bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of cigarette smoking on prepulse inhibition, its attentional modulation, and vigilance performance
Authors: Rissling Anthony J. , Dawson Michael E. , Schell Anne M. , Nuechterlein Keith H.
Published: May 2007

Startle eyeblink modification was measured during a degraded stimulus continuous performance test following both smoking and overnight abstinence among student smokers to measure the effects of smoking on both early and late attentional processes. A group of nonsmokers was tested twice without nicotine manipulation. A startling noise was presented either 240 or 1200 ms following target and nontarget stimuli presented during the task. Startle inhibition at 240 ms was greater following targets than nontargets following smoking and during both nonsmoker tests, but this attentional modulation was absent following abstinence. At the 1200‐ms probe position, target and nontarget stimuli produced nondifferential inhibition during both tests for both groups. Abstinence among smokers produced reliably lower vigilance performance compared to ad lib smoking. The results indicate that smoking abstinence affects the early stages of stimulus processing.
Sequential processing of interaural timing differences for sound source segregation and spatial localization: Evidence from event‐related cortical potentials
Authors: Johnson Blake W. , Hautus Michael J. , Duff Damien J. , Clapp Wes C.
Published: May 2007

Cortical processing of interaural timing differences (ITDs) was investigated with event‐related potential (ERP) measurements in 16 human participants who were required in separate tasks to detect or to spatially localize dichotically embedded pitches. ITDs elicited three ERP components labeled ORN, N2, and P400. The ORN occurred at a latency of 150–250 ms and was elicited by ITDs regardless of location or task. In contrast, the N2 response (250–350 ms) was strongly modulated by location and showed larger amplitudes for the localization task than for the detection task. Finally, ITDs in the detection task elicited a P400 at a latency of 400–500 ms, but this response was entirely absent from ERPs elicited by identical stimuli in the localization task. These results are consistent with a sequential model of auditory perception in which segregation of concurrent sounds is followed by domain‐specific processing of object location and identity.
Polysomnographically measured sleep abnormalities in PTSD: A meta‐analytic review
Authors: Kobayashi Ihori , Boarts Jessica M. , Delahanty Douglas L.
Published: May 2007

Although sleep complaints are common among patients with Posttraumatic stress disorder (PTSD), polysomnographic studies examining sleep abnormalities in PTSD have produced inconsistent results. To clarify discrepant findings, we conducted a meta‐analytic review of 20 polysomnographic studies comparing sleep in people with and without PTSD. Results showed that PTSD patients had more stage 1 sleep, less slow wave sleep, and greater rapid‐eye‐movement density compared to people without PTSD. We also conducted exploratory analyses aimed at examining potential moderating variables (age, sex, and comorbid depression and substance use disorders). Overall, studies with a greater proportion of male participants or a low rate of comorbid depression tended to find more PTSD‐related sleep disturbances. These findings suggest that sleep abnormalities exist in PTSD, and that some of the inconsistencies in prior findings may be explained by moderating variables.
Isolation and characterization of 10 new compound microsatellite markers for a mangrove tree species, Avicennia marina (Forsk.) Vierh. (Avicenniaceae)
Authors: GENG Q. F. , LIAN C. L. , TAO J. M. , LI S. Q. , HOGETSU T.
Published: May 2007

Avicennia marina is an ecologically important mangrove tree species. We isolated 10 polymorphic microsatellite loci from this species using an improved technique. Our isolated loci provided compound microsatellite markers with polymorphism of two to six alleles per locus. The observed and expected heterozygosities ranged from 0.025 to 0.625 and from 0.096 to 0.767, respectively. These markers would be the useful tools for researching on the genetic diversity and population genetic structure of A. marina.
Epithelial grafting for vitiligo requires ultraviolet A phototherapy to increase success rate
Authors: Awad Sherif S , Abdel‐Raof Hamza , Hosam El‐Din Wael , El‐Domyati Moetaz
Published: May 2007

Background  Phototherapeutic techniques were introduced into medical practice by the ancient Egyptians. It is considered a cornerstone in the management of resistant vitiligo; yet, failures are very well known. Recently, the introduction of surgical techniques provided a major development in the management of vitiligo and replaced other conventional unsuccessful therapies.

Objectives  The aim of this work is to find out if phototherapy, which failed to resolve the vitiligo problem in patients, is still required in the treatment strategy after epithelial grafting of the same cases.

Methods  Twenty‐five vitiligo patients, nonresponding to classic phototherapy, were treated surgically. Ultrathin Thiersch grafts and suction blister grafts were used. Phototherapy using untraviolet A (UVA) bulbs in combination with psoralen or khellin was used postoperatively immediately after take of grafts onto recipient sites.

Results  In spite of reactivation of depigmentary effects at grafted areas, phototherapy acted as a stimulator for melanocytic proliferation and function and as an immunosuppressant, halting the melanocytic destructive process. The application of UVA phototherapy resulted in successful treatment in the patients receiving it.

