bluuebunny/crossref_metadata_2025 huggingface dataset:
Excess injury mortality among smokers: a neglected tobacco hazard
Authors: Wen C P , Tsai S P , Cheng T Y , Chan H T , Chung W S I , Chen C J
Published: May 2005

Objective:To assess the mortality risks from injuries for smokers and ex-smokers and to quantify the mortality burden of smoking from injury in Taiwan.

Methods:Smokers’ (and ex-smokers’) mortality risks from injuries were compared with that of non-smokers in a merged cohort from Taiwan. A total of 64 319 male subjects were followed up for 12–18 years. Relative risks (RR) (adjusted for age and alcohol use) and 95% confidence intervals (CI) for cause specific injury deaths were calculated using the Cox proportional hazard model. Relative risks of injury mortality were also calculated to assess the presence of dose–response relations with daily smoking quantity.

Results:Alcohol use adjusted relative mortality risks for all injuries (RR 1.69, 95% CI 1.39 to 2.05) including those from motor vehicle accidents (RR 1.88, 95% CI 1.44 to 2.45) and non-motor vehicle accidents (RR 1.48, 95% CI 1.11 to 1.99) were significantly higher for smokers than non-smokers. Mortality was also increased for most subtypes of non-motor vehicle injuries including falls, fires, and job related injuries. Furthermore, these increases were dose dependent, with the heaviest smokers having the highest risk and the lightest smokers the lowest risk, and ex-smokers, no increase. In 2001, over one fifth (23%) of all male injury deaths in Taiwan was associated with smoking.

Conclusion:This study demonstrated the significant association between fatal injuries and smoking. This relation adds further weight to smoking cessation campaigns.
Increasing taxes to reduce smoking prevalence and smoking attributable mortality in Taiwan: results from a tobacco policy simulation model
Authors: Levy D T , Wen C P , Chen T Y , Oblak M
Published: May 2005

Objective:To develop a simulation model to predict the effects of tax policies on smoking prevalence rates and smoking attributable deaths.

Methods:Using data from Taiwan, a simulation model is developed that projects population using birth and death rate data, future smoking rates using initiation, cessation and relapse data, and smoking attributable deaths using smoking prevalence and relative risk estimates. The model projects the number of smokers and smoking related deaths from a baseline year forward. The effects of taxes of different sizes, indexed and unindexed, and temporary versus sustained are modelled using elasticities based on published studies of demand.

Results:The model predicts that sustained tax increases have the potential to substantially reduce the number of smokers and the number of premature deaths, with the effects growing over time. Indexing taxes to inflation stems erosion of the tax effect. In our model, when the tax increases by 10 times (NT$50) over the recent tax increase (NT$5) and taxes are indexed to inflation, the smoking prevalence rate falls by over 15% soon after the tax increase, and by about 30% in relative terms by the year 2040, resulting in 4500 lives saved per year.

Conclusions:Tax rises have the ability to substantially affect smoking rates in Taiwan. These effects grow over time and lead to substantial savings in lives and health care costs.
Smoking attributable medical expenditures, years of potential life lost, and the cost of premature death in Taiwan
Authors: Yang M C , Fann C Y , Wen C P , Cheng T Y
Published: May 2005

Objective:To estimate the smoking attributable medical expenditures and productivity loss of people aged 35 and over in Taiwan in 2001 from a societal viewpoint.

Methods:A prevalence based approach was used to estimate smoking attributable costs. Epidemiological parameters were obtained from two follow up studies and government statistics. Data on medical care utilisation and expenditure were extracted from the National Health Insurance claim data.

Results:Total smoking attributable medical expenditures (SAEs) amounted to US$397.6 million, which accounted for 6.8% of the total medical expenditures for people aged 35 and over. Mean annual medical expenditures per smoker was US$70 more than that of each non-smoker. Smoking attributable years of potential life lost (YPLL) totalled to 217 761 years for males and 15 462 years for females, and the corresponding productivity loss was US$1371 million for males and US$18.7 million for females.

Conclusion:Medical expenditures attributable to smoking accounted for 6.8% of the total medical expenditure of people aged 35 and over for the year 2001 in Taiwan. Corresponding YPLL and productivity loss also demand that actions be taken to fight cigarette smoking.
Uncovering the relation between betel quid chewing and cigarette smoking in Taiwan
Authors: Wen C P , Tsai S P , Cheng T Y , Chen C-J , Levy D T , Yang H-J , Eriksen M P
Published: May 2005

Objective:To describe the characteristics of betel quid chewers and to investigate the behavioural and mortality relations between betel quid chewing and cigarette smoking.

Method:Prevalence and mortality risks of betel quid chewers by smoking status were calculated, based on the National Health Interview Survey in 2001 and a community based cohort, respectively. Cox’s proportional hazards model was used to adjust mortality risks for age, alcohol use, and education.

