Administration of balanced or BCAA-enriched amino acid solution in septic rats. Effects on protein synthesis in the liver.

Total hepatic protein synthesis was measured in vivo with a flooding-dose technique, and the production of total secreted proteins, albumin, complement component C3, and seromucoid fraction was measured in perfused livers of septic rats that received one of three different solutions infused intravenously; Group 1 received 16.4% dextrose; Group 2 received Aminosyn (25% BCAA) in 10.6% dextrose, and Group 3 received Freamine HBC (45% BCAA) in 10.6% dextrose. All solutions were isocaloric, and the amino acid solutions were isonitrogenous. The solutions were administered for 18 or 48 hours after the induction of sepsis. There were no significant differences in mortality rates in the three treatment groups. The negative nitrogen balance seen in the dextrose-infused animals was reversed to the same degree by the two different amino acid solutions. There were no significant differences in hepatic protein synthesis rates in vivo between the three groups of rats. Synthesis rates of secreted proteins in perfused liver were similar in the different treatment groups in the 18-hour experiments, whereas in the 48-hour experiments, synthesis rates of total secreted proteins, C3, and the serumucoid fraction were higher in Group 1 than in Groups 2 and 3. The results suggest that administration of an amino acid solution improves nitrogen balance in sepsis, but that this effect is not caused by stimulated hepatic protein synthesis. The nitrogen-sparing effect during sepsis of a branched chain amino acid (BCAA)-enriched solution does not seem to be superior to that of a balanced amino acid solution.     

Treatment of an infected silicone right atrial catheter with combined fibrinolytic and antibiotic therapy: case report and review of the literature

Tunnelled silicone rubber right atrial catheters are commonly used to administer long-term total parenteral nutrition (TPN), cancer chemotherapeutic agents, and antimicrobial agents. The indwelling devices potentiate platelet-fibrin thrombi formation, providing a nidus for infection. Although many episodes of sepsis associated with thrombotic tunnelled catheters respond to antimicrobial therapy alone, a significant number require catheter removal. Evidence from case studies and small clinical trials suggests that fibrinolytic agents may increase the response rate and prevent removal of the device when combined with antimicrobial therapy. We present the first case reported of bacterial sepsis secondary to a thrombotic indwelling Hickman catheter for long-term TPN successfully treated with a combination of streptokinase and antibiotic therapies.     

The effect of manipulation on pain and range of motion in the cervical spine: a pilot study.

OBJECTIVE: The objective of this pilot study was to determine the number of patients required for a randomized controlled trial of spinal manipulation for neck pain and to determine if there is a relationship between pain and range of motion (ROM) in the cervical spine. DESIGN: Fifty consecutive outpatients were studied in a pretest-posttest design without long-term follow-up. SETTING: The patients were taken from a primary cae outpatient teaching clinic specializing in back pain. PATIENTS: All patients had unilateral neck pain without neurological deficit. The patients were selected as a consecutive sample. INTERVENTION: All the patients received a single cervical manipulation. MAIN OUTCOME MEASURES: Prior to and immediately after the treatment, cervical ROM was recorded on a goniometer, and pain intensity was rated on the 101-point numerical rating scale. RESULTS: The results show an increase in all planes of post-treatment ROM and a decrease in post-treatment pain scores. Partial correlations between post-treatment ROM and 101-point numerical rating scale scores reveal a significant relationship between a decrease in pain and an increase in cervical rotation (p < .005). CONCLUSIONS: Since the results of this pilot study are not controlled, they cannot be seen as proof supporting the clinical efficacy of manipulation for neck pain. However, the correlation between an increase in cervical rotation and a decrease in pain is clinically instructive. In addition, the outcome measures used in this study could prove to be useful in the design of future randomized controlled trials of cervical manipulation.     

Protein synthesis in liver following infusion of the catabolic hormones corticosterone, epinephrine, and glucagon in rats

The mediator(s) and mechanism(s) of acute-phase protein synthesis in the liver following injury and sepsis are not fully known. Elevated plasma levels of the catabolic hormones cortisol, glucagon, and epinephrine have been reported in trauma and sepsis. In previous reports, when these hormones were infused simultaneously (triple hormone infusion), several, but not all, of the metabolic alterations characteristic of sepsis occurred. In the current investigation, the effect of triple hormone infusion on hepatic protein synthesis was studied. Rats were infused intravenously during 16 hours with a solution containing corticosterone (4.2 mg/kg/h), glucagon (2.5 micrograms/kg/h), and epinephrine (6 micrograms/kg/h). Control animals were infused with a corresponding volume of vehicle. Total hepatic protein synthesis in vivo was measured with a flooding dose technique using [14C]-leucine. The synthesis of total secretory proteins and of the individual proteins albumin, complement component C3, and alpha 1-acid glycoprotein was measured in isolated, perfused liver using [3H]-leucine and a recirculating technique. Urinary excretion of nitrogen and plasma concentration of glucose were higher and plasma total amino acid concentration was lower in hormone-infused than in control rats. Total hepatic protein synthesis in vivo, expressed as the proportion of the protein pool that was replaced each day, was increased from 39% +/- 2% per day to 48% +/- 3% per day (P less than .05) by hormone infusion, but synthesis of secretory proteins in perfused liver was not significantly altered. The results suggest that although total hepatic protein synthesis may be increased by catabolic hormones, other mediator(s) are probably responsible for the stimulation of acute-phase protein synthesis in sepsis.     

