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Biomedical subjects

A Georgopoulos

Publications and source records attributed to A Georgopoulos.

At least 19 recordsLinked to original sources

Antibacterial activity of sparfloxacin against experimental renal infections in mice.

In a murine model of renal infection (Staphylococcus aureus and Escherichia coli), sparfloxacin was compared with ciprofloxacin and fleroxacin. After intrarenal inoculation, mice were treated orally for 5 days. The drugs were administered at five different dosages, ranging from 3.125 to 50 mg/kg of body weight per day for S. aureus and from 0.78 to 12.5 mg/kg/day for E. coli. Evaluation of efficacy was based on the proportional reduction of bacterial counts in the kidney tissues of treated animals compared with those of untreated control animals. For S. aureus, the doses required to clear the infection in 50% of mice were as follows: sparfloxacin, 10 mg/kg/day; ciprofloxacin, 33 mg/kg/day; and fleroxacin, 16 mg/kg/day. For E. coli renal infection, the corresponding dosages were as follows: sparfloxacin, 1.5 mg/kg/day; ciprofloxacin, 2.45 mg/kg/day; and fleroxacin, 1.8 mg/kg/day. Sparfloxacin and fleroxacin have a lower effective dose than ciprofloxacin in these models, probably because ciprofloxacin has a shorter serum half-life than the other two compounds.

Abscess

Normalization of composition of triglyceride-rich lipoprotein subfractions in diabetic subjects during insulin infusion with programmable implantable medication system.

OBJECTIVE: To investigate whether long-term improved glycemic control by intraperitoneal insulin infusion normalizes the compositional abnormalities of triglyceride (TG)-rich lipoproteins in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Seven subjects were studied before and 12-14 mo after initiation of treatment with the programmable implantable medication system (PIMS). Plasma TG levels were measured, and the composition of three TG-rich lipoprotein subfractions (Svedberg flotation [Sf] greater than 400, 100-400, and 20-100) were analyzed before and every 1.5 for 7.5 h after ingestion of corn oil. RESULTS: PIMS significantly improved glycemic control, as measured by mean blood glucose (P less than 0.02), and HbA1 (P less than 0.001, paired t test) levels. Weight loss was also observed during PIMS treatment. Significant changes occurred in the composition of TG-rich lipoprotein subfractions during PIMS treatment in both the fasting (P less than 0.002) and the postprandial (P less than 0.0001) state. Most changes were in the direction of nondiabetic values. PIMS treatment reduced the total cholesterol enrichment in IDDM subjects in all three subfractions in the postprandial state and the very-low-density lipoprotein subfractions (Sf 100-400 and 20-100) in the fasting state. Multivariate analysis showed that the compositional changes were affected by improved glycemic control, as assessed by both mean blood glucose and HbA1, whereas the very-low-density lipoprotein compositional changes were by both the improved glycemic control and body weight. CONCLUSIONS: In IDDM subjects during PIMS treatment, there was normalization of most abnormalities in the composition of fasting and postprandial TG-rich lipoproteins, including enrichment in total cholesterol, which is considered atherogenic.

Adult

[Sequential parenteral and oral therapy with ofloxacin in urogenital infections].

125 hospitalized patients (56 men and 69 women) suffering from urinary tract infection (UTI) and 15 women with endometritis or pelvic inflammatory disease were treated with ofloxacin 6 mg/kg/d i.v. divided into 2 doses. Two thirds of the patients were switched to oral ofloxacin using the same dose regimen after 4 days. The median duration of treatment was 10 days. 98 patients were evaluable for efficacy: 45 had complicated lower UTI, 32 had upper UTI (75% of them with complications), 13 had endometritis and 8 an uncomplicated lower UTI. The most frequent complications of UTI were: obstruction (n = 27), indwelling catheters (n = 23), urinary concrements (n = 12), residual urine (n = 8) and a neurogenic bladder (n = 6). 22 patients had diabetes mellitus. A total of 103 pathogens was isolated from the urine of 85 patients, the most frequent being E. coli, Proteus spp. and Enterococcus faecalis. 98% of patients with UTI and 85% of patients with endometritis were clinically cured. Adverse drug events were observed in 6 patients.

Adolescent

[Epidemiology and pathogen spectrum of urinary tract infections].

Urinary tract infections still are a diagnostic as well as a therapeutical problem. The knowledge on the frequency of the causative organisms and their sensitivity to antibiotics and the different modes of urinary tract infections as well are very important, especially because of remaining organizational and medical-technical problems to identify the organisms. E. coli-bacteria are up to now the most frequent pathogens of urinary tract infections, with a resistance rate of 30% against aminopenicillins. An increase of resistant Enterobacter- and Pseudomonas-aeruginosa-strains against quinolones is known and could be observed also in our hospital. The demand for knowledge of sensitivity pattern of the causative organisms still remain for a successful antibiotic therapy.

