bluuebunny/crossref_metadata_2025 huggingface dataset:
Results of an experimental programme of
in situ
permeability testing in rock
Authors: Wild J.L. , Money M.S.
Published: August 2007

In an earlier pilot programme of tests in shallow drillholes (Pearson & Money, Quarterly Journal of Engineering Geology, 1977) it was shown that significant improvements could be made at low cost to packer testing in rock, which lead to greater reliability in test performance and interpretation. It was also demonstrated that non-equilibrium flow occurred in some tests which, if not recognised, could lead to anomalies in test results.

A second programme of tests has been completed under commercial conditions using significantly deeper arrays of 76 mm drillholes in two rock masses, one in the Old Red Sandstone, and the other a set of basalt flows. Single packer tests were carried out as drilling proceeded using a standard mechanically-expanded packer with continuous autographic recording of flows and of input pressures. Some of the holes were also tested after drilling with a prototype double packer system instrumented with transducers to measure pressure within, above and below the test section. Results of the two methods are compared and individual test behaviour has been examined and it has been found that results were affected by changes in groundwater level produced by drilling. In any test it is unwise to assume that the effective piezometric level in the rock mass at the time and position of a test is necessarily the same as that observed in a completed drillhole.

The tests have produced further practical evidence of the need to consider the scale of tests and observations in relation to the inhomogeneity of the rock mass under investigation. At these test sites there were marked variations in standing water levels, and in measured permeabilities in adjacent closely spaced drillholes.
Groundwater modelling by microcomputer: applications to dam and reservoir slope stability
Authors: Bromhead E. N. , Havouzari A. L. , Brice M. , Rofe B. H.
Published: August 2007

The paper describes the use of computer seepage modelling in three earth dams. In the first case, it is used principally as a design tool; in the second, as an aid to interpreting site investigation data and observations; in the third to investigate the effect of reservoir raising on downstream valley side slopes.

Comments are made on the use of the techniques in practice, and typical results are given.
Predicting piezometric levels in steep slopes
Authors: Lerner D.N.
Published: August 2007

Three methods of predicting piezometric levels in steep slopes are presented and illustrated for a case history in Hong Kong. Statistical correlation of levels with various measures of rainfall showed some promise as a method, but poor choice of an objective function biased the models away from the events of most importance. A groundwater flow model of a cross section through the slopes had too coarse a discretization to be accurate enough, but helped develop an understanding of the slopes' hydrogeology. Empirical methods based on classifying piezometers and extrapolating and regionalising storm and seasonal responses were finally adopted.
Geophysical prediction of fluid flow in sediments
Authors: Lovell M.A.
Published: August 2007

The remote assessment of fluid flow by geophysical means relies largely on empirical formulae relating particular geophysical measurements to the permeability for a specific geological situation. This approach has been proved successful by other workers in the field for delineating and quantifying the nature of aquifers. Recently, however, the proposals to store radioactive waste in deep-sea sediments, together with the increasing interest in hydrocarbon formation processes and basin development, have provided further impetus to the study of geophysical-permeability interactions.

A series of laboratory experiments involving a wide range of natural and artificial sediments has enabled the relationships between the geophysical characteristics and the fluid flow to be investigated. The results show very clearly the interrelationship between permeability and the geophysical parameters, electrical resistivity and compressional wave velocity, and the capability of predicting the one by measuring the other. In particular, extensive measurements of electrical formation factor and permeability in clean sands show the dominance of particle shape, and hence pore shape, in defining the interaction of these energy transfer processes.

In defining a dependence on pore shape the variation of the results effectively identifies differences in the structure of the sediments and hence different distributions of pore geometry. This may in turn be related to depositional environments, and, in extending the results to sedimentary rocks, to the diagenetic and lithification processes involved. Each of these fabrics, however, tends to be anisotropic, and this is borne out by the geophysical measurements. Since the geophysical characteristics are closely linked with permeability then it follows that permeability anisotropy may be reasonably expected also. While this directional dependence may be minimal in surficial marine sediments, it may be considerable at depth in the sediment column, particularly as consolidation progresses. The identification and measurement of anisotropy should help in defining geophysical-fluid flow relationships, especially for fluid flow predictions by remote measurements.
Monitoring and investigation of water inflow into a coal mine in New South Wales, Australia
Authors: Whitfield L.M.
Published: August 2007

The Dams Safety Committee is responsible for ensuring the safety and integrity of all substantial dams and storages in New South Wales. Coal mining is currently taking place beneath the Sydney Water Board catchment where a system of five reservoirs constitute part of the urban water supply for the cities of Sydney and Wollongong.

Pillar extraction of the Wongawilli seam adjacent to Avon storage resulted in an unexpected inflow of water into the mine workings. Algal analysis indicated that a proportion of this inflow may have originated from a surface source.

