Sensorimotor integration is affected by acute whole-body vibration: a coherence study.

Introduction: Several whole-body vibration (WBV) effects on performance have been related to potential changes in the neural drive, motor unit firing rate, and sensorimotor integration. In the present paper, motor unit coherence analysis was performed to detect the source of neural modulation based on the frequency domain. Methods: Thirteen men [25 ± 2.1 years; Body Mass Index (BMI) = 23.9 ± 1.3 kg m2; maximal voluntary force (MVF): 324.36 ± 41.26 N] performed sustained contractions of the Tibialis Anterior (TA) at 10%MVF before and after acute WBV. The vibrating stimulus was applied barefoot through a platform to target the TA. High-Density surface Electromyography (HDsEMG) was used to record the myoelectrical activity of TA to evaluate coherence from motor unit cumulative spike-trains (CSTs). Results: Mean coherence showed a significant decrease in the alpha and low-beta bandwidths (alpha: from 0.143 ± 0.129 to 0.132 ± 0.129, p = 0.035; low-beta: from 0.117 ± 0.039 to 0.086 ± 0.03, p = 0.0001), whereas no significant changes were found in the other ones (p > 0.05). The discharge rate (DR) and the Force Covariance (CovF%) were not significantly affected by acute WBV exposure (p > 0.05). Discussion: According to the significant effects found in alpha and low-beta bandwidths, which reflect sensorimotor integration parameters, accompanied by no differences in the DR and CovF%, the present results underlined that possible neural mechanisms at the base of the previously reported performance enhancements following acute WBV are likely based on sensorimotor integration rather than direct neural drive modulation.

The acute effects of whole-body vibration on motor unit recruitment and discharge properties.

Introduction: several studies have reported improved neuromuscular parameters in response to whole-body vibration (WBV). This is likely achieved by modulation of the central nervous system (CNS). Reduced recruitment threshold (RT), which is the % of Maximal Voluntary Force (%MVF) at which a given Motor Unit (MU) is recruited, may be responsible for the force/power improvements observed in several studies. Methods: 14 men (25 ± 2.3 years; BMI = 23.3 ± 1.5 kg m2 MVF: 319.82 ± 45.74 N) performed trapezoidal isometric contractions of the tibialis anterior (TA) at 35-50-70 %MVF before and after three conditions: WBV, STAND (standing posture), and CNT (no intervention). The vibration was applied through a platform for targeting the TA. High-density surface electromyography (HDsEMG) recordings and analysis were used to detect changes in the RT and Discharge Rate (DR) of the MUs. Results: Mean motor unit recruitment threshold (MURT) reached 32.04 ± 3.28 %MVF before and 31.2 ± 3.72 %MVF after WBV, with no significant differences between conditions (p > 0.05). Additionally, no significant changes were found in the mean motor unit discharge rate (before WBV: 21.11 ± 2.94 pps; after WBV: 21.19 ± 2.17 pps). Discussion: The present study showed no significant changes in motor unit properties at the base of neuromuscular changes documented in previous studies. Further investigations are needed to understand motor unit responses to different vibration protocols and the chronic effect of vibration exposure on motor control strategies.

Ocular surface involvement in patients with neurofibromatosis type 1 syndrome.

PURPOSE: The aim of this study is to evaluate ocular surface morphological and functional changes in patients with neurofibromatosis type 1 (NF1). METHODS: Twenty-eight patients with NF1 and 14 healthy subjects were included in this study. All participants underwent a medical history collection, a complete ophthalmological examination including slit lamp exam and assessment of best-corrected visual acuity (BCVA), corneal sensitivity, and lacrimal function (Schirmer test and fluorescein tear break-up time test). Corneal nerves' morphology and endothelial cells density were evaluated by in vivo corneal confocal microscopy (IVCM). Tear and conjunctiva epithelium samples were collected to evaluate nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) tear levels and conjunctival expression of their receptors TrkA and p75NTR. RESULTS: Patients with NF1 showed a significant decrease of FTBUT when compared with healthy subjects (p < 0.001). Corneal sensitivity was ≤ 50 mm in 46% of NF1 patients. IVCM showed a significant increase of corneal nerve branching and of corneal endothelial cells density. No significant difference was observed between the two groups on NGF and BDNF tear levels and conjunctival expression of their receptors. CONCLUSION: This study demonstrated the presence of ocular surface changes in NF-1 patients including decrease of tear stability and of corneal sensitivity. Patients with NF1 also showed changes of corneal endothelial cells' density.

