Beyond thalidomide : birth defects explained / Janet McCredie.

Format:

Book

Author/Creator:

McCredie, Janet.

Language:

English

Subjects (All):

Abnormalities, Human--Etiology.

Abnormalities, Human.

Thalidomide--Side effects.

Thalidomide.

Congenital Abnormalities--etiology.

Thalidomide--adverse effects.

Medical Subjects:

Congenital Abnormalities--etiology.

Thalidomide--adverse effects.

Physical Description:

xii, 418 pages : illustrations (partly color) ; 26 cm

Place of Publication:

London : Royal Society of Medicine Press, [2007]

Summary:

How do birth defects happen? What goes wrong in the embryo? These perennial questions were brought into sharp focus in the wake of the thalidomide catastrophe (1958-1962). How did thalidomide mutilate the embryo? Despite research efforts, these questions have remained unanswered. The author, a diagnostic radiologist, recognized that there were some clues to a possible answer in the radiographs of thalidomide children, although these had not been fully analysed. Taking a new approach to the disordered anatomy, she found that the character and the distribution of skeletal defects was inconsistent with primary bone disease, which had been the current thinking, but indicated primary damage to embryonic sensory nerves (neural crest), with subsequent failure of formation of bones and joints. Thalidomide is a notorious sensory neurotoxin in adults, and her analysis pointed to the same target tissue in the embryo. The neural crest theory, however, extends beyond thalidomide and could explain the majority of non-genetic birth defects, anatomically similar to those caused by thalidomide, but hitherto unexplained. Thalidomide was the key that opened the lock to reveal the mechanism underlying many, but not all, congenital malformations - its recent revival as a therapeutic agent adds urgency to the need to clarify its mode of action. Beyond Thalidomide examines the neural crest theory in breadth and depth, incorporating evidence from clinical medicine, radiology, biology, pharmacology, neurology, neuroanatomy and neuropathology. Key publications, some now out of print, are restored to their rightful places in the thalidomide saga and background information is provided to help the general reader gain a better understanding of the sciences involved. It will be of particular interest to those involved with birth defects - obstetricians, neonatologists, paediatricians - and also neurologists, scientists in teratology and developmental biology, and thalidomiders themselves.

Contents:

Foreword: Lord Walton of Detchant vii

1 The thalidomide epidemic 1

2 Pharmacology of thalidomide: Interaction with the human embryo 11

3 Animal studies 23

4 Thalidomide polyneuropathy 39

5 Clinical radiology 57

6 Terminology, classification and the rejection of authority 63

7 The pattern of the disease: First radiological analysis (Sydney) 69

8 Verification of the disease pattern: Second radiological analysis (London) 87

9 Congenital reductions of the radius 91

10 Congenital dislocation 101

11 Congenital synostosis 115

12 The hypothesis of neural crest injury 125

13 The neural crest 139

14 Neurotrophism 157

15 Nerve in limb bud 169

16 Regeneration and embryogenesis 185

17 Neural crest ablation and limb morphogenesis 197

18 Thalidomide deformities and their nerve supply: First morphometric study in rabbits 211

19 Thalidomide deformities and their nerve supply: Second morphometric study in rabbits 229

20 The sensory nerve supply of bone 237

21 The sclerotomes 245

22 Sclerotome aplasia/subtraction 257

23 Sclerotome aplasia/subtraction in 203 cases 269

24 Radial/tibial dysmelia: Limb reductions typical of thalidomide 281

25 Associated internal malformations and their embryology 295

26 Neurotomes and multiple malformation syndromes 317

27 Hands and feet in thalidomide embryopathy: Histology and sclerotomes in the digits 333

28 Other disorders of similar sclerotomes 351

29 Segmental and truncal neuropathies in sclerotomes not affected by thalidomide 365

30 Review of actions of thalidomide 387

31 Conclusion: Beyond thalidomide 399.

Notes:

Includes bibliographical references and index.

ISBN:

1853157414

9781853157417

OCLC:

182662820