Conclusion  The success of epithelial grafting in patients with vitiligo can be increased by UVA phototherapy.
Transcriptional effect of an Aframomum angustifolium seed extract on human cutaneous cells using low‐density DNA chips
Authors: Bonnet‐Duquennoy Mathilde , Dumas Marc , Debacker Adeline , Lazou Kristell , Talbourdet Sylvie , Franchi Jocelyne , Heusèle Catherine , André Patrice , Schnebert Sylvianne , Bonté Frédéric , Kurfürst Robin
Published: May 2007

Background  Studying photoexposed and photoprotected skin biopsies from young and aged women, it has been found that a specific zone, composed of the basal layers of the epidermis, the dermal epidermal junction, and the superficial dermis, is major target of aging and reactive oxygen species. We showed that this zone is characterized by significant variations at a transcriptional and/or protein levels.

Aims  Using low‐density DNA chip technology, we evaluated the effect of a natural mixture of Aframomum angustifolium seed extract containing labdane diterpenoids on these aging markers.

Methods  Expression profiles of normal human fibroblasts (NHF) were studied using a customized cDNA macroarray system containing genes covering dermal structure, inflammatory responses, and oxidative stress defense mechanisms. For normal human keratinocyte (NHK) investigations, we chose OLISA™ technique, a sensitive and quantitative method developed by BioMérieux specifically designed to investigate cell death, proliferation, epidermal structure, differentiation, and oxidative stress defense response.

Results  We observed that this extract strongly modified gene expression profiles of treated NHK, but weakly for NHF. This extract regulated antioxidant defenses, dermal–epidermal junction components, and epidermal renewal–related genes.

Conclusion  Using low‐density DNA chip technology, we identified new potential actions of A. angustifolium seed extract on skin aging.
‘Water all around, you cannot even drink’: the scaling of water in James Bay/Eeyou Istchee
Authors: Desbiens Caroline
Published: May 2007

Since the 1970s, the reconfiguration of the La Grande River into a hydroelectric complex has radically altered the James Bay region and brought about new scales of identification and exchanges between peoples and places. Through this process, water emerged as an increasingly globalized entity while at the same time being captured as a local icon of cultural identification both by the Eeyouch (Eastern James Bay Cree) and the Québécois. Using an historical and discursive approach, this paper explores the intersection between the rescaling of water and the rescaling of the nation for each community. The removal of the river from the traditional places of production of the Eeyouch to redirect it into electricity‐generating facilities that put every drop of water to work has dramatically changed the meaning of ‘here’ and ‘there’– as well as ‘us’ and ‘them’– for the Eeyouch and the Québécois, indicating that a theory of the differentiation and hierarchical organization of space needs to inform collaborative efforts toward environmental management in the region.
Mrs Gardner's world: scale in Mormon women's autobiographical writing
Authors: Guelke Jeanne Kay
Published: May 2007

This study of daily experiences of scale focuses on activity patterns recorded in the journal of a Mormon woman living in Pine Valley, Utah c.1890–1920. The household as ‘private’ domestic space was weakly developed, and both the home and village were sites of community activity. Lofland's concept of ‘parochial space’ distinguishes the spaces used by one's social and kinship networks vs areas occupied by strangers. In Pine Valley's isolated situation, large‐scale economic and political involvement appeared limited. More significant for Mormon women was a transcendent religious ideology that furnished simultaneity and integration of scales.
Hope for nanotechnology: anticipatory knowledge and the governance of affect
Authors: Anderson Ben
Published: May 2007

This paper describes how hopes can be, and have been, placed in nanotechnology. Focusing on two recent UK government reports into the future of nanotechnology, by the DTI/OST and MoD, the paper describes how the disclosure of the nanoscale as a place subject to intervention, the act that is taken to define nanotechnology, can be understood in the context of anticipatory knowledge practices that create futures. Because the object of such practices are virtualities, such as opportunities and threats, the paper argues that affect is transversal to both nano‐technoscience and anticipatory governance. In conclusion, I open up a set of questions about anticipatory knowledges and argue that the ground that enables hope to be placed in nanotechnology is the event that defines nano – to simultaneously reduce ‘life’ to matter and to multiply ‘life’ into a limitless set of materialities.
GROWTH AND INCOME POVERTY IN LATIN AMERICA AND THE CARIBBEAN: EVIDENCE FROM HOUSEHOLD SURVEYS
Authors: Gasparini Leonardo , Gutiérrez Federico , Tornarolli Leopoldo
Published: May 2007

This paper provides evidence on growth and income poverty in Latin America and the Caribbean (LAC). Results are obtained by processing microdata from household surveys of 18 LAC countries covering the 1990s and early 2000s. Over this period the LAC economies experienced heterogeneous patterns of growth and poverty changes. Most countries in the region had a rather meager performance in terms of poverty reduction. Episodes of positive, significant and unambiguously pro‐poor income growth have been rare in Latin America.
Acid–base disturbances in critically ill patients with cirrhosis
Authors: Funk Georg Christian , Doberer Daniel , Kneidinger Nikolaus , Lindner Gregor , Holzinger Ulrike , Schneeweiss Bruno
Published: May 2007

Background/Aims: The equilibrium of offsetting metabolic acid–base disorders in stable cirrhosis might be lost during episodes of hepatic decompensation, haemorrhage or sepsis. The purpose of this study was to determine whether the acid–base state is destabilized in critically ill patients with cirrhosis and whether this is associated with mortality.

Patients and Method: One‐hundred and eighty‐one consecutive patients with cirrhosis were investigated in a prospective observational cohort study on admission to a medical intensive care unit (ICU) of a university hospital. Arterial acid–base state was assessed according to the Gilfix methodology. Clinical data, ICU mortality and hospital mortality were recorded.

