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J Roberts

Publications and source records attributed to J Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2002

The behavioural effect of middle cerebral artery occlusion on apolipoprotein-E deficient mice.

The behavioural effects of middle cerebral artery occlusion (MCAO) in apolipoprotein-E deficient (Apo-E KO) mice were investigated using a modified SHIRPA protocol and compared with effects in wild type littermate controls. The MCA was permanently occluded by insertion of an intraluminal filament to its origin on the Circle of Willis and behavioural responses were observed 24 h later. MCAO treatment caused a range of changes in the wild type mice whereas, few differences were observed in the Apo-E KO mice in the behavioural observation. In the rotarod task, MCAO operated wild type mice showed a significant reduction in performance compared with sham-operated and non-operated animals. In contrast, both sham and MCAO operated Apo-E KO mice showed significant impairment compared with non-operated controls. A significant reduction in performance was also observed in sham-operated Apo-E KO compared with sham-operated wild type mice. In locomotor activity tests, no significant reduction in activity was observed between non-operated and sham-operated wild type controls, whereas a significant reduction was found between sham operated and MCAO operated mice. In the Apo-E KO mice, both sham and MCAO-operated animals showed a reduction in locomotor activity compared with non-operated mice. Furthermore, Apo-E KO MCAO mice showed a worsened deficit in locomotor activity, which was significantly correlated with exacerbated cortical lesion volume, unlike wild-type MCAO mice. This study shows that Apo-E KO animals demonstrate an impaired functional recovery post surgery which may be further compounded by post experimental stroke and also demonstrates the utility of the SHIRPA test system for investigating behavioural changes in functional outcome post stroke.

Animals↗
PubMed2002

Design and performance of a multicentre, randomized controlled trial of teleconsulting.

We have designed and performed a multicentre, randomized controlled trial of teleconsulting. The trial investigated the effectiveness and cost implications in rural and inner-city settings of using videoconferencing as an alternative to general practitioner referral to a hospital specialist. The participating general practitioners referred a total of 3170 patients who satisfied the entry criteria. Of these, 1040 (33%) failed to provide consent or otherwise refused to participate in the trial. Of the patients recruited to the trial, a total of 1902 (91%) completed and returned the baseline questionnaire. Although the trial was successful in recruiting sufficient patients and in obtaining high questionnaire response rates, the findings will require careful interpretation to take account of the limits which the protocol placed on the ability of general practitioners to select patients for referral.

Family Practice↗
PubMed2002

A UK operational practitioner view--some challenges of health informatics are trans-national.

OBJECTIVE: To explore the relevance of catalysts and inhibitors to the achievement of an inclusive identity for health informatics; particularly from an operational perspective in the UK. METHODS: Consideration of the different dimensions of health informatics, as practiced in a working healthcare delivery environment; specifically commenting on the synergy and disjunctions with academic and scientific practitioners in the some domain. RESULTS AND CONCLUSIONS: There appear to be common ground and internationally applicable issues across the domain. Recognizing the differences and similarities will contribute towards harmonisation of the field and its ultimate elevation to a mature discipline and profession.

Medical Informatics↗
PubMed2002

The effects of carbamazepine and lorazepam on single versus multiple previous alcohol withdrawals in an outpatient randomized trial.

OBJECTIVE: Benzodiazepines are the mainstay of treatment for mild-to-moderate alcohol withdrawal in outpatient settings, but they can interact with alcohol, cause motor incoordination, or be abused. This study compared the therapeutic responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine for the outpatient treatment of acute alcohol withdrawal in terms of patients' previous detoxification histories, and compared the effects of these 2 medications on drinking behaviors in the immediate postdetoxification period. DESIGN: This was a randomized double-blind trial comparing patient responses to carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or >or=2 previous medicated detoxifications). SETTING: A university medical center substance abuse clinic in Charleston, SC. PATIENTS: One hundred thirty-six patients in moderate alcohol withdrawal were randomized. Major exclusions were significant hepatic or hematologic abnormalities and use of medications that could alter withdrawal symptoms. INTERVENTIONS: Patients received 600-800 mg of carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg of carbamazepine or 2 mg of lorazepam. MAIN OUTCOME MEASURES: The Clinical Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12. Daily drinking was measured by patient report using a daily drinking log and a breath alcohol level with each visit. Side effects were recorded daily. RESULTS: Carbamazepine and lorazepam were equally effective at decreasing the symptoms of alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1 day; on average, carbamazepine patients drank less than 1 drink per drinking day and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among those with multiple past detoxifications, the carbamazepine group drank less than 1 drink per day on average and the lorazepam group drank about 5 drinks per day on average (P =.033). Lorazepam-treated patients had a significant rebound of alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a first drink was 3 times greater (P =.04) than for carbamazepine-treated patients. Twenty percent of lorazepam-treated patients had dizziness, motor incoordination, or ataxia and did not recognize their impairment. Twenty percent of carbamazepine-treated patients reported pruritus but no rash. CONCLUSIONS: Carbamazepine and lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior to lorazepam in preventing rebound withdrawal symptoms and reducing post-treatment drinking, especially for those with a history of multiple treated withdrawals.

