Search PubMed⌕ Search

Biomedical subjects

A Moore

Publications and source records attributed to A Moore.

At least 217 records · Page 12Linked to original sources
PubMed1996

Retroviral gene transfer in autologous bone marrow transplantation for adult acute leukemia.

To evaluate whether marrow contributes to relapse after autologous bone marrow transplantation (AuBMT) for acute leukemia, transplanted marrow was marked with the G1N retroviral vector (Genetic Therapy Inc.) containing the neomycin phosphotransferase gene (neo). Between April 1992 and August 1993, 4 patients were transplanted for acute myeloid leukemia (AML) in second complete remission (CR) and 1 patient for acute lymphoid leukemia in first CR. An average of 12.4% (range 5-19%) of transplanted marrow mononuclear cells were exposed to G1N vector for 4 hr. In the vector-treated portion of the marrow, 4.9% of GM-CFU and 3.6% of erythroid burst-forming units (BFU-E) were resistant to G418 in vitro. In the 5 patients, the polymerase chain reaction (PCR) detected the neo sequence on only two occasions after AuBMT. Of 4 patients surviving 1 year after transplantation, only 1 had evidence of gene marked cells by PCR. Two AML patients have relapsed, one of whom had evidence of neo sequences in the bone marrow at day 100 but not at relapse 11 months after AuBMT. The second patient relapsed 18 months after AuBMT but never had PCR evidence of neo sequences before or after relapse. Our results indicate vector-transduced autologous bone marrow from heavily pretreated adults with acute leukemia mark with low efficiency, although vector sequences have been detected in bone marrow and peripheral blood up to 1 year after transplant. Of the 2 relapsed patients, no evidence of vector-marked leukemic blasts have been detected.

Acute Disease↗
PubMed1996

Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family.

Cytokines in the tumor necrosis factor (TNF) family regulate development and function of the immune system. We have isolated a new member of this family, designated Apo-2 ligand (Apo-2L), via an expressed sequence tag. Apo-2L is a 281-amino acid protein, related most closely to Fas/Apo-1 ligand. Transfected Apo-2L is expressed at the cell surface with its C terminus exposed, indicating a type II transmembrane protein topology. Like Fas/Apo-1 ligand and TNF, the C-terminal extracellular region of Apo-2L (amino acids 114-281) exhibits a homotrimeric subunit structure. Soluble Apo-2L induces extensive apoptosis in lymphoid as well as non-lymphoid tumor cell lines. The effect of Apo-2L is not inhibited by soluble Fas/Apo-1 and TNF receptors; moreover, expression of human Fas/Apo-1 in mouse fibroblasts, which confers sensitivity to induction of apoptosis by agonistic anti-Fas/Apo-1 antibody, does not confer sensitivity to Apo-2L. Hence, Apo-2L acts via a receptor which is distinct from Fas/Apo-1 and TNF receptors. These results suggest that, along with other family members such as Fas/Apo-1 ligand and TNF, Apo-2L may serve as an extracellular signal that triggers programmed cell death.

Amino Acid Sequence↗
PubMed1996

Initial experience with an implantable hemodynamic monitor.

BACKGROUND: Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS: The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS: Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.

Adult↗
PubMed1996

Milt and endocrine responses of mature male Atlantic salmon (Salmo salar L.) parr to water-borne testosterone, 17,20 beta-dihydroxy-4-pregnen-3-one 20-sulfate, and the urines from adult female and male salmon.

Mature male Atlantic salmon (Salmo salar L.) parr responded to the urine from ovulated females with significant increases in plasma gonadotropin II, 17,20 beta-dihydroxy-4-pregnen-3-one, testosterone, and 11-ketotestosterone concentrations and volumes of expressible milt. There were also significant increases in biliary free steroid and steroid conjugate concentrations. Urine from mature adult male salmon also affected male parr, which responded with increased plasma gonadotropin II concentrations and expressible milt. However, male urine did not elevate the plasma and bile concentrations of any of the steroids. When two of the three known steroids which are detected by the mature male salmon parr olfactory epithelium were tested for priming activity, results showed that these compounds had little or no activity when added to the water. Only plasma gonadotropin II concentrations increased in mature male parr exposed to 17,20 beta-dihydroxy-4-pregnen-3-one 20-sulfate. Female and mature adult male urines contain at least one priming pheromone and there was no conclusive evidence for this priming pheromone being one of the tested steroids. However, the fact that water-borne 17,20 beta-dihydroxy-4-pregnen-3-one 20-sulfate can have a physiological effect in male parr suggests that it may have a role as one of a mixture of compounds in female urine that males detect and respond to. The lack of a priming-like effect of testosterone supports a previous hypothesis that the major pheromonal role of this steroid is as an attractant for mature male salmon parr.

