Passive protection against Burkholderia pseudomallei infection in mice by monoclonal antibodies against capsular polysaccharide, lipopolysaccharide or proteins.

Burkholderia pseudomallei, the aetiological agent of melioidosis, is endemic in south-east Asia and northern Australia, where it is an important cause of human disease. There is no vaccine available and antibiotic therapy is associated with high relapse rates. A panel of seven monoclonal antibodies (MAbs) that recognise capsular polysaccharide, lipopolysaccharide or proteins was produced and their ability to protect mice passively against experimental melioidosis was evaluated. The MAbs were capable of protecting mice against intra-peritoneal challenge with 10(4) cfu/250 MLD of a virulent strain of B. pseudomallei (NCTC 4845), when pooled, and four of the MAbs were individually protective. However, at a higher B. pseudomallei challenge level of 10(6) cfu none of the MAbs afforded protection and only the anti-exopolysaccharide MAbs produced a significantly delayed time to death.

Common errors of drug administration in infants: causes and avoidance.

Drug administration errors are common in infants. Although the infant population has a high exposure to drugs, there are few data concerning pharmacokinetics or pharmacodynamics, or the influence of paediatric diseases on these processes. Children remain therapeutic orphans. Formulations are often suitable only for adults; in addition, the lack of maturation of drug elimination processes, alteration of body composition and influence of size render the calculation of drug doses complex in infants. The commonest drug administration error in infants is one of dose, and the commonest hospital site for this error is the intensive care unit. Drug errors are a consequence of system error, and preventive strategies are possible through system analysis. The goal of a zero drug error rate should be aggressively sought, with systems in place that aim to eliminate the effects of inevitable human error. This involves review of the entire system from drug manufacture to drug administration. The nuclear industry, telecommunications and air traffic control services all practise error reduction policies with zero error as a clear goal, not by finding fault in the individual, but by identifying faults in the system and building into that system mechanisms for picking up faults before they occur. Such policies could be adapted to medicine using interventions both specific (the production of formulations which are for children only and clearly labelled, regular audit by pharmacists, legible prescriptions, standardised dose tables) and general (paediatric drug trials, education programmes, nonpunitive error reporting) to reduce the number of errors made in giving medication to infants.

Moving coil linear variable differential transformer.

A moving-coil linear variable differential transformer with no ferromagnetic components is described. The device is essentially interchangeable with a conventional moving-core linear variable differential transformer, but is virtually unaffected by ambient magnetic fields up to 8 T. The transducer is connected to a standard commercially available carrier amplifier for signal conditioning.

Does the gas exchange anaerobic threshold occur at a fixed blood lactate concentration of 2 or 4 mM?

The anaerobic threshold (theta an) is defined as the VO2 at which blood lactate concentration [lactate] begins to systematically increase (lactate "break point") during incremental exercise. Numerous studies have shown that gas exchange break points at the anaerobic threshold correlate highly (r congruent to 0.90) with the lactate break point. Recently, it has been suggested that the anaerobic threshold occurs at a fixed [lactate] of 2 mM or 4 mM. We therefore compared the gas exchange theta an to the three lactate criteria (break point, 2 mM, and 4 mM) for theta an estimation. Fourteen subjects performed an incremental cycle ergometer test. Ventilation and gas exchange were computed every 30 s. During the same 30-s intervals, venous blood was sampled for [lactate]. Four criteria were used for theta an determination: (1) systematic increase in VE/VO2, without a concomitant increase in VE/VCO2; (2) lactate break point; (3) 2 mM [lactate]; and (4) 4 mM [lactate]. Relative to the gas exchange criterion (i.e., #1), theta an was higher by 44, 280, and 1028 ml X min-1 for the three lactate criteria, respectively; the last two being significantly different (P less than 0.05). Thus, the anaerobic threshold discerned from gas exchange or the lactate break point does not correspond with a fixed, absolute [lactate] of 2 mM or 4 mM.

A comparison of gas exchange indices used to detect the anaerobic threshold.

This study was undertaken to determine which of four commonly used ventilatory or gas exchange indices provides the most accurate and reliable detection of the anaerobic threshold (AT). Sixteen subjects performed two cycle ergometer tests to volitional fatigue. After 4 min of unloaded cycling, the work rate was increased 20 W/min. Ventilatory and gas exchange measurements were made every 30 s throughout each test. During one of the two tests (randomly assigned), venous blood was also sampled every 30 s for subsequent determinations of blood lactate (HLa) concentration. Four ventilatory and gas exchange indices (VE, VCO2, R, VE/VO2) were used separately to detect the AT. The AT determined from systematic increases in HLa concentration was used as the criterion measure. AT values (means +/- SE) (VO2, l/min) using VE, VCO2, R, VE/VO2, and HLa were 1.79 +/- 0.11, 1.74 +/- 0.11, 1.58 +/- 0.06, 1.84 +/- 0.11, and 1.85 +/- 0.11 l/min, respectively. The highest correlation between a ventilatory or gas exchange AT and ATHLa (i.e., criterion measure) was found for VE/VO2 (r=0.93, P less than 0.001). The VE/VO2 also provided the highest test-retest correlation for detection of the AT (r = 0.93, P less than 0.001). Multiple correlational analyses did not significantly enhance detection of the AT. These results favor the use of VE/VO2 for noninvasive detection of the AT because it proved to be the most sensitive and reliable ventilatory or gas exchange index studied.