Recognition of thalidomide defects.
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Biomedical subjects
Publications and source records attributed to C G Newman.
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OBJECTIVE: To study early and late mortality after surgical correction of coarctation of the aorta. DESIGN: Data on 223 patients operated on at the Westminster Hospital, London, between 1946 and 1981, were collected and updated by questionnaire. PARTICIPANTS: All 223 patients recorded as undergoing operation for aortic coarctation up to the end of 1981. Fifteen of 197 survivors were lost to follow up; most of them were patients from overseas. OUTCOME AND RESULTS: The early mortality (within one month of operation) was 12% overall, 2.6% for elective surgery, and 0% for the 77 patients undergoing surgery since 1968. Survivors were followed up for a total of 3288 patient years; in 27 follow up lasted more than 30 years. In a few it reached 40 years. Twenty two patients died during this period, 18 from causes that could be attributed to coarctation or its repair. Mortality was highest more than 20 years after the operation. CONCLUSION: Repair increased life expectancy in patients with aortic coarctation. Late problems caused by persistent hypertension or recoarctation became apparent in long term survivors. The increased risk of late mortality associated with the duration of preoperative hypertension was not statistically significant. There were no deaths from cerebrovascular accidents. (In an earlier necropsy series cerebrovascular accidents accounted for 11.8% of deaths.) The incidence of deaths from aneurysms resembled that in the earlier necropsy series.
We report a child with a subarachnoid cyst with hydrocephalus following a mid-trimester amniocentesis. Although fetal trauma is a rare complication, it is important to stress the need to perform amniocentesis under ultrasound control. Children with neurological disease or convulsions of unknown origin in early infancy who are born to mothers who have had mid-trimester amniocentesis should have a CT scan as part of the investigations to exclude this rare but nevertheless important complication.
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Echos of the 1959 to 1961 thalidomide disaster are still with us in the form of the continuing appearance, although more rarely, of similarly malformed children. A teratologic timetable could be fashioned retrospectively, supporting the concept that different body parts and systems have periods of vulnerability and of resistance to thalidomide, probably the most potent primate teratogen known. Something between one in every two to one in every ten fetuses exposed at the critical development period were affected. The clinical affects are described from the literature on approximately 2500 children, and from extensive personal experience, and a complex though finite pattern of malformations is described, indistinguishable from sporadic nonthalidomide cases of malformations that continue to occur.
There is much misinformation in the medical community regarding the thalidomide syndrome. Some physicians and scientists are unaware of the fact that organs other than the limbs were frequently affected. Some believe that thalidomide could produce any type of limb reduction defect. Most were aware of the very narrow period of early organogenesis during which the thalidomide-type malformations could be produced. Important features include the fact that limb reduction defects were primarily preaxial, included concomitant girdle hypoplasia when limb reductions were severe, were almost universally bilateral and did not include distal transverse-type defects often called "hemimelia". While it can be said that some spontaneous (non-thalidomide) malformations can mimic the thalidomide syndrome, it can also be said that many limb reduction defects can be determined not to have been produced by thalidomide. The risks of the various defects can be estimated following exposure, with most certainty for limb defects, with less certainty for other defects. Many defects were not associated with exposure to thalidomide such as cleft lip and severe mental retardation.
The growth of 202 children exposed to thalidomide in utero and having upper (139 children) or lower (63 children) limb deformities has been assess towards the end of pre-pubertal growth. The analyses show that children exposed to thalidomide are shorter than normal children but grow at a normal velocity later. These findings may help in consideration of the mechanism by which thalidomide exerted its teratogenic effect. Analyses of growth may find a wider use in the retrospective assessment of drugs which are potentially harmful in pregnancy.
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Three cases of the neonatal respiratory distress syndrome are described. The babies were treated by prolonged oxygen given by intermittent positive pressure respiration after endotracheal intubation. Two of the infants died and at necropsy the lungs in both cases were consolidated. Both showed widespread haemorrhagic exudate and interstitial oedema. Early organization of the exudate was apparent in one case. The third infant survived but developed a similar exudative condition and a ;honeycomb' lung. It is suggested that many of the changes found in the lungs of these cases could be attributed to the toxicity of oxygen.
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