bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of the Therapeutic Efficacy of Aerosolized and Endotracheally Instilled Antibiotics
Authors: Gough Patricia A. , Jordan Nancy Schuddekopf
Published: December 2015

Achievement of sufficient concentrations of aerosolized antibiotic at the site of infection is limited by technical problems in antibiotic delivery and by drug inactivation. Antibiotic delivery by aerosolization is generally associated with minimal systemic absorption, whereas systemic absorption may be significant after endotracheal instillation. Methodologic problems make correlations between clinical response and sputum antibiotic concentrations difficult. Studies suggest that aerosolized antibiotics are of little value in the treatment of chronic bronchopulmonary infections. Endotracheal instillation appears to be associated with favorable clinical responses, possibly due to enhanced antibiotic delivery to the site of infection. Prophylactic aerosolized antibiotics are effective in altering sputum flora; reduction in mortality from acquired pneumonia has not been demonstrated. The development of resistant organisms may occur as a result of prophylactic treatment.
Oxprenolol Hydrochloride: Pharmacology, Pharmacokinetics, Adverse Effects and Clinical Efficacy
Authors: Russo Mary E. , Covinsky Joel O.
Published: December 2015

Oxprenolol is a nonselective beta‐adrenergic blocking agent that also possesses intrinsic sympathomimetic activity (ISA) and membrane stabilizing effects. Oxprenolol undergoes first pass metabolism with only 30% of an oral dose reaching the systemic circulation. The drug is approximately 80% protein bound and is eliminated primarily by glucuronidation in the liver. Less than 4% of oxprenolol is excreted unchanged in the urine. Oxprenolol may reduce the heart rate and prolong the effective and functional atrioventricular nodal refractory period. Oxprenolol has less negative inotropic and chronotropic effects than propranolol. Plasma renin activity is reduced; however, changes in plasma aldosterone level are not significant. Long term metabolic effects require further study.

Oxprenolol appears to be comparable to other beta blockers in the treatment of hypertension and angina pectoris with no additional adverse reactions. If its partial agonist effect proves useful, it may have an advantage over other agents in treating patients with borderline cardiac reserve. Because of limited data, the use of oxprenolol for the treatment of arrhythmias, migraine, thyrotoxicosis, anxiety, and glaucoma cannot be recommended at this time.
Analgesic Effect of Graded Doses of Flurbiprofen in Post‐Episiotomy Pain
Authors: Sunshine Abraham , Olson Nancy Z. , Laska Eugene M. , Zighelboim Itic , De Castro Ana , De Sarrazin Cherokee
Published: December 2015

Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post‐episiotomy pain. One hundred and fifty‐two evaluable patients completed a randomized, double‐blind, stratified, parallel groups study. They were observed over a six hour period by one nurse‐observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects.
Pharmacology and Clinical Efficacy of Ranitidine, A New H2‐Receptor Antagonist
Authors: Helman Colin A. , Tim Leonard Ou
Published: December 2015

Ranitidine is a new histamine H2‐receptor antagonist that includes a furan ring structure, whereas other H2‐receptor antagonists include an imidazole ring. It is more potent than cimetidine in inhibiting gastric acid secretion and lacks cimetidine's anti‐androgenic and hepatic microsomal enzyme inhibiting effects. In the recommended dosage of 150 mg twice daily, ranitidine is as effective as cimetidine in healing duodenal and gastric ulcers and has the advantages of less frequent dosing and fewer side effects. Ranitidine appears to be the drug of choice in the treatment of the Zollinger‐Ellison syndrome because of its increased potency and lesser effect on endocrine function compared to cimetidine.
Guanadrel Sulfate: A Postganglionic Sympathetic Inhibitor for the Treatment of Mild to Moderate Hypertension
Authors: Palmer John D. , Nugent Charles A.
Published: December 2015

Guanadrel sulfate is structurally and pharmacologically similar to guanethidine but has different pharmacokinetic properties. The drug produces peripheral postganglionic sympathetic blockade as a consequence of interference with neuronal release of norepinephrine and displacement of norepinephrine from storage vesicles. Animal studies using large multiples of human antihypertensive doses suggest a low order of human toxicity. Clinical studies have failed to reveal any major effect on hematologic, hepatic or renal function. The effect on serum lipids and plasma renin is unknown. The drug is well absorbed after oral administration. Peak plasma levels in humans occur 1.5–2 hours after a administration. Protein binding is less than 20%. Data from animal studies and clinical trials demonstrating a lack of central nervous system side effects indicate that little if any drug enters the central nervous system. The drug is partially metabolized by the liver, but nearly 50% of an orally administered dose appears unchanged in the urine. The mean elimination half‐life is approximately 12 hours.

