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Biomedical subjects

E Woods

Publications and source records attributed to E Woods.

At least 19 recordsLinked to original sources

Postnatal renal adaptation in preterm and term lambs.

The present experiments determined if increases in renal reabsorptive capacity during the transition from fetal to neonatal life are gestation dependent. Renal function was studied in chronically-catheterized fetal lambs (133 +/- 1 days; term, 145-150 days). Additionally, renal function was studied in anaesthetized, ventilated, caesarean-delivered preterm lambs (109-139 days gestation) and term lambs (148 days gestation), and in 2-day-old spontaneously-delivered term lambs. Newborns < or = 120 days old received surfactant to facilitate ventilation and maintenance of physiologic blood gases. Two hours after caesarian delivery, urine osmolality, urine flow, glomerular filtration rate (GFR), and fractional sodium excretion (FENa) values were similar for all gestations. Relative to fetal values, caesarean-delivered newborn renal values included lower urine flow rates (0.20 +/- 0.03 v. 0.05 +/- 0.01 mL min-1 kg-1), higher urine osmolalities (118 +/- 15 v. 422 +/- 16 mOsmol kg-1 H2O), and no differences in GFR or FENa. Relative to caesarean-delivered newborns, 2-day newborn renal function included higher values for GFR (0.7 +/- 0.1 v. 3.0 +/- 0.1 mL min-1 kg-1) and urine osmolality (724 +/- 32 mosmol kg-1 H2O), and lower FENa (7.0 +/- 1.5 v. 0.2 +/- 0.02%), and urine flow (0.005 +/- 0.003 mL min-1 kg-1). The 132- and 139-day animals were ventilated for 5 h and 10 h respectively; the only functional change at 10 h was a decrease in FENa (7.0 +/- 1.5 v. 2.8 +/- 0.1%). It is concluded that: (1) relative to fetal animals, renal adaptive responses in anaesthetized, ventilated newborns begin within 2 h following caesarian delivery; (2) initial adaptive responses are not gestation dependent after 109 days; and (3) the combined effects of ventilation and/or anaesthesia delay postnatal renal adaptations for at least 10 h after birth.

Absorption

Surfactant treatment and ventilation effects on surfactant SP-A, SP-B, and SP-C mRNA levels in preterm lamb lungs.

The effects of exogenous surfactant treatment combined with postnatal ventilation on surfactant protein (SP)-A, SP-B, and SP-C steady-state mRNA levels were evaluated in preterm sheep at 120, 132, and 139 days gestation. Three groups were studied at each gestation period: animals ventilated and treated with 100 mg/kg natural sheep surfactant, animals ventilated and not treated with surfactant, and a comparison group of lambs that were neither ventilated nor treated with surfactant. In unventilated lambs, SP-A and SP-C mRNA levels measured by densitometry from Northern blots increased between 120 and 132 days gestation (P < 0.05). At 120 days gestation, no differences in SP-A, SP-B, or SP-C mRNA levels were noted among the three groups. At 132 days gestation, SP-A mRNA levels increased in both ventilated groups (P < 0.01), but no additional surfactant effect on SP-A mRNA expression was detected. There were no changes in SP-B or SP-C mRNA levels among the groups at 132 days gestation. At 139 days gestation, mRNA levels for both SP-A and SP-B increased after ventilation, compared with the unventilated groups (P < 0.05). Furthermore, an additional effect of surfactant treatment to increase SP-A mRNA levels relative to animals undergoing ventilation alone was noted (P < 0.05). We conclude that postnatal changes in mRNA levels for the surfactant proteins are gestationally regulated and protein specific.

Animals

Surfactant protein A labeling kinetics in newborn and adult rabbits.

