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Radioisotope determination of regional colonic transit in severe constipation: comparison with radio opaque markers.

Radio-opaque markers have a well established role in distinguishing between patients with normal and those with slow intestinal transit, but in the latter group their accuracy in defining the region of delay has not been established. To study regional colonic transit accurately the transit of a radioisotope labelled meal was determined and findings were compared with those of simultaneously ingested radio-opaque markers. Twelve healthy controls (mean age 33 years) and 12 severely constipated women (mean age 36 years, bowel frequency < once per week) were studied On day 1, a meal containing 10 MBq 111In bound to 0.7 mm resin microspheres was ingested. Subjects also ingested a set of radiologically distinguishable markers on three successive days. Abdominal scans were obtained three times daily for 7 days. Abdominal radiographs were obtained after 72 or 96 hours and again at 144 or 168 hours. Eight 'regions of interest' were created--one for the small bowel, six for the colon, and one for excreted stool. The constipated patients all showed colonic transit outside the normal range, with a variable site of delay demonstrated by time activity curves for each region. To provide a different measure of the effectiveness of colonic transport, the movement of the 'centre of mass' for the radioisotope and for the markers was then determined. The radioisotope and radiopaque marker methods gave similar results. At all times between 24 and 144 hours there was no significant difference for the position of the centre of mass between the radio-opaque and marker methods. At all times, however, the mean difference between the markers and the radioisotopes was positive, indicating that the center of mass of the markers was always head of that of the radioisotope. The mean difference between the methods was never greater than one region of interest, and ranged from 12 to 72% of one region of interest in the colon. The difference between these two methods could reach up to two colonic segments in certain patients at one time. Radioisotope ingestion provides accurate information about the transit through individual colonic regions because of the possibility of frequent observations and the clear delineation of the entire colon. Although these features were not obtained with radio-opaque markers, they are suitable as a screening test for the presence and pattern of colonic delay.

Adult↗

Advantage of using CBA/N strain mice in a non-radioisotopic modification of the local lymph node assay.

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone test method for determining the skin sensitizing potential of chemicals. It has been incorporated into the official test guidelines published by some authorities, including the OECD. To avoid the use of radioisotopes, efforts have been made recently to develop non-radioisotopic modifications of the LLNA. A non-radioisotopic modification of the LLNA was developed previously using 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA). However, the non-RI LLNA was found to be somewhat less sensitive than the standard assay. This study reports the advantage of using mice of the CBA/N strain in the non-RI LLNA to improve the sensitivity of this method. The non-RI LLNA was performed using CBA/JN and CBA/N mice exposed to one of four confirmed skin sensitizers, 2,4-dinitrochlorobenzene (DNCB), eugenol (EG), isoeugenol (IEG) or alpha-hexylcinnamic aldehyde (HCA), and to one non-sensitizer, propylene glycol (PG). The EC3 values for DNCB, IEG, EG, HCA and PG were calculated to be 0.1%, 9.6%, 40.6%, 45.5% and >50% in CBA/JN mice and 0.08%, 1.9%, 10.7%, 20.3% and >50% in CBA/N mice, respectively. The EC3 values for DNCB, IEG, EG, HCA and PG in the standard LLNA using CBA/Ca mice and radioisotopes were reported elsewhere as being 0.08%, 1.3%, 13.0%, 8.0% and >50%, respectively. The EC3 values derived from the CBA/N mice in the non-RI LLNA were nearly equivalent to the EC3 values obtained using the standard radioisotopic LLNA with CBA/Ca mice. These data suggest that the use of CBA/N mice may provide a realistic opportunity to develop a version of the LLNA that does not have a requirement for the use of radioisotopes, but which nevertheless has sensitivity approaching, or comparable to, the standard method.

Acrolein↗

Assessment of the skin sensitization potency of eugenol and its dimers using a non-radioisotopic modification of the local lymph node assay.