The onset of antihypertensive action after oral administration of guanadrel to humans is 30–120 minutes (mean 77 minutes). The offset of drug action after a single oral dose ranges between 4–14 hours (mean 9 hours). The hypotensive response to guanadrel in hypertensive subjects is the result of a decline in systemic vascular resistance with an impairment of the normal sympathetic reflexes in the erect position. Guanadrel causes a reduction in renal blood flow and glomerular filtration rate in the erect position. Open label clinical trials of antihypertensive efficacy indicate that guanadrel is effective in 60 and 70% of patients in the supine and erect positions, respectively. In comparative clinical trials, guanadrel appears to be as effective as guanethidine or methyldopa in reducing blood pressure in persons with mild to moderately severe hypertension; mean doses ranged from 56–162 mg/day. In other studies, investigators have used doses of 5–600 mg daily. The maximum recommended dosage is 400 mg/day. Side effects reported with guanadrel administration are those that would be predicted for a postganglionic sympathetic inhibitor that does not enter the central nervous system. Sexual dysfunction, orthostatic dizziness and diarrhea occur with the drug but do not seem to be as frequent or as severe as with guanethidine administration. In a comparison of guanadrel to methyldopa, methyldopa caused more complaints of drowsiness, and drowsiness scores of methyldopa patients remained higher than those of guanadrel patients even after two years of therapy. The drug has received approval as a step 2 antihypertensive agent in the United States. The available data suggest that it will serve as a reasonable alternative to other step 2 antihypertensives.
Determination of Theophylline Bioavailability Using Saliva Theophylline Concentrations
Authors: Uden Donald L. , Strand Linda M. , Miller Kenneth W. , Zaske Darwin E.
Published: December 2015

Substantial error occurs when individual saliva theophylline concentrations are used to predict serum theophylline concentrations. However, the use of saliva theophylline concentrations to determine product bioavailability has never been evaluated. Subjects in this study were 18 stable patients (20–51 yr) with a history of chronic obstructive pulmonary disease. Three preparations — a capsule (Elixophyllin 400 mg), elixir (Elixophyllin 373 mg), and tablet (Theolair 375 mg) — were administered in a randomized crossover design. Serum and saliva samples were obtained pre‐dose and 0.25, 0.5, 1, 2, 4, 6, and 8 hours after theophylline administration. The saliva AUC0–∞ and serum AUC0–∞ were highly associated for the elixir (r = 0.84) tablet (r = 0.89), and capsule (r = 0.89). The bioavailability of the tablet and capsule calculated from elixir saliva and elixir serum AUC0–∞ were not significantly different (p = 0.2). The bioavailability of the tablet calculated from saliva and serum was 93% and 102%, respectively. The bioavailability of the capsule calculated from saliva and serum was 113% and 102% respectively. Our data suggests that theophylline bioavailability can be reliably estimated from saliva theophylline concentrations. However, study designs that include larger sample sizes and more frequent sampling may be necessary when determining bioavailability from saliva.
Evaluation of New Indomethacin Dosage Forms
Authors: Waller Elaine S.
Published: December 2015

Indomethacin, an indole derivative nonsteroidal anti‐inflammatory drug, has been available since the early 1960s in gelatin capsules. In 1982, a sustained release product, Indocin® SR, was marketed. Awaiting marketing approval is a unique controlled release form of indomethacin, Indos.® The disposition of indomethacin includes enterohepatic cycling and extensive metabolism to inactive metabolites. Enterohepatic cycling makes interpretation of bioavailability estimates of indomethacin dosage forms difficult. The relationship of indomethacin plasma concentrations to therapeutic effects and side effects is inconclusive. It appears in vivo prostaglandin inhibition occurs at very low plasma concentrations that are achievable with all available dosage forms.

Indocin® SR is a sustained release capsule of indomethacin designed to deliver 25 mg of drug immediately and 50 mg gradually. Absolute bioavailability of the product is 80%. The plasma concentration‐time curves do not show good sustained release characteristics; after four hours plasma concentrations resemble those seen with a single dose of regular capsules. The cost compared with Indocin® is competitive.

Indos® is a zero‐order release form of indomethacin. It is a unique drug delivery system that shows good controlled release characteristics. Bioavailability is 85%.

Both Indocin® SR and Indos® are apparently therapeutically equivalent to indomethacin capsules. In elderly patients, Indos® has been shown to be associated with fewer side effects than Indocin®. Both Indocin® SR and Indos® have the advantage of once or twice daily dosing.
Long‐Acting Propranolol (Inderal LA): Pharmacokinetics, Pharmacodynamics and Therapeutic Use
Authors: Mishriki Amal A. , Weidler Donald J.
Published: December 2015

Long‐acting propranolol (Inderal LA) is a new formulation of propranolol that allows release of the drug in a controlled manner, so that the plasma concentration at 24 hr after dosing is greater with long‐acting propranolol than with conventional tablets. A single dose of 160 mg of long‐acting propranolol can produce cardiac beta‐adrenoceptor blockade throughout a 24 hr period without variability due to multiple peak concentrations. It has been shown that this formulation is as effective in the treatment of angina pectoris, hypertension and hyperthyroidism as the standard formulation. Studies with long‐acting propranolol in cardiac dysrhythmias are lacking. This new dosage form would be a means of simplifying dosing regimens and thereby hopefully enhancing patient convenience and compliance.
A Double‐Blind Clinical Trial of Mianserin Versus Amitriptyline: Differentiation by Adverse Symptomatology
Authors: Guy William , McEvoy Joseph M. , Ban Thomas A. , Wilson William H. , Pate Kirby
Published: December 2015

