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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 181 records · Page 10Linked to original sources

Haemophagocytic syndrome.

Two fatal cases of haemophagocytic syndrome diagnosed on the basis of autopsy findings at the Queen Elizabeth Hospital, Barbados, are presented. They were both young patients, a male 20 years of age and a female 28 years of age, with common clinical features of severe constitutional symptoms, pharyngeal haemorrhages, pancytopenia, and fever. The female patient had elevated titres to herpes simplex virus indicative of recent infection as well as postmortem evidence of overwhelming mixed bacteria sepsis. In both cases, histopathological studies showed lymphoid depletion and histiocytes displaying haemophagocytosis.

Adult↗

Enzymatic digestion, solid-phase extraction, and gas chromatography/mass spectrometry of derivatized intact oxazepam in urine.

Enzymatic digestion with beta-glucuronidase (EC 3.2.1.31) was used to release intact oxazepam from urine samples containing the d5-analog internal standard. The resulting specimens were extracted with Du Pont PREP Type W cartridge (processed by a PREP Automated Sample Processor), Bond Elut Certify, and J.T. Baker "spe" columns for comparison of the columns' extraction recovery and overall effectiveness. Methyl iodide/tetrahexylammonium hydrogen sulfate and N,O-bis(trimethylsilyl)trifluoroacetamide/trimethylchlorosilane (10 g/L) were used for the methylation and trimethylsilylation studies. We used a Hewlett-Packard HP 5790 mass-selective detector equipped with a 13-m J & W DB-5 column (5% phenyl polysiloxane phase) for gas chromatography/mass spectroscopy (GC/MS) analysis and the Thru-Put Target software package for data processing. After several exploratory experiments, we adopted the Du Pont PREP system methylation procedure because of its effective recovery, the superior stability of the derivatization product, the possibility of incorporating a clean-up step, and the potential for high throughput. The extraction recovery from a set of control samples was 87%. Coefficients of variation obtained for six replicates of GC/MS analysis and for the overall procedure were 1% and 3%, respectively. Excellent linearity was established in the 50-8000 micrograms/L concentration range studied. With the use of 3-mL samples, a 20-microL final reconstitution volume, oxazepam at 50 micrograms/L was easily detected under the adopted operation conditions.

Benzodiazepines↗

Purpura and dermal thinning associated with high dose inhaled corticosteroids.

OBJECTIVE: To assess the effect of high dose inhaled corticosteroids on skin. DESIGN: Cross sectional study of patients receiving treatment for chest diseases. SETTING: Outpatient chest clinic in a teaching hospital. PATIENTS: 68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES: Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS: Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION: Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids.

Administration, Inhalation↗

Morphological behavior of cultured bovine adrenal medulla capillary endothelial cells.

Bovine adrenal medulla capillary endothelial cells were isolated and cloned, and their morphological behaviors in vitro were examined. In the culture of primary or early passage, one type of colony formed intracellular lumina both on the dish and in the three dimensional collagen gel. Another type proliferated well and showed morphology ranging from slender-shape to cobblestone shape, and were easily cloned. Cloned cells which showed slender-shapes formed tubular network on plastic dish after addition of PMA, OAG or vanadate, and these cells also formed multicellular tubules in the three dimensional collagen gel. However, the formation of diaphragmed fenestrae by these slender-shape clones was rare. One clone which showed cobblestone shape formed diaphragmed fenestrae, when cultured on collagen gel for more than one month. Isolated colonies or clones showed heterogeneity of cell shape, angiogenic behaviors and fenestrae formation.

Adrenal Medulla↗

Lack of effect of co-trimoxazole on the pharmacokinetics and pharmacodynamics of nifedipine.

The pharmacokinetics of nifedipine and its primary oxidised metabolite, M-I were studied in nine healthy volunteers following a single oral dose of 20 mg nifedipine alone or after pretreatment with oral co-trimoxazole. Following pretreatment with co-trimoxazole, no significant effect was detected on maximum plasma concentration, elimination half-life, or area under the plasma concentration-time curve of either nifedipine or M-I, nor on the blood pressure response to nifedipine.

Adult↗

Ultrasound velocity in human fingernail and effects of hydration: validation of in vivo nail thickness measurement techniques.

Distal nail thickness was measured using an electronic micrometer and both distal and proximal nail ultrasound times were recorded in 20 volunteers (10 male, 10 female), aged 20-39. The fingernail ultrasound velocity was 2.26 X 10(3) m/s (subject range 2.03-2.69) (analysis of variance technique). The proximal ultrasound transit time was greater than distal ultrasound transit time. In three volunteers, five micrometer and one distal midline ultrasound measurement of five nails were repeated on 10 occasions over 2 weeks. For the micrometer readings the average coefficient of variation was 5.3% (SD +/- 2.4%), and for the ultrasound reading the average coefficient of variation was 4.0% (SD +/- 1.3%). To assess the influence of hydration, in five volunteers the distal nail micrometer thickness and the distal nail ultrasound transit time were measured on five nails before and after 30 min of immersion in water initially at 37 degrees C. The mean distal ultrasound transmission time increased from 0.20 +/- 0.04 microseconds to 0.22 +/- 0.04 microseconds (P less than 0.001) after water immersion. The micrometer measurements and ultrasound velocity did not change significantly (mean ultrasound velocity = 2.01 X 10(3) m/s before, 2.04 X 10(3) m/s after immersion).

