bluuebunny/crossref_metadata_2025 huggingface dataset:
The Blood-Testis Barrier as a Target of Some Chemotherapeutic Agents
Authors: Pereira M.L. , Garcia e Costa F.
Published: October 2007

Background: Some chemotherapeutic agents induce testicular damage, thereby affecting fertility potential. Two metal-based antineoplastic complexes, titanocene dichloride and budotitane, were used to demonstrate their effects on the blood-testis barrier (BTB). Methods: Male mice were treated in vivo with the two titanium compounds and fragments of seminiferous tubules were isolated, closed at both ends, and then incubated in vitro with horseradish peroxidase for 10 and 15 min to test the permeability of the BTB at the ultrastructural level. Results: Titanocene dichloride disrupted the BTB as shown by the presence of the tracer inside the tubules, contrarily to the results obtained from budotitane-administered animals. Conclusions: The toxicity of some metal-based antineoplastic drugs on the BTB may not only affect male reproductive health, but also alert for the possible injury within other biological barriers.
Chronic Inflammation and T Cell Zeta-Chain Downregulation in Hemodialysis Patients
Authors: Eleftheriadis Theodoros , Kartsios Charalambos , Yiannaki Efi , Kazila Polizo , Antoniadi Georgia , Liakopoulos Vassilios , Markala Dimitra
Published: October 2007

Background: Clinical and experimental data indicate a deficient immune response in hemodialysis (HD) patients. ζ-Chain phosphorylation is an early and central event in the process that follows antigen recognition by the T cell antigen receptor (TCR). T cell ζ-chain is downregulated in many chronic inflammatory states, such as cancer, autoimmune disease and chronic infection. HD is also characterized as a chronic inflammatory state. The aim of the present study was to evaluate T cell ζ-chain expression in HD patients. Patients and Methods: Thirty-three stable HD patients and 30 healthy volunteers were enrolled into the study. T cell count, the percentage of ζ-chain-positive T cells, as well as T cell ζ-chain mean fluorescence intensity (MFI) were evaluated with flow cytometry. The inflammatory markers C-reactive protein, interleukin-6 and tumor necrosis factor-α were measured in the serum by means of ELISA. Results: All the evaluated markers of inflammation were increased in HD patients. In these patients, T cell ζ-chain MFI was decreased. CD3-Ε MFI did not differ between the two groups indicating that among the TCR complex constituents, ζ-chain is selectively downregulated. Conclusions: HD is a state of chronic inflammation. Like in other pathological chronic inflammatory conditions, T cell ζ-chain is downregulated in HD patients. Since ζ-chain plays a key role in the transduction of the signal that follows antigen recognition by the TCR, its downregulation could be responsible for the deficient cellular immune response observed in HD patients.
Visual Rating and ROI-Based Parametric Analysis of rCBF SPECT in Patients with Mild or Questionable Dementia: A Comparative Study
Authors: Høgh Peter , Teller Ann-Sofie , Hasselbalch Steen , Waldemar Gunhild
Published: October 2007

Background: The aim of this study was to assess the accuracy of visual image rating as compared to parametric analysis of regional cerebral blood flow (rCBF) measured with SPECT in patients referred to a memory clinic for diagnostic evaluation of cognitive symptoms. Methods: SPECT with 99mTc-HMPAO was used to determine rCBF in 47 patients and 26 healthy control subjects. The 47 patients (30 F/17 M) had a mean age of 74.6 years (range = 62–88) and mild or questionable dementia with an MMSE score of 24.8 (range = 20–30). Two experienced image readers blinded to the classifications and identity of subjects performed visual rating in consensus and the global and regional CBF patterns were evaluated and graded according to severity of hypoperfusion. Correlation coefficients were calculated using results from the parametric analyses as gold standard. Results: The sensitivity and specificity of global visual rating (normal vs. abnormal SPECT) was 92 and 86%, respectively, yielding an overall accuracy of 89% for visual rating compared to parametric analysis. The correlation between visual rating and parametric analysis was highly significant (p < 0.001). Conclusion: Visual rating is a valid method for analyzing SPECT images in patients with mild or questionable dementia.
Evaluating Peritoneal Fluid Transport in Continuous Peritoneal Dialysis Patients: A Practical Approach
Authors: Zhe Xing-wei , Tian Xin-kui , Shan Yi-sheng , Cheng Lei , Wang Tao
Published: October 2007

Background/Aims: Evaluating the peritoneal fluid kinetics is of clinical importance in peritoneal dialysis treatment. We have previously developed a simple way to evaluate the peritoneal fluid transport characteristics in continuous ambulatory peritoneal dialysis patients which, however, cannot be applied to those patients on a fixed dialysis schedule. Therefore, in the present study, we tested the possibility to vary the peritoneal dwell time and tried to develop a more patient-friendly ultrafiltration (UF) collection protocol. Methods: The patients’ UF volume was recorded for 10 days. All patients recruited were asked to perform their usual dialysis exchanges with, however, a special UF data collection protocol to improve the accuracy of computer simulation: at least one dwell of 2–4 h, one of 4–7 h, and one of more than 7 h. The fluid transport model was applied to the pooled UF volume for fluid kinetics simulation, and the data from the following day’s UF records using the same glucose concentration and dwell time were used to evaluate reliability and accuracy of the simulated UF value. Results: Fifty-two chronic peritoneal dialysis patients were included in the present study. All of the UF data could be used in the computer simulation, and there was a significant negative correlation between fluid absorption rate (Ke; see text) and actual UF volume on the following day using a glucose concentration of 1.5% and a dwell time of 4 h (r = –0.336, p < 0.05). The estimated UF values correlated significantly with the actually measured UF values. The variability of the results, expressed by the width between the 95% limits of agreement, fell within –139.2 to 131.9 ml, while the mean difference was –3.7 ml. Conclusions: Our present study showed that varying the peritoneal dwell time was a patient-friendly UF data collection protocol for continuous ambulatory peritoneal dialysis patients on a fixed dialysis schedule. Applying the fluid transport model and nonlinear least squares regression analysis to pooled UF values might be a good and simple way to predict the peritoneal UF capacity.
Late Referral to a Nephrologist Increases the Risk of Uremia-Related Cardiac Hypertrophy in Patients on Hemodialysis
Authors: Shin Seok Joon , Kim Hyung Wook , Chung Sungjin , Chung Hyun Wha , Lee Sang Ju , Kim Yong Soo , Bang Byung Kee , Chang Yoon Sik , Park Cheol Whee
Published: October 2007

