Saint Thomas - Rutherford Hospital

BACKGROUND: Actigraphy is increasingly used in sleep research and the clinical care of patients with sleep and circadian rhythm abnormalities. The following practice parameters update the previous practice parameters published in 2003 for the use of actigraphy in the study of sleep and circadian rhythms. METHODS: Based upon a systematic grading of evidence, members of the Standards of Practice Committee, including those with expertise in the use of actigraphy, developed these practice parameters as a guide to the appropriate use of actigraphy, both as a diagnostic tool in the evaluation of sleep disorders and as an outcome measure of treatment efficacy in clinical settings with appropriate patient populations. RECOMMENDATIONS: Actigraphy provides an acceptably accurate estimate of sleep patterns in normal, healthy adult populations and inpatients suspected of certain sleep disorders. More specifically, actigraphy is indicated to assist in the evaluation of patients with advanced sleep phase syndrome (ASPS), delayed sleep phase syndrome (DSPS), and shift work disorder. Additionally, there is some evidence to support the use of actigraphy in the evaluation of patients suspected of jet lag disorder and non-24hr sleep/wake syndrome (including that associated with blindness). When polysomnography is not available, actigraphy is indicated to estimate total sleep time in patients with obstructive sleep apnea. In patients with insomnia and hypersomnia, there is evidence to support the use of actigraphy in the characterization of circadian rhythms and sleep patterns/disturbances. In assessing response to therapy, actigraphy has proven useful as an outcome measure in patients with circadian rhythm disorders and insomnia. In older adults (including older nursing home residents), in whom traditional sleep monitoring can be difficult, actigraphy is indicated for characterizing sleep and circadian patterns and to document treatment responses. Similarly, in normal infants and children, as well as special pediatric populations, actigraphy has proven useful for delineating sleep patterns and documenting treatment responses. CONCLUSIONS: Recent research utilizing actigraphy in the assessment and management of sleep disorders has allowed the development of evidence-based recommendations for the use of actigraphy in the clinical setting. Additional research is warranted to further refine and broaden its clinical value.

Insomnia is highly prevalent, has associated daytime consequences which impair job performance and quality of life, and is associated with increased risk of comorbidities including depression. These practice parameters provide recommendations regarding behavioral and psychological treatment approaches, which are often effective in primary and secondary insomnia. These recommendations replace or modify those published in the 1999 practice parameter paper produced by the American Sleep Disorders Association. A Task Force of content experts was appointed by the American Academy of Sleep Medicine to perform a comprehensive review of the scientific literature since 1999 and to grade the evidence regarding non-pharmacological treatments of insomnia. Recommendations were developed based on this review using evidence-based methods. These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Psychological and behavioral interventions are effective in the treatment of both chronic primary insomnia (Standard) and secondary insomnia (Guideline). Stimulus control therapy, relaxation training, and cognitive behavior therapy are individually effective therapies in the treatment of chronic insomnia (Standard) and sleep restriction therapy, multicomponent therapy (without cognitive therapy), biofeedback and paradoxical intention are individually effective therapies in the treatment of chronic insomnia (Guideline). There was insufficient evidence to recommend sleep hygiene education, imagery training and cognitive therapy as single therapies or when added to other specific approaches. Psychological and behavioral interventions are effective in the treatment of insomnia in older adults and in the treatment of insomnia among chronic hypnotic users (Standard).

These practice parameters pertain to the treatment of hypersomnias of central origin. They serve as both an update of previous practice parameters for the therapy of narcolepsy and as the first practice parameters to address treatment of other hypersomnias of central origin. They are based on evidence analyzed in the accompanying review paper. The specific disorders addressed by these parameters are narcolepsy (with cataplexy, without cataplexy, due to medical condition and unspecified), idiopathic hypersomnia (with long sleep time and without long sleep time), recurrent hypersomnia and hypersomnia due to medical condition. Successful treatment of hypersomnia of central origin requires an accurate diagnosis, individual tailoring of therapy to produce the fullest possible return of normal function, and regular follow-up to monitor response to treatment. Modafinil, sodium oxybate, amphetamine, methamphetamine, dextroamphetamine, methylphenidate, and selegiline are effective treatments for excessive sleepiness associated with narcolepsy, while tricyclic antidepressants and fluoxetine are effective treatments for cataplexy, sleep paralysis, and hypnagogic hallucinations; but the quality of published clinical evidence supporting them varies. Scheduled naps can be beneficial to combat sleepiness in narcolepsy patients. Based on available evidence, modafinil is an effective therapy for sleepiness due to idiopathic hypersomnia, Parkinson's disease, myotonic dystrophy, and multiple sclerosis. Based on evidence and/or long history of use in the therapy of narcolepsy committee consensus was that modafinil, amphetamine, methamphetamine, dextroamphetamine, and methylphenidate are reasonable options for the therapy of hypersomnias of central origin.