Results:Almost all betel quid chewers were smokers, and most started chewing after smoking. Chewers were predominantly male, mostly in their 30s and 40s, more likely being among the lowest educational or income group, and residing in the eastern regions of Taiwan. On average, betel quid chewers who smoked consumed 18 pieces of betel quid a day, and smoked more cigarettes per day. Far more smokers use betel quid than non-smokers (27.5%v2.5%), but ex-smokers quit betel quid more than smokers (15.1%v6.8%). The significantly increased mortality of betel quid users who also smoked, for all causes, all cancer, oral cancer, and cancer of the nasopharynx, lung, and liver, was the result of the combined effects of chewing and smoking. Smokers who chewed betel quid nearly tripled their oral cancer risks from a relative risk of 2.1 to 5.9. Increasing the number of cigarettes smoked among betel quid chewers was associated with a synergistic effect, reflective of the significant interaction between the two.

Conclusion:To a large extent, the serious health consequences suffered by betel quid chewers were the result of the combined effects of smoking and chewing. Betel quid chewing should not be considered as an isolated issue, but should be viewed conjointly with cigarette smoking. Reducing cigarette smoking serves as an important first step in reducing betel quid chewing, and incorporating betel quid control into tobacco control may provide a new paradigm to attenuate the explosive increase in betel quid use in Taiwan.
How effective are tobacco industry bar and club marketing efforts in reaching young adults?
Authors: Gilpin E A , White V M , Pierce J P
Published: May 2005

Objective:Recently, the tobacco industry has focused marketing efforts on young adults through bar and club promotions, such as advertising and distribution of free cigarettes in these settings. This study estimates the fraction of the California young adult population that might be exposed and potentially influenced by these efforts.

Design and participants:Data were from 9364 young adult (18–29 years) respondents to the cross sectional population based 2002 California Tobacco Survey. As background, we analysed social smoking (only smoke with other smokers), and enjoyment of smoking while drinking. Our main focus was on bar and club attendance, what was observed in bars and clubs, and how this might differ according to respondents’ risk for future smoking.

Results:Social smokers comprised 30.0 (2.2)% of all current smokers, including experimenters. Nearly three quarters (74.5 (2.3)%) of current smokers/experimenters said they enjoyed smoking while drinking. About one third (33.8 (1.2)%) of all young adults said they attended bars and clubs at least sometimes; attendance was significantly higher among smokers and those at risk for future smoking. Close to 60% (57.9 (2.2)%) of bar and club attenders reported seeing cigarette advertising and promotions in these settings. Again, smokers and those at risk were more likely to report seeing such advertising and promotions in these settings.

Conclusions:About 20% of all young adults and about 30% of those at risk for future smoking (including current smokers) were exposed to tobacco advertising and promotions in bars and clubs. These California results may be conservative, but nonetheless indicate that the group potentially influenced is sizable.
Adolescent smoking decline during California’s tobacco control programme
Authors: Pierce J P , White M M , Gilpin E A
Published: May 2005

Objective:California’s comprehensive tobacco control programme was 13 years old in 2002; by then, children entering adolescence at the start of the programme were young adults. This study examines whether adolescent smoking declined over this period, whether any decline carried through to young adulthood, and whether it was specific to California.

Setting and participants:Most data were from the 1990–2002 California Tobacco Surveys (CTS) (adolescents 12–17 years, > 5000/survey, young adults 18–24 years, > 1000/survey). Additional data were from the national 1992/93–2001/02 Current Population Survey (CPS) (young adults 18–24 years, > 15 000/survey).

Results:Over the 13 year period in California, ever puffing declined by 70% in 12–13 year olds, by 53% in 14–15 year olds from 1992–2002, and by 34% in 16–17 year olds from 1996–2002 (CTS). As noted, the decline commenced progressively later in each older group. Smoking experimentation (1+ cigarettes) and established smoking (> 100 cigarettes in lifetime) showed similar patterns. Compared to 1990, the percentage of California young adults (CTS data) who ever experimented declined by 14%, with half of the decline from 1999–2002. CPS young adult smoking prevalence (established and now smoke everyday or some days) was constant in the rest of the USA over the entire period, but California showed a recent 18% decline from 1998/99 to 2001/02.

Conclusions:California’s comprehensive programme may have kept new adolescent cohorts from experimenting with cigarettes. Low young adolescent experimentation rates at programme start appeared to carry through to young adulthood, resulting in a recent drop in young adult smoking prevalence in California not observed in the rest of the USA.
Cigarette advertising in Mumbai, India: targeting different socioeconomic groups, women, and youth: Table 1
Authors: Bansal R , John S , Ling P M
Published: May 2005

Background:Despite a recent surge in tobacco advertising and the recent advertising ban (pending enforcement at the time of this study), there are few studies describing current cigarette marketing in India. This study sought to assess cigarette companies’ marketing strategies in Mumbai, India.

Methods:A two week field study was conducted in Mumbai in September 2003, observing, documenting, and collecting cigarette advertising on billboards, storefronts and at point of sale along two major thoroughfares, and performing a content analysis of news, film industry, and women’s magazines and three newspapers.

Results:Cigarette advertising was ubiquitous in the environment, present in news and in film magazines, but not in women’s magazines or the newspapers. The four major advertising campaigns all associated smoking with aspiration; the premium brands targeting the higher socioeconomic status market utilised tangible images of westernisation and affluence whereas the “bingo” (low priced) segment advertisements invited smokers to belong to a league of their own and “rise to the taste” using intangible images. Women were not depicted smoking, but were present in cigarette advertisements—for example, a woman almost always accompanied a man in “the man with the smooth edge” Four Square campaign. Advertisements and product placements at low heights and next to candies at point of sale were easily accessible by children. In view of the iminent enforcement of the ban on tobacco advertisements, cigarette companies are increasing advertising for the existing brand images, launching brand extensions, and brand stretching.

