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PubMedDate not supplied

Ocular motility in thalidomide embryopathy.

Twenty-one individuals, aged 28 to 29 years, with documented thalidomide embryopathy were examined in Sweden. The most noteworthy ophthalmologic finding was the high prevalence of incomitant horizontal strabismus, primarily of the Duane syndrome type. Less frequently seen were cases of both marked abduction and adduction limitation similar to a gaze paresis with no observable fissure changes, as well as a few cases of isolated abduction weakness or inferior oblique under-action. There were many examples of aberrant lacrimation, facial nerve palsy, and ear anomalies combined with horizontal incomitant forms of strabismus. Ear and facial nerve palsies are known to occur with ingestion of thalidomide early in the sensitive period (approximately days 21 to 26 after conception).

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Thalidomide in type-2 lepra reaction--a clinical experience.

A clinical experience of using thalidomide in type-2 lepra reaction (ENL) in 90 male patients--57 with lepromatous leprosy (LL) and 33 with borderline lepromatous leprosy (BL)--is described. All the patients responded well although some took a longer time to improve. No major side effects were observed except for giddiness in 10 and gastrointestinal upsets in 7 patients. Thalidomide thus appears to be a very effective drug in the treatment of severe type-2 lepra reaction and apart from its historically well-documented embryopathic effects, does not seem to have any other serious side effects in the patients under study.

Adolescent↗
PubMed1990

[Stereoselective differences of central nervous system-depressive action of a homologous series of 3-alkyl-thalidomide analysis].

The racemates and the enantiomers of the 3-alkyl-thalidomide analogues 2a-c were synthesized via the lactams 1a-c. The absolute configuration of 1a-c and 2a-c was elucidated, their enantiomeric purity established. From racem. 2a 1,3-dimethylthalidomide (3) was synthesized. By means of the hexobarbital sleeping time prolongating effect in rats it was shown that racem. 2a and 3 were less CNS-depressant active than thalidomide; 3 caused a more prolonged sleeping time than 2a. Both enantiomers of 2a (i.p. 200 mg/kg) exceeded in their sleeping time prolongation action racem. 2a (same dose), whereby the (S)-enantiomer was to a factor of 1.8 more effective than the (R). With both enantiomers of 2a time and dose dependency of the effect were investigated. The enantiomers of 2b + c and 1a-c had also a prolongating effect on the hexobarbital sleeping time. Independently of the alkyl group the (S)-enantiomers were always more active than the respective (R)-enantiomers. (S)-1b (200 mg/kg) caused a long lasting loss of the righting reflexes as "own effect". Stereoselective differences between the enantiomers of 2a and 2b were observed only when a dose of 200 mg/kg was applied, whereas the higher activity of the (S)-enantiomers of 2c, 1b + c was obtained already with a lower dosage range.

Animals↗
PubMedDate not supplied

[Thalidomide: an eclectic medication in dermatology].

The authors review the indications for the use of thalidomide in dermatological conditions. They consider leprotic reaction, prurigo nodularis of Hyde, actinic prurigo, discoid lupus erythematosus, Weber-Christian panniculitis, recurrent mouth aphtosis, Behcet's syndrome, and pyoderma gangrenosum. The dramatic situation created by the use of thalidomide in the sixties not-withstanding, interest in its use is warranted within certain limits due to its wide therapeutic action.

Humans↗
PubMed1989

[The education and occupational status of young adults damaged by thalidomide].

In 1985, 517 of the 2,486 thalidomide-affected Germans were interviewed by mail questionnaire concerning their educational and vocational situation. 250 usable returns were received, and the sample was found to correspond to the overall thalidomide-affected population in terms of age, sex, and residence, with the exception however of above-average social status and educational levels. 49.4% of the interviewees were gainfully employed, 23.7% students; 17.2% however were unemployed, undergoing retraining, or working in a workshop for the disabled. Contrasted to the German population as a whole, our sample included more university graduates and workers in service sector occupations, and fewer in the crafts or in clerical occupations. Women tended more towards social occupations, men more towards technical ones. On account of their disablement, many of our interviewees were inclined to accept white-collar employment, because their desired vocational objectives had been inaccessible to them due to purely technical difficulties or problems related to rejection by others. 80% nonetheless declared themselves content with their situation, only those in a workshop for the disabled were less satisfied on an average. Contentness was found to be linked more with job satisfaction than with the extent of disablement. About one third of our sample lived with their parents, only four in residential accommodation. More than 75% could be considered independent and needing no outside assistance, with the same share holding a driver's licence. In 90%, the majority of private or occupational contacts, or even all of them, were maintained with nondisabled people. More than 80% considered themselves financially and socially equal to their fellow workers.

Abnormalities, Drug-Induced↗
PubMed1986

The thalidomide syndrome: risks of exposure and spectrum of malformations.

