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Biomedical subjects

Jafar Hamzavi

Publications and source records attributed to Jafar Hamzavi.

11 recordsLinked to original sources

Id1 is a critical mediator in TGF-beta-induced transdifferentiation of rat hepatic stellate cells.

Transforming growth factor (TGF)-beta is critically involved in the activation of hepatic stellate cells (HSCs) that occurs during the process of liver damage, for example, by alcohol, hepatotoxic viruses, or aflatoxins. Overexpression of the TGF-beta antagonist Smad7 inhibits transdifferentiation and arrests HSCs in a quiescent stage. Additionally, bile duct ligation (BDL)-induced fibrosis is ameliorated by introducing adenoviruses expressing Smad7 with down-regulated collagen and alpha-smooth muscle actin (alpha-SMA) expression. The aim of this study was to further characterize the molecular details of TGF-beta pathways that control the transdifferentiation process. In an attempt to elucidate TGF-beta target genes responsible for fibrogenesis, an analysis of Smad7-dependent mRNA expression profiles in HSCs was performed, resulting in the identification of the inhibitor of differentiation 1 (Id1) gene. Ectopic Smad7 expression in HSCs strongly reduced Id1 mRNA and protein expression. Conversely, Id1 overexpression in HSCs enhanced cell activation and circumvented Smad7-dependent inhibition of transdifferentiation. Moreover, knock-down of Id1 in HSCs interfered with alpha-SMA fiber formation, indicating a pivotal role of Id1 for fibrogenesis. Treatment of HSCs with TGF-beta1 led to increased Id1 protein expression, which was not directly mediated by the ALK5/Smad2/3, but the ALK1/Smad1 pathway. In vivo, Id1 expression and Smad1 phosphorylation were co-induced during fibrogenesis. In conclusion, Id1 is identified as TGF-beta/ALK1/Smad1 target gene in HSCs and represents a critical mediator of transdifferentiation that might be involved in hepatic fibrogenesis. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Animals↗

Effect of deep insertion of the cochlear implant electrode array on pitch estimation and speech perception.

CONCLUSION: Deeply inserted electrodes offer the possibility that apical stimulation may improve speech performances. Therefore, deep insertion is reasonable and should be performed in patients with profound or total hearing loss. OBJECTIVES: To evaluate the importance of insertion depth beyond 25 mm in a group of cochlear implant patients with deeply inserted electrodes up to 32 mm. PATIENTS AND METHODS: In the first part of the study patients were asked to perform a pitch estimation for channels across the whole length of the electrode array. We evaluated whether pitch discrimination was possible along the whole cochlea and especially in its apical part. Then, the audiological performances of 10 patients were tested in 5 conditions, in which we artificially varied the insertion depth in each patient by activating and deactivating channels. The patients were tested immediately in the new condition to avoid adaptation. RESULTS: The results showed that activating the electrodes in the uppermost region of the cochlea improves speech perception significantly. Furthermore it could be demonstrated that the pitch perceived in the cochlea with electrical stimulation decreases with increasing insertion depth along the whole length of deeply inserted electrode arrays.

Adult↗

The role of intensity upon pitch perception in cochlear implant recipients.

OBJECTIVES: Pitch plays a key role in the perception of speech and music, the recognition of a speaker's voice, and in analyzing complex auditory patterns. To date, little consideration has been given to the influence of stimulation level on pitch perception. The aim of this study was to investigate the impact of a sound's intensity on pitch perception in cochlear implant recipients using monopolar stimulation. STUDY DESIGN: Thirteen patients with an average implant use of 4.13 years took part in this study. All patients were implanted with MedEl Combi 40/40+ cochlear implants. METHODS: In the first part of the study, we performed a pitch ranking procedure to confirm that all patients were able to judge pitch changes. Using a visual scale, study participants were then asked to compare the pitch of an intensity-constant reference tone with the pitch of a test tone of varying intensity. RESULTS: Eleven (85%) patients were found to perceive a clear change in pitch with changing stimulus intensity. Statistical analysis showed a strong positive correlation in 10 patients (correlation coefficients between 0.99 and 0.71) and a strong negative correlation in 1 patient (r = -0.92). CONCLUSIONS: The results suggest that a distinct relationship exists between pitch perception and intensity of the stimulus. To date, speech coding strategies do not support these findings. Nevertheless, we believe that for the optimized most natural perception of sounds, especially music, the described particularities of pitch perception need to be respected, and further investigations on this topic are necessary.

Acoustic Stimulation↗

Surgical considerations in cochlear implantation in children and adults: a review of 342 cases in Vienna.

