bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary Proline-rich Proteins: Biochemistry, Molecular Biology, and Regulation of Expression
Authors: Carlson Don M.
Published: January 2017

The proline-rich proteins (PRPs) in mammalian salivary glands are encoded by tissue-specific multigene families whose members have diverged with respect to structure and regulation of expression. PRPs are expressed constitutively in humans, and comprise about [70%] of the total salivary proteins. Families of similar proteins are dramatically increased or induced in parotid and submandibular glands of rats, mice and hamsters by treatment with the [β-] agonist isoproterenol. Feeding tannins to rats and mice mimics the effects of isoproterenol on the parotid glands. Salivary PRPs may constitute a defense mechanism against tannins and other polyhydroxylated phenols ingested. Putative transcriptional regulatory sequences have been identified in mouse PRP genes.
The Remarkable Evolutionary History of the Human Amylase Genes
Authors: Meisler Miriam H. , Ting Chao-Nan
Published: January 2017

Analysis of the structures of the human amylase genes has demonstrated that this multigene family contains at least five tandem gene copies, closely related in sequence but with distinct tissue specific expression. The structures of the genes demonstrate that the human salivary amylase gene was derived from a preexisting pancreatic amylase gene. Insertion of a retrovirus upstream of the amylase gene is responsible for the alteration in tissue specificity. A parotid specific enhancer has been identified within the retrovirus by expression studies in transgenic mice. The independent origin of salivary amylase in rodents and primates suggests that there has been strong evolutionary selection for amylase in saliva. The amylase genes demonstrate a novel mechanism for evolution of new patterns of tissue specific gene expression.
The B1-Immunoreactive Proteins of the Perinatal Submandibular Gland: Similarity to the Major Parotid Gland Protein, RPSP
Authors: Ball William D. , Hand Arthur R. , Moreira Jorge E. , Iversen Jeanne M. , Robinovitch Murray R.
Published: January 2017

The B1-immunoreactive proteins of type in cells of the perinatal rat submandibular gland are immunologically cross-reactive with proteins of both the sublingual and parotid glands; in particular, protein SMG-A appears similar to a major parotid protein. We isolated SMG-A and the parotid protein (known as M1 or leucine-rich protein), prepared polyclonal antibodies to them, and compared their biochemical properties and immunological reactivities. They were identical in their molecular weight on SDS-PAGE (23.5 kDa), tenacious binding to Affi-gel Blue, isoelectric point (pH 4.53), and proteolysis to a 14 kDa peptide: Antibodies to SMG-A showed reactivity with protein SMG-C, a product of the neonatal type I cells, as well as with proteins SMG-B1 and SMG-B2, contrasted with the absence of reactivity of anti-M1 IgG with these proteins. Anti-M1 reacted with the "parotid secretory protein" (PSP) of the mouse, and M1 appears to be the homologue, in the rat, of mouse PSP.
Molecular Cloning of Developmentally Regulated Neonatal Rat Submandibular Gland Proteins
Authors: Mirels Lily , Girard Lisa R. , Ball William D.
Published: January 2017

At birth, the rat submandibular gland (SMG) contains two transient secretory cell types that produce several characteristic salivary proteins. Proteins SMG-A, B1, and B2 (23.5, 26 and 27.5 kDa) are products of the neonatal type III cells, but not the adult acinar cells. Protein C (89 kDa), a major product of the neonatal type I cells, is either absent or present at greatly diminished levels in the secretory cells of the adult gland. The decrease in biosynthesis of these neonatal salivary proteins occurs concomitantly with the increase in levels of characteristic adult SMG products. In order to understand these developmentally regulated changes in SMG salivary protein gene expression, we have initiated the molecular cloning and characterization of neonatal submandibular gland proteins from a 5-d-old rat submandibular gland cDNA library. Clones encoding SMG-A were isolated by homology to the mouse parotid secretory protein (PSP). SMG-A was shown to be derived from a salivary protein multigene family that also includes PSP. Cloning and characterization of additional neonatal rat submandibular gland proteins was initiated by screening the 5-d-old rat submandibular gland cDNA library with first strand cDNA prepared from 1-d-old rat submandibular glands. Clones corresponding to a highly abundant 3 kb transcript present in the neonatal rat SMG, but not in adult submandibular, sublingual, or parotid gland have been identified. The size, abundance, and organ specificity of this transcript suggest that it may encode protein C. One clone derived from an unknown transcript that is developmentally regulated in the neonatal SMG and is present in the adult parotid, submandibular, and sublingual glands was also identified.
The Effect of Adrenergic Agonists and Antagonists on the Expression of Proteins in Rat Submandibular and Parotid Glands
Authors: Bedi Gurrinder Singh
Published: January 2017

