bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of enalapril on the renal response to tilting in humans.
Authors: Lewis NP , Ferguson DR
Published: July 2012

1. Seventeen normal subjects were tilted on a tilt table and changes in blood pressure, heart rate and renal function were monitored in the absence of drug treatment; the same measurements were repeated during treatment with enalapril in eight of these subjects. 2. In the absence of drug, tilting of the whole body to the 45 degree head up position caused an antidiuresis, antinatriuresis and antikaliuresis; the antinatriuresis resulted from a transient fall in glomerular filtration and from a sustained increase in the tubular reabsorption of sodium, as reflected by a prolonged fall in fractional sodium excretion. 3. Enalapril caused a reduction in blood pressure in the upright position; there was no effect on heart rate. The antinatriuresis of tilt was significantly blunted by enalapril. This resulted from blunting of the transient fall in creatinine clearance and of the increase in tubular sodium reabsorption. Urinary potassium excretion during tilting was not altered by enalapril. 4. These findings are consistent with a direct intrarenal action of angiotensin II, mediating some of the alterations in renal function apparent on assumption of the upright position.
Binding of prazosin and propranolol at variable alpha 1‐acid glycoprotein and albumin concentrations.
Authors: Sager G. , Jaeger R. , Little C.
Published: July 2012

1. The effect of variable alpha 1‐acid glycoprotein (AAG) and albumin (HSA) concentrations on the binding of prazosin and propranolol was assessed in plasma after surgery and in mixtures of AAG/HSA with concentrations mimicking those found in vivo. 2. On the pre‐operative day the binding of prazosin and propranolol was 94.8% and 89.0%, respectively and 97.3% and 93.2%, respectively, 5 days after surgery. 3. In solutions containing mixtures of highly purified AAG and HSA representing the pre‐operative state, 88.6% and 83.9% binding of prazosin and propranolol was observed, whereas for solutions mimicking post‐operative plasma, the equivalent values were 94.6% and 91.4%, respectively. 4. The ratios between bound and unbound concentrations of both drugs were closely correlated to the concentrations of AAG, but not to the concentrations of HSA. 5. The present study demonstrates that AAG is responsible for the binding variability of prazosin and propranolol in plasma from post‐operative patients.
Joint pain and quality of life; results of a randomised trial.
Authors: Parr G. , Darekar B. , Fletcher A. , Bulpitt CJ
Published: July 2012

1. Eight hundred and forty‐six patients with pain in one or two joints of the hip, knee, ankle or wrist participated in a randomised double‐ blind trial to compare the efficacy, tolerability and effect on quality of life of diclofenac sodium slow release (DSR) 100 mg daily and a combination of dextropropoxyphene 180 mg and paracetamol 1.95 g daily (D&P). Health status or quality of life was measured using the Nottingham Health Profile (NHP) questionnaire. 2. Pain as measured by a visual analogue scale (VAS) showed 8% greater pain reduction with DSR as compared with D&P (P less than 0.05). Physical mobility as measured by the NHP improved by 13% more with DSR as compared with D&P (P less than 0.01). Energy, sleep, social isolation and emotional reactions did not differ significantly between the two treatment groups, but both treatment groups showed improvement during the trial. More D&P patients as compared with DSR patients reported problems with their job of work (P less than 0.05), and time lost from work (P less than 0.05). 3. Patients on D&P suffered an excess of tiredness or sleep disturbance (50 vs 21, P less than 0.01) whilst patients treated with DSR had an excess of abdominal or epigastric pain or indigestion (40 vs 18, P less than 0.01). 57 patients were withdrawn from DSR and 65 from D&P.
Cardiovascular (ECG and systolic time intervals) and anticholinergic effects of repeated doses of femoxetine‐a comparison with amitriptyline and placebo in healthy men.
Authors: Warrington SJ , Turner P. , Skrumsager BK
Published: July 2012

1. The cardiovascular and anticholinergic effects of femoxetine and amitriptyline were compared with those of placebo in a double‐blind cross‐over trial in 12 healthy men. The daily doses administered were therapeutic: 600 mg femoxetine and 150 mg amitriptyline. Duration of treatment with each drug was 13 days. 2. The statistically significant effects on systolic time intervals and ECG comprised a larger decrease of QS2 index during femoxetine than during amitriptyline, and an increase of PEP/LVET ratio and QRS duration by amitriptyline. These results suggest that femoxetine and, to a lesser extent, amitriptyline increase contractility compared with placebo, and amitriptyline, but not femoxetine, causes delay in intracardiac conduction. 3. The effects of amitriptyline on the systolic time intervals are difficult to interpret because of the changes in heart rate and intracardiac electrical conduction caused by the drug. These problems of interpretation are discussed. 4. No significant changes in blood pressure were observed. The heart rate during both femoxetine and amitriptyline periods was significantly faster than during the placebo period, amitriptyline causing a significantly greater increase. 5. Salivary secretion was decreased more by amitriptyline (26%) than by femoxetine (8%), the latter being not significantly different from placebo. Femoxetine tended to increase pupil diameter and amitriptyline to increase accommodation near point, but no visual disturbances were reported on any treatment. Symptoms such as dry mouth, constipation and sedation were significantly less frequently reported during femoxetine than during amitriptyline treatment.
Comparison of the cardiovascular and pulmonary effects of oral celiprolol, propranolol and placebo in normal volunteers.
Authors: Busst CM , Bush A.
Published: July 2012

