Ebstein's anomaly may be caused by mutations in the sarcomere protein gene MYH7.

Ebstein's anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. Associated abnormalities of left ventricular morphology and function including left ventricular noncompaction (LVNC) have been observed. An association between Ebstein's anomaly with LVNC and mutations in the sarcomeric protein gene MYH7, encoding ß-myosin heavy chain, has been shown by recent studies. This might represent a specific subtype of Ebstein's anomaly with a Mendelian inheritance pattern. In this review we discuss the association of MYH7 mutations with Ebstein's anomaly and LVNC and its implications for the clinical care for patients and their family members.

Design of immuno-enzymosomes with maximum enzyme targeting capability: effect of the enzyme density on the enzyme targeting capability and cell binding properties.

Immuno-enzymosomes have been proposed for the targeting of enzymes to cancer cells to achieve site specific activation of anticancer prodrugs. Previously, we reported that the enzyme beta-glucuronidase (GUS), capable of activating anthracycline-glucuronide prodrugs, can be coupled to the surface of inmunoliposomes directed against human ovarian cancer cells (OVCAR-3). This study aimed at the design of an immuno-enzymosome formulation with maximum enzyme targeting capability. By purification of the commercially available enzyme beta-glucuronidase (GUS), a 2-fold increase in the enzyme specific activity and a 4-fold increase in the enzymatic activity of immuno-enzymosomes was achieved. As a result, upon incubation with human ovarian cancer cells (OVCAR-3), cell-associated enzymatic activity increased correspondingly. The optimized immuno-enzymosomes were shown to bind to the target cells in a specific fashion. Above a GUS/Fab' molar ratio of 0.5, impairment of the target cell binding ability of the immuno-enzymosomes was observed. This was likely due to a steric hindrance effect mediated by the presence of large amounts of bulky GUS molecules on the liposome surface. Nevertheless, increasing the GUS density on the surface of the immuno-enzymosomes to levels by far exceeding the GUS/Fab' molar ratio of 0.5, yielded a considerably improved enzyme targeting capability.

Ticlopidine-induced phenytoin toxicity.

OBJECTIVE: To report a probable case of ticlopidine-induced phenytoin toxicity. CASE SUMMARY: A 72-year-old white man suddenly developed combative behavior, refused to leave his room, stopped eating, and began falling to the floor 6 weeks after being given ticlopidine. The total phenytoin concentration was measured at 43.6 micrograms/mL; the dosage of phenytoin was decreased and the symptoms later resolved. After ticlopidine was discontinued, the patient was rechallenged with the same dose of phenytoin without symptoms of toxicity. DISCUSSION: Possible mechanisms of the drug interaction are discussed with emphasis on cytochrome P450 metabolism. CONCLUSIONS: Clinicians should be aware of this potentially serious drug interaction and either avoid the phenytoin-ticlopidine combination, or monitor closely for phenytoin toxicity.