Search PubMed⌕ Search

Biomedical subjects

D Bell

Publications and source records attributed to D Bell.

At least 127 records · Page 7Linked to original sources
PubMed1994

A phase II study of carboplatin and cisplatin in advanced ovarian cancer.

In view of the single agent activity of both cisplatin and carboplatin in epithelial ovarian cancer, and their different toxicity profiles, we carried out a phase II study of low dose cisplatin (50 mg/m2) in combination with moderate dose carboplatin (300 mg/m2) in patients with advanced ovarian cancer. Fourteen patients, all of whom had bulky disease and over half of whom had Stage IV disease, were eligible for assessment of response and toxicity. An overall response rate of 71% was demonstrated (57% complete response, 14% partial response), which is at least equivalent to other regimens used in first line treatment of ovarian cancer. Toxicities encountered were nausea/vomiting and myelosuppression, however no serious renal neuro or ototoxicity was observed and the regimen does not cause significant alopecia. This combination may be a practical alternative to regimens which use high dose cisplatin to achieve similar efficacy.

Aged↗
PubMed1993

Structural determinants of quaternary ammonium blockers for batrachotoxin-modified Na+ channels.

Amphipathic quaternary ammonium (QA) compounds are potent blockers of batrachotoxin (BTX)-modified Na+ channels incorporated into planar lipid bilayers. To examine the topology of the QA binding site, we selected two series of QA compounds as structural probes. One series contains two separate hydrophobic moieties but with a common hydrophilic dimethyl QA ion. Most of the QAs within this group bind to BTX-modified Na+ channels with relatively high affinities. For example, benzyldimethyldodecyl ammonium ions, when applied internally, block single, muscle, BTX-modified Na+ channels in bilayers with a one-to-one relationship and display an equilibrium dissociation constant (Kd) of 0.2 microM at +50 mV. Furthermore, the QA dwell times appear to correlate with QA hydrophobic interactions with the channel. These results indicate that there are two large hydrophobic binding domains within the QA binding site. The QAs in the second series contain a hydrophilic head group (trialkylammonium) of variable size but with a common dodecyl hydrophobic tail. Tripropyldodecyl QAs block BTX-modified Na+ channels more effectively (Kd = 0.4 microM at +50 mV) than do trimethyl- and triethyldodecyl QAs, suggesting that the internal Na+ permeation pathway is at least 9 A wide. However, tributyl- and tripentyldodecyl QAs show much lower affinities for BTX-modified Na+ channels at comparable concentrations. These drugs are cut off from binding, probably as a result of the size of their hydrophilic heads (> 10 A), which may be too large to fit in the QA binding site and too bulky to travel freely within the internal permeation pathway. Under whole-cell voltage-clamp conditions, we have further found that BTX-modified Na+ currents in clonal GH3 cells can be blocked by these two series of QA ions, albeit only when the activation gate is open. Closed channels at rest do not bind appreciably with these QA ions. Binding of QA ions is reduced by external Na+ ions in GH3 cells in a manner indicating that external Na+ ions can clear the bound QA ions from the Na+ pore. These results from GH3 cells mirror those obtained with QA blockers in K+ channels of squid axons and suggest that the QA binding domains in BTX-modified Na+ channels and K+ channels may be structurally conserved.

Animals↗
PubMed1993

Arthritis in hemochromatosis.

We reviewed the clinical and radiographic features of arthropathy in 25 subjects with hemochromatosis, 16 probands and 9 discovered homozygous relatives. Clinical arthritis was present in 15/16 probands and 1/9 discovered homozygotes (p < 0.005). Radiologic evidence of arthropathy was seen additionally in 2 asymptomatic discovered homozygotes. The metacarpophalangeal joints and wrists were most commonly involved; severe hip disease occurred in 6. Patients with clinical or radiologic arthropathy were older than patients without. Arthropathy occurred in all 4 female probands, but in none of the 3 female discovered homozygotes. Chondrocalcinosis was seen in 9 subjects but was usually asymptomatic. The arthritis of hemochromatosis may be difficult to differentiate from several other joint diseases, especially calcium pyrophosphate dihydrate deposition disease.

Adult↗
PubMed1992

A calcium model with random absorption: a stochastic approach.

Absorption of calcium, or any mineral, by the body is subject to the random fluctuations typical of diffusion through membranes. In this paper we consider the absorption of calcium from the gut as a white noise process added to the deterministic model of Sen & Mohr (1990, J. theor. Biol. 142, 179-188). The first two moments for the amount of calcium in the extracellular fluid (ECF) have been derived using the Ito Calculus. A confidence interval for the total amount of calcium in the ECF is constructed. The equations for the first two moments of the fraction of dose calcium in the ECF are also given. Suggestions are made for the collection of experimental data in a form which should be helpful in investigating the magnitude of the stochastic effect.

Calcium↗
PubMed1992

Blood conservation.

Explore the source record for details and available documents.

Blood Loss, Surgical↗
PubMed1992

Neutrophil count and activation in vascular disease.