Conclusion:Cigarette companies have developed sophisticated campaigns targeting men, women, and children in different socioeconomic groups. Many of these strategies circumvent the Indian tobacco advertising ban. Understanding these marketing strategies is critical to mimimise the exploitation of loopholes in tobacco control legislation.
Toward a comprehensive long term nicotine policy
Authors: Gray N , Henningfield J E , Benowitz N L , Connolly G N , Dresler C , Fagerstrom K , Jarvis M J , Boyle P
Published: May 2005

Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society’s main nicotine source.
Facilitating the critical process in tobacco control: Figure 1
Authors: Wen C P
Published: May 2005

Mencius, a disciple of Confucius: You do not perform, not because you are not able to
Putative antihyperpyretic factor induced by LPS in spleen of guinea pigs
Authors: Feleder Carlos , Perlik Vit , Tang Ying , Blatteis Clark M.
Published: May 2005

We reported previously that the onset of LPS-induced fever, irrespective of its route of administration, is temporally correlated with the appearance of LPS in the liver and that splenectomy significantly increases both the febrile response to LPS and the uptake of LPS by Kupffer cells (KC). To further evaluate the role of the spleen in LPS fever production, we ligated the splenic vein and, 7 and 30 days later, monitored the core temperature changes over 6 h after intraperitoneal (ip) injection of LPS (2 μg/kg). Both the febrile response and the uptake of LPS by KC were significantly augmented. Like splenectomy, splenic vein ligation (SVL) increased the febrile response and LPS uptake by KC until the collateral circulation developed, suggesting that the spleen may normally contribute an inhibitory factor that limits KC uptake of LPS and thus affects the febrile response. Subsequently, to verify the presence of this factor, we prepared splenic extracts from guinea pigs pretreated with LPS (8 μg/kg ip) or pyrogen-free saline, homogenized and ultrafiltered them, and injected them intravenously into splenectomized (Splex) guinea pigs pretreated with LPS (8 μg/kg ip). The results confirmed our presumption that the splenic extract from LPS-treated guinea pigs inhibits the exaggerated febrile response and the LPS uptake by the liver of Splex guinea pigs, indicating the presence of a putative splenic inhibitory factor, confirming the participation of the spleen in LPS-induced fever, and suggesting the existence of a novel antihyperpyretic mechanism. Preliminary data indicate that this factor is a lipid.
Subdiaphragmatic vagal deafferentation affects body weight gain and glucose metabolism in obese male Zucker (fa/fa) rats
Authors: Ferrari Bettina , Arnold Myrtha , Carr Richard D. , Langhans Wolfgang , Pacini Giovanni , Bodvarsdóttir Thora B. , Gram Dorte X.
Published: May 2005

We investigated the effect of subdiaphragmatic vagal deafferentation (SDA) on food intake, body weight gain, and metabolism in obese ( fa/ fa) and lean ( Fa/?) Zucker rats. Before and after recovery from surgery, food intake and body weight gain were recorded, and plasma glucose and insulin were measured in tail-prick blood samples. After implantation of a jugular vein catheter, an intravenous glucose tolerance test (IVGTT) was performed, followed by minimal modeling to estimate the insulin sensitivity index. Food intake relative to metabolic body weight (g/kg0.75) and daily body weight gain after surgery were lower ( P < 0.05) in SDA than in sham obese but not lean rats. Before surgery, plasma glucose and insulin concentrations were lower ( P < 0.05) in lean than in obese rats but did not differ between surgical groups within both genotypes. Four weeks after surgery, plasma glucose and insulin were still similar in SDA and sham lean rats but lower ( P < 0.05) in SDA than in sham obese rats. IVGTT revealed a downward shift of the plasma insulin profile by SDA in obese but not lean rats, whereas the plasma glucose profile was unaffected. SDA decreased ( P < 0.05) area under the curve for insulin but not glucose in obese rats. The insulin sensitivity index was higher in lean than in obese rats but was not affected by SDA in both genotypes. These results suggest that elimination of vagal afferent signals from the upper gut reduces food intake and body weight gain without affecting the insulin sensitivity index measured by minimal modeling in obese Zucker rats.
Effect of exercise on cerebral perfusion in humans at high altitude
Authors: Imray C. H. E. , Myers S. D. , Pattinson K. T. S. , Bradwell A. R. , Chan C. W. , Harris S. , Collins P. , Wright A. D.
Published: May 2005