1. The effects on heart rate, blood pressure and pulmonary function of single oral doses of celiprolol hydrochloride (400 mg), and propranolol (40 mg) were compared with placebo in 12 healthy volunteers, in a double‐blind three‐period crossover study. 2. Celiprolol had no effect on heart rate while propranolol caused a significant reduction compared with placebo. Systolic blood pressure was reduced by propranolol but not celiprolol, whereas standing diastolic blood pressure was lowered by both drugs. 3. The maximal expiratory flow at 50% vital capacity (MEF.50), was significantly lower after propranolol compared with placebo and celiprolol. Celiprolol had no effect on the flow‐volume loop parameters. 4. Effective pulmonary blood flow was significantly increased by celiprolol, but reduced by propranolol. 5. A high incidence of subjective side‐effects were experienced on celiprolol (10/12; particularly unpleasant in 5). Side‐effects were experienced to a lesser extent on placebo (8/12). Only one volunteer experienced a side‐effect on propranolol. 6. Oral celiprolol exerts its hypotensive effect by vasodilatation without reflex tachycardia. It does not cause airways obstruction in healthy subjects.
Timolol metabolism and debrisoquine oxidation polymorphism: a population study.
Authors: Lennard MS , Lewis RV , Brawn LA , Tucker GT , Ramsay LE , Jackson PR , Woods HF
Published: July 2012

1. The metabolism of orally administered timolol (T) to its ring cleavage ethanolamine (TE) and glycine (TG) products was studied in 108 unrelated hypertensive patients. 2. Statistically significant correlations between the 0‐8 h urinary debrisoquine/4‐hydroxy‐ debrisoquine ratio and the T/TE (rs = 0.74, P less than 0.001), T/TG (rs = 0.42, P less than 0.001) and T/TE + TG (rs = 0.49, P less than 0.001) ratios were found. 3. The log10 T/TE, T/TG and T/TE + TG ratios from poor metabolisers of debrisoquine (PMs) were grouped at the upper end of a unimodal distribution. 4. These results indicate that timolol metabolism is partly under monogenic control of the debrisoquine‐type. 5. The mean +/‐ s.d. plasma timolol concentration in PMs (82 +/‐ 43 ng ml‐1) was double that in extensive metabolisers (45 +/‐ 19 ng ml‐1) (P = 0.011). The clinical significance of this observation remains to be established.
Variability in the elimination of mianserin in elderly patients.
Authors: Begg EJ , Sharman J.R. , Kidd JE , Sainsbury R. , Clark DW
Published: July 2012

1. Two studies of the elimination of mianserin are reported. 2. In the first study, the oral clearance of mianserin was measured in 15 elderly patients at steady state. In a sub‐group of eight patients who completed studies at two different doses there was evidence of enhanced oral clearance at the higher dose. 3. In the second study, the elimination half‐life was estimated in 12 patients who were observed to have disproportionately high mianserin concentrations with respect to dose. All had half‐lives greater than or equal to 2.5 days with a mean of 6 +/‐ 2.8 (s.d.) days. In six of the patients the profile of elimination was suggestive of saturable elimination. 4. The sparteine oxidation status was measured in seven of the patients showing slow mianserin elimination. Only one was a ‘poor oxidiser’ of sparteine, suggesting no concordance with this phenotype. 5. It is concluded that there is marked variability in the elimination of mianserin in elderly patients.
Assessment of the anticholinergic effect of the new antihistamine mizolastine in healthy subjects.
Authors: Danjou P. , Molinier P. , Berlin I. , Patat A. , Rosenzweig P. , Morselli PL
Published: July 2012

1. Twelve healthy subjects were enrolled in a double‐blind placebo controlled cross‐over study in order to assess the possible anticholinergic effects of four doses of a new antihistamine compound, mizolastine, compared with hyoscine butylbromide (HBB) used as a reference anticholinergic drug. 2. Although mizolastine, a potent and selective H1‐receptor blocker has no affinity for muscarinic receptors and does not antagonize the effects of carbachol in rodents, a study was initiated to investigate its effects on various effectors possessing muscarinic receptors (eye, heart, sweat gland, salivary gland). 3. HBB (40 mg, s.c.) impaired accommodation, decreased salivary flow and inhibited cardiac sinus arrhythmia. Pupil diameter and maximum constriction speed, carbachol‐induced skin sweating and Valsalva ratio were unaffected. 4. Mizolastine (5, 10, 20, 40 mg p.o.) did not affect any parameter at any time point, demonstrating a lack of anticholinergic effect.
Selectivity of antagonist and partial agonist activity of celiprolol in normal subjects.
Authors: Wheeldon NM , McDevitt DG , Lipworth BJ
Published: July 2012

1. The aims of this study were to assess the relative beta 1/beta 2 selectivity of the antagonist and partial agonist activity (PAA) of celiprolol in man. 2. Eight normal males received single oral doses of celiprolol 200 mg (C200), 400 mg (C400) and 800 mg (C800); atenolol 50 mg (A50), 100 mg (A100) and 200 mg (A200); nadolol 40 mg (N40) and placebo (PL), administered in a single‐blind, randomised crossover design. 3. At rest, in the presence of low levels of circulating adrenaline and noradrenergic tone, a low dose of celiprolol (C200) showed evidence of beta 1‐PAA by significant increases in systolic blood pressure and resting heart rate. At higher doses (C400, C800), beta 2‐PAA became evident by a significant increase in postural finger tremor, whereas C200 had no effect. 4. In the presence of a beta 1‐ adrenoceptor agonist, as assessed by reduction of exercise tachycardia, increasing doses of celiprolol produced significantly less beta 1‐ adrenoceptor blockade compared with atenolol. Furthermore, there was no increase in beta 1‐adrenoceptor blockade beyond C400. 5. In the presence of a beta 2‐adrenoceptor agonist, as assessed by blunting of terbutaline‐induced chronotropic, hypokalaemic and finger tremor responses, celiprolol exhibited less beta 2‐adrenoceptor blockade than comparable doses of atenolol used in clinical practice. 6. Exercise hyperkalaemia was blunted significantly by C400 and C800 in comparison with all doses of atenolol and nadolol.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of an oral thromboxane TP receptor antagonist BAY u 3405, on prostaglandin D2‐ and histamine‐induced bronchoconstriction in asthma, and relationship to plasma drug concentrations.
Authors: Johnston SL , Bardin PG , Harrison J. , Ritter W. , Joubert J.R. , Holgate ST
Published: July 2012

