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Biomedical subjects

K Bailey

Publications and source records attributed to K Bailey.

At least 19 recordsLinked to original sources

Comparison of extent of tau pathology in patients with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration with Pick bodies and early onset Alzheimer's disease.

In order to gain insight into the pathogenesis of frontotemporal lobar degeneration (FTLD), the mean tau load in frontal cortex was compared in 34 patients with frontotemporal dementia linked to chromosome 17 (FTDP-17) with 12 different mutations in the tau gene (MAPT), 11 patients with sporadic FTLD with Pick bodies and 25 patients with early onset Alzheimer's disease (EOAD). Tau load was determined, as percentage of tissue occupied by stained product, by image analysis of immunohistochemically stained sections using the phospho-dependent antibodies AT8, AT100 and AT180. With AT8 and AT180 antibodies, the amount of tau was significantly (P < 0.001 in each instance) less than that in EOAD for both FTDP-17 (8.5% and 10.0% respectively) and sporadic FTLD with Pick bodies (16.1% and 10.0% respectively). With AT100, the amount of tau detected in FTDP-17 was 54% (P < 0.001) of that detected in EOAD, but no tau was detected in sporadic FTLD with Pick bodies using this particular antibody. The amount of insoluble tau deposited within the brain in FTDP-17 did not depend in any systematic way upon where the MAPT mutation was topographically located within the gene, or on the physiological or structural change generated by the mutation, regardless of which anti-tau antibody was used. Not only does the amount of tau deposited in the brain differ between the three disorders, but the pattern of phosphorylation of tau also varies according to disease. These findings raise important questions relating to the role of aggregated tau in neurodegeneration - whether this represents an adaptive response which promotes the survival of neurones, or whether it is a detrimental change that directly, or indirectly, brings about the demize of the affected cell.

Adult↗

Acquisition of the lateral inconsistency in involuntary behaviour of upper limbs in 12-year-old children during walking at moderate speed.

The aim of this work was to investigate possible lateralisation in the behaviour of periodic motion of the human upper limb, during normal walking at a comfortable speed of locomotion. Ten healthy pre-adolescent, strongly right-handed, 12-year-old males participated in the experiment. Participants were walking on a treadmill with a standardised velocity of 1.1m/s (comfortable speed for all of them). A video analysis system with Silicon software was used to synchronically measure various angles of arms and forearms. The initial, final and interim angular positions of both arms and forearms in 10 cycles of each participant were compared in terms of variations (cycle to cycle) between both upper extremities at corresponding phases of each cycle for distal and proximal segments, respectively. We compared the coefficients of variation in relation to the spatial and temporal data of both limbs and their angular velocities. In addition we investigated the level of cycle-to-cycle regularity (constancy) of behaviour in relation to various positions, periods and velocities of movement of upper extremities (specifically arms and forearms) using the Eta non-linear method of correlation. All participants exhibited a lower level of regularity for the distal segments. The spatial and temporal variations in the dominant limb were also greater than the non-dominant limb for all participants. This may be due to a larger contribution from the right-sided muscles that are considered to be the main contributing factor to the motion of the dominant upper limb during walking, rather than simply gravity force acting alone. A possible practical application of this information may be useful in the objective clinical identification of the level of dominance of the upper extremity (arm plus forearm), in addition to 'traditional' handedness.

Arm↗

Fine structure of the 1s3p 3PJ level in atomic 4He: theory and experiment.

The fine structure intervals in helium have been the focus of many theoretical and experimental studies in recent years with most of them concentrating on the 1s2p (3)P(J) levels. Here, we report on a theoretical calculation and an experimental determination of the 1s2p (3)P(J) fine structure intervals. The values from the theoretical calculation are 8113.730(6) and 658.801(6) MHz for the nu(01) and nu(12) intervals, respectively. The laser spectroscopic measurement reported here yields 8113.714(28) and 658.810(18) MHz for these intervals and is in excellent agreement with the theoretical calculation. Both, however, disagree significantly with the previous most precise experimental results.

Journal Article↗

Use of surgery to aid weight reduction-experience of two regions of Northern England: a database study.

