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

A high-reflectivity high-Q micromechanical Bragg-mirror

We report on the fabrication and characterization of a micromechanical oscillator consisting only of a free-standing dielectric Bragg mirror with high optical reflectivity and high mechanical quality. The fabrication technique is a hybrid approach involving laser ablation and dry etching. The mirror has a reflectivity of 99.6%, a mass of 400ng, and a mechanical quality factor Q of approximately 10^4. Using this micromirror in a Fabry Perot cavity, a finesse of 500 has been achieved. This is an important step towards designing tunable high-Q high-finesse cavities on chip.Comment: 3 pages, 2 figure

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

Large Quantum Superpositions and Interference of Massive Nanometer-Sized Objects

We propose a method to prepare and verify spatial quantum superpositions of a nanometer-sized object separated by distances of the order of its size. This method provides unprecedented bounds for objective collapse models of the wave function by merging techniques and insights from cavity quantum optomechanics and matter wave interferometry. An analysis and simulation of the experiment is performed taking into account standard sources of decoherence. We provide an operational parameter regime using present day and planned technology.Comment: 4 pages, 2 figures, to appear in PR

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

Helicobacter pylori interstrain restriction-modification diversity prevents genome subversion by chromosomal DNA from competing strains

Helicobacter pylori, bacteria that colonize the human gastric mucosa, possess a large number of genes for restriction‐modification (R‐M) systems, and essentially, every strain possesses a unique complement of functional and partial R‐M systems. Nearly half of the H.pylori strains studied possess an active type IIs R‐M system, HpyII, with the recognition sequence GAAGA. Recombination between direct repeats that flank the R‐M cassette allows for its deletion whereas strains lacking hpyIIRM can acquire this cassette through natural transformation. We asked whether strains lacking HpyII R‐M activity can acquire an active hpyIIRM cassette [containing a 1.4 kb kanamycin resistance (aphA) marker], whether such acquisition is DNase sensitive or resistant and whether restriction barriers limit acquisition of chromosomal DNA. Our results indicate that natural transformation and conjugation‐like mechanisms may contribute to the transfer of large (4.8 kb) insertions of chromosomal DNA between H.pylori strains, that inactive or partial R‐M systems can be reactivated upon recombination with a functional allele, consistent with their being contingency genes, and that H.pylori R‐M diversity limits acquisition of chromosomal DNA fragments of ≥1 kb

Campylobacter infections in children exposed to infected backyard poultry in Egypt

Campylobacteriosis is a zoonotic disease which has a worldwide public health impact. The disease is endemic in Egypt; however, the epidemiology in animals and humans has not been fully characterized. The objective of this study was to compare the risk of Campylobacter faecal carriage in children exposed to Campylobacter-infected vs. non-infected backyard poultry and to identify risk factors for a backyard being classified as infected. A total of 103 households which owned backyard poultry were sampled from a rural community in Egypt. Within these households 379 poultry and 106 children were tested for C. jejuni and C. coli; 23·5% and 5·5% of poultry were positive for C. jejuni and C. coli, respectively. In the studied households; 12·3% of children were positive for C. jejuni, and 2·8% were positive for C. coli. Using logistic regression, households with poultry positive for C. jejuni had 3·86 (95% confidence interval 1·0–15·0) times the odds of having children positive for C. jejuni compared to those housed with poultry which all tested negative. Backyard poultry may present a transmission route of C. jejuni to children. Backyards with poor cleaning and disinfection, wet litter and manure disposed of within the backyard had increased odds of being positive for C. jejuni. Enhancing biosecurity and management in poultry backyards may reduce the risk of the disease

Abdominal compliance: A bench-to-bedside review

Abdominal compliance is an important determinant and predictor of available workspace during laparoscopic surgery. Furthermore, critically ill patients with a reduced abdominal compliance are at an increased risk of developing intra-abdominal hypertension and abdominal compartment syndrome both of which are associated with high morbidity and mortality. Despite of this, abdominal compliance is a concept, which has been neglected in the past. Abdominal compliance is defined as a measure of the ease of abdominal expansion, expressed as a change in intra-abdominal volume per change in intra-abdominal pressure: abdominal compliance = delta intra-abdominal volume / delta intra-abdominal pressure. AC is a dynamic variable, dependent on base-line IAV and IAP as well as reshaping and stretching capacity. Whereas abdominal compliance itself can only rarely be measured, it always needs to be considered an important component of intra-abdominal pressure. Patients with decreased abdominal compliance are prone to fulminant development of abdominal compartment syndrome when concomitant risk factors for intra-abdominal hypertension are present. This review aims to clarify the pressure-volume relationship within the abdominal cavity. It highlights how different conditions and pathologies can affect abdominal compliance and which management strategies could be applied to avoid serious consequences of decreased abdominal compliance. We have pooled all available human data to calculate abdominal compliance values in patients acutely and chronically exposed to intra-abdominal hypertension and demonstrated an exponential abdominal pressure-volume relationship. Most importantly, patients with high level of intra-abdominal pressure have a reduced abdominal compliance. In these patients, only small reduction in intra-abdominal volume can significantly increase abdominal compliance and reduce intra-abdominal pressures. A greater knowledge on abdominal compliance may help in selecting a better surgical approach as well as reducing complications related to intra-abdominal hypertension

Walls talk: Microbial biogeography of homes spanning urbanization.

Westernization has propelled changes in urbanization and architecture, altering our exposure to the outdoor environment from that experienced during most of human evolution. These changes might affect the developmental exposure of infants to bacteria, immune development, and human microbiome diversity. Contemporary urban humans spend most of their time indoors, and little is known about the microbes associated with different designs of the built environment and their interaction with the human immune system. This study addresses the associations between architectural design and the microbial biogeography of households across a gradient of urbanization in South America. Urbanization was associated with households' increased isolation from outdoor environments, with additional indoor space isolation by walls. Microbes from house walls and floors segregate by location, and urban indoor walls contain human bacterial markers of space use. Urbanized spaces uniquely increase the content of human-associated microbes-which could increase transmission of potential pathogens-and decrease exposure to the environmental microbes with which humans have coevolved