1. The potent bronchoconstrictors prostaglandin (PG) D2, PG F2 alpha and thromboxane A2 are thought to have a role in the pathogenesis of asthma, mediated via the thromboxane (TP) receptor. 2. BAY u 3405 is a new potent selective competitive TP receptor antagonist. 3. The effect of single oral doses of 20 mg and 50 mg BAY u 3405 was examined against histamine and PG D2 bronchial provocation at 90 min after drug ingestion and, for the 20 mg dose alone, at 60 min after ingestion, in randomised, double‐blind placebo controlled crossover studies. A time course study was performed with the 20 mg dose. 4. BAY u 3405 protected against PG D2 bronchial provocation. The 20 mg dose increased the amount of PG D2 required to produce a fall of 20% in the forced expiratory volume in 1 s by 6‐fold and 16‐fold at 60 min and 90 min after ingestion respectively, and the 50 mg dose by 14‐fold at 90 min after ingestion. 5. The specificity of the drug was confirmed in vivo in that there was no significant protection against histamine bronchial provocation at either dose or at either time point. 6. The time course study showed significant protection against PG D2 bronchial provocation at 1 h and at 3 h after a single 20 mg oral dose. 7. There was no correlation between subjects in plasma BAY u 3405 concentration and drug effect. Within the subjects performing the time course study there was a strong correlation in time between drug effect and plasma BAY u 3405 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
A study of the interaction of omeprazole and warfarin in anticoagulated patients.
Authors: Unge P. , Svedberg LE , Nordgren A. , Blom H. , Andersson T. , Lagerstrom PO , Idstrom JP
Published: July 2012

1. Thirty‐five patients on continuous therapy with warfarin were given omeprazole 20 mg once daily and placebo each for 3 weeks according to a two‐centre randomised double‐blind cross‐over design. 2. Blood samples were obtained once weekly during the run‐in and follow‐up periods as well as during the first 2 weeks of each treatment period, and twice during the last week of each treatment period. Plasma concentrations of R‐ and S‐warfarin were measured by h.p.l.c. and the anticoagulant effect was assessed using the Trombotest. 3. Twenty‐eight patients were evaluated. The mean plasma concentration of R‐warfarin was increased by 9.5% during omeprazole treatment compared with placebo, while that of S‐ warfarin, the more active isomer, was unaffected. The coagulation time was not significantly changed (106 s during omeprazole and 98 s during placebo). Corresponding TT‐values (Trombotest) were 8.8 and 9.9 (NS).
Single and multiple dose pharmacokinetics of tenidap sodium in healthy subjects.
Authors: Gardner MJ , Wilner KD , Hansen RA , Fouda HG , McMahon GF
Published: July 2012

1. The absorption, protein binding, clearance and absolute bioavailability of tenidap sodium were studied after single and multiple dosing. 2. Thirteen healthy male volunteers received a single 120 mg oral dose of tenidap sodium and a 20 mg intravenous infusion of deuterated tenidap ([D3]‐tenidap) on day 1. This was followed by a 6‐ day washout period (days 2‐7) and then further daily doses of oral tenidap sodium 120 mg for 21 consecutive days (days 8‐28) with an additional 20 mg intravenous infusion of [D3]‐tenidap on day 28. Twelve subjects were eligible for pharmacokinetic evaluation. 3. Following multiple oral doses, the half‐life of tenidap is approximately 23 h. 4. Following single and multiple dose administration, the absolute bioavailability is 85%. 5. Systemic clearance of [D3]‐tenidap was 29% greater on day 28 than on day 1 indicating a significant increase in intrinsic clearance (CLint) of tenidap since protein binding of tenidap in plasma did not change during the study. Consistent with the increase in systemic clearance, the half‐life of [D3]‐tenidap decreased and the ratio of AUC(0,24h) day 28/AUC day 1 following oral dosing was less than one. Tenidap is subject to extensive hepatic metabolism, so the increase in CLint may indicate that tenidap induces its own metabolism. 6. Steady‐state was achieved by the eleventh day of dosing. Since numerous studies in patients with rheumatoid arthritis have shown that multiple dosing with tenidap is clinically efficacious, this suggests that the pharmacokinetic differences observed between the first and twenty‐first day of multiple tenidap dosing do not influence the clinical response.
Pharmacokinetics of tenidap sodium administered with food or antacid in healthy volunteers.
Authors: Coates PE , Mesure R
Published: July 2012