Main Results: Patients had net metabolic acidosis owing to unmeasured anions and owing to hyperchloraemic, dilutional and lactic acidosis. Lactic acidosis, acidemia and acute renal failure on ICU admission were associated with increased mortality. Lactate and pH discriminated survivors from non‐survivors. The presence of lactic acidosis could not always be recognized by customary acid–base parameters.

Conclusion: The stable equilibrium of acid–base disorders is lost when patients with cirrhosis become critically ill. Lactic acidosis and acidaemia are associated with increased ICU mortality caused by severe underlying organ dysfunction.
Nodular regenerative hyperplasia: a deleterious consequence of chemotherapy for colorectal liver metastases?
Authors: Hubert Catherine , Sempoux Christine , Horsmans Yves , Rahier Jacques , Humblet Yves , Machiels Jean‐Pascal , Ceratti Antonino , Canon Jean‐Luc , Gigot Jean‐François
Published: May 2007

Aims: This report describes three patients suffering from nodular regenerative hyperplasia (NRH).

Methods: These patients have received six, 16 and 20 cycles of neoadjuvant 5‐fluorouracil and oxaliplatin‐based chemotherapy before planned extended hepatectomy. Two patients underwent uneventful portal vein embolization to hypertrophy the future remnant liver.

Results: At the end of chemotherapy, liver function tests deteriorated and portal hypertension appeared in two patients, including ascites, splenomegaly and oesophageal varices. Liver biopsy was performed through a percutaneous (two patients) or a transjugular approach (one patient) and allowed the diagnosis of NRH, which was considered to be a contraindication for major liver resection in all three patients, associated with extrahepatic disease progression in one patient. All patients died from neoplastic disease progression despite further chemotherapy at 6, 17 and 31 months following the diagnosis of NRH. One patient developed liver failure and ascites at the time of death.

Conclusions: Physicians should be aware of the potential occurrence and therapeutic impact of NRH in patients suffering from CRLM and treated by neoadjuvant 5FU‐oxaliplatin‐based chemotherapy before major liver surgery.
Modeling the Effects of Trophy Selection and Environmental Disturbance on a Simulated Population of African Lions
Authors: WHITMAN KARYL L. , STARFIELD ANTHONY M. , QUADLING HENLEY , PACKER CRAIG
Published: May 2007

Abstract:  Tanzania is a premier destination for trophy hunting of African lions (Panthera leo) and is home to the most extensive long‐term study of unhunted lions. Thus, it provides a unique opportunity to apply data from a long‐term field study to a conservation dilemma: How can a trophy‐hunted species whose reproductive success is closely tied to social stability be harvested sustainably? We used an individually based, spatially explicit, stochastic model, parameterized with nearly 40 years of behavioral and demographic data on lions in the Serengeti, to examine the separate effects of trophy selection and environmental disturbance on the viability of a simulated lion population in response to annual harvesting. Female population size was sensitive to the harvesting of young males (≥3 years), whereas hunting represented a relatively trivial threat to population viability when the harvest was restricted to mature males (≥6 years). Overall model performance was robust to environmental disturbance and to errors in age assessment based on nose coloration as an index used to age potential trophies. Introducing an environmental disturbance did not eliminate the capacity to maintain a viable breeding population when harvesting only older males, and initially depleted populations recovered within 15–25 years after the disturbance to levels comparable to hunted populations that did not experience a catastrophic event. These results are consistent with empirical observations of lion resilience to environmental stochasticity.
Relating Long‐Term Studies to Conservation Practice: the Case of the Serengeti Cheetah Project
Authors: DURANT SARAH M. , BASHIR SULTANA , MADDOX THOMAS , LAURENSON M. KAREN
Published: May 2007

Abstract:  Although detailed, long‐term scientific studies provide potentially crucial information for conservation, they are rare. Moreover, there is often a disjunction between scientists and managers that can affect whether scientific results are applied to help solve conservation problems. Long‐term studies can promote increased communication between scientists and managers and hence offer an opportunity for constructive engagement between the two groups. We examined direct and indirect impacts of a 30‐year study, the Serengeti Cheetah Project (SCP). Much of what is currently known about wild cheetahs comes from the SCP. In particular, the SCP has demonstrated that cheetahs have a combination of semisociality and ranging patterns that is unique among mammals. This system arises because cheetahs need to be mobile to avoid predators and competitors, yet maintain access to prey; this results in densities much lower than for other large carnivores and a requirement for large areas of heterogenous and connected habitat. The SCP started as a research project, but expanded into a national program, developing capacity for carnivore conservation within Tanzania. Long‐term studies such as the SCP are uniquely placed to establish effective working relationships between scientists and managers, engage local and national institutions, and strengthen national capacity for biodiversity conservation. This process is best realized through the establishment of frameworks for conservation that seek to align scientific research with management needs. Long‐term studies also play an important role in identifying international priorities for conservation. Nonetheless, the integration of science and management in conservation is a two‐way process that requires concerted efforts by both sides to improve and maintain dialogue. Ultimately, conservation depends on people, and maintaining a commitment to a particular area over many years—such as through implementation of a long‐term research project—helps establish mutual trust and respect, particularly when combined with development of local and national capacity for scientific research and conservation management.
Planning for Long, Wide Conservation Corridors on Private Lands in the Oak Ridges Moraine, Ontario, Canada
Authors: WHITELAW GRAHAM S. , EAGLES PAUL F. J.
Published: May 2007

