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Biomedical subjects

G Popescu

Publications and source records attributed to G Popescu.

At least 19 recordsLinked to original sources
PubMed2001

Continuous positive airway pressure for sleep apnoea/hypopnoea syndrome: usefulness of a 2 week trial to identify factors associated with long term use.

BACKGROUND: The sleep apnoea/hypopnoea syndrome (SAHS) is common and treatment with continuous positive airway pressure (CPAP) is effective. However, not all patients can cope with the demands of using mask positive pressure. Compliance can be improved with an intensive educational programme and patient support, but this is not practical in most centres given the large numbers of patients coming forward for treatment. Several studies have evaluated correlations between various parameters at diagnosis in order to anticipate patients' behaviour and to avoid the social and health implications of undertreated SAHS. We have evaluated the use of additional data derived during a 2 week home CPAP trial to identify factors associated with longer term use of CPAP and compliance. METHODS: Following a diagnostic study, 209 patients were offered a CPAP machine for a 2 week home trial. After completing the trial, patients were reassessed and scored their overall satisfaction with CPAP treatment on a five point scale ranging from "much worse" to "much better" and an Epworth score relating to the loan period. Machine run time was recorded from the integral clock. These data were added to those available at diagnosis to construct models indicative of continuing CPAP and average nightly use at 1 year. RESULTS: 209 patients were offered the 2 week loan at least a year before June 1999 (90.9% men, mean (SD) age 51.0 (10.6) years, body mass index (BMI) 34.6 (7.7) kg/m(2), Epworth score 15 (IQR 11-18), apnoea/hypopnoea index (AHI) 38.1 (22.9) events/h). 153 patients (73.2%) opted to continue CPAP and 56 declined. One year later data were available for 187 patients; 128 (68.5% on an intention to treat analysis) continued to use the machine with a mean use of 5.0 (2.4) hours/night. A logistic regression model indicated that mean CPAP use during the loan period and the overall satisfaction score accurately defined continuing CPAP and "satisfactory" CPAP use at 1 year. For patients with low machine use and no symptomatic improvement during the loan period, the addition of baseline AHI, baseline Epworth score, and the Epworth score at the end of the loan to the equation identifying factors associated with "satisfactory" CPAP use (mean >2 hours/night) improved the value of the model. CONCLUSION: Data derived from a 2 week CPAP trial are useful in identifying patients who will comply with CPAP treatment to 1 year. It can be used to identify patients with significant symptomatic disease who will struggle with CPAP and may benefit from additional education and support. High mean hourly use and a high degree of overall satisfaction during the loan period identified patients likely to use CPAP and be compliant with it at 1 year.

Adult↗
PubMed2000

Analysis of rat cytosolic 9-cis-retinol dehydrogenase activity and enzymatic characterization of rat ADHII.

We report the characterization of two enzymes that catalyze NAD(+)-dependent 9-cis-retinol dehydrogenase activity in rat liver cystol. Alcohol dehydrogenase class I (ADHI) contributes > 80% of the NA D+-dependent 9-cis-retinol dehydrogenase activity recovered, whereas alcohol dehydrogenase class II (ADHII), not identified previously at the protein level, nor characterized enzymatically in rat, accounts for approximately 2% of the activity. Rat ADHII exhibits properties different from those described for human ADHII. Moreover, rat ADHII-catalyzed rates of ethanol dehydrogenation are markedly lower than octanol or retinoid dehydrogenation rates. Neither ethanol nor 4-methylpyrazole inhibits the 9-cis-retinol dehydrogenase activity of rat ADHII. We propose that ADHII represents the previously observed additional retinoid oxidation activity of rat liver cytosol which occurred in the presence of either ethanol or 4-methylpyrazole. We also show that human and rat ADHII differ considerably in enzymatic properties.

