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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12.

Neuroblastoma immunotherapy using cytokine-modified tumour cells has been tested in clinical trials. However, because of the complex nature of antitumour immune responses, a number of therapies may be required for complete tumour eradication and generation of systemic immunity. We report here the improved antitumour effect of two cytokines, interleukin-2 (IL-2) and interleukin-12 (IL-12), when coexpressed by neuroblastoma cell lines. Initially, transfection of human and mouse neuroblastoma cell lines resulted in high expression levels of biologically active IL-2 and IL-12 in vitro. These cytokines when expressed by transfected Neuro-2A cells completely abolished their in vivo tumorigenicity in a syngeneic neuroblastoma model. Vaccination of established tumours with IL-12-producing cells exhibited a clear effect with reduced tumour growth in the presence of IL-2. In vivo depletion studies showed that CD4(+) and CD8(+) T cells mediate the response against cytokine-producing cells. These results suggest that IL-2 and IL-12, when cotransfected in tumour cells, are effective against established disease and provide a promising immunotherapeutic approach for the treatment of neuroblastoma.

Adjuvants, Immunologic↗
PubMed2003

Ultrastructural and behavioural changes precede amyloid deposition in a transgenic model of Alzheimer's disease.

We describe the thorough characterisation of a new transgenic mouse line overexpressing the 695-amino acid isoform of human amyloid precursor protein harbouring the Swedish double familial Alzheimer's disease mutation. This line, referred to as TAS10, exhibits neuropathological features and cognitive deficits that are closely correlated to the accumulation of Abeta in their brain and that are reminiscent of those observed in AD. Data on the TAS10 line are presented at five time points: 2, 6, 12, 18 and 24 months in a longitudinal study. The TAS10 line is characterised by the following changes: i) significant age-related increases in the levels of total and individual species (1-40, 1-42) of beta-amyloid in the brains of transgenics compared with non-transgenic littermates; ii) transgenic mice showed pronounced spatial learning deficits in the Morris water maze at 6 months and working memory deficits by 12 months; iii) amyloid plaque and associated pathologies were observed by the 12-month time point and the burden increased substantially, particularly in the cortex, by 18 months; iv) electron microscopy of the hippocampus of transgenic mice showed evidence of abnormal ultrastructural features such as dystrophic neurites and lipid deposits that developed from 6 months and increased in number and severity with age. Morphometric studies demonstrate that the synapse to neuron ratio is higher in transgenics than in control mice at 12 months, but this ratio decreases as they age and synapse size increases. Thus, this mouse model exhibits a close correlation of amyloid burden with behavioural deficits and ultrastructural abnormalities and so represents an ideal system to study the mechanisms underlying the impact of amyloid pathology on CNS function.

Alzheimer Disease↗
PubMed2003

Stress at work: the current perspective.

Stress caused by work is costing UK organisations dearly. However, despite numerous appalling statistics and increased publicity around the problem, many organisations are still failing to do anything to reduce it. This article suggests reasons why this is the case and outlines attempts by the Health and Safety Executive (HSE) to try to overcome the problem. It also explains the background behind health and safety initiatives for stress, and provides an overview of the guidelines for employers and employees put forward by the HSE in June 2001. Finally, it describes the latest guidelines for work-related stress which resulted from the Hatton v. Sutherland Court of Appeal verdict in February 2002.

Cost of Illness↗
PubMed2003

'Toothache stories': a qualitative investigation of why and how people seek emergency dental care.

OBJECTIVE: To understand from the patient's perspective the types of dental problem which present at weekends, how they affect people, and the care-seeking behaviour of emergency dental patients. BASIC DESIGN: Consecutive patients attending two emergency dental clinics at weekends were interviewed prior to seeing the dentist. The audio-recorded interview transcripts were analysed using the "framework" method of applied qualitative data analysis. SETTING: A community-based and a dental hospital emergency dental clinic. SUBJECTS: 44 emergency dental patients. RESULTS: Pain was the main presenting symptom, a key domain of quality of life and the underlying cause of most other quality of life effects. However, for patients deciding what symptoms mean--crucially whether they mean they need to see a dentist urgently--a wide range of other contextual factors come into play. These go beyond the individual patient's recent and current perception of symptom intensity. They encompass past experience of similar symptoms, past care-seeking experiences, anticipated effects on quality of life, anticipated service availability, joint decision-making and lay information from family and friends, professional opinions from non-dentists, expectations concerning what work dentists should do, and what symptoms distinguish "simple toothache" from more serious problems. CONCLUSIONS: The effects of, and meanings which people attach to, acute dental symptoms are complex. Combined with poor awareness of the existence of emergency dental services it is not surprising that patients' pathways to care are correspondingly complicated. The planning of emergency dental services should be based on a broader, patient-derived understanding of the need for them.

