The role of inflammation in diabetic retinopathy: a review.

OBJECTIVE: Diabetic retinopathy and diabetes represent serious health conditions, being considered among the main causes of blindness. In recent years, anti-VEGF therapies have been of great help in the treatment of retinal pathology and, until now, they represent the primary choice therapy for diabetic retinopathy. Nevertheless, many patients do not experience significant benefits of vision after an anti-VEGF monotherapy. For this reason, several researchers recently focused their attention on the mechanisms that play a central role in the development and progression of diabetic retinopathy. RESULTS: Available scientific evidence confirms that diabetic retinopathy requires other molecules capable of modifying the mechanisms that, together with angiogenesis, contribute to the development of the condition, such as vascular and neuroinflammation. CONCLUSIONS: This review summarizes the current knowledge of the pathological changes that occur in diabetic retinopathy and that might contribute to identify possible new strategies for the treatment of this condition.

Prediction of hearing recovery in sudden deafness treated with intratympanic steroids.

The present study aims to obtain a probability model allowing prediction of auditory recovery in patients affected by sudden sensorineural hearing loss treated exclusively with intratympanic steroids. A monocentric retrospective chart review of 381 patients has been performed. A Probit model was used to investigate the correlation between the success of treatment (marked or total recovery according to Furuashi's criteria) and the delay between onset of disease and beginning of therapy. The age of patients and audiometric curve shapes were included in the analysis. The results show that delay is negatively correlated with variable success. Considering the entire sample, each day of delay decreases the probability of success by 3%. The prediction model shows that for each day that passes from the onset of the disease the probability of success declines in absence of the medical treatment, hence we conclude that early treatment is strongly recommended.

Does focal mechanical stimulation of the lower limb muscles improve postural control and sit to stand movement in elderly?

BACKGROUNDS: Imbalance in elderly is a common problem strictly related to fall. AIMS: This study investigates the possibility that a new protocol based on the focal mechanical muscle vibration may improve balance and stability in elderly. METHODS: Pre-post non-randomized clinical trial has been used. Patients referring postural disequilibrium with negative vestibular bed-side examinations have been treated with focal muscle vibration applied to quadriceps muscles and evaluated before and immediately after therapy and after 1 week and after 1 month with postural stabilometric examination and with an inertial measurement units during the time up and go test. RESULTS: Stabilometric analysis showed statistically significant differences in both the area (p = 0.01) and sway (p < 0.01) of the center of pressure during the close eyes tests. Moreover, the global time of the time up and go test was reduced (p < 0.05) and the rotation velocity was increased (p < 0.01). CONCLUSIONS: The findings confirm the beneficial role of focal muscle vibration in elderly patients improve postural stability and mobility.

Does the addition of a second daily session of hyperbaric oxygen therapy to intratympanic steroid influence the outcomes of sudden hearing loss?

The aim of this study is to investigate whether, in addition to intratympanic steroid therapy, additional hyperbaric oxygen therapy (HBOT) sessions per day (twice a day for 5 days) is more useful than one session per day for 10 days in patients affected by severe and profound idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 55 patients affected by unilateral severe and profound ISSNHL were recruited. Two protocols were adopted. In the first, 27 patients (13 with profound and 14 with severe hearing loss) underwent one session of HBOT per day for 10 days, 6 days a week. An HBOT session comprised a period of 14 minutes air compression followed by 90 min at 2.4 atm absolute (ATA) followed by a decompression period of 15 min in oxygen. Patients breathed 100% oxygen through an appropriate mask checked for leaks. Patients were given 0.4 ml of 62.5 mg/ml of intratympanic prednisolone during the first three days of the protocol. In the second protocol, 28 patients (10 with profound and 18 with severe hearing loss) received 10 sessions of HBOT, twice a day for five days, 2.4 ATA 90 min 100% oxygen. The intratympanic injections of prednisolone were given between the two sessions of HBOT during the first three days of the protocol. Since there were no significant differences in hearing outcomes between the two protocols, the present study shows that the protocol of two sessions of HBOT per day is a valid treatment and equally effective as the one HBOT session per day, but with shorter treatment time.

