Biomedical subjects

A Georgopoulos

Publications and source records attributed to A Georgopoulos.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effects of dietary fructose on plasma lipids in healthy subjects.

BACKGROUND: About 9% of average dietary energy intake in the United States comes from fructose. Such a high consumption raises concern about the metabolic effects of this sugar. OBJECTIVE: The objective of this study was to determine the effect of dietary fructose on plasma lipids. DESIGN: The study was conducted in the General Clinical Research Center at Fairview-University of Minnesota Medical Center. The participants were 24 healthy adult volunteers (12 men and 12 women; 6 of each sex were aged <40 y and 6 of each sex were aged >/=40 y). All subjects received 2 isoenergetic study diets assigned by using a randomized, balanced crossover design. One diet provided 17% of energy as fructose. The other diet was sweetened with glucose and was nearly devoid of fructose. Each diet was fed for 6 wk. Both diets were composed of common foods and contained nearly identical amounts of carbohydrate, protein, fat, fiber, cholesterol, and saturated, monounsaturated, and polyunsaturated fatty acids. All meals were prepared in the metabolic kitchen of the General Clinical Research Center. RESULTS: The responses to the study diets differed by sex. In men, the fructose diet produced significantly higher fasting, postprandial, and daylong plasma triacylglycerol concentrations than did the glucose diet. The daylong plasma triacylglycerol concentration after 6 wk of the fructose diet was 32% greater in men than the corresponding concentration during the glucose diet (P: < 0.001). The fructose diet had no significant effect on fasting or postprandial plasma triacylglycerol concentrations in women. The fructose diet also had no persistent effect on fasting plasma cholesterol, HDL cholesterol, or LDL cholesterol in either men or women. CONCLUSIONS: Dietary fructose was associated with increased fasting and postprandial plasma triacylglycerol concentrations in men. Diets high in added fructose may be undesirable, particularly for men. Glucose may be a suitable replacement sugar.

Adult↗

PubMed2000

Penetration of cefpirome into the anterior chamber of the human eye after intravenous application.

The penetration of intravenously administered cefpirome into the anterior chamber of the non-inflamed human eye was investigated in this study. A total of 42 patients, all hospitalized for cataract extraction, received a dosage of 1 g or 2 g of cefpirome by iv infusion 1, 2 or 6 h preoperatively. An aqueous humour sample was collected immediately after paracentesis and a blood specimen was simultaneously obtained from each patient. All samples were analysed for cefpirome concentrations using high-pressure liquid chromatography. Mean aqueous humour levels of cefpirome in patients receiving a dosage of 1 g were 1.33 mg/L (1 h), 1.67 mg/L (2 h) and 1.29 mg/L (6 h after application), respectively. When patients received a dosage of 2 g cefpirome the resulting mean aqueous humour concentrations were 1.60 mg/L (1 h), 2.27 mg/L (2 h) and 2.39 mg/L (6 h after application), respectively. A statistically significant difference in aqueous humour concentrations between patients receiving 1 g or 2 g of cefpirome could not be proven. In conclusion, cefpirome penetrates well into the anterior chamber of the non-inflamed human eye in concentrations that are therapeutic for many gram-positive and gram-negative organisms, frequently responsible for anterior segment eye infections.

Aged↗

PubMed2000

In vitro release of vancomycin and tobramycin from impregnated human and bovine bone grafts.

In order to combine the effects of bone repair and eradication of infection, with both Gram-positive and Gram-negative pathogens, the behaviour of a compound of bone graft and antibiotics was investigated. Samples of human and bovine bone, cancellous and cortical, were processed and incubated with vancomycin and tobramycin, respectively. The compound was placed in 5% human albumin and the surrounding liquid was exchanged completely every 24 h. Concentrations of antibiotics in the fluid were measured over < or = 28 days using high pressure liquid chromatography and a bioassay. All tested combinations eluted mainly in the initial phase with a logarithmic decrease over the testing period. The concentration of antibiotics in the albumin was well above the MIC for common pathogens throughout the investigation in all tested specimens. The highest initial concentrations were measured in the compound of bovine bone together with vancomycin (24395.8 +/- 1138.9 mg/L), decreasing to 9.02 +/- 1.3 mg/L after 11 exchanges. Human and bovine bone did not have significantly different properties. The storage capability of cortical bone was generally lower than that of cancellous bone. Tobramycin concentrations were significantly lower in the initial phase; however, it eluted more steadily and over a longer period, so that from day 6 onwards, its concentration was greater than that of vancomycin. After 28 days, the tobramycin concentration was 18.09 +/- 2.46 mg/L (bovine cancellous bone). In conclusion, bone, if processed adequately, is an excellent carrier for vancomycin and tobramycin. Cortical bone is as suitable as cancellous bone. The pharmacokinetics of human and bovine bone are comparable. Using an antibiotic-graft compound, eradication of pathogens and grafting of bony defects may be accomplished in a one-stage procedure.