Adult↗

The effects of nerve terminal activity on non-quantal release of acetylcholine at the mouse neuromuscular junction.

1. Local endplate depolarization induced by anticholinesterase application to mouse nerve-diaphragm preparations was taken as a measure of non-quantal release of acetylcholine. 2. Non-quantal acetylcholine release occurred within 20-60 s after anticholinesterase application, either spontaneously or evoked by nerve stimulation. Non-quantal release declined with time and disappeared after 3-5 min. 3. The amplitude of stimulation-evoked non-quantal release increased with the frequency of stimulation and was maximal at frequencies above 50 Hz. Two stimuli were sufficient to evoke the maximal effect. 4. Micromolar concentrations of atropine, pirenzepine and vesamicol reduced the amplitude and shortened the duration of non-quantal release. Oxotremorine (10(-8) M) enhanced the amplitude and ouabain (10(-4) M) prolonged the duration of non-quantal release. 5. Our results support the idea that the non-quantal release is due to the vesicular acetylcholine transport system which becomes transiently a part of the nerve terminal during exocytotic release of quantal acetylcholine.

Acetylcholine↗

Tissue spaces during development and regression of the decidual cell reaction in ovariectomized, steroid-treated mice.

Changes in the extracellular and blood spaces of the uterus were assessed from the distribution volumes of 51Cr-EDTA and 51Cr-labelled red blood cells during the development and regression of the artificially induced decidual cell reaction in ovariectomized, steroid-treated mice. The normally high values for uterine extracellular space (0.35-0.40 microliter/mg) fell to less than 0.20 microliter/mg in association with decidual growth. Uterine blood space increased from around 0.02 microliter/mg to 0.03-0.05 microliter/mg with decidual development. Induction of decidual regression by removal of s.c. progesterone implants caused a rapid decline in tissue blood volume to reach control values (0.01-0.02 microliter/mg) within 24 h and preceded any reduction in uterine weight. Uterine vascular permeability, as determined from the tissue accumulation of 125I-labelled human serum albumin, fell with a similar time course. Tissue extracellular space returned to the higher control values within 48 h of initiating decidual regression.

Animals↗

A phase II trial of recombinant human interferon-gamma and recombinant tumor necrosis factor in patients with advanced gastrointestinal malignancies: results of a trial terminated by excessive toxicity.

Recombinant human tumor necrosis factor and recombinant human interferon-gamma are two representatives of a novel class of antineoplastic agents. Evaluation of these agents in vitro has suggested that the combination would be more effective than either agent alone. A prior phase I study demonstrated that the maximum tolerated dose for each agent was 150 micrograms/m2/day for 5 days when administered concomitantly. Based on this experience, a phase II trial of patients with biliary tract, pancreatic, and colorectal cancer was planned. Our goal was to treat a minimum of 14 patients with each tumor type. However, in the first 13 patients entered into this trial the toxic effects at the starting doses of 125 micrograms/m2/day for 5 days for each agent were intolerable, with four patients unable to complete planned therapy. In this cohort of patients, no objective responses were observed. Further clinical investigation of this combination should consider alternative treatment schedules to reproduce the in vitro synergistic cytotoxicity of this combination while minimizing host toxicity.

Adolescent↗

Phase I trial of recombinant human gamma-interferon and recombinant human tumor necrosis factor in patients with advanced gastrointestinal cancer.

Recombinant human gamma-interferon and recombinant human tumor necrosis factor are two representatives of a new class of antineoplastic agents. In vitro studies have suggested synergistic cytotoxic activities when the agents are combined. We report a phase I study of these two agents when administered daily for 5 consecutive days every 2 weeks in patients with advanced gastrointestinal cancers. Toxicity resulting from these agents was significant with hyperbilirubinemia representing the dose-limiting toxicity. Significant, although transient, myelosuppression was also observed. The maximal tolerated doses were 150 micrograms/m2/day for 5 days for each agent. Suggestive antineoplastic activity in biliary and pancreatic cancer was observed. Phase II trials of this combination are currently in progress.

Adult↗

Bronchial nerves in chronic obstructive airways disease: a preliminary report.

