Intestinal concentration of 99mTc-pertechnetate into isolated loops of rat bowel.

In scanning patients for Meckel's diverticulum, the colon occasionally visualizes more rapidly than would be expected simply from gastric secretion and intestinal transit. To gain a better understanding of the intestinal physiology of pertechnetate and thereby to make a more intelligent interpretation of abdominal scans, segments of the gastrointestinal tract of Sprague-Dawley rats were isolated by transection between double ligations. After abdominal closure, the animals received an intravenous injection of 99mTcO4 and were killed at 30, 45, or 150 min after injection. Technetium concentrations in the stomach, colon, and appendiceal contents increased significantly with time after dosing, and after 30 min technetium could be clearly imaged in the stomach, upper small intestine, appendix, and colon. These results suggest that technetium is actively secreted by the intestinal mucosa. Additionally, the results indicate caution in the interpretation of scans in patients with suspected Meckel's diverticulum since, in the rat and probably in the human, significant amounts of technetium can accumulate in the gut apart from gastric secretion and intestinal transit.

Measurement of renal function with technetium-99m-MAG3 in children and adults.

UNLABELLED: A single-injection, single-sample procedure for measuring 99mTc-MAG3 clearance is presented that incorporates scaling for patient size and is valid for both children and adults. METHODS: The procedure is based on an empirical formula in which all measurements are expressed in dimensionless combinations. The formula was obtained by fitting data collected from 122 adults and 80 children at several centers. RESULTS: All results were scaled to standard adult surface area and are presented in units of ml/min/1.73 m2. For adult subjects, the residual standard deviation (r.s.d.) calculated from a single sample at 45 min was found to be 23, using the plasma clearance calculated from a multi-sample clearance curve as a reference. This did not differ significantly from the value of 22 obtained with our previous formula, which was valid for adults only. For pediatric subjects, an r.s.d. of 24 was calculated by the new formula from a single sample at 35 min; a comparable value of 33 was found using a pediatric formula previously published. CONCLUSION: The new clearance formula is recommended as a replacement for the formula we previously published, since it is based on a larger and more diverse subject population, and since it now holds for children as well, with no loss of accuracy for adult subjects.

Prediction of urinary excretion of technetium-99m-MAG3.

UNLABELLED: The urinary excretion of 99mTc-mercaptotriacetylglycine (MAG3), like that of 131I-orthoiodohippurate (OIH), can be used to identify acute renal transplant rejection and measure its severity. This parameter is often quantitated as the excretory index (observed excretion/predicted excretion). A new method for predicting the urinary excretion of 99mTc-MAG3 is presented. METHODS: The expected excretion was calculated from multisample plasma time-activity curves in 122 subjects, with correction for the first pass of the initial bolus. The resulting formula was tested prospectively against actual urine measurements in an additional 466 subjects. RESULTS: Least-squares fitting led to the following equation: Predicted excretion = 0.79(1-exp(-0.0066CMAG3), with residual s.d. 0.06, where CMAG3 is MAG3 clearance in ml/min and the predicted excretion is expressed as a fraction of the administered dose. Tested prospectively in the additional 466 subjects, the s.d. was 0.09. CONCLUSION: A new formula to predict the urinary excretion of 99mTc-MAG3 has been developed and prospectively validated. Based on our data, the normal range for the excretory index using MAG3 is the same as that of 131I-OIH, 0.8-1.2.

Gastric emptying measurements: delayed and complex emptying patterns without appropriate correction.

Anteriorly acquired and geometric mean corrected gastric emptying curves of solids and liquid isotopic-labeled meals were compared in 37 subjects given 61 meals of three different sizes. Anterior data alone consistently and significantly underestimated solid-phase gastric emptying rates with all meal sizes when compared to geometric mean acquired data. However, with liquids there were only slight differences between anterior and anterior and posterior geometric mean corrected emptying-rates. The difference probably reflects greater attenuation of the 140 kev photon of 99mTc compared to the 247 keV photon of 111In. With anterior data alone, an apparent early delay in emptying of solids was present with all meal sizes and the resultant emptying curves were nonlinear in shape. Geometric mean correction resulted in the linearization of the solid-phase emptying curves and essentially eliminated the apparent delay in emptying or lag phase noted with the anterior data alone. Based on our results, geometric mean correction techniques are necessary for accurate assessment of radioisotopic-labeled solid meals.

