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Biomedical subjects

John C Hunter

Publications and source records attributed to John C Hunter.

16 recordsLinked to original sources
PubMed2007

Percutaneous gelfoam embolization of chronic enterocutaneous fistulas: report of three cases.

PURPOSE: A relatively simple radiologically guided method for the treatment of enterocutaneous fistula by gelfoam embolization is described. METHODS: Three cases of chronic enterocutaneous fistula are presented. In each case, a sheath was positioned with its tip at the enteric opening of the fistula. Gelfoam was injected to occlude the fistula at its enteric opening. RESULTS: In each case, there was successful closure of the fistula. CONCLUSIONS: Radiologically guided embolization with gelfoam is a safe, relatively simple procedure, which may be useful in the treatment of chronic enterocutaneous fistula.

Adult↗
PubMed2007

Increased risk of posterior glenoid labrum tears in football players.

OBJECTIVE: This study was designed to test our hypothesis that football players with shoulder pain, shoulder instability, or both requiring MR arthrography for evaluation are at an increased likelihood relative to non-football players for having a tear of the posterior glenoid labrum. CONCLUSION: We conclude that posterior glenoid labrum tears are more prevalent in football players than in non-football players.

Adolescent↗
PubMed2006

Acute fracture of the os trigonum.

A 21-year-old man presented with ankle pain after a motor vehicle accident. Imaging revealed an acute fracture of the os trigonum in addition to multiple, other lower-extremity fractures. In this case, the fracture of the os trigonum was a result of a significant traumatic injury. Thus, the presence of this fracture in an acute setting should prompt a search for other associated fractures.

Accidents, Traffic↗
PubMed2006

Tubular acetabular intraosseous contrast tracking in MR arthrography of the hip: prevalence, clinical significance, and mechanisms of development.

OBJECTIVE: The purpose of this study was to describe tubular intraosseous tracking of contrast medium in the acetabular fossa, to our knowledge a previously undocumented imaging finding in MR arthrography of the hip, and to discuss its prevalence, clinical significance, and possible mechanisms of development. CONCLUSION: Tubular acetabular intraosseous contrast tracking is a common MR arthrographic finding that seems to have little clinical significance. Although the exact pathophysiologic mechanism is unknown, we presume repeated pumping of joint fluid through the nutrient foramina of the acetabular fossa may be one mechanism.

Acetabulum↗
PubMed2005

The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: a comparison of efficacy and side-effect profiles.

RATIONALE: Modulation of metabotropic glutamate receptor (mGluR) subtypes represents a novel approach for the treatment of neurological and psychiatric disorders. OBJECTIVES: This study was conducted to investigate the role of the mGluR5 and mGluR1 subtypes in the modulation of pain and anxiety. METHODS: The mGluR5 antagonists, 2-methyl-6-(phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), and the mGluR1 antagonist, (4-methoxy-phenyl)-(6-methoxy-quinazolin-4-yl)-amine HCl (LY456236), were tested in models of pain [mouse formalin test, rat spinal nerve ligation (SNL)] and anxiety [Vogel conflict, conditioned lick suppression (CLS)], and their efficacious effects were compared to any associated side effects. RESULTS: The systemic administration of MPEP, MTEP, and LY456236 reduced hyperalgesia induced by formalin and mechanical allodynia following SNL. However, only LY456236 completely reversed the allodynia. In the anxiety models, MPEP (3--30 mg/kg), MTEP (3--10 mg/kg), and LY456236 (10--30 mg/kg) produced anxiolytic-like effects similar to the benzodiazepine, chlordiazepoxide (CDP, 6 mg/kg). However, only MPEP and MTEP were able to produce a level of anxiolysis comparable to CDP. In a series of tests examining potential side effects, MPEP and MTEP reduced body temperature and locomotor activity and impaired operant responding for food and rotarod performance at doses of 3--30 and 1--30 mg/kg, respectively. LY456236 reduced operant responding at 30 mg/kg. CONCLUSION: Both mGluR5 and mGluR1 antagonists are effective in models of pain and anxiety. However, an mGluR1 antagonist was more efficacious than the two mGluR5 antagonists in the pain models, which, conversely, appeared more efficacious in the anxiety models. These findings support the potential utility of mGluR5 and mGluR1 antagonists for both the treatment of chronic pain and as novel anxiolytics.

Analgesics↗
PubMed2004

Voltage-gated sodium channels and hyperalgesia.

Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.

Analgesics↗
PubMed2003

Increased auditory startle response and reduced prepulse inhibition of startle in transgenic mice expressing a double mutant form of amyloid precursor protein.

