THE ROLE OF TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS AND MANAGEMENT OF ADRENAL TUMORS.

CONTEXT: The variety of tumor-seeking radiopharmaceuticals, which are currently in clinical use, may have a potential role as imaging agents for adrenal gland tumors, due to physiological characteristics of this organ. OBJECTIVE: The purpose of this study was to evaluate the diagnostic potential of 99mTc-HYNIC-TOC, 99mTc(V)-DMSA, and 99mTc-MIBI in the assessment of adrenal tumors, by correlating with imaging findings and histopathologic results. DESIGN: The research is designed as a cross-sectional prospective study. PATIENTS AND METHOD: The study included 50 patients with adrenal tumors (19 hormone-secreting and 31 nonfunctioning) and 23 controls without adrenal involvement. In all patients, single-photon emission computed tomography (SPECT) was performed, using qualitative and semiquantitative analysis. The tumor to non-tumor tracer uptake was conducted by using a region-of-interest technique. Adrenal to background (A/B) ratio was calculated in all cases. RESULTS: 99mTc-HYNIC-TOC scintigraphy showed a high statistical significance between A/B ratios, while other two tracers resulted in a lower sensitivity, specificity and accuracy. Futhermore, 99mTc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumors (the receiver-operating-characteristic curve analysis, A/B ratio cut-off value of 8.40). CONCLUSION: A semiquantitative SPECT analysis showed that 99mTc-HYNIC-TOC is a highly sensitive tumor-seeking agent for the accurate localization of adrenal tumors.

Glucose and lipid abnormalities in patients with adrenal incidentalomas.

Adrenal incidentalomas (AI), defined as masses detected during imaging procedures of non-adrenal disorders, have become a common clinical problem that appear to have impairment of glucose and lipid metabolism. PATIENTS AND METHODS: One hundred and ten patients (mean 53.5 age; 24-72), who were diagnosed with functioning and non-functioning AI, were assessed. Patients with hormone-secreting AI underwent biochemical evaluation regarding metabolic disorders. Data about hormone status (cortisol profile and DEX screening test), lipid profile, glycemia, insulinemia were evaluated. RESULTS: This prospective study included 41 (37.28%) patients with non-functional and 69 (62.72%) with functional AI. Tumors associated with (sub)clinical Cushing's syndrome (functional AI) are considered to have higher cortisol concentration at 8h (p=0.027), 16h (p=0.025) and after DEX screening (p<0.010), compared to the controls. Patients with cortisol-secreting AI have significantly higher concentrations of cholesterol (p=0.040), triglycerides (p=0.027) and insulin (p<0.01) than controls. The patients with metabolic disorders have a significantly higher total cholesterol, triglyceride and insulin concentration (p<0.001) compared to controls. There was significant positive correlation between cortisol concentration after DEX screening and total cholesterol (r=0.727, p=0.007), triglycerides (r=0.564, p=0.041) and insulin (r=0.957, p=0.043) in the group with metabolic disorders. CONCLUSION: The present study demonstrates the patients with functional AI have significantly higher lipid, glucose and insulin concentration than controls. There was a significant positive correlation between metabolic parameters and cortisol concentration.

The influence of 4-alkyl substituents on the formation and reactivity of 2-methoxy-quinone methides: evidence that extended pi-conjugation dramatically stabilizes the quinone methide formed from eugenol.

The effects of para-alkyl substituents on both the cytochrome P450-catalyzed oxidation of phenols to quinone methides (QMs; 4-methylene-2,5-cyclohexadien-1-ones), and on the rates of nucleophilic additions to the QMs were investigated. The derivatives of 4-alkyl-2-methoxyphenol studied were 4-methyl (creosol), 4-ethyl, 4-propyl, 4-isopropyl, and 4-allyl (eugenol). The relative reactivities of QMs derived from these phenols with water were 4-methyl > 4-ethyl = 4-propyl > 4-isopropyl > 4-allyl. These variations in rate were rationalized by differences in stabilization of positive charge density at the site of nucleophilic attack. In particular, saturation of the vinyl substituent on eugenol-QM increases the solvolysis rate 100-fold. This effect is presumably due to the loss of the contribution of an additional aromatic resonance structure to the overall resonance hybrid of the QM from 2-methoxy-4-propylphenol. Finally, the kinetic results show that there is a 472-fold difference in reactivity within this series of QMs. The QM glutathione conjugates were synthesized and characterized by 1H-NMR and electrospray mass spectrometry and a HPLC assay was developed to quantify QM formation in rat liver microsomes. The general trend is increasing alkyl substitution at the para position results in more QM; however, in contrast to the large range of reactivities of the QMs observed in the kinetic experiments, the amounts of P450-derived QM GSH adducts varied only by a factor of 3. In particular, similar amounts of the QMs from eugenol and 2-methoxy-4-propylphenol were produced which suggests that the lack of reported hepatotoxicity for the latter phenol in mice depleted of GSH, may be due to the extreme reactivity of 4-propyl-QM that would be rapidly detoxified by hydrolysis. These data suggest that there may be a threshold cytotoxicity level for QMs related to their reactivity which may affect the relative toxicities of 4-alkyl-2-methoxyphenols.

