bluuebunny/crossref_metadata_2025_split huggingface dataset:
A temperature-sensitive mutation in thenodal-related genecyclopsreveals that the floor plate is induced during gastrulation in zebrafish
Authors: Tian Jing , Yam Caleb , Balasundaram Gayathri , Wang Hui , Gore Aniket , Sampath Karuna 
Published: June 2003

The floor plate, a specialized group of cells in the ventral midline of the neural tube of vertebrates, plays crucial roles in patterning the central nervous system. Recent work from zebrafish, chick, chick-quail chimeras and mice to investigate the development of the floor plate have led to several models of floor-plate induction. One model suggests that the floor plate is formed by inductive signalling from the notochord to the overlying neural tube. The induction is thought to be mediated by notochord-derived Sonic hedgehog (Shh), a secreted protein, and requires direct cellular contact between the notochord and the neural tube. Another model proposes a role for the organizer in generating midline precursor cells that produce floor plate cells independent of notochord specification, and proposes that floor plate specification occurs early, during gastrulation.We describe a temperature-sensitive mutation that affects the zebrafish Nodal-related secreted signalling factor, Cyclops, and use it to address the issue of when the floor plate is induced in zebrafish. Zebrafish cyclops regulates the expression of shh in the ventral neural tube. Although null mutations in cyclops result in the lack of the medial floor plate, embryos homozygous for the temperature-sensitive mutation have floor plate cells at the permissive temperature and lack floor plate cells at the restrictive temperature. We use this mutant allele in temperature shift-up and shift-down experiments to answer a central question pertaining to the timing of vertebrate floor plate induction. Abrogation of Cyc/Nodal signalling in the temperature-sensitive mutant embryos at various stages indicates that the floor plate in zebrafish is induced early in development, during gastrulation. In addition, continuous Cyclops signalling is required through gastrulation for a complete ventral neural tube throughout the length of the neuraxis. Finally, by modulation of Nodal signalling levels in mutants and in ectopic overexpression experiments, we show that, similar to the requirements for prechordal plate mesendoderm fates, uninterrupted and high levels of Cyclops signalling are required for induction and specification of a complete ventral neural tube.
Evaluation of Mexiletine Clearance in a Japanese Population
Authors: Ueno Kazuyuki , Tamamura Akira , Matsumoto Kana , Komamura Kazuo , Kamakura Shiro , Miyatake Kunio , Shibakawa Masahiko 
Published: June 2003

OBJECTIVE: To evaluate mexiletine clearance in a Japanese population and to clarify the roles of CYP2D6 and CYP1A2 in mexiletine disposition. METHODS: Concentrations of serum and urinary mexiletine and its metabolites were determined and mexiletine clearances were estimated in 334 inpatients receiving mexiletine therapy. Concentrations of mexiletine and its metabolites in serum and urine samples were determined by HPLC. RESULTS: Although interindividual variation of mexiletine clearance was small, the effect of age on mexiletine clearance was comparatively large. Mexiletine clearance in patients with dilated cardiomyopathy (DCM) was decreased when compared with other diagnoses (Non-DCM). The fractional contents of p-hydroxymexiletine (POH) and 2-hydroxymexiletine (OHMEX) in urine amounted to approximately 50%. Almost all of the POH was conjugated, whereas less than one-third of the OHMEX was conjugated. Although no significant differences in POH and OHMEX were observed between patients with DCM and those without, a trend toward an increase in conjugation pathway of DCM patients was observed. CONCLUSIONS: The interindividual variation of mexiletine clearance was small, while the effect of age on the mexiletine clearance in Non-DCM was comparatively large. A significant difference in mexiletine clearance between patients with DCM and those with Non-DCM was observed. Therefore, when mexiletine is administered to patients with DCM, careful monitoring is needed.
Vitamin B12 Deficiency Associated with Histamine2-Receptor Antagonists and a Proton-Pump Inhibitor
Authors: Ruscin J Mark , Lee Page Robert , Valuck Robert J 
Published: June 2003

