Polyamines increase in the brain stem and cerebellum following labyrinthectomy

The goal of this investigation was to test the hypothesis that unilateral damage to the vestibular end-organ (labyrinthectomy) stimulates polyamine synthesis in central vestibular neural structures that mediate the process of behavioral recovery (vestibular compensation). Pharmacological studies have shown that compensation can be altered by alpha-difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis. Because polyamines are important in regeneration, development and modulation of N-methyl-D-aspartate (NMDA) excitatory amino acid receptors, which mediate vestibular synaptic plasticity, we investigated changes in polyamines in specific central vestibular structures after unilateral labyrinthectomy. The supernatant fraction of brain tissue homogenates was reacted with dansyl chloride. Dansylated polyamine derivatives were quantified in the vestibular nuclei, cerebellum, and inferior olive in both the control and the unilaterally labyrinthectomized guinea pig by high-performance liquid chromatography-fluorometric detection. No left-right differences in putrescine, spermidine, or spermine were detected in any brain parenchyma of controls. Polyamine imbalance, characterized by increased spermidine in the ipsilateral medial and lateral vestibular nuclei, was noted 12 and 24 h after unilateral labyrinthectomy (UL). In contrast, spermidine, spermine, and putrescine were elevated bilaterally in the cerebellum and inferior olive after UL. These biochemical changes may represent neuronal modifications to establish a balance between the vestibular nuclei after unilateral labyrinthectomy. Elucidation of the role of polyamines in central vestibular function and in vestibular compensation offers promise for the development of novel therapeutic strategies for treatment of vestibular disorders.     

Paediatric reference values for urinary catecholamine metabolites evaluated by high performance liquid chromatography and electrochemical detection

This report summarizes our experiences with the subjective visual vertical (SVV) as a clinical neuro-otological tool. In the SVV test, patients have to orient a dim light bar in an otherwise dark surrounding earth-vertical, using a remote-control. Normal subjects in an upright position did not deviate more than 2 degrees from true vertical. After vestibular neurectomy, the SVV was consistently tilted by some 12 degrees toward the affected ear. Smaller tilts (approximately 7 degrees) of the SVV occurred in patients with spontaneous peripheral vestibular diseases. This shift in SVV disappeared within weeks to months, similar to the spontaneous nystagmus. After stapes surgery slight deviations of the SVV towards the unoperated ear were seen in about 20% of the patients, indicating a slight irritation of the otolith organs. Assessed in an upright position, the SVV thus may be regarded as reflecting tonic otolithic input differences between the two ears. Asymmetries in the shifts of the SVV induced by roll tilts of the gravito-inertial vector by eccentric rotations of the subject have been proposed as a test for otolithic sensitivity. In our studies such asymmetries in the shifts of the SVV could not be induced by 26 degrees or 90 degrees roll tilts of subjects towards the affected or healthy ears. A simple clinical test to reveal unilateral otolithic sensitivity (comparable to an otolithic "caloric test") thus still has to be found.     

Room tilt illusion. A central otolith dysfunction

BACKGROUND: We report a sudden 90 degrees room tilt illusion (RTI) following vestibular stimulation in 3 patients with persistent skew deviation caused by a brain stem lesion. Room tilt illusion is a transient tilt perception of the visual surrounding, on its side or even upside down, that is often reported with brain stem lesions. Although its pathophysiologic cause is not well known, the RTI suggests an impairment of otolith pathways, as reported in skew deviation. METHODS: The 3 patients with brain stem lesions were reexamined as part of a follow-up of patients with signs of otolith dysfunction. A registration of vestibular function was performed with a rotatory chair, including earth-vertical axis rotation for canal stimulation and off-vertical axis rotation (OVAR) for otolith stimulation. Measurement of the subjective visual vertical (SVV) was also performed. RESULTS: The otolith-ocular reflex registered by OVAR was impaired in the 3 patients with skew deviation and the SVV in 2 patients. After each direction of OVAR stimulation, the 3 patients reported an RTI as the room was illuminated. CONCLUSIONS: The coexistence of otolith oculomotor (skew deviation and impaired otolith-ocular reflex) and perceptual (tilt of SVV and RTI) disorders suggests a common otolith dysfunction. However, an RTI occurred specifically after vestibular stimulation and when the room was illuminated. We thus suggest that RTI reflects a dynamic visuo-otolith mismatch.     

