Search PubMed⌕ Search

Biomedical subjects

L Jenkins

Publications and source records attributed to L Jenkins.

At least 19 recordsLinked to original sources
PubMed2005

Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial.

BACKGROUND: AN1792 (beta-amyloid [Abeta]1-42) immunization reduces Abeta plaque burden and preserves cognitive function in APP transgenic mice. The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of IM AN1792 225 microg plus the adjuvant QS-21 50 microg (300 patients) and saline (72 patients) included patients aged 50 to 85 years with probable AD, Mini-Mental State Examination (MMSE) 15 to 26. Injections were planned for months 0, 1, 3, 6, 9, and 12. Safety and tolerability were evaluated, and pilot efficacy (AD Assessment Scale-Cognitive Subscale [ADAS-Cog], MRI, neuropsychological test battery [NTB], CSF tau, and Abeta42) was assessed in anti-AN1792 antibody responder patients (immunoglobulin G titer > or = 1:2,200). RESULTS: Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections. Of the 300 AN1792(QS-21)-treated patients, 59 (19.7%) developed the predetermined antibody response. Double-blind assessments were maintained for 12 months. No significant differences were found between antibody responder and placebo groups for ADAS-Cog, Disability Assessment for Dementia, Clinical Dementia Rating, MMSE, or Clinical Global Impression of Change, but analyses of the z-score composite across the NTB revealed differences favoring antibody responders (0.03 +/- 0.37 vs -0.20 +/- 0.45; p = 0.020). In the small subset of subjects who had CSF examinations, CSF tau was decreased in antibody responders (n = 11) vs placebo subjects (n = 10; p < 0.001). CONCLUSION: Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.

Aged↗
PubMed2005

Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) is characterized by progressive cerebral atrophy that may be measured using MRI. Reported are MRI findings of a Phase IIa immunotherapy trial in AD prematurely terminated owing to meningoencephalitis in a subset of patients. OBJECTIVE: To assess cerebral volume changes in patients immunized with AN1792 (beta-amyloid [Abeta] 1 to 42) who were antibody responders (anti-AN1792 IgG titer of > or =1:2,200) compared with placebo patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of AN1792 225 mug plus QS-21 50 mug included 372 patients with probable AD. Patients received one to three injections of AN1792/QS-21 or saline and were assessed for 12 months. Volumetric MRI was performed pre dose and at month 12 or early termination. Brain, ventricular, and hippocampal volume changes were measured from registered scan pairs. RESULTS: Two hundred eighty-eight patients had paired scans (mean interval 10.9 months). Antibody responders (n = 45) had greater brain volume decrease (3.12 +/- 1.98 vs 2.04 +/- 1.74%; p = 0.007), greater ventricular enlargement as a percentage of baseline brain volume (1.10 +/- 0.75 vs 0.48 +/- 0.40%; p < 0.001), and a nonsignificant greater hippocampal volume decrease (3.78 +/- 2.63 vs 2.86 +/- 3.19%; p = 0.124) than placebo patients (n = 57). Increased losses in brain volume were not reflected in worsening cognitive performance; a composite z score across a Neuropsychological Test Battery showed differences favoring antibody responders over placebo (0.03 +/- 0.39 vs -0.24 +/- 0.45; p = 0.008). CONCLUSIONS: A dissociation between brain volume loss and cognitive function was observed in AN1792/QS-21 antibody responders. The reasons for this remain unclear but include the possibility that volume changes were due to amyloid removal and associated cerebral fluid shifts.

Aged↗
PubMed2005

Evaluation of the safety and immunogenicity of synthetic Abeta42 (AN1792) in patients with AD.

BACKGROUND: Abeta42-immunization reduces plaque burden and improves cognition in transgenic mouse models of Alzheimer disease (AD). This phase 1 study evaluated the safety, tolerability, and immunogenicity of AN1792 (human aggregated Abeta42) in patients with mild to moderate AD. METHODS: Twenty patients were enrolled into each of four dose groups and randomly assigned to receive IM AN1792 (50 or 225 microg) with QS-21 adjuvant (50 or 100 microg) or QS-21 only (control) in a 4:1 active:control ratio on day 0 and at weeks 4, 12, and 24. Patients could receive up to four additional injections of a polysorbate 80 modified formulation at weeks 36, 48, 60, and 72. Safety, tolerability, immunogenicity, and exploratory evidence of efficacy were evaluated. RESULTS: Treatment-related adverse events were reported in 19 (23.8%) patients, but no relationship was observed between AN1792 dose and incidence. One patient developed meningoencephalitis that was diagnosed after death (not directly related to study treatment) and 219 days after discontinuing from the study. Five deaths occurred during the study follow-up, but none was considered to be directly related to study treatment. During the period of the first four injections, 23.4% of AN1792-treated patients had a positive anti-AN1792 antibody titer (an anti-AN1792 antibody titer of > or =1:1,000). This increased to 58.8% after additional injections with the modified formulation. Disability Assessment for Dementia scores showed less decline among active compared with control patients at week 84 (p = 0.002). No treatment differences were observed in three other efficacy measures. CONCLUSIONS: AN1792 + QS-21 elicited a positive antibody response to Abeta42 in more than half of this elderly study population.

