Oxidative stress proteins as an indicator of a low quality of eucalyptus clones for the pulp and paper industry.

Eucalyptus is a genus widely cultivated in many tropical and subtropical regions of the world as one of the main sources of raw materials for the pulp and paper industry. Identification of clones and selection of genotypes with desirable agronomic characteristics would be useful. We assessed eucalyptus full-sibs that varied in wood quality, using a combination of two-dimensional gel electrophoresis and mass spectrometry to identify differentially expressed proteins as candidates for quality markers. Thirty-one differently expressed proteins were identified, including three proteins of clone X1, four of clone X2, and 12 each of clones X3 and X4. These proteins are involved in various biological processes, including polyphosphate biosynthesis, catalytic activity, nucleotide excision repair, cellular metabolic processes, cell redox homeostasis, response to salt stress, response to temperature, oxidation and reduction processes, cellular water homeostasis, and protein phosphorylation. In the cambial region of each clone, the proteins ketol-acid reductoisomerase, uncharacterized protein MG428, receptor-like serine/threonine-protein kinase and a heat shock protein were found in larger quantities in clone X4 than in clone X1. These proteins are known to be related to protection against oxidative stress and biosynthesis of lignin. A high buildup of proteins involved in response to stress in the cambial region of eucalyptus would indicate clones with undesirable characteristics for use in the pulp and paper industry.

Fluid bed porosity mathematical model for an inverse fluidized bed bioreactor with particles growing biofilm.

A new mathematic model to estimate bed porosity as a function of Reynolds and Archimedes numbers was developed based in experimental data. Experiments were performed using an inverse fluidized bed bioreactor filled with polypropylene particles, Lactobacillus acidophillus as the immobilized strain and fluidized with a Man-Rogosa-Sharpe culture medium under controlled temperature and pH conditions. Bed porosity was measured at different flow rates, starting from 0.95 to 9.5 LPM. The new model has several advantages when compared with previously reported. Among them, advantages such as standard deviation values ≤ 1% between experimental and calculated bed porosity, its applicability in traditional and inverse fluidization, wall effects do not take account, it gives excellent agreement with spherical particles with or without biofilm, and inertial drag coefficient allow extend the new model a non-spherical particles.

Intermittent injection vs patient-controlled analgesia for sickle cell crisis pain. Comparison in patients in the emergency department.

BACKGROUND: --The purpose of this study is a prospective assessment of morphine sulfate administration by intermittent intravenous (IV) injections (Int-IV) vs patient-controlled analgesia (PCA) in patients in the emergency department (ED) with sickle cell crisis pain. METHODS: --Patients were at bed rest and received intravenous hydration. Linear analog scale for pain intensity and verbal pain scale, level of alertness, and vital signs were assessed prior to therapy, every 60 minutes thereafter, and at the time of discharge from the ED. Patients were randomized to Int-IV or PCA. During phase 1, patients in the Int-IV group received morphine sulfate 4 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 2 mg bolus then 1.0 mg with a 6-minute lockout. During phase 2, patients in the Int-IV group received morphine sulfate 8 mg IV every 30 to 60 minutes as necessary for a linear analog scale for pain intensity greater than 50 mm. The patients in the PCA group received morphine sulfate 5 mg bolus then 2.7 mg with a 10-minute lockout. Data were analyzed by unpaired t test, general linear modeling, Mann-Whitney U test, and chi 2 test. RESULTS: --During phase 1, 10 patients (28.3 +/- 7.3 years) received Int-IV and 10 patients (33.9 +/- 12.5 years) received PCA. Treatment groups did not differ significantly regarding duration of pain, amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, level of alertness, or vital signs except for a significantly lower final respiratory rate with Int-IV. In phase 2, 12 patients (28.4 +/- 5.6 years) received Int-IV and 13 patients (26.8 +/- 8.1 years) received PCA. The PCA groups had a significantly shorter elapsed time between onset of pain and treatment (7.3 +/- 6.5 hours) when compared with the Int-IV group (18 +/- 16.9 hours). Treatment groups did not differ significantly with respect to total amount of morphine administered, linear analog scale for pain intensity, verbal pain scale, vital signs, or level of alertness. The PCA group had a significant reduction in length of stay in the ED during phase 2 when compared with phase 1. The ED discharge rate and the incidence of side effects did not differ significantly between groups. CONCLUSION: --At both the low- and high-dose regimens, PCA is equally safe and effective and may be used in place of Int-IV administration of morphine in the ED treatment of sickle cell crisis pain.

