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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 307 records · Page 17Linked to original sources
PubMed2000

Systemic consequences of oxidative stress following aortic surgery correlate with the degree of antioxidant defenses.

The purpose of this study was to correlate the preoperative level of antioxidant defenses, measured by the plasma total antioxidant capacity (TAC), to the degree of postoperative systemic inflammatory response, measured by the severity of pulmonary injury following elective aortic surgery. Twenty-four patients had TAC measured preoperatively and 24 hr postoperatively. Chest radiography and arterial blood gases were obtained preoperatively and serially during the first 24 hr after surgery. Using objective radiologic criteria and blood gas analysis, the degree of pulmonary edema and pulmonary dysfunction were quantified. All patients showed evidence of pulmonary dysfunction in the first 24 hr following surgery. Fifteen of the 24 patients showed radiographic evidence of noncardiogenic pulmonary edema in the immediate postoperative period. In this group, the TAC was lower than in those without pulmonary edema immediately following surgery (p = 0.03). Preoperative TAC was associated with the degree of pulmonary edema in the postoperative period (r = -0.372, p = 0.067). These results suggest that preoperative antioxidant supplementation may favorably impact the severity of systemic inflammatory response following ischemia and reperfusion injury.

Aged↗
PubMed2000

Histopathology of arterial lesions in LPA transgenic mice on cholesterol-enriched chow.

The aortic root from 21 LPA transgenic mice and 18 control litter mates on cholesterol enriched chow were studied histologically for the presence of atherosclerotic lesions. Serial sections were cut and the total area of the lesions was measured by use of computerised image analysis. Lipid staining lesions were found in 17 aortas of the transgenic mice and were five times more common than in the controls. Foam cell lesions were the only type of lesion in 12 of the aortas from transgenic animals, while five animals had developed fibrofatty lesions. Immunostaining revealed monocytes/macrophages on the endothelial surface, and in the subendothelial space of foam cell lesions. In fibrofatty lesions, spindle shaped cells formed a cap around the lipid core. This study supports the view that transgenic mice expressing human apolipoprotein (a) on a high fat and cholesterol diet, are more susceptible to aortic lesions than control mice and develop early atherosclerotic lesions comparable to lesions in man. Aminoguanidin in the drinking water had no effect on the aortic lesions, but lesion size was significantly, negatively correlated with plasma glucose concentration.

Animals↗
PubMed2000

Neutralisation of the clotting activity of Australian snake venoms by snake plasma.

Plasmas from Pseudonaja textilis and Notechis scutatus were tested in vitro for their ability to neutralise the procoagulant activity, in human plasma, of nine elapid venoms. Pseudonaja textilis plasma inhibited the procoagulant activity of all Pseudonaja species and in one taipan (Oxyuranus scutellatus). However there was no inhibitory activity against any from the Notechis species. Plasma from Notechis scutatus exhibited no inhibitory activity against any Notechis species, including self, only weak inhibition against the Pseudonaja species and, again, total inhibition of Oxyuranus scutellatus. Thus, protection of a species from the effects of its own venom does not appear to be universal.

Animals↗
PubMed2000

A novel dicentric deleted chromosome 21 arising from tandem translocation.

We present a 26-year-old patient with myelodysplastic syndrome (MDS). Initial bone marrow cytogenetics with G-banding showed a rearranged chromosome 21, which was dicentric and bisatellited on CBG- and NOR-banding. Fluorescence in situ hybridization helped to characterize the structure, using a whole chromosome 21 paint and the locus specific AML1 gene probe. The rearranged 21 consisted solely of chromosome 21 material, contained only one copy of AML1, and was not a trisomy, but a deleted tandem translocation. The MDS transformed to acute myeloid leukemia (AML), and the patient died almost 12 months post-diagnosis. Cytogenetics was performed three times during the course of the disease, and the dicentric chromosome 21 was present throughout. Although there are a number of published rearrangements of chromosome 21 in MDS and AML, most are isodicentrics. We could not find another case of an abnormal chromosome 21 with the same structure as reported here.

Acute Disease↗
PubMed2000

An estimate of the cost of conducting phase II trials in lung cancer.