BACKGROUND: In nursing home residents, the use of tricyclic and other heterocyclic antidepressants is associated with an increased risk of falls. The newer selective serotonin-reuptake-inhibitor antidepressants are largely free of the side effects of the tricyclic agents thought to cause falls and so have been hypothesized to be safer for those at high risk for falls. METHODS: We retrospectively identified an inception cohort of 2428 nursing home residents in Tennessee who were new users of tricyclic antidepressants (665 subjects), selective serotonin-reuptake inhibitors (612 subjects), or trazodone (304 subjects) or nonusers of antidepressants (847 subjects). We ascertained the number of falls during therapy and during a similar follow-up period for nonusers, then calculated the rate ratios for falls with adjustments for an extensive set of potential confounding factors. RESULTS: The new users of each type of antidepressant had higher rates of falls than the nonusers, with adjusted rate ratios of 2.0 (95 percent confidence interval, 1.8 to 2.2) for tricyclic antidepressants, 1.8 (1.6 to 2.0) for selective serotonin-reuptake inhibitors, and 1.2 (1.0 to 1.4) for trazodone. The rate ratios increased with the daily dose for tricyclic antidepressants, reaching 2.4 (95 percent confidence interval, 2.1 to 2.8) for doses of 50 mg or more of amitriptyline or its equivalent, and for the serotonin-reuptake inhibitors, reaching 1.9 (1.7 to 2.2) for 20 mg or more of fluoxetine or its equivalent. The elevated rates of falls persisted through the first 180 days of therapy and beyond. CONCLUSIONS: In this large study of nursing home residents, there was little difference in rates of falls between those treated with tricyclic antidepressants and those treated with selective serotonin-reuptake inhibitors. Hence, the preferential use of the newer antidepressants is unlikely to reduce the higher rate of falls among nursing home residents taking antidepressants.

Background: Nondisplaced scaphoid fractures treated with prolonged cast immobilization may result in temporary joint stiffness and muscle weakness in addition to a delay in return to sports or work. Fixation of scaphoid fractures with a percutaneous cannulated screw has resulted in a shorter time to union and to return to work or sports. The purpose of this prospective, randomized study was to compare cast immobilization with percutaneous cannulated screw fixation of nondisplaced scaphoid fractures with respect to time to radiographic union and to return to work. Methods: Twenty-five full-time military personnel with an acute nondisplaced fracture of the scaphoid waist consented to be randomized to either cast immobilization or fixation with a percutaneous cannulated Acutrak screw (Acumed, Beaverton, Oregon) for the purpose of this study. Time to fracture union, wrist motion, grip strength, and return to work as well as overall patient satisfaction at the time of a two-year follow-up were evaluated. Results: Eleven patients were randomized to percutaneous cannulated screw fixation, and fourteen were randomized to cast immobilization. The average time to fracture union in the screw fixation group was seven weeks compared with twelve weeks in the cast immobilization group (p = 0.0003). The average time until the patients returned to work was eight weeks compared with fifteen weeks in the cast immobilization group (p = 0.0001). There was no significant difference in the range of motion of the wrist or in grip strength at the two-year follow-up evaluation. Overall patient satisfaction was high in both groups. Conclusions: Percutaneous cannulated screw fixation of nondisplaced scaphoid fractures resulted in faster radiographic union and return to military duty compared with cast immobilization. The specific indications for and the risks and benefits of percutaneous screw fixation of such fractures must be determined in larger randomized, prospective studies.

It is noted that the time-scale of the secular variation of the geomagnetic field is rather short compared with the electromagnetic diffusion times appropriate to the earth's core. It is therefore suggested that the secular variation is primarily due to the rearrangement of pre-existing lines of force emanating from the core, and not due to the creation of new (or destruction of old) flux tubes by electromagnetic diffusion. The theoretical consequences of this idea are fully examined.

