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Biomedical subjects

Bernard Cohen

Publications and source records attributed to Bernard Cohen.

At least 37 records · Page 2Linked to original sources
PubMed2004

Expanding the donor pool to increase renal transplantation.

INTRODUCTION: The goal of the Eurotransplant renal allocation scheme is to provide every patient on the waiting list with a reasonably balanced opportunity for a donor offer. New initiatives were taken in order to maximize donor usage while maintaining a successful transplant outcome. METHODS: Two Eurotransplant projects were launched in order to accommodate changes in donor and recipient profiles. A re-addressing of the non-heart-beating donor pool was undertaken and an allocation scheme in which organs from donors aged >65 are allocated to recipients aged >65 [the Eurotransplant Senior Programme (ESP)] was introduced. RESULTS: Especially in The Netherlands, an enormous increase in the number of non-heart-beating donor kidneys has been observed, however with a pace-keeping reduction in heart-beating donors. The organization-wide implementation of the ESP has been successful. The 3 year graft survival rates for these age-matched transplants were as good as the human leukocyte antigen (HLA)-matched transplants (64 vs 67%) (P = 0.4). CONCLUSION: Within the framework of sound research, the utmost flexibility and creativity is needed to keep or even increase the number of renal transplants when faced with a quantitatively stagnating but qualitatively deteriorating donor pool. Both the non-heart-beating donor protocol and the ESP have proven to be quite successful in achieving this goal without compromising the outcome for the individual end-stage renal disease patient.

Adolescent↗
PubMed2004

Texture-based approaches for identifying neuro-anatomical structures and electrode tracks.

An automated approach to identifying electrode tracks and neuro-anatomical structures (nuclei) was developed using texture attributes of their neuro-anatomical stains. The properties that make up the texture features of the nuclei include size, shape and distribution of elemental structures. The electrode tracks are characterized by elongated darkened formations due to gliosis. Based on a Gabor wavelet transform, a texture feature vector was constructed, consisting of localized texture energies along different orientations at different scales. Stained images of brainstem sections in the vestibular nuclei were segmented using partitional clustering in feature space. A metric that computes the location of the tracks relative to the nuclei centers was then implemented. This methodology should be useful for quantifying and automating the procedure by which tracks are localized in anatomical structures.

Algorithms↗
PubMed2004

Evaluation of the Roche LightCycler parvovirus B19 quantification kit for the diagnosis of parvovirus B19 infections.

BACKGROUND: The rapid and quantitative detection of viral DNA is important in the diagnosis of parvovirus B19 infection in immunocompromised patients and in congenital infection. It is also valuable for monitoring progress following therapeutic interventions. OBJECTIVES: To evaluate the diagnostic sensitivity and specificity of the Roche LightCycler (LC) parvovirus B19 quantification kit in comparison with previously described nested PCR and dot blot hybridisation assays. STUDY DESIGN: Two hundred and twenty eight clinical samples and two standard B19 DNA sera were tested to assess the diagnositic performance of the Roche LC kit. RESULTS: Ten clinical samples (4.3%) gave invalid LC results, including three of five bone marrow samples but only two of 165 serum samples. In the remaining 218 samples, the LC assay detected B19 DNA in 97.5% (79/81) samples that were positive by the nested PCR. The two samples (from the same patient) that were LC negative were sequenced in a 511-nucleotide region of the NS gene and 42 nucleotide changes were found. The Roche LC assay detected B19 DNA in 9.5% (13/137) samples that were negative by nested PCR. Analysis of the available clinical and serological data associated with these samples suggested that the LC results in the majority of these cases were true positive. In patients with resolving persistent infection, the LC assay remained positive for longer than nested PCR. CONCLUSIONS: The Roche LC assay was more sensitive than the nested PCR used in this study. The additional sensitivity and the quantitative DNA measurements were valuable for monitoring patients with persistent B19 infection. Practical advantages of the LC assay include a short running time and the possibility to automate the assay. The LC assay provides a controlled and standardised method for quantitative detection of viral DNA for the diagnosis and monitoring of parvovirus B19 infections but failed to detect a variant strain.