Allergic contact dermatitis is a serious health problem. There is a need to identify and characterize skin sensitization hazards, particularly with respect to relative potency, so that accurate risk assessments can be developed. For these purposes the murine local lymph node assay (LLNA) was developed. Here, we have investigated further a modi fi cation of this assay, non-radioisotopic LLNA, which in place of tritiated thymidine to measure lymph node cell proliferation employs incorporation of 5-bromo-2'-deoxyuridine. Using this method we have examined the skin sensitizing activity of eugenol, a known human contact allergen, and its dimers 2,2'-dihydroxyl-3,3'-dimethoxy-5,5'-diallyl-biphenyl (DHEA) and 4,5'-diallyl-2'-hydroxy-2,3'-dimethoxy phenyl ether (DHEB). Activity in the guinea pig maximization test (GPMT) also measured. On the basis of GPMT assays, eugenol was classified as a mild skin sensitizer, DHEA as a weak skin sensitizer and DHEB as an extreme skin sensitizer. In the non-radioisotopic LLNA all chemicals were found to give positive responses insofar as each was able to provoke a stimulation index (SI) of >or=3 at one or more test concentrations. The relative skin sensitizing potency of these chemicals was evaluated in the non-radioisotopic LLNA by derivation of an ec(3) value (the concentration of chemical required to provoke an SI of 3). The ec(3) values calculated were 25.1% for eugenol, >30% for DHEA and 2.3% for DHEB. Collectively these data suggest that assessments of relative potency deriving from non-radioisotopic LLNA responses correlate well with evaluations based on GPMT results. These investigations provide support for the proposal that the non-radioisotopic LLNA may serve as an effective alternative to the GPMT where there is a need to avoid the use of radioisotopes.

Allergens↗

Assessment of radioisotopic micturating cystography for the diagnosis of vesicoureteric reflux in renal transplant recipients with acute pyelonephritis.

BACKGROUND: The gold standard for documenting vesicoureteric reflux is direct (retrograde) micturating cystography (MC). In children, radioisotopic MC has been advocated for increased sensitivity and lesser radiation exposure. In renal transplant recipients, where reflux can induce acute pyelonephritis, this technique has not been evaluated. The aim of this study was to assess the radioisotopic technique in these patients. METHODS: Seventeen renal transplant recipients had developed acute pyelonephritis following the surgical grafting procedure. They were investigated using both MC techniques. Radioisotopic MC was performed using 99mTc-pertechnetate. RESULTS: Reflux was documented in nine patients by radioisotopic MC but in only seven with the conventional technique. All negative patients remained symptom free after the pyelonephritis was cured and it was assumed that they had no reflux. Consequently, using the radioisotopic MC as gold standard, the conventional X-ray technique had a sensitivity of 78% and a specificity of 100%. CONCLUSIONS: Direct radioisotopic MC allowing continuous cystogram recording is more accurate than conventional X-ray MC for the diagnosis of vesicoureteric reflux in transplanted patients with acute pyelonephritis.

Acute Disease↗

Intraoperative subareolar radioisotope injection for immediate sentinel lymph node biopsy.

OBJECTIVE: To determine the identification of sentinel lymph node biopsy (SLNB) in breast cancer patients after intraoperative injection of unfiltered technetium-99m sulfur colloid (Tc-99) and blue dye. BACKGROUND: SLNB guided by a combination of radioisotope and blue dye injection yields the best identification rates in breast cancer patients. Radioisotope is given preoperatively, without local anesthesia, whereas blue dye is given intraoperatively. We hypothesized that, because of the rapid drainage noted with the subareolar injection technique of radioisotope, intraoperative injection would be feasible and less painful for SLN localization in breast cancer patients. METHODS: Intraoperative injection of Tc-99 and confirmation blue dye was performed using the subareolar technique for SLNB in patients with operable breast cancer. The time lapse between injection and axillary incision, the background count, the preincision and ex vivo counts of the hot nodes, and the axillary bed counts were documented. The identification rate was recorded. RESULTS: Ninety-six SLNB procedures were done in 88 patients with breast cancer employing intraoperative subareolar injection technique for both radioisotope (all 96 procedures) and blue dye (93 procedures) injections. Ninety-three (97%) procedures had successful identification; all SLNs were hot; 91 (of 93 procedures with blue dye) were blue and hot. The mean time from radioisotope injection to incision was 19.9 minutes (SD 8.5 minutes). The mean highest 10 second count was 88,544 (SD 55,954). Three of 96 (3%) patients with failure of localization had previous excisional biopsies: 1 circumareolar and 2 upper outer quadrant incisions that may have disrupted the lymphatic flow. CONCLUSION: Intraoperative subareolar injection of radioisotope rapidly drains to the SLNs and allows immediate staging of the axilla, avoiding the need to coordinate diagnostic services and a painful preoperative procedure.

