bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of pseudoracemic nitrendipine to elucidate the metabolic steps responsible for stereoselective disposition of nitrendipine enantiomers.
Authors: Mast V , Fischer C , Mikus G , Eichelbaum M
Published: July 2012

1. The pharmacokinetics, protein binding, bioavailability and metabolism of (+)‐R‐ and (‐)‐S‐nitrendipine were studied in six healthy subjects following random oral administration of 20 mg (+)‐R‐, 20 mg (‐)‐S‐ and 20 mg R,S‐nitrendipine (pseudoracemic mixture of 10 mg [13C4)‐ (+)‐R‐ and 10 mg (‐)‐S‐enantiomer). 2. After administration of the enantiomers pronounced differences in AUC (R: 29.9 +/‐ 20.1; S: 123.8 +/‐ 63.7 ng ml‐1 h; P less than 0.05), bioavailability (R: 10.7 +/‐ 7.4%; S: 44.6 +/‐ 23.1%; P less than 0.05) and Cmax (R: 14.4 +/‐ 7.7; S: 72.5 +/‐ 40.5 ng ml‐1; P less than 0.05) were observed between R‐ and S‐nitrendipine. When racemic nitrendipine was given bioavailability and dose normalized AUC and Cmax values of the S‐enantiomer were not different from the values after S‐nitrendipine‐administration. In contrast, bioavailability (R: 10.7% R,S: 22.1%) and dose normalized AUC (R: 15.0; R,S: 29.5 ng ml‐1 h and Cmax (R: 7.2; R,S: 16.8 ng ml‐1) of R‐ nitrendipine were doubled following R,S‐ as compared with R‐ nitrendipine administration. t1/2 (R: 9.8; S: 9.1 h) and tmax were not different between the enantiomers nor were the values different after administration of the enantiomers or racemate. The fraction unbound in serum of R‐nitrendipine was 0.0098 +/‐ 0.0032 (s.d.) and that of S‐ nitrendipine was 0.0083 +/‐ 0.0015 (s.d.). 3. The AUC values of the major pyridine metabolite M1 were similar after administration of R‐ and S‐nitrendipine (S: 114.7 +/‐ 48.5; R: 71.7 +/‐ 29.9 ng ml‐1 h).(ABSTRACT TRUNCATED AT 250 WORDS)
Phase I trial of a cisplatin‐albumin complex for the treatment of cancer of the head and neck.
Authors: Holding JD , Lindup WE , van Laer C , Vreeburg GC , Schilling V , Wilson JA , Stell PM
Published: July 2012

1. A phase I trial of a cisplatin‐albumin complex for the treatment of end‐stage squamous cell carcinoma of the head and neck is reported. The complex was prepared by overnight incubation of cisplatin with human albumin at 37 degrees C. This resulted in more than 98% of the drug being bound to protein at the start of treatment. The patients were either unable to continue with or had refused conventional therapy with cisplatin. 2. The trial began at a dose of 100 mg cisplatin m‐2 and was increased in 25 mg m‐2 increments to 650 mg m‐2. Despite the absence of the customary protective measures of pre‐hydration and anti‐emetic treatment no serious toxicity was encountered. 3. Unbound plasma platinum concentrations were lower than after conventional cisplatin treatment but total plasma platinum and tumour platinum concentrations were much higher. Urinary excretion of platinum was low and the incidence of nephrotoxicity was greatly diminished. Two responses were seen (one complete and one partial) in 38 patients treated and the median survival time was 109 days, compared with 151 days for patients treated conventionally with cisplatin and 56 days for untreated patients. 4. The complex is not as effective as conventional cisplatin therapy but is much less toxic, offers improved quality of life during treatment and may prove to be of benefit in patients who could not otherwise be treated.
Self‐selection for personality variables among healthy volunteers.
Authors: Pieters MS , Jennekens‐Schinkel A , Schoemaker HC , Cohen AF
Published: July 2012

1. Healthy student volunteers (n = 103) participating in ongoing clinical pharmacological research completed the Dutch Personality Inventory (DPI), the Dutch version of the Spielberger State‐Trait Anxiety Inventory (STAI‐DY) and the Dutch version of the Sensation Seeking Scale (SSS). 2. The volunteers were more extrovert (P less than 0.001), more flexible (P less than 0.001), more tolerant or less impulsive (P less than 0.001), had more self‐confidence and initiative (P less than 0.001), and were more satisfied and optimistic (P less than 0.01) when compared with the general norm. When compared with a student norm, volunteers had lower levels of state (P less than 0.001) and trait (P less than 0.05) anxiety. The general sensation seeking tendency of volunteers was higher than in the student norm group (P less than 0.001). The volunteers had a greater tendency to thrill‐and‐ adventure‐seeking (P less than 0.001) and to disinhibition (P less than 0.01). 3. Hence, volunteers were a selected sample of the total population of students. This may influence the interpretation of pharmacokinetic and pharmacodynamic parameters. 4. Personality screening should be added to the screening procedures for volunteers.
Endothelin‐1 induces a histamine‐dependent flare in vivo, but does not activate human skin mast cells in vitro.
Authors: Brain SD , Thomas G , Crossman DC , Fuller R , Church MK
Published: July 2012

