bluuebunny/crossref_metadata_2025 huggingface dataset:
End‐of‐life care in UK critical care units – a literature review
Authors: Morgan Jane
Published: April 2008

Aim:  To appraise literature concerning end‐of‐life care (ELC) in adult critical care units in the UK in order to improve clinical practice.

Objective:  To understand the interplay between legal and ethical, political, societal aspects of ELC for sustainable quality care.

Background:  Significant changes in health care policy for the critically ill patient have occurred since 1999. Simultaneously, the government is committed to improving care for the dying by integrating the palliative care ethos across the National Institutes of Health (NHS) to include non‐cancer sufferers. Death continues to be a feature of critical illness, particularly following the decision to withhold/withdraw life‐prolonging treatments.

Search strategy:  A search of MEDLINE, BNI, CINAHL and PSYCinfo using key words revealed very few results; consequently, the search was broadened to include ASSIA, King’s Fund, TRIP, Healthstar, NHS Economic Evaluation Data, Cochrane, professional journals and government documents.

Conclusions:  The literature reveals a paradigm shift from critical to palliative care, in other words, from a reductionist approach to a more humanistic approach in the acute setting. When treatment is deemed futile, quality ELC involving the assessment, ongoing assessment and care after death becomes the new goal for the critical care team. To practice ELC competently, nurses require organizational and educational support at local and national levels.

Relevance to clinical practice:  Although medico‐legal decision‐making is not part of their professional role, critical care nurses have an extraordinary opportunity to make a difference to the dying patient and their family and their acceptance of death.
The Price of Bouncing Back: One‐Year Mortality and Payments for Acute Stroke Patients with 30‐Day Bounce‐Backs
Authors: Kind Amy J. H. , Smith Maureen A. , Liou Jinn‐Ing , Pandhi Nancy , Frytak Jennifer R. , Finch Michael D.
Published: April 2008

OBJECTIVES: To examine 1‐year mortality and healthcare payments of stroke patients experiencing zero, one and two or more bounce‐backs within 30 days of discharge.

DESIGN: Retrospective analysis of administrative data.

SETTING: Four hundred twenty‐two hospitals in the southern and eastern United States.

PARTICIPANTS: Eleven thousand seven hundred twenty‐nine Medicare beneficiaries aged 65 and older surviving at least 30 days with acute ischemic stroke in 2000.

MEASUREMENTS: One‐year mortality and predicted total healthcare payments were calculated using log‐normal parametric survival analysis and quantile regression, respectively. Models included sociodemographics, prior medical history, stroke severity, length of stay, and discharge site.

RESULTS: Crude survival at 1 year for the zero, one and two or more bounce‐back groups was 83%, 67%, and 55%, respectively. The one bounce‐back group had 49% shorter (time ratio (TR)=0.51, 95% confidence interval (CI)=0.46–0.56) and the two or more bounce‐backs group had 68% shorter (TR=0.32, 95% CI=0.27–0.38) adjusted 1‐year survival time than the zero bounce‐back group. For high‐ and low‐cost patients, adjusted predicted payments were greater with each additional bounce‐back experienced.

CONCLUSION: Acute stroke patients experiencing bounce‐backs within 30 days have strikingly poorer survival and higher healthcare payments over the subsequent year than their counterparts with no bounce‐backs. Bounce‐backs may serve as a simple predictor for identifying stroke patients at extremely high risk for poor outcomes.
Comparison of Effect of Aerobic Cycle Training and Progressive Resistance Training on Walking Ability After Stroke: A Randomized Sham Exercise–Controlled Study
Authors: Lee Mi‐Joung , Kilbreath Sharon L. , Singh Maria Fiatarone , Zeman Brian , Lord Stephen R. , Raymond Jacquelene , Davis Glen M.
Published: April 2008

OBJECTIVES: To determine whether changes in strength or cardiorespiratory fitness after exercise training improve walking ability in individuals who have had a stroke.

DESIGN: A sham exercise‐controlled, randomized two‐by‐two factorial design, in which the two factors investigated were cycle training (AEROBIC) and resistance training (STRENGTH).

SETTING: University exercise laboratory.

PARTICIPANTS: Fifty‐two individuals with a history of stroke (aged 63±9; time since stroke, 57±54 months).

INTERVENTION: Participants undertook 30 exercise sessions over 10 to 12 weeks. Depending on group allocation, individuals underwent aerobic cycling plus sham progressive resistance training (PRT) (n=13), sham cycling plus PRT (n=13), aerobic cycling plus PRT (n=14), or sham cycling plus sham PRT (n=12).

MEASUREMENTS: Primary outcomes were 6‐minute walk distance, habitual and fast gait velocities, and stair climbing power. Secondary outcomes included measures of cardiorespiratory fitness; muscle strength, power, and endurance; and psychosocial attributes.

RESULTS: Neither AEROBIC nor STRENGTH improved walking distance or gait velocity significantly more than sham exercise, although STRENGTH significantly improved participants' stair climbing power by 17% (P=.009), as well as their muscle strength, power, and endurance; cycling peak power output; and self‐efficacy. Conversely, AEROBIC improved indicators of cardiorespiratory fitness only. Cycling plus PRT produced larger effects than either single modality for mobility and impairment outcomes.