OBJECTIVE: To report a case of vitamin B12 deficiency associated with long-term use (∼4½ y) of histamine2 (H2)-receptor antagonists and a proton-pump inhibitor (PPI) in a patient with gastroesophageal reflux. CASE SUMMARY: A 78-year-old nonvegetarian white woman with symptomatic gastroesophageal reflux (GER) was started on cimetidine 300 mg 4 × daily in February 1990 and took various other antisecretory medications over the course of the next 4½ years. She had a normal serum vitamin B12 concentration of 413 pg/mL in August 1992. In June 1994, her serum vitamin B12 concentration was found to be in the low normal range at 256 pg/mL. Biochemical markers of vitamin B12–dependent enzyme activity were measured at that time, and methylmalonic acid (MMA) and homocysteine (HCYS) were elevated at 757 nmol/L and 27.3 μmol/L, respectively. Serum folate was within the normal range at 4.9 ng/mL, and serum creatinine was slightly elevated at 1.4 mg/dL. MMA and HCYS concentrations decreased dramatically with oral replacement of vitamin B12 1000 μg/d, which confirmed vitamin B12 deficiency. Oral replacement also demonstrated that the woman was able to adequately absorb nonprotein—bound vitamin B12 from the gastrointestinal tract, suggesting that her deficiency was a result of food—cobalamin malabsorption. The accumulation of MMA and HCYS was not a consequence of renal dysfunction, since both metabolites dramatically decreased with vitamin B12 replacement. DISCUSSION: Malabsorption of dietary protein-bound vitamin B12 has been demonstrated with the use of H2-receptor antagonists and PPIs. One previous case report of vitamin B12 deficiency resulting from long-term use of omeprazole has been published. The malabsorption of dietary vitamin B12 is thought to be a result of its impaired release from food protein, which requires gastric acid and pepsin as the initial step in the absorption process. CONCLUSIONS: The use of H2-receptor antagonists and/or PPIs may impair the absorption of protein-bound dietary vitamin B12 and could contribute to the development of vitamin B12 deficiency with prolonged use. Patients taking these medications for extended periods of time, particularly >4 years, should be monitored for vitamin B12 status.
Methodology to Determine Duration of Action for Antihypertensive Drugs
Authors: Lefebvre Jean , Poirier Luc , Lacourcière Yves 
Published: June 2003

OBJECTIVE: To review and comment on methods used to assess the duration of action of antihypertensive drugs. DATA SOURCES: A MEDLINE search (1966–June 2000) using key terms such as trough-to-peak ratio and ambulatory blood pressure monitoring was conducted. STUDY SELECTION: An article was considered for this review if it pertained to the assessment of the duration of action of antihypertensive drugs. Special attention was given to articles dealing with methodologic aspects. DATA SYNTHESIS: Antihypertensive drugs with a long duration of action are thought to provide better therapeutic coverage against hypertensive complications compared with that of short-acting agents. Measuring blood pressure at the end of the dosing interval may be a way to assess the duration of action of a drug. However, the use of high doses of a short-acting agent to obtain sufficient effect when at trough concentrations can potentially cause dose-related adverse effects at the peak time, contributing to nonadherence to therapy and thus to adverse outcomes. To alleviate this problem, the US Food and Drug Administration (FDA) has conceptualized the trough-to-peak (T:P) ratio. Although this arithmetic index has since been widely used to characterize the duration and safety of blood pressure control achieved by antihypertensive agents, several methodologic flaws limit its interpretation in the clinic. Ambulatory blood pressure monitoring (ABPM) is a more reliable approach to assess the duration of action and outcome of antihypertensive therapy. CONCLUSIONS: Different methodologic approaches exist to evaluate the duration of action of antihypertensive drugs. Although the T:P ratio has been suggested by the FDA, it is difficult to establish a fair comparison among various antihypertensive agents based solely on this index. Treatment evaluation based on ABPM may be preferable to those guided by T:P because ABPM is more reproducible and is now established as a predictor of cardiovascular risk.
Alteplase Use for Prevention of Central Line Occlusion in a Preterm Infant
Authors: Lee Edith K 
Published: June 2003