Clinical and Epidemiological Study on Tubercular Uveitis in a Tertiary Eye Care Centre in Italy.

PURPOSE: To describe frequency, clinical characteristics, and visual prognosis of tubercular uveitis (TBU) in a nonendemic country. METHODS: We retrospectively reviewed 3743 charts of patients with endogenous uveitis visited from 2008 to 2018 at a tertiary referral centre in Rome, Italy. We included immunocompetent patients with diagnosis of TBU. Patients were divided in two groups: patients with history of uveitis without a previous diagnosis of TBU (group A) and patients at their first episode of TB uveitis (group B). RESULTS: TBU was diagnosed in 28 (0.75%) out of 3743 patients. Twelve (42.9%) patients came from tuberculosis endemic areas. All patients received specific antitubercular treatment (ATT) and were evaluated for a mean follow-up of 3.2 ± 2.9 years. Group A showed a greater number of ocular complications when compared with group B. ATT was effective in reducing the frequency of recurrences of uveitis in patients of group B. CONCLUSION: Intraocular inflammation can be the first manifestation of tuberculosis. Our data highlight that early diagnosis and specific treatment of TBU may allow to decrease recurrences and to improve visual outcomes.

Allergic conjunctivitis: current concepts on pathogenesis and management.

Allergic conjunctivitis (AC) includes a wide spectrum of clinical entities characterized by different incidence, age of onset, natural course, clinical outcome and response to treatment. Taken together, they represent one of the most frequent ocular surface diseases affecting more than 30% of the young-adult population and show an increasing incidence over the years. Moreover, comorbidities with other systemic atopic conditions such as asthma, atopic dermatitis and rhinitis require a multidisciplinary approach. Recent advances in the knowledge of the pathogenic mechanism overcome the classic role of type I hyper-sensitivity and mast cells’ activation, demonstrating an involvement of innate immunity and neuroinflammation in the pathogenesis of the most severe forms such as atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC). Ocular itching, swelling and tearing are the most frequent symptoms complained by patients with all forms of AC, while photophobia and pain are typical of the most severe forms, such as VKC and AKC, due to the frequent corneal involvement. Upper tarsal papillary reaction represents the main clinical sign of AC associated with conjunctival hyperemia and mucous secretion. Diagnosis is based on clinical history and eye evaluation and can be confirmed through allergological tests. Additional ocular exams include specific allergen conjunctival provocation tests and the presence of eosinophils in the conjunctival scraping. Current treatments of AC include the use of antiallergic eye drops for mild forms, while recurrences of ocular surface inflammations with corneal involvement in severe forms require the use of topical steroids to avoid visual impairment. Novel steroid sparing therapies such as Cyclosporine A eye drops or topical Tacrolimus have been proposed to improve VKC and AKC management.

Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study.

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper-connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC). PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed. RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper-connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices). CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep.

Role of Water Sorption in Tablet Crushing Strength, Disintegration, and Dissolution.

Drugs formulated as tablets are subjected to accelerated stability conditions with the goal of identifying a stable formulation that will exhibit a sufficiently long shelf life. Water sorption at a condition such as 40°C/75% RH can result in significant changes in tablet properties such as a decrease in dissolution rate, the cause of which may be difficult to interpret, given the complex nature of ingredients and their interactions in a tablet. In this research, three drugs, displaying a wide range of physicochemical properties, were formulated with commonly used diluents, disintegrants, and binders, using a design of experiments approach. The tablets were stored at accelerated conditions and assessed for content, dissolution, disintegration, and crushing strength, as well as other properties. The research demonstrated many water-induced effects in tablet properties. Due to the experimental design approach that revealed many interactions, it was possible to interpret all of the changes observed in tablet crushing strength, disintegration, and dissolution for the drugs using a common set of physical principles. Specifically, the relevant factors considered were (1) mechanical properties of materials, (2) water sorption surface effects in surface diffusion and capillary condensation, (3) water sorption bulk effects for amorphous materials such as viscous flow/spreading, and (4) water-induced stress on interparticle bonding arising from volume expansion. These physical principles enable a comprehensive interpretation of the complex changes observed in tablet properties, which should be valuable in the design of tablet formulations that will be stable to accelerated storage conditions.

Cenegermin for the treatment of neurotrophic keratitis.

