bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring unfractionated heparin with the aPTT: Time for a fresh look
Authors: Hirsh Jack , Eikelboom John
Published: December 2006

Laboratory monitoring is widely recommended to measure the anticoagulant effect of unfractionated heparin and to adjust the dose to maintain levels in the target therapeutic range.The most widely used laboratory assay for monitoring unfractionated heparin therapy is the activated partial thromboplastin time (aPTT). A fixed therapeutic range for the aPTT of 1.5 to 2.5 times the control value has become widely accepted,but the evidence supporting this range is weak and the clinical validity of using the aPTT for predicting thrombotic or bleeding events is questionable. The aPTT test is also affected by numerous preanalytic and analytic variables that are unrelated to the anticoagulant effect of unfractionated heparin, further eroding its potential value for monitoring unfractionated heparin treatment. Unfractionated heparin dose appears to be more important than the aPTT in predicting clinical efficacy. Despite serious limitations,the reliance on the aPTT is likely to continue because of its ready availability and familiarity of clinicians with the test. The focus of clinicians who manage unfractionated heparin therapy should be to ensure that an adequate starting dose of unfractionated heparin is used and that the aPTT method is standardized. Future research efforts should be directed towards developing methods to improve standardization of the aPTT assay for monitoring unfractionated heparin. Direct measures of the concentration of unfractionated heparin in the blood are attractive because these assays are not affected by many of the biologic variables that interfere with the aPTT and may be suitable for automation. However, currently available unfractionated heparin assays are much more expensive than the aPTT, are not widely available, and their validity has not been adequately assessed in clinical outcome studies.
Prevention of distal embolization in patients undergoing mechanical revascularization for acute myocardial infarction
Authors: Suryapranata Harry , Chiariello Massimo , De Luca Giuseppe
Published: December 2006

Distal embolization is a relatively common complication in primary angioplasty and is associated with poor perfusion and higher mortality. The aim of this article is to critically review literature on pharmacological and mechanical therapies to prevent distal embolization in patients undergoing primary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to March 2006 and scientific session abstracts (from January 1990 to March 2006) and oral presentation and/or expert slide presentations (from January 2002 to March 2006) (on TCT, AHA, ESC, ACC and EuroPCR websites). No language restrictions were enforced. Several pharmacological and mechanical therapies have been investigated to prevent distal embolization.Abciximab has been shown to reduce mortality,and its early admin-istration may provide additional benefits in outcome due to improvement in preprocedural reperfusion.The results of randomized trials on adjunctive mechanical devices remain controversial. Even though they reduce distal embolization and improve myocardial perfusion, no benefits have been observed in terms of 30-day survival. Adjunctive abciximab has improved survival, and its early administration is to be recommended, particularly when transportation to a primary PCI center is needed. Pending the results of large randomized trials with long-term follow-up data, the routine use of adjunctive mechanical devices to prevent distal embolization cannot be recommended, though selective use of these devices might be considered when large thrombotic burden is present.
The UK National External Quality Assessment Scheme (UK NEQAS) for molecular genetic testing in haemophilia
Authors: Goodeve Anne , Hill Marian , Jennings Ian , Kitchen Steve , Walker Isobel , Perry David ,   UK NEQAS for Blood Coagulation
Published: December 2006

Molecular genetic analysis of families with haemophilia and other inherited bleeding disorders is nowa common laboratory investigation. In contrast to phenotypic testing in which strict quality control is adhered to, in haemophilia molecular genetic testing there has been a lack of any external quality assurance schemes. In 1998 the UK National External Quality Assessment Scheme (UK NEQAS) established a pilot quality assurance scheme for molecular genetic testing in haemophilia. Results from three initial surveys highlighted problems with the quality of samples when used to screen for the intron 22 inversion within the F8 gene. The scheme was re-launched in 2003, and since that time there have been five exercises involving whole blood or immortalised cell line DNA. The results together with an overall summary of the exercise are subsequently returned to participants. Exercises to date have focused exclusively on haemophilia A and QA, material has included screening for the intron 1 and intron 22 inversions as well as sequence analysis. A paper exercise circulated in 2003 highlighted problems with the format of reports and, following feedback to participants, onlya single error has been made in the subsequent four exercises. Participating laboratories now receive QA material every six months. Immortalised cell line material was introduced in 2005 and was shown to perform well. This will allow expansion of the scheme and a reduction in the dependence on blood donation.
No difference in the effects of clopidogrel and aspirin on inflammatory markers in patients with coronary heart disease
Authors: Pettersen Alf , Arnesen Harald , Seljeflot Ingebjørg , Solheim Svein
Published: December 2006