The present investigation was undertaken to study the effect of adrenoreceptor modulators on the expression of salivary proteins. Sprague-Dawley rats were treated for 10 consecutive days with adrenergic agonists isoproterenol, dobutamine, terbutaline, salbutamol, methoxyphenamine, or methoxamine. Antiserum to selected salivary proteins was used to compare the concentration of these proteins in the submandibular and parotid glands of treated animals. Chronic treatments of rats (50 μmol/ kg body weight for 10 d) with either isoproterenol or dobutamine induced synthesis of a cysteine-proteinase inhibitor (cystatin) in the submandibular glands. When isoproterenol was injected concomitantly with the mixed β-antagonist propranolol or the β1-adrenergic antagonists metaprolol, proctocol, or atenolol, the induction of cystatin was totally suppressed. However, the β2-antagonist, ICI-118551, produced only partial reduction in cystatin induction elicited by isoproterenol. On the contrary, rats treated with either isoproterenol or P,-agonists demonstrated a significantly reduced concentration of serine-proteinase kallikrein in submandibular glands. The decrease observed in submandibular kallikrein of rats treated with isoproterenol was prevented by concomitant treatment with β 1,-antagonists but not with β2-antagonists. Because kallikreins are produced by ductal cells and cystatins are produced by acinar cells of submandibular glands, these observations suggest that there may be differential control of expression of proteins synthesized by ductal and acinar cells. Chronic treatment of rats with nonselective P-agonist isoproterenol or β 1,-selective agonists increased markedly the proline-rich proteins (PRP) in parotid glands, but the parotid amylase concentration was not significantly affected by β-adrenergic agonists. Coinjection of β1-antagonists along with isoproterenol blocked the induction of PRP in the parotid glands. These findings suggest that there may be a differential control of expression of proteins by different cell populations of salivary glands.
Genomic Cloning, Physical Mapping, and Expression of Human Type 2 Cystatin Genes
Authors: Dickinson D.P. , Thiesse M. , Dempsey L.D. , Millar S.J.
Published: January 2017

Humans carry one gene encoding cystatin C and six to eight genes with homology to an S-like cystatin hybridization probe. However, the precise composition and organization of the cystatin gene family remains to be established. Further, the pattern of tissue-specific expression has not been fully defined. We have previously shown that the type 2 cystatin genes are clustered together in a ca. 270 kb region (the CST locus). To determine the structure of this region, we have sought to clone the entire CST locus. Our approach has been to isolate cosmid and lambda genomic clones carrying cystatin genes and then to use "walk" probes derived from the end regions of these clones to identify other clones, which extend them. To date, we have obtained over 320 kb of distinct sequences. Based on restriction maps, sequencing, and hybridization analyses, we have identified eight apparently nonallelic copies of cystatin genes. These include one gene for cystatin C, four closely related genes encoding S-like cystatins, and three genes encoding relatively divergent sequences. Complete assembly of these clones into an unambiguous contiguous sequence is hampered by the presence of flanking locus-specific repetitive-like sequences. RNase protection assays used to characterize the tissue-specific patterns of expression showed that cystatin C is expressed at modest, comparable levels in all tissues examined, whereas expression of the CST 1 gene, encoding cystatin SA-I, was found to be restricted to a small subset of tissues, with the highest level in the submandibular gland. The cystatin gene family, therefore, appears to have evolved by tandem gene duplication, followed by the acquisition of control elements influencing the location and level of expression. The cystatin gene family is, thus, a potentially powerful system for the future study of mechanisms of gene regulation in human salivary glands.
Expression of Human Salivary Histatin and Cystatin/ Histatin Chimeric cDNAs in Escherichia coli
Authors: Bobek L.A. , Tsai H. , Levine M.J.
Published: January 2017

We have previously constructed recombinants encoding the full-length and truncated forms of cystatin-SN and expressed these in the Escherichia coli expression system pGEX-2T, which expresses foreign sequences as fusion proteins with glutathione S-transferase (GST). Recombinant cystatins were produced and purified in large quantities. The full-length recombinant cystatin-SN exhibited comparable biological activity and secondary structure to natural cystatin, validating the use of the full-length and mutant recombinant proteins for structure-function studies of salivary molecules. In this study, we have expressed histatin-1 cDNA in the pGEX-3X vector and cystatin-SN/histatin-1 or cystatin-SN/histatin-3 chimeric cDNAs in the pGEX-2T vector. Gene splicing by overlap extension (SOE), a PCR-based method, was used for generating the chimeric cDNAs. Each construct was analyzed by DNA sequencing, which showed the correct junctions and reading frames between the GST/histatin-1 and the GST/cystatin/histatin cDNAs. Expression of histatin and cystatin/histatin chimeras was induced by IPTG and the production of the fusion proteins monitored by SDS-PAGE/Coomassie blue staining and in the case of the GST/cystatin/histatin fusion proteins, also by Western blot using anti-cystatin antibody. The results of these studies showed that we have successfully constructed recombinants encoding the individual and chimeric salivary molecules and efficiently expressed these in E. coli expression system pGEX. Purification and characterization of recombinant histatin and cystatin-histatin hybrid proteins are presently ongoing.
Effects of Food Mastication on Rat Parotid Gland Adrenergic and Cholinergic Cell Surface Receptors
Authors: Johnson Dorthea A. , Lee Cardenas H.
Published: January 2017