Aged↗

Advantages of short-lived positron-emitting radioisotopes for intracoronary radiation therapy with liquid-filled balloons to prevent restenosis.

UNLABELLED: Balloon catheters filled with liquid radioisotopes provide excellent dose homogeneity for intracoronary radiation therapy but are associated with risk for rupture or leakage. We hypothesized that the safety of liquid-filled balloons may be improved once positron emitters with half-lives below 2 h are used instead of the high-energy beta-emitters 166Ho, 186Re, or 188Re, all of which have a longer half-life of at least 17 h. METHODS: To support this concept, the suitability of 18F (half-life, 109.8 min), 68Ga (half-life, 67.6 min), 11C (half-life, 20.4 min), 13N (half-life, 9.97 min), and 15O (half-life, 2.04 min) for intracoronary radiation therapy was evaluated. Potential tissue penetration of positron radiation was assessed in a series of phantom experiments using Gafchromic film. Antiproliferative efficacy of positrons emitted by 68Ga was investigated in vitro using cultured bovine aortic smooth muscle cells (BASMCs), and was compared with gamma-radiation emitted by 137Cs. To characterize the remaining risk, we estimated radiotoxicity after accidental intravascular balloon rupture on the basis of tabulated isotope-specific doses (ICRP 53) and compared these values with 188Re. RESULTS: Half-dose depth of tissue penetration measured in phantom experiments was 0.29 mm for 18F, 0.42 mm for 11C, 0.54 mm for 13N, 0.79 mm for 15O, and 0.9 mm for 68Ga. Irradiation of cultured BASMCs with positron radiation (68Ga) induced dose-dependent inhibition of proliferation with complete proliferative arrest at doses exceeding 6 Gy. ED(50) and ED(80) were 2.5 +/- 0.4 Gy (mean +/- SD) and 4.4 +/- 0.8 Gy, respectively. Antiproliferative efficacy was equal to that of the 662-keV gamma-radiation emitted by 137Cs (ED(50), 3.8 +/- 0.2 Gy; ED(80), 8.0 +/- 0.3 Gy). Estimates made for patient whole-body and organ doses were generally below 50 mSv/1.85 GBq for all investigated positron emitters. The same dose estimates for 188Re were 6-20 fold higher. CONCLUSION: Among the studied radioisotopes, 68Ga is the most attractive source for liquid-filled balloons because of its convenient half-life, sufficient positron energy (2.92 MeV), documented antiproliferative efficacy, and uncomplicated availability from a radioisotope generator. The safety profile for 68Ga is significantly better than that of 188Re, which suggests this radioisotope should be evaluated further in preclinical studies.

Animals↗

Zinc absorption estimated by fecal monitoring of zinc stable isotopes validated by comparison with whole-body retention of zinc radioisotopes in humans.

Knowledge about zinc availability from human diets is limited due to methodological difficulties. Recently developed stable isotope techniques for estimating dietary zinc absorption were compared with radioisotope techniques in five men and three women. Stable and radioactive zinc isotopes were simultaneously administered. Fecal excretion of the isotopes as well as whole-body retention of the radioactive zinc isotope was monitored. Concentration of stable zinc isotope label in fecal samples was determined by inductively coupled plasma mass spectrometry by fully quantitative measurements and from inductively coupled plasma mass spectrometry isotope ratios combined with analysis of total zinc content using atomic absorption spectrometry. Zinc absorption estimated from whole-body retention was 27 +/- 6% (mean +/- SD), estimated zinc absorption obtained by fecal monitoring of radioisotope was 26 +/- 9%, and the two stable zinc measurements resulted in values of 29 +/- 12 and 33 +/- 12%, respectively. There was no significant difference in zinc absorption estimated from whole-body retention and with the fecal monitoring methods. Recovered stable zinc isotope label was significantly lower than recovered radioisotope. For individual fecal samples, systematic differences of 16% and 12%, respectively (P < 0.05), between the radioisotope recovery and the recovery of stable isotopes with the two methods for measurement was observed. The stable zinc isotope technique for measurement of zinc absorption resulted in mean results similar to those of the radioisotope technique, but with a larger variation in the measurements.