OBJECTIVE: To determine the usage of surgery in the management of obesity. DESIGN: Analysis of routine statistics. DATA SOURCES: Hospital Episode Statistics extract held by Public Health Observatories. GEOGRAPHICAL AREAS: Two Government Office Regions in England with a population of 7.6 million. TIME PERIOD: Data analysed in the study covered the 6 y 1996/1997-2001/2002. RESULTS: The availability and uptake of surgery for obesity in the two regions was hugely variable. The overall utilisation of the procedures examined (OPCS operation codes: G30.1, G30.2, G32.10, G61.00) was 5.6 per million per annum, but ranged by Primary Care Trust from zero (the case in eight of the 50 PCTs in the two regions) to 24.0 operations per million per year. The rates of access to this surgery differed over six-fold between the two regions (1.4 operations per year per million population to 7.9 operations per year per million population). The PCTs with the highest rates of surgery, were those closest to the large providers of service. CONCLUSIONS: Access to this intervention is highly variable. Primary Care Trusts in England and service providers need to ensure that there is appropriate access to this effective procedure in carefully selected cases. The surgical expertise required for these operations could be concentrated in fewer centres.

Adult↗

Use of alkaline phosphatase staining to differentiate canine osteosarcoma from other vimentin-positive tumors.

Aspiration of lytic bone lesions is an excellent diagnostic test in the initial evaluation of primary bone neoplasia. However, cytologically, it can be difficult to differentiate osteosarcoma (OSA) from other bone neoplasms, including fibrosarcoma, chondrosarcoma, synovial cell sarcoma, and plasma cell myeloma. The purpose of this study is to determine the sensitivity and specificity of alkaline phosphatase (ALP) staining to differentiate OSA from other tumors that express vimentin by immunocytochemistry or immunohistochemistry. ALP is a hydrolytic enzyme present in multiple tissues including liver, kidney, intestine, placenta, and bone. Hypothetically, neoplasms actively producing bone should be specifically positive for ALP staining. Unstained, cytologic specimens were incubated for 8-10 minutes with nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate toluidine salt-phosphatase substrate. A positive reaction stains the membrane of the cells gray to black. Samples were counterstained with a Romanowsky's stain to determine whether the sample was of representative cellularity. A total of 61 vimentin-positive neoplasms have been evaluated and confirmed histopathologically. Tumors that expressed vimentin and were positive for ALP included 33 OSAs, one multi-lobular tumor of bone, one amelanotic melanoma, and one chondrosarcoma. Tumors that expressed vimentin and were negative for ALP included chondrosarcomas (three of four), multiple fibrosarcomas, and multiple synovial cell sarcomas. The sensitivity is 100%, and the specificity is 89%. In conclusion, ALP appears to be a highly sensitive and fairly specific marker in the diagnosis of OSA.

Alkaline Phosphatase↗

Angular distributions for (3,4)(Lambda)H bound states in the (3,4)He(e,e(')K+) reaction.

The (3,4)(Lambda)H and (4)(Lambda)H hypernuclear bound states have been observed for the first time in kaon electroproduction on (3,4)He targets. The production cross sections have been determined at Q(2)=0.35 GeV2 and W=1.91 GeV. For either hypernucleus the nuclear form factor is determined by comparing the angular distribution of the (3,4)He(e,e(')K+)(3,4)(Lambda)H processes to the elementary cross section 1H(e,e K+)Lambda on the free proton, measured during the same experiment.

Journal Article↗

Laser spectroscopic determination of the 6He nuclear charge radius.

We have performed precision laser spectroscopy on individual 6He (t(1/2)=0.8 s) atoms confined and cooled in a magneto-optical trap, and measured the isotope shift between 6He and 4He to be 43 194.772+/-0.056 MHz for the 2(3)S1-3(3)P2 transition. Based on this measurement and atomic theory, the nuclear charge radius of 6He is determined for the first time in a method independent of nuclear models to be 2.054+/-0.014 fm. The result is compared with the values predicted by a number of nuclear structure calculations and tests their ability to characterize this loosely bound halo nucleus.

Journal Article↗

Counting individual 41Ca atoms with a magneto-optical trap.

Atom trap trace analysis, a novel method based upon laser trapping and cooling, is used to count individual atoms of 41Ca present in biomedical samples with isotopic abundance levels between 10(-8) and 10(-10). The method is calibrated against resonance ionization mass spectrometry, demonstrating good agreement between the two methods. The present system has a counting efficiency of 2x10(-7). Within 1 h of observation time, its 3-sigma detection limit on the isotopic abundance of 41Ca reaches 4.5x10(-10).

