Recurrent pneumothorax after cesarean delivery in the critically ill pregnant with severe COVID-19 ARDS: a case report.

OBJECTIVE: Few data are available on the ICU management and on the possible respiratory complications of invasively ventilated pregnant patients affected by COVID-19 pneumonia, especially in the early phase of pregnancy. Tension pneumothorax has been previously described as a rare cause of respiratory failure after delivery, but its occurrence in the postpartum of COVID-19 patient has not been reported yet. We hereby describe the ICU management of a 23rd gestational week pregnant woman who underwent invasive mechanical ventilation, prone positioning, and cesarean delivery during her ICU stay for COVID-19 related pneumonia. Moreover, we focused on the occurrence and management of recurrent tension pneumothorax after the cesarean delivery. CASE REPORT: A 23rd gestational week pregnant woman was admitted to the ICU for a COVID-19 bilateral pneumonia and underwent invasive mechanical ventilation and prone positioning. Cesarean delivery was planned during the ICU stay, while the patient was receiving invasive mechanical ventilation. After delivery, the patient experienced a recurrent pneumothorax that required the positioning of multiple chest drains. CONCLUSIONS: In pregnant critically ill COVID-19 patients, mechanical ventilation management is particularly challenging, especially in the postpartum period. Prone positioning is feasible and can improve oxygenation and respiratory system compliance, while tension pneumothorax must be suspected if the respiratory function suddenly deteriorates after delivery.

Peripheral loss of regulatory T cells and polyautoimmunity in an HIV-infected patient.

We report a case of a human immunodeficiency virus (HIV)/hepatitis C virus-co-infected patient with an optimal virological status but with a poor CD4+ cell profile, followed up in the University Department of Infectious and Tropical Diseases of Brescia, Italy. He presented several autoimmune diseases (ADs) over the years concomitant with CD4+ cell increase episodes following severe immune depression of unknown cause. We studied T- and B-cell subsets and found low levels of K-deleting Recombination Excision Circles, T-cell Receptor Excision Circles and B and T memory subpopulations, which indicated that the bone marrow and thymic outputs were lower than in healthy controls. The most relevant phenotypic alteration was in the regulatory T-cell (Treg) population, because total Tregs as well as naïve, central memory and effector memory cells were detected at very low levels. This was the first case of polyautoimmunity defined as the presence of more than one AD in the same individual, occurring in an HIV patient. Several factors may be implicated, including genetic susceptibility, environmental factors, concomitant therapies and dysregulation of immune system cells. The extremely low number of Tregs found in our patient may play a major role in the regulation of the immune response and the development of all ADs.

Asymmetric vestibular stimulation reveals persistent disruption of motion perception in unilateral vestibular lesions.

Self-motion perception was studied in patients with unilateral vestibular lesions (UVL) due to acute vestibular neuritis at 1 wk and 4, 8, and 12 mo after the acute episode. We assessed vestibularly mediated self-motion perception by measuring the error in reproducing the position of a remembered visual target at the end of four cycles of asymmetric whole-body rotation. The oscillatory stimulus consists of a slow (0.09 Hz) and a fast (0.38 Hz) half cycle. A large error was present in UVL patients when the slow half cycle was delivered toward the lesion side, but minimal toward the healthy side. This asymmetry diminished over time, but it remained abnormally large at 12 mo. In contrast, vestibulo-ocular reflex responses showed a large direction-dependent error only initially, then they normalized. Normalization also occurred for conventional reflex vestibular measures (caloric tests, subjective visual vertical, and head shaking nystagmus) and for perceptual function during symmetric rotation. Vestibular-related handicap, measured with the Dizziness Handicap Inventory (DHI) at 12 mo correlated with self-motion perception asymmetry but not with abnormalities in vestibulo-ocular function. We conclude that 1) a persistent self-motion perceptual bias is revealed by asymmetric rotation in UVLs despite vestibulo-ocular function becoming symmetric over time, 2) this dissociation is caused by differential perceptual-reflex adaptation to high- and low-frequency rotations when these are combined as with our asymmetric stimulus, 3) the findings imply differential central compensation for vestibuloperceptual and vestibulo-ocular reflex functions, and 4) self-motion perception disruption may mediate long-term vestibular-related handicap in UVL patients.NEW & NOTEWORTHY A novel vestibular stimulus, combining asymmetric slow and fast sinusoidal half cycles, revealed persistent vestibuloperceptual dysfunction in unilateral vestibular lesion (UVL) patients. The compensation of motion perception after UVL was slower than that of vestibulo-ocular reflex. Perceptual but not vestibulo-ocular reflex deficits correlated with dizziness-related handicap.

