Evolution of a form of pure alexia without agraphia in a child sustaining occipital lobe infarction at 21/2 years

The progress of cognitive visual dysfunction over an 8-year period of a child who sustained bilateral occipital-lobe infarctions at the age of 21/2 years is described. She survived with normal intelligence and went on to attend mainstream school. She manifested many features of cognitive visual impairment and, in particular, developed a form of pure alexia without agraphia. She achieved some letter-by-letter reading but no sight vocabulary development, including to her own name. She learned to write imaginatively employing phonetically true spelling but cannot read what she has written. Her progress and the difficulties encountered during the management of her condition are discussed in this first case report of the evolution of pure alexia without agraphia in childhood. The features of this syndrome in the developing child who has never developed the capacity to read are contrasted with that seen in affected adults.     

Comparison of Output Particle Size Distributions from Pressurized Aerosols Formulated as Solutions or Suspensions

The delivery of particles as small as possible (preferably <5 µm) to the respiratory tract should be the aim of those formulating metered dose inhalers (MDIs). This may be facilitated by the formulation of solution, rather than suspension-type, pressurized aerosol units. Two series of MDIs were compared; one contained suspended micronized disodium fluorescein (0.1%, w/v), while the other contained the same concentration of dissolved salicylic acid. Either oleic acid, L--phosphatidylcholine, or sorbitan trioleate was incorporated at 0.15% (w/v) as suspending agent (disodium fluorescein) or solubilizing agent (salicylic acid). The propellant blend was 70% (w/w) Freon 12 and 30% (w/w) Freon 11 in all cases. This exhibited a vapor pressure of 50.6 psig (444.7 kPa) at 21°C. The output particle size distribution of the aerosol reaching the cascade impactor showed a mass median aerodynamic diameter (MMAD) of approximately 4 and 2 µm for the suspension and solution formulations respectively, regardless of the surfactant used. Larger MMADs were observed for solution aerosols formulated with oleic acid (2.32 µm) compared to those containing L--phosphatidylcholine (1.93 µm) or sorbitan trioleate (2.07 µm). Possible reasons for these observations are discussed.     

Use of end-tidalPco 2 and transcutaneousPco 2 as noninvasive measurement of arterialPco 2 in extubated patients recovering from general anesthesia

This study was designed to assess the accuracy of end-tidalPco ₂ and transcutaneousPco ₂ as measurements of arterialPco ₂ in extubated, spontaneously breathing patients recovering from general anesthesia. In 30 patients, measurement of arterial transcutaneous, and end-tidalPco ₂ were taken simultaneously with body temperature approximately every 15 minutes over a 2-hour period. ArterialPco ₂ values were corrected for body temperature. Values for Paco ₂ were compared with those forPetCO₂ and Psco ₂ by linear regression analysis and by calculation of bias ± precision. Thirty-six percent of the capnogram tracings obtained did not develop a plateau phase. We found poor correlation between end-tidal and arterialPco ₂ regardless of the shape of the capnogram tracing, as well as poor correlation between transcutaneous and arterialPco ₂. Although the measurements of bias and precision of noninvasivePco ₂ monitors in this population are comparable to studies in other populations, we advise caution in relying on the routine use ofPetCO₂ or Psco ₂ for the noninvasive assessment of respiratory depression in extubated, spontaneously breathing patients recovering from general anesthesia.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

IMPT1, an imprinted gene similar to polyspecific transporter and multi- drug resistance genes

Human chromosome 11p15.5 and distal mouse chromosome 7 include a megabase-scale chromosomal domain with multiple genes subject to parental imprinting. Here we describe mouse and human versions of a novel imprinted gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a predicted multi-membrane-spanning protein similar to bacterial and eukaryotic polyspecific metabolite transporter and multi- drug resistance pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues with metabolite transport functions, including liver, kidney, intestine, extra-embryonic membranes and placenta, and there is strongly preferential expression of the maternal allele in various mouse tissues at fetal stages. In post-natal tissues there is persistent expression, but the allelic bias attenuates. An allelic expression bias is also observed in human fetal and post-natal tissues, but there is significant interindividual variation and rare somatic allele switching. The fact that Impt1 is relatively repressed on the paternal allele, together with data from other imprinted genes, allows a statistical conclusion that the primary effect of human chromosome 11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative repression of genes on the paternal homolog. Dosage regulation of the metabolite transporter gene(s) by imprinting might regulate placental and fetal growth.