OBJECTIVE: Although it is commonly assumed that clinical trials are more costly than standard therapy, there have been no previous studies of the cost of conducting phase II trials in lung cancer. We retrospectively analyzed two National Cancer Institute of Canada phase II trials in previously untreated small cell lung cancer (SCLC) to determine the costs of conducting the trials in a cancer treatment centre. Both studies were clinical trials undertaken as part of the NCIC's Investigational New Drug program: IND 69 and IND 50 evaluated docetaxel (taxotere) and gemcitabine, respectively. METHODS: data management costs in a Canadian cancer treatment centre were determined from the time estimates provided by data managers to complete various protocol related tasks. Nursing and pharmacy personnel measured the time and supplies necessary to prepare and administer the chemotherapy. Physician fees were determined from the type and number of care visits required by the clinical protocols. Laboratory tests and imaging studies were costed according to the Ontario Health Insurance Plan (OHIP) Schedule of Fees and Benefits. To estimate whether phase II trials are more costly than standard treatment, we determined the cost of four cycles of VP-16-cisplatin, a standard treatment for SCLC. RESULTS: The total cost of performing the docetaxel study was $18443 for an average cost per case of $1317 and an average cost per treatment cycle of $683. The gemcitabine study cost more, due to the fact that the drug proved to be active against SCLC and more cycles of therapy were administered to a larger number of patients. Laboratory and administration costs were also higher, because of the drug administration schedule. The total cost of this study was estimated to be $64670 and the average cost per patient entered was $2230 with an average cost per treatment cycle of $898. In comparison, the estimated cost of four cycles of VP-16-cisplatin chemotherapy was $3948 or $987 per treatment cycle. The major cost drivers in the clinical trials were laboratory and imaging tests which made up 17 and 39%, respectively, of the costs of the taxotere study, and 29 and 27%, respectively, for the gemcitabine study. Data management costs contributed 21 and 13% of the total costs, respectively. CONCLUSION: As the main cost drivers in these phase II clinical trials are laboratory and imaging tests, the cost of clinical trials could potentially be reduced by ensuring that only essential tests are required by protocol. Not surprisingly, the cost of conducting a trial of an active agent is greater than for an inactive agent, because more patients are treated and each patient receives more treatment. The implications for the per-case funding of phase II clinical trials are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

An outbreak of carbon monoxide poisoning after a major ice storm in Maine.

Unintentional carbon monoxide (CO) exposure kills over 500 people in the U.S. annually. Outbreaks of CO poisoning have occurred after winter storms. The objective of this study was to describe clinical features and identify important risk factors of a CO poisoning outbreak occurring after a major ice storm. The study design included a case series of CO poisoning patients, a telephone survey of the general community, and a case-controlled study of households using specific CO sources. The setting was the primary service area of four hospital emergency departments located in the heavily storm-impacted interior region of Maine. Participants included all patients with a laboratory-confirmed diagnosis of CO poisoning during the 2 weeks after the storm onset, and a population-based comparison group of 522 households selected by random digit dialing. There were 100 cases identified, involving 42 common-source exposure incidents, most of them during the first week. Though classic CO symptoms of headache, dizziness, and nausea predominated, 9 patients presented with chest pain and 10 were asymptomatic. One patient died and 5 were transferred for hyperbaric oxygen therapy. Gasoline-powered electric generators were a CO source in 30 incidents, kerosene heaters in 8, and propane heaters in 4. In the community, 31.4% of households used a generator after the ice storm. The strongest risk factor for poisoning was locating a generator in a basement or an attached structure such as a garage. Cases of CO poisoning with various presentations can be expected in the early aftermath of a severe ice storm. Generators are a major CO source and generator location an important risk factor for such disasters.

Adolescent↗
PubMed2000

Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice.

The Prx gene in Schwann cells encodes L- and S-periaxin, two abundant PDZ domain proteins thought to have a role in the stabilization of myelin in the peripheral nervous system (PNS). Mice lacking a functional Prx gene assemble compact PNS myelin. However, the sheath is unstable, leading to demyelination and reflex behaviors that are associated with the painful conditions caused by peripheral nerve damage. Older Prx-/- animals display extensive peripheral demyelination and a severe clinical phenotype with mechanical allodynia and thermal hyperalgesia, which can be reversed by intrathecal administration of a selective NMDA receptor antagonist We conclude that the periaxins play an essential role in stabilizing the Schwann cell-axon unit and that the periaxin-deficient mouse will be an important model for studying neuropathic pain in late onset demyelinating disease.