Animals↗
PubMed1996

Clinical validity of major depression-endogenous subtype in adolescent patients.

This paper explored the validity of the distinction between endogenous and nonendogenous forms of major depression in a clinical sample of adolescents, average age 13.6 years. The criteria used to establish this distinction were features of the disorder itself and the external criteria of demography, family history and psychosocial stressors. Endogenous subjects had a more severe form of depressive disorder than nonendogenous subjects. However, there were no significant differences between the depressed groups on any of the external criteria. The distinction between endogenous and nonendogenous major depression in early and mid-adolescence appears therefore to be quantitative rather than qualitative.

Adolescent↗
PubMed1996

Accumulation of a sulphur-rich seed albumin from sunflower in the leaves of transgenic subterranean clover (Trifolium subterraneum L.).

A gene encoding a sulphur-rich, sunflower seed albumin (23% cysteine plus methionine) was modified to contain the promoter for the 35S RNA of cauliflower mosaic virus, in order to obtain leaf expression in transgenic plants. In addition, a sequence encoding an endoplasmic reticulum-retention signal was added to the 3' end of the coding region so as to stabilize the protein by diverting it away from the vacuole. The modified gene was introduced into subterranean clover (T. subterraneum L.) and its expression was detected by northern and western blots and by immunogold localization. The albumin was accumulated in the lumen of the endoplasmic reticulum, and, among six independent, transformed lines, it accumulated in the leaves of T0 transgenic plants at varying levels up to 0.3% of the total extractable protein. The level of accumulation of the sunflower albumin increased with increasing leaf age, and in the older leaves of the most highly expressing plants of the T1 generation it reached 1.3% of total extractable protein. Expression of the SSA gene was stable in the first and second generation progeny. These results indicate that there is potential for significantly improving the nutritional value of subterranean clover for ruminant animals such as sheep by expressing genes that code for sulphur-rich, rumen-stable proteins in leaves.

Albumins↗
PubMed1996

Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics.

Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events--such as number or proportion of patients with 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean data, at least in acute pain models, indicates that more meaningful overviews or meta-analysis may be possible. This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data, and then used that relationship to derive dichotomous from continuous information in randomised controlled trials (RCTs) of analgesics. Individual patient information from 13 RCTs of parallel-group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) and the proportion of patients with greater than 50% pain relief (> 50%maxTOTPAR) for the different treatments. The relationship between the measures was investigated in 45 actual treatments and 10,000 treatments simulated using the underlying actual distribution; 1283 patients had 45 separate treatments. Mean %maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR (r2 = 0.90). The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50% pain relief in 42 of 45 treatments, and 98.8% of 10,000 simulated treatments. For seven effective treatments, actual numbers-needed-to-treat (NNT) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data.

Analgesics↗
PubMed1996

Developing a database of published reports of randomised clinical trials in pain research.

A database of randomised clinical trials (RCTs) in pain research published from 1950 to 1990 was created following an extensive literature search. By applying a refined MEDLINE search strategy from 1966 to 1990 and by hand-searching more than 1,000,000 pages of a total of 40 biomedical journals published during the period 1950-1990, more than 8000 RCTs were identified. The RCTs were published in more than 800 journals and over 85% appeared between 1976 and 1990. If the trend of the last 15 years persists, a total of more than 15 000 RCTs will be published in pain relief by the year 2000. A detailed description of methods to ensure efficient use of resources during the identification, retrieval and management of the information in pain relief and other fields is given. Emphasis is made on the importance of refining MEDLINE search strategies, on the use of volunteers to hand-search journals and on careful monitoring of each of the steps of the process. The potential uses of the database to guide clinical and research decisions are discussed.

Databases, Bibliographic↗
PubMed1996

Two infant vision screening programmes: prediction and prevention of strabismus and amblyopia from photo- and videorefractive screening.

