Sudden hearing loss and acquired immunodeficiency syndrome

We have presented a case of a male homosexual with documented acquired immune deficiency syndrome in whom sudden sensorineural hearing loss developed after a series of opportunistic infections and before a massive intracerebral hemorrhage. Two major possible causes of his hearing loss are (1) actual involvement of spiral ganglion or acoustic division of the eighth cranial nerve by HTLV III virus, or (2) cryptococcal meningitis. He ultimately died after a series of neurological complications developed. These complications, which are common in patients with AIDS, include progressive dementia, obtundation, and coma. As the number of patients with AIDS in our society increases over the next 5 years, it will become more important for the otolaryngologist to recognize the complications of this disease that involve the ear, nose, throat, head, and neck. Sudden sensorineural hearing loss is one of these complications. The acquired immune deficiency syndrome, at this point, might best be treated by an approach of preventive medicine. However, such an approach would have far-reaching social and political implications--perhaps more so than in other venereally spread diseases. In the interim, the otolaryngologist-head and neck specialist is required to recognize AIDS as it manifests itself in the head and neck. In this case, sudden-onset sensorineural hearing loss was the otolaryngologic presentation of the AIDS.     

Treatment with high-dose simvastatin inhibits geranylgeranylation in AML blast cells in a subset of AML patients

It is currently unknown whether the in?vitro effects observed with statins in acute myeloid leukemia (AML) cells, including lowering of cholesterol, inhibition of isoprenylation, and sensitization to chemotherapy, also occur in?vivo. Therefore, AML mononuclear cells (MNCs) were isolated from 12 patients before and after 7 days of high-dose (7.5-15 mg/kg/day) simvastatin treatment. Parallel mouse studies were performed to have, in addition to AML cells, access to liver tissue, a major target of statins. Serum cholesterol levels were lowered by simvastatin in all patients, however, only limited changes in the messenger RNA expression of cholesterol metabolism genes were seen in patient and mouse MNCs compared to murine liver cells. Still, two out of seven patients displayed an increased in?vitro chemosensitivity of their AML cells upon simvastatin treatment. Gene set enrichment analysis on microarray data of AML patient cells and Western blot analysis for the isoprenylated proteins DnaJ and Rap1 on murine and AML patient MNCs demonstrated that in?vivo simvastatin treatment resulted in inhibition of geranylgeranylation in murine MNCs and in a subset of patient AML MNCs. In summary, our data demonstrate that simvastatin treatment results in chemosensitization and inhibition of geranylgeranylation in AML cells of a subset of patients.