bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality Control Framework for Statutory Audit of Financial Statements: A Comparative Study of USA, UK and India
Authors: Saha Siddhartha Sankar , Roy Mitrendu Narayan
Published: January 2017

Quality control of audit procedure has become extremely important in today’s corporate environment in the backdrop of accounting irregularities and audit failures leading to corporate demise. Accounting firms control the quality of audit procedure with the help of the quality control standard (QCS) and specific auditing standard. These standards provide reasonable assurance of compliance with applicable regulation and issuance of the appropriate report by the engagement team. After discussing the international scenario of quality control framework, in this study a comparative analysis of quality control policies and procedures at firm and engagement in three select countries has been presented. The countries selected are the United States of America (USA), the United Kingdom (UK) and India. The study finds that the QCS and the auditing standard in all three countries are designed in line with International Standards on Auditing (ISAs) and International Standards on Quality Control (ISQC)-1. Naturally, quality control policies and procedures in three countries are comparable barring few minor differences. Based on these differences, it can be concluded that the quality control framework in the UK and India is more stringent as compared to the USA.
The Interaction of Salivary Secretions with the Human Complement System — A Model for the Study of Host Defense Systems on Inflamed Mucosal Surfaces
Authors: Boackle Robert J.
Published: January 2017

When complement first contacts salivary secretions, as when gingival crevicular fluid first meets saliva at the gingival margin, complement function is enhanced. The immediate potentiation of the complement system at equal volume ratios of serum to saliva is due to several factors, including the lower ionic strength of saliva when compared with serum and the presence of certain salivary glyproteins such as the nonimmunoglobulin agglutinins that appear to simultaneously activate Cl and affect (sequester) certain complement control proteins, such as Factor H.

This initial potentiation of the complement cascade by saliva may aid in defending the area immediately above the gingival crevice from oral microbiota that are being coated with a combination of serous exudate components and salivary components.

As serum becomes much more diluted with saliva (i.e., crevicular fluid moves away from the supragingival area), the acidic proline-rich salivary proteins (APRP) begin to disrupt the unbound Clq-Clr2-Cls2 macromolecular complexes. Thus, the APRP along with other C1 fixing substances in saliva appear to restrict complement function, but only when the ratios of saliva to serum exceed 250 :1.

Since certain salivary glycoproteins bind to viruses, the potentiation of the complement system by saliva may also play a role in neutralizing certain viral infections on mucosal surfaces where tissue transudates containing complement begin to contact mucosal secretions such as saliva. Again, the ratio of serous fluid to mucosal secretion appears to be an important factor.

This article also discusses some of our preliminary data and speculations concerning the binding of the self-associating high-molecular-weight nonimmunoglobulin salivary agglutinins (NIA) with the envelope of the human immunodeficiency virus (HIV) and the possible cooperative role of Clq and fibronectin in aiding neutralization of HIV infectivity.
Tooth Movement
Authors: Davidovitch Zeev
Published: January 2017

This article reviews the evolution of concepts regarding the biological foundation of force-induced tooth movement. Nineteenth century hypotheses proposed two mechanisms: application of pressure and tension to the periodontal ligament (PDL), and bending of the alveolar bone. Histologic investigations in the early and middle years of the 20th century revealed that both phenomena actually occur concomitantly, and that cells, as well as extracellular components of the PDL and alveolar bone, participate in the response to applied mechanical forces, which ultimately results in remodeling activities.

Experiments with isolated cells in culture demonstrated that shape distortion might lead to cellular activation, either by opening plasma membrane ion channels, or by crystallizing cytoskeletal filaments. Mechanical distortion of collagenous matrices, mineralized or non-mineralized, may, on the other hand, evoke the development of bioelectric phenomena (stress-generated potentials and streaming potentials) that are capable of stimulating cells by altering the electric charge on their membrane or their fluid envelope. In intact animals, mechanical perturbations on the order of about 1 min/d are apparently sufficient to cause profound osteogenic responses, perhaps due to matrix proteoglycan-related "strain memory".

Enzymatically isolated human PDL cells respond biochemically to mechanical and chemical signals. The latter include endocrines, autocrines, and paracrines. Histochemical and immunohistochemical studies showed that during the early places of tooth movement, PDL fluids are shifted, and cells and matrix are distorted. Vasoactive neurotransmitters are released from periodontal nerve terminals, causing leukocytes to migrate out of adjacent capillaries. Cytokines and growth factors are secreted by these cells, stimulating PDL cells and alveolar bone lining cells to remodel their related matrices. This remodeling activity facilitates movement of teeth into areas in which bone had been resorbed.

