Substituted (2-phenoxyphenyl)acetic acids with antiinflammatory activity. 1.

The synthesis and antiinflammatory activity of a series of substituted (2-phenoxyphenyl)acetic acids are described. Initial screening in the adjuvant arthritis test showed that halogen substitution in the phenoxy ring enhanced activity considerably. Ulcerogenic potential, as measured by the minimum ulcerogenic dose (MUD), was low in almost all the acids tested. [2-(2,4-Dichlorophenoxy)phenyl]acetic acid possessed the most favorable combination of potency with low toxicity, including ulcerogenicity, and this compound is now in therapeutic use.

Substituted (2-phenoxyphenyl)acetic acids with antiinflammatory activity. 2.

A number of polychlorinated (phenoxyphenyl)acetic acids were prepared as close structural analogues of the antiinflammatory compound fenclofenac, [2-(2,4-dichlorophenoxy)phenyl]acetic acid. Increased potency was shown in several of these compounds, in particular, [2-(2,3,5,6-tetrachlorophenoxy) phenyl]acetic acid (8), which was 40 times more potent than fenclofenac in the adjuvant-induced arthritis screen. In further tests it was found to be equipotent with indomethacin but with a much reduced incidence of acute toxicity (LD50 and ulcerogenicity). On chronic dosing, however, serious toxicity problems arose (including anemia, neutrophilia, and severe peritonitis), and this led to the abandonment of further work on the compound. Three further analogues were prepared containing NH, S, and SO moieties bridging the phenyl rings. Although the NH compound bore a very close structural resemblance both to the above O-linked compound and the potent antiinflammatory drug diclofenac, [2-[(2,6-dichlorophenyl)imino]phenyl]acetic acid, it showed low activity in primary screens. Similarly, neither the S- or SO-bridged analogues had potencies that approached that of 8.

Traumatic neurosis in the etiology of alcoholism: Viet Nam combat and other trauma.

Traumatic neurosis from Viet Nam combat or other sources includes many symptoms that can be effectively self-medicated with alcohol, at least initially. These symptoms include chronic anxiety and restlessness, insomnia, and recurrent frightening dreams. Repeated self-medication with alcohol results in tolerance and a need to increase the amount consumed. Attempts to decrease consumption or to abstain can lead to alcohol withdrawal symptoms similar to and exacerbating the initial symptoms of traumatic neurosis. Continuing alcohol use, with the establishment of a vicious circle, can follow. The authors present three case examples. They note that treatment of alcoholism under the conditions described requires specific attention to the underlying traumatic neurosis.

Electromyographic study of duration of muscle activity in sit-up variations.

The external oblique, rectus abdominis, and rectus femoris muscles of 17 college women were studied electromyographically in 8 sit-up variations to determine the best variation for maximizing abdominal muscle activity and minimizing hip flexor activity. Integrated action potentials and movement phases of each variation were recorded simultaneously. The duration of muscle activity within the movement phases was analyzed. The variables of hook-lying/long-lying, feet supported/feet unsupported, and slow/fast speed of performance were examined. The hook-lying unsupported slow and fast variations were best for maximizing abdominal muscle duration of activity and for minimizing rectus femoris muscle duration of activity. Greatest duration of activity for all muscles occurred in the long-lying supported fast variation. Supporting the feet in both hook and long-lying fast variations was more effective for increasing activity duration of all muscles than the slow supported variations. Speed of performance seemed to be as important as support of the feet or leg position in increasing duration of muscle activity.