[Local and transcutaneous pharmacotherapy. Pharmacokinetic principles and clinical evaluation]. / Die lokale und transkutane Pharmakotherapie. Pharmakokinetische Grundlagen und klinische Bewertung.

The pharmacological and pharmacokinetic postulates and preconditions for the various kinds of pharmaco-therapy (topical, systemic and transcutaneous) are presented. Taking into consideration mathematical and physical principles as well as anatomical and physiological factors, the possibilities for influencing the flow of drugs into and through the skin are described (choice of vehicle and concentrations, permeation enhancers). In the clinical part of the study, it is shown that following these guidelines can lead to new forms of therapy and to safer application of drugs and cosmetics.

[Ultrastructure of "acrobullous dermatosis" induced by PUVA-therapy in psoriasis]. / Ultrastruktur der "akrobullösen Dermatose" PUVA-therapierter Psoriatiker.

Report about a 44-year-old psoriatic female who developed recurrent bullous eruptions on her extremities during oral photochemotherapy. Ultrastructural analysis revealed an epidermolytic blister formation due to cytolytic alteration of infranuclear parts of basal cells. Pathogenetically, an initial subclinical phototoxic alteration of the epidermodermal coherence is assumed which may lead to a visible bulla by an additional mechanical trauma. There was no evidence for a subclinical bullous pemphigoid.

[The risks of photochemotherapy (author's transl)]. / Die Risiken der Photochemotherapie.

The side effect of phototherapy with 8-methoxypsoralen was divided in short- and longterm damage. From 1969 till 1980 2 013 patients were treated. The pattern of alteration by PUVA depends on doses, continuance of therapy and type of dermatoses as psoriasis, vitiligo, mycosis fungoides, physical urticarias, chronic eczemas. The spontaneous development of tumors, the initiating or promotion of tumors by PUVA as well as a regression of tumors by PUVA has to be taken into account regarding the absolute numbers of tumors after PUVA-therapy. The risk of the PUVA-therapy depends on the doses of continuance of the treatment including the combination with other sources of radiations or natural sun-exposition. The possibilities of drug combinations to lower the total doses of light energy are discussed according the recommendation of several teams in Germany.

[Granuloma anulare--an indication for photochemotherapy? (author's transl)]. / Granuloma anulare--Eine Indikation fr die Photochemotherapie?

Typical granuloma anulare lesions of 2 years duration on the elbows of a 50-year-old woman cleared completely after intense sunlight exposure. A recurrence resolved under local PUVA-treatment (total dose 10.2 Joule/cm2). An extended study is needed to evaluate the usefulness of PUVA-therapy in granuloma anulare.

Effects of riboflavin on Gunn rats under phototherapy.

Blue and white phototherapy was given to infant (and weanling) homozygous Gunn rats treated with different doses of riboflavin-5-phosphate (ribofl.5'p.) During the first hours after a flavin-injection, the effect of phototherapy with both types of fluorescent lamps was enhanced. With equal radiant power applied, the steepness of serum bilirubin decline depended on the ribofl.5'p. dose injected. After oral or cutaneous application, no similar effect occurred. After a single flavin dose, the serum bilirubin decline lasted for at least 3 hr. Nevertheless, in long-term studies with repeated injections (100 mg/kg every 48 hr), no protective effect beyond that of phototherapy alone could be ascertained on the Purkinje cells in the cerebella of the rats. In the skin of the animals, fluorescence was macroscopically noticeable after ribofl.5'p. injections. When an effective irradiance of about 3.0 mW/cm2 and a high flavin dose (100-200 mg/kg) was administered, histologic investigations of the skin in the abdominal and back region revealed a reversible inflammatory reaction with edema and morphologic changes in the epidermal cells that culminated 12-24 hr after the injection. After a further increase of the effective irradiance, tremendous vesicles on paws, ears, and tails were observed in most of the animals 24-72 hr after the flavin injections. The content of the blisters was primarily serous, later on, often hemorrhagic. Finally, necrosis developed. Acute toxicity of ribofl.5'p. differed markedly when the infant rats (homozygous jaundiced as well as heterozygous nonjaundiced) were kept in the dark or under intense blue phototherapy. Much higher doses were tolerated in the dark. Moreover, it could be demonstrated that ribofl.5'p. does not influence serum bilirubin of jaundiced Gunn rats kept in complete darkness. That suggests that the drug itself does not compete for albumin binding sites. But certain riboflavin ampules (Beflavin) contain stabilizers that considerably displace bilirubin from albumin bonds. Riboflavin disturbs direct photometric bilirubin measurements, but not the diazo reaction. When bilirubin is to be measured in sera containing riboflavin, lights must be extremely dim. Photodegradation in vitro is highly accelerated by the sensitizer.

Treponema pallidum in early syphilitic lesions in humans during high-dosage penicillin therapy. An electron microscopical study.

The alterations of early syphilitic infection occuring in the course of high dosage penicillin (120 mega IU, 36 h) as clinical experimental trial has been studied both from the clinical and the electron microscopical views. By electron microscopical studies, findings revealing the localization and the status of treponemes before and during penicillin treatment could be established. Before treatment started, the majority of treponemes was of intercellular localization. In the course of treatment various forms of destruction could be differentiated. The most striking change in the host tissue after 7-8 h of penicillin therapy was an elimination of treponemes by penetrating phagocytes. 24 h after the beginning of treatment, treponemes could not be demonstrated any more. The clinical and serological findings after the high dosage penicilline will produce results comparable to those of conventional therapie.