Adult male rats were fed diets of differing texture (liquid, powder, standard pelleted, or bulk pelleted) to alter food mastication. After 2 weeks, the parotid glands were removed and adrenergic and muscarinic-cholinergic cell surface receptor density (fM bound/mg protein) and ligand binding dissociation constants (Kd in nM) were determined by radioligand binding techniques on a crude membrane fraction. For all diets, gland weight increased as the requirement for food mastication increased (i.e., liquid < powder < standard pelleted < bulk pelleted). Among the diets, neither beta-two nor alpha-two receptor density was altered. Beta-one receptor density was directly related to dietary mastication. Compared with the standard pelleted diet, beta-one receptor density was reduced 21% for the liquid diet and 7% for the powdered diet; for the bulk-pelleted diet, beta-one receptor density was increased 11%. With respect to alpha-one receptor density, it was not affected by the liquid or powdered diet when compared with the standard pelleted diet, but alpha-one receptors were increased 14% with the bulk-pelleted diet. Muscarinic-cholinergic receptor density for the liquid diet fed rats was 27% less than for the standard-pelleted diet; powdered diet did not differ from standard pelleted, while that for the bulk-pelleted diet was increased 6%. With but minor exceptions, ligand binding affinity was unaffected by the changes in diet texture. These studies demonstrate that dietary mastication as well as affecting parotid gland weight, cell size, and saliva production also influences autonomic cell surface receptor density.
A Contemporary View of Salivary Research
Authors: Mandel Irwin D.
Published: January 2017

The past 50 years of salivary research has been marked by a series of changing perceptions as new techniques and technologies have illuminated the complexities of the secretory mechanism, salivary composition, and function. The modem era began with the innovations of electrophoresis, chromatography, histochemistry, immunochemistry, electron microscopy, and microphysiology. The idea of saliva as primarily a digestive fluid composed of salts, amylase, and mucin was rapidly broadened to encompass a wide spectrum of protective proteins with the dual responsibility of protecting both hard and soft tissues. Characterization of the secretory IgA and nonimmunological antibacterial systems and the proteins responsible for the regulation of calcium and phosphate levels dominated the research in the 1960s and 1970s. An appreciation of the nature, formation, and role of the salivary pellicle and the interplay between bacterial adherence and agglutination provided a clinical thrust. Morphologists and physiologists redefined the secretory process on a molecular level. The 1980s saw the union of structure and function, both in terms of synthesis and release of the secretory products and their specific roles in the oral cavity in health and disease. The excitement of the 1990s is in the genetic control of processes and products, elucidating the mechanisms, and using the information to improve on nature: an era of great expectations and hubris. This article is essentially a personal guided tour through the past 50 years of salivary research.
Candida and Oral Candidosis: A Review
Authors: Scully C. , EI-Kabir M. , Samaranayake Lakshman P.
Published: January 2017

Candida species are the most common fungal pathogens isolated from the oral cavity. Their oral existence both as a commensal and an opportunist pathogen has intrigued clinicians and scientists for many decades, and recent investigations have revealed many attributes of this fungus contributing to its pathogenicity. In addition, the advent of the human immunodeficiency virus infection and AIDS has resulted in a resurgence of oral Candida infections. Clinicians are witnessing not only classic forms of the diseases but also newer clinical variants such as erythematous candidosis, rarely described hithertofore. Therefore, this review is an attempt at detailing the current knowledge on Candida and oral candidoses together with the newer therapeutic regimes employed in treating these mycoses.
HIV-Related Tumors of the Oral Cavity
Authors: Ficarra G. , Eversole L.E.
Published: January 2017

In HIV-infected patients with AIDS the most frequent malignancies are Kaposi's sarcoma and non-Hodgkin's lymphoma. In these patients, the natural history of these tumors is quite different from those of HIV-negative subjects. These tumors may present atypical clinical aspects, may be very aggressive, and the coexistence of immunosuppression and opportunistic infections may render their treatment more difficult. The aim of this article is to provide updated information on the epidemiology, pathogenesis, natural history, and management of tumors that develop in the oral cavity of patients with AIDS.
Saliva-Bacterium Interactions in Oral Microbial Ecology
Authors: Scannapieco Frank A.
Published: January 2017

Saliva is thought to have a significant impact on the colonization of microorganisms in the oral cavity. Salivary components may participate in this process by one of four general mechanisms: binding to microorganisms to facilitate their clearance from the oral cavity, serving as receptors in oral pellicles for microbial adhesion to host surfaces, inhibiting microbial growth or mediating microbial killing, and serving as microbial nutritional substrates. This article reviews information pertinent to the molecular interaction of salivary components with bacteria (primarily the oral streptococci and Actinomyces) and explores the implications of these interactions for oral bacterial colonization and dental plaque formation. Knowledge of the molecular mechanisms controlling bacterial colonization of the oral cavity may suggest methods to prevent not only dental plaque formation but also serious medical infections that may follow microbial colonization of the oral cavity.
Effect of Clarithromycin on Steady-State Digoxin Concentrations
Authors: Tanaka Hideko , Matsumoto Kana , Ueno Kazuyuki , Kodama Mayumi , Yoneda Kohji , Katayama Yoshiaki , Miyatake Kunio
Published: January 2017

OBJECTIVE:

To evaluate the magnitude and dose-relatedness of the effect of clarithromycin on the pharmacokinetics of digoxin, and to compare the effects of clarithromycin with those of P-glycoprotein inhibitors.

METHODS:

Eight Japanese inpatients with congestive heart failure participated in this study. Each patient received oral digoxin therapy for at least 7 days and were coadministered oral clarithromycin to prevent or treat pneumonia. To evaluate the effects of clarithromycin on the pharmacokinetics of digoxin, digoxin concentrations were compared before and after coadministration of clarithromycin.

