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Biomedical subjects

L Kirby

Publications and source records attributed to L Kirby.

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

Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease.

The authors report a patient with Alzheimer disease (AD) without encephalitis who was immunized with AN-1792 (an adjuvanted formulation of Abeta-42). There were no amyloid plaques in the frontal cortex and abundant Abeta-immunoreactive macrophages, but tangles and amyloid angiopathy were present. The white matter appeared normal and minimal lymphocytic infiltration in the leptomeninges was observed. This case illustrates the effects of an Abeta-based immunization on AD pathogenesis in the absence of overt meningoencephalitis and leukoencephalopathy.

Aged↗
PubMed2001

Dialysis for end-stage renal disease. Determining a cost-effective approach.

OBJECTIVE: Renal replacement therapy (RRT) is essential for maintenance of life for those with end-stage renal disease. However, there remain many areas of uncertainty about which method of RRT should be chosen. This paper reports an economic model based on a systematic review that attempts to determine which method of dialysis, continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis, a patient should have as the initial method of RRT. METHODS: A systematic review and a costing exercise carried out in a Scottish hospital were used to populate a Markov model. Scenario analysis was used to model plausible variations in variables included in the model. RESULTS: In 8 of the 16 scenarios developed hemodialysis dominated CAPD. In a further eight scenarios, the cost per life-year displayed considerable variability, ranging from between 5,000 Pounds to 51,000 Pounds. The higher costs per life-year were associated with minimum estimates of additional survival for a patient starting RRT on hospital hemodialysis. CONCLUSION: It may be more cost-effective to manage patients starting on RRT with hospital hemodialysis than CAPD. This has particular implications for the United Kingdom, given that up to 50% of new patients receive CAPD.

Cost-Benefit Analysis↗
PubMed2000

Extent of misclassification of death from Creutzfeldt-Jakob disease in England 1979-96: retrospective examination of clinical records.

OBJECTIVE: To investigate the extent to which deaths from Creutzfeldt-Jakob disease were misclassified during 1979-96. DESIGN: Structured review of clinical records based on predetermined criteria to determine whether death could have been due to sporadic or variant Creutzfeldt-Jakob disease. SETTING: 100 health authorities and 275 NHS trusts in England. SUBJECTS: 1485 people who died aged 15-44 years from selected neurological disorders in England during 1979-96. MAIN OUTCOME MEASURE: Cause of death. RESULTS: The clinical records of 705 (48%) subjects were successfully traced. Tracing of clinical records was highest in subjects who died during 1990-6. There was sufficient information in the records of 640 (91%) of the 705 subjects to exclude Creutzfeldt-Jakob disease as a cause of death. In 61 (9%) subjects, there was insufficient information to reach any conclusion about the validity of the cause of death recorded on the death certificate. The clinical records of four subjects were examined further by the National Creutzfeldt-Jakob Disease Surveillance Unit; none was thought to have died from Creutzfeldt-Jakob disease. CONCLUSIONS: No new cases of sporadic or variant Creutzfeldt-Jakob disease were detected in a sample of deaths most likely to have included misclassified cases. This suggests that the surveillance system is unlikely to have missed a significant number of cases among people aged 15-44 years. Hence, any rapid increase in the number of cases of variant Creutzfeldt-Jakob disease in this age group is likely to be real not artefactual.

Adolescent↗
PubMed2000

Geographic variations in conceptions to women aged under 18 in Great Britain during the 1990s.

This article examines geographic variations in conceptions to women aged under 18. It presents data on conception rates and the percentage leading to abortion for the three countries of Great Britain, the Government Office Regions of England and local authorities within Great Britain. It provides an overview of variations between areas at each of the three geographic levels and examines whether this variation is associated with the social and demographic characteristics of local authority areas. This article is the first occasion on which conception rates for Scotland have been published on a comparable basis to England and Wales and also the first use of the revised ONS classification to examine conceptions to women aged under 18.

Abortion, Induced↗
PubMed1999

Recanalization of an occluded popliteal artery following posterior knee dislocation.

