Molecular characterization of a nosocomial outbreak of influenza B virus in an acute care hospital setting.

AIM: To describe a hospital outbreak of influenza B virus (InfB) infection during season 2015/2016 by combining clinical and epidemiological data with molecular methods. METHODS: Twenty patients diagnosed with InfB from a hospital outbreak over a four-week-period were included. Nasopharyngeal samples (NPS) positive for InfB by multiplex real-time polymerase chain reaction were sent for lineage typing and whole genome sequencing (WGS). Medical records were reviewed retrospectively for data regarding patient characteristics, localization, exposure and outcome, and assembled into a timeline. In order to find possible connections to the hospital outbreak, all patients with a positive NPS for influenza from the region over an extended time period were also reviewed. FINDINGS: All 20 cases of InfB were of subtype B/Yamagata, and 17 of 20 patients could be linked to each other by either shared room or shared ward. WGS was successful or partially successful for 15 of the 17 viral isolates, and corroborated the epidemiological link supporting a close relationship. In the main affected ward, 19 of 75 inpatients were infected with InfB during the outbreak period, resulting in an attack rate of 25%. One probable case of influenza-related death was identified. CONCLUSION: InfB may spread within an acute care hospital, and advanced molecular methods may facilitate assessment of the source and extent of the outbreak. A multi-faceted approach, including rapid diagnosis, early recognition of outbreak situations, simple rules for patient management and the use of regular infection control measures, may prevent nosocomial transmission of influenza virus.

Prognostic and predictive value of thymidylate synthase expression in primary colorectal cancer.

AIM: To investigate thymidylate synthase (TS) expression in primary colorectal cancer (CRC) as a prognostic and predictive marker of benefit for adjuvant chemotherapy. PATIENTS AND METHODS: TS expression was immuno0-histochemically (IHC) assessed on tumors from 1,389 patients with stage II and III CRC randomly assigned to either surgery alone or surgery plus 5-fluorouracil (5-FU)-based adjuvant chemotherapy. RESULTS: In the subgroup treated with surgery alone (n=708), TS expression was prognostic using the classification of TS 0-1 versus 2-3 (p=0.045) as well as TS classified as 0-2 versus 3 (p=0.002). A high TS expression was associated with a shorter overall survival. Among patients with TS grade 3 (n=460), the subgroup treated with adjuvant chemotherapy had a significant longer OS (p=0.005). CONCLUSION: In this study TS, immunohistochemically assessed, is a prognostic factor in CRC patients treated with surgery alone. Patients with the highest level of TS expression (grade 3) had an improved clinical outcome following adjuvant 5-FU-based chemotherapy.

Pro-apoptotic Bax is the major and Bak an auxiliary effector in cytokine deprivation-induced mast cell apoptosis.

The process of apoptosis in immune cells like mast cells is essential to regain homeostasis after an inflammatory response. The intrinsic pathway of apoptosis is ultimately controlled by the pro-apoptotic Bcl-2 family members Bax and Bak, which upon activation oligomerize to cause increased permeabilization of the mitochondria outer membrane leading to cell death. We examined the role of Bax and Bak in cytokine deprivation-induced apoptosis in mast cells using connective tissue-like mast cells and mucosal-like mast cells derived from bax(-/-), bak(-/-) and bax(-/-)bak(-/-) mice. Although both Bax and Bak were expressed at readily detectable protein levels, we found a major role for Bax in mediating mast cell apoptosis induced by cytokine deprivation. We analyzed cell viability by propidium iodide exclusion and flow cytometry after deprivation of vital cytokines for each mast cell population. Upon cytokine withdrawal, bak(-/-) mast cells died at a similar rate as wild type, whereas bax(-/-) and bax(-/-)bak(-/-) mast cells were partially or completely resistant to apoptosis, respectively. The total resistance seen in bax(-/-)bak(-/-) mast cells is comparable with mast cells deficient of both pro-apoptotic Bim and Puma or mast cells overexpressing anti-apoptotic Bcl-2. These results show that Bax has a predominant and Bak a minor role in cytokine deprivation-induced apoptosis in both connective tissue-like and mucosal-like mast cells.

Change of body movement coordination during cervical proprioceptive disturbances with increased age.

