bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA sequence analysis of GJB2, encoding connexin 26: Observations from a population of hearing impaired cases and variable carrier rates, complex genotypes, and ethnic stratification of alleles among controls
Authors: Tang Hsiao‐Yuan , Fang Ping , Ward Patricia A. , Schmitt Eric , Darilek Sandra , Manolidis Spiros , Oghalai John S. , Roa Benjamin B. , Alford Raye Lynn 
Published: October 2006

AbstractMutations in GJB2 are associated with hereditary hearing loss. DNA sequencing of GJB2 in a cohort of hearing impaired patients and a multi‐ethnic control group is reported. Among 610 hearing impaired cases, 43 DNA sequence variations were identified in the coding region of GJB2 including 24 mutations, 8 polymorphisms, 3 unclassified variants (G4D, R127C, M163V), 1 controversial variant (V37I), and 7 novel variants (G12C, N14D, V63A, T86M, L132V, D159, 592_600delinsCAGTGTTCATGACATTC). Sixteen non‐coding sequence variations were also identified among cases including the IVS1+1A>G mutation, 2 polymorphisms, and 13 novel variants. A diagnosis of GJB2‐associated hearing loss was confirmed for 63 cases (10.3%). Heterozygous mutations were found in 39 cases (6.4%). Eleven cases carrying novel or unclassified variants (1.8 %) and 18 cases carrying the controversial V37I variant were identified (3%). In addition, 294 control subjects from 4 ethnic groups were sequenced for GJB2. Thirteen sequence variations in the coding region of GJB2 were identified among controls including 2 mutations, 6 polymorphisms, 2 unclassified variants (G4D, T123N), 1 controversial variant (V37I), and 2 novel variants (R127L, V207L). Nine sequence variations were identified among controls in the non‐coding regions in and around GJB2 exon 2. Of particular interest among controls were the variability in carrier rates and ethnic stratification of alleles, and the complex genotypes among Asians, 47% of whom carried two to four sequence variations in the coding region of GJB2. These data provide new information about carrier rates for GJB2‐based hearing loss in various ethnic groups and contribute to evaluation of the pathogenicity of the controversial V37I variant. © 2006 Wiley‐Liss, Inc.
Genotype–phenotype correlations in cerebral cavernous malformations patients
Authors: Denier Christian , Labauge Pierre , Bergametti Françoise , Marchelli Florence , Riant Florence , Arnoult Minh , Maciazek Jacqueline , Vicaut Eric , Brunereau Laurent , Tournier‐Lasserve Elisabeth 
Published: October 2006

AbstractObjectiveTo compare clinical features of CCM1, CCM2, and CCM3 mutation carriers.MethodsA detailed clinical and molecular analysis of 163 consecutive cerebral cavernous malformation (CCM) families was performed.ResultsA deleterious mutation was detected in 128 probands. Three hundred thirty‐three mutation carriers were identified (238 CCM1, 67 CCM2, and 28 CCM3). Ninety‐four percent of the probands with an affected relative had a mutation compared with 57% of the probands with multiple lesions but no affected relative (p < 0.001). The number of affected individuals per family was lower in CCM3 families (p < 0.05). The proportion of patients with onset of symptoms before 15 years of age was higher in the CCM3 group (p < 0.0025). Cerebral hemorrhage was the most common initial presentation in CCM3 patients. The average number of T2‐weighted imaging lesions was similar in the three groups, in contrast with a significantly lower number of gradient‐echo sequence lesions in CCM2 patients (p < 0.05). The number of gradient‐echo sequence lesions increased more rapidly with age in CCM1 than in CCM2 patients (p < 0.05).InterpretationDespite similarities among the three groups, there is a significantly lower number of affected individuals in CCM3 pedigrees, CCM3 mutations may confer a higher risk for cerebral hemorrhage, particularly during childhood, and the increment of gradient‐echo sequence lesions with age differs between CCM1 and CCM2 patients. Ann Neurol 2006
Simultaneous determination of methenamine and formaldehyde in the urine of humans after methenamine administration
Authors: Gollamudi Ramachander , Meyer Marvin C. , Straughn Arthur B. 
Published: October 2006

