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Biomedical subjects

M Spada

Publications and source records attributed to M Spada.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Diagnosis of metabolic coma in children].

This article describes the metabolic investigations to be applied in any clinical situation consistent with a late acute form of inborn error of metabolism: unexplained coma with or without focal neurological manifestations, recurrent vomiting with lethargy, episodes of ataxia with or without behaviour disorder, fits of psychiatric troubles. In each of these situations, careful medical history is of major importance searching for previous clinical manifestations such as episodes of coma, ataxia or vomiting, anorexia, failure to thrive, developmental delay, all very suggestive of metabolic disorder. The association of neurological symptoms and abnormal hepatic tests is also of great value and must not lead to the diagnosis of Reye's syndrome without considering a metabolic defect of fatty acid oxidation, urea cycle, respiratory chain, or Wilson's disease. When looking for an etiological origin, it is mandatory to collect all the biological information at the same time, also knowing that metabolic abnormalities may be mild and transitory, and that many of them are non specific (metabolic acidosis, hyperlactacidemia, hyperammonemia, hepatic tests disturbances) being encountered in collapsus, shock and multiple organ failure syndrome.

Acute Disease↗
PubMed1993

Hyperphenylalaninemia and pterin metabolism in serum and erythrocytes.

The relationship between blood phenylalanine concentrations and serum and erythrocyte biopterin and neopterin concentrations was investigated in 20 phenylketonuric patients with different dietary compliance. At serum phenylalanine concentrations ranging from 43 to 1004 mumol/l, a good correlation was found with serum biopterin (r = 0.76, P < 0.001) and with red blood cell biopterin (r = 0.62, P < 0.001). A similar correlation was found between serum neopterin and phenylalanine (r = 0.60, P < 0.001). The correlation between red blood cell neopterin and serum phenylalanine was less evident, however (r = 0.47, P < 0.005). After oral loading with phenylalanine (100 mg/kg body weight), serum and red blood cell biopterin concentrations increased in patients with classical phenylketonuria as well as in one patient with dihydropteridine reductase deficiency in response to the induced acute hyperphenylalaninemia. One patient suffering from 6-pyruvoyl tetrahydropterin synthase deficiency was loaded orally with tetrahydrobiopterin (20 mg/kg body weight). The kinetics of administered cofactor confirmed its rapid absorption, with early increase of serum concentrations followed by its transport into the red blood cells. The half-life of biopterin was approximately 7 h in serum and 15 h in red blood cells. Because both values are less than the half-life of phenylalanine (20-30 h) in serum, biopterin measurement offers no advantage in monitoring dietary control in hyperphenylalaninemic patients.

Alcohol Oxidoreductases↗
PubMed1993

Differential diagnosis of hyperphenylalaninaemia by a combined phenylalanine-tetrahydrobiopterin loading test.

We describe a new fully reliable method for the differential diagnosis of tetrahydrobiopterin-dependent hyperphenylalaninaemia (HPA). The method comprises the combined phenylalanine (Phe) plus tetrahydrobiopterin (BH4) oral loading test and enables the selective screening of BH4 deficiency when pterin analysis is not available or when a clear diagnosis has not been previously made. It should be performed together with the measurement of dihydropteridine reductase (DHPR) activity in blood. The new combined loading test was performed in nine patients with primary HPA, three with classical phenylketonuria (PKU), three with DHPR deficiency, and three with 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency. Three hours after oral Phe loading (100 mg/kg body weight), synthetic BH4 was administered orally at doses of either 7.5 or 20 mg/kg body weight. Amino acid (Phe and tyrosine) and pterin (neopterin and biopterin) metabolism and kinetics were analysed. By exploiting the decrease in serum Phe 4 and 8 h after administration, a clear response was obtained with the higher BH4 dose (20 mg/kg body weight), allowing detection of all cases of BH4 deficiency, as well as differentiation of BH4 synthesis from regeneration defects. Since DHPR deficient patients who were previously shown to be non-responsive to the simple BH4 loading test gave a positive response, the combined Phe plus BH4 loading test can be used as a more reliable tool for the differential diagnosis of HPA in these patients. Moreover, it takes advantage of being performed while patients are on a Phe-restricted diet.