Aspirin reduces several pro-inflammatory markers in patients with coronary heart disease (CHD), while limited data exists with clopidogrel. The aim of the present substudy of ASCET was to assess the influence of clopidogrel as compared to aspirin on selected circulating inflammatory markers in patients with stable angiographically verified CHD. Patients on treatment with aspirin 160 mg/day for at least seven days were randomized to either aspirin 160 mg/day (n=105) or clopidogrel 75 mg/day (n=101). Fasting blood samples were drawn at baseline and after one month and after one year for determination of high sensitivity C-reactive protein, tumor necrosis factor α (TNFα), interleukin 6, monocyte chemoattractant protein 1(MCP-1), CD40L, P-selectin, interleukin 10 and transforming growth factor. The groups were similar regarding demographic variables. There were no differences in any variables including changes from baseline to one month and one year between the groups. In the aspirin group we found significantly lower levels of TNFα and MCP-1 after one year; 1.00 versus 1.16 pg/ml (p<0.001) and 245 versus 261 pg/ml (p<0.001), respectively. Likewise, in the clopidogrel group the level of TNFα was significantly reduced after one year; 0.99 versus 1.19 pg/ml (p<0.001). In patients with CHD we found no between-group differences in circulating markers of inflammation after one year treatment with clopidogrel 75 mg/day compared to aspirin 160 mg/day, but in both groups lower levels of TNFα were obtained. The present results indicate similar anti-inflammatory effects of the two drugs.
Immunohistochemistry of thrombi following iliac venous stenting: A novel model of venous thrombosis
Authors: Burches Bobby , Karnicki Krzysztof , Wysokinski Waldemar , McBane Robert
Published: December 2006

Stenting has become a common intervention for venous occlusive disease. Little is known regarding the composition of venous thrombi complicating stent placement. The optimal design of antithrombotic agents in this setting requires this knowledge. Quantitative immunohistochemistry was undertaken to define the platelet, fibrin(ogen) and leukocyte composition and spatial orientation of venous thrombi following percutaneous iliac stent placement in pigs. Venous stent thrombus size was measured by weight and scintillation detection of autologous 111In-platelets. Thrombi were divided in segments (cephalad to caudad), sectioned and stained with monoclonal anti-platelet glycoprotein Ib or polyclonal anti-fibrin(ogen) fluorescent antibodies. Thrombus platelet content was 100-fold greater than paired whole blood samples. The caudal-most segments contained platelet-rich aggregates (p<0.05) with abundant leukocytes (p<0.0001) relative to more cephalad segments. Platelet and fibrin(ogen) content varied over an eight-fold range between segments but were directly correlated with each other (r=0.77; p<0.0001). The platelet co-localization with fibrin(ogen) is consistent with the phospholipid dependence of prothrombin activation. The abundance and caudal distribution of platelet-leukocyte aggregates indicate their preferential accretion from flowing blood early in the genesis of venous stent thrombi. These may represent novel cellular targets for the prevention and treatment of venous thrombosis.
Platelet microparticle formation and thrombin generation under high shear are effectively suppressed by a monoclonal antibody against GPIbα
Authors: Pontiggia Luca , Steiner Beat , Ulrichts Hans , Deckmyn Hans , Forestier Marc , Beer Jürg
Published: December 2006

We studied the inhibition of platelet microparticle (MP) formation and thrombin generation under high shear forces. We hypothesized that an inhibitor of the GPIbα-von Willebrand factor (vWF) interaction would be more effective in suppressing MP formation and thrombin generation than GPIIb/IIIa inhibitors. Platelet-rich plasma (PRP) anticoagulated with PPACK (D-Phe-Pro-Arg chloromethyl ketone) was exposed in a coneand-plate viscometer (shear: 5,000 s−1 for5 min) in the presence of antagonists to GPIbα (the monoclonal antibody [Mab] Ib-23) or to GPIIb/IIIa (abciximab, tirofiban, eptifibatide) at their IC90 determined in platelet aggregometry with ristocetin or ADP, respectively. We used double labeling (CD41-PE and annexin-V-FITC) for flow cytometric detection of MP and their aminophospholipid exposure. Thrombin generation was measured using PRP prepared fromACD anticoagulated blood. About 40% of the thrombin generation was found to be mediated by the MP fraction of the PRP. Blockade of GPIbα with Mab Ib-23 reduced MP formation and thrombin generation by 50%, and was more effective than any GPIIb/IIIa antagonist. The combination of Mab Ib-23 with one of the GPIIb/IIIa inhibitors further reduced the MP formation to ∼30%. The antibody also partially inhibited thrombin induced platelet aggregation. Epitope mapping suggested that Mab Ib-23 binds between the amino acids 201 and 268 of GPIbα, explaining the interference with vWF and thrombin interaction. In contrast to the commonly used GPIIb/IIIa antagonists, the blockade of GPIbα with Mab Ib-23 effectively reduces the prothrombotic MP generation and thrombin formation at shear rates typically found in arterial stenoses.
Chronological expression of PAR isoforms in acute liver injury and its amelioration by PAR2 blockade in a rat model of sepsis
Authors: Jesmin Subrina , Zaedi Sohel , Sakuraya Fumika , Gando Satoshi
Published: December 2006

