bluuebunny/crossref_metadata_2025 huggingface dataset:
The histamine H3 receptor: from discovery to clinical trials with pitolisant
Authors: Schwartz Jean‐Charles
Published: February 2011

The third histamine receptor was discovered in 1983 by a traditional pharmacological approach, consisting of assessing the inhibitory effect of histamine on its own release from depolarized rat brain slices. The same in vitro test was used to design, in 1987, the first highly selective and potent H3‐autoreceptor ligands, the antagonist thioperamide and the agonist (R)alphamethylhistamine which enhances and inhibits, respectively, the activity of histaminergic neurons in brain. The use of these research tools was instrumental in establishing the main functions of cerebral histaminergic neurons, namely their role in maintenance of wakefulness, attention, learning and other cognitive processes. In 1990, the cloning of the gene of the H3‐receptor, a member of the superfamily of heptahelical receptors coupled to G proteins, paved the way to the demonstration of the high constitutive activity of the receptor, including its native form, and its participation in the tonic control of histamine release; it also facilitated the development of H3‐receptor inverse agonist programs in many drug companies. Pitolisant (BF2.649, 1‐{3‐[3‐(4‐chlorophenyl)propoxy]propyl}piperidine, hydrochloride) is the first inverse agonist to be introduced in the clinics. Its wake‐promotion activity was evidenced in excessive diurnal sleepiness of patients with narcolepsy, Parkinson's disease or Obstructive Sleep Apnea/Hypopnea, in which this activity is characterized by a mean decrease of the Epworth Sleepiness Scale by about five units. The procognitive activity of this novel class of drugs may also find therapeutic applications in dementias, schizophrenia or attention deficit hyperactivity disorder.

LINKED ARTICLES

This review is dedicated to the memory of Sir James Black who recently passed away and whose achievements in classical pharmacology and drug design have been examples to the author throughout his career. BJP published an issue in 2010 on Analytical Receptor Pharmacology in Drug Discovery, which was dedicated to the memory of Sir James Black. To view this issue visit http://dx.doi.org/10.1111/bph.2010.161.issue‐6 In 2009 BJP published a Histamine themed issue. To view this issue visit http://dx.doi.org/10.1111/bph.2009.157.issue‐1
Clinging to the past: medievalism in the English ‘Renaissance’ garden
Authors: Henderson Paula
Published: February 2011

When studying the Tudor period, garden historians often over‐emphasize what is deemed new, concentrating on anything that might be linked to continental, particularly Italianate, influences. If some of the greatest architectural triumphs of the period were a quirky combination of ‘antiquarian medieval’ motifs (Wollaton Hall's traceried windows and soaring tourelles, for example) with sophisticated continental features (Wollaton's Italianate plan), it seems likely that the same eclecticism would have been employed in gardens. What needs to be examined is what Tudor builders knew about earlier gardens in Britain (or elsewhere). Because the period is so often treated as a ‘beginning’ (of the early modern period), what remained of important royal and aristocratic medieval gardens, both materially and in the collective memory, has not been adequately determined. Once we have a proper understanding of what survived to be admired by the Tudors, we might be able to assess how gardens reflected both indigenous and Renaissance ideas. Perhaps the best way to differentiate between medieval and classical inspiration is to look carefully at the evolution of individual garden features – fountains, garden buildings, earthworks, planting and basic principles of design – to determine at what point classical ideas began to dominate and when medieval features were revived and to what purpose.
Dissembling his art: ‘Gascoigne's Gardnings’
Authors: Staub Susan C.
Published: February 2011

This essay considers how garden and agricultural manuals from the sixteenth and early seventeenth centuries provide insight into George Gascoigne's negotiation of his role as professional writer in A Hundreth Sundrie Flowres and The Posies. By considering Gascoigne's collection in conjunction with gardening books from the period, we can see more clearly the issues Gascoigne confronts, issues that seem inextricably involved with print culture and changing social values. The same concerns that permeate so much of Gascoigne's work are evident in the gardening manuals of the period with their interrogation of profit and pleasure, art and nature, the reliability of sources – and with their obsession with the vulgarity of men who wrote or gardened for profit. Recent scholarship also suggests the connection between the garden manual and notions of nationhood, the history of the book, and the burgeoning print marketplace – all issues apparent in Gascoigne's work. Gascoigne's analogy then is more than just a convention and is fundamentally connected to the ways that he fashions his identity as gentleman, author, and Englishman.
Association between occult hepatitis B infection and the risk of hepatocellular carcinoma: a meta‐analysis
Authors: Shi Yu , Wu Yi Hua , Wu Wei , Zhang Wan Jun , Yang Jun , Chen Zhi
Published: February 2011

Background: The association between occult hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) remains controversial.

Aims: We conducted a meta‐analysis of prospective studies and retrospective studies to examine whether occult HBV infection increases the risk of HCC.

Methods: Two independent reviewers searched databases for eligible studies published in English or Chinese dated from 1966 to 6 April 2010. The odds ratios or the relative risks (RRs) of each study were considered respectively.

Results: We identified 16 eligible studies. A significantly increased risk of HCC was found in subjects with occult HBV infection in comparison with non‐infected controls in both retrospective [ORunadjusted=6.08, 95% confidence interval (CI)=3.45–10.72] and prospective studies (RRadjusted=2.86, 95% CI=1.59–4.13), and occult HBV increased the risk for HCC in both hepatitis C virus (HCV)‐infected populations (summary RR=2.83, 95% CI=1.56–4.10) and in non‐infected populations (ORunadjusted=10.65, 95% CI=5.94–19.08). A higher prevalence of occult HBV was observed in individuals who were positive for anti‐HBs and anti‐HBc (ORunadjusted=1.81, 95% CI=1.06, 3.09).

