Albert B. Chandler Hospital

OBJECTIVE: Tonsillectomy is one of the most common surgical procedures in the United States, with more than 530,000 procedures performed annually in children younger than 15 years. Tonsillectomy is defined as a surgical procedure performed with or without adenoidectomy that completely removes the tonsil including its capsule by dissecting the peritonsillar space between the tonsil capsule and the muscular wall. Depending on the context in which it is used, it may indicate tonsillectomy with adenoidectomy, especially in relation to sleep-disordered breathing. This guideline provides evidence-based recommendations on the preoperative, intraoperative, and postoperative care and management of children 1 to 18 years old under consideration for tonsillectomy. In addition, this guideline is intended for all clinicians in any setting who interact with children 1 to 18 years of age who may be candidates for tonsillectomy. PURPOSE: The primary purpose of this guideline is to provide clinicians with evidence-based guidance in identifying children who are the best candidates for tonsillectomy. Secondary objectives are to optimize the perioperative management of children undergoing tonsillectomy, emphasize the need for evaluation and intervention in special populations, improve counseling and education of families of children who are considering tonsillectomy for their child, highlight the management options for patients with modifying factors, and reduce inappropriate or unnecessary variations in care. RESULTS: The panel made a strong recommendation that clinicians should administer a single, intraoperative dose of intravenous dexamethasone to children undergoing tonsillectomy. The panel made a strong recommendation against clinicians routinely administering or prescribing perioperative antibiotics to children undergoing tonsillectomy. The panel made recommendations for (1) watchful waiting for recurrent throat infection if there have been fewer than 7 episodes in the past year or fewer than 5 episodes per year in the past 2 years or fewer than 3 episodes per year in the past 3 years; (2) assessing the child with recurrent throat infection who does not meet criteria in statement 2 for modifying factors that may nonetheless favor tonsillectomy, which may include but are not limited to multiple antibiotic allergy/intolerance, periodic fever, aphthous stomatitis, pharyngitis and adenitis, or history of peritonsillar abscess; (3) asking caregivers of children with sleep-disordered breathing and tonsil hypertrophy about comorbid conditions that might improve after tonsillectomy, including growth retardation, poor school performance, enuresis, and behavioral problems; (4) counseling caregivers about tonsillectomy as a means to improve health in children with abnormal polysomnography who also have tonsil hypertrophy and sleep-disordered breathing; (5) counseling caregivers that sleep-disordered breathing may persist or recur after tonsillectomy and may require further management; (6) advocating for pain management after tonsillectomy and educating caregivers about the importance of managing and reassessing pain; and (7) clinicians who perform tonsillectomy should determine their rate of primary and secondary posttonsillectomy hemorrhage at least annually. The panel offered options to recommend tonsillectomy for recurrent throat infection with a frequency of at least 7 episodes in the past year or at least 5 episodes per year for 2 years or at least 3 episodes per year for 3 years with documentation in the medical record for each episode of sore throat and 1 or more of the following: temperature >38.3°C, cervical adenopathy, tonsillar exudate, or positive test for group A β-hemolytic streptococcus.