CONCLUSION: Single‐modality exercises targeted at existing impairments do not optimally address the functional deficits of walking but do ameliorate the underlying impairments. The underlying cardiovascular and musculoskeletal impairments are significantly modifiable years after stroke with targeted robust exercise.
Autonomic Markers as Predictors of Nonfatal Acute Coronary Events after Myocardial Infarction
Authors: Perkiömäki Juha S. , Jokinen Vesa , Tapanainen Jari , Airaksinen K.E. Juhani , Huikuri Heikki V.
Published: April 2008

Background: Autonomic markers, such as heart rate variability (HRV), heart rate turbulence (HRT), and baroreflex sensitivity (BRS) provide information on the risk of all‐cause mortality after an acute myocardial infarction (AMI), but their value in predicting nonfatal cardiac events is not well known.

Methods: A consecutive series of 675 patients with an AMI were followed up to 30 months. At baseline, the patients underwent a 24‐hour Holter recording, and assessment of BRS using phenylephrine test. Several parameters of HRV and HRT were determined.

Results: After the follow‐up, 98 patients (15%) had a nonfatal acute coronary event. Among the studied variables, the short‐term scaling exponent alpha1 (P = 0.002), power‐law slope beta (P = 0.008), low‐frequency component of HRV power spectrum (P < 0.001), turbulence slope (P < 0.001), and BRS (P < 0.001) had the strongest association with the occurrence of nonfatal acute coronary events in univariate comparisons. After adjustment with relevant clinical variables (such as age, gender, ejection fraction, functional class, medication, diabetes) in the Cox proportional hazards model, alpha1 and beta remained as statistically significant predictors of nonfatal acute coronary events (HR = 2.0 [1.2–3.2, 95% CIs, P = 0.006] for alpha1 ≤ 1.025), (HR = 1.9 [1.2–3.1, P = 0.008] for beta ≤–1.507).

Conclusion: Several autonomic markers provide information on the risk of recurrent nonfatal coronary events after an AMI. Altered fractal heart rate behavior seems to be the strongest independent predictor of such events.
Comparison of Wavelet Transform Modulus Maxima and Multifractal Detrended Fluctuation Analysis of Heart Rate in Patients with Systolic Dysfunction of Left Ventricle
Authors: Galaska Rafal , Makowiec Danuta , Dudkowska Aleksandra , Koprowski Andrzej , Chlebus Krzysztof , Wdowczyk‐Szulc Joanna , Rynkiewicz Andrzej
Published: April 2008

Background: In recent years the WTMM (wavelet transform modulus maxima) and MDFA (multifractal detrended fluctuation analysis) methods have become widely used techniques for the determination of nonlinear, multifractal heart rate (HR) dynamics. The purpose of our study was to compare multifractal parameters of heart rate calculated using both methods in a group of 90 patients with reduced left ventricular systolic function (rlvs group) and in a group of 39 healthy persons (nsr group).

Methods: For each subject from the rlvs group (LVEF ≤40%) and the nsr group, a 24‐hour ECG Holter monitoring was performed. The width of the multifractal spectrum and global Hurst exponent were calculated by means of WTMM and MDFA methods for 5‐hour daytime and nighttime subsets.

Results: The width of the multifractal spectrum was significantly lower and the Hurst exponent was significantly higher in rlvs group in comparison to nsr group both during diurnal activity and nocturnal rest according to MDFA and only during diurnal activity according to WTMM method. In both groups we observed significant differences of the multifractal spectrum width and the global Hurst exponent between the nighttime and daytime recordings.

Conclusions: MDFA seems to be more sensitive as compared with WTMM method in differentiation between multifractal properties of the heart rate in healthy subjects and patients with left ventricular systolic dysfunction.
Baroreflex Sensitivity: Measurement and Clinical Implications
Authors: La Rovere Maria Teresa , Pinna Gian Domenico , Raczak Grzegorz
Published: April 2008

Alterations of the baroreceptor‐heart rate reflex (baroreflex sensitivity, BRS) contribute to the reciprocal reduction of parasympathetic activity and increase of sympathetic activity that accompany the development and progression of cardiovascular diseases. Therefore, the measurement of the baroreflex is a source of valuable information in the clinical management of cardiac disease patients, particularly in risk stratification. This article briefly recalls the pathophysiological background of baroreflex control, and reviews the most relevant methods that have been developed so far for the measurement of BRS. They include three “classic” methods: (i) the use of vasoactive drugs, particularly the α‐adrenoreceptor agonist phenylephrine, (ii) the Valsalva maneuver, which produces a natural challenge for the baroreceptors by voluntarily increasing intrathoracic and abdominal pressure through straining, and (iii) the neck chamber technique, which allows a selective activation/deactivation of carotid baroreceptors by application of a negative/positive pressure to the neck region. Two more recent methods based on the analysis of spontaneous oscillations of systolic arterial pressure and RR interval are also reviewed: (i) the sequence method, which analyzes the relationship between increasing/decreasing ramps of blood pressure and related increasing/decreasing changes in RR interval through linear regression, and (ii) spectral methods, which assess the relationship (in terms of gain) between specific oscillatory components of the two signals. The limitations of the coherence criterion for the computation of spectral BRS are discussed, and recent proposals for overcoming them are presented. Most relevant clinical applications of BRS measurement are finally reviewed with particular reference to patients with myocardial infarction and heart failure.
Angiogenic transforming capacity of IgG purified from plasma of type 1 diabetic patients
Authors: Tramentozzi Elisa , Pagetta Andrea , Frasson Martina , Brunati Anna Maria , Montopoli Monica , Finotti Paola
Published: April 2008

