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Biomedical subjects

S Carson

Publications and source records attributed to S Carson.

At least 19 recordsLinked to original sources
PubMed1992

Alternative techniques of cardioplegia.

BACKGROUND: Although normothermic cardioplegia has been used with acceptable clinical results, no studies have previously been performed to determine the metabolic consequences of these various techniques of myocardial protection. Therefore, we have performed a randomized clinical trial to assess the effects of three cardioplegic techniques on myocardial metabolic recovery. METHODS AND RESULTS: Seventy-four patients undergoing coronary artery bypass graft surgery were randomized to receive normothermic antegrade blood cardioplegia (n = 25), normothermic retrograde blood cardioplegia (n = 23), or intermittent cold antegrade blood cardioplegia (n = 26). Myocardial oxygen consumption and lactate production, adenine nucleotides, and adenine nucleotide degradation products were measured during the operation, and cardiac creatine kinase isoenzyme (CK-MB) release was assessed after surgery. Warm antegrade cardioplegia maximized myocardial oxygen consumption during cardioplegic delivery. Postoperative CK-MB release was less after warm antegrade cardioplegia, but the difference was not statistically significant. Warm retrograde cardioplegia resulted in the greatest degree of anaerobic lactate production but did not increase morbidity and mortality. Perioperative myocardial infarctions and postoperative low-output syndrome were most common after cold cardioplegia, but this trend was not statistically significant. During warm antegrade cardioplegia, adenosine triphosphate (ATP) was metabolized to diffusible precursors, which were washed out during cardioplegic infusion. Warm retrograde cardioplegia produced a breakdown of ATP to inosine and hypoxanthine, small molecules that accumulated during the cross-clamp period and were not washed out, perhaps because of inadequate perfusion with retrograde delivery. During cold cardioplegia, ATP was dephosphorylated, and adenosine diphosphate, adenosine monophosphate, and adenosine accumulated. These compounds were not regenerated to ATP but were not washed out of myocytes because they are large anionic molecules. CONCLUSIONS: Intermittent cold cardioplegia inhibited mitochondrial function but prevented the degradation of adenine nucleotides. Warm antegrade cardioplegia had the greatest myocardial oxygen consumption, and warm retrograde cardioplegia had the greatest anaerobic lactate production. There were no differences in clinical outcomes between cardioplegic groups.

Adenosine Triphosphate↗
PubMed1992

The effect of warm heart surgery on postoperative bleeding.

The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets.

Aminocaproic Acid↗
PubMed1991

DNase I hypersensitive sites flank the mouse class II major histocompatibility complex during B cell development.

The mouse class II major histocompatibility complex (MHC) encodes a polymorphic, multigene family important in the immune response, and is expressed mainly on mature B cells, on certain types of dendritic cells and is also inducible by gamma-interferon on antigen presenting cells. To study the regulatory elements which control this expression pattern, we have examined the chromatin structure flanking the class II MHC region, in particular during B cell differentiation. Using a panel of well-characterised mouse cell lines specific for different stages of B cell development (pre-B, B, plasma cell) as well as non-B cell lines, we have mapped the DNase I hypersensitive (DHS) sites adjacent to the mouse MHC class II region. The results presented show, for the first time that there are specific hypersensitive sites flanking the class II MHC locus during pre B cell, B cell and plasma cell stages of B cell differentiation, irrespective of the status of class II MHC expression. These hypersensitive sites are not found in T cell, fibroblast or uninduced myelomonocytic cell lines. This suggests that these DHS sites define a developmentally stable, chromatin structure, which can be used as a marker of B cell lineage commitment and may indicate that a combination of these hypersensitive sites reflect regulatory proteins involved in the immediate expression of a particular class II MHC gene or possibly control of the entire locus.

Animals↗
PubMed1991

Optimal delivery of blood cardioplegia.

A prospective randomized controlled trial was performed to determine optimal flow rates and hemoglobin concentrations for continuous normothermic blood cardioplegia and to compare warm heart surgery with standard intermittent cold blood cardioplegia. Thirty-five patients received intermittent cold blood cardioplegia, low hemoglobin low flow, low hemoglobin high flow, high hemoglobin low flow, or high hemoglobin high flow warm blood cardioplegia (seven patients per group: low hemoglobin, 50 g/l; high hemoglobin, 80 g/l; low flow, less than 80 ml/min; high flow, greater than 80 ml/min). Hypothermia resulted in a significantly greater accumulation of ADP and AMP during cross clamp, consistent with impaired mitochondrial function. Low hemoglobin low flow warm blood cardioplegia increased myocardial oxygen consumption and coronary sinus blood flow after cross clamp release, and also decreased lactate consumption. Postoperative myocardial performance and diastolic compliance were reduced in low hemoglobin low flow warm patients, and diastolic compliance was increased with high hemoglobin high flow warm blood cardioplegia when compared with cold patients. In this study, continuous normothermic cardioplegia was safe when delivered at 80 ml/min or greater, with a hemoglobin concentration of at least 80 g/l, affording myocardial metabolic and functional recovery comparable to that found after intermittent cold blood cardioplegia.

Blood↗
PubMed1990

Maternal-fetal electrocardiographic effects and pharmacokinetics after an acute i.v. administration of caffeine to the pregnant rat.

