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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 217 records · Page 12Linked to original sources
PubMed2001

Distribution of organochlorine pesticides in soils from South Korea.

Soil samples were collected from rice growing and industrial areas in South Korea and analysed for organochlorine pesticide content using gas chromatography with electron capture detection. The soils were monitored for the presence of 18 organochlorine pesticides. The main pesticides found were gamma- and delta-hexachlorocyclohexane, heptachlor epoxide and dieldrin. The range of concentrations, for each compound, was respectively, 0.17-0.94, 0.77-2.97, 1.38-48.0 and 0.32-0.49 ng/g soil. The highest values were found in soil obtained from rice fields indicating that, although the use of organochlorine pesticides has been discontinued since 1980, substantial concentrations of residues particularly the oxidised form of heptachlor remain in the soil.

Agriculture↗
PubMed2001

Iris melanoma: risk factors for metastasis in 169 consecutive patients.

OBJECTIVE: To identify risk factors that predict distant metastases of iris malignant melanoma. DESIGN: Retrospective case series. PARTICIPANTS: The participants included 169 consecutive patients with microscopically confirmed iris malignant melanoma managed on the Oncology Service at Wills Eye Hospital between 1974 and 1999. MAIN OUTCOME MEASURES: The main outcome measure was the development of distant tumor metastasis. Cox proportional regression models were used to calculate the risk of eventual metastatic spread. RESULTS: Of 1054 patients referred with suspicious iris melanocytic tumors (rule out malignant melanoma) over a 25-year period, 169 patients (16%) had microscopically proven iris melanoma, and the remainder (84%) had clinically diagnosed iris nevus. Of the patients with iris melanoma, the mean age at the time of diagnosis was 43 years (median, 45 years; range, 1-90 years). All patients were Caucasian. The mean tumor base was 6 mm (median, 5 mm; range, 1-17 mm), and mean tumor thickness was 2 mm (median, 2 mm; range, 1-4 mm). The mean number of clock hours of tumor involvement in the iris was four, tumor seeding on the iris was four, and tumor seeding into the anterior chamber angle was four. Extraocular extension was present in 10 eyes (6%). The tumor management consisted of local resection (iridectomy, iridocyclectomy, or iridocyclogoniectomy) in 102 patients (60%), enucleation in 51 (30%), plaque radiotherapy in 9 (5%), and observation in 7 patients (4%). Metastasis developed in nine patients (5%). Using Kaplan-Meier life table analysis, metastasis was found in 3% of patients at 5 years, 5% at 10 years, and 10% at 20 years. The clinical factors at initial evaluation predictive of eventual metastasis from iris melanoma included increasing age at diagnosis (P = 0.03), elevated intraocular pressure (P = 0.03), posterior tumor margin at angle or iris root (versus midzone) (P = 0.02), extraocular extension (P: = 0.02), and prior surgical treatment of the tumor elsewhere before referral (versus observation) (P = 0.006). The method of management (resection, radiotherapy, or enucleation) did not have an impact on metastasis. CONCLUSIONS: Microscopically confirmed iris melanoma demonstrates distant metastasis in 5% of patients at 10 years follow-up. Metastases are more likely to develop in those patients who are older and show tumor features of iris root/angle location with elevated intraocular pressure and extraocular extension.

Adolescent↗
PubMed2001

Complex variant t(4;11) characterized by fluorescence in situ hybridization in infant acute lymphoblastic leukemia.

A 6-month-old girl was diagnosed with acute lymphoblastic leukemia (ALL). Chromosome analysis of bone marrow aspirate showed 46,XX,t(4;11)(q21;q23) with an atypical appearance of the 11p on the der(11) chromosome. FISH studies to fully characterize the translocation utilised 8 probes: whole chromosome painting probes for chromosome 11 and chromosome 4; separate chromosome 11 short arm and long arm paints; specific subtelomere probes from 11p, 11q, and 4q; MLL gene probe. Taken together, the results indicated a two-step abnormality: an initial standard t(4;11)(q21;q23), followed by another t(4;11)--this time, between the two derivative chromosomes. The MLL gene was split by the first translocation and its position altered by the second.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Routine fluorescence in situ hybridization with the MLL probe does not reliably detect two separate signals on one chromosome 11 in patients with trisomy 11.