Conclusion: Our findings suggest that occult HBV infection was associated with an increased risk of HCC. Occult HBV may serve as a cofactor in the development of HCV‐related HCC, and it may also play a direct role in promoting Non‐B and Non‐C HCC growth. Suggestive evidence indicates that individuals with a concomitant presence of anti‐HBs and anti‐HBc had an increased risk of occult HBV infection. However, further studies are needed to clarify these observations.
Quality of the daylight sources for industrial colour control
Authors: Hirschler Robert , Oliveira Danielle F , Lopes Lincoln C
Published: February 2011

Information is presented based on measurements, published literature and the findings of the CIE Technical Committee TC1‐44 Practical Daylight Sources for Colorimetry. For visual colour control, filtered incandescent lamps, filtered xenon short‐arc lamps, fluorescent lamps and light‐emitting diode sources are used as daylight simulators, while, in today’s industrial reflectance spectrophotometers, pulsed xenon lamps are used. Practical daylight simulators exist with characteristics satisfying the major national and international standards, but most of the commercially available colour‐matching booths do not comply with these standards, in spite of the claims made by manufacturers. For instrumental control, well‐maintained and calibrated sources may provide acceptable daylight simulation.
Genetic contribution to the relationship between social role function and depressive symptoms in Japanese elderly twins: a twin study
Authors: NISHIHARA Reiko , INUI Fujio , KATO Kenji , TOMIZAWA Rie , HAYAKAWA Kazuo
Published: February 2011

Background:  Social role function is the capacity to maintain interpersonal relationships and is essential for being independent in the community. Limitations in social role function often coexist with depressive symptoms, suggesting a possible common mechanistic basis. We investigated whether the observed association between these traits is mainly a result of genetic or environmental influences.

Methods:  In 2008, a questionnaire was sent to 745 male twins aged 65 years and older. Our sample included 397 male twins. The number of monozygotic twins was 302, and dizygotic was 95. Among the twin pairs for whom data were available for both twins, 75 twin pairs (150 individuals) were monozygotic and 28 pairs (56 individuals) were dizygotic. Social role function was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Depressive symptoms were measured by the 15‐item version of the Geriatric Depression Scale. Relative importance of genes and environments for the phenotypes was calculated using structural equation analyses.

Results:  Our results show that genetic influence was the major contributor to the relationship between social role function and depressive symptoms, and non‐shared environmental influence was important for overall variation in each trait.

Conclusions:  We concluded that focusing on a non‐shared environment is an essential approach for maintaining social role function and psychological well‐being. It is suggested that treatments specific to depressive symptoms are more effective than indirect intervention targeting social role function.
Impact of dementia on cancer discovery and pain
Authors: IRITANI Shuji , TOHGI Mizuho , MIYATA Hiroaki , OHI Gen
Published: February 2011

Background:  Dementia is clinically noted to influence both reporting and experience of cancer pains. However, no systemic evaluation of this aspect has been reported. The aim of the present study was to retrospectively evaluate how dementia modified the cancer discovery process, frequency of cancer pain reports and analgesic‐narcotic use at a large psychiatric hospital.

Methods:  We reviewed all the records of cancer patients with and without dementia treated at the surgical ward of Matsuzawa Hospital from 1993 to 2004. Psychiatric diseases other than dementia, brain metastasis and alcoholism, as well as leukaemia and skin cancer, were excluded. Patients' communicativeness as to pain was ascertained from nursing records.

Results:  A total of 134 cancer patients with and without dementia (50 demented and 84 non‐demented) were included. Demented patients were accidentally discovered to have cancer (48%) or by an unexpected unfolding of clinical signs (44%), whereas most non‐demented patients (63%) voluntarily sought medical evaluation (P= 0.000). Overall, 76% of non‐demented patients had cancer pains (stages I and II, 64%; stages III and IV, 84%), whereas just 22% of demented patients had cancer pains (stages I and II, 16%; stages III and IV, 26%; P= 0.000). Non‐demented patients showed stage‐dependent requirements for both non‐narcotic analgesics (stages I and II, 64%; stages III and IV, 84%) and narcotics (stages I and II, 0%; stages III and IV, 41%). Demented patients required much less analgesics (stages I and II, 11%; stages III and IV, 13%), with only one stage IV patient requiring narcotics (P= 0.000).

Conclusion:  Dementia greatly modifies the cancer discovery process, reduces prevalence of cancer pain and analgesic requirement.
Touch Panel‐type Dementia Assessment Scale: a new computer‐based rating scale for Alzheimer's disease
Authors: INOUE Masashi , JIMBO Daiki , TANIGUCHI Miyako , URAKAMI Katsuya
Published: February 2011

Background:  The Alzheimer's Disease Assessment Scale (ADAS) was designed as a rating scale for the severity of dysfunction in the cognitive and non‐cognitive behaviours that are characteristic of persons with Alzheimer's disease. Its subscale, the ADAS‐cog, is a cognitive testing instrument most widely used to measure the impact of the disease. However, the ADAS‐cog takes more than 45 min to administer and requires a qualified clinical psychologist as the rater. A more comprehensive rating battery is therefore required. In the present study, we developed a computerized test battery named the Touch Panel‐type Dementia Assessment Scale (TDAS), which was intended to substitute for the ADAS‐Cog, and was specifically designed to rate cognitive dysfunction quickly and without the need of a specialist rater.