Adjuvants, Immunologic↗
PubMed2005

Specific loss of connexin 26 expression in ductal sweat gland epithelium associated with the deletion mutation del(GJB6-D13S1830).

A whole array of cutaneous syndromes is associated with distinct dominant mutations in GJB2 encoding the gap junction protein connexin 26 (C x 26), including Vohwinkel's syndrome and keratitis-ichthyosis-deafness syndrome. In contrast, recessive GJB2 mutations occur in a large proportion of individuals with hearing loss but no obvious dermatological phenotype. Recently, a large deletion of approximately 342 kb, encompassing the coding region of GJB6 encoding C x 30, but not affecting GJB2, was shown to be associated with hearing loss. From analysis of patient skin, we provide immunohistochemical and bioinformatic data to show that the expression of C x 26 is affected by del(GJB6-D13S1830) in a cell-type-specific manner within the sweat gland. This putative regulatory element of C x 26 expression may be a key factor related to the severe or profound deafness associated with del(GJB6-D13S1830).

Chromosome Deletion↗
PubMed2005

Measuring the appropriateness of prescribing in primary care: are current measures complete?

BACKGROUND AND OBJECTIVES: Appropriateness of prescribing is often assessed by standard instruments. We wished to establish whether judgements of appropriateness that included patients' perspectives and contextual factors could lead to different conclusions when compared with commonly used instruments. To explore the predictive accuracy of these instruments. METHODS: The design was interviews of patients, audio recordings of the consultation and interviews of the doctors, in varied primary care practices in England. Participants were patients who were likely to discuss a medication issue. The outcome measures were judgements of appropriateness made by the researchers and by two instruments: the Prescribing Appropriateness Index and the Medication Appropriateness Index. Implications for the predictive accuracy of the measures was also investigated. RESULTS: From 35 cases there was agreement between the judges and the instruments in 22 cases, 16 were appropriate and 6 inappropriate. Of 10 cases classified as inappropriate by the instruments the judges thought four were appropriate. Of 18 cases classified as appropriate by the instruments, two were considered inappropriate by the judges. In seven cases the prescribing decisions could not be classified by the instruments because the decision was to not prescribe. CONCLUSIONS: Current measures of appropriateness of prescribing depend predominantly on pharmacological criteria, and so do not represent cases that would be judged appropriate when including the patient's views and contextual factors. If most prescribing is appropriate then use of these measures may lead to more false negatives than real negatives. The instruments should be renamed as measures of 'pharmacological appropriateness' and are useful where the incidence of this type of inappropriate prescribing is relatively high.

Adolescent↗
PubMed2005

In vivo gene transfer to the brain cortex using a single injection of HSV-1 vector into the medial septum.

This study shows that an ICP4-replication-deficient herpes simplex virus containing the Moloney murine leukaemia virus LTR fused with the coding sequence for the beta-galactosidase gene can be used as a very effective vector for delivering the beta-galactosidase reporter gene into the rat brain septum. F344 rats received bilateral stereotaxic injections into the nucleus of the diagonal band and into the medial septum. The X-gal stain was used to detect the activity of the expressed beta-galactosidase enzyme. The delivered reporter gene was expressed successfully not only in the neuronal cells of the injected areas but also in cells that project to the injection area such as cortex cells about 6 mm away from the injection sites. Expression was visible at 1, 3 and 9 weeks following injection. We conclude that this vector can effectively deliver genes into different regions of the mature mammalian brain and also to areas distant from the injection site.

Animals↗
PubMed2003

Developing a measure for the appropriateness of prescribing in general practice.

OBJECTIVE: To explore the feasibility of using a broader definition of the appropriateness of prescribing in general practice by developing ways of measuring this broader definition and by identifying possible relationships between different aspects of appropriateness and patient outcomes. DESIGN: A questionnaire study of patients and general practitioners before and after study consultations, supplemented by data collected from patients' medical records and telephone interviews with patients 1 week later. SETTING: General practices in the south of England. PARTICIPANTS: 24 general practitioners and 186 of their consulting patients. MAIN OUTCOME MEASURES: Unwanted, unnecessary, and pharmacologically inappropriate prescriptions; patients' adherence. RESULTS: Before the consultation 42% of patients said they wanted or expected a prescription for their main problem. Prescriptions were written in two thirds (65%) of study consultations, and 7% of these had not been wanted or expected beforehand. Doctors recorded that one in five prescriptions they wrote were not strictly indicated. Of the 92 independent assessments of these prescriptions, four were judged to be inappropriate and in 19 cases the assessors were uncertain. 41% of prescriptions written were wanted, necessary, and appropriate. Subsequently, 18% of patients for whom a prescription had been written were potentially non-adherent and 25% had worries or concerns about their medication. CONCLUSION: The attempt to measure appropriateness of prescribing along the three dimensions of patients', prescribers', and pharmacological perspectives is both feasible and likely to yield valuable insights into the nature of general practice prescribing and patients' use of medicines.