The role of the mast cell in endothelin‐1 induced flare has been investigated by in vivo and in vitro experiments. The intradermal injection of endothelin‐1 (10 pmol) into human skin induced a pallor with surrounding axon‐reflex flare which is similar to the flare response to histamine (1 nmol). At these doses, chosen to give identical flare areas, blood flow was increased in the area of the endothelin‐induced flare over a longer period. A systemic H1‐receptor antagonist significantly inhibited the area of both flares, although blood flow in the remaining portion of the endothelin‐induced flare remained raised. Endothelin‐1 at concentrations up to 3 x 10(‐5) M failed to release histamine from human dispersed skin mast cells. We suggest from these results that a major component of endothelin‐1 induced flare results from mast cell activation that is secondary to direct stimulation of sensory nerves by the peptide.
Does smoking influence the pharmacokinetics and pharmacodynamics of the H2‐receptor antagonist famotidine?
Authors: Baak LC , Ganesh S , Jansen JB , Lamers CB
Published: July 2012

Twelve healthy habitual cigarette smokers and eight non‐smokers participated in a double‐blind placebo controlled study to determine the effect of smoking on the pharmacokinetics and pharmacodynamics of the H2‐receptor antagonist famotidine. In smokers, cigarette smoking was standardised and started 1 h before (A), or 2 h after (B) drug administration, or was prohibited (C). Intragastric pH‐levels (IGpH) were measured with an ambulatory pH‐recorder. Famotidine (40 mg orally) significantly raised median 22 h IGpH in non‐smokers and smokers in all study periods. The smoking sequence (A, B, C) did not significantly influence median 22 h IGpH in both placebo‐treated and famotidine‐ treated smokers, and no significant difference in median 22 h IGpH was shown between smokers and non‐smokers. Plasma drug concentrations were similar in the various experiments, although famotidine was detected earlier in plasma from non‐smokers compared with smokers (P less than 0.05). Smoking did not interfere significantly with the pharmacokinetics and pharmacodynamics of famotidine.
Inhaled histamine increases the rate of absorption of sodium cromoglycate from the lung.
Authors: Richards R , Fowler C , Simpson S , Renwick AG , Holgate ST
Published: July 2012

Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine challenge to determine the provocative concentration of histamine required to reduce the forced expiratory volume in one second (FEV1) by 20% (PC20) from baseline. On two further visits they inhaled either saline placebo or histamine and 5 min later inhaled an aerosol containing sodium cromoglycate. Measurements of FEV1 were made and blood samples taken for analysis of plasma sodium cromoglycate concentration at intervals for 3 h. In the asthmatic group histamine inhalation led to a 24 +/‐ 4% reduction in FEV1 but had no effect on the normal subjects. When compared with inhaled saline, histamine increased the initial pulmonary absorption of SCG without influencing the total amount of drug absorbed in both asthmatics and normals. These observations suggest that the pharmacokinetics of inhaled sodium cromoglycate may be altered significantly by inflammatory mediators present at the site of drug absorption from the airways.
The treatment of osteoarthritis.
Authors: Jones AC , Doherty M
Published: July 2012

1. The treatment of osteoarthritis is currently purely symptomatic. To enable rational therapy, careful clinical assessment is necessary to identify the origin of symptoms. Often, effective therapy can result from a biomechanical approach such as surgery, orthotics, physiotherapy and dieting. If drugs are required, there is little evidence that the current over‐reliance on non‐steroidal anti‐inflammatory drugs (NSAIDs) is justified. Full dose regular paracetamol should be the first line of analgesic therapy. In the majority of patients, simple analgesics are probably as effective as NSAIDs. If NSAIDs are used it is necessary to review regularly their use and to be aware of potential toxicity. 2. Many alternative strategies of pain management such as topical preparations, intra‐articular steroid injections, acupuncture, radiosynovectomy, transcutaneous nerve stimulation and anti‐ depressants, may be effective but their precise place in the armamentarium is not yet fully established. 3. The realisation that osteoarthritis is not a passive ‘wear and tear’ phenomenon but an active process that may be potentially modified, has led to interest in ‘chondroprotective’ agents, which may beneficially affect the osteoarthritic process. To date there are no convincing data available that such agents are, in fact, chondroprotective in humans.
Prevention of peripheral side‐effects of transdermal hyoscine by adjunctive therapy with low dosage of pyridostigmine.
Authors: Ziv I , Versano D , Ruach M , Izraeli S , Almog S , Alhalel A , Alkalay M , Menahem S , Tochner Z
Published: July 2012

1. The value of low dosage of pyridostigmine (30 mg three times daily) in preventing peripheral anti‐muscarinic side effects of a transdermal controlled‐release formulation of hyoscine, was tested in a double‐ blind placebo‐controlled study, involving 47 healthy subjects. 2. Salivary excretion was repeatedly measured during 48 h of combined therapy of two transdermal hyoscine patches with pyridostigmine and 14 h after its cessation. Blood acetylcholinesterase activity was also measured, serving as an index of pyridostigmine bioavailability. 3. The adjunctive therapy with pyridostigmine was highly effective in preventing the substantial impairment in salivary flow caused by the transdermal formulation. An associated 23% inhibition of blood acetylcholinesterase activity was observed. 4. Small doses of pyridostigmine may therefore have a role in increasing the tolerability of transdermal hyoscine therapy. In some patients this drug combination might also allow some increment of the hyoscine dose.
Effect of frusemide on the induction and potentiation of cough induced by prostaglandin F2 alpha.
Authors: Ventresca PG , Nichol GM , Barnes PJ , Chung KF
Published: July 2012