The liver can be injured and its functions altered by activation of the coagulation and inflammatory processes in sepsis. The objective of the present study was to investigate the pattern of protease-activated receptors (PARs) over time in a model of acute liver injury induced by lipopolysaccharide (LPS); and whether PARs playa role in this process and exert their effects through inflammation and coagulation. Levels of tumor necrosis factor-α (TNF-α) were significantly expressed 1 h after LPS administration followed by: i) an increase in levels of tissue factor, factor VIIa, thrombin and plasminogen activator inhibitor-1; ii) unchanged or steady levels of tissue factor pathway inhibitor; and iii) subsequent deposition of fibrin in the liver tissue, that led to the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are associated with liver injury. The expression of all PAR isoforms (1–4) was elevated, and each isoform had a distinct cellular localization (hepatocytes, Kupffer cells, the portal triad area, and central veins) and a time-dependent pattern of expression. The immuno-reactivity of PAR2 and 4 in Kupffer cells was intense. Interestingly, PAR2 blocking peptide improved the healing of liver injuries, an effect that was associated with suppression of TNF-α elevation, and normalization of coagulation and fibrinolysis. This ultimately led to decreased fibrin formation in the injured liver. The present study reveals a distinct chronological expression and cellular localization of PARs in LPS-mediated liver injury and shows that blockade of PAR2 may playa crucial role in treating liver injury, via normalization of inflammation, coagulation and fibrinolytic pathways.
Tiplaxtinin impairs nutritionally induced obesity in mice
Authors: Alessi Marie-Christine , Frederix Liesbeth , Collen Désiré , Juhan-Vague Irène , Lijnen H.
Published: December 2006

To investigate the effect of tiplaxtinin, designed as a synthetic inhibitor of plasminogen activator inhibitor-1 (PAI-1), on obesity, male C57Bl/6 mice (13–14 weeks old) were kept on a high-fat diet (20.1 kJ/g) for four weeks without or with addition of tiplaxtinin (PAI-039) at a dose of 2 mg/g food. At the time of sacrifice, body weights were significantly lower in the inhibitor-treated mice (p < 0.0005). The weights of the isolated subcutaneous and gonadal fat deposits were also significantly lower (both p < 0.0005), associated with adipocyte hypotrophy. Inhibitor-treated adipose tissues displayed similar blood vessel size, but a higher blood vessel density. Fasting glucose and insulin levels, as well as glucose-tolerance tests were not significantly affected by the inhibitor treatment, whereas plasma triglyceride levels were significantly reduced (p = 0.02) and LDL-cholesterol levels significantly enhanced (p = 0.0002). Insulin-tolerance tests revealed significantly lower glucose levels at the end of the test in the inhibitor treated mice (p = 0.03). Thus, in this model of diet-in-duced obesity in mice administration of tiplaxtinin resulted in impaired adipose tissue development.
Differential effects of the loss of intrachain- versus interchain-disulfide bonds in the cystine-knot domain of von Willebrand factor on the clinical phenotype of von Willebrand disease
Authors: Tjernberg Pernilla , Vos Hans , Spaargaren-van Riel Caroline , Luken Brenda , Voorberg Jan , Bertina Rogier , Eikenboom Jeroen
Published: December 2006

Von Willebrand factor (VWF) contains a large number of cysteine residues, which all form disulfide bonds. Mutations of cysteines located in the cystine-knot (CK) domain of VWF have been identified in both qualitative type 2A (IID) and quantitative type 3 vonWillebrand disease (VWD).Our objective was to test the hypothesis that the difference in phenotype is related to whether the mutated cysteine residue is involved in either interchain- or intrachain-disulfide-bond formation. The effects of three cysteine mutations which are all located in the CK-domain of VWF, C2773S (type 2A(IID)), C2739Y (type 3), and C2754W (type 3), were studied by transient expression in 293T cells. Cotransfection of wild-type (wt) and C2773S VWF constructs reproduced the plasma phenotype of heterozygous type 2A(IID) patients, with normal to high levels of VWF antigen (VWF:Ag), absence of high-molecular-weight multimers, and the presence of intervening bands between the normal multimers.In contrast, single transfections of C2739Y or C2754W resulted in a quantitativeVWF defect with lowVWF:Ag levels, and co-transfections of wt and mutant constructs resulted in a 50% reduction of VWF:Ag and only a minor effect on VWF multimerization. We demonstrated N-terminal dimerization of VWF-C2773S and both Nand C-terminal dimerization of VWF-C2754W. Our data suggest that loss of a single disulfide bond in the CK-domain ofVWF leads toa recessive, quantitativeVWF deficiency if an intrachain-disulfide bond is involved, and to a dominant-negative, qualitative defect of VWF if an interchain-disulfide bond is involved.
Prevalence, Awareness, Treatment, and Control of Hypertension Among United States Adults 1999–2004
Authors: Ong Kwok Leung , Cheung Bernard M.Y. , Man Yu Bun , Lau Chu Pak , Lam Karen S.L.
Published: December 2006

Detection of hypertension and blood pressure control are critically important for reducing the risk of heart attacks and strokes. We analyzed the trends in the prevalence, awareness, treatment, and control of hypertension in the United States in the period 1999–2004. We used the National Health and Nutrition Examination Survey 1999–2004 database. Blood pressure information on 14 653 individuals (4749 in 1999–2000, 5032 in 2001–2002, and 4872 in 2003–2004) aged ≥18 years was used. Hypertension was defined as blood pressure ≥140/90 mm Hg or taking antihypertensive medications. The prevalence of hypertension in 2003–2004 was 7.3±0.9%, 32.6±2.0%, and 66.3±1.8% in the 18 to 39, 40 to 59, and ≥60 age groups, respectively. The overall prevalence was 29.3%. When compared with 1999–2000, there were nonsignificant increases in the overall prevalence, awareness, and treatment rates of hypertension. The blood pressure control rate was 29.2±2.3% in 1999–2000 and 36.8±2.3% in 2003–2004. The age-adjusted increase in control rate was 8.1% (95% CI: 2.4 to 13.8%;
P
=0.006). The control rates increased significantly in both sexes, non-Hispanic blacks, and Mexican Americans. Among the ≥60 age group, the awareness, treatment, and control rates of hypertension had all increased significantly (
P
≤0.01). The improvement in blood pressure control is encouraging, although the prevalence of hypertension has not declined.
Renal Denervation Does Not Abolish Sustained Baroreflex-Mediated Reductions in Arterial Pressure
Authors: Lohmeier Thomas E. , Hildebrandt Drew A. , Dwyer Terry M. , Barrett Austin M. , Irwin Eric D. , Rossing Martin A. , Kieval Robert S.
Published: December 2006

