Development of the lateral line mechanoreceptors in the catfish Silurus glanis.

In fish the neuromasts of the lateral line develop as follows: a "migrating primordium" (MP) migrates from the postotic placode along the future posterior lateral line canal to the tail fin. Its placodal cells are assumed to be the basis for the development of the neuromasts. However, an MP was not found in all fish, e.g., in catfish. In the present study, a search was made for the MP in the larvae of the catfish Silurus glanis. Using light and electron microscopy, an MP was found to migrate along the ventral rim of the tail. It precedes the formation of a ventral row of free neuromasts. An MP preceding the main lateral row of the future canal neuromasts was not found. The necessity of the MP for the ventral-free neuromast development is shown by making incisions which block its migration. The result: caudal to the incision site neuromasts do not develop. On the other hand, the same incision procedure applied to the assumed migration route of a--hypothetical--lateral MP does not block the development of the lateral neuromasts. It is concluded that in this case an MP is not necessary for the development of the canal neuromasts.

Axon guidance during establishment of electroreceptor innervation in the catfish Kryptopterus.

The principles were studied, according to which the characteristic electroreceptor distribution pattern consisting of organ rows and clusters on the tail of the catfish Kryptopterus spec. is formed. As each electroreceptor is induced by its future afferent ('electrosensory') nerve fibre at the site where the outgrowing fibre reaches the epidermis, it is the fibre navigation which controls the organ distribution. Three navigation principles of the outgrowing electrosensory fibres were found. (i) The electrosensory fibre courses are bound to the tail segmentation. Nerve displacement experiments suggest that the fibres are guided by the intersegmental connective tissue sheaths, i.e. the myosepta and myocommata. (ii) The individual fibres have no specificity for a certain route or target area on the tail, but can grow in any direction and into any tail area and induce organs there. This is indicated by experiments with nerve elimination and nerve deflection. (iii) An outgrowing fibre's only orientation is towards a nearby 'free site'; i.e. it aims for a place in clusters with fewer organs than their actual capacity allows. The capacity increases continuously with the specimen's age, so that free sites progressively develop. So, it depends on chance which outgrowing fibre occupies which 'free site'; a free site is targeted by whatever outgrowing fibre happens to be the nearest. The mechanisms of development of the somatotopic projection of the electrosensory fibres to the central nervous system (CNS) are discussed.

Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study.

PURPOSE: To evaluate the effect on survival and quality of life of maintaining hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in women with metastatic breast cancer (MBC) receiving first-line chemotherapy. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive epoetin alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if baseline Hb was < or = 13 g/dL or when Hb decreased to < or = 13g/dL during the study. The primary end point was 12-month overall survival (OS). RESULTS: The study drug administration was stopped early in accordance with a recommendation from the Independent Data Monitoring Committee because of higher mortality in the group treated with epoetin alfa. Enrollment had been completed, with 939 patients enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for placebo recipients (P = .01). Optimal tumor response and time to disease progression were similar between groups. The reason for the difference in mortality between groups could not be determined from additional subsequent analyses involving both study data and chart review. CONCLUSION: In this trial, the use of epoetin alfa to maintain high Hb targets in women with MBC, most of whom did not have anemia at the start of treatment, was associated with decreased survival. Additional research is required to clarify the potential impact of erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.

Development of catfish lateral line organs: electroreceptors require innervation, although mechanoreceptors do not.

In amphibians the lateral line sense organs, i.e., mechanoreceptors (neuromasts) and electroreceptors, develop autonomously from placodal tissue, with no need for innervating nerve fibers. The present study deals with the question whether or not the mechano- and the (ampullary) electroreceptors develop in the same manner in teleosts. On the tail of larval catfish, Silurus, the first mechano- and electroreceptors appear several days after hatching in two longitudinal rows, one along the outgrowing main branch of the lateral line nerve and one along its ventral branch. Prevention of outgrowth of both nerve branches by repeated nerve sectioning, before the receptors form, shows (1) that the mechanoreceptors can develop without innervation as in amphibians, and (2) that the electroreceptors do not develop without innervation, unlike amphibian electroreceptors. These results are discussed with regard to the placodal origin and the phylogeny of the two sense organs.