Longitudinal associations between post-traumatic stress disorder and metabolic syndrome severity.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design. METHOD: A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning ~2.5 years, n = 971 at time 2). RESULTS: The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (ß = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%. CONCLUSIONS: Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions.

Atomic force microscopy reveals defects within mica supported lipid bilayers induced by the amyloidogenic human amylin peptide.

To date, over 20 peptides or proteins have been identified that can form amyloid fibrils in the body and are thought to cause disease. The mechanism by which amyloid peptides cause the cytotoxicity observed and disease is not understood. However, one of the major hypotheses is that amyloid peptides cause membrane perturbation. Hence, we have studied the interaction between lipid bilayers and the 37 amino acid residue polypeptide amylin, which is the primary constituent of the pancreatic amyloid associated with type 2 diabetes. Using a dye release assay we confirmed that the amyloidogenic human amylin peptide causes membrane disruption; however, time-lapse atomic force microscopy revealed that this did not occur by the formation of defined pores. On the contrary, the peptide induced the formation of small defects spreading over the lipid surface. We also found that rat amylin, which has 84% identity with human amylin but cannot form amyloid fibrils, could also induce similar lesions to supported lipid bilayers. The effect, however, for rat amylin but not human amylin, was inhibited under high ionic conditions. These data provide an alternative theory to pore formation, and how amyloid peptides may cause membrane disruption and possibly cytotoxicity.

Overview status of preclinical safety assessment for immunomodulatory biopharmaceuticals.

Scientists from academia, industry, FDA, European and Japanese regulatory groups met to discuss key considerations that are central to the safe and expeditious development of novel biologic agents that are thought to act by modulation of the host immune system. In the presentations and case studies, particular attention was given to the current clinical experience with immunosuppressant agents. Many new biologic agents (such as humanized monoclonal antibodies) have been developed to interact in a highly specific manner with their target. However, their pharmacologic properties may be more complex than originally appreciated, impacting on clinical trial designs. The goal of preclinical safety assessment should be to provide some assurance that patients will be protected from any unacceptable risks by defining "safe" and "active" doses. For immunomodulatory molecules, particular attention is paid to defining potential for increased risks of lymphoproliferative disorders, opportunistic infections, and immune impairment. To address these issues, a wide variety of preclinical studies, mainly in non-human primates, have been performed for the purpose of assessing the potential risk of drug-induced, human immunotoxicity. Case studies presented at this symposium showed the feasibility of assessing humoral and cell-mediated aspects of the immune system, using antigen and neoantigen challenges, immunohistochemical, and flow cytometric (FACS) methods. In some cases, homologous forms of the biologic agent and "humanized" transgenic models have been used to assess potential clinical risks. These data have been useful in providing some assurance that severe adverse effects would not be induced in patients. Despite these limitations, it is important that industry sponsors provide information to regulatory authorities, the clinical investigator, and patients that provides the best feasible basis for risk assessment, safe clinical trial design, informed consent, and eventually, appropriate labeling. It is recognized that existing preclinical models often have significant limitations. Consequently, the sponsor's and regulatory authority's experienced judgement has determined whether or not the purported benefits of the novel therapeutic agent are balanced by the potential short- and long-term risks. In this field of development, preclinical models often need to reflect recent technology innovations; therefore, these models are not always "validated" in a conventional sense. Experience to date suggests that improved methods and approaches are needed as these agents are developed for use in lower or moderate risk patient populations. Consequently, there is an increased need for an industry/regulatory partnership in order to achieve progress in these risk assessment areas.

Computerized medical record in a private neurotology practice.

OBJECTIVE: To develop a computerized medical record for a private neurotology practice using a relational database with templates. BACKGROUND: Computers have been used in the medicine many years for billing, scheduling appointments, and word processing. Neurotology represents a relatively narrow field of medicine, which is particularly suited to a computerized record. A computerized medical record should allow for better data storage and retrieval as well as better documentation of the patient care given. METHODS: Using a commercially available, record-keeping software in a local area computer network. templates were developed for several common neurotologic problems. A template for a neurotologic examination was also developed. These were adapted from templates developed by a group otolaryngology practice in a neighboring city. Data entry templates for vestibular and audiologic tests were also developed. Implementation of the computerized record was accomplished in phases, allowing elimination of the paper record. RESULTS: A fully computerized medical record has been developed and maintained in a private neurotology practice over the past year. Patient response to the computerized record system has been favorable. Office personnel have adapted well to a paperless record, and referring physicians have welcomed the documents generated by the computer. CONCLUSION: Computerizing the medical records of a neurotology practice is possible and allows for improved documentation, ongoing assessment of treatment results, and improved efficiency among office staff.