Chronic cerebrospinal venous insufficiency in patients with Ménière's disease.

To analyze the presence of chronic cerebrospinal venous insufficiency parameter and vascular abnormalities, in the internal jugular veins (IJVs) and/or vertebral veins in sitting and supine posture, in patients with Meniere's disease compared to healthy general population. A prospective study on 32 patients affected by definite Ménière was performed from February 2012 to January 2013. All subjects underwent an echo-color Doppler examination of the cerebrospinal venous flow. 21 of the 32 Menieric patients showed a statistically significant reflux in the intracranial veins versus healthy (65.6 vs 25%; P < 0.001). A high prevalence of IJVs stenosis with hemodynamic changes (increased velocity or absence of flow) was observed (66.7 vs 33.3%; P < 0.05). The other parameters considered did not show statistically significant differences among the two groups. The results obtained showed a vascular pattern of cerebrospinal venous system present in patients affected by definite Meniere. This vascular impairment significantly affects the vascular areas more directly involved in the venous drainage of the inner ear. Thus venous stasis may be considered a further pathogenetic mechanism for development of Meniere's disease.

Contralateral implantation in children affected by postimplant meningitis.

This study was designed to investigate the indication and advantages of contralateral implantation after postimplant meningitis (piM). Speech perception assessment, most comfortable levels and high-resolution computer tomography were used to monitor cochlear fibrosis/ossification and clinical changes in outcomes in 5 children affected by meningitis after a variable-time post-cochlear implantation. Ipsilateral ossification was found in 3 children, 1 of whom developed delayed contralateral ossification. These children were implanted on the contralateral side as they all showed deterioration of hearing performance. Results from the present paper and literature analysis suggest that, (1) piM can induce ipsilateral and contralateral ossification, (2) meningitis-induced cochlear ossification is more prone to develop in the presence of a normal cochlear structure and (3) contralateral implantation after piM has proven to be effective in restoring performance when a full electrode insertion is accomplished.

3D cone beam (CBCT) in evaluation of frontal recess: findings in youth population.

BACKGROUND: Frontal recess is the anatomical region most difficult to manage in endoscopic frontal sinus surgery due to the extreme variability of the cell patterns that may be observed in this area. CT has always been the gold standard in preoperative evaluation, but especially in the assessment of the causes of frontal recess obstruction and surgical failure. In recent years, this accredited and reliable method has been complemented by computed tomography cone beam (CBCT), which provides similarly detailed anatomical information with a lower dose of radiation. AIM: The purpose of this paper is to analyze and validate the use of CBCT in the study of frontal recess, and especially its anatomical variants in a youth population. MATERIALS AND METHODS: We analyzed 500 CBCT images of paranasal sinuses of young subjects with sinus inflammation pathology between 2009 and 2011. RESULTS: We observed that the method is very sensitive in detecting anterior and posterior recess cells, also in a youth population and then report on some significant images. CONCLUSIONS: We confirm the validity of CBCT, which by virtue of its sensitivity and specificity may be used in the analysis of frontal recess pathologies, especially when a young population is involved.

An experience on primary thinning and secondary debulking of anterolateral thigh flap in head and neck reconstruction.

