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Biomedical subjects

C A Farrell

Publications and source records attributed to C A Farrell.

30 records · Page 2Linked to original sources

Frequency of upper gastrointestinal bleeding in a pediatric intensive care unit.

OBJECTIVE: To determine the frequency of upper gastrointestinal (GI) bleeding in pediatric ICUs. DESIGN: Prospective, descriptive study. SETTING: Pediatric ICU in a university hospital. PATIENTS: All children admitted to a pediatric ICU over a 55-wk period. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Upper GI bleeding was considered to be present if there was an episode of hematemesis or if any amount of blood was seen in drainage from a nasogastric tube. Sixty-three (6.4%) upper GI bleeds were detected among 984 patients: 5.2% in 698 patients who did not receive upper GI bleeding prophylaxis, and 9.4% in 286 patients who did receive some prophylaxis. Density was defined as the number of events/1000 days.patient. The mean density was 10.8 GI bleeding episodes/1000 days.patient in a pediatric ICU. A multivariate analysis detected four independent risk factors or risk markers for upper GI bleeding: high Pediatric Risk of Mortality score, coagulopathy, pneumonia, and multitrauma. Age, sex, hepatic and respiratory failures were identified as confounding variables. An upper GI bleeding episode was defined as being clinically important if hypotension, death, or transfusion occurred within 24 hrs after the bleeding. There were four clinically important GI bleeding episodes. All were caused, at least in part, by a coagulopathy. The GI bleeding was associated with a need for transfusion in four children, and with hypotension in two. CONCLUSIONS: The frequency of upper GI bleeding is substantial, but the rate of occurrence of clinically important upper GI bleeding is low, even in a pediatric ICU where most patients do not receive any prophylaxis.

Adolescent↗

Tyrosine phosphorylation is an early signaling event common to Fc receptor crosslinking in human neutrophils and rat basophilic leukemia cells (RBL-2H3).

Phosphotyrosine-containing proteins were detected by western blotting of whole cell lysates of purified human neutrophils or rat basophilic leukemia cells (RBL-2H3) using a polyclonal anti-phosphotyrosine antibody. When either cell type was stimulated with the appropriate Fc crosslinking agent, heat-aggregated IgG for the neutrophil or DNP-HSA for the IgE-sensitized RBL-2H3, a rapid increase in the phosphotyrosine content of several proteins was observed. The kinetics and specificity of both responses suggest that Fc receptor crosslinking activates a receptor-associated tyrosine kinase, probably a member of the src family of tyrosine protein kinases. The subsequent tyrosine phosphorylation events are likely to be important in Fc receptor-mediated stimulus-response coupling in inflammatory cells.

Animals↗

[Prophylaxis of gastroduodenal hemorrhage caused by stress during pediatric intensive care].

Patients admitted to intensive care units frequently develop stress ulcers, erosive gastritis and complications such as upper gastrointestinal bleeding. Stress-related upper gastrointestinal bleeding (UGIB) has been of particular concern to many practitioners working in intensive care units and has led to the treatment of most if not all patients admitted to these units with antacids, H2 receptor antagonists or sucralfate in order to protect the gastric mucosa. It is considered that the 3 aforementioned medications are effective in decreasing the overall incidence of UGIB, but it has not been demonstrated that they are efficacious in reducing the incidence of clinically significant UGIB, ie cases that are complicated by anemia, hemorrhagic shock, or death. In addition, the cost and complications resulting from prophylaxis should be taken into consideration, which raises further questions about the systematic use of these agents. This article reviews the current literature on this subject; the authors propose a conservative use of prophylaxis, and that these agents be prescribed in a selective manner to the patients at the greatest risk of developing UGIB.

Child↗

Octopamine modulates photoreceptor function in the Limulus lateral eye.

Activity at night in efferent nerve fibers from a central circadian clock produces changes in photoreceptor function in the lateral compound eye of Limulus: the response to light is increased; membrane potential fluctuations (bumps) occurring in the dark are suppressed; and the duration of bumps occurring both in the dark and under dim illumination is increased (Barlow et al., 1977; Kaplan & Barlow, 1980; Barlow, 1983; Barlow et al., 1985). Efferent nerve terminals release octopamine when activated (Battelle et al., 1982; Battelle & Evans, 1984, 1986); exogenous octopamine in vitro produces some of the changes resulting from efferent nerve activity in vivo (Kass et al., 1988). We report here that the increase in both on-transient and steady-state response to light induced by octopamine in the lateral eye in vitro are concentration dependent with threshold at or below 100 nM, saturation at or above 100 microM, and half-maximal increase in the range 1-10 microM. Octopamine also reduces bump activity in the dark in a concentration-dependent way. Unlike the increase in light response, the dependence of this effect on octopamine concentration is extremely variable from specimen to specimen. The effects of exogenous octopamine on light response and bump activity can sometimes be reversed by removing octopamine from the medium bathing the in vitro preparation. Octopamine also increases bump duration, apparently in a concentration-dependent manner. We have not succeeded in reversing this increase in bump duration. The concentration dependence of changes in photoreceptor response described here agrees qualitatively with the dependence of cAMP levels on octopamine in Limulus photoreceptors (Kaupp et al., 1982), lending further support to the idea that cAMP acts as a second messenger in the circadian control of photoreceptor function. Our results also suggest that the changes induced in the transient and steady-state response to light by both efferent nerve activity and exogenous octopamine have a common origin, which may differ from that responsible for the modulation of bump activity.