The paper outlines the events which occurred, the monitoring initiated and the results of the investigations.
Control of groundwater by exclusion
Authors: Bell F.G. , Mitchell J.K.
Published: August 2007

The movement of water into an excavation can be impeded by placing a barrier around the excavation. Such excavation barriers include sheet piling, contiguous bored pile walls, slurry trenches, diaphragm walls, grout curtains and panels, and ice walls. Ideally an exclusion barrier should extend into an impermeable stratum. If this does not happen, then upward seepage of water into the excavation may occur which, in turn, may give rise to instability at excavation level. To prevent such instability, the exclusion barrier should be extended horizontally. Of the exclusion techniques mentioned, only grouting and freezing can be used to form a horizontal exclusion barrier.
Groundwater control by groundwater lowering
Authors: Bell F.G. , Cashman P.M.
Published: August 2007

When an excavation is to extend beneath the water table the ground conditions may be improved by lowering the level of the water table beneath the proposed base of the excavation. Groundwater lowering is accomplished by removing water from the ground at a faster rate than recharge can occur. The most appropriate type of system of groundwater lowering depends mainly upon the soil conditions present at the site but the size of the excavation, the amount by which the water table has to be lowered and the length of time during which the excavation has to be maintained in a stable and workable condition also have to be taken into account. Settlement may occur as a result of groundwater lowering. If a site is surrounded by buildings then measures should be taken to prevent settlement taking place.
Groundwater control for a major urban redevelopment project with potential settlement problems and unusual contractual arrangements
Authors: Firth U.R. , Hartwell D.J.
Published: August 2007

A dewatering scheme was required to enable the construction of foundations for a large redevelopment complex close the the town centre at Redhill, Surrey. The drawdown beneath nearby buildings had to be limited due to the poor condition of some of the buildings; in many cases, foundation details were also unavailable. A wellpoint scheme composed of various lines was built up and commissioned progressively to allow a flexible approach to the dewatering. Piezometers were installed inside and outside the site so that the drawdown could be monitored and adjustments to the dewatering system made accordingly. In critical areas, investigation boreholes sunk during construction were completed as monitoring points which could also be used as recharge wells if necessary. A thorough dilapidation survey of existing buildings was carried out before dewatering commenced, and the buildings were surveyed at regular intervals during the work to check for settlement or structural distress.
The investigation and control of groundwater at Ysbytty Reservoir, Gwynedd
Authors: Oulton H. A. , Crowther J. , Oldham P.H.
Published: August 2007

During early site investigations for an underground water storage reservoir at Ysbytty near Caernarfon-North Wales groundwater under artesian conditions was encountered.

A subsequent investigation, including pumping trials from two large diameter boreholes, was conducted in order to establish the feasibility of reducing the artesian pressures during and after construction. The parameters thus defined enabled a scheme to be devised for dealing with groundwater during construction, utilising the wells installed during the investigation, and for the detailed design of an under-floor drainage system as part of the permanent works.

A further problem concerned the effects of prolonged draw-down of the water table below the adjacent clay-lined open service reservoir. Recharge wells were installed to maintain the water table and groundwater levels in the immediate vicinity were monitored throughout construction.

The under-floor drainage system for the new reservoir was designed and installed, incorporating porous pipes in a stone filter layer. Its function is to prevent uplift of the reservoir under all working conditions; a gravity outlet drain eliminated the need for permanent pumping.
Groundwater control by drainage gallery at Aberfan, South Wales
Authors: Siddle H.J.
Published: August 2007

The Aberfan (Merthyr Vale) tip, which failed with disastrous consequences in 1966 (HMSO, 1969), was constructed above rocks subjected to artesian pressures. Two-thirds of the tip were removed after the failure and sub-surface drainage measures have been installed to secure the remainder. These include a drainage gallery, the construction and performance of which are the subject of this paper. The ‘factor of safety’ of a critical slope of the tip has been improved to an acceptable value by a reduction in the artesian pressures within the rock. Investigations before and during construction indicate that water moves towards the seat of the 1966 failure in a 20 m wide flexure in the rock adjacent to a hitherto unrecorded minor fault. It appears that tensional strains created by past mining have been concentrated within this structure the existence of which must be added to the other previously established factors which contributed to the failure. The profound anisotropy within the aquifer caused by this geological structure and mining history is demonstrated by the fact that an estimated 25% of the water entering the potential groundwater catchment is released from a length of aquifer equivalent to less than 1% of the available spring line.
Contractual arrangements for geotechnical work
Authors: Uff Q.C. J.
Published: August 2007

The question of appropriate forms of contract for geotechnical processes has received little attention. Such contracts may involve quite unacceptable levels of risk to employers. It is in the interest of all parties that proper contractual terms are set down so that risks and responsibilities may be appreciated.
Engineering contracts: a legal point of view
Authors: Ludlow M.R.
Published: August 2007

As I am not even a trainee geologist, it seems appropriate to begin this paper defensively with a Biblical quotation:

'So likewise ye, except ye utter by the tongue words easy to be understood, how shall it be known what is spoken? For ye shall speak into the air.

There are, it may be, so many kinds of voices in the world, and none of them is without signification.

But if I know not the meaning of the voice, I shall be unto him that speaketh a barbarian, and he that speaketh shall be a barbarian unto me.'

Despite the illustrations of engineering failures provided by Professor Hanna this quotation, which comes from 1 Corinthians, Ch. 14, v. 9-11, is not intended as the beginning of a sermon.

