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Biomedical subjects

J M Geiger

Publications and source records attributed to J M Geiger.

At least 37 records · Page 2Linked to original sources

A 12-month treatment of severe psoriasis with acitretin: results of a Canadian open multicenter study.

Both etretinate and its principal metabolite, acitretin, are efficacious in the treatment of psoriasis. Because patients with severe psoriasis often require chronic therapy, this study was undertaken to determine the efficacy, tolerability, and safety of acitretin in patients on continuous treatment for 12 months. The initial daily dose of 50 mg was taken for 4 weeks. Thereafter the dose was increased or decreased by 10 mg at monthly intervals (10 to 70 mg) to produce the optimal response with minimal toxicity. Seventy percent of the patients who completed 12 months of treatment showed marked improvement. All patients experienced adverse reactions; dry lips, hair loss, skin peeling, pruritus, and nail disorders were the most frequent. Fourteen patients were withdrawn from the study because of one or more intolerable adverse reactions.

Acitretin↗

Acitretin in the treatment of severe disorders of keratinization. Results of an open study.

The purpose of this open, noncomparative study with acitretin (Ro 10-1670) was to evaluate the clinical response of patients with various nonpsoriatic disorders of keratinization and to establish for these patients the optimal dosage for both efficacy and tolerance. Thirty-three patients (21 adults and 12 children or adolescents) with ichthyoses, palmoplantar hyperkeratosis, or Darier's disease were treated for a period of 4 months. Most patients showed marked improvement or remission. The results obtained in congenital ichthyosiform erythroderma, lamellar ichthyosis, and Papillon-Lefèvre syndrome were judged as better than those usually reported with etretinate. The side effects observed in our patients were similar to those reported with etretinate, with the exception of scaling of palms and soles, which had an incidence and severity greater than expected with etretinate. The optimal acitretin dosage providing the best efficacy with minimal undesirable effects varied from patient to patient. The mean daily dose (+/- SD) was 27 +/- 11 mg in adults and 0.7 +/- 0.2 mg/kg in children or adolescents.

Acitretin↗

Photochemotherapy for severe psoriasis without or in combination with acitretin: a randomized, double-blind comparison study.

In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without acitretin and in 96% of the patients (22 of 23) with adjunctive acitretin administration. The mean cumulative UVA dose given to patients in the acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.

Acitretin↗

A carbon fiber implant to aid interbody lumbar fusion. Mechanical testing.

A carbon-fiber-reinforced polymer implant has been designed to aid interbody lumbar fusion. The cage-like implant has ridges or teeth to resist pullout or retropulsion, struts to support weight bearing, and a hollow center for packing of autologous bone graft. Because carbon is radiolucent, bony healing can be imaged by standard radiographic techniques. The device has been mechanically tested in cadaver spines and compared with posterior lumbar interbody fusion performed with donor bone. The carbon device required a pullout force of 353 N compared with 126 N for donor bone. In compression testing, posterior lumbar interbody fusion performed with the carbon device bore a load of 5,288 N before failure of the vertebral bone. Posterior lumbar interbody fusion performed with donor bone failed at 4,628 N, and unmodified motion segments failed at 6,043 N. The carbon fiber implant separates the mechanical and biologic functions of posterior lumbar interbody fusion.

Biomechanical Phenomena↗

Transpedicular screw fixation.

Spinal fixation employing transpedicular screws has recently been the focus of increased attention at various institutions throughout the world, but concerns about the safety and efficacy of transpedicular screws linger. This study was undertaken to address some of these concerns. The study included evaluation of the internal and external morphology of the vertebral pedicles, which revealed that adequate bone stock is generally available at T2, T7, T12, and L1-L5 spinal levels to accept screws in the 4-7-mm diameter range. The pedicle was observed to be composed of abundant cancellous bone internally with relatively thick cortical walls. The method of pilot hole preparation for pedicle screws was also examined. Screws inserted in pilot holes prepared with a 3.4-mm blunt probe (ganglion knife) resulted in higher pullout forces in eight of 10 trials as compared with those with pilot holes prepared using a 3.2-mm drill. Furthermore, the probes afford greater control of hole depth and alignment. Fatigue studies on three screw designs revealed a graduation of strength between a 7.0-mm pedicle screw, a 5.5-mm pedicle screw, and a modified 6.5-mm cancellous lag screw. The modified cancellous lag screw has an inherent stress riser that affected fatigue life. It was noted that extreme care must be exercised to prevent bending of the pedicle screws during implantation. If bending occurs one can expect a 50% reduction in the number of cycles to failure.

Bone Screws↗

A double-blind comparison of acitretin and etretinate in combination with bath PUVA in the treatment of extensive psoriasis.