The effects of submaximal and maximal exercise on cerebral perfusion were assessed using a portable, recumbent cycle ergometer in nine unacclimatized subjects ascending to 5,260 m. At 150 m, mean (SD) cerebral oxygenation (rSo2%) increased during submaximal exercise from 68.4 (SD 2.1) to 70.9 (SD 3.8) ( P < 0.0001) and at maximal oxygen uptake (V̇o2 max) to 69.8 (SD 3.1) ( P < 0.02). In contrast, at each of the high altitudes studied, rSo2 was reduced during submaximal exercise from 66.2 (SD 2.5) to 62.6 (SD 2.1) at 3,610 m ( P < 0.0001), 63.0 (SD 2.1) to 58.9 (SD 2.1) at 4,750 m ( P < 0.0001), and 62.4 (SD 3.6) to 61.2 (SD 3.9) at 5,260 m ( P < 0.01), and at V̇o2 max to 61.2 (SD 3.3) at 3,610 m ( P < 0.0001), to 59.4 (SD 2.6) at 4,750 m ( P < 0.0001), and to 58.0 (SD 3.0) at 5,260 m ( P < 0.0001). Cerebrovascular resistance tended to fall during submaximal exercise ( P = not significant) and rise at V̇o2 max, following the changes in arterial oxygen saturation and end-tidal CO2. Cerebral oxygen delivery was maintained during submaximal exercise at 150 m with a nonsignificant fall at V̇o2 max, but at high altitude peaked at 30% of V̇o2 max and then fell progressively at higher levels of exercise. The fall in rSo2 and oxygen delivery during exercise may limit exercise at altitude and is likely to contribute to the problems of acute mountain sickness and high-altitude cerebral edema.
A Brevibacillus choshinensis System That Secretes Cytoplasmic Proteins
Authors: Horne Irene , Williams Michelle , Sutherland Tara D. , Russell Robyn J. , Oakeshott John G.
Published: May 2005

Brevibacillus choshinensis has previously been shown to be a useful strain for the secretion of heterologous proteins via the Sec secretory pathway. This pathway involves the secretion of proteins prior to folding, whereas the alternative TAT (twin-arginine translocation) pathway enables pre-folded proteins to be secreted. We have modified the signal peptide of the Brevibacillus expression vector pNCMO2 to accommodate a Sec avoidance signal as well as the twin arginines required for secretion via the TAT system. Use of this modified signal peptide with the phosphotriesterase OpdA enabled B. choshinensis transformants to express and secrete the enzyme in an active and substantially pure form. The system was also used successfully to secrete two cytoplasmic proteins, the phosphotriesterase HocA from Pseudomonas monteilii and the phenylcarbamate-degrading enzyme, PCD, from Arthrobacter oxydans. The inhibitors carbonyl cyanide m-chlorophenyl hydrazine and sodium azide were used to confirm that secretion was occurring via the TAT secretion pathway. The modified B. choshinensis system we have developed may have general utility in secreting a wide range of heterologous proteins in active and conveniently processed form.
Phenotypes of Combined Tet Repressor Mutants for Effector and Operator Recognition and Allostery
Authors: Bertram Ralph , Kraft Christine , Wisshak Stefanie , Mueller Judith , Scholz Oliver , Hillen Wolfgang
Published: May 2005

Tet repressor mutants with a shifted effector specificity, preference for a mutant operator sequence or reversion of activity were combined to construct variants bearing two or three phenotypic alterations. TetR alleles with combinations of altered operator and effector specificities can be created by merging the respective residues in a single polypeptide. The mutations giving rise to revTetR, on the other hand, show drastic influences on the ligand binding phenotypes when combined with respective alterations. One TetR variant displays all three phenotypic alterations and thus demonstrates the general possibility of implementing them in one protein.
Two Decades Experience of the Psoriasis Disability Index
Authors: Lewis Victoria J. , Finlay Andrew Y.
Published: May 2005

The Psoriasis Disability Index (PDI) was formed 20 years ago. Since its introduction it has been used widely as a tool for assessment of quality of life in psoriasis. This paper reviews its use in 23 peer-reviewed articles and over 35 published abstracts, and describes its use in conjunction with other general and psoriasis-specific quality of life assessments, and with a range of physical and psychological measures. The PDI is effective in demonstrating the effects of interventions, both of treatments and in health service research. The PDI has been translated into at least 16 languages and has been used in published research in 20 countries.
Psychophysiological Reactivity under Mental Stress in Atopic Dermatitis
Authors: Seiffert Kristina , Hilbert Edwin , Schaechinger Hartmut , Zouboulis Christos C. , Deter Hans-Christian
Published: May 2005

Background: An association of mental stress with atopic dermatitis is widely accepted. However, no long-term evaluation of psychophysiological reactivity over the course of disease has yet been performed. Objective: We examined whether atopic dermatitis patients have an increased psychophysiological reactivity compared to healthy controls and in between acute and disease-free phases, and whether they differ in psychological state and trait variables. Methods: Fifteen patients with atopic dermatitis underwent a stress test during acute exacerbation and after symptom improvement and were compared to matched controls. Results: Psychophysiological responsesto stress were not stronger in the patient group than in the controls. Nevertheless, the patients had a higher heart rate and lower vagal activity throughout the resting and stress phases at both examination times. The patients showed significantly higher anxiety, depression and emotional excitability, and self-ratings of inactivity clearly distinguished acute phases from remission. Conclusion: There is an increased vegetative excitability level in patients with atopic dermatitis, which cannot be attributed solely to increased disease activity.
A Two-Compound Product Containing Calcipotriol and Betamethasone Dipropionate Provides Rapid, Effective Treatment of Psoriasis vulgaris regardless of Baseline Disease Severity
Authors: van de Kerkhof P.C.M. , Wasel N. , Kragballe K. , Cambazard F. , Murray S.
Published: May 2005

