BACKGROUND
We present a study of the heart malformations found in a collection of mouse fetuses of the iv/iv strain between days 16.5 and 18.5 of gestation.
METHODS AND RESULTS
One hundred hearts were serially sectioned and studied by segmental analysis with a light microscope. Forty additional hearts were analyzed with a scanning microscope. Forty percent of the hearts were found to be malformed. The most frequently occurring heart malformations were persistence of the sinus venosus (9%), common atrium (17%), common atrioventricular canal (24%), double-outlet right ventricle (12%), Fallot's tetralogy (8%), and transposition of the great arteries (5%). These malformations do not usually occur in isolation but rather appear in the formation of complex cardiopathies. The most severe and frequent is the combination of persistence of sinus venosus, common atrium, common atrioventricular canal, and double-outlet right ventricle; this is the "bulboventricular heart." The morphology of each lesion, as well as the degree of association, is similar to that found in human hearts with complex cardiopathies. Some of these cardiopathies appear to be directly related to formation of the cardiac loop. The iv/iv mouse appears to constitute an excellent model with which to study the etiology and pathogenesis of complex heart defects in humans. These hearts show a high phenotypic variability in the presentation of heart lesions. From a genetic viewpoint, there is a basic defect--the bulboventricular heart--which can be considered congenital. The other malformations can be considered formes frustes of the defect type.
CONCLUSIONS
The iv gene is a developmental gene that affects basic developmental mechanisms. In this regard, heart lesions may not be the primary result of the abnormal gene activity but rather are secondary to defective interactions during cardiac development.
Delphi studies have been used in many situations to gather and assess the group opinion of numbers of experts about the possible outcome of particular defined events. Such studies, however, are very costly in time and money.
This paper poses the hypothesis that reduced scale Delphi studies provide more carefully considered viewpoints than the use of single round surveys. The hypothesis is examined through the use of three very different case studies and sufficient evidence is provided to prove that in these studies the hypothesis is valid.
To test the antiinflammatory and analgesic effects of transdermal glyceryl trinitrate (GTN) the authors carried out a double-blind, randomized, controlled clinical study in 21 patients with mild to moderate leg varicose veins who underwent vein sclerotherapy in both legs. GTN or placebo ointment was applied in a blinded protocol along the surface of the sclerosed vein every eight hours until disappearance of inflammation signs. The varicose vein in one leg was treated with GTN and compared with placebo for the vein of the other leg used as control of thrombophlebitis (TP) signs. Fifteen minutes after first application inflammation signs were observed in all cases. The intensity of inflammation signs was assessed as 26% (10.4 +/- 4.1) in GTN-treated veins and as 61.5% (24.6 +/- 6.3) (P < 0.001) in the placebo-treated veins. One hour later only 63% of cases in the GTN group and all cases in the placebo group showed signs of TP (P < 0.001). The reduction in the intensity of signs at this time was 7.7 +/- 3.9 in the GTN group and 19.7 +/- 6.3 in the placebo group (P < 0.001). All veins in the GTN group were free of signs of TP in less than forty-eight hours. In the placebo group, 45% of veins required more than forty-eight hours for complete disappearance of signs of TP (P < 0.001). The authors conclude that GTN has an antiinflammatory effect in TP induced by sclerotherapy. This action may be related to the nitric oxide released from GTN, through a direct action on the vein and the surrounding inflamed tissue.
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