Animals↗

Use of in vitro topoisomerase II assays for studying quinolone antibacterial agents.

Several quinolones and antitumor compounds were tested as inhibitors of purified calf thymus topoisomerase II in unknotting, catenation, radiolabeled DNA cleavage, and quantitative nonradiolabeled cleavage assays. The antitumor agents VP-16 (demethylepipodophyllotoxin ethylio-beta-D-glucoside) and ellipticine demonstrated drug-enhanced topoisomerase II DNA cleavage (the concentration of drug that induced 50% of the maximal DNA cleavage in the test system [CC50]) at levels of less than or equal to 5 micrograms/ml. Nalidixic acid, norfloxacin, and oxolinic acid did not induce significant topoisomerase II DNA cleavage, whereas ciprofloxacin did induce some cleavage above background levels. CP-67,015, a new 6,8-difluoro-7-pyridyl 4-quinolone which possesses potent antibacterial activity, inhibited bacterial DNA gyrase at 0.125 micrograms/ml in a nonradioactive DNA cleavage assay. Unlike other quinolones characterized to date, CP-67,015 was shown to strongly enhance topoisomerase II-induced radiolabeled DNA cleavage with a CC50 of 33 micrograms/ml and demonstrated cleavage in a nonradiolabeled DNA cleavage assay with a CC50 of 73 micrograms/ml. The topoisomerase II-mediated cleavage of DNA by CP-67,015 is consistent with its reported clastogenic effect on DNA in cell culture and its positive mutagenic response in mouse lymphoma cells. In vitro topoisomerase II catalytic and cleavage assays are useful for gaining preliminary information concerning the possible interaction(s) of some quinolones with eucaryotic topoisomerase II which may relate directly to their safety (mutagenicity, clastogenicity, or both) in human and veterinary medicinal usage.

4-Quinolones↗

Affinity purification of renal dipeptidase solubilized with detergent.

A new method is described for purification of the dehydropeptidase I enzyme, renal dipeptidase (EC 3.4.13.11). The six steps used are homogenization of the tissue, extraction with Triton X-100, sedimentation of insoluble material, and ion-exchange, size-exclusion, and affinity chromatographies. The use of Triton X-100 to solubilize the enzyme is a major advantage over the previously described procedure using n-butanol and results in both improvements in yield and interexperimental consistency. Also, the affinity column method we have employed results in higher recovery of active enzyme at the final step and a product which is apparently homogeneous. The method has general utility for this class of enzymes.

Animals↗

Cilastatin-sensitive dehydropeptidase I enzymes from three sources all catalyze carbapenem hydrolysis and conversion of leukotriene D4 to leukotriene E4.

The dipeptidase, dehydropeptidase I (EC 3.4.13.11), was purified to homogeneity from rat lung, rat kidney, and hog kidney. Analysis of physical parameters (subunit molecular weights, Km values for glycyldehydrophenylalanine, Ki values for dehydropeptidase I inhibitors, and immunoreactivity) showed the rat dipeptidases to be similar to each other but different from the hog dipeptidase. However, all three enzymes hydrolyzed imipenem and converted leukotriene D4 to leukotriene E4, and these activities were inhibited by cilastatin.

Animals↗

Diabetes insipidus in a quadriplegic patient.

An incomplete quadriplegic patient underwent investigation for production of copious amounts of dilute urine. Serum osmolality, electrolytes, BUN, glucose, and serum antidiuretic hormone (ADH) were recorded, as well as urinary osmolality, electrolytes, glucose, and pH. In response to subcutaneous vasopressin during the dehydration test, the patient's urinary osmolality increased by 12%, from 620 mOsm/l to 695 mOsm/l. A definitive diagnosis of partial central diabetes insipidus was made. Physicians involved in the care of patients with spinal cord injuries should be aware of the method of evaluating polyuric conditions, particularly while the patient is undergoing catheterization.

Adult↗

Affinity of cephalosporins for beta-lactamases as a factor in antibacterial efficacy.

Strains of Escherichia coli, Enterobacter aerogenes, and Enterobacter cloacae that were resistant to ceftazidime (MIC greater than 16 micrograms/ml) but susceptible to BMY 28142 (MIC less than 4 micrograms/ml) were found to contain higher levels of beta-lactamase activity (50- to 3,340-fold) than control strains of the corresponding species. Ceftazidime was at least as resistant as BMY 28142 to hydrolysis by these enzymes. However, the apparent Ki of BMY 28142 for each enzyme was larger (8- to greater than 20-fold) than that of ceftazidime; i.e., the affinity of these enzymes for BMY 28142 appeared to be lower than that for ceftazidime. Thus, BMY 28142 was affected less than ceftazidime by a mechanism of resistance that depends, at least in part, on the relative affinities of cephalosporins for the beta-lactamases of these species. These results indicate that the affinity between a beta-lactamase and a cephalosporin may be a distinguishing factor in the evaluation of beta-lactamase-resistant cephalosporins and suggest that affinity can play a major role in susceptibility to highly beta-lactamase-resistant cephalosporins.

Bacteria↗