An elevated peripheral leucocyte count is associated with an increased risk of myocardial infarction and progression of coronary artery disease. The aim of this study was to determine neutrophil count and activation, measured as an increase in plasma neutrophil elastase, in patients with stable ischaemic heart disease, insulin-dependent diabetes mellitus and essential hypertension compared with a comparable group of control subjects. Neutrophil count and neutrophil elastase were raised significantly for patients with ischaemic heart disease (p less than 0.005; p less than 0.002), diabetes mellitus (p less than 0.001; p less than 0.01) and hypertension (p less than 0.05; p less than 0.0001) respectively compared to the control subjects. Neutrophil elastase did not correlate with subject age or leucocyte count. This study confirms the association between leucocyte count and vascular disease, and is consistent with neutrophil activation contributing to the progression of vascular disease.

Adult↗
PubMed1992

Integrated approach for evaluating species and interindividual differences in responsiveness to dioxins and structural analogs.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that is produced inadvertently during the synthesis of some organochlorine compounds, such as the chlorinated phenoxy pesticides. It is biologically and ecologically persistent, with an estimated half-life of 7 years in humans. It possesses high acute toxicity in rodents and is a carcinogen, teratogen, and immunotoxin. In chronic bioassays for carcinogenicity, TCDD at a dose of 10 ng/kg/day increases the incidence of liver tumors in female rats, making it one of the most potent animal carcinogens ever tested. A recent study in humans has shown an increase in the incidence of respiratory tract tumors in workers in chlorinated phenoxy herbicide plants. Considerable controversy and uncertainty remain, however, concerning its carcinogenic potency in humans and the reliability of using animal data to predict human risks. It is generally accepted that most, if not all, of the effects of TCDD require its binding to the Ah receptor. In addition to its toxic effects, TCDD produces a number of biochemical effects, such as induction of CYP1A1, downregulation of binding activity of the estrogen and epidermal growth factor (EGF) receptors, and changes in cytokine pathways. These effects suggest that the Ah receptor plays an important role in regulating the cell cycle. A number of structural analogs of TCDD, such as the polychlorinated dibenzofurans, also interact with the Ah receptor, and they produce the same spectrum of responses as TCDD in animal and cell models. The potency of these compounds is strongly correlated with their binding affinity to the Ah receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Treatment of congenital pseudoarthrosis of the tibia using the Ilizarov technique.

The principle of treatment of congenital pseudoarthrosis of the tibia (CPT) with the Ilizarov method corrects all angular deformity and maximizes the cross-sectional area of union of the pseudoarthrosis. Fifteen patients with a total of 16 CPT were treated using the Ilizarov apparatus. Various forces were used to treat the pseudoarthrosis site including compression, distraction, open reduction, resection and shortening, resection and bone transport, and invagination of one end in the other. Lengthening was performed in 12 of the 16. Deformity was corrected in all cases. The union rate was 94% with one treatment and 100% with two treatments. There were five refractures, three early and two late. Previous pin sites, residual angular deformity, and natural history were considered predisposing factors for refractures. One patient refractured twice but remained ununited. Fifteen remained united, with a mean follow-up period of four years (range, two to seven). There were two residual deformities, one in the regenerate and one at the level of the CPT.

Adolescent↗
PubMed1991

Anti-cruciform DNA affinity purification of active mammalian origins of replication.

A novel approach that employs anti-cruciform DNA monoclonal antibodies was used to isolate segments of cruciform-containing DNA from genomic DNA, in an effort to obtain fragments containing active origins of replication. High molecular weight DNA (greater than 50 kb) was extracted from log phase CV-1 cells and 6 micrograms incubated with approximately 2.5 micrograms of a monoclonal antibody, 2D3, specific for cruciform-containing DNA. The 2D3-bound DNA was digested with EcoRI and antibody-bound fragments were recovered using rabbit anti-mouse immunobeads. The beads were washed free of nonspecifically bound DNA and the 2D3-bound DNA was eluted with 2% sodium dodecyl sulphate (SDS). The yield of DNA recovered by 2D3 was 2000-fold less than the initial amount and was 17-20-fold more than that recovered nonspecifically using the control mAb, P3. The 2D3-bound DNA ranged from 0.15- greater than 23 kb with a major peak at approximately 12 kb. Specific enrichment of origin-containing DNA by 2D3 over P3 was suggested by a 10-100-fold greater recovery of a 9 kb fragment hybridizable to a low-copy monkey autonomously replicating sequence, ors 8. 20 ng of affinity-purified DNA was cloned into lambda Zap II and excised into Bluescript phagemids in vivo. Of nine randomly-selected clones between 0.15 and 3.2 kb, four were able to replicate autonomously when transfected into HeLa cells. Two of the nine clones contained sequences hybridizable to both monkey alpha-satellite and human Alu DNA, and two others to Alu alone. The present work provides further evidence for the involvement of cruciforms at active mammalian origins of DNA replication.

Animals↗
PubMed1991

Use of a guideline based questionnaire to audit hospital care of acute asthma.

