bluuebunny/crossref_metadata_2025 huggingface dataset:
The predictability of the epidemic of variant Creutzfeldt-Jakob disease by back-calculation methods
Authors: d’Aignaux Jérôme N Huillard , Cousens Simon N , Smith Peter G
Published: May 2003

We present a back-calculation analysis of the variant Creutzfeldt-Jakob (vCJD) epidemic in the UK to estimate the number of infected individuals and to explore the likely future incidence of the disease. The main features of the model are that the hazard of infection was assumed proportional to the incidence of BSE in the UK with allowance for precautionary control measures taken in 1988 and in 1996, and that the incubation period distribution of vCJD follows an offset generalized F distribution. Our results indicate that current the numbers of cases with onset up to 31 December 2000 data are broadly compatible with numbers of primary infections ranging from a few hundred to several million. However, if a very large number of persons were infected, the model suggests that the mean incubation period is likely to be well beyond the human lifespan, resulting in a disease epidemic of much smaller size (maximum several thousand). A sensitivity analysis indicates that our results are sensitive to the underreporting of vCJD cases before 1996. Finally, we show that, in the absence of a reliable test for asymptomatic infection, uncertainty in estimates of the total number of infections is likely to remain for at least several years, even if the number of clinical cases remains low.
Modelling the epidemic of variant Creutzfeldt-Jakob disease in the UK based on age characteristics: updated, detailed analysis
Authors: Boëlle Pierre-yves , Thomas Guy , Valleron Alain-Jacques , Cesbron Jean-Yves , Will Robert
Published: May 2003

Incubation period of the new variant Creutzfeldt-Jakob disease (vCJD) from infection to clinical onset and the eventual impact of the disease remain major concerns. Based on i) epidemiological conceptualization of human exposure to BSE contaminated material, ii) exponentially decreasing susceptibility after 15 years of age, and iii) typical incubation period (IP) distributions for time from infection to onset, we have previously estimated mean incubation period and projected number of vCJD cases. In this paper, we investigate the robustness of these estimates with respect to i-iii using the UK’s 113 vCJD cases with clinical onset before December 2000. Mean incubation period was estimated at 16.4 years (95% CI 11.4-24.8), 15.9 years (95% CI 11.4-22.0), 14.1 years (95% CI 10.4-24.2) with the log-normal, Gamma and Weibull distributions respectively. Corresponding predictions for the total size of the epidemic ranged from 183 to 304. Maximal susceptibility to infection between 1.3 and 15.9 years and decreasing by 15% per year of age thereafter yielded the best fit. The shape of the IP distribution did not affect the predictions. In summary, within a set of reasonable assumptions, mean incubation period for vCJD ranged from 15 to 20 years, and the eventual impact of vCJD was a few hundred patients.
The geographical distribution of variant Creutzfeldt-Jakob disease cases in the UK: what can we learn from it?
Authors: Cousens Simon , Everington Dawn , Ward Hester JT , Huillard Jerome , Will Robert G , Smith Peter G
Published: May 2003

The causative agents of variant Creutzfeldt-Jakob disease (vCJD) and of bovine spongiform encephalopathy (BSE) are currently indistinguishable. However, the route(s) by which humans became infected remain unknown. The path by which humans were infected with the BSE agent might impact on the geographical distribution of cases and we therefore sought evidence of regional variation and local clustering of vCJD cases. With the notable exception of a group of five cases in Leicestershire, the absence of local clustering of vCJD cases is compatible with most human exposure to the vCJD agent arising through routes that result in the risk of infection being similar over wide geographical areas, rather than through small-scale local events. Infection through the consumption of mechanically recovered meat (MRM) contaminated with the BSE agent was a potential route for such widespread exposure. An ecological analysis relating the regional incidence of vCJD to historical dietary data does not provide a clear evidence that humans became infected through consumption of MRM.
TSE risk assessments: a decision support tool
Authors: Comer Philip J , Huntly Paul J
Published: May 2003

The paper presents a practical approach to assessing the risks of exposure to the infective agents from transmissible spongiform encephalopathies. Current data on the infectivity of bovine tissues have been reviewed and values for use in risk assessment studies proposed for the infectivityof central nervous system and other tissues, the development of infectivity through the incubation period and the cattle-human species barrier. A study to assess the risk of exposure to BSE infectivity in cattle disposed of during the 2001 foot and mouth epidemic in the UK by burning in pyres or burial is used to illustrate the application of TSE risk assessment and the way in which it can be used as an input to decision making.
The impact of spectral power distribution on the performance of an achromatic visual task
Authors: Boyce PR , Akashi Y , Hunter CM , Bullough JD
Published: May 2003

This experiment tests the hypothesis that light sources that produce smaller pupil sizes ensure better achromatic visual task performance at the same photopic illuminance. Two groups of subjects, one in the age range 18-28 years and the other in the range 61-78 years, performed a Landolt ring task for eight different gap sizes, two different illuminances, and two lamp scotopic/photopic ratios. For both age groups, pupil size was determined by both illuminance and lamp spectrum. The speed and accuracy of performance of the task was determined by the gap size, and to a much lesser extent, by the illuminance. Lamp spectrum had no effect on the performance of the task.
Drosophilasecurin destruction involves a D-box and a KEN-box and promotes anaphase in parallel with Cyclin A degradation
Authors: Leismann Oliver , Lehner Christian F.
Published: May 2003

