Interpretation of random urinary catecholamines and their metabolites in neuroblastoma

O'Meara A, Tormey W, Fitz Gerald RJ, Fitzgibbon M, Kenny D. Interpretation of random urinary catecholamines and their metabolites in neuroblastoma. Acta Paediatr 1994;83:88–92. Stockholm. ISSN 0803–5253
This study reports experience in the estimation of urinary catecholamines (uCATs) and their metabolites in the diagnosis and follow-up of neuroblastoma. Random urine samples were assayed for dopamine, noradrenaline and adrenaline, together with their metabolites 4-hydroxy 3-methoxyman-delic acid (HMMA) and homovanillic acid (HVA), using HPLC with electrochemical detection. Twenty of 21 patients had elevation of one or more uCATs metabolites at diagnosis. Patients were monitored serially from diagnosis and, in those patients who had delayed resection of primary tumour (n=13), particular attention was paid to levels at the pre-surgical evaluation as an indicator of persistence of viable disease at the time of surgery; dopamine proved to be the most accurate indicator of persistent disease at this time. Five of these patients developed recurrent disease, 4 of whom had elevation of two or more uCATs metabolites at the time of relapse. Several conclusions can be drawn from this study: (a) results for HMMA, HVA and dopamine in random urine samples will detect all but the most biochemically immature or inert tumours; (b) dopamine may be the most reliable indicator of persistent disease and (c) noradrenaline and adrenaline measurements were of little benefit. As results are Expressed in relation to urinary creatinine, excretion of which may be affected by dietary protein and is therefore not constant, borderline results should be repeated.     

Liposomal amphotericin B in hepatic candidosis

A 4 year old girl treated with a standard chemotherapy protocol for acute lymphoblastic leukaemia developed hepatic candidosis during the consolidation phase. This relapsed after a prolonged course of amphotericin B and flucytosine. An eight week course of liposomal amphotericin produced a marked clinical improvement which was sustained for one year. A subsequent relapse was associated with transformation to myelodysplastic leukaemia.     

Surgical anatomy of the nose

It is imperative to know the details of the anatomy of the nose before understanding any surgical procedure performed on the nose. The details presented in this article should help the experienced and the novice surgeon accomplish the difficult task of a rhinoplasty.     

5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.     

Possibility of selection against mtDNA mutations in tumors

Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.