SPECT thallium-201 scintigraphy for the detection of left-ventricular aneurysm.

We have noted that the presence of left ventricular anterior/apical aneurysm on contrast ventriculography or echocardiography correlates well with the finding of failure of convergence of the left ventricular walls toward the apex on single photon emission computed tomography (SPECT) thallium-201 images. To assess this observation, we analyzed the SPECT thallium scans of 74 sequential patients who had SPECT thallium scintigraphy and contrast ventriculography and/or echocardiography for evaluation of coronary artery disease. Immediate post-stress and 4-hr redistribution thallium-201 SPECT images, obtained following i.v. administration of 2 mCi of thallium-201, were reconstructed with no attenuation correction using three-dimensional linear and nonlinear filters and displayed in short, vertical-long, and horizontal-long axes. Of the 74 patients, contrast ventriculography and/or echocardiography showed anterior/apical aneurysms in 15 and a posterolateral aneurysm in one. SPECT thallium scans detected 14 of the 16 aneurysms, based on the criterion of failure of convergence of the ventricular walls toward the apex. There were two false-positives. Thus SPECT thallium-201 scintigraphy for the detection of left-ventricular aneurysm in this series had a sensitivity of 94%, a specificity of 97%, and an accuracy of 96%.

Failure to detect extramedullary hematopoiesis during bone-marrow imaging with indium-111 or technetium-99m sulfur colloid.

A patient with postpolycythemic myeloid metaplasia developed an enlarging abdominal mass documented on TCT scanning. To distinguish between lymphoma and extramedullary hematopoiesis, marrow elements were imaged with indium-111 chloride and technetium-99m sulfur colloid. Because the mass failed to accumulate either tracer, a presumptive diagnosis of lymphoma was made and exploratory surgery was performed. The excised mass was found to consist of enlarged lymph nodes containing extramedullary hematopoiesis. Caution should be exercised in the use of In-111 or Tc-99m SC bone-marrow scans to diagnose sites of extramedullary hematopoiesis.

Reversibility bull's-eye: a new polar bull's-eye map to quantify reversibility of stress-induced SPECT thallium-201 myocardial perfusion defects.

Myocardial ischemia is currently interpreted from SPECT thallium-201 (201Tl) tomograms by the subjective visual finding of stress-induced perfusion defects which "normalize" or "reverse" by 4 hr. Thus, we have developed a computer method to quantify and display the three-dimensional distribution of reversible segments. Circumferential profiles generated from the short axis slices are normalized to the reference area in the stress study. The stress is subtracted from the normalized delayed data, and then displayed as a polar bull's-eye plot so that positive values show areas that have "reversed" or "improved." Patient profiles are compared to means and standard deviations of reversibility for all pixels determined from the Emory normal male files. Criteria for reversibility were developed from studies of 42 male patients found to have 48 defects, as determined by the consensus of five blinded expert observers. There was computer agreement with the experts on 25 of 31 relatively fixed and 14 of 17 reversible defects. Our preliminary results indicate that this new method promises to aid observers to more consistently identify and quantify the reversibility of SPECT 201Tl myocardial perfusion defects.

Evaluation of the hepatobiliary excretion of technetium-99m-MAG3 and reconstitution factors affecting radiochemical purity.