Unlike the distinguished speaker (Dr J. Uff) who preceded me, I have no engineering qualification of any kind, and in some ways it is important to my job as a solicitor advising on engineering contracts generally that this should be the case. The solicitor enters into the field of engineering contracts at one of two possible stages, in both of which he has to do his best to translate the technical into the simple for others who may have even less expertise. The first stage is at the point where different disciplines within the engineering industry enter into contractual arrangements with each other relating to the design and construction of the different parts of an engineering project which go together to make
Microarrays for Rapid Identification of Plant Viruses
Authors: Boonham Neil , Tomlinson Jenny , Mumford Rick
Published: August 2007

Many factors affect the development and application of diagnostic techniques. Plant viruses are an inherently diverse group that, unlike cellular pathogens, possess no nucleotide sequence type (e.g., ribosomal RNA sequences) in common. Detection of plant viruses is becoming more challenging as globalization of trade, particularly in ornamentals, and the potential effects of climate change enhance the movement of viruses and their vectors, transforming the diagnostic landscape. Techniques for assessing seed, other propagation materials and field samples for the presence of specific viruses include biological indexing, electron microscopy, antibody-based detection, including enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and microarray detection. Of these, microarray detection provides the greatest capability for parallel yet specific testing, and can be used to detect individual, or combinations of viruses and, using current approaches, to do so with a sensitivity comparable to ELISA. Methods based on PCR provide the greatest sensitivity among the listed techniques but are limited in parallel detection capability even in “multiplexed” applications. Various aspects of microarray technology, including probe development, array fabrication, assay target preparation, hybridization, washing, scanning, and interpretation are presented and discussed, for both current and developing technology.
An overlapping binding site in the CYP7A1 promoter allows activation of FXR to override the stimulation by LXRα
Authors: Shang Quan , Pan Luxing , Saumoy Monica , Chiang John Y. L. , Tint G. Stephen , Salen Gerald , Xu Guorong
Published: August 2007

The aim of this study was to explore why in rabbits activation of farnesoid X receptor (FXR) is dominant over activated liver X receptor-α (LXRα) in the regulation of CYP7A1. We cloned the rabbit CYP7A1 promoter and found a fetoprotein transcription factor (FTF) binding element embedded within the LXRα binding site (LXRE). Gel shift assays demonstrated that FTF competes with LXRα for binding to LXRE. Short heterodimer partner (SHP) enhances the competitive ability of FTF. Studies in HepG2 cells showed that SHP combined with FTF had more powerful effect to offset the stimulation of CYP7A1 by LXRα. Gel shift and chromatin immunoprecipitation assays demonstrated that SHP with FTF diminished LXRα binding to the CYP7A1 promoter. In vivo studies in rabbits fed cholesterol for 10 days showed that hepatic expression of SHP but not FTF rose and LXRα-bound LXRE decreased. We propose that the SHP/FTF heterodimer occupies LXRE via the embedded FTF binding element and blocks LXRα from recruiting to LXRE. Therefore, activation of FXR, which upregulates SHP expression, will eliminate the stimulatory effect of LXRα on the CYP7A1 promoter because increased levels of SHP combined with FTF diminish the recruitment of LXRα to CYP7A1 promoter.
Differential regulation of cholera toxin-inhibited Na-H exchange isoforms by butyrate in rat ileum
Authors: Subramanya Sandeep B. , Rajendran Vazhaikkurichi M. , Srinivasan Pugazhendhi , Nanda Kumar Navalpur S. , Ramakrishna Balakrishnan S. , Binder Henry J.
Published: August 2007

Electroneutral Na absorption occurs in the intestine via sodium-hydrogen exchanger (NHE) isoforms NHE2 and NHE3. Bicarbonate and butyrate both stimulate electroneutral Na absorption through NHE. Bicarbonate- but not butyrate-dependent Na absorption is inhibited by cholera toxin (CT). Long-term exposure to butyrate also influences expression of apical membrane proteins in epithelial cells. These studies investigated the effects of short- and long-term in vivo exposure to butyrate on apical membrane NHE and mRNA, protein expression, and activity in rat ileal epithelium that had been exposed to CT. Ileal loops were exposed to CT in vivo for 5 h and apical membrane vesicles were isolated.22Na uptake was measured by using the inhibitor HOE694 to identify NHE2 and NHE3 activity, and Western blot analyses were performed. CT reduced total NHE activity by 70% in apical membrane vesicles with inhibition of both NHE2 and NHE3. Reduced NHE3 activity and protein expression remained low following removal of CT but increased to control values following incubation of the ileal loop with butyrate for 2 h. In parallel there was a 40% decrease in CT-induced increase in cAMP content. In contrast, NHE2 activity partially increased following removal of CT and was further increased to control levels by butyrate. NHE2 protein expression did not parallel its activity. Neither NHE2 nor NHE3 mRNA content were affected by CT or butyrate. These results indicate that CT has varying effects on the two apical NHE isoforms, inhibiting NHE2 activity without altering its protein expression and reducing both NHE3 activity and protein expression. Butyrate restores both CT-inhibited NHE2 and NHE3 activities to normal levels but via different mechanisms.
Age-related resistance to skeletal muscle fatigue is preserved during ischemia
Authors: Chung Linda H. , Callahan Damien M. , Kent-Braun Jane A.
Published: August 2007