Central resetting of baroreflex in the spontaneously hypertensive rat.

The role of central nervous system in the resetting of baroreflex was investigated in 5-month-old spontaneously hypertensive rats (SHR) of Okamoto strain. Age-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. The aortic nerves, which in the rat, contain few or no chemoreceptor fibers, were stimulated electrically using a wide range of stimulus frequencies. The depressor responses (expressed as percent decrease in blood pressure as compared to its blood pressure value prior to aortic nerve stimulation) produced by these stimulations were significantly smaller in SHR than those in WKY. In another series of experiments, changes in the efferent limb of the baroreflex arc (i.e., greater splanchnic nerve activity) in response to stimulation of the baroreceptor afferents in the aortic nerve were recorded. Inhibition of the greater splanchnic nerve activity due to aortic nerve stimulation was found to be significantly smaller in SHR than in the WKY. Control sympathetic nerve activity was greater in SHR than in WKY. These results suggest that the central bulbospinal nervous system may be another site for resetting of baroreflex in hypertension.

Neurotropic action of MSH/ACTH 4-10 on neuromuscular function in hypophysectomized rats.

These studies were designed to determine whether the previously demonstrated [24] enhancement of neuromuscular function by MSH/ACTH 4-10 is due to peptide action on the neurogenic and/or myogenic elements involved. The nerve muscle unit studied incorporated the sciatic nerve and its branches, and the extensors digitorum longus and brevis in the hypophysectomized rat, in situ. Parameters investigated included muscle action potentials (MAP) and muscle contractions (MC) during 30 min of stimulation (supramaximal, 10/sec; 0.05 msec duration). Resting membrane potentials and miniature endplate potential (mepp) characteristics were investigated in situ at neuromuscular junctions in the extensor digitorum brevis. Hypophysectomy results in markedly deleterious changes in neuromuscular function which can be partially alleviated by the administration of ACTH 4-10 (0.01 microgram/kg). This dosage increases MAP and MC amplitudes and reduces fatigue. Higher dosages (1.0 microgram/kg) have a depressing effect on these parameters. The facilitatory actions of ACTH 4-10 are abolished when the muscle is stimulated directly or stimulated through the peripheral stump of the cut nerve. ACTH 4-10 increases mepp frequency (a presynaptic event) but does not affect postsynaptic characteristics as measured by the resting membrane potential. These results indicate that MSH/ACTH 4-10 influences skeletal muscle function through a neurotropic action mediated by spinal motoneurons. Changes in the central excitatory state of higher motor centers are possibly involved.

Antiplatelet therapy in atherosclerotic cardiovascular disease.

Arterial thrombosis frequently leads to death or disability from stroke, peripheral arterial disease, or myocardial infarction (MI). Treating the underlying causes of these diseases is the key to producing significant reduction in morbidity, mortality, and health care costs. Prevention of arterial thrombosis is the primary indication for antiplatelet therapy, and intense research has been conducted in the past decade to develop novel antiplatelet agents with favorable safety profiles. The results of the Antiplatelet Trialists' Collaboration, which definitively established the rationale for antiplatelet agents in the prevention of death, MI, and stroke, were an important stimulus for this research. This large meta-analysis combined data from 145 randomized trials and showed that antiplatelet therapy (most commonly aspirin, 75 to 325 mg/d) reduced the risk of vascular events, including nonfatal MI, nonfatal stroke, and vascular death, by 25% in patients at high risk for occlusive vascular disease. The limitations and adverse effects associated with traditional antiplatelet agents such as aspirin have prompted the search for newer antiplatelet agents. Clinical trials such as the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study, which was the first study to evaluate aspirin and clopidogrel in patients with cerebrovascular, cardiac, and peripheral arterial disease, have established the importance of newer antiplatelet effects in the management of patients with diseases associated with atherosclerosis. The pathophysiology of atherosclerosis, the mechanisms of action of antiplatelet agents, and the results of these and other clinical trials that document the value of antiplatelet agents in atherosclerosis are reviewed in this paper.