Sister chromatid separation during exit from mitosis requires separase. Securin inhibits separase during the cell cycle until metaphase when it is degraded by the anaphase-promoting complex/cyclosome (APC/C). In Drosophila, sister chromatid separation proceeds even in the presence of stabilized securin with mutations in its D-box, a motif known to mediate recruitment to the APC/C. Alternative pathways might therefore regulate separase and sister chromatid separation apart from proteolysis of the Drosophila securin PIM. Consistent with this proposal and with results from yeast and vertebrates, we show here that the effects of stabilized securin with mutations in the D-box are enhanced in vivo by reduced Polo kinase function or by mitotically stabilized Cyclin A. However, we also show that PIM contains a KEN-box, which is required for mitotic degradation in addition to the D-box, and that sister chromatid separation is completely inhibited by PIM with mutations in both degradation signals.
Thrombin induces endothelial cell-surface exposure of the plasminogen receptor annexin 2
Authors: Peterson Erica A. , Sutherland Michael R. , Nesheim Michael E. , Pryzdial Edward L. G.
Published: May 2003

Cell-surface annexin 2 (A2) and its ligand p11 have been implicated in fibrinolysis because of their ability to accelerate tissue plasminogen activator (tPA)-mediated activation of plasminogen to plasmin. Because thrombin is a potent cell modulator obligately produced at the site of clot formation, we hypothesized that the amount of cell-surface A2 and p11 might be altered by thrombin with consequent effects on plasmin generation. In support of this hypothesis, immunofluorescence microscopy and hydrophilic biotinylation experiments showed that both A2 and p11 were significantly increased on the surface of human umbilical vein endothelial cells (HUVECs)treated with thrombin (0.8-8 nM) for 5 minutes followed by 1 hour at 37°C. Intracellular immunofluorescence microscopy and immunoblot analyses of whole cell extracts revealed increased p11 but unchanged A2 in response to thrombin,suggesting that transbilayer trafficking of A2 might be controlled by p11. The thrombin receptor-activating peptide (TRAP) similarly affected cells,demonstrating that cell signaling at least involved the type-1 protease activated receptor (PAR-1). An effect on the fibrinolysis pathway after treatment of HUVECs with thrombin was shown by increased fluorescein-labeled plasminogen binding to cells, which was inhibited by an antibody specific for p11. This was confirmed by observing that thrombin pretreatment of HUVECs increased biotin-modified plasminogen binding. Utilizing a chromogenic assay,pretreatment of HUVECs by thrombin further enhanced activation of the Glu and Lys forms of plasminogen by tPA. These data suggest a novel mechanism that links the coagulation and fibrinolysis pathways by thrombin-mediated feedback.
Increased ploidy and KAR3 and SIR3 disruption alter the dynamics of meiotic chromosomes and telomeres
Authors: Trelles-Sticken Edgar , Loidl Josef , Scherthan Harry
Published: May 2003

We investigated the sequence of chromosomal events during meiotic prophase in haploid, diploid and autotetraploid SK1 strains of Saccharomyces cerevisiae. Using molecular cytology, we found that meiosis-specific nuclear topology (i.e. dissolution of centromere clustering, bouquet formation and meiotic divisions) are significantly delayed in polyploid SK1 meiosis. Thus, and in contrast to the situation in plants, an increase in ploidy extends prophase I in budding yeast. Moreover, we found that bouquet formation also occurs in haploid and diploid SK1 meiosis deficient in the telomeric heterochromatin protein Sir3p. Diploid sir3Δ SK1 meiosis showed pleiotropic defects such as delayed centromere cluster resolution in a proportion of cells and impeded downstream events (i.e. bouquet formation,homologue pairing and meiotic divisions). Meiotic telomere clustering occurred in diploid and haploid sir3Δ strains. Using the haploid system,we further show that a bouquet forms at the kar3Δ SPB. Comparison of the expression of meiosis-specific Ndj1p-HA and Zip1p in haploid control and kar3Δ time courses revealed that fewer cells enter the meiotic cycle in absence of Kar3p. Elevated frequencies of bouquets in kar3Δ haploid meiosis suggest a role for Kar3p in regulation of telomere dynamics.
IRSp53 is colocalised with WAVE2 at the tips of protruding lamellipodia and filopodia independently of Mena
Authors: Nakagawa Hiroyuki , Miki Hiroaki , Nozumi Motohiro , Takenawa Tadaomi , Miyamoto Shigeaki , Wehland Jürgen , Small J. Victor
Published: May 2003

The insulin receptor tyrosine kinase substrate p53 (IRSp53) links Rac and WAVE2 and has been implicated in lamellipodia protrusion. Recently, however,IRSp53 has been reported to bind to both Cdc42 and Mena to induce filopodia. To shed independent light on IRSp53 function we determined the localisations and dynamics of IRSp53 and WAVE2 in B16 melanoma cells. In cells spread well on a laminin substrate, IRSp53 was localised by antibody labelling at the tips of both lamellipodia and filopodia. The same localisation was observed in living cells with IRSp53 tagged with enhanced green florescence protein(EGFP-IRSp53), but only during protrusion. From the transfection of deletion mutants the N-terminal region of IRSp53, which binds active Rac, was shown to be responsible for its localisation. Although IRSp53 has been reported to regulate filopodia formation with Mena, EGFP-IRSp53 showed the same localisation in MVD7 Ena/VASP (vasodilator stimulated phosphoprotein) family deficient cells. WAVE2 tagged with DsRed1 colocalised with EGFP-IRSp53 at the tips of protruding lamellipodia and filopodia and, in double-transfected cells, the IRSp53 signal in filopodia decreased before that of WAVE2 during retraction. These results suggest an alternative modulatory role for IRSp53 in the extension of both filopodia and lamellipodia, through WAVE2.
The SH4-Unique-SH3-SH2 domains dictate specificity in signaling that differentiate c-Yes from c-Src
Authors: Summy Justin M. , Qian Yong , Jiang Bing-Hua , Guappone-Koay Anne , Gatesman Amanda , Shi Xianglin , Flynn Daniel C.
Published: May 2003