During voluntary contractions, the skeletal muscle of healthy older adults often fatigues less than that of young adults, a result that has been explained by relatively greater reliance on muscle oxidative metabolism in the elderly. Our aim was to investigate whether this age-related fatigue resistance was eliminated when oxidative metabolism was minimized via ischemia induced by cuff (220 mmHg). We hypothesized that 1) older men ( n = 12) would fatigue less than young men ( n = 12) during free-flow (FF) contractions; 2) both groups would fatigue similarly during ischemia; and 3) reperfusion would reestablish the fatigue resistance of the old. Subjects performed 6 min of intermittent, maximal voluntary isometric contractions of the ankle dorsiflexors under FF and ischemia-reperfusion (IR) conditions. Ischemia was maintained for the first 3 min of contractions, followed by rapid cuff deflation and reperfusion for 3 additional minutes of contractions. Central activation, peripheral activation, and muscle contractile properties were measured at 3 and 6 min of contractions. Older men fatigued less than young men during FF ( P ≤ 0.02), ischemia ( P < 0.001), and reperfusion ( P < 0.001). During FF, activation and contractile properties changed similarly across age groups. At the end of ischemia, central ( P = 0.02) and peripheral ( P ≤ 0.03) activation declined more in the young, with no effect of age on the changes in contractile properties. Thus age-related fatigue resistance was evident during FF and IR, indicating that differences in blood flow and oxidative metabolism do not explain the fatigue resistance of old age.
Age-related neuromuscular function during drop jumps
Authors: Hoffrén M. , Ishikawa M. , Komi P. V.
Published: August 2007

Muscle- and movement-specific fascicle-tendon interaction affects the performance of the neuromuscular system. This interaction is unknown among elderly and consequently contributes to the lack of understanding the age-related problems on neuromuscular control. The present experiment studied the age specificity of fascicle-tendon interaction of the gastrocnemius medialis (GM) muscle in drop jump (DJ) exercises. Twelve young and thirteen elderly subjects performed maximal squat jumps and DJs with maximal rebound effort on a sledge apparatus. Ankle and knee joint angles, reaction force, and electromyography (EMG) from the soleus (Sol), GM, and tibialis anterior (TA) muscles were measured together with the GM fascicle length by ultrasonography. The results showed that the measured ankle joint stiffness (AJS) during the braking phase correlated positively with the rebound speed in both age groups and that both parameters were significantly lower in the elderly than in young subjects. In both groups, the AJS correlated positively with averaged EMG (aEMG) in Sol during the braking phase and was further associated with GM activation ( r = 0.55, P < 0.01) and TA coactivation (TA/GM r = −0.4 P < 0.05) in the elderly subjects. In addition, compared with the young subjects, the elderly subjects showed significantly lower GM aEMG in the braking phase and higher aEMG in the push-off phase, indicating less utilization of tendinous tissue (TT) elasticity. These different activation patterns are in line with the mechanical behavior of GM showing significantly less fascicle shortening and relative TT stretching in the braking phase in the elderly than in the young subjects. These results suggest that age-specific muscle activation patterns as well as mechanical behaviors exist during DJs.
Risk Factors of Intracranial Cerebral Atherosclerosis among Asymptomatics
Authors: Bae Hee-Joon , Lee Juneyoung , Park Jong-Moo , Kwon Ohyun , Koo Ja-Seong , Kim Byung-Kun , Pandey Dilip K.
Published: August 2007

Background: Little information is available regarding the risk factors for intracranial cerebral atherosclerosis (ICAS), particularly among asymptomatics. Methods: Data from a consecutive series of 1,208 subjects aged ≧40 years, with no history of stroke, and who had undergone transcranial Doppler ultrasonography (TCD) were collected prospectively. The role of classic risk factors was assessed in the presence and severity of asymptomatic ICAS, which was determined by TCD. Results: Regarding the presence of ICAS, the adjusted odds ratios (95% confidence intervals) were as follows: 1.22 (1.08–1.37) for every 10-year increase in age, 1.44 (1.08–1.91) for hypertension and 1.86 (1.33–2.59) for diabetes mellitus. No significant association was observed with regard to male sex, smoking or hyperlipidemia. Conclusion: The findings suggest that age, hypertension and diabetes mellitus are significant risk factors for ICAS in asymptomatic populations.
Inferior Olivary Hypertrophy Is Associated with a Lower Functional State after Pontine Hemorrhage
Authors: Yagura Hajime , Miyai Ichiro , Hatakenaka Megumi , Yanagihara Takehiko
Published: August 2007

Background: Inferior olivary hypertrophy (IOH) may develop after pontine hemorrhage and may become a pacemaker for symptomatic palatal tremor (SPT). However, there is no information available that elucidates how IOH may affect the functional outcome. The purpose of this study was to investigate how frequently IOH was associated with clinical manifestations of involuntary movements, including ocular myoclonus (OM) and SPT, and whether IOH influenced the functional outcome after pontine hemorrhage. Methods: In 20 consecutive patients undergoing inpatient multidisciplinary rehabilitation after pontine hemorrhage, the location of lesions (tegmental vs. ventral) and the presence of IOH were examined by magnetic resonance imaging, and the functional outcome was assessed by means of Fugl-Meyer scale for neurological impairment and Functional Independence Measure for disability on admission and discharge. Results: In 10 patients, IOH was detected, and the tegmentum was involved in 7 of the 10 patients. OM or SPT was present in 7 of these 10 patients. In the remaining 10 patients, IOH was not detected, and the tegmentum was involved only in 2 of these 10 patients. None of them had OM or SPT. The presence of IOH was associated with a lower functional status on admission and discharge. Conclusion: After pontine hemorrhage, IOH may be associated with tegmental lesions with OM or SPT and may impose a detrimental effect on the functional outcome.
Role of Serotonin Transporter Polymorphisms in the Behavioural and Psychological Symptoms in Probable Alzheimer Disease Patients
Authors: Pritchard Antonia L. , Pritchard Colin W. , Bentham Peter , Lendon Corinne L.
Published: August 2007