Trisomy 11 is considered to be a rare cytogenetic abnormality in myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). Duplication of the MLL gene (localized to 11q23) has been found on one chromosome 11 in patients with trisomy 11, detected by DNA techniques. We investigated copy number of MLL in seven patients with trisomy 11 to see if duplication could be assessed by the detection of two separate signals on fluorescence in situ hybridization (FISH). If so, FISH could provide a quick easy screen of MLL status in routine referrals. The diagnostic bone marrow aspirate showed trisomy 11 in five adult patients with MDS/AML as part of a complex karyotype and in two children with acute lymphoblastic leukemia (ALL) as part of a hyperdiploid karyotype. Fluorescence in situ hybridization utilized the suspensions remaining after the cytogenetic harvest. Two FISH probes were used on the adult patients (MLL - Oncor and Vysis), and one (Vysis) for the two children with ALL. Analysis showed that the proximity of the two putative hybridization signals made it very difficult to unambiguously see two separate signals. The hybridisations (Oncor probe) were convincing of MLL duplication (namely two distinct signals) in only one patient, but this was not borne out with the other MLL probe (Vysis). We conclude that conventional FISH with MLL probe is not suited to act as a screen for MLL duplication in patients with trisomy 11.

Adult↗
PubMed2001

A new ultrasensitive assay for quantitation of HIV-1 RNA in plasma.

Nucleic acid-based diagnostic assays for the quantitation of plasma HIV-1 RNA levels are used to monitor disease progression and the response of patients to antiretroviral drug therapy. The LCx HIV RNA Quantitative Assay (Abbott Laboratories, North Chicago, IL) is an assay for the quantitation of HIV type 1 RNA in plasma that uses competitive reverse transcription PCR (RT-PCR) followed by Microparticle Enzyme Immunoassay, and includes an internal control for inhibition and RNA recovery, that is taken through the entire sample preparation procedure. The performance of the assay was assessed for 1 and 0.2 ml sample volumes. For a 1 ml sample volume, the lower limit of detection was found to be 50 copies/ml with a linear range from 50 to 1 million copies/ml. For a 0.2 ml sample volume, the lower limit of detection was found to be 178 copies/ml with a linear range from 178 to 5 million copies/ml. The assay is able to detect and quantitate HIV subtypes A-G and group O. LCx HIV RNA assay quantitation results are highly correlated to the standard and ultrasensitive Amplicor HIV-1 Monitor assay (Roche Molecular Systems) quantitation results. Assay performance is consistent with the use of this test for routine quantitation of HIV-1 RNA in plasma.

Cross Reactions↗
PubMed2001

Randomised controlled trials of staged teaching for basic life support: 2. Comparison of CPR performance and skill retention using either staged instruction or conventional training.

Teaching CPR in stages is a strategy designed to improve skill acquisition and retention. This method has been compared with conventional teaching in a randomised trial involving 495 volunteers. The first ('bronze') stage was simplified by omitting ventilation and giving compressions in sets of 50 with pauses to open the victim's airway; in the second ('silver') stage ventilation was introduced in a ratio of 50 compressions to five breaths, and in the third ('gold') stage, the volunteers were converted to conventional CPR. 51% of those taught by this method reattended for the second ('silver') stage compared with 25% who were taught conventional CPR and advised to return for a revision session. 38% of the staged group reattended for the third ('gold') compared with 8% for the conventional group. Modest improvement in skill acquisition has earlier been reported for the 'bronze' stage teaching, and this has been followed by better performance in some of the components tested after the subsequent stages. Comparisons after the 'gold' stage were limited by the small numbers who reattended for a third session of conventional training, but no special difficulties were noted in changing the ratio of compressions to ventilation that was necessary to convert the staged training volunteers to conventional CPR. The increased number of compressions that can be achieved by teaching 'bronze' stage CPR with no ventilation was retained, to a lesser degree, when the 'silver' ratio of 50 compressions to five breaths was compared with the conventional 15:2 ratio. Our observations suggest that during the first critical 8 min of a resuscitation attempt, 58% more compressions might be delivered by using the 50:5 ratio - an increase that is likely to result in a significant augmentation of blood flow with important clinical implications. More comparative information will become available when the results of unannounced home testing are analysed.

Adult↗
PubMed2001

Psychosocial factors, respiratory viruses and exacerbation of asthma.