OBJECTIVES: The antero-lateral thigh flap (ALTF) has become one of the workhorses of reconstructive procedures of the head and neck. The cosmetic result of this flap is uncertain during the main reconstructive procedure, so free flap contouring in head and neck reconstruction following cancer ablation is usually performed at the end of therapy. To obtain an adequate symmetry of the flap a safe thinning during the primary inset or a secondary defatting may be performed. PATIENTS AND METHODS: The study includes 45 patients underwent reconstruction with ALTF for head and neck tumors. Patients were divided into two groups: Group 1 (20 patients underwent a primary thinning of the flap), Group 2 (25 patient underwent a secondary debulking of the flap). Patients were evaluated in terms of total number of cosmetic reconstruction procedures performed, hospital stay and aesthetic satisfaction. RESULTS: Epidemiological analysis showed an average age of 51 years old in patients. Patients were affected by squamous cell carcinoma in 33 cases. Within Group 1, 14 patients underwent surgery only once, 5 underwent surgery twice and one patient three times. In group 2, 8 patients underwent surgery once, 10 patients twice, 3 patients three times and 4 patients four times. Considering total of hospital stay, the average length of stay was 18.83 days in the group of patients subjected to primary debulking, versus 23.67 days in the group subjected to secondary defatting. CONCLUSIONS: The ALT flap is a safe and reliable free flap for head and neck reconstructive surgery. As showed in the study and in previous reports, the thinning of the flap is a safe procedure, without increasing the flap complications and allowing an immediate symmetry of the recipient site contour. Furthermore, ALTF thinning reduces major defatting revisions requiring general anesthesia and the total number of secondary procedures.

Distortion product otoacoustic emissions in otosclerosis: intraoperative findings.

The aim of the study was to investigate changes in middle ear dynamic characteristics caused by both otosclerosis and stapes surgery (platinotomy, prosthesis positioning, ossicular chain maneuver) and to evaluate distortion product otoacoustic emissions (DPOAEs) before and following surgery. The study included 15 patients (12 women, 3 men; mean age 51 years; range 32-69 years) with advanced otosclerosis. All the patients were evaluated with the use of pure-tone audiograms (preoperatively, 5 and 30 days after surgery), stapedial reflexes (preoperatively), and DPOAE recordings (preoperatively, at the end of surgery, and 5 and 30 days after surgery). Changes in the hearing thresholds and in the DPOAE amplitudes were compared. Preoperative tests showed conductive hearing loss, with a mean air-bone gap of 36.6 dB HL ranging from 0.25 to 1 kHz, and no stapedial reflexes were detected. DPOAEs were not measurable preoperatively, and they were detected only in 2 patients at the end of surgery, with low amplitudes in a narrow frequency range. No significant changes occurred in DPOAEs 5 days postoperatively. A month after surgery, improvement in conductive hearing loss was observed; the mean air-bone gap from 0.25 to 1 kHz was 12.9 dB HL, whereas the higher frequencies were still affected by the disease. DPOAEs increased in amplitude in 4 patients, but this was not significant. It remains unclear why DPOAEs are not detected despite a subjective hearing improvement and a sufficiently closed air-bone gap at least in middle and low frequencies. The results of our study show that DPOAEs cannot replace behavioral threshold tests; they may only be included in a battery of tests for a complete clinical follow-up for efficiency monitoring after stapes surgery.

Extramedullary plasmacytoma of paranasal sinuses. A combined therapeutic strategy.

Extramedullary plasmacytoma of the head and neck region is a rare malignant tumour comprising approximately 3% of all plasma cell tumours. Approximately 80-90% of extramedullary plasmacytomas involve the Mucosa-Associated Lymphoid Tissue of the upper airways, 75% of these involve the nasal and paranasal regions. Radiotherapy is considered the treatment of choice, surgery being limited to biopsy and to excision of residual disease. A case of extramedullary plasmacytoma of the nasal cavity and ethmoid sinus is reported, in which surgical excision is followed by complementary radiotherapy on the site of the tumour.

Effect of superoxide dismutase and allopurinol on impulse noise-exposed guinea pigs--electrophysiological and biochemical study.