Cochlear implantation in Jervell and Lange-Nielsen syndrome.

Jervell and Lange-Nielsen syndrome represents a rare, autosomal recessive cause of congenital deafness. Affected patients have a characteristic prolongation of the QT interval on electrocardiogram, along with cardiac arrhythmias, recurrent syncopal episodes, and a predisposition to sudden death. We present the first reported case of cochlear implantation in a child with Jervell and Lange-Nielsen syndrome. Special perioperative precautions were required, including cardiac monitoring for 48 hours, perioperative beta blockade, and special anesthetic considerations. Because sudden patient death has been associated with exposures to loud sounds in patients with prolonged QT syndrome without hearing loss (Ward-Romano syndrome), initial cochlear implant stimulation was performed with cardiac monitoring. This patient has responded well to cochlear implantation with 11 months of implant use. The patient has achieved limited open-set word comprehension and significantly improved speech, as is expected for her age. Although the patient had no problems with cardiac arrhythmias at surgery, she has since experienced a syncopal episode requiring placement of an automatic pacemaker and defibrillator. The implant has continued to work well despite the pacemaker and defibrillator. Cochlear implantation can be relatively safely performed in patients with Jervell and Lange-Nielsen syndrome, provided proper precautions are followed.

On the self-protective nature of inconsistency-negativity management: using the person memory paradigm to examine self-referent memory.

How do individuals remember feedback that is inconsistent or negative? According to the inconsistency-negativity resolution model, individuals are motivated to reduce uncertainty and resolve inconsistency even when threat to self is potential. They more deeply process and better remember negative self- than other-referent information. According to the inconsistency-negativity neglect model, individuals are motivated to protect the self against threat. They engage in more shallow processing and remember less negative self- than other-referent information. Participants read and recalled either self- or other-referent mixed-valence information. The neglect model was supported in personality and minimal feedback settings. A chronometric exploration of processing mechanisms and the ruling out of a retrieval interference account clarified aspects of the model. Individuals are hypersensitive to threat potential: They will protect the self against even hypothetical threat.

Diagnosis and management of intralabyrinthine schwannomas.

OBJECTIVES/HYPOTHESIS: Describe the symptoms, signs, radiographic findings, and treatment results for four patients with intralabyrinthine schwannoma beginning either primarily within the labyrinth or extending secondarily into the labyrinth from the internal auditory canal. STUDY DESIGN: Retrospective review. METHODS: Review of clinic records, operative records, imaging studies with follow-up telephone interview, and when possible, repeat examination. RESULTS: Four patients with intralabyrinthine schwannoma treated by the first author were identified. Episodic vertigo, indistinguishable from Meniere's disease, was present in all but one of the patients in this study. A progressive unilateral hearing loss was also found in all of the patients. Magnetic resonance imaging revealed tumor isolated to the vestibule in two patients with the cochlea primarily involved in the other two patients. Intracochlear tumor extending into the internal auditory canal had been missed on preoperative imaging in one patient and was found during a translabyrinthine vestibular nerve section. In another patient with an intracanalicular schwannoma, tumor extending into the basal turn of the cochlea was not removed during a translabyrinthine approach to the internal auditory canal. The tumor subsequently recurred, necessitating a transotic approach for removal. A transmastoid/translabyrinthine approach was used to successfully remove tumor in one patient. Another patient with good hearing and no vestibular symptoms at time of this writing is being followed with serial imaging studies. As expected, the three patients who underwent surgery have anacusis in the operated ear and are free of vertigo at follow-up intervals of 12, 26, and 65 months. CONCLUSIONS: Intralabyrinthine schwannomas are rare tumors with optimal treatment being determined by the symptoms, tumor location, and hearing. Findings of an intralabyrinthine schwannoma on magnetic resonance imaging may be easily overlooked and attributed to inflammatory changes.

Bone cement reconstruction of the ossicular chain: a preliminary report.