We examined whether inhaled frusemide could reduce the potentiation of capsaicin‐induced cough by prostaglandin (PG) F2 alpha. Eight non‐ smoking normal subjects, after a baseline capsaicin challenge were given inhaled frusemide or saline followed by capsaicin challenge, then PGF2 alpha and finally capsaicin challenge again. PGF2 alpha‐induced coughs were reduced after frusemide to 3.6 +/‐ 1.0 compared with 5.7 +/‐ 1.2 after saline (P less than 0.05). PGF2 alpha increased capsaicin‐ induced coughs by 11.1 +/‐ 3.7 and 7.9 +/‐ 3.4 after placebo and frusemide, respectively (P less than 0.05). Frusemide had no effect on capsaicin‐induced cough alone. Changes in local ionic concentrations by frusemide, particularly chloride ions within the vicinity of epithelial cough receptors, may determine the cough response to low chloride solutions and to PGF2 alpha, but not to capsaicin which acts directly on the cough receptors, and alter the sensitivity of the receptors to capsaicin.
Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers.
Authors: John DN , Fort S , Lewis MJ , Luscombe DK
Published: July 2012

1. The pharmacokinetics and pharmacodynamics of verapamil administered via the oral and sublingual routes were compared in a randomised, two‐ way cross‐over study involving six healthy male volunteers. 2. Administered sublingually, a verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak plasma concentration (P less than 0.05), a greater rate of absorption (P less than 0.05), and greater bioavailability (P less than 0.05) when compared with orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing, PR intervals were significantly (P less than 0.05) prolonged between 30 and 90 min after sublingual verapamil dosing. 4. Correlations between log plasma verapamil concentration and percentage increase in PR interval were greater after sublingual compared with oral dosing in all volunteers.
The pharmacokinetics of mecillinam and pivmecillinam in pregnant and non‐pregnant women.
Authors: Heikkila A , Pyykko K , Erkkola R , Iisalo E
Published: July 2012

1. The pharmacokinetics of parenteral mecillinam (n = 27) and oral pivmecillinam (n = 12) were studied in pregnant (n = 27) and non‐ pregnant (n = 12) subjects. 2. In early pregnancy (9‐14 weeks of gestation) the mean peak plasma drug concentration (Cmax = 19 +/‐ 9 micrograms ml‐1) after an intravenous injection of 200 mg mecillinam was significantly lower (P less than 0.05) and the volume of distribution (V = 49 +/‐ 20.1) significantly larger (P less than 0.05) than in non‐pregnant subjects (Cmax = 35 +/‐ 18 micrograms ml‐1, V = 29 +/‐ 12.1). In late pregnancy (39‐40 weeks of gestation) the plasma mean peak concentration (Cmax = (29 +/‐ 14 micrograms ml‐1) after parenteral administration of 200 mg mecillinam was slightly lower and the volume of distribution (V = 65 +/‐ 29.1, V = 0.9 +/‐ 0.4 l kg‐1) significantly larger than that in non‐pregnant subjects (V = 0.4 +/‐ 0.3 l kg‐1). Also after oral administration of 200 mg pivmecillinam, equimolar to 136.5 mg mecillinam, the mean peak plasma concentration in pregnant subjects (Cmax = 1.8 +/‐ 1.2 micrograms ml‐1) was slightly lower than that in non‐pregnant subjects (Cmax = 1.7 +/‐ 1.2 micrograms ml‐1). 3. The mean half‐life of elimination after parenteral administration of mecillinam was significantly longer during both early (t1/2,Z = 133 +/‐ 38 min, P less than 0.05) and late pregnancy (t1/2,Z = 107 +/‐ 41 min, P less than 0.05) as compared with the non‐pregnant state (t1/2,Z = 75 +/‐ 21 min).(ABSTRACT TRUNCATED AT 250 WORDS)
Variability of the serum protein binding of theophylline in patients with asthma and cystic fibrosis.
Authors: Blanchard J , Harvey S , Morgan WJ
Published: July 2012

1. The serum protein binding of theophylline was studied in 28 asthmatics and 11 patients with cystic fibrosis (CF) who were receiving the drug regularly. Peak theophylline samples were collected at 2 week intervals on four occasions in each asthmatic and on three occasions in each CF patient. The binding was measured using ultrafiltration at 37 degrees C and pH 7.4. The total and free (unbound) theophylline concentrations were measured using high‐performance liquid chromatography. 2. The mean free‐fractions (+/‐ s.d.) in asthmatics (0.50 +/‐ 0.03) and in CF patients (0.51 +/‐ 0.04) were not significantly different. The intra‐ and inter‐subject variability in the free‐fraction (fu) was relatively small in both patient groups. The binding was found to be concentration‐independent at serum theophylline concentrations up to 30.9 micrograms ml‐1. The effects of age, gender, serum albumin and total serum protein on the free fraction were evaluated. 3. The results indicate that the binding of theophylline is similar in the two disease states. The low degree of variability in serum theophylline binding indicates that measurements of total serum theophylline concentrations will reflect unbound serum concentrations with acceptable accuracy in both patient groups studied.
Inhibitory effects of glyceryl trinitrate on alpha‐adrenoceptor mediated contraction in the human internal mammary artery.
Authors: He GW , Shaw J , Yang CQ , Hughes C , Thomson D , McCaughan B , Hendle PN , Baird DK
Published: July 2012