Adult↗
PubMed2001

Induction of functional and morphological expression of neuropeptide Y (NPY) in cortical cultures by brain-derived neurotrophic factor (BDNF): evidence for a requirement for extracellular-regulated kinase (ERK)-dependent and ERK-independent mechanisms.

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) induces expression of neuropeptide Y (NPY) neurons in aggregate cultures derived from the fetal rat cortex. Using BDNF induction of NPY production and neurite extension of NPY neurons as functional and morphological criteria, respectively, we addressed the question: Does BDNF activate the extracellular-regulated kinase (ERK) pathway and if so, is activated (phosphorylated, P)-ERK required for the induction of both the functional and morphological expression of NPY? BDNF led to a rapid (30 min) and sustained (6 h) phosphorylation of ERK. PD98059 (PD, a specific inhibitor of the ERK kinase MEK), drastically inhibited, LY294002 (LY, a specific inhibitor of phosphatidylinositol-3-kinase, PI-3K) partially inhibited, and GF 109203X (GF, a specific inhibitor of protein kinase C) did not inhibit phosphorylation of ERK. A 24-h exposure to BDNF led to approximately 2-fold increase in the total culture content of NPY ( approximately 60% of which was secreted and approximately 40% remained in the aggregates) and to an abundance of neurite-bearing NPY neurons. BDNF-induced NPY produced and secreted into the medium was inhibited 73% by PD, 52% by LY and not at all by GF. In contrast, BDNF-induced NPY produced and sequestered in the aggregates was not inhibited by any of these inhibitors, suggesting a role for the ERK pathway in induced secretion of NPY. PD or LY did not inhibit BDNF-induced abundance of neurite-bearing NPY neurons. K252a (an inhibitor of TrkB-tyrosine kinase) abolished all the effects of BDNF assessed in our cultures. In summary, we demonstrate that TrkB-mediated activation of the ERK pathway is preferentially required for BDNF induction of NPY produced and secreted but not for the induction of the expression of neurite-bearing NPY neurons. Thus, BDNF induction of the functional and morphological expression of NPY is brought about by ERK-dependent and ERK-independent mechanisms.

Animals↗
PubMed2001

Photochemical studies of A2-E.

Lipofuscin is thought to be involved in age-related macular degeneration as is one of its proposed components, an amphiphillic pyridinium-based bis-retinoid with a quaternary nitrogen atom, known as A2-E. We report the triplet state spectra obtained from photosensitisation using anthracene and 1-nitronaphthalene in benzene and methanol. The triplet state of A2-E has lambda(max) at 550 nm and a lifetime of approximately 30 micros, it is efficiently quenched by molecular oxygen with a second-order quenching rate constant of approximately 1 x 10(9) dm(3) mol(-1) s(-1). There is no significant triplet state formation from direct laser excitation of A2-E and hence its quantum yield of triplet state formation must be <0.01.

Anthracenes↗
PubMed2001

Acute pharyngitis.

Explore the source record for details and available documents.

Acute Disease↗
PubMed2001

Interleukin-1beta induces expression of neuropeptide Y in primary astrocyte cultures in a cytokine-specific manner: induction in human but not rat astrocytes.