UNLABELLED: Technetium-99-MAG3 is a renal tubular function agent. However, sporadic liver and gallbladder visualization have raised questions about kit stability, impurities and nonrenal routes of excretion. To address these issues, studies were conducted to optimize the labeling efficiency of the TechneScan MAG3 kit and to evaluate the hepatobiliary excretion of the MAG3 complex. METHODS: Thirty-six vials of the commercial formulation of 99mTc-MAG3 were prepared according to manufacturer's instructions and evaluated for radiochemical purity using two methods: a combination of high-performance liquid chromatography and paper chromatography (HPLC/PC); and the manufacturer's miniature chromatography system (Sep-Pak procedure). RESULTS: The labeling efficiency was significantly higher when the kit was reconstituted with 10 ml (96.6%) of saline versus 5 ml (91.4%) (p < 0.01). The radiochemical purity of the kits remained stable for up to 6 hr, but the purity determined by Sep-Pak averaged 2.5% higher than that determined by HPLC procedures (p < 0.01). Rat studies to evaluate renal and hepatobiliary elimination of MAG3 showed no difference in the %ID excreted into the urine by 60 min in all groups of animals studied. However, the %ID excreted into the bile was significantly higher for the kit formulation than the HPLC-purified MAG3, 9.9% versus 6.6% (p = 0.0475). CONCLUSION: The radiochemical purity of the TechneScan MAG3 kit can be improved by reconstituting with larger volumes. In addition, the studies in rats suggest that fasting or kit impurities may be a contributing factor to increased hepatobiliary visualization in patient studies.

Technetium-99m-sulfur colloid for lymphoscintigraphy: effects of preparation parameters.

UNLABELLED: There has been a resurgence in the use of lymphoscintigraphy for the external detection of lymph nodes for metastatic melanoma and breast tumors. Technetium-99m-antimony trisulfide colloid was the radiopharmaceutical developed for this procedure and was found to have a narrow distribution of small particles, 0.003-0.03 microns, but it was never approved by the FDA. Technetium-99m-sulfur colloid also forms particles and this article reports on the effects different preparation parameters have on its particle size distribution and stability. METHODS: Four groups of kits were evaluated, kits which utilized: (a) a reduced heating protocol with a new 99mTc-elution, (b) a reduced heating protocol with an old 99mTc-elution, (c) a prolonged heating protocol with a new 99mTc-elution and (d) a prolonged heating protocol with an old 99mTc-elution. The particle size distribution and the stability of the different 99mTc-sulfur colloid kit preparations were evaluated over 6 hr utilizing polycarbonate filters ranging from 0.03 to 10 microns. RESULTS: In vitro studies demonstrated no significant change in the particle size distribution over a 6-hr period and all 99mTc-sulfur colloid preparations had a bimodal particle size distribution pattern. Importantly, heating the kit for shorter periods of times utilizing [99mTc]pertechnetate, which had a longer ingrowth of [99mTc]pertechnetate, produced a formulation which had the largest percentage of particles smaller than 0.03 microns. CONCLUSION: In our clinical setting, 99mTc-sulfur colloid prepared with the reduced heating protocol and utilizing [99mTc]pertechnetate, which has the highest ingrowth of [99mTc]pertechnetate has proved to be an excellent agent for lymphoscintigraphy studies. This preparation has demonstrated rapid movement of the particles from the primary site to the lymph nodes in over 97% (106/109) of the patients we have studied.

Prognostic value of thallium-201 single-photon emission computed tomography for patients with multivessel coronary artery disease after revascularization (the Emory Angioplasty versus Surgery Trial [EAST]).

The aim of this study was to investigate the relation between reversible thallium single-photon emission computed tomography (SPECT) myocardial perfusion defects at 1-year after revascularization and quantitative indexes in Emory Angioplasty versus Surgery Trial (EAST) and outcomes 3 years after revascularization in 336 patients. EAST was a randomized controlled trial assessing cardiac outcomes for angioplasty versus bypass surgery for patients with multivessel coronary artery disease. During this prospective trial, a substudy included the evaluation of the prognostic value of reversible defects on quantitative thallium SPECT. At 1-year after revascularization, 336 patients underwent SPECT thallium-201 stress myocardial perfusion and 3-hour delayed imaging. Subsequent events, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, myocardial infarction, and death, were recorded at 3 years. A stress-induced reversible thallium-201 defect was defined using a quantitative index of a reversibility score >30% and severity score >500. Reversible defects were observed more frequently in the percutaneous transluminal coronary angioplasty than in the coronary artery bypass graft surgery treatment groups (46% vs 27%, p <0.001). A total of 123 patients had stress-induced, reversible thallium defects and more events than patients with other perfusion results (freedom from all events was 81.3% vs 94% [p <0.001], and freedom from myocardial infarction and death 88.3% vs 95.5% [p = 0.031]). Quantitative thallium SPECT at 1 year after revascularization risk stratifies patients as to their likelihood of major cardiac outcomes.