Background/Aims: Alzheimer disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. This is an investigation of whether the linked polymorphic region and variable number tandem repeat variants of the serotonin transporter (SERT) are associated with BPSD. Methods: The longitudinal measures of BPSD of our large cohort of 367 AD patients were assessed by the Neuropsychiatric Inventory. Measures with good evidence of serotonergic involvement (delusions, hallucinations, depression, anxiety, agitation/aggression and irritability) were related to genotype and allele frequencies of the linked polymorphic region and variable number tandem repeat variants. Results: Analysis revealed significant relationships between the linked polymorphic region variant long allele with irritability and the variable number tandem repeat 10-repeat allele with psychosis, but no associations were found with depression, anxiety or agitation/aggression. Conclusion: Our data and review of previous studies suggest SERT could play a minor role in development of psychosis and aggressive/irritable tendencies; however, further investigations are required in large, well-characterized cohorts.
Total Tau Protein in Cerebrospinal Fluid and Diffusion-Weighted MRI as an Early Diagnostic Marker for Creutzfeldt-Jakob Disease
Authors: Satoh Katsuya , Shirabe Susumu , Tsujino Akira , Eguchi Hiroto , Motomura Masakatsu , Honda Hiroyuki , Tomita Iturou , Satoh Akira , Tsujihata Mitsuhiro , Matsuo Hidenori , Nakagawa Masanori , Eguchi Katsumi
Published: August 2007

Background: We have recently begun to doubt the effectiveness of periodic sharp wave complexes observed on electroencephalographs and the detection of 14-3-3 protein in cerebrospinal fluid (CSF) as diagnostic criteria for Creutzfeldt-Jakob disease (CJD). Diffusion-weighted magnetic resonance imaging (DWI) and the detection of total tau (t-tau) protein in CSF may be more sensitive diagnostic criteria. Methods: Among 44 CJD patients, we selected 21 subjects that suffered from early-stage CJD, which was defined as cases in the 6 weeks following the onset of the disease. The sensitivities of DWI and electroencephalographs, as well as those of t-tau protein, 14-3-3 protein, neuron-specific enolase (NSE), and S-100b protein in CSF were compared as diagnostic markers for early-stage CJD. Results: NSE, S-100b protein, t-tau protein, and 14-3-3 protein were detected in the samples from 57.1, 4.8, 95.2, and 76.2% of the 21 early-stage CJD patients, respectively. Additionally, DWI was used to positively identify 90.5% of these cases. Conclusion: We concluded that t-tau protein was the most sensitive of the diagnostic markers for CJD. Moreover, the data in this study showed that detection of t-tau protein combined with DWI identified 98% of the early-stage cases, and these tests should be included as diagnostic criteria for CJD.
Symptoms of Anxiety and Depression in the Course of Cognitive Decline
Authors: Bierman E.J.M. , Comijs H.C. , Jonker C. , Beekman A.T.F.
Published: August 2007

Background/Aims: Anxiety and depression are common inpatients with cognitive decline and Alzheimer’s disease (AD), and recognition and treatment of these symptoms can improve their quality of life. The present study investigates anxiety and depression in different phases of cognitive decline. Methods: The sample consisted of five groups of elderly people in different phases of cognitive decline; four from a community-based sample (Longitudinal Aging Study Amsterdam), and one group of elderly people diagnosed with AD. ANOVAs were performed to investigate group differences in the severity and prevalence of anxiety and depression, and comorbid anxiety and depressive symptoms. Results: The prevalence rates of anxiety, comorbid anxiety and depressive symptoms and depressive symptoms follow a pattern of an increasing prevalence as cognitive performance declines and a decrease in the prevalence when cognitive functioning is severely impaired. AD patients report fewest anxiety symptoms. Conclusion: We found that the prevalence of anxiety symptoms, depressive symptoms and comorbid anxiety and depressive symptoms seems to increase in the early phase of cognitive decline, and decreases as cognitive functioning further declines. Elderly diagnosed with AD report less anxiety as expected, probably due to lack of insight caused by AD.
Validity of Dementia Diagnoses in the Danish Hospital Registers
Authors: Phung Thien Kieu Thi , Andersen Birgitte Bo , Høgh Peter , Kessing Lars Vedel , Mortensen Preben Bo , Waldemar Gunhild
Published: August 2007