c-Src and c-Yes are highly homologous members of the Src family of non-receptor tyrosine kinases. The overall sequence similarity between c-Src and c-Yes allows them to perform many overlapping functions. However, the phenotypes of the c-src and c-yes knockout mice, and cells derived from them, are quite different, indicating functional specificity between the two proteins. Specifically, c-src-/- cells are deficient in several processes that require dynamic regulation of the actin cytoskeleton. In order to begin to understand why c-Yes is unable to compensate for c-Src signaling, we used a series of Src/Yes chimeras in which the non-catalytic functional domains of Src527F were replaced by those of c-Yes. Using chicken embryo fibroblasts as a model system, our results indicate that the c-Yes N-terminal SH4-Unique domains are sufficient to inhibit the ability of Src527F to alter cell morphology, induce actin filament rearrangements or stimulate motility or invasive potential. The data also indicate that the SH4-Unique-SH3-SH2 domains of c-Yes work cooperatively and prevent activation of signaling proteins associated with Src527F transformation, including activation of phosphatidylinositol 3-kinase, phosphorylation of c-Raf and Akt and downregulation of RhoA-GTP. These data indicate that c-Yes may not modulate signals associated with c-Src-induced changes in actin filament integrity and may explain why c-Yes fails to compensate for c-Src signaling in src-/- cells.
Coupling membrane protrusion and cell adhesion
Authors: DeMali Kris A. , Burridge Keith
Published: May 2003

The ability of cells to extend cell membranes is central to numerous biological processes, including cell migration, cadherin-mediated junction formation and phagocytosis. Much attention has been focused on understanding the signals that trigger membrane protrusion and the architecture of the resulting extension. Similarly, cell adhesion has been extensively studied,yielding a wealth of information about the proteins involved and how they signal to the cytoplasm. Although we have learned much about membrane protrusion and cell adhesion, we know less about how these two processes are coupled. Traditionally it has been thought that they are linked by the signaling pathways they employ – for example, those involving Rho family GTPases. However, there are also physical links between the cellular machineries that mediate cell adhesion and membrane protrusion, such as vinculin.
The effect of temporal variation in biochemical markers of trisomy 21 across the first and second trimesters of pregnancy on the estimation of individual patient-specific risks and detection rates for Down's syndrome
Authors: Spencer K , Crossley JA , Aitken DA , Nix ABJ , Dunstan FDJ , Williams K
Published: May 2003

Background: In a previous study we examined the changes in the median multiple of the median (MoM) with gestation of free beta human chorionic gonadotrophin (Fβ-hCG), total human chorionic gonadotrophin (ThCG), α-fetoprotein (AFP) and pregnancy-associated plasma protein A (PAPP-A) in a large series of Down's syndrome pregnancies. Results showed that there was a significant temporal variation of the MoM for each marker. In this paper, we assess the impact of this temporal shift on the estimation of patient-specific risks and the detection rates (DRs) for Down's syndrome pregnancies.

Methods: Individual patient-specific risks, DRs and false positive rates were estimated using statistical modelling techniques and computer simulations. The data for these simulations were the regressed mean log10 analyte MoMs, marker standard deviations (as log10 MoM) and correlation coefficients derived from the analysis of over 1000 cases of Down's syndrome and 150 000 unaffected pregnancies between 6 and 20 weeks of gestation reported in our previous study. Two models were compared: the classical constant median separation model, which assumes no variation in median shift with gestation (model 1), and a variable median separation model (model 2), which takes account of the changes in median shift with gestation as described in our previous study.

Results: When individual patient-specific risks calculated for various MoM values using model 1 were compared with those derived from model 2, considerable differences in risk estimates were observed for all marker combinations, particularly in the first trimester. Using a 1 in 250 cut-off risk, DRs at each gestation in the second trimester for the AFP+Fβ-hCG combination were maximized at 14-17 weeks of gestation and were virtually identical at 63-65% for model 1 and model 2. A similar trend was observed for the AFP+ThCG combination, with an optimum gestational range of 15-18 weeks and DRs of 66-68%. In the first trimester, using a 1 in 250 cut-off risk, DRs were more variable with gestation for the prime marker combination of Fβ-hCG+PAPP-A, varying from 73% at 8 weeks to 65% at 13 weeks with model 1 and from 75% to 66% with model 2.

Conclusion: Risk algorithms should take into account temporal variation in marker MoMs in order to produce accurate patient-specific risks. This also helps to maximize DRs, particularly when samples are taken outwith the optimal gestational range.
Urinary PC-1 and N-acetyl-β-D-glucosaminidase activity in patients with type 2 diabetes treated with metformin, gliclazide or glibenclamide
Authors: Stefanovicć V , Anticć S , Miticć-Zlatkovicć M , Stojiljkovicć S , Milojkovicć M , Bogicevicć M , Vlahovicć P
Published: May 2003

Background: Insulin resistance is a key feature of type 2 diabetes mellitus. Plasma cell differentiation antigen (PC-1) is an inhibitor of insulin receptor tyrosine kinase, and has been implicated in the pathogenesis of insulin resistance.