The trigeminal nerve provides corneal sensitivity and trophic supply to corneal tissues. The impairment of corneal innervation leads to development of neurotrophic keratitis (NK). NK is a rare, degenerative corneal disease characterized by corneal hypo/anesthesia and development of nonhealing corneal epithelial defects and ulcers. NK is a challenging condition with high medical need due to the lack of approved treatments that can restore corneal integrity. Current treatment of NK aims at stimulating corneal healing and preventing disease progression. Cenegermin is a recombinant human nerve growth factor that was safe and well tolerated in preclinical and clinical studies. Cenegermin eye drops were safe and effective in restoring corneal integrity in two phase II clinical trials in patients with NK. The European Commission granted a full marketing authorization to cenegermin eye drops for the treatment of moderate to severe NK in July 2017.

The culturally adapted Italian version of the Barthel Index (IcaBI): assessment of structural validity, inter-rater reliability and responsiveness to clinically relevant improvements in patients admitted to inpatient rehabilitation centers.

The Barthel Index (BI) is widely used to determine eligibility criteria for inpatient rehabilitation and to monitor patients' recovery, irrespective of the illnesses that affect them. The culturally adapted Italian version of the Barthel Index (IcaBI) was recently validated. This paper reports the structural validity and inter-rater reliability of the IcaBI and its responsiveness to the results of inpatient rehabilitation. The IcaBI was administered to a cohort of 264 patients hospitalized in two rehabilitation centers in Rome, Italy. Factor analysis using principal component analysis revealed a monofactorial structure for neurological patients and, after removal of item 1 "feeding", also for orthopedic patients. Substantial to optimal inter-rater reliability was found (0.74 > intraclass correlation coefficient < 0.96). The IcaBI was found to be accurate (area under the curve= 0.72) with a minimal clinically important change score of 35 points. This work confirms that IcaBI is a useful tool for measuring disability in health and social care settings along the continuum of care. Further studies are needed to assess its criterion validity, interpretability and responsiveness in other specific disease conditions.

Effect of exercise training on neuromuscular function of elbow flexors and knee extensors of type 2 diabetic patients.

PURPOSE: The effects of exercise training on neuromuscular function of arm and leg muscles in type 2 diabetic patients (T2D) was investigated. METHODS: Eight T2D sedentary male patients (61.0±2.3years) and eight sedentary healthy age matched control subjects (H, 63.9±3.8years) underwent a 16-week supervised combined endurance and resistance exercise program. Before and after training, maximal isometric (MVIC), isokinetic (15, 30, 60, 120, 180, 240°s(-1)) torque and muscle endurance of the elbow flexors (EF) and knee extensors (KE) were assessed. Simultaneously, surface electromyographic signals from biceps brachii (BB) and vastus lateralis (VL) muscles were recorded and muscle fiber conduction velocity (MFCV) estimated. RESULTS: Following training, maximal torque of the KE increased during MVIC and isokinetic contractions at 15 and 30°s(-1) in the T2D (+19.1±2.7% on average; p<0.05) but not in the H group (+7±0.9%; p>0.05). MFCV recorded from the VL during MVIC and during isokinetic contractions at 15 and 30°s(-1) increased (+11.2±1.6% on average; p<0.01), but in the diabetic group only. Muscular endurance was lower in T2D (20.1±0.7s) compared to H (26.9±1.3s), with an associated increase in the MFCV slope after training in the KE muscles only. CONCLUSION: The effect of a combined exercise training on muscle torque appears to be angular velocity-specific in diabetic individuals, with a more pronounced effect on KE muscles and at slow contraction velocities, along with an associated increase in the MFCV. MFCV appears to be a more sensitive marker than torque in detecting the early signs of neuromuscular function reconditioning.

Are stroke cases affected by sleep disordered breathings all the same?

Sleep disordered breathings (SDB) worsens the clinical prognosis of stroke patients. Continuous positive airway pressure (CPAP) is a promising effective treatment. Unfortunately, not all patients are compliant with CPAP, suggesting that it is not appropriate for all patients with obstructive sleep apnoea (OSA) after stroke. People with the highest likelihood of benefiting have to be identified. We present a classification of cases with stroke and SDB to be adopted in order to identify the best responders to CPAP treatment. We propose to classify patients in four subgroups: (1) patients who terminate the apnoea by arousing from sleep; these cases are those affected either by an anatomical or a functional obstruction of upper airways that may precede or are the consequence of stroke; (2) cases that alternate OSA to central sleep apnoea (CSA) cause of an altered loop gain; (3) cases in whom ischemic damages have altered the sleep microstructure (CAP); (4) cases that manifest a CSA as the direct consequence of stroke on the central neuronal drive to breath. So far, no study has investigated the consequences of stroke on sleep microstructure. In order to better elucidate these relationships, when reviewing the PSG tracings of stroke patients, the microstructure of sleep should be systematically analysed.