RESULTS:

Digoxin concentrations were higher after coadministration of clarithromycin in all patients (before, 0.838 ± 0.329 ng/mL; after, 1.36 ± 0.619 ng/mL); (p < 0.005). A significant correlation was observed between the dose of clarithromycin and the percentage of increase in the digoxin concentration.

CONCLUSIONS:

Digoxin concentrations increased during concomitant administration of clarithromycin, and this effect was dose-dependent on clarithromycin. The percentage increase in digoxin concentrations after the usual oral dose of clarithromycin (400 mg/d) is approximately 70%. Therefore, digoxin concentrations must be monitored carefully after coadministration of clarithromycin, and the doses of digoxin may need readjustment in patients who are concomitantly receiving clarithromycin.
Pseudo-Parkinson Disease Secondary to Ritonavir–Buspirone Interaction
Authors: Clay Patrick G , Adams Molly M
Published: January 2017

OBJECTIVE:

To report a case of Parkinson-like symptoms appearing in a patient after introduction of ritonavir to buspirone therapy.

CASE SUMMARY:

A 54-year-old HIV-positive white man presented to the clinic with a 2-week history of ataxia, shuffling gait, cogwheel rigidity, resting tremor, and sad affect with masked features. This patient had been receiving high-dose buspirone (40 mg every morning and 30 mg every evening) for 2 years prior to the introduction of ritonavir/indinavir combination therapy (400 mg/400 mg twice daily) 6 weeks prior to initiation of the above symptoms. Buspirone was decreased to 15 mg 3 times daily, ritonavir/indinavir was discontinued, and amprenavir 1200 mg twice daily was added. The patient's symptoms began to subside after 1 week, with complete resolution after about 2 weeks. The patient continued to receive buspirone for an additional 12 months without recurrence of symptoms.

DISCUSSION:

This is the first reported interaction of buspirone and antiretrovirals. Buspirone, extensively metabolized by CYP3A4, was likely at supratherapeutic levels due to the inhibitory effect of ritonavir and, secondarily, indinavir. The Parkinson-like symptoms developed rapidly and severely, impacted this patient's quality of life, and necessitated significant clinic expenditures to identify this drug–drug interaction.

CONCLUSIONS:

This case demonstrates a severe drug–drug interaction between buspirone and ritonavir and further demonstrates the need for awareness of the metabolic profile for all agents an HIV-infected patient is receiving.
Macular Exanthema Due to Fumaric Acid Esters
Authors: Guenther Claudia H , Wozel Gottfried , Laske Jörg , Aschoff Roland , Meurer Michael
Published: January 2017

OBJECTIVE:

To report a case of an unusual skin reaction to fumaric acid esters (FAE).

CASE SUMMARY:

A 68-year-old white woman who was treated with FAE for 4 days for lichen planus developed generalized pruritic exanthema. This was suspected to be an allergic drug reaction to FAE, and the treatment was discontinued. After 48–72 hours, the exanthema resolved completely. An objective causality assessment revealed that the adverse drug event was probable. As skin testing for diagnostic purposes is not feasible with FAE, the drug-related origin of the exanthema was confirmed by oral rechallenge with FAE.

DISCUSSION:

The effectiveness of FAE in the systemic treatment of psoriasis vulgaris has been proven by controlled clinical trials. The compound has been shown to be tolerable and safe even during prolonged treatment. The most frequent adverse effects are gastrointestinal symptoms and flushing, which typically occur 4–6 hours after administration of the drug. Allergic reactions to FAE have not yet been reported. Since the patient was rechallenged with the suspected drug, we could confirm the allergic origin of the exanthema.

CONCLUSIONS:

The occurrence of allergic skin reaction should be considered in patients receiving treatment with FAE.
Gabapentin for the Treatment of Tremor
Authors: Faulkner Michele A , Bertoni John M , Lenz Thomas L
Published: January 2017

OBJECTIVE:

To review the use of the antiepileptic drug gabapentin for the treatment of various types of tremor.

DATA SOURCES:

A search of biomedical literature was completed through MEDLINE and EMBASE (1993–May 2002) to identify all clinical trials pertaining to the use of gabapentin for the treatment of tremor in humans.

DATA SYNTHESIS:

Outcome data from the few published studies have varied widely. Patient groups have been small, and conclusions have been based largely on subjective patient and investigator ratings.

CONCLUSIONS:

A trial of gabapentin is warranted in patients who fail therapy with traditional agents. Improvement should be measured by a patient's perceived functional ability.
Figs — The Earliest Known Ancient Drug for Cutaneous Anthrax
Authors: Ben-Noun Liubov Louba
Published: January 2017

BACKGROUND:

Anthrax is an often fatal bacterial infection, occurring in cutaneous, inhalational, gastrointestinal, and meningeal forms. Evaluation of anthrax treatment from ancient history may help healthcare providers to handle this serious disease more efficiently.

OBJECTIVE:

To evaluate the biblical descriptions of anthrax, focusing on its therapy in ancient times.

STUDY SELECTION:

All biblical texts associated with anthrax were examined and passages relating to this disease were studied closely.