OBJECTIVE: To investigate the protective effect of two anti-reactive oxygen species (ROS) substances, copper-zinc superoxide dismutase (CuZn-SOD) and allopurinol, in impulse noise-exposed guinea pigs. MATERIAL AND METHODS: Allopurinol or CuZn-SOD were administered intraperitoneally before exposure to 125 dB SPL noise centered at 2.0-3.0 kHz, with a repetition rate of 4/s, for 1.8 h. Hearing thresholds were tested by means of electrocochleography after implanting the animals with permanent electrodes. The presence of lipoperoxides in the guinea pig cochleae exposed to noise-induced oxidative stress was determined by means of the dosage of malondialdhyde, evaluated by measuring the content of thiobarbituric acid reactive substances in perilymph samples. RESULTS: Acoustic stress induced ROS formation and both allopurinol and CuZn-SOD exerted a protective effect on the cochlea. Comparison of compound action potential thresholds in different animal groups showed that the temporary threshold shift was significantly lower in treated animals than in those without pharmacological protection. CONCLUSION: The protective effect of the antioxidant agents demonstrates that, even at a high level of impulse noise exposure, a metabolic mechanism of cochlear damage may still play an important role in noise-exposed sensorineural hearing loss.

Laser Doppler measurement of cochlear blood flow changes during conditioning noise exposure.

Using laser Doppler flowmetry, cochlear blood flow was assessed in Mongolian gerbils exposed to noise. Anesthetized animals were surgically implanted with permanent electrodes and then exposed for 10 consecutive days (6 h on/18 h off) to an octave band noise centered at 4 kHz (85 dB SPL). The auditory brainstem responses and the blood flow in the basal turn of the cochlea were compared with those of gerbils not exposed to noise. The exposed animals developed an initial threshold shift, followed by a progressive reduction in threshold shift up to complete recovery at the end of the test. In the exposed animals, a reduction in the cochlear blood flow during the first 4 days of exposure was observed, which was then followed by a progressive increase up to the end of the test. The results of this study exclude a possible role of the microvasculature of the lateral cochlear wall in determining the resistance to 4 kHz frequency noise exposure.

[Protective effect of allopurinol in the exposure to noise pulses]. / Effetto protettivo dell'allopurinolo nell'esposizione a rumore impulsivo.

Free oxygen radicals cause particularly severe tissues and organ damage. They appear to play an important role in the cochlea, mediating noise-exposure damage. In the present study 16 guinea pigs were implanted with permanent electrodes to record cochlear action potential. Eight animals were exposed to a 2-3 kHz, 125 dB SPL noise pulse, at a rate of 4 stimulations per second for 1.8 hours. Prior to noise exposure four out of eight animals were treated with a known dose of allopurinol. The remaining eight animals were used as controls. Endolymphatic malondialdehyde concentration was used as indicator of the lipid peroxidization processes exerted by the free radicals. No significant difference was found between the variations in hearing threshold and malondialdehyde concentration in the animals treated with allopurinol and then exposed to noise vs. the control group. The electophysiological and biochemical results have, therefore, demonstrated that preventative administration of allopurinol can provide valid protection vs. noise impulse damage.

Vestibular neurectomy in the guinea-pig: a retrosigmoid approach.

The efferent cochlear system, composed of both ipsi- and contralateral bundles, runs along with the vestibular nerve and may serve as protection for the inner ear. Sectioning of the vestibular nerve could thus create an experimental model for further in-depth study of such a protective role. A personal surgical approach is described, involving a suboccipital (or retrosigmoid) route to the postero-medial aspect of the guinea-pig temporal bone, chosen because of its use for the induction of endolymphatic hydrops in the same species. The crucial step in this approach is the separation of the sigmoid sinus in its entirety, through an intra-dural access with a minimal removal/retraction of cerebellar tissue. This did not affect either the post-operative recovery of the animal or its hearing threshold level as assessed via auditory brainstem responses.

Protective effect of the cochlear efferent system during noise exposure.