Background: A two-compound product containing calcipotriol and betamethasone dipropionate (Daivobet®/Dovobet®) has been evaluated in a large clinical trial programme, providing a wealth of data on the treatment of psoriasis vulgaris. Objective: To determine the effectiveness of the two-compound product in patients with mild, moderate and severe psoriasis vulgaris. Methods: Data from over 1,534 patients with psoriasis vulgaris who received the two-compound product once daily for at least 4 weeks in four randomised, double-blind studies were pooled. A meta-analysis of the pooled data is presented. Severity of psoriasis at baseline was determined by investigator assessment and Psoriasis Area and Severity Index (PASI) score. Results: For patients with severe disease defined by PASI score (PASI baseline ≧17), the mean reduction in PASI after up to 4 weeks of treatment was 71.6% compared with 68.9 and 67.2% for those with moderate (PASI baseline 5.1–16.0) and mild disease (PASI baseline ≤5). Corresponding reductions for investigator-assessed severity were 72.6, 69.1 and 68.7%, respectively. Conclusion: Although the meta-analysis of the data from these four studies was performed post hoc, we may conclude that the two-compound product provided highly effective treatment of psoriasis, regardless of the category of baseline disease severity.
International Cooperation and Networking in Genetic Health Care Provision: Issues Arising from the Genetic Services Plan for the Emilia-Romagna Region, Italy
Authors: Calzolari E. , Baroncini A.
Published: May 2005

The aims of this report are to describe the genetic plan for Emilia-Romagna, a region in Italy, and to contribute to the international exchange of information on developing and applying policy frameworks to provide high-quality and comprehensive genetic health care in the publicly funded health systems. At the present time there is no national policy for genetic medicine in Italy, and only two regions, Emilia-Romagna and Liguria, have formally agreed to a strategic plan for health care in genetics. The current provision of genetic services in Emilia-Romagna is described focusing on the intra- and inter-organizational linkages to ensure a comprehensive system of coordinated activities. Strengths and implementation areas are highlighted. Points that must be solved within the regional or national context are the definition of the level of assistance required in genetic medicine, the formal professional recognition of the genetic counselor and the adjustment of the billing mechanisms to the complexities of clinical genetic services. Issues that need to be addressed at a wider level include full assessment of genetic tests before their introduction into clinical practice, networking to provide tests for the rarest genetic diseases, consensus on fundamental terminology and clinical and administrative data sets to promote a cohesive framework for the flow of information throughout the health care systems with respect to genetics.
Rapid Effects of a Single High Dose of Simvastatin on C-Reactive Protein in Patients with Unstable Angina
Authors: Li Jian-Jun , Fang Chun-Hong , Chen Ming-Zhe , Chen Xin
Published: May 2005

Background: Elevated levels of C-reactive protein (CRP) became widely accepted as a risk factor for a higher incidence of coronary events, and rapid lowering of CRP following the administration of drugs may result in early beneficial effects on the coronary endothelium in patients with coronary heart disease, and reduce angina and coronary events after revascularization. Limited information has been available, however, on the potential effect of a single, high dose of simvastatin on CRP in patients with unstable angina (UA) within 48 h. Hypothesis: The present study was performed to investigate whether a rapid CRP reduction can be achieved by a single, high-dose simvastatin therapy in patients with UA given immediately on admission. Patients and Methods: Forty-two patients with chest pain at rest were randomly assigned to a single placebo dose or 80 mg of simvastatin given at the time of admission in addition to standard therapy. Blood samples were also drawn on admission and 48 h following admission for serum CRP evaluation. Results: The results showed that a single, high dose of 80 mg simvastatin induced significant reductions in median serum CRP levels and in mean CRP levels 48 h following the administration of simvastatin (25.4 and 32.7%, respectively; p < 0.001). Conclusions: Our data suggest that a single, high dose of simvastatin, given during admission, is an effective therapy for controlling inflammatory responses in patients with UA, and its beneficial effect on the vascular endothelium might be reflected by the immediate reduction in CRP levels in this high-risk subgroup, thus improving their prognosis.
Writing the Original Medical Research Paper
Authors: Schmidt Thomas Andersen , Bech Jan , Kjeldsen Keld
Published: May 2005

An original article is generally considered a cornerstone of modern research. It is a detailed written presentation of novel and original data that undergo peer review. The current paper describes in detail how to draw up an original article effectively, using strategies such as modern information technology and a rational sequence of writing title page, materials and methods, figures and tables, legends, results, introduction, discussion, acknowledgements, abstract (summary), key words and reference list. As a preliminary step, important basic facts on medical writing are described, in particular the distinction between generating/collecting data and actually putting fingers to the keyboard. The Vancouver requirements and important aspects of authorship are discussed; how to choose a journal is also outlined. Finally we describe the repeated process of writing, reviewing and revising your manuscript together with your mentor or co-workers to obtain the highest level of quality before submission.
Nitric Oxide Synthase Inhibitors in Refractory Cardiogenic Shock due to Myocardial Infarction after Percutaneous Coronary Intervention
Authors: Kaluski Edo , Milo Olga , Uriel Nir , Vered Zvi , Cotter Gad
Published: May 2005

