bluuebunny/crossref_metadata_2025 huggingface dataset:
The one-stop coronary cholesterol clinic: a multidisciplinary approach to implementing evidence-based treatment
Authors: Giles P D , Ramachandran S , Whitaker A J , Phillips A W , Fell S J , Mitchell A , Coleman T D
Published: December 2008

We describe a ‘one-stop’ cholesterol clinic implementing a regime based on the Scandinavian Simvastatin Survival Study (4S) in patients with established coronary heart disease in a district general hospital. The clinic has been established in collaboration with the cardiac rehabilitation centre. It was commissioned as an audit project by the purchasing authority, Walsall Health, a need having been shown in a previous audit. In the new clinic, audit is inbuilt, rather than being carried out as a separate retrospective exercise, and undertaken prospectively for all patients. Central to this is a database, used for routine correspondence and administration, as well as monitoring outcome. This application of information technology has improved clinical practice. Attendance at the clinic has been excellent. Half the consultations have resulted in therapeutic interventions, many of which may otherwise have been missed. Over 50% of patients were eligible for lipid-lowering medication under the protocol. Cholesterol targets based on 4S were achieved but with much lower drug doses, which may have major cost implications. Cholesterol levels measured within 24 hours of admission for myocardial infarction were poor predictors of results obtained after convalescence. After the clinic visit, most patients were taking aspirin plus one or two other secondary prevention treatments. Guidelines have been issued to primary care. Future plans for audit links with general practitioners, integration of the metabolic and cardiological assessment of survivors of myocardial infarction, and for long-term monitoring of clinical events in treated patients are discussed.
Transoesophageal echocardiography
Authors: Sanderson J E , Chan W W
Published: December 2008

Transoesophageal echocardiography gives unparalleled views of the posterior structures of the heart. It is the investigation of choice for the diagnosis of acute dissection of the aorta, in patients with endocarditis, management of the hypotensive patient in the intensive care unit, and in the search for a potential cardiac source of thromboembolism. However, it is a semi-invasive procedure, and proper training is required to carry it out safely, to ensure that maximum information is obtained at the time of examination, and to avoid diagnostic pitfalls.
Avoidable attendance at accident and emergency by the elderly in Hong Kong
Authors: Lau E M C , Woo J , Chan J T S
Published: December 2008

Twenty per cent of Accident and Emergency department attendance by the elderly in a regional hospital in Hong Kong were deemed ‘avoidable’ by the attending doctors. The ‘avoidable’ attendants were younger and physically more independent than the appropriate attendants, and more of them were illiterate. Half of them attended the Accident and Emergency department for somatic complaints. Strategies to reduce these ‘avoidable’ attendances should be formulated.
The acceptability of personal learning plans in vocational training
Authors: Siriwardena A N
Published: December 2008

Personal learning plans have been advocated as a means of introducing the principles of adult learning into general practice vocational training. The aim of this study was to investigate attitudes amongst general practice trainers and registrars to the introduction and use of personal learning plans. A questionnaire was sent to general practice trainers and registrars in one vocational training scheme prior to the introduction of personal learning plans. Overall, doctors in the training scheme were positive to the idea of personal learning plans. Trainers were significantly more positive towards introducing learning plans than their registrars. Registrars in their final general practice posts were significantly more positive towards the idea of learning plans than their hospital counterparts. Doctors who had completed membership of the Royal College of General Practitioners, usually trainers or final year registrars, were also more positive in their attitude. This pilot study suggests that most trainers and registrars were positive in their attitude towards personal learning plans prior to their introduction in the Lincoln vocational training scheme. The study cautiously suggests a wider use and evaluation of personal learning plans in vocational training.
Maintenance pharmacological immunosuppressive strategies in renal transplantation
Authors: Vella J P , Sayegh M H
Published: December 2008

Current maintenance immunosuppressive regimens for transplantation are based on three classes of drugs: corticosteroids, immunophilin-binding agents (eg, cyclosporin and tacrolimus), and antimetabolites (eg, azathioprine and mycophenolate). Drugs from the various classes inhibit the immune system at different points and are thus synergistic when used in combination.
Stroke complicating adenosine perfusion imaging
Authors: Khan I A , Samual S A
Published: December 2008

Pharmacologic stress-testing using adenosine is increasing in popularity. Side-effects have been limited to the infusion time and a brief recovery period. Long-lasting complications may, however, result rarely.
The use of over-the-counter medication by elderly medical in-patients
Authors: Batty G M , Oborne C A , Swift C G , Jackson S H D
Published: December 2008

Use of over-the-counter (OTC) medications by elderly patients is often not identified. This survey was performed to study the use of OTCs by medical in-patients aged 65 and over. Data on the use of OTC medications before and during hospital admission were collected by questioning patients and case notes were examined for documentation of their use of OTC medications. OTC medications were used by 44 of 138 (32%) patients interviewed. Patients used a total of 70 OTC medications before admission and six OTC medications were being used during hospital admission. There was no documentation of pre-admission and in-hospital OTC medicine use in the clinical notes and patients had little knowledge of the potential harm some products can cause. As more products become available over the counter, doctors should record their use in patients' notes and patients should be encouraged to seek professional advice before purchasing OTC medicines and to read the product information leaflets.
Caecal adenocarcinoma with multiple synchronous small intestinal adenocarcinoma
Authors: Lee J , Tamhane R , Parks T G
Published: December 2008

