The effects of methylmalonate (MMA) on succinate dehydrogenase (SDH) and beta-hydroxybutyrate dehydrogenase (HBDH) activities in brain and liver of 15-day-old rats were studied. The apparent Km of SDH for succinate was 0.45 mmol/L in brain and 0.34 mmol/L in liver. MMA inhibited the enzyme activity in both tissues with Ki values of 4.5 mmol/L and 2.3 mmol/L in brain and liver, respectively, and the inhibition was of the reversible competitive type. The calculated Km for HBDH with beta-hydroxybutyrate as substrate was 1.26 mmol/L in brain and 0.36 mmol/L in liver. MMA inhibited the enzyme with a Ki value of 0.015 mmol/L in brain and 0.275 mmol/L in liver. These results are probably relevant to our understanding of cerebral metabolism in methylmalonic acidaemic children, especially during ketoacidotic and hypoglycaemic crises, and may be related to the pathogenesis of cerebral dysfunction of methylmalonic acidaemia.

These data support the appropriateness of divergent management strategies for typical versus atypical bronchial carcinoids. We propose the following: (1) nonanatomic resection is acceptable only for peripheral typical carcinoids; (2) extended mediastinal dissection should be limited to central presentations, clinically aggressive, or atypical carcinoids; (3) atypical histology, especially with nodal involvement, is prognostic for recurrence and metastasis; (4) nonsurgical therapies only rarely achieve long-term freedom from disease.

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