Lps2: a new locus required for responses to lipopolysaccharide,revealed by germline mutagenesis and phenotypic screening

Both forward and reverse genetic techniques have been used to define components of the mammalian lipopolysaccharide (LPS) receptor. TLR4, identified by a forward genetic approach as the product of the classical Lps locus, is the only known transmembrane component of the mammalian LPS receptor. Gene knockout work has also established that LPS signal transduction requires the integrity of CD14, MD-2, and, in part, MyD88, IRAK4, and TRAF-6. However, there is no reason to believe that these are the only proteins that make up the receptor/transducer apparatus. To examine the possibility that other proteins may be involved, we initiated a mutagenesis program, in which germline mutations are induced in mice using N-ethyl-N-nitrosourea (ENU), and macrophages from individual animals are screened for their competence to respond to LPS. We now report the existence of a new locus, Lps2, which is required for TNF production in response to LPS. The Lps2 mutation that we have identified is co-dominant, is similar in phenotypic effect to Lpsd, and does not represent a novel allele of any of the genes that are known to encode the 'core' LPS signaling apparatus. The Lps2 mutation does not preclude signaling initiated by peptidoglycan or unmethylated DNA. Hence, genetic data suggest that there is at least one 'missing' component of the LPS receptor complex that has yet to be found.     

A comparison of two patient-friendly ERG electrode

The ideal electroretinography (ERG) electrode does not exist. In deciding which electrode should be used in clinical practice the capacity to provide reproducible waveforms, maximal amplitudes and minimal irritation to the patient's eyes are the most important characteristics. This study tested two patient friendly electrodes, the gold foil (CH Electrodes, UK) and the H-K loop (Avanta, Slovenia). Seventeen normal volunteers were subjected to three standard measurements namely flash ERGs under photopic and scotopic conditions and the transient pattern ERG (PERG). Each test followed the guidelines set by the International Society for Clinical Electrophysiology of Vision (ISCEV). It was found that the mean values of the flash ERG a and b wave amplitudes and the PERG P50 and N95 amplitudes from the gold foil electrodes were approximately a factor of two larger than those from the H-K loop. In addition most of the subjects (13/17) felt less discomfort with the gold foil electrodes. We reached the conclusion that gold foil electrodes are the electrode of choice because they provide good patient comfort, reasonably high amplitudes and relatively reproducible results.     

The Iowa Model of Evidence-Based Practice to Promote Quality Care.

The UIHC Department of Nursing is nationally known for its work on use of research to improve patient care. This reputation is attributable to staff members who continue to question "how can we improve practice?" or "what does the latest evidence tell us about this patient problem?" and to administrators who support, value, and reward EBP. The revisions made in the original Iowa Model are based on suggestions from staff at UIHC and other practitioners across the country who have implemented the model. We value their feedback and have set forth this revised model for evaluation and adoption by others.     

Airway management after maxillectomy: routine tracheostomy is unnecessary

OBJECTIVES/HYPOTHESIS: There is a paucity of data to guide the optimal management of the airway in patients after maxillectomy. The decision on whether a concomitant tracheostomy is needed is often dictated by the surgeon's training and experience. We reviewed our experience with maxillectomy to assess the need for tracheostomy in postoperative airway management. STUDY DESIGN: Retrospective analysis at a university hospital. METHODS: We identified 121 patients who underwent 130 maxillectomies between October 1990 and September 2001. Twenty-four of these were total (all six walls removed), 45 were subtotal (two or more walls removed), and 61 were limited (only one wall removed). Reconstruction ranged from none to microvascular free flap, with split-thickness skin graft being the most common reconstructive option. RESULTS: Only 10 tracheostomies (7.7%) were performed at the time of maxillectomy. These included four tracheostomies in patients who underwent bulky flap reconstruction, two tracheostomies in patients who underwent both flap reconstruction and mandibulectomy, one tracheostomy in a patient who underwent mandibulectomy, one tracheostomy in a patient with mucormycosis in anticipation of prolonged ventilatory support postoperatively, and two tracheostomies at the surgeons' discretion because of concern for upper airway edema. Among the 111 patients who underwent 120 maxillectomies without concomitant tracheostomy, 1 patient (0.9%), a 74 year-old man with oxygen-dependent chronic obstructive pulmonary disease, required repeat intubation on day 3 and again on day 10 after the surgery, because of respiratory failure; fiberoptic examination confirmed the absence of upper airway compromise. CONCLUSIONS: The routine performance of tracheostomy in patients undergoing maxillectomy is unnecessary. Selective use of tracheostomy may be indicated in situations in which mandibulectomy or bulky flap reconstruction is performed or a concern for postoperative oropharyngeal airway obstruction because of edema or packing exists.     