Previous studies have demonstrated that astrocyte cultures express neuropeptide Y (NPY) in a regulated manner, namely, phorbol ester leads to an increase in proNPY-mRNA and NPY production. In this respect, the behavior of astrocytes derived from the human fetal or rat neonatal brain is similar (Regul. Pept. 75 (1998) 293). Since astrocytes can be exposed to high levels of IL-1beta, we addressed the question: Does IL-1beta regulate NPY expression by the astrocytes? Primary astrocytes derived from the human fetal or rat neonatal cortex were cultured in serum-free medium. IL-1beta, but not IL-6 or TNF-alpha, led to an increase in NPY production dose-dependently. IL-1beta action manifested in the human but not in the rat astrocytes and it was completely abolished by IL-1 receptor antagonist. The responsiveness to IL-1beta did not diminish upon sub-culture of the astrocytes (five passages). In addition, IL-1beta led to an increase in the abundance of proNPY-mRNA, which was preceded by a rapid and transient increase in cFos-mRNA and a rapid and sustained increase in JunB-mRNA. In contrast to cFos/JunB, IL-1beta did not alter the abundance of cJun-mRNA. In summary, we demonstrate that IL-1beta induction of NPY expression in astrocytes is species- and cytokine-specific and that IL-1 receptor is involved. Moreover, induction of NPY expression is preceded by a rapid increase in the expression of two transcription factors (cFos, JunB) that have been previously (Oncogene 9 (1994) 2369; J. Neurochem. 70 (1998) 1887) implicated in transcriptional regulation of the human NPY gene.

Animals↗
PubMed2001

Nontropic actions of neurotrophins: subcortical nerve growth factor gene delivery reverses age-related degeneration of primate cortical cholinergic innervation.

Normal aging is associated with a significant reduction in cognitive function across primate species. However, the structural and molecular basis for this age-related decline in neural function has yet to be defined clearly. Extensive cell loss does not occur as a consequence of normal aging in human and nonhuman primate species. More recent studies have demonstrated significant reductions in functional neuronal markers in subcortical brain regions in primates as a consequence of aging, including dopaminergic and cholinergic systems, although corresponding losses in cortical innervation from these neurons have not been investigated. In the present study, we report that aging is associated with a significant 25% reduction in cortical innervation by cholinergic systems in rhesus monkeys (P < 0.001). Further, these age-related reductions are ameliorated by cellular delivery of human nerve growth factor to cholinergic somata in the basal forebrain, restoring levels of cholinergic innervation in the cortex to those of young monkeys (P = 0.89). Thus, (i) aging is associated with a significant reduction in cortical cholinergic innervation; (ii) this reduction is reversible by growth-factor delivery; and (iii) growth factors can remodel axonal terminal fields at a distance, representing a nontropic action of growth factors in modulating adult neuronal structure and function (i.e., administration of growth factors to cholinergic somata significantly increases axon density in terminal fields). These findings are relevant to potential clinical uses of growth factors to treat neurological disorders.

Aging↗
PubMed2001

Adoptive immunotherapy of cancer with pharmacologically activated lymph node lymphocytes: a pilot clinical trial.

Adoptive immunotherapy (AIT) of cancer with T lymphocytes may be limited by the need to activate tumor antigen-sensitized cells in vitro. In murine models, we have shown that AIT with tumor-sensitized T cells that have been pharmacologically activated with bryostatin 1 and ionomycin plus interleukin-2 can induce tumor regression. A Phase I clinical trial was carried out to assess the feasibility and toxicity associated with using tumor- or vaccine-draining lymph node cells, activated pharmacologically and expanded in culture with low-dose interleukin-2 and infused intravenously, followed by IL-2 infusion. Nine patients were entered into the trial, and six were treated as planned. Average expansion of cell numbers over 13 to 27 days in culture was 118-fold. No patient's cells reached the target cell number (2.5 x 10(10)). Infusion of these cells did not result in any unexpected toxicities. The toxicities observed were related to IL-2 infusion, and conformed to the expected range of side-effects. Based on these Phase I results, additional trials, with tumor antigen vaccine-sensitized DLN and technical modifications of the culture technique, are planned.

Adult↗
PubMed2001

A randomized, controlled trial of a low-dose contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel for acne treatment.

