bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steady‐state pharmacokinetic interaction of modified‐dose indinavir and rifabutin
Authors: Hamzeh Fayez M. , Benson Constance , Gerber John , Currier Judith , McCrea Jackie , Deutsch Paul , Ruan Ping , Wu Hulin , Lee Jin , Flexner Charles ,   for the AIDS Clinical Trials Group 365 Study Team
Published: March 2003

BackgroundCombined administration of the human immunodeficiency virus protease inhibitor indinavir (800 mg every 8 hours) with the antimycobacterial rifabutin (300 mg daily) results in a significant decrease in indinavir concentrations with subsequent risk of treatment failure, as well as a significant increase in rifabutin concentrations with increased toxicity. Therefore this study was designed to evaluate alternative dosing regimens.MethodsEighteen healthy volunteers received 300 mg rifabutin daily alone for 14 days and then 1000 mg indinavir every 8 hours plus rifabutin at a reduced dose of 150 mg daily, given at 8 AM or noon in a randomized crossover sequence for 14 days. Ten human immunodeficiency virus‐infected subjects received 800 mg indinavir every 8 hours for 14 days and then 1000 mg indinavir every 8 hours plus 150 mg rifabutin daily at 8 AM for 14 days. Twenty‐four‐hour pharmacokinetic sampling was performed at the end of each 14‐day study period.ResultsIndinavir, 1000 mg every 8 hours, coadministered with 150 mg rifabutin daily produced an area under the concentration‐time curve similar to that of 800 mg indinavir every 8 hours. The mean area under the concentration‐time curve values of rifabutin and 25‐desacetyl rifabutin, when 150 mg rifabutin every morning was coadministered simultaneously with 1000 mg indinavir every 8 hours, were 70% and 120% higher than with 300 mg rifabutin daily alone. Drug concentrations were not different when rifabutin and indinavir were administered simultaneously at 8 AM or staggered by 4 hours.ConclusionsIncreasing indinavir's dose to 1000 mg every 8 hours when coadministered with rifabutin at a reduced dose of 150 mg daily compensates for rifabutin induction of indinavir metabolism. Rifabutin concentrations were still higher than with rifabutin alone despite a 50% reduction of rifabutin dose, which is the current recommendation when these 2 drugs are combined. The clinical significance of the increase in rifabutin and 25‐desacetyl rifabutin concentrations is not known.Clinical Pharmacology & Therapeutics (2003) 73, 159–169; doi: 10.1067/mcp.2003.3
Disposition and miotic effects of oral alfentanil: A potential noninvasive probe for first‐pass cytochrome P4503A activity
Authors: Kharasch Evan D. , Hoffer Christine , Walker Alysa , Sheffels Pamela 
Published: March 2003

Background and ObjectivesSystemic clearance of the opioid alfentanil after intravenous administration is an excellent in vivo probe for hepatic cytochrome P4503A (CYP3A) activity and drug interactions. Alfentanil effect (miosis) is a surrogate for plasma alfentanil concentrations, and alfentanil effect kinetics may be a suitable noninvasive probe for hepatic CYP3A. Oral alfentanil might be a probe for first‐pass CYP3A activity; however, it is not used clinically, and oral alfentanil disposition is unknown. This investigation evaluated the disposition and miotic effects of oral alfentanil.MethodsTen healthy volunteers were studied in a dose‐escalation fashion, receiving 23, 30, 43, and 75 μg/kg oral alfentanil on different days. Dark‐adapted pupil diameter was measured at the time of venous blood sampling. Alfentanil was quantified by liquid chromatography‐mass spectrometry. Plasma concentrations of alfentanil and pupil diameter change versus time data were analyzed by noncompartmental modeling.ResultsAlfentanil was rapidly absorbed (time to maximum concentration [Tmax], 0.7 ± 0.5 hour). Mean values for area under the plasma concentration‐time curve extrapolated to infinity (AUC∞) (27 ± 14, 38 ± 22, 57 ± 31, and 105 ± 59 ng · h · mL−1) and maximum concentration (16 ± 8, 23 ± 16, 31 ± 18, and 50 ± 22 ng/mL) were linear with dose, although there was considerable interindividual variability. Tmax, elimination half‐life (1.0 ± 0.2 hours), total body clearance after oral administration (20 ± 18 mL · kg−1 · min−1), and dose‐normalized AUC∞ were independent of dose. Dose‐dependent alfentanil disposition was mirrored by commensurate changes in clinical effect, although miosis was variable and not detectable in all subjects at the lowest dose. Mean miosis AUC (AUEC) and peak miosis were log‐dose linear. Effect half‐life (1.3 ± 0.9 hours) was similar to plasma half‐life.ConclusionOral alfentanil is rapidly absorbed, exhibits linear and dose‐independent kinetics, and undergoes substantial first‐pass metabolism. Oral alfentanil may be a suitable probe for first‐pass CYP3A activity. Alfentanil effect (miosis) may be an acceptable surrogate for plasma alfentanil concentrations. Oral alfentanil effect may be a noninvasive surrogate for conventional pharmacokinetics. Further studies are warranted to determine whether oral alfentanil and alfentanil effect kinetics may be a suitable noninvasive in vivo probe for first‐pass CYP3A activity.Clinical Pharmacology & Therapeutics (2003) 73, 199–208; doi: 10.1067/mcp.2003.30
Effect of single and repeated oral doses of telithromycin on cardiac QT interval in healthy subjects
Authors: Démolis Jean‐Louis , Vacheron Françoise , Cardus Stéphane , Funck‐Brentano Christian 
Published: March 2003