1. Sympathomimetic amines have been considered to be related to vasospasm. Previous studies showed that the human internal mammary artery (IMA) was capable of weak beta‐adrenoceptor mediated relaxation and that alpha‐adrenoceptor agonists may induce contraction in the human IMA. 2. We investigated the effects of glyceryl trinitrate (GTN), a vasodilator agent often used perioperatively, on alpha‐adrenoceptor mediated contraction in the human IMA. 3. Discarded human IMA segments were taken from 37 patients who underwent IMA‐coronary artery bypass graft operations and equilibrated in an organ bath. 4. A specially designed technique was used to normalize the vessel segments under the pressure similar to the in vivo situation. Noradrenaline (NA), phenylephrine (PE), and methoxamine (MO) were used to contract the vessel segments. 5. GTN fully relaxed PE or MO (submaximal concentration) induced precontraction. Therapeutic plasma concentration of GTN relaxed 40‐90% of the PE induced contraction (2.82 g, EC50 = 7.92 +/‐ 0.06 ‐log M) and 20‐90% of the MO induced contraction (1.8 g, EC50 = 7.63 +/‐ 0.16 ‐log M). Pretreatment by the therapeutic plasma concentration of GTN inhibited the contraction induced by NA, PE in a different range. It reduced the NA induced contraction (6.9 g) by 14.8‐ 38% (P greater than 0.05) and the PE induced contraction (4.3 g) by 7.9‐ 39.3% (P greater than 0.05). The alpha 1‐adrenoceptor antagonist prazosin, at the therapeutic plasma concentration, nearly totally abolished the NA or PE induced contraction (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
TP53 pathway analysis in paediatric Burkitt lymphoma reveals increased MDM4 expression as the only TP53 pathway abnormality detected in a subset of cases
Authors: Leventaki Vasiliki , Rodic Vladimir , Tripp Sheryl R. , Bayerl Michael G. , Perkins Sherrie L. , Barnette Phillip , Schiffman Joshua D. , Miles Rodney R.
Published: July 2012

The TP53 (p53) pathway can be inhibited by TP53 mutation or deletion or by MDM2 overexpression. Both occur in Burkitt lymphoma (BL), but many cases lack either abnormality. Expression patterns of the TP53 inhibitor MDM4 have not been reported in BL, and increased MDM4 could deregulate the TP53 pathway in cases without TP53 or MDM2 abnormalities. We investigated TP53 pathway disruption in paediatric BL patient samples (n = 30) by studying MDM4, MDM2, and CDKN1A (p21) protein and mRNA expression; TP53 mutations; TP53 protein expression; and gene copy number abnormalities. MDM4 protein was expressed in 30/30 tumours, and MDM2 protein was weakly expressed in 7/30 (23%). All cases were negative for CDKN1A protein, and CDKN1A mRNA levels were decreased. TP53 mutations were detected in 5/28 (18%) cases and confirmed by sequencing. TP53 protein was expressed in 15/30 (50%) cases, including 7/8 with TP53 genetic alterations. MDM2 protein and mRNA expression levels did not correlate with lack of TP53 genetic changes or TP53 protein expression; however, there was an inverse relationship between detectable TP53 protein expression and MDM4 copy number gains and mRNA expression. The TP53 pathway is deregulated in paediatric BL cases, and increased MDM4 expression may be the primary mechanism in some cases.
Desert Pavement—the most ancient surface or a more recent development?
Authors: Dickerson Robert
Published: July 2012

Desert pavement comprises a surficial layer of gravel clasts and cobbles underlain by dust and silt that mantles mature alluvial surfaces in arid regions around the world. Once thought to originate from either deflation or expansion and contraction of wet desert soils, desert pavement is now known to form in place from the aeolian accumulation of dust beneath a surface layer of gravel. Desert pavement affects the type and distribution of desert plants on arid land surfaces, as well as inhibits the activities of small burrowing animals. Considerable debate surrounds the age of pavement surfaces and how well they survive changes in climatic conditions. Some researchers maintain that most desert pavements developed during the Holocene, whereas others indicate that some of the oldest surface soils on the planet are desert pavements in the Middle East.
Climate change and ocean acidification effects on seagrasses and marine macroalgae
Authors: Koch Marguerite , Bowes George , Ross Cliff , Zhang Xing‐Hai
Published: July 2012

Although seagrasses and marine macroalgae (macro‐autotrophs) play critical ecological roles in reef, lagoon, coastal and open‐water ecosystems, their response to ocean acidification (OA) and climate change is not well understood. In this review, we examine marine macro‐autotroph biochemistry and physiology relevant to their response to elevated dissolved inorganic carbon [DIC], carbon dioxide [CO2], and lower carbonate [CO32−] and pH. We also explore the effects of increasing temperature under climate change and the interactions of elevated temperature and [CO2]. Finally, recommendations are made for future research based on this synthesis. A literature review of >100 species revealed that marine macro‐autotroph photosynthesis is overwhelmingly C3 (≥ 85%) with most species capable of utilizing HCO3−; however, most are not saturated at current ocean [DIC]. These results, and the presence of CO2‐only users, lead us to conclude that photosynthetic and growth rates of marine macro‐autotrophs are likely to increase under elevated [CO2] similar to terrestrial C3 species. In the tropics, many species live close to their thermal limits and will have to up‐regulate stress‐response systems to tolerate sublethal temperature exposures with climate change, whereas elevated [CO2] effects on thermal acclimation are unknown. Fundamental linkages between elevated [CO2] and temperature on photorespiration, enzyme systems, carbohydrate production, and calcification dictate the need to consider these two parameters simultaneously. Relevant to calcifiers, elevated [CO2] lowers net calcification and this effect is amplified by high temperature. Although the mechanisms are not clear, OA likely disrupts diffusion and transport systems of H+ and DIC. These fluxes control micro‐environments that promote calcification over dissolution and may be more important than CaCO3 mineralogy in predicting macroalgal responses to OA. Calcareous macroalgae are highly vulnerable to OA, and it is likely that fleshy macroalgae will dominate in a higher CO2 ocean; therefore, it is critical to elucidate the research gaps identified in this review.
Enzymatic interesterification of palm and coconut stearin blends
Authors: Khatoon Sakina , Khan Mohammad I. , Jeyarani Thangaraj
Published: July 2012