OBJECTIVE: To report the use of alteplase for catheter clearance in a neonate of 27 weeks' gestation at day 50 of life. SETTING: Neonatal Intensive Care Unit, Naval Medical Center. CASE SUMMARY: At day 50 of life, a neonate boy of 27 weeks' gestation had a clotted peripherally inserted central catheter line. He required central access to complete a 28-day course of amphotericin B. An alteplase dose of 0.3 mg/0.3 mL was instilled into the catheter, for an indwelling time of 1 hour. The initial attempt was successful, and the patient was able to finish the course of amphotericin B. DISCUSSION: When a catheter becomes occluded, the cause must be determined initially; then an appropriate treatment option can be initiated. Hydrochloric acid and ethanol are some of the pharmacologic agents available, with their use dependent on the precipitating cause of the occlusion. Thrombolytic agents, such as streptokinase and urokinase, have also been used in catheter clearance. The potential risk of anaphylactic reactions with streptokinase and the unavailability of urokinase have clinicians searching for other pharmacologic alternatives. Alteplase, a synthetic tissue plasminogen actitvator, has been shown to be a promising alternative agent. There are various reports of alteplase use in pediatric patients for catheter clearance, with different suggested doses ranging from 0.25 to 2 mg. To minimize the risk of bleeding events, initiation with low doses from the suggested range is recommended. CONCLUSIONS: Alteplase was shown to be safe and effective for clearance of an occluded central line in a preterm infant.
Opioid Dependence Treatment, Including Buprenorphine/Naloxone
Authors: Raisch Dennis W , Fye Carol L , Boardman Kathy D , Sather Mike R 
Published: June 2003

OBJECTIVE: To review opioid dependence (OD) and its treatment. Pharmacologic treatments, including the use of buprenorphine/naloxone, are presented. Pharmaceutical care functions for outpatient OD treatment are discussed. DATA SOURCES: Primary and review articles were identified by MEDLINE and HEALTHSTAR searches (from 1966 to November 2000) and through secondary sources. Tertiary sources were also reviewed regarding general concepts of OD and its treatment. STUDY SELECTION/DATA EXTRACTION: Relevant articles were reviewed after identification from published abstracts. Articles were selected based on the objectives for this article. Studies of the treatment of OD with buprenorphine were selected based on the topic (pharmacology, pharmacokinetics, adverse reactions) and study design (randomized, controlled clinical trials in patients with OD with active/placebo comparisons and/or comparisons of active OD treatments). Articles regarding pharmacists' activities in the treatment and prevention of OD were reviewed for the pharmaceutical care section. DATA SYNTHESIS: OD is considered a medical disorder with costly adverse health outcomes. Although methadone maintenance treatment (MMT) is cost-effective for OD, only about 12% of individuals with OD receive this treatment. Psychological and pharmacologic modalities are used to treat OD, but patients often relapse. Drug therapy includes α2-agonists for withdrawal symptoms, detoxification regimens with or without opioids, opioid antagonists, and opioid replacement including methadone, levomethadyl acetate, and buprenorphine. The Drug Addiction Treatment Act of 1999 allows for office-based opioid replacement therapies. Sublingual buprenorphine with naloxone can be used in this milieu. Buprenorphine with naloxone is currently under new drug application review with the Food and Drug Administration. Clinical research shows buprenorphine to be equal in effectiveness to methadone, but safer in overdose due to its ceiling effect on respiratory depression. It has lower abuse potential and fewer withdrawal symptoms when discontinued. Naloxone is included to decrease diversion and injection of the tablets. Pharmacists in outpatient settings who are familiar with OD have opportunities to provide pharmaceutical care to patients receiving this treatment. Pharmaceutical care functions for OD include ensuring appropriate drug administration, monitoring adverse effects, alleviating withdrawal symptoms, treating intercurrent illnesses, minimizing diversion, and preventing relapse. CONCLUSIONS: OD is a critical unmet health problem in the US. Buprenorphine combined with naloxone represents an innovative treatment for OD in outpatient settings. This new treatment has advantages over MMT.
Acute Cholestatic Hepatitis after Exposure to Isoflurane
Authors: Malnick Stephen DH , Mahlab Keren , Borchardt Jakob , Sokolowski Nadia , Attali Malka 
Published: June 2003