Methods: Urinary excretion of PC-1 was determined in 45 newly detected, obese diabetic patients treated with metformin (16 patients), gliclazide (14 patients) or glibenclamide (15 patients). Urinary N-acetyl-β-D-glucosaminidase (NAGA), a lysosomal enzyme, was determined as a marker of tubular damage in diabetes.

Results: Basal urinary PC-1 excretion in all three groups of diabetic patients was at the level of healthy controls. Treatment with oral hypoglycaemic drugs did not change significantly the group level or the number of patients in each group with increased PC-1 activity. Urinary excretion of NAGA in patients with type 2 diabetes was not statistically different from the control level. Metformin and gliclazide treatment did not change significantly the group levels of NAGA excretion. However, glibenclamide treatment produced an increased urinary NAGA excretion in the whole group, and in about twice as many patients as in the pre-treatment period.
Measurement of cardiac troponin I in striated muscle using three experimental methods
Authors: Fredericks Salim , Bainbridge Katie , Murray Joanne F , Collinson Paul O , Carter Nicholas D , Holt David W
Published: May 2003

Background: Qualitative and quantitative measures of cardiac troponin I (cTnI) in striated muscle have been reported as part of diverse investigations. However, there is disparity in the literature regarding the findings of these analyses. The cTnI molecule can exist in phosphorylated, non-phosphorylated, reduced, non-reduced, complexed or non-complexed forms. Each of these forms can change the antigenicity of cTnI, resulting in different antibody-antigen interactions in different experimental formats, thereby giving rise to the disparities in the literature.

Methods: cTnI in heart and skeletal muscles were investigated by three techniques employing the same specific cTnI antibodies: the recently revised Dade-Behring Dimension RXL assay, immunoblotting and immunohistochemistry.

Results: cTnI was detected in heart muscle but not skeletal muscle using the quantitative assay and immunoblotting. Unexpectedly, using the same antibodies, cTnI was not immunolocalized to either heart or skeletal muscle.

Conclusion: The antibody-cTnI interaction might be impeded on fixed immunohistochemistry sections. Our findings reflect those of a previous study, showing that cTnI was not detected in skeletal muscle extracts using a quantitative assay. The behaviour of cTnI antibodies varies depending on experimental design. Conclusions drawn from experiments using qualitative methods cannot necessarily be extrapolated to the quantitative assay and vice versa.
Interference caused by the contents of serum separator tubes in the Vitros CRP assay
Authors: Chang Chia-Yu , Lu Jin-Ying , Chien Tzu-I , Kao Jau-Tsuen , Lin Mei-Chun , Shih Pei-Chun , Yan Shiao-Ni
Published: May 2003

Background: We have observed discrepancies between C-reactive protein (CRP) measured in serum prepared from a serum separator tube (SST) and that obtained from a plain tube, when using the Vitros CRP assay. Our study aimed at elucidating the cause of these discrepancies.

Methods: Eighty-seven specimens from hospitalized patients with various types of inflammatory disease were analysed using a fixed-point immuno-rate method on a Vitros CRP slide. The serum was prepared simultaneously in both vacuum and SSTs. We also performed mixing tests by adding 47 samples of serum prepared from plain tubes to SSTs and incubating for 15 min before CRP analysis.

Results: Lower values of CRP were found in serum prepared from plain tubes than in serum from SSTs. Addition of serum prepared from plain tubes to SSTs and incubating for 15 min increased the CRP values significantly. The ratio of CRP measured in serum prepared from plain tubes and from SSTs did not differ significantly from the ratio obtained when serum was prepared in a plain tube then added to an SST.

Discussion: We propose that SSTs can adsorb some macromolocules that form complexes with CRP. The addition of SST gel to serum results in the release of CRP molecules from these complexes, which enhances the antigen-antibody reaction on the Vitros CRP slide and increases the measured CRP concentrations.
A sensitive and practical competitive radioassay for plasma biotin
Authors: Harthé Catherine , Claustrat Bruno
Published: May 2003

Background: Biotin is a water-soluble vitamin which plays an important biochemical role in a variety of carboxylase-mediated metabolic reactions. Determination of biotin status for the diagnosis of biotin deficiency is crucial.

Methods: We describe a solid-phase protein-binding assay involving [125I]iodostreptavidin as a tracer for the determination of biotin in plasma. The assay was conducted in one step by incubation of a fixed amount of [125I]iodostreptavidin as binding reagent with varying amounts of biotin, diluted in biotin-free plasma (standard curve) or unknown samples in tubes previously coated with biotin linked to goat antirabbit IgG. Increasing amounts of biotin in the standard or unknown samples in tubes previously coated with biotin occupy more sites on iodostreptavidin, resulting in fewer counts bound to tubes. The effects of the incubation time and temperature on the competitive binding of biotin with iodostreptavidin were tested.

Results: The detection limit of the plasma assay for biotin was 100 pmol/L. Only 100 µL of plasma were necessary for the assay, which was performed within 6 h. The dilutions of plasma and synthetic biotin gave a parallel response. Plasma biotin levels ranged from 0·49 to 1·33 nmol/L (mean 0·76 nmol/L) in healthy subjects. The intraand inter-assay coefficients of variation were 3·5% and 10%, respectively, at a concentration of 0·27 nmol/L.