BACKGROUND: To date, there are very few studies on postural stability in older adults using body movement recordings to capture the postural movement pattern. Moreover, the importance of proprioception at key areas such as the calf or neck on the postural movement pattern in older adults has rarely been investigated. OBJECTIVE: To investigate whether the body movement coordination strategy to calf or neck vibration was affected by aging. METHODS: Body movement measurements were taken at five locations (ankle, knee, hip, shoulder and head) from 18 younger (mean age 29.1 years) and 16 older (mean age 71.5 years) adult subjects using a 3D movement measuring system while subjected to 50 s of pseudo-random calf or neck vibratory stimulation pulses with eyes open or closed. The positions from the knee, hip, shoulder and head markers were correlated against one another to give an indication of the body coordination. RESULTS: During quiet standing, older adults had greater correlation between the head and trunk than the young. There was an age effect in the body movement coordination strategy. Older adults had a different movement pattern with neck vibration involving mainly more independent knee movements, indicating balance difficulty. CONCLUSIONS: Neck vibration affects the movement pattern in older adults more compared with younger adults and calf vibration, suggesting that, the regulation of body orientation in older adults is more difficult, especially during cervical proprioceptive disturbances.

Vestibular PREHAB and gentamicin before schwannoma surgery may improve long-term postural function.

BACKGROUND: Unilateral vestibular deafferentation (uVD), as performed in vestibular schwannoma surgery, results in a chronic vestibular deficit, though most of the insufficiency can be compensated by other sensory input. By vestibular training (prehabituation) performed before surgery, motor adaptation processes can be instigated before the actual lesion. The adaptation processes of the altered sensory input could be affected if the vestibular ablation and surgery were separated in time, by pretreating patients who have remaining vestibular function with gentamicin. OBJECTIVE: To determine whether presurgical deafferentation would affect postsurgery postural control also in a long-term perspective (6 months). METHOD: 41 patients subjected to trans-labyrinthine schwannoma surgery were divided into four groups depending on the vestibular activity before surgery (with no clinical significant remaining function n = 17; with remaining function n = 8), whether signs of central lesions were present (n = 10), and if patients with remaining vestibular activity were treated with gentamicin with the aim to produce uVD before surgery (n = 6). The vibratory posturography recordings before surgery and at the follow-up 6 months after surgery were compared. RESULTS: The subjects pretreated with gentamicin had significantly less postural sway at the follow-up, both compared with the preoperative recordings and compared with the other groups. CONCLUSION: The results indicate that by both careful sensory training and separating the surgical trauma and the effects of uVD in time, adaptive processes can develop more efficiently to resolve sensory conflicts, resulting in a reduction of symptoms not only directly after surgery but also perhaps up to 6 months afterwards.

Mondini-like malformation mimicking otosclerosis and superior semicircular canal dehiscence.

In 2003, it was reported that superior semicircular canal dehiscence can mimic otosclerosis because of low-frequency bone conduction hearing gain and dissipation of air-conducted acoustic energy through the dehiscence. We report the case of a 17-year-old girl with left-sided combined hearing loss thought to be due to otosclerosis. Bone conduction thresholds were -10 dB at 250 and 500 Hz and she had a 40 dB air-bone gap at 250 Hz. When a tuning fork was placed at her ankle she heard it in her left ear. Acoustic reflexes and vestibular evoked myogenic potentials could be elicited bilaterally. Imaging of the temporal bones showed no otosclerosis, superior semicircular canal dehiscence or large vestibular aqueduct, but a left-sided, Mondini-like dysplasia of the cochlea with a modiolar deficiency could be seen. Mondini-like cochlear dysplasia should be added to the causes of inner-ear conductive hearing loss.

Treatment of phobic postural vertigo. A controlled study of cognitive-behavioral therapy and self-controlled desensitization.

In balance clinic practice, phobic postural vertigo is a term used to define a population with dizziness and avoidance behavior often as a consequence of a vestibular disorder. It has been described as the most common form of dizziness in middle aged patients in dizziness units. Anxiety disorders are common among patients with vestibular disorders. Cognitive-behavioral therapy is an effective treatment for anxiety disorders, and vestibular rehabilitation exercises are effective for vestibular disorders. This study compared the effect of additional cognitive-behavioral therapy for a population with phobic postural vertigo with the effect of self-administered vestibular rehabilitation exercises. 39 patients were recruited from a population referred for otoneurological investigation. Treatment effects were evaluated with the Dizziness Handicap Inventory, Vertigo Symptom Scale, Vertigo Handicap Questionnaire, and Hospital Anxiety and Depression Scale. All patients had a self treatment intervention based on education about the condition and recommendation of self exposure by vestibular rehabilitation exercises. Every second patient included was offered additional cognitive behavioral therapy. Fifteen patients with self treatment and 16 patients with cognitive- behavioral treatment completed the study. There was significantly larger effect in the group who received cognitive behavioral therapy than in the self treatment group in Vertigo Handicap Questionnaire and the Hospital Anxiety and Depression scale and its subscales. Cognitive-behavioral therapy has an additional effect as treatment for a population with phobic postural vertigo. A multidisciplinary approach including medical treatment, cognitive-behavioral therapy and physiotherapy is suggested.