We describe a patient who presented with iron deficiency anaemia in whom both upper and lower gastrointestinal investigation were initially negative. Management included successive blood transfusions. Repeat investigation six months later revealed caecal adenocarcinoma. At laparotomy, the patient was also found to have two separate primary synchronous adenocarcinomas of the proximal small bowel. Right hemicolectomy and excision of the small bowel lesions were carried out. The patient eventually succumbed to the disease six weeks after discharge from hospital.
Meningismus, fever and macular rash as presenting features of the primary antiphospholipid syndrome?
Authors: Houghton T , Davies A G
Published: December 2008

We report here, we believe for the first time, the primary antiphospholipid syndrome, presenting with fever, meningismus and skin rash. Serology was positive for antiphospholipid antibodies but negative for antinuclear factor. Such presentations, once meningitis has been excluded, should be screened for antiphospholipid antibodies. If serology proves to be positive, anticoagulation for life should be considered to avoid thrombotic episodes and death due to pulmonary embolism.
Characteristics of patients with shingles admitted to a district general hospital
Authors: Morgan R , King D
Published: December 2008

Little is known about why some patients with shingles are admitted to hospital. We reviewed 72 case notes from a list of 80 patients admitted to hospital with shingles over a six-year period. Pain was the main complaint of the patients admitted, most of whom were elderly and lived alone. The commonest site of involvement in hospital admissions was the eye (herpes zoster ophthalmicus). Diagnosis of shingles was made after admission in 12 patients, eight of whom had originally been diagnosed as having an acute medical or surgical condition. We conclude that the prodromal phase of shingles may lead to misdiagnosis.
Rapid recurrence of pulmonary hypertension following cessation of nifedipine
Authors: Gallagher M M , Hart C M , Vaughan C J , Fennell W H
Published: December 2008

In a young woman with primary pulmonary hypertension, treatment with low-dose nifedipine resulted in resolution of symptoms and of tricuspid regurgitation. On withdrawal of nifedipine, symptomatic pulmonary hypertension recurred within 48 hours and was controlled by reintroduction of low-dose nifedipine.
A collaborative audit of the management of hypertension in general practice
Authors: Raman G V , Neal A , Lewis C
Published: December 2008

We carried out an audit of the management of essential hypertension in general practice, against standards based on current guidelines. We examined the records of 882 hypertensive subjects (on medication) in whom hypertension had been diagnosed between January 1989 and December 1993, from 14 general practices in the Portsmouth and South East Hampshire Health Authority. The overall prevalence of hypertension was 3.5%. Pretreatment blood pressure had been measured on three or more occasions in 87% of patients. Pretreatment blood pressure was equal to or greater than 150/95 mmHg in 96% and 160/100 mmHg in 86.5% of patients. A thiazide diuretic was the initial drug of choice in 30% of patients, with beta-blockers being the most popular initial treatment. Ninety per cent of patients had had their blood pressure measured at least once during the preceding year. In 82.5% of patients, current blood pressure was less than 150/95 mmHg, while 44% achieved a current blood pressure less than 140/90 mmHg. We conclude that the prevalence of hypertension in this population was lower than expected, suggesting the need for improved screening. We also propose that the initial treatment choice should be a thiazide in the majority, which would result in significant cost saving. The blood pressure control was suboptimal compared to current guidelines.
Medical treatment of erectile dysfunction
Authors: Burns-Cox N , Gingell C
Published: December 2008

There has been a tremendous increase in demand for the treatment of erectile dysfunction in the last 10 years. This has occurred partly because of a greater understanding and awareness by both the general public and clinicians, and also because there now exists a range of effective treatments. The choice of treatments is increasing rapidly and novel delivery systems which may be more patient-friendly than intracavernosal injections are now becoming available. We review the published data on effectiveness and safety of the currently available treatments and discuss recent advances in oral therapy, as these drugs are likely to become available in the near future.
Intracoronary ultrasound
Authors: Hammond C , Causer J P , Perry R A
Published: December 2008

Although contrast angiography is important in the diagnosis and treatment of atherosclerotic disease, it does have limitations. Intracoronary ultrasound more accurately assesses the amount of atherosclerosis and has given us new insights into the pathophysiology of coronary plaque accumulation and remodelling. It also allows the monitoring of therapeutic intervention. Intracoronary ultrasound is a new gold standard. It does not obviate the need for angiography but provides complementary information that enables us to perform optimal interventional procedures.
Hospital doctors' assessment of baseline spirometry
Authors: Stephenson N , Morgan R , Abdel-Rahman-Abdel-Wahab E , Turnbull C J
Published: December 2008

Baseline spirometry is useful in diagnosing and managing pulmonary disease. In a questionnaire survey of 100 hospital doctors in two hospitals in the Mersey region, their views and ability to interpret baseline spirometry was assessed. Of the 70 doctors who responded, 65% felt they could accurately interpret baseline spirometry. However, only 12% accurately interpreted all five vitalographs in the questionnaire. The majority (72%) felt they had not had adequate teaching in interpretation of spirometry, and 63% would prefer a report from a respiratory technician. These result suggest that improvement needs to be made in interpretation of baseline spirometry.
Recent advances in the drug treatment of heart failure
Authors: McAlister F A , Teo K K
Published: December 2008