Abstract:  We explored the role of conservation biology in the planning of a natural‐heritage system that includes long, wide conservation corridors situated primarily on private lands, and established to connect natural core areas in the Oak Ridges Moraine of Ontario, Canada. We based our review on government documents, semi‐structured interviews with participants involved in this land‐use planning process, and our involvement with the issue from 1990 through 2002. Conservation biology had a major influence on the outcome of the land‐use planning process for this moraine. The landform was identified as an area of value by the environmental movement within the context of a number of ongoing government studies that began in the late 1980s and early 1990s. Conservation biologists and planners in government, the environmental movement, and the private sector carried out work related to conservation biology, including inventories and the development and application of criteria for the delineation of core areas and conservation corridors. Once the political timing was favorable (2001–2002), decision makers linked the science of conservation biology to planning policies and law in Ontario. The Oak Ridges Moraine land‐use planning process was precedent setting in Canada, and possibly internationally. To our knowledge this is the first time long, wide conservation corridors on private lands were regulated through land‐use‐planning legislation and led to restrictions on urban development and aggregate resource extraction.
Historical Perspectives on the Management of Hypertension
Authors: Moser Marvin
Published: May 2007

As late as the 1950s, elevated blood pressure was considered by many expert physicians to be necessary for the adequate per fusion of vital organs. Although the morbidity and mortality risks of hypertension were known at that time to insurance companies, which often refused life insurance policies to people with high blood pressure, there was a lag in the recognition of the dangers of hypertension in the medical community, following the pioneering efforts of researchers who began to treat patients with malignant hypertension, the results of clinical trials and population studies, and the availability of effective antihypertensive agents, hypertension management improved rapidly. This review traces the history of hypertension management from the 1940s, when President Franklin Delano Roosevelt died of a cerebrovascular accident—a result of uncontrolled hypertension—to today, when a large number of patients, even those with less severe hypertension, are being treated successfully, with a resulting dramatic decrease in hypertension‐related vascular disease.

The greatest danger to a man with high blood pressure lies in its discovery, because then some fool is certain to try and reduce it.—J.H. Hay, 1931

Hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we could control it. —Paul Dudley White, 1937
Nitric Oxide Mechanisms in the Pathogenesis of Global Risk
Authors: Mason R. Preston
Published: May 2007

Identification and management of cardiovascular risk factors, such as hypertension, diabetes mellitus, and dyslipidemia, is essential not only for prevention of cardiovascular disease, but also for slowing the progression of existing cardiovascular disease. A major underlying mechanism that links various cardiovascular risk factors and manifestations of cardiovascular disease is endothelial dysfunction, characterized by impaired nitric oxide bioactivity. Oxidative stress is an important cause of impaired nitric oxide bioactivity, and a major pathogenic mechanism of atherosclerosis. Several pharmacologic therapies, including angiotensin‐converting enzyme inhibitors, calcium channel blockers, statins, and the vasodilating β blocker nebivolol, have been shown to enhance nitric oxide bioactivity and improve endothelial function. This effect may help explain the cardioprotective benefits of these agents and may stimulate further use of nitric oxide modulation for the treatment of cardiovascular risk factors and manifestations of cardiovascular disease.
Aspects of Nitric Oxide in Health and Disease: A Focus on Hypertension and Cardiovascular Disease
Authors: Giles Thomas D.
Published: May 2007

Nitric oxide (nitrogen monoxide) (NO) plays an important role in a wide range of physiologic processes. A major mediator of endothelial function, NO regulates vasodilatory and antithrombotic actions in the vasculature and plays a role in reproductive functions, bronchodilation, bone formation, memory, insulin sensitivity, and gastrointestinal relaxation. NO is formed from NO synthase. Impaired NO bioactivity is strongly associated with endothelial dysfunction and cardiovascular disease, but is also implicated in a broad range of other disorders, including pulmonary hypertension, insulin resistance, erectile dysfunction, and preeclampsia. Numerous therapies designed to target NO are being investigated and developed, including NO donors and stimulants. The recent African‐American Heart Failure Trial (A‐HeFT) showed that the NO donor isosorbide dinitrate, combined with the vasodilator hydralazine, significantly reduced morbidity and mortality in black patients with moderate‐to‐severe heart failure. Antihypertensive drugs, including angiotensin‐converting enzyme inhibitors, calcium channel blockers, and third‐generation β‐blockers, are NO stimulants that have demonstrated significant improvement of endothelial function and NO bioactivity. Other cardiovascular therapies that may improve NO bioactivity include statins, L‐arginine, and hydralazine approaches such as exercise and dietary changes.
Nitric Oxide in the Pathogenesis of Cardiac Disease
Authors: Raij Leopoldo
Published: May 2007

