Biomedical subjects
E R Gonzalez
Publications and source records attributed to E R Gonzalez.
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.
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.
Shifting paradigms of antiplatelet therapy: assessing new drugs versus old. Introduction.
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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.
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.
Clinical safety and efficacy of clopidogrel--implications of the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study for future management of atherosclerotic disease.
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Prolonged weakness after cisatracurium infusion: a case report.
OBJECTIVE: To present the first documented case report of myopathy persisting for >48 hrs in a patient treated with cisatracurium and concomitant high-dose corticosteroids. DESIGN: Anecdotal observations in one patient. SETTING: Medical-respiratory intensive care unit (ICU) at a tertiary care, university teaching hospital. PATIENT: A 45-yr-old female admitted status for post-bilateral total knee replacement complicated by aspiration pneumonitis and acute respiratory distress syndrome (ARDS). INTERVENTIONS: The patient required pressure control ventilation and sedation with midazolam and fentanyl infusions. On ICU day 2, the patient was placed on inverse ratio ventilation and paralyzed with cisatracurium. On ICU day 6, methylprednisolone 125 mg i.v. every 6 hrs was initiated for fibroproliferative ARDS. On ICU day 11, methylprednisolone was reduced to 60 mg i.v. every 6 hrs and tapered over several weeks. Cisatracurium infusion rates ranged from 6.3 to 10.5 microg/kg/min, with an average of 8.0 microg/kg/min. MEASUREMENTS AND MAIN RESULTS: Train-of-Four was assessed before initiation of therapy and every 4 hrs, thereafter. Train-of-Four values were maintained from 1 to 4 throughout therapy and a value of 4 was recorded when therapy was discontinued. On day 13, neuromuscular blocking agent therapy was discontinued, but severe proximal and distal muscle weakness was observed bilaterally. Creatinine kinase concentrations on 3 and 13 days after discontinuation of the paralytic agent were 181 and 96 units/L, respectively. On day 24, the patient moved her fingertips. On ICU day 30, the patient was weaned from the mechanical ventilator. The patient was transferred to the ward on day 33. Extensive rehabilitation with physical and occupational therapy was required for several months. CONCLUSION: Clinicians should remember that irrespective of chemical structural, neuromuscular blocking agents might produce prolonged paralysis in predisposed patients.
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.
Assessing the value and affordability of cholesterol reduction in the managed care setting.
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Evidence that the integrin beta3 and beta5 subunits contain a metal ion-dependent adhesion site-like motif but lack an I domain.
The amino-terminal domain of each integrin beta subunit is hypothesized to contain an ion binding site that is key to cell adhesion. A new hypothesis regarding the structure of this site is suggested by the crystallization of the I domains of the integrin alphaL and alphaM subunits (Lee, J.-O., Rieu, P., Arnaout, M. A., and Liddington, R. (1995) Cell 80, 631-638; Qu, A., and Leahy, D. J. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 10277-10281). In those proteins, an essential metal ion is bound by a metal ion-dependent adhesion site (MIDAS). The MIDAS is presented at the apex of a larger protein module called an I domain. The metal ligands in the MIDAS can be separated into three distantly spaced clusters of oxygenated residues. These three coordination sites also appear to exist in the integrin beta3 and beta5 subunits. Here, we examined the putative metal binding site within beta3 and beta5 using site-directed mutagenesis and ligand binding studies. We also investigated the fold of the domain containing the putative metal binding site using the PHD structural algorithm. The results of the study point to the similarity between the integrin beta subunits and the MIDAS motif at two of three key coordination points. Importantly though, the study failed to identify a residue in either beta subunit that corresponds to the second metal coordination group in the MIDAS. Moreover, structural algorithms indicate that the fold of the beta subunits is considerably different than the I domains. Thus, the integrin beta subunits appear to present a MIDAS-like motif in the context of a protein module that is structurally distinct from known I domains.
Eccentric dosage regimen for isosorbide dinitrate.
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Chemical compatibility of inotropic and vasoactive agents delivered via a multiple line infusion system.
