ro13-9904 and Heroin-Dependence

Infectious sacroiliitis (ISI) is an uncommon cause of back and hip pain in which the sacroiliac joint, either unilateral or bilateral, is inflamed from an infectious source. Historically, this has been an easily missed diagnosis due to nonspecific presenting symptoms along with subtle nondistinguishable laboratory abnormalities.. We describe an injection drug user presenting with right-sided ISI who presented with hip and back pain and inability to walk. The patient had tenderness over his right sacroiliac joint, and despite negative plain radiographs, a magnetic resonance imaging (MRI) scan was obtained from the Emergency Department (ED) given the patient's risk factors for infection. Concerning findings of ISI on this MRI led to a computed tomography-guided biopsy during the patient's hospital admission, which revealed alpha-hemolytic Streptococcus as the responsible pathogen. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Infectious sacroiliitis is a rare condition that is difficult to diagnose, and carries increasing morbidity when diagnosis is delayed. We aim to increase awareness through a case report of a patient encountered in the ED.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Ceftriaxone; Emergency Service, Hospital; Heroin Dependence; Humans; Magnetic Resonance Imaging; Male; Mobility Limitation; Sacroiliitis; Substance Abuse, Intravenous; Vancomycin; Young Adult

Topics: Adult; Atlanto-Axial Joint; Cardiopulmonary Resuscitation; Ceftriaxone; Heart Arrest; Heroin Dependence; Humans; Hypothermia, Induced; Male; Methicillin-Resistant Staphylococcus aureus; Odontoid Process; Osteomyelitis; Quadriplegia; Substance Abuse, Intravenous; Tomography, X-Ray Computed; Vancomycin

Reducing the enduring vulnerability to relapse is a therapeutic goal in treating drug addiction. Studies with animal models of drug addiction show a marked increase in extrasynaptic glutamate in the core subcompartment of the nucleus accumbens (NAcore) during reinstated drug seeking. However, the synaptic mechanisms linking drug-induced changes in extrasynaptic glutamate to relapse are poorly understood. Here, we discovered impaired glutamate elimination in rats extinguished from heroin self-administration that leads to spillover of synaptically released glutamate into the nonsynaptic extracellular space in NAcore and investigated whether restoration of glutamate transport prevented reinstated heroin seeking. Through multiple functional assays of glutamate uptake and analyzing NMDA receptor-mediated currents, we show that heroin self-administration produced long-lasting downregulation of glutamate uptake and surface expression of the transporter GLT-1. This downregulation was associated with spillover of synaptic glutamate to extrasynaptic NMDA receptors within the NAcore. Ceftriaxone restored glutamate uptake and prevented synaptic glutamate spillover and cue-induced heroin seeking. Ceftriaxone-induced inhibition of reinstated heroin seeking was blocked by morpholino-antisense targeting GLT-1 synthesis. These data reveal that the synaptic glutamate spillover in the NAcore results from reduced glutamate transport and is a critical pathophysiological mechanism underling reinstated drug seeking in rats extinguished from heroin self-administration.

Topics: Animals; Aspartic Acid; Ceftriaxone; Conditioning, Operant; Disease Models, Animal; Down-Regulation; Drug-Seeking Behavior; Excitatory Postsynaptic Potentials; Glutamic Acid; Heroin; Heroin Dependence; In Vitro Techniques; Male; Morpholinos; Neurons; Nucleus Accumbens; Potassium; Rats; Rats, Sprague-Dawley; Secondary Prevention; Synapses

We present a case of chronic posterior hip dislocation after severe joint destruction following septic arthritis. In the absence of trauma, infection must be considered in the differential diagnosis of a dislocated joint particularly in patients with risk factors such as intravenous drug abuse and immune compromise. Excision arthroplasty of the hip was performed with good pain relief and functional outcomes. This is an excellent temporary or permanent solution in managing such complex cases although alternative management options are discussed.

Topics: Anti-Bacterial Agents; Arthritis, Infectious; Arthroplasty; Ceftriaxone; Clindamycin; Debridement; Floxacillin; Heroin Dependence; Hip Dislocation; Hip Joint; Humans; Male; Methadone; Middle Aged; Opiate Substitution Treatment; Osteomyelitis; Radiography; Staphylococcal Infections; Substance Abuse, Intravenous