The aim of the present study was to confirm the hypothesis that the cochlear efferent system is involved in the mechanisms underlying the "toughening" effect at high frequencies. The toughening effect is defined as a progressive threshold shift reduction when repeated exposures to the same noise are applied. Vestibular neurectomy was performed through a posterior cranial fossa approach in six healthy pigmented guinea pigs, and it assured the interruption of both crossed and uncrossed olivocochlear bundles to one ear only, before their entrance in the internal auditory meatus. The animals were then implanted with permanent electrodes for the electrocochleographic findings. Ten days after the operation the animals were exposed to octave-band toughening noise, centered at 4 kHz, at 85-dB SPL, for 10 consecutive days, 6 hours on/18 hours off. The hearing threshold was registered before and at the end of each exposure session. The behavior of the hearing threshold in the operated ears was then compared to that of the controlateral, nonoperated ears. Complete recovery from TS in the control ear began after four days of exposure, whereas in the operated ear hearing loss increased to day 7 (55 dB), with only a partial reduction (45 dB) beyond ten days of exposure. The results of the present study clearly demonstrated that sectioning of the OCB in guinea pigs causes persistent hearing loss during noise-exposure conditioning, in comparison to the contralateral, nonoperated ear. Thus, one can assume that the lack of decrease of TS during intermittent noise exposure could be due to the loss of the protective effect of the efferent fibers, perhaps mediated by the lateral OC neurons that synapse beneath the IHCs.

Development of resistance to noise.

Recent investigations have demonstrated that in animal models repeated exposures to mid-intensity noise induce a progressive reduction of the temporary threshold shift (TTS) following the exposures. This phenomenon is named "conditioning" and it is actually able to reduce the permanent threshold shift (PTS) following exposure to high intensity noise; this finding is named "toughening". In the present work the fundamental steps of the research concerning the toughening are reviewed and the biological mechanisms supposed to be underlying this phenomenon discussed. The few preliminary results of the studies on humans are also reported.

Osmotic drugs in the treatment of cochlear disorders: a clinical and experimental study.

On the grounds of positive results obtained with Meniere's patients, agents such as glycerol and mannitol have been included in the therapeutical protocol of other cochlear disorders presenting with hearing loss either of sudden onset, but not observed at an early stage, or accompanied by tinnitus and aural pressure. Intravenous infusions of either 10% glycerol or 18% mannitol were given to selected patients 3 to 6 times with a time interval of 1 to 3 days. Hearing loss, tinnitus and aural pressure were evaluated as improved, unchanged or worsened. In 33% of the glycerol group and 23.8% of the mannitol group we observed hearing threshold improvement, while aural fullness improved in 45% of the glycerol and 56.2% of the mannitol groups, and tinnitus was only relieved in 13.1% of the glycerol and 5.8% of the mannitol group. A parallel experimental study was carried out on guinea-pigs in order to shed light on the effects of mannitol and glycerol on the inner ear. Cochlear blood flow was measured with a laser Doppler flowmeter at the level of the basal turn of the cochlear lateral wall, both in normal and hydropic guinea-pigs, before and after osmotic intraperitoneal infusion. Basal values in the normal cochlea were much higher than in the hydropic one, and both mannitol and glycerol markedly influenced the local blood flow in the normal cochlea, giving few or no changes in the hydropic one.

Localization of F-actin and fodrin along the organ of Corti in the chinchilla.

The distribution of the two cytoskeletal proteins, filamentous actin (F-actin) and fodrin, was investigated along the organ of Corti of the chinchilla using laser scanning confocal fluorescence microscopy. High intensity labeling of F-actin was seen in outer and inner hair cells, including the stereocilia. High intensity staining was also seen for fodrin in outer and inner hair cells, but not in their stereocilia. Staining intensity of both proteins along the lateral cell wall of the outer hair cells appeared to be greater in the middle and basal cochlear turns than in the apical turn. Pillars and Deiters cells also exhibited high intensity labeling of F-actin. The lack of significant differences in the distribution of fodrin between outer and inner hair cells makes the role of this protein in the active processes still unclear. Comparison of the distribution of F-actin and fodrin in the chinchilla with those reported in the guinea pigs suggest possible species differences.