1. The effects of food and antacid on the pharmacokinetics of tenidap were investigated in this randomised, 3‐way cross‐over study. 2. Twenty‐ one healthy young men, mean age 27.4 years, received single oral doses of tenidap sodium 120 mg at weekly intervals after either an overnight fast, with food or with 20 ml of the antacid Maalox (aluminum hydroxide 1.8 g and magnesium hydroxide 1.2 g). Plasma samples collected immediately before and up to 96 h after each tenidap dose were assayed for tenidap using a validated h.p.l.c. method. The assay data were used to determine the pharmacokinetic parameters of tenidap in each group. 3. Co‐administration of tenidap with food produced a statistically significant delay in the rate of absorption (tmax, 4.4 h) (P < 0.001). There was no statistically significant change in Cmax. However, co‐ administration with the antacid significantly decreased both the mean rate and extent of absorption of tenidap compared with the fasting state: AUC, 420.93 micrograms ml‐1 h (antacid), 476.31 micrograms ml‐1 h (fasting) (P = 0.026); Cmax 14.3 micrograms ml‐1 (antacid), 18.0 micrograms ml‐1 (fasting) (P = 0.001); tmax 4.5 h (antacid), 2.9 h (fasting) (P < 0.001). Neither food nor the antacid had any effect on the elimination of tenidap. These changes in tmax are unlikely to be of any clinical significance owing to the long half‐life of tenidap. 4. Treatment was well tolerated. Only two adverse events were reported that were considered by the investigator to be related to tenidap. There were no reports of laboratory or cardiovascular abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)
Cimetidine does not alter the clearance or plasma binding of tenidap in healthy male volunteers.
Authors: Wilner KD , Gardner MJ
Published: July 2012

1. An open‐label, placebo‐controlled study was conducted to examine the effect of cimetidine on the steady‐state pharmacokinetics of tenidap. 2. Twenty‐four healthy volunteers received tenidap sodium (120 mg) each morning throughout the study. On day 14 plasma levels of tenidap had reached steady state; half of the subjects were treated concomitantly with cimetidine 800 mg at night, while the other half received placebo. Allocation of cimetidine or placebo was randomised. Plasma profiles of tenidap were measured on days 14 and 16. 3. The addition of cimetidine did not significantly affect the Cmax, tmax, or lambda z of tenidap. The AUC(0,24h) increased by 4% between days 14 and 16 in the cimetidine treatment group, compared with a decrease of 2% in the placebo group. This small difference is statistically significant (P = 0.047), but it is not considered to be clinically relevant. 4. It is concluded that concomitant administration of cimetidine does not significantly affect the pharmacokinetics of tenidap at steady state.
Tenidap sodium decreases renal clearance and increases steady‐state concentrations of lithium in healthy volunteers.
Authors: Apseloff G , Wilner KD , von Deutsch DA , Gerber N
Published: July 2012

1. An open‐label, randomised placebo‐controlled study was conducted to determine the effects of tenidap sodium, a novel, cytokine‐modulating anti‐rheumatic drug, on the steady‐state concentrations and renal clearance of lithium carbonate. 2. Eighteen healthy male volunteers received 450 mg lithium carbonate twice daily for 15 days and once on day 16. On days 9‐16 subjects also received either placebo or 120 mg day‐1 tenidap 2 h prior to the morning dose of lithium. 3. Following a single dose of tenidap, the renal clearance of lithium decreased significantly by 0.36 l h‐1 (‐23%) compared with the clearance in the placebo group, which increased by 0.18 l h‐1 (+14%). Steady‐state serum lithium levels increased after a single dose of tenidap by 0.069 mEq l‐ 1 (+13%), and in the placebo group levels increased by 0.003 mEq l‐1 (+0.5%); this difference was not significant. 4. After 7 days' continuous administration of tenidap, the renal clearance of lithium had decreased by 0.38 l h‐1 (‐25%), compared with the placebo group in which clearance had increased by 0.16 l h‐1 (+12%). The steady‐state serum concentration of lithium increased by 0.208 mEq l‐1 (+39%) in the tenidap group and by 0.063 mEq l‐1 (+10%) in the placebo group. Both of these differences were significant. 5. Two subjects who received lithium plus tenidap experienced gastrointestinal side effects, compared with none of those who were administered lithium plus placebo. 6. It is recommended that serum lithium levels be monitored when tenidap and lithium are administered concomitantly.
Effect of tenidap sodium on digoxin pharmacokinetics in healthy young men.
Authors: Dewland PM , Grimwood VC , Rapeport WG , Coates PE
Published: July 2012

1. The effects of tenidap sodium and placebo on digoxin pharmacokinetics were compared in 14 healthy young men, in a double‐ blind, parallel‐group study lasting for 24 days. 2. Subjects were administered digoxin alone for the first 10 days and digoxin plus tenidap 120 mg day‐1 or placebo for the remaining 14 days. 3. Changes in the means between day 10 (digoxin monotherapy) and day 24 (combined therapy) for renal clearance, area under the plasma concentration‐time curve during the dosing interval, and the minimum and maximum plasma digoxin concentrations did not differ significantly between the tenidap and placebo groups. There was a small but statistically significant increase (0.5 h) in the time taken to reach maximum plasma digoxin concentration following 14 days' continuous tenidap co‐administration compared with placebo, but this was not considered to be clinically meaningful. 4. Co‐administration of tenidap and digoxin was well tolerated. No subject withdrew from the study during combination treatment. Treatment‐related adverse events were of mild to moderate severity and were reported by four subjects on digoxin monotherapy, four on tenidap and digoxin, and by two on digoxin and placebo. Those reported by the tenidap group predominantly affected the gastrointestinal system and were mild in severity. There were no reports of laboratory test abnormalities or cardiovascular abnormalities related to combined digoxin and tenidap administration. 5. The results of this study indicate that, in healthy young men, co‐ administration of tenidap with digoxin does not have any apparent clinically significant effects on the pharmacokinetic profile of digoxin, and the treatment is well tolerated.
Morbidity and mortality in ageing HIV‐infected haemophilia patients
Authors: van de Putte D. E. Fransen , Fischer K. , Roosendaal G. , Hoepelman A. I. M. , Mauser‐Bunschoten E. P.
Published: July 2012