This emerging information suggests that in the living mammal, many cell types are involved in the biological response to applied mechanical stress to teeth, and thereby to bone. Essentially, cells of the nervous, immune, and endocrine systems become involved in the activation and response of PDL and alveolar bone cells to applied stresses. This fact implies that research in the area of the biological response to force application to teeth should be sufficiently broad to include explorations of possible associations between physical, cellular, and molecular phenomena. The goals of this investigative field should continue to expound on fundamental principles, particularly on extrapolating new findings to the clinical environment, where millions of patients are subjected annually to applications of mechanical forces to their teeth for long periods of time in an effort to improve their position in the oral cavity. Recently developed research tools such as cell culture techniques and immunologic probes, are the best hope for enhancing this development.
Structural Characteristics of Human Salivary Statherin: A Model for Boundary Lubrication at the Enamel Surface
Authors: Ramasubbu Narayanan , Thomas Leonard M. , Bhandary Krishna K. , Levine Michael J.
Published: January 2017

A three-dimensional structural model for salivary statherin in aqueous phase has been developed using structure prediction, circular dichroism, molecular modeling, and mechanics. The relevant structural features of statherin are N-terminal helix segment connected to a long poly-L-proline type II segment, which is followed by a short extended structure. Using this model, the hydroxyapatite binding ability of statherin has been explained. The hydroxyapatite binding region is comprised of the N-terminal acidic residues (Asp-pSer-pSer-Glu-Glu) and Glu-26, which are clustered together in space. Partial conformational unfolding and oriented aggregation of several statherin molecules at the enamel surface provides an amphipathic film that is responsible for the boundary lubrication exhibited by statherin.
Signaling Mechanisms That Regulate Saliva Formation
Authors: Baum Bruce J. , Yanshan Dai  , Hiramatsu Yukiharu , Horn Valerie J. , Ambudkar Indu S.
Published: January 2017

The precipitating event in the formation of saliva is the binding of neurotransmitter molecules to cell surface receptor proteins. The principal neurotransmitters involved are acetylcholine and norepinephrine that bind, respectively, to muscarinic-cholinergic, and a- and β-adrenergic receptors. The transduction of the extracellular signal requires an integral membrane protein capable of binding GTP, a G protein, that specifically interacts with the receptor. The components of G protein transduction systems are fairly well studied, but the pathways by which signals are routed are just being recognized. Delineation of such routing pathways is essential to understanding the regulation of saliva formation.
Sorting and Secretion of Salivary Proteins
Authors: Castle J. David , Castle Anna M.
Published: January 2017

Most salivary proteins are stored in secretion granules prior to export from acinar cells in response to neural stimuli. A small subset of these proteins undergo unstimulated secretion without apparent storage. This pathway probably comprises vesicles that bud from maturing storage granules and carries proteins that do not aggregate efficiently at the storage site. Expression of a parotid proline-rich protein (and deletion mutants) in pituitary AtT-20 cells has shown that an N-terminal domain is necessary for storage in secretion granules. Evidence suggests that self-aggregation of proline-rich protein mediated by this domain may function in both efficient intracellular transport and storage. Thus selective aggregation may be an important secretory sorting mechanism.
Molecular Biology of Human Salivary Cysteine Proteinase Inhibitors
Authors: Saitoh Eiichi , Isemura Satoko
Published: January 2017

The synthesis of human cystatins of family II is controlled by a multigene family having at least 7 members that are localized on chromosome 20, the cystatin gene family. Proteolytic degradation and phosphorylation of the gene products give rise to heterogeneity and multiplicity of cystatins in human saliva. These cysteine proteinase inhibitors, as well as other members of the cystatin superfamily, are evolutionally and functionally related to Bowman-Birk type serine proteinase inhibitors.
Developmental Aspects of Fluid and Electrolyte Secretion in Salivary Glands
Authors: Martinez J. Ricardo
Published: January 2017

The salivary glands of rodents undergo considerable cytodifferentiation after birth and are useful models for the study of functional development, including the mechanisms of fluid and electrolyte secretion. In the rat submandibular gland, secretion of salivary fluid cannot be elicited until approximately 2 weeks of age. The currently accepted model of salivary fluid secretion indicates that this process depends on the activation, on stimulation of cholinergic receptors, of several ion transport systems, resulting in a net transport of osmotically active ions (primarily Cl- and Na +) across the acinar epithelium. This creates the necessary osmotic gradient for the transacinar movement of water. The process is associated with a signal transduction pathway involving the formation of phosphoinositide products (primarily inositol triphosphate or IP3) and the mobilization of Ca2+. The latter regulates monovalent ion conductances (K+, CI-), which are critical for the secretory process. Immature submandibular glands and cells of early postnatal rats have a lower density of cholinergic receptors and release less K+ and Cl- than mature cells and gradually develop other ion transport systems (such as a Na, K, 2Cl cotransport system) involved in the secretory process. Surprisingly, they form more IP3 and show a larger increase in cytosolic Ca2+ when stimulated with maximal or supramaximal concentrations of agonist. Therefore, they show some interesting dissociations in the signal transduction mechanism that suggest differences in the coupling between receptors and membrane phosphoinositides, between IP3 and IP3-dependent Ca2+ stores, and between the Ca2+ signal and the monovalent ion transport systems which are critical for secretion.
Aminoglycoside-Associated Nephrotoxicity in the Elderly
Authors: Baciewicz Anne M , Sokos Denise R , Cowan Ronald I
Published: January 2017

OBJECTIVE:

To determine whether there was an increased incidence of nephrotoxicity in elderly patients (≥65 y) prescribed single-dose (SD) versus multiple-dose (MD) aminoglycosides and whether aminoglycoside-induced nephrotoxicity was associated with length of therapy and other risk factors.

