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Biomedical subjects

J M Geiger

Publications and source records attributed to J M Geiger.

At least 55 records · Page 3Linked to original sources

Clinical and ultrastructural effects of acitretin in Darier's disease.

Thirteen patients with Darier's disease with a mean extent of the lesions of 29.4 +/- 10% of the total skin area were treated with acitretin (the main metabolite of etretinate) for 16 weeks. The dose was 30 mg/day during the initial 8 weeks and was later adjusted individually to 10-30 mg/day in order to achieve optimal results. Three patients cleared completely, 7 patients showed marked improvement and 3 patients became slightly better during treatment. The mean extent of the lesions after the treatment was 7.3 +/- 8% of the skin area. Despite good clinical clearing, the improvement at the ultrastructural level was incomplete in the 3 patients studied by electron microscopy. Normal stratification did not develop and the size and number of desmosomes remained reduced. The main side effects during treatment were pruritus in 5 patients, diffuse alopecia in 2 patients and marked elevation in serum triglycerides in 4 patients. On the basis of this study, acitretin would seem to be a useful alternative to etretinate for the treatment of Darier's disease.

Acitretin↗

Intra-epidermal accumulation of polymorphonuclear leukocytes in persistent palmoplantar pustulosis during treatment with acitretin.

Six patients with persistent palmoplantar pustulosis were treated with acitretin, and the clinical response was compared with the effect on the intra-epidermal accumulation of polymorphonuclear PMN leukocytes. A prompt improvement of pustule formation and subsequently decreased scaling and erythema was seen in all patients. Following discontinuation of therapy, a relapse occurred within 2 weeks. With dosages of 45 or 55 mg/day, the clinical scores were only slightly better than with 25 or 35 mg/day. In patients using 25 mg acitretin a day, the leukotriene B4-induced intra-epidermal accumulation of polymorphonuclear leukocytes was not affected. However, a dosage of 35 mg/day resulted in a significant inhibition of PMN accumulation, dosages of 45 and 55 mg/day causing an even more pronounced inhibition of this process. Although the effect of different dosages of acitretin is not clearly expressed in the severity scores, the dose-dependent effect on PMN chemotaxis in vivo might be of relevance when combination therapies are considered, in order to achieve a complete clinical clearance.

Acitretin↗

Acitretin in the symptomatic therapy for severe recessive x-linked ichthyosis.

Eight men with severe recessive x-linked ichthyosis were treated with acitretin, the main metabolite of etretinate, during four months. All of the patients showed marked clinical improvement of scaling during therapy. Hypervitaminosis A-type adverse reactions were observed in all patients. Although the overall tolerance was good, therapy was interrupted in one atopic patient because of pruritus. There were no undesirable laboratory changes in values. Thirty-five milligrams of acitretin daily provided the best efficacy, with minimal side effects. The beneficial effect of this retinoid lasted between four and six weeks after therapy was stopped. These results suggest that acitretin is a useful agent in the symptomatic therapy of severe recessive x-linked ichthyosis resistant to topical therapeutic modalities. Good results with this agent can be achieved with interval therapy adjusted to seasonal variations of the skin symptoms.

Acitretin↗

Residual plasma concentrations of acitretin (Ro 10-1670) and its metabolite (Ro 13-7652) after chronic administration.

In order to study the elimination of Ro 10-1670 (acitretin) and Ro 13-7652, its 13-cis-isomeric metabolite after chronic administration, determination of the residual plasma concentrations of these two compounds were assayed in 9 patients in a range of 22-30 days following cessation of a 2- to 7.5-month course with daily oral doses of 10-50 mg of acitretin. A highly sensitive HPLC method was used (2 ng/ml). Residual plasma concentrations of Ro 10-1670 were below the quantification limit in all cases. Residual plasma concentrations of Ro 13-7652 were below the quantification limit in 7 cases and respectively of 3 and 4 ng/ml in the other 2 cases. These data appear to confirm the absence of storage of acitretin even after an extended course of therapy.