BackgroundTelithromycin is the first member of a new class of antimicrobials—the ketolides. The main objective of this study was to assess the effect of various oral doses of telithromycin on QT interval during single and repeated administrations.MethodsSeventeen men and 17 women participated in double‐blind, placebo‐controlled, crossover studies. Of these subjects, 18 (9 men and 9 women) received single and repeated oral doses of telithromycin (800 mg daily), clarithromycin (500 mg twice daily), or placebo (protocol 1). The other 16 subjects received a single oral dose (800 mg, 1600 mg, and 2400 mg) of telithromycin or placebo (protocol 2). At the time of expected telithromycin maximum concentration, several electrocardiographic recordings were obtained at rest and during the course of a submaximal exercise test. QT intervals were measured within a wide range of R‐R intervals in each subject.ResultsANOVA showed that telithromycin did not increase QT interval at any dose compared with placebo. The greatest effect observed during any study period was a mean (±SD) change in QT‐interval duration of 4.2 ± 15.2 ms (ie, +1.2% ± 4.0%, P not significant) at R‐R = 1000 ms after repeated doses of 800 mg telithromycin. Outlier values (change in Bazett QTc from baseline >60 ms) from resting 12‐lead electrocardiograms did not differ across treatment groups, including placebo.ConclusionsTelithromycin administered as repeated doses of 800 mg (recommended doses) or as single doses of up to 3 times this recommended dose did not increase the QT interval at any heart rate at rest and during effort. Telithromycin did not prolong QT‐interval duration when administered to healthy young male and female subjects.Clinical Pharmacology & Therapeutics (2003) 73, 242–252; doi: 10.1067/mcp.2003.4
Do Micrometastases Detected with Cytokeratin Immunoperoxidase Reactivity Affect the Treatment Approach to Neck in Supraglottic Cancers?
Authors: Kocatürk Sinan , Yilmazer Demet , Önal Binnur , Erkam Ünsal , Ürünal Bilge 
Published: March 2003

OBJECTIVESThe aim of this study was to determine the occult lymph node metastasis rates with immunoperoxidase staining for cytokeratin in supraglottic larynx cancers and to assess our approach to the neck.STUDY DESIGNTwenty‐two patients who had squamous cell carcinoma in the supraglottic region and no histopathologic metastasis in the neck who had their cancer detected with the use of hematoxylineosin were included in the study. All of the specimens were reevaluated with the use of immunoperoxidase staining for cytokeratin.RESULTSMicrometastatic disease (pN1) has been detected in 3 patients (13.61%) in whom no metastasis was detected with routine histopathologic examination.CONCLUSION AND SIGNIFICANCEResults suggest that the occult metastasis rates are higher than those detected with routine hematoxylin‐eosin staining. However, because it is accepted that neck dissection alone has adequate therapeutic efficiency in pN1 patients, the detected 13.61% rate of micrometastases has not changed our treatment plan in the neck.
Headache after Removal of Vestibular Schwannoma Via the Retrosigmoid Approach: A Long‐Term Follow‐Up‐Study
Authors: Schaller Bernhard , Baumann Ariane 
Published: March 2003