A number of important questions surrounding the treatment of systolic congestive heart failure have been answered by randomised clinical trials completed within the past 2 years. In particular, these studies have established that high-dose angiotensin-converting enzyme (ACE) inhibition is more beneficial than low dose therapy, and that angiotensin II receptor antagonists are an acceptable alternative in patients unable to tolerate ACE inhibitors. Digoxin has been shown to be the only inotropic agent not associated with increased mortality, while amiodarone exerts a modest survival benefit in arrhythmiaprone patients. Beta-blockers appear to be beneficial for selected patients although their precise role remains to be defined by ongoing studies.
Systemic activity of inhaled and swallowed beclomethasone dipropionate and the effect of different inhaler devices
Authors: Trescoli C , Ward M J
Published: December 2008

Inhaled glucocorticoids such as beclomethasone dipropionate, which are used in the treatment of asthma, may be associated with systemic adverse effects. To determine whether any systemic absorption following the inhalation of beclomethasone was a result of drug being absorbed from the lung (inhaled fraction) or the gastrointestinal tract (swallowed fraction), we studied normal subjects after the inhalation or swallowing of 2 mg beclomethasone dipropionate. Systemic activity was assessed using early morning cortisol suppression. Both inhaled and swallowed fractions produced significant systemic activity, the degree of which depended on the inhaler device used. Systemic activity was greater using a dry powder inhaler (52%) than using a metered dose inhaler with a large volume spacer (28%). These findings suggest that to limit potential adverse effects from high-dose beclomethasone dipropionate it is better to use a metered dose aerosol with large volume spacer than a dry powder.
Clostridium difficile-associated diarrhoea
Authors: Wight N , Curtis H , Hyde J , Borriello S P , Mahida Y R
Published: December 2008

At our hospital, the number of cases of Clostridium difficile-associated diarrhoea increased from 29 in 1993 to 210 in 1995. The case notes of 110 patients with C difficile-associated diarrhoea during the first 6 months of 1995 were analysed retrospectively. The majority of the patients (106) had received antibiotics before the onset of diarrhoea; 46 had received three or more different antibiotics and 28 had received metronidazole. In 19 patients, the first stool sample after the onset of diarrhoea was negative for C difficile cytotoxin, with a mean delay of 8.2 days before a positive stool sample. We conclude that C difficile-associated diarrhoea was associated with the usage of multiple antibiotics, and that metronidazole did not protect against colonisation by C difficile. We also recommend that more than one stool sample should be tested for the C difficile cytotoxin.
A QUASI-ISOMETRY INVARIANT LOOP SHORTENING PROPERTY FOR GROUPS
Authors: BRICK STEPHEN G. , CORSON JON M. , RYANG DOHYOUNG
Published: December 2008

We first introduce a loop shortening property for metric spaces, generalizing the property considered by M. Elder on Cayley graphs of finitely generated groups. Then using this metric property, we define a very broad loop shortening property for finitely generated groups. Our definition includes Elder's groups, and unlike his definition, our property is obviously a quasi-isometry invariant of the group. Furthermore, all finitely generated groups satisfying this general loop shortening property are also finitely presented and satisfy a quadratic isoperimetric inequality. Every CAT(0) cubical group is shown to have this general loop shortening property.
THE FUNDAMENTAL GROUP OF GALOIS COVER OF THE SURFACE 𝕋 × 𝕋
Authors: AMRAM MEIRAV , TEICHER MINA , VISHNE UZI
Published: December 2008

This is the final paper in a series of four, concerning the surface 𝕋 × 𝕋 embedded in ℂℙ8, where 𝕋 is the one-dimensional torus. In this paper we compute the fundamental group of the Galois cover of the surface with respect to a generic projection onto ℂℙ2, and show that it is nilpotent of class 3. This is the first time such a group is presented as the fundamental group of a Galois cover of a surface.
Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning
Authors: Naitoh Kazuyuki , Yano Toshiyuki , Miura Tetsuji , Itoh Takahito , Miki Takayuki , Tanno Masaya , Sato Takahiro , Hotta Hiroyuki , Terashima Yoshiaki , Shimamoto Kazuaki
Published: December 2008

Ischemic preconditioning (PC) suppresses chemical coupling of cardiomyocytes via gap junctions (GJs) during ischemia, which is an adjunct mechanism of protection. The aim of this study was to characterize roles of protein kinases in PC-induced GJ modulation. In isolated rat hearts, ventricular tissues were sampled before and after ischemia with or without PC, and intercalated disc-rich fractions were separated for immunoprecipitation and immunoblotting. Levels of protein kinase C (PKC)-ε, p38mitogen-activated protein kinase (MAPK)-α, and Src coimmunoprecipitated with connexin-43 (Cx43) were increased after ischemia, whereas p38MAPKβ was not detected in the Cx43 immunoprecipitates. PC did not modify the level of Cx43-Src complex after ischemia. However, PC enhanced Cx43-PKCε complex formation, which was abolished by PKCε translocation inhibitory peptide (TIP). In contrast, PC reduced Cx43-p38MAPKα complex level and p38MAPK activity in the Cx43 immunoprecipitates after ischemia. The effect of PC on Cx43-p38MAPKα interaction was mimicked by SB-203580, a p38MAPK inhibitor. PC reduced permeability of GJs to Lucifer yellow in the myocardium at 25 min after ischemia, and this effect was abolished by PKCε-TIP. SB-203580 increased the GJ permeability at 15 min after ischemia compared with that in untreated controls, but the difference became insignificant 25 min after ischemia. In conclusion, PC has distinct effects on interaction of GJ Cx43 with PKCε, p38MAPKα, and Src during ischemia. Suppression of GJ permeability during ischemia by PC is primarily achieved by enhanced interaction of Cx43 with PKCε, which overwhelms the counterbalancing effect of reduced Cx43-p38MAPKα interaction.
N-acetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin
Authors: Liu Yun-He , D'Ambrosio Martin , Liao Tang-dong , Peng Hongmei , Rhaleb Nour-Eddine , Sharma Umesh , André Sabine , Gabius Hans-J. , Carretero Oscar A.
Published: December 2008