Methods:  The hardware for the TDAS comprises a 14‐inch touch panel display and computer devices built into one case. The TDAS runs on Windows OS and was bundled with a custom program made with reference to the ADAS‐cog. Participants in the present study were 34 patients with Alzheimer's disease. Each participant was administered the ADAS‐cog and the TDAS. The test scores for each patient were compared to determine whether the severity of cognitive dysfunction of the patients could be rated equally as well by both tests.

Results:  Pearson's correlation coefficient showed a significant correlation between the total scores (r= 0.69, P < 0.01) on the two scales for each patient. The Kendall coefficients of concordance obtained for the three corresponding pairs of tasks (word recognition, orientation, and naming object and fingers) showed the three TDAS tasks can rate symptoms of cognitive decline equally as well as the corresponding items on the ADAS‐cog.

Conclusions:  The TDAS appears to be a sensitive and comprehensive assessment battery for rating the symptoms of Alzheimer's disease, and can be substituted for the ADAS‐cog.
Genetic association between clusterin polymorphisms and Alzheimer's disease in a Japanese population
Authors: KOMATSU Miwa , SHIBATA Nobuto , KUERBAN Bolati , OHNUMA Tohru , BABA Hajime , ARAI Heii
Published: February 2011

Background:  Previous papers have reported that clusterin (CLU, also called apolipoprotein J) maintains amyloid β‐peptide (Aβ) solubility and protects against Aβ neurotoxicity. Recently, two large genome‐wide association studies (GWAS) identified that a specific single nucleotide polymorphism (SNP) on the gene has been reported to modify the risk for Alzheimer's disease (AD). The present study aimed to investigate whether common single nucleotide polymorphisms (SNP) of the CLU gene are associated with AD.

Methods:  Six SNP, genotyped using TaqMan technology, were analyzed using a case–control study design. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case–control dataset consisted of 180 AD patients and 130 age‐matched controls.

Results:  The present study failed to detect any association between the SNP of the CLU gene and AD. Although rs7982 and rs1532277 showed marginal association in the APO E4 negative group, the linkage disequilibrium analysis results suggest this to be a false positive.

Conclusion:  The negative associations were mainly the result of our small sample size. Larger genetic studies in different ethnics and future meta‐analysis are needed to clarify the relationship between the CLU gene and AD.
Effects of a topical enamel matrix derivative on skin wound healing
Authors: Mirastschuski Ursula , Konrad Daniel , Lundberg Eva , Lyngstadaas Staale Petter , Jorgensen Lars N. , Ågren Magnus S.
Published: February 2011

Enamel matrix derivative, obtained from developing porcine teeth, is composed mainly of amelogenin proteins and used topically in periodontal surgery for advanced periodontitis to regenerate lost connective tissues. The primary objective of this study was to investigate the effects of enamel matrix derivative on skin wound healing. Secondly, in vitro effects of enamel matrix derivative on dermal fibroblasts and microvascular endothelial cells were examined. Full‐thickness, circular 2‐cm skin wounds in white 16‐week‐old rabbits were treated thrice weekly with enamel matrix derivative (30 mg/ml) in the vehicle propylene glycol alginate or with vehicle alone. Enamel matrix derivative treatment increased the amount of granulation tissue and accelerated time to complete epithelialization by 3 days (ρ < 0.001) compared to vehicle treatment. In cultured fibroblasts, vascular endothelial growth factor levels in conditioned media were increased more than fivefold (ρ < 0.001) with enamel matrix derivative treatment (0.1 mg/ml) over control, measured by specific enzyme‐linked immunosorbent assay. Enamel matrix derivative also increased release of matrix metalloproteinase‐2 more than threefold from fibroblasts (ρ < 0.001) and from endothelial cells (ρ < 0.001). Thus, enamel matrix derivative significantly accelerated wound closure in rabbits, possibly by increasing levels of growth factors and proteinases important for granulation tissue formation and remodeling.
Alternative Headache Treatments: Nutraceuticals, Behavioral and Physical Treatments
Authors: Sun‐Edelstein Christina , Mauskop Alexander
Published: February 2011

There is a growing body of evidence supporting the efficacy of various complementary and alternative medicine approaches in the management of headache disorders. These treatment modalities include nutraceutical, physical and behavioral therapies. Nutraceutical options comprise vitamins and supplements (magnesium, riboflavin, coenzyme Q10, and alpha lipoic acid) and herbal preparations (feverfew, and butterbur). Although controversial, there are some reports demonstrating the benefit of recreational drugs such as marijuana, lysergic acid diethylamide and psilocybin in headache treatment. Behavioral treatments generally refer to cognitive behavioral therapy and biobehavioral training (biofeedback, relaxation training). Physical treatments in headache management are not as well defined but usually include acupuncture, oxygen therapy, transcutaneous electrical nerve stimulation, occlusal adjustment, cervical manipulation, physical therapy, massage, chiropractic therapy, and osteopathic manipulation. In this review, the available evidence for all these treatments will be discussed.
Effect of the Selective NMDA NR2B Antagonist, Ifenprodil, on Acute Tolerance to Ethanol‐Induced Motor Impairment in Adolescent and Adult Rats
Authors: Ramirez Ruby Liane , Varlinskaya Elena I. , Spear Linda P.
Published: February 2011

Background:  Adolescent rats have been observed to be less sensitive than adults to a number of acute ethanol effects, including ethanol‐induced motor impairment. These adolescent insensitivities may be related in part to the more rapid emergence of within session (acute) tolerance in adolescents than adults. Adolescent‐related alterations in neural systems that serve as ethanol target sites, including changes in NMDA receptor subunit expression, may influence the responsiveness of adolescents to acute ethanol effects. This study explored the role of NMDA NR2B receptors in the development of acute tolerance to ethanol‐induced motor impairment in male adolescent [postnatal day (P)28–30] and adult (P68–70) Sprague–Dawley rats.