OBJECTIVEOur goal was to study the occurrence and source of origin of postcraniotomy headache syndrome after removal of vestibular schwannoma via the retrosigmoid approach.METHODSA retrospective chart analysis was conducted of all patients with headache at 3 months after removal of vestibular schwannoma from January 1981 through March 1997 and with a minimum of 24 months of follow‐up. Diagnosis was made according to the headache classification and was graded using the HARNER scale. Recovery outcome was compared in selected groups of patients with and without headache. A descriptive statistical analysis was used to analyze differences between groups.RESULTSOf the patients who underwent retrosigmoid craniotomy for removal of vestibular schwannomas, 52 of 155 patients (34%) reported having severe headache of requiring medication every day and/or feeling incapacitated 3 months after surgery. Headache was more prevalent in those who had the bone flap replaced (94% versus 27%), if there was duraplastic or direct dura closure (0% versus 100%). Laboratory‐proven aseptic meningitis, most likely due to the use of fibrin glue and drilling of posterior aspect of the internal auditory canal, was mainly associated with postoperative headache (81% versus 2%). In 75% of these cases, calcifications along the brainstem had been noted.CONCLUSIONThe origin of postoperative headaches after retrosigmoid vestibular schwannoma resections is not yet fully understood. Different factors may play a role in preventing or reducing headache: dural adhesions to nuchal muscles or to subcutaneous tissues and dural tension in the case of direct dural closure may explain postoperative headache from dural tension. Intradural drilling and the use of fibrin glue may be the source of aseptic meningitis as the etiology of persistent postoperative headache. Prevention of postoperative headache may include the replacement of bone flap at the end of surgery, duraplastic instead of direct dural closure, and prevention of the use of fibrin glue or extensive drilling of the posterior aspect of internal auditory canal.
Study of Some “Intrinsic Risk Factors” that Can Enhance an Iatrogenic Injury of the External Branch of the Superior Laryngeal Nerve
Authors: Furlan Julio Cesar , Cordeiro Anói Castro , Brandã Lenine Garcia 
Published: March 2003

OBJECTIVEThis study evaluates some “intrinsic risk factors” for a surgical injury of the external branch of superior laryngeal nerve (EBSLN) based on its anatomic relationship with the thyroid gland.STUDY DESIGN AND SETTINGSeventy‐two neck dissections were performed in 36 fresh human adult cadavers. Every EBSLN was dissected and categorized using Cernea's classification. All data regarding gender, ethnicity, stature, side of the neck, and volume of hemi thyroid were collected and statistically analyzed by the χ2–test and analysis of variance.RESULTSAlthough no statistical differences were observed between genders (P = 0.3770), ethnicities (P = 0.9780) or sides of the neck (P = 0.2523), statistical significance was reached regarding the nerve type when the groups were divided by stature (P = 0.0006) and glandular volume (P = 0.0007).CONCLUSIONIndividual stature and volume of the hemi thyroid gland are probably involved in risk of the surgical EBSLN injury.SIGNIFICANCESurgeons should be aware of these anatomic findings in order to obtain a good voice‐related outcome in the thyroidectomies.
Nonattended Home Automated Continuous Positive Airway Pressure Titration: Comparison with Polysomnography
Authors: Woodson B. Tucker , Saurejan Adrian , Brusky Laura T. , Han Joseph K. 
Published: March 2003

OBJECTIVEAutomatic adjusting nasal continuous positive airway pressure titration (APAP) has been introduced as an alternative method of establishing pressures for patients with sleep apnea. The performance and accuracy of APAP in nonattended home environment are controversial. This study assessed APAP polysomnographic outcomes and accuracy in a nonattended home environment.STUDY DESIGN AND SETTINGWe conducted a retrospective consecutive case series of 24 consecutive patients who had nonattended APAP and simultaneous full polysomnography (PSG).RESULTSAPAP was tolerated and reduced obstructive Apnea‐Hypopnea Index (AHI) to < 10 events/h in all patients. Mean AHI decreased from 38.4 (21.2) to 5.9 (6.6) events/h. Central apneas worsened in one patient. A therapeutic pressure was determined in 91% of patients. Autoset accurately measured residual AHI compared with PSG (R = 0.77, P < 0.001). APAP overestimated the AHI by 1.4 events/h.CONCLUSIONSNonattended APAP is successful in many patients in determining a therapeutic positive pressure setting. Reported AHI via Autoset is similar to that of PSG.SIGNIFICANCEAPAP reduces AHI and is tolerated in a nonattended environment.
Child Abuse and the Otolaryngologist: Part I
Authors: Crouse C. D. , Faust R. A. 
Published: March 2003