Calcium Radioisotopes↗

A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease.

The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD). The possible influence of APO E epsilon4 allele acting in concert with ACE D allele was assessed. The extent of ML did not differ between D/D, I/D and I/I genotype groups when data from all four brain regions were combined. However, separate analysis showed that the frontal and temporal cortex tended to be affected more severely by ML in patients with D/D genotype compared to those with I/D and I/I genotypes. Stratification according to APO E epsilon4 allele revealed a greater overall ML in patients bearing at least one copy of ACE D allele and one APO E epsilon4 allele, especially in individuals homozygous for both. The APO E epsilon4 allele may therefore act synergistically in patients with AD (and other subjects) bearing ACE D/D genotype to increase the risk of ML, perhaps through transient ischaemic episodes consequent upon poor cardiac output associated with coronary atherosclerosis in patients with the APO E epsilon4 allele.

Adult↗

Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer's disease.

Pathological relationships between damage to the deep white matter of the cerebral cortex [as evidenced by myelin loss (ML)], cerebral amyloid angiopathy (CAA) and arteriosclerosis (ART) were investigated in the brains of 137 patients with autopsy-confirmed Alzheimer's disease (AD), in order to better understand the causes of white matter damage in AD, and the contribution of this to the pathogenesis of the disorder. All 137 patients had some degree of CAA in one or more brain regions although the occipital cortex was severely affected by CAA more frequently, and consequently mean CAA severity score was significantly greater, than other cortical regions. Eighty-seven patients (63.5%) were affected by ML, with more patients showing ML from occipital cortex than from other cortical regions leading to a significantly higher mean ML severity score in this region. One hundred and twenty-six patients (92%) were affected by ART, although the occipital cortex was not more frequently affected by ART than other cortical areas, the mean ART severity score in occipital cortex was nonetheless significantly greater than that of frontal and temporal cortex. Eighty-seven patients showed both CAA and ML, although there was only a weak correlation between degree of CAA and extent of ML (P = 0.035). Forty-seven patients showed ML and significant ART, 16 patients showed significant ART but no ML, 40 patients showed ML in the absence of significant ART and 34 patients showed neither significant ART nor ML. Overall, and for each of the four brain regions, the extent of ML correlated significantly (P < 0.001) with degree of ART. However, when only those 47 patients with ML and significant ART were considered, much stronger correlations between the extent of ML and the degree of ART were achieved both overall and within each of the four brain regions. The overall ART severity score (and overall scores for each pathological marker of ART) significantly correlated with that of CAA (P < 0.001). Pathological processes leading to white matter damage, in terms of ML at least, in AD are thus likely to be heterogeneous. Many patients suffer ML in association with ART, but in others ML cannot be explained by presence of ART or CAA. In such patients, autoregulatory changes in blood vessels might be responsible for ML. The association between the extent of CAA and ART suggests shared risk factors for each pathological change.

Age of Onset↗

Association between apolipoprotein E e4 allele and arteriosclerosis, cerebral amyloid angiopathy, and cerebral white matter damage in Alzheimer's disease.