Acitretin↗

Cis-trans interconversion of acitretin in man.

The major plasma metabolite of acitretin (trans-acitretin) is its 13-cis isomer, cis-acitretin. Interconversion of cis-acitretin to trans-acitretin was demonstrated in man following administration of a single oral dose of cis-acitretin. Plasma concentrations of Ro 13-7652 (cis-acitretin) and Ro 10-1670 (trans-acitretin) were much higher after cis-acitretin administration than after trans-acitretin administration. Surprisingly, these high concentrations were not associated with a clear therapeutic effect in dermatoses (e.g. psoriasis) which are usually responsive to oral retinoids. Interactions between the cis and trans isomers formed in vivo may explain the difference in therapeutic activity of each stereoisomer when administered orally.

Acitretin↗

Treatment of severe psoriasis with etretin (RO 10-1670).

Eighty patients with severe psoriasis were treated in a double-blind fashion with either an initial dose of 10 mg, 25 mg or 50 mg of etretin daily or with placebo. Follow-up examinations were carried out monthly and the efficacy of treatment was evaluated by using the PASI score. Adverse effects of the treatment were recorded monthly; liver enzymes, cholesterol and triglycerides were measured. After 2 months of treatment the maintenance dose was reduced in some of the patients either because of complete remission or adverse effects. After 2 months treatment, groups receiving 25 mg/day and 50 mg/day showed significantly lower PASI scores than the placebo group. The 10 mg/day group showed a response intermediate between the 25 mg and 50 mg groups and the placebo group. Thus, the optimal initial dose seems to be approximately 25 mg/day and the maintenance dose somewhat lower. Six months after the start of treatment there were no significant differences between the four groups; the last follow-up examination took place during the summer and some of the patients probably experienced spontaneous improvement. Although clinical adverse effects were frequent in all groups, severe side effects, namely hair loss and paronychia, occurred frequently only among patients treated with an initial dose of 50 mg of etretin daily. The effect of treatment on liver enzymes, cholesterol and triglycerides was minimal.

Acitretin↗

Arotinoid ethyl ester (Ro 13-6298): a long term pilot study in various dermatoses.

The arotinoid ethyl ester Ro 13-6298 is a third generation retinoid shown to be thousand-fold more potent than etretinate (Tigason, Tegison) in animal testing and in human therapy. In an open uncontrolled trial, we treated 57 patients suffering from psoriasis (32) and various severe skin disorders (25) with daily doses ranging from 20 to 150 micrograms, during 1 to 130 weeks (mean = 12 weeks). Four patients were treated for 1 year or more. Given in micrograms per kg range, Ro 13-6298 showed a spectrum of clinical activity and mucocutaneous side effects similar to that of etretinate given in mg per kg range. One patient developed diffuse idiopathic skeletal hyperostosis after 2 years of continuous therapy. No increase in either serum triglycerides or cholesterol levels was observed, even in patients treated for 33 to 130 weeks. This might prove to be an advantage of this new retinoid. Furthermore, this series suggests that potent mucocutaneous (therapeutical and side) effects are not necessarily linked to all other signs of retinoid toxicity.

Adult↗

Use of tricalcium phosphate or electrical stimulation to enhance the bone-porous implant interface.

Implant stabilization by biologic ingrowth into a porous surface offers a durable method of prosthetic fixation. These systems, however, lack the immediate stability offered by the use of acrylic bone cement. The interface strength of porous coated Co--Cr--Mo in a canine model does not approach that of acrylic bone cement until two weeks postoperatively. It is expected that this would be a minimum time period in clinical applications. Both chemical and electrical means have been advocated as methods to affect tissue ingrowth. A study using a canine model was undertaken to determine tissue ingrowth rates utilizing examples of these two methods: (1) impregnation of the porous structures with tricalcium phosphate powder (TCP); or (2) the application of an electrical stimulator to the implant with the implant itself serving as the cathode. Ten implants were coated with TCP, two each at weekly intervals from 1 to 5 weeks. Plain porous rods were likewise implanted, serving as the controls. While histology did reveal a slightly more dense bony structure, the interface bond strength was not affected by TCP. Electrical stimulation of the implant was similarly investigated with an additional time period of 10 weeks. Compared to the controls, the electrically stimulated implants reveal no statistically demonstratable difference in interface strength. Histologic specimens indicate larger areas of calcification than are observed in the controls.