Animals↗

PubMed2000

A combined in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate target site pharmacodynamics of antibiotics in humans.

We describe a new approach to quantify in vivo anti-infective activity by simulating effect site pharmacokinetics of antibiotics in vitro. This approach is based on (i) the in vivo measurement of interstitial drug pharmacokinetics (PK) at the target site and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. To demonstrate the feasibility of this approach, individual time-concentration profiles of ciprofloxacin were measured in the interstitial space fluid of eight healthy volunteers by microdialysis following iv administration of 200 mg. Thereafter, different isolates of Pseudomonas aeruginosa were exposed in vitro to the interstitial ciprofloxacin concentration profile obtained from in vivo experiments. This led to a 1- to 3-log10 decrease in the number of viable organisms after 8 h. Significant correlations were observed between the maximal bactericidal effect and several PK surrogate parameters, notably the AUC/MIC ratio (P: = 0.0005), the C:max/MIC ratio (P: = 0.006) and the time > MIC (P: = 0.02). Furthermore, the data were analysed with an integrated PK-PD model allowing a much more detailed evaluation of the data than using MIC. The model employed an E:max relationship to link unbound ciprofloxacin concentration to bacterial kill rate. In conclusion, our experiments show that therapeutic success and failure in antimicrobial therapy may be explained by pharmacokinetic variability at the target site. Therefore, the in vivo PK-in vitro PD approach presented in our study may provide valuable guidance for drug and dose selection of antimicrobial agents.

Anti-Bacterial Agents↗

PubMed2000

A high carbohydrate versus a high monounsaturated fatty acid diet lowers the atherogenic potential of big VLDL particles in patients with type 1 diabetes.

The objective of the present study was to compare the effects of two diets on the atherogenic potential of two VLDL subfractions harvested from fasting subjects by measuring the number and composition of particles and the amount of esterified cholesterol accumulated in macrophages. A high (25%) monounsaturated fatty acid (Mono) diet and a high (61%) carbohydrate (CHO) diet were provided for 4 wk in a randomized crossover design to 19 normolipidemic, nonobese patients with type 1 diabetes. The two diets were matched for protein, polyunsaturated/saturated fatty acids, cholesterol and fiber content. The number of circulating big VLDL (S:(f) 100-400) particles was greater during the high Mono than during the high CHO diet based on the levels of apolipoprotein B (means +/- SEM): 31.4 +/- 7.4 versus 20.0 +/- 3.8 mg/L (P: < 0.025, paired t test). The following variables did not differ during the diet periods: number of small VLDL (S:(f) 20-100) particles, esterified cholesterol accumulated in THP-1 macrophages incubated with the same number of big and small VLDL particles and particle composition. We conclude that a high CHO diet might be preferable to a high Mono diet, on the basis of the premise that more big VLDL particles could increase the atherosclerotic risk in patients with diabetes.

Adult↗

PubMed2000

Distribution and antimicrobial activity of fosfomycin in the interstitial fluid of human soft tissues.

Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. For this purpose fosfomycin concentrations in vivo in the fluid of the interstitial space of human soft tissues were measured by microdialysis following intravenous infusion of 4 or 8 g of fosfomycin (n = 6). Subsequently, bacterial isolates with relevance for soft tissue infections were exposed to concentrations according to the in vivo pharmacokinetic profile in the interstitial space fluid obtained by microdialysis. Our experiments indicated a high degree of soft tissue penetration for fosfomycin, with ratios of the area under the concentration-time curve from 0 to 8 h for muscle (AUC(0-8(muscle)))/AUC(0-8(serum)) of 0.48+/-0.08 and 0.53+/-0.04 and ratios of AUC(0-8(adipose tissue))/AUC(0-8(serum)) of 0.74+/-0.12 and 0.71+/-0.11 following administration of 4 and 8 g, respectively. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus, Enterobacter cloacae, and Serratia marcescens for which MICs were 16 microg/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

Adipose Tissue↗

PubMed2000

National and local antibiotic policies in Central and Eastern Europe.