AbstractMethenamine (hexamethylenetetramine) and its hydrolysis product formaldehyde are determined in the presence of each other in urine by a spectrophotometric method. Formaldehyde is assayed by a colour reaction with tryptophan, sulphuric acid and ferric chloride after precipitating methenamine by three treatments with mercuric chloride. Methenamine is indirectly analysed by hydrolysis to formaldehyde with dilute hydrochloric acid. Formaldehyde levels as low as 5·0 μg ml−1 in the presence of methenamine concentrations as high as 2·5 mg ml−1 can be assayed. Of practical significance is the feature that urine may be stored up to 1 week for analysis, by appropriate dilution and freezing, without excessive loss of methenamine or formaldehyde. The method was applied to the determination of the bioavailability of methenamine hippurate in ten human volunteers.
Animal model for investigation of fluphenazine kinetics after administration of long‐acting esters
Authors: Altamura A. C. , Whelpton R. , Curry S. H. 
Published: October 2006

AbstractA model was developed for studying fluphenazine availability and disposition. Rats were given doses of radioactively labelled esters of fluphenazine by intramuscular injection. Radioactivity excreted in urine, faeces, and expired air was assessed for fluphenazine esters, fluphenazine, and CO2 content. Levels of fluphenazine and its esters were measured in plasma, brain, and muscle (injected and non‐injected samples). The data mimicked those obtained in other studies involving the same material given to human subjects, and posed new questions concerning the factors controlling fluphenazine availability when given as ‘long‐acting’ intramuscular injections.
Rapid fluorimetric procedure for the analysis of Fendosal in plasma and data following oral dosing
Authors: Hill H. M. , Chamberlain J. , Hajdu P. , Damm D. 
Published: October 2006

AbstractA simple, rapid, and sensitive procedure is described for the determination of Fendosal in plasma. After extraction of Fendosal from buffered plasma, the drug is determined by measurement of the fluorescence induced by irradiation with short‐wave ultra‐violet (UV) light. The complete procedure can be completed in less than 2 h; one technician can perform up to 50 assays in one working day. The limit of detection corresponds to 0–1 μg ml−1 plasma. Drug concentration and induced fluorescence were linearly related over the concentration range 0–8 μg ml−1.
Disposition kinetics of disopyramide in patients with renal insufficiency
Authors: Shen Danny D. , Cunningham John L. , Shudo Isami , Azarnoff Daniel L. 
Published: October 2006

AbstractThe pharmacokinetics of an intravenous injection of disopyramide was studied in five normal subjects and six patients with varying degrees of renal impairment. The elimination rate constant (β) was related to the endogenous creatinine clearance (Clcr). However, a decrease in β was not observed until the Clcr was reduced below 40 ml min−1. Below 40 ml min−1 a linear relationship existed between β and Clcr. Similarly, the plasma elimination half‐life (t½β) showed a significant increase when the Clcr was less than 30 ml min−1. Hence, dosage modification for disopyramide is necessary only when renal function is severely impaired. Overall, the apparent volume of distribution in patients with renal insufficiency was reduced to two‐thirds of that in normal subjects. Therefore, in patients with Clcr less than 40 ml min−1 both the loading and maintenance dose of disopyramide should be reduced.
Relative bioavailability of three commercial quinidine dosage forms
Authors: Sirois Gerard , Eshaque Mohammad , Chabot Michel 
Published: October 2006

AbstractBioavailabilities of three quinidine formulations were compared. Two tablets of each dosage form were administered to 12 healthy volunteers according to a repeated Latin square design; plasma levels of unchanged and total drug were determined. Quinidine was absorbed significantly more rapidly from one of the formulations than the other two; the bioavailability of this formulation, calculated from intact drug data, normalized for subject differences, was also significantly greater than that of the other two, 68 and 76 per cent respectively. Individual comparisons of area under the curve (AUC) indicated that estimated relative bioavailability depends on the specificity of the assay, the adjustment of the AUC for the area beyond the last measurable plasma concentration and the normalization of the AUC. The data suggest there is a correlation between dissolution rate and peak plasma concentration.
Pharmacokinetic characteristics of ketoprofen suppositories
Authors: Caillé G. , Besner J. G. , Lacasse Y. , Vézina M. 
Published: October 2006