Recent studies indicate that suppression of renal sympathetic nerve activity and attendant increments in renal excretory function are sustained baroreflex-mediated responses in hypertensive animals. Given the central role of the kidneys in long-term regulation of arterial pressure, we hypothesized that the chronic blood pressure–lowering effects of the baroreflex are critically dependent on intact renal innervation. This hypothesis was tested in 6 dogs by bilaterally activating the carotid baroreflex electrically for 7 days before and after bilateral renal denervation. Before renal denervation, control values for mean arterial pressure and plasma norepinephrine concentration were 95±2 mm Hg and 96±12 pg/mL, respectively. During day 1 of baroreflex activation, mean arterial pressure decreased 13±1 mm Hg, and there was modest sodium retention. Daily sodium balance was subsequently restored, but reductions in mean arterial pressure were sustained throughout the 7 days of baroreflex activation. Activation of the baroreflex was associated with sustained decreases in plasma norepinephrine concentration (≈50%) and plasma renin activity (30% to 40%). All of the values returned to control levels during a 7-day recovery period. Two weeks after renal denervation, control values for mean arterial pressure, plasma norepinephrine concentration, plasma renin activity, and sodium excretion were comparable to those measured when the renal nerves were intact. Moreover, after renal denervation, all of the responses to activation of the baroreflex were similar to those observed before renal denervation. These findings demonstrate that the presence of the renal nerves is not an obligate requirement for achieving long-term reductions in arterial pressure during prolonged activation of the baroreflex.
Cyclic Stretch–Induced Reactive Oxygen Species Generation Enhances Apoptosis in Retinal Pericytes Through c-Jun NH
2
-Terminal Kinase Activation
Authors: Suzuma Izumi , Murakami Tomoaki , Suzuma Kiyoshi , Kaneto Hideaki , Watanabe Daisuke , Ojima Tomonari , Honda Yoshihito , Takagi Hitoshi , Yoshimura Nagahisa
Published: December 2006

Hypertension is known to exacerbate diabetic complications, such as retinopathy and nephropathy. Apoptosis of retinal vascular pericytes has been well established as the earliest conceivable change in diabetic retinopathy. In this study, we investigated the contribution of cyclic stretch, which mimics a hypertensive state to pericyte apoptosis. A 48-hour cyclic stretch induced DNA fragmentation in porcine retinal pericytes and increased the number of TUNEL+ cells at a pathophysiologically relevant extension level (10%/60 cycles per minute). Stretch also increased intracellular reactive oxygen species generation and increased c-Jun NH
2
-terminal kinase phosphorylation in a time- and magnitude-dependent manner, which were reduced by the nicotinamide-adenine dinucleotide phosphate oxidase inhibitor diphenylene iodonium or dominant-negative protein kinase C-δ. Stretch activated protein kinase C-δ and increased its association with p47phox. Stretch induced cleavage of caspase-9 and -3 and increased caspase-3 activity. Protein kinase C-δ or c-Jun NH
2
-terminal kinase inhibition normalized stretch-induced caspase-3 activity and prevented stretch-induced apoptosis. These data indicate that cyclic stretch induces apoptosis in porcine retinal pericytes by activation of the reactive oxygen species–c-Jun NH
2
-terminal kinase–caspase cascades, suggesting a novel molecular mechanism to explain the exacerbation of early diabetic retinopathy by concomitant hypertension.
Aliskiren Reduces Blood Pressure and Suppresses Plasma Renin Activity in Combination With a Thiazide Diuretic, an Angiotensin-Converting Enzyme Inhibitor, or an Angiotensin Receptor Blocker
Authors: O’Brien Eoin , Barton John , Nussberger Juerg , Mulcahy David , Jensen Chris , Dicker Patrick , Stanton Alice
Published: December 2006