Cervical muscle afferents play a dominant role over vestibular afferents during bilateral vibration of neck muscles.

A previous study showed that vibratory stimulation of neck muscles in humans induced short-latency electromyographic (EMG) activation of lower leg muscles, producing postural reactions at the feet. These findings indicated that cervical proprioception contributes to stabilization of stance through rapidly integrated pathways. However, as vibration may excite both proprioceptive and vestibular afferents, and because of the proximity of neck muscles to the vestibular apparatus, neck muscle vibration could also have activated the vestibular system thereby contributing to the effect observed. To investigate any possible contribution of vestibular stimulation, vibratory stimuli were applied bilaterally and separately to the splenius muscles of the neck and the planum mastoideum overlying the vestibular organs. Ten normal subjects, with eyes closed, were exposed to vibratory stimulation of two different amplitudes and frequencies. Responses were assessed by EMG activity recorded from tibialis anterior and gastrocnemius muscles of both legs and by changes in center of pressure as measured by a force platform. Results indicated that vibration induced reproducible EMG and postural responses in the anteroposterior direction, particularly on cessation of vibration. EMG and postural responses were considerably lower and less consistent with mastoid vibration compared with neck muscles vibration. Previous reports suggest that vibratory stimulation could propagate to the vestibular organs and generate a vestibular-induced postural activation. However, our findings indicate that cervical muscles afferents play a dominant role over vestibular afferents when vibration is directed towards the neck muscles.

Effects of hypothermic anesthesia of the feet on vibration-induced body sway and adaptation.

The aim of this study was to investigate the significance of information from the plantar cutaneous mechanoreceptors in postural control and whether postural control could compensate for reduced cutaneous information by adaptation. Sixteen healthy subjects were tested with eyes open or eyes closed with hypothermic and normal feet temperature during posturography where body sway was induced by vibratory proprioceptive stimulation towards both calf muscles. The hypothermic anesthesia was obtained by cooling the subject's feet in ice water for 20 minutes. Body movements were evaluated by analyzing the anteroposterior and lateral torques induced towards the supporting surface by a force platform during the posturography tests. The reduction of cutaneous sensor information from the mechanoreceptors of the feet significantly increased the vibration-induced torque variance mainly in the anteroposterior direction. However, the effects of disturbed mechanoreceptors information was rapidly compensated for through postural adaptation and torque variance was in level with that without anesthesia within 50 to 100 seconds of stimulation, both when standing with eyes open and eyes closed. Our findings suggest that somatosensory input from mechanoreceptors in the foot soles contribute significantly in maintaining postural control, but the sensory loss could be compensated for.

Inferior vestibular neuritis.

Sudden, spontaneous, unilateral loss of vestibular function without simultaneous hearing loss or brain stem signs is generally attributed to a viral infection involving the vestibular nerve and is called acute vestibular neuritis. The clinical hallmarks of acute vestibular neuritis are vertigo, spontaneous nystagmus, and unilateral loss of lateral semicircular function as shown by impulsive and caloric testing. In some patients with vestibular neuritis the process appears to involve only anterior and lateral semicircular function, and these patients are considered to have selective superior vestibular neuritis. Here we report on two patients with acute vertigo, normal lateral semicircular canal function as shown by both impulsive and caloric testing, but selective loss of posterior semicircular canal function as shown by impulsive testing and of saccular function as shown by vestibular evoked myogenic potential testing. We suggest that these patients had selective inferior vestibular neuritis and that contrary to conventional teaching, in a patient with acute spontaneous vertigo, unilateral loss of lateral semicircular canal function is not essential for a diagnosis of acute vestibular neuritis.

Multi-stimulus multi-response posturography.