Adult↗
PubMed2004

Atopic dermatitis and the hygiene hypothesis: a case-control study.

BACKGROUND: The notion that lack of exposure to infection in early life leads to development of atopic disease has come to be known as the hygiene hypothesis. It has arisen from observations of the rapidly rising prevalence of atopic diseases in recent decades and the lower prevalence of atopy with rising birth order. Direct evidence for the hypothesis to date is inconsistent. METHODS: A case-control study set in Norfolk, UK of 602 children aged 1-5 years. Cases and controls were defined using the UK Diagnostic Criteria for atopic dermatitis (AD) and a range of direct and indirect methods were used to measure exposure to infection during infancy. Odds ratios (OR) for the effect of these measures were calculated using logistic regression with adjustment for possible biological and social confounding factors. RESULTS: Reduced odds of AD were associated with rising birth order (OR for one older sibling 0.59, 95% CI: 0.42, 0.84 and for >or=2 older siblings 0.49, 95% CI: 0.31, 0.77). None of the measures of infection reduced the odds of AD significantly, either in the unadjusted or adjusted analyses. None of the measures of infection explained the protective effect of older siblings. CONCLUSIONS: Increased exposure to infection does not explain the reduced risk of AD in second and subsequent siblings. More generally, these data cast doubt on the hygiene hypothesis as a causal explanation for AD in young children.

Case-Control Studies↗
PubMed2004

Gravity-dependent and gravity-independent gain changes during vertical vestibulo-ocular reflex (VOR) adaptation.

The gain of the vertical angular vestibulo-ocular reflex (aVOR) was adaptively increased or decreased with monkeys in a side down position, and the gains were tested with the axis of rotation tilted in 10 degrees increments from left- to right-side-down. Gain changes, expressed as a percentage of the preadapted values, were plotted as a function of head tilt, and fit with a cosine function. The amplitude of the cosine was half of the gravity-dependent component of the gain change and the bias, the gravity independent component. The largest changes in the gain of both components occurred in the first 30 min and continued at a slower rate throughout adaptation. The gravity-dependent and -independent gain changes were larger for gain decreases than for gain increases, but both components had similar dynamics. We conclude that the alteration in gain of the aVOR always occurs in the context of gravity.

Adaptation, Physiological↗
PubMed2003

The relation of motion sickness to the spatial-temporal properties of velocity storage.

Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45 degrees over 2 s to and from the upright position while being rotated at 138 degrees /s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the more severe the motion sickness. Thus, promethazine neither reduced the nausea associated with RWR, nor retarded or hastened habituation. The inverse relationship between the aVOR time constants and number of head movements to motion sickness, and the association of the severity of motion sickness with the extent, strength, and time of deviation of eye velocity from gravity supports the postulate that the spatiotemporal properties of velocity storage, which are processed between the nodulus and uvula of the vestibulocerebellum and the vestibular nuclei, are likely to represent the source of the conflict responsible for producing motion sickness.

Adult↗
PubMed2003

The elimination of indigenous measles transmission in England and Wales.

Following a school-based measles-rubella vaccination campaign in November 1994, enhanced surveillance of measles, including IgM antibody testing of oral fluid from clinically diagnosed case-patients, was introduced in England and Wales. Between 1995 and 2001, 665 cases of measles were confirmed, including 371 (56%) confirmed only by IgM detection in oral fluid. Two hundred thirty-nine cases (36%) were sporadic and 426 (64%) were associated with 61 clusters. Fifty-four (23%) of the 239 sporadic cases and 26 (43%) of the 61 clusters were associated with a probable or possible importation of infection from overseas, and a wide variety of genotypes were identified in each calendar year. The effective reproduction number for measles over the period was estimated to be below 0.7. These data suggest that most measles in the UK is acquired following limited transmission from an imported infection, and they confirm that measles elimination has been achieved and sustained over this period.