Hard fractions of palm oil and coconut oil, blended in the ratios of 90:10, 85:15, 80:20 and 75:25, were interesterified for 8 h using Lipozyme TL IM. Major fatty acids in the blends were palmitic acid (41.7–48.4%) and oleic acid (26.2–30.8%). Medium‐chain fatty acids accounted for 4.5–13.1% of the blends. After interesterification (IE), slip melting point was found to decrease from 44.8–46.8 °C to 28.5–34.0 °C owing to reduction in solids content at all temperatures. At 37.5 °C, the blends containing 25% coconut stearins had 17.4–19% solids, which reduced to 0.4–1.5% on IE, and the slip melting point (28.6 and 28.8 °C) indicated their suitability as margarine base. The reduction in solid fat index of the interesterified fats is attributed to the decrease in high‐melting triacylglycerols in palm oil (GS3 and GS2U type) and increase in triolein (GU3) content from 1 to 9.2%. Retention of tocopherols and β‐carotene during IE was 76 and 60.1%, respectively, in 75:25 palm stearin and coconut stearin blend.
Kinetics of anthocyanin degradation and polymeric colour formation in black carrot juice concentrates during storage
Authors: Türkyılmaz Meltem , Özkan Mehmet
Published: July 2012

The changes in anthocyanins (ACNs) and polymeric colour of black carrot juice concentrate (BCJC) samples were monitored during storage at −23, 5 and 20 °C for 319 days and at 30 °C for 53 days. While ACN degradation was fitted to a first‐order reaction model, polymeric colour formation was fitted to a zero‐order reaction model during the storage. Half‐life periods for ACN degradation in BCJCs were 603, 137 and 29 days at 5, 20 and 30 °C, respectively. The reaction rate constants for polymeric colour formation were 0.0207, 0.1435 and 0.5581%/days at 5, 20 and 30 °C, respectively. HPLC‐MS analyses of BCJC showed that cyanidin‐3‐galactoside‐xyloside‐glucoside‐ferulic acid (56%) was the major ACN, followed by cyanidin‐3‐galactoside‐xyloside (19%) and cyanidin‐3‐galactoside‐xyloside‐glucoside‐sinapic acid (10%). Cyanidin‐3‐galactoside‐xyloside‐glucoside‐ferulic acid was the most stable ACN in BCJC at storage temperatures. BCJCs should be kept at sub‐freezing temperatures to minimise ACN degradation.
‘Uninterested in anything except food’: the work of nurses feeding the liberated inmates of Bergen‐Belsen
Authors: Brooks Jane
Published: July 2012

Aims and objectives. The aim of this article is to explore the work of nurses feeding and helping liberate the inmates of Bergen‐Belsen concentration camp in the spring of 1945.

Background. A considerable amount has been published on the relief of Belsen, but the majority of the research has focused on the medical staff and the army in general. The exception to this is an article published by Ellen Ben‐Sefer, but its analysis of the actual work of the nurses is limited.

Design. The data are explored through the medium of nurses' work, especially feeding work and its place in the historiography.

Methods. This article will offer an analysis of archival material, including official reports and personal testimony and published primary sources.

Results. Nurses were very much hidden from the liberation picture, partly through government policy, partly because of gendered ideologies and partly because of the desire of many to hide their memories. However, the data identify the pivotal role of nurses in the saving of lives and rehabilitation of inmates. This article demonstrates this role through the work of feeding.

Conclusion. The nurses had to continually negotiate and renegotiate their place in the liberation. As women, their place at Belsen was problematic and often thwarted by the ideologies of the day. Nevertheless, the services of registered nurses during the war had proved indispensible. The Allied governments and Royal Army Medical Corps were ultimately to rely on their professional expertise. The nurses’ work in the feeding of starving inmates demonstrates their value.

Relevance to clinical practice. This article demonstrates the importance of nurses’ feeding work and their role in the caring of people’s humanity.
An exploration of undergraduate nursing and physiotherapy students’ views regarding education for patient handling
Authors: Kneafsey Rosie , Ramsay Jill , Edwards Helen , Callaghan Helen
Published: July 2012

Aims and objectives.  To ascertain the views of undergraduate student nurses and physiotherapists regarding their education in patient handling.

Background.  Musculo‐skeletal injuries are an important cause of staff sickness absence and attrition from the nursing profession and are a recognised problem within the physiotherapy profession. Nurses and physiotherapists are at risk of musculo‐skeletal injuries as a result of their role in assisting patients with movement.

Methods.  A questionnaire survey was undertaken of undergraduate nursing and physiotherapy students (n = 371) at one university.

Results.  Most students agreed that university teaching about moving and handling prepared them for clinical practice (64%). Over a third reported that they had never undertaken a written moving and handling risk assessment in clinical practice (38%). Almost half of the sample (40%) admitted undertaking unsafe moving and handling activities. Half (50%) also stated that they would rather ‘fit’ into the team than challenge unsafe practice. Almost a third (29%) stated that they had begun to experience pain since becoming a student. There were significant differences between nursing and physiotherapy students. Physiotherapy students were more likely to report being supervised when moving and handling and reported being more assertive about adhering to safe practice.

Conclusions.  The well‐being of both nursing and physiotherapy undergraduate students is threatened when students undertake work placements in clinical settings. University‐based education in safe patient handling, though important, can be undermined by workplace settings where unsafe practices occur. Collaboration is needed between university educators, managers and practice‐based mentors to support students to maintain safe approaches to moving and handling patients.