Adult↗

Regulatory controls over the medical use of radioisotopes.

The medical uses of radioisotopes involve two broad areas: clinical nuclear medicine and biomedical research using radioisotopes. Clinical nuclear medicine includes both diagnosis and treatment of disease, while biomedical research includes the study of normal body functions and disease processes using radioisotopes. This paper discusses the use of radioisotopes in the practice of medicine, lists the areas of concern associated with that usage, and outlines the many regulatory controls that have been established to deal with some of the concerns. This material was originally prepared and distributed as a "background paper" for 1977 meetings between the Nuclear Regulatory Commission (NRC) staff, the public, and NRC's Advisory Committee on the Medical Uses of Isotopes Concerning NRC's future policy for the regulation of the medical uses of radioisotopes. Information is included on how to obtain Nuclear Regulatory Commission regulations along with a listing of NRC's Washington and regional offices.

Government Agencies↗

Validation of a non-invasive radioisotope method of imaging ureteric urine transport.

Measurement of ureteric function has hitherto involved the use of invasive techniques. A non-invasive, radioisotope method of imaging and displaying individual ureteric boluses has been described, a refinement of which is used in this department. Each "spindle" displayed using this technique theoretically represents an individual ureteric bolus of urine, but the technique has never been validated in the normal ureter in either the experimental model or man. A porcine model was set up to allow simultaneous measurement of ureteric bolus transmission using the radioisotope (compressed image) method and by the accepted techniques of electromyography (EMG) and urine drop counting. The timing of each urinary bolus, as recorded by the different modalities was then compared. The results from 11 studies showed a significant correlation between the radioisotope and EMG methods (mean r = 1.00, P = 0.0003). There was a constant relationship between the part of the radioisotopic image representing the rear end of the bolus and the EMG complex (mean time difference = 5.32 +/- 1.067s), thus defining that part of the image representing the peristaltic contraction wave. There was a variable relationship between the EMG and the part of the image representing the leading edge of the bolus (mean time difference = 13.36 +/- 5.23s), emphasising that bolus length is variable, being dependent on bolus volume. The radioisotope "spindle" concurs with EMG activity in the porcine ureter. The compressed image technique is thus validated as a non-invasive method of demonstrating ureteric urine transport.

Animals↗

[Out line of measurement of gastric emptying using by radioisotope and its problems awaiting solution].

The radioisotopic technique has been recognized as the best method of measuring gastric emptying all over the world, but several problems which must be solved have remained in it. The first is the confusion in the choice of a standard meal of ordinary food labeled with radioisotope. A meal for use in this studies must be reproducible in quality, and radioisotope must be homogenously distributed in it. It is necessary to consider the efficiency of examination, and to release a examinee's agony, therefore a meal must leave the stomach within the tolerable limits of a patient who keeps himself unshaken during measurement. If a liquid meal is used, we can easily make use of foods on the market. But, if a solid meal, a practical difficulty stands in front of us; Who prepares to cook it? Unless this problem has been solved, the radioisotopic method is never found general acceptance as a clinical examination. The second is the confusion in the choice of a posture during measurement. We must select such posture that never alter a patient's characteristics of his gastric emptying. For example, it is difficult to prove rapid evacuation in a patient with dumping syndrome, if we examine him in supine position. A final problem is to re-examine what kinds of index are necessary to investigate the gastric emptying curve with many variations except of half-emptying time which has been used popularly as the index of the rate of it. We gave an out-line of the methods of measuring gastric emptying using radioisotope and a suggestion of its some problems awaiting solution.

Gastric Emptying↗

Local lymph node assay with non-radioisotope alternative endpoints.