Galectin-3 (Gal-3) is secreted by activated macrophages. In hypertension, Gal-3 is a marker for hypertrophic hearts prone to develop heart failure. Gal-3 infused in pericardial sac leads to cardiac inflammation, remodeling, and dysfunction. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a naturally occurring tetrapeptide, prevents and reverses inflammation and collagen deposition in the heart in hypertension and heart failure postmyocardial infarction. In the present study, we hypothesize that Ac-SDKP prevents Gal-3-induced cardiac inflammation, remodeling, and dysfunction, and these effects are mediated by the transforming growth factor (TGF)-β/Smad3 signaling pathway. Adult male rats were divided into four groups and received the following intrapericardial infusion for 4 wk: 1) vehicle (saline, n = 8); 2) Ac-SDKP (800 μg·kg−1·day−1, n = 8); 3) Gal-3 (12 μg/day, n = 7); and 4) Ac-SDKP + Gal-3 ( n = 7). Left ventricular ejection fraction, cardiac output, and transmitral velocity were measured by echocardiography; inflammatory cell infiltration, cardiomyocyte hypertrophy, and collagen deposition in the heart by histological and immunohistochemical staining; and TGF-β expression and Smad3 phosphorylation by Western blot. We found that, in the left ventricle, Gal-3 1) enhanced macrophage and mast cell infiltration, increased cardiac interstitial and perivascular fibrosis, and causes cardiac hypertrophy; 2) increased TGF-β expression and Smad3 phosphorylation; and 3) decreased negative change in pressure over time response to isoproterenol challenge, ratio of early left ventricular filling phase to atrial contraction phase, and left ventricular ejection fraction. Ac-SDKP partially or completely prevented these effects. We conclude that Ac-SDKP prevents Gal-3-induced cardiac inflammation, fibrosis, hypertrophy, and dysfunction, possibly via inhibition of the TGF-β/Smad3 signaling pathway.
Glucosamine improves cardiac function following trauma-hemorrhage by increased proteinO-GlcNAcylation and attenuation of NF-κB signaling
Authors: Zou Luyun , Yang Shaolong , Champattanachai Voraratt , Hu Shunhua , Chaudry Irshad H. , Marchase Richard B. , Chatham John C.
Published: December 2008

We have previously demonstrated that in a rat model of trauma-hemorrhage (T-H), glucosamine administration during resuscitation improved cardiac function, reduced circulating levels of inflammatory cytokines, and increased tissue levels of O-linked N-acetylglucosamine ( O-GlcNAc) on proteins. The mechanism(s) by which glucosamine mediated its protective effect were not determined; therefore, the goal of this study was to test the hypothesis that glucosamine treatment attenuated the activation of the nuclear factor-κB (NF-κB) signaling pathway in the heart via an increase in protein O-GlcNAc levels. Fasted male rats were subjected to T-H by bleeding to a mean arterial blood pressure of 40 mmHg for 90 min followed by resuscitation. Glucosamine treatment during resuscitation significantly attenuated the T-H-induced increase in cardiac levels of TNF-α and IL-6 mRNA, IκB-α phosphorylation, NF-κB, NF-κB DNA binding activity, ICAM-1, and MPO activity. LPS (2 μg/ml) increased the levels of IκB-α phosphorylation, TNF-α, ICAM-1, and NF-κB in primary cultured cardiomyocytes, which was significantly attenuated by glucosamine treatment and overexpression of O-GlcNAc transferase; both interventions also significantly increased O-GlcNAc levels. In contrast, the transfection of neonatal rat ventricular myocytes with OGT small-interfering RNA decreased O-GlcNAc transferase and O-GlcNAc levels and enhanced the LPS-induced increase in IκB-α phosphorylation. Glucosamine treatment of macrophage cell line RAW 264.7 also increased O-GlcNAc levels and attenuated the LPS-induced activation of NF-κB. These results demonstrate that the modulation of O-GlcNAc levels alters the response of cardiomyocytes to the activation of the NF-κB pathway, which may contribute to the glucosamine-mediated improvement in cardiac function following hemorrhagic shock.
LPS-induced autophagy is mediated by oxidative signaling in cardiomyocytes and is associated with cytoprotection
Authors: Yuan Hua , Perry Cynthia N. , Huang Chengqun , Iwai-Kanai Eri , Carreira Raquel S. , Glembotski Christopher C. , Gottlieb Roberta A.
Published: December 2008