Randomised clinical study: gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity.

BACKGROUND: It is unknown whether symptoms in non-coeliac patients (non-CD) meeting clinical diagnostic criteria for noncoeliac gluten sensitivity (NCGS) are specifically triggered by gluten. AIM: To assess gluten sensitivity in patients diagnosed with NCGS. METHODS: We studied 35 non-CD subjects (31 females) that were on a gluten-free diet (GFD), in a double-blind challenge study. Participants were randomised to receive either gluten-containing flour or gluten-free flour for 10 days, followed by a 2-week washout period and were then crossed over. The main outcome measure was their ability to identify which flour contained gluten. Secondary outcome measures were based upon Gastrointestinal Symptoms Rating Scale (GSRS) scores. RESULTS: The gluten-containing flour was correctly identified by 12 participants (34%), who were classified as having NCGS. Their mean GSRS dimension scores were significantly higher following gluten challenge compared to baseline. The scores were: pain, 1.7 ± 0.8 vs. 2.6 ± 1.0; reflux, 1.6 ± 0.5 vs. 2.2 ± 0.9; indigestion, 1.9 ± 0.7 vs. 3.2 ± 1.1; diarrhoea, 1.6 ± 0.7 vs. 2.9 ± 1.5 and constipation, 1.9 ± 0.9 vs. 2.9 ± 1.3. Seventeen participants (49%) erroneously considered the gluten-free flour to contain gluten. Their mean GSRS dimension scores were significantly higher following gluten-free flour challenge compared to baseline. The scores were: pain, 1.6 ± 0.9 vs. 3.0 ± 0.9; reflux, 1.4 ± 0.5 vs. 2.3 ± 1.1; indigestion, 2.0 ± 1.1 vs. 3.7 ± 1.1; diarrhoea, 1.6 ± 0.7 vs. 3.0 ± 1.2 and constipation, 1.6 ± 0.9 vs. 2.6 ± 1.3. The other six participants (17%) were unable to distinguish between the flours. CONCLUSION: Double-blind gluten challenge induces symptom recurrence in just one-third of patients fulfilling the clinical diagnostic criteria for non-coeliac gluten sensitivity.

Incidence of AIDS-defining cancers and virus-related and non-virus-related non-AIDS-defining cancers among HIV-infected patients compared with the general population in a large health district of Northern Italy, 1999-2009.

OBJECTIVES: The aim of the study was to investigate the incidence of AIDS-defining cancers (ADCs) and virus-related and non-virus-related non-AIDS-defining cancers (NADCs) in HIV-infected patients compared with the general population, and to assess the risk factors associated with these malignancies. METHODS: We performed a retrospective cohort study for the period from 1999 to 2009 of HIV-infected patients residing in the Local Health Authority of Brescia (northern Italy). Observed cancers in patients with HIV infection were compared with expected cancers in the population living in the same area using standardized incidence ratios (SIRs). Risk factors were assessed using Poisson regression analysis. RESULTS: A total of 5090 HIV-infected patients were included in the study, with 32 390 person-years of follow-up. We recorded 416 tumours in 390 HIV-infected patients. Two hundred of these (48.1%) were ADCs, 138 (33.2%) were non-virus-related NADCs and 78 (18.7%) were virus-related NADCs. An increased risk (SIR = 4.2) of cancers overall was found in HIV-infected patients. A large excess of ADCs (SIR = 31.0) and virus-related NADCs (SIR = 12.3) was observed in HIV-infected patients, while the excess risk for non-virus-related NADCs was small (SIR = 1.6). The highest SIRs were observed for Kaposi sarcoma among ADCs and for Hodgkin lymphoma among virus-related NADCs. Conversely, among non-virus-related NADCs, SIRs for a broad range of malignancies were close to unity. In multivariate analysis, increasing age and CD4 cell count < 50 cells/µL were the only factors independently associated with all cancers. CONCLUSIONS: Among HIV-infected people there was an excess of ADCs and also of NADCs, particularly those related to viral infections. Ageing and severe immunodeficiency were the strongest predictors.