Conclusions: This assay was suitable for the direct measurement of biotin in human plasma and was robust and sensitive enough for screening for biotin deficiency.
Definitive angiographic detection of subarachnoid haemorrhage compared with laboratory assessment of intracranial bleed in CT-negative patients
Authors: O'Connell Daniel M , Watson Ian D
Published: May 2003

Background: Between 2·5% and 5% of cases of subarachnoid haemorrhage (SAH) give negative results for computed tomography (CT) scanning. Recent UK guidelines make recommendations as to standardization of laboratory methodology for the detection of SAH in individuals with a negative CT scan. We have compared this approach with our routine assessment using first-order derivative spectrophotometry, a recently reported iterative computer prediction model and measurement of cerebrospinal fluid (CSF) ferritin concentration. All methods were judged against cerebral angiography as the definitive means of determining patient outcome.

Methods: Scanning spectrophotometry of CSF is necessary for both the UK guidelines and our in-house method. Absorbance measurements at 360, 405, 414 and 455 nm are required for the computer model. CSF ferritin concentration was measured using a serum method on a DPC Immulite 2000. This gave a value of <12 µg/L for normal CSF. Ethical approval and informed patient consent to additional investigation were obtained.

Results: The sensitivity and specificity for the UK guidelines method, derivative spectrophotometry (in-house), iterative computer model and CSF ferritin were, respectively: 0·8, 1·0; 0·9, 1·0; 0·9, 0·5; 1·0, 0·78.

Conclusion: First-order derivative spectrophotometry had best concordance with angiography. Combination of this with CSF ferritin measurement may improve sensitivity, although the zero-order method recommended in the UK guidelines for the detection of an intracranial bleed is more amenable and has comparable performance.
Laboratory results in the elderly: the Sydney Older Persons Study
Authors: Janu Margaret R , Creasey Helen , Grayson David A , Cullen John S , Whyte Scott , Brooks William S , Waite Louise M , Broe G Anthony
Published: May 2003

Background: The use of laboratory intervals based on younger and healthier populations is of questionable validity in older populations. The aim of this study was to examine haematological and biochemical profiles in a sample of community-dwelling older people and to study the impact of age, disease, disability and medications.

Methods: Basic haematological and biochemical values were obtained for 338 survivors of a random sample of community-living people aged 75 years or over at time of recruitment. These values were compared to the laboratory reference intervals and the effects of age, disease, medication and disability examined.

Results: The distribution of the 35 parameters measured differed from those described by the laboratory reference intervals in all but four of the variables. The values showed few significant age associations but did show associations with disease, disability and drug use.

Conclusions: Abnormalities identified in haematological and biochemical testing are not due to age but to age-related illnesses. This is contrary to previous studies reporting a change in haematological and biochemical parameters purely on the basis of age. In the presence of abnormalities, identification and clarification of disease states should be made.
Hypercarotenaemia or hypercarotenoidaemia
Authors: Saldana Chaparro R , Carr E , Barron JL
Published: May 2003

Background: Serum carotenoids consist of a variety of different compounds. Xanthoderma may result from an increased concentration of any of the carotenoids.

Method and results: High-performance liquid chromatography of serum carotenoids shows that a normal chromatogram contains mainly β-carotene, lutein and lycopene. Serum α- and β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin were found to be increased in the investigation of hypercarotenaemia.

Conclusion: Patients presenting with possible xanthoderma should have a dietary history taken and serum sent for carotenoid analysis.
Clinical biochemical tissue monitoring during ischaemia and reperfusion in major vascular surgery
Authors: Klaus S , Staubach KH , Eichler W , Gliemroth J , Heringlake M , Schmucker P , Bahlmann L
Published: May 2003

Background: Major vascular surgery with aortic cross-clamping is associated with temporary ischaemia of the lower limb due to lack of tissue blood flow. The present study was designed to determine if the short-term changes in cellular metabolism occurring during this situation can be detected by subcutaneous microdialysis. It was also hoped to ascertain if this new technique is useful in the continuous bedside monitoring of metabolism during aortic surgery.

Methods: In a controlled clinical study 20 patients undergoing elective aortic surgery were monitored using microdialysis probes that were inserted in the subcutaneous tissue of the left lower limb and a non-ischaemic region (shoulder). Interstitial fluid was obtained and the concentrations of glucose and lactate during lower limb ischaemia and during reperfusion were measured and compared with concentrations observed in fluid obtained from the non-ischaemic control tissue.

Results: Circulatory occlusion caused an immediate and significant decrease in the glucose/lactate ratio from 3·1±1·3 to 0·48±0·5 (P<0·05) that returned to preocclusion values within 2 h of commencing reperfusion.