To assess the antibiotic policies of Central European countries, we performed an overview of antibiotic stewardship, prescription habits and antibiotic prescription regulatory procedures. Since most Central European countries have had centralized health care and drug policies, the situation 10 years after decentralization is surprising. Only 3 of 10 Central European countries have some regulation of prescription of antibiotics, only 4 restrict some antibiotics, only 5 have hospital and only 3 national antibiotic policies. In all but 3 countries physicians can prescribe quinolones and/or 3rd generation oral cephalosporins as first-line antibiotics. Information on local and national antibiotic policies in Central and Eastern European countries is given including prescription guidelines for antibiotic use in community and hospital.

Anti-Bacterial Agents↗

PubMed2000

Codon-54 polymorphism of the fatty acid-binding protein 2 gene is associated with elevation of fasting and postprandial triglyceride in type 2 diabetes.

Patients with type 2 diabetes are frequently dyslipidemic or hypertriglyceridemic. To assess whether increased intestinal triglyceride input leads to elevated fasting and postprandial triglycerides in type 2 diabetes, we used the codon 54 polymorphism of the fatty acid-binding protein 2 gene, which results in the substitution of threonine (Thr) for alanine and is associated with increased intestinal input of triglyceride. Of the 287 diabetic patients screened, 108 (37.6%) were heterozygous and 31 (10.8%) were homozygous for the Thr-54 allele. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild-type (n = 80), those heterozygous for the Thr-54 allele (n = 57), and those homozygous for it (n = 18) were 2.0 +/- 0.09, 2.7 +/- 0.20, and 3.8 +/- 0.43 mmol/L, respectively. A linear relationship of mean fasting plasma triglyceride levels (r2 = 0.97) between the 3 groups was found. After fat ingestion, the postprandial area under the curve of plasma triglyceride (P = 0.025) and chylomicrons (Sf > 400, P = 0.013) was higher in the Thr-54/Thr-54 (n = 6) than in the wild-type (n = 9). Our results are consistent with the hypothesis that, in type 2 diabetes, increased intestinal input of triglyceride can lead to elevated fasting and postprandial plasma triglycerides.

Alleles↗

PubMed1999

Functional mapping in the human brain using high magnetic fields.

An avidly pursued new dimension in magnetic resonance imaging (MRI) research is the acquisition of physiological and biochemical information non-invasively using the nuclear spins of the water molecules in the human body. In this trial, a recent and unique accomplishment was the introduction of the ability to map human brain function non-invasively. Today, functional images with subcentimetre resolution of the entire human brain can be generated in single subjects and in data acquisition times of several minutes using 1.5 tesla (T) MRI scanners that are often used in hospitals for clinical purposes. However, there have been accomplishments beyond this type of imaging using significantly higher magnetic fields such as 4 T. Efforts for developing high magnetic field human brain imaging and functional mapping using MRI (fMRI) were undertaken at about the same time. It has been demonstrated that high magnetic fields result in improved contrast and, more importantly, in elevated sensitivity to capillary level changes coupled to neuronal activity in the blood oxygenation level dependent (BOLD) contrast mechanism used in fMRI. These advantages have been used to generate, for example, high resolution functional maps of ocular dominance columns, retinotopy within the small lateral geniculate nucleus, true single-trial fMRI and early negative signal changes in the temporal evolution of the BOLD signal. So far these have not been duplicated or have been observed as significantly weaker effects at much lower field strengths. Some of these high-field advantages and accomplishments are reviewed in this paper.

Brain↗

PubMed1999

Postprandial triglyceride metabolism in diabetes mellitus.

Individuals with diabetes have a two to four times higher risk of cardiovascular morbidity and mortality than nondiabetics. Patients with both type 1 and type 2 diabetes share a similar risk. Studies in individuals with type 1 diabetes have shown a decreased clearance of postprandial triglyceride-rich lipoprotein particles of abnormal composition. Particles isolated from diabetic individuals show abnormal composition and an increased tendency to cause cholesteryl ester accumulation in macrophages and are therefore potentially atherogenic. Various interventions may alter these abnormalities and improve the atherosclerotic risk. These include adopting a high-carbohydrate diet over a high monounsaturated diet, improving glycemic control, infusing insulin intraperitoneally, and using pharmacologic therapies such as the statins.

Coronary Disease↗

PubMed1999

Bacteremia after dental treatment in mentally handicapped people.

