A short history of thalidomide embryopathy

Lenz, W

doi:10.1002/tera.1420380303

Cited by 709 publications

(264 citation statements)

References 2 publications

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“…The drug was on the market in Canada for only 11 months during 1962 (23). The pattern of anomalies found in this study is congruent with the expected pattern characteristic for this teratogen (1). At least 25 different hypotheses have been suggested to explain the teratogenic mechanism of this chemical, none of them elucidating the mechanism of action satisfactorily (24).…”

Section: Discussionsupporting

confidence: 84%

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Maternal factors, medications, and drug exposure in congenital limb reduction defects.

Froster

Baird

1993

Environ Health Perspect

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As part of an ongoing study on all limb reduction defects occurring among 1,213,913 consecutive live births in the province of British Columbia, Canada, during 1952-1984, cases with documented maternal drug exposure and chronic maternal diseases were analyzed separately. This population-based study was made possible through the existence of an ongoing Health Surveillance Registry, which documents all infants born with congenital, genetic, or chronically handicapping conditions in the province of British Columbia. Strict rules of confidentiality are obeyed. For this part of the analysis of limb reduction defects, cases with documented maternal illness, drug abuse, and exposure to environmental hazards early in pregnancy were analyzed as a separate group to identify specific, recurring patterns of anomalies. A total of 51 cases with possibly related maternal factors were identified. Among them were five cases with maternal epilepsy, four cases with documented maternal diabetes, and three cases with uterine anomalies. Three infants, all born in 1962, had documented thalidomide exposure. It is rarely possible to identify particular teratogenic factors or specific maternal factors as etiologically related to the pattern of limb reduction defects or a spectrum of congenital malformations. Exposure to environmental factors during pregnancy is not reliably registered and can thus only occasionally be ascertained in retrospective studies. This means that very large numbers of cases and cross-referencing to other family members are required to assess whether a potential teratogen is related to limb defects or not.

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Section: Discussionsupporting

confidence: 84%

“…One of the cases also had prenatal alcohol exposure. The three cases display the well-established pattern of anomalies caused by thalidomide, affecting the skeletal system and causing cardiovascular and functional anomalies (1). It is of interest that the case with alcohol exposure also had mental retardation.…”

Section: Acute Maternal Infections During Pregnancymentioning

confidence: 81%

Maternal factors, medications, and drug exposure in congenital limb reduction defects.

Froster

Baird

1993

Environ Health Perspect

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“…Amelia of one or more limbs occurs with a frequency of 1.5 per 100'000 live births. While upper and lower limbs are affected comparably often, there is a preponderance of left-sided over right-sided defects (unless they are thalidomideinduced; Lenz 1988). The present review is not primarily concerned with the physical aspects of limb reduction defects, but with the observation that a minority of individuals, who show such defects, report phantom sensations of the congenitally absent limb (henceforth referred to as "congenital phantoms").…”

Section: Animation Without Incarnation: Phantom Sensations Of Congenimentioning

confidence: 98%

Incarnation and animation: physical versus representational deficits of body integrity

Hilti

Brugger

2009

Exp Brain Res

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Hilti, L; Brugger, P (2010). Incarnation and animation: physical versus representational deficits of body integrity. Experimental Brain Research, 204(3) AbstractTwo apparently disparate phenomena of defective body integrity are reviewed. The first concerns dysmelia, characterized by the congenital absence or deformation of limbs, and the focus of the review is on phantom sensations of people with this kind of physical integrity disorder. The second phenomenon consists of non-psychotic individuals' desire to have a healthy limb amputated, which is interpreted as a mismatch between the physical integrity of a particular limb and its representation in multimodal cortical areas of the brain. We outlined commonalities and differences between the two conditions and note the absence, in both areas of research, of a unified theory that would account for the reported phenomenology. Phantom limbs in dysmelia and the desire for limb amputation most likely are the consequence of very early developmental dissociations between physical and phenomenal body shapes. They are mirror images of one another in that the former constitutes an "animation without incarnation" and, the latter, an "incarnation without animation". Keywords-body integrity identity disorder (BIID) -paraphilias -parietal lobes -body image, body schema -borderlands of psychiatry and neurology 2 This paper examines two apparently disparate phenomena of corporeal awareness. In both, the completeness or integrity of one's own body is hampered. The first is the occurrence of phantom limbs in individuals born with an "incomplete" body, in which the physical body is incomplete, but the missing limb seems to be represented in the subject's brain, at least as can be inferred from its phenomenal presence. The second phenomenon is the strong desire, by non-psychotic and otherwise well-adjusted healthy individuals, to have a fully functional limb removed. In this condition, it can be argued that despite the physical presence of a limb, the lack of acceptance is due to some underrepresentation in the subject's brain. We review the literature on both conditions and propose that phantom sensations of physically absent limbs and the request for removal of normally developed extremities may be mirror images of one another on the conceptual level: an animation without incarnation and an incarnation without animation, respectively.

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“…Thalidomide was distributed in the late 1950s as a sedative and an anti-nausea medication for first trimester pregnancy (1). Prenatal use of the drug, however, produced severe developmental defects to the human fetus, including limb deformities (2).…”

mentioning

confidence: 99%

Inhibition of NF-κB Activity by Thalidomide through Suppression of IκB Kinase Activity

Keifer

Guttridge

Ashburner

et al. 2001

Journal of Biological Chemistry

450

255

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The sedative and anti-nausea drug thalidomide, which causes birth defects in humans, has been shown to have both anti-inflammatory and anti-oncogenic properties. The anti-inflammatory effect of thalidomide is associated with suppression of cytokine expression and the anti-oncogenic effect with inhibition of angiogenesis. It is presently unclear whether the teratogenic properties of thalidomide are connected in any way to the beneficial, anti-disease characteristics of this drug. The transcription factor NF-B has been shown to be a key regulator of inflammatory genes such as tumor necrosis factor-␣ and interleukin-8. Inhibition of NF-B is associated with reduced inflammation in animal models, such as those for rheumatoid arthritis. We show here that thalidomide can block NF-B activation through a mechanism that involves the inhibition of activity of the IB kinase. Consistent with the observed inhibition of NF-B, thalidomide blocked the cytokine-induced expression of NF-B-regulated genes such as those encoding interleukin-8, TRAF1, and c-IAP2. These data indicate that the therapeutic potential for thalidomide may be based on its ability to block NF-B activation through suppression of IB kinase activity.

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A short history of thalidomide embryopathy

Cited by 709 publications

References 2 publications

Maternal factors, medications, and drug exposure in congenital limb reduction defects.

Maternal factors, medications, and drug exposure in congenital limb reduction defects.

Incarnation and animation: physical versus representational deficits of body integrity

Inhibition of NF-κB Activity by Thalidomide through Suppression of IκB Kinase Activity

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