Over 25 years of follow‐up is now available for HIV‐infected haemophilia patients. The aim of this study was to retrospectively asses the morbidity and mortality of HIV infection and the effects of HAART in these patients. Data on HIV infection, its treatment and all types of comorbidity were collected from medical records of all 60 HIV‐positive haemophilia patients who were treated at the Van Creveldkliniek since 1980 and compared with data from 152 HIV‐negative patients with severe haemophilia and the general age‐matched male population. AIDS developed in 27 patients (45%), while 31 patients died (52%). Death was solely or partially AIDS‐related in 71%. Development of AIDS and AIDS‐related deaths declined strongly after the introduction of HAART. Only one major ischaemic cardiovascular event occurred in our study population. Of the 27 patients who were still treated at our clinic in 2010, 25 (93%) were on HAART. They had more often hypertension and diabetes, but less often overweight and obesity and lower cholesterol levels than the general population. The occurrence of spontaneous intracranial bleeding was higher in HIV‐positive haemophilia patients on HAART than in HIV‐negative patients with severe haemophilia (16.6 vs. 1.2 per 1000 patient years). Since the introduction of HAART, the impact of HIV infection on morbidity and survival has decreased. The increased prevalences of hypertension and diabetes, however, warrant regular screening. HIV‐positive haemophilia patients on HAART appear to have an increased risk of spontaneous intracranial bleeding.
The NsrR regulon in nitrosative stress resistance of Salmonella enterica serovar Typhimurium
Authors: Karlinsey Joyce E. , Bang Iel‐Soo , Becker Lynne A. , Frawley Elaine R. , Porwollik Steffen , Robbins Hannah F. , Thomas Vinai Chittezham , Urbano Rodolfo , McClelland Michael , Fang Ferric C.
Published: July 2012

Nitric oxide (NO·) is an important mediator of innate immunity. The facultative intracellular pathogen Salmonella has evolved mechanisms to detoxify and evade the antimicrobial actions of host‐derived NO· produced during infection. Expression of the NO·‐detoxifying flavohaemoglobin Hmp is controlled by the NO·‐sensing transcriptional repressor NsrR and is required for Salmonella virulence. In this study we show that NsrR responds to very low NO· concentrations, suggesting that it plays a primary role in the nitrosative stress response. Additionally, we have defined the NsrR regulon in Salmonella enterica sv. Typhimurium 14028s using transcriptional microarray, qRT‐PCR and in silico methods. A novel NsrR‐regulated gene designated STM1808 has been identified, along with hmp, hcp‐hcr, yeaR‐yoaG, ygbA and ytfE. STM1808 and ygbA are important for S. Typhimurium growth during nitrosative stress, and the hcp‐hcr locus plays a supportive role in NO· detoxification. ICP‐MS analysis of purified STM1808 suggests that it is a zinc metalloprotein, with histidine residues H32 and H82 required for NO· resistance and zinc binding. Moreover, STM1808 and ytfE promote Salmonella growth during systemic infection of mice. Collectively, these findings demonstrate that NsrR‐regulated genes in addition to hmp are important for NO· detoxification, nitrosative stress resistance and Salmonella virulence.
A brief intervention to improve food allergy knowledge among US pediatricians: lessons learned
Authors: Springston Elizabeth E. , Lau Claudia H. , Patel Parav , Warrier Manoj R. , Sohn Min‐Woong , Pongracic Jacqueline , Gupta Ruchi S.
Published: July 2012

Objective:  To evaluate a brief educational tool for pediatricians developed to address known gaps in food allergy knowledge.

Study Design:  Pre‐ and post‐assessments were administered to a convenience sample of 61 US pediatricians completing the Food Allergy Comprehension Tool between February and March of 2010. McNemar’s and Wilcoxon signed rank tests were used to determine whether clinical knowledge of food allergy and level of comfort in caring for food‐allergic children increased significantly after reviewing the tool. Logistic regression models were used to measure the association of participant characteristics with increased knowledge and comfort.

Results:  Sixty‐one percent of surveyed physicians answered more knowledge questions correctly after reviewing the tool. Significantly more participants correctly indicated that anaphylaxis poses the greatest threat to teenagers rather than young children, and correctly rejected chronic nasal problems as a symptom of food allergy (p < 0.05). Comfort in caring for food‐allergic children increased significantly on all items post‐intervention (p < 0.05). Odds of increased knowledge and comfort were significantly higher among pediatricians without previous training in food allergy.