Methods:  Motor‐impairing effects of ethanol on the stationary inclined plane and blood ethanol concentrations (BECs) were examined following challenge at each age with a functionally equivalent ethanol dose (adolescents: 2.25 g/kg; adults: 1.5 g/kg). Data were collected at two postinjection intervals (10 or 60 minutes) to compare rate of recovery from ethanol intoxication with BEC declines using the Radlow approach (Radlow, 1994) and changes in motor impairment/BEC ratios over time for assessing acute tolerance.

Results:  Both vehicle‐treated adolescent and adult animals showed similar acute tolerance development to the motor‐impairing effects of ethanol at these functionally equivalent doses on the stationary inclined plane, as indexed by an increasing time‐dependent dissociation between BECs and ethanol‐induced motor impairment, with motor impairment declining faster than BECs, as well as by significant declines in motor impairment/BEC ratios over time. Acute tolerance development was reliably blocked by administration of the NR2B antagonist, ifenprodil, (5.0 mg/kg), in adult rats, whereas adolescents were affected by a higher dose (10.0 mg/kg).

Conclusions:  These data support the suggestion that alterations in NMDA receptor systems occurring during adolescence may contribute to reduced sensitivity to ethanol by enhancing the expression of acute tolerance development in adolescents relative to adults.
Event‐Related Potentials During Visual Target Detection in Treatment‐Naïve Active Alcoholics
Authors: Fein George , Andrew Colin
Published: February 2011

Background:  Reduced P3b event‐related potentials (ERP) amplitude during visual target detection in alcoholics is a robust phenomenon. However, this finding is based primarily on samples of treated alcoholics, who comprise only about 25% of alcoholics. We studied visual target detection in a treatment‐naïve alcohol‐dependent sample (TNAD) versus age and gender comparable nonalcoholic controls (NAC) to investigate whether reduced P3 amplitudes generalize to TNAD.

Methods:  EEGs were recorded from 74 TNAD and 63 age and gender comparable NAC during visual target detection. ANOVA was applied at midline electrodes to amplitudes and latencies of N2 and P3 ERP components during target and rare nontarget conditions.

Results:  Treatment‐naïve alcohol‐dependent subjects had a modestly lower P3b amplitude (p = 0.05) and a more robustly lower N2b amplitude (p = 0.29). In the target condition, TNAD showed a significant reduction in P3b amplitude and a larger reduction in N2b amplitude, with these phenomena being independent of each other. Latencies to P3b, N2b, and P3a were earlier in TNAD than NAC, with this effect correlating with our reported effect of better attention in TNAD versus NAC.

Conclusion:  The significant reduction in P3b amplitude in TNAD suggests that this phenomenon is present in TNAD, but dramatically smaller than that observed in treated samples (we reported an effect over 5 times as large in treated long‐term abstinent alcoholics). The N2b amplitude reduction (not present in long‐term abstinent alcoholics) may reflect the effects of active alcohol abuse. Finally, the shorter latencies of these components in TNAD is associated with better scores on tests of attention and may reflect compensatory attentional effort in the context of active drinking.
A comparison of fibrinogen measurement methods with fibrin clot elasticity assessed by thromboelastometry, before and after administration of fibrinogen concentrate in cardiac surgery patients
Authors: Solomon Cristina , Cadamuro Janne , Ziegler Bernhard , Schöchl Herbert , Varvenne Michael , Sørensen Benny , Hochleitner Gerald , Rahe‐Meyer Niels
Published: February 2011

BACKGROUND: Fibrinogen concentrate administration can be guided by measuring fibrinogen concentration or quality of the fibrin‐based clot. This study compared different fibrinogen concentration measurement methods with maximum clot firmness (MCF) of the fibrin clot, assessed by thromboelastometry (FIBTEM), in 33 cardiovascular surgery patients receiving fibrinogen concentrate for hemostatic therapy.

STUDY DESIGN AND METHODS: Blood samples were collected after cardiopulmonary bypass (CPB) and after fibrinogen concentrate administration. FIBTEM MCF was measured using a rotational thromboelastometry device (ROTEM, Tem International). Fibrinogen concentration was measured using photo‐optical (CA‐7000, Siemens Healthcare Diagnostics), mechanical (KC‐10 steel ball, Schnitger and Gross hook, Amelung GmbH), and electromechanical (STA‐R, Diagnostica Stago) coagulometers. Assessments included agreement between fibrinogen concentration measurements and correlations between fibrinogen concentration and FIBTEM MCF.

RESULTS: After CPB, correlations were significant (p < 0.001) between FIBTEM MCF and fibrinogen concentration determined by steel ball (r = 0.71), hook (r = 0.73), STA‐R (r = 0.81), and CA‐7000 (r = 0.82) coagulometers. After fibrinogen concentrate administration, agreement between fibrinogen measurement methods was severely impaired, and correlations with FIBTEM MCF were 0.39 (steel ball), 0.33 (hook), 0.59 (STA‐R), and 0.33 (CA‐7000).