AbstractThe pharmacokinetic profile of ketoprofen suppositories following single and chronic (32 doses) administration to 12 healthy adult male volunteers was established. Each subject received a single rectal dose of 100 mg of ketoprofen on day 1, followed by one suppository of 100 mg b.i.d. for days 8–22, and finally one suppository on day 23. Plasma samples were analysed by gas‐liquid chromatography. Following single doses, the mean maximum observed concentrations of ketoprofen in plasma (6·56 μg ml−1) were achieved at 1·1 h; the mean elimination half‐life was 1·78 h. The results indicate that ketoprofen is rapidly and reproducibly absorbed and eliminated from the suppository dose form.
Isoniazid‐induced intolerance to ethanol in rabbit, guinea pig and rat
Authors: Whitehouse L. W. , Paul C. J. , Thomas B. H. 
Published: October 2006

AbstractIsoniazid (50 or 100 mg kg−l p.o.) inhibited the elimination of ethanol (0·5, 1·0, and 2·5 g kg−l p.o.) from the plasma of rabbit, guinea pig, and rat. The effect of isoniazid, isonicotinic acid, N‐acetylisoniazid, N‐acetylhydrazine, N,N‐diacetylhydrazine, and hydrazine on the in vitro metabolism of alcohol by rabbit liver alcohol dehydrogenase was examined. Only isoniazid, hydrazine, and acetylisoniazid showed significant inhibitory activity with I50's of 17·7, 1·25, and 0·78 mmol 1−1 respectively. Intolerance to ethanol following isoniazid treatment was attributed to isoniazid inhibition of liver alcohol dehydrogenase.
Pharmacokinetics of drugs in blood I. Unusual distribution of gentamicin
Authors: Lee Myung G. , Chen Mei‐Ling , Huang Shiew‐Mei , Chiou Win L. 
Published: October 2006

AbstractDistribution kinetics of gentamicin in whole blood were studied. After spiking human blood to an initial concentration of 20 μg ml−1, plasma gentamicin concentrations dropped to minima at about 5 min then increased to maxima at about 15 min and remained constant afterwards. A difference of up to 36 per cent between the maximum and minimum was found. The equilibration was faster with lower initial concentrations. These unusual distribution phenomena might be attributed to the Schiff base formation between nonprotonated amino groups of gentamicin and free fatty aldehyde groups on blood cell membrane. The mean equilibrium blood cells/plasma partition ratio was about 0.1. Similar equilibration kinetics were observed with blood of rabbits after being intravenously dosed with gentamicin. Therefore, the time elapsed between the collection and centrifugation of blood samples, especially shortly after dosing, may have a significant effect on the ‘measured’ plasma gentamicin concentration. Distribution between plasma and blood cells may also occur in a similar manner with other drugs which have primary amino groups. It is recommended that distribution kinetics of drugs and metabolites in blood be included in pharmacokinetic studies.
Rectal infusion of the model drug antipyrine with an osmotic delivery system
Authors: De Leede L. G. J. , De Boer A. G. , Breimer D. D. 
Published: October 2006

AbstractAn osmotically‐powered rectal drug delivery system, was used for the rectal infusion of the model drug antipyrine. The system, which is slightly larger than a normal suppository, has a nominal pumping rate of 43 μl h− 1 over at least 30 h. Four healthy volunteers kept two such systems in their rectum for a sum total of 98 h. Saliva and plasma concentrations were determined at regular intervals and in all cases a very constant steady‐state saliva and plasma concentration was reached and maintained. Defecation and reinsertion of the drug delivery system did not cause any irregularities in the concentration profile. The system was very well tolerated by the volunteers.
Platinum levels in human erythrocytes following intravenous administration of cisplatin: Importance of erythrocytes as a distribution site for platinum species
Authors: Long D. F. , Patton T. F. , Repta A. J. 
Published: October 2006

AbstractRecent reports of the extent of uptake of cisplatin and possible biotransformation products of cisplatin by red blood cells of humans receiving this drug have been conflicting. In vitro and in vivo studies of the platinum content of washed red blood cells following exposure to cisplatin have been conducted. Low levels of platinum were found in the red cell lysate of the erythrocytes of humans receiving cisplatin. The platinum was primarily associated with red cell lysate and little, if any, platinum appeared to be associated with the cell membrane. The in vivo studies indicated that the intracellular platinum levels are rapidly achieved following cisplatin administration and the platinum concentration appears to be linearly related to the administered dose. However, the fraction of platinum found within the erythrocytes is slight, representing only about 1 per cent of the administered dose. In light of the reactivity of cisplatin with compounds containing divalent sulphur and the millimolar glutathione levels present within erythrocytes, it is unlikely that the platinum released from the red blood cell is in the form of cisplatin. Therefore, it is doubtful that the red blood cell is a major site for cisplatin distribution and the anticancer activity of the platinum released from red blood cells is questionable.
Bioavailability in man of atenolol and chlorthalidone from a combination formulation
Authors: McAinsh James , Bastain William , Young Jean , Harry John D. 
Published: October 2006

