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Biomedical subjects

J Barker

Publications and source records attributed to J Barker.

At least 19 recordsLinked to original sources
PubMed2001

Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors.

BACKGROUND: Umbilical-cord blood from unrelated donors who are not HLA-identical with the recipients can restore hematopoiesis after myeloablative therapy in children. We studied the use of transplantation of umbilical-cord blood to restore hematopoiesis in adults. METHODS: Sixty-eight adults with life-threatening hematologic disorders received intensive chemotherapy or total-body irradiation and then transplants of HLA-mismatched umbilical-cord blood. We evaluated the outcomes in terms of hematologic reconstitution, the occurrence of acute and chronic graft-versus-host disease (GVHD), relapses, and event-free survival. RESULTS: Of the 68 patients, 48 (71 percent) received grafts of umbilical-cord blood that were mismatched for two or more HLA antigens. Of the 60 patients who survived 28 days or more after transplantation, 55 had neutrophil engraftment at a median of 27 days (range, 13 to 59). The estimated probability of neutrophil recovery in the 68 patients was 0.90 (95 percent confidence interval, 0.85 to 1.0). The presence of a relatively high number of nucleated cells in the umbilical-cord blood before it was frozen was associated with faster recovery of neutrophils. Severe acute GVHD (of grade III or IV) occurred in 11 of 55 patients who could be evaluated within the first 100 days after transplantation. Chronic GVHD developed in 12 of 33 patients who survived for more than 100 days after transplantation. The median follow-up for survivors was 22 months (range, 11 to 51). Of the 68 patients, 19 were alive and 18 of these (26 percent) were disease-free 40 months after transplantation. The presence of a high number of CD34+ cells in the graft was associated with improved event-free survival (P=0.05). CONCLUSIONS: Umbilical-cord blood from unrelated donors can restore hematopoiesis in adults who receive myeloablative therapy and is associated with acceptable rates of severe acute and chronic GVHD.

Acute Disease↗
PubMed2001

Predictors of arteriovenous graft patency after radiologic intervention in hemodialysis patients.

Arteriovenous grafts in hemodialysis patients are prone to recurrent stenosis and thrombosis, requiring frequent radiologic and surgical interventions to optimize their long-term patency. Little is known about the factors that determine graft outcome after a radiologic intervention. The present study examined the clinical and radiologic predictors of intervention-free graft survival after elective angioplasty or thrombectomy. A prospective computerized database was used to determine the outcomes subsequent to all graft angioplasties (n = 330) and thrombectomies (n = 326) performed at the University of Alabama at Birmingham between April 1, 1996, and June 30, 1999. Primary graft survival rates after angioplasty and thrombectomy were 86% versus 43% at 1 month, 71% versus 30% at 3 months, 51% versus 19% at 6 months, and 28% versus 8% at 12 months, respectively. The median intervention-free graft survival time was substantially longer after angioplasty than thrombectomy (6.7 versus 0.6 months; P < 0.001). The superior outcome of angioplasty over thrombectomy was observed even for the subset of procedures with no residual stenosis (median survival, 6.9 versus 2.5 months; P < 0.001). The median graft survival was inversely related to the magnitude of residual stenosis for both elective angioplasty and thrombectomy. Median intervention-free graft survival after angioplasty was inversely related to the postangioplasty intragraft to systemic systolic pressure ratio (7.6, 6.9, and 5.6 months for ratios <0.4, 0.4 to 0.6, and >0.6, respectively; P < 0.001). Intervention-free graft survival after angioplasty or thrombectomy was not affected by graft location (forearm versus upper arm), number of stenotic sites, or presence of diabetes. In conclusion, graft survival is substantially longer after elective angioplasty than thrombectomy, even when the radiologic appearance after the procedure suggests complete resolution of the stenotic lesion. Moreover, the risk for requiring a subsequent graft intervention can be predicted from two simple radiologic measurements: grade of stenosis and intragraft to systemic systolic blood pressure ratio. These parameters may help determine the frequency of monitoring for recurrent stenosis in a given graft.

Aged↗
PubMed2001

Semantic factors in the production of number agreement.