METHODS:

A prospective, observational audit at a university teaching hospital was conducted. Physician prescribing was used to stratify subjects according to dosing regimen: MD (n = 60) or SD (n = 26). Nephrotoxicity was defined as an increase in the serum creatinine level of 0.5 mg/dL sustained over 2 days.

RESULTS:

Eighty-six patients were included; 9.3% developed nephrotoxicity, of whom 62.5% received SD therapy. The incidence of nephrotoxicity did not differ between regimens (p = 0.051). There was an increased length of therapy in those who developed nephrotoxicity (mean ± SD 6.1 ± 6.2 vs. 3.7 ± 2.8 d; p = 0.044). Additionally, patients who developed nephrotoxicity had an increased length of hospitalization (20.3 ± 16.1 vs. 8.4 ± 5.4 d; p < 0.001). Nephrotoxicity correlated with a diagnosis of diabetes mellitus (OR 15.1; 95% CI 1.11 to 205), concomitant angiotensin-converting enzyme (ACE) inhibitor therapy (OR 28.0; 95% CI 2.15 to 365), and SD therapy (OR 20.7; 95% CI 1.45 to 297).

CONCLUSIONS:

Our overall incidence of nephrotoxicity is consistent with that reported in the literature. A diagnosis of diabetes mellitus, concomitant use of ACE inhibitors, and SD regimens were risk factors for the development of nephrotoxicity. An adequately powered, randomized trial is needed to assess whether a difference in the incidence of nephrotoxicity exists between SD and MD therapy in the elderly.
Antifungal Susceptibility Testing in Teaching Hospitals
Authors: Pai Manjunath P , Pendland Susan L
Published: January 2017

BACKGROUND:

An assessment of antifungal susceptibility testing (AST) has not been conducted since the introduction of the National Committee for Clinical Laboratory Standards (NCCLS) M27-A document.

OBJECTIVE:

To determine AST practices in teaching hospitals.

METHODS:

A questionnaire was mailed to the heads of 386 randomly assigned microbiology departments from teaching hospitals identified through the 2000 American Hospital Association Guide. Identifiers were used to delineate responders from nonresponders. A reminder letter was mailed 3 weeks after the initial mailing to all nonresponders. The hospital bed-size and number of inpatient days for respondents were obtained through the American Hospital Directory.

RESULTS:

The questionnaire was returned by 171 (44.3%) institutions. The total and median (range) number of candida isolates were 137 088 and 8.5 (1–145)/1000 inpatient days for the year 2000, respectively. Approximately 1% (1300) of candida isolates, from predominantly blood specimens, underwent AST. AST was reported by 115 (67.2%) hospitals, with testing on site at 27 hospitals and off site for 88 hospitals. NCCLS methodology (80% broth microdilution) was used by 75% of the hospitals performing on-site AST. The median time to obtain AST results was significantly lower when testing was performed on site (3 d) compared with off site (7–10 d).

A large number of candida bloodstream isolates undergoes AST annually. AST results are obtained sooner when performed on site compared with off site.
Acute Liver Failure with Concurrent Bupropion and Carbimazole Therapy
Authors: Ai-Leng Khoo , Lai-San Tham , Kang-Hoe Lee , Gek-Kee Lim
Published: January 2017

OBJECTIVE:

To report a case of fatal liver failure possibly associated with concurrent use of bupropion and carbimazole.

CASE SUMMARY:

A 41-year-old Chinese man with a history of hyperthyroidism had been treated with carbimazole and propranolol for the past 5 years. He received a 10-day course of bupropion as an aid for smoking cessation 10 weeks prior to presentation. He developed acute liver failure with rapid deterioration of renal function. Liver biopsy showed evidence of nonspecific drug-induced acute liver injury. His condition was further complicated by sepsis and coagulopathy. Death resulted 19 days after the onset of symptoms. The likelihood that bupropion induced hepatotoxicity in our patient was possible, based on the Naranjo probability scale.

DISCUSSION:

Although there is increasing evidence of hepatotoxicity induced by bupropion, this is the first case of fatality that could have resulted from acute liver failure in a patient receiving bupropion while on concomitant treatment with carbimazole.

CONCLUSIONS:

Clinicians should be aware of the possibility of acute liver insult induced by bupropion given concurrently with other hepatotoxic drugs.
Fulminant Hepatic Failure Associated with Propylthiouracil
Authors: Ruiz Jorge K , Rossi Giorgio V , Vallejos Humberto A , Brenet Rosemarie W , Lopez Isabel B , Escribano Alfonso A
Published: January 2017

OBJECTIVE:

To report 2 fatal cases of fulminant hepatic failure associated with propylthiouracil treatment against hyperthyroidism.

CASE SUMMARY:

Two women, 30 and 32 years old with no previous liver disease, were treated with propylthiouracil against Graves' disease. Both patients developed jaundice after a 4- and 5-month treatment period, respectively. The disease was similar to viral hepatitis, with a progressive course to severe liver dysfunction and death, along with multisystem organ failure despite extensive therapeutic measures. One of the patients was pregnant and subsequently miscarried. Neither patient had a history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. A submassive necrosis was shown in a postmortem histologic study.