CONCLUSIONS: Our data represent the experience of the largest cochlear implant program in Austria. In conclusion, cochlear implantation is a safe procedure, associated with a low rate of intra- and postoperative complications. Nevertheless, patients should be informed about possible problems and especially about the risk of a reoperation due to device failure. OBJECTIVES: To evaluate the cause of deafness, the intraoperative findings and the complication rate for all cochlear implant operations performed consecutively between 1994 and 2003 at Vienna General Hospital. MATERIAL AND METHODS: Including all surgeries for bilateral implantation and revision, a series of 342 operations performed on 164 adults (age range 14.5-81 years; mean age 50.79 years) and 128 children (age range 0.75-14 years; mean age 5.00 years) was retrospectively analyzed. RESULTS: The etiology of deafness was predominantly congenital or progressive (66.89%). The routine mastoidectomy approach was chosen in 300 patients (87.72%) and the suprameatal approach in 42 (12.28%). Intraoperatively, 4 children (2.53%) had a cerebrospinal fluid fistula and 35 patients (10.23%) showed cochlear ossification. Three adults (1.63%) and two children (1.27%) had facial nerves with an aberrant course. The overall complication rate was 12.2%, the rate of major complications was 4.97% and the rate of minor complications was 4.09%. There were no cases of either postoperative meningitis or facial nerve palsy. Both flap necrosis and electrode dislocation occurred in one adult patient (0.54%), but in none of the children. Formation of cholesteatoma was found in one adult (0.54%) and one child (0.63%). The rate of device failure was 7.07% for adults and 13.92% for children.

Adolescent↗

Audiological performance after cochlear implantation in children with inner ear malformations.

OBJECTIVES: To prove that cochlear implantation is a beneficial method of rehabilitation in deaf children with malformations of the inner ear. DESIGN: The evaluation of auditory responses to speech (EARS) test battery was performed on the children in this study after an average implant use of 3 years. RESULTS: Individual results of six children with inner ear anomalies receiving cochlear implants are presented in this study. Three of the patients showed an incomplete partition (Mondini dysplasia), one had a cochlear hypoplasia and two suffered from an intraoperative cerebrospinal fluid leak. The majority of the children in this study are successful implant users. Wherever possible, test scores are included and subjective case reports given. CONCLUSIONS: Results are similar to those in children with normal cochleas, therefore inner ear malformations found in as many as 20% of patients with congenital sensorineural hearing loss are no contraindication for cochlear implantation. Nevertheless, factors influencing the success of implantation are multiple, including a thorough preoperative radiological examination, a well-performed surgery and an individually tailored postoperative rehabilitation programme.

Audiometry, Speech↗

Speech perception with a cochlear implant used in conjunction with a hearing aid in the opposite ear.

The aim of this study was to determine the improvement in speech recognition provided by a cochlear implant (CI) in conjunction with a hearing aid (HA) in the opposite ear. The study was a retrospective cohort study in the context of a university teaching hospital CI programme. Seven CI patients who still use their HA in the opposite ear were tested. The scores with the CI alone and the CI in conjunction with an HA were evaluated by using three speech perception tests in quiet (Freiburger Numbers. Freiburger Monosyllables, and Innsbrucker Sentence Test). In the majority of tests and subjects. the CI alone performed better than the HA alone, and the bimodal (CI + HA) condition was superior to the CI alone. On the sentence test, the patients as a group improved from 47 96% (mean: 79%; CI alone) to 50-100% (mean: 88.1%; CI + HA, pv < 0.05). With the more difficult monosyllable test, the scores improved from 15-52% (mean: 37.2%; CI alone) to 15 82% (mean: 48.7%; CI + HA, p < 0.05). On the numbers test. scores increased from 65-98% (mean: 83%; CI alone) to 75-98% (mean: 88.7%; CI + HA, p < 0.05). All patients in this study were implanted in the poorer ear. The results of the present study suggest the advantage of CI usage in conjunction with an HA in the opposite ear.

Acoustic Stimulation↗

Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats.

BACKGROUND & AIMS: Numerous studies implicate transforming growth factor (TGF)-beta signaling in liver fibrogenesis. To perturb the TGF-beta pathway during this process, we overexpressed Smad7, an intracellular antagonist of TGF-beta signaling, in vivo and in primary-cultured hepatic stellate cells (HSCs). METHODS: Ligation of the common bile duct (BDL) was used to induce liver fibrosis in rats. Animals received injections of an adenovirus carrying Smad7 cDNA into the portal vein during surgery and via the tail vein at later stages. The effect of Smad7 on TGF-beta signaling and activation of HSC was further analyzed in primary-cultured cells. RESULTS: Smad7-overexpressing BDL rats displayed reduced collagen and alpha-SMA expression and reduced hydroxyproline content in the liver, when compared with animals administered AdLacZ. Such a beneficial effect was also observed when Smad7 was expressed in animals with established fibrosis. Accordingly, Smad7 arrested transdifferentiation of primary-cultured HSCs. AdSmad7 infected cells remained in a quiescent stage and retained storage of vitamin A droplets. Smad7 expression totally blocked TGF-beta signal transduction, shown by inhibiting Smad2/3 phosphorylation, nuclear translocation of activated Smad complexes, and activation of (CAGA)(9)-MLP-Luc, resulting in decreased collagen I expression. Smad7 also abrogated TGF-beta-dependent proliferation inhibition of HSC. Smad7 did not decrease expression of alpha-SMA, but immunofluorescent staining with anti alpha-SMA antibodies displayed destruction of the fibrillar organization of the actin cytoskeleton. CONCLUSIONS: In summary, gene transfer of Smad7 inhibits experimental fibrogenesis in vivo. Studies with isolated HSC suggest that the underlying mechanisms involve inhibition of TGF-beta signaling and HSC transdifferentiation.