Relevance to clinical practice.  A third of students reported developing pain since becoming a healthcare student. Students entering their professions already injured may leave the workforce owing to poor physical well‐being. It is vital that the clinical workplace supports safe systems of working.
Factors influencing doctors’ selection of dabigatran in non‐valvular atrial fibrillation
Authors: Huang Cindy , Siu Michele , Vu Lily , Wong Soo , Shin Jaekyu
Published: July 2012

Rationale, aims and objectives

This study was designed to examine the factors that influence doctors’ decision in initiating or switching from warfarin to dabigratran.

Method

A survey questionnaire was sent to 181 doctors who were most likely to prescribe dabigatran (e.g. cardiologists and general internists) at the University of California, San Francisco Medical Center between November 2011 and February 2012. Survey participants were asked to complete an electronic or a paper version of the questionnaire, which consisted of 17 multiple‐choice questions. Fisher's exact test and Cochran–Mantel–Haenszel test were used to compare survey responses between cardiologists and general internists.

Results

A total of 65 survey responses were received (35.9% response rate). There were 13 cardiologists and 51 general internists who participated in the study. Cost (25%), renal function (21%) and CHADS
2 score (18%) were the three factors doctors considered most often to determine a patient's eligibility for dabigatran in warfarin‐naïve patients. On the other hand, histories of unstable international normalized ratio (37%) and missed appointments (17%) along with cost (19%) were most often considered in patients on warfarin. Cardiologists had prescribed dabigatran more often and had a significantly higher level of comfort with prescribing the drug than general internists (P = 0.003; 77% vs. 27%).

Conclusions

Cost was the most important factor influencing doctors’ decision to prescribe dabigatran. Safety and effectiveness of dabigatran as well as patient preference were additional factors influencing their decision. General internists were less comfortable with prescribing dabigatran than cardiologists.
Run, robber, run: parasitic acacia ants use speed and evasion to steal food from ant‐defended trees
Authors: AMADOR‐VARGAS SABRINA
Published: July 2012

Ants that are obligate plant associates protect their host against herbivores and aggressively defend the resources offered by the plant. Workers of Pseudomyrmex nigropilosus Emery (Hymenoptera: Formicidae), an acacia ant that parasitizes the mutualism by not defending the tree, are seen stealing food from other ant‐defended acacia trees. In the present study, hypotheses of evasion, chemical crypsis, chemical repellence and temporal activity patterns are tested in the field aiming to determine how P. nigropilosus enters other acacia trees, successfully circumventing the defence of the resident ants. When parasitic ants are stealing, resident ants are evaded by stopping walking, changing their walking direction or walking faster. Resident and parasitic workers have similar temporal activity patterns. Parasitic workers can walk 2.6‐fold faster compared with any of the three species of acacia‐ants from which they usually steal food. Behavioural assays suggest that P. nigropilosus do not have chemical repellence but that chemical crypsis may be involved in the evasion strategy. This last hypothesis needs to be explored further by chemical and olfactory analyses. The combination of speed and evasive reactions allows parasitic ants to access well‐defended acacia trees.
Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta‐analysis
Authors: Gigante Alexandre Duarte , Bond David J , Lafer Beny , Lam Raymond W , Young L Trevor , Yatham Lakshmi N
Published: July 2012

Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta‐analysis. Bipolar Disord 2012: 14: 478–487. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objectives:  Bipolar disorder (BD) is a common and highly disabling disease characterized by substantial cognitive and functional impairment. The exact neurobiological mechanisms underlying the expression of symptoms in this condition remain unknown but there is growing evidence that glutamate might play an important role. Using proton magnetic resonance spectroscopy (1H‐MRS), a number of studies have examined brain glutamate/glutamine levels in patients with bipolar disorder, but they have produced conflicting results. The objective of this paper was to conduct a systematic review and meta‐analysis of the literature on brain glutamate/glutamine in BD as measured by 1H‐MRS.

Methods:  A Medline search for the period January 1980–April 2010 was conducted to identify published studies that used 1H‐MRS to measure glutamate + glutamine (Glx), the Glx/creatine (Cr) ratio, glutamate (Glu), or the Glu/Cr ratio in any brain region in adult or child/adolescent patients with BD and healthy subjects. A meta‐analysis of the pooled data was conducted.

Results:  BD patients were found to have increased Glx compared to healthy subjects when all brain areas were combined. This finding remained true in medicated and non‐medicated patients, and in frontal brain areas in adults. There was a non‐significant trend (p = 0.09) for an increase in whole‐brain Glx/Cr and Glu in patients compared with healthy subjects. No significant difference was found in Glu/Cr.

Conclusions:  The results of this meta‐analysis suggest that brain Glx levels are elevated in BD patients and support the idea that glutamate might play an important role in the pathophysiology of BD.
Pharmacokinetics after a single intravenous dose of the opioid ketobemidone in neonates
Authors: LUNDEBERG S. , STEPHANSON N. , STILLER C.‐O. , EKSBORG S.
Published: July 2012

Background

Ketobemidone is often used as an alternative to morphine in children in the Scandinavian countries. In an earlier study, we have examined the pharmacokinetic properties in children in different age groups but have not focused on neonates. The aim of this clinical trial was to explore the pharmacokinetics of ketobemidone in neonates.

Methods

Fifteen full‐term neonates (eight females) from 37 gestational weeks at birth and scheduled for elective surgery were included in the trial. Their median age was 3 days (range 1–18 days). Ketobemidone hydrochloride was administered as a single intravenous bolus dose, and ketobemidone concentrations were measured by liquid chromatography‐mass spectrometry over 10 h. Pharmacokinetic parameters were calculated with standard compartmental methods.

