Metabolism of I4C-Codeine in the Isolated,Perfused Rat Liver

Abstract: The metabolism of ¹⁴C-codeine in the isolated rat liver was studied in single-pass and recirculation perfusion experiments. The perfusate, a semi-synthetic medium with bovine erythrocytes, was delivered at a constant rate (12 ml/min.) and contained codeine in the range of 3–57 nmol/ml. Samples of perfusate were collected and analyzed for codeine and its metabolites after extraction and thin-layer chromatographic separation. In single-pass perfusion, steady state was reached within 20 min. The codeine concentration in the effluent perfusate varied from 17 to 48% of that in the affluent corresponding to extraction ratios of 0.83 to 0.52. There was a significant negative correlation between codeine dose and extraction ratio (r = 0.86, P<0.05, N = 6). The steady state concentration of free and conjugated morphine made a total of 21 to 49% of the molar concentration of codeine at the inflow side. The recovery of radioactivity at the end of the perfusions was on an average 89%. In recirculation perfusion experiments the codeine extraction ratios varied from 0.65 to 0.35. The amount of free morphine in the reservoir increased to a maximum within 25–45 min. Our results suggest a relatively high hepatic first-pass metabolism of codeine in the rat which is apparently dose-dependent. The quantitatively most significant metabolites of codeine are morphine and conjugated morphine. The rate and extent of morphine formation is compatible with the hypothesis that metabolically produced morphine may be responsible for the analgesic effect of codeine.     

Use of the insertable loop recorder to detect cardiac arrhythmias during syncopal episodes.

The Reveal Plus insertable loop recorder (ILR) is an implantable device used to detect cardiac arrhythmias in patients suffering from undiagnosed syncope. It has a high diagnostic yield, is easily inserted, and results in better patient outcomes. As medical-surgical nurses begin to see more patients with ILRs, they need an understanding of device use and care.     

MRI appearances of the asymptomatic patellar tendon on gradient echo imaging

Thickening of the patellar tendon and foci of increased signal intensity have been described as characteristic features of jumper's knee (chronic patellar tendinitis) on magnetic resonance imaging (MRI). It was our impression that such appearances may be seen in the patellar tendons of patients without symptoms referable to the anterior part of the knee when using gradient echo images. The appearances of the asymptomatic patellar tendon on three-dimensional gradient echo sequences were studied by retrospectively reviewing the images of 60 patients, none of whom had symptoms related to the anterior part of the knee. The anteroposterior width of the patellar tendon was measured at three levels (superior, middle and inferior) on the central sagittal image of a gradient echo sequence. The relative signal intensities at the same levels were recorded. In 97% of subjects the superior part of the tendon was wider than the midpoint, and in 97% the inferior part was wider than the midpoint. The range of widths was wide, and there was no significant difference between sexes. Focal increased signal intensity in the superior part was shown in 75%, and in the inferior part in 43%. The asymptomatic patellar tendon shows uniform thickness throughout most of its length, but there are focal expansions at the proximal and distal ends. It usually demonstrates low signal on MRI, but may contain foci of increased signal intensity at either or both ends when imaged on gradient-echo sequences.     

Selective Modified Radical Neck Dissection for Papillary Thyroid Cancer—Is Level I, II and V Dissection Always Necessary?