Background: The prognosis and outcome of patients with end-stage renal disease are related to the quality of predialysis care and the timing of referral. Late referral (LR) has been correlated with more frequent hospital admissions, malnutrition and cardiovascular mortality after hemodilaysis (HD) is started. Methods: We investigated the effects of LR on cardiac hypertrophy, uremia-related metabolic risk factors and mortality in patients on HD. A baseline echocardiography was performed in 119 patients on HD, 67 of whom were early referrals (ER, referred more than 3 months before the start of HD) and 52 were LR (referred less than 3 months before the start of HD; median (range): 22.5 (4–120) vs. 1.0 (0–3) months, respectively). Results: The survival curves showed a higher mortality rate in the LR patients than in the ER patients (log rank, p = 0.004). More patients in the LR group died of cardiovascular disease compared to the ER patients (p = 0.04). The plasma levels of albumin were significantly lower (p < 0.05), and the intact parathyroid hormone (iPTH) and log C-reactive protein (log CRP) were significantly higher in the LR patients compared to the ER patients (p < 0.05 and p < 0.001, respectively). The LR patients, especially nonsurvivors, showed greater impairment of systolic cardiac function and more concentric left ventricular hypertrophy (LVH) than ER patients, as determined by interventricular septal thickness (p < 0.001), left ventricular posterior wall thickness (p < 0.001), relative wall thickness (p = 0.02), and the left ventricular mass index (LVMi, p < 0.001). Interestingly, the duration of the pre-HD treatment, after referral, was positively associated with the plasma albumin (r = 0.229; p = 0.01) and negatively associated with the log CRP (r = –0.350; p < 0.001), iPTH (r = –0.309; p = 0.001) and LVMi (r = –0.268; p = 0.004). Multiple linear regression analysis also demonstrated that the log CRP and iPTH as well as the LR were independently associated with LVMi in the HD patients (p < 0.05). Conclusions: The results of this study demonstrated that the LR HD patients were at an increased risk for more cardiovascular related mortality, severe concentric LVH and systolic dysfunction accompanied by inflammatory and malnutrition indices, as well as with increased iPTH levels. In the LR patients, the more severe LVH associated with severe inflammatory indices, as well as the higher iPTH levels, may be one of the causes of LR-related mortality.
Nutrition and Cardiovascular Disease
Authors: Getz Godfrey S. , Reardon Catherine A.
Published: October 2007

The major cardiovascular diseases affecting the developed world have at their core atherosclerosis and hypertension, both of which are profoundly affected by diet and can be approached, at least in part, from a nutritional point of view, as can the increasing “epidemic” of obesity. Diet is a multi-component mixture of many nutrients, which may interact with one another. The definitive study of nutrients and their impact on cardiovascular disease can be a daunting enterprise. Many dietary risk factors contribute to these diseases in various environmental and ethnic settings. These risk factors are often in evidence in youth so that preventive measures must be initiated early in life. Although most of the information about nutritional risk factors and cardiovascular disease derives from studies in the developed world, the situation is rapidly evolving toward epidemic proportions in the developing world where a major burden on the economy and health services will be imposed.
International Day for the Evaluation of Abdominal Obesity (IDEA)
Authors: Balkau Beverley , Deanfield John E. , Després Jean-Pierre , Bassand Jean-Pierre , Fox Keith A.A. , Smith Sidney C. , Barter Philip , Tan Chee-Eng , Van Gaal Luc , Wittchen Hans-Ulrich , Massien Christine , Haffner Steven M.
Published: October 2007

Background—

Abdominal adiposity is a growing clinical and public health problem. It is not known whether it is similarly associated with cardiovascular disease (CVD) and diabetes mellitus in different regions around the world, and thus whether measurement of waist circumference (WC) in addition to body mass index (BMI) is useful in primary care practice.

Methods and Results—

Randomly chosen primary care physicians in 63 countries recruited consecutive patients aged 18 to 80 years on 2 prespecified half days. WC and BMI were measured and the presence of CVD and diabetes mellitus recorded. Of the patients who consulted the primary care physicians, 97% agreed to participate in the present study. Overall, 24% of 69 409 men and 27% of 98 750 women were obese (BMI≥30 kg/m
2
). A further 40% and 30% of men and women, respectively, were overweight (BMI 25 to 30 kg/m
2
). Increased WC (>102 for men and >88 cm for women) was recorded in 29% and 48%, CVD in 16% and 13%, and diabetes mellitus in 13% and 11% of men and women, respectively. A statistically significant graded increase existed in the frequency of CVD and diabetes mellitus with both BMI and WC, with a stronger relationship for WC than for BMI across regions for both genders. This relationship between WC, CVD, and particularly diabetes mellitus was seen even in lean patients (BMI<25 kg/m
2
).

