The retinoids. A review of their clinical pharmacology and therapeutic use.

With the introduction of the synthetic retinoids, oral therapy with an acceptable risk/benefit ratio became possible for a variety of skin diseases including severe acne, psoriasis and numerous genodermatoses. This article reviews the clinical pharmacology, mechanisms of action and therapeutic use of the retinoids, particularly isotretinoin (13-cis-retinoic acid) and etretinate. The free aromatic acid of etretinate, etretin, and the new polyaromatic retinoid compounds (arotinoids) are also discussed. Isotretinoin is used clinically for oral therapy of severe acne, but is also recommended for severe Gram-negative folliculitis and rosacea not responding to traditional therapy. The results of several studies have established that acne therapy should be started with 1.0 mg/kg/day for 2 to 3 months after which the daily dosage should be lowered to 0.2 to 0.5 mg/kg/day for another 2 to 3 months. This therapeutic regimen of isotretinoin has proven to be the most successful in preventing relapses. Etretinate is particularly useful for oral therapy of widespread plaque-like, pustular and erythrodermic psoriasis, and of generalised lichen planus, Darier's disease and severe congenital ichthyoses. Whereas pustular forms of psoriasis require a high daily dosage of 1.0 mg/kg/day, erythrodermic psoriasis should be treated with a lower dosage of 0.25 to 0.35 mg/kg/day. In chronic plaque-like psoriasis, a mean daily dosage of 0.5 mg/kg/day over several weeks to months, usually combined with photo(chemo)therapy, tar or dithranol, is recommended. Other indications for oral etretinate therapy are adequately treated with a moderate dosage of 0.4 to 0.75 mg/kg/day. Etretin differs from etretinate in having a much shorter elimination half-life of 2 to 3 days, in contrast to 80 to 100 days after long term administration of etretinate. Moreover, it has not been shown to increase serum cholesterol levels. However, its clinical efficacy is not yet clearly established. Among the arotinoids, arotinoid ethylester (Ro 13-6298) has revealed the best anti-psoriatic and anti-inflammatory effects at extremely low dose levels. Furthermore, no significant elevations of serum lipids have been observed. Taking its prolonged elimination half-life and its efficacy/side effect ratio into account, the drug is comparable to etretinate. The free arotinoid carboxylic acid (Ro 13-7410) is currently undergoing clinical investigation. Another arotinoid, the parent compound Ro 15-0778, has not demonstrated any convincing clinical efficacy in acne or psoriasis, but topical anti-inflammatory effects were evident in some models.(ABSTRACT TRUNCATED AT 400 WORDS)

An experimental evaluation of impedance cardiographic and electromagnetic measurements of stroke volumes.

The reliability of impedance cardiography for absolute and relative measurements of stroke volumes is assessed by comparing data with electromagnetic flowmeter measurements in 14 anaesthetized mongrel dogs. Cardiac output was altered in each dog (as much as possible) by a variety of physical and pharmacological interventions. Impedance cardiography does not provide absolute values for stroke volumes, although relative changes may be calculated with reasonable reliability if a correction factor ('CIMP') is employed. 'CIMP' is around 0 . 8 in subjects breathing spontaneously or when alternative pressure ventilation is applied. However, this factor can only be used in an intermediate range of stroke volumes (10-30 ml in the dog). At lower and higher cardiac output levels other correction factors must be observed accordingly. Intermittent positive pressure ventilation increases the sensitivity of relative stroke volume measurements by transthoracic impedance, leading to an average 'CIMP' of 1 . 5. For calculation of relative stroke volume changes by impedance cardiography, the simple formula: (formula; see text) is satisfactory instead of the more complicated Kubicek formula.

[Aplasia of the inferior vena cava]. / Aplasie der Vena cava inferior.

A 12-hour-old white female infant is reported who suffered from multiple combined visceral malformations. Inversion of the caecum and ascending colon was noted. An extremely rare finding was the absent inferior vena cava. There was a left-sided Bochdalek's hernia with subsequent hypoplasia of the left lung. Thus respiratory failure immediately after birth required emergency surgery. Besides, a single umbilical artery was found. Manifestations and embryologic background are discussed.