Adolescent↗
PubMed2002

Use of electrical impedance scanning in the differentiation of sonographically suspicious and highly suspicious lymph nodes of the head-neck region.

Sonographic differentiation between inflammatory and malignant lymph nodes is difficult, due in part to almost unchanged morphology of small lymph node metastases; however, as cancer cells exhibit altered dielectric properties, measurement of local electrical field distortions may be useful as adjunct to ultrasound in detection of malignancy. In this study, we evaluated the ability of electrical impedance scanning (EIS) to differentiate cervically located sonographically suspicious or highly suspicious lymph nodes. Seventy patients with 106 sonographically suspicious lymph nodes (mean size 20 x 13 x 13 mm, mean depth 8 mm) were examined using TransScan TS2000 (Siemens, Erlangen, Germany; manufactured by TransScan Research and Development Co., Israel). Included in the study were cervical ( n=64), inframandibular/periparotideal ( n=32) and nuchal/supraclavicular ( n=10) nodes. The EIS results were compared with histopathological ( n=100) and serological ( n=6) findings. Sixty-two of 64 malignant lymph nodes were correctly detected using EIS; 19 of 42 inflammatory/benign lymph nodes were correctly identified as benign (true positive 96.9%, true negative 45.2%; accuracy 71.3%, negative predictive value 90.5%, positive predictive value 59.6%). The high tumour detection rate achieved in this study suggests that EIS may be of value as an adjunctive technique in differentiation of lymph nodes of the head-neck region. Software changes to reduce the high number of false-positive markers are, however, necessary to improve the value in the evaluation during a regular clinical routine.

Carcinoma, Squamous Cell↗
PubMed2002

Endogenous adenosine regulates neutrophil pro-inflammatory activities by cyclic AMP-dependent accelerated clearance of cytosolic calcium.

OBJECTIVE AND DESIGN: To identify the involvement of adenosine in restoration of Ca2+ homeostasis to activated human neutrophils. MATERIALS: Neutrophils were isolated from venous blood taken from healthy, adult, human volunteers. TREATMENT: The cells were exposed to adenosine deaminase (ADA, 0.1-2 units/ml) for 10 min at 37 degrees C prior to activation with N-formyl-L-methionyl-L-leucyl-L-phenylala-nine (FMLP, 1 microM). METHODS: Cytosolic Ca2+ concentrations and transmembrane fluxes of the cation in FMLP-activated neutrophils +/- ADA were measured using spectrofluorimetric and radiometric procedures respectively, while intracellular cAMP and inositol triphosphate were measured by radioassay, and superoxide production and elastase release by, chemiluminescence and colourimetric methods respectively. Levels of statistical significance were calculated using the Mann-Whitney U-test and ANOVA. RESULTS: Although FMLP-activated generation of inositol triphosphate and mobilisation of Ca2+ from neutrophil internal stores, as well as the magnitude of the subsequent efflux and store-operated influx of the cation were unaffected by ADA, there was a prolonged elevation in cytosolic Ca2+ in the presence of the enzyme, which was associated with failure to activate adenylate cyclase and with increased production of superoxide and release of elastase. These effects of ADA were attenuated by dibutyryl cAMP (4 mM), CGS 21680 (1 microM) and rolipram (0.5 microM), as well as by EGTA (10 mM). CONCLUSIONS: These results are compatible with a physiological role for adenosine in promoting deactivation of neutrophils, possibly by promoting cAMP-dependent clearance of Ca2+ from the cytosol of the cells by the endo-membrane Ca2+-ATPase.

Adenosine↗
PubMed2002

Reconstructing the history of 14C discharges from Sellafield: part 1--atmospheric discharges.