The aim of this research was study the role of psychosocial factors in exacerbations of asthma in adults induced by upper respiratory tract infections (URTIs). It involved a longitudinal study (one year) of 92 adults with asthma. The volunteers were 27 men and 65 women 19-46 years of age with a mean duration of wheeze of 19 years. The main outcome measure was symptomatic colds producing asthma exacerbations (infections confirmed by laboratory assays and exacerbation of asthma confirmed by objective changes in peak expiratory flow rate). The results showed that about 20% of the sample did not report an episode. This sub-group had a high proportion of males, low negative affectivity scores and consumed more alcohol. When volunteers with at least one episode were considered it was found that those who reported more negative life events and had low levels of social support had more episodes. Smokers were more likely to have to visit their doctor when they developed a cold-induced exacerbation of asthma. Overall, these results show that health-related behaviours, demographic and psychosocial factors influence susceptibility to and severity of exacerbations of asthma by URTIs.

Adult↗
PubMed2001

The role of vascular endothelial growth factor (VEGF) in vasculogenesis, angiogenesis, and hematopoiesis in zebrafish development.

Vascular endothelial growth factor (VEGF, VEGF-A), a selective mitogen for endothelial cells is a critical factor for vascular development. Two isoforms that differ in the presence of exons 6 and 7, Vegf(165) and Vegf(121), are the dominant forms expressed in zebrafish embryo. Simultaneous overexpression of both isoforms in the embryo results in increased production of flk1, tie1, scl, and gata1 transcripts, indicating a stimulation of both endothelial and hematopoietic lineages. We also demonstrate that vegf can stimulate hematopoiesis in zebrafish by promoting the formation of terminally differentiated red blood cells. Simultaneous overexpression of both isoforms also causes ectopic vasculature and blood cells in many of the injected embryos as well as pericardial edema in later stage embryos. Overexpression of vegf also resulted in earlier onset of flk1, tie1, scl, and gata1 expression in the embryo, indicating a possible role of vegf in stimulating the differentiation of both vascular and hematopoietic lineages. Co-injection of RNAs for both isoforms results in increased expression of three of these markers over and above that observed when either RNA is singly injected and analysis of vegf expression in the notochord mutants no tail and floating head suggests that the notochord patterns the formation of the dorsal aorta by stimulating adjacent somite cells to express vegf, which in turn functions as a signal in dorsal aorta patterning. Finally, studies of vegf expression in cloche mutant indicate that vegf expression is generally independent of cloche function. These results show that in the zebrafish embryo, vegf can not only stimulate endothelial cell differentiation but also hematopoiesis. Moreover, these effects are most dramatic when both vegf isoforms are co-expressed, indicating a synergistic effect of the expression of the two forms of the VEGF protein.

Animals↗
PubMed2001

Genomics of unrelated-donor hematopoietic cell transplantation.

Unrelated-donor hematopoietic cell transplantation is a proven curative modality for hematologic malignancies. The success of unrelated-donor transplantation has been achieved through a better understanding of the immunobiology of the HLA system and through more precise and comprehensive matching of donors and recipients. The extensive polymorphism of HLA genes confers important biological implications affecting engraftment, graft-versus-host disease and overall survival. Although more-complete HLA identity of the donor and recipient is associated with optimal transplant outcome, new information suggests that not every HLA disparity is functionally relevant. Future advances in unrelated-donor transplantation must include the identification of tolerable HLA mismatches, so that more patients may benefit from this therapeutic modality. Furthermore, the role of cytokine-gene polymorphisms and minor histocompatibility genes in transplant outcome requires investigation. Delineation of the function of these markers as transplantation determinants may provide alternative means for optimizing the results of hematopoietic cell transplantation.

Animals↗
PubMed2001

Effects of reduction and ligation of heme iron on the thermal stability of heme-hemopexin complexes.

Hemopexin has two homologous domains (N- and C-terminal domains), binds 1 mole of heme per mole with high affinity (Kd < 1 pM) in a low-spin bis-histidyl complex, and acts as a transporter for the heme. Transport is accomplished via endocytosis without degradation of the protein. Factors that affect stability of the heme coordination complex and potentially heme release in vivo were examined. The effects of temperature on hemopexin, its N-terminal domain, and their respective ferri-, ferro-, and CO-ferro-heme complexes were studied using absorbance and circular dichroism (CD) spectroscopy. As monitored with second-derivative absorbance spectra, the higher order structure of apo-hemopexin unfolds with a Tm of 52 degrees C in 50 mM sodium phosphate buffer and is stabilized by 150 mM NaCl (Tm 63 degrees C). Bis-histidyl heme coordination by hemopexin, observed by Soret absorbance, is substantially weakened by reduction of ferri-heme-hemopexin (Tm 55.5 degrees C) to the ferro-heme form (Tm 48 degrees C), and NaCl stabilizes both complexes by 10-15 degrees C. CO binding to ferroheme-hemopexin restores complex stability (Tm 67 degrees C). Upon cooling, unfolded apo- and ferriheme-hemopexin extensively refold and recover substantial heme-binding activity, but the characteristic ellipticity of the native protein (UV region) and heme complex (Soret region) are not regained, indicating that altered refolded forms are produced. Lowering the pH from 7.4 to 6.5 has little effect on the stability of the apo-protein but increases the Tm of heme complexes by 5-12 degrees C. The stability of the apo-N-terminal domain (Tm 53 degrees C) is similar to that of intact hemopexin, and the ferri-, ferro-, and CO-ferro-heme complexes of the N-terminal domain have Tm values of 53 degrees C, 33 degrees C, and 75 degrees C, respectively.