Bacterial endotoxin lipopolysaccharide (LPS) is responsible for the multiorgan dysfunction that characterizes septic shock and is causal in the myocardial depression that is a common feature of endotoxemia in patients. In this setting the myocardial dysfunction appears to be due, in part, to the production of proinflammatory cytokines. A line of evidence also indicates that LPS stimulates autophagy in cardiomyocytes. However, the signal transduction pathway leading to autophagy and its role in the heart are incompletely characterized. In this work, we wished to determine the effect of LPS on autophagy and the physiological significance of the autophagic response. Autophagy was monitored morphologically and biochemically in HL-1 cardiomyocytes, neonatal rat cardiomyocytes, and transgenic mouse hearts after the administration of bacterial LPS or TNF-α. We observed that autophagy was increased after exposure to LPS or TNF-α, which is induced by LPS. The inhibition of TNF-α production by AG126 significantly reduced the accumulation of autophagosomes both in cell culture and in vivo. The inhibition of p38 MAPK or nitric oxide synthase by pharmacological inhibitors also reduced autophagy. Nitric oxide or H2O2induced autophagy in cardiomyocytes, whereas N-acetyl-cysteine, a potent antioxidant, suppressed autophagy. LPS resulted in increased reactive oxygen species (ROS) production and decreased total glutathione. To test the hypothesis that autophagy might serve as a damage control mechanism to limit further ROS production, we induced autophagy with rapamycin before LPS exposure. The activation of autophagy by rapamycin suppressed LPS-mediated ROS production and protected cells against LPS toxicity. These findings support the notion that autophagy is a cytoprotective response to LPS-induced cardiomyocyte injury; additional studies are needed to determine the therapeutic implications.
Cellular localization of mitochondria contributes to Kv channel-mediated regulation of cellular excitability in pulmonary but not mesenteric circulation
Authors: Firth Amy L. , Gordienko Dmitri V. , Yuill Kathryn H. , Smirnov Sergey V.
Published: December 2008

Mitochondria are proposed to be a major oxygen sensor in hypoxic pulmonary vasoconstriction (HPV), a unique response of the pulmonary circulation to low oxygen tension. Mitochondrial factors including reactive oxygen species, cytochrome c, ATP, and magnesium are potent modulators of voltage-gated K+ (Kv) channels in the plasmalemmal membrane of pulmonary arterial (PA) smooth muscle cells (PASMCs). Mitochondria have also been found close to the plasmalemmal membrane in rabbit main PA smooth muscle sections. Therefore, we hypothesized that differences in mitochondria localization in rat PASMCs and systemic mesenteric arterial smooth muscle cells (MASMCs) may contribute to the divergent oxygen sensitivity in the two different circulations. Cellular localization of mitochondria was compared with immunofluorescent labeling, and differences in functional coupling between mitochondria and Kv channels was evaluated with the patch-clamp technique and specific mitochondrial inhibitors antimycin A (acting at complex III of the mitochondrial electron transport chain) and oligomycin A (which inhibits the ATP synthase). It was found that mitochondria were located significantly closer to the plasmalemmal membrane in PASMCs compared with MASMCs. Consistent with these findings, the effects of the mitochondrial inhibitors on Kv current ( IKv) were significantly more potent in PASMCs than in MASMCs. The cytoskeletal disruptor cytochalasin B (10 μM) also altered mitochondrial distribution in PASMCs and significantly attenuated the effect of antimycin A on the voltage-dependent parameters of IKv. These findings suggest a greater structural and functional coupling between mitochondria and Kv channels specifically in PASMCs, which could contribute to the regulation of PA excitability in HPV.
In vitro hypoxia impairs β2-adrenergic receptor signaling in primary rat alveolar epithelial cells
Authors: Baloğlu Emel , Ke Alberto , Abu-Taha Issam Hissam , Bärtsch Peter , Mairbäurl Heimo
Published: December 2008

Hypoxia inhibits β2-adrenergic receptor (β2-AR) signaling in a variety of tissues, but effects in alveolar epithelium are unclear. We therefore examined the effect of 24 h of hypoxia on β2-AR function in primary rat alveolar epithelial [alveolar type II (ATII)] cells. ATII cells were isolated, cultured to confluence, and incubated in normoxia or hypoxia (3% O2) for 24 h. Hypoxia decreased maximal terbutaline-stimulated cAMP production by 37%; potency of terbutaline was not affected. Reoxygenation (3 h) reversed this effect. Density of β2-AR assessed by (−)-[125I]iodocyanopindolol binding was decreased in hypoxia (−22%). Hypoxia did not affect terbutaline binding affinity to β2-AR. Hypoxia decreased Gsprotein levels by 27%, whereas no change was observed in Gi1/2, Gi3, and Gβ subunits. Forskolin-stimulated cAMP production was not inhibited by hypoxia. Pertussis toxin (PTX; 0.5 μg/ml, 2 h), an inhibitor of Gi/oproteins, restored terbutaline-stimulated cAMP production of hypoxic ATII cells to normoxic control values. Cholera toxin (CTX)-stimulated Gsprotein activity did not change in hypoxia. Hypoxia increased the sensitivity of β2-AR to desensitization. These results indicate that despite the decrease in Gsprotein level Gsprotein was still functional and that hypoxia impairs β2-AR signaling due to an increased activity of Gi/oproteins.
Inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model
Authors: Kuramoto Emi , Nishiuma Teruaki , Kobayashi Kazuyuki , Yamamoto Masatsugu , Kono Yuko , Funada Yasuhiro , Kotani Yoshikazu , Sisson Thomas H. , Simon Richard H. , Nishimura Yoshihiro
Published: December 2008