Alcohol Dehydrogenase↗
PubMed2000

Evidence of scattering anisotropy effects on boundary conditions of the diffusion equation

We present experimental evidence that the diffusion process close to the boundary is fundamentally different from the bulk diffusion in the sense that it is affected by the scattering properties of the individual centers. Systematic measurements show a nontrivial behavior of the extrapolation length ratio on the scattering anisotropy of individual particles. The results are compared with other works and are supported by an independent Monte Carlo simulation. A simple analytical model that emphasizes the influence of the last scattering event successfully describes the results.

Journal Article↗
PubMed1998

[The effect of bile secretion on the pharmacokinetics of a theophylline sustained-release preparation].

Bile excretion changes the physiological milieu of the duodenum, possibly resulting in enhanced absorption of a drug due to increased solubilisation. This possible influence of bile salts following stimulation of gallbladder emptying by the release of cholecystokinin on the pharmacokinetics of a sustained release theophylline (CAS 58-55-9) preparation (Bronchoretard) was evaluated in this study. An open, randomised, 3-way crossover study in 12 healthy, non-smoking volunteers was selected to prove or reject this hypothesis. All subjects received 500 mg of the sustained release theophylline formulation under two different cholagogia stimulating test conditions compared with a fasting reference condition. A standard breakfast and i.m. administration of cholecystokinin enabled a reproducible modulation of bile flow: a moderate and extreme contraction of the gallbladder could be induced after a standard breakfast and after i.m. administration of cholecystokinin, respectively. Following a standard breakfast, gallbladder volumes were approximately halved (50.6%) compared to the baseline volume after 79 min. Injection of 0.3 microgram/kg body weight cholecystokinin resulted in fast and complete gallbladder evacuation (94.6%) 36 min after the application of this cholagogue stimulus. Gallbladder volumes remained more or less constant under fasting conditions. This manipulation of bile flow did not influence concentration/time profiles of the sustained release theophylline preparation compared to the fasting condition. Even almost complete evacuation of the gallbladder after administration of cholecystokinin did not modify the concentration/time profile of theophylline in a relevant way. An unintentional rapid release of theophylline could be excluded for this sustained release formulation for all three treatments, as not a single case of dose dumping was observed. Furthermore, in vitro dissolution investigations using synthetic surfactants can predict neither food effects nor bile influence on the in vivo absorption at least for the sustained release formulation tested.

Adult↗
PubMed1996

Effect of gallbladder contraction induced cholagogia on the pharmacokinetic profile of a sustained-release theophylline formulation.

Bile excretion might change the physiological milieu of the duodenum resulting in enhanced absorption of a drug due to increased solubilisation. This possible influence of bile salts following stimulation of gallbladder emptying via the release of cholecystokinin on the pharmacokinetics of a sustained-release theophylline (CAS 58-55-9) preparation (Bronchoretard) was evaluated in this study. An open, randomised 3-way cross-over study in 12 healthy, non-smoking volunteers was selected to prove or reject this hypothesis. All subjects received 500 mg of the sustained-release theophylline formulation under two different cholagogia stimulating test conditions and under a fasting reference condition. A standard breakfast and i.m. application of cholecystokinin enabled modulation of bile flow; a moderate and extreme contraction of the gallbladder could be induced after a standard breakfast and after i.m. application of cholecystokinin, respectively. Following a standard breakfast, gallbladder volumes were approximately halved (50.6%) compared to the baseline volume after 79 min. Injection of 0.3 micrograms/kg body weight cholecystokinin resulted in quick and complete gallbladder evacuation (94.6%) 36 min after the application of this cholagogue stimulus. Gallbladder volumes remained approximately constant under fasting conditions. This manipulation of bile flow did not influence concentration/time profiles of the sustained-release theophylline preparation compared to the fasting condition. Even almost complete evacuation of the gallbladder after application of cholecystokinin did not modify concentration/time profiles of theophylline in a relevant way. An unintentional rapid release of theophylline could be excluded for this sustained-release formulation for all three treatments, as not a single case of dose-dumping was observed. Furthermore, in vitro dissolution investigations using surfactants are neither predictive of food effects nor bile influence on in vivo absorption at least for the sustained-release formulation tested.