CONCLUSION: Agreement between fibrinogen concentration measurement methods decreased considerably after fibrinogen concentrate administration. All methods correlated acceptably with FIBTEM MCF at the end of CPB, but not after hemostatic therapy. Further investigation is needed to explain these findings.
Teaching Assistants’ Self‐Efficacy in Teaching Literature: Sources, Personal Assessments, and Consequences
Authors: MILLS NICOLE
Published: February 2011

Byrnes (2001) has suggested that the disconnection between language and literature instruction within many foreign language departments has consequences on the professionalization of graduate students. These structural issues lead to questions about graduate students’ development. How do teaching assistants (TAs) perceive their competency as “language” and “literature” instructors? What are the sources and consequences of their self‐beliefs? Teacher self‐efficacy (TSE), or a teacher's perception of his or her capabilities to bring about desired objectives in student engagement and learning (Tschannen‐Moran & Woolfolk‐Hoy, 2001), was explored to gain insight into TAs’ perceptions of teaching competence. This qualitative study evaluated 10 French literature doctoral students’ TSE beliefs to teach literature and their accompanying sources, personal assessments and analyses, and consequences. Results revealed that although the TAs found the graduate program to be highly effective in its formation of literary scholars and language instructors, they found that the pedagogy of literature “falls in a gap between these two holes” (teaching assistant, study data excerpt).
The Economic Impact of Anticipated House Price Changes—Evidence from Home Sales
Authors: Miller Norman G. , Peng Liang , Sklarz Michael A.
Published: February 2011

If realized house prices have the wealth effect and the collateral effect on the economy, anticipated house price changes should have similar economic effects. This article empirically analyzes the effects of single‐family home sales, which are shown to be able to predict house prices in the literature, on economic production, using 372 metropolitan statistic areas in the United States from the first quarter of 1981 to the second quarter of 2008 in a panel vector error correction model. Changes in home sales are found to Granger because the growth rate of per‐capita gross metropolitan product and the dynamic effects are visualized with impulse response functions. Supporting evidence for the economic impact of home sales is also found in contemporaneous regressions.
The Wealth Effects of Property Acquisitions: Evidence from Japanese and Singaporean REITs
Authors: Ooi Joseph T.L. , Ong Seow‐Eng , Neo Poh‐Har
Published: February 2011

This article examines the wealth effects of 228 property acquisition announcements made by REITs publicly traded in Singapore and Japan, which are the two largest REIT markets in Asia. Adopting an aggressive growth‐by‐acquisition strategy, the newly listed REITs acquired a number of properties within a short time period. Despite their regular activities, we observe the acquisition announcements are associated with a significantly positive abnormal increase in shareholder wealth averaging 0.38% in a 5‐day window around the event date. Controlling for the method of payment, buyer's acquisition strategy and seller's relationship with the acquiring REIT, the regression results show that the likely sources of economic gains associated with acquisitions are economies of scale and better management by acquiring firms. We also find strong evidence that the market reacts less favorably to acquisitions involving a portfolio of properties as opposed to a single property and weaker evidence that it reacts less favorably to mixed‐use acquisitions. These findings suggest the presence of premiums on transparency and corporate focus.
Market Conditions and Housing Choices: A Comparison of Homeownership Across Three Decades
Authors: Boehm Thomas P. , Schlottmann Alan M.
Published: February 2011

This article uses information on out‐of‐pocket housing cost and house price appreciation along with the geo‐coded version of the Panel Study of Income Dynamics to consider the differences in the impact of these and other variables on the tenure choices of sample households across three time periods, the 1970s, the 1980s and the 1990s. Specifically, an extended continuous time probability model is used to examine households' transitions from renting to owning and subsequent possible transitions either back to rental tenure or to another owned home during our three observation periods. Coefficient estimates show that financial variables such as house price appreciation and out‐of‐pocket housing cost play an important role in determining all the transitions. In addition, the analysis demonstrates the interesting result that the cumulative likelihoods of homeownership derived from the model are consistently lower than the probabilities of an initial transition to homeownership from rental tenure during the observation period. Finally, the magnitude and timing of the impact on homeownership of a policy experiment that eliminates the mortgage interest deduction are shown to differ substantially across the three decades.
Rescue and Worsening of Congenital Heart Block‐Associated Electrocardiographic Abnormalities in Two Transgenic Mice
Authors: KARNABI EDDY , QU YONGXIA , MANCARELLA SALVATORE , BOUTJDIR MOHAMED
Published: February 2011

Transgenic Murine Models of CHB. Introduction: Congenital heart block (CHB) is a passively acquired autoimmune disease considered to be due to the transfer of maternal autoantibodies, anti‐SSA/Ro –SSB/La, to the fetus resulting in atrioventricular (AV) block and sinus bradycardia. We previously established a murine model for CHB where pups born to immunized wild‐type (WT) mothers exhibited electrocardiographic abnormalities similar to those seen in CHB and demonstrated inhibition of L‐type Ca channels (LTCCs) by maternal antibodies. Here, we hypothesize that overexpression of LTCC should rescue, whereas knockout of LTCC should worsen the electrocardiographic abnormalities in mice.

Methods and Results: Transgenic (TG) mice were immunized with SSA/Ro and SSB/La antigens. Pups born to immunized WT mothers had significantly greater sinus bradycardia and AV block compared to pups from nonimmunized WT. TG pups overexpressing LTCC had significantly less sinus bradycardia and AV block compared to their non‐TG littermates and to pups born to immunized WT mothers. All LTCC knockout pups born to immunized mothers had sinus bradycardia, advanced degree of AV block, and decreased fetal parity. No sinus bradycardia or AV block were manifested in pups from control nonimmunized WT mothers. IgG from mothers with CHB children, but not normal IgG, completely inhibited intracellular Ca transient ([Ca]iT) amplitude.

