Sonographic assessment of amniotic fluid volume between 11 and 24 weeks of gestation: construction of reference intervals related to gestational age.

OBJECTIVE: At present, most of the methods for sonographic assessment of amniotic fluid volume are unreliable in the second trimester of pregnancy, or else they do not present nomograms related to gestational age. DESIGN: The aim of this prospective cross-sectional study was to construct normal reference ranges of four ultrasound parameters for the evaluation of amniotic fluid volume which could be applied in the second trimester. For these parameters we calculated normal curve limits suitable for use in clinical practice. SUBJECTS: From a population of normal pregnant women between the 12th and the 24th weeks of gestation undergoing a routine ultrasound examination during 1997 at our institute, 273 were found to be suitable for the study, after the exclusion of all cases which presented any feto-maternal pathology or complications up to the 24th week. METHODS: The largest 'amniotic pocket' in a vertical direction, free of small fetal parts and umbilical cord, was measured: the maximum vertical and transverse diameters were measured on the same scan; the mean diameter and the product of the two diameters were calculated. The 'mean amniotic fluid diameter', the 'two-diameter pocket', the 'largest vertical pocket' and the 'largest transverse pocket' were the four sonographic parameters considered. RESULTS: The four parameters correlated well with gestational week and with the biparietal diameter; the normal reference intervals and normal curve were then calculated. All these parameters were found to have good intra- and interoperative reproducibility. CONCLUSIONS: We conclude that the use of an ultrasound semiquantitative method based on the measurement of a single amniotic fluid pocket and involving normal reference intervals according to gestational age could improve the early diagnosis of amniotic fluid variations during the second trimester, although this has yet to be confirmed by extensive clinical trials.

Synthesis and cardiotonic activity of novel pyrimidine derivatives: crystallographic and quantum chemical studies.

The synthesis of ethyl or methyl 4-substituted or unsubstituted 2-(dimethylamino)-5-pyrimidinecarboxylates 10-20, which is mainly carried out by reaction of ethyl or methyl 2-[(dimethylamino)methylene]-3-oxoalkanoates with 1,1-dimethylguanidine, is described. The above esters were hydrolyzed to the relative carboxylic acids 21-30, which were decarboxylated to the corresponding 2,4-disubstituted pyrimidines 31-40. All the new synthesized pyrimidines were evaluated in spontaneously beating and electrically driven atria from reserpine-treated guinea pigs. Their effects were compared to those induced by milrinone in both atria preparations. Compound 28 (4-benzyl-2-(dimethylamino)-5-pyrimidinecarboxylic acid) was the most effective positive inotropic agent, while the corresponding methyl ester 17 reduced both the contractile force and the frequency of guinea pig atria. An antagonism toward the negative influence exerted by endogenous adenosine on the heart seems to be involved in the contractile activity of compound 28. By contrast, compound 17 might be partial agonist at the purinergic inhibitory (A1) receptor. X-ray analysis carried out on 17 and 28 and molecular modeling investigations extended also to related derivatives allowed a possible rationalization between structure and inotropic activity for this series of compounds.

Synthesis, antiviral (HSV-1) and antimycotic activities of ethyl or methyl 2,4-disubstituted 5-pyrimidinecarboxylates, 2,4-disubstituted 5-pyrimidinecarboxylic acids and 2,4-disubstituted pyrimidines.

The synthesis of ethyl or methyl 4-substituted or unsubstituted 2-methylthio-5-pyrimidinecarboxylates 3 a-i and 8 o mainly by reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with 2-methylisothiourea is described. Also some ethyl 2-substituted (NH2, CH3, C6H5) 4-trifluoromethyl-5-pyrimidinecarboxylates were prepared. Some of the above esters were hydrolyzed to the relative carboxylic acids, which were decarboxylated to the corresponding 2,4-disubstituted pyrimidines. Esters 3 a-i and 8 o were tested for their toxicity on Vero cultured cells and for their inhibitory activity against herpes simplex virus type 1 (HSV-1) infectivity in a short-term plaque assay. At non toxic concentrations, each ester was found to be active, the most interesting compound being 3 h, which achieved a 80.9% inhibition of HSV-1 infectivity at 12 micrograms/ml. Moreover, esters 3 f, 8 l and acid 9 o were active against some fungal strains.

1-Phenyl-1H-indazole derivatives with analgesic and anti-inflammatory activities.

The synthesis of 4-hydroxy-1-phenyl-1H-indazole-5-acetic acid 5 4-methoxy-1-phenyl-1H-indazole-5-yl-acetic acid 7 and 5-benzyl-1-phenyl-1H-indazol-4-ol 8, starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one, is described. These compounds showed in mice an analgesic activity superior to that of acetylsalicylic acid and comparable to that of dipyrone; moreover, compound 5 exhibited an appreciable anti-inflammatory activity in rats. Grossbehavioral effects and acute toxicity in mice are also reported.

S-7 inhibition of Herpes simplex virus type 1 infectivity and replication in cultured cells.

The effect of ethyl 2-methylthio-4-methyl-5-pyrimidine, carboxylate (S-7) on the infectivity and replication of herpes simplex virus type 1 in Vero cells was studied. S-7, at the highest concentration lacking toxic effect on cells (40 microg/ml), produced, at various inocula, a 40% inhibition of HSV-1 infectivity with respect to the plaque formation detected in control infected cultures. This inhibitory activity was substantiated by studies on progeny production. We cannot conclude that the inhibition of viral cytopathic effect resides in a specific inhibition of viral enzymes, however, the possibility of a more specific antiviral effect cannot be totally ruled out.