We previously demonstrated that plasma of type 1 diabetic patients contains antibodies complexed irreversibly with Grp94 that also display proteolytic activity. In this work, we wanted to test whether antibodies obtained from diabetic plasma may convey an inflammatory risk on vascular cells. To this aim, IgG were purified on the Protein‐G column from individual plasma of eight type 1 diabetic patients, and then tested on HUVECs to measure effects on cell growth and morphologic changes at different incubation times. The purified fractions of IgG contained a significant amount of Fab/(Fab)2, both free and in big aggregates, and anti‐Grp94 antibodies, mostly irreversibly linked with, but also free of Grp94. The purified fractions of both Fab/(Fab)2 and whole IgG stimulated the proliferation and sustained the angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) at sub‐nanomolar concentrations. IgG from normal plasma neither stimulated the cell growth nor induced any differentiation of HUVECs. The maximum cell growth stimulation occurred at 6–9 hrs and associated with the strong activation of the ERK1/2 pathway, whereas angiogenic transformation was completed later when the ERK1/2 activation was silenced and cell growth stimulation significantly reduced. Neither proteolytic activity of MMP‐9 nor VEGF were apparently involved in mediating the angiogenic differentiation of HUVECs that mostly correlated with an increased expression of HSP70 closely coupled with cell membrane‐bound inactive species of MMP‐9. Results indicate that effects displayed on HUVECs by antibodies purified from diabetic plasma are likely sustained by immune complexes with Grp94 that may thus predict an increased risk of angiogenic transformation in vivo.
Topical application of statin affects bone healing around implants
Authors: Moriyama Yasuko , Ayukawa Yasunori , Ogino Yoichiro , Atsuta Ikiru , Koyano Kiyoshi
Published: April 2008

Objectives: 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors (statins) are widely used for hyperlipidemia. Recent studies demonstrate that statins stimulate bone morphogenetic protein‐2 expression and lead to bone formation. The aim of this study was to evaluate whether the topical application of statin enhances the osteogenesis around a titanium implant.

Materials and methods: Ten‐week‐old female rats received pure titanium rods in both tibiae with or without fluvastatin. Propylene glycol alginate (PGA) was used as a carrier. The rats were divided into five groups: implant‐only group, implant with PGA group, low‐dose group [implant+PGA containing 3 μg of fluvastatin (FS)], medium‐dose group (15 μg of FS), and high‐dose group (75 μg of FS). The animals were sacrificed at 1 and 2 weeks after implantation. Peri‐implant bone formation was assessed by histomorphometric procedures, i.e., measuring the bone–implant contact (BIC) and peri‐implant bone volume (BV). A mechanical push‐out test was also performed to evaluate the implant fixation strength. Statistical differences among the groups were determined by ANOVA and P<0.05 was considered significant.

Results: At week 1, there was no significant difference in BIC among the groups, however, BV and the push‐out strength were significantly higher in the high‐dose group than in the implant‐only group. At week 2, BIC and BV had significantly increased in the high‐dose group in comparison with the non‐statin groups. The fluvastatin‐treatment group showed a significant increase in push‐out strength compared with the non‐statin groups.

Conclusion: Our histomorphometrical and mechanical evaluations revealed the positive effect of topically applied fluvastatin on the bone around the implant.
The expression of molecular mediators in the idiopathic cutaneous calcification and ossification
Authors: Kim So Young , Choi Hae Young , Myung Ki Bum , Choi You Won
Published: April 2008

Background:  Idiopathic cutaneous calcification and ossification occur in the absence of an abnormal serum calcium level or pre‐existing tissue abnormality. The pathogenesis has not been fully elucidated. The aim of this study was to investigate the expression of several molecular mediators in the idiopathic cutaneous calcification and ossification.

Methods:  Immunohistochemical study was used to evaluate the expression of molecular mediators, bone morphogenetic protein 4 (BMP‐4), β‐catenin, osteopontin, osteonectin and osteocalcin, and cell markers, smooth muscle actin, CD29 and CD44. And confocal laser scanning microscopy was used to evaluate the colocalization of BMP‐4 and BMP receptor type IA.

Results:  BMP‐4, β‐catenin, osteopontin, osteonectin and osteocalcin were expressed on the calcified and ossified tissue. Especially, BMP‐4 was expressed on the surrounding mesenchymal cells. Smooth muscle actin positive mesenchymal cells were on around the immature ossified tissue. Mesenchymal stem cell markers, CD29 and CD44 were not expressed.

Conclusion:  Our data suggest that BMP‐4, β‐catenin, osteopontin, osteonectin and osteocalcin may be involved in the idiopathic cutaneous calcification and ossification. And smooth muscle actin positive mesenchymal cells may be involved in the cutaneous ossification. This study suggests that the idiopathic cutaneous calcification and ossification is highly complicated and regulated active process like ectopic calcification of other tissues.
TrkA Receptor Endolysosomal Degradation is Both Ubiquitin and Proteasome Dependent
Authors: Geetha Thangiah , Wooten Marie W.
Published: April 2008

Gaps in our knowledge exist regarding the degradation of the tropomyosin‐regulated kinase A (TrkA) receptor after addition of neurotrophin, nerve growth factor (NGF). TrkA is rapidly and transiently ubiquitinated upon addition of NGF. Here, we demonstrate that the polyubiquitin tag plays a definitive role in receptor sorting. Treatment of PC12 cells with lactacystin prevented NGF‐dependent deubiquitination and degradation of TrkA. However, treatment with methylamine, bafilomycin or leupeptin, did not prevent NGF‐dependent deubiquitination but blocked the degradation of TrkA. Employing co‐immunoprecipitation, biochemical fractionation and confocal microscopy, the kinetics of receptor trafficking post‐internalization was observed to occur as a sequel from endosome/multivesicular body, proteasomes, culminating with degradation in the lysosomes. The trafficking of the polyubiquitin‐deficient TrkA receptor mutant K485R was impaired and likewise failed to degrade revealing that the receptor escapes degradation. The interaction of TrkA with proteasomes was confirmed by purification and co‐immunoprecipitation. We provide evidence that proteasomal deubiquitinating enzymes trim K63‐ubiquitin chains from the TrkA receptor prior to its delivery to lysosomes for degradation. Taken together, our results reveal the existence of a novel proteasome‐dependent step in receptor degradation.
Research: Dying with dementia: The views of family caregivers about quality of life
Authors: Russell Cherry , Middleton Heather , Shanley Chris
Published: April 2008

Objective:  To document the views of family caregivers of persons with dementia about quality of life for their relative during the late and terminal stages of the disease, as part of an exploratory study of best quality care and support.