This paper examines the role of semantic factors in the production of subject-verb number agreement. As an ostensibly grammatical process, number agreement provides an interesting case for examining the flow and interaction of semantic and syntactic information through the language-production system. Using a sentence-completion task, agreement errors can be elicited from subjects by presenting them with sentence fragments containing a complex noun-phrase, in which the nonhead noun is plural (e.g., The key to the cabinets ... WERE missing.). Previous research has demonstrated that the probability of making an error can be affected by varying the properties of the nouns in the complex noun phrase. By investigating which variables do and do not affect error rates, constraints on the flow of information through the production system can be inferred. In three experiments, we investigated the possible effects of three different semantic manipulations of the nouns in the complex NP: animacy, semantic overlap, and plausibility of modification by the sentence predicate. We found that both animacy and semantic relatedness had reliable effects on error rates, indicating that the mechanism involved in implementing agreement cannot be blind to semantic information. However, the plausibility with which each noun could serve as the subject of the sentence predicate had no effect on error rates. Taken together, these results suggest that while semantic information is visible to the agreement mechanism, there are still constraints on when this information can affect the process. Specifically, it may be the case that only information contained within the complex NP is considered for the purposes of implementing agreement.

Humans↗
PubMed2001

Corneodesmosin expression in psoriasis vulgaris differs from normal skin and other inflammatory skin disorders.

SUMMARY: Corneodesmosin (Cdsn) is a late differentiation epidermal glycoprotein putatively involved in keratinocyte adhesion. The Cdsn gene lies within the susceptibility region on chromosome 6p21.3 (PSORS1) for psoriasis, a common chronic disfiguring skin disease. A particular allelic variant of Cdsn has a strong association with psoriasis. Therefore, genetically and biologically, Cdsn is a possible candidate gene for psoriasis susceptibility. To investigate a potential role for Cdsn in psoriasis pathogenesis, protein expression studies were performed by quantitative immunohistochemistry on normal skin, psoriatic skin (lesional and nonlesional), and other skin disorders using monoclonal antibodies (G36-19 and F28-27). In normal and nonlesional skin, Cdsn was expressed in stratum corneum and one or two layers of superficial stratum granulosum. In lesional psoriasis, there was a significant increase in Cdsn expression, which was observed in multiple layers of stratum spinosum and in stratum corneum. The expression pattern varied from granular, cytoplasmic immunoreactivity to cell surface labeling with weakly immunoreactive cytoplasm. In chronic atopic dermatitis, lichen planus, mycosis fungoides, and pityriasis rubra pilaris, Cdsn immunoreactivity was confined to stratum corneum and upper stratum granulosum with no stratum spinosum immunoreactivity. Immunoelectron microscopy of normal and lesional psoriatic skin demonstrated Cdsn release concomitant with involucrin incorporation into cell envelopes and completed before mature envelope formation. Extracellular release of Cdsn occurred at a lower level of the epidermis in psoriasis than normal skin. These protein expression studies provide evidence of altered Cdsn expression in psoriasis consistent with a role of Cdsn in disease pathogenesis. Further functional and genetic studies of Cdsn are justified to determine its role as a potential psoriasis-susceptibility factor.

Chromosomes, Human, Pair 6↗
PubMed2001

Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors.

Gene therapy using recombinant adeno-associated virus vectors (rAAV) is generally considered safe. During the course of a study designed to determine the long-term efficacy of rAAV-mediated gene therapy initiated in newborn mice with the lysosomal storage disease, mucopolysaccharidosis type VII (MPSVII), a significant incidence of hepatocellular carcinomas and angiosarcomas was discovered. A hepatocellular carcinoma was first detected in a 35-week-old mouse and by 72 weeks of age, three out of five rAAV-treated MPSVII mice had similar lesions. These types of tumors had not been seen previously in long-term studies of MPSVII mice using recombinant enzyme or bone marrow transplantation. In an attempt to ascertain whether mouse strain or GUSB expression confers susceptibility to tumor formation, we histopathologically examined untreated normal mice of the same strain, untreated MPSVII mice, and normal mice overexpressing human GUSB for the presence of tumors and increased hepatocyte replication. The results of these studies do not indicate that MPSVII mice or mice overexpressing human GUSB are susceptible to tumor formation; however, the number of animals examined is too small to draw definitive conclusions. Results from quantitative PCR performed on the tumor samples suggest that the tumors are probably not caused by an insertional mutagenesis event followed by the clonal expansion of a transformed cell. In a separate study, a relatively large group of mice injected with varying doses and types of rAAV vectors had no evidence of hepatic or vascular tumors. Although the mechanism of tumor formation is currently unknown, the tumorigenic potential of rAAV vectors must be rigorously determined in long-term in vivo studies.

