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Biomedical subjects

D Simpson

Publications and source records attributed to D Simpson.

At least 91 records · Page 5Linked to original sources
PubMed2000

Design and construction of a uniaxial cell stretcher.

In vitro mechanical cell stimulators are used for the study of the effect of mechanical stimulation on anchorage-dependent cells. We developed a new mechanical cell stimulator, which uses stepper motor technology and computer control to achieve a high degree of accuracy and repeatability. This device also uses high-performance plastic components that have been shown to be noncytotoxic, dimensionally stable, and resistant to chemical degradation from common culture laboratory chemicals. We show that treatment with glow discharge for 25 s at 20 mA is sufficient to modify the surface of the rubber to allow proper adhesion for polymerization of aligned collagen. We show through finite element analysis that the middle area of the membrane, away from the clamped ends, is predictable, homogeneous, and has negligible shear strain. To test the efficacy of the mechanical stretch, we examined the effect of mechanical stimulation on the production of beta(1)-integrin by neonatal rat cardiac fibroblasts. Mechanical stimulation was tested in the range of 0-12% stretch and 0-10-cycles/min stretch frequency. The fibroblasts respond with an increase in beta(1)-integrin at 3% stretch and a decrease at 6 and 12% stretch. Stretch frequency was found to not significantly effect the concentration of beta(1)-integrin. These studies yield a new and improved mechanical cell stimulator and demonstrate that mechanical stimulation has an effect on the expression of beta(1)-integrin.

Animals↗
PubMed2000

Ground reaction force after a sideways push as a measure of balance in recovery from stroke.

OBJECTIVE: To investigate if measuring ground reaction force after a sideways push at the hips gives a measure of standing balance in stroke subjects. METHODS: Fifteen control subjects and 13 right hemiparetic subjects who were able to stand independently stood with their feet on a single forceplate. Horizontal sideways pushes of 3% body weight were delivered to each side of the pelvis with the subjects held firmly in a semi-rigid belt. Measurements were made of lateral pelvic displacement (sway) and the lateral sheer component of ground reaction force (GRF). RESULTS: Right hemiparetic subjects showed significantly greater sway after a sideways push (p < 0.01) and later onset of GRF (p < 0.01) when pushed to their weak side compared with control subjects. There was also a positive correlation between sway after a sideways push and the onset latency of GRF in both strokes (0.41) and controls (0.61). The hemiparetic subjects swayed more (p < 0.01) when pushed to their weak side compared with their stronger side and their GRF latency was longer, but this latter measurement failed to reach statistical significance. No difference was seen between sides in sway or GRF latency in controls. CONCLUSIONS: The latency of GRF onset after a push at the hips in controls and in stroke subjects is related to sway and both measurements increase after a stroke. This test offers a method of measuring balance after a stroke, and serial testing of an individual after a stroke may prove a useful measure of an individual's recovery of balance.

Adolescent↗
PubMed2000

The search for effective and efficient ambulatory teaching methods through the literature.

OBJECTIVE: Education in ambulatory settings is characterized by the conflicting agendas of clinical efficiency and educational effectiveness. In recognition of the challenge to teach more effectively, this review was undertaken to identify literature-based teaching methods for ambulatory-based education. DESIGN: Literature search resources included electronic databases and relevant journal indices. After preliminary title/abstract review, final critical review using a coding sheet was undertaken to define the teaching behavior or characteristic in each article, and to evaluate empirical data related to effectiveness and/or efficiency. RESULTS: Our literature search and subsequent article analysis yielded 11 clinical teaching methods, but no agreed upon descriptor or key features for these methods. Synthesis of this literature lead to succinct descriptions of each method and a label. CONCLUSIONS: There is limited evidence regarding the effectiveness of ambulatory teaching methods in cited literature. By establishing a common nomenclature and descriptions for 11 methods, this review lays the foundation for investigators to systematically study the effectiveness and efficiency of ambulatory-focused clinical teaching methods both within and across specialties.