Adolescent

Abnormal clearance of postprandial Sf 100-400 plasma lipoproteins in insulin-dependent diabetes mellitus.

Studies were carried out in three normolipidemic non-obese men with insulin-dependent diabetes mellitus (IDDM) and three normal men, to assess whether the clearance of postprandial Sf 100-400 lipoproteins is decreased in IDDM. Sf greater than 100 lipoproteins isolated from plasma 4.5 h after fat ingestion were labeled with 125I and injected into the same subject intravenously. ApoB radioactivity was measured over time in Sf greater than 400, Sf 100-400, and Sf 20-100 lipoproteins isolated from plasma and analyzed using a kinetic model that included both fast and slow delipidation cascades, where lipolysis and uptake of particles by the liver and other tissues were represented. Fractional catabolic rates of Sf 100-400 lipoproteins (min-1) were decreased in diabetic versus control subjects: fast = 0.170 +/- 0.126 versus 0.680 +/- 0.242 (mean +/- SD) (P less than 0.05, two-tailed) and slow = 0.011 +/- 0.006 versus 0.031 +/- 0.015 (P less than 0.05, one-tailed). Kinetic analysis showed that the data were consistent with decreased uptake by the tissues for the fast cascade (diabetic, 0.084 +/- 0.082, vs. control, 0.617 +/- 0.328, P less than 0.05, one-tailed). A similar trend was observed for the slow cascade. There were no significant differences between the two groups in the intraplasma lipolysis rates of Sf 100-400 particles. Analysis of the composition of the injected particles showed that they were total cholesterol (TC)- versus triglyceride (TG)-enriched (P less than 0.001, log-ratio analysis of composition) in IDDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Physicochemical characterization of a polypeptide present in uremic serum that inhibits the biological activity of polymorphonuclear cells.

A granulocyte inhibitory protein was isolated and characterized from uremic serum by using ion-exchange column chromatography, high-performance size-exclusion chromatography, and immunochemical procedures. The purification process concentrated the protein 240-fold and to a purity of greater than 95%. An overall recovery of 45% was achieved; the purified protein had a specific activity of 104 units per mg of protein. The polypeptide had a molecular weight of approximately 28,000 and an isoelectric point of 4.0-4.5. Amino acid sequencing of the NH2 terminus revealed a single sequence (Asp-Ile-Val-Met-Thr-Gln-Ser-Pro-Gly-Thr-Leu-Ser-Val-Ser-Pro-Gly-Glu-Arg-Ala- Thr) that proved to be nonhomologous with other serum proteins that appear during an inflammatory state. The polypeptide inhibited the uptake of deoxyglucose, chemotaxis, oxidative metabolism, and intracellular bacterial killing by polymorphonuclear leukocytes. A specific rabbit polyclonal antibody raised against the protein nullified these inhibitory changes. We contend that the protein is responsible for the leukocyte dysfunction that is commonly seen in patients with uremia.

Amino Acid Sequence

Ceftriaxone monotherapy for bacterial meningitis in children.

A total of 33 patients with bacterial meningitis were treated with single daily doses of ceftriaxone (CTR 100 mg/kg/day i.v.) for a median duration of 13 days. Pathogens isolated by culture and/or determined by latex agglutination were 15 Haemophilus influenzae b, 7 Neisseria meningitidis, 2 Streptococcus pneumoniae, 1 group B streptococcus, 2 Streptococcus viridans and 2 Staphylococcus epidermidis. In 4 cases a diagnosis of purulent meningitis could only be made by means of the inflammatory liquor parameters. All cerebrospinal fluid (CSF) drug levels even at the end of the dosing interval were at least 10-fold higher than the MICs of the respective bacterial isolates. The average penetration of CTR into the CSF was 6.6%. Within 12-46 h after the first dose, control spinal taps were performed. Cultures were sterile in all cases. Side effects encountered were diarrhea, exanthema, neutropenia and transient elevation of glutamic oxaloacetic transaminase, but none caused a change of therapy. One patient developed a biliary concrement. No patient died; 5 patients had prolonged fever (greater than 5 days), and 2 were left with persistent hearing deficiencies. CTR can be recommended as a safe and effective antibiotic agent for once daily treatment of bacterial meningitis in children.

Adolescent

Abnormalities in the metabolism of postprandial and fasting triglyceride-rich lipoprotein subfractions in normal and insulin-dependent diabetic subjects: effects of sex.