Surfactant protein A (SP-A), the major hydrophilic protein specifically associated with surfactant, has multiple metabolic and host defense functions as well as primary surfactant biophysical functions in association with the other surfactant proteins and lipids. To characterize its kinetics of secretion and clearance from the airspace, we measured specific activity-time curves for alveolar and lamellar body associated SP-A following the intravascular and/or intratracheal administration of the radiolabeled precursors Tran 35S-label containing primarily methionine and cysteine or [3H]methionine to newborn and adult rabbits. Alveolar SP-A specific activity peaked 30 min after precursor injection in both newborn and adult rabbits, and labeled SP-A was not detected in lamellar bodies until after 2 h. In newborns, a second peak of labeled SP-A appeared at 15 h. In both newborns and adult rabbits, lamellar body specific activity-time curves were most consistent with SP-A entering lamellar bodies via a recycling pathway from the airspaces. The airspace clearance of SP-A in adult rabbits had a biologic half-life of about 4.5 h. There was very little decrease in SP-A specific activity in the newborn rabbits, indicating minimal catabolism. These studies demonstrate secretion of endogenously synthesized SP-A by a pathway separate from lamellar bodies. The kinetics of secretion of SP-A and the surfactant phospholipid in newborn and adult rabbits indicate separate metabolic pathways.

Animals

Double-blind comparison of the efficacy of diclofenac/misoprostol and diclofenac in the treatment of rheumatoid arthritis.

A double-blind, randomised, parallel-group study was conducted in eight countries to compare the efficacy of a fixed combination of diclofenac sodium (50 mg) and misoprostol (200 mcg) with a fixed combination of diclofenac sodium (50 mg) and placebo in treating the signs and symptoms of rheumatoid arthritis (RA). A total of 346 patients with RA who had been stabilised on diclofenac for at least 30 days were randomly assigned to receive either diclofenac/misoprostol BID or TID (n = 177) or diclofenac/placebo BID or TID (n = 169) for 12 weeks. Primary analyses of efficacy, made upon admission and at 4-week intervals, consisted of physician's global assessment of the arthritic condition, patient's global assessment of the arthritic condition, patient's global assessment of joint tenderness/pain, and physician's assessment of joint swelling. In this study, the fixed combination tablet of diclofenac sodium 50 mg/misoprostol 200 mcg administered BID or TID demonstrated no statistically significant difference in efficacy in the treatment of the signs and symptoms of RA compared with diclofenac sodium 50 mg/placebo administered BID or TID.

Arthritis, Rheumatoid

Design and rationale of a randomised comparison of cyclophosphamide, methotrexate and fluorouracil vs fluorouracil, epirubicin and cyclophosphamide in node-positive premenopausal women with operable breast cancer. A trial of the International Collaborative Cancer Group (ICCG).

In 1984, the International Collaborative Cancer Group (ICCG) started a randomised trial comparing adjuvant treatment with cyclophosphamide 100 mg/m2 orally on days 1 to 14, methotrexate 40 mg/m2 intravenously on days 1 and 8 plus fluorouracil 600 mg/m2 intravenously on days 1 and 8 every 4 weeks for 6 cycles (CMF) vs fluorouracil 600 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 600 mg/m2 (FEC), all given intravenously on day 1 for 8 cycles at 3-week intervals in premenopausal patients with node-positive breast cancer. However, a large French institution that joined the ICCG shortly after the trial was initiated utilised different schedules of both CMF and FEC. Because different dose intensities were also employed, particularly of FEC, both patient groups, the French and non-French, will be analysed separately. A total of 761 patients were randomised as of March 1992. Patients were well balanced for prognostic factors. The median follow-up is now 3.5 years. Preliminary data have previously been reported in abstract form. Final data will be presented pending further follow-up.

Administration, Oral

Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin.