Plasma Retinoid Concentrations Are Altered in Pregnant Women

Vitamin A is vital to maternal–fetal health and pregnancy outcomes. However, little is known about pregnancy associated changes in maternal vitamin A homeostasis and concentrations of circulating retinol metabolites. The goal of this study was to characterize retinoid concentrations in healthy women (n = 23) during two stages of pregnancy (25–28 weeks gestation and 28–32 weeks gestation) as compared to ≥3 months postpartum. It was hypothesized that plasma retinol, retinol binding protein 4 (RBP4), transthyretin and albumin concentrations would decline during pregnancy and return to baseline by 3 months postpartum. At 25–28 weeks gestation, plasma retinol (−27%), 4-oxo-13-cis-retinoic acid (−34%), and albumin (−22%) concentrations were significantly lower, and all-trans-retinoic acid (+48%) concentrations were significantly higher compared to ≥3 months postpartum in healthy women. In addition, at 28–32 weeks gestation, plasma retinol (−41%), retinol binding protein 4 (RBP4; −17%), transthyretin (TTR; −21%), albumin (−26%), 13-cis-retinoic acid (−23%) and 4-oxo-13-cis-retinoic acid (−48%) concentrations were significantly lower, whereas plasma all-trans-retinoic acid concentrations (+30%) were significantly higher than ≥3 months postpartum. Collectively, the data demonstrates that in healthy pregnancies, retinol plasma concentrations are lower, but all-trans-retinoic acid concentrations are higher than postpartum.     

Effect of indomethacin on proteolysis in septic muscle.

The effect of indomethacin on protein degradation in skeletal muscle from septic rats was investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. Protein degradation rate was estimated by measuring release of tyrosine from incubated soleus (SOL) and extensor digitorum longus (EDL) muscles. Three experiments were performed. In the first experiment, indomethacin was administered subcutaneously (3 mg/kg) at the time of CLP and again after 3 hours. Control rats received corresponding volumes of solvent. Groups of rats were studied after 8 hours (early sepsis) or 16 hours (late sepsis). In the second experiment, the animals were pretreated 45 minutes before induction of sepsis with indomethacin (3 mg/kg) and again 3 hours after CLP and were studied during early sepsis. In the third experiment, indomethacin was added in vitro (3 microM) to incubated normal or septic muscle or to normal muscle incubated in the presence of plasma from septic animals, and release of prostaglandin E2 (PGE2) by incubated muscle was measured in addition to protein degradation. There was no mortality in early sepsis. Survival rate 16 hours after CLP was 8/16 (50%) in rats receiving control injections and 7/15 (47%) in indomethacin-treated rats (NS). Proteolytic rate in incubated EDL and SOL was increased by 20-25% during early sepsis and by 30-50% during late sepsis. The increased proteolytic rate was not affected by administration of indomethacin, neither in the first nor in the second experiment. When indomethacin was added in vitro, release of PGE2 by septic muscles and by normal muscles incubated in the presence of septic plasma was reduced by about 50%, but the increased proteolytic rate in these muscles was not affected. In normal muscle, neither release of PGE2 nor protein degradation was affected by indomethacin in vitro. The present results do not support a role for prostaglandins in the enhancement of muscle proteolysis during sepsis. Since neither survival rate nor protein breakdown was affected by indomethacin, recent suggestions to use this substance in the treatment of septic patients might be questioned.     

Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association

This report reviews the state of the literature and opportunities for research related to "executive control function" (ECF). ECF has recently been separated from the specific cognitive domains (memory, language, and praxis) traditionally used to assess patients. ECF impairment has been associated with lesions to the frontal cortex and its basal ganglia-thalamic connections. No single putative ECF measure can yet serve as a "gold standard." This and other obstacles to assessment of ECF are reviewed. ECF impairment and related frontal system lesions and metabolic disturbances have been detected in many psychiatric and medical disorders and are strongly associated with functional outcomes, disability, and specific problem behaviors. The prevalence and severity of ECF deficits in many disorders remain to be determined, and treatment has been attempted in only a few disorders. Much more research in these areas is necessary.