cruciate ligament—injured athletes demonstrated significantly slower reaction time (F1,158 = 9.66, P = .002) and processing speed (F1,158 = 12.04, P = .001) and performed worse on visual (F1,158 = 19.16, P = .000) and verbal memory (F 1,158 = 4.08, P = .045) composite scores when compared with controls.

Conclusion

Neurocognitive differences may be associated with the loss of neuromuscular control and coordination errors, predisposing certain intercollegiate athletes to noncontact anterior cruciate ligament injuries.
Physical Examination for Partial Tears of the Biceps Tendon
Authors: Gill Harpreet S. , El Rassi George , Bahk Michael S. , Castillo Renan C. , McFarland Edward G.
Published: March 2007

Background

The accuracy of the physical examination for tears of the long head of the biceps remains controversial.

Purpose

The goals were 1) to characterize the occurrence of partial tears of the long head of the biceps tendon in a group of consecutive patients, and 2) to analyze the diagnostic value of various clinical tests for pathologic lesions of the proximal biceps tendon.

Study Design

Cohort study (diagnosis); Level of evidence, 2.

Methods

Of 847 consecutive patients who underwent arthroscopic procedures for a variety of shoulder conditions, 40 were found at the time of arthroscopy to have partial biceps tendon tears. The average age of these 24 men and 16 women was 59 years (range, 18-83). Preoperative physical examinations had included 9 commonly used tests for shoulder examination. Statistical analysis included sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios for these tests.

Results

The prevalence rate of partial tears was 5% (40/847) of all arthroscopic procedures. The most commonly associated conditions included rotator cuff tears (85% [34/40]) and anterior instability (7.5% [3/40]). Tenderness on palpation of the long head of the biceps tendon had a sensitivity of 53%, a specificity of 54%, and a likelihood ratio of 1.13. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios for Speed's test were 50%, 67%, 8%, 96%, and 1.51, respectively.

Conclusion

In patients with rotator cuff abnormality, the diagnosis of partial biceps tears cannot be made reliably with existing physical examination tests. Diagnostic arthroscopy is recommended, if clinically indicated, for potential partial tears of the long head of the biceps tendon. The treating physician should be prepared to treat unsuspected tears of the long head of the biceps tendon at the time of surgery.
Fibrillar Network Adaptive Structure with Ion-transport Actuation
Authors: Philen M.K. , Shan Y. , Prakash P. , Wang K.W. , Rahn C.D. , Zydney A.L. , Bakis C.E.
Published: March 2007

The overall objective of this research is to create a new actuation system, emulating the ability of plants to generate large strains while carrying significant structural loads. Specifically, the authors aim to create high-authority active structures by exploring a revolutionary combination of two innovative ideas inspired by the mechanical, chemical, and electrical properties of the plants. The first idea, inspired by the fibrillar network in plant cell walls, is to create a high-mechanical-advantage actuator structure based on flexible matrix composites (FMCs). Through fiber—matrix tailoring of FMC tubes, one can cause the structure to actuate in certain desired directions when pressurized. Second, the actuator concept is combined with a novel electroosmotic (EO) transport mechanism to regulate pressure inside the FMC tube, inspired by the ion-transport and volume-control phenomena in plant cells. By adjusting the applied voltage across a charged porous membrane, one can control the internal pressure and actuator response. The performance of the system (pressure, response time, stroke, load, etc.) can be tuned by proper selection of the membrane (e.g., pore size, surface charge, membrane pore area, etc.) and FMC (materials, fiber angle, etc.) properties. The new system can use natural seawater (ideal for naval applications) or a small amount of onboard solution with appropriate properties for electroosmotic pumping. This approach has several advantages over traditional actuators, such as large stroke/force, design flexibility/scalability, and electrical activation with quiet operation and no moving parts. In this research, the FMC structure and EO pump (EOP) models are developed and validated, and the integrated model is analyzed to provide guidelines for designing the overall actuation system.
Combination of a Time Reversal Process and a Consecutiv Outlier Analysis for Baseline-free Damage Diagnosis
Authors: Sohn Hoon , Hyun Woo Park  , Law Kincho H. , Farrar Charles R.
Published: March 2007

