Human pharmacology of 5-epi-sisomicin (Sch 22591) following intramuscular administration

5-epi-sisomicin was given as a single intramuscular injection of 1 mg/kg to six healthy male adults. Serum peak concentrations averaged 3.07 mg/l, the mean elimination half life was 179 min and the mean 24 h urinary recovery was 85.3%. Local and systemic tolerance was goo

Computer-controlled in-vitro simulation of multiple dosing regimens

The bactericidal effect of gentarrucin on Pseudomonas aeruginosa ATCC 27853 was investigated in a computer controlled dynamic in-vitro model, which allows the simultaneous simulation of three different dosing regimens for several days. The same total dose reduced cfu-counts of Pseudomonas aeruginosa most effectively, when administered with peak concentrations of 32 mg/l every 32 h, whereas the other dosing regimens with peak concentrations of 16 mg/l every 16 h and 8 mg/l every 8 h were distinctly less effective following the second and subsequent doses. It was shown that the use of a microcomputer facilitates the in-vitro investigation of multiple dosing regimens but counting of cfu cannot be substituted by automatic measurements of turbidity when rapid bactericidal effects occu

Human pharmacokinetics and CSF penetration of clavulanic acid

Clavulanic acid, a product of Streptomyces clavuligerus with β-lactam structure, is a potent inhibitor of several β-lactamases. To study its pharmacokinetic and CSF penetration in patients without meningeal inflammation, a single oral dose of 250 mg of clavulanic acid was given to 21 patients. One patient was studied in a multiple dose schedule. Fifteen of these 21 patients had a diagnostic lumbar puncture and 3 neurosurgical patients had a continuous CSF drainage. Serum and urine concentrations of clavulanic acid were available from 22 patients. The mean peak serum concentration was 4·3 mg/l and individual peak serum concentrations ranged from 0·1-9·5 mg/i between 40 and 60 mm after ingestion of clavulanic acid. Urinary recovery between 300 and 400 mm ranged from 0·8-54·3% of the administered dose. The mean absorption half life was 0·26 h and the mean elimination half life was 0·9 h. Considerable degradation of clavulanic acid occurred in vitro at 37°C. In pooled human serum, phosphate buffer pH 7 and 5, an hourly loss of activity of about 10, 7 and 10% respectively, was observe

Adhesion of oral streptococci to all-ceramics dental restorative materials invitro

In recent years, patients have benefited from the development of better and more esthetic materials, including all-ceramics dental restorative materials. Dental plaque formation on teeth and restorative materials plays an important role in the pathogenesis of oral diseases. This study investigates initial adhesion of stationary phase streptococcal species to different all-ceramics dental restorative materials. The saliva-coated materials were incubated with the bacteria for 1h in an invitro flow chamber which mimics environmental conditions in the oral cavity. Number and vitality of adhering bacteria were determined microscopically after staining. Surface roughness and the composition of the materials had no distinctive influence on bacterial adhesion. However, S.mutans and S.sobrinus adhered about tenfold less numerous to all materials than the other streptococcal species. Further, there was a correlation between bacterial vitality and materials' glass content. The results showed that early plaque formation was influenced predominantly by the presence of the salivary pellicle rather than by material dependent parameters whereas the composition of the all-ceramics appeared to have influenced the percentage of viable cells during the adhesion process. This presented invitro technique may provide a useful model to study the influence of different parameters on adherence of oral streptococcal specie

Investigations on the slope efficiency of a pulsed 2.8-µm Er3+:LiYF4 laser

A slope efficiency of 40% from an Er3+:LiYF4 laser is demonstrated under pulsed Ti:sapphire pumping at 973 nm. With reduction of the pump-pulse duration a significant decrease of the slope efficiency and an increase of the threshold is observed in the experiment and confirmed with high accuracy in a computer simulation. This behavior is due to interionic upconversion from the lower laser level, which leads to energy recycling into the upper laser level. The upconversion rate is negative at threshold but increases strongly with rising pump pulse energy, thus enhancing the slope efficiency. The conditions are derived that are necessary for achieving the high slope efficiency of the energy-recycling regime

Nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics of once versus thrice daily dosing of netilmicin in patients with serious infections