Actins↗

Variables affecting speech perception in postlingually deaf adults following cochlear implantation.

OBJECTIVE: To evaluate the time span over which there is greatest improvement in postlingually deaf adults undergoing cochlear implantation. Additionally, to quantify potential patient and device factors that may predict the postoperative results. MATERIAL AND METHODS: A longitudinal study was conducted. Numbers, monosyllables and sentence test results were collected for 66 cochlear implant subjects [Combi 40/40 +, n = 60; Clarion HF2, n = 2; Nucleus 24m/k, n = 4] at regular intervals for up to 6 years following cochlear implantation. RESULTS: All patients showed a steady improvement over time on all tests. Progress during the first 12 months was statistically significant, with further improvements being recorded after the 12-month testing period. The duration of deafness and the number of electrodes (8 for the Combi 40, 12 for the Combi 40 + ) appeared to be weakly correlated with postoperative performance. Re-implantation after device failure had no negative effect on speech reception. Subjects who were "upgraded" from an analogue to a digital cochlear implant improved their test results almost twofold. CONCLUSION: All the patients in our study gained substantial benefit from their cochlear implants. It is encouraging to note that the factors examined were not deemed to be relevant predictors of performance. Even long-term deaf subjects and re-implantees are able to achieve an excellent level of speech perception.

Cochlear Implantation↗

The role of age in pediatric cochlear implantation.

OBJECTIVE: To document progress, benefit and importance of age in paediatric cochlear implantation. DESIGN: The EARS (Evaluation of Auditory Responses to Speech) test battery was performed on 33 prelingually deaf children at regular intervals up to 36 months following implantation. All children participated in individually tailored intensive audiological rehabilitation programs after receiving their implants. In this respect, it was attempted to evaluate speech perception scores in children implanted before and after the age of 3 in a homogenous group. RESULTS: All children demonstrated encouraging improvements over time in their speech recognition abilities. Furthermore, it was observed that the children who were implanted under the age of 3 achieved higher levels of speech perception performance. CONCLUSION: In order to shorten the process of central maturation of the auditory system, it is desirable to implant the children as young as possible. Early intervention seems to be the ideal strategy in enabling prelingually deaf children to derive maximum benefit from cochlear implantation.

Age Factors↗

Vestibular symptoms as a complication of sildenafil: a case report.

Potential vasodilator side effects of sildenafil such as headache, flushing, dyspepsia, heartburn, nasal congestion, dizziness and visual changes have been frequently observed. We report a 79-year-old man who developed severe vestibular neuritis-like symptoms (horizontal nystagmus with rotatory components and vomiting) two hours after taking 50 mg sildenafil. Additionally, the patient complained of tinnitus in both ears. Internal and neurological examination revealed no pathological findings and the patient had no history of cardiovascular disease. The symptoms lasted for 24 hours and then resolved completely. All of the patient's complaints indicated a drug-related phenomenon. This drug related adverse reaction should be included in the long list of potential side effects of sildenafil.

Adverse Drug Reaction Reporting Systems↗

Does cochlear reimplantation affect speech recognition?

Although cochlear implantation has been proven to be a very effective method of rehabilitation for post-lingually deaf adults and pre-lingually deaf children, as electronic devices, cochlear implants are occasionally subject to damage or breakdowns. In these cases, reimplantation would be necessary. The aim of this study was to find out whether or not there are any negative effects on speech abilities after reimplantation with the same type of multichannel digital implant in the same ear. Seven patients were provided with a digital multi-channel cochlear implant. One subject suffered manipulative damage to the implant, and in six subjects an implant failure was observed. All reimplantations were performed on the same ear as the initial implantation. with the same implant type. Parameters such as insertion depth and number of active channels were the same in all subjects before and after reimplantation. Immediately following the revision surgery, three patients attained the same level of hearing that they had with their original implants. Three months following reimplantation, five subjects achieved almost the same scores that they had before reimplantation. The results showed that cochlear implant patients undergoing re-implantation can anticipate achieving nearly the same level of speech recognition as they had with their original implant. Nevertheless, patients need to be aware of potential problems before undergoing reimplantation so that expectations are not too high.

Aged↗