Thiazide diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers all cause reactive rises in plasma renin activity. We hypothesized that renin inhibition with aliskiren would prevent this reactive rise and also enhance blood pressure lowering. In 3 open-label studies in which blood pressure was assessed with ambulatory measurement, aliskiren was administered to patients with mild-to-moderate hypertension in combination with hydrochlorothiazide (n=23), ramipril (n=21), or irbesartan (n=23). In the diuretic combination study, the addition of 25 mg of hydrochlorothiazide to 150 mg of aliskiren daily for 3 weeks significantly lowered daytime pressure, compared with aliskiren monotherapy (systolic/diastolic mean change from baseline [SEM]: daytime: −18.4 [2.1]/ −10.6 [1.7] versus −10.4 [1.8]/−5.8 [1.4]; nighttime: −15.6 [2.7]/−8.1 [1.8] versus −8.8 [2.9]/−5.0 [2.2]). In the angiotensin-converting enzyme inhibitor combination study, the addition of 75 or 150 mg of aliskiren to 5 mg of ramipril alone for 3 weeks further lowered both daytime and nighttime pressures compared with ramipril monotherapy (daytime: −10.5 [2.9]/−8.1 [2.1] and −14 [3.7]/−8.7 [2.3] versus −6.1 [2.4]/−5.9 [1.5]; nighttime: −8.1 [2.6]/−5.3 [2.4] and −9.6 [3.4]/−5.3 [2.4] versus −2 [2.3]/−0.7 [2.2]). In the angiotensin receptor blocker combination study, the addition of 75 or 150 mg of aliskiren to 150 mg of irbesartan alone, for 3 weeks, resulted in significantly lower nighttime pressures compared with irbesartan monotherapy (daytime: −14.8 [2]/−8.2 [1.3] and −13.3 [1.6]/−6.8 [0.9] versus −11.4 [1.6]/−6.5 [1.1]; nighttime: −16.1 [2.4]/−8.6 [1.7] and −13.2 [2.7]/−7.2 [1.9] versus −9.0 [2.5]/−4.7 [1.9]). Aliskiren (150 mg) alone significantly inhibited plasma renin activity by 65% (
P
<0.0001). Ramipril and irbesartan monotherapy caused 90% and 175% increases in plasma renin activity, respectively. By contrast, when aliskiren was coadministered with hydrochlorothiazide, ramipril, or irbesartan, plasma renin activity did not increase but remained similar to baseline levels or was decreased (combination therapy versus untreated; median [interquartile range]; aliskiren and hydrochlorothiazide: 0.4 [0.2 to 1.1] versus 0.7 [0.5 to 1.3]; ramipril and aliskiren: 0.5 [0.3 to 0.9] versus 0.6 [0.5 to 0.8]; irbesartan and aliskiren: 0.4 [0.2 to 0.9] versus 0.6 [0.4 to 0.9]). These results suggest that renin inhibition with aliskiren in these combinations increases renin-angiotensin system suppression, improves 24-hour blood pressure control, and may ultimately provide better end-organ protection in patients with hypertension.
Angiotensin Type 2 Receptor in Resistance Arteries of Type 2 Diabetic Hypertensive Patients
Authors: Savoia Carmine , Touyz Rhian M. , Volpe Massimo , Schiffrin Ernesto L.
Published: December 2006

The role of angiotensin type 2 receptor (AT2R) on vascular responses to angiotensin II in humans remains unclear. In this study we explored whether AT2R is expressed and functionally active on peripheral resistance arteries of hypertensive diabetic patients treated for 1 year with either the angiotensin receptor blocker valsartan or the β-blocker atenolol. Twenty-six hypertensive type 2 diabetic patients treated with oral hypoglycemic and antihypertensive agents (not receiving angiotensin receptor blockers or β-blockers) were randomly assigned to double-blind treatment for 1 year with valsartan or atenolol once daily added to their previous therapy in a clinical trial that we reported recently and compared with 10 normal subjects. Resistance arteries dissected from gluteal subcutaneous tissues were assessed on a pressurized myograph. Vasomotor response curves to angiotensin II (1 nmol/L to 1 μmol/L) were performed on norepinephrine precontracted vessels in the presence of valsartan (10 μmol/L) with or without the AT2R inhibitor PD123319 (1 μmol/L). AT2R expression was evaluated by confocal microscopy. After 1 year of treatment, systolic and diastolic blood pressure was controlled and comparable in the valsartan and atenolol groups. Angiotensin II evoked a significant vasodilatory response only on resistance arteries from patients treated with valsartan, effect blocked by PD123319. AT2R expression was 4-fold higher in small arteries of valsartan-treated patients. In conclusion, AT2Rs are upregulated and contribute to angiotensin II–induced vasodilation in resistance arteries of hypertensive diabetic patients treated with angiotensin type 1 receptor blockers and may mediate, in part, vascular actions of these drugs in high cardiovascular risk patients.
Transposition of the Great Arteries
Authors: Warnes Carole A.
Published: December 2006

Many patients with ventriculoarterial discordance have survived to adulthood. Those with complete transposition of the great arteries have often had an atrial switch procedure (Mustard or Senning operation) performed, which leaves the morphological right ventricle (RV) supporting the systemic circulation. RV failure and tricuspid regurgitation are common. Some patients may ultimately require cardiac transplantation. Sinus node dysfunction is increasingly common with longer follow-up, and some patients need pacemaker implantation. Atrial arrhythmias are frequent, and atrial flutter may be a marker for sudden death. Patients with an arterial switch procedure are also surviving to adulthood. Long-term problems include coronary stenoses, distortion of the pulmonary arteries, dilatation of the neoaortic root, and aortic regurgitation. Patients with congenitally corrected transposition have both atrioventricular and ventriculoarterial discordance and therefore also have a morphological RV and delicate tricuspid valve in the systemic circulation. Associated defects, such as abnormalities of the tricuspid valve, ventricular septal defect, and pulmonary stenosis, occur in the majority of patients. Heart block occurs with increasing age. Atrial arrhythmias occur frequently, and their occurrence should prompt a search for a hemodynamic problem. Progressive tricuspid regurgitation occurs with age and is associated with deterioration of RV function. Surgical treatment should be considered at the earliest sign of RV dilatation or dysfunction. All patients should be seen periodically in a center where expertise in the clinical evaluation, imaging, and hemodynamic assessment of adult congenital heart disease is available.
Risks Associated With Statin Therapy
Authors: Kashani Amir , Phillips Christopher O. , Foody JoAnne M. , Wang Yongfei , Mangalmurti Sandeep , Ko Dennis T. , Krumholz Harlan M.
Published: December 2006

Background—

Although statins reduce the risk of cardiovascular events, concerns about adverse effects may deter physicians from prescribing these agents. We performed a systematic overview of randomized statin trials to quantify the risks of musculoskeletal, renal, and hepatic complications associated with therapy.