Results

The median (range) values for ketobemidone clearance, apparent volume of distribution, volume of central compartment, distribution half‐life and elimination half‐life were 0.46 (0.23–0.84) l/h/kg, 4.64 (3.50–7.31) l/kg, 1.71 (0.16–3.47) l/kg, 2.85 (1.04–10.78) min and 7.26 (3.5–11.3) h.

Conclusion

Compared with our previous study in children older than 1 year of age, the elimination of ketobemidone appeared to be slower in full‐term neonates. Despite a low pharmacokinetic variability of ketobemidone as observed in the present neonatal patient population, we recommend individualizing the dose of ketobemidone based on observations of analgesic efficacy.
Dual guidance improves needle tip placement for peripheral nerve blocks in a porcine model
Authors: VASSILIOU T. , EIDER J. , NIMPHIUS W. , WIESMANN T. , DE ANDRES J. , MÜLLER H.‐H. , WULF H. , STEINFELDT T.
Published: July 2012

Background

The objective of the study was to evaluate whether the use of ultrasound (US) together with nerve stimulation (USNST) provides a better needle tip position for performing peripheral regional anaesthesia than the use of US or nerve stimulation (NST) alone.

Methods

Needle placements were applied at the brachial plexus and sciatic nerves in 32 anaesthetised pigs. Following needle placement near the target nerve, using either the USNST or the US or NST, a volume of 0.3 ml synthetic resin was injected mimicking a ‘test‐dose’ injection. The primary outcome was the incidence of close needle‐to‐nerve placement assessed by injectate localisation in direct contact with the nerve epineurium. Secondary endpoints were the incidences of intraneural injection and haematoma formation in direct contact with the target nerve.

Results

A total of 611 punctures were performed. The evaluation for the criterion ‘close needle placement’ revealed significant differences in favour of the USNST group (98.5%) compared with the NST (90.1%) and the US group (81.6%) (P = 0.001). Significant differences were observed regarding ‘intraneural needle placement’ between the groups as well (USNST, 0.5%; US, 4%; NST, 2.5%; P = 0.034). The incidence of haematoma formation was significantly higher in the NST group (10.8%) than in the US group (2.5%) and in the USNST group (1.5%) (P = 0.001).

Conclusion

These findings suggest that the USNST approach combines the benefits of the US and the NST techniques in terms of a higher rate of close needle tip placements and a lower incidence of haematoma formation.
Interleukin‐12 and interleukin‐2 alone or in combination against the infection in invasive pulmonary aspergillosis mouse model
Authors: Zhang Chang‐Ran , Lin Jian‐Cong , Xu Wen‐Ming , Li Ming , Ye Hui‐Shao , Cui Wei‐Ling , Lin Qing
Published: July 2012

Aspergillus fumigatus is an intracellular opportunistic fungus causing invasive pulmonary mycosis, characterised by hyphal invasion and destruction of pulmonary tissue. Th1 cytokines could enhance fungicidal activity. The effects from the combination of interleukin‐12 (IL‐12) and IL‐2 are rarely known in invasive pulmonary aspergillosis infection. To assess the cleaning of A. fumigatus infection in the pulmonary tissues by IL‐12 and IL‐2, interferon‐γ (IFN‐γ) was detected in the sera using ELISA, quantification of IFN‐γ mRNA using real‐time RT‐PCR and lung Colony‐forming unit was assayed by cultivation. Morphology was analysed by histopathological examination. Our results showed that IL‐12 and/or IL‐2 could enhance the IFN‐γ expression in the pulmonary tissue, reduce the colony load in the pulmonary tissue and increase the survival rate of mouse. The combination of IL‐12 and IL‐2 could assist in increasing the IFN‐γ expression in the pulmonary tissue, but neither reduce colony load in the pulmonary tissue nor increase the survival rate of mouse significantly. It was demonstrated that IL‐12 and IL‐2 were strong immunomodulatory cytokines as a prerequisite for protecting the host from infectious agents.
Cell Cycle Synchronization of Skin Fibroblast Cells in Four Species of Family Felidae
Authors: Wittayarat M , Thongphakdee A , Saikhun K , Chatdarong K , Otoi T , Techakumphu M
Published: July 2012

Contents

This study was examined whether the species of felid affects synchronization accuracy at the G0/G1 stage of the cell cycle and the occurrence of apoptosis by different protocols, such as serum starvation, confluent and roscovitine treatment. Skin fibroblast cells were obtained from the Asian golden cat, marbled cat, leopard and Siamese cat. The cells from each animal were treated with either serum starvation for 1–5 days, cell confluency‐contact inhibition for 5 days or roscovitine at various concentrations (7.5–30 μm). Flow cytometric analysis revealed that serum starvation for 3 days provided the highest cell population arrested at the G0/G1 stage, irrespective of the felid species. In all species, 100% confluency gave a significantly higher percentage of cells arrested at the G0/G1 stage compared with the non‐treated control cells. The effects of roscovitine treatment and the appropriate concentration on the rates of G0/G1 cells differed among the felid species. Serum starvation for more than 4 days in the marbled cat and Siamese cat and roscovitine treatment with 30 μm in the Asian golden cat and leopard increased the rates of apoptosis. In conclusion, different felid species responded to different methods of cell cycle synchronization. Asian golden cat and Siamese cat fibroblast cells were successfully synchronized to G0/G1 stage using the serum starvation and roscovitine treatment, whereas only confluency‐contact inhibition treatment induced cell synchronization in the leopard. Moreover, these three methods did not successfully induce cell synchronization of the marbled cat. These findings may be valuable for preparing their donor cells for somatic cell nuclear transfer in the future.
Efficacy of cryospray ablation for the treatment of chronic radiation proctitis in a pilot study
Authors: Moawad Fouad J. , Maydonovitch Corinne L. , Horwhat J David
Published: July 2012

Aim

Radiation proctitis, a common condition associated with radiotherapy for the treatment of pelvic cancers, is characterized by difficult to manage rectal pain and bleeding. Cryotherapy is a novel technique, previously used in the treatment of vascular ectasias in the upper gastrointestinal tract. The aim of the present study was to determine the efficacy of cryospray application in the treatment of radiation proctitis.