Greater splanchnic nerve activity in the rat.

The greater splanchnic nerve trunks in the rat, unlike in other experimental animals, do not join celiac plexus directly. These nerve trunks join small ganglia, the cardiac ganglia, on either side. The cardiac ganglia are located about 1 cm rostro-lateral to unpaired celiac ganglion. The greater splanchnic nerve activity immediately proximal to celiac ganglion is predominantly post-ganglionic in the rat. On the other hand, the activity of the greater splanchnic nerve proximal to the celiac ganglion is predominantly preganglionic in other experimental animals, (e.g., cat), In the rat, preganglionic sympathetic nerve activity is predominant in the segment of the greater splanchnic nerve proximal to the cardiac ganglion.

Low-molecular-weight heparins for acute coronary syndromes: an emergency medicine perspective.

Patients with chest pain represent one of the largest and most challenging populations for emergency departments to treat. Diagnostic and treatment modalities implemented in the emergency department are associated with significant clinical outcomes and financial implications. Critical pathways are being developed to increase the speed and efficiency with which these patients are managed. Of particular importance is the evolving role of low-molecular-weight heparins, which have both clinical and economic advantages over unfractionated heparins in treating unstable angina and non-Q wave myocardial infarction.

Clinical decision analysis modeling: short-term control of ventricular response rate in atrial fibrillation or atrial flutter-digoxin versus diltiazem.

OBJECTIVE: To develop a clinical decision model to compare the outcome of therapy with digoxin versus diltiazem for short-term control of ventricular response rate (VRR) in patients with atrial fibrillation or atrial flutter. DESIGN: Review of data from two studies that examined the percentages of response and frequency of adverse reactions in patients treated with intravenous digoxin or diltiazem to control VRR in atrial fibrillation or flutter. We constructed a clinical decision model and performed sensitivity analysis to determine if the model's predictions could be altered. SETTING: Large teaching, university hospitals. PARTICIPANTS: Adults age 18 years or older treated with intravenous digoxin or intravenous diltiazem for atrial fibrillation or flutter (VRR > or = 120 beats/min). Patients with severe heart failure New York Heart Association class III or IV, a surgical procedure prior to the exacerbation, or an acute myocardial infarction were excluded. MEASUREMENTS AND MAIN RESULTS: We measured VRR control after 1 and 24 hours of therapy (VRR < 100 beats/min or decrease of > or = 20%) and assessed the likelihood that a patient would suffer an adverse drug reaction. Initial assumptions were that the probability digoxin would achieve VRR control was 0.10 (95% confidence interval 0.04-0.20) at 1 hour and 0.70 (95% CI 0.56-0.80) at 24 hours; the probability that diltiazem would achieve VRR control was 0.94 (95% CI 0.82-0.99) at 1 hour and 0.83 (95% CI 0.68-0.94) at 24 hours; and the probability of no serious adverse drug reaction would be 0.90 (95% CI 0.80-0.96) for digoxin and 0.96 (95% CI 0.86-0.98) for diltiazem. RESULTS: Diltiazem was superior to digoxin with respect to the composite end point score at 1 hour (91.20 vs 17.29) and 24 hours (81.65 vs 66.43). Digoxin was superior to diltiazem at 24 hours only if the VRR was assumed to be at the highest 95% CI limit for digoxin and simultaneously at the lowest 95% CI for diltiazem (74.62 vs 68.63). CONCLUSIONS: Clinical decision analysis suggests that intravenous diltiazem is superior to intravenous digoxin in controlling VRR in patients with atrial fibrillation or flutter.

Intravenous amiodarone for ventricular arrhythmias: overview and clinical use.