Methods and Results—

Major statin trials were identified by electronic search of the MEDLINE database from 1966 to December 2005. We included English language reports of adults with documented hyperlipidemia; double-blind, random allocation of ≥100 patients to statin monotherapy versus placebo; and reports of myalgia, creatine kinase elevations, rhabdomyolysis, transaminase elevations, and discontinuation due to adverse events. Among 74 102 subjects enrolled in 35 trials (follow-up range, 1 to 65 months), statin therapy (excluding cerivastatin) did not result in significant absolute increases in risks of myalgias (risk difference/1000 patients [RD], 2.7; 95% CI, −3.2 to 8.7), creatine kinase elevations (RD, 0.2; 95% CI, −0.6 to 0.9), rhabdomyolysis (RD, 0.4; 95% CI, −0.1 to 0.9), or discontinuation due to any adverse event (RD, −0.5; 95% CI, −4.3 to 3.3). The absolute risk of transaminase elevations was significantly higher with statin therapy (RD, 4.2; 95% CI, 1.5 to 6.9).

Conclusions—

On the basis of data available from published clinical trials, statin therapy is associated with a small excess risk of transaminase elevations, but not of myalgias, creatine kinase elevations, rhabdomyolysis, or withdrawal of therapy compared with placebo. Further study is necessary to determine whether the results from these published clinical trials are similar to what occurs in routine practice, particularly among patients who are older, have more severe comorbid conditions, or receive higher statin doses than most patients in these clinical trials.
Increasing Use of Cardiopulmonary Resuscitation During Out-of-Hospital Ventricular Fibrillation Arrest
Authors: Rea Thomas D. , Helbock Michael , Perry Stephen , Garcia Michele , Cloyd Don , Becker Linda , Eisenberg Mickey
Published: December 2006

Background—

The most recent resuscitation guidelines have sought to improve the interface between defibrillation and cardiopulmonary resuscitation; the survival impact of these changes is unknown, however. A year before issuance of the most recent guidelines, we implemented protocol changes that provided a single shock without rhythm reanalysis, stacked shocks, or postdefibrillation pulse check, and extended the period of cardiopulmonary resuscitation from 1 to 2 minutes. We hypothesized that survival would be better with the new protocol.

Methods and Results—

The present study took place in a community with a 2-tiered emergency medical services response and an established system of cardiac arrest surveillance, training, and review. The investigation was a cohort study of persons who had bystander-witnessed out-of-hospital ventricular fibrillation arrest because of heart disease, comparing a prospectively defined intervention group (January 1, 2005, to January 31, 2006) with a historical control group that was treated according to previous guidelines of rhythm reanalysis, stacked shocks, and postdefibrillation pulse checks (January 1, 2002, to December 31, 2004). The primary outcome was survival to hospital discharge. The proportion of treated arrests that met inclusion criteria was similar for intervention and control periods (15.4% [134/869] versus 16.6% [374/2255]). Survival to hospital discharge was significantly greater during the intervention period compared with the control period (46% [61/134] versus 33% [122/374],
P
=0.008) and corresponded to a decrease in the interval from shock to start of chest compressions (28 versus 7 seconds). Adjustment for covariates did not alter the survival association.

Conclusions—

These results suggest the new resuscitation guidelines will alter the interface between defibrillation and cardiopulmonary resuscitation and in turn may improve outcomes.
Long-Term Outcomes of Significant Mitral Regurgitation After Percutaneous Mitral Valvuloplasty
Authors: Kim Mi-Jeong , Song Jae-Kwan , Song Jong-Min , Kang Duk-Hyun , Kim Young-Hak , Lee Cheol Whan , Hong Myeong-Ki , Kim Jae-Joong , Park Seong-Wook , Park Seung-Jung
Published: December 2006

Background—

Mild commissural mitral regurgitation (MR) is associated with significantly higher restenosis-free survival after percutaneous mitral valvuloplasty (PMV), which suggests that different mechanisms of significant MR after PMV may have different clinical courses. We therefore analyzed long-term prognostic factors of significant MR after PMV.