Nearly 1 million infants and children are neglected and abused yearly in the United States, with a greater than 1% resulting mortality rate. One half of these children are seen by physicians for abuse‐related injuries, and nearly 75% have injuries of the head and neck. Physicians, however, account for reporting only 11% of all cases. As experts trained in diseases and injuries of the head and neck, otolaryngologists are particularly well positioned to recognize abuse in the clinic and in the emergency room and during other consultations. We present an overview of child abuse definitions, risk factors, and legal obligations of the physician. We also review the manifestations of child abuse within the head and neck, with particular attention to the role of the otolaryngologist. We briefly discuss some conditions that may be mistaken for abuse and suggest a practical protocol for management of suspected cases in the clinic.
Harmonic Scalpel Tonsillectomy in Children: A Randomized Prospective Study
Authors: Willging J. Paul , Wiatrak Brian J. 
Published: March 2003

OBJECTIVEIn this randomized prospective study, we evaluated postoperative morbidity after use of the Harmonic Scalpel (HS), an ultrasonic dissector coagulator (Ethicon Endo‐Surgery Inc, Cincinnati, OH), or conventional electrocautery (EC) during tonsillectomy.STUDY DESIGN AND SETTINGSPediatric subjects at 2 sites were randomized and underwent tonsillectomy. Intraoperative blood loss and operation duration were recorded. Postoperative parameters and complications were recorded.RESULTSOne hundred seventeen subjects completed the study. For the HS group, mean operative time was significantly longer (P < 0.001), but intraoperative blood loss was equivalent (P = 1.000). HS subjects slept soundly on postoperative days 1, 2, 3, and 14 (P = 0.041, 0.013, 0.022, and 0.038, respectively, compared with EC group). Mean postoperative pain scores trended lower for HS subjects on postoperative days 2, 3, and 4.CONCLUSIONThe use of the HS in pediatric tonsillectomy showed no increase in intraoperative or postoperative blood loss compared with the use of EC, and HS provided possible clinical advantages over EC in patient comfort.SIGNIFICANCETonsillectomy subjects in the HS group showed a statistically significant ability to sleep soundly, suggesting that the subjects experienced less pain. These data correlate with the observed decrease in pain scores.
Viscoelastic Properties of Rabbit Vocal Folds after Augmentation
Authors: Hertegård Stellan , Dahlqvist Åke , Laurent Claude , Borzacchiello Assunta , Ambrosio Luigi 
Published: March 2003

BACKGROUNDVocal fold function is closely related to tissue viscoelasticity. Augmentation substances may alter the viscoelastic properties of vocal fold tissues and hence their vibratory capacity.OBJECTIVESWe sought to investigate the viscoelastic properties of rabbit vocal folds in vitro after injections of various augmentation substances.STUDY DESIGN AND SETTINGPolytetrafluoroethylene (Teflon), cross‐linked collagen (Zyplast), and cross‐linked hyaluronan, hylan b gel (Hylaform) were injected into the lamina propria and the thyroarytenoid muscle of rabbit vocal folds. Dynamic viscosity of the injected vocal fold as a function of frequency was measured with a Bohlin parallelplate rheometer during small‐amplitude oscillation.RESULTSAll injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Vocal fold samples injected with hylan b gel showed the lowest dynamic viscosity, quite close to noninjected control samples. Vocal folds injected with polytetrafluoroethylene showed the highest dynamic viscosity followed by the collagen samples.CONCLUSIONSThe data indicated that hylan b gel in short‐term renders the most natural viscoelastic properties to the vocal fold among the substances tested. This is of importance to restore/preserve the vibratory capacity of the vocal folds when glottal insufficiency is treated with injections.
Hand-arm vibration syndrome in Swedish car mechanics
Authors: Barregard L , Ehrenström L , Marcus K 
Published: March 2003