Alcohol Oxidoreductases↗
PubMed1993

Catalytic activity of tetrahydrobiopterin in dihydropteridine reductase deficiency and indications for treatment.

It is now widely accepted that tetrahydrobiopterin (BH4), the natural cofactor of aromatic amino acid hydroxylases, in the absence of its regenerating enzyme dihydropteridine reductase (DHPR), will function only stoichiometrically in the phenylalanine (Phe) hydroxylating system. This has limited the use of pterin cofactor in diagnosis and treatment of patients suffering from inherited DHPR deficiency, one of the most common forms of hyperphenylalaninemia caused by BH4 deficiency. This is despite the observation of a dramatic fall in serum Phe concentration after BH4 loading in such patients. In this study, quantitation of this phenomenon was obtained by comparing the kinetics of serum Phe after either a simple Phe or a combined Phe plus BH4 oral loading in patients with Phe hydroxylase or with DHPR deficiency. Only in the latter was the total body clearance of Phe enhanced up to 5 times by the cofactor administration, resulting in the molar equivalent of Phe hydroxylated/mol of BH4 ranging from at least 6 to 10, against the postulated 1. As a consequence, BH4 administration should be attempted therapeutically in DHPR-deficient patients, thus avoiding a lifelong Phe-restricted diet. Preliminary experience with such treatment is given with two cases.

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

[Hemodynamic changes in liver and multi-organ transplantation].

Multivisceral transplantation is a surgical technique developed as treatment for abdominal metastatic and/or multifocal malignancies. At present its clinical employment is reduced by our fragmentary knowledge of the intraoperative and postoperative outcome. The aim of this study is to compare intraoperative hemodynamic and respiratory changes during multivisceral transplantation (MTV, n = 12) and liver transplantation (OLTX, n = 14). The observations have been carried out a 4 phases: basal (I), visceral (II), reperfusion (III), final (IV). Phase I does not show differences between MTV and OLTX. In phase II MTV presents a lower temperature (T) and pulmonary arterial pressure (PAP) (p > 0.05). Phase III is marked by increasing T differences (p < 0.05), lower cardiac frequency (CF), pH and base excess (BE) (p < 0.05). PAP and cardiac output (CO) show a higher value in MTV (p < 0.05). Phase IV reports the vital signs close to normality in both groups, except pH in MTV (p > 0.05).

Animals↗
PubMed1987

Effects of alpha 1-adrenergic blockade on pulsatile luteinizing hormone, follicle-stimulating hormone, and prolactin secretion in polycystic ovary syndrome.

Central noradrenergic mechanisms may participate in the regulation of pulsatile gonadotropin secretion in women with the polycystic ovary syndrome (PCO). To examine this possibility we measured serum LH, FSH, and PRL concentrations at 10-min intervals and total testosterone and 17 beta-estradiol at 60-min intervals for 8 h basally and during the infusion of the alpha 1-adrenoceptor antagonist thymoxamine (10 micrograms/kg X min) in 10 young women with PCO. Mean and integrated serum LH concentrations as well as LH pulse frequency were not significantly altered (P = NS) during the thymoxamine infusion. However, we found an increase in LH pulse amplitude as both net (P less than 0.002) and percent (P less than 0.002) increment, as well as mean LH peak values (P less than 0.05) during alpha 1-adrenergic blockade. There were no significant changes in pulsatile FSH and PRL secretion or gonadal sex steroids during these experimental conditions. These data suggest that in PCO patients, 1) brain noradrenergic mechanisms do not play a stimulatory role in regulating the frequency of pulsatile LH secretion, 2) central noradrenergic activity inhibits LH pulse amplitude, and 3) PRL and FSH pulsatility are not altered by central noradrenergic blockade.

Adolescent↗