Rapid preparation of patients with Graves' hyperthyroidism for urgent thyroidectomy.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
H H Nguyen
Publications and source records attributed to H H Nguyen.
Why multiple small subunits (Y2 and Y4) for yeast ribonucleotide reductase? Toward understanding the role of Y4.
Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides. Class I RNRs are composed of two homodimeric subunits: R1 and R2. R1 is directly involved in the reduction, and R2 contains the diferric-tyrosyl radical (Y*) cofactor essential for the initiation of reduction. Saccharomyces cerevisiae has two RNRs; Y1 and Y3 correspond to R1, whereas Y2 and Y4 correspond to R2. Y4 is essential for diferric-Y* formation in Y2 from apoY2, Fe(2+), and O(2). The actual function of Y4 is controversial. Y2 and Y4 have been further characterized in an effort to understand their respective roles in nucleotide reduction. (His)(6)-Y2, Y4, and (His)(6)-Y4 are homodimers, isolated largely in apo form. Their CD spectra reveal that they are predominantly helical. The concentrations of Y2 and Y4 in vivo are 0.5-2.3 microM, as determined by Western analysis. Incubation of Y2 and Y4 under physiological conditions generates apo Y2Y4 heterodimer, which can form a diferric-Y small middle dot when incubated with Fe(2+) and O(2). Holo Y2Y4 heterodimer contains 0.6-0.8 Y* and has a specific activity of 0.8-1.3 micromol.min.mg. Titration of Y2 with Y4 in the presence of Fe(2+) and O(2) gives maximal activity with one equivalent of Y4 per Y2. Models for the function of Y4 based on these data and the accompanying structure will be discussed.
Apoenzymes↗
High-frequency (140-GHz) time domain EPR and ENDOR spectroscopy: the tyrosyl radical-diiron cofactor in ribonucleotide reductase from yeast.
High-frequency pulsed EPR and ENDOR have been employed to characterize the tyrosyl radical (Y*)-diiron cofactor in the Y2-containing R2 subunit of ribonucleotide reductase (RNR) from yeast. The present work represents the first use of 140-GHz time domain EPR and ENDOR to examine this system and demonstrates the capabilities of the method to elucidate the electronic structure and the chemical environment of protein radicals. Low-temperature spin-echo-detected EPR spectra of yeast Y* reveal an EPR line shape typical of a tyrosyl radical; however, when compared with the EPR spectra of Y* from E. coli RNR, a substantial upfield shift of the g(1)-value is observed. The origin of the shift in g(1) was investigated by 140-GHz (1)H and (2)H pulsed ENDOR experiments of the Y2-containing subunit in protonated and D(2)O-exchanged buffer. (2)H ENDOR spectra and simulations provide unambiguous evidence for one strongly coupled (2)H arising from a bond between the radical and an exchangeable proton of an adjacent residue or a water molecule. Orientation-selective 140-GHz ENDOR spectra indicate the direction of the hydrogen bond with respect to the molecular symmetry axes and the bond length (1.81 A). Finally, we have performed saturation recovery experiments and observed enhanced spin lattice relaxation rates of the Y* above 10 K. At temperatures higher than 20 K, the relaxation rates are isotropic across the EPR line, a phenomenon that we attribute to isotropic exchange interaction between Y* and the first excited paramagnetic state of the diiron cluster adjacent to it. From the activation energy of the rates, we determine the exchange interaction between the two irons of the cluster, J(exc) = -85 cm(-)(1). The relaxation mechanism and the presence of the hydrogen bond are discussed in terms of the differences in the structure of the Y*-diiron cofactor in yeast Y2 and other class I R2s.
Deuterium↗
Montelukast dose selection in children ages 2 to 5 years: comparison of population pharmacokinetics between children and adults.
