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We noninvasively investigated the effects of a single 30-min i.v. infusion of a 2-mg dose of niravoline, a new selective kappa-opioid agonist, on systemic and regional (brachial artery) hemodynamics, on plasma levels of the main hormones regulating the cardiovascular system, on diuresis and on plasma and urinary osmolalities and electrolytes. This was a placebo-controlled, randomized, double-blind, crossover study performed in 12 healthy volunteers. Compared with placebo, niravoline induced a significant, early and potent diuresis, which peaked within 2 hr (urine output increased 2.4-fold) and lasted for 4 hr. Niravoline significantly decreased, between 0 and 2 hr, urine osmolality (-71%) and sodium (-38%) and potassium (-29%) excretion and significantly increased plasma osmolality and natremia, without changing kalemia. Niravoline induced a slight, but significant, increase in blood pressure (+8% at 0.5 hr), which disappeared within 2 hr. Because heart rate, stroke volume and cardiac output were not modified, this effect was due to an increase in total peripheral resistance (+22% at 0.5 hr). Niravoline did not modify brachial artery diameter and flow and corresponding vascular resistance. Niravoline tended to decrease plasma vasopressin levels and urinary excretion and significantly increased plasma levels of norepinephrine (+44% at 0.5 hr), active renin (+22% at 1.25 hr), aldosterone (+52% at 1.25 hr) and atrial natriuretic factor (+20% at 2 hr). We conclude that niravoline induces a potent aquaretic effect associated with antinatriuresis and antikaliuresis. These main effects are accompanied by a stimulation of the sympathetic and reninangiotensin systems and a slight and transient increase in blood pressure.

We report a case of azathioprine-induced haemorrhagic alveolitis, in a 14-year-old boy, after renal transplantation. On day 25 the patient developed haemoptysis, fever and hypoxaemia. Chest X-ray showed diffuse reticulo-nodular shadows in both lung fields. Bronchoalveolar lavage samples were haemorrhagic and demonstrated a relative neutrophilia and a mild lymphocytosis, with a normal CD4/CD8 ratio. Azathioprine was discontinued on day 26. The patient required mechanical ventilation for 4 days. A positive leucocyte migration inhibition test and the recurrence of the symptoms after a second short course of azathioprine therapy suggested a cell-mediated mechanism. This patient is, to our knowledge, the first child to suffer from azathioprine-induced pulmonary haemorrhage.

Abstract: We report 2 cases of thoracic neural crest tumors complicating the course in patients with Beckwith-Wiedemann syndrome (BWS). In the first patient, a thoracic neuroblastoma was fortuitously discovered at age 3 months on a chest film prior to a partial glossectomy. In the follow-up left nephroblastoma and a right kidney simple cyst appeared. In the second patient, a thoracic tumor which proved to be a mature ganglioneuroma was discovered at age 4 years on a follow up spinal radiograph. Although less frequent than nephroblastoma and/or adrenal tumors, the occurrence of thoracic neuroblastoma in BWS suggests that periodic chest radiograph and assays of HVA, VMA and Dopamine should be included in the follow-up protocol.