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Biomedical subjects

M Litt

Publications and source records attributed to M Litt.

At least 19 recordsLinked to original sources

Safety and cost effectiveness of high-osmolality as compared with low-osmolality contrast material in patients undergoing cardiac angiography.

BACKGROUND AND METHODS: Low-osmolality contrast agents produce fewer hemodynamic and electrophysiologic alterations during cardiac angiography, but they are 20 times more expensive than high-osmolality contrast agents. In a randomized, double-blind trial comparing a nonionic low-osmolality contrast agent (Omnipaque 350) with a high-osmolality agent that does not avidly bind calcium (Hypaque 76) in 505 patients undergoing cardiac angiography, we determined the incidence of minor, mild, moderate, and severe adverse reactions, identified risk factors for such reactions, and evaluated the cost effectiveness of various strategies for the use of contrast material. RESULTS: The 253 patients who received a high-osmolality contrast agent were three times more likely to have a moderate adverse reaction (95 percent confidence interval for the relative risk, 1.6 to 5.5) but no more likely to have a severe reaction (95 percent confidence interval, 0.2 to 2.3) than the 252 patients who received a low-osmolality agent. All 10 severe reactions occurred in patients who were older than 60 years or had unstable angina. Patients with these characteristics were also 3.5 times more likely (95 percent confidence interval, 1.8 to 6.8) to have a moderate reaction (44 of 310 patients, or 14 percent) than those without either characteristic (8 of 195 patients, or 4 percent). We estimated that the incremental cost of each moderate reaction avoided would be $1,698 with a strategy that involved giving a low-osmolality contrast agent only to patients who were over 60 years of age or had unstable angina, instead of giving a high-osmolality agent to all patients. The incremental cost per moderate reaction avoided by giving a low-osmolality contrast agent to all patients rather than only to those over 60 or with unstable angina would be $5,842. CONCLUSIONS: The use of contrast agents with low rather than high osmolality during cardiac angiography reduces the risk of moderate, but not of severe, adverse reactions to the agent used. A strategy of reserving low-osmolality contrast agents for use in patients at high risk for adverse reactions would be more cost effective than one requiring their use in all patients.

Age Factors

The CEPH consortium linkage map of human chromosome 15q.

The CEPH consortium map of chromosome 15q is presented. The map contains 41 loci defined by genotypes generated from CEPH family DNAs with 45 different probe and restriction enzyme combinations contributed by 10 laboratories. A total of 29 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from 15q13 to 15q25-qter. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 127, 190, and 158 cM, respectively. The largest interval is 21 cM and is between D15S37 and D15S74. The on-average locus spacing is 5.6 cM and the mean genetic distance between the 21 uniquely placed loci is 8 cM.

Chromosome Mapping

Linkage map of eight human chromosome 11q markers, including DRD2, spanning 60 cM.

We have constructed a linkage map of eight RFLP markers located on chromosome 11q in the region of the dopamine D2 receptor gene (DRD2) recognized by probe hD2G1. Abnormalities in dopaminergic neurotransmission mediated by this receptor have been implicated in several psychiatric disorders. The map was generated using six large reference families (from 294 to 419 individuals per locus), which are largely independent of the CEPH families, primarily using the LINKMAP and ILINK programs of the LINKAGE package of Lathrop and Lalouel. The most likely order and recombination frequencies are: [sequence: see text] The relative order of D11S84-STMY, DRD2-D11S29, and D11S146-INT2 could not be resolved reliably. There were no significant sex differences in recombination frequency. We introduce here a version of LINKMAP adapted to run under distributed parallel processing (LINDA-LINKMAP). Using pairwise analyses, we have also placed D11S421 proximal to this group.

Chromosome Mapping

Linkage analysis of the D1 dopamine receptor gene and manic depression in six families.

Disturbances in dopaminergic activity may play an important role in the pathogenesis of manic depression. The effects of dopamine are mediated by at least five G protein coupled receptors, D1, D2, D3, D4 and D5. Recently, three separate research groups have cloned and characterized the D1 dopamine receptor, which localizes to 5q35.1. We undertook a linkage analysis between the D1 receptor polymorphisms and manic depression in six families in which segregation of the disease was consistent with autosomal dominant inheritance. A highly polymorphic flanking DNA marker, CRI-L1200, was also analyzed as the D1 gene RFLPs were relatively uninformative in our families. Multipoint analyses of manic depression and these DNA markers resulted in lod scores of less than -3.0 at the D1 locus, indicating that the D1 dopamine receptor gene does not confer an inherited susceptibility to manic-depressive illness in the families studied.

Bipolar Disorder

High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA) locus.

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. We have extended our previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analyses gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a human/rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosities of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that cosegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXS732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively.

Base Sequence