Treatment of life-threatening lithium toxicity with continuous arterio-venous hemodiafiltration.
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Biomedical subjects
Publications and source records attributed to J Love.
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We have developed a technique which allowed us to isolate sex-specific repeats of chickens (Gallus g. domesticus) from a genomic library originally containing one sex-specific repeat clone per 300 clones. Using this plus/minus selection method, we were able to enrich a sub-library in which the sex-specific repetitive clones made up over half of the population (170-fold increase in representation). This enrichment technique used hybridization kinetics to collect clones which are bound (plus selection) or not bound (minus selection) to their respective driver DNAs immobilized on nitrocellulose paper. Plus selections enriched for repetitive sequences and removed from the library most unique sequences as well as vectors containing no inserted sequences. These plus-selected sub-libraries were enriched for repetitive clones, yet still contained sequences representing as little as 10(-4) of the genome. Minus selection removed repetitive sequences shared between the driver and the library. When a plus-selected sub-library was minus selected, the doubly selected sub-library was enriched in repetitive sequences present in the library but not the minus driver.
Activation of T lymphocytes leads to the production of the T cell growth factor IL-2 that regulates T cell proliferation. This activation is associated with several potential intracellular signalling events including increased activity of phospholipase C (PLC) and resultant increases in production of inositol phosphates and diacylglycerols. In addition, phosphorylation of specific intracellular proteins on serine, threonine, and tyrosine residues increases. The role of each of these events in IL-2 production is unclear. Using Western blotting with antiphosphotyrosine antibodies, we demonstrate that activation of murine T cells with mitogenic lectins or anti-CD3 antibodies leads to a rapid increase in tyrosine phosphorylation of proteins of 120, 72, 62, 55, and 40 kDa. Similar patterns of antiphosphotyrosine antibodies reactivity were observed in splenocytes, a T cell hybridoma, and a T lymphoma. Tyrosine phosphorylation was detectable within minutes of addition of mitogenic lectins and persisted for at least 6 h. Pretreatment of the cells with pertussis toxin did not inhibit tyrosine phosphorylation indicating that a pertussis toxin-sensitive G protein is not involved in signal transduction. Neither increasing cytosolic-free calcium nor activating protein kinase C mimicked the effects of mitogenic lectins suggesting that tyrosine phosphorylation was not a consequence of activation of PLC. This was confirmed by demonstrating that mitogenic lectins induced similar patterns of tyrosine phosphorylation in cells in which activation of the TCR leads to increased PLC activity and in cells in which PLC is not stimulated. To test whether tyrosine phosphorylation is linked to IL-2 secretion, we determined the effect of three specific tyrosine kinase inhibitors (tyrphostins) on tyrosine phosphorylation, IL-2 secretion, and cellular proliferation. The concentration dependence of inhibition of tyrosine phosphorylation and IL-2 production were similar. However, higher concentrations of the tyrphostins were required to inhibit constitutive proliferation of the T cell line indicating that inhibition of IL-2 secretion was not secondary to nonspecific toxic effects of the tyrphostins. Addition of the tyrphostins after mitogenic lectin decreased the amount of tyrosine phosphorylation and IL-2 secretion in parallel. This indicates that both tyrosine kinases and phosphatases are activated and that continuous tyrosine phosphorylation is likely required for IL-2 secretion. Therefore, tyrosine phosphorylation appears to represent an obligatory event in the transmembrane signaling processes that lead to IL-2 secretion.
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We report the results of continuous arteriovenous haemodiafiltration (CAVHD) treatment in 12 critically ill intensive care patients with acute renal failure (eight males, four females - mean age 60.9 years - range 47 to 76) (APACHE II score 28.8, range 18-37). All patients were oligoanuric or had a rising creatinine (greater than or equal to 100 microM/L per day). Vascular access was obtained by Scribner shunt or wide-bore femoral arterial and venous cannulae. At the beginning of CAVHD therapy the mean plasma urea was 38 mM/L (SE 4.5, 95% confidence interval (CI) 25.1 to 75.6 mM/L) and the mean creatinine was 604 microM/L (SE 70, 95% CI 450-756 microM/L). After 72 hours of therapy, despite oligoanuria, urea concentration had fallen to a mean of 15.7 mM/L (SE 2.4, 95% CI 12.5-22.9 mM/L) and the creatinine concentration to 297 microM/L (SE 25, 95% CI 243-351 microM/L), respectively. The mean ultrafiltrate volume was 441 mL/hr (SE 33, 95%, range 50-1050 mL/hr). There were no complications related to the extracorporeal circuit, the filter, anticoagulant therapy, electrolyte status or changes in patients' haemodynamic state. Excellent biochemical control of azotaemia was uniformly achieved during CAVHD therapy. Five patients (41.6%) survived to be discharged from the Intensive Care Unit. CAVHD is a simple, safe and effective continuous renal replacement therapy. CAVHD offers technical advantages over alternative therapy while providing equivalent or better biochemical control of azotaemia and volume status in critically ill patients with acute renal failure.