Numerous pharmacological agents with varying cellular electrophysiological effects are available to treat cardiac arrhythmias. Amiodarone is predominantly a Vaughan Williams Class III agent, but also possesses electrophysiological characteristics of the other three Vaughan Williams classes (Class I and IV and minor Class II effects). Amiodarone's primary mechanism is to prolong the cardiac action potential and repolarization time leading to an increased refractory period and reduced membrane excitability. The efficacy and tolerability of intravenous (IV) amiodarone for acute treatment of recurrent and refractory ventricular tachycardia and ventricular fibrillation has been demonstrated in clinical trials. The ARREST trial, a randomized trial comparing IV amiodarone to placebo, found a significant improvement in the proportion of patients surviving to the emergency department following out-of-hospital cardiac arrest in amiodarone-treated patients. Intravenous amiodarone is an effective anti-arrhythmic agent for the acute treatment of life-threatening ventricular arrhythmias and represents an important treatment option for emergency anti-arrhythmic therapy for patients suffering from cardiac arrest.

Cardiac vagolytic action of some neuromuscular blockers.

Cardiac vagolytic effect of four commonly used neuromuscular blockers, (viz. D-tubocurarine, decamethonium, pancuronium and gallamine) was compared in midcollicular decerebrate rats. The intravenous doses of neuromuscular blockers used (d-tubocurarine: 0.1 mg/kg; decamethonium: 2 mg/kg; pancuronium: 0.1 mg/kg; gallamine: 20 mg/kg) were sufficient to produce the paralysis of respiratory muscles. Bradycardia was induced by electrical stimulation of the vagus or by injecting dimethyl-phenyl-piperazinium (DMPP; a ganglionic stimulant). It was observed that d-tubocurarine and decamethonium were devoid of cardiac vagolytic action. On the other hand, pancuronium and gallamine inhibited significantly the bradycardia induced by electrical stimulation of the vagus or injection of DMPP; gallamine was found to have greater vagolytic action. The pressor responses to DMPP were not attenuated by pancuronium and gallamine indicating that in the dose administered, these agents did not block the ganglia. Bradycardia induced by the administration of acetylcholine in the left atrium was also attenuated by pancuronium and gallamine suggesting that the drugs produce cardiac vagolytic action by acting on the post-synaptic cholinergic receptors of the heart.

The pharmacoeconomic benefits of cholesterol reduction.

Recent studies show that cholesterol-lowering therapy can reduce morbidity and mortality in hypercholesterolemic patients without preexisting coronary heart disease (primary prevention) and with coronary heart disease (secondary prevention). The high cost of treatment per event prevented, especially for primary prevention, raises concerns about widespread use of cholesterol-lowering therapy. Does cholesterol reduction reduce utilization of healthcare resources, and can society afford to pay for reducing cholesterol in all patients with hypercholesterolemia, irrespective of risk factors? Is cost-effectiveness of therapy affected by differing cholesterol levels, age of the patients, the duration of therapy, or the presence of risk factors? Current pharmacoeconomic studies support the use of the statins for secondary prevention, and primary prevention in high-risk patients, and provide key information for policy decision making in the treatment of patients with hypercholesterolemia.

Atherosclerosis: a unifying disorder with diverse manifestations.

The epidemiology, costs, and comorbidities associated with atherosclerosis and the role of newer antiplatelet agents are reviewed. Cardiovascular disease is the leading cause of death in the United States. More than 60 million Americans have one or more types of cardiovascular disease. The total annual cost of coronary heart disease has been estimated at $95 billion. Patients with an existing atherosclerotic disease in one vascular bed are at high risk of having an ischemic vascular event in the same or another vascular bed. Peripheral arterial disease is a strong marker for underlying cerebrovascular and cardiovascular disease. The common link among these diseases is atherosclerosis leading to atherothrombosis. Platelets play an integral role in atherosclerosis and the formation of arterial thrombus as well as in subsequent acute events such as ischemic stroke, myocardial infarction, and vascular death. Arterial thrombosis can be mediated by shear-stress-induced platelet aggregation. Currently, only one third to one half of all eligible patients with stroke, myocardial infarction, or peripheral arterial disease receive antiplatelet therapy. Thienopyridines such as ticlopidine and clopidogrel are effective inhibitors of shear-stress-induced and endothelial-injury-induced platelet aggregation. Advances in antiplatelet therapy provide an opportunity to use newer antiplatelet agents in the prevention of atherosclerosis-related morbidity and mortality; therapeutic approaches should be directed toward recognizing atherosclerosis as a generalized disease process and preventing ischemic events in multiple vascular beds.