Lymphoscintigraphy, the sentinel node concept, and the intraoperative gamma probe in melanoma, breast cancer, and other potential cancers.

There is a resurgence of interest in lymphoscintigraphy because of attention to the sentinel node concept and the availability of the surgical gamma probe that can be used in the operating room to localize radiolabeled sentinel nodes. Conventional surgical management of melanoma has been altered for intermediate thickness tumors such that lymph node dissection is performed for a lymph node bed only if the sentinel node is tumor positive on histological exam after gamma probe-guided excision. This approach is cost effective, saving about 80% of these patients (sentinel node tumor negative) the cost and morbidity of unnecessary "elective lymph node dissection." In addition, a biopsy can be performed on all lymph node beds that receive lymphatic drainage from the tumor site thereby improving staging and perhaps survival by providing the most appropriate therapy. Substantial work has been done to develop optimum imaging techniques and the best radiopharmaceutical preparation to achieve accurate, reproducible lymphatic drainage images. Our methodology includes the following intradermal injections of a technetium 99m sulfur colloid (modified preparation) are followed by dynamic imaging (10 seconds per frame); static imaging up to 30 minutes and late imaging at 1 to 2 hours. Images show lymphatic channels that lead to sentinel nodes in 1, 2, 3, or more anatomic locations. Surgical management is altered to include sampling sentinel nodes of nodal beds, many of which would not have been sampled by previous conventional surgical estimates of lymphatic drainage. While clinical success of lymphoscintigraphy and intraoperative probe localization of the sentinel node in melanoma is evident, use of lymphoscintigraphy and the sentinel node concept in breast cancer is investigative, but promising. The radiopharmaceutical is injected around the tumor in the breast followed by imaging to delineate lymphatic drainage to the sentinel node(s). Optimum methodologies for radiopharmaceutical, volume and/or activity of injectate, and imaging have yet to be determined. Breast lymphatic drainage can be to axilla, internal mammary, and/or supraclavicular nodes in any combination.

Multiorgan scans for staging lung cancer. Correlation with clinical evaluation.

One hundred consecutive patients with findings suggestive of resectable bronchogenic carcinoma were studied prospectively to determine if routine liver, brain, and bone scans (multiorgan scans) detected metastases which were not suggested by a history, physical examination, and serum chemistries. Multiorgan scans were compared with clinical evaluations in 52 patients found to have operable bronchogenic carcinoma. There was a discordance between scans and clinical evaluations in 25/153 scans (16 per cent). Two of the 22 negative scans in patients with abnormal clinical findings were false negative. Sixteen of the 17 positive scans in patients with normal clinical findings were false positive. One of the 131 scans done in patients with no evidence of metastases on clinical evaluation was true positive. These data indicate that the routine use of multiorgan scans in the initial staging of potentially resectable bronchogenic carcinoma is not justified.

Uptake of cadmium-109, a metallothionein-binding radiometal, by tumors in mice as a function of the transformed phenotype.

Metallothionein (MT) is an intracellular protein that binds many metals with isotopes having imaging or radiotherapeutic potential. To determine whether uptake of radioisotopes that bind to MT is increased in tumors, we measured the uptake of cadmium-109 (Cd-109) in tumors and in normal tissues of mice. Tumors were grown in Balb/C mice from cultured Balb/3T3 cells transformed by the Moloney murine sarcoma virus (MMSV). Uptake of Cd-109 by MMSV tumors exceeded that by normal tissues examined, with the exception of liver and kidney (the organs known to be richest in metallothionein). The MMSV tumor:background ratios of activity were greater for Cd-109 than for gallium-67 for many of the normal tissues examined. The magnitude of uptake of Cd-109 by tumors from four related cell lines paralleled their degree of expression of two indices of the transformed, or malignant, phenotype. We conclude that metals that bind to MT may be useful for imaging or radiotherapy of cancer.

