Reversible Deafness Research Articles

A phase I pharmacokinetic (PK) and molecular pharmacodynamic (PD) study of the combination of two anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts) with advanced colorectal (CRC), head and neck (HNC) and non-small cell lung cancer (NSCLC)

3006 Background: C and G are two anti-EGFR agents with different mechanisms of action. We had previously shown a synergistic effect combining the two agents in preclinical models (Matar et al, Clin Cancer Res 2004). This study aims to explore safety, PK and PD changes in tumor and skin at different doses of C/G to define the recommended dose (RD) for further development. Methods: pts were treated at the RD of weekly iv C (400 mg/m2 initial dose, 250 mg/m2 weekly) and oral daily G (250 mg/d) as single agents (5 pts each) and in successive cohorts of combined C/G (3–6 pts each): C (320/200) / G (100), C (400/250) / G (100), C (400/250) / G (250), C (320/200) / G (500) & C (400/250) / G (500) (ongoing). Dose escalation depended on dose limiting toxicity (DLT) rate during the first 28 d. Pre- & on-treatment steady-state (14 d) tumor & skin biopsies were obtained and have been evaluated by IHC for total (t) and phospho (p)-EGFR, p-MAPK, p-Akt, proliferation (Ki67), p27 expression and apoptosis by TUNEL. Gene profiling analysis is ongoing. Results: 35 pts have been treated so far: 20 CRC, 13 HNC & 2 NSCLC; median KI 90 % (70–100); median age 60 years (38–80); 24 males, 11 females. DLTs occurred in 3 pts: 1 pt with G alone with reversible ILD; 1 pt with G (250) / C (400/250) with reversible deafness & 1 pt with G (500) / C (320/200) with grade 3 anorexia and nausea. There were 1 CR (HNC) and 5 PRs (CRC) in the C/G cohorts, and 1 PR (CRC) in the C cohort. Overall, 5 out of 9 (56%) pts with CRC treated in the C/G cohorts presented a PR. PD studies show superior inhibition of p-EGFR, p-MAPK and p-Akt, reduction of proliferation and increased apoptosis (all p values <0.05) in the tumors of pts treated with C/G compared with the single agent cohorts. PK evaluation shows no PK interactions with the 2 drugs. Conclusions: This combination of an anti-EGFR MAb (C) and a TKI (G) is feasible at the RD of both agents. Our findings show encouraging clinical activity, especially in CRC, and superior PD signaling inhibition with the combination without any significant PK interaction. Combined anti-EGFR therapy deserves further evaluation. [Table: see text]

Bilateral Reversible Deafness after Surgery for Unilateral Epidermoid Tumor: An Unusual Complication: Case Report

We present an unusual complication of bilateral hearing loss after surgery for unilateral epidermoid tumor situated at the right pontocerebellar junction. The neurosurgeon must know the possible causes of this catastrophic complication and should take every possible measure to avoid it. A 43-year-old male patient presented with progressive hearing loss in the right ear. A radiological examination demonstrated a mass lesion at the right pontocerebellar junction. A pure tone audiogram revealed sensorineural hearing impairment of the right ear. A brainstem auditory evoked potential test confirmed this with reduced amplitudes and a prolonged I-V interval. The patient was operated on via a right paramedian suboccipital craniectomy. The tumor was completely excised, and all of the cranial nerves were preserved during the operation. Postoperatively, the patient developed total bilateral hearing loss, which improved significantly over time. Controlled cerebrospinal fluid drainage during exposure and tumor excision may reduce the possibility of shift and traction on the neural structures and help to prevent ischemic injury. Frequent irrigation of the surgical field and minimizing the spilling of the tumor contents may reduce the risk of chemical irritation. The use of corticosteroids may also help during the postoperative period.