High-dose aspirin therapy for rheumatoid arthritis is frequently associated with severe gastrointestinal injury. To explore the possibility of reversing such damage, we conducted a double-blind, multicenter study with misoprostol, a prostaglandin E1 analog, which has demonstrated mucosal protective, gastric antisecretory, and ulcer healing properties. We also studied possible interference of misoprostol with continuing aspirin treatment in the management of patients with rheumatoid arthritis. Patients with confirmed rheumatoid arthritis and endoscopically documented gastroduodenal lesions were randomly assigned to receive 200 micrograms of misoprostol four times a day (123 patients) or placebo (116 patients). Each concurrently received 650 to 1300 mg of aspirin four times a day. After eight weeks of treatment, misoprostol was statistically superior to placebo in healing gastric mucosal injury (70% vs 25%) and duodenal mucosal injury (86% vs 53%). Patients with gastric or duodenal ulcers on admission had superior ulcer healing rates with misoprostol (67% vs 26%). There was no evidence of interference with the antirheumatic properties of aspirin. Mild to moderate adverse experiences were equally noted in misoprostol and placebo groups. Misoprostol, coadministered with aspirin, is well tolerated and highly effective in healing aspirin-associated gastroduodenal lesions in patients with rheumatoid arthritis without altering the therapeutic benefits of aspirin.

Adult

Assessment of the safety of chemicals administered intravenously in the neonatal rat.

A 3-day-old neonatal rat model for the safety assessment of various drugs, chemicals, and nutrients administered intravenously is described. This model was used to assess the safety of di(2-ethylhexyl) phthalate (DEHP), cyclohexanone, and a 3:1 mixture of medium and long-chain triglyceride emulsions following subchronic administration using the intravenous route. The administration of DEHP at dosage of 164.8 mg/kg for 18 consecutive days resulted in a small but statistically significant increase in liver weight and SGOT activity. However, no conclusive histopathological alternations could be discerned between livers from DEHP and normal saline (control) animals. No effects were observed among neonates treated with cyclohexanone at dosages up to 25 mg/kg for 18 consecutive days. Because of technical difficulties emanating from high dosage volumes, the administration of lipid emulsion mixture lasted 9 consecutive days only. Except for transient ataxia and sedation, no adverse effects were observed among neonates that received 3:1 medium- and long-chain triglyceride emulsion for 9 consecutive days beginning on day 3 postpartum. No adverse effects were observed among neonates receiving the lipid emulsions for 7 consecutive days beginning on day 12 postpartum.

Animals

Tissue distribution and excretion of tri-(2-ethylhexyl)trimellitate in rats.

The disposition kinetics of tri-(2-ethylhexyl)trimellitate (TEHTM), a new plasticizer for polyvinyl chloride (PVC) plastic, was studied in rats following intravenous administration of [14C-carbonyl]tri-(2-ethylhexyl)trimellitate using an oil in water emulsion as the vehicle. The distribution half-life, elimination half-life, and clearance values estimated from the plasma concentration of radioactivity data obtained following iv administration of 10.5 mg/kg of TEHTM (59.9 muCi/kg), were 46.2 min, 5.34 d, and 40.5 ml/kg X h, respectively. Following iv dosage of 15.6 mg/kg of TEHTM (28.0 muCi/kg), significant accumulation of radioactivity was found in the liver, lungs, and spleen, with liver accounting for 72% of the administered dosage at 24 h. Excretion of TEHTM and its biotransformation products was slow, with 21.3% of the administered radioactivity found in the feces and 2.8% in the urine during the 14-d collection period. Biliary excretion seems to be the major route of elimination of TEHTM. The pharmacokinetic data gathered in the present investigation are compared to di-(2-ethylhexyl)phthalate (DEHP), a widely used plasticizer for PVC.

Animals

Ethylene oxide sensitivity in hemodialysis patients.

Sera from 138 patients who had experienced hypersensitivity-type reactions while on hemodialysis (reactors) were examined retrospectively by the radioallergosorbent test (RAST) for specific IgE antibody to ethylene oxide (ETO). Seventy-eight hemodialysis patients without a history of reaction were also evaluated as controls. Elevated serum RAST values (greater than 2.0) were more common in reactors (63%) than in controls (11%, p less than 0.001). In a second study, RAST assays were performed using human serum albumin conjugated to ETO (HSA-ETO) as antigen and also using a concentrate of fluid used to rinse ETO-sterilized dialyzers ("dialyzer extract") as antigen. The RAST ratios obtained with HSA-ETO were similar to those obtained using the dialyzer extract (rank order correlation coefficient = 0.829, p less than 0.001). In a third study, RAST inhibition was demonstrated both by HSA-ETO and dialyzer extract. Our results, extending previously published reports, suggest that hypersensitivity to ETO might play an important role in hemodialysis-associated hypersensitivity-type reactions.