Conclusion:  The Food Allergy Comprehension Tool is a rapid way to address known knowledge gaps among pediatricians and to identify areas in need of further intervention. We recommend integration of the tool with current food allergy guidelines.
Japonica cultivars' susceptibility to the rice water weevil Lissorhoptrus oryzophilus (Coleoptera: Curculionoidea: Brachyceridae)
Authors: Lupi D. , Giudici M. L. , Cenghialta C. , Rocco A. , Jucker C. , Colombo M.
Published: July 2012

Italy is the largest rice‐producing country in the European Union. In Italy, only japonica cultivars are listed in the Italian National Register. Almost all of the rice production is concentrated in the Po Valley, where the rice water weevil Lissorhoptrus oryzophilus Kuschel was first detected and settled. This study investigated the performance of this pest in terms of feeding, reproduction and plant injury on 10 rice cultivars chosen among the most widely grown in Italy. No‐choice experiments were conducted to evaluate the plant susceptibility to larval attack and to find out how cultivars can influence the adult leaf area consumption. The results gave evidence of different types of attack depending on the density of the insect (0.6 adults/plant vs. 0.9 adults/plant), the cultivar type and climatic conditions. Different cultivars with the same level of infestation gave different results in terms of productivity. Production was significantly affected by the larval presence in 4 of the 10 cultivars tested. A different population structure reflected a different damage severity. Statistically different values for total adult leaf area consumption were found according to adult female age and to the cultivar.
Successful treatment of a patient with tumor necrosis factor receptor‐associated periodic syndrome using a half‐dose of etanercept
Authors: Kusuhara Koichi , Hoshina Takayuki , Saito Mitsumasa , Ishimura Masataka , Inoue Hirosuke , Horiuchi Takahiko , Sato Tetsuji , Hara Toshiro
Published: July 2012

TNF receptor‐associated periodic syndrome (TRAPS) is caused by mutations of TNFRSF1A gene and characterized by recurrent febrile episodes of prolonged duration and initial good response to steroids. Etanercept, a TNF blocker, has been used as a putative molecular‐targeted agent for TRAPS, with some patients showing limited efficacy. Here, we report a patient with TRAPS who recovered from steroid dependency by etanercept and kept remission with a reduced dose of etanercept. The pathophysiology of TRAPS still remains to be elucidated and several hypotheses have been proposed. In the most recent hypothesis, the concerted action of wild‐type and mutant TNF receptors plays an important role in provoking enhanced inflammation in TRAPS. The excellent response to etanercept in our patient suggested that there is heterogeneity in TRAPS patients in terms of the contribution of normal TNF signaling to autoinflammation.
Atomoxetine improves communication in a girl with semantic‐pragmatic disorder
Authors: Inoko Kayo , Kodaira Kayano , Osawa Makiko
Published: July 2012

This report describes the case of an ADHD girl (hereafter referred to as K) with semantic‐pragmatic disorder, she was treated with atomoxetine. K was a 9‐year‐old girl. She had difficulty understanding words or sentences, finding words, and producing sentences. K also displayed symptoms of severe inattentiveness. K was diagnosed with DSM‐IV‐defined1 ADHD, predominantly the inattentive type. Her communication impairment was considered symptomatic of semantic‐pragmatic disorder. K was started on atomoxetine, the dose was increased to 50 mg/day (dosage based on weight: 1.8 mg/kg). Her communication activities were improved a few weeks after atomoxetine 50 mg/day was administered. She was unable to organize information pertaining to words, and so could not use words in expressive language. These problems were mitigated through the administration of atomoxetine. Further prospective studies are needed to better understand the therapeutic effects of atomoxetine in patients with semantic‐pragmatic disorder.
Myocarditis in a pediatric case of pandemic 2009H1N1 influenza
Authors: Jibiki Toshiaki , Sakamoto Ryota , Nakaya Mitsuru , Kanazawa Masaki , Gotoh Fumihiro , Yamaguchi Seiichi , Kutsuna Satoru , Hashimoto Yuji , Anzai Satoshi , Abe Katsuaki
Published: July 2012

We report a 6‐year‐old boy with no major disease history or allergic conditions initially presented with pneumonia, progressed to acute respiratory distress syndrome and acute myocarditis caused by pandemic 2009H1N1 influenza diagnosed with RT‐PCR testing, successfully managed with mechanical ventilation and percutaneous cardiopulmonary support system. Marked transient elevation of IgE in acute phase of the disease and the subsequent diagnosis of atopic asthma in our patient suggested a possible role of an underlying allergic condition in the clinicopathological process. Critically ill 2009H1N1‐infected patient with acute respiratory failure should carefully be physiologically monitored together with serial assessment of biomarkers aiming at a favorable cardiac outcome by giving the timely diagnosis and intervention.
Recovery of evidence‐based practice
Authors: Gordon Sarah E. , Ellis Pete M.
Published: July 2012

Consumer recovery is now enshrined in the national mental health policy of many countries. If this construct, which stems from the consumer/user/survivor movement, is truly to be the official and formal goal of mental health services, then it must be the yardstick against which evidence‐based practice (EBP) is judged. From a consumer‐recovery perspective, this paper re‐examines aspects of services chosen for study, methodologies, outcomes measures, and standards of evidence associated with EBP, those previously having been identified as deficient and in need of expansion. One of the significant differences between previous investigations and the present study is that the work, writing, perspectives, and advocacy of the consumer movement has developed to such a degree that we now have a much more extensive body of material upon which to critique EBP and inform and support the expansion of EBP. Our examination reinforces previous findings and the ongoing need for expansion. The consumer recovery‐focused direction, resources, frameworks, and approaches identified through the present paper should be used to expand the aspects of services chosen for study, methodologies, outcomes measures, and standards of evidence. This expansion will ultimately enable services to practice in a manner consistent with the key characteristics of supporting personal recovery.
MODEL‐BASED DIRECT ESTIMATION OF SMALL‐AREA DISTRIBUTIONS
Authors: Salvati Nicola , Chandra Hukum , Chambers Ray
Published: July 2012