Animals↗

Arotinoid Ro 13-6298 and etretin: two new retinoids inferior to isotretinoin in sebum suppression and acne treatment.

Thirty patients have been treated with either etretin, the main derivative of etretinate, or arotinoid Ro 13-6298, a polyaromatic retinoid, or isotretinoin. Sebum production was measured before and during the treatments. While no change was observed in the patients treated with etretin, a reduction of 33% of the sebum excretion rate was observed for those treated with arotinoid Ro 13-6298 but only after long treatment periods of 20 to 30 weeks. The sebum excretion rate decreased by 92% in the patients treated with isotretinoin. Four patients suffering from severe nodulocystic acne were treated with arotinoid Ro 13-6298 for 2-5 months without improvement. Substantial improvement, however, resulted after a subsequent treatment with isotretinoin; sebum production decreased markedly as well. This study suggests that neither etretin nor arotinoid Ro 13-6298 will replace isotretinoin in the treatment of severe nodulocystic acne.

Acitretin↗

Aspirin and recurrent hyphema after blunt ocular trauma.

Recurrent hyphema after traumatic blunt injury to the eye is associated with a more serious prognosis than that occurring from the initial trauma, resulting in a higher risk of glaucoma, corneal staining, surgical intervention, poor visual acuity, and enucleation. Risk factors associated with the development of recurrent bleeding are not well defined, but recent evidence suggests a high association with concurrent aspirin ingestion. Of 25 consecutive patients with hyphemas (20 males and five females, ranging in age from 2 to 53 years), 12 took aspirin after the initial trauma and seven had recurrent hyphemas. Platelet aggregation determinations in these seven patients showed defects associated with aspirin. Only one of 13 patients without aspirin intake had recurrent bleeding.

Adolescent↗

[Long-term treatment of severe nodulo-cystic acne with 13-cis retinoic acid].

15 patients with severe nodulo-cystic acne were treated with 13-cis retinoic acid (Ro 4-3780) for 6 to 12 months. The initial dose was 40 mg/day in all the cases. In 14 out of 15 cases this dose was progressively reduced depending on improvement of the acne lesions and on the occurrence of side effects. In one case the initial dose was later increased to 60 mg/day because of lack of response to the treatment. A 75 p. 100 improvement in the severity of the acne lesions was achieved within 4 to 5 months. Complete disappearance of the lesions was achieved in most of the patients after between 6 and 12 months of treatment. The most frequent clinical side effects were dryness of the lips, cheilitis with rhagades and facial dermatitis. Abnormal increased values of hepatic enzymes and triglycerides were found in some patients.

Acne Vulgaris↗

[Action of estrogens on pituitary gonadotrophic function and follicular growth during diestrous in the rat (author's transl)].

LH and FSH release during the afternoon of diestrus 1 on the one hand, and the rate of follicular growth on the morning of diestrus 1 or diestrus 2, on the other hand, were studied in 4-day cyclic female rats after injection of estradiol benzoate (10 microgram, s.c.) on the morning of estrus. LH and FSH release was observed between 15.00 and 19.00 h during diestrus 1, but did not occur after an injection of pentobarbital (30 mg/kg, i.p.) in diestrus 1 at 13.30 h. No luteinization resulted from an injection of estrogen. Slowed follicular growth was observed on the morning of either diestrus 1 or diestrus 2. These results suggest the existence of a "critical period" for LH and FSH release in diestrus 1 during the afternoon. They indicate that the ovarian response to the endogenous release of gonadotropins is dependent upon the state of development of the ovarian follicles.

Animals↗