Conclusion: We suggest that microdialysis may be used both to assess acute changes in tissue metabolism during ischaemic periods and also to act as an additional tool for the detection of peri-operative acute variations in limb blood flow.
Prolactin and macroprolactin: a case report of hyperprolactinaemia highlighting the interpretation of discrepant results
Authors: Ismail AAA , Walker PL , Fahie-Wilson MN , Jassam N , Barth JH
Published: May 2003

Immunoassay methods for prolactin detect macroprolactin (i.e. high molecular mass complexes of prolactin) to various degrees. Therefore it is generally assumed that the widely differing results by methods that measure both moieties to a differing extent are due to the presence of macroprolactin. We present a case which challenges such an assumption and suggest that precipitation by polyethylene glycol is the most reliable screen for identifying macroprolactin (and/or interfering antibodies if present).
Three-dimensional computer-aided endoscopic sinus surgery
Authors: Uddin F. J. , Sama A. , Jones N. S.
Published: May 2003

Three-dimensional computer-aided surgery adds a ‘third-dimension’ to endoscopic sinus surgery. The images it provides have the potential to provide the surgeon with further information that might result in safer and more effective surgery with less surgical morbidity. The gold test, as yet untested, will be whether the technique leads to fewer revision procedures and complications as a result of more complete and safe initial surgery. Its greatest asset lies in reinforcing the surgeons’ estimate of an instrument’s position in a difficult anatomical area. It can augment the learning curve and enhance teaching and training in endoscopic sinus surgery but it is not a substitute for a thorough knowledge of paranasal sinus anatomy.
Transmission of heat to the vestibule during revision stapes surgery using a KTP laser: an in vitro study
Authors: Szymanski Marcin , Mills Robert , Abel Eric
Published: May 2003

The transmission of heat to the vestibule during revision stapes surgery with a piston in situ has been studied using a KTP laser in an in vitro model. A type K thermocouple was placed around the medial of each piston tested in a ‘vestibule’ filled with saline. The effect of laser hits on fluoroplastic, fluoroplastic-wire and stainless steel stapes prostheses was investigated. The effect of adding blood to the operative field, of introducing a vein graft to seal the stapedotomy and of vaporizing soft tissue in the oval window were also examined. Greater temperature rises occurred with stainless steel than with the other piston types and smaller rises occurred when there was a vein graft in situ. The maximum temperature rise recorded was 2.6°C. We conclude that the use of the KTP laser to clear soft tissue from the oval window is safe when operated at the power levels recommended by the manufacturer.
Posture changes in diabetes mellitus
Authors: Ahmmed A. U. , Mackenzie I. J.
Published: May 2003

The weight distribution and postural sway was measured in diabetic subjectswith, and without, neuropathy, and then compared with age and sex matched non-diabetic subjectsusing a cheap and highly portable sway plate – SwayWeigh. The SwayWeigh was found to be very practical and the results obtained confirmed the increased postural sway in the absence of proprioceptive information in neuropathy subjects. The study shows that peripheral neuropathy increases the postural sway especially in the absence of visual clues but this did not result inpostural strategies causing significant limb load asymmetry.
An evaluation of functional outcomes (speech, swallowing) in patients attending speech pathology after head and neck cancer treatment(s): results and analysis at 12 months post-intervention
Authors: Perry Alison R. , Shaw Margaret A. , Cotton Susan
Published: May 2003

We have earlier reported establishing a computerized database to audit functional outcomes in patients who underwent head and neck cancer treatment in Victoria, Australiaand attended speech pathology services from April 1997–April 1999. This paper presents the statistical analyses and results from this study.

Speech pathologists collected, prospectively, functional outcome data on 293 patients who underwent head and neck cancer treatment, and sent these for analysis to La Trobe University. Clinician and patient assessments of outcomes: speech, swallowing, activity, pain, employment, health, QOL status were made.

Initial data on 293 patients were collected and data on mortality and morbidity were compiled at three, six and 12 months post-treatment. Within twelve months, 74 patients had died. Three, six and/or 12-month follow-up data was available on 219 patients, with both clinician and patient assessments of status completed. The status forms are presented as appendices to this paper. Complete status forms on 179 patients at 12 months were obtained.

This clinical audit of functional outcomes represents the first study of this kind, collecting data from speech pathologists and patients in a multi-centre study of patients with head and neck cancer. We present data to demonstrate optimal recovery of function at six months, such that this may represent a good reference point for reporting and comparison of functional outcomes.
The comparison of an empiric proton pump inhibitor trial vs 24-hour double-probe Ph monitoring in laryngopharyngeal reflux
Authors: Bilgen Cem , Ögüt Fatih , Kesimli-Dinç Hatice , Kirazli Tayfun , Bor Serhat
Published: May 2003

Laryngopharyngeal reflux (LPR), which is defined as the backflow of gastric contents into the upper aerodigestive tract, is a relatively common disorder. However, its diagnosis still poses many problems. Twenty-four-hour double-probe pH monitoring is currently the diagnostic test of choice, but it has many disadvantages. Thus, an empiric trial of antireflux therapy has been suggested as an alternative method for diagnosis. The purpose of this article is to evaluate the validity of this alternative method in the management of LPR. The study group consisted of 36 patients with symptoms and physical findings suggesting LPR. The control subjects were 23 healthy adults. Twenty-four-hour double-probe pH monitoring was performed both in the study group and the control group, and the results were compared. In addition, the symptoms and physical findings in the study group was scored by the modified reflux symptom index (MRSI) and reflux finding score (RFS) at four intervals: before the start of therapy and at the second, fourth and sixth months of the therapy. The results of the 24-hour double-probe pH monitoring showed no significant difference between the study and the control groups (p>0.05). In the study group, the MRSI before the therapy was 13.6±4.4. This index improved significantly to 4.3±1.9 at the second month; to 1.5±0.6 at the fourth month, and to 0.5±0.2 at the sixth month of the therapy (p<0.05). The RFS before the start of the therapy was 14.8±3.8; and it improved significantly to 7.7±3.8 at the second month; to 4.5±2.3 at the fourth month, and to 1.4±0.9 at the sixth month of the therapy (p<0.05). The significant improvement in the MRSI and the RFS during the course of proton pump inhibitor therapy relates the patients’ symptoms and physical findings to LPR. This implies the validity of the method, not only in the treatment of LPR, but in the diagnosis of this disorder, as well. Unfortunately, 24-hour double-probe pH monitoring has failed to differentiate LPR patients from healthy individuals.
Repair of anterior floor of mouth defects by a central or paramedian island tongue flap
Authors: Fischinger Janez , Žargi Miha
Published: May 2003