Montelukast, a leukotriene receptor antagonist, has demonstrated efficacy and tolerability in the treatment of asthma in patients age 6 years and older. The purpose of this open, one-period, multicenter population pharmacokinetic study was to identify a chewable tablet (CT) dose of montelukast for administration to children ages 2 to 5 years with asthma, yielding a single-dose pharmacokinetic profile (area under the plasma concentration-time curve [AUC]) comparable to that of the 10 mg film-coated tablet (FCT) dose in adults. Because patient numbers were small and the volume of blood that could be collected from individual 2- to 5-year-old patients was limited, a population pharmacokinetic approach was used to estimate population AUC (AUCpop). The 4 mg CT dose of montelukast was well tolerated and yielded an AUCpop (2721 ng.h/mL) similar to that of the adult AUCpop (2595 ng.h/mL) observed after a 10 mg FCT dose. These results support the selection of a 4 mg once-daily CT dose of montelukast for future efficacy and safety studies in children ages 2 to 5 years with asthma.
Acetates↗
Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years.
BACKGROUND: The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been reported. One potential advantage of montelukast is the ease of administering a once-daily chewable tablet; additionally, no tachyphylaxis or change in the safety profile has been evidenced after up to 140 and 80 weeks of montelukast therapy in adults and pediatric patients aged 6 to 14 years, respectively. To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children. OBJECTIVE: Our primary objective was to determine the safety profile of montelukast, an oral leukotriene receptor antagonist, in preschool children with persistent asthma. Secondarily, the effect of montelukast on exploratory measures of asthma control was also studied. DESIGN AND STATISTICAL ANALYSIS: We conducted a double-blind, multicenter, multinational study at 93 centers worldwide: including 56 in the United States, and 21 in countries in Africa, Australia, Europe, North America, and South America. In this study, we randomly assigned 689 patients (aged 2-5 years) to 12 weeks of treatment with placebo (228 patients) or 4 mg of montelukast as a chewable tablet (461 patients) after a 2-week placebo baseline period. Patients had a history of physician-diagnosed asthma requiring use of beta-agonist and a predefined level of daytime asthma symptoms. Caregivers answered questions twice daily on a validated, asthma-specific diary card and, at specified times during the study, completed a validated asthma-specific quality-of-life questionnaire. Physicians and caregivers completed a global evaluation of asthma control at the end of the study. Efficacy end points included: daytime and overnight asthma symptoms, daily use of beta-agonist, days without asthma, frequency of asthma attacks, number of patients discontinued because of asthma, need for rescue medication, physician and caregiver global evaluations of change, asthma-specific caregiver quality of life, and peripheral blood eosinophil counts. Although exploratory, the efficacy end points were predefined and their analyses were written in a data analysis plan before study unblinding. At screening and at study completion, a complete physical examination was performed. Routine laboratory tests were drawn at screening and weeks 6 and 12, and submitted to a central laboratory for analysis. Adverse effects were collected from caregivers at each clinic visit. An intention-to-treat approach, including all patients with a baseline measurement and at least 1 postrandomization measurement, was performed for all efficacy end points. An analysis-of-variance model with terms for treatment, study center and stratum (inhaled/nebulized corticosteroid use, cromolyn use, or none) was used to estimate treatment group means and between-group differences and to construct 95% confidence intervals. Treatment-by-age, -sex, -race, -radioallergosorbent test, -stratum, and -study center interactions were evaluated by including each term separately. Fisher's exact test was used for between-group comparisons of the frequency of asthma attacks, discontinuations from the study because of worsening asthma, need for rescue medication, and the frequencies of adverse effects. Because of an imbalance in baseline values for eosinophil counts for the 2 treatment groups, an analysis of covariance was performed on the eosinophil change from baseline with the patient's baseline as covariate. STUDY PARTICIPANTS: Of the 689 patients enrolled, approximately 60% were boys and 60% were white. Patients were relatively evenly divided by age: 21%, 24%, 30%, and 23% were aged 2, 3, 4, and 5 years, respectively. For 77% of the patients, asthma symptoms first developed during the first 3 years of life. During the placebo baseline period, patients had asthma symptoms on 6.1 days/week and used beta-agonist on 6.0 days/week. RESULTS: In over 12 weeks of treatment of patients aged 2 to 5 