Animals↗
PubMed2001

Validation of DNA-based HLA-A and HLA-B testing of volunteers for a bone marrow registry through parallel testing with serology.

A total of 42,160 individuals were typed for HLA-A and HLA-B by both serology and PCR-based typing. The HLA assignments included all of the known serological equivalents. The majority of the individuals (99.9%) were from U.S. minority population groups. The serologic typing was performed between 1993 and 1997 at the time of recruitment for the National Bone Marrow Program (NMDP) registry. The polymerase chain reaction (PCR)-based typing was carried out in two phases. In phase I, DNA typing was performed by PCR using sequence-specific oligonucleotide probes (PCR-SSOP) or PCR using sequence-specific primers (PCR-SSP) without knowledge of the serologic assignments. Discrepancies were identified between the serologic and DNA assignments in 24% of the volunteers (8% of volunteers differed for only HLA-A assignments, 13% for HLA-B, and 3% for both HLA-A and -B) and a potential explanation was assigned each discrepant serology/DNA pair. In phase II, a random sampling scheme was used to select a statistically significant number of individuals for repeat DNA typing from each of these categories. The categories included antigens missed by serology, nonexpressed (null) alleles, PCR amplification failures, misassignment of antigens and nomenclature issues. Only a single individual was found to carry a null allele. DNA-based testing correctly typed nearly 99% of the donors at HLA-A, more than 98% at HLA-B, and more than 97% at both HLA-A and -B validating this methodology for registry typing.

Bone Marrow Examination↗
PubMed2001

The effects of defendant conduct on jury damage awards.

Laws of negligence dictate that jurors' decisions about damages be influenced by the severity of plaintiffs' injuries and not by the reprehensibility of defendants' conduct. The authors simulated an automobile negligence trial to assess whether jurors' decisions are in accord with those expectations. Conduct of the defendant and severity of the plaintiff's injuries were manipulated. Jurors listened to the evidence, completed predeliberation questionnaires, deliberated as a jury, and completed postdeliberation questionnaires. Severity of the plaintiff's injury had a strong impact on damage awards, but evidence related to the defendant's conduct was also influential, particularly when the plaintiffs injuries were mild. Here, jurors with any conduct-related evidence gave larger damage awards than jurors with no conduct-related evidence. Findings suggest an effect of defendant conduct on damage awards that may be mediated by judgments that the defendant was negligent.

Adolescent↗
PubMed2001

Hematopoietic recovery of ex vivo perfusion culture expanded bone marrow and unexpanded peripheral blood progenitors after myeloablative chemotherapy.

Ex vivo culture of hematopoietic progenitor cells for autologous transplantation has generated world-wide interest, since it offers the prospect of using a limited cell number, and may allow more efficient gene transfer and passive elimination of contaminating tumor cells. In this study, we expanded bone marrow (BM) cells from 10 breast cancer patients to determine whether small BM aliquots can durably restore hematopoiesis, and whether thrombopoietin (TPO) improves hematopoietic reconstitution after myeloablative chemotherapy. We used the AastromReplicell System (ARS), performing a computer-controlled, stromal-based cell expansion process with frequent medium, cytokine and gas exchange. For the inoculation of 9 x 10(8) MNC, a median BM volume of 97.8 ml (range, 72.4-272) was harvested. We found a median 4.5-fold nucleated cell expansion, an 18-fold CFU-GM expansion, and 69% of input LTC-IC numbers. Nucleated and Lin-/CD34+ cells were infused with a median of 43.5 x 10(6)/kg (range, 34.1-71.7) and 2.8 x 10(5)/kg (range, 0.95-5.9), respectively. Despite tumor cell detection by immunocytochemical staining in 3/10 patients before expansion, tumor cells were not detectable in 9/10, and in one patient 1 log reduced post ARS culture. Following high-dose STAMP V chemotherapy, all patients received 12-day expanded BM cells. The median time to engraftment was 17 days (range, 11-20) for WBC >1000/microl, and 28 days (range, 21-55) for platelets >20,000/microl. A correlation between post-expansion Lin-/CD34+ cells and engraftment for ANC >500/microl, WBC >1000/microl and platelets >20,000/microl was observed. Hematopoiesis has been maintained for a median of 15 (range, 6-24) months. Our results demonstrate that transplantation of ex vivo expanded small BM aliquots allows hematopoietic reconstitution after myeloablative chemotherapy. Ex vivo generated ARS cells can reduce the risk of tumor cell reinoculation with autotransplants and may be valuable in settings in which only small stem cell doses are available, eg when using cord blood transplants or in non-mobilizing patients.