A 6‐week double‐blind comparison of mianserin, a new antidepressant, and amitriptyline allowed us to explore the problem of demonstrating main effect differences in drug/drug trials when the focus is primarily only upon efficacy or upon common adverse symptomatology. Statistical analyses of standard psychiatric rating scales revealed no significant treatment differences, while both treatment groups exhibited significant parallel improvement across time. Examination of treatment emergent symptoms indicated that, while it evoked fewer anticholinergic symptoms than amitriptyline, mianserin exhibited a different profile of adverse symptomatology. The usefulness of a measure of the benefit/risk ratio was described as a means of clarifying drug/drug comparisons.
Oxprenolol Hydrochloride: Pharmacology, Pharmacokinetics, Adverse Effects and Clinical Efficacy
Authors: Russo Mary E. , Covinsky Joel O.
Published: December 2015

Oxprenolol is a nonselective beta‐adrenergic blocking agent that also possesses intrinsic sympathomimetic activity (ISA) and membrane stabilizing effects. Oxprenolol undergoes first pass metabolism with only 30% of an oral dose reaching the systemic circulation. The drug is approximately 80% protein bound and is eliminated primarily by glucuronidation in the liver. Less than 4% of oxprenolol is excreted unchanged in the urine. Oxprenolol may reduce the heart rate and prolong the effective and functional atrioventricular nodal refractory period. Oxprenolol has less negative inotropic and chronotropic effects than propranolol, Plasma renin activity is reduced; however, changes in plasma aldosterone level are not significant. Long term metabolic effects require further study.

Oxprenolol appears to be comparable to other beta blockers in the treatment of hypertension and angina pectoris with no additional adverse reactions. If its partial agonist effect proves useful, it may have an advantage over other agents in treating patients with borderline cardiac reserve. Because of limited data, the use of oxprenolol for the treatment of arrhythmias, migraine, thyrotoxicosis, anxiety, and glaucoma cannot be recommended at this time.
The Bentiromide Test for Pancreatic Exocrine Insufficiency
Authors: Toskes Phillip P.
Published: December 2015

The bentiromide test, a test of pancreatic exocrine function, has recently been approved for clinical use by the Food and Drug Administration. The test has been studied in adult patients with chronic pancreatic disease and in children with cystic fibrosis. The 500‐mg dose and 6‐hour urine collection period appear optimal for separating patients with chronic pancreatic disease from control subjects. Side effects with the 500‐mg dose are virtually nonexistent. This simply performed outpatient test of chymotrypsin function appears to be an excellent means of confirming the diagnosis of pancreatic exocrine insufficiency.
Antihypertensive and Biochemical Effects of Indacrinone Enantiomers
Authors: Jain Adesh K. , Michael Ronald , Ryan Jerome R. , McMahon F. Gilbert
Published: December 2015

The enantiomers of indacrinone (I), an investigational loop diuretic, have different pharmacologic activity. The (–) enantiomer is natriuretic, and the (+) enantiomer is uricosuric. To determine the antihypertensive effects and an isouricemic ratio of indacrinone enantiomers, 37 patients with sitting diastolic blood pressure (BP) between 90 and 104 mm Hg, after a 4‐week placebo washout, randomly received one of the ratios of I enantiomers, namely −2.5/ + 80 mg (A), −5/ + 80 mg (B), −10/ + 80 mg (C) or placebo (P), once daily for 12 weeks in a double‐blind, parallel study. The mean reductions (baseline‐end of treatment) in BP of 23/8, 20/10 and 25/10 mm Hg with treatments A, B and C respectively were greater (p < 0.01) than that on P (0/3). Initially, serum uric acid decreased with treatments A and B but not with C. Mean changes in serum uric acid were −0.3, −0.4, 0.2 and 0.3 mg/dl respectively with treatments A, B, C and P. The ratio of −10/+ 80 mg produced least variation in serum uric acid. Reduction in serum K+ and Cl− appeared to be dose related to (–) enantiomer. No serious adverse effects were reported. A 1:9 ratio of I enantiomers intended for wide‐scale use as a diuretic also showed good antihypertensive activity, a favorable uric acid profile and absence of hepatic toxicity in 14 patients.
Pentoxifylline: A New Drug for the Treatment of Intermittent Claudication; Mechanism of Action, Pharmacokinetics, Clinical Efficacy and Adverse Effects
Authors: Aviado Domingo M. , Porter John M.
Published: December 2015

During the past decade, the effectiveness of peripheral vasodilator drugs in the treatment of chronic occlusive arterial disease has been questioned. Pentoxifylline is a hemorheologic agent with primary actions that include increasing erythrocyte flexibility, reducing blood viscosity and increasing microcirculatory flow and tissue perfusion. The result is improved supply of oxygen to ischemic muscles of the limbs. In several double‐blind studies, pentoxifylline increased walking distance of patients with intermittent claudication in comparison to placebo or vasodilators. Like other methylxanthines, pentoxifylline is well absorbed in the gastrointestinal tract, almost completely metabolized in the body and excreted in the urine. The most significant difference in its pharmacokinetics is that, unlike other methylxanthines, it is bound to the erythrocytic membrane where it is initially metabolized. Although pentoxifylline has been shown to be effective in the treatment of intermittent claudication, additional research is needed to determine its use as adjunctive therapy in patients with concurrent coronary or cerebrovascular disease.
Oral Neomycin Sulfate and Erythromycin Base Before Colon Surgery: A Comparison of Serum and Tissue Concentrations
Authors: DiPiro Joseph T. , Patrias John M. , Townsend Raymond J. , Bowden Talmadge A. , Hooks Vendie H. , Smith Randal B. , Spiro Theodore E.
Published: December 2015