Background There is ongoing controversy as to the indications for and extent of lateral cervical lymphadenectomy for patients with papillary thyroid cancer (PTC). While most now agree that prophylactic lymph node dissections (LND) play no role, at the University of California, San Francisco (UCSF) we limit LND selectively on a level by level basis, and resect only the levels thought to harbor disease or to be at increased risk of metastases. This initial ‚selective LND’ usually includes levels III and IV (due to the well-documented increased likelihood of metastases to these levels) and levels I, II, and V are included when there is clinical or radiological evidence of disease or increased risk of it. Methods A retrospective review of the clinical charts and hospital records of 106 consecutive patients who had metastatic PTC and who underwent at least one lateral cervical LND at UCSF between January 1995 and December 2003 was carried out. Data were collected to assess which patients had levels I, II, and/or V included in their initial ipsilateral and/or contralateral LND and to determine the recurrence rates at these levels if they had previously been excised compared with if they had not. Chi-squared and Fisher exact tests were utilized for statistical comparison, where appropriate. Results A total of 140 initial lateral LND were performed: 104 ipsilateral and 36 contralateral. In these initial LND, 3.9%, 72.5%, and 18.6% of patients had levels I, II, and V resected on the ipsilateral side, and 2.9%, 60.0%, and 37.1% of patients had levels I, II, and V resected on the contralateral side. Recurrence at levels I and V was uncommon in all patient populations. Recurrence at level II was 19% ipsilaterally and 10% contralaterally when the level was previously resected and 21% ipsilaterally and 14% contralaterally when the level was not previously resected. There was no statistically significant difference in recurrence at level II when the level had previously been resected compared with when it had not. Conclusions If utilized in the appropriate patient population, a selective approach to lateral cervical LND for PTC can be a successful alternative to the routine modified radical LND. Levels I and V do not require resection unless there is clinical or radiological evidence of disease. Guidelines for which patients may be considered for this less aggressive approach to level II nodal metastases are suggested.     

Extent of Disease at Presentation and Outcome for Adrenocortical Carcinoma: Have We Made Progress?

Background Adrenocortical carcinoma (ACC), a rare and aggressive malignancy, accounts for up to14% of adrenal incidentalomas. The only chance of cure for ACC is diagnosis at an early stage; therefore, a main indication for adrenalectomy in patients with adrenal incidentaloma has been the potential risk of ACC. Recent studies suggest that this has led to earlier stage of ACC at diagnosis, more curative operations, and better survival. Methods We analyzed data on ACC from The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. Four equal time quartiles (1973–1979, 1980–1986, 1987–1993, and 1994–2000) were compared for changes in demographics, pathology, treatment, and cause-specific mortality. Results The average age was 51.2 years (range: 1–97), and 45.9% of patients were men. The average tumor size was 12 cm (range: 2–36 cm), and only 4.2% were ≤ 6 cm. Most (88%) patients had surgical resection of their tumor, and external beam radiotherapy was used in only 12% of patients. Between the time quartiles compared (as well as annually), there was no significant difference at presentation in age at diagnosis, sex, race/ethnicity, tumor size, tumor grade, the frequency of distant metastasis, and overall TNM stage. Low tumor grade, lower stage of ACC, later time quartile, and surgical resection were associated with a lower cause-specific mortality by univariate analysis (P ≤ 0.002) and by multivariate analysis (P ≤ 0.031). Conclusions Although adrenal incidentalomas have become a common indication for adrenalectomy, this has not resulted in patients with ACC being diagnosed earlier or treated at a lower stage of disease at the national level. The most important predictors of survival in these patients are tumor grade, tumor stage, and surgical resection.     

Supragingival root surface removal during maintenance procedures utilizing an air-powder abrasive system or hand scaling. An in vitro study

The purpose of this study was to determine the amount of root surface removal in vitro using an air-powder abrasive system or sharp curet on root surfaces simulating the cumulative effects of an every 3-month periodontal maintenance regimen over a 3-year period and to compare the amount of time spent in the utilization of each instrument. Fifty extracted teeth with fully formed roots were cleaned and mounted in one of 10 different artificial alveolar arches. Each arch contained one central incisor, one lateral incisor, one canine, one first and one second premolar. The buccal and mesial tooth root diameters were measured initially and after each treatment with a digital point micrometer. All teeth were stained with coffee and repositioned in their artificial alveolae and treated by the air-powder abrasive system or curet until all visible stain was removed. Time required for removal of stain in both treatment groups was recorded. Both groups were restained, retreated, and retimed 12 times to reproduce a 3-month maintenance interval for 3 years. The average root structure removed by the air-powder abrasive system following each treatment was 10.68 micron while the curet removed an average of 27.09 micron. Stain was removed 3.15 times faster by the air-powder abrasive system than with a curet.