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Biomedical subjects

J A Stone

Publications and source records attributed to J A Stone.

At least 19 recordsLinked to original sources
PubMed2001

An LC-MS-MS method for the determination of indinavir, an HIV-1 protease inhibitor, in human plasma.

A method for the determination of indinavir (IDV) (L-735 524) in human plasma by LC-MS-MS is discussed, and the validation data is presented. The analyte and internal standard are isolated from plasma by a simple acetonitrile precipitation of plasma proteins followed by centrifugation. LC-tandem mass spectrometry in positive ion, multiple reaction monitoring mode used pairs of ions at m/z of 614/421 for indinavir and 628/421 for internal standard, respectively. The calibration curve had a linear range from 3.0 to 12320 ng/ml when linear least square regression weighing 1/x was applied to the concentration versus peak area plot. The advantages of this method are the fast sample preparation, wide dynamic assay range and quick analysis taking only 5 min for each sample run. The robust nature of this assay has been further verified during routine use over several months involving multiple analysts.

Calibration↗
PubMed2001

Malignant schwannoma of the trigeminal nerve.

SUMMARY: We present the MR imaging, CT, and clinical findings of a patient with malignant schwannoma of the trigeminal nerve. Local tumor recurrence is frequent and may be mistaken for lymphatic spread. In this report, we emphasize the natural history of this rare tumor and discuss the importance of imaging in diagnosis and surveillance.

Aged↗
PubMed2001

Demyelinating diseases, leukodystrophies, and other myelin disorders.

Magnetic resonance (MR) imaging recently has become the most sensitive clinical test in the detection of white matter disorders, yet neuropathologic evaluation remains the most specific. This article describes the gross and microscopic pathology of various diseases primarily or selectively affecting white matter. The discussion should provide deeper insight into the nature of white matter disease and assist in the interpretation of CT and MR images. The subject of white matter damage caused secondarily by such entities as neoplasia, trauma, infarction, or neuronal degeneration is not included.

Adolescent↗
PubMed2001

Canadian guidelines for cardiac rehabilitation and atherosclerotic heart disease prevention: a summary.

Atherosclerotic heart disease (AHD) is the leading cause of death in Canadian women and men. Cardiac rehabilitation has been repeatedly shown to reduce cardiac morbidity and mortality significantly among patients with documented AHD. The Canadian Association of Cardiac Rehabilitation (CACR) has defined cardiac rehabilitation as "the enhancement and maintenance of cardiovascular health through individualized programs designed to optimize physical, psychological, social, vocational and emotional status. This process includes the facilitation and delivery of secondary prevention through heart hazard (risk factor) identification and modification in an effort to prevent disease progression and the recurrence of cardiac events". This summary presents a limited amount of background information and the majority of clinical practice recommendations contained within the previously published CACR Guidelines. These evidence-based clinical recommendations are intended as guidelines to good clinical practice rather than as standards of care. The key focus of this summary is the need for complete and targeted intervention of all heart hazards in patients at high or very high risk for, or with documented, AHD. To achieve this goal, the CACR Guidelines and this summary present risk stratification strategies designed to determine unambiguously a patient's risk of exercise-related cardiac events (short term absolute risk or disease prognosis) and their risk of recurrent AHD events (long term absolute risk from disease progression). The establishment of the short term and long term absolute AHD risks can then be used to determine heart hazard targets and the type of exercise program prescribed for patients with AHD. Despite the use of evidence-based medical practices, none of the recommendations presented in this document can replace the expert judgment of properly trained and experienced cardiac rehabilitation professionals. Health care providers must always be free to choose where and when clinical practice guidelines are applied, modified or superceded, depending on individual patient circumstances.

Canada↗
PubMed2000

The ability of tumor volume to predict local control in surgically treated squamous cell carcinoma of the supraglottic larynx.

PURPOSE: Pretreatment CT volumetric measurement of the primary tumor has been shown to be a predictor of local control in patients with laryngeal carcinoma treated with radiation therapy (RT) alone. A direct association has been demonstrated between tumor volume of supraglottic squamous cell carcinoma (SGSCCA) and local control. However, the association between tumor volume of SGSCCA and local control has not been investigated in patients treated surgically. The purpose of this study was to determine the relationship between SGSCCA tumor volume and local control in patients treated surgically. MATERIALS AND METHODS: Primary site tumor volume was calculated from pretreatment CT studies in 37 laryngeal supraglottic carcinomas treated surgically. All patients had clinical follow-up for evidence of recurrent tumor along the surgical margins at the primary site for a minimum of 2 years after completion of treatment. Statistical analysis consisted of Mantel-Haenszel chi-square tests and Fisher's exact test. RESULTS: Overall local control rate was 92% (33 of 37). Tumor volume was significantly associated with local control (p <. 05). Local control rate for tumors with volumes <16 cc was 94% (32 of 34) (p <.05). CONCLUSIONS: Pretreatment CT volumetric analysis is useful for predicting local control in patients with SGSCCA carcinoma treated surgically.

