Alpha 2 macroglobulin and the protease-inhibitory activity of colloid pancreatic preservation solutions.
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Colloids↗
Biomedical subjects
C Edwards
Publications and source records attributed to C Edwards.
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↗
A safe and quick method for endoscopic retrieval of multiple gastric foreign bodies using a protective sheath.
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Endoscopes, Gastrointestinal↗
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↗
Improved medium for recovery and enumeration of the farmer's lung organism, Saccharomonospora viridis.
A new medium, which we propose to call R8, was developed for the isolation and enumeration of the thermophilic actinomycete, Saccharomonospora viridis. This organism has been implicated in a range of hypersensitivity pneumonitides, including farmer's lung, but is generally isolated in small numbers from contaminated environments. Recovery of S. viridis from moldy hay and mushroom compost on R8 medium was compared with recovery on conventional media. S. viridis was isolated from both substrates but in highest numbers and most consistently on the R8 medium. The selectivity of this medium was best observed when the sedimentation chamber method was used for hay samples. Here S. viridis accounted for up to 80% of the total number of actinomycetes recovered on R8 and could not be recovered on rifampin selective medium under the same conditions. R8 was also found to be an efficient recovery medium for a range of thermophilic actinomycetes from mushroom compost and for another allergenic species, Faenia rectivirgula, from moldy hay. Contamination of isolation plates by thermophilic bacilli was reduced on R8 compared with the activity on half-strength tryptone soy agar, supplemented with 0.2% casein hydrolysate, and this, together with specific improvements in S. viridis growth, accounts for the selective effect. It is possible that the occurrence of S. viridis and its role as a causative agent of hypersensitivity pnuemonitis have been underestimated by the use of suboptimal recovery protocols. It is hoped that use of R8 in conjunction with dilution plate techniques will generate information on the ecology of S. viridis and contribute to health risk assessment studies.
Actinomycetales↗
The use of indium-111 labeled platelet scanning for the detection of asymptomatic deep venous thrombosis in a high risk population.
Five hundred indium-111 labeled platelet imaging studies (387 donor and 113 autologous) were performed postoperatively in 473 patients who had undergone total hip replacement, total knee replacement, or internal fixation of a hip fracture to detect occult deep venous thrombosis. All patients had been anticoagulated prophylactically with aspirin, warfarin sodium (Coumadin), or dextran. Thirty-four possible cases of proximal deep venous thrombosis were identified in 28 asymptomatic patients. To verify the scan results, 31 venograms were performed in 25 patients (three refused). In 21 of 31 cases, totally occlusive thrombi were detected; in 5 cases, partially occlusive thrombi were detected; in 5 cases, no thrombus was seen. No patient who had a negative scan nor any patient who had a verified positive scan (and received appropriate heparin therapy) subsequently developed symptoms or signs of pulmonary embolism. One hundred forty-one indium study patients also underwent Doppler ultrasonography/impedance plethysmography (Doppler/IPG) as a comparative non-invasive technique. In 137 cases, the results of the indium study and Doppler/IPG studies were congruent. The indium study had no false negative results that were detected by Doppler/IPG. No patient had any clinically evident toxicity. These results suggest that indium-111 labeled platelet scanning is a safe, noninvasive means for identifying DVT in high risk patients.
Adult↗
Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.
Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments.
Adenocarcinoma↗
Exocytosis of bovine chromaffin granules in Ficoll captured by rapid freezing.
Exocytosis of cultured bovine adrenal chromaffin cells was examined in a balanced salt solution containing Ficoll using rapid freezing followed by freeze-substitution. In solution without Ficoll, exposure to Ba2+ produced many exocytotic lumina between the cells; in most cases, these lumina were large and empty. When chromaffin cells were exposed to Ba2+ in Ficoll, it was possible to observe a small pore between the plasmalemma and each granule. The granule retained the dense contents when the pore was approximately 20 nm in diameter, and became empty when the pore was widened in 14% Ficoll. The addition of Ficoll made it easy to catch the events occurring during exocytosis of individual bovine chromaffin granules.