ST-elevation myocardial infarction complicated by cardiogenic shock (CS), warrants optimal medical support and urgent revascularization usually by percutaneous coronary intervention (PCI). However, contemporary studies report that half of these post-PCI patients will succumb to intractable heart stunning, failure, and death. Most of those who survive, however, become asymptomatic or mildly symptomatic. We discuss current definitions of CS, and pump function, as well as the potential deleterious effects of nitric oxide on the stunned and failing heart. We review the studies employing nitric oxide synthase inhibitors for post-PCI cardiogenic shock, and point out future studies.
Utility of Intravenous β-Blocker Administration in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Intervention
Authors: Halkin Amir , Stone Gregg W.
Published: May 2005

The clinical effects of intravenous β-adrenoreceptor- blocking agents (β-blockers) administered during evolving acute myocardial infarction (AMI) have varied among published studies, depending on whether or not reperfusion therapy was employed. Primary percutaneous coronary intervention (PCI) is accepted as the superior form of reperfusion therapy for AMI if it can be performed by an experienced team in a timely fashion. Intravenous β-blockers are not routinely used in this setting and their role as adjunctive medical therapy to catheter-based reperfusion requires definition. Emerging data strongly indicate that in the absence of cardiogenic shock or specific contra-indications, pre-procedural intravenous β-blockade improves survival and recovery of left ventricular function after primary PCI, and that these effects are modulated by oral β-blocker use at the time of AMI onset. In the absence of contra-indications, the available evidence supports the routine administration of intravenous β-blockers to patients with ST-segment elevation AMI managed by catheter-based reperfusion therapy, especially in patients in whom oral β-blockers were not used before admission. While no data are available on the effects of intravenous β-blocker therapy with catheter-based intervention for acute coronary syndromes other than ST-segment elevation AMI, it is reasonable to apply the aforementioned recommendations regarding primary PCI to these patients as well.
Metabolic Changes in Pelvic Lesions: Findings at Proton MR Spectroscopic Imaging
Authors: Hascalik Seyma , Celik Onder , Sarac Kaya , Meydanli M. Mutlu , Alkan Alpay , Mizrak Bulent
Published: May 2005

Objective: The purpose of this study is to investigate the in vivo magnetic resonance spectroscopic (MRS) features of pelvic lesions using long echo time and to characterize the spectral patterns of various pathological entities. Materials and Methods: 17patients with surgically and histopathologically confirmed pelvic lesions underwent long echo-time MRS, and the results obtained were analyzed. Before laparotomy, choline (Cho), lactate, lipid and creatine (Cr) levels of all lesions were measured by single voxel MRS (point-resolved spectroscopy technique, TE 136 ms). Voxels were placed in the center of the lesions. The MRS results of lesions were compared with the final histopathological diagnoses. Results: Spectroscopy analysis of serous, mucinous and undifferentiated carcinoma of the ovary revealed Cho, lactate and lipid signals, but granulosa-theca cell tumor showed only a lipid signal. The Cho signal was obtained from only 3 patients with mature cystic teratoma but none of the other benign ovarian tumors and pelvic abscesses. A lipid signal was detected in 3 patients diagnosed with pelvic abscess and all benign ovarian tumors. In addition to the lipid signal, a lactate signal was detected in the spectra of two pelvic abscesses. One case of endometrioma and 1 case of teratoma did not show any signal. Conclusion: MRS demonstrates significant differences in metabolite concentration between benign and malignant ovarian tumors and pelvic abscesses. MRS may therefore be helpful in the differential diagnosis of adnexal lesions.
No Effect of C-Reactive Protein on Early Atherosclerosis Development in Apolipoprotein E*3-Leiden/Human C-Reactive Protein Transgenic Mice
Authors: Trion A. , de Maat M.P.M. , Jukema J.W. , van der Laarse A. , Maas M.C. , Offerman E.H. , Havekes L.M. , Szalai A.J. , Princen H.M.G. , Emeis J.J.
Published: May 2005

Objective—C-reactive protein (CRP) has been associated with risk of cardiovascular disease. It is not clear whether CRP is causally involved in the development of atherosclerosis. Mouse CRP is not expressed at high levels under normal conditions and increases in concentration only several-fold during an acute phase response. Because the dynamic range of human CRP is much larger, apolipoprotein E*3-Leiden (E3L) transgenic mice carrying the human CRP gene offer a unique model to study the role(s) of CRP in atherosclerosis development.

Methods and Results—Atherosclerosis development was studied in 15 male and 15 female E3L/CRP mice; E3L transgenic littermates were used as controls. The mice were fed a hypercholesterolemic diet to induce atherosclerosis development. Cholesterol exposure did not differ between E3L/CRP and E3L mice. Plasma CRP levels were on average 10.2±6.5 mg/L in male E3L/CRP mice, 0.2±0.1 mg/L in female E3L/CRP mice, and undetectable in E3L mice. Quantification of atherosclerosis showed that lesion area in E3L/CRP mice was not different from that in E3L mice.