It is accepted that the use of oral neomycin sulfate and erythromycin base before colon surgery results in decreased numbers of intestinal bacteria. Intraluminal levels of these agents are reported to be very high, but systemic availability is still debated. The systemic levels were studied in 8 patients undergoing colon surgery. Each patient received neomycin sulfate and erythromycin base, 1 g each, 19, 18 and 9 hours preoperatively. Twelve samples from serum, one from wound muscle and one from the intestinal wall were obtained from each patient in the 26 hours after the initial dose. Considerable variation was observed among levels. The following means were calculated: peak serum levels were 3.4 and 0.59 μg/ml, muscle levels were 1.68 and 0.23 μg/g and intestinal wall levels were 6.4 and 12.9 μg/g for erythromycin and neomycin respectively. Observed times to peak levels were 19 and 12 hours after the initial dose for erythromycin and neomycin respectively. The detectable systemic concentrations that result when these agents are given orally for bowel preparation before colon surgery may contribute to the drugs' efficacy.
Cardiac Electrophysiologic Testing: Its Role in the Selection of Antiarrhythmic Drug Regimens for Supraventricular and Ventricular Arrhythmias
Authors: Cameron James , Isner Jeffrey M. , Salem Deeb M. , Estes N. A. Mark
Published: December 2015

Cardiac electrophysiology studies use intracardiac recording and programmed stimulation to define the mechanisms and most appropriate therapy for supraventricular and ventricular arrhythmias. Using these techniques, the majority of clinical tachycardias can be reproducibly initiated and terminated in the electrophysiology laboratory, thereby allowing the most appropriate therapy to be selected. With this approach, antiarrhythmic agents can be tested in a systematic, serialized fashion for efficacy, safety and patient tolerance. With both supraventricular and ventricular tachycardias, suppression of arrhythmia induction predicts freedom from recurrence, whereas inducibility carries a poor prognosis in clinical follow‐up. Electrophysiology studies provide a safe and effective approach to the treatment of selected patients with cardiac arrhythmias.
Flecainide: A New Prototype Antiarrhythmic Agent
Authors: Nappi Jean M. , Anderson Jeffrey L.
Published: December 2015

Flecainide acetate is the first class IC antiarrhythmic agent marketed in the United States. In vitro, animal and human studies have shown that the drug markedly prolongs conduction and has minimal effect on repolarization. Efficacy trials have shown flecainide to be effective in a wide range of ventricular and selected atrial arrhythmias. The drug is generally well tolerated, although minor adverse effects are common. These generally are related to the central nervous system and respond to a reduction in dosage. Like other antiarrhythmic agents, flecainide may demonstrate proarrhythmic effects. It is excreted in the urine as the parent compound and inactive metabolites. The elimination half‐life ranges from 12–27 hours in patients with normal renal function, allowing convenient dosing regimens of 100–200 mg twice daily in most patients. Flecainide has the potential for widespread use.
Ceftriaxone: A Beta‐lactamase—stable, Broad‐spectrum Cephalosporin with an Extended Half‐life
Authors: Beam Thomas R.
Published: December 2015

Ceftriaxone is an aminothiazolyl‐oxyimino cephalosporin. It possesses the typical in vitro activity of a third‐generation cephalosporin with excellent activity against many gram‐negative aerobic bacilli: Escherichia coli; species of Proteus, Klebsiella, Morganella, Providencia and Citrobacter; and Enterobacter agglomerans. Ceftriaxone also has outstanding bactericidal action against pneumococci, group B streptococci, meningococci, gonococci and Hemophilus influenzae. In healthy volunteers, it has an exceptionally long serum half‐life of 5.8–8.7 (mean 6.5) hours. It distributes well throughout all body spaces, including cerebrospinal fluid in the presence of inflammation. Dosage modification is necessary only when there is combined hepatic and renal dysfunction. Adverse reactions characteristic of cephalosporins have been observed with the administration of ceftriaxone. No unique toxicities have been identified, and hypoprothrombinemic bleeding is not part of the adverse reaction profile. Ceftriaxone has been used to treat serious bacterial infections in neonates, infants, children and adults. Bacteriologic and clinical success rates have consistently exceeded 90%. The drug has also been used as single‐dose chemoprophylaxis in coronary artery bypass, biliary tract, vaginal hysterectomy and prostatic surgery. Efficacy and safety were similar to multiple‐dose cefazolin. Ceftriaxone warrants special consideration because its extended half‐life allows for less frequent dosing than other antimicrobials. Significant cost savings can be realized with proper use of this antibiotic.
Should Corticosteroids Be Used in the Treatment of Acute, Severe Asthma?
Authors: Fiel Stanley B.
Published: December 2015

Corticosteroids have been used for over 3 decades in the treatment of asthma. There are theoretic reasons and long‐standing clinical support for their use, but little in the way of good objective data on their efficacy. I have reviewed this information and concluded that notwithstanding rare side effects, corticosteroids should be used in acute asthma, and objective data exist to support this premise.
A Review of Selected Investigational Nonsteroidal Antiinflammatory Drugs of the 1980s
Authors: Marsh Charles C. , Schuna Arthur A. , Sundstrom Walter R.
Published: December 2015