AbstractIn this comparative bioavailability study in 12 healthy volunteers the blood level profiles and urinary recoveries of both atenolol and chlorthalidone were studied following the administration of the drug as a fixed combination (‘Tenoretic’), as a free combination, and individually, at doses of 100 mg atenolol, and 25 mg chlorthalidone.There were no statistically significant differences between the three formulations of atenolol in terms of individual blood levels, half‐life, area‐under‐the‐curve, and urinary excretion. The half‐lives were between 5 and 6 h in agreement with other published data. Thus the bioavailability of atenolol from the fixed combination is equivalent to that from the free combination and from the atenolol tablet.The chlorthalidone blood levels were slightly higher following the administration of the fixed combination when compared with the free combination or the chlorthalidone tablet. This observation was reflected in estimates of the area under the curves and the urinary recoveries. The half‐lives of all three formulations were similar at about 60 h.It is concluded that combining chlorthalidone and atenolol in a single tablet does not reduce the systemic bioavailability of either component.
Bioavailability of terfenadine in man
Authors: Okerholm R. A. , Weiner D. L. , Hook R. H. , Walker B. J. , Leeson G. A. , Biedenbach S. A. , Cawein M. J. , Dusebout T. D. , Wright G. J. , Myers Mary , Schindler Valerie , Cook C. E. 
Published: October 2006

AbstractFourteen normal male subjects were given either 60 mg or 180mg of terfenadine suspension in a randomized two‐way crossover study. Peak plasma concentrations of 1.544 ± 0.726 (mean ± S.D.) ng ml−1 were obtained in 0.786 ± 0.426 h following the 60 mg dose and displayed an AUC of 11.864 ± 3.369 ng h ml−1. Whereas peak plasma concentrations of 4.519.2 ± 002ng ml−1in 1.071 ± 0.514h were obtained following the 180mg dose. The AUC following the 180 mg dose was 44.341 ± 22.041 ng h ml−1. When 60 mg of 14C terfenadine was given to six additional subjects, the peak plasma concentrations of 351.43ng equivalents per ml were obtained in 1.67 ± 0.41 h and the AUC was 2297.71 ± 310.85ng‐equivalentshml−1. This indicates that approximately 99.5 per cent of the terfenadine related material that is absorbed undergoes biotransformation. Urinary excretion of 14C accounted for 39.89 ± 5.29 per cent of the dose while 60.58 ± 2.44 per cent of the dose was recovered in the feces in twelve days. Thin‐layer chromatographic (TLC) examination of fecal extracts showed only a trace of material chromatographing with terfenadine. This may indicate that the 14C present in the feces is not due to lack of absorption.
Interrelation between plasma protein binding, rate of injection and the anesthetic effect of thiopental
Authors: Kurz H. , Fichtl B. 
Published: October 2006

Abstract

Following thiopental injection to rabbits in doses of 5 mg kg−1 intravenously (i.v.) the sleeping time lasted longer after injection by bolus than after administration made more slowly over 30 or 60 s, respectively.
Peak concentration in the blood of the animals after bolus injection was about four times higher than after slow injection.
The determination of protein binding showed that the unbound fraction of thiopental at the high concentration following bolus injection is almost doubled compared with the unbound concentration following the slow injections. Therefore it is concluded that this contributes to an increased concentration of thiopental in the brain during the initial phase of distribution thus extending the sleeping time.
The results from experiments using a distribution model give additional evidence supporting this conception.
Normal pharmacokinetics of 99mTc‐diphosphonate after intravenous administration
Authors: Castronovo Frank P. 
Published: October 2006