The airway remodeling that occurs in asthma is characterized by an excess of extracellular matrix deposition in the submucosa, hyperplasia/hypertrophy of smooth muscle, goblet cell metaplasia, and accumulation of fibroblasts/myofibroblasts. The urokinase-type plasminogen activator (uPA)/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors. In a mouse ovalbumin (OVA) asthma model, we increased plasminogen activator activity in the lung by administering exogenous uPA or by using mice genetically deficient in the uPA inhibitor plasminogen activator inhibitor-1 (PAI-1) to assess the role of this system in asthma pathogenesis. After intraperitoneal OVA sensitization, mice inhaled OVA plus uPA (500 IU/mouse) or saline by ultrasonic nebulization for 3 wk. When studied 24 h after the final exposure, the groups with upregulated plasmin activity had significantly reduced subepithelial fibrosis within the airway walls and had decreased airway hyperresponsiveness (AHR) to methacholine. Morphometric analysis showed that subepithelial wall thickening of the bronchi (subepithelial area ratio) was also reduced, as were collagen and α-smooth muscle actin. Upregulation of plasmin activity also increased the level of hepatocyte growth factor activity in bronchoalveolar lavage fluid, whereas the release of transforming growth factor-β was decreased. The administration of uPA 1 wk after the last OVA inhalation also significantly reduced lung hydroxyproline content and AHR. These results show that enhancing uPA/plasmin activity lessens the airway remodeling in a murine asthma model.
Myeloid cells control termination of lung inflammation through the NF-κB pathway
Authors: Han Wei , Joo Myungsoo , Everhart M. Brett , Christman John W. , Yull Fiona E. , Blackwell Timothy S.
Published: December 2008

Although acute lung inflammation in response to local or systemic infection involves myeloid and nonmyeloid cells, the interplay between different cell types remains poorly defined. Since NF-κB is a key transcription factor for innate immunity, we investigated whether dysregulated NF-κB activation in myeloid cells impacts inflammatory signaling in nonmyeloid cells and generation of neutrophilic lung inflammation in response to systemic endotoxemia. We generated bone marrow chimeras by fetal liver transplantation of cells deficient in IκBα or p50 into lethally irradiated NF-κB reporter transgenic mice. No differences were apparent between bone marrow chimeras in the absence of an inflammatory stimulus; however, following intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS), IκBα- or p50-deficient bone marrow chimeras showed increased NF-κB activation in nonhematopoietic cells, exaggerated neutrophilic inflammation, and higher mortality compared with untransplanted reporter mice and wild-type bone marrow chimeras. Primary bone marrow-derived macrophages (BMDM) from IκBα−/−or p50−/−exhibited increased NF-κB activation and macrophage inflammatory protein-2 production after LPS treatment compared with wild-type cells, and coculture of BMDM with lung epithelial (A549) cells resulted in increased NF-κB activation in A549 cells and excess IL-8 production by these epithelial cells. These studies indicate an important role for inhibitory members of the NF-κB family acting specifically within myeloid cells to limit inflammatory responses in the lungs.
Virulence factors ofStaphylococcus aureusinduce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o- human airway epithelial cells
Authors: Below Sabine , Konkel Anne , Zeeck Cathrin , Müller Christian , Kohler Christian , Engelmann Susanne , Hildebrandt Jan-Peter
Published: December 2008

Part of the innate defense of bronchial epithelia against bacterial colonization is regulated secretion of salt, water, and mucus as well as defensins and cytokines involving MAP kinase activation and alterations in early gene expression. We tested two different types of immortalized human airway epithelial cells (S9, 16HBE14o-) for activation of Erk-type MAP kinases and for expression of c-Fos on treatment with Staphylococcus aureus culture supernatants from the stationary growth phase [optical density (OD)540nm= 10] or with recombinant S. aureus hemolysins A and B (Hla, Hlb). OD10 supernatants activated Erk-type MAP kinases and c-Fos expression in a concentration-dependent manner. Hla induced Erk-type kinase phosphorylation in S9 but not in 16HBE14o- cells. Hlb induced Erk activation in either cell type. Basal and stimulated levels of Erk-type MAP kinase phosphorylation were sensitive to the Mek1 inhibitor PD-98059, indicating that the bacterial products activated the entire signaling cascade that coregulates IL-8 induction and secretion. While c-Fos expression was enhanced by OD10 supernatants, Hla, and Hlb in S9 cells, 16HBE14o- cells responded to OD10 supernatant and Hlb but not to Hla. In S9 cells, PD-98059 suppressed c-Fos upregulation by OD10 supernatant, Hla, or Hlb, indicating that c-Fos expression requires activation of Erk-type MAP kinases. In 16HBE14o- cells, however, c-Fos expression by OD10 supernatant was sensitive to PD-98059, while that induced by Hlb was not. This indicates that ingredients of OD10 supernatants other than Hla or Hlb are activating Erk-type MAP kinases in 16HBE14o- cells and that other intracellular signaling systems apart from Erk-type MAP kinases contribute to Hlb-mediated regulation of c-Fos. Thus interaction of bacterial factors with airway epithelial cells may be highly cell type specific.
Prevalence and Impact of Diabetes Mellitus in Patients With Acute Myocardial Infarction: A 10-year Experience
Authors: El-Menyar Ayman A. , Albinali Hajar A. , Bener A. , Mohammed Ibrahim , Al Suwaidi Jassim
Published: December 2008