Two infant vision screening programmes on total populations in the Cambridge Health District have been designed to identify manifest strabismus and strabismogenic and amblyogenic refractive errors at 7-9 months of age. The first, completed, programme used the isotropic photorefractor with cycloplegia together with a standard orthoptic examination. The second, current, programme uses the VRP-1 isotropic videorefractor to identify infants with accommodative lags which are followed up by refraction under cycloplegia. Both programmes show good agreement between infants identified at screening and retinoscopic refractions at follow-up, showing that photo- and videorefraction (with or without cycloplegia) can be effective methods for screening for ametropia in infants and young children. In each programme 5-6% of infants showed abnormal levels of hyperopia (> or = 3.5 D in any meridian), less than 1% showed anisometropia > or = 1.5 D; very few infants (0.25%) showed -3D myopia or greater. Less than 1% showed manifest strabismus. Hyperopic and anisometropic children entered a randomised controlled trial of partial refractive correction. All children identified at screening, alongside appropriate control groups, are extensively followed up to age 4 years. The first programme has found that children who were hyperopic in infancy were 13 times more likely to become strabismic, and 6 times more likely to show measurable acuity deficits by 4 years, compared with controls. Wearing a partial spectacle correction reduced these risk ratios to 4:1 and 2.5:1 respectively. The impaired acuity can be attributed, in part, to meridional amblyopia resulting from persisting astigmatism. Both hyperopic and myopic infants showed refractive changes in the direction of emmetropia between 9 months and 4 years. Wearing a partial spectacle correction did not affect this process of emmetropisation, but does provide the possibility of reducing the incidence of common pre-school vision problems.

Aging↗
PubMed1996

Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor.

Mice that have been made deficient for the cystic fibrosis transmembrane conductance regulator (Cftr) usually die of intestinal obstruction. We have created Cftr-deficient mice and demonstrate prolonged survival among backcross and intercross progeny with different inbred strains, suggesting that modulation of disease severity is genetically determined. A genome scan showed that the major modifier locus maps near the centromere of mouse chromosome 7. Electrophysiological studies on mice with prolonged survival show that the partial rectification of Cl- and Na+ ion transport abnormalities can be explained in part by up-regulation of a calcium-activated Cl- conductance. Identification of modifier genes in our Cftr(m1HSC)/Cftr(m1HSC) mice should provide important insight into the heterogeneous disease presentation observed among CF patients.

Animals↗
PubMed1996

Establishing the cut-off concentration for the detection of etorphine in horse urine.

An 125I radioimmunoassay to determine the pattern of urinary excretion of etorphine (a semisynthetic opiate agonist) after its administration to horses is described. Three thoroughbred horses were each given 5, 15, 30 and 100 micrograms of etorphine intramuscularly. Urine was collected for up to 72 after administration. The maximum etorphine concentration after administration of a dose of 5 micrograms was 711 pg ml-1 (concentrations were greater than 100 pg ml-1 after 23 h in all three horses); a 15 micrograms gave 2661 pg ml-1 (levels remained above 100 pg ml-1 for more than 44 h in each horse); a 30 micrograms dose gave a maximum of 3344 pg ml-1 (levels were above 100 pg ml-1 for 24, 72 and 72 h); and 100 micrograms gave in excess of 10,000 pg ml-1 (levels were greater than 300 pg ml-1 for up to 70 h). Forty-eight urine samples from horses not given etorphine all had levels of etorphine less than 100 pg ml-1. There was no increase in apparent etorphine concentrations after hydrolysis of samples with beta-glucuronidase and aryl sulfatase. The half-lives of etorphine equivalents (calculated with a mono-exponential equation after the 100 micrograms dose) in the urine of the three horses were 569, 803 and 821 min, respectively. We conclude that radioimmunoassay can provide a useful first line screening procedure for the assessment of etorphine use in racing horses.

Animals↗
PubMed1996

Omitting nitrous oxide in general anaesthesia: meta-analysis of intraoperative awareness and postoperative emesis in randomized controlled trials.

We have reviewed randomized controlled trials to assess the effectiveness and safety of anaesthetics which omitted nitrous oxide (N2O) to prevent postoperative nausea and vomiting (PONV). Early and late PONV (6 and 48 h after operation, respectively), and adverse effects were evaluated using the numbers-needed-to-treat (NNT) method. In 24 reports with information on 2478 patients, the mean incidence of early and late vomiting with N2O (control) was 17% and 30%, respectively. Omitting N2O significantly reduced vomiting compared with a N2O regimen; the combined NNT to prevent both early and late vomiting with a N2O-free regimen was about 13 (95% confidence intervals (CI) 9, 30). The magnitude of the effect depended on the incidence of vomiting in controls. In studies with a baseline risk higher than the mean of all reports, the NNT to prevent both early and late vomiting with a N2O-free anaesthetic was 5 (95% CI 4, 10). When the baseline risk was lower than the mean, omitting N2O did not improve outcome. Omitting N2O had no effect on complete control of emesis or nausea. The NNT for intraoperative awareness with a N2O-free anaesthetic was 46 compared with anaesthetics where N2O was used. This clinically important risk of major harm reduces the usefulness of omitting N2O to prevent postoperative emesis.

Anesthesia, General↗