The nerves lying within 300 microns of the basement membrane were studied in the named bronchi of five normal subjects and nine patients with chronic obstructive airways disease (COAD), using S-100 protein as a marker. Two types of change were found. Firstly, there was patchy proliferation of fine nerve twigs, associated with focal increase in fibroelastic tissue. This proliferation was present to a minor degree in two normal subjects, and to a much greater extent in all patients with COAD. The second type of change was most marked in the main and lobar bronchi of the patients with COAD and cor pulmonale, and consisted of enlargement of nerves to a maximum of 150 microns in diameter. The overall mean nerve diameter in these latter patients was 22.3 microns, significantly greater than the mean diameter, 15.8 microns, in the normal subjects (P less than 0.001).

Aged↗

Single calcium-activated potassium channel in cultured mammary epithelial cells.

The properties of Ca2+-activated K+ channels in mouse mammary epithelial cells in primary culture were studied by the patch-clamp technique. In cell-attached patches, spontaneous channel openings were sometimes observed; the slope conductance of the currents was about 12 pS at negative membrane potentials with a physiological solution (152 mM Na+, 5.4 mM K+) in the pipette. External application of A23187, a calcium ionophore, activated this channel. In excised inside-out patches, the channel was activated by increasing the internal Ca2+ concentration (10(-7) to 10(-6) M). No voltage dependence of the channel was activated was observed. Internal Na+ blocked the outward K+ current in a voltage dependent manner and this block led to the non-linear I-V relationship at positive membrane potentials. The channel was blocked by internal Ba2+ (0.1 mM) and tetraethylammonium (TEA+, 20-50 mM). Ba2+ reduced the open probability but not the single channel conductance, whereas TEA+ reduced the single channel conductance. The single channel conductance of this channel, measured from the inward current with a high-K+ solution (150 mM K+) in the pipette, was large (about 40 pS), and showed inward rectification. These results suggest that this channel is different from the usual small conductance Ca2+-activated K+ channels observed in many other cells.

Animals↗

The effects of temperature on growth and production of the antibiotic granaticin by a thermotolerant streptomycete.

The synthesis of granaticin, a polyketide-derived antibiotic synthesized as a secondary metabolite by Streptomyces thermoviolaceus strain NCIB 10076, was studied at different growth temperatures. Quantitative measurements of the antibiotic made during batch fermentations showed that the yield was greatest at 45 degrees C, whereas the rate of synthesis was most rapid at 37 degrees C. The timing of the appearance of granaticin in culture could not be assigned to any particular phase of growth or to de-repression due to depletion of any particular nutrient. However, at all temperatures, appearance of the antibiotic coincided with a rise in ammoniacal nitrogen presumably due to deamination of glutamate, the carbon source for growth. We have previously shown that production of the antibiotic is pH sensitive and that some carbon sources result in higher titres than others. This paper examines the effect of temperature on the physiology of growth and on antibiotic production in more detail under conditions that also allow an exact measurement of granaticin yield.

Anti-Bacterial Agents↗

The use of A-scan ultrasound in the assessment of small skin tumours.

This study describes the use of A-scan ultrasound for the measurement and characterization of tumour tissue in small skin tumours--basal cell carcinoma, melanocytic naevus, hypertrophic scars and intraepidermal epithelioma. Assessment of the A-scan traces by measurement of: (i) the amplitude of echoes within the area of interest; (ii) the density (number per unit depth) of these echoes; (iii) the regularity of spacing and amplitude of the echoes, and (iv) the amplitude of echoes beneath the area of interest, was used to assist in the differential diagnosis. The results show significant differences in echo amplitude between all the tumours and normal skin. When the tumour A-scan traces were analysed the results indicated that the best discriminating feature between tumours was that of amplitude, followed by regularity, density, non-normalized thickness and finally amplitude of echoes from beneath the tumour. Ultrasound-derived skin thickness measurements were compared to histological measurements for the lesions, and an excellent correlation was found (r = 0.96). It was considered that the A-scan ultrasound investigation of small tumours of the skin was able to provide information on the nature of the tissues contained and may assist in their differential diagnosis.

Adult↗

Optimization of blood sampling time after intravenous bolus doses of gentamicin.

Comparisons were made, based on a one-compartment model, between predicted serum concentrations obtained at various sampling times after i.v. bolus and i.m. injections of gentamicin. Post-dose concentrations 1 h after i.m. injection were within 3% of the maximum concentration at steady-state, indicating that this was the optimal sampling time. Serum concentrations 1 h post-i.v. bolus were less than 7% different from those 1 h post-i.m. injection. In a clinical trial, blood samples taken earlier during the distribution phase of the drug, after an i.v. bolus, resulted in serum concentrations which were up to 74% higher than concentrations at 1 h. A survey of a sample of U.K. hospitals showed that only 41% were taking samples at 1 h post i.v. bolus of gentamicin. The majority of hospitals recommended a range of post-dose serum concentrations between 4 and 12 mg/l for patients with septicaemia, but when adjusted for errors related to sampling time, 36% of hospitals recommended a minimum which was equivalent to less than 4 mg/l at 1 h post dose. Post-dose concentrations of gentamicin should be measured in samples taken 1 h after either i.v. bolus and i.m. injections.

Gentamicins↗