Conclusions—

Among men and women who consulted primary care physicians, BMI and particularly WC were both strongly linked to CVD and especially to diabetes mellitus. Strategies to address this global problem are required to prevent an epidemic of these major causes of morbidity and mortality.
Apolipoprotein C-I Is Crucially Involved in Lipopolysaccharide-Induced Atherosclerosis Development in Apolipoprotein E–Knockout Mice
Authors: Westerterp Marit , Berbée Jimmy F.P. , Pires Nuno M.M. , van Mierlo Geertje J.D. , Kleemann Robert , Romijn Johannes A. , Havekes Louis M. , Rensen Patrick C.N.
Published: October 2007

Background—

Lipopolysaccharide (LPS), which is released from Gram-negative bacteria on multiplication or lysis, aggravates atherosclerosis in humans and rodents by inducing inflammation via toll-like receptors. Because apolipoprotein C-I (apoCI) enhances the LPS-induced inflammatory response in macrophages in vitro and in mice, we investigated the effect of endogenous apoCI expression on LPS-induced atherosclerosis in mice.

Methods and Results—

Twelve-week-old
apoe
−/−
apoc1
−/−
and
apoe
−/−
apoc1
+/+
mice received weekly intraperitoneal injections of LPS (50 μg) or vehicle for a period of 10 weeks, and atherosclerosis development was assessed in the aortic root. LPS administration did not affect atherosclerotic lesion area in
apoe
−/−
apoc1
−/−
mice but increased it in
apoe
−/−
apoc1
+/+
mice. In fact, apoCI expression increased the LPS-induced atherosclerotic lesion area by 60% (
P
<0.05), concomitant with an increase in LPS-induced plasma levels of fibrinogen and E-selectin. This indicated that apoCI increased the LPS-induced inflammatory state, both systemically (ie, fibrinogen) and at the level of the vessel wall (ie, E-selectin). In addition, both macrophage-derived apoCI and HDL-associated apoCI increased the LPS-induced tumor necrosis factor-α response by macrophages in vitro.

Conclusions—

We conclude that apoCI is crucially involved in LPS-induced atherosclerosis in
apoe
−/−
mice, which mainly relates to an increased inflammatory response toward LPS. We anticipate that apoCI plasma levels contribute to accelerated atherosclerosis development in individuals who have chronic infection.
Improvement in Congenital Heart Surgery in a Developing Country
Authors: Larrazabal Luis A. , Jenkins Kathy J. , Gauvreau Kimberlee , Vida Vladimiro L. , Benavidez Oscar J. , Gaitán Guillermo A. , Garcia Flor , Castañeda Aldo R.
Published: October 2007

Background—

In 1997, an effort was made to disseminate US pediatric cardiac surgical practices to create a new comprehensive program in Guatemala. The objective of this study was to describe the improvement of the program by exploring the reduction in risk-adjusted in-hospital mortality.

Methods and Results—

A retrospective cohort study of surgical procedures performed in Guatemala from February 1997 to July 2004 was conducted. Data were divided into 3 time periods (1997 to 1999, 2000 to 2002, and 2003 to 2004) and compared with a US benchmark (2000 Kids’ Inpatient Database of 27 states and 313 institutions). The risk adjustment for congenital heart surgery (RACHS-1) method was used to adjust for case mix. Mortality rates, standardized mortality ratios, and 95% confidence intervals were calculated. A total of 1215 surgical procedures were included. Median age was 3.1 years (range, 1 day to 17.9 years). The overall mortality was 10.7% (n=130). The RACHS-1 method showed better discrimination than in prior reports (area under receiver operating characteristic curve=0.854). A decreasing trend in mortality rate was observed in every RACHS-1 risk category over the 3 time periods. When compared against the US benchmark, the reduction in risk-adjusted mortality was noted by a decrease of standardized mortality ratio from 10.0 (95% confidence interval, 7.2 to 13.7) in 1997–1999, to 7.8 (95% confidence interval, 5.9 to 10.0) in 2000–2002, and to 5.7 (95% confidence interval, 3.8 to 8.3) in 2003–2004.

Conclusions—

In a short time period, mortality after congenital heart surgery has been reduced substantially in Guatemala. Measurement of risk-adjusted mortality is a useful method to assess pediatric cardiac program improvement in the developing world.
Pioglitazone Increases Macrophage Apoptosis and Plaque Necrosis in Advanced Atherosclerotic Lesions of Nondiabetic Low-Density Lipoprotein Receptor–Null Mice
Authors: Thorp Edward , Kuriakose George , Shah Yatrik M. , Gonzalez Frank J. , Tabas Ira
Published: October 2007

Background—

Thiazolidinediones (TZDs), which have actions that involve both peroxisome proliferator–activated receptor (PPAR)-γ–dependent and –independent effects, improve insulin sensitivity in type II diabetes and inhibit early atherogenesis in mice. However, the effects of TZDs on advanced lesion progression are unknown.