The local lymph node assay has recently been accepted by regulatory agencies as a stand-alone alternate method for predicting allergic contact dermatitis. To compare the sensitivity of non-radioisotope methods with that of the standard assay, we determined if these modified methods would affect evaluation of sensitization potency. For this reason, we used 2,4-dinitrochlorobenzene (DNCB) and benzocaine for different sensitizing criteria. Female CBA mice were treated for 3 days with a test compound or vehicle applied to each side of both ears. Bilateral auricular lymph node proliferative activity was assessed by the following endpoints with incorporation of 3H-methyl thymidine (3H-TdR), bromodeoxyuridine (BrdU) in vivo, and BrdU ex vivo, IL-2 production, and proliferating cell nuclear antigen (PCNA) expression. Ear thickness was also tested. The strong sensitizer DNCB was detectable by any of the non-radioisotope endpoints as well as by radioisotope-dependent standard assay. On the other hand, when evaluating the weak sensitizer benzocaine, significant changes were evident in BrdU incorporation ex vivo and in vivo, and IL-2 production. We believe that these non-radioisotope methods can assess allergic contact dermatitis caused by chemicals even in the laboratory, where it can be difficult to handle radioisotopes.

Allergens↗

Considerations on the use of radioisotopes in human nutrition research.

Tracer methodology using radioisotopes in human nutrition and metabolism research has been very productive but its use has been the object of unjustified limitations because of modeling decisions without adequate consideration of new data. These limitations have encumbered research studies in the metabolism of micro- and macronutrients particularly where nutritional deficiencies are prevalent. Even though stable isotope methodologies in human research are very useful in specific applications they are expensive and are often fraught with serious pitfalls, when compared to studies for the same purposes using radioisotopes. We have been developing safe radioisotopic methods to study the absorption and metabolism of micronutrients, especially iron and zinc, that can be applied to populations in the developing world. These and other applications of radioisotopes should allow scientists to conduct research diminishing the dependence on stable isotopes and on facilities and laboratories existing only in selected sites in the industrial world, and thus should enhance productive local and collaborative research. All radioisotopic research must be subjected to strict safety criteria, based on scientific evidence of risk, but should not be hampered by exaggerated fears of unfounded risk. Examples on the use of radio and stable isotopes to study iron and zinc absorptions are given including the radiation exposure and risk calculations.

Dose-Response Relationship, Radiation↗

[Exposure of patients as a criterion justifying radioisotope examinations (in vivo)].

Exposure of patients, known as medical exposure, is an inevitable consequence of the diagnostic and therapeutic application of ionizing radiation. This includes among others radioisotope examination in vivo. The authors evaluate diagnostic radioisotope examinations in vivo, as an artificial source of patients' exposure, in comparison with radiological diagnostics, the most common type of medical exposure, and diagnostic methods, employing physical agents other than ionizing radiation (ultrasound, magnetic field). It is expected that the results of the evaluation will provide the justifying grounds for a sensible choice of a diagnostic method among those available. On the basis of the precise data collected in 21 laboratories, the frequency of radioisotope examinations during the years 1998-2000 was estimated at about three per 1000 inhabitants. It was found that the examination of the thyroid gland, skeleton and heart were performed most frequently. The information gathered and the literature data helped to calculate an average dose per one inhabitant of Poland. The values are as follows: average effective dose per one examination--6 mSv; average effective dose per one inhabitant--0.033 mSv. It should be stressed that apart from the examinations of the thyroid gland performed with use of 1311 (16% of the total number of examinations), the average effective dose received by patients during other examinations is equal to only 2.2 mSv. Finally, the authors present the data on patients' exposure during radioisotope examinations and diagnostic examinations employing other methods. They indicate that many radioisotope examinations provide valuable diagnostic information that could not be obtained by means of other methods. Moreover, these examinations involve relatively low levels of effective doses received by patients.

Environmental Exposure↗

The influence of radioisotope vehicle on breast sentinel node detection.