BACKGROUND: Resistance to carbapenems among Acinetobacter baumannii and Klebsiella pneumoniae presents a serious therapeutic and infection control challenge. We describe the epidemiology and genetic basis of carbapenem resistance in A. baumannii and K. pneumoniae in a six-hospital healthcare system in Northeast Ohio. METHODS: Clinical isolates of A. baumannii and K. pneumoniae distributed across the healthcare system were collected from April 2007 to April 2008. Antimicrobial susceptibility testing was performed followed by molecular analysis of carbapenemase genes. Genetic relatedness of isolates was established with repetitive sequence-based PCR (rep-PCR), multilocus PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) and PFGE. Clinical characteristics and outcomes of patients were reviewed. RESULTS: Among 39 isolates of A. baumannii, two predominant genotypes related to European clone II were found. Eighteen isolates contained bla(OXA-23), and four isolates possessed bla(OXA-24/40). Among 29 K. pneumoniae isolates with decreased susceptibility to carbapenems, two distinct genotypes containing bla(KPC-2) or bla(KPC-3) were found. Patients with carbapenem-resistant A. baumannii and K. pneumoniae were elderly, possessed multiple co-morbidities, were frequently admitted from and discharged to post-acute care facilities, and experienced prolonged hospital stays (up to 25 days) with a high mortality rate (up to 35%). CONCLUSION: In this outbreak of carbapenem-resistant A. baumannii and K. pneumoniae across a healthcare system, we illustrate the important role post-acute care facilities play in the dissemination of multidrug-resistant phenotypes.

CONTEXT: The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification. OBJECTIVE: The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid. SETTING: The study was conducted at the Vanderbilt University endocrine surgery center. SUBJECTS AND METHODS: Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings. MAIN OUTCOME MEASURE: The detection rate of parathyroid glands was measured. RESULTS: The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state. CONCLUSION: NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.

Normative standards are provided for permanent tooth mineralization stages for blacks and whites of the middle southern United States. The data cover tooth development from 3.5 to 13 years of age. Females develop more rapidly than males, and blacks are nearly twice as sexually dimorphic (7.2%) as whites (3.7%). Within each sex, blacks achieve mineralization stages significantly earlier, by about 5%, than whites. This complements earlier findings that teeth erupt at appreciably earlier mean ages in blacks.

The normal lateral meniscus is morphologically more variable than the medial meniscus. The abnormal lateral meniscus also varies with respect to size, shape, and stability. Variations can occur in patients of all ages. The underlying causes of lateral meniscal abnormalities are multifactorial. The spectrum of abnormalities includes the most common variant, discoid lateral meniscus, as well as less common conditions, such as a lateral meniscal variant with absence of the posterior coronary ligament. Treatment should be based on the severity of symptoms and the type of pathologic lesion.

PURPOSE: To help practitioners avoid adverse perioperative events in patients with obstructive sleep-disordered breathing. REVIEWERS: Members of the American Academy of Sleep Medicine's Clinical Practice Review Committee. METHODS: A search of MEDLINE database using MeSH terms apnea, obstructive sleep apnea and anesthesia was conducted in October 2001. This review focuses on articles published in English between 1985 and 2001 that pertain to non-upper airway surgery in obstructive sleep apnea patients. RESULTS AND CONCLUSIONS: Scientific literature regarding the perioperative risk and best management techniques for OSAHS patients is scanty and of limited quality. There is insufficient information to develop an AASM standards of practice recommendation. Therefore, the Clinical Practice Review Committee (CPRC) used the available data to make this statement based upon a consensus of clinical experience and published peer-reviewed medical evidence. Important components of the perioperative management of OSAHS patients include a high degree of clinical suspicion, control of the airway throughout the perioperative period, judicious use of medications, and appropriate monitoring. Further research is needed to define the magnitude of risk and optimal perioperative care.