Methods and Results—

Pioglitazone and rosiglitazone enhanced macrophage apoptosis by a number of stimuli, including those thought to be important in advanced atherosclerosis. Macrophage death was not enhanced by non-TZD PPARγ activators, and TZD-induced apoptosis was still observed in PPARγ-deficient macrophages. In wild-type macrophages, death enhancement was associated with reduced activation of the cell-survival mediator nuclear factor-κB. TZDs also increased the ability of macrophages to phagocytically clear apoptotic cells, which is proposed to protect against plaque necrosis in advanced lesions. The mechanism of this effect was complex, involving both PPARγ-dependent and -independent mechanisms. To explore the net effect on advanced atherosclerosis in vivo,
Ldlr
−/−
mice were fed a nondiabetogenic cholesterol-enriched diet to promote midstage lesions. Then, pioglitazone was administered with the diet for an additional 10 weeks. Aortic root lesions from the pioglitazone-treated mice showed a substantial increase in apoptotic cells and plaque necrosis compared with lesions from non–drug-treated mice.

Conclusions—

The potential atheroprotective effects of TZDs conferred by insulin sensitization may be partially offset by adverse effects on advanced atherosclerosis. Because the mechanisms of the beneficial and proposed adverse effects may differ, these findings have potentially important implications for drug optimization.
Omega-3 Polyunsaturated Fatty Acids Prevent Atrial Fibrillation Associated With Heart Failure but Not Atrial Tachycardia Remodeling
Authors: Sakabe Masao , Shiroshita-Takeshita Akiko , Maguy Ange , Dumesnil Chloe , Nigam Anil , Leung Tack-Ki , Nattel Stanley
Published: October 2007

Background—

There is epidemiological evidence that omega-3 polyunsaturated fatty acids (PUFAs) reduce the risk of atrial fibrillation (AF), but clinical data are conflicting. The present study assessed the effects of PUFA on AF in experimental models.

Methods and Results—

We studied the effects of oral PUFA supplements in 2 experimental AF paradigms: electrical remodeling induced by atrial tachypacing (400 bpm for 1 week) and congestive heart failure–associated structural remodeling induced by ventricular tachypacing (240 bpm for 2 weeks). PUFA pretreatment did not directly change atrial effective refractory period (128±6 [mean±SEM] versus 127±2 ms; all effective refractory periods at 300-ms cycle lengths) or burst pacing–induced AF duration (5±4 versus 34±18 seconds). Atrial tachypacing dogs had shorter refractory periods (73±6 ms) and greater AF duration (1185±300 seconds) than shams (119±5 ms and 20±11 seconds;
P
<0.01 for each). PUFAs did not significantly alter atrial tachypacing effects on refractory periods (77±8 ms) or AF duration (1128±412 seconds). PUFAs suppressed ventricular tachypacing–induced increases in AF duration (952±221 versus 318±249 seconds;
P
<0.05) and attenuated congestive heart failure–related atrial fibrosis (from 19.2±1.1% to 5.8±1.0%;
P
<0.001) and conduction abnormalities. PUFAs also attenuated ventricular tachypacing–induced hemodynamic dysfunction (eg, left ventricular end-diastolic and left atrial pressure from 12.2±0.5 and 11.4±0.6 mm Hg, respectively, to 6.4±0.5 and 7.0±0.8 mm Hg;
P
<0.01) and phosphorylation of mitogen-activated protein kinases (extracellular-signal related and P38 kinase).

Conclusions—

PUFAs suppress congestive heart failure–induced atrial structural remodeling and AF promotion but do not affect atrial tachycardia–induced electrical remodeling. The beneficial effects of PUFAs on structural remodeling, possibly related to prevention of mitogen-activated protein kinase activation, may contribute to their clinical anti-AF potential.
Normal Vascular Function Despite Low Levels of High-Density Lipoprotein Cholesterol in Carriers of the Apolipoprotein A-I
Milano
Mutant
Authors: Gomaraschi Monica , Baldassarre Damiano , Amato Mauro , Eligini Sonia , Conca Paola , Sirtori Cesare R. , Franceschini Guido , Calabresi Laura
Published: October 2007

Background—

Carriers of the apolipoprotein A-I
Milano
(apoA-I
M
) mutant have very low plasma high-density lipoprotein cholesterol (HDL-C) levels but do not show any history of premature cardiovascular disease or any evidence of preclinical vascular disease. HDL is believed to prevent the development of vascular dysfunction, which may well contribute to HDL-mediated atheroprotection. Whether the low HDL level of apoA-I
M
carriers is associated with impaired vascular function is presently unknown.

Methods and Results—

The vascular response to reactive hyperemia, assessed by measuring postischemic increase in forearm arterial compliance, and the plasma concentration of soluble cell adhesion molecules were evaluated in 21 adult apoA-I
M
carriers, 21 age- and gender-matched nonaffected relatives (control subjects), and 21 healthy subjects with low HDL-C (low-HDL subjects). The average plasma HDL-C and apoA-I levels of apoA-I
M
carriers were remarkably lower than those of control subjects and significantly lower than those of low-HDL subjects. The postischemic increase in forearm arterial compliance in the apoA-I
M
carriers was 2-fold greater than in low-HDL subjects and remarkably similar to that of control subjects. Plasma soluble cell adhesion molecule levels were similar in apoA-I
M
carriers and control subjects but were greater in low-HDL subjects. When incubated with endothelial cells, HDL isolated from apoA-I
M
carriers was more effective than HDL from control and low-HDL subjects in stimulating endothelial nitric oxide synthase expression and activation and in downregulating tumor necrosis factor-α–induced expression of vascular cell adhesion molecule-1.