Conclusions: Cardiac‐specific overexpression of LTCC significantly reduced the incidence of AV block and sinus bradycardia in pups exposed to anti‐SSA/Ro ‐SSB/La autoantibodies, whereas exposure of LTCC knockout pups to these autoantibodies significantly worsened the electrocardiographic abnormalities. These findings support the hypothesis that maternal antibodies inhibit LTCC and [Ca]iT thus contributing to the development of CHB. Altogether, the results are relevant to the development of novel therapies for CHB. (J Cardiovasc Electrophysiol, Vol. 22, pp. 922‐930, August 2011)
Effect of Intravenous Dipyridamole on Coronary Flow Parameters in Patients with Isolated Coronary Artery Ectasia: Assessment by Transesophageal Echocardiography
Authors: Hossam Khaled , AbdelDayem Tarek M.K. , Gamal Mohamed , Ismail Mohamed , Nammas Wail , Abdel‐Dayem M. Khairy
Published: February 2011

Background: In a prospective study design, we sought to assess the effect of dipyridamole on coronary flow parameters in patients with isolated coronary artery ectasia (CAE) as compared to subjects with normal coronaries. Methods: We enrolled 30 patients with ectasia of the left anterior descending (LAD) artery (study group), and 10 subjects with normal coronaries (control group). All subjects underwent transesophageal echocardiography to record flow velocities in the proximal LAD coronary artery, and velocity time integrals were calculated. The diameter of the proximal LAD coronary artery was measured and flow was calculated. Dipyridamole (0.56 mg/kg) was administered intravenously and measurements were repeated 5 minutes later. Results: At baseline, systolic and diastolic velocities, systolic, diastolic, and total velocity time integrals were significantly higher in the control group (P < 0.05 for all), yet, systolic, diastolic, and total coronary flow were significantly higher in the study group (P < 0.05 for all). Following dipyridamole administration, systolic, diastolic, and total coronary flow were still significantly higher in the study group (P < 0.05 for all), yet, there was no significant difference between the two groups regarding the other parameters, and regarding coronary reserve values (P > 0.05 for all). Conclusions: We concluded that patients with isolated CAE have a higher resting coronary flow as compared to control subjects with normal coronaries. Intravenous dipyridamole administration in these patients maintained a significantly higher coronary flow, with a coronary flow reserve similar to controls. (Echocardiography 2011;28:350‐357)
Controlled Mild Hypothermia Prolongs Survival in a Rat Model of Large Scald Burns
Authors: Singer Adam J. , Wang Eric , Taira Breena R. , Steinhauff Nicole , Rooney Jean , Zimmerman Thomas
Published: February 2011

ACADEMIC EMERGENCY MEDICINE 2011; 18:287–291 © 2011 by the Society for Academic Emergency Medicine

Objectives:  Early surface cooling of burns reduces pain and depth of injury and improves healing. However, there are concerns that cooling of large burns may result in hypothermia and worsen outcomes. In contrast, controlled mild hypothermia improves outcomes after cardiac arrest and traumatic brain injury. The authors hypothesized that controlled mild hypothermia would prolong survival in a rat model of large scald burns.

Methods:  Thirty‐six Sprague‐Dawley rats (250–300 g) were anesthetized with 40 mg/kg intramuscular ketamine and 5 mg/kg xylazine, with supplemental inhalational isoflurane as needed. A single full‐thickness scald burn covering 40% of total body surface area was created on each of the rats using a Mason‐Walker template placed in boiling water (100°C) for a period of 10 seconds. The rats were then randomized to hypothermia (n = 18) or no hypothermia (n = 18). Core body temperature was continuously monitored with a rectal temperature probe. In the experimental group, mild hypothermia was induced by applying ice packs over the prone rats until their rectal temperature was reduced by 2°C for a period of 2 hours. After 2 hours of hypothermia, the rats were rewarmed back to their baseline temperature with a heating pad. The control rats were not cooled. The rats were monitored until death or for a period of 7 days, whichever was greater. The primary outcome was time to death. The difference in survival between the groups was determined using Kaplan‐Meier analysis and the log‐rank test.

Results:  Hypothermia was induced in all experimental rats within a mean of 22 minutes (95% confidence interval [CI] = 17 to 27). The numbers of nonhypothermic and hypothermic rats that were dead at each time point were as follows: 2 hours, five versus none; 18 hours, 16 versus five; 24 hours, 18 versus eight; and 48 hours, 18 versus 13 (p = 0.05). There were no additional deaths after 48 hours. The mean time to survival of the hypothermic rats was significantly greater than that of the nonhypothermic rats (p < 0.001).

Conclusions:  Induction of brief, mild hypothermia prolongs survival and increases the survival rate in nonresuscitated rats with large scald burns.

ACADEMIC EMERGENCY MEDICINE 2011; 18:1–5 © 2011 by the Society for Academic Emergency Medicine
Orbital Fracture Clinical Decision Rule Development: Burden of Disease and Use of a Mandatory Electronic Survey Instrument
Authors: Yadav Kabir , Cowan Ethan , Wall Stephen , Gennis Paul
Published: February 2011

ACADEMIC EMERGENCY MEDICINE 2011; 18:313–316 © 2011 by the Society for Academic Emergency Medicine

Objectives:  In preparation for development of a clinical decision rule (CDR) to promote more efficient use of computed tomography (CT) for diagnosing orbital fractures, the authors sought to estimate the annual incidence of orbital fractures in emergency departments (EDs) and the usage of CT to make these diagnoses. The authors also sought to evaluate a mandatory electronic data collection instrument (EDCI) administered to providers to facilitate CDR data collection.