Comparative approaches to the avian song system

The aim of this paper is to: i) review the behavioural, electrophysiological, pharmacological and biochemical evidence relating to the involvement of N-methyl-D-aspartate (NMDA) receptors in the vestibular compensation process which follows unilateral peripheral vestibular deafferentation (UVD); and ii) suggest a unifying hypothesis based on this literature and recent studies of long-term depression (LTD)-like phenomena in the brainstem vestibular nucleus complex (VNC). It is suggested that NMDA receptors may induce a form of heterosynaptic LTD in the ipsilateral VNC, which is partly responsible for the extent of the hypoactivity which occurs immediately following UVD, and the severity of the associated vestibular syndrome. It is also suggested that vestibular compensation may develop as this LTD dissipates, allowing remaining synaptic inputs and the intrinsic properties of ipsilateral VNC neurons to re-establish the resting activity which is responsible for static vestibular compensation. It is argued that this hypothesis accounts for the majority of the available data on NMDA receptors in relation to vestibular compensation, and may serve as a useful working hypothesis, in order to formulate further experiments to investigate the contribution of NMDA receptors to the compensation process.     

Three-dimensional modeling of static vestibulo-ocular brain stem syndromes

Static vestibulo-ocular brain stem syndromes characterized by skew deviation, a vertical disconjugacy of the eyes, and ocular torsion are the result of a vestibular tone imbalance in the frontal (roll) plane. Similar physiological changes in static eye position, ocular counter-roll and conjugated deviations of vertical eye position, are caused by the influence of gravity mediated by the utricles. These observations prompted our approach with the model described here: based on the known deviations of static eye position, we devised a three-dimensional mathematical model of otolith-ocular function including detailed brain stem anatomy. This model is able to explain and predict the differential effects of unilateral and bilateral peripheral or central vestibular lesions on static eye position in roll, pitch, and yaw planes.     

Vestibular compensation in a patient with a cerebellar infarction

We report the case of a 67-year-old man who suffered a traumatic unilateral peripheral vestibular injury subsequent to an unrelated prior cerebellar infarction that occurred at least 2 years earlier. The patient's clinical course was marked by poor compensation for his peripheral vestibular loss. Four months after his vestibular injury, his symptoms of dizziness had not resolved. He had a spontaneous vestibular nystagmus, and laboratory testing indicated an asymmetric semicircular canal-ocular reflex. The otolith-ocular reflex, tested using off-vertical axis rotation, also was asymmetric but had a preserved modulation component. Visual-vestibular interaction and semicircular canal-otolith interaction were normal. An MRI indicated preservation of the flocculo-nodular lobe but infarction of the pyramis and uvula. Taken together, the findings in this case suggest that despite structural and functional preservation of the flocculo-nodular lobe, an anatomic region often labeled the "vestibulo-cerebellum", a lesion of the cerebellum that can impair CNS compensation for a unilateral peripheral lesion in humans.     

Brachytherapy in early prostate cancer--early experience

Intravenous lidocaine has been reported to alleviate vertigo in Meniere's disease and suggested as a possible antivertigo agent after unilateral labyrinthectomy in a study of cats. To further evaluate the effects of intravenous lidocaine on the acute phase of postural compensation, we subjected 13 pigmented guinea pigs to unilateral labyrinthectomy. Seven received intravenous lidocaine (4 mg/kg) immediately after labyrinthectomy. The other six served as controls and received an equivalent-volume injection of normal saline solution. Total body curvature, trunk curvature, yaw head tilt, and roll head tilt were measured at frequent intervals for up to 30 hours after surgery. Both groups had immediate difficulties with posturing that gradually improved. The lidocaine group tended to exhibit delayed postural compensation, but this was only statistically significant for roll head tilt. These results do not show improvement in postural compensation from unilateral labyrinthectomy after the administration of intravenous lidocaine. A species-specific effect on the vestibular pathways is suggested, and we conclude that further evaluation of lidocaine and the vestibular system is warranted.     