Methods:  Fifteen former caregivers (five wives, five husbands, two sons, three daughters) participated in in‐depth semistructured interviews.

Results:  Participants identified three main sets of indicators of quality of life: the physical body, the physical and social environment and treatment with respect and dignity. The constructs ‘quality of life’ and ‘quality of care’ tended to be conflated in the experience of caregivers. An important role for caregivers was to interpret and represent the subjective experience of the person with dementia.

Conclusion:  Quality of life needs to be understood from multiple perspectives. Caregivers’ views are a central part of this understanding and should be used to inform future research and service development.
Research: Ageing, social capital and the Internet: Findings from an exploratory study of Australian ‘silver surfers’
Authors: Russell Cherry , Campbell Andrew , Hughes Ian
Published: April 2008

Objective: To document the sociodemographic characteristics and online use patterns of older Australian Internet users as part of an exploratory study of the relationship between Internet communication and access to social capital in later life.

Methods: A purposive sample of 154 Internet users aged 55 years or older and not employed full time completed an electronic survey about their social characteristics and patterns of Internet use. A subsample of 30 participated in follow‐up in‐depth interviews.

Results: The majority of participants comprised married, home‐owning, English‐speaking women and men in good health. They made extensive use of the communication and information functions of the Internet to supplement and enhance their connections with friends and family and their engagement with wider social networks.

Conclusion: Policy development should be informed by better understanding of the potential and limitations of the Internet as a tool for generating and sustaining social capital in old age.
Molecular basis of perinatal hypophosphatasia with tissue‐nonspecific alkaline phosphatase bearing a conservative replacement of valine by alanine at position 406
Authors: Numa Natsuko , Ishida Yoko , Nasu Makiko , Sohda Miwa , Misumi Yoshio , Noda Tadashi , Oda Kimimitsu
Published: April 2008

Hypophosphatasia, a congenital metabolic disease related to the tissue‐nonspecific alkaline phosphatase gene (TNSALP), is characterized by reduced serum alkaline phosphatase levels and defective mineralization of hard tissues. A replacement of valine with alanine at position 406, located in the crown domain of TNSALP, was reported in a perinatal form of hypophosphatasia. To understand the molecular defect of the TNSALP (V406A) molecule, we examined this missense mutant protein in transiently transfected COS‐1 cells and in stable CHO‐K1 Tet‐On cells. Compared with the wild‐type enzyme, the mutant protein showed a markedly reduced alkaline phosphatase activity. This was not the result of defective transport and resultant degradation of TNSALP (V406A) in the endoplasmic reticulum, as the majority of newly synthesized TNSALP (V406A) was conveyed to the Golgi apparatus and incorporated into a cold detergent insoluble fraction (raft) at a rate similar to that of the wild‐type TNSALP. TNSALP (V406A) consisted of a dimer, as judged by sucrose gradient centrifugation, suggestive of its proper folding and correct assembly, although this mutant showed increased susceptibility to digestion by trypsin or proteinase K. When purified as a glycosylphosphatidylinositol‐anchorless soluble form, the mutant protein exhibited a remarkably lower Kcat/Km value compared with that of the wild‐type TNSALP. Interestingly, leucine and isoleucine, but not phenylalanine, were able to substitute for valine, pointing to the indispensable role of residues with a longer aliphatic side chain at position 406 of TNSALP. Taken together, this particular mutation highlights the structural importance of the crown domain with respect to the catalytic function of TNSALP.
Structural flexibility of the methanogenic‐type seryl‐tRNA synthetase active site and its implication for specific substrate recognition
Authors: Bilokapic Silvija , Rokov Plavec Jasmina , Ban Nenad , Weygand‐Durasevic Ivana
Published: April 2008

Seryl‐tRNA synthetase (SerRS) is a class II aminoacyl‐tRNA synthetase that catalyzes serine activation and its transfer to cognate tRNASer. Previous biochemical and structural studies have revealed that bacterial‐ and methanogenic‐type SerRSs employ different strategies of substrate recognition. In addition to other idiosyncratic features, such as the active site zinc ion and the unique fold of the N‐terminal tRNA‐binding domain, methanogenic‐type SerRS is, in comparison with bacterial homologues, characterized by a notable shortening of the motif 2 loop. Mutational analysis of Methanosarcina barkeri SerRS (mMbSerRS) was undertaken to identify the active site residues that ensure the specificity of amino acid and tRNA 3′‐end recognition. Residues predicted to contribute to the amino acid specificity were selected for mutation according to the crystal structure of mMbSerRS complexed with its cognate aminoacyl‐adenylate, whereas those involved in binding of the tRNA 3′‐end were identified and mutagenized on the basis of modeling the mMbSerRS:tRNA complex. Although mMbSerRSs variants with an altered serine‐binding pocket (W396A, N435A, S437A) were more sensitive to inhibition by threonine and cysteine, none of the mutants was able to activate noncognate amino acids to greater extent than the wild‐type enzyme. In vitro kinetics results also suggest that conformational changes in the motif 2 loop are required for efficient serylation.
PCR METHOD FOR THE DETECTION OF GENUS FUSARIUM AND FUMONISIN‐PRODUCING ISOLATES FROM FRESHLY HARVESTED SORGHUM GRAINS GROWN IN KARNATAKA, INDIA
Authors: SREENIVASA M.Y. , DASS REGINA SHARMILA , RAJ A.P. CHARITH , JANARDHANA G.R.
Published: April 2008