Correlates of muscle strength in diabetes: The study on the assessment of determinants of muscle and bone strength abnormalities in diabetes (SAMBA).

BACKGROUND AND AIMS: Apart from late motor nerve dysfunction, factors affecting muscle strength in diabetes are largely unknown. This study was aimed at assessing muscle strength correlates in diabetic subjects encompassing a wide range of peripheral nerve function and various degrees of micro and macrovascular complications. METHODS AND RESULTS: Four-hundred consecutive patients with type 1 and 2 diabetes (aged 46.4 ± 13.9 and 65.8 ± 10.3 years, respectively) from the Study on the Assessment of Determinants of Muscle and Bone Strength Abnormalities in Diabetes (SAMBA) were examined for upper and lower body muscle isometric maximal voluntary contraction by dynamometry. Univariate and multivariate regression analyses were applied to identify strength correlates. Isometric force at both the upper and lower limbs was significantly lower in subjects with than in those without any complication. At univariate analysis, it was strongly associated with age, diabetes duration, physical activity (PA) level, cardio-respiratory fitness, anthropometric parameters, surrogate measures of complications, and parameters of sensory and autonomic, but not motor (except amplitude) neuropathy. Multivariate analysis revealed that upper and lower body strength correlated independently with male gender and, inversely, with age, autonomic neuropathy score (or individual autonomic function abnormalities), and vibration perception threshold, but not sensory-motor neuropathy score. Diabetes duration and PA level were excluded from the model. CONCLUSIONS: Both upper and lower body muscle strength correlate with measures of diabetic complications and particularly with parameters of sensory and especially autonomic nerve function, independently of diabetes duration and PA level, thus suggesting the involvement of mechanisms other than manifest motor nerve impairment.

Cardio-respiratory and electromyographic responses to ergometer and on-water rowing in elite rowers.

The aim of this study was to compare muscle activation and cardio-respiratory response during ergometer and on-water rowing. Nine internationally competitive rowers (five Olympic Games medal winners, age 25.6 ± 4.8 years) were requested to perform a 1,000 m race simulation test in the two conditions. Surface electromyographic (sEMG) signals from trapezius superior (TRS), latissimus dorsi (LD), biceps brachii (BB), rectus femoris (RF), vastus medialis (VAM), vastus lateralis (VAL), biceps femoris (BF) and tibialis anterior (TA) muscles were recorded continuously during the tests together with other cardio-respiratory parameters: heart rate (HR), ventilation (VE), oxygen consumption (VO2). On-water, subjects covered the same distance in a longer time (218.4 ± 3.8 s vs. 178.1 ± 5.6 s during ergometer test). TRS, LD, BB, RF, VAM and VAL muscle activation on-water was lower than off-water during the rowing race. VO2 and VE responses were similar between the two conditions even if the time to complete the 1,000 m race simulation test was higher on-water. The results indicate that for most of the analyzed muscles EMG activation on the ergometer is higher than on-water with the maximal activity at the beginning of the on-water test due reasonably to overcome the forces opposing the forward motion, while the ergometer task elicited increasing muscle activation over time. The present data may be considered by coaches when choosing a rowing ergometer in substitution for the training on-water or when relying on the indoor tests to select the crew.

Post stroke sleep apnea hypopnea syndrome: a series of 12 consecutive stable stroke cases.