Animals↗
PubMed2001

Organisational change: a methodology to uncover the business idea.

A study was undertaken to identify the "Business Idea", as defined by van der Heijden (1996), in The Family Planning Association of WA Inc (FPWA) which is a Non-Government Organisation (NGO) in Perth, Western Australia. This organisation was chosen as, along with many other NGOs, it was undergoing major changes in its funding, role and required outcomes. A qualitative interpretivist single case study methodology employing grounded theory research principles and methods was used to study the Business Idea framework in this setting. Thirty-four members of FPWA's staff were interviewed and data was managed using NUD*IST4 and Decision Explorer data storage, data retrieval and graphical reproduction facilities. Results indicated that images of the Business Idea model within FPWA were largely consistent across all staff levels excepting members of the Board of Management. Changes within the organisation were impacting heavily on staff, who needed to be assisted over the transitional phase. Strong leadership and corporate direction were identified as essential if the FPWA was to balance the strongly held sense of social justice amongst its staff with a need for greater productivity efficiency and accountability across the organisation.

Commerce↗
PubMed2001

A novel model of murine mucopolysaccharidosis type VII due to an intracisternal a particle element transposition into the beta-glucuronidase gene: clinical and pathologic findings.

We describe the clinical and pathologic findings in a murine model of mucopolysaccharidosis VII (Sly disease) that arose spontaneously in the C3H/HeOuJ mouse strain. Affected gus(mps2J)/gus(mps2J) mice are deficient in beta-glucuronidase because of insertion of an intracisternal A particle element into intron 8 of the gus structural gene. This is the first model of a human lysosomal storage disease caused by an intracisternal A particle element insertion. Mice with the gus(mps2J)/gus(mps2J) genotype have < 1% of normal beta-glucuronidase activity and secondary elevations of other lysosomal enzymes. The phenotype includes shortened life-span, dysmorphic features, and skeletal dysplasia. Lysosomal storage of glycosaminoglycans is widespread and affects the brain, skeleton, eye, ear, heart valves, aorta, and the fixed tissue macrophage system. Thus the phenotypic and pathologic alterations in gus(mps2J)/gus(mps2J) mice are similar to those in patients with mucopolysaccharidosis VII. The finding of antibodies to beta-glucuronidase in some older gus(mps2J)/gus(mps2J) mice suggests the mice produce sufficient enzyme to elicit an immune response. The gus(mps2J)/gus(mps2J) model provides another well-defined genetic system for the study of the pathophysiology of mucopolysaccharidosis and for evaluation of experimental therapies for lysosomal storage diseases. The disease in gus(mps2J)/gus(mps2J) mice is less severe than that seen in the previously characterized B6.C-H2(bm1)/ByBir-gus(mps)/gus(mps) mouse model. Furthermore, unlike gus(mps)/gus(mps) mice, gus(mps2J)/gus(mps2J) mice are fertile and breed to produce litters, all of which are mucopolysaccharidosis VII pups. This feature makes them extremely useful for testing intrauterine therapies.

Animals↗
PubMed2000

A validation study comparing accelerator MS and liquid scintillation counting for analysis of 14C-labelled drugs in plasma, urine and faecal extracts.