DISCUSSION:

Naranjo probability scale criteria applied to both cases confirm the adverse reactions as probable. These cases fit the requirements of drug hepatotoxicity proposed by Hanson and the Council of the International Organization of Medical Sciences. Eight deaths associated to propylthiouracil were found in our review of the medical literature up to December 2000.

CONCLUSIONS:

Despite the widespread use of propylthiouracil, fulminant hepatitis with death is exceptionally rare; these 2 cases could be added to the fatal outcomes published to date.
Factors Influencing Consumer Use of Written Drug Information
Authors: Koo Michelle M , Krass Ines , Aslani Parisa
Published: January 2017

OBJECTIVE:

To provide an overview of the use and impact of written drug information (WDI) on consumers, and to review the literature on the factors influencing the use of WDI by consumers.

DATA SOURCES:

Relevant articles published in English since the late 1970s were identified based on searches of on-line databases, texts, and cited references in published articles.

STUDY SELECTION:

Articles reporting findings on the origin, use, and impact of WDI were included. Due to limited literature, articles reporting findings on factors influencing the use of written drug as well as disease information were included.

DATA EXTRACTION:

Due to the lack of design consistency between studies and the comparatively small volume of work, subjective assessment rather than a criteria-based objective review was deemed more appropriate.

DATA SYNTHESIS:

To date, research on WDI has focused on its use and impact. WDI has the potential to increase patients' knowledge, compliance, and satisfaction. However, there is also the potential for anxiety or premature cessation of therapy due to fear of possible adverse effects. Multiple factors may potentially influence the use of WDI by consumers including those associated with the written information document (readability, presentation), the patient (health literacy, role of caregiver, demographic factors, health locus of control, coping style, health belief model), and the environment (timing of provision, experience).

CONCLUSIONS:

WDI has the potential to impact consumers positively and negatively. Although not widely investigated, a number of factors can potentially influence the use of WDI by consumers. The findings of this review can form the basis for much needed further research.
Treatment of Disseminated Herpes Zoster Infections
Authors: Hopefl Alan W.
Published: January 2017

Of all the infectious complications which plague the immunosuppressed patient, viral infections are the least amenable to drug therapy. Disseminated herpes zoster infections are relatively uncommon in immunosuppressed patients, but affect as many as 25 percent of patients with Hodgkin's disease. Herpes zoster infections are caused by the varicella-zoster virus (VZV), a DNA containing virus which is the etiological agent of both chickenpox and shingles. Vidarabine (ara-A) is a synthetic nucleoside which inhibits viral induced DNA-dependent DNA polymerase, and therefore viral replication. While vidarabine is remarkably nontoxic at a daily dose of 10 mg/kg, there is at present little evidence that early therapy of disseminated herpes zoster prevents visceral disease, further dissemination, or affects the incidence of postherpetic neuralgia. Initial studies employing human leukocyte interferon show promise, but large scale trials have been hampered by limited supplies of interferon.
The Utilization of a Clinical Pharmacist—A Way of Decreasing Medications in a Community Hospital
Authors: Massoud Neil , Gudauskas Gedy
Published: January 2017

This article summarizes the results of a study designed to evaluate clinical pharmacy services as a means of reducing drug usage in a 170-bed community hospital. A total of 591 medication orders for 93 hospitalized patients were evaluated. A pharmacy resident made recommendations regarding the appropriateness of the medication order to the attending physicians. A team of reviewing physicians later evaluated these recommendations. The resident's suggestions were also monitored by a university-affiliated and experienced clinical pharmacist. The number of medications ordered which the pharmacy resident would have prescribed during consultation with physicians was 312 (53 percent), while the overseeing clinical pharmacist would have prescribed 352 (60 percent). Two hundred and fifteen therapeutic recommendations were provided by the pharmacy resident, of which 38 (17.6 percent) were carried out by the attending physician. The reviewing physicians did not agree with 37 of these recommendations. Twenty-two drug interactions were detected, of which eleven were thought to be of definite clinical significance by the pharmacy resident. The study demonstrated that a 40 percent reduction in medication utilization could result in a community hospital, while the same level of therapeutic effectiveness was maintained, by using the services of a properly trained clinical pharmacist. The patient care appraisal committee which was appointed to evaluate the study reviewed the results and agreed that, based on the cost factor and improvement of patient care, clinical pharmacy services would be beneficial.
Correlation between the Total Cholesterol Serum Concentration Data and Carbamazepine Steady-State Blood Levels in Humans
Authors: Wichliński Leslaw M. , Sieradzki Edmund , Gruchala Maria
Published: January 2017

The purpose of this study was to investigate the pharmacokinetics of carbamazepine at steady state, after multiple doses in patients with elevated serum cholesterol levels. Twelve patients participated in the investigation; patients were divided into two groups according to their total serum cholesterol levels. Each patient received multiple doses of carbamazepine 600 mg po once per day. Blood samples were collected and analyzed for carbamazepine by gas-liquid chromatography. The clearance concept was used to describe the pharmacokinetic behavior of carbamazepine in high and low cholesterol patients. The area under the plasma concentration-time curve was determined by the trapezoidal rule method. This value was used to determine the oral dose clearance. In this study, the authors found that the elevated serum cholesterol and elevated total lipids cause a decrease in drug concentration. The significantly higher values of the total body clearance of carbamazepine, obtained in patients with elevated serum cholesterol levels, may have significance in clinical practice.
Hemolytic Anemia and Pancytopenia Induced by Cefoxitin
Authors: DeTorres Olga H.
Published: January 2017

