Citations

The case of a patient with intractable temporal lobe seizures and inadvertent unilateral intraventricular depth electrode placement is presented. The resting electroencephalograph (EEG) showed marked amplitude differences between the intraventricular electrode on the left and the parenchymal electrode on the right. All recorded seizures originated on the left side and in spite of its intraventricular location, frequency power spectra during the early ictal phase showed a marked increase in power for all frequency bands in the left depth electrode, exceeding that on the right. Analysis with Brain Electrical Source Analysis (BESA) software demonstrated marked ictal baseline shifts which were initially limited to the left side but changed to the right during clinical secondary generalization. In the immediate postictal state, all, except for infraslow, frequencies were markedly reduced in power. We conclude that intraventricular depth electrode contacts placed adjacent to the hippocampal structure can record interictal and ictal activity for all frequency bands, albeit at reduced amplitudes. Furthermore, infraslow activity can provide supplementary information about the epileptogenic zone.

Although US health care expenditures reached 17.6 percent of GDP in 2009, quality measurement in this important service sector remains limited. Studying quality changes associated with 11 years of health care for patients with diabetes, we find that the value of reduced mortality and avoided treatment spending, net of the increase in annual spending, was $9,094 for the average patient. These results suggest that the unit cost of diabetes treatment, adjusting for the value of health outcomes, has been roughly constant. Since input prices have not been declining, our results are consistent with productivity improvement in health care.

Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting. Mice homozygous for targeted disruption of the PAPPA gene were viable but 60% the size of wild-type littermates at birth. The impact of the mutation was exerted during the early embryonic period prior to organogenesis, resulting in proportional dwarfism. PAPPA, IGF2 and IGFBP4 transcripts co-localized in wild-type embryos, and expression of IGF2 and IGFBP4 mRNA was not altered in PAPPA-deficient embryos. However,IGFBP4 proteolytic activity was completely lacking in fibroblasts derived from PAPPA-deficient embryos, and IGFBP4 effectively inhibited IGF-stimulated mitogenesis in these cells. These results provide the first direct evidence that PAPPA is an essential growth regulatory factor in vivo, and suggest a novel mechanism for regulated IGF bioavailability during early fetal development.