Physician acceptance of clinical pharmacy service in a skilled nursing home.

A study was made of physician acceptance of pharmacist-recommended changes in the drug therapy of elderly institutionalized patients. The records of 92 such patients were reviewed by the pharmacist. In 33 instances the pharmacist recommended changes in drug therapy. In 75.8% (25 of these 33 patients) the recommendations were judged appropriate and were accepted by the physician concerned.

Improved health-related quality of life with SSRIs and other antidepressants.

STUDY OBJECTIVE: To document the health-related quality of life (HRQOL) of depressed patients receiving antidepressant drugs. DESIGN: Cross-sectional study. SETTING: Community pharmacy-based setting. PATIENTS: Fifty-seven depressed patients. INTERVENTION: Independent pharmacist members of the Community Pharmacists Research Network in Georgia administered the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) to subjects. MEASUREMENTS AND MAIN RESULTS: Sixty-one percent of patients were treated with a selective serotonin reuptake inhibitor (SSRI) and 38.6% were treated with a non-SSRI. Those receiving SSRIs scored higher on the mean physical (PCS) and mental (MCS) health summary scores of the SF-36 than those not receiving the drugs. No significant differences were seen in PCS or MCS scores of men and women. CONCLUSION: Community pharmacists documented better HRQOL in patients receiving SSRIs than in those given other antidepressants.

A single-injection, two-sample method for measuring renal 99mTc-MAG3 clearance in both children and adults.

We present a method for estimating 99mTc-MAG3 clearance from both a single injection and two blood samples that is valid for both adults and children. It was obtained by fitting a scaled two-compartment model (having only two adjustable parameters) to adult and pediatric data from multiple centers.

The expanding role of pharmacy and therapeutics committees. The 1990s and beyond.

Traditionally, pharmacy and therapeutics (P&T) committees have been responsible for overseeing the drug use process, using formulary systems to control drug costs. Primarily, these committees act in an advisory capacity as policy-recommending bodies within healthcare systems, for the specific purpose of promoting rational drug therapy. Methodologies utilised by these committees include drug use evaluation, medical staff education, continuous quality improvement, formulary restriction and therapeutic interchange. Future roles of P&T committees will include the evaluation of clinical outcomes information, including quality-of-life issues, to establish policies governing the use of drugs at all levels and in all types of healthcare.

Office therapeutic drug monitoring.

Considerations necessary for appropriate therapeutic drug monitoring in the office practice setting have been presented. Practical issues focusing on clinical pharmacokinetics as well as serum drug concentration evaluation methods and techniques have been reviewed, with emphasis on orally administered medications.

Back from the cuspid.

Denture reduction in formal orthodontic treatment does not appear to prevent the impaction of lower third molars. The extraction of premolar teeth is best carried out as close as possible to the eruption time of the cuspids. The posterior part of the mandibular arch should be evaluated by the study of lateral oblique roentgenograms and one of several options regarding treatment should then be adopted.

Glucocorticoids in clinical practice.

The many unique features of glucocorticoids makes therapy with these steroids challenging. The anti-inflammatory potency, relative mineralocorticoid activity, plasma half-life, and route of administration of the synthetic cortisol preparations are compared. Because they produce profound anti-inflammatory and immunosuppressive effects, exogenously administered glucocorticoids are effective therapy for a variety of diseases and conditions. The appropriate dosing regimen is an adequate dose administered for a sufficient period to precipitate an acceptable response. It is impossible to predict the regimen that will suppress the hypothalamic-pituitary-adrenocortical (HPA) axis and thereby increase the risk of developing adrenal insufficiency during periods of stress. Until recovery of the axis is complete, patients require daily physiologic replacement doses; high-dose supplemental therapy may be required during a major illness or surgery. Once there are signs of improvement, the dosing regimen should be adjusted to a single morning dose, then to an alternate-day regimen, and, as soon as possible, the steroid should be discontinued. This tapering process maintains disease suppression while minimizing toxicity; however, it is often complicated by exacerbation of the disease and withdrawal symptoms. Potential complications associated with glucocorticoid therapy are numerous, involve all organ systems, and are potentially more devastating than the HPA axis suppression.