DATA SYNTHESIS:

Biblical passages such as: “Take a cluster of figs. And they took and laid it on the boil [anthrax], and he recovered,” and “Let them take a cluster of figs, and lay it upon the boil [anthrax], and he shall recover,” convincingly indicate that figs have healing properties in cutaneous anthrax lesions.

CONCLUSIONS:

On the basis of this study, the National Institutes of Health together with the pharmaceutical industry may consider to work on isolation of compounds from fig plants to develop products against cutaneous and possibly other forms of anthrax once screening tests are completed.
Its Valence and Methods of Quantification in Parenteral Solutions
Authors: Hermann Joachim J.
Published: January 2017

The rationale for computing the valence of phosphate in parenteral solutions is presented, and the dependence of this variable on pH and ionic strength is graphically illustrated. In view of valence considerations, several commonly employed methods of expressing the phosphate content in injectables are examined for their merit. Some definite recommendations are offered regarding the appropriateness of these different methods of phosphate quantification.
A ‘Mini-Residency’ in Drug Information for the Practicing Pharmacist
Authors: Ivey Marianne F. , Smith Gary H.
Published: January 2017

Continuing education “mini-residencies” in drug information services were sponsored by the University of Washington School of Pharmacy's Division of Continuing Education and the University of Washington Drug Information Service (DIS) in August of 1976, 1977, and 1978. Each mini-residency covered a two-week period (a total of 80 hours) and was divided into didactic and experiential sessions. The university's DIS was the major resource for the residents. The two-week residency was designed to provide education and experience in the areas of drug information retrieval, analysis, and dissemination. The program was assessed through pre- and post-testing and a midcourse evaluation session. The residency format of the program allowed practicing pharmacists to return to the university to develop their skills in the area of drug information. The article presents a model for other drug information pharmacists who may want to offer similar training programs.
Bumetanide: A New Loop Diuretic (Bumex, Roche Laboratories)
Authors: Halstenson Charles E. , Matzke Gary R.
Published: January 2017

Bumetanide is a recently introduced diuretic that inhibits sodium transport in the thick ascending limb of the loop of Henle. It is structurally and pharmacologically similar to furosemide, but is approximately 40 times as potent on a milligram-for-milligram basis. After oral administration, it is rapidly absorbed, with peak serum concentrations attained at approximately 30 minutes. Its pharmacokinetic parameters are similar to those of furosemide. Bumetanide has demonstrated efficacy in the management of edema associated with congestive heart failure, hepatic cirrhosis, and renal insufficiency.

Bumetanide has demonstrated an adverse-reaction profile similar to that of furosemide, although the incidence of hypochloremia and hypokalemia is greater with bumetanide. The incidence of hyperglycemia and ototoxicity is greater with furosemide. The principal indication for bumetanide may be in patients with increased risk of ototoxicity. Cost considerations should relegate bumetanide to a secondary role for the treatment of sodium and fluid retention in most clinical settings.
The Role of the Institutional Review Board in Research Involving Human Subjects
Authors: Bosso John A.
Published: January 2017

Concern with the rights and welfare of human experimental research subjects has given rise to the evolution of institutional review boards. This article describes the basic composition and purposes of these boards, as well as the federal regulations by which they are governed. Since many of these regulations are open to interpretation, the policies and procedures of one such board are included to represent an example of how these regulations are interpreted and applied.
Postgraduate Pharmacy Fellowships (1983–1984)
Authors: Kaul Alan F. , Powell Stephen H. , Miller Cynthia R.
Published: January 2017

During June and July 1983, the Pharmacy Services Department of the Brigham and Women's Hospital conducted its third annual national survey by mail questionnaire regarding postgraduate pharmacy fellowships. There was a total response of 76 percent to the questionnaire. Eighty-three fellowships are offered at 31 fellowship sites. Information regarding type of specialty fellowship, fellowship characteristics, fellowship location and contact person, and qualifications of applicants is reported.
Hospital Pharmacy in Portugal and its Future Trends
Authors: Leal Aluísio Marques , Silveira Carlos
Published: January 2017

The authors begin by presenting a brief historical summary of hospital pharmacists' activities in Portugal, especially since the 1950s. They state their views on the present situation of hospital pharmacy in various aspects, namely: general legislation; activities and premises of pharmacy services; pharmaceutical career and staff recruitment; the National Hospital Formulary of Medicines and Pharmacy and Therapeutic Committees; acquisition, production and distribution of medicines; and clinical pharmacy activities. Future trends of hospital pharmacy in Portugal are summarized, stressing the following points: evolution of production and information, unit dose distribution, and steady increase of other clinical pharmacy activities.
Enzyme Induction: Rifampin-Disopyramide Interaction
Authors: Staum John M.
Published: January 2017

A 62-year-old woman with a history of supraventricular tachycardia, paroxysmal atrial tachycardia, and premature ventricular contractions was admitted with palpitations and anxiety. Previous therapy with antiarrhythmics had resulted in intolerable adverse effects or no effect on the arrhythmia. She had been taking rifampin prior to admission for acid-fast bacilli. Disopyramide was started on admission for supraventricular tachycardia. Subtherapeutic disopyramide blood concentrations were noted with concomitant administration of rifampin and disopyramide at normal doses. This case report demonstrates a possible drug interaction between these two drugs and the importance of careful monitoring. It was found that it takes three to five days after rifampin is discontinued before the enzyme induction of disopyramide disappears and disopyramide concentrations return to normal.
Toxic Psychosis following Cycloplegic Eyedrops
Authors: Kortabarría Rafael P. , Durán José A. , Chacón José R. , Domínguez Francisco J. , Pino Miguel A.
Published: January 2017

A case of toxic psychosis due to cycloplegic eyedrops is reported. The characteristic mental symptoms of atropine intoxication include confusion with vivid visual hallucinations, restlessness, muscular incoordination, and later emotional lability. These symptoms and a short period of retrograde amnesia occurred in our patient. The adverse drug reaction was confirmed following rechallenge. The possible preventive measures against intoxication caused by atropine eyedrops are described. All healthcare professionals should be aware of the possible temporal relationship between the appearance of pathology and the administration of a drug.