(Martin) Associate Professor, Department of Anesthesiology/Critical Care Medicine, The Johns Hopkins Medical Institutions.(Plevak) Associate Professor, Department of Anesthesiology and Critical Care Medicine, The Mayo Clinic and Mayo Foundation.(Flannery) Research Assistant, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions.(Charlton) Hepatology Fellow, Department of Gastroenterology, The Mayo Clinic and Mayo Foundation.(Poterucha) Senior Hepatologist, Department of Gastroenterology, The Mayo Clinic and Mayo Foundation.(Humphreys) Staff Anesthesiologist, Luther Hospital, The Middleford Clinic.(Derfus) Staff Hepatologist, The Middleford Clinic.(Pohl) Chief, Section on Molecular and Cellular Toxicology, The Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute.Received from the The Johns Hopkins Medical Institutions, Baltimore, Maryland; The Mayo Clinic and Mayo Foundation, Rochester, Minnesota; The Middleford Clinic, Eau Claire, Wisconsin; and the National Heart, Lung and Blood Institute, Bethesda, Maryland. Submitted for publication March 7, 1995. Accepted for publication June 12, 1995. Supported in part by a grant from The Robert Wood Johnson Foundation (to J.L.M.).Address correspondence to Dr. Martin: Department of Anesthesiology/Critical Care Medicine, The Johns Hopkins Hospital, Tower 715, Baltimore, Maryland 21287.SEVERAL fluorinated inhalation anesthetics have been associated with hepatotoxicity. Yet to date, desflurane has not been reported to cause liver damage in humans. The following is a report of a patient who experienced hepatitis after receiving a desflurane anesthetic and who may have been sensitized by prior halothane exposure.A 65-yr-old woman underwent a left hemithyroidectomy for a thyroid adenoma. The patient had a history of hypertension, which was treated with 50 mg atenolol per day. Her medical history was notable for pneumonia at age 9, pancreatitis at age 52, and recurrent urinary tract infections. Previous surgical and anesthetic history included a tonsillectomy in 1935 for which no records were available; a post partum tubal ligation in 1952, for which she received nitrous oxide, oxygen, cyclopropane, and d-tubocurare; total abdominal hysterectomy and unilateral oophorectomy in 1969, under sodium thiopental, succinylcholine, d-tubocurare, scopolamine, nitrous oxide, oxygen, and cyclopropane; an exploratory laparotomy and ovarian cystectomy in 1976, for which she received sodium thiopental, succinylcholine, pancuronium, nitrous oxide, oxygen, and halothane; and elective cholestectomy in 1982, during which she received sodium thiopental, succinylcholine, pancuronium, nitrous oxide, oxygen, and halothane. Each of these anesthetics were uneventful. The halothane anesthetics in 1976 and 1982 lasted approximately 45 min each. There was no history of jaundice, and the patient had never received a transfusion of blood or blood products. There was no history of intravenous drug abuse, tattoos, acupuncture, or occupational exposure to hepatotoxins. Alcohol consumption was less than 10 g per month. Hives had developed after she took sulfamethoxazole and trimethoprim (Bactrim) 15 yr earlier. She was also allergic to iodine-based dyes. The only other medication was 600 mg Ibuprofen once per day. She was a homemaker who had raised two children, a son who had died in his 40s from what was described as complications of myasthenia gravis, and a daughter who was alive and well. The patient had worked for 5 yr in a manufacturing facility, where she was exposed on occasion to paint products. Her last exposure was 10 yr earlier. There was no family history of liver disease.The left hemithyroidectomy was performed on September 8, 1994. The patient was 157 cm tall and weighed 71 kg. She was afebrile with normal vital signs. The patient received 2 mg midazolam intravenously for sedation approximately 45 min before transport to the operating room. After placement of a blood pressure cuff, an electrocardiogram, and a pulse oximeter, general anesthesia was induced with 100 mg propofol, 100 micro gram fentanyl citrate, 40 mg atracurium, and 130 mg lidocaine, all given intravenously before tracheal intubation. Anesthesia was maintained with a mixture of 37–39% Oxygen2in nitrous oxide with 3–7% desflurane and intravenous fentanyl. Continuous mechanical ventilation was used without positive end expiratory pressure. Except for a brief decrease in blood pressure (systolic in the mid-80s) just before surgical incision, the patient remained hemodynamically stable. This was treated with 5 mg ephedrine and 0.3 mg glycopyrrolate intravenously. The pulse rate was 55 beats/min at the time of hypotension and increased to 90 beats/min after ephedrine administration. Blood loss was minimal. No blood or blood products were given. The total surgical time was 70 min with an anesthetic time of 90 min. The patient was discharged from the hospital in good condition the following day.On September 20, 1994, 12 days postoperatively, the patient experienced pruritus, malaise, nausea, and polyarthralgias. There was no fever. At the same time, a macular erythematous rash appeared over the buttocks and thighs. The patient noted that her urine was unusually dark. She received nizatidine for her nausea and 1% hydrocortisone cream for her rash the following day. By the 16th postoperative day, the patient complained of dermal jaundice and epigastric abdominal pain. She was admitted to the hospital.Physical examination on admission revealed the patient to be afebrile with a blood pressure of 140/80 mmHg and a pulse rate of 90 beats/min. There was an irregular macular erythematous rash over the posterior thorax. Examination results of the head and face were normal with the exception of conjunctival and scleral jaundice. Cardiopulmonary findings were normal. Abdominal examination revealed a nontender liver, which was 8 cm in size by percussion. There was no splenomegaly. No ascites was present. The patient was neurologically intact, without evidence of asterixis or other evidence of encephalopathy. Admission laboratory values are listed in Table 1. Albumin was 3.6 g/dl, hemoglobin was 14.8 g/dl, leukocyte count was 3.9 x 109/l, with platelets of 177 x 109/l and ferritin 554 micro gram/l. Anti-HAV (IgG and IgM), hepatitis B surface antibody, hepatitis B surface antigen, hepatitis B core antibody, and hepatitis C antibody (second generation ELISA) were not detected. Although antinuclear antibody was not detected, antismooth muscle antibodies were detected to a titer of 1:40 dilutions.On September 30, 1994 (postoperative day 22), the patient was transferred to a hepatology unit for further observation and potential liver transplantation. The physical examination was unchanged except for the presence of ascites. The patient's biochemical and hematologic data are summarized in T1-30. An ultrasound of the upper abdomen revealed diffuse hepatic parenchymal heterogeneity, with normal bile ducts and normal Doppler examination of the hepatic, portal, and splenic vessels. Repeat viral serology for hepatitis A and B (including epsilon antigen and antibody) and hepatitis C were negative. Cultures for cytomegalovirus were negative. Serology for Epstein-Barr and Herpes simplex viruses indicated past infection (anti-VCA/IgG 1:2560, IgM negative, anti-HSV IgG 1:160, IgM negative). By October 5, 27 days after surgery, the patient's liver function and symptoms were improving (T1-30), and she was discharged from the hospital the following day. By December 14 (postoperative day 97), the patient was