OBJECTIVE: To evaluate the efficacy of a low-dose oral contraceptive (OC) containing 100 microg of levonorgestrel (LNG) and 20 microg of ethinyl estradiol (EE) compared with placebo for the treatment of moderate acne. DESIGN: Multicenter, randomized, double-blind, placebo-controlled clinical trial. SETTING: Outpatient dermatology clinics. PATIENT(S): Women (> or =14 years old; n = 350) with normal menstrual cycles and moderate acne were randomized to receive LNG/EE or placebo for six cycles. INTERVENTION(S): Twenty microg of EE and 100 microg of LNG. MAIN OUTCOME MEASURE(S): Acne lesion counts and clinician global assessment were performed at baseline and at each cycle. Patient self-assessment was carried out at baseline and at cycles 4 and 6; blood pressure and weight were measured at baseline and at cycles 1, 3, and 6. RESULT(S): Inflammatory, noninflammatory, and total lesion counts at cycle 6 with LNG/EE were significantly lower compared to placebo. Patients in the LNG/EE group also had significantly better clinician global and patient self-assessment scores than those in the placebo group at cycle. Changes in weight from baseline were similar between patients in the LNG/EE and placebo groups at all measured time points. CONCLUSION(S): This double-blind, placebo-controlled study demonstrates that a low-dose OC containing 20 microg of EE and 100 microg of LNG is an effective and safe treatment for moderate acne.

Acne Vulgaris↗
PubMed2001

Obesity and preeclampsia: the potential role of inflammation.

OBJECTIVE: Systemic inflammation might contribute to the pathogenesis of preeclampsia. In addition, the association between obesity and inflammation in preeclampsia has not been examined in detail. We determined whether first-trimester elevation of serum C-reactive protein, an index of systemic inflammation, was associated with preeclampsia. METHODS: We conducted a prospective, nested case-control study among women enrolled in the Massachusetts General Hospital Obstetrical Maternal Study cohort. High-resolution C-reactive protein assays were performed on first-trimester (11 +/- 2 weeks' gestation) serum samples in 40 women in whom preeclampsia developed (blood pressure [BP] greater than 140/90 mmHg, and proteinuria, either 2+ or more by dipstick or greater than 300 mg per 24 hours), and in 80 matched controls. This sample size had greater than 80% power to detect a difference in C-reactive protein levels between cases and controls. We used nonparametric tests to compare C-reactive protein levels and conditional logistic regression to control for confounding variables. RESULTS: First-trimester C-reactive protein levels were significantly higher among women in whom preeclampsia subsequently developed compared with controls (4.6 compared with 2.3 mg/L, P =.04). When women were subdivided into C-reactive protein quartiles, the odds ratio (OR) of being in the highest quartile of C-reactive protein was 3.2 (95% confidence interval [CI] 1.1, 9.3, P =.02) among cases of preeclampsia compared with controls. When body mass index (BMI) was added to the multivariable model, the highest quartile of C-reactive protein was no longer associated with increased risk of preeclampsia (OR 1.1, 95% CI.3, 4.3, P =.94). In the same model without BMI, the highest quartile of C-reactive protein was associated with increased risk of preeclampsia (OR 3.5, 95% CI 1.3, 9.5, P =.01). CONCLUSION: In women with preeclampsia, there was evidence of increased systemic inflammation in the first trimester. Inflammation might be part of a causal pathway through which obesity predisposes to preeclampsia.

Adult↗
PubMed2001

When the bough breaks: provider-initiated comprehensive care is more effective and less expensive for sole-support parents on social assistance.

This 5-year study conducted in Ontario, Canada is designed to assess the effects and expense of adding a mix of provider-initiated interventions to the health and social services typically used in a self-directed manner by sole-support parents and their children receiving social assistance in a national system of health and social insurance. Results from a 2-year interim analysis show that providing social assistance families with proactive comprehensive care (health promotion, employment retraining, and recreation activities for children) compared to allowing families to fend for themselves in a self-directed manner, results in 15% more exits from social assistance within 1 year and substantial savings to society in terms of social assistance payouts. It is no more expensive to provide health and social services in a comprehensive fashion, and equivalent reductions in parent mood disorder and child behavior disorders, as well as equivalent increases in parent social adjustment and child competence levels were also observed. This study presents clear evidence that providing comprehensive care to social assistance recipients produces tremendous short- and long-term financial gains and societal benefits.

Adolescent↗
PubMed2001

Results of autologous stem cell transplant in multiple myeloma patients with renal failure.