Three-dimensional stapes footplate motion in human temporal bones

The literature provides conflicting information on whether the motion of the stapes footplate is piston-like or some other type of motion, such as rotational or rocking. Examination of the three-dimensional (3D) motion of the stapes footplate appears to be an excellent way to understand this complicated motion. Five microsphere reflective targets were placed on the stapes footplate in ten fresh human cadaver temporal bone preparations, and their vibration measured through an extended facial recess approach using a laser Doppler vibrometer. The five target sites on the stapes footplate were center, anterior, posterior, superior and inferior. The stimulus was a sound input of 80-120 dB SPL at the tympanic membrane over a frequency range of 0.1 to 10 kHz. The 3D motion of the stapes footplate was calculated using the velocity amplitude and phase obtained for each target. For frequencies up to 1.0 kHz the vibration of the stapes footplate was primarily piston-like; this motion became complex at higher frequencies, with rotary motion along both the long and short axis of the footplate. When the cochlea was drained, stapes footplate motion became essentially piston-like for all frequencies.     

Human middle-ear sound transfer function and cochlear input impedance

The middle-ear pressure gain, defined as the ear canal sound pressure to cochlear vestibule pressure gain, GME, and the ear canal sound pressure to stapes footplate velocity transfer function, SVTF, simultaneously measured in 12 fresh human temporal bones for the 0.05 to 10 kHz frequency range are reported. The mean GME magnitude reached 23.5 dB at 1.2 kHz with a slope of approximately 6 dB/octave from 0.1 to 1.2 kHz and -6 dB/octave above 1.2 kHz. From 0.1 to 0.5 kHz, the mean GME phase angle was 51 degrees, rolling off at -78 degrees /octave above this frequency. The mean SVTF magnitude reached a maximum of 0.33 mm s(-1)/Pa at 1.0 kHz with nearly the same shape in magnitude and phase angle as the mean GME. The ratio of GME and SVTF provide the first direct measurements of Z(c) in human ears. The mean Z(c) was virtually flat with a value of 21.1 acoustic GOmega MKS between 0.1 and 5.0 kHz. Above 5 kHz, the mean Z(c) increased to a maximum value of 49.9 GOmega at 6.7 kHz. The mean Z(c) angle was near 0 degrees from 0.5 to 5.0 kHz, decreasing below 0.5 kHz and above 5 kHz with peaks and valleys.     

An outbreak of food poisoning in a military establishment

Background: An outbreak of food poisoning in a military establishment mess was investigated and remedial measures suggested.     

Sleep-disordered breathing as a mechanism for nocturia: preliminary findings

Nocturia is commonly associated with prostate or bladder problems but is also an important symptom of obstructive sleep apnea, a potentially lethal condition. The primary purpose of this study was to test the relationship between symptoms of sleep-disordered breathing and increased nocturnal urine production as described by the Sleep-Disordered Breathing--Nocturia Model. The purpose of the first phase of this three-phase study was to survey community-dwelling older adults (> 55 years) about nocturia and sleep-disturbance symptoms. A random sample of 1,000 older adults, balanced by ethnicity and gender, were surveyed via a mailed questionnaire. The brief questionnaire included characterizing poor sleep quality, obstructive sleep apnea symptoms, nocturia, lower urinary tract symptoms, naps, and self-rated health. The return rate was low (18%, n = 176), but respondents were equally represented by gender and ethnicity across the targeted age groups. Half of the respondents (n = 87) reported > or = 2 voids per night, two-thirds of whom reported nocturia as bothersome. The data showed that African-American women had significant associations between episodes of nocturia and symptoms of obstructive sleep apnea, poor sleep quality, naps, and lower urinary tract symptoms, thus failing to support the notion that nocturia or sleep-disordered breathing are prostate or gender related. As expected, subjects (n = 80) who volunteered for the later phases of the study, had significantly more problems. These preliminary data suggest that the relationship between obstructive sleep apnea and nocturia is important because older adults are at higher risk of injury due to falls that may occur while attempting to toilet in the dark. Also, older adults may also be at higher risk of receiving inappropriate urologic treatment if they are not screened for sleep disorders when reporting nocturia along with symptoms of excessive daytime sleepiness and sleep-disordered breathing. Phases II and III of the parent study will include a detailed examination of hormonal, biochemical, and physical variables to further test the proposed Sleep-Disordered Breathing--Nocturia Model.     

Eye protection in the paralyzed face.

All patients with a VIIth nerve paralysis with any limitation of closure of the eye should have in the office or out-patient clinic setting: 1. paper tarsorrhaphy of the upper or possibly lower lid; 2. artificial tears and/or ointment; and 3. glasses to protect the cornea from air currents. Kinetic and static surgical procedures are discussed. The kinetic procedures include facial nerve repair and grafting, VIIth-XIIth nerve anastamosis, muscle nerve block transplantation, transposition of nonparalyzed muscle and cross over. The principals of VIIth nerve repair and grafting and presented in the intracranial, internal auditory canal, labyrinthine, tympanomastoid and extratemporal sites. The static procedures include resection of redundant skin, fascia lata strip suspension, weakening of contralateral non-paralyzed musculature, and adjunctive procedures such as resection of ptotic melolabial fold, plication of parotid-masseteric fascia, dermal graft suspension, blepharoplasty, brow lift, canthoplasty, horizontal shortening of lower lid, fascial suspension of lower lip, McLaughlin tarsorrhaphy, and palpebral spring. Patient counseling is emphasized.