Endothelial dysfunction is characterized by a vasoconstrictive and prothrombotic state in the vasculature; it plays a role in all stages of cardiac disease and is a significant independent predictor of cardiovascular outcomes. Nitric oxide (NO) performs multiple biologic activities in the endothelium, including vasodilation and antithrombotic actions. Reduced NO bioactivity is a major component of endothelial dysfunction. Impaired NO bioactivity is an important factor in the pathogenesis of atherosclerosis and in the metabolic syndrome. The functions of NO bioactivity in the heart go well beyond those in the endothelium, as all 3 NO synthase (NOS) isoforms—endothelial NOS, neuronal NOS, and inducible NOS—are expressed in cardiac myocytes and mediate systolic, diastolic, and chronotropic cardiac functions. Impairment of NO bioactivity is a pathogenic factor in various forms of cardiac disease. Although these findings support the potential use of NO‐targeted therapies for treatment of cardiac disease, the complexities of the biologic actions of NO in the vasculature and heart are such that development of therapies is still largely in the preliminary stages.
The Role of Nitric Oxide in Erectile Dysfunction: Implications for Medical Therapy
Authors: Burnett Arthur L.
Published: May 2007

Erectile dysfunction is a common, multifactorial disorder that is associated with aging and a range of organic and psychogenic conditions, including hypertension, hypercholesterolemia, diabetes mellitus, cardiovascular disease, and depression. Penile erection is a complex process involving psychogenic and hormonal input, and a neurovascular nonadrenergic, noncholinergic mechanism. Nitric oxide (NO) is believed to be the main vasoactive nonadrenergic, noncholinergic neurotransmitter and chemical mediator of penile erection. Released by nerve and endothelial cells in the corpora cavernosa of the penis, NO activates soluble guanylyl cyclase, which increases 3′,5′‐cyclic guanosine monophosphate (cGMP) levels. Acting as a second messenger molecule, cGMP regulates the activity of calcium channels as well as intracellular contractile proteins that affect the relaxation of corpus cavernosum smooth muscle. Impaired NO bioactivity is a major pathogenic mechanism of erectile dysfunction. Treatment of erectile dysfunction often requires combinations of psychogenic and medical therapies, many of which have been only moderately successful in the past. The advent of oral phosphodiesterase type 5 (PDE‐5) inhibitors, however, has greatly enhanced erectile dysfunction treatment; patients have demonstrated high tolerability and success rates for improved erectile function. The efficacy of the PDE‐5 inhibitors also serves to illustrate the importance of the NO‐cGMP pathway in erectile function since these agents counteract the degradation of NO‐generated cGMP. Because not all patients respond to PDE‐5 inhibitors, additional therapies are being investigated, such as soluble guanylyl cyclase activators and NO donors, which act on NO‐independent and NO‐dependent pathways, respectively.
Nitric Oxide in Hypertension
Authors: Hermann Matthias , Flammer Andreas , Lüscher Thomas F.
Published: May 2007

Hypertension is a major risk factor for cardiovascular disease, and reduction of elevated blood pressure significantly reduces the risk of cardiovascular events. Endothelial dysfunction, which is characterized by impairment of nitric oxide (NO) bioavailability, is an important risk factor for both hypertension and cardiovascular disease and may represent a major link between the conditions. Evidence suggests that NO plays a major role in regulating blood pressure and that impaired NO bioactivity is an important component of hypertension. Mice with disruption of the gene for endothelial NO synthase have elevated blood pressure levels compared with control animals, suggesting a genetic component to the link between impaired NO bioactivity and hypertension. Clinical studies have shown that patients with hypertension have a blunted arterial vasodilatory response to infusion of endothelium‐dependent vasodilators and that inhibition of NO raises blood pressure. Impaired NO bioactivity is also implicated in arterial stiffness, a major mechanism of systolic hypertension. Clarification of the mechanisms of impaired NO bioactivity in hypertension could have important implications for the treatment of hypertension.
Targeting Nitric Oxide With Drug Therapy
Authors: Mason R. Preston , Cockcroft Jhon R.
Published: May 2007

Increasing knowledge of the role of nitric oxide (NO) in physiology and disease has stimulated efforts to target the NO pathway pharmacologically. These therapeutic strategies include NO donors that directly or indirectly release NO and agents that increase NO bioactivity. Traditional organic nitrates such as nitroglycerin, which indirectly release NO, were believed to have limited long‐term efficacy and tolerability, chiefly because of nitrate tolerance. Recent studies, however, suggest more effective ways of using these agents and new applications for them. Nicorandil, a hybrid organic nitrate that also activates potassium channels, has demonstrated significant benefits in acute coronary syndromes. Other nitrates are being investigated for use in neurodegenerative diseases. Direct NO donors include NO gas, which is useful in respiratory disorders, and the more recent classes of diazeniumdiolates, sydnonimines, and S‐nitrosothiols. Preliminary data suggest that these agents may be effective as anti‐atherosclerotic agents as well as in other disease states. In addition, hybrid agents that consist of an NO donor coupled with a parent anti‐inflammatory drug, including nonsteroidal anti‐inflammatory drugs, have demonstrated enhanced efficacy and tolerability compared with the anti‐inflammatory parent drug alone in diverse experimental models. Established drugs that enhance NO bioactivity include antihypertensive agents, particularly angiotensin‐converting enzyme inhibitors, calcium channel blockers, and newer vasodilating β‐blockers. In addition, 3‐methylglutaryl coenzyme A reductase inhibitors (statins) promote NO bioactivity, both through and independent of lipid lowering. The NO‐promoting actions of these established drugs provide some insight into their known benefits and suggest possible therapeutic potential.
Changes in red blood cell transfusion practice during the past two decades: a retrospective analysis, with the Mayo database, of adult patients undergoing major spine surgery
Authors: Wass C. Thomas , Long Timothy R. , Faust Ronald J. , Yaszemski Michael J. , Joyner Michael J.
Published: May 2007

BACKGROUND: Others have reported significant changes in red blood cell (RBC) transfusion practice during the past two decades during knee, hip, prostate, and carotid surgery. Similar data for patients undergoing major spine surgery, however, are not available.

