Abstract.-Methylmalonic acidemia is an inherited metabolic disorder thus far found in children and characterized by the excessive excretion of methylmalonate in the urine. Typically these children exhibit vomiting, lethargy, ketoacidosis, and failure to grow. Many of the patients are mentally retarded and die early in life. Two variants of this disease are known. In one, the administration of vitamin B12 will reverse or prevent these clinical findings, whereas in a second variant vitamin B12 therapy is of no value.This paper presents the first enzymatic evidence (obtained with cell-free liver extracts) that bears on two important aspects of the disease. It has been found that methylmalonylCoA carbonylmutase activity is essentially absent in the livers of patients suffering from one variant (vitamin B12-unresponsive) of the disease. Secondly, it has been found that the livers of patients with the second variant (vitamin BH2-responsive) of the disease show normal enzymatic behavior in the presence of the coenzyme form of vitamin B,2, but are identical to the vitamin B,2-unresponsive variant in the absence of the added coenzyme. Thus the enzyme studies fully support the clinical observations that two types of this disease exist.Introduction.-Two variants of inherited methylmalonic acidemia have been described since the original report of this inborn error of metabolism by Oberholzer et al. ' The metabolic pathway involved is the conversion of propionate to succinate, one step of which requires the cobamide coenzyme form of vitamin

Purpose and methods As a part of reviewing the Multinational Association of Supportive Care in Cancer (MASCC) antiemetic guidelines in Perugia in 2009, an expert group identified directions for future antiemetic research. Results and conclusions In future trials, the prediction of nausea and vomiting may combine algorithms based on observed prognostic factors relating to the patient and the anticancer therapy, the identification of the genes that code for receptors, and pharmacogenetic studies of the metabolism of drugs. Design issues for future trials include standardising the emetic stimulus across studies and finding the minimum tolerated effective dose and schedule of an antiemetic. Also control of delayed emesis is not independent of the control of acute emesis. The full range of side effects and the impact on global quality of life scores should be part of the routine assessment of an antiemetic. With current high rates of control of acute vomiting, future trials will need to consider new primary endpoints such as nausea, a complex symptom, where improvement is needed. Economic endpoints should be incorporated to ascertain the cost benefit of antiemetic prophylaxis, taking into account the impact of nausea on work capacity. New antiemetic drugs may be targeted at different receptors, such as opioid, cannabinoid and peptide YY receptors. New research is needed into determining the extent of corticosteroid use. The emetic potential of a range of newer cytotoxics particularly when used in combinations and different scheduling, such as prolonged oral dosing of cytotoxics and use of targeted therapies, are all areas in need of research. More antiemetic studies are needed in niche areas such as in patients receiving high dose chemotherapy, radiation therapy or combined modality therapy. Further evidence of the efficacy of newer antiemetic agents is required in children.

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