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J A Stone

Publications and source records attributed to J A Stone.

54 records · Page 3Linked to original sources

An update on digoxin.

This review deals briefly with recent developments in the therapeutic drug monitoring of digoxin. Strategies for decreasing the interference by digoxin metabolites, digoxin-like factors, and spironolactone metabolites in immunoassays of digoxin are discussed. Other issues addressed include the development of alternative methods of analysis, such as receptor assays and "high-pressure" liquid chromatography; digoxin-like factors in hypertension; drug-drug interactions; redistribution of digoxin stores in the body; and forensic considerations.

Digoxin↗

Improved liquid chromatographic/immunoassay of digoxin in serum.

This HPLC/immunoassay procedure measures digoxin in serum with no interference from digoxin metabolites or digoxin-like factors. We used solid-phase (C18 and Diol) extraction, a C18 column with a tetrahydrofuran/water mobile phase, and final quantification by fluorescence polarization immunoassay. Deslanoside and gitoxigenin were used as the internal standard and the retention-time marker, respectively. The average CV for 300-microL samples at digoxin concentrations between 0.9 and 3.9 nmol/L was 9.3%. Minimum column lifetime with daily use was three months. We also compared results, for 49 samples from patients taking digoxin, obtained with the Abbott "TDx FPIA digoxin I" and the present procedure. Discrepancies between the two methods were substantial for 20% of the samples.

Chromatography, High Pressure Liquid↗

Tolerance to isosorbide dinitrate: rate of development and reversal.

The circulatory response and plasma concentrations of isosorbide dinitrate (ISDN) were determined in 10 patients with chronic, stable angina after administration of 5 mg of sublingual ISDN during the control stage, after 48 hr of therapy with 15 mg of ISDN orally every 6 hr, and subsequently after a 48 hr period when ISDN was substituted by placebo four times daily. Initially, sublingual ISDN induced major reductions in both supine and standing systolic and diastolic blood pressure, but after 45 hr of therapy with oral ISDN, there was a significantly diminished vasodepressor response in both positions. Subsequently, when placebo was substituted for ISDN, the circulatory response initially seen was restored within 21 hr. Plasma ISDN concentrations after the test sublingual dose were slightly higher after 48 hr of oral ISDN dosing (i.e., the tolerant state) than at the start of the study. This suggests that tolerance is unlikely to be caused by reduced bioavailability or accelerated elimination of ISDN. It is possible that tolerance is related to accumulation of ISDN metabolites. The attenuation of the circulatory response to ISDN may be related to the altered antianginal efficacy commonly seen during sustained therapy with ISDN.

Administration, Oral↗

Effects of disease, route of administration, cigarette smoking, food intake on the pharmacokinetics and circulatory effects of isosorbide dinitrate.

The major goal of this study was to examine the clinical pharmacology of isosorbide dinitrate (ISDN) under various conditions of clinical use. Orally administered ISDN is subjected to extensive metabolism during its first passage through the liver. It is not known, however, whether the systemic availability and the circulatory effects of oral ISDN might be affected in clinical conditions under which hepatic blood flow and/or metabolic activity might have been altered. Sublingual (5 mg) and oral (30 mg) ISDN were given under fasting conditions on two separate occasions to (a) patients with angina pectoris (AP), n = 8; (b) patients with chronic congestive heart failure (CHF), n = 9; (c) smoking AP patients, n = 7; and (d) nonsmoking AP patients, n = 9. Patients in group (a) were also given oral ISDN after a standard breakfast. Circulatory effects, i.e., heart rate, systolic and diastolic pressures were measured over 3 h after sublingual dosing and 6 h after oral dosing in both the supine and standing positions. Plasma ISDN concentrations were measured by gas chromatography over the same periods. The systemic availability of oral ISDN was found to be about half that of sublingual ISDN, but the intersubject variability was large. Thus some individuals absorbed oral ISDN as well as they did sublingual ISDN, while others only absorbed oral ISDN minimally. The extent of oral ISDN absorption was not statistically different between patients with AP and CHF, between smokers and nonsmokers, or between the fasting and postprandial conditions, although there was a trend for higher plasma ISDN concentrations in smokers. Food reduced the apparent absorption rate of oral ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

O2 transport during exercise following blood reinfusion.

