Internal anomalies in thalidomide embryopathy: results of imaging screening by CT and MRI

Tajima, T.; Wada, Tatsuya; Yoshizawa, Atsuto; Masuda, Tomoshige; Okafuji, Takashi; Nakayama, Tomohiro; Kanehiro, Hiromichi

doi:10.1016/j.crad.2016.07.015

Cited by 9 publications

(7 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the multiple effects of thalidomide, the most striking upon the embryo was to the limbs. Upper limb deficiencies were more common and presentation ranged from triphalangeal thumb, to radial dysplasia (complete loss of radius and thumb and sometimes index finger), to phocomelia (severe shortening and/or loss of the proximal long bones while retaining parts of the distal hand/foot plate structures) and even amelia (Lenz and Knapp, 1962;McCredie and Willert, 1999;Newman, 1985Newman, , 1986Smithells and Newman, 1992;Tajima et al, 2016). Multiple clinical studies have ascertained that some limb elements are more sensitive to thalidomide than others and an order of limb element loss can be determined, for example, the thumb is the most sensitive, followed by the radius, then the humerus, the ulna and finally fingers on the ulnar side (middle, ring and small) (Kajii et al, 1973;Lenz and Knapp, 1962;McCredie and Willert, 1999;Newman, 1985Newman, , 1986Smithells and Newman, 1992).…”

Section: Thalidomide-induced Limb Differencesmentioning

confidence: 99%

“…Several other studies have demonstrated thalidomide induces vessel loss and/or haemorrhages in embryos (Jurand, 1966;Sorensen et al, 2017;Tamilarasan et al, 2006). We also know that thalidomide survivors themselves exhibit a wide range of cardiovascular changes, including heart defects, some of which might actually contribute to the differences seen in thalidomide survivors (Tajima et al, 2016; see also Vargesson and Hootnick, 2017). In further support of this mechanism, multiple anti-angiogenic drugs used as anti-cancer agents, for example sunitinib and sorafenib (Beedie et al, 2016a), which induce cell death, have a wide range of molecular targets and all of these can cause limb damage (Beedie et al, 2016a(Beedie et al, , 2017.…”

Section: Anti-angiogenesis Modelmentioning

confidence: 99%

“…The type of birth defects seen were severe and striking. Damage to multiple tissues and organs was seen including the eyes, ears, genitals, internal organs including gastrointestinal tract, facial nerves, heart and cardiovascular system as well as limbs (Kajii et al., 1973; Lenz and Knapp, 1962; McCredie and Willert, 1999; Smithells and Newman, 1992; Tajima et al., 2016).…”

Section: Thalidomide – a Brief Historymentioning

confidence: 99%

See 2 more Smart Citations

The teratogenic effects of thalidomide on limbs

Vargesson

2018

J Hand Surg Eur Vol

View full text Add to dashboard Cite

Thalidomide remains notorious as a result of the damage it caused to children born to mothers who used it to treat morning sickness between 1957 and 1961. The re-emergence of the drug to treat a range of conditions including erythema nodosum leprosum (a complication of leprosy) has led to a new generation of thalidomide damaged children being born in Brazil. Although thalidomide affects most of the developing tissues and organs of the body, the damage to the limbs is striking. Indeed phocomelia, the severe reduction or loss of the proximal long bones with retention of the distal hand/foot plate remains the stereotypical image of thalidomide. This review focuses on the type and range of damage thalidomide caused to the limbs, reviews current understanding of the mechanisms underlying thalidomide-induced limb malformations and outlines some of the challenges remaining in elucidating its teratogenicity.

show abstract

Section: Thalidomide-induced Limb Differencesmentioning

confidence: 99%

Section: Anti-angiogenesis Modelmentioning

confidence: 99%

Section: Thalidomide – a Brief Historymentioning

confidence: 99%

See 1 more Smart Citation

The teratogenic effects of thalidomide on limbs

Vargesson

2018

J Hand Surg Eur Vol

View full text Add to dashboard Cite

show abstract

“…Indeed, the drugs antiangiogenic action is widely viewed as part of the key in the drugs teratogenic actions where the drug may target angiogenic, smooth muscle negative vessels resulting in their loss, or preventing them to transition to an adult state as well as then resulting in changes in molecular signaling pathways and ultimately tissue loss/malformation [67][68][69]. It is of further interest to note that several studies in thalidomide survivors (children and adult) with limb anomalies, have reported cardiovascular malformations and vascular changes and/or missing vessels in the limbs which might help explain the damage [70,71]. The hypothesis is that thalidomide induces vessel loss or may interfere with the vascular transition which could lead to localized cell death resulting in missing or lost tissue, resulting in bony elements being shorter or lost [67,68].…”