Posterior knee dislocation results in popliteal artery injury in up to one-third of cases. Prompt recognition and treatment of arterial injury is essential for limb salvage. We report a case of complete occlusion of the popliteal artery following posterior knee dislocation treated with saphenous vein bypass without exclusion of the injured arterial segment. Follow-up duplex scanning demonstrated a patent vein graft and a patent ipsilateral popliteal artery. This report suggests that, in some instances, a traumatically occluded popliteal artery may recanalize, and that revascularization with a bypass graft may be the preferred method of repair, particularly in young patients.

Child↗
PubMed1999

Development of obstructive hydrocephalus with lumboperitoneal shunting following subarachnoid hemorrhage.

Hydrocephalus is a frequent complication of subarachnoid hemorrhage (SAH). The optimum method of treating hydrocephalus in this setting has not been determined. We review our experience with patients developing communicating hydrocephalus secondary to SAH and subsequently treated with lumboperitoneal (LP) shunts. Following hospitalization for the treatment of SAH, patients who developed clinical symptoms and radiologic signs of hydrocephalus were treated with (ventriculoperitoneal) VP or LP shunting. Eighteen patients received an LP shunt, of which seven (28%) developed a non-communicating or obstructive hydrocephalus. These seven patients underwent replacement with a VP shunt and have not had further complications. In the setting of post-SAH communicating hydrocephalus, obstructive hydrocephalus may develop after LP shunt placement. Patients who develop this complication and have their LP shunts converted to VP shunts have a favorable prognosis.

Adult↗
PubMed1999

Preliminary assessment of whole-blood, red-cell and platelet- leucodepleting filters for possible induction of prion release by leucocyte fragmentation during room temperature processing.

Universal leucodepletion is being introduced in the U.K. to reduce a theoretical risk of Creutzfeldt-Jakob disease (CJD) transmission. If CJD infectivity is associated with leucocytes, any cell fragmentation associated with filtration could reduce the potential benefit. Four types each of whole blood, red cell and platelet leucodepletion filters were assessed after holding of blood units for at least 4 h at 22 degrees C. In all cases the mean residual leucocyte content was <1 000 000 per unit, with only two individual filtered whole blood units having a leucocyte content exceeding this. Evidence of leucocyte fragmentation during filtration was sought but not found by assay of soluble elastase, beta-thromboglobulin and normal prion protein, as well as by isotopic labelling of leucocyte external membrane. These preliminary studies indicate that it was possible to prepare leucodepleted blood components by filtration at room temperature, and that this appeared not to be associated with overt cell fragmentation. Definitive demonstration that fragmentation does not occur requires the development of improved general (non-specific) assays for cell membrane fragments.

Blood Component Removal↗
PubMed1999

Application of a time-resolved fluoroimmunoassay for the analysis of normal prion protein in human blood and its components.

BACKGROUND AND OBJECTIVES: To quantify the cellular isoform of prion protein (PrP(c)) in human blood using a new time-resolved dissociation-enhanced fluoroimmunoassay (DELFIA). MATERIALS AND METHODS: The DELFIA was optimised for human blood samples and applied to isolated cell and plasma fractions from blood donations. The physicochemical properties of PrP(c) were analysed. RESULTS: 26. 5% of blood PrP(c) was associated with the platelet fraction, 0.8% with polymorphonuclear leucocytes, 2.4% with mononuclear leucocytes, 1.8% with red cells and 68.5% with plasma (mean values from 4 processed donations). CONCLUSION: The majority of blood PrP(c) is found in the platelet and plasma compartments.

Antigens↗
PubMed1999

Interleukin-10 inhibits inducible nitric oxide synthase in an animal model of necrotizing enterocolitis.

