Lyme disease presenting as urinary retention

We report a case of Lyme disease that presented with urinary retention. The individual then experienced lower extremity paralysis. Paralysis and urinary retention resolved with intravenous ceftriaxone antibiotic. To our knowledge this is the first report of a urological manifestation as the initial clinical presentation of Lyme disease. Recognition of clinical symptoms and urological complications of Lyme disease also are discussed.     

Pituitary fossa: chemical shift effect in MR imaging

The effect of chemical shift on magnetic resonance (MR) imaging of the pituitary fossa was studied. Healthy volunteers underwent conventional MR imaging of the pituitary fossa and then imaging with the frequency-encoding gradient reversed or with the phase- and frequency-encoding gradients interchanged. Comparison of the image pairs in each subject showed that the thin, black stripe evident at the water-fat interface within the pituitary fossa was altered when the gradients were changed. Therefore, the low-intensity signal within the pituitary fossa is a chemical shift misregistration effect.     

Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.     

Osteopetrosis: MR characteristics at 1.5 T

Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements.     

Estimation of brain receptor occupancy for trazodone immediate release and once a day formulations

Trazodone is approved for the treatment of major depressive disorders, marketed as immediate release (IR), prolonged release, and once a day (OAD) formulation. The different formulations allow different administration schedules and may be useful to facilitate patients’ compliance to the antidepressant treatment. A previously verified physiologically‐based pharmacokinetic model based on in vitro and in vivo information on trazodone pharmacokinetics was applied, aiming at predicting brain receptor occupancy (RO) after single and repeated dosing of the IR formulation and repeated dosing of the OAD formulation in healthy subjects. Receptors included in the simulations were selected using static calculations of RO based on the maximum unbound brain concentration (C_max,brain,u) of trazodone for each formulation and dosing scheme, resulting in 16 receptors being simulated. Seven receptors were simulated for the IR low dose formulation (30 mg), with similar t _onset and duration of coverage (range: 0.09–0.25 h and 2.1–>24 h, respectively) as well as RO (range: 0.64–0.92) predicted between day 1 and day 7 of dosing. The 16 receptors evaluated for the OAD formulation (300 mg) showed high RO (range: 0.97–0.84 for the receptors also covered by the IR formulation and 0.73–0.48 for the remaining) correlating with affinity and similar duration of time above the target threshold to the IR formulation (range: 2–>24 h). The dose‐dependent receptor coverage supports the multimodal activity of trazodone, which may further contribute to its fast antidepressant action and effectiveness in controlling different symptoms in depressed patients.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

The antidepressant efficacy of trazodone has been shown to be significantly correlated to its steady‐state plasma levels, and previous work has shown some understanding of trazodone range of affinity for different receptors, at different doses, but without considering the different available formulations. Trazodone is commonly available as: immediate release (IR), prolonged release (PR), and once a day (OAD) tablets. The IR formulation has a rapid onset and short duration of action, whereas the PR formulation is characterized by an absorption boost as soon as it is administered and has a comparatively delayed maximum concentration (C_max). Conversely, the OAD formulation provides a controlled release of trazodone over 24 h without the early high peak plasma concentration seen with the IR and PR formulations.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This work aims to identify the brain receptors reaching a threshold occupancy of 50% through static predictions and determine the occupancy versus time profile for those of interest following administration of short‐ and long‐acting trazodone formulations.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Brain receptor occupancy (RO) for key targets were predicted based on free drug concentrations, allowing for a physiologically relevant assessment of the different pathways affected by each formulation and dose.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

The presented physiologically‐based pharmacokinetic approach to assess RO can be used to guide formulation selection and dosing in clinical studies.