Prolonged asymmetric vestibular stimulation induces opposite, long-term effects on self-motion perception and ocular responses.

Self-motion perception and the vestibulo-ocular reflex (VOR) were investigated in healthy subjects during asymmetric whole body yaw plane oscillations while standing on a platform in the dark. Platform oscillation consisted of two half-sinusoidal cycles of the same amplitude (40°) but different duration, featuring a fast (FHC) and a slow half-cycle (SHC). Rotation consisted of four or 20 consecutive cycles to probe adaptation further with the longer duration protocol. Self-motion perception was estimated by subjects tracking with a pointer the remembered position of an earth-fixed visual target. VOR was measured by electro-oculography. The asymmetric stimulation pattern consistently induced a progressive increase of asymmetry in motion perception, whereby the gain of the tracking response gradually increased during FHCs and decreased during SHCs. The effect was observed already during the first few cycles and further increased during 20 cycles, leading to a totally distorted location of the initial straight-ahead. In contrast, after some initial interindividual variability, the gain of the slow phase VOR became symmetric, decreasing for FHCs and increasing for SHCs. These oppositely directed adaptive effects in motion perception and VOR persisted for nearly an hour. Control conditions using prolonged but symmetrical stimuli produced no adaptive effects on either motion perception or VOR. These findings show that prolonged asymmetric activation of the vestibular system leads to opposite patterns of adaptation of self-motion perception and VOR. The results provide strong evidence that semicircular canal inputs are processed centrally by independent mechanisms for perception of body motion and eye movement control. These divergent adaptation mechanisms enhance awareness of movement toward the faster body rotation, while improving the eye stabilizing properties of the VOR.

Lung cancer in HIV-infected patients: the experience in Brescia from 1999 to 2009.

Lung cancer (LC) is the most common cancer among the non AIDS-defining malignancies in the highly active antiretroviral therapy (HAART) era. We described 23 HIV infected patients with a LC diagnosis followed in the Clinic of Tropical and Infectious Diseases of Brescia during the period of 1999-2009. All of these patients except two (n = 21, 91.3%) were cigarette smokers and all had at least one risk factor for developing cancer of the lung, or predisposing comorbidities, such as a COPD (chronic obstructive pulmonary disease) or a previous pneumonia. The median age at LC diagnosis was 53.6 years (range 21.2-71.4 years). Adenocarcinoma and squamous cell carcinoma were diagnosed in 10 cases (43.5%) respectively. In 21 subjects (91.3%) cancer was detected at stage IV with metastases. The median survival was 5.95 months. Greater intervention focused on the cessation of smoking is necessary, as well as the implementation of closer screening policies, especially in HIV-positive subjects with LC risk factors.

Head position modulates optokinetic nystagmus.

Orientation and movement relies on both visual and vestibular information mapped in separate coordinate systems. Here, we examine how coordinate systems interact to guide eye movements of rabbits. We exposed rabbits to continuous horizontal optokinetic stimulation (HOKS) at 5°/s to evoke horizontal eye movements, while they were statically or dynamically roll-tilted about the longitudinal axis. During monocular or binocular HOKS, when the rabbit was roll-tilted 30° onto the side of the eye stimulated in the posterior â†’ anterior (P â†’ A) direction, slow phase eye velocity (SPEV) increased by 3.5-5°/s. When the rabbit was roll-tilted 30° onto the side of the eye stimulated in the A â†’ P direction, SPEV decreased to ~2.5°/s. We also tested the effect of roll-tilt after prolonged optokinetic stimulation had induced a negative optokinetic afternystagmus (OKAN II). In this condition, the SPEV occurred in the dark, "open loop." Modulation of SPEV of OKAN II depended on the direction of the nystagmus and was consistent with that observed during "closed loop" HOKS. Dynamic roll-tilt influenced SPEV evoked by HOKS in a similar way. The amplitude and the phase of SPEV depended on the frequency of vestibular oscillation and on HOKS velocity. We conclude that the change in the linear acceleration of the gravity vector with respect to the head during roll-tilt modulates the gain of SPEV depending on its direction. This modulation improves gaze stability at different image retinal slip velocities caused by head roll-tilt during centric or eccentric head movement.