Echos of the 1959 to 1961 thalidomide disaster are still with us in the form of the continuing appearance, although more rarely, of similarly malformed children. A teratologic timetable could be fashioned retrospectively, supporting the concept that different body parts and systems have periods of vulnerability and of resistance to thalidomide, probably the most potent primate teratogen known. Something between one in every two to one in every ten fetuses exposed at the critical development period were affected. The clinical affects are described from the literature on approximately 2500 children, and from extensive personal experience, and a complex though finite pattern of malformations is described, indistinguishable from sporadic nonthalidomide cases of malformations that continue to occur.

Ectromelia↗
PubMedDate not supplied

Thalidomide in leprosy--study of 94 cases.

Thalidomide has a beneficial effect on type II Lepra reaction especially chronic and recurrent reaction. It helps to minimise steroid dependency. Thalidomide was given to 94 cases of type II lepra reaction, who had not responded to steroids or had repeated reactions. This clinical data was analysed regarding clinical improvement, relapse of reaction, side effects of the drug, etc. The analysis showed that all the patients improved remarkably and steroids could be withdrawn. If the competence of staff using this drug is enhanced, morbidity due to leprosy can considerably be reduced.

Adolescent↗
PubMed1979

Treatment of steroid dependant cases of recurrent lepra reaction with a combination of thalidomide and clofazimine.

22 Adult Male Lepromatous patients suffering from recurrent lepra reaction have been allotted to either a regimen of combined treatment with Clofazimine and Thalidomide alone. The initial dosage of either of the drugs was 300 mg daily administered in divided doses of 100 mg three times a day. The preliminary assessment of the ongoing study, indicates that the combined treatment controls the reactional state more rapidly than monotherapy with Thalidomide alone. Results of treatment as regards relief of neuritis and arthritis are particularly gratifying. Four month.ases relapsed into reactional status from 2 days to 15 days. 5 cases on the combined therapy relapsed from one to three months. Three other cases required six months and three cases 8 months treatment before clofazimine could be withdrawn. It would appear that a maintenance therapy of 6 months with flofazimine would be necessary for maintaining the control of reactional episodes while employing this combined therapy.

Adult↗
PubMed1983

[Treatment of Jessner-Kanof disease with thalidomide].

Five patients present a Jessner-Kanof's lymphocytic infiltration of the skin with 6-year duration for 4 of them. The skin lesions are numerous on the face and the back and characteristic of this disease. Histologic examination shows a lymphocytic infiltrate in the dermis without any modification of epidermis. Direct immunofluorescent study is negative in all cases. In 3 cases, response to chloroquine had been inconsistent or negative. The 5 cases have a excellent result with 100 mg/day of Thalidomide. In 4 cases the skin lesions reappear when treatment is stopped. With a continuous treatment of 25-50 mg/day for more than 2 years, 3 of 5 patients have normal skin. Thalidomide appears to be the best treatment of Jessner-Kanof's disease.

Adult↗
PubMed1982

[Thalidomide in the treatment of aphthosis and Behçet's disease. 4 years' experience].

The authors summarize their experience in the treatment of recurrent, necrotic and giant mucocutaneous aphthosis (9 cases) and Behçet's disease (9 cases) with Thalidomide during four years. In recurrent mucocutaneous aphthosis the results were very good, with fast disappearance of pain, healing of the ahthae and disappearance or delay of recurrence. The result in Behçet's disease is similar, possibly less, in mucocutaneous lesions. Uveitis also reacts favorably but we can not say that the results were superior to those obtained by other drugs (corticoids, cytostatics immunosuppressives), although its side effects are less. On the other hand it does not appear to have any effect on other symptoms such as arthritis (in which colchicine is active), thromboflebitis or fever. There is not sufficient experience to judge its action on neurological symptoms. The recommended dose is 100 mgr./day for 10 days, a higher dose does not appear to give better results. Patients who have received treatment several times appear to have the same results, but slower. Neurotoxicity has not been observed and the only side effect which has been noted is digestive intolerance in two cases, after which the medication was stopped. The authors consider that Thalidomide, with due precaution, which must be scrupulously determined, is the most active medicament in particularly severe cases with profusion of necrotic aphthae, mutilating and recurring mucocutaneous aphthosis, also being useful in controlling some symptoms of Behçet's disease.

Adolescent↗
PubMed1983

Bioactivation of thalidomide by a monkey liver fraction in a rat limb culture system.

The effect of thalidomide on a rat limb bud system has been studied in vitro. Thalidomide and adult monkey liver supernatants activated with cofactors for the mixed function monooxygenase system inhibited growth. Similar preparations from the rat did not inhibit growth. Planimetric measures of the surface area of limb buds were found to correlate closely with their protein contents. The ability to compare metabolizing systems from different mammals may be useful in extrapolating teratologic data between different species.