Sixty‐four isolates of Fusarium species isolated from 44 sorghum samples collected during 2004–2005 were subjected to polymerase chain reaction (PCR) analysis. PCR detection was performed on all Fusarium species using two different sets of primers, namely, internal transcribed spacer (ITS) and FUM1. The developed protocol is rapid for small‐scale extraction of DNA from fungal mycelia for the detection of Fusarium species using diagnostic PCR. Sixty‐four Fusarium isolates, namely, Fusarium verticillioides (45), Fusarium proliferatum (4), Fusarium anthophilum (4), Fusarium sporotrichioides (3), Fusarium pallidoroseum (6) and Fusarium oxysporum (2), were analyzed by PCR using the ITS and FUM1 set of primers. All Fusarium species scored positive with the ITS set of primers. Among the 64 isolates, 53 have scored positive with the FUM1 set of primers. These 53 isolates represent F. verticillioides (45), F. proliferatum (4) and F. anthophilum (4), respectively. The results of the study revealed that PCR‐based technique could be used to identify a group of potential fumonisin‐producing Fusarium species.

PRACTICAL APPLICATIONS

Polymerase chain reaction (PCR) method provides the basis for a simple, accurate, rapid and precise detection of potential fumonisin producing Fusarium species, which are of considerable risk to animal and human health. The detection of Fusarium species is therefore crucial for the prevention of toxins entering the food chain. The protocols developed in this study are helpful for a rapid and small‐scale extraction of nucleic acid from fungal mycelia, occurring on contaminated sorghum samples. A large number of samples can be screened in relatively less time using this PCR protocol when compared with the conventional methods.
EFFECTIVENESS OFPHYLLANTHUS EMBLICAL. ESSENTIAL OIL TO INHIBIT THE GROWTH OF FOOD‐SPOILING YEASTS
Authors: LIU XIAOLI , ZHAO MOUMING , WANG JINSHUI , WEI LUO
Published: April 2008

This study aimed to verify the effectiveness ofPhyllanthus emblicaL. essential oil to inhibit the growth of various food‐spoiling yeasts. Antiyeast activity was studied by determining the minimum inhibitory concentration (MIC) by solid medium diffusion and microplate bioassay, as well as evaluating the effect of the essential oil at MIC on the yeast cell viability. The essential oil can effectively inhibit the growth of all tested yeasts with MIC values of 12.5 and 0.8 µL/mL for most yeasts. The essential oil in the solid medium diffusion MIC presented significant inhibitory effects on all yeast cell viabilities. In contrast, the essential oil in the microplate MIC significantly inhibitedCandida kruseiandPichia ohmeri.The essential oil was analyzed by gas chromatography–mass spectrometry analysis. Thirty compounds representing 92.91% of the essential oil were tentatively identified. β‐Bourbonene, heptadecanol, pentadecanone, thymol, β‐caryophyllene, β‐neoclovene, nerol and borneol were the major compounds.

PRACTICAL APPLICATIONS

The study can be considered as the first report on thein vitroantiyeast activity ofPhyllanthus emblicaL. essential oil. The results showed that the essential oil had significant effectiveness to inhibit the growth of all tested yeasts with minimum inhibitory concentration values of 12.5 and 0.8 µL/mL for most yeasts. We hope that our results introduce a unique natural source that possesses strong antimicrobial substances. The essential oil could be used as a natural preservative in food and/or pharmaceutical industry.
Implementing the National Institute of Clinical Excellence improving outcome guidelines for head and neck cancer: developing a business plan with reorganisation of head and neck cancer services
Authors: Jeannon J.‐P. , Abbs I. , Calman F. , Gleeson M. , Lyons A. , Hussain K. , McGurk M. , O’Connell M. , Probert D. , Ng R. , Simo R.
Published: April 2008

Keypoints

The implementation of the National Institute of Clinical Excellence improving outcome guidelines (NICE‐IOG) manual for head and neck cancer may have a huge potential cost implication.

Head and neck cancer is a rare disease which utilises large quantities of resources which can only be provided in a tertiary centre.

Head and neck cancer services should be centralised into a single site for each cancer network.

A new higher tariff rate for complex head and neck cancer cases is needed which recognises the true cost of this work.

Each network should set its own tariff to make head and neck cancer care financially viable.
Safety and efficacy of endoscopic pharyngeal pouch stapling in a large UK study
Authors: Lieder A. , Nasseri F. , Sharma A. , Jani P.
Published: April 2008

Keypoints

Endoscopic stapling of pharyngeal pouch is minimally invasive surgery, ensuing fast recovery and shorter hospitalisation, but previous small case series may have biased outcome.

Perioperative and long‐term outcome of endoscopic stapling of pharyngeal pouch were examined retrospectively in the largest (n = 62) UK case series.

Stapling was not possible in seven patients because of small size of the pouch. Most patients made a full recovery immediately post‐operatively. Two patients developed a leak at the stapling site, but critical complications or direct mortality were not observed.

Persistence or recurrence of symptoms were observed in 18% of patients and successfully treated by revision endoscopic stapling or open procedure.

We recommend endoscopic stapling for all patients with moderate or large pharyngeal pouches.
Ionomer cement for reconstruction of the long process of the incus: the Pécs experience
Authors: Ráth G. , Bauer M. , Pytel J. , Vóna I. , Szanyi I. , Lujber L. , Gerlinger I.
Published: April 2008

Keypoints

Experience gained with the repair of the defects of the long process of the incus with ionomer cement in 35 patients is reported.

The integrity of the reconstructed tympanic membrane and the four‐frequency average of the air‐bone gaps of the postoperative audiograms (best, most recent and at around 1 year) were evaluated.

This ‘physiological’ reconstruction of the ossicular chain fulfilled our expectations in 40% of the patients (air‐bone gap ≤ 10 dB).

The background of the unsuccessful cases was investigated.
Intra‐operative parathyroid hormone monitoring using a laboratory based multichannel analyser
Authors: Mace A.D. , Randhawa P.S. , Woolman E. , Stearns M.P.
Published: April 2008

Keypoints

Parathyroid hormone has a short half life in vivo.

Intraoperative parathyroid hormone measurement can guide the surgeon by confirming successful removal of parathyroid adenomas.

Point of care testing with a dedicated analyser and technician in theatre is expensive.

This study shows that intraoperative parathyroid hormone is feasible using a central laboratory based analyser available in most hospitals.

There are potential cost savings when compared with point of care testing.
Identification of predictors and development of a screening protocol for cerebello‐pontine lesions in patients presenting with audio‐vestibular dysfunction
Authors: Chatrath P. , Frosh A. , Gore A. , Nouraei R. , Harcourt J.
Published: April 2008

Objectives:  Magnetic resonance imaging (MRI) scanning in the investigation of cerebellopontine angle lesions represents a finite resource, the use of which needs to be carefully rationalised. Our aim was to identify predictive factors that can distinguish between patients with and without cerebellopontine angle lesions, and develop a screening protocol which could be useful in the clinical setting as an aid to clinical judgment.

Design:  Case–control study.

Setting:  Secondary care.

Participants:  Audio‐vestibular features were collated on 136 patients (M : F 1.39 : 1) and 288 controls (M : F 1 : 1.1).

Intervention:  Diagnostic by analysis of symptoms and audiometric data using logistic regression, receiver‐operator characteristic curves and backwards elimination.

Main outcome measures:  Development of a predictive algorithm comprising those factors which are most strongly predictive of the presence of a cerebellopontine angle lesion.

Results:  Positive predictors of a cerebellopontine angle lesion include the interaural threshold difference at 1 (P = 0.044) and 4 kHz (P = 0.034). The threshold in the better hearing ear at 0.25 kHz exerts a negative predictive (i.e. protective) effect (P = 0.005). The presence of tinnitus does not appear to influence the outcome on logistic regression. Although vertigo does exert an influence on the overall model, its impact is highly equivocal.

Conclusions:  We have identified audiometric factors which exert a positive and negative predictive influence on the presence of a cerebellopontine angle lesion, and audiovestibular symptoms which appear to exert little effect on the model. Our predictive equation represents a user‐friendly standardised method of risk‐stratification of patients within a general otolaryngology clinic.
Superficial temporal vein graft in stapedotomy: a functional and aesthetic alternative
Authors: Javed F. , Leong A.C. , Fairley J.W.
Published: April 2008

Keypoints

The Causse technique of performing stapedotomy with vein graft interposition is widely‐employed, with the vein graft harvested from the dorsum of the hand/wrist.

Donor site scarring may be of cosmetic concern, especially in female patients.

A prospective series of 19 patients undergoing stapedotomy with vein graft harvested from the superficial temporal vein is evaluated from aesthetic and functional perspectives.

Results show that vein interposition from this donor site is not only aesthically acceptable but just as successful in improving hearing outcome after stapedotomy.

We suggest the use of the superficial temporal vein and/or its branches as an alternative vein graft in stapedotomy.
Touch screen computer‐assisted health‐related quality of life and distress data collection in head and neck cancer patients
Authors: De Bree R. , Verdonck‐de Leeuw I.M. , Keizer A.L. , Houffelaar A. , Leemans C.R.
Published: April 2008

Keypoints

Touch screen computer‐assisted health‐related quality of life data collection in head and neck cancer patients is feasible.

Touch screen computer‐assisted health‐related quality of life data collection can be used for scientific documentation as well as in clinical setting.

Patients are willing to complete the questionnaire on a touch‐screen and find the equipment easy to use.

Compliance needs improvement by instructing clinicians and nurses and a better alert system.
No Long‐Term Effect Two Years after Intrauterine Exposure to Dexamethasone on Dentate Gyrus Volume, Neuronal Proliferation and Differentiation in Common Marmoset Monkeys
Authors: Tauber Simone C. , Bunkowski Stephanie , Schlumbohm Christina , Rühlmann Malte , Fuchs Eberhard , Nau Roland , Gerber Joachim
Published: April 2008