years, montelukast administered as a 4-mg chewable tablet produced significant improvements compared with placebo in multiple parameters of asthma control including: daytime asthma symptoms (cough, wheeze, trouble breathing, and activity limitation); overnight asthma symptoms (cough); the percentage of days with asthma symptoms; the percentage of days without asthma; the need for beta-agonist or oral corticosteroids; physician global evaluations; and peripheral blood eosinophils. The clinical benefit of montelukast was evident within 1 day of starting therapy. Improvements in asthma control were consistent across age, sex, race, and study center, and whether or not patients had a positive radioallergosorbent test. Montelukast demonstrated a consistent effect regardless of concomitant use of inhaled/nebulized corticosteroid or cromolyn therapy. Caregiver global evaluations, the percentage of patients experiencing asthma attacks, and improvements in quality-of-life scores favored montelukast, but were not significantly different from placebo. There were no clinically meaningful differences between treatment groups in overall frequency of adverse effects or of individual adverse effects, with the exception of asthma, which occurred significantly more frequently in the placebo group. There were no significant differences between treatment groups in the frequency of laboratory adverse effects or in the frequency of elevated serum transaminase levels. Approximately 90% of the patients completed the study. CONCLUSIONS: Oral montelukast (4-mg chewable tablet) administered once daily is effective therapy for asthma in children aged 2 to 5 years and is generally well tolerated without clinically important adverse effects. Similarly, in adults and children aged 6 to 14 years, montelukast improves multiple parameters of asthma control. Thus, this study confirms and extends the benefit of montelukast to younger children with persistent asthma.
Acetates↗
High-dose intra-arterial cisplatin therapy followed by radiation therapy for advanced squamous cell carcinoma of the head and neck.
OBJECTIVE: To assess the effectiveness of a protocol consisting of 4 cycles of high-dose intra-arterial cisplatin infusions followed by radiation therapy for improving chemotherapy response rates, organ preservation, and survival in patients with advanced-stage untreated and previously treated squamous cell carcinoma of the head and neck. DESIGN AND SETTING: A prospective study of sequentially enrolled patients treated in an academic medical center. The Kaplan-Meier method was used for survival analysis. PATIENTS: Fifty-eight nonpregnant adults, 18 years of age or older, with measurable untreated or recurrent advanced biopsy-proven squamous cell carcinoma of the head and neck. MAIN OUTCOME MEASURES: Response rate to targeted intra-arterial cisplatin infusions, organ preservation, and survival. RESULTS: Fifty-eight patients (44 men and 14 women) were followed up for at least 2 years (median duration of follow-up, 27 months). Twenty-nine (67%) of the 43 previously untreated patients had a complete response to intra-arterial cisplatin therapy. Of the untreated patients, 28 are alive and disease free after a median follow-up time of 30 months. Five of the patients with recurrent disease had a complete response to intra-arterial cisplatin therapy. There were 4 survivors after a median follow-up time of 17.5 months. Of note, there were no deaths or serious complications related to the treatment in either group. CONCLUSIONS: High-dose intra-arterial cisplatin therapy provides a high complete and partial response rate (91%). The combination of high-dose intra-arterial cisplatin and radiation therapy is effective in improving survival and organ preservation rates in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. This treatment protocol is much less effective for recurrent disease.
Adult↗
Heterosubtypic immunity to influenza A virus infection requires B cells but not CD8+ cytotoxic T lymphocytes.
Heterosubtypic immunity (HSI), defined as protective cross-reactivity to lethal infection with influenza A virus of a serotype different from the virus initially encountered, is thought to be mediated by cross-reactive cytotoxic T lymphocytes (CTL). This study provides direct evidence for the role of effector CTL versus B cells in HSI in mice with a targeted disruption in the alpha chain of CD8 molecule (CD8(+) T cell deficient) or the immunoglobulin mu heavy chain (B cell deficient), respectively. CD8(+) T cell-deficient mice developed complete HSI. These mice displayed normal humoral immune responses, as determined by titers of subtype cross-reactive antibodies and virus-neutralizing antibodies specific for the immunizing influenza strain. In contrast, HSI was not observed in B cell-deficient mice, although these mice could mount cross-reactive CTL responses. These results show that B cells are required for HSI and provide new insight into the mechanisms of HSI, with significant implications in vaccine development.