Reasons for an increase in maximal O2 consumption (VO2max) following blood reinfusion remain unclear; thus the present investigation was undertaken to examine the arterial and femoral venous blood gases during submaximal and maximal exercise. Four untrained males (22-25 yr) performed modified Balke work capacity tests under control conditions (Hct = 42.4 +/- 0.8%; Hb = 14.7 +/- 0.5 g X 100 ml-1) and following autologous blood reinfusion (Hct = 46.2 +/- 1.3%; Hb = 16.4 +/- 0.9 g X 100 ml-1). VO2 was determined by open-circuit spirometry and cardiac output by the N2O method; radial arterial and deep femoral venous blood were sampled at each work load throughout the incremental work tests. Following blood reinfusion, subjects' VO2max increased (P less than 0.05) from 4.0 (in control) to 4.5 1 X min-1. Throughout submaximal exercise arterial PO2 remained relatively constant (between 80.1 +/- 4.4 and 89.1 +/- 5.0 Torr) and cardiac output unchanged, comparing the two experimental conditions. Femoral venous PO2 values were almost identical throughout the work capacity tests, declining at exhaustion to 15.7 +/- 1.5 Torr in control and to 13.8 +/- 3.3 Torr postreinfusion. It appeared that the subjects' increase in VO2max postreinfusion was due to an increased O2 supplied to the tissue [i.e., cardiac output (Q) X arterial O2 content (CaO2)] by the central circulation. This resulted from a small (10%) increase in Q and a constant elevation in CaO2 of 1.7-2.2 ml X 100 ml-1, since virtually no changes were observed in the femoral venous blood postreinfusion and the acid-base status and temperature, important determinant of O2 dissociation, were (almost) identical, comparing the two experimental conditions.

Acid-Base Equilibrium↗

Unusual cells in lupus erythematosus bullae.

We saw a case of bullous lupus erythematosus (LE) in which there were pre-LE cells and hematoxylin bodies in clear bullous fluid. Pre-LE cells are degenerated leukocytes with pyknotic nuclei. The diagnosis of lupus erythematosus was substantiated by immunofluorescence studies.

Adolescent↗

Quantitative analysis of fentanyl in pharmaceutical preparations by gas chromatography-mass spectrometry.

Fentanyl (1-[2-phenethyl]-4-N-[N-propionylanilino]piperidine) is a potent synthetic opiate commonly used for surgical analgesia and sedation. Reports of abuse of this highly addictive drug among health care personnel have prompted the need to verify the concentration in the unused portion of single-dose ampules returned to the pharmacy. We describe a simple quantitative method for the analysis of fentanyl citrate (Sublimaze) in syringes returned to the pharmacy following surgery. Fentanyl citrate (0.1 mL) and 2H5-fentanyl (internal standard, 0.05 mL, 100 mg/L) were extracted with Toxi-A tubes (Toxi-Lab, Irvine, CA) and analyzed by gas chromatography-mass spectrometry. Calibration was linear from 1 to 60 mg/L (correlation coefficient of 0.997, n = 13) and had a limit of detection of 0.4 mg/L. Mean recovery at concentrations from 5 to 50 mg/L was 89% (range, 69-104%). No interferences were found with morphine, ketamine, midazolam, sufentanil, or alfentanil. These drugs were not selected for their potential chromatographic interference but for their availability in surgical syringes. This assay is useful in verifying that any unused fentanyl is discarded according to narcotic regulations, thereby avoiding the possibility of diversion for illicit consumption.

Alfentanil↗

Normal canals at the fundus of the internal auditory canal: CT evaluation.

PURPOSE: Knowledge of the normal anatomy of the four bony canals located at the fundus of the internal auditory canal (IAC) is necessary during evaluation of temporal bone trauma, congenital anomalies affecting the individual nerves, and some neuro-otologic surgeries. The purpose of this work was therefore to characterize the normal appearance of the four bony canals and to measure their dimensions. METHOD: A retrospective study was performed using CT studies of the temporal bones in 50 patients to identify and characterize the bony canals for the labyrinthine segment of the facial nerve (BCFN), superior vestibular nerve (BCSVN), cochlear nerve (BCNC), and the inferior vestibular nerve (singular canal; SC) located at the fundus of the IAC. All the patients underwent high resolution temporal bone CT for evaluation of uncomplicated inflammatory (n = 49) and neoplastic (n = 1) diseases involving the temporal bone. CT studies were done using 1-mm-thick contiguous sections in axial and coronal planes. Measurements of the canals were performed by one radiologist. No patient had a prior history of trauma, vertigo, and sensorineural hearing loss or facial nerve paralysis. RESULTS: The BCFN, BCSVN, and BCNC were identified in all studies, whereas the SC was seen in 93% of studies. The BCFN, BCSVN, and BCNC arise from the fundus of the IAC, whereas the SC arises medial to the fundus. Mean +/- SD measurements (in mm) of the length and width were as follows: BCFN = 2.92+/-0.48 and 0.91+/-0.28; BCSVN = 2.36+/-0.53 and 0.89+/-0.28; BCNC = 0.93+/-0.21 and 2.13+/-0.44; and SC = 3.22+/-0.73 and 0.50+/-0.14. CONCLUSION: These small canals are routinely visualized on thin section (1 mm) CT of the temporal bone and should not be confused with fractures. This study provides baseline measurements that may be used to evaluate congenital anomalies of these canals. These data may also be helpful in the presurgical evaluation of patients undergoing singular neurectomies for benign positional vertigo.