Bacteremia may occur after disruption of the oral mucous membrane, particularly after dental treatment. 18 mentally handicapped patients who underwent dental treatment with general anesthesia were included in our study. None of the patients had general illnesses or received antibiotic protection. From each patient several blood samples were drawn aseptically during dental treatment and cultured. The majority of aerobic bacteria recovered belonged to Streptococcus sp and Gemella sp., anaerobic bacteria mainly belonged to Porphyromonas gingivalis and Peptostreptococcus sp. Resistance of the isolated bacteria to penicillin as well as to oxacillin, erythromycin and Co-trimoxazole was substantial. The highest resistance rate could be shown against fucidic acid.

Adolescent↗

PubMed1999

Efficacy of beta-lactam and inhibitor combinations in a diffusion chamber model in rabbits.

Using a diffusion chamber in rabbits, we evaluated therapy with the combination of ceftriaxone plus the beta-lactamase inhibitor tazobactam in comparison with ceftriaxone alone. One sensitive and one resistant strain of Escherichia coli, Enterobacter cloacae and Klebsiella pneumoniae were inoculated into one of the six diffusion chambers, implanted in the same animal. In order to simulate pharmacokinetics in humans, both substances were administered in decreasing doses. Ceftriaxone was given 0, 2, 4 and 6 h after infection in dosages of 45, 35, 25 and 15 mg/kg of body weight, while tazobactam was administered either in one dose at 0 h, or divided into two doses at 0 and 1 h or 0 and 4 h, or divided into three doses at 0, 1 and 4 h after infection. The ratio of ceftriaxone:tazobactam was fixed at 8:1. Ceftriaxone, in combination with tazobactam, given in one dose immediately after infection showed a significant reduction in bacterial count. All other combinations of ceftriaxone and tazobactam did not differ from ceftriaxone in monotherapy. Co-administration of the beta-lactamase inhibitor tazobactam significantly enhanced the activity of ceftriaxone against all three tested species.

Animals↗

PubMed1999

Comparative susceptibility to penicillin and quinolones of 1385 Streptococcus pneumoniae isolates. Austrian Bacterial Surveillance Network.

Antibiotic resistance among Streptococcus pneumoniae isolates has spread rapidly throughout the world since the first description of a strain with diminished susceptibility to penicillin in Australia in 1967. A total of 1385 strains of S. pneumoniae, collected in several centres throughout Austria, were assessed for their sensitivity to moxifloxacin, trovafloxacin, ciprofloxacin, ofloxacin, levofloxacin and lomefloxacin. The MICs were determined using the agar dilution method, according to NCCLS guidelines. Both moxlfloxacin and trovafloxacin showed good anti-pneumococcal activity in terms of MIC50 (both 0.125 mg/L) and MIC90 (both 0.25 mg/L). Less active, but with similar activity to each other, were ciprofloxacin and levofloxacin, each with an MIC50 of 1 mg/L and an MIC90 of 2 mg/L. Ofloxacin showed only moderate activity (MIC50, 1 mg/L; MIC90, 2 mg/L) and lomefloxacin was the least active compound (MIC50, 4 mg/L; MIC90, 8 mg/L). Both moxifloxacin and trovafloxacin at a concentration of < or = 0.5 mg/L inhibited all of the S. pneumoniae strains tested.

Anti-Infective Agents↗

PubMed1999

Endothelial cell compatibility of clindamycin, gentamicin, ceftriaxone and teicoplanin in Bier's arterial arrest.

In patients with infected diabetic foot lesions, and gangrenous, peripheral, occlusive arterial disease, it is important to achieve high concentrations of antibiotics in the tissues, as the extent of amputation is often influenced by the presence of infection. Local transvenous pressure injection of antibiotics, in Bier's arterial arrest, allows high local tissue concentrations to be attained in the extremities. Information on the endothelial compatibility of antibiotics in high concentrations combined with the effect of reperfusion injury following tissue hypoxia is lacking. To evaluate the effect of clindamycin, gentamicin, ceftriaxone and teicoplanin injected in Bier's arterial arrest, on endothelial cells, an in-vitro model using human umbilical venous endothelial cells (HUVEC) has been devised. The intracellular levels of purine nucleotides, reflecting DNA/RNA synthesis, energy production and signal transduction of these cells were measured by means of high-performance liquid chromatography. Incubation of cells with 10 mg/mL clindamycin, gentamicin, ceftriaxone and teicoplanin for 20 min resulted in no significant decline of intracellular purines. Levels of purines obtained after exposure of the cells to 0.1 mmol/L hydrogen peroxide (H2O2), to simulate reperfusion injury, were not significantly different from those obtained from cells allowed to recover after antibiotic exposure. These findings indicate that the infusion of high doses of antibiotics, during Bier's arterial arrest, is compatible with maintenance of endothelial cell function, even in the presence of increased free radical activity, provided the exposure is limited to 20 min.

