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.

Ultrastructural demonstration of trypsin-like protease in acrosomes of sea urchin sperm.

Two independent cytochemical techniques were used to demonstrate that a trypsin-like protease is bound to the acrosomal tubule of the sea urchin sperm. The enzyme is associated with binding on the reacted acrosome and presumably functions in the early phases of fertilization.

Use of tritiated 3-O-methyl-D-glucose for studies of membrane transport. Caveat.

Tritiated 3-O-methyl-D-glucose has many useful attributes as a model substance for studies of the transport of glucose across cell membranes. However, preparations of high specific radioactivity can decompose within a few months, producing radioactive impurities that can cause a several-fold increase in the apparent rate of sugar transport. In our investigation radioactive contaminants entered frog skeletal muscle cells by free diffusion rather than by facilitated transport. Much of the contaminating radioactive material could be removed by evaporating the solvent and redissolving the sugar. Tritiated sugar samples that had a specific activity below 0.1 Ci/mmol remained stable and suitable for transport measurements after several years of storage at -20 degrees C. In order to evaluate the suitability of a given tritiated preparation of sugar for transport measurements, it is recommended that its behavior be compared with that of a stable reference standard of low specific activity.

Selective loss of a plasma membrane protein associated with contraction of skeletal muscle.

Muscle proteins were labeled by incubating isolated frog sartorius muscles with [3H]- or [14C]phenylalanine. Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of plasma membrane fractions revealed a major protein band with an apparent molecular weight of approx. 96,000. Radioactivity in this band showed a clearly delineated decrease, relative to other bands, when previously labeled muscles were induced to contract either by electrical stimulation or by increasing the influx of Ca2+ from the incubation medium. It is postulated that a Ca2+-activated neutral protease may account for this decrease in labeled membrane protein.

Isolation of plasma membrane vesicles, derived from transverse tubules, by selective homogenization of subcellular fractions of frog skeletal muscle in isotonic media.

A new technique for isolating fragmented plasma membranes from skeletal muscle has been developed that is based on gentle mechanical disruption of selected homogenate fractions. (Na+ + K+)-stimulated, Mg2+-dependent ATPase was used as an enzymatic marker for the plasma membrane, Ca2+-stimulated, Mg2+-dependent ATPase as a marker for sarcoplasmic reticulum, and succinate dehydrogenase for mitochondria. Cell segments in an amber low-speed (800 x g) pellet of a frog muscle homogenate were disrupted by repeated gentle shearing with a Polytron homogenizer. Sarcoplasmic reticulum was released into the low-speed supernatant, whereas most of the plasma membrane marker remained in a white, fluffy layer of the sediment, which contained sarcolemma and myofibrils. Additional gentle shearing of the white low-speed sediment extracted plasma membranes in a form that required centrifugation at 100,000 x g for pelleting. This pellet, the fragmented plasma membrane fraction, had a relatively high specific activity of (Na+ + K+)-stimulated ATPase compared with the other fractions, but it had essentially no Ca2+-stimulated ATPase activity and only a small percentage of the succinate dehydrogenase activity of the homogenate. Experimental evidence suggests that the fragmented plasma membrane fraction is derived from delicate transverse tubules rather than from the thicker, basement membrane-coated sarcolemmal sheath of muscle cells. Electron microscopy showed small vesicles lined bu a single thin membrane. Hydroxyproline, a characteristic constituent of collagen and basememt membrane, could not be detected in this fraction.

Three-dimensional structure of a lipoyl domain from the dihydrolipoyl acetyltransferase component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli.

The structure of a lipoyl domain from the pyruvate dehydrogenase multienzyme complex of Escherichia coli has been determined by means of nuclear magnetic resonance spectroscopy. A total of 549 nuclear Overhauser effect distance restraints, 52 phi torsion angle restraints and 16 slowly exchanging amide protons were employed as input for the structure calculations. These were performed using a combined distance geometry-simulated annealing strategy. The domain is a hybrid between the N and C-terminal halves of the first and third lipoyl domains, respectively, of the dihydrolipoyl acetyltransferase component of the E. coli multienzyme complex, representing residues 1 to 33 and 238 to 289 (wild-type numbering). The lipoyl-lysine residue was also replaced by glutamine. Nonetheless, its structure, two four-stranded beta-sheets forming a flattened beta-barrel, closely resembles that of the lipoyl domain from the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus determined previously. As before, the lipoylation site is physically exposed in a tight turn in one of the beta-sheets, and the N and C-terminal residues are close together at the other end of the molecule in adjacent strands of the other beta-sheet. Another prominently conserved feature of the structure is the 2-fold axis of quasi-symmetry relating the N and C-terminal halves of the domain. Consistent with the high level of sequence similarity between lipoyl domains of 2-oxo acid dehydrogenase multienzyme complexes from many different sources, these results confirm that all lipoyl domains are likely to have closely related structures.

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.

Assay of succinate dehydrogenase activity by the tetrazolium method: evaluation of an improved technique in skeletal muscle fractions.

An improved spectrophotometric method for measuring succinate dehydrogenase (EC 1.3.99.1) activity with the use of 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride (INT) is described. The procedure has been evaluated in mitochondrial fractions and homogenates of frog skeletal muscle. For mitochondrial suspensions, extraction of formazan with alcohol was found to be superior to extraction with ethyl acetate. For homogenates, complete extraction of formazan required sequential treatment with alcohol and ethyl acetate; the generally employed procedure of extracting once with ethyl acetate alone led to serious underestimation of the amount of formazan in the tissue. Observations of mitochondrial suspension incubated with various concentrations of INT led to the selection of 0.8 mM INT for optimal results. Higher concentrations, although commonly used, can exert undesirable inhibitory effects on succinate dehydrogenase activity, especially at low concentrations of mitochondria and after longer periods of incubation. The problem of instability of succinate dehydrogenase was solved by the addition of buffer at pH 7.5.

Effect of short-term infusion of recombinant human relaxin on blood pressure in the late-pregnant rhesus macaque (Macaca mulatta).

OBJECTIVE: To test a recombinant human relaxin preparation, developed for potential therapeutic application, for possible hypotensive actions in near-term pregnant rhesus monkeys. METHODS: Groups of four females received 1-hour intravenous infusions of 0, 0.1, or 2.0 mg recombinant human relaxin/kg on gestation day 147 (term = 165 days). Maternal heart rate, electrocardiogram, and diastolic, systolic, and mean arterial pressure; and fetal heart rate were monitored before, during, and after the infusion. After spontaneous delivery, physical, neurobehavioral, and physiologic examinations were conducted on the newborn. RESULTS: No effects of recombinant human relaxin were detected by statistical analysis or examination of data records. CONCLUSION: Intravenous infusion of up to 2.0 mg recombinant human relaxin/kg in conscious pregnant rhesus monkeys had no effect on maternal cardiovascular indices or fetal heart rate.

Efficacy of an intraperitoneal antibiotic to reduce the incidence of infection in the trauma patient: a prospective, randomized study.

BACKGROUND: Antibiotic therapy in patients with blunt trauma remains an area of investigation. This study was undertaken in trauma patients evaluated with diagnostic peritoneal lavage to determine the effect of an intraperitoneal antibiotic on the following factors: infectious complications, length of hospital stay, and mortality. METHODS: A prospective, randomized double-blinded study compared using either 500 mg of intraperitoneal kanamycin or a saline control in 69 adult trauma patients requiring diagnostic peritoneal lavage was conducted over a 24-month period. Advanced trauma life support indications for performing diagnostic peritoneal lavage were used. Patients were randomized to receive 50 mL of solution intraperitoneally through a lavage catheter and were evaluated for all septic complications, length of hospital stay, and outcome. RESULTS: Over a 24-month period, 40 patients received kanamycin, and 29 patients received a placebo. Of patients receiving kanamycin, 27.5 percent experienced infectious complications compared to 65.5 percent of the control patients (p = 0.001, chi-square analysis). The average length of stay in the intensive care unit was 4.18 days in the kanamycin group and 6.96 days in the control group (p = 0.04, chi-square analysis). The average length of stay was 12.32 days for patients receiving kanamycin and 17.36 days for the control group (p = 0.03, chi-square analysis). The mortality rate for each group was 13 percent. CONCLUSIONS: Intraperitoneal kanamycin given to trauma patients requiring diagnostic peritoneal lavage within the first three hours following injury reduces the incidence of infectious complications and shortens intensive care unit and hospital stay.

Anterior subluxation of the cervical spine: hyperflexion sprain.

Anterior subluxation (hyperflexion sprain) is localized, purely ligamentous disruption of the cervical spine caused by a limited flexion force. When associated with a simple wedge fraction, also a flexion injury, anterior subluxation may be the more significant lesion. Radiographically, anterior subluxation is characterised by (1) a localized kyphotic angulation at the level of injury; (2) anterior rotation, or displacement, of the subluxed vertebra; (3) anterior narrowing and posterior widening of the disc space; (4) widening of the space between the subluxed vertebral body and the subjacent articular masses; (5) displacement of the inferior articulating facets of the subluxed vertebra with respect to their contiguous subjacent facets; and (6) widening of the interspinous space ("fanning"). The localized kyphotic angulation at the level of ligamentous disruption distinguishes pathologic anterior subluxation from diffuse "reversal of the normal cervical lordosis"; produced by voluntary positioning or muscle spasm. Anterior subluxation is clinically significant because of the approximate 20% incidence of delayed instability due to impaired ligamentous healing.

Conservative management of acoustic neuroma: an outcome study.

OBJECTIVE: This study analyzed selection criteria, clinical outcome, and tumor growth rates in patients with acoustic neuromas in whom the initial management strategy was observation. METHODS: A retrospective review of patients with conservatively managed unilateral acoustic neuromas was conducted. Minimum follow-up was 6 months. Patients with neurofibromatosis Type II were excluded. Differences in tumor growth rates were analyzed by use of the Wilcoxon rank sum test. RESULTS: Sixty-eight patients (31 men and 37 women) with a mean age of 67.1 years were followed for an average of 3.4 years after diagnosis. The reasons for a trial of observation included advanced age (55%), patient preference (21%), minimal symptoms (9%), poor general medical condition (7%), asymptomatic tumor (4%), and tumor in the only hearing ear (4%). Fifty-eight patients (85%) were successfully managed with observation alone. Ten patients (15%) ultimately required treatment (nine received microsurgical treatment and one patient underwent radiosurgical intervention) at a mean time interval of 4.0 years after diagnosis. Forty-eight tumors (71%) showed no growth and 20 (29%) enlarged during the study period. The mean tumor growth rate at the 1-year follow-up was significantly higher in the group requiring treatment (3.0 mm) than in the group not requiring treatment (0.36 mm) (P < 0.0001). Thus, the tumor growth rate at the 1-year follow-up was a strong predictor of the eventual need for treatment. CONCLUSION: Observation is a reasonable management strategy in carefully selected patients with acoustic neuromas. Diligent follow-up with serial magnetic resonance imaging is recommended, because some tumors will enlarge to the point at which active treatment is required.

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.

Utilization of homologous proteins to evaluate the safety of recombinant human proteins--case study: recombinant human interferon-gamma (rhIFN-gamma).

Interferon-gamma is an immunomodulatory cytokine that has an extremely restricted host range of activities. RhIFN-gamma was one of the first species-specific recombinant proteins to be assessed in conventional safety models typically utilized for xenobiotics. Acute, subchronic and Segment I and II reproductive studies in rats revealed no evidence of toxicity at any of the doses tested; these results were not predictive of clinical toxicity, which is not unexpected since rodents are known to be pharmacologically nonresponsive to rhIFN-gamma. In contrast, 4- and 13-week multidose toxicity studies in cynomolgus monkeys with rhIFN- were predictive of many of the dose-limiting clinical toxicities. RhIFN- is active on non-human primate cells, though not at the same level as on human cells. In addition, qualitative similarities were observed between toxicity studies employing rhIFN-gamma in the cynomolgus monkey and recombinant murine interferon-gamma (rmuIFN-gamma) in the mouse. These results suggest that in situations where a high degree of species specificity is encountered, studies employing a recombinant protein in a homologous species may provide a useful test system for preclinical safety assessment. This information should be evaluated in conjunction with data from studies conducted with the human protein in pharmacologically responsive animal models when possible.

Feeding and respiration in the New Zealand copepod Calamoecia lucasi brady.

Filtering rates of the various growth stages of Calamoecia lucasi were determined in cultures of yeast labelled with 14C, and the effects of food concentrations and temperature on filtering and feeding rates examined. Filtering rates decreased with increasing food concentration, and above a limiting value of 0.8×104 cells·ml-1 feeding rates were maximal and did not increase further. Filtering rates increased with increasing temperature up to 20°C, and from nauplius to adult, although weight specific feeding rates were highest in CII. Assimilation efficiencies of the adults averaged 65%. The effect of temperature on the rate of oxygen consumption of C. lucasi, Boeckella delicata and B. symmetrica was measured using the micro-Winkler technique, and the regression relationship between log oxygen uptake, temperature and log weight calculated for the three species. Using these data a preliminary energy budget was calculated for C. lucasi. The balance between food intake and respiratory output was positive in all stages except the nauplius, and was greatest in CII-IV. This concurs with information from field studies of C. lucasi in which daily P/B ratios were greatest in these stages also.

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.

Iatrogenic facial nerve injury during otologic surgery.

Perhaps the most devastating complication in otologic surgery is that of inadvertent injury to the facial nerve. A review of 22 patients who had sustained an iatrogenic facial nerve injury was conducted. Although the most common procedure being performed during the injury was mastoidectomy (55%), a surprising number of patients had injury during tympanoplasty (14%) or during removal of exostoses (14%). The most common area of injury to the facial nerve in this series was in the tympanic segment. In 79% of the patients, the facial nerve injury was not detected at the time of surgery. All patients underwent surgical exploration of the facial nerve. Otologic surgeons are cautioned to be familiar with the normal course of the facial nerve and to be aware of the potential for facial nerve injury when performing transcanal surgery.

Neoplasms of the vagus nerve.

A tumor of the vagus nerve often is discovered unexpectedly at operation. We report 36 of these rare neoplasms in 35 patients. The majority of the tumors presented as a mass in the upper cervical or parapharyngeal region. Usually the mass was asymptomatic. The following types and frequencies of neoplasms of the vagus nerve were noted: paragangliomas, 50%; neurilemmomas, 31%; neurofibromas, 14%; and neurofibrosarcomas, 6%. Surgical resection, with preservation of the vagus nerve when possible, is the treatment of choice. The clinical features, diagnosis, management, and prognosis of the tumors are presented. Special problems that occur with vagal neoplasms include postoperative dysfunction, catecholamine secretion, and intracranial or skull-base extension.

Three-dimensional reconstruction of the temporal bone.

Study of the complex anatomy and pathology of the temporal bone has traditionally used microscopy which permits analysis in only two dimensions. Recent advances in bioimaging technology have permitted visualization and reconstruction of computed tomography images in three dimensions. We have developed a technique that applies this technology in the imaging and reconstruction of human temporal bones. Data taken from serial histologic sections of the temporal bone are entered into a computer. The sections are edited and, through the use of specially developed software, a realistic three-dimensional reconstruction is produced. The reconstructed image can be rotated along any of three axes, and structures within the temporal bone can be isolated for more detailed analysis. Applications for the study of pathologic conditions of the temporal bone will be discussed.

Surgical management of previously untreated glomus jugulare tumors.

The treatment of glomus jugulare tumors is controversial. Changes in the surgical treatment of glomus jugulare tumors at The House Ear Clinic have allowed complete resection in 85% of patients with minimal morbidity and no surgical mortalities. Our experience with 52 previously untreated patients with glomus jugulare tumors is reviewed. Two primary surgical techniques were used. The mastoid/neck approach was used in 9 patients with small tumors limited to the jugular bulb. The infratemporal fossa approach was used in the remaining 43 tumors. Lower cranial nerve preservation was possible in the majority of patients with normal preoperative function. Modifications in the management of the facial nerve during the infratemporal fossa approach have resulted in good recovery of facial function (House grade I/VI or II/VI) in 95% of patients. Most patients (85%) were able to fully resume all preoperative activities. Our results suggest that surgical management is the treatment of choice in younger patients with glomus jugulare tumors.