BACKGROUND: Nitric oxide (NO) and its role in surgical inflammation are well documented; demonstrating the role of NO in necrotizing enterocolitis (NEC) and ways in which it may be suppressed may provide avenues for immune modulation in the treatment of NEC. AIMS: We sought to demonstrate an increase in inducible nitric oxide synthase (iNOS) mRNA and nitric oxide in an experimental model of necrotizing enterocolitis. In addition, we hypothesized that interleukin-10 (IL-10) would attenuate this response. METHODS: Newborn rats were treated with 25 microliters intraperitoneal IL-10 or vehicle prior to laparotomy, 1 h superior mesenteric artery (SMA) occlusion, 50 micrograms/kg intraluminal platelet activating factor administration, and SMA reperfusion. iNOS mRNA and nitric oxide levels were measured in the liver, small bowel, and serum and compared using Student's t-test. RESULTS: Small bowel iNOS mRNA increased after NEC induction from 0.058 +/- 0.02 to 0.144 +/- 0.05 relative intensity units (RIU) at 2 h (p < 0.01) and from 0 to 0.09 +/- 0.02 RIU at 6 h (p < 0.03). Liver mRNA increased from 0.026 +/- 0.002 to 0.485 +/- 0.09 RIU (p < 0.002) and from 0 to 0.069 +/- 0.02 RIU (p < 0.0001) at 2 and 6 h, respectively. Serum nitric oxide increased in NEC induced animals at 2 h from 28.04 +/- 10.5 to 45.18 +/- 6.8 microM (p < 0.001). IL-10 suppressed iNOS mRNA and nitric oxide expression at 2 h in small bowel, liver, and serum by 60%, 89%, and 11%, respectively. CONCLUSIONS: IL-10 decreases iNOS mRNA response in experimental NEC. This down-regulation may be an avenue for anti-inflammatory intervention in NEC.

Animals↗
PubMed1998

An enzyme-linked immunosorbent assay for the detection of agents which interfere with the DNA binding activities of transcription factors--exemplified by NF-IL6.

Binding of transcription factors to DNA is usually detected by the electrophoretic mobility shift assay also known as gel-shift or band-shift assay. Recently the use of biosensors has allowed factor/DNA interactions to be followed in real time. However, neither of these approaches lends itself easily to high-throughput screening of agents which might interfere with this process. We have therefore developed a 96-well plate-based enzyme-linked immunosorbent assay for this purpose. Biotinylated oligonucleotides bound to streptavidin-coated plates are used to capture recombinant transcription factor proteins which can then be detected using specific antibodies which in turn are recognised by peroxidase-conjugated antisera. The peroxidase catalyzes conversion of a colorless substrate to a colored product which can be quantified by optical densitometry on a plate reader. Agents which interfere with the binding of the transcription factor to DNA reduce the optical density in the well. Using the NF-IL6 transcription factor we show that the assay can detect reductions to 86% at significant levels. The assay may be readily adapted for robotic manipulation, making it ideal for high-throughput screening.

Base Sequence↗
PubMed1998

Transposed basilic vein versus polytetrafluorethylene for brachial-axillary arteriovenous fistulas.

BACKGROUND: Both transposed basilic vein (BV) and polytetrafluorethylene (PTFE) upper arm arteriovenous fistulas (AVF) are common angioaccess operations. To evaluate the patency and complication rates after AVF, a concurrent series of patients was reviewed. METHODS: Ninety-eight patients underwent brachial artery to axillary vein AVF: 30 BV and 68 PTFE. The PTFE grafts were performed in the standard fashion, whereas the basilic veins were translocated subcutaneously to the brachial artery. RESULTS: Risk factors were similar between the two groups. Basilic vein AVF had better patency at 24 months (70% BV versus 46% PTFE, P = 0.023). The dialysis access complications were higher in the BV group (20%) versus PTFE (5%), but the PTFE group had a higher infection rate (10%) than BV (0%). CONCLUSIONS: The primary and secondary patency rates were superior in the BV AVFs. The BV AVF preserves the venous outflow tract after AVF thrombosis for a future PTFE AVF operation.

Arteriovenous Shunt, Surgical↗
PubMed1998

Activated keratinocytes in the epidermis of hypertrophic scars.