Animals↗
PubMed2000

A unique case of ventricular isomerism?

Isomerism of the atria has often been described with various complex cardiac malformations. As far as is known, a case of 'ventricular isomerism' has never been recorded. Described is a specimen where, on the basis of morphological criterions, there are two right ventricles.

Aorta, Thoracic↗
PubMed2000

Heme binding by hemopexin: evidence for multiple modes of binding and functional implications.

Hemopexin binds 1 mol of heme per mol with high affinity (Kd < 1 pM) in a low-spin complex and acts as a transport vehicle for the heme. Circular dichroism (CD) spectroscopy was used to examine the heme environment in the ferri-, ferro-, and CO-ferro complexes of four iron tetrapyrroles [meso-, proto-, deutero-, and (2-vinyl, 4-hydroxymethyl)-deutero-heme] with three species (human, rabbit, and rat) of hemopexin. All ferri-heme-hemopexin complexes exhibit a band of positive ellipticity near the Soret maximum, except for the human ferri-protoheme hemopexin complex, which has a bisignate spectrum. The ferro-heme and CO-ferro-heme complexes display a variety of spectra, demonstrating redox- and ligand-linked shifts in conformation that alter the environment of the heme. The rabbit mesoheme-N-domain complexes have absorbance spectra almost indistinguishable from those of intact hemopexin, but present CD spectra that are distinctly different. However, adding the C-domain to mesoheme-N-domain restores most of the CD characteristics of the intact hemopexin complexes.

Amino Acid Sequence↗
PubMed2000

Large-scale DNA-based typing of HLA-A and HLA-B at low resolution is highly accurate specific and reliable.

DNA-based typing of HLA class I alleles of the HLA-A and HLA-B loci using sequence-specific oligonucleotide primers and/or probes has been used for the large-scale typing of individuals for the National Marrow Donor Program unrelated donor registry. Typing was performed by 16 laboratories at a low level of resolution (e.g. A*01, B*07). The results of blinded quality control analysis for the first 12 months of the project show the typing to be highly accurate, specific and reliable. The total error rate based on 11,545 HLA-A and 11,428 HLA-B assignments was 1.1% for HLA-A and 1.9% for HLA-B. This level of accuracy is particularly remarkable because the quality control samples could not be distinguished from 64,180 donor samples tested at the same time by the laboratories.

Bone Marrow Transplantation↗
PubMed2000

Pulmonary artery pressure measurement during exercise testing in patients with suspected pulmonary hypertension.

It is recognized that exercise produces abnormally large increases in pulmonary artery pressure in patients with pulmonary vascular disease as a consequence of a variety of disorders, but the relationship between pressure and cardiopulmonary exercise performance is poorly understood. This lack of understanding is due (in part) to difficulty making measurements of pulmonary haemodynamics using conventional fluid filled catheters. This article seeks to improve understanding by comparing variables measured during formal exercise testing with simultaneous measurements of pulmonary artery pressure using a micro-manometer tipped catheter. Ten patients with suspected pulmonary hypertension were studied using a micromanometer tipped pulmonary artery catheter, during cardiopulmonary exercise testing. Ventilatory equivalents for oxygen and carbon dioxide correlated with the pulmonary artery pressure measured on exercise, but oxygen pulse and oxygen uptake did not. Ventilatory equivalents, noninvasively measured during exercise, may merit further study as potential surrogates of pulmonary artery pressure and hence be useful in identifying individuals at risk of developing pulmonary hypertension.

Adult↗
PubMed2000

TCR Vbeta expression in the small bowel of patients with dermatitis herpetiformis and gluten sensitive enteropathy. Limited expression in dermatitis herpetiformis and treated asymptomatic gluten sensitive enteropathy.