A comparison has been made between accelerator mass spectrometry (AMS) analysis and liquid scintillation counting (LSC) of plasma, urine and faecal samples containing 14C-labelled drugs. In an in vitro study in which human plasma was spiked (the term spiked is used in Section 2.6) with 14C-Fluconazole (14C-FL) over a concentration range of 0.1-2.5 dpm/ml, a correlation coefficient of 0.999 was determined for AMS analysis versus extrapolated LSC data. No significant day to day (or inter-day)variation was seen (P < 0.05 by ANOVA). Coefficients of variation for these analyses ranged from 2.68 to 6.50%. In vivo studies in which rats were given a high (11.5 microCi/kg) or low (18.1 nCi/kg) radioactive dose (to model an exposure of 0.9 microSievert to man) of 14C-Fluticasone propionate(14C-FP) showed that there was also a good correspondence between AMS and LSC data. A mass balance study in a single the faeces by 96 h; less than 1% of the administered dose was excreted in the urine. The limit of reliable measurement of drug related material, above background concentrations, by AMS analysis in this study was approximately 0.1 dpm/ml for plasma, 0.01 dpm/ml for urine without any sample extraction or concentration and 0.01 dpm/ml for faecal extracts. The data reported here demonstrate that AMS is an ultrasensitive and reliable method for analysing 14C-labelled drugs in human and animal body fluids.

Animals↗
PubMed2000

Ambulatory management of burns.

Burns often happen unexpectedly and have the potential to cause death, lifelong disfigurement and dysfunction. A critical part of burn management is assessing the depth and extent of injury. Burns are now commonly classified as superficial, superficial partial thickness, deep partial thickness and full thickness. A systematic approach to burn care focuses on the six "Cs": clothing, cooling, cleaning, chemoprophylaxis, covering and comforting (i.e., pain relief). The American Burn Association has established criteria for determining which patients can be managed as outpatients and which require hospital admission or referral to a burn center. Follow-up care is important to assess patients for infection, healing and ability to provide proper wound care. Complications of burns include slow healing, scar formation and contracture. Early surgical referral can often help prevent or lessen scarring and contractures. Family physicians should be alert for psychologic problems related to long-term disability or disfigurement from burn injuries.

Acute Disease↗
PubMed2000

Helicopter in transit care of the critically ill--the Whangarei experience.

AIMS: To describe our experience in transit care of the critically ill in Northland and to highlight the multidisciplinary co-operation which renders this an efficient model of transit care in suburban and rural areas. METHODS: Since its inception in 1988, Northland's wholly community owned rescue helicopter has played an integral part in transit Intensive Care in Northland. This aids in transportation of medical and nursing intensive care staff to outlying primary hospitals for patient stabilisation, subsequent transfer of the patient to the intensive care unit (ICU) in Whangarei and, occasionally, for transfer to specialised critical care services in Auckland. RESULTS: As of August 1999, over 3,900 helicopter missions have been accomplished. A doctor, vetting each request for Medevac, minimises over-triage, thus ensuring adequate levels of transit care and effective utilisation of expensive resources. More than 90% of non-obstetric adult patients were ventilated and the number of Medevac missions increased over the years. The Accident Compensation Corporation (ACC) funds 40% of all flights, another 40% of flights are funded by Northland Health and the Order of St John funds the remainder. CONCLUSIONS: With a widespread geography, efficient transit care of the critically ill is imperative to quality hospital care and ensures equity of access to the rural populace. The Whangarei system of transit intensive care is an ideal template for suburban and rural areas.

Air Ambulances↗
PubMed2000

Criminal investigation of child sexual abuse: a comparison of cases referred to the prosecutor to those not referred.

OBJECTIVE: The present study sought to identify characteristics of child sexual abuse cases which differentiate cases referred for criminal prosecution ("criminal-action") from those not referred ("dropped") by investigators. METHOD: The study sample consisted of 1043 children who completed a forensic interview for sexual abuse that allegedly occurred at the hands of an adult between January 1, 1993 and December 31, 1996 in Bernalillo County of New Mexico. Data was systematically obtained from forensic interview files and offender records at the local prosecutor's office. RESULTS: Differences between criminal-action and dropped cases were found in relation to the children (age, sex and ethnicity), the alleged offenders (age, sex and relationship to child), and the case characteristics (disclosure and injury to the child). CONCLUSIONS: The present study provided insight into the characteristics of a previously ignored population (reported child sexual abuse cases that are not referred for prosecution). Recommendations are made to address the needs of these children and their families.

