Gerbils aged in quiet show a decline of the endocochlear potential (EP) and elevated auditory nerve compound action potential (CAP) thresholds. However, establishing a direct relationship between an age-related reduction in the EP and changes in the activities of primary auditory neurons is difficult owing to the complexity of age-related histological changes in the cochlea. To address this issue, we developed a young gerbil model of "metabolic" presbyacusis that uses an osmotic pump to deliver furosemide into the round window niche for 7 days, resulting in a chronically reduced EP. In this model, the only major histopathologic changes were restricted to the hook region of the cochlea and consisted of loss of strial intermediate cells and massive edema in the lateral wall. The morphological and physiological evidence suggests that the cochlea can adapt to furosemide application over time. The morphology of spiral ganglion cells and hair cells appeared normal throughout the cochlea. CAP responses and EP values in this model are similar to those of quiet-aged ears. The spontaneous activity of single auditory fibers (n= 188) was assessed in 15 young gerbils treated with furosemide for 7 days. The percentage of recorded low-spontaneous rate (SR) fibers at characteristic frequencies (CFs)≥6 kHz was significantly lower in furosemide-treated than in control ears. Recovery function tests of CAP responses after prior stimulation also showed a decline in activity of the low-SR population with CFs≥6 kHz in the treated cochleas. A similar loss in the activity of low-SR fiber has been previously shown in quiet-aged gerbils. These results suggest that dysfunction of the cochlear lateral wall and subsequent chronic reduction in the EP can directly affect the activity patterns of primary auditory neurons in a manner similar to that seen in aged gerbils.

With the exception of humans, the somata of type I spiral ganglion neurons (SGNs) of most mammalian species are heavily myelinated. In an earlier study, we used Ly5.1 congenic mice as transplant recipients to investigate the role of hematopoietic stem cells in the adult mouse inner ear. An unanticipated finding was that a large percentage of the SGNs in this strain were unmyelinated. Further characterization of the auditory phenotype of young adult Ly5.1 mice in the present study revealed several unusual characteristics including: 1) large aggregates of unmyelinated SGNs in the apical and middle turns; 2) symmetrical junction-like contacts between the unmyelinated neurons; 3) abnormal expression patterns for CNPase and connexin 29 in the SGN clusters; 4) reduced SGN density in the basal cochlea without a corresponding loss of sensory hair cells; 5) significantly delayed auditory brainstem response (ABR) wave I latencies at low and middle frequencies as compared to control mice with similar ABR threshold and 6) elevated ABR thresholds and deceased wave I amplitudes at high frequencies. Taken together, these data suggest a defect in Schwann cells that leads to incomplete myelinization of SGNs during cochlear development. The Ly5.1 mouse strain appears to be the only rodent model so far identified with a high degree of the "human-like" feature of unmyelinated SGNs that aggregate into neural clusters. Thus, this strain may provide a suitable animal platform for modeling human auditory information processing such as synchronous neural activity and other auditory response properties.

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Alloimmunization to red cell antigens can seriously compromise the treatment of chronically transfused sickle cell patients by increasing the risk of delayed hemolytic transfusion reactions and decreasing the availability of suitable red cell units. In an effort to reduce the rate of alloimmunization, many institutions routinely provide transfusions that are phenotypically matched for selected red cell antigens. Controversy exists in this approach with some advocating the use of extensive matching protocols in which 9 or more red cell antigens are screened while others follow a more limited approach in which only 3–5 antigens are screened. Neither the relative clinical efficacy nor the cost-effectiveness of these approaches has been compared. In our institution a limited phenotype matching program was instituted in June 1999 in which red cells provided to all pediatric sickle cell patients are negative for C, E, and Kell antigens only. All patients are screened for the presence of red cell allo-antibodies prior to each transfusion and additional phenotype matching was performed for patients who develop specific antibodies other than C, E and/or Kell. We present here our experience with this limited phenotype matching approach in 169 pediatric sickle cell patients. The patients in our study have received a mean of 100.7 red cell transfusions (range 1–555). Overall, 36 (21.3%) patients developed at least one red cell alloantibody. However, 15 of these patients had developed antibodies to C, E, or Kell (or a combination) as a result of transfusion prior to referral to our hospital or as a result of transfusion here, prior to the routine implementation of our limited matching program. Therefore, only 21 patients (12.4%) developed red cell alloantibodies that could not be prevented by the consistent use of our protocol. These antibodies include; Jka (4), M (4), Fya (3), S (3), Cw (3), Lua (3), V (2), Jsa (2), and Lea, Leb, Kpa, Kna, Jkb, c (1 each). The rate of antibody production was 0.17/100 units transfused. Our results favorably compare with other reports of more extensive phenotypic matching programs (e.g, 6.7% of patients with red cell alloantibodies; 0.06 antibodies/100 units transfused). In addition, only 6 of our patients (3.6%) developed multiple (non-C, E, Kell) allo-antibodies. In 3 of these patients the antibodies developed were of questionable clinical significance (Lea, Leb, Kna) or would generally not be screened even in the most thorough phenotype matching program (Cw, Lua). Among our patients with multiple alloantibodies, compatible red cell units were easily available with 4–13% of ABO/Rh compatible units collected from a non-ethnically selected population being suitable. The extended screening carried out for this limited number of patients (3.6%) is a far more cost-effective and sustainable approach for a large sickle cell treatment program than would be possible with an extended phenotyping program including essentially all patients. It should be noted that none of our patients have demonstrated clinical evidence of either acute or delayed hemolysis. Finally, it is important to consider the relative cost-effectiveness of various phenotype matching protocols. At an approximate cost of $200 for each red cell unit and a fee of $85 for each additional antigen screened by our local blood supplier, each unit of red cells for our patients costs $455. In screening programs requiring more extensive matching (8–9 antigens screened) the cost per unit would be almost double this amount ($880–$965). Our study suggests that this limited antigen matching is effective in reducing alloimmunization in chronically transfused pediatric sickle cell patients and additionally does so in a more cost-effective manner than more extensive screening programs. Finally, even in those patients who ultimately developed red cell antibodies, the availability of suitable red cell products was never seriously compromised.