Conclusions—

Despite their very low HDL levels, apoA-I
M
carriers do not display typical features of impaired vascular function because of an improved activity of apoA-I
M
HDL in maintaining endothelial cell homeostasis.
NF1
Regulates a Ras-Dependent Vascular Smooth Muscle Proliferative Injury Response
Authors: Xu Junwang , Ismat Fraz A. , Wang Tao , Yang Jifu , Epstein Jonathan A.
Published: October 2007

Background—

Neurofibromatosis type I (NF1) is a common autosomal dominant disorder with a broad array of clinical manifestations, including benign and malignant tumors, osseous dysplasias, and characteristic cutaneous findings. In addition, NF1 patients have an increased incidence of cardiovascular diseases, including obstructive vascular disorders. In animal models, endothelial expression of the disease gene,
NF1
, is critical for normal heart development. However, the pathogeneses of the more common vascular disorders are not well characterized.

Methods and Results—

To examine the role of
NF1
in vascular smooth muscle, we generated mice with homozygous loss of the murine homolog
Nf1
in smooth muscle (
Nf1
smKO). These mice develop and breed normally. However, in response to vascular injury, they display a marked intimal hyperproliferation and abnormal activation of mitogen- activated protein kinase, a downstream effector of Ras. Vascular smooth muscle cells cultured from these mice also display enhanced proliferation and mitogen-activated protein kinase activity. Smooth muscle expression of the
NF1
Ras-regulatory domain (GTPase activating protein–related domain) rescues intimal hyperplasia in
Nf1
smKO mice and normalizes vascular smooth muscle cell Ras effector activity and proliferation in vitro, similar to blockade of downstream effectors of Ras.

Conclusions—

In this in vivo model of NF1 obstructive vascular disease, we have shown that
Nf1
regulation of Ras plays a critical role in vascular smooth muscle proliferation after injury. These results suggest opportunities for targeted therapeutics in the prevention and treatment of NF1-related vascular disease and in the treatment of neointimal proliferation in other settings.
CD36 Expression Contributes to Age-Induced Cardiomyopathy in Mice
Authors: Koonen Debby P.Y. , Febbraio Maria , Bonnet Sebastien , Nagendran Jayan , Young Martin E. , Michelakis Evangelos D. , Dyck Jason R.B.
Published: October 2007

Background—

Cardiac remodeling and impaired cardiac performance in the elderly significantly increase the risk of developing heart disease. Although vascular abnormalities associated with aging contribute to the age-related decline in cardiac function, myocardium-specific events may also be involved.

Methods and Results—

We show that intramyocardial lipid accumulation, as well as a reduction in both fatty acid and glucose oxidation and a subsequent deterioration in cardiac ATP supply, also occurs in aged mice. Consistent with an energetically compromised heart, hearts from aged mice display depressed myocardial performance and cardiac hypertrophy. Associated with this is a dramatic increase in the fatty acid transport protein CD36 in aged hearts compared with young hearts, which suggests that CD36 is a mediator of these multiple metabolic, functional, and structural alterations in the aged heart. In accordance with this, hearts from aged CD36-deficient mice have lower levels of intramyocardial lipids, demonstrate improved mitochondria-derived ATP production, have significantly enhanced function compared with aged wild-type mice, and have a blunted hypertrophic response.

Conclusions—

These findings provide evidence that CD36 mediates an age-induced cardiomyopathy in mice and suggest that inhibition of CD36 may be an approach for the treatment of the detrimental age-related effects on cardiac performance.
Physical Activity and Reduced Risk of Cardiovascular Events
Authors: Mora Samia , Cook Nancy , Buring Julie E. , Ridker Paul M , Lee I-Min
Published: October 2007

Background—

Higher levels of physical activity are associated with fewer cardiovascular disease (CVD) events. Although the precise mechanisms underlying this inverse association are unclear, differences in several cardiovascular risk factors may mediate this effect.

Methods and Results—

In a prospective study of 27 055 apparently healthy women, we measured baseline levels of hemoglobin A1c, traditional lipids (total, low-density lipoprotein, and high-density lipoprotein cholesterol), novel lipids [lipoprotein(a) and apolipoprotein A1 and B-100], creatinine, homocysteine, and inflammatory/hemostatic biomarkers (high-sensitivity C-reactive protein, fibrinogen, soluble intracellular adhesion molecule-1) and used women’s self-reported physical activity, weight, height, hypertension, and diabetes. Mean follow-up was 10.9±1.6 years, and 979 incident CVD events occurred. The risk of CVD decreased linearly with higher levels of activity (
P
for linear trend <0.001). Using the reference group of <200 kcal/wk of activity yielded age- and treatment-adjusted relative risk reductions associated with 200 to 599, 600 to 1499, and ≥1500 kcal/wk of 27%, 32%, and 41%, respectively. Differences in known risk factors explained a large proportion (59.0%) of the observed inverse association. When sets of risk factors were examined, inflammatory/hemostatic biomarkers made the largest contribution to lower risk (32.6%), followed by blood pressure (27.1%). Novel lipids contributed less to CVD risk reduction compared with traditional lipids (15.5% and 19.1%, respectively). Smaller contributions were attributed to body mass index (10.1%) and hemoglobin A1c/diabetes (8.9%), whereas homocysteine and creatinine had negligible effects (<1%).