STUDY DESIGN AND METHODS: After institutional review board approval, adult patients undergoing elective major spine surgery were stratified into one of two transfusion‐related groups: 1) 1980 to 1985 (i.e., before human immunodeficiency virus screening, early practice group; n = 699) or 2) 1995 to 2000 (i.e., late practice group; n = 610).

RESULTS: Patients in the late practice group were older, had greater numbers of preoperative coexisting diseases (e.g., hypertension, cardiac dysrhythmias, coronary artery disease, prior myocardial infarction, diabetes mellitus, renal disease, cerebrovascular disease, and asthma), and were exposed to longer operations (p  < 0.01 for each variable). Over time, allogeneic RBC administration significantly decreased, whereas autologous and intraoperative autotransfusion significantly increased. Compared to the early practice group, all perioperative Hb concentrations were significantly lower than the late practice group, yet no significant difference in major morbidity or mortality was observed between groups.

CONCLUSION: In this retrospective analysis, significantly lower acceptable perioperative Hb concentrations were observed in older patients having substantially worse baseline comorbidity and exposed to longer major spine operations, without significant change in the incidence of perioperative morbidity or mortality.
Frequent detection of the parvoviruses, PARV4 and PARV5, in plasma from blood donors and symptomatic individuals
Authors: Fryer Jacqueline F. , Delwart Eric , Hecht Frederick M. , Bernardin Flavien , Jones Morris S. , Shah Nita , Baylis Sally A.
Published: May 2007

BACKGROUND: Plasma pools used in the manufacture of blood‐ and plasma‐derived medicinal products are frequently contaminated with parvovirus B19. The presence of the novel human parvovirus PARV4 and a related variant PARV5 in manufacturing plasma pools was recently demonstrated. Another recently identified parvovirus, human bocavirus (HBoV), has been identified in respiratory samples from children with lower respiratory tract disease.

STUDY DESIGN AND METHODS: Recent and archived manufacturing plasma pools, as well as plasma from healthy blood donors (individual donations; pools of 16 donations) and febrile patients, were examined for the presence of PARV4 and PARV5 with conventional and TaqMan polymerase chain reaction assays. In addition, highly sensitive assays were used to examine the presence of HBoV DNA in manufacturing pools.

RESULTS: Of 351 recent manufacturing plasma pool samples, 14 (4%) tested positive for the presence of PARV4 and PARV5. This frequency was elevated in the archived pools. Viral loads ranged from less than 100 up to 4 million copies per mL plasma, with some pools containing a mixture of both viruses. In individual plasma samples from healthy blood donors and febrile patients, the frequencies of detection were 2 and 6 percent, respectively. No HBoV sequences were identified in manufacturing plasma pools (n = 167).

CONCLUSION: PARV4 and PARV5 are readily detected in manufacturing plasma pools, test pools (constructed from 16 donations), and individual donations derived from healthy blood donors. The prevalence of these viruses was increased in plasma samples from febrile patients. Despite the use of highly sensitive assays for HBoV, it was not possible to identify manufacturing plasma pools containing HBoV sequences.
A path analysis of intention to redonate among experienced blood donors: an extension of the theory of planned behavior
Authors: France Janis L. , France Christopher R. , Himawan Lina K.
Published: May 2007

BACKGROUND: The need for blood products is constant and unremitting, yet only a small percentage of eligible individuals answer the appeal to donate. Further, most new donors never return to provide a repeat donation. The ongoing need to attract and retain new donors has led to the examination of psychosocial factors that may predict the likelihood of blood donation behavior. By use of regression techniques, prior studies have established that elements of the Theory of Planned Behavior (e.g., attitude, subjective norm, personal moral norm, and perceived control or self‐efficacy) can predict intention to donate among nondonors.

STUDY DESIGN AND METHODS: Path analysis was used to further examine the utility of the Theory of Planned Behavior in predicting donation intention in a sample of 227 experienced donors who completed an online survey. Experiential measures relating to previous donations, including the experience of vasovagal reactions and overall donor satisfaction, were added to the model.

RESULTS: The final model, which provided an excellent fit to the data, characterized 1) three direct pathways from attitude, subjective norm, and self‐efficacy to donation intention and 2) four indirect pathways, wherein self‐efficacy, personal moral norm, vasovagal reactions, and overall donor satisfaction influence donation intention through attitude. In total, 65 percent of the variance in donation intention and 50 percent of the variance in attitude is accounted for in this model.