Glucocorticoids are prenatally administered to promote the maturation of the lungs. They, however, can affect neuronal proliferation and differentiation. In newborn marmoset monkeys, intrauterine hyperexposure to dexamethasone (DEX) resulted in a significantly decreased proliferation rate in the hippocampal dentate gyrus without affecting neuronal differentiation. In this study, marmoset monkeys received 5 mg/kg body weight DEX either during early (days 42–48) or late (days 90–96) pregnancy. The volume of the dentate granule cell layer as well as the proliferation and neuronal differentiation in the dentate gyrus of their 2‐year‐old offspring were investigated. The density of proliferating cells (Ki‐67), apoptotic cells (in situ tailing) and cells differentiating to neurons (double cortin, TUC‐4 and calretinin) were determined immunohistochemically. Analysis of the dentate granule cell layer volume showed no significant differences between early or late DEX‐exposed marmosets and untreated control animals. Similarly, proliferation and neuronal differentiation in DEX‐treated animals was not significantly different in comparison with controls. In summary, the decreased proliferation rate observed in newborn marmosets after intrauterine exposure to DEX was no longer detectable in their 2‐year‐old siblings suggesting no long‐lasting effect of prenatal hyperexposure to DEX on neuronal proliferation and differentiation in the dentate gyrus of marmoset monkeys.
Ultrastructural analysis of collagen fibrils and proteoglycans in keratoconus
Authors: Akhtar Saeed , Bron Anthony J. , Salvi Sachin M. , Hawksworth Nicolas R. , Tuft Stephen J. , Meek Keith M.
Published: April 2008

Purpose:  To investigate ultrastructural alterations in the distribution of collagen fibrils (CFs) and proteoglycans (PGs) in the keratoconus cornea.

Methods:  Four normal corneas (donor age 24–75 years) and four severe and one mild keratoconus corneas (donor age 24–47 years) were fixed in 2.5% glutaraldehyde containing 0.05% cuprolinic blue dye for electron microscopy. Analyses were carried out on approximately 39 000 CF and 66 000 PG filaments in the anterior, middle and posterior stroma, using analySIS® soft imaging software.

Results:  In severe keratoconus, stromal lamellae were seen to undulate in most regions, whereas in mild keratoconus only the middle and posterior lamellae were affected. In keratoconus corneas the mean diameter and interfibrillar spacing of CFs was reduced in all zones (p < 0.0001) and the CF and PG number density and area fractions were significantly increased (p < 0.0001) compared with in normal corneas and were higher (p < 0.0001) in the corneas with severe keratoconus than in that with mild keratoconus. The lamellae contained microfibrils (8–9 nm wide) and, in addition, PGs embedded within CFs. Degenerate keratocytes containing PGs were found in all keratoconus corneas.

Conclusions:  These studies suggest that as keratoconus progresses, the PG content of the stroma increases, whereas fibril diameter is reduced. The altered stromal content of PGs may influence CF diameters and their organization in keratoconus, weakening lateral cohesion and resulting in significant disorder of CF packing.
Evaluation of platelet count and its association with plateletcrit, mean platelet volume, and platelet size distribution width in a canine model of endotoxemia
Authors: Yilmaz Zeki , Eralp Oya , Ilcol Yesim Ozarda
Published: April 2008

Background: Platelets are of great importance in the pathogenesis of endotoxemia. Although thrombocytopenia is used as a diagnostic sign of endotoxemia, changes in values for platelet indices (plateletcrit [PCT], mean platelet volume [MPV], and platelet size distribution width [PDW]) in response to endotoxin are still unknown.

Objective: The aim of this study was to evaluate platelet count and its relations with platelet indices in a canine model of endotoxemia.

Methods: Twenty dogs were divided into 2 groups of 10 each, and treated intravenously with Escherichia coli endotoxin (1 mg/kg) or vehicle. Venous blood samples were collected before treatment (0 hour) and 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after treatment. Platelet counts and indices were determined on a CELL‐DYN hematology analyzer.

Results: The platelet count and PCT decreased by a mean of 73% and 93%, respectively (P<.001), at 0.5 hour, and remained 70% and 85% lower than baseline values (P<.001) for 24 hours after endotoxin injection. MPV and PDW increased by a mean of 28% and 45%, respectively (P<.01), at 0.5 hour, and remained increased by 7% and 16% over baseline values for 24 hours (P<.01–.001). Platelet count correlated positively with PCT (P<.001), but correlated negatively with MPV (P<.001) and PDW (P<.01).

Conclusions: Changes in platelet count and its association with platelet indices may reflect changes in platelet production and reactivity. Platelet indices have potential value in the diagnosis and monitoring of dogs and humans with endotoxemia.
Role of sarcolemmal ATP‐sensitive K+channels in the regulation of sinoatrial node automaticity: an evaluation using Kir6.2‐deficient mice
Authors: Fukuzaki Koichi , Sato Toshiaki , Miki Takashi , Seino Susumu , Nakaya Haruaki
Published: April 2008

The role of cardiac sarcolemmal ATP‐sensitive K+(KATP) channels in the regulation of sinoatrial node (SAN) automaticity is not well defined. Using mice with homozygous knockout (KO) of the Kir6.2 (a pore‐forming subunit of cardiac KATPchannel) gene, we investigated the pathophysiological role of KATPchannels in SAN cells during hypoxia. Langendorff‐perfused mouse hearts were exposed to hypoxic and glucose‐free conditions (hypoxia). After 5 min of hypoxia, sinus cycle length (CL) was prolonged from 207 ± 10 to 613 ± 84 ms (P< 0.001) in wild‐type (WT) hearts. In Kir6.2 KO hearts, CL was slightly prolonged from 198 ± 17 to 265 ± 32 ms. The CL of spontaneous action potentials of WT SAN cells, recorded in the current‐clamp mode, was markedly prolonged from 410 ± 56 to 605 ± 108 ms (n= 6,P< 0.05) with a decrease of the slope of the diastolic depolarization (SDD) after the application of the K+channel opener pinacidil (100 μm). Pinacidil induced a glibenclamide (1 μm)‐sensitive outward current, which was recorded in the voltage‐clamp mode, only in WT SAN cells. During metabolic inhibition by 2,4‐dinitrophenol, CL was prolonged from 292 ± 38 to 585 ± 91 ms (P< 0.05) with a decrease of SDD in WT SAN cells but not in Kir6.2 KO SAN cells. Diastolic Ca2+concentration, measured by fluo‐3 fluorescence, was decreased in WT SAN cells but increased in Kir6.2 KO SAN cells after short‐term metabolic inhibition. In conclusion, the present study using Kir6.2 KO mice indicates that, during hypoxia, activation of sarcolemmal KATPchannels in SAN cells inhibits SAN automaticity, which is important for the protection of SAN cells.
Presynaptic (Type III) cells in mouse taste buds sense sour (acid) taste
Authors: Huang Yijen A. , Maruyama Yutaka , Stimac Robert , Roper Stephen D.
Published: April 2008