The relationship between fetal exposure and cardiovascular functional effects in the caffeine-treated pregnant rat was investigated. Caffeine (100 mg/kg) was administered intravenously to dams on day 21 of gestation. The transplacental transport of caffeine was studied by obtaining maternal and fetal blood (umbilical vein) samples at designated times after drug administration. Concurrent maternal-fetal electrocardiograms (ECGs) were measured and evaluated for caffeine-induced changes. Maternal and fetal plasma caffeine levels as well as area under the curve values were proportionally related throughout the experiment, indicative of equal exposure to caffeine. The fetal ECG exhibited more extensive changes associated with caffeine than did the dam's, but the effects were not detected in the first 30 min, suggesting a lag period for the action of caffeine on the fetal heart. The frequency of fetal ectopic beats and abnormal T waves were directly related to fetal plasma caffeine levels. Fetal ECG combined with the fetal blood microsampling technique was a practical method of testing for prefunctional effects of caffeine in the rat fetus.

Animals↗
PubMed1989

A linkage map of the mouse immunoglobulin lambda light chain locus.

The mouse immunoglobulin lambda light chain locus has been linked using field inversion gel electrophoresis. The lambda light chain locus classically contains two V and four J-C gene segments in inbred mouse strains, and was physically mapped in the BALB/c cell line Wehi-3 which contains unrearranged lambda light chain gene segments. The locus is relatively small and spans 300 kb, as defined by a variety of single and double digests using methylation-sensitive restriction enzymes. The order of the lambda gene segments is V2-J2C2J4C4-V1-J3C3J1C1, as was originally proposed. No evidence for nonmethylated CpG rich areas (HTF islands) within the region was found. Fine mapping using the lambda 1, lambda 3 rearranged cell line J558 mapped the gap between the V and J-C gene segments in the lambda 1 gene cluster (V1-J3C3J1C1) to approximately 70 kb. The similar distance (60-100 kb) found in the lambda 2 gene cluster (V2-J2C2J4C4) is further evidence that duplication of an ancestral locus occurred.

Animals↗
PubMed1989

Hypothalamo-pituitary-adrenal activity in endogenously depressed post-traumatic stress disorder patients.

We studied the hypothalamo-pituitary-adrenal (HPA) system in Vietnam veterans with post-traumatic stress disorder (PTSD) who also met Research Diagnostic Criteria for endogenous depression (MDD-ED). Over half also abused alcohol, and many complained of pain-confounding factors usually associated with increased HPA activity. Nonetheless, not even one patient had elevated basal plasma cortisol concentrations or an abnormal dexamethasone suppression test (DST); the subjects' post-dexamethasone cortisol values and plasma cortisol per ng plasma dexamethasone were in the low-normal range. These results highlight the biological heterogeneity of endogenous depression and its possible influence by past psychological trauma, and they raise questions about the use of current typological criteria for research purposes.

Adult↗
PubMed1986

Effects of diflubenzuron on the mouse liver.

Diflubenzuron (DFB), a potent inhibitor of insect chitin synthesis, was administered to Swiss Webster mice in a 30-day oral intubation study. Animal groups received either no treatment, vehicle control (Polyethylene glycol 400), or DFB suspensions at doses of 125, 500, and 2,000 mg/kg body weight. Hepatic glutathione S-transferase activity as well as morphological characteristics were studied. DFB was shown to elicit hepatocellular changes at all dose levels. The activities of three glutathione S-transferases (S-aryl, S-aralkyl, and S-epoxide) were all altered after DFB administration. Light microscopy revealed radial arrays of hepatocellular vacuolization between the portal and central vein areas. Electron-microscopic examination, verified by morphometric analysis, revealed degenerative changes as well as an increased volume density of the endoplasmic reticulum.

Animals↗
PubMed1986

An isolated beta 1 exon next to the DR alpha gene in the HLA-D region.

A cosmid clone containing the DR alpha gene and a beta 1 exon of a DR beta-related gene was isolated from a human cosmid clone bank made from the consanguineous DR7 cell line MANN. No other DR beta-related exons were found on this clone. The beta 1 exon was located about 15 kb away from the DR alpha gene in a tail-to-tail (3' to 3') orientation. The exon contained several deleterious mutations: a defective splice site at the 5' end, two translational frame shifts (a 1 bp deletion and a 1 bp insertion), and three extra cysteine residues. Nucleotide and amino acid sequence comparisons of the beta 1 exon indicated that although it is substantially different from other class II beta-chain genes, it is slightly more related to DR than to any other class II gene. The DR beta-related sequence was on a DNA fragment which showed no polymorphism on a panel of cell lines with Eco RI or Pst I. These Southern blots, however, revealed a related, polymorphic sequence in the human genome. Nucleotide sequences in the intron flanking the beta 1 exon shared greater sequence homology than the beta 1 exon itself when compared with the DR beta genomic sequence. The exon may play a role in the generation of variation in expressed class II beta-chain genes and it may be a relic of a different subset of class II products.

Base Sequence↗
PubMed1985

Structure, sequence and polymorphism in the HLA-D region.

Molecular analysis of the HLA-D region has uncovered a complex array of related genes encompassing a minimum of 6 alpha and 7 beta chain sequences. A high level of polymorphism is characteristic of the DQ alpha and beta genes, as well as DR beta. The DP genes, both alpha and beta, are also polymorphic, though to a lesser extent. The genes fit into the previously established loci: DP, DQ and DR, except for a newly-discovered sequence, DZ alpha, which is approximately equally related to all of the other alpha chain genes. Analysis of the polymorphism and evolution of the HLA-D region, by examination of the sequences, calls for several independent duplication events in the generation of this family of genes.

Base Sequence↗
PubMed1979

Biocompatibility evaluation of casting alloys in hamsters.

A number of base metal and low gold-content alloys were evaluated in hamster cheek pouches for biocompatibility. No adverse weight changes and no abnormal behavioral patterns were noted in any of the test groups over the 14-day period of the study. Gross examination of the cheek pouches containing the alloys was no different from that of the controls. None of the alloys tested showed significant adverse histopathologic reactions. The recorded changes in incidences and degree of response were essentially no different from those of the negative control material.

Animals↗