The limbs and soft tissues
Spencer W. Beasley, John Hutson, Mark Stringer, Sebastian K. King, Warwick J. Teague in Paediatric Surgical Diagnosis, 2018
There are many rare causes of deformity of the limbs, including limb deficiency. Phocomelia, or telescopic foreshortening or a limb, is a rare congenital abnormality that became well known because it was the characteristic defect produced by thalidomide toxicity in the 1960s. Sprengel shoulder is a rare condition caused by failure of the scapula to descend from its original cervical position in the embryo. Craniocleidodysostosis, and cervical rib are seen occasionally. Scurvy once was common but now is rare. Another rare genetic cause of deformity is osteogenesis imperfecta. Birth injuries or other accidents can produce secondary deformity. In the leg, aplasia of the fibula may occur as part of the VACTERL association analogous to radial aplasia. Intrauterine compression causes severe growth failure in the leg. Lumps on the toes may be an exostosis or a digital fibroma.
Reproductive and Developmental Toxicity
Frank A. Barile in Barile’s Clinical Toxicology, 2019
The thalidomide disaster of 1961 initiated a significant effort to establish a program for teratogenicity testing. Developed as a sedative/hypnotic with no particular advantage over drugs of the same class, thalidomide was initially shown to lack teratogenic effects in all species tested except rabbits. Soon after its introduction to the European market, the drug was linked to the development of a relatively rare birth defect known as phocomelia. The epidemic proportions of the teratogenic effect of thalidomide prompted the passage of the Harris–Kefauver Amendment in 1962, one of many additions since to the Federal Pure Food and Drug Act. The Amendment requires extensive pharmacological and toxicological preclinical research before a therapeutic compound can be marketed.*
Specific Current Therapy for Myelomas
Tariq I Mughal, John M Goldman, Sabena T Mughal in Understanding Leukemias, Lymphomas, and Myelomas, 2017
Thalidomide was initially developed as a sedative in the early 1950s and found to be an effective antiemetic for pregnant women with morning sickness. The drug resulted in catastrophic teratogenic effects resulting in gross birth defects, in particular limb deformities known as phocomelia (derived from the Greek word ϕώκη, meaning “seal” and μέλεα, meaning “limb”), when used in pregnant patients (Fig. 10.3). The drug was subsequently withdrawn in the early 1960s and re-entered the clinics in the late 1980s for the treatment of a variety of inflammatory conditions, such as cutaneous (skin) leprosy (erythema nodosum leprosum) and graft-versus-host disease. In 1998, the drug received Food and Drug Administration (FDA) approval for these conditions. The potent anti-angiogenesis property of thalidomide led to a pilot study led by Seema Singhal and her colleagues in Little Rock, Arkansas, USA, for patients with myeloma. They observed responses in about a third of the patients with relapsed and/or refractory myeloma, having failed conventional therapy.
Phantom Phenomena—An Introduction to “Phantom Penis: Extrapolating Neuroscience and Employing Imagination for Trans Male Sexual Embodiment”
Published in Studies in Gender and Sexuality, 2020
Paul D. McGeoch, V. S. Ramachandran
As almost everyone with xenomelia dates their desire for an amputation to their childhood, this suggests that despite a lifetime of living with the offending limb, it fails to fully incorporate into their body image. We were able to demonstrate the converse of this observation in a 57-year-old woman (RN) with right upper limb phocomelia (McGeoch and Ramachandran, 2012). RN was born with a severely foreshortened right arm and a markedly deformed right hand. In her case it was due to chance and not in utero exposure to thalidomide. She only had the rudiment of a thumb, no index finger, and the middle and ring fingers were shorter than on the left hand and fixed in flexion. Only her right little finger was functional. Unfortunately, at the age of 18 years she was involved in a car crash and her right upper limb was crushed. Her orthopedic surgeons struggled to get it to heal for six months, but eventually it had to be amputated.
Etonogestrel-releasing contraceptive implant in a patient using thalidomide for the treatment of erythema nodosum leprosum: a case report
Published in Gynecological Endocrinology, 2022
Edson Santos Ferreira-Filho, Luis Bahamondes, Daniele Coelho Duarte, Ana Lúcia Monteiro Guimarães, Patrícia Gonçalves de Almeida, José Maria Soares-Júnior, Edmund Chada Baracat, Isabel Cristina Esposito Sorpreso
The use of thalidomide by women of reproductive age had neonatal and perinatal repercussions and caused severe congenital defects in more than 10,000 children between 1957 and 1962. Impairment was primarily seen in the limbs, face, eyes, ears, genital organs, heart, kidneys, gastrointestinal tract, and spine. Phocomelia remains the most striking deformity brought on by thalidomide as well as the stereotyped image of thalidomide embryopathy. Thalidomide use is carefully monitored through successful strategies for supervising patients to ensure they do not get pregnant during treatment [5]. The Brazilian Ministry of Health states that a thalidomide-based medication may only be prescribed for women of reproductive age after medical evaluation has ruled out pregnancy by a sensitive method and through proof of use of at least 2 (two) effective contraceptive methods for women using thalidomide [6]. However, to the best of our knowledge, there are no studies showing an absence of drug interaction between thalidomide and hormonal contraception.
A review of translational medicine. The future paradigm: how can we connect the orthopedic dots better?
Published in Current Medical Research and Opinion, 2018
Mohamed Mediouni, Daniel R. Schlatterer, Henning Madry, Magali Cucchiarini, Balwant Rai
From a historical perspective, much can be learned from several examples where the bench-side knowledge progressed too quickly to the bedside. The most glaring example was the use of thalidomide1,2,3. Developed in West Germany in 1957, it was effective in treating pregnant women experiencing morning sickness. What was not known at the time was that thalidomide use could also cause severe birth defects such as phocomelia and amelia4,5. As thousands of cases were reported its use was abruptly discontinued and more stringent rules were written regarding medication development and clinical application. This is an example of two-way bedside to bench-side communication and collaboration ultimately resulting in the development of much safer morning sickness and anti-anxiety medications.
Related Knowledge Centers
- Birth Defect
- Encephalocele
- Hypertelorism
- Micrognathism
- Thalidomide
- Nausea
- Hydrocephalus
- Bicornuate Uterus
- Thalidomide Scandal
- Dysmelia