14C specific activities, above ambient background levels, were determined in individual treerings (corresponding to the years 1950-1999) sectioned from an oak tree that was felled in autumn 1999, from a location 1.5 km east of the Sellafield nuclear fuel reprocessing plant in Cumbria. north-west England. The data were used to produce a new, improved, reconstruction of Sellafield's annual atmospheric 14C discharges between 1951 and 1999, using the most reliable discharge data set (1994-1999) as the primary basis for the determination of a new calibration factor that relates excess 14C activity in individual tree rings to the annual discharge during the corresponding year. The results indicate that the current British Nuclear Fuels plc (BNFL) estimate of total 14C discharges to the atmosphere prior to 1978 is significantly overestimated, while the current estimate of total 14C discharges after 1978 is very similar to that determined in this study. In this study, the total activity of 14C discharged to the atmosphere from Sellafield between 1951 and 1999 is estimated to be 259+/-63 TBq (at 2 std. dev.). The BNFL current estimate is 360TBq.

Air Pollutants, Radioactive↗
PubMed2002

Botulinum toxin A as a treatment for excessive drooling in children.

Drooling is problematic for some neurologically impaired children. Botulinum toxin A injection to salivary glands has effectively reduced drooling in adults but has only recently been used to treat children. This was a preliminary study to determine the efficacy and safety of botulinum toxin in children. Children identified as having severe daily drooling were enrolled. The preinjection assessment included measurement of the amount and frequency of drool. Each parotid gland was injected with 5 U of botulinum toxin A. Follow-up was for a minimum of 16 weeks. Nine children were enrolled, 4-17 years of age. All children had moderate or severe mental retardation. At week 4, all patients had a reduced drooling frequency and eight of nine patients had a reduction in the weight of saliva. Overall, five of nine parents (55%) deemed the treatment successful. This preliminary study demonstrates that botulinum toxin A is a relatively effective treatment for some children with significant drooling without serious side effects.

Adolescent↗
PubMed2002

Auditory evoked potential monitoring with the AAITM-index during spinal surgery: decreased desflurane consumption.

BACKGROUND: The auditory evoked potential (AEP) is sensitive to the depth of anesthesia. The A-line monitor is a novel device that processes the amplitude and latency of the AEP during the mid-latency time window to provide a simple numerical index, the AAItrade mark-index. The hypothesis of the present study was that titration of anesthetic depth (desflurane) by means of the AAItrade mark-index could decrease the consumption of the main anesthetic and shorten emergence times. METHODS: Thirty ASA I-II patients scheduled for elective open spine surgery under general anesthesia were randomly allocated to two groups. Group I (n=15), the main anesthetic, desflurane, was titrated with a target AAItrade mark-index of 20+/-5. Group II (n=15), desflurane was titrated according to routine clinical signs, including heart rate, blood pressure, sweating and tears. No fixed MAC-multiple was sought. The primary study variable was desflurane consumption; and secondary study variables were time to extubation and orientation. RESULTS: All patients had an uncomplicated course and no patients showed signs of awareness or had any recall postoperatively. AAItrade mark-index guidance reduced desflurane consumption by 29% and improved emergence. Time until extubation and orientation and ability to state name and date of birth was significantly shortened among AAItrade mark-index titrated patients. CONCLUSION: Titrating depth of desflurane anesthesia using AAItrade mark-index guidance decreased main anesthetic consumption and improved emergence during spine surgery.

Aged↗
PubMed2002

Platelet-activating factor and lyso-PAF possess direct antimicrobial properties in vitro.

The effects of platelet-activating factor (PAF) and lyso-platelet-activating factor (L-PAF) at concentrations of 0.25-20 microg/ml on potassium transport and growth of gram-positive and gram-negative bacteria have been investigated in vitro and compared with those of lysophosphatidylcholine (LPC). Potassium transport was determined using 86Rb+ as tracer, while growth was measured according to the extent of uptake of radiolabeled amino acids. All of the test phospholipids caused dose-related inhibition of 86Rb+-uptake and growth of gram-positive bacteria, the order of potency being PAF>LPC>L-PAF. Gram-negative bacteria, on the other hand, were less sensitive to the inhibitory effects of the phospholipids on K+ transport and growth. Some, but not all, of the gram-positive and gram-negative bacteria were able to degrade LPC, but not PAF or L-PAF, demonstrating that enzymatic degradation of phospholipids does not explain the differential sensitivity to these agents. The bioactive phospholipids LPC, PAF and L-PAF may represent an oxygen-independent antimicrobial host defense system operative primarily against gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed2002

Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway.