Stickler syndrome in Pierre-Robin sequence prenatal ultrasonographic diagnosis and postnatal therapy: two cases report.

The Pierre-Robin Syndrome (PRS) is a rare congenital abnormality, with an approximately 1/30,000 estimated rate, characterized by the presence of the combination of mandibular hypoplasia (micrognathia or small jaw), glossoptosis (retrusion of the tongue into the pharyngeal airway) and, often, a posterior cleft of the secondary palate. It may be an isolated occurrence or part of a more complex syndrome and it is associated with long-term respiratory, nutritional, and developmental difficulties. Stickler syndrome (SS) is a rare autosomal dominant connective tissue disorder estimated to affect approximately 1/7500 newborns. It is diagnosed clinically and, at present, there is no consensus on a minimal clinical diagnostic criterion. The most frequent diagnosis in patients with syndromic Pierre Robin sequence is Stickler syndrome, which may be complicated by congenital high myopia and substantial risk of retinal detachment. However, cases of Stickler syndrome with probable visual complications are rarely identified among this group of patients by members of the cleft team. The patient had an acute unilateral hydrops, with a monolateral keratoconus. The ocular abnormalities included: severe myopia, abnormalities of the vitreous, and high risk of retinal detachment (with subsequent blindness). We report two extremely rare cases of prenatal diagnosis of PRS and SS, prematurely identified by prenatal ultrasonography and successively managed by oculists ophthalmogists.

Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss.

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day 1 after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 mm from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors. Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications.

Protective effects of alpha-tocopherol and tiopronin against cisplatin-induced ototoxicity.

OBJECTIVE: To investigate the possible protective effects of alpha-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species. Antioxidants, such as alpha-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage. MATERIAL AND METHODS: Hartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+alpha-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+alpha-tocopherol acetate+tiopronin, (V) alpha-tocopherol acetate alone or (VI) tiopronin alone. Changes in cochlear function were characterized by means of compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. RESULTS: Cisplatin induced progressive high-frequency hearing loss of 40-50 dB SPL. Alpha-tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with alpha-tocopherol acetate or tiopronin alone was less effective. Morphological observations showed an important loss of outer hair cells and degeneration of the organ of Corti in the basal and middle turns. Injection of both alpha-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of alpha-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed. CONCLUSION: This study supports the hypothesis that alpha-tocopherol and tiopronin interfere with cisplatin-induced damage, and suggests that concurrent treatment with the two drugs can be useful in protecting against hearing loss.

The role of antioxidants in protection from ototoxic drugs.

A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus alpha-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20 degrees. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by alpha-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. In conclusion, antioxidants such as alpha-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.

The role of antioxidants in protection from ototoxic drugs.

A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus α-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20°. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by α-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. In conclusion, antioxidants such as α-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.

Angiotensin II stimulates contraction and growth of testicular peritubular myoid cells in vitro.