Animals↗
A method for quantification of absolute amounts of nucleic acids by (RT)-PCR and a new mathematical model for data analysis.
Accurate quantification of nucleic acids by competitive (RT)-PCR requires a valid internal standard, a reference for data normalization and an adequate mathematical model for data analysis. We report here an effective procedure for the generation of homologous RNA internal standards and a strategy for synthesizing and using a reference target RNA in quantification of absolute amounts of nucleic acids. Further, a new mathematical model describing the general kinetic features of competitive PCR was developed. The model extends the validity of quantitative competitive (RT)-PCR beyond the exponential phase. The new method eliminates the errors arising from different amplification efficiencies of the co-amplified sequences and from heteroduplex formation in the system. The high accuracy (relative error <2%) is comparable to the recently developed real time detection 5'-nuclease PCR. Also, corresponding computer software has been devised for practical data analysis.
Cell Line↗
Is the head position during preoperative image data acquisition essential for the accuracy of navigated brain tumor surgery?
OBJECTIVE: To analyze the influence of head positioning during preoperative image data acquisition on intraoperative accuracy of modern neuronavigation systems. MATERIAL AND METHODS: All measurements were performed preoperatively before opening the head. In 24 patients, preoperative MR image data acquisition was performed twice on a 0.5 T scanner using a contrast-enhanced T1-weighted sequence; first in the neutral head position, and thereafter in the surgical head position for pterional craniotomy. For both data sets, the Sylvian fissure, the central sulcus, and the superior and inferior temporal sulci were depicted on the patient's scalp using the frameless neuronavigation system EasyGuide Neurotrade mark. At the beginning of surgery, with the head fixed in a Mayfield clamp and an articulated instrument holder being used for fixation of the navigation system's pointer, the distances of 10 correlating points of the sulci for the two data sets were measured. To evaluate the accuracy of the navigation system in this experimental set-up, a phantom study was also performed. RESULTS: The phantom study revealed a mean inaccuracy of 1.6 mm (range 0.1-2.3 mm, standard deviation 0.6 mm). The patient study revealed a mean inaccuracy of 1.8 mm (range 0.4-2.8 mm, standard deviation 0.5 mm). CONCLUSIONS: The data suggest that the positioning of the patient's head during preoperative imaging plays no relevant role in intraoperative accuracy of neuronavigation. However, further studies and a larger number of patients with various pathologies in different regions of the brain are necessary to obtain a better understanding of the problem of brain shift in neuronavigation due to patient positioning alone, and to avoid procedure-related operative morbidity.
Adult↗
Virtual pointer projection of the central sulcus to the outside of the skull using frameless neuronavigation -- accuracy and applications.
BACKGROUND: The purpose of this prospective study was to localize the central sulcus by frameless neuronavigation and to project this anatomical structure to the outside of the skull on the skin. This method was analyzed in respect to its practicability, accuracy, and potential applications. METHOD: In 27 patients investigated (28 unaffected hemispheres), the central sulcus was virtually projected to the outside of the skull using frameless neuronavigation and a virtual pointer elongation of 15 or 20 mm. The following parameters were measured on the scalp: 1. the distance between the bregma and the midline junction of the central sulcus, and 2. the angle between the central sulcus and the midline. These dada were compared with measurements based on the original axial MR images of these patients. Finally, a laboratory phantom study was designed in analogy to a patient's examination for estimation of the overall accuracy of the neuronavigation system in the experimental setup used in this study. FINDINGS: Virtual pointer projection of the central sulcus to the outside of the skull using frameless neuronavigation was found to be easily possible. The distance between the bregma and the midline junction of the central sulcus amounted to a mean of 55 mm on the left and 56 mm on the right. The angle between the central sulcus and the midline reached a mean of 63 degrees on the left and 60 degrees on the right. These data confirmed results of other studies with no frameless neuronavigation devices. The phantom study revealed a mean overall inaccuracy of 0.9 mm at a virtual pointer elongation of 15 mm. At a virtual pointer elongation of 20 mm, the mean overall inaccuracy of our study was 1.1 mm. These results correspond to the inaccuracy of frame based stereotaxy. INTERPRETATION: It is easily possible, valid, and reliable to virtually project the central sulcus to the outside of the skull with an acceptably low inaccuracy using frameless neuronavigation. This is important for research studies that correlate and integrate different functional imaging methods with the aid of frameless neuronavigation.