In this study a method for the analysis of simultaneous multiple measurements of kinematics and stabilizing forces related to human postural dynamics is proposed. Each subject in a group of normal subjects (n=10) was tested with eyes-open and eyes-closed with simultaneous but uncorrelated vestibular and proprioceptive stimuli in order to investigate the contributions of individual sensory feedback loops. Statistical analysis was made by means of multi-input multi-output identification of a transfer function from stimuli to stabilizing forces of the feet and the resulting body position, the transfer function being compatible with a biomechanical model formulated as a stabilized segmented inverted pendulum subject to feedback of body sway and position. Each individual model estimated is effective in predicting a subject's response to new stimuli and in describing the interacting effects of stimuli on body kinetics. The proposed methodology responds to the current needs of data analysis of multi-stimulus multi-response experiments.

Individual semicircular canal function in superior and inferior vestibular neuritis.

OBJECTIVE: To examine the concept of selective superior and inferior vestibular nerve involvement in vestibular neuritis by studying the distribution of semicircular canal (SCC) involvement in such patients. BACKGROUND: Vestibular neuritis was traditionally thought to involve the superior and inferior vestibular nerves. Recent work suggests that in some patients, only the superior nerve is involved. So far there are no reported cases of selective involvement of the inferior vestibular nerve. METHODS: The authors measured the vestibuloocular reflex from individual SCC at natural head accelerations using the head impulse test. The authors studied 33 patients with acute unilateral peripheral vestibulopathy, including 29 with classic vestibular neuritis and 4 with simultaneous ipsilateral hearing loss, 18 healthy subjects and 15 surgical unilateral vestibular deafferented patients. RESULTS: In patients with preserved hearing, eight had deficits in all three SCC, suggesting involvement of the superior and inferior vestibular nerves. Twenty-one had a lateral SCC deficit or a combined lateral and anterior SCC deficit consistent with selective involvement of the superior vestibular nerve. Two patients with ipsilateral hearing loss had normal caloric responses and an isolated posterior SCC deficit on impulsive testing. The authors propose that these two patients had a selective loss of inferior vestibular nerve function. CONCLUSION: Vestibular neuritis can affect the superior and inferior vestibular nerves together or can selectively affect the superior vestibular nerve.

The effects of galvanic stimulation on the human vestibulo-ocular reflex.

We studied the effects of 5 mA bilateral or unilateral, bipolar or monopolar, galvanic stimulation on the horizontal vestibulo-ocular reflex (hVOR) in six normal subjects during 0.01, 0.05, 0.1, 0.5 and 1 Hz yaw rotations and in two subjects during high-acceleration, low-amplitude yaw head rotations (head impulses). Bipolar galvanic stimulation induced horizontal nystagmus in all subjects and an asymmetry of the hVOR only during rotations below 0.1 Hz. Monopolar stimulation had no significant effect. The findings suggest that in humans galvanic stimulation affects those primary horizontal semicircular canal neurons that mediate the hVOR via indirect pathways through the velocity storage mechanism.

Neck muscle vibration alters visually-perceived roll after unilateral vestibular loss.

Unilateral sternocleidomastoid muscle vibration was applied to 21 normal and six unilateral vestibular deafferented (uVD) human subjects at head erect and during 30 degrees left and right whole body roll-tilt. In normal subjects, neck vibration had no effect upon the settings of a visual bar to subjective visual horizontal (SVH) in any roll-tilt condition. In uVD subjects settings to SVH were significantly altered by neck vibration, with ipsilesional neck vibration increasing the SVH bias at head erect. Further, during contralesional roll-tilt, ipsilesional neck vibration in uVD subjects significantly increased the E-effect. These results suggest that compensation after vestibular loss allows cervical signals to influence visual perception of roll-tilt.

Direction of galvanically-induced vestibulo-postural responses during active and passive neck torsion.

The direction of a postural response induced by galvanic vestibular stimulation depends on the head and trunk position. The relative importance of afferent information (proprioception) and efferent motor command/corollary discharge is unknown. We studied the direction of body sway evoked by galvanic vestibular stimulation in 9 healthy subjects during active and passive head positioning at 0 degrees frontal position, 35 degrees to the left, and 75 degrees to the right, using a custom-built collar. At 0 degrees and 75 degrees there were no significant differences in sway direction between active and passive head positioning. The galvanic stimulation invoked sway toward the anode, mainly in the inter-aural direction. The sway direction differed significantly between active and passive positioning at 35 degrees to the side (p < 0.05). When the head was actively kept in this position, the body sway was mainly in an inter-aural direction. The sway shifted to a naso-occipital direction when the head was passively positioned at 35 degrees. Our results indicate that the afferent proprioceptive information has the largest influence on the direction of the galvanically-induced postural response, although some dependence on efferent motor commands and non-linear cervical proprioception cannot be ruled out entirely.