AIM: To assess the relationship between carrier molecule size and time elapsing between marker injection and sentinel node(s) biopsy in patients with breast cancer. MATERIAL: The study performed on 122 women, in whom the sentinel node(s) was identified according to the procedure described below. In Group I (n=72 patients), SN identification was done with radioisotope marker of 400-3000 nm molecule size (tin colloid). In Group II (n=50 patients) radioisotope marker of <100 nm molecule size (colloidal albumin) was used. METHODS: All the patients of both groups received the markers with a single-point, intradermal, periareolar injection. Four hours after the injection (Group I - surgery in the next day) or immediately before the surgery (in this same day) (Group II), stationary lymphoscintigraphy was performed. RESULTS: Mean numbers of sentinel nodes identified with the radioisotope method in Groups I and II were 1.22 and 1.48, respectively. The difference was statistically significant (p<0.01). CONCLUSIONS: There is a relationship between the radioisotope marker molecule size and the injection-to-intra-operative evaluation time. Administration of small molecule size radioisotope marker several hours prior to the planned surgery appears to be the optimum procedure in this method of SN identification in patients with breast cancer.

Breast Neoplasms↗

Area of nodal metastasis and radioisotope uptake in sentinel nodes of upper gastrointestinal cancer.

BACKGROUND: Sentinel node navigation surgery has been introduced for the treatment of gastrointestinal tumor. As few studies have examined relationships between metastatic area and radioisotope uptake in sentinel nodes, the present study examined this relationship for gastric and esophageal cancers. METHODS: Subjects comprised 43 patients (esophageal cancer, n = 19; gastric cancer, n = 24) with < or =3 lymph node metastases in whom sentinel node mapping with radio-guided methods was performed. Radioisotope uptake was measured after surgery for all dissected lymph nodes. Metastatic area was calculated using the following formula: metastatic area (%) = (area of metastasis/total area of lymph node) x 100. Based on radioisotope uptake, lymph nodes were divided into RI(-) and RI(+) groups. RESULTS: In 35 patients, > or =1 metastatic node was present among the sentinel nodes. In 1 patient, no sentinel nodes were detected. No lymph node metastasis was found in sentinel nodes in the remaining seven patients. Lymph nodes were diagnosed as metastatic using preoperative imaging. Mean (+/-SD) metastatic area was significantly higher for RI(-) (68.3 +/- 20.5%) than for RI(+) (15.1 +/- 20.8%; P < 0.0001). Radioisotope uptake was decreased in lymph nodes with >60% metastatic area. CONCLUSIONS: The fact that radioisotope uptake is not detectable in some lymph nodes with >60% metastatic area must be considered when planning sentinel node navigation surgery.

Aged↗

Biodistribution of 225Ra citrate in mice: retention of daughter radioisotopes in bone.

Alpha-particle-emitting radionuclides have potential for therapy of localized disease due to their high linear energy transformation and short pathlengths. Radiometals that home naturally to bone can be exploited for this purpose, and 223Ra (t(1/2)=11.4 days) recently has been studied for therapy of bone tumors in mice and rats. Actinium-225 (t(1/2)=10 days) is also an attractive radioisotope for endoradiotherapy. In a single decay of a 225Ac nucleus and its subsequent decay daughters, over 27 MeV ( approximately 90% of total energy) is released by sequential emission of four alpha particles, ranging in energy from 5.7 to 8.4 MeV. Although Ac3+ does not home naturally to bone, its parent radioisotope 225Ra (beta(-), t(1/2)=15 days) can be used as an in vivo source for 225Ac. Thus, injection of 225Ra takes advantage of the bone-homing properties of radium coupled with the significant amount of energy released from the 225Ac decay chain. Our data confirm that a large fraction of radium citrate injected intravenously into mice localizes rapidly in bone. Injected doses per gram (ID/g) for 225Ra range from 25% in skull to about 10% in sternum. Once deposited, the 225Ra remains in the bone with a biological half life of >40 days. Furthermore, >95% of the daughter radioisotope, 225Ac, is retained in the bone. However, a significant fraction of one of the daughter radioisotopes, 213Bi, is found in kidney. The biodistribution data indicate that 225Ra injection should be a powerful agent for killing cells associated with bone; however, the toxicity of this radioisotope which is similar to that of other alpha emitters limits the dose that can be tolerated.