Conclusions—

The inverse association between physical activity and CVD risk is mediated in substantial part by known risk factors, particularly inflammatory/hemostatic factors and blood pressure.
Impact of the Metabolic Syndrome on Macrovascular and Microvascular Outcomes in Type 2 Diabetes Mellitus
Authors: Cull Carole A. , Jensen Christine C. , Retnakaran Ravi , Holman Rury R.
Published: October 2007

Background—

The metabolic syndrome (MetS) and type 2 diabetes mellitus are both associated with increased cardiovascular disease risk. We examined retrospectively the degree to which the presence of MetS in individuals with type 2 diabetes mellitus increased their risk of diabetic complications using United Kingdom Prospective Diabetes Study data.

Methods and Results—

Of 5102 United Kingdom Prospective Diabetes Study patients recruited with newly diagnosed type 2 diabetes mellitus and followed up for a median of 10.3 years, 4542 had the requisite data for these analyses. After a 3-month dietary run-in, MetS, diagnosed with National Cholesterol Education Program Adult Treatment Panel III, World Health Organization, International Diabetes Federation, or European Group for the Study of Insulin Resistance criteria, was present in 61%, 38%, 54%, and 24%, respectively. Those with MetS by these criteria had increased cardiovascular disease risks relative to those without MetS of 1.33 (95% confidence interval 1.14 to 1.54), 1.45 (95% confidence interval 1.26 to 1.66), 1.23 (95% confidence interval 1.07 to 1.42), and 1.31 (95% confidence interval 1.10 to 1.57), respectively, but similar risks for microvascular complications. The positive predictive value of MetS for cardiovascular disease events, however, was only 18%, 13%, 18%, and 39%, respectively.

Conclusions—

MetS, diagnosed by Adult Treatment Panel III, World Health Organization, or International Diabetes Federation criteria, identifies diabetic patients at greater risk of macrovascular but not microvascular complications. Poor discrimination by MetS with respect to cardiovascular disease outcomes means that it is of limited clinical value for cardiovascular disease risk stratification in type 2 diabetes mellitus.
Poverty and Stroke in India
Authors: Pandian Jeyaraj D. , Srikanth Velandai , Read Stephen J. , Thrift Amanda G.
Published: October 2007

In developed countries, the predominant health problems are those lifestyle-related illnesses associated with increased wealth. In contrast, diseases occurring in developing countries can largely be attributed to poverty, poor healthcare infrastructure, and limited access to care. However, many developing countries such as India have undergone economic and demographic growth in recent years resulting in a transition from diseases caused by poverty toward chronic, noncommunicable, lifestyle-related diseases. Despite this recent rapid economic growth, a large proportion of the Indian population lives in poverty. Although risk factors for stroke in urban Indian populations are similar to developed nations, it is likely that they may be quite different among those afflicted by poverty. Furthermore, treatment options for stroke are fewer in developing countries like India. Well-organized stroke services and emergency transport services are lacking, many treatments are unaffordable, and sociocultural factors may influence access to medical care for many stroke victims. Most stroke centers are currently in the private sector and establishing such centers in the public sector will require enormous capital investment. Given the limited resources available for hospital treatments, it would be logical to place a greater emphasis on effective populationwide interventions to control or reduce exposure to leading stroke risk factors. There also needs to be a concerted effort to ensure access to stroke care programs that are tailored to suit Indian communities and are accessible to the large majority of the population, namely the poor.
Hypotonic Versus Isotonic Maintenance Intravenous Fluid Therapy in Hospitalized Children: A Systematic Review
Authors: Beck Carolyn E.
Published: October 2007

A systematic review of studies comparing hypotonic versus isotonic intravenous maintenance fluids in hospitalized children was conducted to determine whether hypotonic solutions increase the risk of acute hyponatremia. Studies were identified from electronic databases and hand-searched reference lists. A total of 283 abstracts were reviewed, 55 full-text articles were retrieved, and 3 studies were included. All studies were observational and were overall inconclusive. All authors cautioned against the routine use of hypotonic maintenance fluids, but hypotonic fluid administration did not always explain the development of acute hyponatremia. Further evidence is required as to the appropriate maintenance solution for hospitalized children.
A Strategy for Controlling Item Exposure in Multidimensional Computerized Adaptive Testing
Authors: Lee Yi-Hsuan , Ip Edward H. , Fuh Cheng-Der
Published: October 2007

Although computerized adaptive tests have enjoyed tremendous growth, solutions for important problems remain unavailable. One problem is the control of item exposure rate. Because adaptive algorithms are designed to select optimal items, they choose items with high discriminating power. Thus, these items are selected more often than others, leading to both overexposure and underutilization of some parts of the item pool. Overused items are often compromised, creating a security problem that could threaten the validity of a test. Building on a previously proposed stratification scheme to control the exposure rate for one-dimensional tests, the authors extend their method to multidimensional tests. A strategy is proposed based on stratification in accordance with a functional of the vector of the discrimination parameter, which can be implemented with minimal computational overhead. Both theoretical and empirical validation studies are provided. Empirical results indicate significant improvement over the commonly used method of controlling exposure rate that requires only a reasonable sacrifice in efficiency.
Pharmacokinetics of Lenalidomide in Subjects With Various Degrees of Renal Impairment and in Subjects on Hemodialysis
Authors: Chen Nianhang , Lau Henry , Kong Linghui , Kumar Gondi , Zeldis Jerom B. , Knight Robert , Laskin Osca L.
Published: October 2007