Adolescent↗

Contrast-enhanced 3D FISP MR angiography of the aortic arch ostia: preliminary results.

PURPOSE: The goal of this work was to evaluate three-dimensional (3D) contrast-enhanced MR angiography (MRA) for the detection of ostial stenoses of the aortic arch. METHOD: Sixteen patients with suspected carotid atherosclerotic disease prospectively underwent digital subtraction angiography of the aortic arch followed by contrast-enhanced MRA using a 3D fast imaging with steady-state precession (FISP) technique (TR = 5 ms, TE = 2 ms, flip angle = 30 degrees). Three neuroradiologists blindly measured stenoses on the catheter angiograms and MRA. Evaluation included the ostia of the innominate, left carotid, and left subclavian arteries. Any significant disagreement on catheter angiography was resolved by consensus. The MRA grades of each of the three observers were then compared with the consensus grades of the contrast angiogram. RESULTS: Forty-eight vessels were scored, of which five had significant stenoses. MRA demonstrated 100% sensitivity, 89% specificity, 52% positive predictive value, and 100% negative predictive value. The Bowker test for symmetry indicated no significant difference between conventional angiography and MRA scores (p = 0.32-0.75), and there was good agreement between the three observers (weighted kappa = 0.75-0.86). CONCLUSION: Contrast-enhanced 3D FISP MRA may be a useful imaging modality for the detection of significant stenoses at the ostia of the major aortic arch branches.

Adult↗

CT evaluation of prosthetic ossicular reconstruction procedures: what the otologist needs to know.

Postoperative otologic evaluation of patients who have undergone ossicular reconstruction is often difficult. However, thin-section computed tomography (CT) can help determine the type of prosthesis used for reconstruction and adequately assess for complications that may be causing postoperative conductive hearing loss. A variety of prostheses may be used in ossicular reconstruction (eg, stapes prosthesis, incus interposition graft, Applebaum prosthesis, Black oval-top prosthesis, Richards centered prosthesis, Goldenberg prosthesis) and can usually be identified at CT by their shapes and locations. Several causes of prosthetic failure are readily demonstrated at CT, including recurrent cholesteatoma and otitis media, formation of granulation tissue or adhesions, and various mechanical problems (eg, subluxation, dislocation, extrusion, fracture, bending). Perilymphatic fistula can be difficult to identify at CT but may be suggested by the presence of pneumolabyrinth, unexplained middle ear effusion, or fluid accumulation within the mastoid air cells. The presence of soft tissue within the oval window niche 4-6 weeks following surgery may indicate poststapedectomy granuloma or fibrosis. Familiarity with the normal and abnormal CT appearances of ossicular prostheses will enable the radiologist to assist the otologist in identifying patients in whom revision surgery is most appropriate.

Equipment Failure Analysis↗

The choline/creatine ratio in five benign neoplasms: comparison with squamous cell carcinoma by use of in vitro MR spectroscopy.

BACKGROUND AND PURPOSE: The choline (Cho)/creatine (Cr) ratio has been shown to be a reliable proton MR spectroscopy metabolic marker for differentiating squamous cell carcinoma (SCCA) from normal muscle in the upper aerodigestive tract. However, it is unclear whether the Cho/Cr ratio can be used to differentiate a malignant tumor from a benign neoplasm in the extracranial head and neck. Our purpose was to determine whether the Cho/Cr ratio can be used to differentiate benign from malignant tumors in this region. METHODS: In vitro one-dimensional proton MR spectroscopy (2,000/136,272 [TR/TE]) was performed at 11 T on tissue specimens obtained from glomus tumors (n = 3), inverting papilloma (n = 1), and schwannoma (n = 1). Cho/Cr area ratios were calculated and compared with similar, previously reported in vitro (11 T) findings and with samples of SCCA and normal muscle. RESULTS: The Cho/Cr ratio was elevated in relation to muscle in all benign tumors at TE = 136 (glomus tumors = 4.52, inverting papilloma = 3.85, schwannoma = 2.2) and at TE = 272 (glomus tumors = 8.01, inverting papilloma = 2.1, schwannoma = 4.28). The average Cho/Cr ratio for benign lesions was 3.92 (TE = 136) and 6.11 (TE = 272). The Cho/Cr ratio was significantly higher in benign tumors than in both SCCA and muscle. The average Cho/Cr ratio for muscle at TEs of 136 and 272 was 1.16 and 1.31, respectively, whereas for SCCA the average Cho/Cr ratio at TEs of 136 and 272 was 1.67 and 2.45, respectively. CONCLUSION: In our small group, the Cho/Cr ratio was significantly higher in benign tumors than in muscle and SCCA of the extracranial head and neck.

Area Under Curve↗