Dermatitis herpetiformis (DH) is a blistering skin disease characterized by cutaneous deposits of IgA and an associated, most often asymptomatic, gluten sensitive enteropathy (GSE). Gluten sensitive enteropathy is also seen in patients that do not have skin disease or cutaneous IgA deposits, but do have significant gastrointestinal (GI) complaints. Patients with DH and with GSE without skin disease have similar small bowel morphologic changes and HLA associations and both the skin disease and the GI symptoms can be controlled by a gluten free diet. It is not known what factors allow almost all patients with DH to continue to eat gluten and not develop symptomatic gastrointestinal disease. We have examined the expression of the Vbeta T-cell receptor (TCR) in the small bowel of patients with DH (n=11) and of patients with both symptomatic (n=10) and asymptomatic (n=7) GSE without skin disease to determine if differences in the pattern of TCR Vbeta expression are associated with differences in the clinical manifestations of these diseases. TCR Vbeta expression was analyzed using RT-PCR from small bowel biopsies. Patients with DH and those with GSE without skin disease that were on a gluten free diet and asymptomatic were found to express 6.6 and 5.6 out of 20 Vbeta families respectively, with no single family preference. Examination of peripheral blood lymphocytes from these patients did not reveal any restriction of TCR Vbeta family expression. In contrast, patients with symptomatic GSE expressed 12.6 Vbeta families (P< 0.05), with no consistent preferential expression of any single Vbeta family between patients. Patients with DH, who are continuing to ingest wheat, show a more restricted pattern of TCR Vbeta utilization, similar to that of treated patients with GSE without skin disease, and significantly different from GSE without skin disease patients eating gluten. These findings suggest that the restricted nature of the TCR Vbeta expression may play a role in the different clinical manifestations of dermatitis herpetiformis and isolated gluten sensitive enteropathy.

Adolescent↗
PubMed2000

Allogeneic or autologous bone marrow transplantation (BMT) for non-Hodgkin's lymphoma (NHL): results of a provincial strategy. Ontario BMT Network, Canada.

In 1986, the bone marrow transplant centers in Ontario agreed to a strategy for the treatment of patients with NHL. Suitable patients would undergo autotransplant but be referred for allotransplant if they had persistent marrow involvement or an inadequate marrow/stem cell harvest. Data of all patients were recorded in a database. We reviewed this database to compare these transplant modalities with respect to overall survival, rate of relapse and treatment-related mortality. Between January 1986 and August 1997, 429 patients underwent BMT for NHL - 385 autotransplants and 44 allotransplants. Sixty-eight percent of patients received their transplant for aggressive NHL, while the others had indolent lymphoma. Three-year actuarial survival did not differ between allogeneic and autologous BMT: 71% vs 62%, respectively (P = 0.5330 by log-rank testing). Three-year actuarial rate of relapse was lower after allotransplant than autotransplant: 6% vs 41%, respectively (P = 0.0006 by log-rank testing). Treatment-related mortality was higher after allotransplant than autotransplant: 23% vs 6%, respectively (P = 0.001 by chi2 analysis). For further comparison, autotransplant patients were randomly matched 2:1 with the allotransplant patients for age +/- 5 years, disease status at BMT, disease histology, and year of BMT. In the matched comparison, survival did not differ (relative risk of death after allotransplant: 0.711 (95% CI: 0.309-1.637)). Relapse rate was significantly lower in the allotransplant group (relative risk of relapse for allotransplant: 0.190 (95% CI: 0.043-0.834)) and treatment-related mortality was not significantly different (relative risk for allotransplant: 1.425 (95% CI: 0.527-3.851)). In conclusion, a review of a provincial strategy for treatment of NHL, shows that survival is not different after allogeneic or autologous BMT, but the rate of relapse is lower after allotransplant. These data support continuing the current provincial strategy.

Adolescent↗
PubMed2000

On the assessment of stability and patterning of speech movements.

Speech requires the control of complex movements of orofacial structures to produce dynamic variations in the vocal tract transfer function. The nature of the underlying motor control processes has traditionally been investigated by employing measures of articulatory movements, including movement amplitude, velocity, and duration, at selected points in time. An alternative approach, first used in the study of limb motion, is to examine the entire movement trajectory over time. A new approach to speech movement trajectory analysis was introduced in earlier work from this laboratory. In this method, trajectories from multiple movement sequences are time- and amplitude-normalized, and the STI (spatiotemporal index) is computed to capture the degree of convergence of a set of trajectories onto a single, underlying movement template. This research note describes the rationale for this analysis and provides a detailed description of the signal processing involved. Alternative interpolation procedures for time-normalization of kinematic data are also considered.

Adult↗