Dopamine-induced increase in atrioventricular conduction in atrial fibrillation-flutter.

We report a patient with controlled atrial fibrillation-flutter (AFF) and mitral stenosis who developed a marked increase in atrioventricular conduction during an infusion of low dose dopamine with development of hemodynamic compromise. This side effect has not been previously described in humans. Dopamine infusion should be used with caution in patients with AFF.

Changes in the pharmacotherapy of CPR.

The objective of this study was to review current changes in the pharmacologic management of cardiac arrest (ventricular fibrillation, pulseless ventricular tachycardia, asystole, and electromechanical dissociation) as put fourth by the American Heart Association's 1992 Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care. We concluded that the 1992 Guidelines provide a reference base for all clinicians involved in emergency cardiac care. The newly revised recommendations are classified on the basis of the true clinical merit of the intervention, for example, an intervention that has been proved effective (i.e., high-dose epinephrine) versus one that is possibly effective (i.e., high-dose epinephrine). The preferred intravenous fluid to be used in resuscitation is saline solution or lactated ringers solution because of possible adverse neurologic outcomes seen with dextrose-containing fluids. The dose of all drugs administered via the endotracheal route should be 2 to 2.5 times the intravenous dose. Modifications in the dose or dosing interval have been recommended for epinephrine, atropine, lidocaine, bretylium, and procainamide during cardiopulmonary resuscitation. Options for high-dose epinephrine therapy are offered, but neither recommended or discouraged. Magnesium sulfate has been added for the management of torsades de points, severe hypomagnesemia, or refractory ventricular fibrillation. The maximum total dose of atropine in the treatment of asystole and electromechanical dissociation has been increased from 2 mg to 0.04 mg/kg. The use of sodium bicarbonate should be limited to the treatment of hyperkalemia, tricyclic antidepressant overdose, overdoses requiring urinary alkalinization, or preexisting bicarbonate sensitive acidosis.

The management of lower-extremity diabetic ulcers.

Lower-extremity ulcers occur in approximately 15% of the estimated 16 million Americans with diabetes. The most important risk factors are neuropathy, ischemia, and poor glycemic control. Early identification of the patient at risk, patient education, and implementation of preventive measures are keys to curtailing morbidity and mortality. Diabetic foot care clinics allow enhanced patient accessibility to health care and improved quality of care. Novel treatment options have expanded the alternatives available to clinicians treating these difficult and prevalent wounds.

Single-dose intravenous H2 blocker prophylaxis against aspiration pneumonitis: assessment of drug concentration in gastric aspirate.

This placebo-controlled trial compared the effects of preoperative, intravenous cimetidine (300 mg) or ranitidine (50 mg) on gastric pH and gastric volume in 31 adult patients requiring general anesthesia. The elapsed time from drug administration to initial gastric sampling did not differ significantly between ranitidine (45 minutes), cimetidine (48 minutes), or placebo (52 minutes) treated patients. Ranitidine, but not cimetidine, significantly (P = 0.02) increased gastric pH when compared with placebo. Gastric pH correlated (r = 0.7, P = 0.01) with cimetidine concentration in gastric fluid at induction. Gastric pH was directly proportional to ranitidine concentration in gastric fluid at induction, but the correlation was weak (r = 0.54, P = 0.1). The H2 blockers did not significantly alter gastric volume when compared with placebo. The number of patients with gastric pH less than = 2.5 and gastric volume = greater than 25 ml did not differ significantly between cimetidine (8%), ranitidine (10%), and placebo (22%). No clinical evidence of aspiration pneumonitis was found in our study patients.

Designing a disease management program: how to get started.

To successfully design and implement disease management programs, clinicians must understand the disease's natural course and cost drivers, base the diagnosis and treatment on the disease process and not the reimbursement schedules, educate and reinforce compliance to improve treatment outcomes, and focus on commonly occurring and costly chronic diseases. This article describes a 7-step process for developing a disease management program based on those concepts. The changing role and functions of the P & T Committee in disease management programs are also presented.