The effect of dosing regimen on nephrotoxicity, high frequency ototoxicity, efficacy and serum kinetics was studied in a prospective, randomised clinical study. Therapy was started with total daily doses of 6 mg/kg given once (od) or thrice (tid) daily to 56 and 57 patients, respectively. Subsequent doses were adjusted according to serum levels. No major differences in toxicity or efficacy were noticed between od and tid regimens: clinical failures occurred in two and two patients, four and five patients suffered from a decrease of ≥20 dB at least unilaterally at one frequency between 8 and 18 kHz, six and seven patients had a >25 μmol/L or >25% increase in serum creatinine, respectively. Serum creatinine or creatinine clearance did not change significantly during either therapy. Major differences between the two study groups were limited to pharmacokinetic parameters. Od dosing resulted in higher peak (mean of 21.6 vs 7.2 mg/L) and lower trough levels (0.5 vs 1.4mg/L). Half-lives of netilmicin determined between 1 and 8 h increased significantly during therapy with tid (from a mean of 2.75 to a mean of 3.33 h, P<0.01) but not significantly with od (rise from 2.8 to 3.03 h). Much longer half-lives were determined between 8 and 24 h in the od group (mean of 5.7 h, P<0.01). In conclusion, only minimal differences in toxicity and efficacy were observed. Their clinical relevance appears to be minima

Serological diagnosis of Q fever endocarditis

The diagnosis of Q fever endocarditis cannot be made by bacterial cultures and necessitates serological identification of specific antibodies to Coxiella burnetii which stimulates mainly the production of anti-phase II antibodies during the acute diséase, but primarily anti-phase I antibodies in endocarditis. Indirect micro-immunofluorescence allows rapid detection of specific IgA, IgG and IgM. The results of serological analyses of 191 acute cases of Q fever were compared with those of 8 cases of Coxiella burnetii endocarditis. All sera were evaluated by complement fixation and microimmunofluorescence tests. The highest titre differences between primary Q fever and Q fever endocarditis were observed with anti-phase IIgA and IgG antibodies measured by microimmunofluorescence followed by anti-phase I antibodies measured by complement fixation tests. Anti-phase IIgG and IgM titres were consistently higher than anti-phase II titres in endocarditis. The reverse is true in acute Q fever. In addition, anti-phase I Ig A appeared to be diagnostic for Coxiella burnetii endocarditis. Accordingly we recommend the testing of these specific IgA, IgG, and IgM by microimmunofluorescence in cases of culture-negative endocarditis. These tests could also prove useful for following the development of Coxiella burnetii endocarditis in patients under treatmen

Augmented serum levels of the IGF-I/IGF-binding protein-3 ratio in pre-menopausal patients with type I breast cysts

Objective: Gross cystic disease (GCD) is the most common benign breast pathology. Although breast cysts are not considered pre-malignant lesions, an increased risk of breast cancer has been reported for patients with type I cysts (Na+/K+ < 3). Furthermore, an augmented IGF-I/IGF-binding protein-3 (IGFBP-3) ratio has been described in breast cancer patients. The objective was to evaluate serum IGF-I and binding protein concentrations of type I and type II cyst patients as compared with healthy women. Methods: Twenty-four patients with type I cysts, 17 with type II cysts and 25 healthy women were evaluated. Serum IGF-I, IGFBP-3 and IGFBP-1 concentrations were measured by IRMA. Results: IGF-I concentrations were significantly higher in sera from patients with type I cysts than in patients with type II cysts. A highly significant decrease of IGFBP-3, the major IGFBP, was found in patients with type I cysts with respect to healthy women, whereas no significant difference was evident between the different cyst types. The IGF-I/IGFBP-3 ratio, an estimate of biologically active IGF-I, was very significantly higher in patients with type I cysts than in both type II patients and healthy women. IGFBP-1 levels were significantly lower in patients with type I than in controls and type II cysts. The IGF-I/IGFBP-1 ratio was significantly higher in patients with type I cysts than in type II bearers and healthy women. Estrogen levels correlated with IGF-I in patients and controls. Conclusions: The enhanced levels of IGF-I/IGFBP-3 found in patients with type I cysts could eventually be associated with the increased risk of breast cancer described for this group.Facultad de Ciencias Exacta

Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.

In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia