Heritable spina bifida in sheep: A potential model for fetal repair of myelomeningocele.

BACKGROUND/PURPOSE: In 2004, a heritable occurrence of spina bifida was reported in sheep on a farm in the United States. We maintained and characterized the spina bifida phenotype in this flock to assess its potential as an alternative surgical model. METHODS: A breeding strategy was developed in which the sheep were crossed to maintain or increase the occurrence of spina bifida. Measurements and observations were recorded regarding lesion size, birthweight, ambulatory capacity, or urological function, and necropsies were performed on spina bifida afflicted lambs in conjunction with magnetic resonance imaging to determine the character of the spina bifida defects and assess the presence of Chiari-like malformations or hydrocephalus. RESULTS: The defects were observed to be more prevalent in ram lambs, and the rate of spina bifida per litter could be increased through backcrossing or by selection of a productive ewe breed. The lambs displayed a range of ambulatory and urological deficits which could be used to evaluate new fetal repair methodologies. Finally, affected lambs were shown to demonstrate severe Chiari malformations and hydrocephalus. CONCLUSIONS: We have determined that use of these sheep as a natural source for spina bifida fetuses is feasible and could supplement the deficits of current sheep models for myelomeningocele repair. LEVEL OF EVIDENCE: Level IV.

Severe physical exertion, oxidative stress, and acute lung injury.

We report the case of a 27-year-old male athlete presenting with severe dyspnoea 24 hours after completing an "Ironman Triathlon." Subsequent chest radiology excluded pulmonary embolus but confirmed an acute lung injury (ALI). Echocardiography corroborated a normal brain natriuretic peptide level by demonstrating good biventricular systolic function with no regional wall motion abnormalities. He recovered well, without requiring ventilatory support, on supplemental oxygen therapy and empirical antibiotics. To date, ALI following severe physical exertion has never been described. Exercise is a form of physiological stress resulting in oxidative stress through generation of reactive oxygen/nitrogen species. In its extreme form, there is potential for an excessive oxidative stress response--one that overwhelms the body's protective antioxidant mechanisms. As our case demonstrated, oxidative stress secondary to severe physical exertion was the most likely factor in the pathogenesis of ALI. Further studies are necessary to explore the pathological consequences of exercise-induced oxidative stress. Although unproven as of yet, further research may be needed to demonstrate if antioxidant therapy can prevent or ameliorate potential life-threatening complications in the acute setting.

Antipsychotic-drug-induced dilated cardiomyopathy.

A man in his 30s presented with symptoms of shortness of breath (SOB). He was on clozapine for schizophrenic symptoms. From the initial two presentations it was thought to be and managed as a chest infection, and a perfusion ventilation scan was done to rule out pulmonary embolism. However, with worsening SOB on exertion, he presented for a third time, and was referred and seen in the Department of Medicine on this occasion. The ECG showed evidence of left atrial and ventricular enlargement. The chest x ray showed an increased cardiothoracic ratio. An urgent echocardiogram showed the presence of dilated cardiomyopathy with severe left ventricular systolic function impairment. The patient had a coronary angiogram and other relevant investigations to look for the cause of the dilated cardiomyopathy. These investigations did not reveal any significant abnormality. The cause appeared to be related to the drug clozapine. The patient was treated for heart failure, and clozapine was stopped. He improved and repeat echocardiogram at follow-up showed a definite improvement in the symptoms and the echocardiogram.