Fell off of a horse--journey from Emergency Department to Stroke clinic.

The authors present a case of a young woman who presented with transient episodes of left-sided weakness after she fell off a horse. She attended Emergency Department twice before being referred to the Stroke clinic, where she was diagnosed with carotid artery dissection.

Do weekend plan standard forms improve communication and influence quality of patient care?

Weekends are critical times in an inpatient stay, when daily review of patients is not routine and the usual team of doctors responsible for a patient's care is often not available. Communication between the patient's own doctors and the on call team is vital for continuity of care and to maintain patient safety. The provision and completeness of weekend plans was assessed before and after the introduction of a standard form. The introduction of the form led to a significant improvement in the proportion of notes containing a weekend plan and the proportion of notes containing a resuscitation decision (p<0.05), which will have a significant impact on patient care.

Evaluation of human diacylglycerol kinase(iota), DGKI, a homolog of Drosophila rdgA, in inherited retinopathy mapping to 7q.

PURPOSE: To determine the genomic organization of diacylglycerol kinase(iota) and to test whether defects in this gene are present in individuals affected with autosomal dominant retinitis pigmentosa (adRP). Diacylglycerol kinase(iota) has been mapped to the RP10 locus on 7q and shows 49% sequence similarity to the Drosophila DGK2 rdgA gene. Since mutations in the DGK2 rdgA gene cause photoreceptor degeneration in Drosophila, it is possible that mutations in diacylglycerol kinase(iota) could be responsible for human retinal degeneration. METHODS: DNA sequence from genomic clones containing diacylglycerol kinase(iota) was compared with the cDNA sequence to identify intron/exon boundaries. Single-strand conformational analysis and PCR product sequencing were used to screen members of one family previously mapped to the RP10 locus and 47 small unmapped families with autosomal dominant retinitis pigmentosa. RESULTS: Diacylglycerol kinase(iota) is divided into 35 exons with the initiation codon being present in exon 2. Mutational analysis found a missense change (Lys153Phe) in three adRP families; however, it did not segregate with disease in one of the families. Silent substitutions were seen in codons 865 and 875. Intronic variation was detected in the amplifications of exons 3,5,18, 28, and 32; these do not affect splice site consensus sequences. Typing of a polymorphic variant detected in intron 31 in members of the RP10 family gave a LOD score of -4.2 at 0% recombination. CONCLUSIONS: No evidence of disease-associated mutations was found in any of the samples tested. Based on the linkage data and mutation screening, diacylglycerol kinase(iota) is excluded as a candidate for the RP10 form of adRP and cannot be a frequent cause of other forms of adRP. Mutations in diacylglycerol kinase(iota) may yet be the cause of recessive forms of retinal degeneration in humans, either in homozygous or compound heterozygous forms. The data provided here will permit testing of this hypothesis.

The cloning and characterization of a novel human diacylglycerol kinase, DGKiota.

Diacylglycerol (DAG) plays a central role in both the synthesis of complex lipids and in intracellular signaling; diacylglycerol kinase (DGK) catalyzes the phosphorylation of DAG, which yields phosphatidic acid. A family of DGKs has been identified in multicellular organisms over the past few years, but the physiological function(s) of this diversity is not clear. One clue has come from the Drosophila DGK2, rdgA, since mutations in this gene cause retinal degeneration. We isolated a novel DGK, which we designated DGKiota, from human retina and brain libraries. DGKiota contains two cysteine-rich repeats, a region similar to the phosphorylation site domain of myristoylated alanine-rich C kinase substrate, a conserved catalytic domain, and four ankyrin repeats at its C terminus. By primary structure, it is most similar to human DGKzeta and Drosophila rdgA. An >12-kilobase mRNA for DGKiota was detected only in brain and retina among the tissues examined. In cells transfected with the DGKiota cDNA, we detected an approximately 130-kDa protein by immunoassay, and activity assays demonstrated that it encodes a functional DAG kinase. The protein was found to be in both the cytoplasm and nucleus with the localization controlled by PKC isoforms alpha and gamma. The gene encoding DGKiota was localized to human chromosome 7q32.3-33, which is known to be a locus for an inherited form of retinitis pigmentosa. These results have defined a novel isoform of DAG kinase, which may have important cellular functions in the retina and brain.

The inducible prostaglandin biosynthetic enzyme, cyclooxygenase 2, is not mutated in patients with attenuated adenomatous polyposis coli.

Germ-line mutations in the APC gene cause adenomatous polyposis coli (APC), a syndrome in which patients develop hundreds to thousands of precancerous adenomatous colorectal polyps. We described previously an attenuated form of APC (AAPC) resulting from very 5' mutations in APC in which affected patients exhibit fewer colorectal polyps and a later age of onset of colorectal cancer. However, because striking variations in colorectal polyp numbers occur among patients carrying identical AAPC mutations, alleles of another gene may modify the expression of the APC disease phenotype. We tested the hypothesis that loss of function of human cyclooxygenase 2 (COX-2), known to modify the APC phenotype in the Apc delta716 mouse, results in a decreased tumor burden in AAPC patients that develop very few colorectal polyps. Genomic DNA sequence analysis of human COX-2 revealed a silent mutation in exon 3 that was evenly distributed between two classes of patients with AAPC, those with small or large numbers of colorectal polyps. We also found no difference in levels of COX-2 mRNA in transformed blood lymphocytes among AAPC patients of either class or patients with classical APC, and no alterations that correlated with a lesser or greater number of colorectal polyps were detectable within approximately the first 1 kb of the promoter sequence. Therefore, mutation of the human COX-2 gene does not appear to be responsible for a low tumor burden among AAPC subjects.

Cloning, expression, and chromosomal localization of human long-chain fatty acid-CoA ligase 4 (FACL4).

Long-chain fatty acid-CoA ligase (also called fatty acid acyl-CoA synthetase) plays an essential role in lipid biosynthesis and fatty acid degradation. We report herein the cDNA cloning of the human long-chain fatty acid-CoA ligase 4 from a brain library. The cDNA encodes a functional long-chain fatty acid-CoA ligase that shows preference for arachidonic acid as substrate. We also studied the tissue distribution of gene expression by Northern hybridization. Human placenta, brain, testis, ovary, spleen, and adrenal cortex have the highest levels of expression of the long-chain fatty acid-CoA ligase 4, whereas the GI system has the lowest. Finally, this gene was localized to chromosome Xq23 in human by FISH analysis.