Prepulse inhibition (PPI), a form of sensorimotor gating, occurs when an auditory startle response is markedly inhibited by a preceding sub-threshold stimulus (prepulse). Deficits in PPI have been demonstrated in patients with certain psychiatric disorders, such as schizophrenia, and in laboratory animals following specific pharmacological manipulations. Patients with Alzheimer's disease (AD) have not been tested in PPI, but have been shown to have abnormal sensory gating in another paradigm. Transgenic (Tg) CRND8 mice, which model Alzheimer's disease, carry the Swedish and Indiana familial Alzheimer's disease mutations of the human amyloid precursor protein gene and show age-related increases in beta-amyloid (Abeta) production, as well as plaque deposition. The present experiment investigated auditory startle threshold and PPI in TgCRND8 mice at various ages. In two longitudinal studies, PPI was examined in male TgCRND8 mice and non-transgenic (non-Tg) controls at 6-8 weeks of age (pre-plaque), and every 2 weeks thereafter until all mice were at least 16 weeks old (post-plaque). In a cross-sectional study, three different age sets of nai;ve TgCRND8 and non-Tg mice were tested: 10-12, 12-14, and 15-17 weeks old. In all three studies, TgCRND8 mice consistently and robustly demonstrated an enhanced response to a range of auditory startle stimuli compared to non-Tg mice. In addition, the TgCRND8 mice exhibited modest reductions in PPI, compared to non-Tg controls. These PPI deficits were present at pre- and post-plaque time points and did not appear to intensify with age; thus, they do not seem to correlate with the known neuropathology of TgCRND8 mice.

Acoustic Stimulation↗
PubMed2003

The role of voltage-gated sodium channels in neuropathic pain.

Use-dependent inhibitors of voltage-gated sodium channels (VGSC) are important therapeutic tools for chronic pain management, but are limited by possible severe side effects. Recent studies have provided much new information on the function of several voltage-gated sodium channels that are predominantly expressed in peripheral sensory neurons, and on their possible link to pathological pain states arising from injuries to the sensory nerve. The use of antisense oligonucleotides to target specific channel subtypes shows that the functional localization of the channel subtype Na(V)1.8 after nerve injury is essential for persistent pain states. The putative roles of Na(V)1.3 and Na(V)1.9 in neuropathic pain are also discussed. These studies may form a basis for developing inhibitors to target specific channel subtype(s) for use in chronic pain treatment.

Animals↗
PubMed2003

Web-based image review and data acquisition for multiinstitutional research.

OBJECTIVE: In this article, we describe a user-friendly Web-based interface that allows review of images combined with integrated data collection and entry for use at multiple sites involved in a large multicenter research project. CONCLUSION: The Web-based system that we present uses a commercially available Internet browser and Web platform and allows automated data entry that can be easily uploaded into standard data analysis programs. The system simplifies the complex logistics of using multiple sites and reviewers for radiology research and can preserve human subject confidentiality. We tested the system using a large-scale multicenter cohort study of pelvic fracture-related hemorrhage (the "Evaluating Pelvic Hemorrhage" study). Program testing revealed seamless remote image interpretation and data acquisition.

Biomedical Research↗
PubMed2002

Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8.

Neuropathic pain is a debilitating chronic syndrome that often arises from injuries to peripheral nerves. Such pain has been hypothesized to be the result of an aberrant expression and function of sodium channels at the site of injury. Here, we show that intrathecal administration of specific antisense oligodeoxynucleotides (ODN) to the peripheral tetrodotoxin (TTX)-resistant sodium channel, NaV1.8, resulted in a time-dependent uptake of the ODN by dorsal root ganglion (DRG) neurons, a selective "knock-down" of the expression of NaV1.8, and a reduction in the slow-inactivating, TTX-resistant sodium current in the DRG cells. The ODN treatment also reversed neuropathic pain induced by spinal nerve injury, without affecting non-noxious sensation or response to acute pain. These data provide direct evidence linking NaV1.8 to neuropathic pain. As NaV1.8 expression is restricted to sensory neurons, this channel offers a highly specific and effective molecular target for the treatment of neuropathic pain.

Anesthetics, Local↗
PubMed2002

The "reverse Segond" fracture: association with a tear of the posterior cruciate ligament and medial meniscus.

OBJECTIVE: We describe three patients who presented with radiographic findings of a fragment on the medial side of the tibial plateau of the knee that represented an avulsion of the deep portion of the medial collateral ligament. These findings were all associated with disruption of the posterior cruciate ligament and a peripheral medial meniscal tear-the so-called reverse Segond fracture. CONCLUSION: Avulsion fracture at the tibial insertion of the deep component of the medial collateral ligament is a rare finding. When this type of injury is diagnosed, the radiologist should consider posterior cruciate ligament injury and peripheral medial meniscal tears as possible associated findings.

Accidents, Traffic↗
PubMed1999

Synergistic antiallodynic effects of spinal morphine with ketorolac and selective COX1- and COX2-inhibitors in nerve-injured rats.