Adult↗
PubMed2000

Embryology and anatomy of the neck.

As a prelude to understanding pathologic conditions of the pediatric neck, this article presents the embryologic development of the neck, fascial planes, and key anatomic structures. Detailed discussion includes the normal development of the neck and illustrates, using selected CT and MR images, the fascial spaces, larynx and trachea, thyroid, parathyroid, and vascular and lymphatic anatomy.

Child↗
PubMed2000

Imaging of congenital anomalies of the branchial apparatus.

One of the most challenging topics for radiologists is congenital anomalies arising from abnormal embryogenesis of the branchial apparatus. Defects of the branchial apparatus result in a spectrum of anomalies that includes fistulas, sinuses, cysts, temporal bone anomalies, craniofacial malformations, and systemic disorders. A better understanding of the various radiologic abnormalities is aided by an understanding of their embryonic origins. This article reviews the spectrum of abnormalities that are secondary to anomalous embryogenesis of the branchial arches.

Branchial Region↗
PubMed1999

Proton-bound cluster ions in ion mobility spectrometry.

Gaseous oxygen and nitrogen bases, both singly and as binary mixtures, have been introduced into ion mobility spectrometers to study the appearance of protonated molecules, and proton-bound dimers and trimers. At ambient temperature it was possible to simultaneously observe, following the introduction of molecule A, comparable intensities of peaks ascribable to the reactant ion (H2O)nH+, the protonated molecule AH+ and AH+ H2O, and the symmetrical proton bound dimer A2H+. Mass spectral identification confirmed the identifications and also showed that the majority of the protonated molecules were hydrated and that the proton-bound dimers were hydrated to a much lesser extent. No significant peaks ascribable to proton-bound trimers were obtained no matter how high the sample concentration. Binary mixtures containing molecules A and B, in some cases gave not only the peaks unique to the individual compounds but also peaks due to asymmetrical proton bound dimers AHB+. Such ions were always present in the spectra of mixtures of oxygen bases but were not observed for several mixtures of oxygen and nitrogen bases. The dimers, which were not observable, notable for their low hydrogen bond strengths, must have decomposed in their passage from the ion source to the detector, i.e. in a time less than approximately 5 ms. When the temperature was lowered to -20 degrees C, trimers, both homogeneous and mixed, were observed with mixtures of alcohols. The importance of hydrogen bond energy, and hence operating temperature, in determining the degree of solvation of the ions that will be observed in an ion mobility spectrometer is stressed. The possibility is discussed that a displacement reaction involving ambient water plays a role in the dissociation.

Air↗
PubMed1999

Simultaneous investigation of indinavir nonlinear pharmacokinetics and bioavailability in healthy volunteers using stable isotope labeling technique: study design and model-independent data analysis.

Indinavir follows nonlinear pharmacokinetics upon oral administration at clinical doses. A study employing the stable isotope administration technique in a three-treatment design was conducted to identify the source of the nonlinearity and to determine the dose-dependency of systemic bioavailability. In treatment A, 400 mg of unlabeled indinavir (D0) was coadministered orally with 16 mg of a hexadeutero analogue of indinavir (D6) intravenously. In treatment B, 800 mg of D0 po was coadministered with 16 mg of D6 intravenously. In treatment C, 16 mg of iv D6 was infused concurrently with 16 mg iv of D0. Plasma concentrations of D0 and D6 were determined by an LC/MS/MS assay method. Concentrations of indinavir in plasma increased greater than dose-proportionally over the 400- to 800-mg dose range. No meaningful kinetic isotope effects were found in treatment C. Plasma concentrations of D6 were dependent on the coadministered D0-indinavir dose and were lowest in treatment C, higher in treatment A, and highest in treatment B. The bioavailability of indinavir was high (60-65%) and comparable between the 400- and 800-mg doses. There was a significant contribution of nonlinear kinetics in the systemic circulation to the observed disproportional increase in plasma concentrations following oral dosing. The high bioavailability at clinically relevant doses suggests a high degree of saturation of first-pass metabolism. These results further demonstrate that the concomitant administration technique in combination with the LC/MS/MS method can provide a realistic and reliable means of elucidating important pharmacokinetic properties of drug candidates during product development.

Adult↗
PubMed1999

Evaluation of CSF leaks: high-resolution CT compared with contrast-enhanced CT and radionuclide cisternography.