OBJECTIVE: To report a case of acute cholestatic hepatitis following exposure to the inhalational anesthetic isoflurane. CASE SUMMARY: A 70-year-old healthy woman from Iraq developed acute cholestatic hepatitis 3 weeks following repair of the right rotator cuff under general anesthesia. There was no evidence for viral, autoimmune, or metabolic causes of hepatitis. No other medications were involved except for dipyrone for analgesia. The alanine aminotransferase was elevated to a peak concentration of 1533 U/L and the serum bilirubin reached a peak of 17.0 mg/dL. There was slow improvement over 4 months. Accidental reexposure by the patient to dipyrone was uneventful. DISCUSSION: The clinical and histologic picture of this case resembles halothane hepatitis, which has a significant mortality rate. CONCLUSIONS: Isoflurane, a common anesthetic agent, can cause severe cholestatic hepatitis.
Celecoxib-Induced Nonoliguric Acute Renal Failure
Authors: Alkhuja Samer , Menkel Robert A , Alwarshetty Mamata , Ibrahimbacha Ahmad M 
Published: June 2003

OBJECTIVE: To report a case of nonoliguric acute renal failure secondary to use of celecoxib in a patient with rheumatoid arthritis. CASE SUMMARY: A 43-year-old Hispanic woman started receiving celecoxib 200 mg/d for treatment of rheumatoid arthritis. Fourteen days after initiating therapy, she developed nonoliguric acute renal failure. Celecoxib was discontinued. Renal function improved, but had not returned to normal 30 days after presentation. DISCUSSION: Only 2 cases of reversible oliguric acute renal failure and volume overload have been reported 13 and 14 days after initiating therapy with celecoxib. Renal function in the 2 patients returned to baseline after treatment with diuretics. To our knowledge, the development of nonoliguric acute renal failure secondary to treatment with celecoxib has not previously been reported. CONCLUSIONS: Celecoxib can probably result in reversible, or nonoliguric, acute renal failure. Although renal function improves after discontinuation of celecoxib, it may not return to baseline. Celecoxib should be used cautiously in individuals at risk of developing acute renal failure.
Telithromycin: The First of the Ketolides
Authors: Shain Christopher S , Amsden Guy W 
Published: June 2003

OBJECTIVE: To review the chemistry, spectrum of activity, pharmacology, clinical efficacy, and safety of telithromycin. DATA SOURCES: A MEDLINE search from 1966 to December 2000 was performed via OVID and PubMed using the following search terms: HMR 3647, HMR3647, Ketek, RU 66647, and telithromycin. An extensive review of retrieved literature, abstracts from international scientific conferences, and minutes from regulatory authority meetings was also performed. DATA EXTRACTION: Medicinal chemistry, in vitro, animal, and human trials were reviewed for information on the antimicrobial activity, clinical efficacy, pharmacology, and safety of telithromycin. DATA SYNTHESIS: Several chemical modifications to the macrolide structure have led to the development of telithromycin, the first ketolide antimicrobial that demonstrates improved activity against penicillin- and macrolide/azalide-resistant Streptococcus pneumoniae due to its unique binding to the ribosomal target site. Although telithromycin may be useful in the treatment of community-acquired respiratory tract infections due to its activity against common typical and atypical pathogens, questions concerning its reliable activity against Haemophilus influenzae need to be addressed. Telithromycin's pharmacokinetics permit once-daily dosing for abbreviated periods and good distribution into lung tissue and phagocytic cells. Clinical and bacteriologic cure rates have been similar to those of comparator agents in human efficacy trials; however, the incidence of adverse gastrointestinal events were generally higher with telithromycin patients. Like other macrolides and many newer fluoroquinolones, telithromycin's ability to prolong the QTc interval is a potential safety issue, especially in elderly patients with predisposing conditions or those who are concurrently receiving drugs that are substrates for CYP2D6 and 3A4. Liver function test elevations demonstrated during clinical trials, although not overtly severe, may warrant monitoring in some patients taking multiple hepatically metabolized/cleared agents. CONCLUSIONS: Telithromycin offers potential advantages over traditional macrolides/azalides for community-acquired respiratory tract infections caused by macrolide-resistant pathogens. Further studies are needed to elucidate its clinical efficacy against H. influenzae, potential drug interactions, and safety in various subpopulations.
Factors Affecting Medication Adherence in Hypertensive Patients
Authors: Patel Rosalie P , Taylor Stephanie D 
Published: June 2003