Ambulatory Care↗
PubMed2000

Transitional care for neonates.

The development of a transitional care ward at Peterborough Maternity Unit has improved the care given to all women and their babies. A slight reorganisation of services has resulted in a better working environment for everyone. Babies requiring additional care receive timely and appropriate attention and mothers whose babies are in NICU are able to support each other at this emotional and stressful time. With such clear benefits for everyone, I recommend that all maternity units consider developing a transitional care ward.

Female↗
PubMed2000

Different patterns of allelic loss (loss of heterozygosity) in recurrent human pituitary tumors provide evidence for multiclonal origins.

Sporadic human pituitary tumors are benign adenomas of monoclonal origin. This implies that they arise from de novo somatic mutation(s) within a single pituitary cell. The availability of original and recurrent/regrown tumors from the same patient allowed testing of the prediction that recurrent/regrown tumors have identical genetic abnormalities as the original tumor sample. We used PCR amplification, from archival slide-extracted DNA, to allelotype microsatellite polymorphisms as an indication of clonality and confirmed this by X chromosome inactivation analysis in samples from women. Tumors from 33 of 49 (67%) patients with two or more specimens showed loss of heterozygosity (LOH) of at least one marker in at least one of their samples. Two patterns of LOH were observed. In pattern A in 14 of 33 (42%) of patients, the LOH pattern of the first tumor was preserved in the second recurrent sample, with some recurrent tumors also showing additional LOH. In these patients, the original and second tumors are presumed to arise from the same original clone with or without progressive accumulation of LOH. In pattern B [19 of 33 (58%) patients], LOH seen in the first tumor was not preserved in the second or subsequent tumors, as evidenced by retention of heterozygosity compared with the first tumor. The simplest explanation is that the second tumor, although still monoclonal, arises from another independently abnormal clone. This was confirmed by X chromosome inactivation analysis in all 11 women where this was informative. These results show that initial and recurrent tumors, of a benign tumor type, are frequently derived from separate independent clones. This suggests that either: (a) more than one abnormal clone is present from the outset though only one dominates; or (b) several clones arise independently at different times. In both scenarios, the initiating event(s) that predisposes to transformation might result in multiclonal hyperplasia, possibly as a consequence of exogenous stimulation.

Adolescent↗
PubMed1999

Programmed cell death in castor bean endosperm is associated with the accumulation and release of a cysteine endopeptidase from ricinosomes.

The cells of the endosperm of castor bean seeds (Ricinus communis) undergo programmed cell death during germination, after their oil and protein reserves have been mobilized. Nuclear DNA fragmentation first was observed at day 3 in the endosperm cells immediately adjacent to the cotyledons and progressed across to the outermost cell layers by day 5. We also detected the accumulation of small organelles known as ricinosomes, by using an antibody against a cysteine endoprotease. By the time the nuclear DNA was susceptible to heavy label by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling, the ricinosomes had released into the cytoplasm their content of cysteine endoprotease, which became activated because of the cleavage of its propeptide. The cysteine endoprotease is distinguished by a C-terminal KDEL sequence, although it is not retained in the lumen of the endoplasmic reticulum and is a marker for ricinosomes. Homologous proteases are found in the senescing tissues of other plants, including the petals of the daylily. Ricinosomes were identified in this tissue by electron microscopy and immunocytochemistry. It seems that ricinosomes are not unique to Ricinus and play an important role in the degradation of plant cell contents during programmed cell death.

Apoptosis↗
PubMed1999

Tackling multi-pollutant multi-effect problems--an iterative approach.