We reviewed the literature on 7 investigational nonsteroidal antiinflammatory drugs (NSAIDs): fenbufen, flurbiprofen, tiaprofenic acid, diclofenac, fenclofenac, etodolac and proquazone. These drugs all appear to be at least as effective as currently marketed NSAIDs. Toxicity reported with these newer agents is similar to that seen with other drugs in this class, with gastrointestinal complaints being most commonly reported. The frequency of gastritis and the extent of gastrointestinal microbleeding are less than what occur with aspirin therapy. Fenclofenac may affect thyroid function tests, an effect not noted with other NSAIDs. Proquazone and fenclofenac may have some effect on immunologic function similar to those of slow‐acting antirheumatic drugs. These drugs decrease immunoglobulins, rheumatoid factor and C‐reactive protein. The place for these drugs in the management of rheumatic diseases has yet to be defined. They may prove to be more beneficial than currently marketed drugs for some patients.
Book Review
Authors: Weiner Bruce
Published: December 2015

Arrhythmia Diagnosis and Management: A Clinical Electrocardiographic Guide. By Erik Sandoe and Bjarne Sigurd.
Bethanidine Sulfate in Paroxysmal Ventricular Tachycardia: Toxicity and Antifibrillatory Actions
Authors: Bauman Jerry L. , Gallastegui Jose , Prechel Darrel , Anderson Jeffrey L.
Published: December 2015

Programmed ventricular stimulation was used to test oral bethanidine sulfate in 10 patients with life‐threatening ventricular arrhythmias. These patients had previously documented, recurrent, sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) complicating stable heart disease. During control electrophysiologic studies, VT could be induced in all 10 patients: 6 with nonsustained VT, 3 with sustained VT, and 1 with VT/VF. After control, bethanidine 20–30 mg/kg was administered orally and beginning 60 minutes later, programmed ventricular stimulation was repeated. After bethanidine administration, VT could be induced in nine patients; in four, the VT was essentially unchanged from that induced during control studies. In four others, worse VT was induced after bethanidine. The remaining two patients had a potentially beneficial response to the drug. Bethanidine was poorly tolerated: seven patients had symptomatic orthostatic hypotension that persisted for several days despite concurrent protriptyline therapy. Furthermore, in four patients, spontaneous VT or VT/VF occurred 3–8 hours after the last dose. Nausea, vomiting, flushing, and blood pressure elevation were also noted. Bethanidine sulfate in the dosages used usually does not prevent the induction of VT by programmed ventricular stimulation and frequently causes serious toxicity. These findings suggest that the drug would be ineffective and poorly tolerated for long‐term therapy in patients with serious ventricular arrhythmias.
A Double‐blind Study Comparing Single Dose of Intramuscularly Injected Zomepirac to Meperidine in the Treatment of Postoperative Pain
Authors: Baird Walter M. , Turek M. DiAnn , Minn Fredrick L. , Brown Robert H.
Published: December 2015

Eighty‐eight patients with moderate or severe postoperative pain were entered into a double‐blind, single‐injection trial designed to assess the analgesic efficacy of intramuscular zomepirac 100 mg. Patients were randomly selected to receive zomepirac injection, meperidine 100 mg or meperidine 50 mg. By most criteria of analgesic efficacy, zomepirac was superior to meperidine 50 mg and as effective as meperidine 100 mg. In terms of peak analgesia (and of patients' global evaluations), both meperidine 100 mg and zomepirac were superior to meperidine 50 mg. Total analgesia provided by zomepirac was greater than that with meperidine 100 mg, which was greater than that with meperidine 50 mg. Significantly fewer patients needed remedication during the observation period, and mean time to remedication was significantly longer for the zomepirac group than for either meperidine group. No serious adverse effects were reported.
An Analytic Approach To Quantifying Pain Scores
Authors: Laska Eugene M. , Meisner Morris , Takeuchi Kei , Wanderling Joseph A. , Siegel Carole , Sunshine Abraham
Published: December 2015

Statistical problems in clinical trials frequently involve fitting regression lines when the underlying data are categorical or ordinal response variables. Usually an ad hoc a priori quantification is used to assign values to these ordinal responses. For pain intensity data collected in analgesic trials, the usual approach is to set none equal to 0, mild equal to 1, moderate equal to 2, and severe equal to 3. While this scheme has been generally accepted, on the basis that for similar clinical trials reasonably similar results are obtained by different investigators, concern exists that the distances between pain scores are probably not equal. A method is presented for quantifying categorical responses so that the resulting scores maximize the simultaneous fit of the dose‐response regression lines. The optimal scores derived by this technique may then be used in a bioassay analysis to estimate the relative potency of 2 compounds. As illustrative examples, this method was applied to data from 2 clinical trials and the results were compared to the usual method.
Potential Therapeutic Indications for Growth Hormone and Growth Hormone‐releasing Hormone in Conditions other than Growth Retardation
Authors: Williams Timothy C. , Frohman Lawrence A.
Published: December 2015

Growth hormone (GH) previously was available in limited supply and only for the treatment of GH‐deficient children. The recent production of GH by recombinant DNA technology has provided a potential surfeit of this hormone and raises the possibility of its use in other conditions. In addition, the isolation, characterization, and synthesis of GH‐releasing hormone (GRH) provides an opportunity to use this peptide in conditions in which increased circulating levels of GH are desired. Both GH and GRH have potential therapeutic uses in conditions other than growth retardation.
Impact of Prophylactic Therapy for Postoperative Thromboembolism on Prospective Payment
Authors: Hamilton Cindy W. , Romankiewicz John A.
Published: December 2015