Section: Drugs Taken During Pregnancy Leading To Vascular Disruption mentioning

confidence: 99%

Arterial dysgenesis and limb defects: Clinical and experimental examples

Vargesson

Hootnick

2017

Reproductive Toxicology

View full text Add to dashboard Cite

Limb malformations are amongst the most common and visible birth effects. Causes have been purported to include genetic aberrations as well as teratogens, such as thalidomide. Here we review the evidence for vascular disruption in the genesis of limb malformations through abnormal arterial transitioning and from events such as amniocentesis, uterine constriction, and through teratogen exposure. We use several clinical and experimental examples and highlight the need to understand more about the role the vascular system plays in the molecular mechanisms underpinning normal limb development. AbstractLimb malformations are amongst the most common and visible birth effects. Causes have been purported to include genetic aberrations as well as teratogens, such as thalidomide. Here we review the evidence for vascular disruption in the genesis of limb malformations through abnormal arterial transitioning and from events such as amniocentesis, uterine constriction, and through teratogen exposure. We use several clinical and experimental examples and highlight the need to understand more about the role the vascular system plays in the molecular mechanisms underpinning normal limb development.

show abstract

“…However, several surveys focusing on the physical or orthopedic situations of thalidomiders have recently been conducted (Ghassemi Jahani et al, ; Ghassemi Jahani et al, ; Ghassemi Jahani, Danielson, Karlsson, & Danielsson, ; Ghassemi Jahani, Danielsson, Karlsson, & Brisby, ; Kowalski, Sanseverino, Schuler‐Faccini, et al, ). For example, one recent study focused mainly on lifestyle‐related diseases among middle‐aged thalidomiders (Shiga, Shimbo, & Yoshizawa, ), while a few others investigated internal organ and vascular anomalies using imaging screening (Tajima, Wada, & Yoshizawa, ; Weinrich et al, ). In addition, reports have been published on mental disorders and psychological problems in thalidomiders in Sweden and Japan (Ghassemi Jahani, Karlsson, et al, ; Imai et al, ), and on peripheral nerve dysfunction in thalidomiders in the UK (Nicotra et al, ).…”

Section: Introductionmentioning

confidence: 99%

A nationwide survey regarding the life situations of patients with thalidomide embryopathy in Japan, 2018: First report

Hinoshita

Beppu

Shioji

et al. 2019

Birth Defects Research

View full text Add to dashboard Cite

Background: Clinical studies on the effects of thalidomide-induced damage on thalidomide victims as they age have only recently started to be conducted, but no studies have examined socioeconomic differences in terms of healthcare and social status between thalidomiders and the age-matched general population in Japan. Therefore, we carried out a nationwide survey focusing on the life situations of thalidomiders. Method: Questionnaires were sent to 274 thalidomiders in Japan. The questionnaire items basically matched those of the Comprehensive Survey of Living Conditions (CSLC) in the general population conducted by the Japanese Government. The results were compared with those of the CSLC for individuals aged 55-59 years, which was the cohort most similar in age to the average thalidomider living in Japan. Results: More thalidomiders rated their health condition as relatively bad or bad compared with the general population (20.2% vs. 13.3%, respectively). A much higher percentage of thalidomiders reported having some health or physical problem caused by a disease or injury (68.8% vs. 32.6%, respectively), and thalidomiders reported visiting medical and healthcare-related facilities more frequently. A higher proportion of thalidomiders (9.2%) were unemployed, and thalidomiders tended to feel higher levels of worry and stress, especially in terms of the future. Conclusions: The results of this nationwide survey of the life situations of thalidomiders in Japan clarified their health conditions and the related associations with socioeconomic status. These findings could be expected to help improve the provision of medical and healthcare, welfare measures, and financial support for thalidomiders in the near future. K E Y W O R D Shealth, life situations, nationwide survey, questionnaire, thalidomide embryopathy

show abstract

Internal anomalies in thalidomide embryopathy: results of imaging screening by CT and MRI

Cited by 9 publications

References 18 publications

The teratogenic effects of thalidomide on limbs

The teratogenic effects of thalidomide on limbs

Arterial dysgenesis and limb defects: Clinical and experimental examples

A nationwide survey regarding the life situations of patients with thalidomide embryopathy in Japan, 2018: First report

Contact Info

Product

Resources

About