One method for restoring the anterior floor of mouth defects resulting from T1 and especially T2 cancer excision involves the creation of a myomucosal island flap from the dorsal median portion of the tongue and transferring it as a transit flap to the floor of the mouth.

We are not the first to advocate this method. In this paper we present a previously unreported, slightly modified technique utilizing this tongue flap. The modification consists of a 90° twisting of the flap to achieve a more appropriate adaptation to the defect. In the case ofspreading carcinoma from the floor of the mouth to the central portion of the tongue, a similarparamedian one-sided tongue flap was created instead of a central island tongue flap. Our present experience consists of a small series of 12 patients. The procedures were successful in all patients. No remarkable disturbances of speech or deglutition were observed in any of the patients. There were two complications: one haematoma and one partial necrosis of the tip of the tongue. In our opinion, the reconstruction of the anterior floor of mouth defects using a central island tongue flap has not gained the popularity it deserves.
Bilateral sudden sensorineural hearing loss caused by Charcot-Marie-Tooth disease
Authors: Papadakis Chariton E. , Hajiioannou Jiannis K. , Kyrmizakis Dionysios E. , Bizakis John G.
Published: May 2003

Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy (HMSN) is a relatively common neurological syndrome, which has seldom been associated with hearing dysfunction, particularly sudden sensorineural hearing loss (SNHL). Families with autosomal dominant, autosomal recessive and X-linked forms of inheritance have been described.

Sudden sensorineural hearing loss is a frustrating and frightening condition, especially if the hearing loss is bilateral. Regarding the site of the lesion, the evidence from the literature on HMSN suggests that either the VIIIth nerve or central auditory pathways are primarily involved in patients with hearing loss.

We report the first case in the English literature of a patient with Charcot-Marie-Tooth type II disease presenting bilateral SNHL in the course of his disease. The patient was hospitalized for 15 days, and undergoing treatment without any audiological improvement. Detailed clinical, audiological and laboratory examination was performed.

The aetiology and prognostic indicators of bilateral SNHL are discussed, as well as, the incidence of hearing loss in CMT patients.
Focal mucinosis: clinical and histological features of an unusual condition
Authors: McDermott Ann-Louise , Biswas Chandrani , Morgan Kate , Kay Nicholas J.
Published: May 2003

Mucinoses constitute a diverse group of disorders that have in common the deposition of basophilic, finely granular and stringy material in the connective tissues of the dermis (known as dermal mucinoses); this also can occur in the hair follicles (follicular mucinoses) and finally in the epidermis (epithelial mucinoses). We present the clinical and histological findings of a case of focal mucinosis in a 76-year-old man who was otherwise fit and healthy. A literature review revealed a sparse number of such cases none of which was reported in the ENT literature. Focal cutaneous mucinosis is a benign condition but the authors believe it isof local and systemic interest to the Otolaryngologist as an addition to his or her armentariumof diagnoses.
Measurement of Trailing EDGE Noise Using Directional Array and Coherent Output Power Methods
Authors: Hutcheson Florence V. , Brooks Thomas F.
Published: May 2003

The use of a directional array of microphones for the measurement of trailing edge (TE) noise is described. The capabilities of this method are evaluated via measurements of TE noise from a NACA 63-215 airfoil model and from a cylindrical rod. This TE noise measurement approach is compared to one that is based on the cross spectral analysis of output signals from a pair of microphones (COP method). Advantages and limitations of both methods are examined. It is shown that the microphone array can accurately measures TE noise and captures its two-dimensional characteristic over a large frequency range for any TE configuration as long as noise contamination from extraneous sources is within bounds. The COP method is shown to also accurately measure TE noise but over a more limited frequency range that narrows for increased TE thickness. Finally, the applicability and generality of an airfoil self-noise prediction method was evaluated via comparison to the experimental data obtained using the COP and array measurement methods. The predicted and experimental results are shown to agree over large frequency ranges.
Sound Sources of Screech Tone Radiated from Circular Supersonic Jet Oscillating in the Helical Mode
Authors: Umeda Yoshikuni , Ishii Ryuji
Published: May 2003

The generation mechanism of the screech tone in the helical oscillation mode is investigated using a series of instantaneous schlieren photographs. From the photographs, six evanescent sound sources are observed as prominent points along the jet axis. These sound sources move along circular orbits in the planes perpendicular to the jet axis and just downstream of the rear edges of each shock cell. The speed of moving sound sources is supersonic and the moving Mach cones generated behind the moving sound sources form the helical-shaped wave front of the screech tone. Existence of the moving Mach cones about the jet axis was confirmed by comparing schlieren photographs and drawings of the envelopes of the moving Mach cones. The helical vortical structure appears to overlap on the envelopes of the moving Mach cones.
Oscillation of Impinging Jet with Generation of Acoustic Waves
Authors: Sakakibara Y. , Iwamoto J.
Published: May 2003