OBJECTIVE: Sudden hearing loss (SHL) is a frightening symptom that often prompts an urgent or emergent visit to a physician. This guideline provides evidence-based recommendations for the diagnosis, management, and follow-up of patients who present with SHL. The guideline primarily focuses on sudden sensorineural hearing loss (SSNHL) in adult patients (aged 18 and older). Prompt recognition and management of SSNHL may improve hearing recovery and patient quality of life (QOL). Sudden sensorineural hearing loss affects 5 to 20 per 100,000 population, with about 4000 new cases per year in the United States. This guideline is intended for all clinicians who diagnose or manage adult patients who present with SHL. PURPOSE: The purpose of this guideline is to provide clinicians with evidence-based recommendations in evaluating patients with SHL, with particular emphasis on managing SSNHL. The panel recognized that patients enter the health care system with SHL as a nonspecific, primary complaint. Therefore, the initial recommendations of the guideline deal with efficiently distinguishing SSNHL from other causes of SHL at the time of presentation. By focusing on opportunities for quality improvement, the guideline should improve diagnostic accuracy, facilitate prompt intervention, decrease variations in management, reduce unnecessary tests and imaging procedures, and improve hearing and rehabilitative outcomes for affected patients. RESULTS: The panel made strong recommendations that clinicians should (1) distinguish sensorineural hearing loss from conductive hearing loss in a patient presenting with SHL; (2) educate patients with idiopathic sudden sensorineural hearing loss (ISSNHL) about the natural history of the condition, the benefits and risks of medical interventions, and the limitations of existing evidence regarding efficacy; and (3) counsel patients with incomplete recovery of hearing about the possible benefits of amplification and hearing-assistive technology and other supportive measures. The panel made recommendations that clinicians should (1) assess patients with presumptive SSNHL for bilateral SHL, recurrent episodes of SHL, or focal neurologic findings; (2) diagnose presumptive ISSNHL if audiometry confirms a 30-dB hearing loss at 3 consecutive frequencies and an underlying condition cannot be identified by history and physical examination; (3) evaluate patients with ISSNHL for retrocochlear pathology by obtaining magnetic resonance imaging, auditory brainstem response, or audiometric follow-up; (4) offer intratympanic steroid perfusion when patients have incomplete recovery from ISSNHL after failure of initial management; and (5) obtain follow-up audiometric evaluation within 6 months of diagnosis for patients with ISSNHL. The panel offered as options that clinicians may offer (1) corticosteroids as initial therapy to patients with ISSNHL and (2) hyperbaric oxygen therapy within 3 months of diagnosis of ISSNHL. The panel made a recommendation against clinicians routinely prescribing antivirals, thrombolytics, vasodilators, vasoactive substances, or antioxidants to patients with ISSNHL. The panel made strong recommendations against clinicians (1) ordering computerized tomography of the head/brain in the initial evaluation of a patient with presumptive SSNHL and (2) obtaining routine laboratory tests in patients with ISSNHL.

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate significant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.

Excessive cerebral accumulation of the 42-residue amyloid beta-protein (Abeta) is an early and invariant step in the pathogenesis of Alzheimer's disease. Many studies have examined the cellular production of Abeta from its membrane-bound precursor, including the role of the presenilin proteins therein, but almost nothing is known about how Abeta is degraded and cleared following its secretion. We previously screened neuronal and nonneuronal cell lines for the production of proteases capable of degrading naturally secreted Abeta under biologically relevant conditions and concentrations. The major such protease identified was a metalloprotease released particularly by a microglial cell line, BV-2. We have now purified and characterized the protease and find that it is indistinguishable from insulin-degrading enzyme (IDE), a thiol metalloendopeptidase that degrades small peptides such as insulin, glucagon, and atrial natriuretic peptide. Degradation of both endogenous and synthetic Abeta at picomolar to nanomolar concentrations was completely inhibited by the competitive IDE substrate, insulin, and by two other IDE inhibitors. Immunodepletion of conditioned medium with an IDE antibody removed its Abeta-degrading activity. IDE was present in BV-2 cytosol, as expected, but was also released into the medium by intact, healthy cells. To confirm the extracellular occurrence of IDE in vivo, we identified intact IDE in human cerebrospinal fluid of both normal and Alzheimer subjects. In addition to its ability to degrade Abeta, IDE activity was unexpectedly found be associated with a time-dependent oligomerization of synthetic Abeta at physiological levels in the conditioned media of cultured cells; this process, which may be initiated by IDE-generated proteolytic fragments of Abeta, was prevented by three different IDE inhibitors. We conclude that a principal protease capable of down-regulating the levels of secreted Abeta extracellularly is IDE.

Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls. These data can be interpreted to indicate that oxidation of cellular proteins may be a critical determinant of brain function. Moreover, it also implies that there is an age-related increase in vulnerability of tissue to oxidation that can be modified by free radical trapping compounds.

This article describes the use of the policy Delphi method in building consensus for public policy and proposes a technique for measuring the degree of consensus. The policy Delphi method is a systematic method for obtaining, exchanging, and developing informed opinion on an issue. It can be used to develop consensus either for or against policy issues. The method includes a multistage process involving the initial measurement of opinions (first stage), followed by data analysis, design of a new questionnaire, and a second measurement of opinions (second stage). The interquartile deviation is presented as one way of measuring consensus, and the McNemar test is described as a way to quantify the degree of shift in responses from the first to second stage. The application of the method is illustrated by a case example from a study of state legislators’ views on tobacco policy.

Although the cellular functions of TSC2 and its protein product, tuberin, are not known, somatic mutations in the TSC2 tumor suppressor gene are associated with tumor development in lymphangioleiomyomatosis (LAM). We found that ribosomal protein S6 (S6), which exerts translational control of protein synthesis and is required for cell growth, is hyperphosphorylated in the smooth muscle-like cell lesions of LAM patients compared with smooth muscle cells from normal human blood vessels and trachea. Smooth muscle (SM) cells derived from these lesions (LAMD-SM) also exhibited S6 hyperphosphorylation, constitutive activation of p70 S6 kinase (p70S6K), and increased basal DNA synthesis. In parallel, TSC2-/- smooth muscle cells (ELT3) and TSC2-/- epithelial cells (ERC15) also exhibited hyperphosphorylation of S6, constitutive activation of p70S6K, and increased basal DNA synthesis. Re-introduction of wild type tuberin into LAMD-SM, ELT3, and ERC15 cells abolished phosphorylation of S6 and significantly inhibited p70S6K activity and DNA synthesis. Rapamycin, an immunosuppressant, inhibited hyperphosphorylation of S6, p70S6K activation, and DNA synthesis in LAMD-SM cells. Interestingly, the basal levels of phosphatidylinositol 3-kinase, Akt/protein kinase B, and p42/p44 MAPK activation were unchanged in LAMD-SM and ELT3 cells relative to levels in normal human tracheal and vascular SM. These data demonstrate that tuberin negatively regulates the activity of S6 and p70S6K specifically, and suggest a potential mechanism for abnormal cell growth in LAM.

BACKGROUND: The risk, severity, and patient-reported outcomes of radiation-induced mucositis among head and neck cancer patients were prospectively estimated. METHODS: A validated, patient-reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales were used to measure mucositis (reported as mouth and throat soreness), daily functioning, and use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT. RESULTS: Contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3-4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3-4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity. The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at Week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of 1 or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6. CONCLUSIONS: Mucositis occurs among virtually all patients who are undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed.

PURPOSE: We document the incidence of complications associated with laparoscopic nephrectomy in a multi-institutional study. MATERIALS AND METHODS: The study included the initial 185 patients undergoing laparoscopic nephrectomy at 5 centers in the United States between June 1990 and July 1993. RESULTS: A total of 30 patients (16%) had 34 complications. There was no mortality. Access-related complications included 2 cases of hernia formation at the trocar site, 1 abdominal wall hematoma and 1 trocar injury to a hydronephrotic kidney. Intraoperative complications included 5 cases of vascular injury, 1 splenic laceration and 1 pneumothorax. Postoperative complications involved the gastrointestinal tract in 6 cases, cardiovascular system in 6, genitourinary tract in 4, respiratory system in 4 and musculoskeletal system in 2. Miscellaneous complications occurred in 3 patients. Open surgical intervention was required electively in 8 patients and on an emergency basis in 2. The incidence of complications decreased with experience: 71% occurred during the initial 20 cases at each institution. CONCLUSIONS: In our early experience the complication rate for laparoscopic nephrectomy was 12% in patients with benign renal disease and 34% in those with renal cancer. Based on this collective experience, recommendations for prevention, recognition and treatment of complications are made.

Serum amyloid A (SAA) proteins comprise a family of apolipoproteins synthesized in response to cytokines released by activated monocytes/macrophages. Acute-phase protein concentrations have been advocated as objective biochemical indices of disease activity in a number of different inflammatory processes. Clinical studies in large groups of patients with a variety of disorders confirmed the rapid production and exceptionally wide dynamic range of the SAA response. It is as sensitive a marker for the acute-phase as C-reactive protein (CRP). Recent studies indicate that SAA is the most sensitive non-invasive biochemical marker for allograft rejection. Further studies comparing the measurement of SAA to CRP could reveal other indications for its specific use. These studies are now more feasible given newer assays to measure this acute-phase reactant. Observations that the acutephase response is tightly coupled to lipoprotein abnormalities and the fact that acute-SAA proteins are mainly associated with plasma lipoproteins of the high density range suggested a possible role of this apolipoprotein (apo SAA) in the development of atherosclerosis. The expression of SAA mRNA in human atherosclerotic lesions and the induction of acute-phase SAA by oxidized low-density lipoproteins strengthen the hypothesis that SAA might play a role in vascular injury and atherogenesis.

A RECENT report by Scott et al. described antibodies to a soluble tissue ribonucleoprotein antigen called Ro(SS-A) in the serum of 34 of 41 mothers who had given birth to infants with congenital complete heart block.1 Less than half the mothers had clinical evidence of connective tissue disease. The same antibody was found in 7 of 8 serum samples collected from affected infants under three months of age but in none of 13 samples obtained from older infants. The authors suggested that maternal antibody to Ro(SS-A) might serve as a marker to identify women at risk of having an infant . . .

OBJECTIVE: The authors determine the reliability, validity, and usefulness of the Objective Structured Clinical Examination (OSCE) in the evaluation of surgical residents. SUMMARY BACKGROUND DATA: Interest is increasing in using the OSCE as a measurement of clinical competence and as a certification tool. However, concerns exist about the reliability, feasibility, and cost of the OSCE. Experience with the OSCE in postgraduate training programs is limited. METHODS: A comprehensive 38-station OSCE was administered to 56 surgical residents. Residents were grouped into three levels of training; interns, junior residents, and senior residents. The reliability of the examination was assessed by coefficient alpha; its validity, by the construct of experience. Differences between training levels and in performance on the various OSCE problems were determined by a three-way analysis of variance with two repeated measures and the Student-Newman-Keuls post hoc test. Pearson correlations were used to determine the relationship between OSCE and American Board of Surgery In-Training Examination (ABSITE) scores. RESULTS: The reliability of the OSCE was very high (0.91). Performance varied significantly according to level of training (postgraduate year; p < 0.0001). Senior residents performed best, and interns performed worst. The OSCE problems differed significantly in difficulty (p , 0.0001). Overall scores were poor. Important and specific performance deficits were identified at all levels of training. The ABSITE clinical scores, unlike the basic science scores, correlated modestly with the OSCE scores when level of training was held constant. CONCLUSION: The OSCE is a highly reliable and valid clinical examination that provides unique information about the performance of individual residents and the quality of postgraduate training programs.

The present study examined the neuropathology of the lateral controlled cortical impact (CCI) traumatic brain injury (TBI) model in mice utilizing the de Olmos silver staining method that selectively identifies degenerating neurons and their processes. The time course of ipsilateral and contralateral neurodegeneration was assessed at 6, 24, 48, 72, and 168 h after a severe (1.0 mm, 3.5 M/sec) injury in young adult CF-1 mice. At 6 hrs, neurodegeneration was apparent in all layers of the ipsilateral cortex at the epicenter of the injury. A low level of degeneration was also detected within the outer molecular layer of the underlying hippocampal dentate gyrus and to the mossy fiber projections in the CA3 pyramidal subregions. A time-dependent increase in cortical and hippocampal neurodegeneration was observed between 6 and 72 hrs post-injury. At 24 h, neurodegeneration was apparent in the CA1 and CA3 pyramidal and dentate gyral granule neurons and in the dorsolateral portions of the thalamus. Image analysis disclosed that the overall volume of ipsilateral silver staining was maximal at 48 h. In the case of the hippocampus, staining was generalized at 48 and 72 h, indicative of damage to all of the major afferent pathways: perforant path, mossy fibers and Schaffer collaterals as well as the efferent CA1 pyramidal axons. The hippocampal neurodegeneration was preceded by a significant increase in the levels of calpain-mediated breakdown products of the cytoskeletal protein alpha-spectrin that began at 6 h, and persisted out to 72 h post-injury. Damage to the corpus callosal fibers was observed as early as 24 h. An anterior to posterior examination of neurodegeneration showed that the cortical damage included the visual cortex. At 168 h (7 days), neurodegeneration in the ipsilateral cortex and hippocampus had largely abated except for ongoing staining in the cortical areas surrounding the contusion lesion and in hippocampal mossy fiber projections. Callosal and thalamic neurodegeneration was also very intense. This more complete neuropathological examination of the CCI model shows that the associated damage is much more widespread than previously appreciated. The extent of ipsilateral and contralateral neurodegeneration provides a more complete anatomical correlate for the cognitive and motor dysfunction seen in this paradigm and suggests that visual disturbances are also likely to be involved in the post-CCI neurological deficits.

The Center for Epidemiologic Studies-Depression Scale (CES-D; L. S. Radloff, 1977) assesses the presence and severity of depressive symptoms occurring over the past week. Although it contains only 20 items, its length may preclude its use in a variety of clinical populations. This study evaluated psychometric properties of 2 shorter forms of the CES-D developed by F. J. Kohout, L. F. Berkman, D. A. Evans, and J. Cornoni-Huntley (1993): the Iowa form and the Boston form. Data were pooled from 832 women representing 6 populations. Internal consistency estimates, correlations with the original version of the CES-D, and omitted-included item correlations supported use of the Iowa form over the Boston form when a shortened version of the scale is desired. Regression statistics are provided for use in estimating scores on the original CES-D when either shortened form is used. Factor analytic results from two populations support a single-factor structure for the original CES-D as well as the short forms.

Behavioral research has demonstrated three major components of the lexical-semantic processing system: automatic activation of semantic representations, strategic retrieval of semantic representations, and inhibition of competitors. However, these component processes are inherently conflated in explicit lexical-semantic decision tasks typically used in functional magnetic resonance imaging (fMRI) research. Here, we combine the logic of behavioral priming studies and the neurophysiological phenomenon of fMRI priming to dissociate the neural bases of automatic and strategic lexical-semantic processes across a series of three studies. A single lexical decision task was used in all studies, with stimulus onset asynchrony or linguistic relationship between prime and target being manipulated. Study 1 demonstrated automatic semantic priming in the left mid-fusiform gyrus (mid-FFG) and strategic semantic priming in five regions: left middle temporal gyrus (MTG), bilateral anterior cingulate, anterior left inferior prefrontal cortex (aLIPC), and posterior LIPC (pLIPC). These priming effects were explored in more detail in two subsequent studies. Study 2 replicated the automatic priming effect in mid-FFG and demonstrated that automatic priming in this region is preferential for the semantic domain. Study 3 demonstrated a neural dissociation in regions contributing to the strategic semantic priming effect. Strategic semantic facilitation was observed in the aLIPC and MTG, whereas strategic semantic inhibition was observed in the pLIPC and anterior cingulate. These studies provide reproducible evidence for a neural dissociation between three well established components of the lexical-semantic processing system.

Campylobacter jejuni produces a toxin called cytolethal distending toxin (CDT). The genes encoding this toxin in C. jejuni 81-176 were cloned and sequenced. The nucleotide sequence of the genes revealed that there are three genes, cdtA, cdtB, and cdtC, encoding proteins with predicted sizes of 30,11-6, 28,989, and 21,157 Da, respectively. All three proteins were found to be related to the Escherichia coli CDT proteins, yet the amino acid sequences have diverged significantly. All three genes were required for toxic activity in a HeLa cell assay. HeLa cell assays of a variety of C. jejuni and C. coli strains suggested that most C. jejuni strains produce significantly higher CDT titers than do C. coli strains. Southern hybridization experiments demonstrated that the cdtB gene is present on a 6.0-kb ClaI fragment in all but one of the C. jejuni strains tested; the cdtB gene was on a 6.9-kb ClaI fragment in one strain. The C. jejuni 81-176 cdtB probe hybridized weakly to DNAs from C. coli strains. The C. jejuni 81-176 cdtB probe did not hybridize to DNAs from representative C. fetus, C. lari, C. "upsaliensis," and C. hyointestinalis strains, although the HeLa cell assay indicated that these strains make CDT. PCR experiments indicated the probable presence of cdtB sequences in all of these Campylobacter species.

Key Points Over the last decade, allogeneic HCT has been increasingly administered in the United States to adults aged 70 and older with hematologic malignancies. Allogeneic transplant outcomes were reasonable; high comorbidity and ablative conditioning regimens were associated with inferior outcomes.

A self-referencing technique utilizing two microelectrodes on a ceramic-based multisite array is employed for confirmation and elimination of interferences detected by enzyme-based microelectrodes. The measurement of L-glutamate using glutamate oxidase was the test system; however, other oxidase enzymes such as glucose oxidase can be employed. One recording site was coated with Nafion with L-glutamate oxidase and bovine serum albumin (BSA) cross-linked with glutaraldehyde while the other had Nafion with BSA cross-linked with glutaraldehyde. Differences in the chemistry of the two recording sites allowed for identification and elimination of interfering signals to be removed from the analyte response. The electrode showed low detection limits (LOD = 0.98 +/- 0.09 microM, signal-to-noise ratio of 3), fast response times (T90 approximately 1 s), and excellent linearity (R2 = 0.999 +/- 0.000) over the concentration range of 0-200 microM for calibrations of L-glutamate in vitro. The selectivity and dimensions of the multisite electrode allow in vivo glutamate measurements. This electrode has been applied to in vivo measurements of the clearance of locally applied glutamate and release of glutamate in the prefrontal cortex of anesthetized rats. In addition, a aimilar approach has been applied to the development of a microelectrode for measures of glucose.

Mycelial extracts from Phytophthora infestans caused necrosis and elicited the accumulation of antimicrobial stress metabolites in potato tubers. A portion of the material with elicitor activity could be extracted from the mycelium by a mixture of chloroform and methanol. The most active elicitors of stress metabolites in these extracts were eicosapentaenoic and arachidonic acids. These fatty acids were found in either free or esterified form in all active fractions of the mycelial extracts.

BACKGROUND: There is no consensus as to the optimal treatment paradigm for patients presenting with hemorrhage from severe pelvic fracture. This study was established to determine the methods of hemorrhage control currently being used in clinical practice. METHODS: This prospective, observational multi-center study enrolled patients with pelvic fracture from blunt trauma. Demographic data, admission vital signs, presence of shock on admission (systolic blood pressure < 90 mm Hg or heart rate > 120 beats per minute or base deficit < -5), method of hemorrhage control, transfusion requirements, and outcome were collected. RESULTS: A total of 1,339 patients with pelvic fracture were enrolled from 11 Level I trauma centers. Fifty-seven percent of the patients were male, with a mean ± SD age of 47.1 ± 21.6 years, and Injury Severity Score (ISS) of 19.2 ± 12.7. In-hospital mortality was 9.0 %. Angioembolization and external fixator placement were the most common method of hemorrhage control used. A total of 128 patients (9.6%) underwent diagnostic angiography with contrast extravasation noted in 63 patients. Therapeutic angioembolization was performed on 79 patients (5.9%). There were 178 patients (13.3%) with pelvic fracture admitted in shock with a mean ± SD ISS of 28.2 ± 14.1. In the shock group, 44 patients (24.7%) underwent angiography to diagnose a pelvic source of bleeding with contrast extravasation found in 27 patients. Thirty patients (16.9%) were treated with therapeutic angioembolization. Resuscitative endovascular balloon occlusion of the aorta was performed on five patients in shock and used by only one of the participating centers. Mortality was 32.0% for patients with pelvic fracture admitted in shock. CONCLUSION: Patients with pelvic fracture admitted in shock have high mortality. Several methods were used for hemorrhage control with significant variation across institutions. The use of resuscitative endovascular balloon occlusion of the aorta may prove to be an important adjunct in the treatment of patients with severe pelvic fracture in shock; however, it is in the early stages of evaluation and not currently used widely across trauma centers. LEVEL OF EVIDENCE: Prognostic study, level II; therapeutic study, level III.