Adult↗
PubMed2001

Comprehensive methylation analysis in typical and atypical PWS and AS patients with normal biparental chromosomes 15.

Imprinting defects in 15q11-q13 are a rare but significant cause of Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Patients with an imprinting defect have apparently normal chromosomes 15 of biparental origin, but are recognised by @parental DNA methylation at D15S63 (PW71) or SNURF-SNRPN exon 1. We have investigated the methylation status of five additional loci in 12 such patients with or without a deletion in the imprinting centre. In each patient, the imprinting defect affected all loci tested. During routine diagnostic testing we identified four patients who had a normal methylation pattern at SNURF-SNRPN exon 1, but an abnormal pattern at D15S63. In two of these patients, who were suspected of having PWS, this change was restricted to D15S63. In two patients suspected of having AS, several but not all loci were affected. Using a newly developed methylation-specific PCR test for D15S63 we found that these methylation changes are rare in patients suspected of having AS. Although we can not prove that the methylation changes in the four patients are causally related to their disease, our findings demonstrate that spatially restricted changes in methylation can occur. In some cases, these changes may reflect incomplete imprint spreading.

Angelman Syndrome↗
PubMed2001

Speech motor stability in IPD: effects of rate and loudness manipulations.

Increasing phonatory effort, an integral component of the Lee Silverman Voice Treatment, LSVT, has been identified as an effective management strategy for adults with hypokinetic dysarthria associated with Parkinsonism. The present study compares the effects of increased loudness on lower lip movements to those of changes in speaking rate, another approach to the treatment of hypokinetic dysarthria. Movements of the lower lip/jaw during speech were recorded from 8 adults with IPD, 8 healthy aged adults, and 8 young adults. The spatiotemporal index (STI), a measure of spatial and temporal variability, revealed that for all speaker groups slow rate was associated with the most variability. Compared to the other conditions, STI values from the loud condition were closest to those from habitual speech. Also, the normalized movement pattern for the loud condition resembled that of habitual speech. It is hypothesized that speaking loudly is associated with a spatial and temporal organization that closely resembles that used in habitual speech, which may contribute to the success of the LSVT.

Aged↗
PubMed2001

A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation.

The primary objective of this study was to determine the complete remission (CR) rate achieved with the FLAG (fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor) regimen in patients with relapsed or refractory acute myeloid leukaemia (AML) or de novo refractory anaemia with excess of blasts in transformation (RAEB-t). Secondary objectives were to evaluate survival and toxicity. Induction treatment consisted of between one and two courses of FLAG. Patients achieving CR received between one and two courses of consolidation treatment. Eighty-three of the 89 patients entering the study were eligible for assessment. CR rates were: 17 out of 21 (81%) in late relapse AML (Group 1), 13 out of 44 (30%) in early relapse/refractory AML (Group 2), and 10 out of 18 (56%) in de novo RAEB-t (Group 3). Thirty-four of the 40 responders (85%) achieved CR after one induction course. Median survival times were 1.4 years, 3 months and 1.6 years in Groups 1, 2 and 3 respectively. Other than myelosuppression, the FLAG regimen was not generally associated with clinically significant toxicity and was well tolerated by most patients including the elderly. The FLAG regimen offers a very effective alternative treatment for CR induction in poor prognosis adult patients with either relapsed or refractory AML or de novo RAEB-t. FLAG delivers high-dose treatment without increasing overall toxicity, an approach which is of particular value in older patients, who constitute the majority in these diseases. It is therefore an important advance in developing new treatment options for these patients.

Acute Disease↗