Within both the UN ECE and the European Union, there has been a strong move towards the so-called multi-pollutant multi-effect approach to air pollution strategies. In this approach a number of pollutants are considered, and emission reductions are determined after looking at the effect of each of these pollutants on a number of environmental problems. This new approach is very ambitious and raises a number of problems in balancing the effects and costs of different emission reductions against achieved environmental benefits. We describe an iterative method designed for addressing such multi-pollutant multi-effect type problems. In the examples given here, the method is used to estimate combinations of NOx and VOC emission reductions from all European countries so as to reduce environmental problems associated with acidification and ozone in a cost-effective manner. The iterative technique is designed to be flexible and transparent, so that a number of different approaches to multi-pollutant-multi-effect problems can be considered. This technique can be used to provide early guidance on various control strategy options, and allows rapid exploration of the many targets and measures possible with these approaches. It also demonstrates how even complex multi-dimensional environmental problems may be amenable to understandable solutions.

Acid Rain↗
PubMed1999

3-nitropropionic acid oxidase from horseshoe vetch (Hippocrepis comosa): a novel plant enzyme.

A novel enzyme that catalyses the oxygen-dependent oxidation of 3-nitropropionic acid (3NPA) to malonate semialdehyde, nitrate, nitrite and H2O2 has been purified from leaf extracts of the horseshoe vetch, Hippocrepis comosa, and named 3NPA oxidase. The enzyme is a flavoprotein with a subunit molecular mass of 36 kDa containing 1 molecule of FMN and exhibits little specificity for all nitroalkanes tested other than 3NPA (apparent Km 620 microM). The maximum enzyme activity in vitro was expressed at pH4.8 and was inhibited strongly by the products nitrate and nitrite. 3NPA oxidase activity was detected in green shoots, which also contain high concentrations of 3NPA, from plants grown with nitrate, ammonium or N2 as sources of nitrogen. Enzyme activity was absent from roots and cell cultures, neither of which accumulate high levels of 3NPA.

Amino Acid Sequence↗
PubMed1999

Organophosphate neuropathy due to methamidophos: biochemical and neurophysiological markers.

Neuropathy target esterase (NTE), the putative target enzyme for organophosphate induced delayed polyneuropathy (OPIDP), can be measured in lymphocytes but has rarely been assessed in acute human poisoning. Serum autoantibodies to nervous system proteins develop in hens poisoned with neuropathic insecticides and also have not been studied after human poisoning. Serial lymphocyte NTE (LNTE) was measured in a 16-year-old boy after acute poisoning with methamidophos for evaluation as a predictor of subsequent neuropathy. The profiles of serum autoantibodies to neurofilament triplet proteins, myelin basic protein, and glial fibrillary acidic protein were measured in order to characterize changes occurring as a result of OPIDP. Clinical neuropathy characterized by steppage gate and profound lower extremity weakness, decreased grip and pinch strength, and decreased ulnar and absent tibial compound muscle action potentials developed 2 weeks following poisoning. Sensory examination and nerve conduction studies were normal. On day 3 following poisoning LNTE was depressed (77% compared with subsequent baseline enzyme activity). Marked increases in serum immunoglobulin G (IgG) autoantibodies to glial fibrillary acidic protein and to neurofilament 200 were observed after the development of OPIDP. We conclude that inhibition of lymphocyte NTE is predictive of subsequent OPIDP. Serum autoantibody titers to nervous system proteins may be useful markers of neuropathy.

Adolescent↗
PubMed1999

Modelling photochemical oxidant formation, transport, deposition and exposure of terrestrial ecosystems.

The chemical processes responsible for production of photochemical oxidants within the troposphere have been the subject of laboratory and field study throughout the last three decades. During the same period, models to simulate the atmospheric chemistry, transport and deposition of ozone (O(3)) from individual urban sources and from regions have been developed. The models differ greatly in the complexity of chemical schemes, in the underlying meteorology and in spatial and temporal resolution. Input information from land use, spatial and temporally disaggregated emission inventories and meteorology have all improved considerably in recent years and are not fully implemented in current models. The development of control strategies in both North America and Europe to close the gaps between current exceedances of environmental limits, guide values, critical levels or loads and full compliance with these limits provides the focus for policy makers and the support agencies for the research. The models represent the only method of testing a range of control options in advance of implementation. This paper describes currently applied models of photochemical oxidant production and transport at global and regional scales and their ability to simulate individual episodes as well as photochemical oxidant climatology. The success of current models in quantifying the exposure of terrestrial surfaces and the population to potentially damaging O(3) concentrations (and dose) is examined. The analysis shows the degree to which the underlying processes and their application within the models limit the quality of the model products.