Antigens

Patella alta and the adolescent growth spurt.

The presence of patella alta has been linked to recurrent dislocation of the patella and the patello-femoral stress syndrome. It is not known whether patella alta is an inherited or acquired trait. To investigate the relationship of patella during the adolescent growth spurt, serial orthoroentgenograms (growth study films) were retrospectively analyzed in 19 patients. Two were found in whom proximal patella migration could be correlated (r = 0.85) with femoral growth rate. This was significant at the p = 0.01 level. Girls had a higher correlation of patella height to growth rate than boys. In certain cases, patella alta is an acquired rather than inherited condition; this supports the theory that overgrowth during the growth spurt can lead to patella alta in some individuals.

Adolescent

Assessment of potential toxic effects of treated Hemofil injection in rats and mice and on the systemic hemodynamics in dogs.

The toxic effects of treated Hemofil (T-AHF) injection were evaluated by acute and subchronic intravenous administration to rats, mice, and dogs. Acute iv administration of T-AHF to rats and mice at dosages of 1320 units (U) of Factor VIII/kg did not produce toxic signs. Both species were found to have an LD50 greater than 1320 U. Seven-day iv administration to rats of T-AHF at dosages of 20, 40, and 60 U/kg and 3-mo administration (3 times/wk for 13 wk) of T-AHF at dosages of 100 and 200 U/kg did not produce any signs of toxicity. There were no treatment-related effects on body weights, hematology, clinical chemistry, urinalysis, ocular tissues, or histopathology. Intravenous administration to dogs at 0.5, 1.0, and 5.0 ml/min . kg (28 U/ml, 100 U/kg at each rate) produced no significant adverse effects on mean arterial pressure, cardiac output, or heart rate. No adverse changes in pulmonary function, as reflected by arterial blood-gas profiles, were observed. It is concluded that animals tolerated well T-AHF administered at dosages and rates similar to or greater than dosages used clinically. The results obtained from these studies establish a reasonable margin of safety and support the acceptability of the T-AHF for clinical use.

Analysis of Variance

The Angelchik antireflux prosthesis. Effects on the lower esophageal sphincter of primates.

It has been shown that the ACAP causes significant increases in the LES pressure of supine primates which are maximal when properly placed at the EGJ. This effect appears to be due to posterior padding of the EGJ in supine animals and can be reproduced by dowel rods or Maloney dilators. Further studies to evaluate the contribution of this effect to the prevention of acid reflux are underway.

Animals

Effect of cavosurface treatment on marginal leakage in class V composite resin restorations.

Under the experimental conditions used in this in vitro study, the following conclusions may be drawn: 1. Etching of the enamel walls in butt and beveled preparations significantly reduces incisal marginal leakage. 2. The application of a low-viscosity bonding resin to the etched enamel walls of preparations prior to the insertion of the composite resin is not necessary to obtain minimal incisal leakage at the composite resin/etched enamel interface. 3. Cavosurface configuration has no significant effect on incisal marginal leakage. 4. Cavosurface configuration and the restorative techniques used in this study affect the degree of gingival microleakage to some extent but do not eliminate it.

Acid Etching, Dental

Micromethod for lipid-chromatographic determination of cholesterol in lipemic sera.

A micromethod involving "high-performance" lipid chromatography was developed for determining cholesterol in sera obtained from animals that has been infused with high doses of lipid emulsions. Only 50 micro L of serum is required, and there is no interference from turbidity, bilirubin, fat-soluble vitamins, and sterols. Correlation with the commonly used Abell-Kendall method was good at cholesterol concentrations as great as 10.0 g/L (r = 0.998). The assay is ideal for determinations on samples from pediatric and hyperlipidemic patients. It is particularly useful for monitoring patients on lipid-emulsion therapy and for toxicological studies with small animals.

Animals