Retinal axons are led out of the eye by netrin-1, an attractive guidance cue which is secreted at the optic nerve head. In the optic pathway, however, netrin-1 is expressed in areas that exclude retinal axon growth. This suggests that axons may change in their responsiveness to netrin-1 as they advance along the pathway. Indeed, in our 'whole-pathway' preparation in Xenopus, a gradual change from attraction to repulsion occurred as retinal axons emerged from progressively distal points along the pathway. We also found that axons that were aged in culture without pathway experience underwent a similar change, which correlated with a decline in cyclic AMP (cAMP) and netrin-1 receptor expression. Cyclic AMP elevators and adenosine A2b receptor agonists rejuvenated the behavior of old growth cones, causing them to regain attraction to netrin-1, whereas antagonists caused young growth cones to be repelled. These findings show that netrin-1 responsiveness is developmentally regulated and suggest that intrinsic changes that lower cAMP levels underlie this regulation.

Aging↗
PubMed2002

Dissociation of the PAF-receptor from NADPH oxidase and adenylate cyclase in human neutrophils results in accelerated influx and delayed clearance of cytosolic calcium.

The magnitude and duration of the abruptly occurring increases in cytosolic Ca2+ in human neutrophils following activation with PAF (20 and 200 nM) and FMLP (1 microM), have been compared and related to alterations in NADPH oxidase activity, membrane potential and intracellular cyclic AMP. Cytosolic Ca2+ and membrane potential were measured by spectrofluorimetry, transmembrane fluxes of Ca2+ by radiometric procedures, and NADPH oxidase activity and cyclic AMP by chemiluminescence and radioimmunoassay respectively. Activation of neutrophils with both PAF (200 nM) and FMLP (1 microM) was accompanied by an abrupt increase in cytosolic Ca2+, which was of similar magnitude for each activator (393+/-9 and 378+/-17 nM respectively). Unlike FMLP-activated cells in which Ca2+ was rapidly removed from the cytosol, peak levels of cytosolic Ca2+ were sustained for longer (0.14+/-0.02 vs 1.16+/-0.04 min, P<or=0.0001) and declined at a slower rate in PAF-treated neutrophils. The prolonged elevation of cytosolic Ca2+ in PAF-treated cells was due to accelerated store-operated influx of extracellular cation and was attenuated by dibutyryl cyclic AMP (4 mM), the Ca2+-chelator, EGTA (5 mM), and SKF 96365 (10 microM). In contrast to FMLP, basal levels of superoxide production and cyclic AMP were unaltered in PAF-activated neutrophils, while only moderate membrane depolarization was detected. These observations demonstrate that mechanisms which restore Ca2+ homeostasis to FMLP-activated neutrophils, viz. activation of NADPH oxidase and adenylate cyclase, are not operative in PAF-treated cells, presenting the potential hazard of Ca2+ overload and hyperactivity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2002

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis.

Fifty-seven patients receiving unrelated donor (UD) BMT were matched for disease and stage with 57 recipients of genotypically matched related donor (MRD) BMT. All UD recipients were matched serologically for A and B and by high resolution for DR and DQ antigens. All patients received CsA and 'short course' methotrexate with folinic acid. Unrelated donor BMT patients also received thymoglobulin 4.5 mg/kg (6 mg/kg if <30 kg) in divided doses over 3 days pretransplant. For UD and RD BMT, respectively, incidence of acute GVHD grade II-IV was 19 +/- 6% vs 36 +/- 8%, grade III-IV 10 +/- 6% vs 18 +/- 7%, chronic GVHD 44 +/- 8% vs 51 +/- 8%, non-relapse mortality 15 +/- 5% vs 8 +/- 4% at 100 days, 28 +/- 8% vs 36 +/- 7% at 3 years. At 3 years, relapse was 45 +/- 7% vs 42 +/- 7%, and disease-free survival 39 +/- 7% vs 37 +/- 7%. None of these differences are significant. Three-year overall survival was identical at 42 +/- 7%. For 29 patients with low/intermediate risk leukemia, disease-free survival was 68 +/- 10% after UD BMT vs 59 +/- 9% for RD BMT recipients (P = NS). Corresponding figures for high risk patients were 14 +/- 7% and 21 +/- 8%, respectively. We conclude that UD BMT recipients matched as above and given pretransplant ATG have similar outcomes to recipients of MRD BMT using conventional drug prophylaxis. Unrelated donor BMT should be considered in any circumstance where MRD BMT is routine.