TOXIC PSYCHOSIS due to anticholinergic eyedrops is well documented in the medical literature, although there are few detailed cases. We report a case of toxic psychosis due to cycloplegic eyedrops in which the cause was documented by rechallenge.
What is the Clinical Role of Aerosolized Ribavirin?
Authors: Hebert Mary F. , Guglielmo B. Joseph
Published: January 2017

Aerosolized ribavirin is the first approved agent for the treatment of respiratory syncytial virus (RSV) infection. However, the clinical use of ribavirin is controversial. Although ribavirin-treated patients appear to be subjectively improved, the benefit in terms of decreased morbidity and mortality is not well established. Furthermore, the drug has been found to be teratogenic, carcinogenic, and mutagenic, depending upon the scientific model. Because of its unique mode of administration, environmental exposure of healthcare personnel and other patients may occur. Although administration in mechanically ventilated patients decreases the amount of ribavirin liberated into the atmosphere, the drug crystallizes in the endotracheal tube, occasionally resulting in reduced ventilation. The lack of data documenting efficacy and the above environmental concerns result in difficult decisions for hospitals. Further studies are necessary to clarify the value and safety of ribavirin in the treatment of RSV infection.
Drug Information Centers as Bases for Continuing Education Programs in Kuwait
Authors: Tarifi Hashem A. , Assad Abdulla M. , Ani Faisal M.
Published: January 2017

Over the past few years, there has been a modernization of pharmaceutical services in Kuwait. In 1983 a drug information center was opened. A one-year postgraduate, long-distance program leading to a diploma in clinical pharmacy was started in October 1987 in cooperation with Queen's University of Belfast, Ireland. Pharmacist and physician tutors were assigned to supervise students in the major hospitals in Kuwait. A questionnaire was developed and distributed to 50 practicing pharmacists to assess the feasibility of using the Drug Information Center at Adan Hospital (DICAH) as a base for continuing education programs. Although certain difficulties were identified, it was concluded that the DICAH has the potential to be used as a base for future continuing education for pharmacists in Kuwait, especially as there is no school of pharmacy in the country.
Patterns of Nicotine Gum Use in a Health Maintenance Organization
Authors: Johnson Richard E. , Hollis Jack F. , Stevens Victor J. , Woodson Gary T.
Published: January 2017

Nicotine chewing gum is designed as an aid to smokers who intend to stop smoking. However, the efficacy of the gum in general medical practice has been questioned. This study describes the extent of nicotine chewing gum use among health maintenance organization members, the characteristics of prescribers and users, and the patterns of gum use over a two-year period. About 0.4 percent of Kaiser Permanente, Northwest Region members were exposed to the gum. Over the two-year observation period, 1970 members received at least one box (96 pieces) of the gum. Almost 70 percent of users received only one box of the gum. About 1.5 percent of users appeared to use the gum continuously at a daily dosage around the level needed to replace the nicotine addiction among most smokers, and for longer than the recommended three months. Another 2.5 percent appeared to use the gum continuously but at less than a nicotine-addiction replacement dose for longer than the recommended maximum of six months. The presence of a prepaid prescription drug benefit directly affected whether or not a person received the gum and how long he used it. The extreme variation in the patterns of use raises the questions of why the gum is used in this manner, and how effective it is when used in this manner.
Digoxin Assay Anomalies Due to Digoxin-Specific FAB Immunotherapy
Authors: Natowicz Marvin , Shaw Leslie
Published: January 2017

We demonstrate that digoxin-specific Fab antibody fragments, used in the treatment of severe digitalis intoxication, cause a marked interference with both fluorescence excitation transfer immunoassays and radioimmunoassays for digoxin. In addition, we describe a rapid ultrafiltration method that avoids the Fab-induced interference and affords excellent accuracy and precision. This technique will provide a useful adjunct to the clinical evaluation of patients with digoxin toxicity who are recipients of antidigoxin immunotherapy by enabling a precise determination of their serum digoxin concentrations. By separating the free and protein-bound digoxin this technique also may be useful in evaluating serum digoxin concentrations in patients with abnormal plasma protein concentrations.
Acute Hemolysis and Renal Failure following Discontinuous Use of Rifampin
Authors: Levine Marc , Collin Kathleen , Kassen Barry O.
Published: January 2017