Widescale implementation of prospective payment systems as a means of reimbursing hospitals on the basis of diagnosis‐related group designation has important implications with respect to the selection of drug therapy. Instead of analyzing costs on a departmental basis, pharmacists need to identify the impact of optimal drug therapy on overall profitability. Clinically evident deep venous thrombosis and pulmonary embolism occur in approximately 3.5% and 1.8% of patients undergoing general surgery. Treatment of these complications consumes hospital resources, but the hospital absorbs the cost of treatment under the prospective payment system. Effective prophylactic measures increase profitability by preventing complications and minimizing the proportion of outliers due to increased length of stay. In selecting prophylactic measures, this impact on overall profitability is as important as acquisition cost. For example, in comparison with no prophylaxis, dihydroergotamine‐heparin reduces the frequency of deep venous thrombosis in patients undergoing general surgery by 61.5% and heparin alone reduces it by 31.2%. The relative effect of this combination on postoperative complications and resultant savings in terms of treating them compensates for differences in acquisition costs between these measures.
Indications for Immunotherapy
Authors: Solinger Alan M.
Published: December 2015

Underlying immunodeficiency should be suspected in every patient, irrespective of age, who has recurrent, persistent, severe, or unusual infections. Defects in immunity can be classified into primary or secondary disorders involving specific or nonspecific immune mechanisms. Several forms of primary and secondary immunodeficiency exist for which various immunotherapeutic modalities are available. Significant among these are immunoglobulins commercially available for intravenous infusion. Other therapies include transplantation of tissue such as bone marrow, fetal liver, and fetal thymus. Enzyme replacement therapy is being developed, as is the use of products unique to immunocompetent cells, such as thymus extract, thymosin, interleukins, and transfer factor. Forms of nonspecific immune modulators and stimulators are other possibilities, especially in the context of the immunotherapy of tumors.
Recent Advances in Solid Organ Transplantation
Authors: Canafax Daniel M. , Sutherland David E. R.
Published: December 2015

Advances in organ transplantation have come rapidly and consistently in recent years as the result of improved surgical techniques and immunosuppressive drug therapies. Experience gained in renal transplantation over the past 30 years has made this a standard therapeutic approach for treating chronic renal failure. This knowledge has been successfully applied to the transplantation of other organs to produce steadily increasing survival rates and improved quality of life. This article reviews the advances that have been made in solid organ transplantation and immunosuppressive drug therapy.
Antibody Immunotherapy of Gram‐negative Bacterial Sepsis
Authors: Dunn David L
Published: December 2015

Gram‐negative bacterial sepsis continues to represent a significant cause of morbidity and mortality in hospitalized patients. Currently available medical therapy (antimicrobial agents, hemodynamic monitoring, aggressive fluid resuscitation, and nutritional support) for this disease process has reduced but not eliminated the severe consequences that may ensue. Recent investigations have demonstrated the ability of antibody directed against gram‐negative bacterial lipopolysaccharide (LPS or endotoxin) to afford protection during experimental gram‐negative bacillary sepsis. The core LPS‐lipid A portion of endotoxin represents a determinant shared by many common gram‐negative microorganisms that is luxuriantly expressed on the cell surface of rough mutants of Escherichia coli and Salmonella minnesota. These organisms or the outer membrane LPS isolated from them thus represent suitable immunogens for the development of cross‐protective antibody preparations. Large quantities of highly cross‐reactive antibody may potentially be obtained from several sources: (1) murine or human monoclonal antibodies, (2) immunization of large animals or humans with subsequent plasmaphoresis and antibody isolation, (3) affinity purification of large amounts of normal antibody, and (4) pooling of prescreened lots of normal animal or human antibody that react to a particular bacterial antigen.
Methodology and Safety Considerations in the Production of an Intravenous Immunoglobulin Preparation
Authors: Friedli Hans R.
Published: December 2015

Intravenous immunoglobulins are biologic substances and differ in many respects from chemical pharmaceuticals. To produce a safe and efficacious preparation, special points must be considered. Careful screening procedures and excluding high‐risk donor populations reduce the risk of transmitting viral disease from the starting material. With plasma fractionation the immunoglobulins are purified, and safety is further improved by eliminating potentially remaining viruses. Cold ethanol‐fractionation methods have proved to be safe and economical. Anticomplementary aggregates, responsible for anaphylactoid reactions in agammaglobulinemic patients, are removed to achieve intravenous tolerance. Enzymatic digestion or chemical modifications impair the efficacy of the preparation. Ion‐exchange adsorption removes immunoglobulin subpopulations. Mild acid treatment at pH 4 yields a safe product with intact potency. Optimal stability is ensured by freeze‐drying. A fine net of quality controls virtually guarantees a safe preparation.
Review of Intermittent Dobutamine Infusions for Congestive Cardiomyopathy
Authors: Thomas Robert L. , Watson Donald , Marshall Laine E.
Published: December 2015