Aims:To assess the occurrence of hand-arm vibration syndrome (HAVS) in Swedish car mechanics, and the relation between HAVS and duration of exposure.Methods:A total of 806 mechanics answered a questionnaire on vascular and neurological symptoms, and exposure to vibrations. Mechanics with symptoms, and some mechanics without symptoms, were invited to a clinical examination, including also a timed Allen test. Vascular and neurological symptoms were classified using the Stockholm Workshop scales. The mean daily exposure (mainly using nut-runners) was 14 minutes and the mean exposure duration, 12 years. Published data have shown vibration levels in nut-runners of about 3.5 m/s2.Results:In the questionnaire, 24% reported cold induced white finger (WF), 25% persistent numbness, and 13%, reduced grip force. The clinical examination showed a prevalence of vibration induced white finger (VWF) of about 15%, mainly in stage 2, and after 20 years, of 25%. A survival analysis showed similar results. We found that the International Organisation for Standardisation (ISO) model underestimates the risk of VWF. The incidence after 1975 was 19 cases per 1000 person-years. Slow refill times in the timed Allen test were common (15% had a refill time of >20 seconds), and associated with the presence of VWF. The clinical examination revealed neurological symptoms in the hands in about 25% of subjects, mainly at stage 2. After 20 years, the prevalence was 40%. The questionnaire items on WF and numbness both showed likelihood ratios of 13.Conclusion:HAVS is common among Swedish car mechanics in spite of short daily exposure times. This underlines the need for preventive measures.
Organochlorine compounds and concentrations of thyroid stimulating hormone in newborns: Table 1
Authors: Ribas-Fitó N , Sala M , Cardo E , Mazón C , de Muga M E , Verdú A , Marco E , Grimalt J O , Sunyer J 
Published: March 2003

Aims:To assess the association between prenatal exposure to organochlorine compounds and thyroid status in newborns from an area with high levels of hexachlorobenzene (HCB).Methods:A total of 98 mother-infant pairs (83.1% of all children born during the period 1997–99 in a specific area polluted with HCB) were recruited. Levels of organochlorine compounds were measured in 70 cord serum samples. Concentrations of thyroid stimulating hormone (TSH) were measured in plasma of all newborns three days after birth.Results:All newborns had concentrations of TSH within the range of normal reference values (<25 mU/l). Dichlorodiphenyl dichloroethylene (p,p′DDE), beta-hexachlorocyclohexane (β-HCH), polychlorinated biphenyl (PCB) 138 and 118 were related to higher concentrations of TSH, although only significant for β-HCH. Levels of HCB were not associated with TSH.Conclusions:Although this community is highly exposed to HCB, no association was found between this organochlorine and TSH concentrations at birth.
THE SPECTRAL SCALE AND THE NUMERICAL RANGE
Authors: AKEMANN CHARLES A. , ANDERSON JOEL 
Published: March 2003

Suppose that c is an operator on a Hilbert Space H such that the von Neumann algebra N generated by c is finite. Let τ be a faithful normal tracial state on N and set b1= (c + c*)/2 and b2= (c - c*)/2i. Also write B for the spectral scale of {b1, b2} relative to τ. In previous work by the present authors, some joint with Nik Weaver, B has been shown to contain considerable spectral information about the operator c. In this paper we expand that information base by showing that the numerical range of c is encoded in B also.We begin by proving that the k-numerical range of an arbitrary operator d in B(H) coincides with the numerical range of d when the von Neumann algebra generated by d contains no finite rank operators. Thus, the k-numerical range is not useful for most operators considered here.We next show that the boundary of the numerical range of c is exactly the set of radial complex slopes on B at the origin. Further, we show that points on this boundary that lie in the numerical range are visible as line segments in the boundary of B. Also, line segments on the boundary which lie in the numerical range show up as faces of dimension two in the boundary of B. Finally, when N is abelian, we prove that the point spectrum of c appears as complex slopes of 1-dimensional faces of B.
THE STRUCTURE OF SPIN SYSTEMS
Authors: ARVESON WILLIAM , PRICE GEOFFREY 
Published: March 2003

A spin system is a sequence of self-adjoint unitary operators U1, U2, … acting on a Hilbert space H which either commute or anticommute, UiUj = ±UjUi for all i, j; it is called irreducible when {U1, U2, …} is an irreducible set of operators. There is a unique infinite matrix (cij) with 0, 1 entries satisfying [Formula: see text] Every matrix (cij) with 0, 1 entries satisfying cij = cji and cii = 0 arises from a nontrivial irreducible spin system, and there are uncountably many such matrices. In cases where the commutation matrix (cij) is of "infinite rank" (these are the ones for which infinite dimensional irreducible representations exist), we show that the C*-algebra generated by an irreducible spin system is the CAR algebra, an infinite tensor product of copies of [Formula: see text], and we classify the irreducible spin systems associated with a given matrix (cij) up to approximate unitary equivalence. That follows from a structural result. The C*-algebra generated by the universal spin system u1, u2, … of (cij) decomposes into a tensor product [Formula: see text], where X is a Cantor set (possibly finite) and [Formula: see text] is either the CAR algebra or a finite tensor product of copies of [Formula: see text]. We describe the nature of this decomposition in terms of the "symplectic" properties of the ℤ2-valued form [Formula: see text]x, y ranging over the free infninite dimensional vector space over the Galois field ℤ2.