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A patient with subacute-cutaneous lupus erythematosus showed no response to corticosteroids and azathioprine. Treatment with thalidomide resulted in a dramatic clearing of skin lesions but failed to improve pathological laboratory tests.
In the 1977-1979 period, 84 thalidomide-affected young people who had followed secondary education up to level I (Sekundarstufe I; school leaving age approx. 16 years), had been interviewed on their sexual experiences. The group was composed of young people with purely orthopaedical impairments, which were rank-ordered in four degrees of disability severity according to the extent of medical lesion. The group under examination was matched by a parallel group of non-disabled young people who had been selected on the criteria of sex, age, educational level, vocational objectives, and occupational status of the father. In comparison to the non-disabled, physically disabled young people are demonstrated to have deficits in sexual experience, which are getting more pronounced with increasing severity of the disability. These deficits in sexual experience do not seem to stem from a lack of social contacts, but rather from their perceived non-compliance with the norms that govern non-disabled people's concepts of performance, attractiveness, and sexuality. The physically disabled young people are aware of these problems; they however seem to be able to cope with them through their leading a "normal" life as regards such aspects as school education, vocational training, and social contacts. Special emotional problems may however develop in the severely disabled young people. An additional sexual problem may arise from their partly less pronounced acquisition of typical sex-role identities, which may however also be viewed as a potentially positive circumstance.
Ninety-three Brazilian teenagers with thalidomide embryopathy were studied. The pattern of distribution of their most significant defect was: upper limbs, 66; lower limbs, 8; all four limbs, 12; head, 7. Only 10 individuals presented the major defect unilaterally. In 30 of 83 with bilateral defects there were differences in severity between the two sides. Of the 31 patients whose spines had been X-rayed, 16 showed defects, the most common being spina bifida occulta at S1. Gynecomasty was found in three of the patients having major upper limb defects.
The results of an X-ray investigation of 480 patients suffering from thalidomide embryopathy demonstrate that, beside dysmelia, spinal alterations are an important factor in malformations of the postural and locomotion apparatus. The pattern of malformations consists-according to the frequency of accumulated incidences - of spondylolysis, scoliosis, malformations of the intervertebral disc and dysgenesia of the sacrum. As in the case of extremities this pattern of malformations can only be established by radiological morphology. It necessarily entails alterations of varying functional value. There is no doubt that spinal alterations influence the fate of affected patients in the future.
Thalidomide-induced deformities, affecting some 400 British children, caused various combinations of malformations. Classified by type of defect and whether confined to upper and/or lower limbs, the malformations can be treated on a radional basis. The treatment from infancy to the present time includes the fitting of carbon dioxide gas-powered upper limb prostheses, initially in their simplest form and finally in the most sophisticated form. For a baby with bilateral lower phocomelia, a special "sitting socket" was devised to enable sitting in an upright position. When each child was about 12 to 15 months of age, extension protheses were supplied and the effects on walking when upper limbs are malformed or absent were noted. The methods of achieving personal independence and developing constructive youngests' pastimes are important. One patient was so well rehabilitated that she was able to marry and start a healthy family.
The case history of a fifteen year old patient with Thalidomide induced malformation who developed a lymphoma of high malignancy is presented.
Although it is usually accepted that the pathogeny of HIV infection is related to the direct cytotoxic effect of the virus or indirectly by the invasion of T4 cells altering the T4/T8 ratio, clinical and serological and biochemical manifestations of the B cell polyclonal activation were described early in HIV infection epidemy. It is postulated that the central pathophysiologic mechanism in HIV infection is a high and inefficient production of interferon-gamma, genetically determined, leading to a production of autoantibodies that blocks the target organs even the immune system as well as a progressive interleukins levels increase, including tumor necrosis factor-alpha (TNF-alpha), responsible for many of the symptoms of these patients like fever, headache, fatigue, myalgia, hypotension, seizure and other neurological disorders, hematologic and hepatic disorders. Thalidomide reduces polyclonal hypergammaglobulinemia, that is associated with a clinical and laboratorial improvement, in a dose dependent manner as well as TNF-alpha levels. It seems that HIV infection is more a disease of abnormal host response triggered by HIV than an HIV disease.
All children suffering from thalidomide embryopathy should undergo a careful clinical and radiographic follow-up examination. This frequently detects hidden defects, especially of the spine and hip joints. It is clear that defects are frequently present, though unsuspected by the clinical examination. A special problem which needs further investigation is the alteration of the knee joints, which has also often been overlooked; Early osteoarthritis is expected to occur in the future. There is an urgent need for additional study of the general functional capacity and also the manual efficiency of the children under consideration for their occupational integration. We shall be engaged with this problem in future studies.
Thalidomide is now available as an investigational drug in the USA. A synthetic derivative of glutamic acid, it was marketed in Europe in 1957 as a sedative but withdrawn four years later after being associated with severe human teratogenicity (PF D'Arcy and JP Griffin, Adverse Drug React Toxicol Rev, 13:65, 1994). The drug has since been found effective for several different indications.
A 40-year-old Turkish man on busulphan treatment for chronic myeloid leukaemia was hospitalized with steroid resistant (up to 100 mg prednisolone/24 h for over 4 weeks) colitis. On the basis of concomitant orogenital ulceration and unusual, deep punched out ulcers in the colon and smaller ulcers in the terminal ileum, Behçet's disease of the bowel, manifesting as ileocolitis, was diagnosed. Leukaemic infiltration, Crohn's colitis, neutropenic colitis and infectious colitis were excluded by histology and cultures. Treatment with colchicine 2 mg/day improved the orogenital ulcers but with only minor improvement of the colitis. Thalidomide treatment (400 mg/day), however, dramatically improved the colitis within 7 days: fever and diarrhoea disappearing. Colonoscopy after 4 weeks of treatment revealed previously giant ulcers practically healed.
The authors describe a case of idiopathic nodular panniculitis (Weber-Christian disease) with recurrent febrile episodes resistant to glucocorticosteroids and methotrexate (MTX) in various combinations with hydroxychloroquine, azathioprine, cyclosporine, colchicine, and doxycycline. Thalidomide at 100 mg/day has induced a remission for 3 years.
We discovered a thalidomide analogue [5-hydroxy-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33)] with antiproliferative activity against nine cancer cell lines in vitro. Flow cytometric analyses showed that the compound caused G2-M arrest, which occurred mainly at the mitotic phase. In addition, immunofluorescence microscopy and in vitro tubulin polymerization studies showed that 5HPP-33 has antimicrotubule activity with a paclitaxel-like mode of action. It is effective against four different paclitaxel-resistant cell lines. Thus, 5HPP-33 represents a potential antitumor agent.
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