OBJECTIVE: To investigate the association between white matter damage, as evidenced by myelin loss (ML), the extent of cerebral amyloid angiopathy (CAA), or arteriosclerosis (Art), and apolipoprotein E (ApoE) e4 allele in Alzheimer's disease (AD), in order to understand the causes of damage to white matter in AD and its contribution to the pathogenesis of the disorder. MATERIALS AND METHODS: Brain tissues were obtained from 94 patients with AD confirmed by autopsy. ApoE genotyping was performed by PCR on DNA extracted from frontal cortex or cerebellum. CAA and Art were assessed on Weigert's haematoxylin and eosin stained sections in frontal, temporal, parietal, and occipital cortices; the extent of ML was scored on Luxol fast blue stained sections of these regions. RESULTS: The ApoE e4 allele frequency in the 61 patients with ML was not significantly different from that in the 33 patients without ML, nor did this differ in the 84 patients with Art from that in the 10 patients without Art. There were no significant differences in the proportions of patients with genotypes containing 0, 1, or 2 ApoE e4 alleles in the presence or absence of ML or Art. The mean ML, Art, or CAA scores within each region, and the total scores summed across all four brain regions, did not differ between patients with 0, 1, or 2 ApoE e4 alleles. However, the mean ML severity score in the occipital cortex was significantly greater than that in the frontal or temporal cortices in patients with 1 or 2 ApoE e4 alleles. The severity of CAA in the occipital cortex was significantly higher than that in other areas of cortex in patients with 0 or 2 ApoE e4 alleles. The mean Art score in the occipital cortex was greater than that in the temporal cortex in patients with two ApoE e4 alleles and was higher than that in the frontal cortex in patients with one ApoE e4 allele. CONCLUSIONS: The likelihood of patients with AD suffering from CAA, Art, or ML is not influenced by ApoE e4 allele, nor is the overall burden of these pathological changes in the brain. However, the distribution of ML, CAA, and Art within the brain is at least partly influenced by genotype and dosage of ApoE e4 allele, with the occipital cortex being more severely affected by all of these pathological changes in e4 allele bearers, particularly when two ApoE e4 alleles are present.

Aged↗

Negative association between amyloid plaques and cerebral amyloid angiopathy in Alzheimer's disease.

Cerebral amyloid angiopathy (CAA) is an important, though still relatively neglected, aspect of the pathology of Alzheimer's disease (AD), and both the source of amyloid beta protein (Abeta) in CAA, and its relationship to senile plaque (SP) Abeta, remain unclear. We have investigated the relationship between Abeta deposition in SP and CAA in four regions of brain from 69 patients with AD in order to gain insight into the pathogenetic mechanism(s) underlying these pathologies. CAA was present to some degree in all 69 patients, with the occipital cortex being affected more often and more severely than frontal, temporal and parietal cortices. By definition, SPs were present in all brain areas in all 69 patients, with greater uniformity of distribution than CAA, though the occipital cortex was less severely affected than the other brain regions. There was no significant (positive) correlation between CAA rating and that of SP for any one cortical region, but on combining data from all four regions there was a significant inverse correlation (P=0.037) between CAA and SP ratings. Such data suggest that the cellular sources and mechanisms leading to Abeta deposition as SP or CAA are likely to differ and may proceed independently of each other.

Aged↗

Genetic transformation of Dichanthium annulatum (Forssk)--an apomictic tropical forage grass.

Eleven Dichanthium annulatum (Forssk) plants were regenerated from embryogenic callus co-transformed with two plasmids encoding either the hygromycin phosphotransferase gene (hph) or the beta-glucuronidase (GUS) gene (uidA). Analysis of these putative transformants showed that three plants were transformed with the hph gene, showed the presence of the hph transcript and expressed hygromycin resistance after transfer to soil. Two of these also contained the uidA gene but did not express GUS and were shown to be the same transformation event. All three of the transformants set seed. Hygromycin resistance varied from 68-100% in the progeny of the three transformants. Transgene transmission appeared to have been mainly through apomixis.

Blotting, Southern↗

Clinical decision-making in hypertension using an automated (BpTRU) measurement device.

Mercury sphygmomanometers are being removed from clinical practice in the United States due to environmental concerns about mercury toxicity. Accurate blood pressure measurement is central to high-quality hypertension management. In this study of 106 patients, the BpTRU(TM) device was compared to nurse blood pressure measurements that complied with all the JNC VII/American Heart Association guidelines in evaluation of a random casual blood pressure. The intermethod difference in systolic blood pressure was +1.8+/-5.1 mmHg, and for diastolic blood pressure it was 4.8+/-5.1 mmHg (both P<0.001). For the primary study end point of clinical decision-making, there was 92% (97/106) agreement between the hypertension nurse specialist and the BpTRU (kappa 0.8280, 95% confidence interval, 0.721-0.9350). The oscillometric blood pressure measurement with the BpTRU is recommended as a replacement for poorly performed auscultatory blood pressure measurement in clinical practice.

Adolescent↗

Accuracy of routine data on MMR vaccination coverage and validity of parental recall of vaccination.