Contrasting immunopathogenic properties of highly homologous peptides from rat and human thyroglobulin

Morphological changes in the vestibular nerves and superior vestibulocular neurons (SVON) after unilateral labyrinthectomy in cats revealed a progressive loss of axons in the ipsilateral vestibular nerve (35%) and synaptic profiles (SP) on ipsilateral SVON (60%) up to a 1-year survival period. Although the ipsilateral vestibular nerve showed further degeneration (45%) at 2 years post ablation, the number of SP on ipsilateral SVON increased to 60% of normal (40% loss). These SP likely represent sprouting from crossing commissural or cerebellar pathways. Contralateral vestibular nerves at 1 and 2 years post ablation revealed normal numbers and size spectrum, but the number of SP contacting the contralateral SVON at 8 weeks, 1 and 2 years paralleled the levels of SP found on ipsilateral SVON. The symmetry in adjustment of SP on the SVON of both sides of the brainstem after ablation may be explained by the neurotrophin hypothesis.     

Gain and delay of human vestibulo-ocular reflexes to oscillation and steps of the head by a reactive torque helmet. I. Normal subjects

Vestibulo-ocular reflexes (VOR) were evaluated with a reactive torque helmet that imposed high-frequency oscillation (2-20 Hz) or step displacements of the head in the horizontal plane. The present paper describes the results in patients with vestibular deficiencies (labyrinthine defective; LD); experimental and analytical techniques and results for normal subjects were described in Part 1 of this paper. The patient groups included: total unilateral LD (related to acoustic neuroma; n = 40); severe (clinically total) bilateral LD (n = 7); bilateral hyporeflexia (n = 14); unilateral hyporeflexia (n = 11); and patients with LD phenomena that had subsided (n = 3). Helmet-induced head steps provided the most specific information. Characteristically, gain was lowered in one direction or both directions after unilateral or bilateral vestibular lesions, respectively; in general, the magnitude of the gain reduction correlated well with the degree of complaints and disability. Surprisingly, delay was systematically prolonged (up to several tens of milliseconds) in all groups of subjects with manifest vestibular pathology. These results suggest that the determination of delay, in addition to gain of the VOR, is feasible and important in the evaluation of vestibular function. The results of head oscillation generally supported the results for steps, but were somewhat less specific. The responses to manually generated head steps roughly agreed with those to helmet-induced steps, but because of the non-uniform acceleration they allowed a less exact analysis of VOR function.     

Nonsmoking, non-alpha 1-antitrypsin deficiency-induced emphysema in nonsmokers with healed spontaneous pneumothorax, identified by computed tomography of the lungs

This case-control study is based on an investigation of 27 nonsmoking patients with radiologically verified spontaneous pneumothorax (SP) and ten healthy never-smoker control subjects. The posteroanterior and lateral radiographs of patients and control subjects were normal. They were all submitted to the same clinical, laboratory, and radiologic examinations, including computed tomography (CT) of the lungs, with the aim of detecting any parenchymatous lung changes. Emphysema-like changes (ELCs) were detected on CT in 22 (81 percent) of the 27 patients, and if the ELC cases detected during interventional surgery are added, the frequency increases to 24/27 (89 percent). In 20 patients with unilateral SP, at least one ELC was found in 13 of the 20 SP-affected lungs, but only in five of the 20 lungs that were not diagnosed as having SP (p < 0.05). ELCs were found more frequently in the upper than in the lower lung regions (p < 0.05) and more frequently in the radiologically peripheral than in central regions (p < 0.001). No ELC was detected in the control group on CT. No alpha 1-antitrypsin deficiency was found in the 27 nonsmoking patients with radiologically verified SP who had ELCs despite the absence of these known promoters of emphysema.     