BACKGROUND AND PURPOSE: Radiologic evaluation of CSF leaks is a diagnostic challenge that often involves multiple imaging studies with the associated expense and patient discomfort. We evaluated the use of screening noncontrast high-resolution CT in identifying the presence and site of CSF rhinorrhea and otorrhea and compared it with contrast-enhanced CT cisternography and radionuclide cisternography. METHODS: We retrospectively reviewed the imaging studies and medical records of all patients who were evaluated for CSF leak during a 7-year period. Forty-two patients with rhinorrhea and/or otorrhea underwent high-resolution CT of the face or temporal bone and then had CT cisternography and radionuclide cisternography via lumbar puncture. The results of the three studies were compared and correlated with the surgical findings in 21 patients. RESULTS: High-resolution CT showed bone defects in 30 of 42 patients (71%) with CSF leak. High-resolution, radionuclide cisternography and CT cisternography did not show bone defects or CSF leak for 12 patients (29%) who had clinical evidence of CSF leak. Among the 30 patients with bone defects, 20 (66%) had positive results of their radionuclide cisternography and/or CT cisternography. For the 21 patients who underwent surgical exploration and repair, intraoperative findings correlated with the defects revealed by high-resolution CT in all cases. High-resolution CT identified significantly more patients with CSF leak than did radionuclide cisternography and CT cisternography, with a moderate degree of agreement. CONCLUSION: Noncontrast high-resolution CT showed a defect in 70% of the patients with CSF leak. No radionuclide cisternography or CT cisternography study produced positive results without previous visualization of a defect on high-resolution CT. CT cisternography and radionuclide cisternography may be reserved for patients in whom initial high-resolution CT does not identify a bone defect or for patients with multiple fractures or postoperative defects.

Adult↗
PubMed1998

Single-dose pharmacokinetics of indinavir and the effect of food.

Indinavir sulfate is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor indicated for treatment of HIV infection and AIDS in adults. The purpose of this report is to summarize single-dose studies which characterized the pharmacokinetics of the drug and the effect of food in healthy volunteers. Indinavir concentrations in plasma and urine were obtained by high-pressure liquid chromatography and UV detection assay methods. The results indicate that indinavir was rapidly absorbed in the fasting state, with the time to the maximum concentration in plasma occurring at approximately 0.8 h for all doses studied. Over the 40- to 1,000-mg dose range studied, concentrations in plasma and urinary excretion of unchanged drug increased greater than dose proportionally. The nonlinear pharmacokinetics were attributed to the dose-dependent oxidative metabolism of first-pass metabolism as well as to metabolism in the systemic circulation. Renal clearance slightly exceeded the glomerular filtration rate, suggesting a net tubular secretion component. At high concentrations in plasma, tubular secretion appeared to be lowered because there was a trend for a decreased renal clearance. Administration of 400 mg of indinavir sulfate following a high-fat breakfast resulted in a blunted and decreased absorption (areas under the concentration-time curves [AUCs], 6.86 microM.h in the fasted state versus 1.54 microM.h in the fed state; n = 10). However, two types of low-fat meals were found to have no significant effect on the absorption of 800 mg of indinavir sulfate (AUCs, 23.15 microM.h in the fasted state versus 22.71 and 21.36 microM.h, respectively, in the fed state; n = 11). Immediately following dosing, the concentrations of indinavir in urine often exceeded its intrinsic solubility. To reduce the risk of nephrolithiasis, it is recommended that indinavir sulfate be administered with water.

Adult↗
PubMed1998

High-resolution MR imaging of the auditory pathway.

MR imaging is a valuable tool in the evaluation of the auditory pathway. The current techniques in high-resolution MR imaging of the temporal bone are presented followed by a review of normal anatomy. Several diseases involving the middle ear, inner ear, internal auditory canal, and cerebellopontine angle are then presented. A radiologic-pathologic approach is used to illustrate the nature of these diseases and their appearance on MR imaging.

Auditory Diseases, Central↗
PubMed1997

Electrospray mass-spectrometric, spectrophotometric and electrochemical methods do not provide evidence for the binding of nitric oxide by pyocyanine at pH 7.

In several recent publications on pyocyanine, its mechanism of action has been attributed to an ability to react with nitric oxide (NO), resulting in the formation of an adduct. We examined the chemical interaction of pyocyanine and NO using electrospray (ES) MS, spectrophotometry and voltammetry at neutral pH and with 10-100 microM pyocyanine. No binding of NO to pyocyanine was observed. Alternative mechanisms for the inhibition of NO-induced vasorelaxation by pyocyanine should be sought.

Binding Sites↗