Background: Diabetes mellitus is associated with a higher incidence of acute myocardial infarction. Objective: To study the prevalence and outcome of patients with diabetes among patients with acute myocardial infarction. Methods: Retrospectively, patients who presented with acute myocardial infarction in a 10-year period were identified from the coronary care unit database. Results: A total of 1598 Qatari patients were admitted with acute myocardial infarction, 863 (54%) of them had diabetes mellitus (females 68.5% vs males 48.3%; P < .001). In-hospital mortality rate was non-significantly higher in diabetic patients (18% vs 15% P = .15). Aspirin (odds ratio 2.39, 95% confidence interval 1.96-2.90, P = .003] and β-blocker use (odds ratio 1.75, 95% CI 1.21-2.52, P = .0001) were independently associated with reduced mortality risk. Conclusions: The prevalence of diabetes mellitus among patients with acute myocardial infarction in a geographically defined population in the developing world is high with a trend for poor outcomes. However, mortality was not significantly higher in diabetes mellitus than non-diabetes mellitus patients.
The Association Between Ankle Brachial Pressure Index and Pulse Wave Velocity: Clinical Implication of Pulse Wave Velocity
Authors: Khandanpour Nader , Armon Matthew P. , Jennings Barbara , Clark Allan , Meyer Felicity J.
Published: December 2008

Objective: The aim of this study was to assess the relationship between ankle brachial pressure index and pulse wave velocity in patients with peripheral arterial disease.

Methods: Brachial-knee and brachial-ankle pulse wave velocity were measured by pneumoplethysmography using cuffs in a standard technique. Correlation between pulse wave velocity and Doppler-ankle brachial pressure index was assessed by Spearman correlation and receiver operating curves.

Results: A total of 133 claudicants were assessed. Analysis by developing receiver operating curves for ankle brachial pressure index and pulse wave velocity showed that patients with ankle brachial pressure index over 0.6 were more likely to have a bk-pulse wave velocity over 9.2 m/s and ba-pulse wave velocity over 9.5 m/s.

Conclusion: These results show for the first time that nondiabetic vascular patients may have measurable significant arterial stiffness independent of an impaired ankle brachial pressure index. These data suggest that pulse wave velocity may be valuable in screening and evaluating the severity of peripheral arterial disease.
Clinical Outcome in Patients With Peripheral Artery Disease and Renal Artery Stenosis
Authors: Esteban Carlos , Perez Paulina , Fernández-Llamazares Jaume , Suriñach Josep Maria , Camafort Miquel , Martorell Albert , Monreal Manuel
Published: December 2008

Background: There is controversy on the influence of renal artery stenosis on outcome in patients with peripheral artery disease. Patients and Methods: The 12-month impact of renal artery stenosis on declining renal function, control of hypertension, and incidence of major cardiovascular events in 100 consecutive patients undergoing angiography for peripheral artery disease was evaluated. Results: A total of 60 patients had renal artery stenosis: 32 mild, 16 moderate, and 12 severe stenosis. There were no significant differences in either the decline of renal function (2.7 ± 18% vs 0.9 ± 16%), control of hypertension (139 ± 16 vs 139 ± 22 mm Hg) or number of antihypertensive drugs (1.8 ± 1.0 vs 1.6 ± 0.8). Patients with renal artery stenosis had an increased incidence of major cardiovascular events (odds ratio: 2.3; 95% confidence interval: 1.03-5.4), but on multivariate analysis its influence disappeared. Conclusions: Patients with peripheral artery disease having renal artery stenosis had similar decline of renal function and control of hypertension. They had an increased incidence of major cardiovascular events, but it may be explained by the confounding effect of additional variables.
Sexual Arousal and Self-Control
Authors: Bouffard Jeffrey , Kunzi Tasha
Published: December 2008

A central proposition of Gottfredson and Hirschi’s (1990) General Theory of Crime is the relative stability of low self-control, however research on “selfcontrol strength” suggests that it may vary across contexts. The current study examines these differing conceptions by randomly assigning participants to one of two sexual arousal conditions or to a no-arousal condition. Group differences in the six components of self control, as captured on the Grasmick et al. (1993) scale were then examined. Unexpectedly, individuals in the most intense arousal condition actually reported higher self-control than those in the other conditions (both in absolute value and in changes in relative rank within the sample). Such findings provide additional empirical support for the recent conceptualization of self-control strength as a personal characteristic that can be both exercised and potentially depleted when overused.
Floor Effects Associated With Universal Screening and Their Impact on the Early Identification of Reading Disabilities
Authors: Catts Hugh W. , Petscher Yaacov , Schatschneider Christopher , Sittner Bridges Mindy , Mendoza Katherin
Published: December 2008

Response to intervention (RTI) holds great promise for the early identification and prevention of reading disabilities. The success of RTI rests in part on the accuracy of universal screening tools used within this framework. Despite advancements, screening instruments designed to identify children at risk for reading disabilities continue to have limited predictive validity. In this study, the authors examined a common screening instrument for the presence of floor effects and investigated the impact that these effects have on the predictive validity of the instrument. Longitudinal data (kindergarten to third grade) from a large cohort of children were used. These data included children's performance on five measures from the Dynamic Indicators of Basic Early Literacy Skills (DIBELS) and two reading achievement outcome measures. The results showed that DIBELS measures were characterized by floor effects in their initial administrations and that these effects reduced the predictive validity of the measures. The implications of these findings for early identification are discussed.
Test Review Nos. 13 & 14: Visual Efficiency Scale
Authors: Proger Barton B.
Published: December 2008