To investigate the effect of sex and diabetes on postprandial lipoprotein metabolism, 15 normal and 12 normolipidemic subjects with insulin-dependent diabetes mellitus (IDDM) were studied. Plasma triglyceride (TG) levels were measured and three TG-rich lipoprotein subfractions (Sf greater than 400, 100 to 400, and 20 to 100) were isolated and their composition analyzed before and every 1.5 hours for a total of 7.5 hours following ingestion of corn oil. Normal women compared with men had lower postprandial plasma TG levels (P less than .05) mostly due to lower TG in Sf 100 to 400. The composition of Sf 100 to 400 and Sf 20 to 100 lipoproteins differed in the two sexes (P less than .01), with normal women having particles poorer in TG in both the fasting and postprandial states. Diabetic men compared with normal men had smaller Sf greater than 400 particles following fat ingestion, as shown by a lower TG protein (PR) ratio (7.6 v 12.8, respectively, P less than .05). The composition of Sf 100 to 400 and 20 to 100 lipoproteins was abnormal in IDDM men due to enrichment in total cholesterol (TC) as shown by higher TC/TG, TC/PR, and TG/phospholipid (PL) ratios in both the fasting (P less than .03 to P less than .003) and the postprandial state (P less than .03 to P less than .0001). A lower PL and TG content was also consistently present. A similar enrichment in TC was observed in diabetic v normal women following fat ingestion in Sf greater than 400 only (P less than .003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Improved glycemic control lowers plasma apoprotein E and triglyceride levels following ingestion of a fat load in insulin-dependent diabetic subjects.

To assess the effect of glycemic control on triglyceride (TG) and apoprotein E (apo E) metabolism, plasma levels of TG and apo E were studied in nine nonobese subjects with insulin-dependent diabetes mellitus (IDDM) following acute ingestion of polyunsaturated fat. Each subject was studied twice: before and after ten days of continuous subcutaneous insulin infusion (CSII). Each subject ingested identical meals on both study days. Plasma glucose was determined in all patients before and two hours after each meal and at 3 AM, and a mean value was calculated for each patient. CSII reduced mean plasma glucose from 205 to 113 mg/dL (P less than .005, paired t test); there was no change in the total daily insulin dose. Plasma TG and apo E levels were measured before and 3.5, 5, and 7 hours after a breakfast which contained 50 g of fish oil (five subjects) or vegetable oil (four subjects). A repeated-measures ANOVA was performed to assess the effects of the following three factors on plasma TG and apoE levels: type of oil ingested (Oil, factor A), glycemic control (Glycemic control, factor B), and the response to fat ingestion over time (Times, factor C). Plasma levels of both apo E and TG increased significantly after fat ingestion (F test, ANOVA, P less than .005 and P less than .001, respectively). Glycemic control significantly reduced the rise in both apo E and TG levels (P less than .005 and P less than .05, respectively). The effect of the type of oil and the interactions tested (AB, AC, BC, ABC) were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of improved glycemic control on the response of plasma triglycerides to ingestion of a saturated fat load in normotriglyceridemic and hypertriglyceridemic diabetic subjects.

This study tests the hypothesis that improved glycemic control decreases the postprandial plasma triglyceride (TG) response to ingestion of a saturated fat load. Fifteen normotriglyceridemic subjects with insulin-dependent diabetes mellitus (IDDM, group I) and six hypertriglyceridemic subjects with non-insulin-dependent diabetes mellitus (NIDDM, group II) were studied. Each subject was studied before and after 12 days of continuous subcutaneous insulin infusion (CSII). Each subject ingested identical meals on both study days. Plasma glucose was determined in all patients before and two hours after each meal and at 3 AM, and a mean value was calculated for each patient. CSII reduced mean plasma glucose from 252 to 140 mg/dL in group I, and from 209 to 120 mg/dL in group II (P less than .001 in both groups, paired t test). Plasma TG levels were measured before and 1.5, 3, 4.5, 6, and 7.5 hours after a breakfast which contained 50 g of mostly saturated fat. A repeated-measures ANOVA was performed to assess the effects of glycemic control (factor A) and TG response (factor B) to fat ingestion. In both groups plasma TG levels increased significantly after fat ingestion (P less than .001), and were significantly reduced during improved glycemic control (P less than .001). The reduction was observed in 14 of 15 patients in group I and in all patients in group II. In group I the lowering of the postprandial plasma TG levels after CSII was secondary to a decrease in the fasting plasma TG levels, as shown by the unchanged mean percent TG elevation over the baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Differing complement-mediated opsonic activity of rabbit interstitial fluids from autologous serum.