Drug Prescriptions↗
PubMed2002

Dilated pupils and loss of accommodation following diode panretinal photocoagulation with sub-tenon local anaesthetic in four cases.

AIM: To describe pupillary abnormalities associated with diode laser photocoagulation with subTenon's local anaesthetic. METHODS: We describe four cases of tonic pupils following diabetic panretinal photocoagulation with subTenon's local anaesthetic. RESULTS: Six pupils of four patients became dilated and sustained loss of accommodation with denervation hypersensitivity with 0.1% pilocarpine after undergoing panretinal photocoagulation with a subTenon's local anaesthetic. The numbers of burns were not excessive and in one patient it even occurred after only 1200 laser burns. CONCLUSION: Diode laser causes histological changes deeper in the retina and the choroid than in Argon laser. Intense diode laser burns may cause damage to the short ciliary nerves traversing the choroid. In the unanaesthetised patient, pain arises when the laser burn hits these nerves and so may protect the eye from excess damage to the nerves. When the eye is anaesthetised with a subTenon's, local anaesthetic damage to the choroidal nerves may occur without the laser operator being aware that the burns are too intense.

Adult↗
PubMed2000

Noxious hot and cold stimulation produce common patterns of brain activation in humans: a functional magnetic resonance imaging study.

We used functional magnetic resonance imaging (fMRI) to determine whether similar brain regions activate during noxious hot and cold stimulation. Six male subjects underwent whole brain fMRI during phasic delivery of noxious hot (46 degrees C) and noxious cold (5 degrees C) stimulation to the dorsum of the left hand. Mid-brain regions activated included thalamus, basal ganglia and insula. Cortical areas activated included cingulate, somatosensory, premotor and motor cortices, as well as prefrontal and inferior parietal cortex. Most regions activated bilaterally but with stronger activation contralateral to the stimulus. Noxious cold stimulation produced significantly increased volumes of activation compared to noxious heat in prefrontal areas only. Our results suggest a similar network of regions activate common to the perception of pain produced by either noxious hot or cold stimulation.

Adult↗
PubMed2000

Multimethod psychoeducational intervention for preschool children with disruptive behavior: two-year post-treatment follow-up.

This paper describes the 2-year post-treatment follow-up of preschool children identified as having high levels of disruptive behavior at kindergarten entry. They were assigned to four treatment conditions: A no-treatment group, parent-training only, treatment classroom only, and the combination of parent training with the treatment classroom. Interventions lasted the entire kindergarten academic year. Initial post-treatment results reported previously indicated no effects for the parent-training program but some efficacy for the classroom intervention program. For this report, the disruptive behavior (DB) children were subdivided into those who did (n = 74) and did not (n = 77) receive the treatment classroom. Two-year post-treatment follow-up results indicated no differences between the classroom treated and untreated DB groups. These groups also failed to differ in the percentage of children using available treatments across the follow-up period. The DB children in both groups had significantly more symptoms of ADHD and ODD than a community control group (N = 47) at follow-up. They also received higher ratings of externalizing problems on the parent Child Behavior Checklist, more severe ratings of behavior problems at home, and ratings of more pervasive behavior problems at school, and had poorer academic skills. Results suggested that early intervention classrooms for DB children may not produce enduring effects once treatment is withdrawn, and that better approaches are needed for identifying those DB children at greatest risk for later maladjustment.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed2000

Converging evidence that visuospatial cognition is more age-sensitive than verbal cognition.

In 3 separate experiments, the same samples of young and older adults were tested on verbal and visuospatial processing speed tasks, verbal and visuospatial working memory tasks, and verbal and visuospatial paired-associates learning tasks. In Experiment 1, older adults were generally slower than young adults on all speeded tasks, but age-related slowing was much more pronounced on visuospatial tasks than on verbal tasks. In Experiment 2, older adults showed smaller memory spans than young adults in general, but memory for locations showed a greater age difference than memory for letters. In Experiment 3, older adults had greater difficulty learning novel information than young adults overall, but older adults showed greater deficits learning visuospatial than verbal information. Taken together, the differential deficits observed on both speeded and unspeeded tasks strongly suggest that visuospatial cognition is generally more affected by aging than verbal cognition.