Adult↗
PubMed1996

Atomic force microscopy investigation of radiation-induced DNA double strand breaks.

We have used atomic force microscopy (AFM) to study radiation-induced DNA double strand breaks. Double-stranded plasmid DNA was irradiated with 18-MeV electrons in aqueous buffer, using a medical linear accelerator. Doses of 50, 100, 150, and 200 Gy were delivered to DNA samples, and atomic force microscopy was used to measure the length of each DNA fragment. From these measurements, we obtained the average length of the irradiated DNA for each sample and found a linear-quadratic relationship between the average length and radiation dose.

DNA↗
PubMed1995

Cloning of a cDNA for a second retinol dehydrogenase type II. Expression of its mRNA relative to type I.

A retinol dehydrogenase, RoDH(1), which recognizes holo-cellular retinol-binding protein (CRBP) as substrate, has been cloned, expressed, and identified as a short-chain dehydrogenase/reductase (Chai, X., Boerman, M. H. E. M., Zhai, Y., and Napoli, J. L. (1995) J. Biol. Chem. 270, 3900-3904). This work reports the cloning and expression of a cDNA encoding a RoDH isozyme, RoDH(II). The predicted amino acid sequence verifies RoDH(II) as a short-chain dehydrogenase/reductase, 82% identical with RoDH(I). RoDH(II) recognized the physiological form of retinol as substrate, CRBP, with a Km of 2 mM. Similar to microsomal RoDH and RoDH(I), RoDH(II) had higher activity with NADP rather than NAD, was stimulated by ethanol and phosphatidyl choline, was not inhibited by the medium-chain alcohol dehydrogenase inhibitor 4-methylpyrazole, but was inhibited by phenylarsine oxide and the short-chain dehydrogenase/reductase inhibitor carbenoxolone. Northern blot analysis detected RoDH(I) and RoDH(II) mRNA only in rat liver, but RNase protection assays revealed RoDH(I) and RoHD(II) mRNA in kidney, lung, testis, and brain. These data indicate that short-chain dehydrogenases/reductase isozymes expressed tissue-distinctively catalyze the first step of retinoic acid biogenesis from the physiologically most abundant substrate, CRBP.

Alcohol Oxidoreductases↗
PubMed1992

Radiotherapy of malignant subdiaphragmatic implants in advanced ovarian carcinoma: a new technique.

We report the development of a new technique using remote afterloading intraoperative radiation therapy to deliver a tumoricidal dose to diaphragmatic tumor implants. A multi-positional lucite applicator was designed based on anatomic studies of the diaphragmatic surface to accommodate a high dose rate iridium source in a series of needles placed 1.5 cm apart. The applicator curvature can vary from planar to full accommodation of the diaphragmatic surface with a constant source to surface distance of 0.5 cm. The applicator has been piloted in three patients with ovarian carcinoma with residual subdiaphragmatic disease found at second look laparotomy, to deliver a dose of 1,500 to 2,000 cGy at 0.5 cm. Tolerance of the diaphragm and hepatic surface has been excellent. There were no postoperative complications and no deterioration in liver function studies. The additional postoperative external beam irradiation directed with the aid of surgically placed clips and gated to respiratory movements permits achievement of a tumoricidal dose while limiting the treated volume and related toxicities.

Brachytherapy↗
PubMed1990

Hysterectomy with extended surgical staging and radiotherapy versus hysterectomy alone and radiotherapy in stage I endometrial cancer: a comparison of complication rates.

