Projections of cochlear root neurons, sentinels of the rat auditory pathway.

In certain rodents, the root of the cochlear nerve contains a population of large neurons, known as cochlear root neurons (CRNs), an essential element of the primary acoustic startle pathway. To characterize the projections of the CRNs, we made stereotaxically guided, iontophoretic injections of biotinylated tracers into the cochlear nerve root of albino rats. CRN axons, which are remarkably thick, enter the trapezoid body, cross the midline, and ascend in the rostral aspect of the lateral lemniscus to reach the upper levels of the midbrain. As a group, CRN axons produce a characteristic pattern of profusely ramified collaterals that innervate specific brainstem regions. The main target of CRN axons is the contralateral pontine reticular formation, where collaterals terminate in the caudal pontine reticular nucleus (PnC) and, to a lesser degree, in the ventrolateral tegmental area, the oral pontine reticular nucleus, and the rostral and medial paralemniscal regions. Other targets of CRN axons include the lateral paragigantocellular nucleus of both sides, the ipsilateral facial motor nucleus and PnC, and the contralateral intercollicular tegmentum and superior colliculus. Notably, CRNs apparently do not innervate any of the nuclei of the auditory brainstem, as usually defined, even though their axons pass through or in close proximity to them. The fact that CRNs innervate several reticular and tectal structures that mediate auditory alerting and escape behaviors suggests that they are "early warning neurons," i.e., true sentinels of the auditory pathway.     

Neonatal cholestasis and hypopituitarism

The diagnosis of optic nerve hypoplasia and hypopituitarism must be entertained in infants who present for evaluation of cholestatic jaundice, particularly if there is associated hypoglycaemia and wandering nystagmus. Although the hepatic dysfunction seems to resolve, the long term prognosis of liver disease in optic nerve hypoplasia remains unknown.     

Incidence of inhibitor development in a group of young hemophilia A patients treated exclusively with lyophilized cryoprecipitate

The incidence of neutralizing isoantibody formation to infused factor VIII in a cohort of 67 hemophilia A patients, born between January 1, 1971 and April 30, 1990, who had been treated exclusively with lyophilized cryoprecipitate, was 6% (5.3 per 1,000 patient years of observation). The age-dependent cumulative risk was 4.6% at 4 years of age and 6.7% at 8 years of age. Recent reports in patients treated with a variety of more pure concentrates show a much higher incidence of inhibitor formation and tend to be used as a reference when new concentrates are introduced. We believe that a patient group, such as the one studied here, is a more suitable reference population because these patients have been exclusively treated with a single factor VIII preparation.     

Phase I trial with recombinant human interleukin-3 in patients with lymphoma undergoing autologous bone marrow transplantation

Recombinant human interleukin-3 (rhIL-3) was administered to 30 patients undergoing autologous bone marrow transplant (ABMT) for treatment of lymphoma. In this phase I dose escalation study, rhIL-3 was administered from day 0 to 20 after ABMT by 2-hour intravenous infusion at dose levels of 1, 2, 5, and 10 micrograms/kg/d. Seventeen patients did not complete therapy with rhIL-3. Eleven requested early discontinuation for malaise, confusion, transplant complications, or rapid engraftment and were removed from the study, whereas six patients developed grade III toxicity, including fever (three patients), or headache (three patients) possibly attributable to rhIL3. Other common toxicities included diarrhea, rigors, mucositis, and rash. The maximum tolerated dose of rhIL-3 was 2 micrograms/kg/d. No evidence of earlier hematopoietic cell recovery was observed compared with similar historical patients treated with recombinant human granulocyte- macrophage colony-stimulating factor. Future trials will be needed to determine alternate schedules of administration of rhIL-3 or the use of rhIL-3 in combination or in sequence with other growth factors.     

Posterior atlantooccipital subluxation in Down syndrome

Three Down syndrome patients with posterior atlantooccipital (AO) subluxation are described. All are asymptomatic. The subluxation becomes manifest during active extension of the neck and reduces in flexion. Methods of assessing posterior AO subluxation are discussed. The abnormality is attributed to ligamentous laxity in patients with Down syndrome.     

Immune human lymphocytes produce an acid-labile α-interferon

We have described in this paper a novel human interferon (IFN) with antigenic and cross-species reactivity of α-IFN and physicochemical properties of γ-IFN. This IFN is produced by normal peripheral blood mononuclear cells during an immune response but has also been associated with autoimmune disease (10). The system described here will be useful in elucidating the biological significance and cell of origin of this IFN.