The possible role of spinal prostanoids in the tactile allodynia and thermal hyperalgesia associated with an experimental model of neuropathic pain was investigated. Neuropathic pain was induced by tight ligation of the L5 and L6 spinal nerves. Tactile allodynia was assessed 7 days after the surgery by measuring hindpaw withdrawal threshold to probing with von Frey filaments. Thermal hyperalgesia and nociception were determined by the 52 degrees C warm-water tail-flick test and by applying radiant heat to the plantar aspect of the hindpaw ipsilateral to the ligation. Minimal antiallodynic effect was produced by intrathecal (i.th.) administration of ketorolac or morphine up to the highest testable dose (100 microg) or by the (R)- or (S)-enantiomers of ketorolac (up to 6 microg) when administered alone. However, i.th. administration of a fixed ratio (1:1) of morphine plus racemic ketorolac or of morphine plus the (S)-enantiomer of ketorolac (S-ketorolac) produced a dose- and time-related antiallodynic effect: ED50 114 +/- 35.9 microg (total dose) for morphine plus ketorolac and 70.5 +/- 21.0 microg (total dose) for morphine plus S-ketorolac. The combination of i.th. morphine plus the (R)-enantiomer of ketorolac (R-ketorolac) (up to 200 microg total dose) was without effect. Similar antiallodynic activity was obtained for the co-administration of i.th. morphine and intravenous (i.v.) racemic ketorolac. In order to investigate the role of cyclooxygenase (COX) isozymes, relatively selective COX1 (piroxicam) and COX2 N-[2-cyclohexyloxy-4-nitrophenyl] metanesulfonamide (NS-398) inhibitors were administered i.th. (60 microg) alone or together with i.th. morphine. Piroxicam, NS-398, morphine and vehicle (90% DMSO) were without significant antiallodynic effect when administered alone, but moderate antiallodynic effects were produced by i.th. administration of fixed ratio (1:1) combinations of morphine with 60 microg each (highest soluble dose) of piroxicam (%MPE = 40.8 +/- 10.2) or NS-398 (%MPE = 32.4 +/- 9.5). Further, the combined i.th. administration of morphine, piroxicam and NS-398 in fixed 1:1:1 ratio (60 microg each) resulted in a supraadditive antiallodynic effect (%MPE = 70.4 +/- 10.8). Finally, morphine, but not ketorolac, given i.th. produced dose-dependent anti nociception in either the tail-flick or the paw-flick tests. However, there was no synergy between morphine and ketorolac against thermal nociception in either of the tests. These findings suggest that spinal prostanoids produced via both COX1 and COX2 pathways may play a role in neuropathic pain states and suggest the clinical utility of opioid plus COX-inhibitor combination therapy.

Analgesics, Opioid↗
PubMed1998

A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A.

Neuropathic pain may be produced, at least in part, by the increased activity of primary afferent neurons. Studies have suggested that an accumulation of voltage-gated sodium channels at the site of peripheral nerve injury is a primary precursory event for subsequent afferent hyperexcitability. In this study, a human sodium channel (hPN3, SCN10A) has been cloned from the lumbar 4/5 dorsal root ganglia (DRG). Expression of hPN3 in Xenopus oocytes showed that this clone is a functional voltage-gated sodium channel. The amino acid sequence of hPN3 is most closely related to the rat PN3/SNS sodium channels which are expressed primarily in the small neurons of rat DRGs. The homologous relationship between rPN3 and hPN3 is defined by (i) a high level of sequence identity (ii) sodium currents that are highly resistant to tetrodotoxin (TTX) (iii) similar tissue distribution profiles and (iv) orthologous chromosomal map positions. Since rPN3/SNS has been implicated in nociceptive transmission, hPN3 may prove to be a valuable target for therapeutic agents against neuropathic pain.

Amino Acid Sequence↗
PubMedDate not supplied

Regional variation and clinical indicators of antipsychotic use in residential treatment: a four-state comparison.

The last decade saw an increase in psychotropic use with pediatric populations. Antipsychotic prescriptions are used frequently in residential treatment settings, with many youth receiving antipsychotics for off-label indications. Residential treatment data from 4 states were examined to determine if regional variation exists in off-label prescription and what clinicalfactors predict use. The study used clinical and pharmacological data collected via retrospective chart reviews (N = 732). The Child and Adolescent Needs and Strengths Assessment-Mental Health Version was used to measure symptom and risk severity. Of youth receiving antipsychotics, 42.9% had no history of or current psychosis. Statistical analyses resulted in significant regional variation in use across states and yielded attention deficit/impulsivity, physical aggression, elopement, sexually abusive behavior, and criminal behavior as factors associated with antipsychotic prescription in nonpsychotic youth. Antipsychotic prescription is inconsistent across states. Off-label prescription is frequent and likelihood of use increases with behavior problems.

Adolescent↗