On reversible deafness, generalized anxiety disorder, and the motoric brain: a psychophysiological perspective

Electromyographic (EMG) recording during presentation of loud sounds revealed central motor inhibition in a rare case of conversion disorder with deafness. Two subjects in whom hypnotic deafness was induced resembled the patient. In contrast, patients with generalized anxiety disorder (GAD) showed a significantly delayed return of EMG to baseline, compared with normals and schizophrenics following administration of auditory startle stimuli. Blood pressure (BP) of GAD patients was also slower to return to baseline than that of normals and schizophrenics. BP recorded continuously during seven consecutive tests revealed a striking difference between GAD patients and controls. While the controls’ BP generally decreased during the session, pressure of the GAD patients remained at their initial levels. These data are interpreted in relation to allodynamic autonomic regulation as affected by vagal blockade, which appeared to decrease in controls while remaining undiminished in GAD patients. It is suggested that intrusions of uncontrollable worry in GAD patients, and their consequent overuse of certain rostral neural pathways involved in preparation for action prolonged their vagal blockade. A GAD case with typically high frontalis EMG is presented. Frontalis EMGs may provide an exceptionally sensitive indication of neural activity of relevance to GAD. EMG gradients in normal subjects draw attention to Sperry's motoric brain concept, whose influence is strong throughout the paper. Sperry's principle states that the main function of the brain is that of moving the animal in ways that are advantageous for satisfying basic needs and avoiding dangers. Also, with a focus on the motoric brain, some discoveries resulting from brain-recording experiments in freely moving rats are described.

Reversible deafness caused by biotinidase deficiency

We present a child with complete biotinidase deficiency who developed bilateral sensorineural deafness without a response to a maximal stimulus of 90 dB in brainstem acoustic-evoked response. After treatment with 20 mg biotin daily, a repeated brainstem acoustic-evoked response demonstrated an improved hearing threshold of 65 dB, and the child began to talk. The case is a rare example of reversible hearing loss caused by to biotinidase deficiency and highlights the need for immediate replacement therapy once the diagnosis is established.

Mitomycin-C, Vinblastine, and Lonidamine as Salvage Treatment of Advanced Breast Cancer

Thirty-two patients with advanced breast cancer were treated with mitomycin-C 10 mg/m2 IV and vinblastine 6 mg/m2 IV every 21 days in combination with lonidamine 450 mg/day P.O. and prednisone 15 mg/day P.O. given continuously. Among the 29 evaluable patients (all but three pretreated with an anthracycline-based regimen), one complete remission (CR) and six partial remissions (PR) (response rate, 24%) were seen. The median duration of response was 14 months (range, 4-30 months). Median survival for responders was 18 months (range, 4-30 months). Hematological toxicity was uncommon; the main lonidamine-related side effects were myalgia, abdominal cramps, and reversible deafness; these side effects were severe in two, one, and one patients, respectively. The regimen seems to have a reasonable degree of activity and toxicity in advanced, refractory breast cancer. The role of lonidamine in the treatment of this disease warrants further evaluation.

Reversible Deafness as Model of Pressure Damage to the VIIIth Nerve

Frequency-specific compound action potentials (CAP) of the VIIIth nerve were registered in patients in which surgery confirmed retrocochlear pathology. A different pathologic behaviour of threshold latency was encountered for 2 and 4 kHz CAP, respectively. This was due to the question of whether transmission of neural information by the acoustic nerve's fibres was blocked completely by retrocochlear pathology or not. A totally reversible hearing loss in a case of cystic arachnitis can offer a reasonable explanation.

A REPORT ON 2 CASES OF INNER EAR DEAFNESS WITH REVERSIBLE CHANGE

The author reported 2 cases of inner ear deafness with reversible change, together with their audiograms.The first case was Streptomycin allergy with generalized exanthema.It was thought that the deafness was due to locol symptoms of allergy in the inner ear, such as edema.The second case had episods of sudden, reversible deafness and tinitus for several years.The deafness was perceptic in nature with reduced bone conduction.The cause of deafness was considered to be hypofunction inproper function of the inner ear windows.The author also pointed out that as a rule, the bone conduction was reduced when the inproper unction of the both inner ear windows was present.

Pearly tumor of the cerebellopontine angle, report of a case with reversible deafness.

Pearly tumor of the cerebellopontine angle, report of a case with reversible deafness.