Animals↗

Sensitivity and specificity of radioisotope right-left shunt measurements and pulse oximetry for the early detection of pulmonary arteriovenous malformations.

STUDY OBJECTIVES: To assess the effectiveness of pulse oximetry and radioisotope measurement of right-to-left (R-L) shunt for the early detection of pulmonary arteriovenous malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia (HHT). DESIGN: Patients with HHT had serial measurements of the following: (1) arterial oxygen saturation (SaO2) by pulse oximetry in erect and supine positions, and on maximal exercise using cycle ergometry; (2) quantitative radioisotope measurements of R-L shunt using IV 99mTc-labeled macroaggregates of albumin; and (3) routine pulmonary function. After percutaneous transcatheter embolization of all PAVMs with feeding vessel diameters > 3 mm, residual PAVMs were assessed with selective digital subtraction pulmonary angiography. Using postembolization angiography as the "gold standard," SaO2 and radioisotope shunt measurements after embolization were analyzed retrospectively using logistic regression to assess the ability of each test to predict for the presence of residual PAVMs. RESULTS: Of the 66 patients included, 40 had small PAVMs remaining postembolization. Using univariate logistic regression, radioisotope shunt and erect saturation showed a significant relationship with the presence of residual PAVMs (p=0.001, 0.005, respectively). Erect SaO2 < or = 96% had 73% sensitivity and 35% specificity for detecting PAVMs. Radioisotope shunt >3.5% of cardiac output had 87% sensitivity and 61% specificity for detecting PAVMs. CONCLUSIONS: These results confirm that noninvasive measurements are useful in the screening of patients with HHT for the presence of PAVMs without need for angiography and its associated risks, and that radionuclide scanning is better than pulse oximetry.

Angiography, Digital Subtraction↗

How alternative are immunoassay systems employing non-radioisotopic labels? A comparative appraisal of their main analytical characteristics.

The immunoassay is one of the most sensitive and reliable analytical techniques available in the clinical laboratory. The original label for immunoassays was radioisotopes, and these methods, radioimmunoassay (RIA) and immunoradiometric assay (IRMA) are still the reference methods, because of invulnerability of the radioactive emission with respect to environmental interference. Labels other than radioisotopes have been tested for use in immunoassay to improve the sensitivity and reliability and to avoid some of the disadvantages of radioisotopic techniques. New labels have continued to be developed (Horseradish peroxidase-HPR-, pyrophosphatase, luciferases, pyrodopirazines, europium cryptates, porphirins, phosphors) and new label detection methods have been set up (e.g. chemiluminescence assay, thermometric assay, NADP+ and FADP- based coupled assay). New immunoassay strategies such as simultaneous multianalyte automated test have been developed and the reliability of the assays has in some cases caused division among researchers about the choice between the radioisotopic immunoassay or the non-radioisotopic immunoassay, as considerable effort and investment had been devoted to the search for more sensitive and practicable tests than the classic RIA-IRMA methods. The evolution of immunoassays (Monoclonal Antibodies, non-radioactive tracers, automation) has produced systems which allow a large number of laboratories to determine a great number of analytes with very good practicability. The availability of fully automated systems has generated the opinion that analytical performance of immunoassays can be considered similar to that of many traditional parameters of clinical chemistry. This conclusion seems however too optimistic, in fact data collected from interlaboratory studies demonstrate that problems concerning the analytical reliability of the measurements still remain not completely solved. In the authors' opinion, this opposition between immunological assay based on isotopic or non-isotopic labels is misleading, because each assay (whether it uses isotopic, enzymatic, fluorimetric or luminescent labels) has its own analytical characteristics and performance. For this reason the term "alternative", used to indicate all non-isotopic assays as a unique class of tests, should be abandoned. From a theoretical point of view the choice should not be between isotopic and non isotopic techniques. For each analyte to be tested, it is advisable to use the immunological assay that suits the requirements of the laboratory, irrespective of type of label. From a practical point of view, the choice should be based on the analytical performance and on the characteristics of each assay, on its cost and the type of instrumentation available in the laboratory, and on the experience and the knowledge of the laboratory personnel.

Costs and Cost Analysis↗