Thirty-four patients with extensive psoriasis were treated in a double-blind parallel fashion with either acitretin plus bath PUVA (trimethylpsoralen bath + UVA) or etretinate plus bath PUVA. Each group consisted of 17 patients. The dose of retinoid was 40 mg/day during the 2-week monotherapy phase and subsequently 20 mg/day during the combination treatment. Bath PUVA was given three times a week starting with a UVA dose of 0.06 J/cm2. Remission (greater than 90% improvement) was achieved in all patients in 6-10 weeks. There were no significant differences in clinical response between the two groups; the mean +/- SD PASI score (psoriasis area and severity index) before treatment was 22.6 +/- 7.1 in the acitretin-PUVA group and 19.4 +/- 7.8 in the etretinate-PUVA group. The corresponding figures after treatment were 0.6 +/- 0.6 and 1.0 +/- 0.5, respectively. Side-effects related to retinoid treatment were frequent in both groups but they were usually mild and well-tolerated. There was only one case of diffuse alopecia after 8 weeks in the etretinate-PUVA group. Scaling of the palms and soles was seen in six patients in the acitretin-group but only in two patients in the etretinate-group. Triglycerides were elevated in about half of the patients in both groups. The present study shows that acitretin is as effective as etretinate in the combination with bath PUVA.

Acitretin↗

Benefit of progressively increasing doses during the initial treatment with acitretin in psoriasis.

The purpose of this double-blind study was to compare the therapeutic effects of a low initial dosage of acitretin, increased at 2-week intervals (group 1: 10, 30, 50 mg/day) with a high initial dosage decreased at similar intervals (group 3: 50, 30, 10 mg/day) and with a constant dosage (group 2: 30 mg/day) in 66 patients (47 men and 19 women) with severe psoriasis. At the end of the double-blind phase, the mean percent improvement, calculated by the Psoriasis Area and Severity Index score, was as follows: 62.7% in group 1, 55.9% in group 2 and 67.1% in group 3. The double-blind phase of 6 weeks was followed by an open phase of 6 weeks, during which the patients were treated either with 10, 30 or 50 mg/day, according to the therapeutic response. At the end of treatment (12 weeks), a mean improvement of more than 80% was obtained in all three groups. Hypervitaminosis A signs and symptoms were observed in all patients. The frequency and severity of these adverse reactions were shown to be dose-dependent. This study shows that a low dose progressively increased is advisable because of similar activity and better acceptability.

Acitretin↗

Acitretin treatment of severe psoriasis.

Fourteen male patients suffering from severe psoriasis were treated with 30 to 50 mg/day acitretin during 12 weeks. At the end of the treatment, 6 patients were in remission and 7 showed a marked improvement of the disease. One patient did not show any change. All patients experienced the usual retinoid side effects.

Acitretin↗

Acitretin versus etretinate in severe psoriasis. A double-blind randomized Nordic multicenter study in 168 patients.

The efficacy and tolerability of acitretin (etretin) in severe psoriasis was compared with that of etretinate in a double-blind randomized study for 12 weeks. A total of 127 patients received acitretin and 41 received etretinate. The initial daily dose was 40 mg/day over 4 weeks and was subsequently adjusted according to individual response. From week 5-12 the mean daily dose was 42.9 mg of acitretin (0.58 mg/kg) versus 49.2 mg of etretinate (0.65 mg/kg). Acitretin gave a PASI score reduction from baseline of 70.5% and etretinate a reduction of 68.4% (mean values). Acitretin tended to give more discomfort than etretinate, particularly with regard to hair loss and peeling of palms and soles. The differences found between acitretin and etretinate may be related to higher maximum plasma concentrations of acitretin. The considerably shorter half-life of acitretin, gives it a great advantage over etretinate with regard to risk of teratogenicity after cessation of treatment.

Acitretin↗

Determination of acitretin and 13-cis-acitretin in skin.

The aim of the study was to investigate the concentrations of Ro 10-1670 (acitretin) and its isomeric metabolite Ro 13-7652 (cis-acitretin) after multiple oral dosing of acitretin. We used a highly sensitive HPLC method for simultaneous determination of the 2 retinoids with a quantification limit of 2 ng/ml in plasma and 10 ng/g in total skin (epidermis and dermis). In hairless rats receiving orally 8 mg/kg acitretin once daily during 8 days, blood and skin samples were taken at different time points between 5 and 96 h after the last dose. After 96 h, appreciable concentrations of Ro 10-1670, but not Ro 13-7652 could be measured in the skin, whereas both isomers were below the quantification limit in plasma. In psoriatic patients treated with a once daily dose of 30 mg acitretin, blood samples and biopsies were taken after 1 month of treatment (i.e. under steady state conditions). 24 h after the last drug intake, skin concentrations of acitretin were approximately 10 times higher than those observed in plasma. Ro 10-1670 concentrations in the skin were approximately 3-5 times higher than for Ro 13-7652 and concentrations of both isomers were higher in lesional compared to uninvolved skin.

Acitretin↗

A double-blind comparison of acitretin and etretinate in the treatment of severe psoriasis. Results of a Nordic multicentre study.