Adult↗
Montelukast adult (10-mg film-coated tablet) and pediatric (5-mg chewable tablet) dose selections.
Montelukast is a selective leukotriene receptor antagonist that has been shown to be effective in the treatment of chronic asthma. It is approved in more than 70 countries for patients 6 years of age and older. For adults (> or = 15 years of age), a 10-mg film-coated tablet (FCT) is available, and for children (aged 6 to 14 years), a 5-mg chewable tablet (CT) is available. The adult montelukast dose (10-mg FCT) was selected on the basis of classic dose-ranging studies as the lowest dose that produces maximal improvement in both measures of airway function and patient-reported outcomes in chronic asthma and in the attenuation of exercise-induced bronchoconstriction. The strategy used for the pediatric dose selection for montelukast was based on the determination of a CT dose that would provide an overall systemic exposure to montelukast in children similar to that in adults who receive a 10-mg FCT dose. Because montelukast was to be given chronically for the treatment of asthma, the area under the plasma concentration-time curve was considered to be the pharmacokinetic measurement that best represented systemic exposure to the drug. A 5-mg CT yielded a comparable single-dose area under the plasma concentration-time curve profile to that of the adult 10-mg FCT dose and, therefore, was selected as the pediatric dose for children aged 6 to 14 years with asthma. Subsequently, 2 studies of efficacy and tolerability validated the choice of the 5-mg CT dose.
Acetates↗
Gamma interferon is not required for mucosal cytotoxic T-lymphocyte responses or heterosubtypic immunity to influenza A virus infection in mice.
Heterosubtypic immunity (HSI) is defined as cross-protection against influenza virus of a different serotype than the virus initially encountered and is thought to be mediated by influenza virus-specific cytotoxic T lymphocytes (CTL). Since gamma interferon (IFN-gamma) stimulates cytotoxic cells, including antigen-specific CTL which may control virus replication by secretion of antiviral cytokines such as tumor necrosis factor alpha and IFN-gamma, we have investigated the mechanism of HSI by analyzing the role of IFN-gamma for HSI in IFN-gamma gene-deleted (IFN-gamma(-/-)) mice. It has been reported that IFN-gamma is not required for recovery from primary infection with influenza virus but is important for HSI. Here, we conclusively show that IFN-gamma is not required for induction of secondary influenza virus-specific CTL responses in mediastinal lymph nodes and HSI to lethal influenza A virus infection. Although T helper 2 (Th2)-type cytokines were upregulated in the lungs of IFN-gamma(-/-) mice after virus challenge, either Th1- or Th2-biased responses could provide heterosubtypic protection. Furthermore, titers of serum-neutralizing and cross-reactive antibodies to conserved nucleoprotein in IFN-gamma(-/-) mice did not differ significantly from those in immunocompetent mice. These results indicate that lack of IFN-gamma does not impair cross-reactive virus-specific immune responses and HSI to lethal infection with influenza virus. Our findings provide new insight for the mechanisms of HSI and should be valuable in the development of protective mucosal vaccines against variant virus strains, such as influenza and human immunodeficiency virus.
Adaptation, Physiological↗
Purification of ribonucleotide reductase subunits Y1, Y2, Y3, and Y4 from yeast: Y4 plays a key role in diiron cluster assembly.