symptom-free and had a nearly normal liver function. Her medications at this time consisted of spironolactone and furosemide for ascites.A serum sample collected 48 days after surgery was screened by an enzyme-linked immunosorbent assay for antibodies that reacted to liver microsomes from halothane-treated rats as compared to reactivity to liver microsomes from untreated rats. This assay has been used previously for the detection of serum antibodies in patients with halothane hepatitis. The assay is based on the finding that only patients with halothane hepatitis have serum antibodies that react with one or more liver microsomal proteins that have been trifluoroacetylated (TFA) by the reactive trifluoroacetyl chloride (CF3COCI) metabolite of halothane. As seen in Table 2, compared to a group of 20 normal patients, the patient's antibody reactivity was significantly greater against microsomes from halothane-treated rats than microsomes from control rats. The reactivity with the TFA-proteins was markedly increased when 0.1% sodium deoxycholate (DOC) extracts of liver microsomes were used as test antigen in place of the intact liver microsomes (T2-30). This is due to the preferential extraction by DOC of those proteins from the liver microsomes targeted by the CF3COCI metabolite of halothane. .Halothane, enflurane, and isoflurane, have been associated with jaundice, hepatitis, and death. Hepatotoxicity associated with halothane is most common and has been studied extensively. Halothane produces two types of hepatotoxicity. The first is a mild form seen in 20% of patients given halothane anesthesia and is characterized by nausea, lethargy, low grade fever, and mild transient elevations in liver amino transferase enzymes (ALT, AST). In contrast, a fulminant hepatic necrosis (halothane hepatitis) occurs in approximately 1/20,000 adult patients exposed to halothane and is characterized by markedly increased serum ALT, AST, and bilirubin concentration, hepatomegaly, hepatic encephalopathy, jaundice, and, often, death. The predominant histologic feature is acute hepatitis with centrilobular necrosis. A variety of risk factors have been identified, which are commonly associated with halothane hepatitis. These include obesity, female sex, middle age, and having multiple anesthetics over a short period. Compared to adults, relatively few cases of halothane hepatitis have been reported in children. .Current evidence suggests that halothane hepatitis may have an immunologic basis. For example, repeat halothane administrations increase the incidence of hepatitis, with fever, rash, arthralgias, and peripheral eosinophilia often observed. Serum from patients with a clinical diagnosis of halothane hepatitis have been shown to contain circulating IgG antibodies directed against liver microsomal proteins that have been covalently modified by the reactive CF sub 3 COCI metabolite of halothane (Figure 1). In addition, it was found that halothane hepatitis patients' antibodies bind to epitopes consisting of the TFA hapten and structural determinants of the carrier proteins. Several of the TFA-proteins recognized by the serum antibodies of patients with halothane hepatitis have been purified and identified from rat liver microsomes. It also appears that similar TFA-proteins are found in the livers of patients who have been administered halothane. It is thought that these proteins are immunogenic in certain patients and lead to the production of specific antibodies, or possibly specific T cells, which may be the cause of the hepatitis.Enflurane and isoflurane are oxidatively metabolized by liver cytochrome P-450 to form acylated liver protein adducts by mechanisms similar to that of halothane (F1-30). The adduct formed by isoflurane is expected to be identical to that formed by halothane. Similarly, desflurane could form a TFA-adduct. This raises the possibility that enflurane, isoflurane, and desflurane might cause hepatotoxicity by a mechanism similar to that of halothane, but at a lower incidence, because the degree of anesthetic metabolism appears to be directly related to the potential for hepatic injury. For example, 20% of administered halothane undergoes metabolism, and numerous cases of halothane-associated hepatotoxicity have been reported. Approximately 2.4% of enflurane is metabolized, with 15–24 cases of hepatotoxicity having been well described. Less than 0.2% of isoflurane undergoes metabolism, with five cases of hepatotoxicity having been reported. Desflurane strongly resists biodegradation, with only 0.01% being metabolized. Therefore, from the standpoint of an immune-mediated mechanism of hepatotoxicity, desflurane should represent the safest inhalation anesthetic because it would lead to the lowest level of adduct formation. However, because antibodies reacting with liver microsomal TFA-proteins were detected in the serum of the patient (T2-30), and her clinical symptoms of pruritus, rash, and polyarthralgias suggested that she may have had an immune-mediated reaction, it appears that very small amounts of adduct may be able to precipitate massive hepatotoxicity, particularly if the patient was previously sensitized against TFA-proteins. The desflurane patient had received halothane on two prior occasions. Similarly, halothane may be able to sensitize patients against protein adducts formed by other fluorinated inhalation anesthetics. .It might be argued that Ibuprofen was a precipitating cause of this patient's hepatotoxicity. However, the evidence argues against this possibility. First, this dose of Ibuprofen (600 mg) is rarely associated with liver injury. Second, the patients' liver function test results were normal in January 1994, while taking Ibuprofen (T1-30). Third, the patient reinstituted her Ibuprofen after surgery, and she continues to take this medication without ill effects. This is analogous to a negative rechallenge test to Ibuprofen. Fourth, her liver function tests and clinical course continue to show improvement, despite her use of Ibuprofen. Finally and most importantly, the patient's antibody response is specific to patients with anesthetic-induced hepatitis and is not seen in patients with other forms of liver disease.To our knowledge, this represents the first report of desflurane-associated hepatotoxicity. This patient demonstrated several features commonly observed in hepatotoxicity after exposure to fluorinated anesthetics. Liver injury developed 12 days after desflurane anesthesia. This temporal relationship between exposure and injury is consistent with that of patients experiencing liver injury after halothane anesthesia. Also, she was an older female with drug allergies and a history of multiple exposures to halothane. She experienced a rash, jaundice, and marked increases in liver transaminases. The negative serologies, the otherwise negative medical history, and the presence of serum antibodies that reacted with TFA-liver microsomal proteins support the diagnosis of desflurane-induced hepatitis in this patient. It is likely that either or both of the halothane anesthetics received in 1976 and 1982 may have sensitized this patient, such that subsequent reexposure to desflurane or possibly other fluorinated anesthetics may have precipitated hepatotoxicity. One report describes a case of halothane anesthetics given 28 yr apart resulted in hepatitis and death in a patient. The current case serves to remind the clinician that anesthetic-induced hepatotoxicity may occur after anesthesia with any of the fluorinated anesthetic agents.