The present study investigated the effect of renal impairment and hemodialysis on the pharmacokinetics of lenalidomide following a single 25‐mg oral dose in 30 subjects aged 39 to 76 years. A single 25‐mg dose was well tolerated by renally impaired subjects. Renal impairment did not alter the oral absorption, protein binding, or nonrenal elimination of lenalidomide. Mean urinary recovery of unchanged lenalidomide was 84% of the dose in subjects with normal renal function (creatinine clearance [CLCr] > 80 mL/min), and it declined to 69%, 38%, and 43% in subjects with mild (50 ≤ CLCr ≤ 80 mL/min), moderate (30 ≤ CLCr < 50 mL/min), and severe (CLCr < 30 mL/min) renal impairment, respectively. The differences in pharmacokinetic parameters between normal renal function and mild renal impairment were minor to modest (11%–32%). As renal impairment progressed to moderate, severe, or end‐stage renal disease, total and renal lenalidomide clearance decreased drastically, area under the concentration‐time curve increased by approximately 185% to 420%, and t1/2 was prolonged by approximately 6 to 12 hours. A 4‐hour hemodialysis removed 31% of lenalidomide in the body. Therefore, lenalidomide dose adjustments should be considered for patients with CLCr < 50 mL/min, and the recommendations are given for the starting doses.
Childhood Adverse Events and Current Traumatic Distress
Authors: Messina Nena , Grella Christine , Burdon William , Prendergast Michael
Published: October 2007

This study describes the prevalence of childhood adverse events (CAEs) among men and women prisoners and assesses the relationship of CAEs to adult symptoms of traumatic distress. Interview data for 427 men and 315 women were analyzed assessing childhood abuse and household dysfunction, drug and criminal histories, and symptoms of traumatic distress. Women offenders had much greater exposure to CAEs than did men and more often reported continued sexual abuse in adolescence and as an adult. Linear regression results showed that the impact of CAEs on traumatic distress was strong and cumulative for both men and women (greater exposure to CAEs increased the likelihood of 6 out of 7 mental health outcomes, although women had higher levels of traumatic distress overall). The findings indicate the need for early prevention and intervention as well as trauma-based treatment within the correctional setting.
Assessing Suitability for Offender Rehabilitation
Authors: Casey Sharon , Day Andrew , Howells Kevin , Ward Tony
Published: October 2007

Although the need to assess appropriate candidates for offender rehabilitation programs is widely acknowledged, few assessment tools are available that have been validated for use with offender populations. This article reports on the development and validation of a brief self-report measure designed to assess treatment readiness in offenders who have been referred to a cognitive skills program. The measure, the Corrections Victoria Treatment Readiness Questionnaire, displayed acceptable levels of convergent and discriminant validity, and was able to predict treatment engagement and treatment performance at the midpoint of the program. Suggested cutoff points are reported for use in assessing offenders for this type of program. It is concluded that the measure can play a valuable role in the assessment of offenders who are being considered for rehabilitative treatment.
Belief in a Personal Just World, Justice Judgments, and Their Functions for Prisoners
Authors: Dalbert Claudia , Filke Eva
Published: October 2007

This study focuses on the relationship between the experience of justice, belief in a just world (BJW), and the feelings of adult male prisoners. The sample comprised 100 adult male prisoners from a German prison. Regression analysis provided evidence for the assimilation function of the BJW: High believers evaluated the legal proceedings, their interpersonal treatment by their corrections officers, and decisions on prison affairs as more just; they reported better well-being and were less likely to express anger as outburst behavior. Interpersonal justice was particularly important in explaining well-being. The results persisted when controlling for social desirability, criminal background, and personal background. The role of BJW and interpersonal justice as a resource for adaptive social behavior and subjective well-being is discussed.
A Multisite Evaluation of Prison-Based Therapeutic Community Drug Treatment
Authors: Welsh Wayne N.
Published: October 2007

A quasi-experimental study examined multiple postrelease outcomes up to 2 years for inmates who participated in therapeutic community (TC) drug treatment programs ( n = 217) or comparison groups ( n = 491) at five state prisons. Statistical controls included level of need for treatment, current and prior criminal history, and postrelease employment. Prison TC was effective even without mandatory community aftercare, although main effects and interactions varied somewhat across different outcome measures and sites. TC significantly reduced rearrest and reincarceration rates but not drug relapse rates. Postrelease employment predicted drug relapse and reincarceration, and employment interacted with age to predict rearrest. Two sites had higher drug relapse rates than the other three. Implications for research and policy are discussed.
An Empirical Portrait of Community Reentry Among Serious Juvenile Offenders in Two Metropolitan Cities
Authors: He Len Chung  , Schubert Carol A. , Mulvey Edward P.
Published: October 2007

This study examined the community reentry process among 413 serious adolescent offenders released from juvenile court commitments in two metropolitan areas. Data are provided about postrelease court supervision and community-based services (CBSs) during the first 6 months in the community as well as indicators of antisocial activity, formal system involvement, school attendance, and employment. Findings indicate that a far greater proportion of offenders reported receiving supervision than CBSs, but when utilized, the frequency of CBS use was high, and intensive services reduced the odds of formal system involvement. In addition, court supervision increased the likelihood of positive adjustment during community reentry. These results held after controlling for social context variables, including peer deviance, parental monitoring, and contact with caring adults.
Two-Phase Item Selection Procedure for Flexible Content Balancing in CAT
Authors: Ying Cheng  , Chang Hua-Hua , Qing Yi
Published: October 2007