Seminiferous tubule contraction, an important step in the regulation of spermatogenesis and testicular sperm output, is regulated by several agonists. In the present paper, we investigated whether angiotensin II (Ang II) may have a place among them. In binding experiments performed to assess the presence of specific receptors in rat peritubular myoid cells (TPMC), binding of (125)I-Ang II to TPMC was saturable in a time-dependent manner. Competition binding experiments performed with Losartan and PD 123319 showed that Losartan was able to inhibit the binding of (125)I-Ang II, whereas PD 123319 was ineffective. Ang II induced a dose-dependent rise in intracellular Ca(2+). Depletion of intracellular calcium stores by thapsygargin resulted in a lower rise of intracellular calcium, and the L-type voltage-operated calcium channel (VOCC-L) blocker verapamil abolished the Ca(2+) influx in rat TPMC. Altogether, these findings indicate that the Ang II-induced increase in [Ca(2+)](i) involves both extracellular influx and Ca(2+) release from intracellular stores. Ang II induced a dose-dependent TPMC contraction, and Losartan and not PD 123319 inhibited the response. Ang II-induced contraction was inhibited by adrenomedullin, previously shown to antagonize endothelin 1-provoked contraction in those cells. Ang II elicited (3)H-thymidine DNA incorporation and proliferation in a dose-dependent manner in TPMC. Losartan and both MAPK inhibitor PD 98059 and tyrosine kinase inhibitor AG18 were able to inhibit Ang II-induced (3)H-thymidine uptake and cell proliferation. In conclusion, the present study documents that angiotensin II, the active mediator of the tissue and circulating renin-angiotensin system present in the mammalian testis, induces contraction, growth and rise in intracellular calcium in rat peritubular myoid cells via angiotensin II type 1 receptors, and suggests that Ang II is involved in the paracrine regulation of the seminiferous tubule function.

Cerebellar nodulectomy impairs spatial memory of vestibular and optokinetic stimulation in rabbits.

Natural vestibular and optokinetic stimulation were used to investigate the possible role of the cerebellar nodulus in the regulation and modification of reflexive eye movements in rabbits. The nodulus and folium 9d of the uvula were destroyed by surgical aspiration. Before and after nodulectomy the vertical and horizontal vestibuloocular reflexes (VVOR, HVOR) were measured during sinusoidal vestibular stimulation about the longitudinal (roll) and vertical (yaw) axes. Although the gain of the HVOR (G(HVOR) = peak eye movement velocity/peak head velocity) was not affected by the nodulectomy, the gain of the VVOR (G(VVOR)) was reduced. The gains of the vertical and horizontal optokinetic reflexes (G(VOKR), G(HOKR)) were measured during monocular, sinusoidal optokinetic stimulation (OKS) about the longitudinal and vertical axes. Following nodulectomy, there was no reduction in G(VOKR) or G(HOKR). Long-term binocular OKS was used to generate optokinetic afternystagmus, OKAN II, that lasts for hours. After OKAN II was induced, rabbits were subjected to static pitch and roll, to determine how the plane and velocity of OKAN II is influenced by a changing vestibular environment. During static pitch, OKAN II slow phase remained aligned with earth-horizontal. This was true for normal and nodulectomized rabbits. During static roll, OKAN II remained aligned with earth-horizontal in normal rabbits. During static roll in nodulectomized rabbits, OKAN II slow phase developed a centripetal vertical drift. We examined the suppression and recovery of G(VVOR) following exposure to conflicting vertical OKS for 10-30 min. This vestibular-optokinetic conflict reduced G(VVOR) in both normal and nodulectomized rabbits. The time course of recovery of G(VVOR) after conflicting OKS was the same before and after nodulectomy. In normal rabbits, the head pitch angle, at which peak OKAN II velocity occurred, corresponded to the head pitch angle maintained during long-term OKS. If the head was maintained in a "pitched-up" or "pitched-down" orientation during long-term OKS, the subsequently measured OKAN II peak velocity occurred at the same orientation. This was not true for nodulectomized rabbits, who had OKAN II peak velocities at head pitch angles independent of those maintained during long-term OKS. We conclude that the nodulus participates in the regulation of compensatory reflexive movements. The nodulus also influences "remembered" head position in space derived from previous optokinetic and vestibular stimulation.

Eye instability induced by vestibular stimulation in rabbits.

The slow compensatory phases of the vestibulo-ocular reflex (VOR) in the rabbit tend to drift and the drift reverses the direction. This periodic alternating drift (PAD) has two peculiar characteristics: (1) it is induced by sinusoidal vestibular stimulation in naive animals, being evoked immediately after stimulus onset and persisting after the end of stimulation; (2) the peak velocity and period of the drift are dependent on stimulus amplitude. PAD of the rabbit has strong similarities with PAN, a periodic alternating nystagmus observed in humans with cerbellar disorders and in monkeys after nodulo-uvulectomy, although its peak velocity is smaller. It is hypothesized that PAD is due to a slight instability, caused by vestibular stimulation in darkness, of the cerebellar adaptive loop, which exerts a variable gain control on the time constant of the velocity storage integrator.