Antilymphocyte Serum↗
PubMed2002

The effects of nitrous oxide on the auditory evoked potential index during sevoflurane anaesthesia.

We have studied the effects of nitrous oxide on the auditory evoked response index (AAI-index) derived from the A-line monitoring device during sevoflurane anaesthesia in 21 patients undergoing minor ambulatory surgery. During sevoflurane anaesthesia with an AAI-index < 30, the addition or withdrawal of nitrous oxide in a concentration of 66% end tidal did not show any linear dose dependent change in AAI-index . However, comparing nitrous oxide > 40% to nitrous oxide < 10% end tidal concentration the AAI-index did decrease, p < 0.05. The AAI-index is either non-linear at deeper anaesthetic levels or is insensitive to the anaesthetic effects of nitrous oxide in terms of MAC-multiples.

Adult↗
PubMed2002

Electrical impedance scanning of lymph nodes: initial clinical and technical findings.

PURPOSE: The sonographic differentiation between inflammatory and malignant lymph node enlargement remains imprecise. Electrical impedance scanning (EIS) is of more value in malignant breast lesions, and this study was undertaken to determine if it was of use in differentiating nodal enlargement. MATERIALS AND METHODS: Two hundred and thirty-six sonographically suspicious lymph nodes (146 patients) of mean size 18 x 11 x 11 mm mean depth 9 mm were examined using a commercially available electrical impedance imaging system. The following locations of lymph nodes were included in the study: cervical, axillary, inguinal, supraclavicular and chest/abdominal wall. The EIS results were compared to histopathological, serological or follow up findings. RESULTS: Using EIS 105/115 malignant nodes were correctly diagnosed, while 70/121 inflammatory or benign lymph nodes were correctly identified as benign by EIS (10 false-negative, 51 false-positive). Sensitivity (91.3%) and specificity (57.9%) were obtained. Corresponding negative and positive predictive values were 87.5% and 67.3%, respectively. CONCLUSIONS: Results from this initial study suggest potential value for EIS as an imaging adjunct in the differentiation of sonographically equivocal lesions. Best accuracy was achieved at chest/abdominal wall and inguinal locations. Due to technical restrictions with the present system, the examination of inframandibular and para-aortal lymph nodes should be limited to special cases.

Diagnosis, Differential↗
PubMed2002

Neutropenic enterocolitis (typhlitis) after pediatric bone marrow transplant.

BACKGROUND/PURPOSE: Neutropenic enterocolitis (typhlitis) is a common consideration after bone marrow transplantation. This study reviews the authors' experience with abdominal pain and typhlitis in an active pediatric bone marrow transplant program. METHODS: The Pediatric Bone Marrow Transplant Program Database was reviewed for patients presenting with abdominal pain or typhlitis. RESULTS: From 1993 to 2000 a total of 142 transplants have been performed. Of these, 97 patients had abdominal pain, and 5 had radiologically proven typhlitis. Nonspecific abdominal pain developed on the 12 +/- 11th day posttransplant, whereas patients in whom typhlitis developed were diagnosed on day 15.5 +/- 7. All patients were treated with prophylactic antibiotics consisting of acyclovir, fluconazole, and septra. With the onset of abdominal pain, 73 of 97 patients were placed on therapeutic antibiotics; patients identified with typhlitis had amphotericin plus GCSF added. No clinical features differentiated abdominal pain patients from typhlitis. Oral feeding and time of discharge was similar in both groups. Surgical intervention was not required, and no patients died with typhlitis. CONCLUSIONS: Abdominal pain is a common symptom after bone marrow transplant; however, typhlitis is relatively rare, and surgical intervention was not required in this series. Broad-spectrum (including fungal) antibiotic therapy appears to be an effective treatment for typhlitis in this patient population.

Abdominal Pain↗