Taste buds contain two types of cells that directly participate in taste transduction – receptor (Type II) cells and presynaptic (Type III) cells. Receptor cells respond to sweet, bitter and umami taste stimulation but until recently the identity of cells that respond directly to sour (acid) tastants has only been inferred from recordings in situ, from behavioural studies, and from immunostaining for putative sour transduction molecules. Using calcium imaging on single isolated taste cells and with biosensor cells to identify neurotransmitter release, we show that presynaptic (Type III) cells specifically respond to acid taste stimulation and release serotonin. By recording responses in cells isolated from taste buds and in taste cells in lingual slices to acetic acid titrated to different acid levels (pH), we also show that the active stimulus for acid taste is the membrane‐permeant, uncharged acetic acid moiety (CH3COOH), not free protons (H+). That observation is consistent with the proximate stimulus for acid taste being intracellular acidification, not extracellular protons per se. These findings may also have implications for other sensory receptors that respond to acids, such as nociceptors.
Cardiac autonomic neuropathy in diabetes mellitus: prevalence, risk factors and utility of corrected QT interval in the ECG for its diagnosis
Authors: Pappachan J M , Sebastian J , Bino B C , Jayaprakash K , Vijayakumar K , Sujathan P , Adinegara L A
Published: April 2008

Objectives

To study the prevalence and risk factors for cardiac autonomic neuropathy (CAN) and the utility of prolongation of corrected QT interval (QTc) in the ECG to diagnose CAN in patients with diabetes mellitus.

Design and setting

Cross-sectional study conducted among patients attending the diabetic clinic of a teaching hospital.

Methods

The prevalence of CAN among 100 patients with type 1 and type 2 diabetes mellitus was assessed by the five autonomic function tests by Eving's methodology. The CAN score in each patient and its relationship to the QTc interval were analysed. Possible influences of age, duration of diabetes and coexistent peripheral neuropathy on the occurrence of CAN also were studied.

Results

The prevalence of CAN was 60%. Univariate analysis showed a significant association between CAN and higher age (odds ratio (OR) 15.75), prolongation of QTc (OR 5.55), duration of disease over 10 years (OR 2) and peripheral neuropathy (p<0.001) in patients with type 1 diabetes. Significant risks for CAN among patients with type 2 diabetes were coexistent peripheral neuropathy (OR 14), prolonged QTc (OR 9.75), higher age (OR 7.2) and disease duration over 10 years (OR 1.92) in univariate analysis, but none of them showed independent risk in multivariate analysis. Disease duration over 10 years resulted in QTc prolongation in a significant numbers of cases with type 1 (p<0.001) and type 2 (p = 0.006) diabetes. The sensitivity, specificity and positive predictive value of QTc prolongation for the diagnosis of CAN were 77%, 62.5% and 77% in type 1 and 76.5%, 75% and 81.3% in type 2, respectively. Higher CAN scores correlated with longer QTc intervals (coefficient of correlation 0.73; p<0.001).

Conclusions

The prevalence of CAN in diabetes mellitus is high. Higher age, longer duration of diabetes and peripheral neuropathy are significant risk factors. QTc interval in the ECG can be used to diagnose CAN with reasonable sensitivity, specificity and positive predictive value.
Characterization of self-incompatibility inCampanula rapunculoides(Campanulaceae) through genetic analyses and microscopy
Authors: Good-Avila S. V. , Majumder D. , Amos H. , Stephenson A. G.
Published: April 2008

In this paper, we seek to identify the genetic basis of self-incompatibility (SI) in Campanula rapunculoides L. through diallel analysis of full siblings; to characterize the growth of pollen tubes in vivo after incompatible and compatible pollination; and to determine whether the SI system is based on pistil S-RNases. Pollinations were performed among individuals from five diallel crosses and scored for both fruit set and pollen-tube growth to determine the genetic basis of SI. On a subset of these individuals with known cross-(in)compatibility relationships, additional crosses were performed and pistils collected 1, 3, 6, 12, and 24 h after pollination to assess both the percentage of pollen grains that had germinated on the stigma, and the number of pollen tubes that had grown 20%, 40% 60%, 80%, and 100% of the distance down the pistil over five time intervals. Finally, total pistillate proteins were extracted and subjected to isoelectric focusing and RNase activity staining to find evidence of a highly basic S-RNases associated with SI in the Solanaceae. We found evidence that the SI system was based on the haplotype of the male gametophyte, and was not sporophytic. Protein analyses showed that SI was not based on a pistillate S-RNase. The existence of modifiers of SI and possible polyploidy at the S-locus complicated the expression of SI in this species, and single-gene inheritance could not be determined. This represents the first published characterization of incompatibility in the family Campanulaceae.