Comparison of Simulated and in-Vivo Plasma Levels of Cilastatin Following Intravenous in-Line Drug Administration

The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data.     

The CT criteria for conservative treatment — but under close clinical observation — of posterior fossa epidural haematomas

Summary In order to assess whether the indications for conservative treatment of supratentorial epidural haematomas are applicable also to posterior fossa epidural haematomas (PFEDH), the author reviewed the records of 25 patients. With a PFEDH volume of no more than 10 ml, a thickness of no more than 15 mm, a midline shift of no more than 5 mm, and in the absence of a significant intracranial haematoma elsewhere on computed tomography (CT) scans, the patients undergoing conservative treatment achieved the same excellent outcome as those undergoing early surgery. These CT criteria for conservative treatment of PFEDHs are similar to those of supratentorial epidural haematomas except the volume factor, namely, 10 ml in the former against 30 ml in the latter. That means a PFEDH of 10 ml or larger in the small posterior fossa may produce the same degree of midline shift and compression, and be as dangerous as an epidural haematoma of 30 ml or larger in the more capacious supratentorial compartment. But also for epidural haematomas of the posterior fossa, which initially are smaller than 10 ml, the general rule remains valid that they should be under close clinical supervision     

Alternative brain organization after prenatal cerebral injury: convergent fMRI and cognitive data.

The current study presents both longitudinal behavioral data and functional activation data documenting the effects of early focal brain injury on the development of spatial analytic processing in two children, one with prenatal left hemisphere (LH) injury and one with right hemisphere (RH) injury. A substantial body of evidence has shown that adults and children with early, lateralized brain injury show evidence of spatial analytic deficits. LH injury compromises the ability to encode the parts of a spatial pattern, while RH injury impairs pattern integration. The two children described in this report show patterns of deficit consistent with the site of their injury. In the current study, their longitudinal behavioral data spanning the age range from preschool to adolescence are presented in conjunction with data from a functional magnetic resonance imaging (fMRI) study of spatial processing. The activation results provide evidence that alternative profiles of neural organization can arise following early focal brain injury, and document where in the brain spatial functions are carried out when regions that normally mediate them are damaged. In addition, the coupling of the activation with the behavioral data allows us to go beyond the simple mapping of functional sites, to ask questions about how those sites may have come to mediate the spatial functions.     

Arterial and Venous Pharmacokinetics of Ropivacaine with and without Epinephrine after Thoracic Paravertebral Block

Background: Animal and volunteer studies indicate that ropivacaine is associated with less neurologic and cardiac toxicity than bupivacaine. Ropivacaine may offer advantages when used for thoracic paravertebral block. This study was designed to describe the pharmacokinetics of ropivacaine after thoracic paravertebral block.

Methods: Twenty female patients undergoing elective unilateral breast surgery were randomly assigned to receive a single bolus thoracic paravertebral injection of 2 mg/kg ropivacaine, with or without 5 [mu]g/ml epinephrine. Simultaneous arterial and venous blood samples were obtained for plasma ropivacaine assay. Data were analyzed with NONMEM, using two possible absorption models: conventional first-order absorption and absorption following the inverse gaussian density function.

Results: Epinephrine reduced the peak plasma concentrations and delayed the time of peak concentration of ropivacaine in both the arterial and venous blood. The time course of drug input into the systemic circulation was best described by two inverse gaussian density functions. The median bioavailability of the rapid component was approximately 20% higher when epinephrine was not used. The mean absorption times were 7.8 min for the rapid absorption phase and 697 min for the slow absorption phase, with wide dispersion of the absorption function for the acute phase. The half-time of arterial-venous equilibration was 1.5 min.     

Criteria for conservative treatment of supratentorial acute subdural haematomas

Summary In this report we describe 3 patients with syringomyelia in association with tumours of the posterior fossa. In each patient the syrinx was demonstrated on pre-operative magnetic resonance imaging (MRI). After total or partial removal of the tumour the syrinx collapsed. It is concluded that the pathogenesis of syrinx formation in this entity requires interference with normal cerebrospinal fluid (CSF) flow at the foramen magnum. We suggest that the obstruction to the flow of CSF causes alterations in the passage of extracellular fluid (ECF) in the spinal cord which lead to syringomyelia.     

An epidemiological study of Vibrio cholerae O1 in the Australian environment based on rRNA gene polymorphisms.

Since 1977, Vibrio cholerae O1 has been isolated from the Australian aquatic environment and periodically cholera cases have occurred following exposure to these environments. To study the relationships between clinical isolates and environmental isolates from rivers and aquatic life, widely distributed throughout the country, a wide range of molecular typing methods were employed. In this paper we report the analysis of the 180 Australian isolates (10 clinical and 170 environmental) using ribotyping. Seven ribotype patterns were observed among the Australian inaba isolates, 2 of which included all clinical inaba isolates and 84% environmental inaba isolates collected from 9 rivers and creeks in eastern Australia during an 8-year period. Isolates from epidemiologically related clinical cases, asymptomatic household contacts and sewage were indistinguishable. The ogawa isolates were more diverse, with 9 ribotypes observed among 24 isolates from 8 rivers during the same period. Ribotype patterns were not shared between the serotypes with the exception of one ogawa isolate which could be distinguished using PFGE. Ribotyping has been useful in confirming an association between epidemiologically related clinical isolates and the aquatic environment and the persistence of several clones of the O1 serovar in the Australian environment during an 8-year period.