Methods

This is a prospective case‐series pilot study. Ten patients with symptomatic chronic radiation proctitis were consecutively enrolled over a 2‐year period. Baseline clinical data were collected and an endoscopic score was calculated based on the density of ectasias and circumferential involvement. Subjects underwent up to four cryospray ablation treatment sessions at approximately 4‐week intervals or until resolution of the proctitis. The endpoints of the study were endoscopic and clinical improvement in radiation proctitis.

Results

Ten patients (nine males and one female) with a mean age of 74 ± 7 years underwent cryospray treatment; sessions ranged from one to four (six patients had one session, three patients had two sessions, and one patient underwent four sessions). Endoscopic score significantly decreased from a mean of 10.2 ± 3.0 to 4.0 ± 2.8 (P = 0.016). Rectal pain significantly decreased from a mean of 3.1 ± 3.0 to 1.2 ± 1.7 (P = 0.042) and rectal bleeding improved in 86% (six out of seven) of patients. Nine patients reported improvement in overall well‐being. No major complications were encountered.

Conclusions

Cryotherapy is an effective method in the management of chronic radiation proctitis with minimal complications.
Urinary symptoms and pelvic floor muscle function during the third trimester of pregnancy in nulliparous women
Authors: Frederice Claudia Pignatti , Amaral Eliana , Ferreira Néville de Oliveira
Published: July 2012

Aim:  To evaluate pelvic floor muscle (PFM) function and its association with urinary symptoms in the third trimester of pregnancy.

Material and Methods:  A cross‐sectional study was conducted among 91 nulliparous women at 30–34 weeks of pregnancy. PFM was evaluated by surface electromyography (sEMG) and manual muscle testing, while urinary symptoms were identified by interview. Chi‐square and Fisher's exact tests were used to analyze proportions and Mann–Whitney test was used to analyze differences in means.

Results:  Average sEMG values were 4.8 µV for basic tonus (BT), 19.2 µV for maximum voluntary contraction (MVC), and 12.9 µV for average sustained contraction (ASC), and 48.4% presented muscle strength grade 3. Nocturia was reported by 80.2%, followed by increased daytime frequency (59.3%), stress urinary incontinence (50.5%), and urge urinary incontinence (25.3%). No association was found between urinary symptoms and MVC or ASC or PFM manual tested strength.

Conclusion:  No association was observed between PFM function and urinary incontinence, except decreased BT among late third trimester pregnant women with irritative bladder symptoms.
Ultrasonic analysis of the anatomical relationships between vertebral arteries and internal jugular veins in children
Authors: Kayashima Kenji , Ueki Masaya , Kinoshita Yuki
Published: July 2012

Background:  Accidental puncture of the vertebral arteries (VAs) can occur through the internal jugular veins (IJVs) during central venous catheterization (CVC). We evaluated the anatomic relation of the VAs to the IJVs in children undergoing IJV cannulation.

Methods:  Fifty‐five patients were placed in the supine position under general anesthesia. The right IJV, common carotid artery (CCA), and VA were described with an ultrasound probe perpendicular to all planes of the skin at the mid‐portion between the suprasternal notch and mastoid process. The depth from the skin to VAs (D), width of the VAs (W), and distance from the IJVs to VAs (DIV) were measured. The extent of overlap between the IJVs and VAs was classified into overlapping, partially overlapping, and nonoverlapping. The risk was scored as 0–3 for each measurement. The scores were added and categorized into a low‐risk group (L), 0–3, moderate‐risk (M) group, 4–7; and high‐risk (H) group, 8–10.

Results:  Mean (sd) age was 20.3 (33.9) months, height was 72.1 (26.0) cm, and weight was 8.9 (9.0) kg. The mean D, W, and DIV were 15.1 (3.3), 2.8 (1.1), and 4.6 (1.8) mm, respectively. Of the 55 patients, 7 were in group H, 33 in group M, and 15 in group L.

Conclusions:  Seven of the 55 children were categorized under the H group for accidental puncture of the VAs. Thus, it is important to identify the presence of the VAs to avoid accidental puncture during pediatric CVC.
Case report: airway and concurrent hemodynamic management in a neonate with oculo‐auriculo‐vertebral (Goldenhar) syndrome, severe cervical scoliosis, interrupted aortic arch, multiple ventricular septal defects, and an unstable cervical spine
Authors: Char Danton S. , Gipp Melanie , Boltz M. Gail , Williams Glyn D.
Published: July 2012

We report the challenging case of a 1‐week‐old, term, 2.4 kg neonate with Goldenhar syndrome (including microcephaly, left microtia, left facial palsy, dextro‐scoliosis of the cervical spine, and cervico‐thoracic levoscoliosis), multiple ventricular septal defects, a type B interrupted aortic arch, a large patent ductus arteriosis, and radiographic and clinical signs concerning for an unstable cervical spine. Our anesthesia team was consulted for perioperative management of this patient during her surgical repair. This case report describes the use of the Air‐Q size 1 laryngeal airway (LA) to assist fiberoptic intubation in an ASA 4 neonate with cardiac disease, an anticipated difficult airway with the addition of an unstable cervical spine, as well as the anesthetic techniques used to maintain hemodynamic stability while the airway was secured.