Looks at broad approaches to organizational culture and offers a brief review of some recent work on gender and organizational culture. The possibility of seeing culture as a means of closure is explored. Seeks to define and operationalise organizational culture, in order to test the theoretical hypothesis on two case studies, and identify the ways in which aspects of culture acted to close off areas of work to women managers. Describes the constituents of this definition with reference to data from two case studies, and considers examples of the ways in which these different constituents of culture may act as means of closure to women managers in the organizations. Suggests that the approach provides a useful starting point for further research on organizational culture and gender, as well as giving a practical model for practitioners and consultants looking to develop a diversity inclusive culture.

Summary Adrenocortical adenoma, nodular hyperplasia, or carcinoma was diagnosed in 50 ferrets. Thirty-five (70%) ferrets were female and 15 (30%) were male. The mean age at which clinical signs were first noticed was 3.4 years (range, 1 to 7 years). Clinical signs included large vulva (n = 31; 89% of females), alopecia (n = 43; 86%), pruritus (n = 20; 40%), and increased consumption of water and increased urine output (n = 4; 8%). A mass was palpated at the cranial pole of the kidney during physical examination of 17 (34%) ferrets. Ultrasonography, performed on 39 of 50 ferrets, revealed a unilateral adrenal gland mass in 19 (49%). Four ferrets were anemic, and 2 ferrets were thrombocytopenic. Baseline plasma concentrations of cortisol and corticosterone were within or below the reference range in all 17 ferrets tested, whereas baseline plasma estradiol concentrations were high in 4 of the 11 ferrets (36%) tested. After adrenocorticotropic hormone ( acth ) administration, only 1 ferret had a slightly exaggerated response on the basis of plasma cortisol concentrations, and all 17 had normal responses on the basis of plasma corticosterone concentrations. There was little or no increase in plasma estradiol concentrations after acth administration. Of the 50 ferrets, 39 were treated by adrenalectomy. Unilateral adrenalectomy was performed in 34 ferrets in which 1 adrenal gland was large, whereas subtotal bilateral adrenalectomy was performed in 5 ferrets with bilateral adrenal disease. Five ferrets died in the immediate postoperative period, and follow-up information was available for the remaining 34, 1 to 34 months after surgery. A decrease in vulvar size was generally noticed by 2 days after surgery, and complete hair regrowth was noticed by 2 months. Because clinical signs resolved after adrenalectomy, it was likely that the adrenocortical tumors and nodular hyperplasias of the adrenal gland were hyperfunctional. However, these ferrets did not have excessively high circulating concentrations of cortisol. At present, we recommended that diagnosis of adrenocortical disease in ferrets be made on the basis of characteristic clinical signs, results of abdominal ultrasonography, and finding large adrenal glands during surgery. Results of acth stimulation tests, with determination of plasma cortisol or corticosterone concentrations, were of no value in the diagnosis.