Conclusion—This study demonstrates that mildly elevated levels of CRP in plasma do not contribute to the development of early atherosclerosis in hypercholesterolemic E3L/CRP mice.
Peroxisome Proliferator-Activated Receptor-γ2 P12A Polymorphism and Risk of Coronary Heart Disease in US Men and Women
Authors: Pischon Tobias , Pai Jennifer K. , Manson JoAnn E. , Hu Frank B. , Rexrode Kathryn M. , Hunter David , Rimm Eric B.
Published: May 2005

Objective—Activation of the peroxisome proliferator-activated receptor-γ (PPARγ) improves insulin sensitivity and exerts antiatherogenic effects. A common alanine for proline substitution at codon 12 in thePPARG2gene is related to lower receptor activity. Studies suggest that the A12 allele is associated with reduced risk of type 2 diabetes; however, data on the risk of coronary heart disease (CHD) are scarce and controversial.

Methods and Results—We examined the relationship betweenPPARG2P12A and CHD risk in women (Nurses’ Health Study) and men (Health Professionals Follow-Up Study) in nested case control settings. Among participants free of cardiovascular disease at baseline, 249 women and 266 men developed nonfatal myocardial infarction (MI) or fatal CHD during 8 and 6 years of follow-up, respectively. Using risk-set sampling, controls were selected 2:1 matched on age, smoking, and date of blood draw. The relative risk (RR) of nonfatal MI or fatal CHD of carriers compared with noncarriers of the A12 allele was 1.17 (95% CI, 0.82 to 1.68) among women and 1.44 (95% CI, 1.00 to 2.07) among men (pooled RR, 1.30 [95% CI, 1.00 to 1.67]). We found a significantly increased risk associated with the A12 allele among individuals with a body mass index ≥25 kg/m2(women: RR, 1.88; 95% CI, 1.01 to 3.50; men: RR, 1.55; 95% CI, 0.92 to 2.60; pooled: RR, 1.68; 95% CI, 1.13 to 2.50) but not among those <25 kg/m2(pooled RR, 0.86; 95% CI, 0.37 to 1.97;Pheterogeneity overweight versus nonoverweight 0.16).

Conclusions—These data do not support the hypothesis that the A12 allele is associated with a decreased risk of CHD. The potential interaction betweenPPARG2P12A, overweight, and increased CHD risk needs further evaluation.
Impaired Revascularization in a Mouse Model of Type 2 Diabetes Is Associated With Dysregulation of a Complex Angiogenic-Regulatory Network
Authors: Schiekofer Stephan , Galasso Gennaro , Sato Kaori , Kraus Benjamin J. , Walsh Kenneth
Published: May 2005

Objective—

Diabetes is a risk factor for the development of cardiovascular diseases associated with impaired angiogenesis or increased endothelial cell apoptosis.

Methods and Results—

Here it is shown that angiogenic repair of ischemic hindlimbs was impaired in Lepr
db/db
mice, a leptin receptor–deficient model of diabetes, compared with wild-type (WT) C57BL/6 mice, as evaluated by laser Doppler flow and capillary density analyses. To identify molecular targets associated with this disease process, hindlimb cDNA expression profiles were created from adductor muscle of Lepr
db/db
and WT mice before and after hindlimb ischemia using Affymetrix GeneChip Mouse Expression Set microarrays. The expression patterns of numerous angiogenesis-related proteins were altered in Lepr
db/db
versus WT mice after ischemic injury. These transcripts included neuropilin-1, vascular endothelial growth factor-A, placental growth factor, elastin, and matrix metalloproteinases implicated in blood vessel growth and maintenance of vessel wall integrity.

Conclusion—

These data illustrate that impaired ischemia-induced neovascularization in type 2 diabetes is associated with the dysregulation of a complex angiogenesis-regulatory network.
Role of the Intrinsic Coagulation Pathway in Atherogenesis Assessed in Hemophilic Apolipoprotein E Knockout Mice
Authors: Khallou-Laschet J. , Caligiuri G. , Tupin E. , Gaston A.-T. , Poirier B. , Groyer E. , Urbain D. , Maisnier-Patin S. , Sarkar R. , Kaveri S.V. , Lacroix-Desmazes S. , Nicoletti A.
Published: May 2005

Objective—

The contribution of thrombosis and coagulation in atherogenesis is largely unknown. We investigated the contribution of the coagulation intrinsic factor VIII (FVIII)–dependent pathway in atherogenesis.

Methods and Results—

Apolipoprotein E and FVIII double–deficient mice (E°/FVIII°) were generated. Aortic root lesions were analyzed in 14-week-old and 22-week-old female mice maintained for 8 or 16 weeks, respectively, on a normal chow diet or a hypercholesterolemic diet.

