Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

CONTEXT: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. OBJECTIVE: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. METHODS: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. RESULTS: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. CONCLUSIONS: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.

[Initial evaluation of febrile neutropenic patients: risk quantification]. / Valoración inicial del paciente neutropénico con fiebre: cuantificación del riesgo.

Infection in immunocompromised hosts represents a serious clinical situation due the high morbidity and mortality it produces and is one of the most frequent complications in patients with cancer. In patients treated with chemotherapy the risk of infection mainly depends on the duration and intensity of neutropenia. It is essential to evaluate which pathogens are involved so that the most appropriate treatment can be selected a priori, as well as to determine the patient's general clinical status so that more or less aggressive treatment can be provided from the beginning, bearing in mind that "low risk" patients can be managed in the home. These questions can be determined by evaluating the patient's clinical history, physical examination, laboratory investigations, and radiological tests. Prompt initiation of broad-spectrum antibiotic therapy adapted to the the patient's risk is crucial.