Dobutamine is a potent inotropic agent traditionally used for treatment of acute cardiac decompensation of congestive heart failure (CHF). It acts primarily by increasing myocardial contractility and cardiac output. It has a rapid onset of action, a half‐life of 2 minutes, and a duration of action of 10 minutes. Recently, the therapeutic effect of dobutamine was noted to be prolonged beyond the discontinuation of an infusion, persisting for 4–10 weeks after infusion of 48–72 hours. Because of this prolonged effect, dobutamine infusions were evaluated in outpatients with intractable CHF and were effective in improving their functional status. No effect on survival rates may be expected, but this form of therapy may improve the patient's lifestyle. Although several factors may limit the application of dobutamine infusion to outpatients, it offers an effective alternative to traditional therapy for select patients.
Acyclovir‐Associated Fever: A Case Report
Authors: Shea Brian F. , Harbison Mary Alice , Sesin G. Paul , Benotti Peter N. , Hammer Scott M.
Published: December 2015

Drug‐induced fever has been associated with many agents. We treated a patient who developed high, spiking fevers while receiving intravenous acyclovir. Rechallenge with the drug was not attempted. Clinicians should be aware of the possibility of drug‐induced fever in patients who receive systemic acyclovir.
Lack of Interaction Between Cimetidine and Buspirone
Authors: Gammans Richard E. , Pfeffer Morris , Westrick Mary L. , Faulkner Harry C. , Rehm Klaus D. , Goodson Peter J.
Published: December 2015

Simultaneous administration of cimetidine and many benzodiazepine anxiolytics has resulted in decreased body clearance and marked prolongation of the half‐life of these agents. The pharmacokinetic interaction of buspirone, a new nonbenzodiazepine anxiolytic, and cimetidine was studied in 10 healthy male volunteers. Each received, in order, buspirone 45 mg/day (days 1–7), no drug (days 8–14), cimetidine 1 g/day (days 15–21), buspirone 45 mg/day plus cimetidine 1 g/day (days 22–28), and cimetidine 1 g/day (days 29–31). Buspirone and 1‐pyrimidinyl piperazine (1‐PP), an active metabolite, pharmacokinetics, urinary excretion of cimetidine, a manual dexterity test, the Stroop color‐word interference test, and a visual analog mood scale were evaluated on each treatment. There were no significant (p > 0.05) differences among treatments for any measurement except for a slight (31%) but significant (p < 0.05) increase in the 1‐PP Cmax value. These results suggest that within the normal therapeutic dosage ranges for both drugs, it is unlikely that a clinically significant interaction between them will occur.
Pathophysiology and Mechanisms of Stress Ulcer Injury
Authors: Levine Barry A.
Published: December 2015

Stress ulceration, a disease associated with the stress of severe injury, sepsis, and organ failure, has declined in frequency during the last decade. Factors contributing to this decrease include more rapid transport of trauma patients, early resuscitation, avoidance and treatment of complications, and prophylactic maintenance of increased gastric mucosal pH. The pathophysiology of these lesions remains to be elucidated completely; however, both aggressive factors (acid, duodenal reflux, etc.) and a deficiency in defensive mechanisms (gastric mucosal blood flow, gastric mucosal barrier, mucus, bicarbonate, etc.) play a role in their inception. The hemorrhagic complication of stress ulcer, which is usually seen between the fifth and tenth days after admission, remains a sequela associated with a significant rate of mortality.
Immunologic Effects of Cimetidine: Potential Uses
Authors: Mavligit Giora M.
Published: December 2015

Suppressor T lymphocytes play a major regulatory role in the function of the immune system. Since the discovery of histamine (H2) receptors on the surface of these immune cells, studies have demonstrated that cimetidine diminishes the effect of suppressor T cells in both cellular‐ and humoral‐mediated (antibody) immune reactions. Preliminary clinical results demonstrate that cimetidine has a beneficial effect on a variety of immune functions. An antineoplastic effect among tumor‐bearing animals has also been found, suggesting the drug may be effective against certain human cancers, probably as an immune potentiator. Cimetidine has been used in the treatment of human cancer in combination with interferon or coumarin and as a single agent. Modest tumor response rates have been observed. The finding that cimetidine accelerates healing of herpesvirus infections is intriguing. These encouraging, albeit preliminary, results emphasize the need for additional studies on the drug's antiviral properties.
Increased Frequency of Doxycycline Side Effects
Authors: Bryant Stephen G. , Fisher Seymour , Kluge Ronica M.
Published: December 2015

As part of a study investigating new methods of detecting adverse drug reactions, adult outpatients receiving new prescriptions for 1 of 4 antibiotics (doxycycline, penicillin VK, ampicillin, or tetracycline) were assigned to 1 of 2 methods of monitoring adverse drug reactions. Data were collected from a total of 457 staff‐initiated interviews and from 1467 patients who were asked to telephone to report possible adverse effects. Doxycycline is considered by authoritative sources to be generally comparable in side effects to other tetracyclines and penicillins, with the exception that it increases photosensitivity. Results from both monitoring methods consistently indicated at least a 3‐fold higher frequency of nausea or vomiting with doxycycline relative to the other antibiotics. Complaints of skin rash also were at least 4 times more frequent with doxycycline, depending on the particular sample.
Encainide: Its Electrophysiologic and Antiarrhythmic Effects, Pharmacokinetics, and Safety
Authors: Tordjman Therese , Estes N. A. Mark
Published: December 2015