Methods and Results—

Echocardiographic and clinical follow-up data on 380 patients were analyzed (286 women, mean age 44±11 years) who underwent PMV with the Inoue balloon technique between 1995 and 2000. Significant MR developed in 47 patients (12.4%). The survival rate at 8 years was 96±3% and 98±10% in patients with and without significant MR, respectively (
P
=0.084). The most frequent mechanism was commissural MR, or MR that originated at the site of successful commissurotomy, which occurred in 27 of 47 patients (57%), whereas noncommissural MR occurred in 20 (43%) patients, 12 (26%) with subvalvular damage resulting in chordae rupture and flail motion and 8 (17%) with leaflet laceration. The 8-year event-free survival rate was significantly lower in patients with significant MR than in those without (47±8% versus 83±3%,
P
<0.001) and was significantly higher in patients with commissural versus noncommissural MR (63±11% versus 29±11%,
P
<0.001). Of the 47 patients with significant MR, who were followed up for 74±29 months, 19 patients (40%) underwent mitral valve replacement, and 28 patients (60%) received medical treatment only. Patients with commissural MR had a significantly lower rate of mitral valve replacement than patients with noncommissural MR (15% versus 70%,
P
<0.001). Multivariate analysis showed that atrial fibrillation (odds ratio, 7.4; 95% CI, 1.1 to 56.4;
P
=0.038), mean mitral gradient immediately after PMV (odds ratio, 1.5; 95% CI, 1.1 to 2.0;
P
=0.009), and the mechanism of MR (odds ratio, 16.7; 95% CI, 2.3 to 122.2;
P
=0.005) were independent factors associated with mitral valve replacement.

Conclusions—

Clinical outcome of patients with significant MR after PMV varied according to MR mechanism and the adequacy of hemodynamic improvement, which is easily assessed by echocardiography immediately after PMV.
Conceptions of Spirituality among Israeli Arab and Jewish Late Adolescents
Authors: Rich Yisrael , Cinamon Rachel Gali
Published: December 2006

Considerable research has demonstrated that spirituality is generally a positive force in human functioning. Reasoning that one's perceptions of spirituality are based on particular cultural, religious, and social contexts and that adult and adolescent conceptions may differ meaningfully, the authors examine understandings of spirituality among Arab and Jewish Israeli late adolescents. Participants are 36 high school students or college freshmen, Arab and Jewish, male and female, and religious and secular. The authors use semistructured interviews to collect data and the consensual qualitative research method to analyze them. Results indicate broad agreement regarding transcendence as the essential component of spirituality and show that religious and humanistic modes of spirituality exist. Religious and cultural groups develop divergent conceptions of spirituality with overlapping and contrasting features. Gender yielded few differences. Finally, limited correspondence appears between components of spirituality in this study and those found among adults in earlier research.
Combat Trauma: Treatment from a Mystical/Spiritual Perspective
Authors: Decker Larry R.
Published: December 2006

Psychological recovery from combat trauma may depend on discovering a personal meaning in the traumatic experience. Veterans traumatized in combat struggle with finding meaning in the war and in civilian life. Spiritual concepts and experiences can generally help in the discovery of meaning. However, the term spirituality is traditionally reserved for the experience of prayer and worship. This article presents a rationale for the integration of the spirituality of combat and civilian life into the clinical treatment of traumatic sequelae via a mystical perspective. The spiritual may be viewed as either immanent or transcendent. These perspectives are integrated into an individual treatment program for the reduction of serious psychological difficulties stemming from combat trauma.
Advancing Research on the Community College
Authors: Bers Trudy H.
Published: December 2006

Arthur M. Cohen and his colleagues at the Center for the Study of Community Colleges have made significant and broad contributions to the scholarly literature and empirical research about community colleges. Although Cohen’s interests are comprehensive and his writings touch on multiple issues associated with community colleges, his empirical work is particularly important in three areas: curriculum, transfer, and faculty. This article provides an overview of the work Cohen and his colleagues have conducted in these areas.
The Cohen Contribution to Community College Leadership
Authors: Eaton Judith S.
Published: December 2006

Arthur M. Cohen has spoken to community college leaders on a diverse array of issues for many years. This article focuses on his contributions to this leadership in three major areas: (a) providing a vision of community colleges as collegiate institutions, (b) offering valuable and thought-provoking insight into the current context for community college operation and its future operation, and (c) sharing probing commentary on enduring community college issues.
Teaching and Mentoring Future Leaders in the Field
Authors: Ignash Jan M.
Published: December 2006

Any discussion of Arthur M. Cohen’s contributions to community colleges must include the students he taught and mentored during his 40 years as a professor at the University of California, Los Angeles. Arthur Cohen and his colleague and spouse, Florence Brawer, had a huge impact on community colleges through the sheer number of former students who graduated and became community college leaders and scholars. Through frequent contact with students, deep understanding of the field, passion for the work, and willingness to include students in a community of scholars, Cohen and Brawer demonstrated what it truly means to be a mentor and teacher.
The Effect of Examinee Motivation on Test Construction Within an IRT Framework
Authors: van Barneveld Christina
Published: December 2006

The purpose of this study is to examine the effects of a false assumption regarding the motivation of examinees on test construction. Simulated data were generated using two models of item responses (the three-parameter logistic item response model alone and in combination with Wise’s examinee persistence model) and were calibrated using a Bayesian method. For the conditions studied, biased item parameter estimates resulted from responses from poorly motivated examinees. Bias in item parameter estimates resulted in bias in item information estimates and test information estimates for an optimally constructed test. The direction and magnitude of the bias depended on conditions studied. The implications of the results for test development companies, examinees, and users of test results are discussed.
Impact of Migration on African American Family Development and Relationships
Authors: Stewart Pearl
Published: December 2006