OBJECTIVE: To determine the feasibility and efficacy of using a bone cement, Oto-Cem, to reconstruct the ossicular chain. STUDY DESIGN: Prospective clinical trial on nine consecutively chosen adult patients with ossicular chain defects. PATIENTS AND SETTING: Nine patients with ossicular chain defects involving the long process of the incus were treated at the Carolina Ear and Hearing Clinic. The ossicular chain was reconstructed using bone cement by itself or in conjunction with a stapes prosthesis. MAIN OUTCOME MEASURES: Preoperative audiograms were compared with audiograms 3, 6, and 12 months after reconstruction. RESULTS: There was a mean pure-tone average (PTA) improvement of 15 dB in patients undergoing incus to stapes suprastructure reconstruction with the bone cement. The incus to mobile footplate reconstruction (using a stapes prosthesis attached to the newly reconstructed incus) resulted in a 34-dB PTA postoperative improvement. Two of the three patients with incus to oval window repairs experienced a 10-dB improvement in PTA. One of the three patients experienced a loss in speech discrimination and a 2-dB loss in PTA. CONCLUSIONS: Despite the limited number of patients, this preliminary study demonstrates the effectiveness of Oto-Cem in reconstructing a foreshortened incus. There was a substantial hearing improvement in all but one patient in the incus to stapes or the incus to footplate categories.

In vitro Characteristics of a Glass Ionomer Cement.

Glass ionomer cements were first described by Wilson and Kent and have been used in dentistry since 1969. It has been recommended for bridging ossicular chain defects, fixation of ossicular chain prosthesis, anchoring of cochlear implants, mastoid obliteration, and repair of tegmen and posterior canal wall defects. The biocompatability and stability of this material over time is vital to its usefulness in neurotologic surgery. The purpose of this study was to assess the stability of a glass ionomer cement in the presence of bacteria and in different pH environments. We demonstrated that bacteria readily adhere to the surface and their presence is associated with accelerated loss of matrix. We found the cement to be susceptible to low pH and to release a visible cloud of debris upon contact with fluid. Calcium concentration in the solution was elevated at all pH levels. Although we are able to demonstrate these findings in vitro the clinical relevance is unclear. There have been several cases of aseptic meningitis possibly due to intracranial release of components of the cement. Until further studies are done use of the cement in contact with cerebral spinal fluid should be avoided. This cement, or a similar material, would be useful in neurotologic surgery but prior to widespread use further testing should be done to assess safety.

The effects of methoxychlor on early sea urchin development.

Methoxychlor (MXC) is a widely used pesticide which has been found in water sources near agricultural sites. Embryos of aquatic organisms are likely to encounter MXC due to land runoff. The sea urchin embryo (Strongylocentrotus purpuratus) was used as a model system to document the effects of MXC on early development up to the pluteus stage. Fertilized eggs and embryos were exposed to several concentrations (0.1, 1.0, 10, and 100 ppm) of the pesticide in both chronic and acute exposure regimens. With chronic exposure, percentages of embryos completing normal first cleavage decreased with increased concentrations of MXC, and subsequent cleavages became even more irregular in that blastomeres divided asymmetrically and asynchronously. Ten parts per million MXC allowed development through the hatched blastula stage, whereas embryos in 100 ppm MXC did not hatch. In acute exposure trials, fertilized eggs were pulsed (i.e., exposed for brief durations) to MXC for 30, 60, or 90 min. The MXC was then washed out. Recovery of normal development was proportional to the amount and duration of MXC exposure. Development was delayed in embryos exposed to 100 ppm MXC for 30 or 60 min. The embryos exposed to 100 ppm MXC for 90 min were abnormal as early as the four-cell stage, and by 72 hr more than 90% had abnormal gut development, indicating disruption of gastrulation. These data show that MXC exposure resulted in retardation of cleavage and abnormal gastrulation, basic morphogenetic processes.

A modification of sub-mental intubation.

In patients who have sustained base of skull fractures, the mode of intubation is controversial, with many anaesthetists arguing against nasal intubation. In several maxillofacial procedures temporary intermaxillary fixation (IMF) in the intraoperative period may be essential to achieve optimal results in fixation. For patients with combined facial and base of skull injury, tracheotomy may have to be performed. The submental approach to intubation allows IMF to be used without resort to nasal intubation or tracheotomy. We describe a modification of the original technique which is applicable to any reinforced tracheal tube and which does not compromise the airway.