Acitretin, the free acid of etretinate, is less lipophilic and has a much shorter terminal half-life than the parent compound. The present double-blind, randomized study compared the therapeutic effectiveness and the tolerability of acitretin (n = 127) and etretinate (n = 41) in psoriasis. Patients were treated with 40 mg daily for the first 4 weeks and with an individually adjusted dose for the subsequent 8 weeks. The average daily doses of acitretin (0.54 mg/kg/day) and etretinate (0.65 mg/kg/day) were similar. The PASI (Psoriasis Area and Severity Index) scores improved in parallel in the 2 treatment groups. At the completion of the study, the PASI score improvement was 75.8% for acitretin and 70.8% for etretinate. Both acitretin and etretinate resulted in mucocutaneous side effects. Assessments of tolerability by investigators and patients showed a statistically significant difference in favour of etretinate. These results demonstrate that acitretin and etretinate have similar therapeutic effectiveness in psoriasis. Although the tolerance to acitretin was lower than to etretinate, acitretin offers the important advantage of a much shorter period of potential teratogenicity and is, therefore, to be preferred in women of childbearing potential.

Acitretin↗

Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial.

Sixty patients with palmoplantar pustulosis were treated in a double-blind trial with either acitretin (etretin, Ro 10-1670) or with etretinate. The study consisted of 4 weeks of therapy with three 10 mg capsules/day followed by 8 weeks of therapy with a varying number of capsules given daily according to therapeutic response. At the end of the 12-week treatment period, the mean number of pustules (+/- SEM) had decreased from 57.8 (+/- 8.6) to 3.9 (+/- 1.6) in the acitretin group and from 57.1 (+/- 14.1) to 5.7 (+/- 2.7) in the etretinate group. With regard to influence on erythema, infiltration, scaling, and area involved, similar improvements were obtained in both treatment groups. Adverse reactions of the hypervitaminosis A type were observed with almost the same frequency and severity in both treatment groups. The mean number of 10 mg capsules used daily was comparable in the two groups: 2.82 (range 1.23-4.67) for acitretin and 2.77 (range 1.60-4.82) for etretinate. It can be concluded that acitretin and etretinate do not significantly differ with regard to efficacy and overall safety in the treatment of patients with palmoplantar pustulosis.

Acitretin↗

Acitretin (Ro 10-1670) in the treatment of severe psoriasis. A randomized double-blind parallel study comparing acitretin and etretinate.

A randomized double-blind parallel trial comparing acitretin and etretinate was performed in 20 patients with severe psoriasis during a treatment period of 12 weeks. The initial dose was 30 mg/day for 4 weeks, and the mean dose at the end of the study was slightly lower in the acitretin group when compared to the etretinate group (30.7 mg/day and 33.4 mg/day, respectively). Follow-up examinations were carried out every 2 weeks, and the efficacy of treatment was evaluated by using the PASI score. Percentage improvement in the PASI score was 50% at week 10 in both groups, and the difference between them at week 12 was insignificant. Both quantitatively and qualitatively, acitretin and etretinate do not significantly differ.

Acitretin↗

Randomized double-blind multicenter study comparing acitretin-PUVA, etretinate-PUVA and placebo-PUVA in the treatment of severe psoriasis.

A randomized double-blind study was designed with 65 patients in order to clarify two points: (1) does addition of a retinoid to psoralen-ultra violet A photochemotherapy (PUVA) of severe psoriasis decrease the UVA energy required to achieve remission, and (2) is there a difference between two retinoids, i.e. etretinate and acitretin. Acitretin-PUVA treatment was significantly superior to placebo-PUVA with respect to several items (decrease in lesional scores after 6 weeks of therapy, number of PUVA exposures, and total dose of UVA until remission). There were also differences between the etretinate-PUVA and placebo-PUVA groups, but only the decrease in lesional scores reached statistical significance.

Acitretin↗

Acitretin (Ro 10-1670, etretin): overall evaluation of clinical studies.

Acitretin (Ro 10-1670, etretin) is the free acid derivative of etretinate. This compound possesses a much shorter half-life of elimination than etretinate and was therefore proposed for clinical development. A total of 635 patients with various dermatoses were studied in 12 main clinical trials performed in Europe and in the United States. It was shown that acitretin is effective in the treatment of psoriasis and other diseases of keratinization. Doses between 25 and 35 mg per day are recommended to initiate treatment since marked improvement or clearing was obtained in the majority of patients within this range. Hypervitaminosis A signs and symptoms have been observed in patients treated with acitretin. It is concluded that the efficacy and safety profile of acitretin resembles that of etretinate.

Acitretin↗

Estrous cycle lengthening by pentobarbital in the rat: prolactin involvement.

Pentobarbital lengthens the estrous cycle when injected on diestrus 1 afternoon in the 4-day cyclic female rat. The present study was undertaken to elucidate the mechanisms involved. Bromocriptine (2.5 mg/kg sc) given 30 min before pentobarbital (30 mg/kg ip) prevented the effects of pentobarbital on both cycle lengthening and progesterone levels in diestrus 2. Serum prolactin concentrations rose 10 min after pentobarbital injection, peaked at 30 min, and returned to control values after 60 min. Our results suggest that pentobarbital-induced cycle lengthening is due to a high progesterone production on diestrus 2 morning related to the luteotropic action of prolactin.

Animals↗