A 77-year-old man received cefoxitin for the treatment of peritonitis. He developed hemolytic anemia and became clinically jaundiced. The patient was switched from cefoxitin to doxycycline. His total bilirubin decreased and his hematocrit increased. Several weeks later he developed septicemia. For an infiltration in the left lower lobe, he was treated with cefoxitin and gentamicin. The patient proceeded to develop a mild granulocytopenia and thrombocytopenia. Anemia was not seen because the patient was transfused several times. Bone marrow aspiration showed a mildly hypocellular marrow with a depression of all cell series, suggesting drug-induced bone marrow toxicity. Nine days after discontinuing cefoxitin, his blood elements had gone back to normal. This is the fourth case on file at Merck Sharp & Dohme of hemolytic anemia induced by cefoxitin. There have been several reports of hemolytic anemia or pancytopenia caused by cephalothin, but few, if any, citing the other cephalosporins, particularly cefoxitin. Clinicians should be made aware of the possibility of hematologic toxicities occurring with cefoxitin therapy. Patients should have their erythrocytes, leukocytes, and platelets monitored while on this drug.
Correlation of Delayed Peak Concentration with Infusion-Site Irritation following Diazepam Administration
Authors: Hussey Elizabeth K. , Dukes George E. , Messenheimer John A. , Brouwer Kim L.R. , Donn Karl H. , Krol Thomas F. , Hak Lawrence J.
Published: January 2017

Diazepam 10 mg/2 mL iv was administered undiluted over five minutes to nine healthy men on two separate occasions. The infusion site was evaluated before and after each infusion by subject assessment of pain on a severity scale of zero (none) to ten (most). Blood samples were collected at 0, 5, 20, 30, 45, and 60 minutes, and periodically for 72 hours postinfusion. Diazepam plasma concentrations were determined by HPLC. Concentrations at five minutes (end of infusion) ranged from 0 to 889 ng/mL. Maximum plasma concentration (Cmax) was observed at 5 minutes for 10 treatments, at 20 minutes for 7 treatments, and at 30 minutes for 1 treatment. The observed Cmax ranged from 221 to 889 ng/mL. When time to reach peak plasma concentration (tmax) was 5 minutes, the Cmax was significantly greater than when tmax was 20 minutes (670 ± 87 vs. 267 ± 40 ng/mL, p<0.005). The area under the curve did not differ significantly between these two groups. The pain score at the end of infusion ranged from zero to five and was inversely related to the concentration at five minutes (r2 = 0.45, p=0.002). The association between venous irritation, a low plasma concentration at the end of the infusion, and a delayed Cmax suggests that diazepam precipitated in the vein.
Lack of Weight Gain Associated with Short-Term Astemizole Treatment
Authors: Ellison Mark J. , Horner Ronnie D. , Lawler Frank H. , Jones James G.
Published: January 2017

The effect of treatment with astemizole for three weeks on weight was assessed in 44 patients with seasonal allergic rhinitis who participated in a randomized, double-blind, placebo-controlled clinical trial. Astemizole 10-mg tablets and identical placebo tablets were used. Compared with baseline, weight increased significantly in astemizole-treated patients (1.07 ± 1.39 kg; p = 0.0004); however, the mean change in weight in astemizole-treated patients was not statistically significantly different than that seen in placebo-treated patients (0.85 ± 1.68 kg). No relationship was found between changes in weight and age, sex, initial weight, percentage of obesity, and plasma astemizole concentrations.
Comparative Bioavailability Characteristics of Commercial Quinidine Polygalacturonate and Sulfate Tablets
Authors: Dahl Jeffrey R. , Ueda Clarence T. , Meyers David G. , Wulf Bradley G.
Published: January 2017

This study compared the relative bioavailability characteristics of quinidine polygalacturonate (QP) and quinidine sulfate (QS) after oral administration of commercial tablets and a liquid form prepared from crushed tablets in 13 healthy adult male volunteers. Each subject received the following four single-dose treatments in a randomized, crossover manner with a one-week washout period between treatments: 400 mg QS liquid, two 200-mg QS tablets, 550 mg QP liquid, and two 275-mg QP tablets. All four treatments were equivalent in terms of the dose of quinidine base. Multiple serum samples and two 24-hour urine specimens were collected over 24 and 48 hours, respectively, and assayed for quinidine with a specific HPLC assay method. For the absorption and disposition parameters measured (maximum serum concentration, time to reach maximum concentration, area under the concentration-time curve [0–48 hours], absorption and elimination rate constants, absorption and elimination half-lives, apparent total body clearance, apparent volume of distribution, and dose fraction excreted in the urine) no significant differences were observed for any of the parameters among the four treatments (p>0.05). The results of the present investigation demonstrated that QP and QS produced identical serum quinidine concentration-time curves when given in the form of a tablet or liquid. The clinical implications of these observations with respect to the dosing of QP are discussed.
Intravenous Immune Globulin for the Treatment of Presumed Quinidine-Induced Thrombocytopenia
Authors: Ray James B. , Brereton William F. , Nullet Francis R.
Published: January 2017