Adolescent↗
PubMed2000

Word frequency effects on the processing of subject-verb number agreement.

This paper examines the role of word frequency in the computation of subject-verb number agreement. Previous research in both production and comprehension has demonstrated that processing difficulties can arise in sentence structures containing a singular subject noun followed by a plural "distractor" noun, as in The key to the cabinets.... A whole sentence reading task was employed to determine whether the relative frequency with which the distractor noun appears in its singular or plural form would affect the degree of processing difficulty experienced by readers. Results suggest that the agreement process is, indeed, sensitive to this factor and this finding is compatible with activation-based accounts of the implementation of number agreement.

Humans↗
PubMed2000

A novel in vitro model of early human adult B lymphopoiesis that allows proliferation of pro-B cells and differentiation to mature B lymphocytes.

To develop a model of early human adult B lymphopoiesis, we cultured CD34+CD38+CD10+ pro-B cells in contact with AFT024 stroma in X-VIVO10 media with 5% serum. The cytokines FLT3L + SCF + IL7 + IGF1 were added at day 0, IL4 + IL5 + IL6 + IL10 and soluble CD40 ligand at day 14, and Staph. aureus Cowan particles on day 21. Greater than 25-fold expansion of CD34+CD38+CD10+ cells was seen at 2 weeks, the majority being CD34-CD19+ pre-B cells. Differentiation to immature IgM+ B cells was seen at 3 weeks and mature IgD+ B cells at 4 weeks, with secretion of IgM into the media. Immature and mature B cells could also be generated from culture of CD34+CD10+CD19- and CD34+CD10+CD19+ cells under similar conditions. In conclusion, we have demonstrated in vitro differentiation of early pro-B cells, and possibly common lymphoid progenitor cells, to mature B cells. Additional stimuli, provided by T helper cells or dendritic cells for example, may be required for the generation of IgG+ B cells or plasma cells. However, our culture system should be a valuable tool to further investigate B cell biology and B cell malignancies such as multiple myeloma and lymphoma.

Adolescent↗
PubMed2000

Plants as biomarkers for monitoring heavy metal contaminants on landfill sites using sequential extraction and inductively coupled plasma atomic emission spectrophotometry (ICP-AES).

There have been a number of studies investigating metal uptake in plants on contaminated landfill sites, but little on their role as biomarkers to identify metal mobility for continuous monitoring purposes. Vegetation can be used as a biomonitor of site pollution, by identifying the mobilisation of heavy metals and by providing an understanding of their bioavailability. Plants selected were the common nettle (Uritica Dioica), bramble (Rubus Fruticosa) and sycamore (Acer Pseudoplatanus). A study of the soil fractionation was made to investigate the soil properties that are likely to influence metal mobility and a correlation exercise was undertaken to investigate if variations in concentration of metals in vegetation can reflect variations in concentration of the metals in soil. The soil was digested using aqua regia in a microwave closed vessel. The vegetation was digested using both microwave and a hydrogen peroxide-nitric acid mixture, refluxed on a heating block and a comparison made. The certified reference materials (CRMs) used were Standard Reference Material (SRM) 1547, peach leaves for vegetation (NIST) and for soil CRM 143R, sewage sludge-amended soil (BCR). The relative standard deviations (RSDs) were 2-6% for the analyses. Our findings show evidence of phytoextraction by some plants, (especially bramble and nettle), with certain plants, (sycamore) exhibiting signs of phytostabilisation. The evidence suggests that there is a degree of selectivity in metal uptake and partitioning within the plant compartments. It was also possible to correlate mobility phases of certain metals (Pb, Cu and Zn) using the soil and plant record. Zn and Cu exhibited the greatest potential to migrate from the roots to the leaves, with Pb found principally in the roots of ground vegetation. Our results suggest that analysis of bramble leaves, nettle leaves and roots can be used to monitor the mobility of Pb in the soil with nettle, bramble and sycamore leaves to monitor Cu and Zn.

Biomarkers↗