A study was conducted to re-validate the measles, mumps and rubella (MMR) coverage and measles susceptibility in children resident in Bolton and born between 1991 and 1995; also to examine the accuracy of parental recall of children's MMR vaccination status. Using general practitioner/practice held records, a validation survey was conducted on a random sample of 171 reportedly unvaccinated children. A questionnaire survey was used to assess parental recall. 'Records' to 'recall' agreement was examined. One- and two-dose population coverage according to routine data was 94.6% and 75.2% respectively, with measles susceptibility of 8.1%. Based on the 'records' survey, one- and two-dose population coverage estimates were 97.4% (+2.8%) and 78.9% (+3.7%), with a revised susceptibility estimate of 5.2%, respresenting a 36% reduction in the susceptibility fraction. Routine data may modestly underestimate vaccination coverage and significantly overestimate measles susceptibility. Many parents of MMR unvaccinated children believe that their children have been vaccinated.

Chi-Square Distribution↗

Longitudinal electroproduction of charged pions from (1)H, (2)H, and (3)He.

Separated longitudinal and transverse cross sections for charged pion electroproduction from (1)H, (2)H, and (3)He were measured at Q(2) = 0.4 (GeV/c)(2) for two values of the invariant mass, W = 1.15 GeV and W = 1.60 GeV, in a search for a mass dependence which would signal the effect of nuclear pions. This is the first such study that includes recoil momenta significantly above the Fermi surface. The longitudinal cross section, if dominated by the pion-pole process, should be sensitive to nuclear pion currents. Comparisons of the longitudinal cross section target ratios to a quasifree calculation reveal a significant suppression in (3)He at W = 1.60 GeV. The W = 1.15 GeV results are consistent with simple estimates of the effect of nuclear pion currents, but are also consistent with pure quasifree production.

Journal Article↗

Gabapentin and methylphenidate treatment of a preadolescent with attention deficit hyperactivity disorder and bipolar disorder.

Gabapentin is an anticonvulsant drug released in the United States in 1993 for use as adjunctive therapy in refractory partial epilepsy. The mechanism of action of gabapentin is unknown, but the drug has very favorable pharmacokinetics and a good safety profile, which allows its use in high-risk patients. Several reports have described the successful use of gabapentin for bipolar disorders in adults, but there are no controlled studies in the use of gabapentin in children and adolescents. We describe a 12-year-old boy with a history of attention deficient hyperactivity disorder (ADHD), reading disorder, mixed receptive and expressive language disorder, encopresis, and bipolar disorder II who was treated with gabapentin 200 mg/day added to methylphenidate 30 mg/day. Within 3 weeks the improvement and stabilization of mood symptoms was remarkable, as noted by mother, teacher, and clinician, and remained so for 6 months of follow-up. Comorbid bipolar disorder and ADHD is a hotly debated topic in the child and adolescent psychiatric literature, with rates of comorbid ADHD and bipolar disorder ranging from 22% to 90%. Controlled studies are needed to evaluate the possible antimanic mood stabilizing and/or antidepressant properties or gabapentin in youths.

Acetates↗

Pharmacodynamic evaluation of RWJ-270201, a novel neuraminidase inhibitor, in a lethal murine model of influenza predicts efficacy for once-daily dosing.

We examined RWJ-270201 in a lethal model of influenza in BALB/c mice. The aim was to delineate the pharmacodynamically linked variable for the drug. Challenge was performed with influenza virus A/Shongdong/09/93 (H3N2). Treatment was administered by gavage. Five doses (1 to 10 mg/kg of body weight) and three schedules (every 24, 12, and 8 h) were evaluated with 10 mice per group. There were 39 placebo-treated mice. Drug exposure was evaluated for infected mice. Exposures were calculated after population modeling of all the plasma concentration-time data simultaneously using the NPEM3 program. Evaluation of dose and schedule with Kaplan-Meier analysis and Cox proportional hazards modeling demonstrated that schedule offered no explanatory power relative to dose alone. Evaluation of peak concentration, trough concentration, and area under the concentration-time curve (AUC) by the same methods revealed that AUC was the dynamically linked variable. Again, schedule offered no further explanatory power when included in the model with AUC. This indicates that AUC is the linked variable and that the anti-influenza effect of RWJ-270201 is independent of schedule. We conclude that once-daily dosing of RWJ-270201 should be evaluated in clinical trials of influenza therapy.

Acids, Carbocyclic↗