CONCLUSION: The Theory of Planned Behavior can be used to predict donation intentions among experienced donors. Further, the model's predictive utility is improved by considering the influence of previous donation experiences on donor attitudes.
Inactivation of parvovirus B19 in human platelet concentrates by treatment with amotosalen and ultraviolet A illumination
Authors: Sawyer Lynette , Hanson Deborah , Castro Grace , Luckett William , Dubensky Thomas W. , Stassinopoulos Adonis
Published: May 2007

BACKGROUND: The human erythrovirus B19 (B19) is a small (18‐ to 26‐nm) nonenveloped virus with a single‐stranded DNA genome of 5.6 kb. B19 is clinically significant and is also generally resistant to pathogen inactivation methods. Photochemical treatment (PCT) with amotosalen and ultraviolet A (UVA) inactivates viruses, bacteria, and protozoa in platelets (PLTs) and plasma prepared for transfusion. In this study, the capacity of PCT to inactivate B19 in human PLT concentrates was evaluated.

STUDY DESIGN AND METHODS: B19 inactivation was measured by a novel enzyme‐linked immunosorbent spot (ELISPOT) erythroid progenitor cell infectivity assay and by inhibition of long‐range (up to 4.3 kb) polymerase chain reaction (PCR), under conditions where the whole coding region of the viral genome was amplified. B19‐infected plasma was used to test whether incubation of amotosalen with virus before PCT enhanced inactivation compared to immediate PCT.

RESULTS: Inactivation of up to 5.8 log of B19 as measured by the infectivity assay, or up to 6 logs as measured by PCR inhibition can be achieved under non‐limiting conditions. Inactivation efficacy was found to increase with incubation prior to UVA illumination. Without incubation prior to illumination 2.1 +0.4 log was inactivated as determined by infectivity assay. When measured by PCR inhibition, inactivation varied inversely with amplicon size. When primers that spanned the entire coding region of the B19 genome were used, maximum inhibtion of PCR amplification was demonstrated.

CONCLUSION: Under defined conditions, PCT with amotosalen combined with UVA light can be used to inactivate B19, a clinically significant virus that can be transmitted through blood transfusion, and heretofore has been demonstrated to be refractory to inactivation.
Use of X‐linked short tandem repeat loci in routine parentage casework
Authors: Silveira Debora , Silva Fabiana F. , Jesus Priscila R. , Whittle Martin R.
Published: May 2007

BACKGROUND:Dealing with genetic inconsistencies in parentage testing, especially in motherless cases, remains a continual difficulty.

STUDY DESIGN AND METHODS:Four difficult cases, comprising two trios and two duos, were selected from routine parentage testing casework. In these, relatively low combined paternity indices were observed as a result of few discrepant loci that were treated as being due to paternal mutations. An additional eight short tandem repeat (STR) loci along the X chromosome were studied in the alleged father and female child to try and help resolve these cases.

RESULTS:In all four cases, the X chromosome haplotypes in the alleged father were different from those in the child, showing decisively that the alleged father could be excluded from being the biologic father of the child.

CONCLUSION:In recent times the study of X chromosome haplotypes has been shown to be useful in parentage testing where the alleged father is absent and where only his close relatives are available for testing. This work demonstrates that such studies can also prove valuable in the testing of standard trios and duos in cases where there only a few genetic inconsistencies amongst the loci tested, making it difficult to distinguish between paternal mutations and a close relative of the alleged father being the biologic father.
Recombinant human C1‐inhibitor in the treatment of acute angioedema attacks
Authors: Choi Goda , Soeters Maarten R. , Farkas Henriette , Varga Lilian , Obtulowicz Krystyna , Bilo Barbara , Porebski Greg , Hack C. Erik , Verdonk René , Nuijens Jan , Levi Marcel
Published: May 2007

BACKGROUND: Patients with hereditary C1‐inhibitor deficiency have recurrent attacks of angioedema, preferably treated with C1‐inhibitor concentrate. A recombinant human C1‐inhibitor (rHuC1INH) was developed, derived from milk from transgenic rabbits. This study was undertaken to investigate the effects of rHuC1INH in the treatment of acute angioedema attacks in patients with a hereditary C1‐inhibitor deficiency.

STUDY DESIGN AND METHODS: Patients with hereditary C1‐inhibitor deficiency were treated with rHuC1INH (at a dose of 100 U/kg) within 8 hours after onset of an acute attack. Time to initiation of relief and time to minimal symptoms were reported by both the patient and the treating physician.

RESULTS: Thirteen severe angioedema attacks in 9 patients with hereditary C1‐inhibitor deficiency were treated with rHuC1INH. There was rapid improvement of clinical conditions for all attacks, with approximately 80 percent of treated patients experiencing symptom relief within 2 hours and minimal symptoms within 12 hours. There were no drug‐related adverse events or immunogenic reactions to C1‐inhibitor or rabbit proteins.

CONCLUSION: The transgenically produced rHuC1INH was successfully used in the treatment of acute angioedema attacks in patients with hereditary C1‐inhibitor deficiency.
Evaluation of a new apheresis system for the collection of leukoreduced single‐donor platelets
Authors: Zingsem Jürgen , Strasser Erwin , Ringwald Jürgen , Zimmermann Robert , Weisbach Volker , Eckstein Reinhold
Published: May 2007

BACKGROUND: The Fresenius COM.TEC cell separator is a new device for producing white cell concentrates (WBCs) and leukoreduced single‐donor platelet concentrates (SDPs) and performing therapeutic cytapheresis and plasmapheresis that might replace the Fresenius systems AS104 and AS.TEC 204. This novel system's performance was evaluated for producing leukoreduced SDPs.