Journal Article↗
PubMed1999

Intravesicular instillation of E-aminocaproic acid for patients with adenovirus-induced hemorrhagic cystitis.

Hemorrhagic cystitis (HC) is a known complication of allogenic BMT. We report a case of a 28-year-old female with CML in chronic phase, which was treated with a matched unrelated donor (MUD) transplant, complicated by hemorrhagic cystitis on day +42 after the transplant. Adenovirus was isolated from the urine and she was treated with ribavirin, 1 g twice a day for 8 days. We report the use of Amicar (E-aminocaproic acid), 2.5 g solution as bladder instillation to treat the intractable hematuria.

Adenoviridae Infections↗
PubMed1999

Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma.

Randomized trials conducted by the Intergroupe Française du Myelome (IFM) demonstrate that the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT) improves event-free (EFS) and overall survival (OS) in younger patients with multiple myeloma (MM). Nevertheless, current HDCT regimens remain inadequate as all patients ultimately relapse following SCT. In an attempt to improve the OS of MM patients post-SCT we used an escalated HDCT regimen incorporating both intensified melphalan (160 mg/m2) and fractionated total body irradiation (12 Gy) to maximize the dose response of myeloma cells to these agents and included infusional etoposide 60 mg/kg in an attempt to eradicate clonal B cells potentially contributing to the myeloma clone. One hundred patients with MM received this intensified SCT regimen. The 100-day treatment-related mortality was 12% predominantly reflecting the development of interstitial pneumonitis (IP) in 28% of patients of whom 7/28 (25%) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60% and 35%, respectively. The median OS from the time of transplant is 41 months and the median EFS is 28 months. More than two prior chemotherapy regimens, previous radiation therapy (RT) and the presence of an abnormal karyotype involving chromosomes 11 or 13 were significantly predictive of poor outcome. Interferon maintenance was not associated with improved outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens.

Adult↗
PubMed1999

Ebola (subtype Reston) virus among quarantined nonhuman primates recently imported from the Philippines to the United States.

In April 1996, laboratory testing of imported nonhuman primates (as mandated by quarantine regulations) identified 2 cynomolgus macaques (Macaca fascicularis) infected with Ebola (subtype Reston) virus in a US-registered quarantine facility. The animals were part of a shipment of 100 nonhuman primates recently imported from the Philippines. Two additional infected animals, who were thought to be in the incubation phase, were identified among the remaining 48 animals in the affected quarantine room. The other 50 macaques, who had been held in a separate isolation room, remained asymptomatic, and none of these animals seroconverted during an extended quarantine period. Due to the rigorous routine safety precautions, the facility personnel had no unprotected exposures and remained asymptomatic, and no one seroconverted. The mandatory quarantine and laboratory testing requirements, put in place after the original Reston outbreak in 1989-1990, were effective for detecting and containing Ebola virus infection in newly imported nonhuman primates and minimizing potential human transmission.

Animals↗
PubMed1999

Persistent pulmonary hypertension of the newborn associated with pulmonary atresia and intact interventricular septum.

Neonates with pulmonary atresia and intact interventricular septum (PAIVS) do not have pulmonary vascular disease secondary to their heart abnormality. Persistent pulmonary hypertension of the newborn has not been described in association with this condition. The case is reported of a female neonate born with PAIVS, who preoperatively had no clinical evidence or any risk factors for persistent pulmonary hypertension of the newborn, but whose postoperative course was highly suggestive of persistent pulmonary hypertension; necropsy confirmed the features of pulmonary vascular disease.

Fatal Outcome↗