The pharmacokinetics of multiple-dose linezolid were determined following administration of five 600-mg oral doses given every 12 h to each of six healthy male volunteers. Concentrations of the drug were determined in plasma and inflammatory blister fluid using high-pressure liquid chromatography. A mean peak concentration in plasma of 18.3 g/ml (standard deviation [SD], 6.0) was attained at a mean time of 0.7 h (SD, 0.3) after the final dose. The penetration into the inflammatory fluid was 104% (SD, 20.7). A mean peak concentration of 16.4 g/ml (SD, 10.6) was attained in the inflammatory fluid at 3 h (SD, 0.6) after the final dose. The elimination half-life from serum and inflammatory fluid was 4.9 (SD, 1.8) and 5.7 (SD, 1.7) h, respectively. The area under the concentration-time curve in plasma and blister fluid was 140.3 (SD, 73.1) and 155.3 (SD, 80.1) g ⅐ h/ml, respectively. These data suggest that linezolid has good tissue penetration, and we can predict that it will be successful in the treatment of a variety of gram-positive infections.Linezolid belongs to a new class of antibiotics, the oxazolidinones. It acts by selectively inhibiting the initiation of bacterial protein synthesis and has been shown to possess in vitro and in vivo activity against gram-positive organisms, including Streptococcus pneumoniae strains that are resistant to penicillin, methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium with phenotypes Van A, B, and C (2,6,9,11,13). The aim of this study was to assess the pharmacokinetics and tissue penetration of linezolid following multiple oral doses of 600 mg. A blister technique was used to assess tissue penetration since blister fluid mimics inflammatory exudate and hence is a model of likely pharmacokinetics at the site of infection (10). MATERIALS AND METHODSSubjects. Eight healthy volunteers, with a mean age of 29.6 years (standard deviation [SD], 8.7), a mean weight of 78.6 kg (SD, 7.1), and a mean height of 180.4 cm (SD, 14.1), gave written informed consent to participate in this study. One volunteer was unable to attend the actual study day due to febrile illness; therefore, only seven participants were studied. Exclusion criteria for the trial included any history of significant illness or atopy, recent participation in another drug trial, and use of prescription or nonprescription drugs (particularly monoamine oxidase inhibitors) within 14 or 7 days of the study, respectively. All volunteers underwent a full medical history, an examination and a full blood count, clotting, renal, and liver function tests, and urinalysis and a urine drugsof-abuse screen, all of which were normal. The hospital's ethics committee granted approval for this study.Drug administration. The volunteers were given one 600-mg linezolid tablet every 12 h for 2.5 days (a total of five doses). The first dose was given in the hospital with the physician present for the first hour. Doses two and three were self-administered by the volunteer at home. This was confirmed b...

A new technic for continuously recording the dimensions of internal organs in intact unanesthetizcd animals has been developed as a modification of sonar technics. A sound is emitted by a small barium titanatc crystal mounted on one side of the left ventricle, and the time required for the sound waves to pass through the chamber to another crystal on the opposite side is monitored \ ,000 to 2,500 times/sec. Such crystals have continued to function reliably for more than 3 months after installation in the animal. Changes in left ventricular diameter have been recorded during spontaneous cardiac responses to various conditions including physical exertion on a treadmill. T HE function of the heart can be characterized and analyzed by measuring the changes in pressure, volume and flow of blood in the individual cardiac chambers. Although internal pressures can be readily measured by means of catheters, changes in the volume of the heart have been measured primarily by cardioineters in thoracotomized animals or by roentgenography in intact animals and men. These methods are not well suited to the study of cardiac control, which necessitates continuously measuring the absolute pressures and dimensions of the individual heart chambers in intact animals and man with regulating mechanisms intact and functioning. The volume of the individual cardiac chambers has never been measured satisfactorily in intact animals. Several technics have been employed in this laboratory to continuously record changes in the internal and external dimensions of the heart chambers. Initially, changes in the size and shape of the atria and ventricles were observed and measured on motion picture films obtained by cinefluorographic angiocardiography. 1 ' 2 Subsequently, new methods for continuously recording the changing dimensions have been explored. 1 ' 4 Variable resistance

Seventy seven patients with soft tissue shoulder lesions including adhesive capsulitis and disorders of the rotator cuff and acromioclavicular joint were admitted to a trial comparing two different methods of corticosteroid injection with local anaesthetic in a randomly allocated double blind study. The method of anatomical injection after diagnosis by the technique of selective tissue tension gave 60% success compared with the method using tender or trigger point localisation, giving 20% success (p <0 001).

This study was designed to assess the value of measurement of plasma catecholamine concentrations as an objective index of anxiety. A preliminary study was undertaken on 11 healthy volunteers (medically qualified), to determine if venous cannulation per se produced any change in plasma catecholamine concentrations. There were no changes in plasma catecholamine concentrations in the 2 h following insertion of an i.v. cannula, suggesting that venous cannulation did not induce a measurable stress response. A second study was performed on 48 surgical patients who were asked to rate their perceived anxiety on a linear analogue scale immediately before premedication and immediately before induction of anaesthesia. Venous blood was obtained at the same time as these ratings. There were no significant changes in perceived anxiety or plasma noradrenaline concentrations following premedication. However, compared with values before premedication, there was a mean percentage increase in plasma adrenaline concentration of 40% before induction of anaesthesia. A significant correlation was shown between mean percentage change in Linear Analogue Anxiety Score and mean percentage change in plasma adrenaline concentrations (r = 0.32).

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