An update on peritoneal dialysis and hemodialysis in the pediatric population

Drugs acting as agonists (SKF38393 and quinpirol) or antagonists (SCH23390 and sulpiride) on dopamine receptors were administered at various doses (1, 2 or 4 mg kg-1 day-1) to aged male rats of the Sprague-Dawley strain subjected to labyrinth unilateral lesion. The time course of vestibular compensation was evaluated by recording spontaneous eye nystagmus and by scoring ambulation and rearing with the open field test and motor ability and coordination with the rotorod test. Treatment started 3 days prior to surgery and continued until day 7 after surgery. The vestibular compensation of untreated young male rats was also studied with the same methods. The decline of spontaneous nystagmus in aged animals was slower than that of young rats and was facilitated by the large doses of quinpirol (D2 receptor agonist) and inhibited by sulpiride (D2 receptor antagonist) 4 mg kg-1 day-1, while the other drugs did not affect this parameter. After operation, ambulation and rearing of aged rats increased more slowly as compared to that of young animals. Moreover, motor performance and coordination in aged rats improved less rapidly than those of young controls. Dopamine receptor agonists increased ambulation and improved motor performance and coordination in aged rats, while dopamine receptor antagonists exerted opposite effects. Rearing was not affected by any kind of drug treatment. These results suggest that dopamine neurotransmission plays a role in vestibular compensation process following unilateral labyrinthectomy in aged animals, and this may have clinical relevance in vestibular pathologies of peripheral origin that are associated to brain ageing.     

Effects of MK801 on Fos expression in the rat brainstem after unilateral labyrinthectomy

Unilateral labyrinthectomy (UL) causes ocular and postural asymmetries, which disappear over time in the processes of equilibrium recovery known as vestibular compensation. It has been reported that N-methyl-D-aspartate (NMDA) receptors are involved in vestibular compensation. In the present study, in order to elucidate the NMDA receptor-mediated neural circuit responsible for the development of vestibular compensation, we used Fos expression as a marker of neural activation and examined the effects of MK801, a specific antagonist of NMDA receptors, on UL-induced Fos expression in the rat brainstem. After UL, Fos-like immunoreactive (-LIR) neurons were observed in the ipsilateral medial vestibular nucleus (ipsi-MVe), the contralateral prepositus hypoglossal nucleus (contra-PrH) and the contralateral inferior olive beta subnucleus (contra-IOb). Fos-LIR neurons gradually disappeared in the processes of vestibular compensation. It is suggested that the activation of the ipsi-MVe, the contra-PrH and the contra-IOb neurons after UL are the initial event of vestibular compensation. Intraperitoneal injection of MK801 in the processes of vestibular compensation caused reappearance of UL-induced behavioral deficits. During the decompensation induced by MK801, Fos-LIR neurons appeared in the contra-MVe, the ipsi-PrH and the bilateral-IOB. It is suggested that the contra-MVe, the ipsi-PrH and the bilateral-IOb neurons are inhibited by glutamatergic synapses driving inhibitory neurons via NMDA receptors in the processes of vestibular compensation and that disinhibition of these nuclei induced by MK801 causes decompensation. However, MK801 caused neither Fos expression nor behavioral decompensation after vestibular compensation is accomplished. All these findings that the NMDA receptor-mediated inhibitory modulation in the central vestibular system plays an important role for the initial processes of the development of vestibular compensation.     

Ocular tilt reaction associated with a sudden idiopathic unilateral peripheral cochleovestibular loss

We recently observed a female patient who was suffering from acute right peripheral cochleovestibular loss associated with a marked vertical diplopia. Otoneurological examination showed profound deafness, and absence of nystagmic response to caloric and pendular rotatory test in the right ear. Neuroophthalmological examination showed skew deviation with right hypotropia, excyclotorsion, and tilt of the static visual vertical directed to the right side. Immunological and serological examinations were normal. Neurological examination and extensive neuroradiological investigations failed to demonstrate any central nervous system involvement. In this patient, skew deviation and tilt of the static visual vertical were interpreted as signs of an acute unilateral otolithic dysfunction, due to a sudden idiopathic peripheral vestibular loss.     

Weekly CAF chemotherapy for advanced breast cancer patients

BACKGROUND: Seromas and impaired shoulder function are well-known complications after modified radical mastectomy for breast cancer. Early postoperative physiotherapy is a common treatment to avoid shoulder dysfunction. The aim of this study was to evaluate if the frequency of postoperative seromas could be reduced, without increasing shoulder dysfunction, by delayed postoperative shoulder exercises. METHODS: In a prospective study 163 patients with breast cancer undergoing modified radical mastectomy were randomized to physiotherapy starting on postoperative day 1 or day 7. Patients were seen by the surgeons and the physiotherapists during hospital stay and in the outpatient department. Seromas and other complications were registered by the surgeons. The physiotherapists instructed the patients pre- and postoperatively and assessed shoulder function. RESULTS: There was a significantly higher incidence of postoperative seromas in the group of patients that started physiotherapy postoperative day 1 (38%) compared to the group that started physiotherapy postoperative day 7 (22%) (p < 0.05). There was no significant difference between the groups in the late outcome of shoulder function. CONCLUSION: The incidence of seromas after modified radical mastectomy for breast cancer is reduced by delaying shoulder exercises one week postoperatively. Earlier postoperative physiotherapy is not necessary to avoid impaired shoulder function.     