Sudden unilateral hearing loss with simultaneous ipsilateral posterior semicircular canal benign paroxysmal positional vertigo: a variant of vestibulo-cochlear neurolabyrinthitis?

We describe 4 patients who all simultaneously developed a sudden total or partial unilateral sensorineural hearing loss and an unusual acute peripheral vestibulopathy in the same ear characterized by posterior semicircular canal benign paroxysmal positional vertigo with intact lateral semicircular canal function. Two patients also had ipsilateral loss of otolith function. The vertigo resolved in all 4 patients after particle-repositioning maneuvers. The findings of audiometry and vestibular tests indicated that the lesion responsible for this syndrome was probably located within the labyrinth itself rather than within the vestibulocochlear nerve and that it was more likely a viral vestibulocochlear neurolabyrinthitis than a labyrinthine infarction.

What inner ear diseases cause benign paroxysmal positional vertigo?

Benign paroxysmal positional vertigo (BPPV) originating from the posterior semicircular canal (pSCC) is a common vestibular disorder that is easy to diagnose and usually easy to treat. The majority of patients with BPPV have no known inner ear disease; they have "primary" or "idiopathic" BPPV. However, a minority does have objective evidence of an inner ear disease on the same side as the BPPV and this group has "secondary" or "symptomatic" BPPV. Previous publications differ on the prevalence of secondary BPPV and about the types of inner ear diseases capable of causing it. In order to determine what proportion of patients have secondary as opposed to primary BPPV and which inner ear diseases are capable of causing secondary BPPV, we searched our database for the 10-year period from 1988 to 1997 and found a total of 2847 patients with BPPV. Of these, 81 (3%) had definite pSCC-BPPV secondary to an ipsilateral inner ear disease. Sixteen had Menière's disease, 24 had an acute unilateral peripheral vestibulopathy, 12 had a chronic unilateral peripheral vestibulopathy, 21 had chronic bilateral peripheral vestibulopathy and 8 had unilateral sensorineural hearing loss. It seems that any inner ear disease that detaches otoconia and yet does not totally destroy pSCC function can cause BPPV and that a case can be made for audiometry and caloric testing in all patients with BPPV.

Passive sustained turning of the head induces asymmetric gain of the vestibulo-ocular reflex in healthy subjects.

In order to test the hypothesis of an interaction between neck proprioception and the vestibulo-ocular reflex (VOR), we rotated 16 healthy subjects both facing forward and with their heads passively turned 70 degrees to either side. We found that gain tended to be lower when the subjects were rotated with their heads turned opposite to the direction of rotation compared to when they were rotated in the same direction, but facing forward. Although our findings were not statistically significant, they suggest that there is a measurable interaction between neck proprioception and the VOR in subjects with normal vestibular function. Asymmetric neck muscle proprioceptive signals seem to give rise to asymmetric functioning of the VOR, which, at least in part, could be the pathogenesis of cervical dizziness. If so, this could lead to misinterpretation of vestibular assessments in patients with neck pain who also complain of dizziness.

Head movement restriction and postural stability in patients with compensated unilateral vestibular loss.

OBJECTIVE: To study whether restriction of head-neck movements improves postural performance in patients with compensated unilateral total vestibular loss. DESIGN: Randomized controlled experimental study. SETTING: Laboratory for clinical and experimental vestibular testing at a tertiary referral center. PATIENTS: Fifteen consecutive patients (seven men, eight women, mean age 53 years) at routine follow-up, 6 months after translabyrinthine extirpation of acoustic neurinomas (mean tumor size 13.5mm, range 5 to 25mm). None of the patients had signs or symptoms of central nervous system dysfunction. INTERVENTION: Posturographic tests comparing patients with and without a semirigid neck collar. Test order was randomized between patients to reduce training effects. MAIN OUTCOME MEASURE: Posturography measuring velocity and variance of quiet stance and measuring body sway induced by vibration at 60, 80, and 100Hz to the calf muscles. Tests were conducted with eyes open and closed. RESULTS: In tests with vibration at 100Hz to the calf muscles and with eyes open, body sway velocity was significantly higher when patients were wearing a neck collar. No significant difference was found in any other test. CONCLUSION: Restricting head-neck movements with a neck collar does not improve postural stability in patients with compensated unilateral total vestibular loss. A tendency toward impaired postural performance leads to the conclusion that it is not appropriate to treat such patients with neck collars to improve their balance.