Interrupted aortic arch and aortopulmonary window associated with complete atrioventricular septal defect.

We report a rare case of a neonate with interrupted aortic arch, aortopulmonary window and complete atrioventricular septal defect. To the best of our knowledge, this unusual triad has not been previously described. The main question of the surgical strategy for CAVSD, in setting of associated defects, is to classify the CAVSD as balanced or unbalanced.

Interrupted Aortic Arch and Aortopulmonary Window Associated with Complete Atrioventricular Septal Defect.

We report a rare case of a neonate with interrupted aortic arch, aortopulmonary window and complete atrioventricular septal defect. To the best of our knowledge, this unusual triad has not been previously described. The main question of the surgical strategy for CAVSD, in setting of associated defects, is to classify the CAVSD as balanced or unbalanced.

Evidence that 4-allyl-o-quinones spontaneously rearrange to their more electrophilic quinone methides: potential bioactivation mechanism for the hepatocarcinogen safrole.

Several naturally occurring aromatic ethers, of which safrole [1-allyl-3,4-(methylenedioxy)-benzene] is one example, are hepatocarcinogens. One bioactivation pathway previously proposed for safrole involves hydroxylation of the benzyl carbon, conjugation with sulfate, and then alkylation of DNA with displacement of the sulfate group [Miller, J.A., and Miller, E.C. (1983) Br. J. Cancer 48, 1-15]. The fact that safrole is O-dealkylated to the corresponding catechol (hydroxychavicol, 1-allyl-3,4-dihydroxybenzene) indicates that quinoid formation is also possible and may contribute to the genotoxic and/or cytotoxic activity of this compound. In the present investigation we selectively oxidized hydroxychavicol to the corresponding o-quinone (HC-quinone, 4-allyl-3,5-cyclohexadiene-1,2-dione) or p-quinone methide (HC-QM, 2-hydroxy-4-allylidene-2,5-cyclohexadien-1-one) and trapped these reactive electrophiles with glutathione (GSH). The GSH adducts were fully characterized by UV, NMR, and mass spectrometry. Microsomal incubations with safrole or hydroxychavicol in the presence of glutathione produced only o-quinone glutathione conjugates. However, if the trapping agent (GSH) was added after an initial incubation of 10 min, both o-quinone and p-quinone methide GSH conjugates were observed. The first-order rate constant of isomerization was estimated from the decrease in HC-quinone GSH adducts to be 1.9 x 10(-3) s-1 (t1/2 = 9 min). Kinetic studies showed that while HC-QM reacts rapidly with water, the model o-quinone (4-tert-butyl-3,5-cyclohexadiene-1,2-dione), which cannot isomerize to a quinone methide, was remarkably resistant to hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of the p-alkyl substituent on the isomerization of o-quinones to p-quinone methides: potential bioactivation mechanism for catechols.

Previously, we have shown that an additional bioactivation pathway for the hepatocarcinogen safrole (1-allyl-3,4-(methylenedioxy)benzene) exists which may contribute to its toxic effects: initial O-dealkylation of the methylenedioxy ring, forming the catechol, hydroxychavicol (HC, 1-allyl-3,4-dihydroxybenzene), 2-electron oxidation to the o-quinone (4-allyl-3,5-cyclohexadien-1,2-dione), and isomerization, forming the more electrophilic p-quinone methide (2-hydroxy-4-allylidene-2,5-cyclohexadien-1-one) [Bolton, J. L., Acay, N. M., & Vukomanovic, V. (1994) Chem. Res. Toxicol. 7, 443-450]. In the present investigation, we explored the effects of changing pi-conjugation at the 4-position on both the rate of isomerization of the initially formed o-quinones to the QMs and the reactivity of the quinoids formed from 4-propylcatechol (1), 2,3-dihydroxy-5,6,7,8-tetrahydronaphthalene (2), and 4-cinnamylcatechol (3). We selectively oxidized the catechols to the corresponding o-quinones or p-quinone methides and trapped these reactive electrophiles with glutathione (GSH). The GSH adducts were fully characterized by UV, NMR, and mass spectrometry. Microsomal incubations with the parent catechols in the presence of glutathione produced only o-quinone glutathione conjugates. However, if the trapping agent (GSH) was added after an initial incubation time, both o-quinone and p-quinone methide GSH conjugates were observed. The results indicate that extended pi-conjugation at the para position enhances the rate of isomerization of the o-quinone to the quinone methide. Thus the half-life of the o-quinones decreased in the following order: the o-quinone of 1 > 2 > HC > 3.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ultrasound diagnosis of aneurysm of the vein of Galen in children]. / Diagnostika aneurizme Galenove vene metodom ultrazvuka kod dece.

Aneurysm of the vein of Galen is rare and complex vascular disorder that develops during embriogenesis and provokes significant haemodynamic changes. Boys are more frequently involved. During the foetal period Ballantyne syndrome may develop, and postnatal clinical presentation vary with ages. Serious haemodynamic changes are followed by congestive heart failure and, if not treated, with lethal exitus. Fast and correct diagnosis is very important. Ultrasound examination of central nervous system supported with Duplex-Doppler and Colour-Doppler examination of the head and heart enables the diagnosis. This text comments ultrasound presentation of the malformation and ultrasound diagnostic possibilities.