Ribonucleotide reductases (RNRs) catalyze the conversion of nucleotides to deoxynucleotides. Class I RNRs are composed of two types of subunits: RNR1 contains the active site for reduction and the binding sites for the nucleotide allosteric effectors. RNR2 contains the diiron-tyrosyl radical (Y.) cofactor essential for the reduction process. Studies in yeast have recently identified four RNR subunits: Y1 and Y3, Y2 and Y4. These proteins have been expressed in Saccharomyces cerevisiae and in Escherichia coli and purified to approximately 90% homogeneity. The specific activity of Y1 isolated from yeast and E. coli is 0.03 micromol.min(-1).mg(-1) and of (His)(6)-Y2 [(His)(6)-Y2-K387N] from yeast is 0.037 micromol. min(-1).mg(-1) (0.125 micromol.min(-1).mg(-1)). Y2, Y3, and Y4 isolated from E. coli have no measurable activity. Efforts to generate Y. in Y2 or Y4 using Fe(2+), O(2), and reductant have been unsuccessful. However, preliminary studies show that incubation of Y4 and Fe(2+) with inactive E. coli Y2 followed by addition of O(2) generates Y2 with a specific activity of 0.069 micromol.min(-1). mg(-1) and a Y. A similar experiment with (His)(6)-Y2-K387N, Y4, O(2), and Fe(2+) results in an increase in its specific activity to 0.30 micromol.min(-1).mg(-1). Studies with antibodies to Y4 and Y2 reveal that they can form a complex in vivo. Y4 appears to play an important role in diiron-Y. assembly of Y2.
Base Sequence↗
Heterosubtypic immunity to lethal influenza A virus infection is associated with virus-specific CD8(+) cytotoxic T lymphocyte responses induced in mucosa-associated tissues.
Heterosubtypic immunity, defined as cross-reactive immune responses to influenza virus of a different serotype than the virus initially encountered, was investigated in association with virus-specific cytotoxic T lymphocyte (CTL) responses induced in systemic and mucosa-associated lymph nodes after immunization via different routes. Mice immunized by the pulmonary route with live nonpathogenic influenza virus, strain Udorn (H3N2), survived challenge with mouse-adapted pathogenic influenza virus, strain PR/8/34 (H1N1). These mice developed strong heterosubtypic CTL responses in spleen, cervical lymph nodes (CLN), and mediastinal lymph nodes (MLN). Alternately, only 20% of mice immunized intravenously, intraperitoneally, or intranasally survived the challenge; all of these developed CTL responses in spleen and CLN, but not in MLN. Direct correlation between short-term and long-term memory heterosubtypic CTL responses induced in MLN and host recovery after lethal infection indicates that these CTL responses may play an important role in heterosubtypic immunity. Furthermore, induction and maintenance of memory CTL in regional mucosa-associated lymphoid tissues are highly dependent on mucosal immunization. The results implicate the mechanism of heterosubtypic immunity and should be an important consideration in the development of protective mucosal vaccines against variant strains of influenza and HIV.
Adaptation, Biological↗
Current perspectives in the surgery of multiple endocrine neoplasias.
Multiple endocrine neoplasia is an uncommon but fascinating condition. In this review we examine the multifaceted presentations, the diagnostic challenges and different management strategies for various syndromes. This is an attempt to share our knowledge and experience towards achieving better outcomes in the management of the diseases.
Adrenal Gland Neoplasms↗
Tumour size: the only predictive factor for 131I MIBG uptake in phaeochromocytoma and paraganglioma.