Methods:  National estimates were made by analyzing the 2007 National Hospital Ambulatory Medical Care Survey (NHAMCS) database, while hospital billing system and coding data were used to make local estimates. An EDCI was integrated into the CT ordering system such that providers had to complete the form to perform a CT. Because the EDCI had to be filled out for every CT ordered, data collection efficiency was measured by compliance (counting the number of unrealistic data collection instrument answers) and by timing a convenience sample of providers completing the EDCI.

Results:  Out of 116.8 million ED visits in the United States in 2007, 4.1 million patients were treated for injuries of the eye and face. Of those, 820,252 patients underwent CT imaging, with 102,999 patients (12.5%) diagnosed with an orbital fracture. In our local hospital system with 122,500 annual ED visits, 752 CTs of orbits were performed, with 172 (23%) orbital fractures. The EDCI compliance rate was 94.9% and took less than 5 minutes to complete.

Conclusions:  National and local data demonstrate a low yield for CT imaging in identifying orbital fractures. Data collection using a mandatory EDCI linked to computerized provider order entry can provide prospective, consecutive patient data that are needed to develop a CDR for the selective use of CT imaging in orbital trauma. Such a decision rule could increase the efficiency in diagnosing orbital fractures, thereby improving patient care, reducing radiation exposure, and decreasing costs.

ACADEMIC EMERGENCY MEDICINE 2011; 18:1–4 © 2011 by the Society for Academic Emergency Medicine
Regeneration of infarcted myocardium with resveratrol‐modified cardiac stem cells
Authors: Gorbunov Nikolai , Petrovski Goran , Gurusamy Narasimman , Ray Diptarka , Kim Do Han , Das Dipak K.
Published: February 2011

The major problem in stem cell therapy includes viability and engraftment efficacy of stem cells after transplantation. Indeed, the vast majority of host‐transfused cells do not survive beyond 24–72 hrs. To increase the survival and engraftment of implanted cardiac stem cells in the host, we developed a technique of treating these cells with resveratrol, and tested it in a rat model of left anterior descending (LAD) occlusion. Multi‐potent clonogenic cardiac stem cells isolated from rat heart and stably transfected with EGFP were pre‐treated with 2.5 μM resveratrol for 60 min. Rats were anaesthetized, hearts opened and the LAD occluded to induce heart attack. One week later, the cardiac reduced environment was confirmed in resveratrol treated rat hearts by the enhanced expression of nuclear factor‐E2‐related factor‐2 (Nrf2) and redox effector factor‐1 (Ref‐1). M‐mode echocardiography after stem cell therapy, showed improvement in cardiac function (left ventricular ejection fraction, fractional shortening and cardiac output) in both, the treated and control group after 7 days, but only resveratrol‐modified stem cell group revealed improvement in cardiac function at the end of 1, 2 and 4 months time. The improvement of cardiac function was accompanied by enhanced stem cell survival and engraftment as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the expression of EGFP up to 4 months after LAD occlusion in the resveratrol‐treated stem cell group. Expression of stromal cell‐derived factor and myosin conclusively demonstrated homing of stem cells in the infarcted myocardium, its regeneration leading to improvement of cardiac function.
The potential utility of telomere‐related markers for cancer diagnosis
Authors: Heaphy Christopher M. , Meeker Alan K.
Published: February 2011

Introduction

Methods for telomere length and telomerase detection

Telomere length as a potential diagnostic marker in cancer

Telomerase activity as a potential diagnostic marker in cancer

Future directions

Conclusions

The role telomeres and telomerase play in the initiation and progression of human cancers has been extensively evaluated. Telomeres are nucleoprotein complexes comprising the hexanucleotide DNA repeat sequence, TTAGGG and numerous telomere‐associated proteins, including the six member Shelterin complex. The main function of the telomere is to stabilize the ends of the chromosomes. However, through multiple mechanisms, telomeres can become dysfunctional, which may drive genomic instability leading to the development of cancer. The majority of human cancers maintain, or actively lengthen, telomeres through up‐regulation of the reverse transcriptase telomerase. Because there are significant differences in telomere length and telomerase activity between malignant and non‐malignant tissues, many investigations have assessed the potential to utilize these molecular markers for cancer diagnosis. Here, we critically evaluate whether measurements of telomere lengths and telomerase levels may be clinically utilized as diagnostic markers in solid tumours, with emphasis on breast and prostate cancer as representative examples. Future directions focusing on the direct detection of dysfunctional telomeres are explored. New markers for telomere dysfunction may eventually prove clinically useful.
Two patterns of development of interstitial cells of Cajal in the human duodenum
Authors: Radenkovic Goran
Published: February 2011