Background:The validity of dementia diagnoses in the Danish nationwide hospital registers was evaluated to determine the value of these registers in epidemiological research about dementia. Methods: Two hundred patients were randomly selected from 4,682 patients registered for the first time with a dementia diagnosis in the last 6 months of 2003. The patients’ medical journals were reviewed to evaluate if they fulfilled ICD-10 and/or DSM-IV criteria for dementia and specific dementia subtypes. The patients who were still alive in 2006 were invited to an interview. Results: One hundred and ninety-seven journals were available for review and 51 patients were interviewed. A registered diagnosis of dementia was found to be correct in 169 (85.8%) cases. Regarding dementia subtypes, the degree of agreement between the registers and the results of the validating process was low with a kappa of 0.36 (95% CI 0.24–0.48). Conclusion: The validity of dementia syndrome in the Danish hospital registers was high and allows for epidemiological studies about dementia. Alzheimer’s disease, although underregistered, also had a good validity once the diagnosis was registered. In general, other ICD-10 dementia subtypes in the registers had a low validity and are less suitable for epidemiological research.
Incidence and Outcome of Traumatic Brain Injury in an Urban Area in Western Europe over 10 Years
Authors: Maegele M. , Engel D. , Bouillon B. , Lefering R. , Fach H. , Raum M. , Buchheister B. , Schaefer U. , Klug N. , Neugebauer E.
Published: August 2007

Introduction: Valid epidemiological data on incidence and outcome of traumatic brain injury (TBI) show great variability. A study on incidence, severity and outcome of TBI was conducted in an urban area of one million inhabitants. Materials and Methods: 130,000 prehospital emergencies were screened for TBI. Inclusion criteria: Glasgow Coma Scale (GCS) score ≤8 and/or Abbreviated Injury Scale for head injuries (AIShead) score ≧2 with confirmed TBI via appropriate diagnostics. Results: Annual incidence was 7.3/100,000. Overall mortality rate was 45.8%: 182 (28%) were prehospital deaths, 116 (17.8%) patients died in hospital. Two hundred and fourteen of 352 (60.8%) surviving patients were sufficiently rehabilitated at discharge [Glasgow Outcome Scale (GOS) score = 1], but 138 patients (39.2%) survived with persisting deficits. GOS was associated with initial GCS and AIShead. Conclusion: The incidence of TBI was lower compared to the literature. The overall mortality was high, especially prehospital and early in-hospital mortality rates.
Three Different Bradycardic Agents, Zatebradine, Diltiazem and Propranolol, Distinctly Modify Heart Rate Variability and QT-Interval Variability
Authors: Yamabe Motoko , Sanyal Shamarendra N. , Miyamoto Shinji , Hadama Tetsuo , Isomoto Shojirou , Ono Katsushige
Published: August 2007

Zatebradine, diltiazem and propranolol are all antiarrhythmic agents, and all induce bradycardia, but each is known to have a different initial molecular mechanism: zatebradine is a channel blocker of the hyperpolarization-activated inward current (If ); diltiazem is a blocker of the L-type Ca2+ channel (ICaL), and propranolol is a β-blocker. To further investigate the mechanisms underlying their clinical effects, we studied their effects on heart rate variability (HRV) and QT-interval variability (QTV). To this end, guinea pigs were treated with either zatebradine (1.5 mg/kg, i.p.), diltiazem (40 mg/kg, i.p.) or propranolol (20 mg/kg, i.p.). A dose of each agent that decreased HR by 20–22% was used in this study. HRV and QTV were analyzed by a fast Fourier and/or a wavelet transform algorithm. Zatebradine, an If channel blocker, had no significant effect on HRV and QTV. Diltiazem, a non-dihydropyridine ICaL blocker, increased high frequency (HF) power and decreased the power ratio of the low frequency (LF) range to the HF range (L/H) in HRV, and increased QTV. Propranolol, a non-selective β-antagonist, decreased LF power and L/H ratios in HRV, and appreciably reduced QTV. These differences in pharmacological action may help us better understand the antiarrhythmic and/or proarrhythmic actions of these agents when they are used clinically for reducing HR.
Prognoses and Prognostic Factors of Carcinosarcoma, Endometrial Stromal Sarcoma and Uterine Leiomyosarcoma: A Comparison with Uterine Endometrial Adenocarcinoma
Authors: Akahira Jun-ichi , Tokunaga Hideki , Toyoshima Masafumi , Takano Tadao , Nagase Satoru , Yoshinaga Kosuke , Tase Toru , Wada Yuichi , Ito Kiyoshi , Niikura Hitoshi , Yamada Hidekazu , Sato Akira , Sasano Hironobu , Yaegashi Nobuo
Published: August 2007

Aims: The aims of this study were to evaluate the factors affecting prognosis in patients with uterine sarcomas and to demonstrate that carcinosarcoma bears a similarity to high-grade endometrial carcinoma in terms of its prognosis and clinicopathological parameters. Methods: In June 2004, 17 Japanese institutions received questionnaires regarding uterine sarcomas. Study patients had uterine sarcomas initially treated at each institution between January 1990 and May 2004. Survival analyses and comparisons were performed by univariate methods. Patient data of 921 cases of endometrial adenocarcinoma were also analyzed and compared to the data with the uterine sarcomas. Results: One hundred twenty-one patients with uterine sarcomas were identified who met study eligibility criteria. In uterine sarcomas, carcinosarcoma had a worse prognosis than other sarcomas, but the difference was not significant (p = 0.302). In carcinosarcoma, significant differences were observed with age (p = 0.0388), stage (p < 0.01) and surgical procedure (with or without pelvic lymphadenectomy, p = 0.0316). In carcinosarcoma and G3 adenocarcinoma, no significant difference was identified with regard to overall survival in univariate (p = 0.191) and multivariate (p = 0.168) analyses. Conclusion: Our results demonstrate that the clinical behavior of carcinosarcoma strongly resembles that of G3 endometrial adenocarcinoma, setting it apart from other ‘pure’ uterine sarcomas.
Twist Expression Predicts Poor Clinical Outcome of Patients with Clear Cell Carcinoma of the Ovary
Authors: Kajiyama Hiroaki , Hosono Satoyo , Terauchi Mikio , Shibata Kiyosumi , Ino Kazuhiko , Yamamoto Eiko , Nomura Seiji , Nawa Akihiro , Kikkawa Fumitaka
Published: August 2007