Data are presented on 81 multiple myeloma (MM) patients with renal failure (creatinine > 176.8 micromol/l) at the time of autologous stem cell transplantation (auto-SCT), including 38 patients on dialysis. The median age was 53 years (range: 29-69) and 26% had received more than 12 months of prior chemotherapy. CD34+ cells were mobilized with granulocyte colony-stimulating factor (G-CSF) alone (n = 51) or chemotherapy plus G-CSF (n = 27), yielding medians of 10 and 16 x 106 CD34+ cells/kg respectively (P = 0.003). Sixty patients (27 on dialysis) received melphalan 200 mg/m2 (MEL-200). Because of excessive toxicity, the subsequent 21 patients (11 on dialysis) received MEL 140 mg/m2 (MEL-140). Thirty-one patients (38%) completed tandem auto-SCT, including 11 on dialysis. Treatment-related mortality (TRM) was 6% and 13% after the first and second auto-SCT. Median times to absolute neutrophil count (ANC) > 0.5 x 109/l and to platelets > 50 x 109/l were 11 and 41 d respectively. Non-haematological toxicities included mucositis, pneumonitis, dysrhythmias and encephalopathy. At a median follow up of 31 months, 30 patients have died. Complete remission (CR) was achieved in 21 patients (26%) after first SCT and 31 patients (38%) after tandem SCT. Two patients discontinued dialysis after SCT. Median durations of complete remission (CR) and overall survival (OS) have not been reached; probabilities of event-free survival (EFS) and OS at 3 years were 48% and 55% respectively. Dialysis dependence and MEL dose did not affect EFS or OS. Sensitive disease prior to SCT, normal albumin level and younger age were independent prognostic factors for better OS. In conclusion, renal failure had no impact on the quality of stem cell collections and did not affect engraftment. MEL-140 had an acceptable toxicity and appeared equally effective as MEL-200. In the setting of renal failure, the role of auto-SCT early in the disease course and benefits of tandem SCT require further evaluation.

Adult↗
PubMed2001

Components of a proper hospital discharge for elders.

SIGNIFICANCE: Effective discharge planning is a vital link in continuity of care for elders. Previous studies identify problems with planning for elders' discharge from the hospital and problems elders encounter managing care post-discharge. However, little attention has been given to identifying effective discharge planning processes. Explicating the components of effective discharge planning is critical to replicate the process in other health care settings and predict post-discharge outcomes. PURPOSE: The purpose of this study was to identify the components of effective discharge planning for elders and factors that impede planning. METHODS: Ethical approvals were obtained from the University and National Health Service (NHS) Trust. Qualitative methods were used and data were collected from two wards in a 78-bed geriatric rehabilitation hospital that was part of a National Health Service Trust serving Southwest London. Data included semi-structured interviews and documents related to discharge planning, care delivery, and community resources. A total of 24 semi-structured interviews were conducted with health care professionals who were part of the hospital's multidisciplinary team, those affiliated with the Community Trust that provided aftercare, elders, and family carers. RESULTS: Participants consistently used the term "proper discharge" when referring to effective discharge planning. The multidisciplinary team comprised a vital context for a proper discharge. The findings indicated that three circles of communication were central in a four stage discharge process. Different circles of communication were key at different stages. CONCLUSIONS: The findings provide insights for educating nurses about effective planning practices and examining the global significance of impediments to a proper hospital discharge.

Age Factors↗
PubMed2001

Consistency, context and confidence in judgements of affective communication in adults with profound intellectual and multiple disabilities.

Twenty-four service providers rated 12 video samples of four service users with whom they were familiar for affective behaviour (i.e. 'like'/'dislike') and confidence (i.e. 'certain'/'uncertain') in their judgement. Each video sample had been recorded as part of a stimulus preference assessment during which a wide range of specific stimuli were presented to each service user. Each video sample was presented twice in a counterbalanced design either with contextual information, i.e. what the presented stimulus was (C) or without such information, i.e. context free (CF). The observers showed considerable individual variation in their judgements, largely uninfluenced by the availability or otherwise of contextual information. However, as a group, observers significantly distinguished between video samples with regard to affective communication (determined through multiple analyses of variance) and the pattern of judgements, i.e. the relative judgement of positive or negative affect, from one sample to another. This showed a good level of consistency between observers (determined through principal components analysis). The impact of contextual information was not apparent for all video samples. However, contextual information significantly influenced judgements in four samples, typically making them more extreme; for example, a response indicative of positive affect in the CF situation became more positive when contextual information was provided, indicating that the stimulus was one that the participant was thought to like.

Adult↗