This article examines the short-and long-term influences of African American migration on the development and functioning of African American families and family relationships. Using existing research and the results from an ethnographic study of a large, African American, extended family, this article confirms the findings of previous studies and begins to examine the meaning and definition of contemporary types of migration. The study suggests that family members who have “migrated” with respect to socioeconomic status have many of the same issues as those who have migrated with respect to physical distance.
Multi-objective reverse logistics model for integrated computer waste management
Authors: Ahluwalia Poonam Khanijo , Nema Arvind K.
Published: December 2006

This study aimed to address the issues involved in the planning and design of a computer waste management system in an integrated manner. A decision-support tool is presented for selecting an optimum configuration of computer waste management facilities (segregation, storage, treatment/processing, reuse/recycle and disposal) and allocation of waste to these facilities. The model is based on an integer linear programming method with the objectives of minimizing environmental risk as well as cost. The issue of uncertainty in the estimated waste quantities from multiple sources is addressed using the Monte Carlo simulation technique. An illustrated example of computer waste management in Delhi, India is presented to demonstrate the usefulness of the proposed model and to study tradeoffs between cost and risk. The results of the example problem show that it is possible to reduce the environmental risk significantly by a marginal increase in the available cost. The proposed model can serve as a powerful tool to address the environmental problems associated with exponentially growing quantities of computer waste which are presently being managed using rudimentary methods of reuse, recovery and disposal by various small-scale vendors.
Report: Biomedical waste management practices at Balrampur Hospital, Lucknow, India
Authors: Gupta Saurabh , Boojh Ram
Published: December 2006

Biomedical waste has become a serious health hazard in many countries, including India. Careless and indiscriminate disposal of this waste by healthcare establishments and research institutions can contribute to the spread of serious diseases such as hepatitis and AIDS (HIV) among those who handle it and also among the general public. The present study pertains to the biomedical waste management practices at Balrampur Hospital, a premier healthcare establishment in Lucknow, in North India. The study shows that infectious and non-infectious wastes are dumped together within the hospital premises, resulting in a mixing of the two, which are then disposed of with municipal waste at the dumping sites in the city. All types of wastes are collected in common bins placed outside the patients wards. For disposal of this waste the hospital depends on the generosity of the Lucknow Municipal Corporation, whose employees generally collect it every 2 or 3 days. The hospital does not have any treatment facility for infectious waste. The laboratory waste materials, which are disposed of directly into the municipal sewer without proper disinfection of pathogens, ultimately reach the Gomti River. All disposable plastic items are segregated by the rag pickers from the hospital as well as municipal bins and dumps. The waste is deposited either inside the hospital grounds, or outside in the community bin for further transportation and disposal along with municipal solid waste. The open dumping of the waste makes it freely accessible to rag pickers who become exposed to serious health hazards due to injuries from sharps, needles and other types of material used when giving injections. The results of the study demonstrate the need for strict enforcement of legal provisions and a better environmental management system for the disposal of biomedical waste in the Balrampur Hospital, as well as other healthcare establishments in Lucknow.
Sulphur mineralization kinetics of cattle manure and green waste compost in soils
Authors: Saviozzi Alessandro , Cardelli Roberto , Cipolli Silvia , Levi-Minzi Renato , Riffaldi Riccardo
Published: December 2006

Sulphur mineralization of cattle manure (CM) and green waste compost (GWC) added to six agricultural soils with different chemical properties was monitored over 10 weeks in a laboratory incubation experiment. Although the amount of sulphur was higher in CM than in GWC, the cumulative SO42--S values in GWC-treated soils were higher than in soil amended with CM. The percentages of mineralized S were always higher in GWC-treated soil (in the range 1.3-8.5%) than in CM-treated soil (in the range 0.9-3.8%). In three of the six soils, particularly for CM, an immobilization of sulphur was observed. Three kinetic models were evaluated for their suitability to describe the mineralization process. The first-order model best described S mineralization for both amended and control soils. The GWC substantially increased the amount of potentially mineralizable S ( S0) relative to the controls. In GWC-treated soils, the rates of S mineralization ( k) were higher than rates in the controls. The k of CM-amended soils was often lower than the k of control soils. Parameters derived from the model were tested as indices for assessing the relationships between S mineralization and soil characteristics. The S0was positively correlated to the amount of cumulative SO42--S and also to the content of organic C, N and S in soil.
Report: Recycling of flame-retarded plastics from waste electric and electronic equipment (WEEE)
Authors: Schlummer Martin , Mäurer Andreas , Leitner Thomas , Spruzina Walter
Published: December 2006

Shredder residues produced in plants processing waste electric and electronic equipment are excluded from material recycling due to a variety of polymeric materials and the presence of brominated flame retardants (BFR), which might contain banned polybrominated diphenyl ethers or toxic polybrominated dioxins and furans (PBDD/F). Herein we present a technological approach to transfer a significant portion of the shredder residue into recycled polymers. The technological approach consists of a density-based enrichment of styrenics, which are subjected to a solvolysis process (CreaSolv® process) in a second stage. This stage allows the elimination of non-target polymers and extraction of BFR and PBDD/F. Pilot processing of 11.5 and 50 kg shredder residues indicated a material yield of about 50% in the density stage and 70-80% in the CreaSolv® process, and an effective removal of BFR additives. The recycled products were proved to comply with threshold values defined by the European directive on the restriction of hazardous substances (RoHS) and the German Chemikalienverbotsverordnung. Mechanical material properties exhibited high tensile and flexural modules as well as slight impact strength, which qualify the products for applications in new electronic equipment.