AbstractIn the past several years bone imaging has become a routine diagnostic tool for the nuclear medicine clinician. However, increased information may be derived by determinating the radio‐pharmacokinetic parameters associated with blood, urine, and bone. In an adult male population of normals (N = 5–6) blood clearance, urinary excretion, and skeletal uptake of 99mTc‐Diphosphonate were determined as a function of time after intravenous (i.v.) administration. The quantitative imaging studies (lower lumbar region) were performed up to 1 h post administration with a scintillation camera interfaced to a computer. Blood levels exhibited a triexponential clearance pattern and urinary excretion of the radiopharmaceutical was essentially complete by 4 h. The computer‐generated images showed an initial early uptake in bone, kidneys, and soft tissue. Thereafter, a parallel fall‐off in activity was observed in kidneys and soft tissue, with a concomitant increase in bone.
A comparison of intravenous and subarachnoid lidocaine pharmacokinetics in the rhesus monkey
Authors: Denson Donald D. , Ritschel Wolfgang A. , Turner Patricia A. , Ohlweiler David F. , Bridenbaugh Phillip O. 
Published: October 2006

AbstractA comparative study between intravenous and subarachnoid lidocaine in the rhesus monkey was conducted in an effort to compare the kinetics of lidocaine in the monkey with reported intravenous human data, and to determine the rate and extent of systemic absorption of lidocaine following subarachnoid injection. Each animal received an intravenous and subarachnoid treatment in an effort to determine the fraction of drug absorbed. Pharmacokinetic parameters were calculated for each animal based on arterial blood concentrations of lidocaine. In the case of the intravenous data, a standard two‐ compartment model was used. Subarachnoid injections were evaluated by fitting data to an extravascular one‐compartment model and by analog computer fitting of the blood level data to an extravascular two‐compartment model. Data for both intravenous and subarachnoid injection were also analysed independent of compartment model.
Blood levels following multiple oral dosing of chlorpheniramine conventional and controlled release preparations
Authors: Vallner J. J. , Kotzan J. A. , Stewart J. T. , Brown W. J. , Honigberg I. L. , Needham T. E. , Dighe S. V. 
Published: October 2006

AbstractAn examination of steady‐state performance of chlorpheniramine conventional versus controlled release products was conducted using 15 male subjects in a 3‐way crossover study with a 2‐week washout period between studies. The study was designed to determine if chlorpheniramine formulations provide consistent pharmacokinetic performance between individual units upon going from single dose to multiple dose therapy. In addition, the validity of predicting steady‐state levels for these kinds of products using only single oral dose data was examined. The dosage forms evaluated were a conventional 4mg tablet, and 8 mg barrier coated‐bead capsule, and an 8 mg repeat action tablet. Multiple doses of each product were orally administered to each subject for 6 days prior to the study day to achieve steady‐state levels and on the actual study day. Serum samples were collected at specific time intervals on the study day, and chlorpheniramine levels assayed by HPLC. Pharmacokinetic analysis was based on a two‐compartment open model. The mean plasma elimination half‐lives of the various dosage forms were in the range 24.5–25.4h. There was no rapid release of drug from the controlled release products nor did they have drug release problems during the dosing interval. Good agreement was obtained between predicted average drug concentration at steady‐state and drug concentration actually present for all the formulations studied. Based upon comparative examination of AUC, Cmax, and fraction of dose absorbed data, the controlled release products administered every 12h were comparable in performance to a conventional release tablet administered every 6 h. Since the half‐life of chlorpheniramine is approximately 1 day, therapeutic management may possibly be gained with dosing the patient once daily with a controlled release product or twice daily with a conventional tablet.
The relative bioavailability of a commercial propranolol hydrochloride tablet in man
Authors: Roscoe R. , Cooper J. , Wilson T. W. , Joshi N. N. , Midha K. K. 
Published: October 2006

AbstractA relative bioavailability study of a conventional tablet of propranolol hydrochloride was conducted in a group of 18 healthy volunteers employing the innovator's product as the reference tablet formulation. Based on plasma levels of propranolol for the 24 h following administration of 2 ± 40 mg oral propranolol hydrochloride tablets, the relative extent of bioavailability was shown to be 100.8 per cent for the test tablet formulation; no significant differences were detected between formulations with respect to any of the pharmacokinetic parameters examined. Large intersubject variations in plasma propranolol concentrations and the subsequently calculated areas under the plasma concentration/time curves were attributed to substantial presystemic biotransformation differences.