BACKGROUND: 131I Meta-iodobenzylguanidine (131I MIBG) scintigraphy can detect chromaffin tumours with a high specificity but its sensitivity remains limited. In this study, the influence of clinical features and tumour pathology on the results of 131I MIBG of patients with phaeochromocytomas and paragangliomas was examined. METHODS: The records of 104 patients operated on for chromaffin tumours who had pre-operative 131I MIBG were reviewed. Demographic data, clinical features, biochemical results and pathology of tumours were analysed. The size of the tumour was assessed by the three measured diameters of the specimen and its calculated volume. Univariate relationship between tumours' characteristics and the results of 131I MIBG were examined. RESULTS: Out of 119 tumours, 104 (87%) were detected by 131I MIBG. Mean +/- SD largest diameter and volume of the tumours were 6.0 +/- 2.4 cm (range 0.8-11.5 cm) and 68 +/- 74 cm3 (range 0.2-421 cm3). Results of 131I MIBG were significantly correlated with both the largest diameter of the tumour (P < 0.01) and by its volume (P < 0.001). 131I MIBG was negative in 35.5% of tumours < 20 cm3 and in 2.6% of those < 20 cm3. No other criteria were correlated with positive 131I MIBG, including aetiology, pathology or catecholamine secretion pattern. CONCLUSIONS: The result of 131I MIBG scanning in patients with chromaffin tumours is significantly correlated with the size of the tumour.
3-Iodobenzylguanidine↗
Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults.
Montelukast, an oral leukotriene-receptor antagonist, has demonstrated efficacy and tolerability for the treatment of chronic asthma in adults. A once-daily 10 mg dose (film-coated tablet) was selected as the optimal adult dose based on dose-ranging studies. Asthma is a similar disease and is treated with the same medications in children and adults. These observations suggested that a dose of montelukast in children providing overall drug exposure (i.e., montelukast plasma concentrations) similar to that of the 10 mg film-coated tablet dose in adults would be efficacious, well tolerated, and obviate the need for separate dose-ranging studies in children. Therefore, the dose of montelukast for 6- to 14-year-old children was selected by identifying the chewable tablet dose of montelukast yielding a single-dose area under the plasma concentration-time curve (AUC) comparable to that achieved with the adult 10 mg film-coated tablet dose. Based on this approach, which included dose normalization of data from several pediatric pharmacokinetic studies, a 5 mg chewable tablet dose of montelukast was selected for use in clinical efficacy studies in 6- to 14-year-old children with asthma.
Acetates↗
The particulate methane monooxygenase from methylococcus capsulatus (Bath) is a novel copper-containing three-subunit enzyme. Isolation and characterization.
The particulate methane monooxygenase (pMMO) is known to be very difficult to study mainly due to its unusual activity instability in vitro. By cultivating Methylococcus capsulatus (Bath) under methane stress conditions and high copper levels in the growth medium, membranes highly enriched in the pMMO with exceptionally stable activity can be isolated from these cells. Purified and active pMMO can be subsequently obtained from these membrane preparations using protocols in which an excess of reductants and anaerobic conditions were maintained during membrane solubilization by dodecyl beta-D-maltoside and purification by chromatography. The pMMO was found to be the major constituent in these membranes, constituting 60-80% of total membrane proteins. The dominant species of the pMMO was found to consist of three subunits, alpha, beta, and gamma, with an apparent molecular mass of 45, 26, and 23 kDa, respectively. A second species of the pMMO, a proteolytically processed version of the enzyme, was found to be composed of three subunits, alpha', beta, and gamma, with an apparent molecular mass of 35, 26, and 23 kDa, respectively. The alpha and alpha' subunits from these two forms of the pMMO contain identical N-terminal sequences. The gamma subunit, however, exhibits variation in its N-terminal sequence. The pMMO is a copper-containing protein only and shows a requirement for Cu(I) ions. Approximately 12-15 Cu ions per 94-kDa monomeric unit were observed. The pMMO is sensitive to dioxygen tension. On the basis of dioxygen sensitivity, three kinetically distinct forms of the enzyme can be distinguished. A slow but air-stable form, which is converted into a "pulsed" state upon direct exposure to atmospheric oxygen pressure, is considered as type I pMMO. This form was the subject of our pMMO isolation effort. Other forms (types II and III) are deactivated to various extents upon exposure to atmospheric dioxygen pressure. Under inactivating conditions, these unstable forms release protons to the buffer (approximately 10 H+/94-kDa monomeric unit) and eventually become completely inactive.
Amino Acid Sequence↗