BACKGROUND: Adherence to medication is a critical factor in the continued health and well-being of patients with hypertension. Patients' acceptance of medical advice and information may be influenced by their subjective beliefs about their health condition; therefore, it is essential that their beliefs be taken into account when giving health advice or medical treatment. OBJECTIVE: To determine whether a relationship exists between illness attribution, perceived control, and adherence to antihypertensive medications. METHODS: A prospective, cross-sectional survey of hypertensive patients was conducted at the University of Michigan Medical Centers, Hypertension Clinic, Ann Arbor, MI. One hundred two patients with a goal to reduce their blood pressure were included in the study. Written and follow-up telephone survey questions assessing patients' illness attributions, perceived control, and medication adherence were administered. Associations between these variables were analyzed using correlation analyses. RESULTS: The majority of patients (67.7%) were adherent with their hypertensive medications. Patients indicated that modifiable variables were the most common attribution believed to cause hypertension; however, there was no significant relationship to medication adherence. A significant inverse relationship was found between perceived control over hypertension and medication adherence (p < 0.01). CONCLUSIONS: The findings suggest that patients' greater perception of control over trying to reduce blood pressure may result in decreased reliance on medications and subsequent nonadherence to drug therapy. Implications of these findings on pharmacy practice are discussed.
Ziprasidone: The Fifth Atypical Antipsychotic
Authors: Caley Charles F , Cooper Chandra K 
Published: June 2003

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of ziprasidone as a treatment for schizophrenia. DATA SOURCES: Information was selected from a MEDLINE search (July 2000–October 2001) of English-language medical literature using ziprasidone as the search term. Manual searches of pertinent journal article references, request for medical information from Pfizer, and access of the Web site of the Food and Drug Administration were also performed. STUDY SELECTION: All available published information regarding the pertinent characteristics of ziprasidone were considered for selection. DATA EXTRACTION: Pharmacology and pharmacokinetic studies were selected to provide a comprehensive description of these characteristics. Clinical investigations were evaluated for design, sample size, diagnosis, duration, and outcome. Data from all investigations were selected by 1 author and reviewed by both authors. DATA SYNTHESIS: Ziprasidone is a benzisothiazolyl piperazine—type atypical antipsychotic that shares the serotonin2A/dopamine2 (5-HT2A/D2) profile of the available atypical antipsychotics. Ziprasidone has demonstrated in vitro activity as a 5-HT1A receptor agonist and as a very weak inhibitor of serotonin and norepinephrine reuptake. These data do not support ziprasidone as being a clinically meaningful inhibitor of serotonin/norepinephrine reuptake. Oral bioavailability of ziprasidone taken with food is approximately 60%, half-life is approximately 6–7 hours, and protein binding is extensive at >99%. Twelve metabolites have been identified, yet only 4 of these are considered to be primary metabolites. Metabolism of ziprasidone by aldehyde oxidase produces its only metabolite with potential pharmacologic activity; CYP3A4 also contributes to the metabolism of ziprasidone. Clinical studies support ziprasidone as efficacious for the treatment of patients with acute exacerbations of schizophrenia or schizoaffective disorder. Daily doses permitted in these clinical trials ranged from 40 to 160 mg, but only doses between 120 and 160 mg/d have been superior to placebo. Future research efforts should be directed toward refractory schizophrenia, cognitive impairment in schizophrenia, affective and anxiety symptoms associated with schizoaffective disorder, and bipolar disorder. Adverse effect characteristics of ziprasidone commonly include headache, nausea, and somnolence; infrequent effects include extrapyramidal symptoms and weight gain. Ziprasidone has been reported to cause an average QTc prolongation of approximately 20 msec; there have only been 2 patients (0.06%) reported by the manufacturer to have a measured QTc interval >500 msec. CONCLUSIONS: Ziprasidone is a safe and efficacious atypical antipsychotic for the acute management of schizophrenia. Efficacy data and most safety data for ziprasidone support its use as a first-line treatment for schizophrenia; however, its potential effects on ventricular repolarization relegate it to second-line status in patients with comorbid cardiovascular risks.