Encainide is a class IC antiarrhythmic agent that has been under clinical investigation for the last decade. Laboratory and clinical studies have demonstrated it to be a potent suppressor of ventricular extrasystoles. It is effective in approximately one‐half of patients with malignant ventricular arrhythmias. The preliminary experience in patients with supraventricular arrhythmias indicates that the drug is particularly effective in arrhythmias associated with an accessory pathway. Side effects most commonly include blurred vision, nausea, heart block, and proarrhythmic effects. The hemodynamic effects of oral encainide are insignificant in patients with well‐preserved left ventricular function. Despite minimal myocardial depression in patients with left ventricular dysfunction, there is the potential for worsening of heart failure. Encainide has a short half‐life of 3 hours, but has 2 active metabolites with longer half‐lives. No clinically significant drug interaction has been demonstrated with encainide therapy.
The Therapeutic Use of Azathioprine in Renal Transplantation
Authors: Chan Gary L. C. , Canafax Daniel M. , Johnson Curtis A.
Published: December 2015

This review discusses the pharmacokinetics, mechanism of action, clinical use, toxicities, drug interactions, and possible approaches for therapeutic monitoring of azathioprine (AZA). The drug has been used extensively in posttransplant immunosuppressive protocols. Its therapeutic use is hampered by the development of toxicities, however, especially leukopenia, which is a common criterion for dosage adjustment. Azathioprine is rapidly converted in the liver and erythrocytes to 6‐mercaptopurine (6MP), which is eventually metabolized to inactive 6‐thiouric acid (6TU). The terminal half‐lives of AZA and 6MP are 50 and 74 minutes, respectively. While renal dysfunction does not alter the disposition of AZA, hepatic insufficiency attenuates the pharmacologic activity. Immunosuppression depends on the formation of active intracellular thiopurine ribonucleotides, although AZA itself may block antigen recognition. Individualization of AZA regimens by determining tissue concentrations of thioguanine nucleotides, and plasma concentrations of AZA, 6MP, or 6TU may improve the risk:benefit ratio.
Hemodynamic Profiles of Antianginal Agents
Authors: Tonkon Melvin
Published: December 2015

The 3 main classes of antianginal drugs are nitrates, beta blockers, and calcium channel blockers. Nitrates have been viewed classically as affecting myocardial demand by reducing intraventricular volume and lowering the filling pressure of the left ventricle. They have been used increasingly to improve oxygen supply in myocardial ischemia by increasing coronary blood flow and actually causing coronary vasodilatation, and by having an effect on endothelial competence. Beta blockers are used to decrease myocardial blood flow by reducing myocardial demand, with reduction of myocardial contractility, afterload, and heart rate. No major improvement of oxygen supply is seen with this class of medication, and in fact, there is some potential for augmenting coronary vasoconstriction. Calcium channel blockers not only reduce myocardial demand by reducing afterload and, in some cases, heart rate, but similar to nitrates, they enhance myocardial oxygen supply.
Role of Arachidonic Acid Metabolites in Cardiac Ischemia and Reperfusion Injury
Authors: Fiedler Volker B.
Published: December 2015

Myocaradial reperfusion after prolonged periods of ischemia may result in the acceleration and exacerbation of ventricular injury. This is associated with intramitochondrial calcium overload and gross alterations in ultrastructure. Prostaglandins (PGs) (e.g., PGE2, PGE2α, thromboxane A2, PGI2) are synthesized by the heart during myocardial infarction, and cardiotoxic influences of arachidonate on contractile recovery with enhanced efflux of enzymes occur after reperfusion. Accumulation of arachidonic acid in early ischemia indicates degradation of phospholipids as structural components of myocyte membranes. One major cause for reperfusion‐induced exacerbation of ischemic damage is a free radical‐induced peroxidation of lipids with cellular disruption. On reperfusion, both vasoconstrictive and dilator PGs are released from platelets, myocytes, and endothelium, and flushed downstream. This may cause additional vasoconstriction in the microcirculation of normally and/or hypoperfused cardiac regions. Locally released vasodilating PGs can improve cardiac perfusion and prevent plugging of blood elements, thereby antagonizing cell destruction during flow restoration. Several drugs are available that modify blood cell and myocyte arachidonate metabolism, and may favor synthesis of dilating and antiaggregatory PGs.
Preoperative Flurbiprofen in Oral Surgery: A Method of Choice in Controlling Postoperative Pain
Authors: Dupuis Remy , Lemay Hélène , Bushnell M. Catherine , Duncan Gary H.
Published: December 2015

The analgesic efficacy of a single 50‐mg preoperative dose of flurbiprofen was compared with ACC‐30 (aspirin 375 mg, codeine 30 mg, caffeine 30 mg) and a placebo. Forty patients scheduled for the surgical removal of impacted maxillary third molars were enrolled in a double‐blind, randomized study. Using a within‐subject design we compared the analgesic efficacy of (1) preoperative flurbiprofen 50 mg with placebo in 20 patients, and (2) preoperative ACC‐30 with placebo in 20 other patients. Using a between‐group design, we then compared the analgesic efficacy of (3) each drug given preoperatively and postoperatively, and (4) each drug given postoperatively only. Patients rated 2 pain dimensions, intensity and unpleasantness, hourly for 8 hours after the presurgical dose. The results of this study indicate that better analgesia was obtained when flurbiprofen was given preoperatively compared to only after surgery. Conversely, preoperative administration of ACC‐30 did not demonstrate any significant influence on postsurgical analgesia. When comparing the 2 drugs, flurbiprofen proved to be superior in providing pain relief only when it was given prior to surgery. There was no difference between them when given only after surgery. Side effects were moderate and not significantly different between patients receiving flurbiprofen and those receiving ACC‐30.