Objectives: Twist is a highly conserved basic helix-loop-helix transcription factor that regulates the expression of E-cadherin and promotes the epithelial-mesenchymal transition, which is critical for tumor infiltration. We examined the distribution and expression of this molecule in clear cell carcinoma of the ovary (CCC) to elucidate their clinical significance. Methods: Paraffin sections from CCC tissues (n = 27) were immunostained with Twist antibody and staining intensities were evaluated. Stratified with various clinicopathological factors, overall survival (OS) and progression-free survival (PFS) were evaluated. Results: In the 27 carcinomas, negative Twist immunoexpression was observed in 14 cases (51.9%), and positive immunoexpression in 13 (48.1%). Twist, when categorized into negative versus positive expression, was associated with FIGO stage and peritoneal cytology. In addition, positive Twist expression significantly predicted a poorer OS and PFS compared with negative expression (p < 0.0001). Furthermore, the multivariate analyses revealed that positive Twist expression was an independent prognostic factor for OS and PFS of patients with CCC in this study (p = 0.0077 and 0.0033, respectively). Conclusion: The current findings suggest that the assessment of Twist immunoreactivity may be a useful prognostic indicator and that Twist may play a critical role in the progression of CCC.
The Synergistic Effect of 5-Aza-2′-Deoxycytidine and 5-Fluorouracil on Drug-Resistant Tumors
Authors: Morita Shinji , Iida Satoru , Kato Keiji , Takagi Yoko , Uetake Hiroyuki , Sugihara Kenichi
Published: August 2007

Purpose: We investigated whether a 5-fluorouracil (5-FU)-resistant tumor could regain chemosensitivity after the administration of 5-aza-2′-deoxycytidine (DAC) as a demethylating agent. Methods: Human colorectal cancer cells (SW48) are characterized by the hypermethylation of proapoptotic genes. They were transplanted into 20 athymic BALB/c nu/nu mice which were randomly placed into 4 groups (1 = control; 2 = 5-FU alone; 3 = DAC alone; 4 = DAC followed by 5-FU). We evaluated the synergistic effect of DAC and 5-FU on the growth of these xenografts. Reactivation of proapoptotic genes in these cells was analyzed by methylation-specific PCR. Gene expression was determined by a quantitative reverse-transcription PCR assay. Results: Compared with the control group, relative tumor volumes were statistically significantly decreased only in group 4 mice (p = 0.006). In groups 3 and 4, p14, p16 and death-associated protein kinase (DAPK) promoter regions were demethylated and p14 gene expression was gradually increased after DAC administration. Conclusion: DAC could be a useful medicine that breaks the silencing of various genes and recovers some expressions. By pretreating with DAC at a nontoxic level, we confirmed the restoration of 5-FU chemosensitivity and apoptosis induction. The combination of demethylating agents and several cytotoxic drugs has potential in clinical practice.
Prognosis of Occult Breast Carcinoma Presenting as Isolated Axillary Nodal Metastasis
Authors: Varadarajan Ramya , Edge Stephen B. , Yu Jihnhee , Watroba Nancy , Janarthanan Bagi R.
Published: August 2007

Axillary metastasis from an occult breast carcinoma is an uncommon presentation and presents a therapeutic dilemma. The objective of this study is to describe the presenting clinical features, management approach and treatment outcomes for occult breast carcinoma. We conducted a retrospective review of patients who presented with axillary nodal metastases from an occult breast carcinoma between 1997 and 2004 at the Roswell Park Cancer Institute; 2,150 patients were diagnosed and treated for breast cancer during this period. After excluding stage I and IV patients, we identified 642 who had disease metastatic to lymph nodes, 10 of these had no primary tumor in the breast despite a thorough evaluation including bilateral mammography and breast ultrasound. Of these, 7 had undergone breast magnetic resonance imaging as well. All patients underwent axillary nodal dissection. The breast was managed with radiotherapy alone in 8 patients, wide local excision with radiation therapy in 1 patient and 1 patient underwent mastectomy. No patient had a recurrence with a median 57 months of follow-up. Breast conservation with radiation therapy alone can be considered as a management option for women with occult breast cancer presenting with axillary nodal metastasis.
Apolipoprotein E Expression in Anaplastic Thyroid Carcinoma
Authors: Ito Yasuhiro , Takano Toru , Miyauchi Akira
Published: August 2007