Rifampin is frequently used in the treatment of mycobacterial infections. Intermittent or discontinuous therapy with rifampin has been associated with systemic symptoms referred to as the “flu syndrome” and, less frequently, acute hemolysis and acute renal failure. We report the case of a 73-year-old woman who experienced acute hemolysis and renal failure while being treated with rifampin and ethambutol for a respiratory infection caused by Mycobacterium fortuitum and M. avium-intracellulare. This patient had interrupted her therapy for periods of one week or more due to a rash and flu-like symptoms, which she ascribed to her medications. A review of the literature indicated that these adverse effects of rifampin appear to be immunologically mediated and that the symptoms of the flu syndrome may be due to mild intravascular hemolysis. Intermittent therapy with rifampin should be avoided and noncompliant patients should be given alternative treatment when possible.
Goserelin Acetate Implant: A Depot Luteinizing Hormone-Releasing Hormone Analog for Advanced Prostate Cancer
Authors: Goldspiel Barry R. , Kohler David R.
Published: January 2017

Goserelin acetate implant is a newly approved depot formulation of a luteinizing hormone-releasing hormone (LHRH) agonist indicated for palliation of advanced prostate cancer. LHRH superagonists suppress gonadotropin release from the pituitary gland by causing down-regulation of receptors. The sustained-release dosage form contains goserelin acetate dispersed in a biodegradable copolymer matrix and is designed to release active drug over 28 days. Pharmacokinetic studies have demonstrated that, despite nonzero order release of goserelin from the matrix, goserelin acetate implant maintains serum concentrations of testosterone in the range normally found in castrated men (<2 nmol/L) throughout the recommended 28-day dosing interval. Response rates similar to those for orchiectomy and estrogen administration have been demonstrated. Combination therapy with either diethylstilbestrol or flutamide has produced favorable results, although the major advantage appears to be a reduction in the tumor flare seen during the first week of LHRH agonist therapy rather than an increase in response rate or survival. Adverse effects are similar to other LHRH agonists and include tumor flare during the first week of therapy, decreased libido, decreased erectile potency, hot flashes, and gynecomastia. In combination with flutamide, additional adverse effects include diarrhea, nausea, vomiting, and elevated hepatic aminotransferases, all of which can be attributed to flutamide administration. Local reactions are minimal; however, some patients require a local anesthetic before goserelin acetate implant injection. The recommended dose is 3.6 mg administered subcutaneously into the upper abdominal wall every 28 days. The average wholesale cost is approximately $320 per month. Formulary addition is recommended.
Comparative Study of Saudi-Marketed Products and US Drug Labeling
Authors: Bawazir Saleh A. , Al-Hassan Mohammed I. , Al-Khamis Khalil I. , Abou-Auda Hisham S. , Gubara Othman A.
Published: January 2017

Drug package inserts from ten nonsteroidal antiinflammatory drugs marketed in Saudi Arabia were compared with their corresponding US labels to determine possible differences in their information content. These variations were assessed with special regard to the number of words used and the type of the information provided. The study showed that inserts of Saudi-marketed products generally conveyed limited and incomplete information. Possible adverse reactions, drug-drug interactions, and date of revision often were not included, although this information was present on the corresponding US labels. Comparisons of the package inserts of the same product from various pharmaceutical companies show wide variations in the amount of information provided. Determining the minimal level of information that must be included by the manufacturer in the package insert and the establishment of firm international guidelines by the World Health Organization could effectively reduce such variations.
Relationships among Prescription Payment Methods and Interactions between Community Pharmacists and Prescribers
Authors: Raisch Dennis W.
Published: January 2017

OBJECTIVE:

This research was performed to examine community pharmacists' interactions with prescribers and to determine if these interactions are related to payment method.

DESIGN:

Randomly selected pharmacists (47 in chain pharmacies and 26 in independent pharmacies) collected data concerning prescriber interactions for a 40-hour period. These interactions were analyzed in terms of payment methods, prescriber acceptance, and types of information discussed.

RESULTS:

Information concerning 730 interactions by 72 pharmacists was obtained. Payment methods were related to the frequency of interactions per pharmacist (p<0.01). There were higher percentages of interactions for self-pay (median 2.2 percent) and Medicaid (median 1.8 percent) prescriptions than for third-party fee-for-service (mode 0 percent) or capitation prescriptions (mode 0 percent). Type of information discussed was related to payment method. The vast majority of information provided by pharmacists (91 percent) was accepted by prescribers. The rate of acceptance was 97 percent for prescriber-initiated interactions versus 88 percent for pharmacist- or patient-initiated interactions (p<0.01).

CONCLUSIONS:

Relationships between payment method and interactions were identified. These findings may be attributable to prescribing policies and reimbursement policies. Prescribing policies that restrict prescribers to a formulary may help make them become more adept at using those products; thus, they will make fewer prescribing errors. Reimbursement policies that require patients to consistently use a specific pharmacy (i.e., capitation) may help pharmacists become more familiar with the patient's prescription history. Therefore, interactions with prescribers are needed less frequently for these patients' prescriptions.
Nightmare Cessation following Alteration of Ophthalmic Administration of a Cholinergic and a Beta-Blocking Agent
Authors: Mort Jane R.
Published: January 2017

OBJECTIVE:

To document the termination of nightmares brought about by an alteration in the ophthalmic administration of beta-blocking and cholinergic agents.

PATIENT:

A 75-year-old man residing in a long-term care facility experienced nightly nightmares of approximately one-year duration.