OBJECTIVES: Sleep Disordered Breathing (SDB) is a negative prognostic factor for stroke patients. In order to reveal: (1) the frequency of Sleep Apnea-Hypopnea Syndrome (SAHS) in the stable phase of the illness; (2) the type of SAHS, either obstructive (OSAHS) or central (CSAHS); (3) the possible association between SAHS and daily sleepiness, cardiac arrhythmias, stroke / TIA recurrence and location of the brain lesion, an observational study is on-going at Sapienza University of Rome. We report here the results of cases included in the feasibility study. PATIENTS AND METHODS: clinical evaluations, brain images and polisomnographic study were performed at discharge and after 4 and 9 months of stroke. RESULTS: Eleven out of the 12 patients included (91.6%) had an Apnea/Hypopnea Index-AHI >= 5. In 5 cases, the majority of total respiratory events were purely central in origin. In 3 of these 5 cases, a concomitant obstruction of the upper airways was revealed; the 2 remaining had risk factors for OSAHS (smoke, hypertension, BMI > 25). A significant association was found between central apnea/hypopnea events and cardiac arrhythmias (p value 0.017). CONCLUSIONS: These findings confirm the high prevalence of SDB, either obstructive or/and central, even in the stable phase of the illness, which in those patients who had accumulated risk factors for OSAHS result in Complex-sleep apnea/hypopnea syndrome (CompSAHS). As patients with CompSAHS are left with very disrupted breathing on continuous positive airway pressure, in order to select cases with stable stroke who benefit from continuos-positive airway pressure (C-PAP) treatment, further and more detailed clinical studies are needed to better distinguish CompSAHS from mixed SAHS.

Mitochondrial DNA haplogroups and mutations in children with acquired central demyelination.

OBJECTIVE: We investigated mitochondrial DNA (mtDNA) variants in children with a first episode of acquired demyelinating syndromes (PD-ADS) of the CNS and their relationship to disease phenotype, including subsequent diagnosis of multiple sclerosis (MS). METHODS: This exploratory analysis included the initial 213 children with PD-ADS in the prospective Canadian Pediatric Demyelinating Study and 166 matched healthy sibling controls from the Canadian Autism Genome Project. A total of 31 single nucleotide polymorphisms (SNPs) were analyzed, including haplogroup-defining SNPs and mtDNA variants previously reported to be associated with MS. RESULTS: Primary Leber hereditary optic neuropathy (LHON) mutations and other known pathogenic mtDNA mutations were absent in both patients with pediatric acquired demyelinating syndromes and controls. The 13708A haplogroup J-associated variant, previously linked to adult MS, was more frequent among subjects with PD-ADS (13.0%) compared to controls (6.2%; odds ratio [OR] 2.27; 95% confidence interval [CI] 1.06 to 4.83) and haplogroup M was associated with an earlier age at onset of PD-ADS (-1.74 years; 95% CI -3.33 to -0.07). In contrast, the haplogroup cluster UKJT, as well as 3 other SNPs, were each associated with a lower risk of PD-ADS. A total of 33 subjects with PD-ADS were diagnosed with MS during a mean follow-up period of 3.11 ± 1.14 (SD) years. No single SNP was associated with the risk of subsequent diagnosis of MS. However, haplogroup H was associated with an increased risk of MS (OR 2.60; 95% CI 1.21 to 5.55). CONCLUSION: These data suggest an association between mtDNA variants and the risk of PD-ADS and of a subsequent MS diagnosis. Replication of these findings in an independent population of subjects with PD-ADS is required.

Muscle fibre conduction velocity and cardiorespiratory response during incremental cycling exercise in young and older individuals with different training status.

We investigated the effect of ageing and training on muscle fibre conduction velocity (MFCV) and cardiorespiratory response during incremental cycling exercise. Eight young (YT; 24+/-5 yrs) and eight older (OT; 64+/-3 yrs) cyclists, together with eight young (YU; 27+/-4 yrs) and eight older (OU; 63+/-2 yrs) untrained individuals underwent to an incremental maximal test on a cycle ergometer. Ventilatory threshold (VT), respiratory compensation point (RCP) and maximal oxygen uptake (VO(2)max) were identified and MFCV recorded from the vastus lateralis muscle using surface electromyography with linear arrays electrodes. In YT MFCV increased with the exercise intensity, reaching a peak of 4.99+/-1.02 [m/s] at VT. Thereafter, and up to VO(2)max, MFCV declined. In YU MFCV showed a similar trend although the peak [4.55+/-0.53m/s] was observed, at 75% of VO(2)max an intensity higher than VT (66% of VO(2)max). In both YT and YU MFCV did not decline until RPC, which occurred at 78% VO(2)max in YU and at 92% VO(2)max (P<0.01) in YT. Differently from young individuals, MFCV in older subjects did not increase with exercise intensity. Moreover, maximal MFCV in OU was significantly lower [3.53+/-0.40 m/s;] than that of YT (P<0.005) and YU (P<0.05). The present study shows that, especially in young individuals, MFCV reflects cardiorespiratory response during incremental dynamic cyclic exercise and hence can be used to investigate motor unit recruitment strategies.