Conclusion—

Despite a higher plasma total cholesterol concentration compared with E° mice, E°/FVIII° mice developed dramatically less early-stage atherosclerotic lesions. Whereas early lesions in E° mice contained abundant fibrin(ogen) deposits on which few platelets adhered, lesions in E°/FVIII° were almost devoid of fibrin(ogen), and no platelets could be detected. The genotype effect on development and composition of lesions tended to decrease with time. This study demonstrates that the activation of the intrinsic pathway of coagulation is potently proatherogenic at the early stage of atherogenesis.
Neuropilin-1 Regulates Vascular Endothelial Growth Factor–Mediated Endothelial Permeability
Authors: Becker Patrice M. , Waltenberger Johannes , Yachechko Robin , Mirzapoiazova Tamara , Sham James S.K. , Lee Chun Geun , Elias Jack A. , Verin Alexander D.
Published: May 2005

Neuropilin-1 (Npn-1) is a cell surface receptor that binds vascular endothelial growth factor (VEGF), a potent mediator of endothelial permeability, chemotaxis, and proliferation. In vitro, Npn-1 can complex with VEGF receptor-2 (VEGFR2) to enhance VEGFR2-mediated endothelial cell chemotaxis and proliferation. To determine the role of Npn-1/VEGFR2 complexes in VEGF-induced endothelial barrier dysfunction, endothelial cells were stably transfected with Npn1 or VEGFR2 alone (PAE/Npn and PAE/KDR, respectively), or VEGFR2 and Npn-1 (PAE/KDR/Npn-1). Permeability, estimated by measurement of transendothelial electrical resistance (TER), of PAE/Npn and PAE/KDR cell lines was not altered by VEGF
165
. In contrast, TER of PAE/KDR/Npn-1 cells decreased in dose-dependent fashion following VEGF
165
(10 to 200 ng/mL). Activation of VEGFR2, and 2 downstream signaling intermediates (p38 and ERK1/2 MAPK) involved in VEGF-mediated permeability, also increased in PAE/KDR/Npn-1. Consistent with these data, inhibition of Npn-1, but not VEGFR2, attenuated VEGF
165
-mediated permeability of human pulmonary artery endothelial cells (HPAE), and VEGF
121
(which cannot ligate Npn-1) did not alter TER of HPAE. Npn-1 inhibition also attenuated both VEGF
165
-mediated pulmonary vascular leak and activation of VEGFR2, p38, and ERK1/2 MAPK, in inducible lung-specific VEGF transgenic mice. These data support a critical role for Npn-1 in regulating endothelial barrier dysfunction in response to VEGF and suggest that activation of distinct receptor complexes may determine specificity of cellular response to VEGF.
Involvement of FrzA/sFRP-1 and the Wnt/Frizzled Pathway in Ischemic Preconditioning
Authors: Barandon Laurent , Dufourcq Pascale , Costet Pierre , Moreau Catherine , Allières Cécile , Daret Danièle , Santos Pierre Dos , Lamazière Jean-Marie Daniel , Couffinhal Thierry , Duplàa Cécile
Published: May 2005

Phosphorylation and subsequent inactivation of glycogen synthase kinase (GSK)-3β via the Akt/PI3-Kinase pathway during ischemic preconditioning (PC) has been shown to be cardioprotective. As FrzA/sFRP-1, a secreted antagonist of the Wnt/Frizzled pathway, is expressed in the heart and is able to decrease the phosphorylation of GSK-3β in vitro on vascular cells, we examined its effect during PC using transgenic mouse overexpressing FrzA in cardiomyocytes (α-MHC promoter) under a conditional transgene expression approach (tet-off system). Overexpression of FrzA inhibited the increase in GSK-3β phosphorylation as well as protein kinase C (PKC) epsilon activation in transgenic mice after PC as compared with littermates. Phospho-Akt (P-Akt), phospho-JNK, or the cytoplasmic β-catenin levels were not modified, phospho-p38 (P-p38) was slightly increased in transgenic mice after PC as compared with littermates. FrzA transgenic mice displayed a larger infarct size and a greater worsening of cardiac function compared with littermates. All these differences were reversed by the addition of doxycycline. This study demonstrates for the first time that disruption of a β-catenin independent Wnt/Frizzled pathway induces the activation of GSK-3β and reverses the benefit of preconditioning.
Communication Instruction in a Mature Institutional Partnership
Authors: Thomas Martha Wetterhall , Hardy Samuel B.
Published: May 2005

Since 1994, the University of South Carolina at Columbia and the Wirtschaftsuniversität Wien (Vienna University of Economics and Business Administration) have offered a joint master’s degree in international business. Communication instruction was initially a stable component of the program, with a week-long course at the beginning and a report-writing workshop at the end, followed by individual instruction in preparing deliverables for a consulting field project. Since the field projects were phased out in 2003, students continue to receive the one-week communication course in Vienna; after that, they have voluntary access to individual instruction from the Center for Business Communication at the University of South Carolina and exposure to in-class communication workshops as scheduled by faculty across the business disciplines. Although student feedback is positive, these instructional methods currently lack consistency. To achieve such consistency, a communication center can help to integrate instruction within MBA programs through communication intensive courses, writing studios, or a communication capstone course.
Management Communication in Non-U.S. MBA Programs
Authors: Knight Melinda
Published: May 2005

A study of top-ranked, full-time, global MBA programs suggests that management communication is indeed both an important focus and component in the curriculum. The methods of delivery, however, do not seem to follow any particular model, such as the common U.S. practice of a separate program or department. Required courses are found at 10 of the 24 schools, including two at 2 schools. Elective communication courses are offered at 8 schools, and related courses, those with a communication component, appear at all but 1 school. Communication is perceived as being an integral part of overall management development and global leadership, as opposed to a skill that could be assessed via testing or other assessment.