OBJECTIVES: To determine the chemical compatibility of three different triple drug admixtures diluted with either 5% dextrose in water or 0.9% NaCl solution when administered via a multiple line infusion system (Omni-Flow 4000, Abbott Laboratories, Abbott Park, IL). The triple drug admixtures were: a) dobutamine, dopamine, and norepinephrine; b) nitroglycerin, sodium nitroprusside, and dobutamine; and c) nitroglycerin, dopamine, and dobutamine. DESIGN: Two phase in vitro compatibility study. SETTING: Pharmaceutical laboratory. SUBJECTS: None. INTERVENTIONS: Phase I assessed chemical stability when the triple drug admixture was placed in a single container. In phase II, individual drug components of the admixtures were infused via the multiple line infusion system. Samples were collected at time 0, 1 hr, 2 hrs, 4 hrs, 12 hrs, and 24 hrs. All samples were frozen and stored at -70 degrees C until assayed. MEASUREMENTS AND MAIN RESULTS: Samples were assayed using stability-indicating high performance liquid chromatography. The triple drug admixtures were considered to be chemically stable if there was < or = 10% loss of stated potency over 24 hrs. In phase I, chemical stability was observed for all triple drug admixtures at 24 hrs. In phase II, dobutamine, dopamine, norepinephrine, and sodium nitroprusside showed chemical stability at 24 hrs. Nitroglycerin showed a two-fold increase in concentration at 24 hrs compared with the initial concentration through the test infusion system; however, this amount was still one third lower than originally anticipated. CONCLUSIONS: All triple drug admixtures were chemically stable when placed in single containers. Dobutamine, norepinephrine, and sodium nitroprusside showed chemical stability when delivered via a multiple line infusion system. The reduced recovery of nitroglycerin from the test infusion system may result from adsorption of the nitroglycerin to the polyvinyl chloride plastic cassette and tubing during infusion.
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.
Safety and efficacy of rectal prochlorperazine for the treatment of migraine in the emergency department.
STUDY OBJECTIVE: To assess the safety and efficacy of rectal prochlorperazine in the treatment of acute migraines. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: Emergency department of an inner-city university hospital. PARTICIPANTS: ED patients with documented diagnosis of migraines. INTERVENTIONS: Vital signs and level of alertness were monitored immediately before drug administration and 120 minutes after dosing. Pain intensity and adverse events were monitored immediately before drug administration and at 30, 60, and 120 minutes after dosing. RESULTS: A positive outcome was defined as a pain score less than or equal to 5 on a 10-point scale or a 50% reduction in pain intensity from baseline at 120 minutes after dosing. All patients treated with prochlorperazine suppositories experienced a positive treatment outcome; only 50% of patients treated with placebo experienced a positive result at 120 minutes after dosing (P = .016). Pain intensity scores were significantly lower in the prochlorperazine group at 120 minutes (P = .018). There were no adverse reactions in either group, and there were no significant differences in vital signs or levels of alertness between groups. Patients who failed therapy were given rescue medication 120 minutes after dosing. CONCLUSION: Prochlorperazine administered as a 25-mg rectal suppository provides excellent pain relief within 2 hours in patients with acute migraines.
Over-the-counter histamine2-blocker therapy.
In determining whether a prescription medication should be granted OTC status, the risks and benefits of treatment with the medication must be weighed. Ultimately, the decision must be made with some degree of uncertainty. Pharmacists must take advantage of this uncertainty to demonstrate their professional expertise and value to society. The Rx-to-OTC switch for H2-blockers may benefit many, although not all, patients with acid peptic complaints, and it offers pharmacists an opportunity to demonstrate their willingness and ability to assist in the use of cost-effective OTC drug therapy.
How to develop a proactive formulary system.
To develop a quality formulary system, a proactive approach is necessary. This approach incorporates a prospective product and concurrent product analyses. A prospective product analysis, in turn, involves a review of current formulary agents, those likely to enter the marketplace shortly, and the formation of an expert review panel. This panel's tasks are to examine therapeutic, economic, and humanistic aspects of therapy and to set initial parameters for appropriate and cost-effective use of accepted products. Keys to a successful formulary system are to continuously monitor drug use and compliance with criteria and to work collaboratively with all institutional professionals in the development, implementation, and monitoring of the system.
Retrobulbar ischemic optic neuropathy associated with sickle cell disease.
A 52-year-old black man with a history of sickle cell SS disease presented with sudden loss of vision in his right eye. Examination of the right eye revealed no light perception and an amaurotic pupil, but an otherwise normal neuro-ophthalmic examination. On initial presentation, there was no evidence of an acute vascular event on funduscopy. Computed tomography failed to demonstrate pathology of the brain or orbit. Repeat fundus examination, 2 weeks later, still failed to demonstrate retinal or optic nerve disease. However, optic nerve pallor and central cupping became evident after 2 months and continued to progress in the ensuing year. Magnetic resonance imaging performed at that time did not disclose the presence of demyelinating disease, or aneurysmal dilation of the carotid or ophthalmic artery. A diagnosis of retrobulbar ischemic optic neuropathy is considered likely in this patient. The association of retrobulbar ischemic optic neuropathy and sickle cell anemia has not been previously reported.