Content balancing is an important issue in the design and implementation of computerized adaptive testing (CAT). Content-balancing techniques that have been applied in fixed content balancing, where the number of items from each content area is fixed, include constrained CAT (CCAT), the modified multinomial model (MMM), modified constrained CAT (MCCAT), and others. In this article, four methods are proposed to address the flexible content-balancing issue with the a-stratification design, named STR_C. The four methods are MMM+, an extension of MMM; MCCAT+, an extension of MCCAT; the TPM method, a two-phase content-balancing method using MMM in both phases; and the TPF method, a two-phase content-balancing method using MMM in the first phase and MCCAT in the second. Simulation results show that all of the methods work well in content balancing, and TPF performs the best in item exposure control and item pool utilization while maintaining measurement precision.
Linking Parameters Estimated With the Generalized Graded Unfolding Model: A Comparison of the Accuracy of Characteristic Curve Methods
Authors: Anderson Koenig Judith , Roberts James S.
Published: October 2007

Methods for linking item response theory (IRT) parameters are developed for attitude questionnaire responses calibrated with the generalized graded unfolding model (GGUM). One class of IRT linking methods derives the linking coefficients by comparing characteristic curves, and three of these methods—test characteristic curve (TCC), item characteristic curve (ICC), and operating characteristic curve (OCC)—are extended for use with the GGUM. Alternate versions of these methods are developed to produce both symmetric and asymmetric solutions. The adequacy of these methods for use with the GGUM is evaluated in a simulation that varied the distributions of θ in the groups to be linked and the number of individuals and anchor items used for linking. All methods performed well under the conditions studied. Statistically significant effects were found for sample size and number of anchor items. It is recommended that choice of linking method should consider the context and intent of the linking.
Social Control Theory and the Connection With Ideological Offenders Among Israeli Youth During the Gaza Disengagement Period
Authors: Shechory Mally , Laufer Avital
Published: October 2007

The present study examined whether social control theory is capable of explaining youth's law violations in instances of conflict between the ideological religious worldview and the laws of the country in which they reside. Differences in the control factors (commitment, belief, attachment, and involvement) were examined among Israeli adolescents who took part in legal activity ( n = 163) and illegal activity ( n = 99) during the resistance to the Gaza evacuation. The findings indicate that the model provides a partial explanation for ideological delinquency. It was found that involvement with friends and the absence of belief in the formal legal system were associated with illegal ideology activity. Attachment to friends and parents and involvement with parents had no effect on youth's participation in illegal ideological activities.
Criminal Recidivism in Sexual Homicide Perpetrators
Authors: Hill Andreas , Habermann Niels , Klusmann Dietrich , Berner Wolfgang , Briken Peer
Published: October 2007

Forensic psychiatric reports on 166 sexual homicide perpetrators in Germany were retrospectively analyzed for criminal risk factors. Follow-up information about release and reconvictions from federal criminal records was available for 139 offenders; 90 (64.7%) had been released. The estimated recidivism rate (Kaplan—Meier analyses) for 20 years at risk was 23.1% for sexual and 18.3% for nonsexual violent reoffences. Three men (3.3%) were reconvicted for attempted or completed homicide. Only young age at the time of sexual homicide resulted in higher sexual recidivism, whereas increased nonsexual violent recidivism was related to previous sexual and nonsexual delinquency, psychopathic symptoms, and higher scores in risk assessment instruments. Increased recidivism with any violent reoffence was associated with age-related factors: young age at first sexual offence, at homicide, and at release and duration of detention. The impacts of the results for risk assessment, relapse prevention, and supervision are discussed.
Standards in the Privatization of Probation Services
Authors: Schloss Christine S. , Alarid Leanne F.
Published: October 2007

Privatization of probation services has increased nationwide in at least 10 states. When private probation initially began in the 1970s, there were few regulatory requirements for the supervision of misdemeanor offenders. The authors present the history of private probation and a review of statutory requirements for private probation companies providing supervision in several states. Missouri statutory requirements are compared with those of other states providing such services. The authors examine contractual agreements between the government and private entities, private probation officer training, education, salaries, private probationer supervision costs, and standards for private agencies providing ancillary treatment services. Analysis found statutes to lack standardization both between and within some states. Although some state statutes address private probation operations and contracts adequately, the authors question whether existing statutory guidelines in other jurisdictions are sufficient for operation of private probation supervision agencies and recommend more specific standards governing the use of private probation.
An Investigation of the General Abilities Index in a Group of Diagnostically Mixed Patients
Authors: Harrison Allyson G. , DeLisle Michelle M. , Parker Kevin C. H.
Published: October 2007

The General Ability Index (GAI) was compared with Wechsler Adult Intelligence Scale—Third Edition (WAIS-III) Full Scale Intelligence Quotient (FSIQ) from the WAIS-III in data obtained from 381 adults assessed for reported learning or attention problems between 1998 and 2005. Not only did clients with more neurocognitively based disorders (i.e., learning disabilities, attention deficit hyperactivity disorder, and brain injury) demonstrate a larger discrepancy between GAI and FSIQ than did those with mainly psychological conditions (i.e., depression, anxiety, posttraumatic stress disorder), but specific neurocognitive diagnosis also moderated the relationship between these two indices. In neurocognitive disorders, GAI was found to be generally higher than FSIQ, a finding that distinguished this group from a nonclinical sample. There were significant differences in GAI among the clinical groups, and FSIQ was closely related to GAI. Implications for use of the GAI in clinical practice are discussed.