No ages specified but appears suitable for visually impaired young children about 4 to 8 years old; VES; dated 1970; 5 scores: Section 1 (discrimination of geometric form, object contour, light-dark intensity, and size and position), Section 2 (discrimination of size, object and abstract figure detail, position in space, image constancy of outlines, and pattern details and objects), Section 3 (visual closure, spatial perspective, and discrimination of object and abstract figure details), Section 4 (discrimination of size, position, sequence and relationship of letter and word symbols and groups of symbols), and Total; 1 form (1970, 8 pages); manual (1970, 73 pages); separate administration directions (1970, 8 pages); scoring sheet (n.d., 1 page); graphic profile sheet (n.d., 1 page); sample measurement set is available as part of Low Vision Kit, $2.50; package of 10 VES test booklets with set of directions, $6.00; unlimited administration time; author; Natalie Barraga (University of Texas) and Ruth Holmes (Illinois Braille and Sight Saving School), assisted by Douglas Ozias and Mildred Smith (both University of Texas) and Carson Nolan (American Printing House for the Blind); publisher: American Foundation for the Blind, 15 West 16th Street, New York, N.Y. 10011 (telephone 212-924-0420).
The Least Restrictive Alternative: Implications for Service Providers
Authors: Miller Ted L. , Switzky Harvey N.
Published: December 2008

The phrase "least restrictive alternative" has repeatedly appeared in professional literature and in legislation. Despite the prevalence of the phrase, there is reason to believe that the concept is neither well defined nor simple to implement properly. This article traces the probable history of the least restrictive alternative and relates some concerns about actual implementation. A number of specific problems are recounted, particularly the field's reliance on administrative-determined norm-based special placements. Similarly, some ameliorative alternatives are suggested, chief among them the need to determine restriction based on the likelihood of achieving ecologically determined goals. Finally, the authors conclude that conflict between norm placement and individual achievement must be resolved before least restriction can truly occur.
The Talent-Search Concept: an Identification Strategy for the Intellectually Gifted
Authors: George William C.
Published: December 2008

Using the empirically based evidence that has resulted from the previous five Talent Searches of the Study of Mathematically Precocious Youth, the article develops the rationale and success behind the talent-search concept as a useful strategy for identifying the intellectually gifted. Its practicality as a model is further demonstrated through the systematic curricular programming that has resulted at school-district levels after students have been identified as talented in a specific aptitude area. The identification issue is discussed as it pertains to efficiency and effectiveness related to cost, predictive validity, and feasibility.
Suggestions for Modifications in Testing Low-Achieving Adolescents
Authors: Bachor Dan G.
Published: December 2008

Tests used to estimate mental abilities are critically examined. Three weaknesses in mental measurement are identified that may inhibit the test performance of low-achieving adolescents, and modifications are suggested to correct these weaknesses. The modifications are derived from a developmentally based information-processing theory.
Teaching Community Survival Skills To Mentally Retarded Adults: A Review and Analysis
Authors: Martin James E. , Rusch Frank R. , Heal Laird W.
Published: December 2008

A revolution in providing residential alternatives for mentally retarded (MR) individuals has made in vivo training a part of the deinstitutionalization process. The literature indicates that institutional teaching programs may not be as effective as in vivo community training. MR adults can acquire a variety of community survival skills — the skills curriculum developers must address when they devise new and innovative community integration experiences. This paper reviews the training procedures and results of studies in 10 community survival skills: travel, money management, meal preparation, clothing and personal care, telephone use, housekeeping, self-medication, leisure, social skills, and conversation. Several suggestions are made for future research into training MR citizens for community living.
Dyslexia: a Term in Search of a Definition
Authors: White Michael , Miller Sidney R.
Published: December 2008

For more than 10 years investigators have suggested that there are various types of reading disorders. Articles appearing in the Journal of Learning Disabilities, from 1971 through 1980, were reviewed to determine what effects this notion has had on reading research. Two questions guided the focus for the review: (a) How is reading disorder currently defined? and (b) Do researchers specify the type of disorder under investigation? It was found that the disorders were most often defined in terms of a deficient reading or spelling score on a standardized test. Of the 45 studies reviewed, only 1 specified the type of disorder being examined. It is evident that the notion of distinct types of reading disorders has not been incorporated into current research.
Adaptive Behavior and Low Incidence Handicaps
Authors: Pollingue Alice
Published: December 2008

Individuals who have physical impairments are a very heterogeneous group. Teachers and other direct care personnel of the physically handicapped have traditionally received medical diagnoses and medical information with very few educational and/or treatment implications. The use of adaptive behavior scales with the physically handicapped offers a functional assessment tool that can be directly applied to individual treatment plans. This article examines problems in the traditional assessment procedures used with the physically handicapped and discusses the use of adaptive behavior scales with emphasis on application of the results through a multidisciplinary approach. Selected adaptive behavior scales are described, and guidelines for test administration with the physically handicapped are suggested.