Much of the small‐area estimation literature focuses on population totals and means. However, users of survey data are often interested in the finite‐population distribution of a survey variable and in the measures (e.g. medians, quartiles, percentiles) that characterize the shape of this distribution at the small‐area level. In this paper we propose a model‐based direct estimator (MBDE, Chandra and Chambers) of the small‐area distribution function. The MBDE is defined as a weighted sum of sample data from the area of interest, with weights derived from the calibrated spline‐based estimate of the finite‐population distribution function introduced by Harms and Duchesne, under an appropriately specified regression model with random area effects. We also discuss the mean squared error estimation of the MBDE. Monte Carlo simulations based on both simulated and real data sets show that the proposed MBDE and its associated mean squared error estimator perform well when compared with alternative estimators of the area‐specific finite‐population distribution function.
Repetition and Spacing Effects on True and False Recognition in the DRM Paradigm
Authors: DUBUISSON JEAN‐BAPTISTE , FIORI NICOLE , NICOLAS SERGE
Published: July 2012

Dubuisson, J.‐B., Fiori, N. & Nicolas, S. (2012) Repetition and spacing effects on true and false recognition in the DRM paradigm. Scandinavian Journal of Psychology 53, 382–389.

With the Deese‐Roediger‐McDermott (DRM) paradigm, the repetition effect on false memory had never been clarified. More importantly, the spacing effect on false memory was never directly investigated. So, we carried out two experiments to examine these effects on true and false recognition. In experiment 1, participants studied DRM lists which were presented one, three or five times. In experiment 2, we manipulated the repetition mode (massed vs. spaced with a short interval or a long interval) to explore the spacing effect. The results showed that true recognition increased monotonically with list repetition (experiment 1) and repetition spacing (experiment 2). The most striking finding was a similar spacing effect but no repetition effect on false recognition. Thus, these results were principally discussed in the light of the activation‐monitoring framework.
Decomposition of Variance for Spatial Cox Processes
Authors: JALILIAN ABDOLLAH , GUAN YONGTAO , WAAGEPETERSEN RASMUS
Published: July 2012

Abstract.  Spatial Cox point processes is a natural framework for quantifying the various sources of variation governing the spatial distribution of rain forest trees. We introduce a general criterion for variance decomposition for spatial Cox processes and apply it to specific Cox process models with additive or log linear random intensity functions. We moreover consider a new and flexible class of pair correlation function models given in terms of normal variance mixture covariance functions. The proposed methodology is applied to point pattern data sets of locations of tropical rain forest trees.
Youth Crime and Education Expansion
Authors: Machin Stephen , Vujić Sunčica , Marie Olivier
Published: July 2012

We present new evidence on the causal impact of education on crime, by considering a large expansion of the UK post-compulsory education system that occurred in the late 1980s and early 1990s. The education expansion raised education levels across the whole education distribution and, in particular for our analysis, at the bottom end enabling us to develop an instrumental variable strategy to study the crime- education relationship. At the same time as the education expansion, youth crime fell, revealing a significant cross-cohort relationship between crime and education. The causal crime reducing effect of education is estimated to be negative and significant, and considerably bigger in (absolute) magnitude than ordinary least squares estimates. The education boost also significantly impacted other productivity-related economic variables (qualification attainment and wages), demonstrating that the incapacitation effect of additional time spent in school is not the sole driver of the results.
ON ASYMPTOTIC PROPERTIES OF THE PARAMETERS OF DIFFERENTIATED PRODUCT DEMAND AND SUPPLY SYSTEMS WHEN DEMOGRAPHICALLY CATEGORIZED PURCHASING PATTERN DATA ARE AVAILABLE*
Authors: Myojo Satoshi , Kanazawa Yuichiro
Published: July 2012

We derive asymptotic properties of an estimator for supply and demand models extended with additional moments relating consumer demographics to the characteristics of purchased products. We clarify the structure of a practical sampling scheme in which the extended estimator is consistent, asymptotically normal, and more efficient than the original estimator. We provide conditions guaranteeing the asymptotic theorems hold for the random coefficient logit model of demand with oligopolistic suppliers. Extensive simulation studies demonstrate significant benefits of the additional moments in estimating the random coefficient logit model.
The Occurrence of Mixed Infections ofSymbiodinium(Dinoflagellata) within Individual Hosts
Authors: Fay Scott A. , Weber Michele X.
Published: July 2012

Coral reef ecosystems depend on symbiosis between dinoflagellates of the genusSymbiodiniumFreudenthal and their various hosts. The physiological characteristics associated with a particular lineage or species ofSymbiodiniumcan determine a host's susceptibility to harmful bleaching. Therefore, the threat posed by global climate change on a host may be reduced if it can switch or shuffle its dominant algal symbiont type. An important prerequisite to this potential to switch or shuffle is the ability to host multiple alternative dominant symbiont genotypes. To examine the distribution of this trait, we review reports of mixedSymbiodiniuminfections in corals and nonscleractinian hosts from a phylogenetic perspective. Hosts showing evidence of mixed infection are broadly distributed across the most deeply divergent host lineages, including foraminifera, mollusks, sponges, and cnidarians. The occurrence of mixed infections is also broadly distributed across most clades of scleractinian corals. Individual colonies of certain well‐studied cosmopolitan coral genera, such asAcropora,Montastraea, andPocillopora,yield many reports of mixed infection, while other genera, such asPorites, do not. We further discuss mixedSymbiodiniuminfections in the context of evolutionary ecology theory. Selection pressures that affect the prevalence of mixed infection may be exerted by variation in host environment, host ontogeny, symbiont transmission strategy, host regulation of symbiont populations, availability of free‐living symbiont lineages, competition between symbiont lineages, and niche partitioning of the internal host environment.
Evaluation of 5‐Year Risk of Cardiovascular Events in Patients after Acute Myocardial Infarction Using Synchronization of 0.1‐Hz Rhythms in Cardiovascular System
Authors: Kiselev Anton R. , Gridnev Vladimir I. , Prokhorov Mikhail D. , Karavaev Anatoly S. , Posnenkova Olga M. , Ponomarenko Vladimir I. , Bezruchko Boris P. , Shvartz Vladimir A.
Published: July 2012