Anti-Bacterial Agents↗

PubMed1999

Distribution and antimicrobial activity of ciprofloxacin in human soft tissues.

Interstitial ciprofloxacin concentrations in soft tissues were measured by microdialysis following intravenous administration of 200 mg to each of eight healthy volunteers. Interstitial ciprofloxacin concentrations were significantly lower than corresponding total serum drug concentrations; the interstitium-to-serum concentration ratios ranged from 0.55 to 0.73. An in vitro simulation based on interstitial pharmacokinetics showed a substantially lower antimicrobial activity than did the simulation based on serum pharmacokinetics. Thus, ciprofloxacin concentrations at the site of effect may be subinhibitory although effective concentrations are attained in serum.

Adult↗

PubMed1999

Black-white differences in risk of developing retinopathy among individuals with type 2 diabetes.

OBJECTIVE: To assess racial differences in risk of developing retinopathy among individuals with type 2 diabetes, after taking into account differences in the distribution of risk factors for retinopathy. RESEARCH DESIGN AND METHODS: The participants were 105 individuals with type 2 diabetes, aged 40-69 years, who had no evidence of retinopathy at the time of a diabetic eye disease screening project. After an average of 4 years of follow-up, the subjects were reevaluated using nonmydriatic funds photography. RESULTS: Retinopathy occurred more often among black than white participants (50 vs. 19%). This difference could not be explained by differences in risk factors for retinopathy or potential confounders (odds ratio [95% CI] 2.96 [1.00-8.78] after adjustment for level of glycosylated hemoglobin, systolic blood pressure, type of diabetes treatment, and sex). CONCLUSIONS: These results are consistent with the concept that racial differences in risk of developing retinopathy exist among individuals with type 2 diabetes and that these differences may be caused by differential (genetic) susceptibility to the adverse effects of increased levels of blood glucose and/or blood pressure. Discovery of the etiology of this differential susceptibility would allows us to identify and target secondary prevention efforts to individuals with type 2 diabetes who are at increased risk of retinopathy.

Adult↗

PubMed1999

Effects of imipenem and meropenem on purine content of endothelial cells.

UNLABELLED: Intravenous compatibility of antibacterial agents has been tested in animal models. Use of human umbilical venous endothelial cells (HUVEC) to test antibiotic solutions for intravenous tolerance provides a valuable alternate model. OBJECTIVE: Evaluation of the effect of imipenem and meropenem on intracellular purines reflecting viability, energy production, signal transduction, and DNA/RNA synthesis of these cells. MATERIALS AND METHODS: Levels of intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP), guanosine 5' triphosphate (GTP) and guanosine 5' diphosphate (GDP) were measured by means of high performance liquid chromatography (HPLC). RESULTS: The total amount of ATP after incubation of cells with 10.0 mg/ml imipenem and meropenem for 20 minutes (12.93 +/- 0.93 nmol/million cells and 13.27 +/- 0.89 nmol/million cells, respectively) did not result in a decrease compared to controls (12.34 +/- 0.87 nmol/million cells). In addition, ATP levels were maintained or actually increased after 60 minutes. Incubation of cells with 5.0 mg/ml and 2.5 mg/ml of imipenem or meropenem for 20 and 60 minutes showed similar results. Purine nucleotide profiles of ADP, GTP, GDP following exposure of 10.0 mg/ml, 5.0 mg/ml and 2.5 mg/ml of imipenem and meropenem did not differ markedly. CONCLUSIONS: These in vitro data show an excellent endothelial compatibility of imipenem and meropenem even in high concentrations.

Adenosine Diphosphate↗

PubMed1998

Determination of glutamate by high-performance liquid chromatography with fluorescence detection in superfusates of rat brain preparations.

A method is described for the determination of glutamate in superfusates of cortical or hippocampal rat brain slices. This method is based on the precolumn derivatization of amino acids with orthopthaldialdehyde and mercaptopropionic acid, separation by high-performance liquid chromatography, and detection by fluorescence. By adjusting the concentrations of reagents and with the minimum dilution of the sample, it was possible to reproducibly measure the Ca2+-dependent K+-evoked release of neurotransmitter glutamate in superfusates of brain slices.

Animals↗