Transient changes in flocculonodular lobe protein kinase C expression during vestibular compensation

Protein kinase C (PKC) is a family of intracellular signal transduction enzymes, comprising isoforms that vary in sensitivity to calcium, arachidonic acid, and diacylglycerol. PKC isoforms alpha, gamma, and delta are expressed by cerebellar Purkinje cells and neurons in the cerebellar nuclei and vestibular nuclei of the Long-Evans rat. In control rats, these PKCs are distributed symmetrically in the flocculonodular-lobe Purkinje cells. Behavioral recovery from vestibular dysfunction produced by unilateral labyrinthectomy (UL) is accompanied by asymmetric expression of PKC isoforms in these regions within 6 hr after UL. These expression changes were localized within parasagittal regions of the flocculus and nodulus. The distribution of PKCalpha, -gamma, and -delta were identical, suggesting that they are coregulated in cerebellar Purkinje cells during this early compensatory period. The pattern of Purkinje cell PKC expression returned to the control, symmetric distribution within 24 hr after UL. It is hypothesized that these regional changes in Purkinje cell PKC expression are an early intracellular signal contributing to vestibular compensation. In particular, regulation of PKC expression may contribute to changes in the efficacy of cerebellar synaptic plasticity during the acute post-UL period.     

Overtraining and immune system: a prospective longitudinal study in endurance athletes

A prospective longitudinal study investigated for 19 +/- 3) months whether immunophenotypes of peripheral leukocytes were altered in periods of severe training. Leukocyte membrane antigens (CD3, CD4, CD8, CD14, CD16, CD19, CD45, CD45RO, and CD56) of endurance athletes were immunophenotyped (dual-color flow cytometry) and list mode data analyzed by a self-learning classification system in a state of an overtraining syndrome (OT; N = 15) and several occasions without symptoms of staleness (NS; N = 70). Neither at physical rest nor after a short-term highly intensive cycle ergometer exercise session at 110% of the individual anaerobic threshold did cell counts of neutrophils, T, B, and natural killer cells differ between OT and NS. Eosinophils were lower during OT, activated T cells (CD3+HLA/DR+) showed slight increases (NS: 5.5 +/- 2.7; OT 7.3 +/- 2.4% CD3+ of cells; means +/- SD; P < 0.01) during OT without reaching pathological ranges. The cell-surface expression of CD45RO (P < 0.001) on T cells, but not cell concentrations of CD45RO+ T cells, were higher during OT. OT could be classified with high specificities (92%) and sensitivities (93%). It is concluded that OT does not lead to clinically relevant alterations of immunophenotypes in peripheral blood and especially that an immunosuppressive effect cannot be detected. Immunophenotyping may provide help with the diagnosis of OT in future, but the diagnostic approach presented here requires improvements before use in sports medicine practice is enabled.     

Thoracic actinomycosis: CT findings

PURPOSE: To characterize computed tomographic (CT) findings of thoracic actinomycosis. MATERIALS AND METHODS: Chest CT scans and radiographs obtained in 22 patients with histopathologically proved thoracic actinomycosis were retrospectively reviewed. All patients were immunocompetent; they were aged 12-73 years (mean, 42.6 years; 14 male, eight female). CT findings were correlated with histopathologic findings in nine patients who underwent surgery (lobectomy [n = 8] or segmental resection [n = 1]). RESULTS: All of the lesions were unilateral, with an average diameter of 6.5 cm (range, 2-12 cm). Patchy air-space consolidation (n = 20) or a mass (n = 2) was seen on CT scans. Fifteen (75%) of the 20 patients with air-space consolidation had central areas of low attenuation (5-30 mm in diameter) within the consolidation. Thirteen of the 15 patients underwent contrast medium-enhanced CT. Ten (77%) of the 13 patients showed ring-like rim enhancement. Adjacent pleural thickening was seen in 16 patients (73%). At histopathologic examination, central low-attenuation areas at CT were seen as microabscesses with sulfur granules or a dilated bronchus that contained inflammatory cells and Actinomyces colonies. Peripheral enhancement of the low-attenuation areas was wall of the microabscess or surrounding parenchyma composed of granulation tissue rich in vascularity. CONCLUSION: Findings of chronic segmental air-space consolidation that contained low-attenuation areas with peripheral enhancement or adjacent pleural thickening at CT were suggestive of thoracic actinomycosis.     