We present a new gauge-independent approach to resonant transition amplitudes with nonconserved external currents, based on the pinch technique method. In the context of 2\ensuremath{\rightarrow}2 and 2\ensuremath{\rightarrow}3 scattering processes we show explicitly that the analytic results derived respect U(1${)}_{\mathrm{em}}$ gauge symmetry and do not depend on the choice of the SU(2${)}_{\mathit{L}}$ gauge fixing. Our analytic approach treats, on equal footing, fermionic as well as bosonic contributions to the resummed gauge boson propagators, does not contain any residual spacelike threshold terms, shows the correct high-energy unitarity behavior, admits renormalization, and satisfies a number of other required properties, including the optical theorem. Even though our analysis has mainly focused on the standard model gauge bosons, our method can easily be extended to the top quark, and be directly applied to the study of unstable particles present in renormalizable models of new physics. \textcopyright{} 1996 The American Physical Society.

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large.

The effects of aminophylline, 1 mg/kg/min infused intravenously for 10 minutes, were examined on left ventricular (LV) diameter, pressure, an indexes of myocardial contractility, as well as systemic, coronary and regional hemodynamics in conscious dogs. Aminophylline increased mean arterial pressure 12 +/- 2%, LV systolic pressure 8 +/- 1%, LV dP/dt 20 +/- 2%, velocity of myocardial fiber shortening 13 +/- 2% and heart rate 5 +/- 2%, and reduced LV end-diastolic diameter 2 +/- 0.5%. Vascular resistance rose in the systemic bed 13 +/- 5%, the coronary bed 26 +/- 3%, the mesenteric bed 26 +/- 5% and the iliac bed 36 +/- 4%, but did not rise in the renal bed. Both beta-adrenergic receptor blockade with propranolol and chronic treatment with reserpine attentuated but did not abolish the positive inotropic response induced by aminophylline. Alpha-adrenergic receptor blockade with phentolamine prevented aminophylline-induced vasoconstriction in the systemic, coronary, mesenteric and iliac beds. In contrast to the vasoconstriction with i.v. aminophylline, when the drug was infused directly into the iliac artery, it elicited marked iliac vasodilation. Thus, in the intact conscious dog, i.v. aminophylline, in a dose that had little effect on heart rate, increased LV contractility and reduced preload. The increase in contractility was dependent in part on intact beta-adrenergic nervous activity and endogenous catecholamine stores. The increase in systemic, coronary, iliac and mesenteric resistances involved alpha-adrenergic mechanisms. These actions appear to involve autonomic mechanisms, because the only direct effect of aminophylline on the iliac artery was marked vasodilation.