Animals↗
Sequencing and synthesis of pardaxin, a polypeptide from the Red Sea Moses sole with ionophore activity.
Pardaxin, an amphipathic polypeptide secreted by the Red Sea flatfish Pardachirus marmoratus whose sequence is NH2-G-F-F-A-L-I-P-K-I-I-S-S-P-L-F-K-T-L-L-S-A-V-G-S-A-L-S-S-S-G-G-Q-E, was synthesized by the solid-phase method. The structure was verified by sequencing. The synthetic polypeptide changed the resistance of lipid bilayers by forming pores. At 10(-7)-10(-8) M, the synthetic pardaxin increased the frequency of the spontaneous release of quanta of acetylcholine at the neuromuscular junction by up to 100-fold, resembling the native product. Synthetic pardaxin seems to be a suitable tool for investigating the molecular structures underlying channel selectivity.
Acetylcholine↗
Aberrant growth of regenerating retinotectal axons subsequent to optic tract ablation in goldfish.
This study examined the effect of optic tract ablation on retinotectal fiber regeneration in goldfish. Approximately two-thirds of the left optic tract was removed, and, at various times post lesion (10-75 days), the course of regenerating retinotectal fibers was traced using horseradish peroxidase. In all experimental animals, axons were observed regenerating through the visual pathway but at the brachia most of the fibers were channeled through the ventral brachium. We present evidence that fibers in the ventral brachium originated from ganglion cells in all regions of retina and that these fibers grew almost exclusively into ventral half tectum even though some of these fibers would normally synapse in dorsal half tectum. These observations suggest that optic tract ablation does not prevent retinal fiber regeneration but results in aberrant growth through the brachia and significant inhibition of exploratory fiber growth within the tectum.
Animals↗
Differences in the pore sizes of the N-methyl-D-aspartate and kainate cation channels.
The cation channels in central nervous system neurons gated by the glutamate agonists N-methyl-D-aspartate (NMDA) and kainate have been shown to be similar, but not identical. To analyze the differences in more detail, the permeabilities of the channels to cations of different sizes have been measured. The kainate channel appears to be larger, and the cation permeabilities are similar to those of the acetylcholine gated channel at the neuromuscular junction. The NMDA channel appears to be about 10% smaller in size.
Animals↗
A reexamination of the role of the RAD52 gene in spontaneous mitotic recombination.
The RAD52 gene is required for much of the recombination that occurs in Saccharomyces cerevisiae. One of the two commonly utilized mutant alleles, rad52-2, increases rather than reduces mitotic recombination, yet in other respects appears to be a typical rad52 mutant allele. This raises the question as to whether RAD52 is really necessary for mitotic recombination. Analysis of a deletion/insertion allele created in vitro indicates that the null mutant phenotype is indeed a deficiency in mitotic recombination, especially in gene conversion. The data also indicate that RAD52 is required for crossing-over between at least some chromosomes. Finally, examination of the behavior of a replicating plasmid in rad52-1 strains indicates that the frequency of plasmid integration is substantially reduced from that in wild type, a conclusion consistent with a role for RAD52 in reciprocal crossing-over. Analysis of recombinants arising in rad52-2 strains suggests that this allele may result in the increased activity of a RAD52-independent recombinational pathway.
Alleles↗
Development of a surgical case review system.
Quality assurance professionals at Wayne County (Pennsylvania) Memorial Hospital have successfully implemented a surgical case review system for evaluating all inpatient surgical and same-day surgical procedures (including those where no tissue is removed) as well as post-hospitalization infections or complications that may signal unusual events or potential risk factors. The occurrence of such an event triggers a review of the case. Physician members of a surgical case review committee review and evaluate the surgical procedure in such cases and take immediate action to resolve quality of care issues.
Ambulatory Surgical Procedures↗