Emamectin benzoate: new insecticide against Helicoverpa armigera.

Emamectin benzoate is a new insecticide of Syngenta Crop Protection, with a new mechanism of action and a strong activity against Lepidoptera as well as with and a high selectivity on useful organisms. This molecule acts if swallowed and has some contact action. It penetrates leaf tissues (translaminar activity) and forms a reservoir within the leaf. The mechanism of action is unique in the panorama of insecticides. In facts, it inhibits muscle contraction, causing a continuous flow of chlorine ions in the GABA and H-Glutamate receptor sites. During 2006 and 2007, experimentation was performed by the Bioagritest test facility, according to EPPO guidelines and Principles of Good Experimental Practice (GEP), aiming at establishing the biological efficacy and the selectivity of Emamectin benzoate on industry tomato against Helicoverpa armigera (Lepidoptera: Noctuidoe). The study was performed in Tursi-Policoro (Matera), southern Italy. Experimental design consisted in random blocks, in 4 repetitions. A dosage of 1.5 Kg/ha of the formulate was compared with two commercial formulates: Spinosad 0.2 kg/ha (Laser, Dow Agrosciences Italia) and Indoxacarb 0.125 kg/ha (Steward EC insecticide, Dupont). Three foliage applications were applied every 8 days. The severity of damage induced by H. armigera was evaluated on fruits. Eventual phytotoxic effects were also evaluated. Climatic conditions were optimal for Lepidoptera development, so that the percentage of fruits attacked in 2007 at the first scouting was 68.28%. Emamectin benzoate has shown, in two years of testing, a high control of H. armigera if compared with the standards Indoxacarb and Spinosad. No effect of phytotoxicity was noticed on fruits.

Nonspecific provocation of target organs in allergic diseases: EAACI-GA(2)LEN consensus report.

It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli.

Upregulation of ICAM-1 expression in the conjunctiva of patients with chronic graft-versus-host disease.

PURPOSE: To correlate conjunctival intercellular adhesion molecule 1 (ICAM-1) expression with cytologic and clinical findings of chronic graft-versus-host disease (GVHD). METHODS: Seven patients with chronic GVHD-related keratoconjunctivitis and five age-matched normal controls were recruited for the study. Clinical examination included medical history, visual acuity, evaluation of ocular signs and symptoms (scored from 0 to 3), corneal fluorescein staining (scored from 0 to 5 on the basis of the number of corneal sectors involved), Schirmer test type I, and break-up time (BUT). Impression cytology samples were collected from the nasal and inferior bulbar conjunctiva of patients and controls. Goblet cells were counted in three randomly selected fields and averaged. Immunofluorescent staining for ICAM-1 was carried out and the percentage of cells expressing the marker was evaluated. RESULTS: All patients showed signs and symptoms of keratoconjunctivitis sicca. Schirmer test type I and BUT were reduced (4.8+/-6.7 mm/5 min and 3.9+/-2.7 seconds, respectively). Goblet cells were significantly reduced in GVHD eyes with respect to normal eyes (65+/-30.5 and 192+/-16.9 cells/field respectively; p<0.001). Goblet cell number was directly related to Schirmer test values (p<0.01, rho=0.817) and inversely related to total sign score (p<0.01, rho=-0.939). ICAM-1 expression was increased in GVHD eyes with respect to normal controls, in which no staining was observed. ICAM-1 expression showed an inverse relation to goblet cell number (p<0.01, rho=-0.852) and Schirmer test values (p<0.01, rho=-0.926), and was directly correlated to total sign score (p<0.01, rho=0.982). CONCLUSIONS: Conjunctival ICAM-1 expression is increased in GVHD patients. The severity of the disease is associated with tear parameters, goblet cell decrease, and inflammatory markers, such as ICAM-1.

Specific therapies for ischaemic stroke: rTPA and others.

In the last few years there have been several important advances in the understanding of cerebrovascular disorder pathophysiology that have impacted on stroke management. The development of timely and effective treatment strategies was and is still considered a high priority issue. Therapeutic options dramatically increased both in the prevention and overall in the treatment of acute ischaemic stroke (AIS). At present, whereas neuroprotection remains experimental, intravenous (i.v.) thrombolysis is the only specific therapy effective in reducing mortality and disability associated with stroke. The efficacy and safety of the antithrombotic therapy in AIS treatment are not well established, and few issues in clinical stroke management are more controversial. However, some studies have brought new light and new doubts on the roles of these traditional therapies.