STUDY DESIGN AND METHODS: In an investigational phase, each of 200 donors underwent plateletpheresis with the AS.TEC 204 and the COM.TEC systems. The collection efficiency (CE) and WBC contamination of the different techniques were compared. After some hard‐ and software modifications, the system was evaluated in an additional 800 procedures in the confirmatory phase.

RESULTS: In the investigational phase, the CE of the COM.TEC device was increased significantly in comparison to the AS.TEC 204 device's CE (by 45 ± 32% when collecting 1 unit of platelets [PLTs] and 1 unit of fresh‐frozen plasma and by 43 ± 42% when collecting only 1 unit of PLTs). Although all AS.TEC products proved to be leukoreduced, 2 percent of the COM.TEC procedures led to PLT concentrates containing more than 1 × 106 WBCs. In the confirmatory phase, all 1300 products from 800 COM.TEC procedures proved to be leukoreduced. Furthermore, the CE increased significantly from 53.5 ± 4.6 percent in the investigational phase to 55.5 ± 4.9 percent (p  < 0.001) in the confirmatory phase.

CONCLUSIONS: These data suggest that the new COM.TEC system offers a significantly and importantly improved CE in plateletpheresis procedures in comparison to the AS.TEC system. In the final version, the PLT products collected with this system fulfill the most stringent criteria for leukoreduced PLTs. This aim was achieved without additional filtration steps and thus without filtration‐related PLT loss.
Temporal Trends, Safety, and Efficacy of Bivalirudin in Elective Percutaneous Coronary Intervention: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium
Authors: GURM HITINDER S. , SMITH DEAN E. , CHETCUTI STAN J. , SHARE DAVID , KHANAL SANJAYA , RIBA ARTHUR , CARTER ANDREW J. , LALONDE THOMAS , KLINE‐ROGERS EVA , O'DONNELL MICHAEL , O'NEILL WILLIAM , SAFIAN ROBERT , MOSCUCCI MAURO
Published: May 2007

Objective: To evaluate the safety and efficacy of bivalirudin based therapy among patients undergoing percutaneous coronary intervention (PCI) for stable coronary artery disease in a large multicenter registry.

Background: The REPLACE
II trial demonstrated the non‐inferiority of a strategy of bivalirudin compared with heparin and glycoprotein (GP) IIbIIIa inhibition in patients undergoing PCI. There is a paucity of outcome data with bivalirudin use in the setting of real‐world PCI practice.

Methods: We evaluated the outcome of 11,719 patients who underwent elective PCI for stable coronary artery disease (CAD) from 2002 to 2004 in a large regional consortium, and who were treated with bivalirudin (n = 2051) or with heparin and GP IIbIIIa inhibitors (n = 9,668). The primary endpoints were transfusion and in‐hospital major adverse cardiovascular events (MACE) defined as the composite of death, MI, stroke, and any coronary artery bypass grafting (CABG) or target lesion revascularization.

Results: Compared with patients who received heparin plus GP IIbIIIa inhibitors, patients who received bivalirudin had a similar incidence of post‐procedural MI, stroke, in‐hospital death, MACE (2.88 vs. 2.48, P = 0.30), or transfusion (2.83% vs. 2.41%, P = 0.27). Patients at greater risk of bleeding were more likely to be treated with bivalirudin. After adjusting for the propensity to receive bivalirudin and for baseline co‐morbidities, there was no difference in the odds of MACE or the need for transfusion between the two groups.

Conclusion: Compared with heparin plus GP IIbIIIa inhibition, use of bivalirudin in patients undergoing PCI for stable CAD is associated with similar ischemic and bleeding complications. Given the ease of administration and lower cost, bivalirudin provides an attractive treatment option in this patient population.
Immunopathology and molecular diagnosis of autoimmune bullous diseases
Authors: Mihai Sidonia , Sitaru Cassian
Published: May 2007

Introduction

Pemphigus diseases

Pemphigus variants

Pemphigoid diseases

Anti‐p200 pemphigoid

Epidermolysis bullosa acquisita

Dermatitis herpetiformis Duhring

Autoimmune bullous diseases are associated with autoimmunity against structural components maintaining cell–cell and cell matrix adhesion in the skin and mucous membranes. Pemphigus diseases are characterized by autoantibodies against the intercellular junctions and intraepithelial blisters. In pemphigoid diseases and epidermolysis bullosa acquisita, sub‐epidermal blistering is associated with autoantibodies targeting proteins of the hemidesmosomal anchoring complex. The autoantigens in autoimmune blistering diseases have been extensively characterized over the past three decades. In general, the pathogenicity of autoantibodies, already suggested by clinical observations, has been conclusively demonstrated experimentally. Detection of tissue‐bound and circulating serum autoantibodies and characterization of their molecular specificity is mandatory for the diagnosis of autoimmune blistering diseases. For this purpose, various immunofluorescence methods as well as immunoassays, including immunoblotting, enzyme‐linked immunosorbent assay and immunoprecipitation have been developed. This review article describes the immunopathological features of autoimmune bullous diseases and the immunological and molecular tests used for their diagnosis and monitoring.