Lack of appropriate methods for withdrawing extravascular or interstitial fluid from an animal host has limited in vitro study on the role of complement in the local defence of the extravascular space. In the present study, we obtained fluids from membrane diffusion chambers (porosity 0.22 micron) implanted into the kidneys, peritoneal cavity and soft tissues in rabbits. The complement-mediated opsonic activity (CMOA) of these fluids for Staphylococcus aureus ATCC 502A and Escherichia coli 01 was then compared to that of autologous sera. Soft tissue and renal interstitial fluids were as opsonic for E. coli as autologous sera but were however, poor opsonins for S. aureus. The peritoneal fluid was marginally effective in opsonization of both bacterial strains. While chelation of the fluids with MgEGTA (to block the classical pathway) did not diminish CMOA for E. coli, it reduced the CMOA for S. aureus by half. Conversely, heat-inactivation of the fluids and serum eliminated the opsonic activity for E. coli but only decreased the opsonic activity for S. aureus by half. Following a 24 h in vivo growth of E. coli in the implanted chambers, the CMOA was drastically reduced. Concomitant to the reduction in functional complement in the fluids, E. coli recovered from the chambers were found coated, though not maximally, with C3b as evidenced by studies with fluorescent antibody. The differences in opsonic content of extravascular fluids observed here might explain why certain sites of the body may be more vulnerable to attack by some bacterial species which are not effectively opsonized and therefore phagocytized.

Animals

Efficacy of coumermycin, ofloxacin and vancomycin against methicillin-resistant Staphylococcus aureus in vitro and in experimental infections of mice.

In vitro, coumermycin (a bis-hydroxicoumarin gyrase inhibitor) proved significantly more active than ofloxacin and vancomycin against 100 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC90 was 0.5 microgram/ml, whereas the corresponding figures for the other antimicrobials were 2.0 and 4.0 micrograms/ml. In vivo, an otherwise lethal septicemia, induced by intraperitoneal administration of a MRSA in mice, was "successfully treated" in 50% of the animals (ED50) with the following dosages (microgram/g b. wt.): coumermycin 0.9, ofloxacin 10.8, vancomycin 22.4. The ED50 of coumermycin was significantly (2 p less than 0.01) different from those of the other drugs. Renal infection as produced in mice by transcutaneous inoculation of the same MRSA was treated with either of the antimicrobials at different dosages (single doses of 0.0 or 1.6 or 6.3 or 25.0 micrograms/g b. wt., twice daily) during 6 days. The largest reductions of viable counts in the kidneys at each dosage as compared to the bacterial counts of untreated animals were achieved with coumermycin (3.4 or 5.5 or 7.7 log10). These reductions are significantly (2 p less than 0.01) different from those achieved with the comparable dosages of ofloxacin and vancomycin which were 0.1 or 1.8 or 2.8 and 0.4 or 1.4 or 3.0 log10 respectively. After a single subcutaneous injection of 250 micrograms mean concentrations in serum of mice for coumermycin were 6.2-5.0 micrograms/ml for 8 h, for ofloxacin 2.0-0.5 micrograms/ml for 2 h, and for vancomycin 14.7-2.5 micrograms/ml for 2 h. Coumermycin and ofloxacin could be alternatives to vancomycin in the therapy of human infections due to MRSA.

Aminocoumarins

In-vitro activity of fleroxacin.

Fleroxacin is a new synthetic fluorinated quinolone antimicrobial agent. The in-vitro activity of fleroxacin and five comparative quinolones against 541 clinical isolates was studied. Minimum inhibitory concentrations (MIC90) of fleroxacin were less than or equal to 2.0 mg/l for Enterobacteriaceae, less than or equal to 8.0 mg/l for Pseudomonas aeruginosa and 1.0 mg/l for Acinetobacter calcoaceficis and 8 mg/l for streptococci. The activity of fleroxacin was comparable with that of ofloxacin, pefloxacin and norfloxacin, but less than that of ciprofloxacin. All quinolones showed little difference between MIC and minimum bactericidal concentrations (MBCs).

Anti-Infective Agents

In vitro evaluation of teicoplanin and other antimicrobials against streptococci group D bacteria.

In vitro activities of teicoplanin were compared with those of ampicillin, imipenem, rifampicin, coumermycin and vancomycin against clinical isolates of Streptococcus faecalis (n = 100) and Streptococcus faecium (n = 30). Against Str. faecalis, ampicillin and imipenem had an MIC90 and MBC90 of 3.9 micrograms/ml. Coumermycin and rifampicin had poor bactericidal activity with MBC90 values of 31.2 and 62.5 micrograms/ml. Teicoplanin was extremely active with an MIC90 of 0.95 microgram/ml and an MBC90 of 1.86 micrograms/ml.

Anti-Bacterial Agents

[Clinical microbiology and chemotherapy in the spirit of Escherich].

One hundred years ago Billroth and Escherich were engaged with microbiological investigations. They are representative of intimate relationship between clinic and microbiological laboratory. In 1979 the Department of Chemotherapy was founded and this tradition was resumed and continued.

Anti-Bacterial Agents