Adolescent↗
PubMed2003

Development of a measles specific IgM ELISA for use with serum and oral fluid samples using recombinant measles nucleoprotein produced in Saccharomyces cerevisiae.

In order to develop sensitive assays for detecting measles antibodies in oral fluid specimens, we have produced recombinant measles virus nucleoprotein (rMVN) in a yeast expression system and prepared monoclonal antibodies to the protein. Measles nucleoprotein gene from the Schwarz vaccine strain was cloned into a yeast expression vector, pFX7 under the control of the hybrid GAL10-PYK1 promoter. High levels of rMVN (20 mg/litre of yeast culture) were generated. Electron microscopy showed that the purified rMVN assembled into typical herring-bone structures. Monoclonal antibodies produced to the rMVN also reacted with native measles virus N in immunofluorescence tests. The purified rMVN and a monoclonal antibody to the rMVN conjugated to horseradish peroxidase were used to develop a measles specific IgM capture EIA (MACEIA) in both serum and oral fluid specimens. Evaluations of the MACEIA were performed by testing a) serum samples (n=80) and b) paired oral fluid/serum samples from measles cases (n=50, representing 16 cases) and oral fluids from controls with non-measles rash (n=59, representing 48 cases). The samples were also tested for measles IgM, using a reference radioimmunoassay (MACRIA). The sensitivity and specificity of the MACEIA compared with MACRIA for a) the serum samples were 100 and 96.6% respectively and b) for paired serum/oral fluids samples 100 and 100%, respectively.

Animals↗
PubMed2003

Vesicular pemphigoid in a 16-year-old boy.

We describe a case of a 16-year-old African-American boy with bullous pemphigoid (BP), an acquired autoimmune blistering disease that is rarely seen in children. The patient's lesions, however, were distinctly herpetiform, complicating initial diagnosis and therapy. A diagnosis of BP was made by direct and indirect immunofluorescence. Immunoblotting and enzyme-linked immunosorbent assay analysis confirmed the presence of autoantibodies directed against the BP180 antigen. The autoantibodies reacted with the same epitopes within the immunodominant BP180 NC16A domain that have previously been shown to be the target of autoantibodies in BP. This case describes an uncommon disease in the pediatric population and should be included in the differential diagnosis in young patients with an unusual generalized vesicular eruption.

Adolescent↗
PubMed2003

Gravity-specific adaptation of the angular vestibuloocular reflex: dependence on head orientation with regard to gravity.

The gain of the vertical angular vestibuloocular reflex (aVOR) was adaptively altered by visual-vestibular mismatch during rotation about an interaural axis, using steps of velocity in three head orientations: upright, left-side down, and right-side down. Gains were decreased by rotating the animal and visual surround in the same direction and increased by visual and surround rotation in opposite directions. Gains were adapted in one head position (single-state adaptation) or decreased with one side down and increased with the other side down (dual-state adaptation). Animals were tested in darkness using sinusoidal rotation at 0.5 Hz about an interaural axis that was tilted from horizontal to vertical. They were also sinusoidally oscillated from 0.5 to 4 Hz about a spatial vertical axis in static tilt positions from yaw to pitch. After both single- and dual-state adaptation, gain changes were maximal when the monkeys were in the position in which the gain had been adapted, and the gain changes progressively declined as the head was tilted away from that position. We call this gravity-specific aVOR gain adaptation. The spatial distribution of the specific aVOR gain changes could be represented by a cosine function that was superimposed on a bias level, which we called gravity-independent gain adaptation. Maximal gravity-specific gain changes were produced by 2-4 h of adaptation for both single- and dual-state adaptations, and changes in gain were similar at all test frequencies. When adapted while upright, the magnitude and distribution of the gravity-specific adaptation was comparable to that when animals were adapted in side-down positions. Single-state adaptation also produced gain changes that were independent of head position re gravity particularly in association with gain reduction. There was no bias after dual-state adaptation. With this difference, fits to data obtained by altering the gain in separate sessions predicted the modulations in gain obtained from dual-state adaptations. These data show that the vertical aVOR gain changes dependent on head position with regard to gravity are continuous functions of head tilt, whose spatial phase depends on the position in which the gain was adapted. From their different characteristics, it is likely that gravity-specific and gravity-independent adaptive changes in gain are produced by separate neural processes. These data demonstrate that head orientation to gravity plays an important role in both orienting and tuning the gain of the vertical aVOR.

Adaptation, Physiological↗
PubMed2003

The critical role of velocity storage in production of motion sickness.

We propose that motion sickness is mediated through the orientation properties of velocity storage in the vestibular system that tend to align eye velocity produced by the angular vestibulo-ocular reflex (aVOR) with gravito-inertial acceleration (GIA). (GIA is the sum of the linear accelerations acting on the head. In the absence of translational accelerations, gravity is the GIA.) We further postulate that motion sickness produced by cross-coupled vestibular stimulation can be characterized by a metric composed of the disparity between the axis of eye rotation and the GIA, the strength of the response to angular motion, and the response duration, as determined by the central vestibular time constant, that is, by the time constant of velocity storage. The nodulus and uvula of the vestibulocerebellum are likely to be the central sites where the disparity is sensed, where the vestibular time constants are habituated, and where links are made to the autonomic system to produce the symptoms and signs.

Adult↗
PubMed2003

Adaptive changes in the angular VOR: duration of gain changes and lack of effect of nodulo-uvulectomy.

Alterations in the gain of the vertical angular vestibulo-ocular reflex (VOR) are dependent on the head position in which the gain changes were produced. We determined how long gravity-dependent gain changes last in monkeys after four hours of adaptation, and whether the adaptation is mediated through the nodulus and uvula of the vestibulocerebellum. Vertical VOR gains were adaptively modified by rotation about an interaural axis, in phase or out of phase with the visual surround. Vertical VOR gains were modified with the animals in one of three orientations: upright, left-side down, or right-side down. Monkeys were tested in darkness for up to four days after adaptation using sinusoidal rotation about an interaural axis that was incrementally tilted in 10 degrees steps from vertical to side down positions. Animals were unrestrained in their cages in normal light conditions between tests. Gravity-dependent gain changes lasted for a day or less after adaptation while upright, but persisted for two days or more after on-side adaptation. These data show that gravity-dependent gain changes can last for prolonged periods after only four hours of adaptation in monkeys, as in humans. They also demonstrate that natural head movements made while upright do not provide an adequate stimulus for rapid recovery of vertical VOR gains that were induced on side. In two animals, the nodulus and uvula were surgically ablated. Vertical gravity-dependent gain changes were not significantly different before and after surgery, indicating that the nodulus and uvula do not have a critical role in producing them.

Adaptation, Physiological↗
PubMed2003

Ocular and perceptual responses to linear acceleration in microgravity: alterations in otolith function on the COSMOS and Neurolab flights.

In this paper we review space flight experiments performed by our laboratory. Rhesus monkeys were tested before and after 12 days in orbit on COSMOS flights 2044 (1989) and 2229 (1992-1993). There was a long-lasting decrease in post-flight ocular counter-rolling (70%) and vergence (50%) during off-vertical axis rotation. In one animal, the orientation of optokinetic after-nystagmus shifted by 28 degrees from the spatial vertical towards the body vertical early post-flight. Otolith-ocular and perceptual responses were also studied in four astronauts on the 17-day Neurolab shuttle mission (STS-90) in 1998. Ocular counter-rolling was unchanged in response to 1-g and 0.5-g Gy centrifugation during and after flight and to post-flight static roll tilts relative to pre-flight values. Orientation of the optokinetic nystagmus eye velocity axis to gravito-inertial acceleration (GIA) during centrifugation was also unaltered by exposure to microgravity. Perceptual orientation to the GIA was maintained in-flight, and subjects did not report sensation of translation during constant velocity centrifugation. These studies suggest that percepts and ocular responses to tilt are determined by sensing the body vertical relative to the GIA. The findings also raise the possibility that 'artificial gravity' during the Neurolab flight counteracted adaptation of these otolith-ocular responses.

Acceleration↗
PubMed2002

A quantitative immuno-PCR assay for the detection of mumps-specific IgG.

Sensitive assays are required for seroprevalence studies of measles, mumps and rubella (MMR)-vaccinated populations where many may have low levels of antibodies. This protocol describes a quantitative immuno-PCR assay to detect mumps-specific IgG antibodies. The purpose of the protocol is to determine the immune status of individuals to mumps. Mumps-specific IgG from a dilution of patients serum is bound by recombinant mumps nucleoprotein coated on the surface of microtitre plate wells. Bound antibody is detected by PCR using a conjugate of anti-human IgG covalently coupled to an oligonucleotide. The oligonucleotide is detected by the addition of target DNA, designed to hybridise to the oligonucleotide and serve as a template for real-time PCR using the LightCycler. The quantity of target DNA detected by the PCR depends upon the level of specific antibody in the test sample.

Antibodies, Viral↗
PubMed2002

Stability of total and rubella-specific IgG in oral fluid samples: the effect of time and temperature.

Oral fluid (saliva) samples are increasingly used as a minimally invasive alternative to serum to detect antibody for viral diagnostics and population-based surveys of immunity to common infections. Postal collection of these samples is convenient, but it is uncertain how oral fluid antibody levels may deteriorate during transit. In this study multiple oral fluid samples, from a group of individuals, were collected and kept at two different temperatures (10 and 20 degrees C, simulating winter and summer conditions ) for periods of up to 7 days. They were then tested for total immunoglobulin G (IgG) and for rubella-specific IgG. Total IgG concentrations ranged from 2.0 to 48.6 mg/l but showed no significant decrease over the 7-day period. There was also no significant change in rubella-specific IgG measured using an antibody capture ELISA, but testing with an indirect rubella IgG ELISA revealed a significant decrease in absorbance values between day 1 and day 7 at 20 degrees C. The difference in the rubella assay results may reflect the different assay formats with the signal in the indirect procedure related to the concentration of rubella IgG in the oral fluid sample, rather than the proportion of virus-specific IgG measured with the antibody capture format. The study demonstrated that total and rubella specific IgG in oral fluid samples were stable for up to 7 days at differing temperatures and that an antibody capture assay format should be used for virus-specific testing to minimise inaccurate results due to low IgG concentrations in oral fluid samples.

Antibodies, Viral↗
PubMed2002

Suboptimal measles-mumps-rubella vaccination coverage facilitates an imported measles outbreak in ireland.

The year 2000 saw a dramatic increase in the incidence of measles infections in Ireland, with >1500 cases documented. Initial cases were reported from an area of Dublin with low vaccine uptake and a large immigrant population. Molecular epidemiologic findings revealed that the strain of measles virus responsible for this outbreak was the genotype D2 strain, which is closely related to strains initially identified in South Africa. It is suggested that suboptimal vaccine uptake facilitated the spread of imported measles infection.

Diagnostic Errors↗
PubMed2002

The vestibulo-ocular reflex in three dimensions.

The purpose of this paper is to review the kinematics and dynamics of the vestibulo-ocular reflex (VOR) in three dimensions. We give a brief, didactic tutorial on vectors and matrices and their importance as representational schemes for describing the kinematics and dynamics of the angular and linear accelerations that activate the vestibular system. We show how the vectors associated with angular and linear head accelerations are transformed by the peripheral and central vestibular systems to drive the oculomotor system to produce eye movements in three-dimensional space. We also review critical questions and controversies related to the compensatory and orientation behavior of the VOR. One such question is how the central vestibular system distinguishes tilts of the head, which generate interaural linear acceleration from translations along the interaural axis. Another question is how the velocity-position integrator is implemented centrally. The review has been placed in the context of a model that explains the behavior of the VOR in three dimensions. Model processes have been related to peripheral and central neural behavior in order to gain insight into the nature of the three-dimensional organization and the controversial questions that are addressed.

Adaptation, Physiological↗