A structural health monitoring system is developed for continuous online monitoring of delamination initiation and growth in composite structures. Structural health monitoring problems are often cast in the context of a statistical pattern recognition paradigm, in which a damage state of a structure is inferred by comparing test data with baseline data. However, subtle signal changes due to damage can often be masked by larger ambient variation of operational and environmental conditions of an in-service structure. Therefore, it is critical for the development of a robust monitoring system to minimize false-positive indications of damage caused by the undesired operational and environmental variation of the structure. The issue of minimizing damage misclassification has been addressed in this article by developing an instantaneous damage detection scheme that does not rely on past baseline data. The proposed instantaneous damage diagnosis is based on the concepts of time reversal acoustics and consecutive outlier analysis, and the proposed damage diagnosis has been tested for detecting delamination in composite plates.
Screening for depression among patients with multiple sclerosis: two questions may be enough
Authors: Mohr Dc , Hart Sl , Julian L , Tasch Es
Published: March 2007

Background

Depression among patients with multiple sclerosis (MS) is common and has a significant impact on quality of life. As many as two-thirds of depressed MS patients receive no treatment for their depression. While guidelines for depression management suggest screening, the only validated screening tools are questionnaires, which have not been widely implemented in practice. This is the first study on the effectiveness of using two questions assessing mood and anhedonia (loss of interest or pleasure) in screening for major depressive disorder (MDD) in MS.

Methods

MS patients under the care of neurologists were recruited from a large health maintenance organization (HMO). The MDD module of the Structured Clinical Interview for the DSM-IV and screening questions was administered.

Results

Of the 260 participants, 26% met the criteria for MDD. Among patients with MDD, 67% received no anti-depressant medication. The MDD screen identified 99% (95% CI: 91–100%) of cases.

Discussion

A brief, two question screen is reliable in identifying MS patients with MDD. This suggests that asking these two brief questions could identify almost all MS patients meeting MDD criteria, with minimal numbers of false positives. Multiple Sclerosis 2007; 13: 215–219. http://msj.sagepub.com
The 795CT polymorphism in osteopontin gene is not associated with multiple sclerosis in a Spanish population
Authors: Mas A , Martínez A , Heras V De Las , Bartolomé M , Concha Eg De La , Arroyo R , Urcelay E
Published: March 2007

Multiple sclerosis (MS) is an inflammatory disease affecting the central nervous system. The dysregulation of the cytokine network is an important component of its pathogenesis. One of the cytokines produced by activated T-cells is osteopontin (OPN). OPN enhances the production of the pro-inflammatory cytokines, interleukin-12 and interferon-gamma, while reducing interleukin-10 levels. Therefore, OPN is considered a pro-inflammatory cytokine, and could play a key role in MS pathogenesis. The OPN gene contains several common polymorphisms, distributed in two main haplotypes, which may modulate its production or activity. A total of 326 MS patients and 484 healthy controls were typed for 795CT OPN polymorphism. In order to perform a familial study, 51 progenitor pairs were also included. No difference was found in the case-control or family study. This negative finding is inconsistent with a previous haplotype study in an Italian population, where the haplotype associated carried the low-frequency allele in position 795. In a Japanese population, a similar study yielded no association with this polymorphism. In conclusion, our data suggest that the 795 polymorphism does not play an etiological role per se and the haplotype structure may differ from one population to another. Multiple Sclerosis 2007; 13: 250–252. http://msj.sagepub.com
Rapid cognitive screening in multiple sclerosis accomplished by the Free Recall and Recognition Test
Authors: Claesson Im , Ytterberg C , Johansson S , Almkvist O , Koch L Von
Published: March 2007

This study sought to investigate the feasibility of the Free Recall and Recognition Test (FRRT) as a practical screening tool for cognitive impairment in multiple sclerosis (MS). Persons with MS (n =227) were consecutively recruited and assessed with four cognitive tests; FRRT, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and the Mini-Mental State Examination (MMSE). Disease severity was assessed by the Expanded Disability Status Scale (EDSS). The FRRT, which was completed by 99% of the cohort in approximately 5 minutes per assessment, correlated significantly with the other cognitive tests, as well as with the disease severity rating. A cut-off of 4 for the FRRT recall rendered 90% sensitivity and 25% specificity, and a cut-off of 4.2 for the FRRT recognition resulted in 70% sensitivity and 51% specificity. We conclude that the FRRT proved feasible as a practical screening tool for cognitive impairment in MS within a clinical setting. Multiple Sclerosis 2007; 13: 272–274. http://msj.sagepub.com