Animals↗
PubMed1982

[Thalidomide in the treatment of chronic lupus erythematosus].

The effect of thalidomide was investigated in 12 patients with chronic lupus erythematosus resistant to classical treatment (antimalarial drugs, topical steroids). 10 patients were improved and 2 were not sensitive to the treatment. The doses were 100 mg/day for a minimum period of 2 months. With the exception of 1 case, the treatment was well tolerated. The indications of thalidomide in dermatology and the mechanism of action of the drug are briefly discussed.

Adult↗
PubMed1981

Comparative teratological investigation of compounds structurally and pharmacologically related to thalidomide.

Compounds differing from thalidomide in either the phthalimide or the 2,6-dioxopiperidine moiety of the molecule were synthetized and tested for teratogenic potency in White New Zealand rabbits. Both the 2,6-dioxopiperidine and 2-oxopiperidine derivatives of phthalimide and phthalimidine were found to be highly teratogenic. A somewhat higher teratogenic potential appeared to be associated with the 2,6-dioxopiperidine derivatives. The most potent teratogen investigated was clearly 3-(1,3-dihydro-1-oxo2H-isoindol-2-yl)-2,6-dioxopiperidine (EM12). Compounds in which the phthalimide ring was replaced by 2,3-dihydro-1,1-dioxido-3-oxo-1,2-benzisothiazol, did not induce any embryopathic effect differing from control data. No consistent correlation between teratogenic activity and sedative properties of the compounds was detected. The results are discussed in respect to current views of the molecular mechanism leading to thalidomide embryopathy.

Animals↗
PubMed1980

Treatment with thalidomide in steroid dependency and neuritis.

Thalidomide is found effective and useful in cases of lepromatous ENL in Corticosteroid dependent cases which had been on treatment with dapsone and lamprene. But eventually due to recurrence these cases had to be put back on steroids because of easier availability. Cases of neuritis responded much more satisfactorily and there was no change in the muscle deficity before or after treatment with thalidomide.

Adrenal Cortex Hormones↗
PubMed1994

Embryotoxicity in chick embryo of thalidomide hydrolysis products following metabolic activation by rat liver homogenate.

Three and four-day-old chick embryos were exposed to thalidomide as well as to its hydrolysis products before and after in vitro biotrasformation of these compounds with rat liver homogenate. Significant embryotoxic effects of 30 and 100 micrograms doses per embryo encountered only in the case when the products of alkaline hydrolysis of thalidomide were pretreated with rat liver homogenate.

Animals↗
PubMed1993

[Thalidomide treatment of prurigo nodularis].

Twenty-two patients suffering from prurigo nodularis were treated with thalidomide 50-300 mg daily for an average of 12 months (two weeks to five years), following a special arrangement between the Danish Government and the producer Grünenthal GMBH, by which the Government took full economical responsibility for any claims related to the treatment. All patients received prior to treatment a detailed written information about all potential side-effects from the treatment, and had by their signature acknowledged, that they wished to be treated. All but two of the patients had an immediate pronounced effect on their main symptom, the tormenting itching. The same patients had a significant decrease in size and numbers of skin lesions after one to two months of treatment. However, the therapy had to be discontinued in thirteen patients (59%) due to side-effects. The most important side-effect, neuropathy, was the reason for discontinuation of thalidomide in five patients (22%). In spite of the high frequency of side-effects, we consider that this treatment modality should still be offered to the patients with the most severe symptoms due to the pronounced effect on this otherwise therapy resistant disease.

Adult↗
PubMedDate not supplied

Treatment of the cutaneous lesions of systemic lupus erythematosus with thalidomide.

Twenty three patients with SLE and cutaneous lesions not responsive to chloroquine, photoprotectors and corticosteroid in doses < 0.5 mg/kg/day were treated with thalidomide 300 mg/day. Three patients presented side effects and had to discontinue treatment. Eighteen of the remaining 20 patients (90%) had complete remission of the cutaneous lesions and 2 had partial improvement. Another important parameter of improvement was a reduction in the average prednisone dose required from 40.5 mg/day to 17.4 mg/day. The most frequent side effects were drowsiness in 52% of cases and abdominal distention in 22%. These symptoms were reversed by dose reductions in all but one patient. Thalidomide was shown to be efficient in the treatment of cutaneous lesions unresponsive to more usual treatments.

Adolescent↗
PubMed1996

Thalidomide responsive chronic pulmonary GVHD.

A 29-year-old male underwent allogeneic bone marrow transplantation for progressive multiple myeloma. His post-transplant course was complicated by severe chronic pulmonary graft-versus-host disease (GVHD) resistant to cyclosporin A, corticosteroids and azathioprine. The introduction of thalidomide resulted in a dramatic improvement in his lung function which has been maintained even after cessation of thalidomide. He remains well 40 months after transplantation.

Adrenal Cortex Hormones↗