Quinidine is cited as one of the most frequent causes of drug-induced thrombocytopenia. This case report describes the use of high-dose intravenous gamma globulin to rapidly reverse qunidine-induced thrombocytopenia in a patient at increased risk for bleeding because of the presence of an antitachycardia pacemaker and an automatic implantable cardiac defibrillator. This report suggests that this treatment may aid in a more rapid reversal of quinidine-induced thrombocytopenia in patients at high risk of bleeding.
Ciprofloxacin Penetration into Human Breast Milk: A Case Report
Authors: Cover Darra L. , Mueller Bruce A.
Published: January 2017

The concentration of ciprofloxacin achieved in human breast milk following oral administration of a single 500-mg dose was investigated. A 24-year-old white woman, 17 days postpartum, was being treated for resolving acute renal failure. Oral ciprofloxacin was prescribed for a suspected urinary tract infection. Due to suspected pediatric toxicity and a lack of published information describing ciprofloxacin excretion in breast milk, the antibiotic was discontinued after one 500-mg dose. All breast milk was collected at four-hour intervals and was tested for the presence of ciprofloxacin by bioassay. Ciprofloxacin breast milk concentrations were 9.1, 9.1, 9.1, and 6.0 μmol/L at 4, 8, 12, and 16 hours postdose, respectively. These ciprofloxacin concentrations were similar to other published body fluid concentrations following a single oral 500-mg dose.
Severe Verapamil (Sustained-Release) Overdose
Authors: Krick Stacie E. , Gums John G. , Grauer Ken , Cooper Gary R.
Published: January 2017

Vasodilators, specifically calcium-channel modulators, are currently in widespread use for the treatment of essential hypertension. Several reports of toxicity from immediate-release verapamil have appeared in the literature. We present a case of sustained-release verapamil overdose as a consequence of an attempted suicide. The treatment measures used in a verapamil toxicity are discussed, as well as a review of the current literature on verapamil overdose.
Pharmacologic Interventions for the Treatment of Opioid Dependence and Withdrawal
Authors: Guthrie Sally K.
Published: January 2017

This article discusses current pharmacologic methods in the treatment of heroin dependence and withdrawal. Methadone hydrochloride, the most commonly used opiate agonist, is used for both withdrawal and maintenance therapy. However, it produces dependence and withdrawal results upon abrupt discontinuation. Other opiate agonists including l-alpha acetyl methadyl (LAAM) and propoxyphene napsylate have been used for both withdrawal and maintenance therapy. LAAM is currently available only as an investigational agent and propoxyphene is easily accessible but has been associated with hallucinations and dysphoria at high doses. Alpha2-adrenergic agonists decrease opiate withdrawal symptoms by decreasing the central adrenergic hyperarousal that is associated with withdrawal. Clonidine effectively attenuates but does not totally eliminate withdrawal symptoms. Other alpha2-adrenergic agonists (e.g., lofexidine hydrochloride, guanfacine hydrochloride, and guanabenz) have undergone only preliminary investigations. Although alpha2 agonists effectively decrease most withdrawal symptoms they often cause hypotension. Buprenorphine hydrochloride is a partial opiate agonist that shows some promise in the treatment of the heroin-dependent population. It attenuates opiate craving and causes only minimal withdrawal upon abrupt discontinuation. Because it is well accepted by the heroin-dependent population, however, it may ultimately become an abused substance. Naltrexone is a potent, orally acting opiate antagonist that blocks all opiate-agonist effects and causes no euphoria. Unfortunately, it has not been well accepted by the heroin-dependent population. Scant research has been conducted concerning the use of adjunctive medications during opioid withdrawal.
Clomipramine: A Tricyclic Antidepressant Effective in Obsessive Compulsive Disorder
Authors: Kelly Michael W. , Myers Carol W.
Published: January 2017

Clomipramine hydrochloride, a chlorinated analog of imipramine, is a widely used antidepressant recently approved for use in the U.S. for the treatment of obsessive-compulsive disorder (OCD), a potentially incapacitating affliction. Its primary pharmacologic action is blockade of the reuptake of the neurotransmitter serotonin. Its metabolite, desmethylclomipramine, is a potent norepinephrine reuptake inhibitor. Significant first-pass metabolism reduces oral bioavailability to <62 percent. The drug is widely distributed throughout the body (volume of distribution 9–25 L/kg) and is 90–98 percent protein-bound. Clomipramine follows first-order elimination pharmacokinetics, with a plasma half-life of 20–24 hours. Recent double-blind controlled clinical trials have demonstrated the drug's effectiveness in the treatment of OCD. Response is most often associated with doses >75 mg/d, with 250 mg the maximum recommended daily dose. Relapse upon withdrawal is frequently reported. The adverse effect profile of clomipramine is similar to other tricyclic antidepressants, with anticholinergic, cardiovascular, sexual, and central nervous system effects the most prominent.
Zidovudine Update: 1990
Authors: Morse Gene D. , Lechner Judith L. , Santora Julie A. , Rozek Susan L.
Published: January 2017

