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Ian Williams

Publications and source records attributed to Ian Williams.

23 records · Page 2Linked to original sources

Intracellular accumulation of human immunodeficiency virus protease inhibitors.

Intracellular accumulation of the protease inhibitors (PIs) saquinavir (SQV), ritonavir (RTV), and indinavir (IDV) was determined in 50 human immunodeficiency virus-positive patients. Following extraction, PIs were quantified by mass spectrometry. Paired plasma and intracellular samples were collected over a full dosing interval from patients (13 on SQV, 6 on RTV, 8 on IDV, 16 on SQV plus RTV, 7 on IDV plus RTV) with a plasma viral load of <400 copies/ml. Data were expressed as intracellular/plasma drug concentration ratios. A hierarchy of intracellular accumulation was demonstrated by the following medians: 9.45 for SQV > 1.00 for RTV > 0.51 for IDV. Coadministration of RTV did not boost ratios of SQV or IDV within the cell or in plasma, although absolute plasma and intracellular SQV concentrations were increased by RTV. Seven individuals receiving SQV in hard-gel capsule form (median, 32 months) had higher intracellular/plasma drug ratios than all other patients receiving SQV (median, 17.62 versus 4.83; P = 0.04), despite consistently low plasma SQV concentrations. How this occurs may provide insight into the mechanisms that limit adequate drug penetration into sanctuary sites.

Adolescent↗

Antimicrobial postexposure prophylaxis for anthrax: adverse events and adherence.

We collected data during postexposure antimicrobial prophylaxis campaigns and from a prophylaxis program evaluation 60 days after start of antimicrobial prophylaxis involving persons from six U.S. sites where Bacillus anthracis exposures occurred. Adverse events associated with antimicrobial prophylaxis to prevent anthrax were commonly reported, but hospitalizations and serious adverse events as defined by Food and Drug Administration criteria were rare. Overall adherence during 60 days of antimicrobial prophylaxis was poor (44%), ranging from 21% of persons exposed in the Morgan postal facility in New York City to 64% of persons exposed at the Brentwood postal facility in Washington, D.C. Adherence was highest among participants in an investigational new drug protocol to receive additional antibiotics with or without anthrax vaccine--a likely surrogate for anthrax risk perception. Adherence of <60 days was not consistently associated with adverse events.

Adolescent↗

Flow cytometry and other techniques show that Staphylococcus aureus undergoes significant physiological changes in the early stages of surface-attached culture.

The techniques of flow cytometry, scanning and transmission electron microscopy, and confocal scanning laser microscopy were used to study the physiology of Staphylococcus aureus in the early stages of surface-attached culture, and to make direct comparisons with planktonic bacteria grown under the same conditions. Attached bacteria growing in nutrient-rich batch culture were found to go through the same growth phases as equivalent planktonic cultures, but with an exponential growth rate of about half that of the planktonic bacteria. Viability of attached bacteria was very high (around 100%) throughout the first 24 h of growth. The size and protein content of attached bacteria varied with growth phase, and both measurements were always smaller than in planktonic bacteria at equivalent growth phases. Respiratory activity per bacterium, as measured by flow cytofluorimetry, and corrected for cell volume, peaked very early in attached cultures (before the first cell division) and declined from then on, whereas in planktonic bacteria it peaked in late exponential phase. Attached and planktonic bacteria showed thicker cell walls in stationary phase than in exponential phase. Membrane potentials of planktonic and attached bacteria were similar in stationary phase, but were much lower in exponential-phase attached cells than in the equivalent planktonic cells. It is apparent that a range of significant physiological adaptations occur during the early phases of attached growth.

Bacterial Adhesion↗

The effects of adherence to silicone surfaces on antibiotic susceptibility in Staphylococcus aureus.

Sensitivity of Staphylococcus aureus to the antibiotics tetracycline, benzylpenicillin and vancomycin was found to decrease by 2-10 fold when cells were grown adherent to silicone catheter surfaces. Sensitivity to rifampicin and fusidic acid was not significantly altered in adherent cells. Susceptibility further decreased with increased adherence time prior to antibiotic challenge. The resistance observed was not genotypic, or due to the presence of a specialized subpopulation of bacteria, as it disappeared when the bacteria were removed from the catheter, subcultured and retested. Also, adherent bacteria were found to grow more slowly than bacteria growing planktonically. It is concluded that the decrease in antibiotic susceptibility of adherent bacteria is a function of the physiological status of the individual cells rather than a function of biofilm formation or slime production. The decrease in growth rate of the adherent bacteria is a result of the adherence process rather than a result of nutrient depletion. The decrease in growth rate is implicated, but is not the sole factor, in the decreased antibiotic susceptibility of adherent bacteria.

Anti-Bacterial Agents↗

Blood transportation for medical retrieval services.

INTRODUCTION: Medical retrieval services resuscitate and retrieve the critically ill and injured. Lifesaving treatment includes the transfusion of red blood cells (RBCs). To ensure patient safety and maximum therapeutic benefit for the patient, the transportation of RBCs for transfusion must occur under optimal conditions. Blood shippers currently in use in Australia are principally polystyrene containers, often selected for low cost, although performance validation is becoming increasingly important. The quality of the blood to the consumer may be compromised by the use of inappropriate shippers and transport systems. METHODS: A prototype of a user-friendly soft pack blood shipper was developed and tested in various climatic conditions over 24 hour periods with the RBC temperature monitored. RESULTS: The blood shipper was validated to maintain blood temperature within an acceptable range (2 degrees to 10 degrees C (35.6 degrees-50 degrees F) for up to 16 hours during transport of ambient temperatures ranging from 8 degrees to 35 degrees C. (46.4 degrees-95 degrees F). CONCLUSION: The blood shipper provides adequate storage for blood products under a range of climatic conditions and time periods adequate for most retrieval purposes. This allows optimal blood transport system for the medical retrieval service, helping to ensure maximum patient safety and therapeutic benefit from transfusion. The validated blood shipper is also important to blood banks and blood consumers for nonretrieval blood transportation.

Blood↗