Adolescent↗
PubMed2000

Instance-based automaticity and aging: acquisition, reacquisition, and long-term retention.

This research examined age differences in the acquisition and reacquisition of instance-based automaticity. In 2 experiments, young and older adults were trained to enumerate targets presented in otherwise empty displays or in displays that contained distractors. Experiment 1 revealed that older adults required more practice to reach asymptote than young adults. For both age groups, modifications of the identities and locations of targets produced substantial disruptions in performance, whereas modifications of the identities or locations of distractors produced little interference. However, no age differences in the representations of instances in memory were obtained in participants who reached asymptote. Experiment 2 revealed age deficits in the long-term retention and rate of reacquisition of instance-based automaticity 18 months after initial training.

Adolescent↗
PubMed2000

Aging and the development of automaticity in conjunction search.

In two experiments, younger and older observers carried out feature searches for targets defined by their luminance contrast and orientation. Additionally, they received consistent-mapping (CM) training in luminance contrast by orientation conjunction search, followed by a brief exposure to conjunction search under reversal conditions. In Experiment 1, display size effects on reaction time suggested that both younger and older observers were conducting a parallel search in all conditions and showed equivalent disruption at reversal. Experiment 2 was a substantive replication of the first using more difficult conjunction search displays. In addition to latency, we measured the number, duration, and feature-based selectivity of fixations made during conjunction search. Display size effects were larger than in Experiment 2 and were of equivalent magnitude in younger and older people. There were no age differences in improvement in conjunction search and minimal age differences in disruption following reversal. Both age groups demonstrated early in training that they could select items possessing target features (i.e., the color white), and both age groups demonstrated that they could not completely reverse this selectivity when these features no longer defined the target. These experiments have several implications for models of visual attention and age differences therein.

Adult↗
PubMed2000

Multi-method psycho-educational intervention for preschool children with disruptive behavior: preliminary results at post-treatment.

Annual screenings of preschool children at kindergarten registration identified 158 children having high levels of aggressive, hyperactive, impulsive, and inattentive behavior. These "disruptive" children were randomly assigned to four treatment conditions lasting the kindergarten school year: no treatment, parent training only, full-day treatment classroom only, and the combination of parent training with the classroom treatment. Results showed that parent training produced no significant treatment effects, probably owing largely to poor attendance. The classroom treatment produced improvement in multiple domains: parent ratings of adaptive behavior, teacher ratings of attention, aggression, self-control, and social skills, as well as direct observations of externalizing behavior in the classroom. Neither treatment improved academic achievement skills or parent ratings of home behavior problems, nor were effects evident on any lab measures of attention, impulse control, or mother-child interactions. It is concluded that when parent training is offered at school registration to parents of disruptive children identified through a brief school registration screening, it may not be a useful approach to treating the home and community behavioral problems of such children. The kindergarten classroom intervention was far more effective in reducing the perceived behavioral problems and impaired social skills of these children. Even so, most treatment effects were specific to the school environment and did not affect achievement skills. These findings must be viewed as tentative until follow-up evaluations can be done to determine the long-term outcomes of these interventions.

Achievement↗
PubMed1999

Selective interference with verbal and spatial working memory in young and older adults.

Young and older adults were administered digit and location memory span tasks with and without verbal and spatial secondary tasks. Age differences were greater in location span than in digit span; however, there were no age differences in either the magnitude or pattern of effects of secondary tasks. There were also no age differences in the effects of secondary tasks on a combined (digit and location) task. On the digit and location span tasks, both young and older adults showed only domain-specific interference: naming colors selectively interfered with memory for digits, leaving memory for locations unaffected; pointing to matching colors selectively interfered with memory for locations, leaving memory for digits unimpaired. The results of the present study suggest a greater age deficit in spatial working memory than in verbal working memory, but provide no evidence of an age deficit in susceptibility to interference by secondary tasks in either domain.

Adolescent↗
PubMed1999

Individual and developmental differences in working memory across the life span.

The effects of secondary tasks on verbal and spatial working memory were examined in multiple child, young adult, and older adult samples. Although memory span increased with age in the child samples and decreased with age in the adult samples, there was little evidence of systematic change in the magnitude of interference effects. Surprisingly, individuals who had larger memory spans when there was no secondary task showed greater interference effects than their age-mates. These findings are inconsistent with the hypothesis that age and individual differences in working memory are due to differences in the ability to inhibit irrelevant information, at least as this hypothesis is currently formulated. Moreover, our results suggest that different mechanisms underlie developmental and individual differences in susceptibility to interference across the life span. A model is proposed in which memory span and processing speed both increase with development but are relatively independent abilities within age groups.

Adult↗