INTERVENTION:

Other potential causes for the nightmares were eliminated. The administration of the ophthalmic agents was evaluated and the resident was then instructed to alter administration to include closure of his eyes for one to two minutes after administration.

OUTCOME:

Following the alteration in administration the nightmares were not present and have not reappeared in the ensuing year.

CONCLUSIONS:

Ophthalmic application of beta-blocking and cholinergic agents is used for the treatment of glaucoma and has been reported to cause a wide variety of central nervous system effects. Researchers have documented reduced systemic absorption and enhanced ocular retention time with specific modifications in the administration of the ophthalmic products. Based on this research the suggestion has been made that systemic adverse effects may be reduced by altering administration through use of lid closure and lacrimal occlusion. This case validates this hypothesis and provides strong evidence for the need to counsel all patients receiving ophthalmic agents on proper administration, including techniques to reduce absorption in order to avoid undesirable systemic effects.
Implication of Dispensing Cups in Dosing Errors and Pediatric Poisonings: A Report from the American Association of Poison Control Centers
Authors: Litovitz Toby
Published: January 2017

OBJECTIVE:

To characterize reports to poison centers involving liquid medication errors associated with the use of dispensing cups. design: Case series reported by 16 US poison centers over an eight-day period.

SETTING:

Calls to poison control centers, predominantly but not exclusively from homes.

PATIENTS:

Children and adults.

RESULTS:

Of 34 reported cases, most (79 percent) involved a two- to threefold dosing error, and most (94 percent) involved an error in a single dose of medication. Cough and cold preparations were implicated in 65 percent; acetaminophen elixirs in 18 percent. Three major causes of dosing errors were identified, including teaspoon/tablespoon confusion, assumption that the dispensing cup was the unit of measure, and assumption that the full dispensing cup was the actual dose.

CONCLUSIONS:

Dispensing cup markings should use a single unit of measure, and a uniform labeling system should be implemented. Teaspoon/tablespoon abbreviations should be avoided, and dispensing cup lettering should be more legible. Consumer education is essential to correct the misimpression that the full cup is always the recommended dose.
Ciprofloxacin-Induced Psychosis
Authors: Reeves Roy R.
Published: January 2017

OBJECTIVE:

To report a case of ciprofloxacin-induced psychosis and to discuss occurrence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this adverse reaction.

DATA SOURCES:

Case reports and review articles identified by MEDLINE.

DATA EXTRACTION:

Data from pertinent published sources were reviewed and abstracted.

DATA SYNTHESIS:

A 49-year-old man developed symptoms of severe psychosis concomitant with ciprofloxacin (250 mg bid) treatment. Central nervous system effects secondary to ciprofloxacin treatment are uncommon and usually consist only of minor dizziness or mild headache, although rare occurrences of seizures and hallucinations have been reported. The mechanism by which ciprofloxacin causes these adverse effects is not fully understood. It has been suggested that quinolones may produce an epileptogenic effect by inhibiting the binding of gamma-aminobutyric acid to its receptor sites in the brain. There is yet no explanation for the occurrence of hallucinations or psychosis.

CONCLUSIONS:

Caution should be exercised when using ciprofloxacin in the treatment of patients with personality abnormalities or symptoms of psychosis.
Medication Assistance: The Development of Drug Surveillance and Drug Information in the Netherlands
Authors: van Gruting Cornelis W.D. , de Gier Johan J.
Published: January 2017

OBJECTIVE:

To describe the development of drug surveillance and drug information in The Netherlands.

DATA SYNTHESIS:

Historically, the professions of medicine and pharmacy have existed separately with little contact between them. Since the 1960s, this situation has changed in The Netherlands. Both professions are cooperating to an ever-increasing degree, primarily in the areas of computerized drug surveillance and individualized patient drug information, resulting in greater patient benefit.

CONCLUSIONS:

Exchange of knowledge between physicians and pharmacists, greater cooperation among professionals, use of computerized patient medical records, and involvement of the patient in his own healthcare will have a positive influence on the development of drug assistance in the future.
Hematologic Effects of Ethanol Consumption in Trauma Patients
Authors: Erstad Brian L. , Harlander Diana K. , Daller John A.
Published: January 2017

OBJECTIVE:

To determine the effects of ethanol (EtOH) ingestion by trauma patients on the hematologic system as evidenced by coagulation abnormalities and transfusion requirements.

DESIGN:

Retrospective chart review. The injury severity score (ISS) was determined for each patient. Patients were grouped according to presence of EtOH (+EtOH) and absence of EtOH (-EtOH) with further subdivision based on an ISS ≤8 or ≥9.

SETTING:

University medical center.

PATIENTS:

All adult trauma patients admitted during a one-month period.

MAIN OUTCOME MEASURES:

The volume of resuscitation fluids (including blood products) administered, laboratory parameters indicative of bleeding, and length of stay.

RESULTS:

Of 104 evaluable patients, 38 had measurable EtOH concentrations, 46 had undetectable EtOH concentrations, and the remaining 20 patients had not been tested. Although isolated, statistically significant differences were found among groups for some of the outcome measures, there were no clinically important differences.

CONCLUSIONS:

EtOH ingestion prior to injury did not appear to cause significant alterations in the hematologic system of trauma patients, but a larger study is needed to confirm these findings.