Assessment of nutrient supplement to reduce gentamicin-induced ototoxicity.

Gentamicin is an aminoglycoside antibiotic used to treat gram-negative bacterial infections. Treatment with this antibiotic carries the potential for adverse side effects, including ototoxicity and nephrotoxicity. Ototoxic effects are at least in part a consequence of oxidative stress, and various antioxidants have been used to attenuate gentamicin-induced hair cell death and hearing loss. Here, a combination of nutrients previously shown to reduce oxidative stress in the hair cells and attenuate hearing loss after other insults was evaluated for potential protection against gentamicin-induced ototoxicity. Guinea pigs were maintained on a nutritionally complete standard laboratory animal diet or a diet supplemented with ß-carotene, vitamins C and E, and magnesium. Three diets with iterative increases in nutrient levels were screened; the final diet selected for study use was one that produced statistically reliable increases in plasma levels of vitamins C and E and magnesium. In two separate studies, significant decreases in gentamicin-induced hearing loss at frequencies including 12 kHz and below were observed, with less benefit at the higher frequencies. Consistent with the functional protection, robust protection of both the inner and outer hair cell populations was observed, with protection largely in the upper half of the cochlea. Protection was independently assessed in two different laboratories, using two different strains of guinea pigs. Additional in vitro tests did not reveal any decrease in antimicrobial activity with nutrient additives. Currently, there are no FDA-approved treatments for the prevention of gentamicin-induced ototoxicity. The current data provide a rationale for continued investigations regarding translation to human patients.

Opsoclonus-myoclonus-ataxia syndrome in neuroblastoma: clinical outcome and antineuronal antibodies-a report from the Children's Cancer Group Study.

BACKGROUND: Opsoclonus-myoclonus-ataxia (OMA) is a paraneoplastic neurologic syndrome affecting 2-3% of children with neuroblastoma. Although children with OMA and neuroblastoma may have higher survival, many experience a significant amount of late neurologic impairment, which may be immunologically mediated. The aim of this study was to compare the outcome of neuroblastoma patients with and without OMA, relating to prognostic factors, treatment, and the presence or absence of anti-neuronal antibodies. PROCEDURE: Questionnaires were mailed out requesting information on the current neurologic status of patients who submitted sera at diagnosis to the Children's Cancer Group serum bank from 1980 to 1994. Information was requested on clinical and biological patient characteristics as well as clinical aspects of the patients identified as having OMA syndrome, including presentation and treatment for OMA, late sequelae of OMA, the presence or absence of antineuronal antibodies, and survival. Sera from 16 of the OMA patients and 48 case-controls with neuroblastoma were assayed for anti-neuronal antibodies. RESULTS: Of the 675 responses received, 21 patients had OMA. Ninety percent of OMA patients presented with non-metastatic disease, vs. 35% of non-OMA patients. Estimated 3-year survival for the OMA patients with nonmetastatic disease (stage I, II, III) greater than 1 year of age was 100% vs. 77% for similar non-OMA patients (P = 0.0222). At follow-up, 14/19 evaluable OMA patients displayed some form of developmental or neurologic abnormality. There was no significant correlation of late sequelae with antineuronal antibodies, age, time between OMA symptoms and diagnosis, or treatment given for tumor or OMA. There was a significant correlation of late sequelae with lower stage disease (I and II) compared to more advanced disease (III and IV). CONCLUSIONS: Patients with OMA and neuroblastoma have excellent survival but a high risk of neurologic sequelae. Favorable disease stage correlates with a higher risk for development of neurologic sequelae. The role of anti-neuronal antibodies in late sequelae of OMA needs further clarification.

Emergency airway management in hanging victims.

STUDY OBJECTIVE: To determine the incidence, demographics, clinical indicators of survival, and frequency of cervical-spine fractures to define appropriate emergency airway management in hanging victims. DESIGN: Medical examiner records, paramedic reports, and emergency department and hospital medical records were reviewed retrospectively for the period January 1, 1978, to January 1, 1990. SETTING: Urban paramedic system with nine receiving hospitals. PARTICIPANTS: A total of 160,724 medical examiner and paramedic records were reviewed to identify a total study population of 306 hanging victims. One hundred eighty-two victims (59%) were found dead at the scene, and the emergency medical system was not notified. An additional 57 (19%) were seen by paramedics and declared dead at the scene. Sixty-seven (22%) were treated and transported to nine receiving EDs; 39 of these 67 received oral or nasal endotracheal intubation. RESULTS: The incidence of hanging was 0.19% of all medical examiner cases and paramedic runs during the 12-year study. Those hanging victims who survived to receive paramedic transport and treatment by physicians were typically male and attempted suicidal hanging in a public place (most frequently jail) with available bedding or clothes. No hanging victim treated and transported by paramedics had documentation of cervical-spine or spinal cord injury. CONCLUSION: In nonjudicial hanging victims seen by paramedics and transported to an ED, cervical-spine injury is rare. Cerebral hypoxia rather than spinal cord injury is the probable cause of death and should be the primary concern in treatment of this patient population. Following external stabilization of the neck, nasal or oral endotracheal intubation is appropriate emergency airway management in hanging victims.