At the end of the embryonic period of human development, c‐kit immunoreactive (c‐kit IR) cells identifiable as interstitial cells of Cajal (ICC) are present in the oesophagus and stomach wall. In the small and large bowel, c‐kit‐IR cells appear later (in the small bowel at 9 weeks, and in the colon at 10–12 weeks), also in the MP region. The object of this study was to determine the timing of appearance and distribution of c‐kit IR cells in the human embryonic and foetal duodenum. I used immunohistochemistry to examine the embryonic and foetal duodenum for cells expressing CD117 (Kit), expressed by mature ICC and ICC progenitor cells and CD34 to identify presumed ICC progenitors. Enteric plexuses were examined by way of antineuron‐specific enolase and the differentiation of smooth muscle cells was studied using antidesmin antibodies. At the end of the embryonic period of development, c‐kit IR cells were solely present in the proximal duodenum in the form of a wide belt of densely packed cells around the inception of the myenteric plexus (MP) ganglia. In the distal duodenum, c‐kit IR cells emerged at the beginning of the foetal period in the form of thin rows of pleomorphic cells at the level of the MP. From the beginning of the fourth month, the differences in the distribution of ICC in the different portions of the duodenum were established, and this relationship was still present in later developmental stages. In fact, in the proximal duodenum, ICC of the MP (ICC‐MP), ICC of the circular muscle (ICC‐CM) and ICC of the septa (ICC‐SEP) were present, and in the distal duodenum ICC‐MP and ICC‐SEP only. In conclusion, in the humans there is a difference in the timing and patterns of development of ICC in the proximal duodenum compared to the distal duodenum.
Clustering of polyclonal VanB‐type vancomycin‐resistant Enterococcus faecium in a low‐endemic area was associated with CC17‐genogroup strains harbouring transferable vanB2‐Tn5382 and pRUM‐like repA containing plasmids with axe‐txe plasmid addiction systems
Authors: BJØRKENG EVA , RASMUSSEN GUNLÖG , SUNDSFJORD ARNFINN , SJÖBERG LENNART , HEGSTAD KRISTIN , SÖDERQUIST BO
Published: February 2011

Bjørkeng E, Rasmussen G, Sundsfjord A, Sjöberg L, Hegstad K, Söderquist B. Clustering of polyclonal VanB‐type vancomycin‐resistant Enterococcus faecium in a low‐endemic area was associated with CC17‐genogroup strains harbouring transferable vanB2‐Tn5382 and pRUM‐like repA containing plasmids with axe‐txe plasmid addiction systems. APMIS 2011; 119: 247–58.

VanB‐type vancomycin‐resistant Enterococcus faecium isolates (n = 17) from 15 patients at the Örebro University hospital in Sweden during a span of 18 months was characterized. All patients had underlying disorders and received broad‐spectrum antimicrobial therapy. Pulsed‐field gel electrophoresis (PFGE) grouped 14 isolates in three PFGE types and three isolates in unique PFGE patterns. All isolates had multi‐locus sequence types [ST17 (n = 5); ST18 (n = 3); ST125 (n = 7); ST262 (n = 1); ST460 (n = 1)] belonging to the successful hospital‐adapted clonal complex 17 (CC17), harboured CC17‐associated virulence genes, were vanB2‐positive and expressed diverse vancomycin minimum inhibitory concentration (MICs; 8 to >256 mg/L). Isolate 1 had a unique PFGE type and a chromosomal transferable vanB2‐Tn5382 element. Interestingly, the other five PFGE types had Tn5382 located on plasmids containing pRUM‐like repA and a plasmid addiction system (axe‐txe) shown by co‐hybridization analysis of PFGE‐separated S1‐nuclease digested total DNA. The resistance plasmids were mainly of 120‐kb and supported intraspecies vanB transfer. Two strains were isolated from patient 6 and we observed a possible transfer of the vanB2‐resistance genes from PFGE type III ST460 to a more successful PFGE type I ST125. This latter PFGE type I ST125 became the predominant type afterwards. Our observations support the notion that vanB‐type vancomycin‐resistant Enterococcus faecium can persist in a low‐endemic area through successful clones and plasmids with stability functions in hospital patients with known risk factors.
Retrospective assessment of β‐d‐(1,3)‐glucan for presumptive diagnosis of fungal infections
Authors: BELLANGER ANNE‐PAULINE , GRENOUILLET FREDERIC , HENON THIERRY , SKANA FLORENCE , LEGRAND FAEZEH , DECONINCK ERIC , MILLON LAURENCE
Published: February 2011

Bellanger A‐P, Grenouillet F, Henon T, Skana F, Legrand F, Deconinck E, Millon L. Retrospective assessment of β‐d‐(1,3)‐glucan for presumptive diagnosis of fungal infections. APMIS 2011; 119: 280–6.

β‐d‐(1,3)‐glucan (BG) is a component of the cell walls of many fungal organisms. Our aims were to investigate the feasibility of the BG assay and its contribution to early diagnosis of different types of invasive fungal infections (IFI) commonly diagnosed in a tertiary care centre. The BG serum levels of 28 patients diagnosed with six IFI [13 probable invasive aspergillosis (IA), 2 proven IA, 2 zygomycosis, 3 fusariosis, 3 cryptococcosis, 3 candidaemia and 2 pneumocystosis] were retrospectively evaluated. The kinetic variations in BG serum levels from the 15 patients diagnosed with IA were compared with those of the galactomannan antigen (GM). In 5/15 cases of IA, BG was positive earlier than GM (time lapse from 4 to 30 days), in 8/15 cases, BG was positive at the same time as GM and, in 2/15 cases, BG was positive after GM. For the five other fungal diseases, BG was highly positive at the period of diagnosis except for the two cases of zygomycosis and one of the three cases of fusariosis. This study, which reflects the common activity of a tertiary care centre, confirms that BG detection could be of interest for IFI screening in patients with haematological malignancies.