Zidovudine (ZDV) is the only approved antiviral for the treatment of human immunodeficiency virus infection (HIV) in the U.S. Although newer antivirals have reached Phase II testing, ZDV is now the accepted therapy against which all other agents will be compared. Zidovudine 1500 mg/d was previously prescribed only to adult HIV-infected patients who had developed AIDS or AIDS-related complex (ARC). However, results obtained from recently completed studies indicate that a lower daily dose (500 mg) appears to be equivalent. In addition, ZDV therapy appears to be beneficial to asymptomatic HIV-infected patients with CD4+ counts >500/mm3. The toxicity profile of ZDV, previously obtained from patients receiving 1500 mg/d, consisted of either acute (e.g., fever, rash, headache) or chronic (e.g., anemia, neutropenia, myopathy) adverse effects. ZDV pharmacokinetics are variable within and between the different subpopulations of HIV-infected patients who have been studied. Bioavailability ranges from 50 to 70 percent, and values for half-life, total body clearance, and volume of distribution are 1–2 h, 20–40 mL/min/kg, and 1–2 L/kg, respectively. Drug interactions occur primarily between ZDV and other agents that undergo hepatic glucuronidation (e.g., probenecid, sulfamethoxazole) resulting in decreased ZDV clearance. ZDV is currently measured by HPLC, radioimmunoassay and FPIA; however, the role of therapeutic monitoring is currently under investigation. Studies of ZDV therapy in neonates, pediatric patients, patients with resistant isolates of HIV, and HIV-infected patients receiving combined treatment with other reverse transcriptase inhibitors or immunomodulators are ongoing.
Evaluation of a Non-Food and Drug Administration-Approved Use of Cimetidine: Treatment of Pruritus Resulting from Epidural Morphine Analgesia
Authors: Raisch Dennis W. , Barreuther Alan D. , Osborne Robert C.
Published: January 2017

The purpose of this study was to evaluate the efficacy of a frequently used treatment at our hospital, intravenous cimetidine hydrochloride for pruritus resulting from epidural morphine sulfate analgesia in cesarean-section patients. Fifty-two patients were randomly assigned to receive either placebo or cimetidine 300 mg iv. Thirty-nine patients experienced itching. Thirty-three patients completed the study (17 in the cimetidine group, 16 in the placebo group). For pruritus unrelieved by the study drug, bolus doses of naloxone hydrochloride 0.2 mg iv were administered at 30-minute intervals, if needed. Pruritus was assessed by two subjective rating scales and the number of naloxone doses needed for unrelieved pruritus. Using independent Student's t-tests, we identified no significant differences between the two groups. The mean numbers of naloxone boluses administered were 1.9 for placebo and 2.5 for cimetidine (p=0.49). Our study demonstrates the importance of objectively evaluating the use of drugs for non-Food and Drug Administration-approved indications.
Meperidine Serum Concentrations and Analgesic Response in Postsurgical Patients
Authors: Baumann Terry J. , Smythe Maureen A. , Marikis Bessie , Bivins Brack A.
Published: January 2017

We examined the relationship between serum concentrations of meperidine hydrochloride and analgesic response in postsurgical patients allowed to use patient-controlled analgesia (PCA) and compared these findings with those of patients receiving conventional intramuscular (IM) dosing. Six patients who had undergone abdominal surgery were randomly assigned to receive postoperative analgesia with either PCA or IM therapy. A sequence of five-point pain and sedation scores and serum meperidine concentrations were obtained in all patients the day after surgery. Minimum effective concentration (MEC) was defined as that concentration of meperidine at which patients felt pain relief as indicated by a decrease in pain rankings. The mean MEC for patients using PCA, 296 ± 112 ng/mL, was significantly lower than the mean MEC in patients receiving IM dosing (551 ± 164 ng/mL, p<0.05). The mean maximum change in meperidine concentrations in the PCA group, 177± 88 ng/mL, was significantly lower than that of the IM group (484±125 ng/mL, p<0.05). Mean maximum changes in pain and sedation scores for patients in the PCA group were not significantly different from those of the IM group. During this investigation patients using PCA experienced smaller swings in meperidine concentrations than did patients receiving IM injections. MEC analysis suggests that PCA patients may experience pain relief at lower meperidine concentrations than those needed by IM patients.
Mechanism of Interaction between Theophylline and Mexiletine
Authors: Ueno Kazuyuki , Miyai Kazuyoshi , Kato Motoichi , Kawaguchi Yoshihiro , Suzuki Toshio
Published: January 2017