BACKGROUND: Patients undergoing thyroidectomy may have inadvertent damage or removal of the parathyroid gland(s) due to difficulty in real-time parathyroid identification. Near-infrared autofluorescence (NIRAF) has been demonstrated as a label-free modality for intraoperative parathyroid identification with high accuracy. This study presents the translation of that approach into a user-friendly clinical prototype for rapid intraoperative guidance in parathyroid identification. METHODS: A laboratory (lab)-built spectroscopy system that measures NIRAF in tissue was evaluated for identifying parathyroid glands in vivo across 162 patients undergoing thyroidectomy and/or parathyroidectomy. Based on these results, a clinical prototype called PTeye was designed with a user-friendly interface and subsequently investigated in 35 patients. The performance of the lab-built system and the clinical prototype were concurrently compared side by side by a single user with 20 patients in each group. The influence of (i) intrapatient and interpatient variability of NIRAF in thyroid and parathyroid glands and (ii) thyroid and parathyroid pathology on intraoperative parathyroid identification were investigated. The effect of blood on NIRAF intensity of parathyroid and thyroid was tested ex vivo with the PTeye system to assess if a hemorrhagic surgical field would affect parathyroid identification. Accuracy of both systems were determined by correlating the acquired data with either visual confirmation by a surgeon for unexcised parathyroid glands or histology reports for excised parathyroid glands. RESULTS: The overall accuracy of the lab-built system in guiding parathyroid identification was 92.5%, while the PTeye system achieved an accuracy of 96.1%. Unlike the lab-built system, the PTeye could guide parathyroid identification even as the operating room lights remained on and required only 25% of the laser power used by the lab-built setup. Parathyroid glands had elevated NIRAF intensity compared to thyroid and other neck tissues, regardless of thyroid or parathyroid pathology. Blood did not seem to affect tissue NIRAF measurements obtained with both systems. CONCLUSION: In this study, the clinical prototype PTeye demonstrated high accuracy for label-free intraoperative parathyroid identification. The intuitive interface of the PTeye that can guide in identifying parathyroid tissue in the presence of ambient room lights suggests that it is a reliable and easy-to-use tool for surgical personnel.

OBJECTIVE AND IMPORTANCE: A rare case of dura-based primary cerebral Hodgkin's disease clinically and radiographically indistinguishable from a meningioma is described. CLINICAL PRESENTATION: A 55-year-old immunocompetent woman presented with headaches and ataxia. Magnetic resonance images demonstrated a circumscribed diffusely enhancing mass with a dural tail attached to the cerebellar tentorium. INTERVENTION: Operative inspection also suggested a meningioma, but a frozen section of the firm mass revealed an inflammatory lesion. Subsequent pathological analysis demonstrated Hodgkin's disease, nodular sclerosing type. An extensive workup revealed no systemic disease. CONCLUSION: This case illustrates the rare occurrence of primary intracranial Hodgkin's disease and its mimicry of meningioma.

To assess sex disparities in AIDS clinical and laboratory outcomes in the highly active antiretroviral therapy (HAART) era we conducted a systematic review of the published literature on mortality, disease progression, and laboratory outcomes among persons living with HIV and starting HAART. We performed systematic PubMed and targeted bibliographic searches of observational studies published between January, 1998, and November, 2013, that included persons starting HAART and reported analyses of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Risk ratios (relative risks, odd ratios, and hazard ratios) and 95% confidence intervals were obtained. Sixty-five articles were included in this review. Thirty-nine studies were from North America and Europe and 26 were from Latin America, Asia, and Africa. Forty-four studies (68%) showed no statistically significant difference in risk of mortality, progression to AIDS, or virologic or immunologic treatment outcomes by sex. Decreased risk of death among females compared to males was observed in 24 of the 25 articles that included mortality analyses [pooled risk ratio 0.72 (95% confidence interval=0.69-0.75)], and decreased risk of death or AIDS was observed in 9 of the 13 articles that examined the composite outcome [pooled risk ratio=0.91 (0.84-0.98)]. There was no significant effect of sex on the risk of progression to AIDS [pooled risk ratio=1.15 (0.99-1.31)]. In this systematic review, females starting HAART appeared to have improved survival compared to males. However, this benefit was not associated with decreased progression to either AIDS or to differences in virologic or immunologic treatment outcomes.