The etiology of hypertrophic scarring, a pathological end point of wound healing, is unknown. The scars most commonly occur when epithelialization has been delayed during, for example, the healing of deep dermal burn wounds. Hypertrophic scars are conventionally described as a dermal pathology in which the epidermis has only a passive role. In this study, the expression of keratin intermediate filament proteins and filaggrin has been investigated in the epidermis of hypertrophic scars and site-matched controls from the same patients. Hypertrophic scar epidermis was found to express the hyperproliferative keratins K6 and K16 in interfollicular epidermis in association with K17 and precocious expression of filaggrin. K16 mRNA was localized by in situ hybridization using a highly specific cRNA probe. In contrast to the immunohistochemical location of K16 protein, the K16 mRNA was found to be expressed in the basal cell layer of normal skin. In hypertrophic scars the mRNA distribution corroborated the abnormal K16 protein distribution. These results suggest the keratinocytes in hypertrophic scar epidermis have entered an alternative differentiation pathway and are expressing an activated phenotype. Activated keratinocytes are a feature of the early stages of wound healing producing growth factors that influence fibroblasts, endothelial cells, and the inflammatory response. We propose that cellular mechanisms in the pathogenesis of hypertrophic scarring are more complex than isolated dermal phenomena. The persistence of activated keratinocytes in hypertrophic scar epidermis implicates abnormal epidermal-mesenchymal interactions.

Adult↗
PubMed1998

Dementia in people aged 65 years and older: a growing problem?

This study examines trends in death rates from dementias and neurodegenerative disorders in people aged 65 and over in England and Wales between 1979 and 1996. In total, there were 171,590 deaths from dementias and neurodegenerative disorders, with the number of deaths per year increasing from 3,021 in 1979 to 10,415 in 1996. Age-standardised death rates for all diagnoses combined increased from 39 to 96 per 100,000 for men and from 45 to 101 for women between 1979 and 1996. The most dramatic increase was seen in death rates from Alzheimer's disease which increased from less than 1 per 100,000 in 1979 to 19 for men and 21 for women in 1996.

Aged↗
PubMed1994

Non-acute casemix in the Illawarra.

There are problems associated with the use of acute care diagnosis-related groups for prospective payment for rehabilitation medicine services. As a preliminary effort to assist in the development of the National Non-Acute Inpatient Casemix Project, a modified costing study was done in the rehabilitation and geriatrics ward of the Illawarra Regional Hospital; its aim was to assess the validity of the functional independence measure (FIM) and the resource utilization group (RUG) system as predictors of staff time involvement in inpatient rehabilitation services. Data collected on 51 patients over 3 months showed that in a standard Australian rehabilitation unit the costs of staff involvement varied depending on the type of functional impairment and severity of carer burden. The FIM alone was not predictive of rehabilitation costs and the RUG 2 instrument was not comprehensively predictive of cost. The RUG 3 instrument developed in the USA did not allocated weightings appropriate to Australian costs. If, however, functional impairment groups were combined with one of these measures of carer burden, then costs did fall into categories reflective of staff time involvement. An Australian system which incorporates an instrument measuring functional capacity may be useful for resource allocation in rehabilitation care.

Activities of Daily Living↗
PubMed1993

Selection and integration of a radiology information system.

A comprehensive and reliable computer-based RIS can significantly improve patient care. The authors present case studies that illustrate different approaches to selection and implementation of an RIS. Detailed coverage is given to criteria for the RIS, the selection process, integration with hospital information systems and planning for the future.

Arizona↗
PubMed1992

Activation of a cryptic streptomycin-resistance gene in the Bacteroides erm transposon, Tn4551.

Bacteroides compound transposons encoding erm resistance are highly homologous but previous studies have shown some divergence of Tn4551. Results presented here describe a novel Tn4551 streptomycin-resistance gene, aadS, that was phenotypically silent in wild-type Bacteroides. However, aadS expression could be activated by a trans-acting chromosomal mutation. The aadS-encoded peptide displayed significant homology to Gram-positive streptomycin-dependent adenyltransferases, and enzymatic analysis confirmed the production of this activity. Examination of the nucleotide sequence showed that 200 bp upstream of aadS, the DNA base composition changed abruptly from 31% G+C to 48% G+C. These two regions were demarcated by a DNA sequence with homology to the recombination hot spots reported for Tn21 and the Bacteroides ermFU gene and to sequences at the ends of the chromosomal Bacteroides conjugal element, XBU4422.

Amino Acid Sequence↗