OBJECTIVES: To design an audit questionnaire and pilot its use by an audit assistant to monitor inpatient management of acute asthma and to compare the care given by chest physicians and general physicians. DESIGN: Retrospective review by a chest physician and audit assistant of a random sample of 76 case records of patients by a criterion based questionnaire developed from hospital guidelines on management of acute asthma. SETTING: One district general hospital. PATIENTS: 76 adult patients with acute asthma: 38 admitted with a relevant primary diagnosis between April 1988 and March 1989 and a further 38 admitted through the accident and emergency department between April 1989 and March 1990. MAIN OUTCOME MEASURES: Conformity with recognised standards for assessment and management of acute asthma before and after the audit and by chest physicians and general physicians. RESULTS: Age and sex did not differ significantly between the different groups of patients. Overall, deviations from the guidelines occurred in recording measures of severity of asthma, emergency treatment with beta 2 agonists (60/76, 79%) and steroids (43/76, 57%), and prescription of antibiotics in accordance with at least one criterion of the guidelines (29/45, 64%). Chest physicians were more rigorous than general physicians in recording severity measures, especially serum potassium concentration (chi 2 = 3.6, df = 1, p = 0.06), emergency steroid treatment within the correct period (chi 2 = 3.9, df = 1, p = 0.05), and referral for follow up at an outpatient chest clinic. Recording of arterial blood gas tensions improved significantly between the 1988-9 and 1989-90 samples (chi 2 = 7.0, df = 1, p = 0.08). CONCLUSIONS: The questionnaire proved easy to use for both doctor and audit assistant. The audit improved few standards of care and emphasises the need for further reinforcement and feedback.

Acute Disease↗
PubMed1991

Thermodynamics of hydrolysis of oligosaccharides.

Microcalorimetry has been used to determine enthalpy changes for the hydrolysis of a series of oligosaccharides. High-pressure liquid chromatography was used to determine the extents of reaction and to check for any possible side reactions. The enzyme glucan 1,4-alpha-glucosidase was used to bring about the following hydrolysis reactions: (A) maltose(aq) + H2O(liq) = 2D-glucose(aq); (B) maltotriose(aq) + 2H2O(liq) = 3D-glucose(aq); (C) maltotetraose(aq) + 3H2O(liq) = 4D-glucose(aq); (D) maltopentaose(aq) + 4H2O(liq) = 5D-glucose(aq); (E) maltohexaose(aq) + 5H2O(liq) = 6D-glucose(aq); (F) maltoheptaose(aq) + 6H2O(liq) = 7D-glucose(aq); (G) amylose(aq) + nH2O(liq) = (n + 1) D-glucose(aq); and (H) panose(aq) + 2H2O(liq) = 3D-glucose(aq); (J) isomaltotriose(aq) + 2H2O(liq) = 3D-glucose(aq). The enzyme beta-fructofuranosidase was used for the reactions: (K) raffinose(aq) + H2O(liq) = alpha-D-melibiose(aq) + D-fructose(aq); and (L) stachyose(aq) + H2O(liq) = o-alpha-D-galactopyranosyl-(1----6)- alpha-o-D-galactopyranosyl-(1----6)-alpha-D-glucopyranose + D-fructose(aq). The results of the calorimetric measurements (298.15 K, 0.1 M sodium acetate buffer, pH 4.44-6.00) are: delta H0A = -4.55 +/- 0.10, delta H0B = -9.03 +/- 0.10, delta H0C = -13.79 +/- 0.15, delta H0D = -18.12 +/- 0.10, delta H0E = -22.40 +/- 0.15, delta H0F = -26.81 +/- 0.20, delta H0H = 1.46 +/- 0.40, delta H0J = 11.4 +/- 2.0, delta H0K = -15.25 +/- 0.20, and delta H0L = -14.93 +/- 0.20 kJ mol-1. The enthalpies of hydrolysis of two different samples of amylose were 1062 +/- 20 and 2719 +/- 100 kJ mol-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylose↗
PubMed1991

Estimating the size of myocardial infarction by magnetic resonance imaging.

OBJECTIVE: To develop a method to measure myocardial infarct size by magnetic resonance imaging and to compare the results with pyrophosphate scanning by single photon emission computed tomography. DESIGN: All patients underwent magnetic resonance imaging and pyrophosphate scanning 5-7 days after the onset of symptoms. Both measurements of infarct size were compared with the release of creatine kinase MB and with ventricular performance estimated by radionuclide ventriculography. PATIENTS: 19 patients (age 40-68 years) who had sustained their first uncomplicated myocardial infarction and who had not been treated with thrombolytic therapy. RESULTS: The site of infarction was clearly shown by both imaging techniques and was identical in each patient. The volume of infarcted tissue measured by magnetic resonance imaging agreed well with the infarct size measured by single photon emission tomography (mean difference 2.7 cm3). Correlations of both imaging techniques with the release of creatine kinase MB were best when total release rather than peak release was used. Both imaging techniques correlated closely with the subsequent ventricular performance. CONCLUSIONS: Magnetic resonance imaging after acute infarction allows measurement of infarct size and this may prove useful in assessing new treatments designed to salvage myocardium.

Adult↗