Background: Synchronization between 0.1‐Hz rhythms in cardiovascular system is deteriorated at acute myocardial infarction (AMI) leading to a disruption of natural functional couplings within the system of autonomic regulation.

Objective: This study evaluates the prognostic value of autonomic regulation indices for the 5‐year risk of fatal and nonfatal cardiovascular events in patients after AMI.

Methods and Results: We studied 125 patients (53 [42%] female) after AMI aged between 30 and 83 years. The period of observation was 5 years with checkpoints at the first week after AMI and after each year after AMI. We compared the prognostic value of established clinical characteristics and degree S of synchronization between 0.1‐Hz rhythms in heart rate and microcirculation for evaluation of the 5‐year risk of mortality and recurrent myocardial infarction (MI) in patients after AMI. Acute heart failure Killip 2–4 at AMI and S < 20% at the first week after AMI were identified as the most important factors for evaluation of the risk of 5‐year mortality in patients after AMI (χ2= 14.2, P = 0.003). Sensitivity and specificity of low S (<20%) at the first week after AMI were 76% and 43%, respectively. For evaluation of the 5‐year risk of recurrent MI index S had no advantage over established clinical characteristics.

Conclusion: The value of S below 20% in patients with AMI is a sensitive marker of high risk of mortality during the subsequent five years. It is characterized by better prognostic value than most of established clinical characteristics.
Enhancing the Reliability in the Noninvasive Measurement of the His Bundle Magnetic Field Using a Novel Signal Averaging Methodology
Authors: Senthilnathan Sengottuvel , Chandrasekaran Parasakthi , Narayanan Mariyappa , Patel Rajesh , Katholil Gireesan , Janawadkar Madhukar P. , Thimmakudy Radhakrishnan S. , Thoddi Muralidharan R.
Published: July 2012

Background: Extraction of the weak electrical activity of the “His Bundle” (HB) by noninvasive methods has not been very successful in the past. The study reassesses the use of signal averaged magnetocardiography (SAMCG), overcoming some of the limitations in earlier studies including in the signal averaging methodology.

Methods: SAMCG on healthy subjects (14 male and 1 female) were performed using R‐peak as the fiducial point in all cases and also using QRS‐onset as the fiducial point in select cases.

Results: A conspicuous feature (H) with a magnitude up to 200 femto Tesla (fT) attributed to the HB activity was observed in the PR segment at several spatial positions on the thorax, with onset at 35–50 ms before the QRS‐onset (V) in 15 out of 18 trials constituting 83% of cases studied. The QRS‐onset as the fiducial point resolved the feature better compared to the conventionally used R‐peak, especially in trials exhibiting spread in heart rate (HR). This is attributed to the fluctuations in QonRD (the time interval between QRS‐onset and R‐peak) compared to the temporal stability of the H‐V duration.

Conclusions: SAMCG reveals a well‐resolved H feature. The double hump morphology of the feature extended at least up to a frequency of 150 Hz. The importance of the choice of QRS‐onset as the fiducial point is unequivocally demonstrated, illustrated by measurements on subjects exhibiting considerable heart rate variability. The latter has a general validity and should be applicable to SAECG as well.
P‐Wave Morphologic Characteristics Predict Cardiovascular Events in a Community‐Dwelling Population
Authors: Kabutoya Tomoyuki , Ishikawa Shizukiyo , Ishikawa Joji , Hoshide Satoshi , Kario Kazuomi
Published: July 2012

Background: There have been few reports on the relationship between P‐wave characteristics and long‐term cardiovascular events.

Methods: A nested case‐control study was conducted as part of the Jichi Medical School cohort study, which enrolled 12,490 subjects in a community‐dwelling population. The mean follow‐up period was 10.7 years. The P‐wave characteristics of 526 patients who suffered cardiovascular events (fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, and sudden death) within the follow‐up period (case group) were compared with those of 1578 matched controls (control group). The P‐wave morphology was classified as normal, deflected, and notched type in precordial leads. A broad P wave was defined as a maximum P‐wave duration of more than 120 ms in any of the 12 leads.

Results: The mean age was 64 ± 8 years and the percentage of males was 54% in both groups. A notched P wave at baseline was observed in 10.1% of the case group and 6.0% of the control group (P = 0.001). A notched P wave was a significant predictor of cardiovascular events after adjustment for covariates (odds ratio = 1.59; 95% confidence interval = 1.08–2.33). Among the patients with left ventricular hypertrophy as evaluated by the Sokolow–Lyon criteria or Cornell product criteria, there was no significant difference in cardiovascular events between those with and those without a notched P wave, but in the absence of left ventricular hypertrophy, patients with a notched P wave suffered more cardiovascular events than those without a notched P wave by each criteria.

Conclusion: P‐wave morphologic characteristics were effective for predicting cardiovascular events.