The mechanism of an interaction between theophylline and mexiletine hydrochloride was investigated in 6 male inpatients coadministered both drugs and 16 inpatients (13 men, 3 women) administered theophylline only. Serum theophylline and mexiletine concentrations and urinary concentrations of theophylline and its metabolites were monitored. Theophylline clearance was 0.0278 ± 0.0047 L/kg/h (mean ± SD) in patients coadministered theophylline and mexiletine and 0.0441 ± 0.0096 in patients administered theophylline only (p<0.05). The fractional urine contents of 1-methyluric acid and 3-methylxanthine were 18.7 ± 2.5 and 12.6 ± 2.1 percent in the former group and 26.5 ± 6.0 and 17.1 ± 2.0 percent in the latter group, respectively (p<0.05). The fractional urine content of 1,3-dimethyluric acid was 51.8 ± 3.2 in the former and 44.7 ± 4.1 percent in the latter, respectively (p<0.05). An inverse correlation was obtained between serum mexiletine concentrations and total fractional urine content of 1-methyluric acid and 3-methylxanthine (r = 0.704). These results suggest that the mechanism of an interaction between theophylline and mexiletine is an inhibition of demethylation of theophylline by mexiletine.
Altered Absorption of Digoxin, Sustained-Release Quinidine, and Warfarin with Sucralfate Administration
Authors: Rey Aixa M. , Gums John G.
Published: January 2017

A case is reported of a 71-year-old woman who displayed altered absorption of digoxin, quinidine sulfate, and warfarin sodium after being given sucralfate. The administration of sucralfate resulted in subtherapeutic serum concentrations of digoxin and quinidine, and also reduced the patient's prothrombin time (PT). Discontinuation of sucralfate increased PT and reestablished therapeutic concentrations of digoxin, quinidine, and warfarin. Patients receiving sucralfate concomitantly with digoxin, quinidine, and warfarin should be monitored frequently with regard to serum drug concentration and disease symptomatology.
Controversies in Cardiopulmonary Resuscitation: Pediatric Considerations
Authors: Thompson Dennis F. , Raebel Marsha A. , Sagraves Rosalie , Kamper Claudia
Published: January 2017

This article addresses some therapeutic controversies concerning medications that may be needed during advanced pediatric life support (APLS) and the routes of administration that may be selected. The controversies that are discussed include the appropriateness and selection of various routes for drug administration during APLS; the determination of whether epinephrine hydrochloride is the adrenergic agent of choice for APLS and its appropriate dose; treatment of acidosis associated with a cardiopulmonary arrest; recommendations for atropine sulfate doses; and the role, if any, of calcium in APLS. Background information differentiating pediatric from adult cardiopulmonary arrest is presented to enable the reader to have a better understanding of the specific needs of children during this life-threatening emergency. The article also presents an overview of various drugs used for APLS and a table of their typically recommended doses and routes of administration.
The Dose of Epinephrine during Cardiopulmonary Resuscitation in Humans: What Should it Be?
Authors: Gonzalez Edgar R. , Ornato Joseph P.
Published: January 2017

The objective of vasopressor therapy during closed-chest cardiopulmonary resuscitation (CPR) is to augment coronary perfusion pressure so that spontaneous circulation can be reestablished. Epinephrine, an endogenous catecholamine with both alpha- and beta-adrenergic activity, is the vasopressor of choice for use during CPR. Epinephrine's potent alpha,- and alpha2-adrenergic effects improve cerebral and myocardial blood flow by preventing arterial collapse and by increasing peripheral vasoconstriction. The optimal dose of epinephrine in humans during closed-chest CPR is unknown. Studies suggest that the dose of epinephrine currently recommended during CPR may be five to ten times lower than the dose required to produce the beneficial pharmacologic effects observed in animal models of closed-chest CPR. Data from patients with prehospital cardiac arrest indicate that a 5-mg dose of epinephrine may be required to increase diastolic blood pressure above 30 mm Hg. Until additional data are available, our clinical experience suggests that all patients should receive at least one 1-mg dose of epinephrine. If the patient fails to respond, the administration of 3–5 mg of epinephrine every five minutes or the use of continuous infusions of epinephrine (0.2–0.6 mg/min) may be indicated.

The results of ongoing clinical trials comparing conventional epinephrine regimens with high-dose regimens will provide valuable information and will assist clinicians in establishing an optimal dosage range for epinephrine during CPR in humans. What is the best vasopressor regimen to use during CPR in humans? Although dopamine, methoxamine, phenylephrine, or norepinephrine have been used during resuscitation, epinephrine is still the vasopressor agent of choice.5 The optimal dose of epinephrine during CPR in humans remains to be determined. It is likely that a range of dosages will be needed to account for differences in vascular reactivity between prehospital cardiac arrest victims with prolonged down-times and inpatients with witnessed cardiac arrest and immediate ACLS. The use of high-dose epinephrine is not without risks. Epinephrine may precipitate myocardial ischemia, tachyarrhythmias, hypertensive crisis, pulmonary edema, digitalis toxicity, and cardiac arrest.5 Antidepressants, anesthetics, sympathomimetics, bretylium, and phosphodiesterase inhibitors potentiate epinephrine's arrhythmogenic effect.50 Until definitive data are available, our clinical experience suggests that all patients should receive at least one dose of epinephrine 1 mg. If the patient fails to respond, the administration of epinephrine 3–5 mg every five minutes or the use of continuous infusions of epinephrine (0.2–0.6 mg/min) may be indicated. Whenever possible the administration of epinephrine, especially at a higher dose or by continuous infusion, should be accomplished through an indwelling central venous catheter.