This paper presents an oscillatory phenomenon of the underexpanded jet which issues from a convergent nozzle and impinges on a flat plate perpendicularly. As the characteristics of the generating noise deeply depend on the oscillation of the impinging jet, the flow field is visualized using the shadowgraph method and the pressure on the plate is measured to classify the oscillation modes for different parameters such as the nozzle pressure ratio and the distance between the nozzle and the plate. For the comparison, the jet is numerically simulated using Total Variation Diminishing (TVD) scheme under the assumption of the non-viscous flow. Simulating the impinging main jet and the radial wall jet on the plate separately, the sound waves propagating around the jet are shown and the frequency of the oscillation for each jet is tested. The wall-jet oscillation which is caused by the small vortices from the main jet occurs at high frequency when the nozzle-plate distance is comparatively small, while the main-jet oscillation induced by the grown vortices are shown to generate at large nozzle-plate spacing and the frequencies under such condition have well-known saw-tooth characteristics. With the correlation of pressure on the plate, three types of the oscillation – axisymmetric mode, whirling mode and non-regular pattern – are shown.
Safety and Pharmacokinetics of an Endotoxin-Binding Phospholipid Emulsion
Authors: Gordon Bruce R , Parker Thomas S , Levine Daniel M , Saal Stuart D , Hudgins Lisa Cooper , Sloan Betty-Jane , Chu Cindy , Stenzel Kurt H , Rubin Albert L
Published: May 2003

BACKGROUND:

Lipids and lipoproteins have been shown to bind and neutralize endotoxin and to improve outcomes in animal models of sepsis.

OBJECTIVE:

To provide safety and pharmacokinetic data for a protein-free, phospholipid-rich emulsion developed as an agent to neutralize endotoxin, and to study the changes in lipids and lipoproteins following emulsion administration.

METHODS:

Thirty healthy male volunteers (aged 18–45 y) were given an emulsion containing 92.5% soy phospholipid, 7.5% soy triglyceride, and 18 mM sodium cholate using a double-blind, placebo-controlled crossover protocol. Emulsion at 3 escalating doses (75, 150, 300 mg/kg) based on phospholipid content was administered by intravenous infusion over 2 hours in the low- and mid-dose groups and 6 hours in the high-dose group.

RESULTS:

All subjects completed the protocol without significant toxicities. A slight dose-dependent increase in indirect bilirubin at the 24-hour time point was observed in the emulsion treatment period, with a maximum difference between placebo and emulsion of 0.9 mg/dL. Mean ± SD peak phospholipid levels were 316 ± 30, 533 ± 53, and 709 ± 86 mg/dL, and phospholipid half-lives were 5.4 ± 0.6, 5.4 ± 0.5, and 8.0 ± 0.8 hours for the low, mid, and high doses, respectively. Increases in total cholesterol, low-density lipoprotein cholesterol and apolipoprotein A-I and B levels were observed. High-density lipoprotein cholesterol decreased immediately following emulsion infusion, but rebounded to above placebo levels by 24 hours.

CONCLUSIONS:

A unique phospholipid-rich emulsion was shown to have a favorable safety profile and to expand the blood lipid and lipoprotein pool without the use of human-derived blood products. Lipid levels expected to protect against the physiologic effects of bacterial endotoxin were achieved.
Argatroban Dosing in Patients with Heparin-Induced Thrombocytopenia
Authors: Verme-Gibboney Catherine N , Hursting Marcie J
Published: May 2003

OBJECTIVE:

To retrospectively evaluate clinical experiences with argatroban dosing, particularly incremental dosage adjustments, during a clinical trial of argatroban anticoagulation in heparin-induced thrombocytopenia (HIT).

METHODS:

Records of 304 patients with HIT administered argatroban during a prospective study were reviewed to determine each dose, incremental dosage adjustment, and duration of therapy. Dosing information (stratified by patient initial dose) and incremental adjustments (overall, and stratified by dose from which adjustment occurred) were summarized. The relationship between median incremental adjustments and adverse outcomes, including bleeding, was investigated.

RESULTS:

Two hundred seventy-one (89%) patients received initial doses of 1.9–2.1 μg/kg/min (group B). Twenty-six (9%) patients were started at a lower dose. Group B's median (5–95th percentile) final dose was 1.6 (0.25–4.0) μg/kg/min. During a median of 6 days of argatroban therapy, patients underwent a median of 3.0 dosage adjustments using a median and mode incremental adjustment of 0.5 μg/kg/min (5–95th percentile, 0.1–2.0 μg/kg/min). Fifty-two (17%) patients required no dosage adjustment. Incremental adjustments decreased with decreasing current dose (e.g., median 0.25 μg/kg/min from doses of 0.26–0.75 μg/kg/min). Outcomes were similar between patients with no adjustment or with median incremental adjustments of ≤0.4, 0.41–0.75, or >0.75 μg/kg/min.

CONCLUSIONS:

Based on this clinical experience, together with the established linear pharmacokinetics and pharmacodynamics of argatroban, appropriate dosage increments may be proposed for argatroban-treated patients with HIT. Incremental adjustments of 0.5 μg/kg/min are reasonable for most patients. Smaller adjustments (e.g., 0.25 μg/kg/min) should be used when modifying lower doses, such as those recommended for use in hepatically impaired patients.