Objectives: Apolipoprotein E (Apo E) has been known to play a role in cholesterol transport and metabolism. However, recently the relationship between Apo E and carcinoma progression has been investigated. In this study, we investigated Apo E expression in thyroid carcinoma at both the protein and molecular levels. Methods: We investigated Apo E expression at the protein and molecular level in 124 thyroid neoplasms. Results: In RT-PCR and in situ hybridization, the Apo E mRNA expression level was very low in papillary and follicular carcinomas as well as normal thyroid, but was dramatically elevated in anaplastic carcinoma. In an immunohistochemical study, 32 of 33 anaplastic carcinomas (97.0%) showed high levels of Apo E expression, but this phenomenon was seen only in 1 of 51 papillary carcinomas (2.0%). None of the follicular carcinomas or adenomas showed high levels of Apo E expression. Conclusions: These findings suggest that Apo E is one of the typical biological characteristics of anaplastic thyroid carcinoma.
Ubiquitin Carboxyl-Terminal Hydrolase L1, a Novel Deubiquitinating Enzyme in the Vasculature, Attenuates NF-κB Activation
Authors: Takami Yoichi , Nakagami Hironori , Morishita Ryuichi , Katsuya Tomohiro , Cui Tai-Xing , Ichikawa Tomonaga , Saito Yukihiro , Hayashi Hiroki , Kikuchi Yasushi , Nishikawa Tomoyuki , Baba Yoshichika , Yasuda Osamu , Rakugi Hiromi , Ogihara Toshio , Kaneda Yasufumi
Published: August 2007

Objective—

We identified a ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene, which encodes a deubiquitinating enzyme and is expressed in the vasculature, by functional screening of a human endothelial cell (EC) cDNA library. UCHL1 is expressed in neurons, and abnormalities in UCHL1 are responsible for inherited Parkinson’s disease via its effects on the ubiquitin-proteasome system. Therefore, the goal of present study was to clarify the role of the UCHL1 gene in vascular remodeling by evaluating nuclear factor-κB (NF-κB) inactivation in ECs and vascular smooth muscle cells (VSMCs).

Methods and Results—

From Northern blot and immunohistochemical analysis, the UCHL1 gene was endogenously expressed in vascular ECs, VSMCs, and brain tissue. Expression of UCHL1 was markedly increased in the neointima of the balloon-injured carotid artery and was also present in atherosclerotic lesions from human carotid arteries. Overexpression of the UCHL1 gene significantly attenuated tumor necrosis factor (TNF)-α–induced NF-κB activity in vascular cells and increased inhibitor of kappa B-α (IκB-α), possibly through the attenuation of IκB-α ubiquitination, leading to decreased neointima in the balloon-injured artery. In contrast, knockdown of UCHL1 by small interfering RNA resulted in increased NF-κB activity in VSMCs.

Conclusions—

These data suggest that UCHL1 may partially attenuate vascular remodeling through inhibition of NF-κB activity.
Fatty Liver
Authors: Kotronen Anna , Yki-Järvinen Hannele
Published: August 2007

Although the epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, not all obese develop the syndrome and even lean individuals can be insulin resistant. Both lean and obese insulin resistant individuals have an excess of fat in the liver which is not attributable to alcohol or other known causes of liver disease, a condition defined as nonalcoholic fatty liver disease (NAFLD) by gastroenterologists. The fatty liver is insulin resistant. Liver fat is highly significantly and linearly correlated with all components of the metabolic syndrome independent of obesity. Overproduction of glucose, VLDL, CRP, and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease associated with the metabolic syndrome and NAFLD. Both of the latter conditions also increase the risk of type 2 diabetes and advanced liver disease. The reason why some deposit fat in the liver whereas others do not is poorly understood. Individuals with a fatty liver are more likely to have excess intraabdominal fat and inflammatory changes in adipose tissue. Intervention studies have shown that liver fat can be decreased by weight loss, PPARγ agonists, and insulin therapy.
Defective Leptin/Leptin Receptor Signaling Improves Regulatory T Cell Immune Response and Protects Mice From Atherosclerosis
Authors: Taleb Soraya , Herbin Olivier , Ait-Oufella Hafid , Verreth Wim , Gourdy Pierre , Barateau Véronique , Merval Régine , Esposito Bruno , Clément Karine , Holvoet Paul , Tedgui Alain , Mallat Ziad
Published: August 2007

Objective—

Obesity is a major risk factor for atherosclerosis and is associated with increased cardiovascular morbidity and mortality. However, the precise molecular pathways responsible for this close association remain poorly understood.

Methods and Results—

In this study, we report that leptin-deficiency (
ob/ob
) in low-density lipoprotein receptor knockout (
ldlr
−/−
) mice induces an unexpected 2.2- to 6-fold reduction in atherosclerotic lesion development, compared with
ldlr
−/−
mice having similar total cholesterol levels.
Ldlr
−/−
/
ob/ob
mice show reduced T cell helper type 1 (Th1) response, enhanced expression of
Foxp3
, the specification transcription factor of regulatory T (Treg) cells, and improved Treg cell function. Leptin receptor-deficient (
db/db
) mice display marked increase in the number and suppressive function of Treg cells. Supplementation of Treg-deficient lymphocytes with Treg cells from
db/db
mice in an experimental model of atherosclerosis induces a significant reduction of lesion size and a marked inhibition of interferon (INF)-γ production, compared with supplementation by Treg cells from wild-type mice.

Conclusions—

These results identify a critical role for leptin/leptin receptor pathway in the modulation of the regulatory immune response in atherosclerosis, and suggest that alteration in regulatory immunity may predispose obese individuals to atherosclerosis.