Extended surgical staging (ESS) has been added to total hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) in patients with clinical Stage I endometrial cancer in order to better define patterns of metastatic spread and the response to treatment. Adjuvant radiotherapy has a demonstrated efficacy in decreasing central recurrence in Stage I disease. The combined use of radical surgery and pelvic radiotherapy for cervical cancer patients results in an increased incidence of complications. This study compares major complication rates in Stage I endometrial cancer patients who underwent either TAHBSO with ESS or TAHBSO alone followed by adjuvant external beam radiotherapy (RT). Records of 52 patients with clinical stage I endometrial cancer were reviewed. Thirty-two patients underwent TAHBSO plus ESS and 20 patients had TAHBSO alone. All patients received postoperative, whole pelvis external radiotherapy. Four patients suffered complications potentially related to treatment which required rehospitalization, and all 4 were in the group which had undergone ESS. A comparison of complication rates between the ESS + RT group (4/37 or 10.8%) and TAHBSO + RT group (0/20) suggested a trend toward significance (P less than 0.10). Treatment protocols using extended surgical staging prior to adjuvant radiotherapy in Stage I endometrial cancer should examine complications potentially related to this combination, to further define treatment risks and benefits.

Adult↗
PubMed1989

Postoperative adjuvant external-beam radiotherapy in surgical stage I endometrial carcinoma.

A combined surgical and radiotherapeutic approach is widely in Stage I endometrial adenocarcinoma. The technique and timing of the radiotherapy varies from center to center. Postoperative external-beam (EB) radiotherapy has the advantage of patient selection based upon surgical findings, comprehensive treatment of the pelvic nodal and vaginal cuff areas, and elimination of the need for an intracavitary procedure. Although frequently utilized, this technique is surprisingly poorly described in the medical literature. From 1979 to 1986, 46 surgical Stage I patients received adjuvant postoperative EB therapy at Georgetown University Hospital (GUH) (Washington, DC). Indications for treatment were Grade greater than or equal to 2 and/or depth of myometrial invasion of greater than 33%. The 5-year actuarial survival was 90% with a disease-free survival of 82%. The failure rate within the irradiated field was 6.5% with a distant failure rate of 8.7%. The rate of significant long-term complications was acceptable at 6.5%. The authors conclude that postoperative EB radiotherapy is an effective adjuvant therapy with results comparable to other available radiotherapeutic techniques.

Adenocarcinoma↗
PubMed1986

Prelesional events in atherogenesis. Accumulation of extracellular cholesterol-rich liposomes in the arterial intima and cardiac valves of the hyperlipidemic rabbit.

Biochemical, physiologic, and ultrastructural modifications which appear in the aortic intima and atrioventricular valves before monocyte diapedesis and foam cell formation were investigated in rabbits fed a cholesterol-rich diet. In the first 2 weeks of the diet, while plasma beta-VLDL cholesterol was increased up to 15-fold, the intima showed an enhanced uptake and deposition of dietary 3H-cholesterol, 125I-beta-VLDL, and the fluorescent beta-VLDL-1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine conjugate. beta-VLDL-gold complex perfused in situ was transcytosed across endothelium by plasmalemmal vesicles. Concomitantly, within the intima, a progressive accumulation of extracellular densely packed uni- or multilamellar vesicles took place. These commonly occurred in cell-free subendothelial spaces and were not associated with any sign of cytolysis. In freeze-fracture preparations, these vesicles appeared as smooth surfaces, suggesting the absence of translamellar proteins. Upon incubation with filipin, these extracellular liposomes (EL) displayed characteristic approximately 20 nm filipin-sterol complexes, revealing the presence of preparations unesterified cholesterol in the phospholipid lamellas. EL deposition was paralleled by proliferation of basal lamina-like material, microfibrils, and proteoglycans, and continued to increase during foam cell formation. For the entire period of our experiments, the endothelium was morphologically intact, and no platelet involvement was detected. The results show that an early prelesional ultrastructural change in lesion-prone aortic and valvular areas is the accumulation of extracellular phospholipid liposomes rich in unesterified cholesterol.

Animals↗