Ductectatic mucinous cystic neoplasms of the pancreas: evaluation with MR cholangiopancreatography

OBJECTIVE: The aim of the present study was to investigate the efficacy of two frequently used physiotherapies (PTs) for the removal of bronchial secretions in cystic fibrosis (CF) lung disease: autogenic drainage (AD) and the Flutter (Desitin in Germany). AD is believed to improve mucus clearance from peripheral to central airways due to airway caliber changes in combination with a special breathing technique. The Flutter is an easy-to-use physiotherapy device based on oscillations of a steel ball during expiration through a pipe-type device. MATERIALS AND METHODS: To evaluate the acute and chronic physiotherapy effects of these two techniques, 14 CF patients underwent either twice daily AD or Flutter treatment for 4 consecutive weeks in a randomized crossover design. Prior to each therapy interval, for a 1-week wash-out period, no PT was administered, but patients continued regular medication. At the beginning and end of each 4-week interval, pulmonary function was measured before and after an acute 30-min therapy. At the end of the PT session, sputum was collected, weighed, and deep frozen until analyzed. The viscoelasticity of the sputum was evaluated using a magnetic microrheometer. RESULTS: No significant changes were noted for FVC, FEV1, or sputum volume throughout the study. Sputum viscoelasticity (rigidity index), however, was significantly lower (p<0.01) after therapy with the Flutter in comparison with AD, predicting improvements in mucociliary and cough clearability of the secretions. In a companion in vitro experiment, oscillations generated by passing humidified air over CF sputum lining an acrylic tube connected to a Flutter de-ice were found to decrease sputum elasticity, as measured by a filancemeter. These findings suggest that applied oscillations are capable of decreasing mucus viscoelasticity within the airways at frequencies and amplitudes achievable with the Flutter device, and provide direct evidence that PT can reduce the viscoelasticity of sputum.     

Metabolic sequelae of pancreatic transplantation using two different surgical techniques

BACKGROUND: By transplantation of the pancreas in diabetics type 1 long-term-term independence on exogenous insulin can be achieved. The extent of normalization of the carbohydrate metabolism can depend on the applied surgical technique. The objective of the submitted work was to compare indicators of compensation of diabetes one year after combined transplantation of the kidney and pancreas, using the method of transplantation of a segment of the pancreas with obliteration of the pancreatic duct by a polymer and the method of transplantation of the whole pancreas with drainage of the pancreatic duct into the urinary bladder. METHODS AND RESULTS: The authors examined two groups of recipients, 13 subjects each with full function of the pancreatic graft one year after transplantation where a combined transplantation of the kidney and pancreatic segment (group SP) had been performed or of the kidney and whole pancreas (group CP). The authors investigated the blood sugar level, glycated haemoglobin, intravenous glucose tolerance test, free insulin level and C-peptide as well as some indicators of the lipid metabolism and acid base balance. In both groups normal blood sugar levels were achieved, though the mean values in the course of the day were higher in group SP than in group CP (mean +/- SE 5.48 +/- 0.11 as compared with 4.98 +/- 0.09; p < 0.01). Glycated haemoglobin declined in group SP from the pretransplantation value of 9.31 +/- 0.09 to 6.40 +/- 0.10% and in group CP from 9.49 +/- 0.15 to 4.92 +/- 0.08%. In group CP the glycated haemoglobin after transplantation was significantly lower (p < 0.01), similarly as the coefficient of glucose assimilation (1.83 +/- 0.03 as compared with 1.25 +/- 0.15; p < 0.05). Indicators of the acid base balance did not differ. Recipients in group CP were however permanently treated with bicarbonate. CONCLUSIONS: With both transplantation method it is possible to achieve compensation of diabetes close to normal. The carbohydrate tolerance is however better after transplantation of the whole pancreas.