Potassium nitrate has been found to be an effective ingredient for reducing dentinal hypersensitivity. The purpose of this study was to evaluate the effectiveness of a patient-applied 10% potassium nitrate glycerine-based gel in decreasing dentinal sensitivity on cold on teeth with exposed dentin apical to the cemento-enamel junction, 12 patients, each having 3 hypersensitive teeth, were tested. The patients were divided into 3 treatment groups: group 1 was treated with a glycerine-based 10% potassium nitrate gel: group 2 was treated with a glycerine gel without potassium nitrate; and group 3 received no gel and no treatment (control). Following brushing and flossing, groups 1 and 2 applied the gel to the test teeth using custom-made soft acrylic trays, for a period of 5 min/day for 4 weeks. Patient responses to cold water stimuli of 20 degrees C, 10 degrees C and 0 degrees C, were measured at baseline (week 0), then at 1-, 2-, 3- and 4-week intervals. Group 1 patients showed a significant decrease in sensitivity to cold at week 2 only. The group 2 patients showed a significant decrease in sensitivity to cold after 3 and 4 weeks. A statistically significant decrease in sensitivity was noted between group 2 and group 3 patients at week 3. The most sustained decrease in sensitivity to cold was found on teeth treated with plain glycerine.
Eosinophilia-myalgia syndrome (EMS) is characterized by intense eosinophilia and, very often, debilitating generalized myalgia in the absence of infectious or neoplastic causation. The Centers for Disease Control have established that the latter two features, along with an eosinophil count greater than 1000 cells per cu mm, are criteria for the syndrome. EMS has been reported in epidemic proportions over the last several months. Early data strongly suggested that in at least a small percentage of patients the syndrome leads to death. Epidemiological work in New Mexico, Minnesota, and Oregon has linked EMS most impressively to L-tryptophan-containing products (LTCPS).
Mutants of Rhodobacter capsulatus unable to grow photoautotrophically with H2 and CO2 were isolated. Those lacking uptake hydrogenase activity as measured by H2-dependent methylene blue reduction were analyzed genetically and used in complementation studies for the isolation of the wild-type genes. Results of further subcloning and transposon Tn5 mutagenesis suggest the involvement of a minimum of five genes. Hybridization to the 2.2-kilobase-pair SstI fragment that lies within the coding region for the large and small subunits of Bradyrhizobium japonicum uptake hydrogenase showed one region of strong homology among the R. capsulatus fragments isolated, which we interpret to mean that one or both structural genes were among the genes isolated.
Initial investigations have demonstrated the effectiveness of a new contra-rotary powered electric toothbrush in removing plaque supragingivally, subgingivally, and interproximally following a single use. The purpose of this study was to evaluate the effectiveness of a counter-rotary toothbrush following 1) one time instruction, 2) reinstruction and 1 week practice; and 3) a third instruction and 3 weeks of practice and home use. Twenty-four patients were studied; 12 using the counter-rotary toothbrush and 12 using a conventional toothbrush. Using O'Leary and Turesky plaque indices, both brushes significantly reduced supragingival plaque from baseline at all intervals. The counter-rotary brush, however, was more efficient than the conventional brush at all intervals (P less than 0.01). Using a Surface Area Plaque Index, both brushes significantly reduced supragingival plaque from baseline at all intervals but there were no significant differences between brushes. A timed bleeding index showed significant reduction in gingival bleeding following 28 days of brushing with both brushes. Again, the counter-rotary toothbrush was superior to the conventional toothbrush (P less than 0.01).
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The whole blood pharmacokinetics of intravenously administered 99mTc-disofenin (DISIDA) have been studied in dogs. Serial blood sampling permitted calculation of whole blood disposition rates, which principally represent liver clearance. There were striking differences in these rates between 6 normals and 7 animals in whom liver damage was induced by chronic bile duct ligation (256 vs 58 ml/min, P less than 0.001). Blood levels of radioactivity fell in a biexponential fashion characterized by rapid and slow disposition phases, whose half times were 2.4 and 58 min in normal animals. On 3 occasions, plasma was obtained from 1 animal by exsanguination 35 min after the administration of DISIDA and rapidly transfused into a 2nd animal. The whole blood pharmacokinetics of the second (recipient) animal showed a predominance of the slow disposition phase and a small rapid phase. The hepatic extraction ratio of blood radioactivity was measured in 3 dogs and was high (75%-90%) early after injection of DISIDA, but fell rapidly to remain around 10%. These experiments suggest the presence of two different species in the radiopharmaceutical studied, each being removed from the blood stream by the liver, but at different rates. The contribution of renal clearance to overall whole blood pharmacokinetics was negligible, since three nephrectomized dogs displayed similar pharmacokinetics to normals. Whole blood DISIDA pharmacokinetics are more complex than previously thought but appear to be capable of providing an accurate measure of liver function.
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Incubation of [3H]-sidechain-labeled and [14C]-C(4)-ring-labeled cyclophosphamide (CPA) with purified cytochrome P-450 from liver microsomes of rats treated with phenobarbital resulted in the production of a major metabolite that contained both labels, was unaffected by diazomethane, possessed high polarity, was identical in TLC and HPLC behavior to a synthetic standard, didechlorodihydroxy -CPA, and was converted to CPA and bis(2-chloroethyl)amine by thionyl chloride . These results indicate that phenobarbital-inducible cytochrome P-450 is able to dechlorinate CPA and may account, in part, for the inability of phenobarbital to enhance the therapeutic activity and toxicity of this important anticancer and immunosuppressive agent.
In the past few years, a correlation has been recognized between calcific aortic stenosis and lower gastrointestinal bleeding in elderly patients. It has been suggested by several authors that mucosal arteriovenous malformations, usually in the right colon, are the cause of bleeding in those patients. Although attention is usually focused on doing a partial colectomy (usually right hemicolectomy) for treating colonic arteriovenous malformation bleeding, several patients with calcific aortic stenosis and gastrointestinal bleeding have been reported in whom bleeding stopped after aortic valve replacement alone. The purpose of this paper is to review the possible mechanisms of lower intestinal bleeding in patients with calcific aortic stenosis, delineate the methods of diagnosis, and finally, to outline the appropriate surgical management.