Functional recovery after extra-ocular muscle deafferentation in the rabbit.

The present research analysed on chronic animals the functional recovery of eye motility after impairment of the proprioceptive input at the level of the semilunar ganglion. The horizontal vestibulo-ocular reflex (HVOR) was recorded in normal pigmented rabbits before and after a partial electrolytic lesion of the semilunar ganglion. The recordings were repeated daily for 8-10 days to evaluate the recovery. Immediately after the lesion, as previously observed, HVOR slow phases were unaffected, while quick phases (QPs) showed a reduction in peak velocity and a deviation of trajectories from the horizontal plane. QP peak velocity was almost completely restored within 3-5 days, while trajectory deviation was not corrected during the observation period. Furthermore, in some animals, the variability of trajectories showed, starting from days 3-5, a progressive increase that led to a greater spatial disorganization. A process of lesion-induced plasticity takes place. but only the velocity of QPs can be recovered rapidly, while the QP trajectory impairment does not appear to be compensated substantially, which underlines a determinant role in the control of QP spatial orientation exerted by EOM proprioceptive signals.

Optokinetic and vestibular stimulation determines the spatial orientation of negative optokinetic afternystagmus in the rabbit.

Prolonged binocular optokinetic stimulation (OKS) in the rabbit induces a high-velocity negative optokinetic afternystagmus (OKAN II) that persists for several hours. We have taken advantage of this uniform nystagmus to study how changes in static head orientation in the pitch plane might influence the orientation of the nystagmus. After horizontal OKS, the rotation axis of the OKAN II remained almost constant in space as it was kept aligned with the gravity vector when the head was pitched by as much as 80 degrees up and 35 degrees down. Moreover, during reorientation, slow-phase eye velocity decreased according to the head pitch angle. Thereafter, we analyzed the space orientation of OKAN II after optokinetic stimulation during which the head and/or the OKS were pitched upward and downward. The rotation axis of OKAN II did not remain aligned with an earth vertical axis nor a head vertical axis, but it tended to be aligned with that of the OKS respace. The slow-phase eye velocity of OKAN II was also affected by the head pitch angle during OKS, because maximal OKAN II velocity occurred at the same head pitch angle as that during optokinetic stimulation. We suggest that OKAN II is coded in gravity-centered rather than in head-centered coordinates, but that this coordinate system may be influenced by optokinetic and vestibular stimulation. Moreover, the velocity attenuation of OKAN II seems to depend on the mismatch between the space-centered nystagmus rotation axis orientation and that of the "remembered" head-centered optokinetic pathway activated by OKS.

Interaction of visual and vestibular stimulation on spatial coordinates for eye movements in rabbits.

NASA: Researchers investigated how vestibular and optokinetic signals alter the spatial transformation of the coordinate system that governs the spatial orientation of reflexive eye movements. Also examined were the effects of sensory stimulation when vestibular and optokinetic signals act synergistically and when the two signals are in conflict.^ieng

Difference in quick phases induced by horizontal and vertical vestibular stimulations: role of the otolithic input.

Quick phases (QPs) induced by horizontal and vertical sinusoidal vestibular stimulations were studied in rabbits, cats, and humans. In all the animals, large and frequent horizontal QPs were observed following yaw stimulation in prone position. By contrast, QPs were almost absent during roll stimulation in rabbits, and they were small and oblique during pitch stimulation in cats and humans. As a result of these differences, the range of gaze displacement induced by vestibular stimulations was greater in the horizontal plane than in the vertical one. We also found that the trajectory of the QPs in rabbits was kept horizontal even when the yaw rotation was off vertical axis of +/- 45 degrees in the sagittal plane. Moreover, in the rabbit, the rare horizontal QPs induced by roll stimulation did not change their orientation at various pitch angles of roll stimulation axis. The QPs were also analyzed following roll stimulation of the rabbit in supine position. In this condition, in which the otolithic receptors were activated in the opposite way compared to prone position, large vertical QPs were elicited. We concluded that these results provide evidence that the otolithic signal plays a role in controlling occurrence and trajectory orientation of the QPs.