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Radionuclides and the patient with coronary artery disease.

The emergence in the past 20 years of nuclear medicine as a distinct diagnostic discipline has been a major clinical advance. The relatively rapid evolution from the small laboratory limited primarily to the study of thyroid disease to the large unit in which radioactive tracers (radionuclides) are utilized to evaluate structure and function of most organ systems has been accelerated by major advances in instrumentation, new radioactive tracers and application of computer techniques. Application of these radionuclide techniques to the study of coronary artery disease has been quite recent, and has in part been limited by the need for a coordinated effort between the cardiologist and the specialist in nuclear medicine. However, realization of the potential usefulness of these techniques has fostered an increasingly productive liaison between the two specialties. The potential advantages of these radionuclides in evaluating patients with cardiovascular disease is twofold: first, they may permit the noninvasive or atraumatic acquisition of data that might otherwise be obtained only at the time of cardiac catheterization; second, and perhaps more important, they may permit the acquisition of physiologic measurements or observations not attainable by more conventional modes of study. Functionally, these techniques can be divided into those that evaluate cardiac performance and those that evaluate coronary blood flow, regional myocardial perfusion and myocardial viability.

Cesium↗

[Use of the lymphoscintigraphy in detection of sentinel lymph nodes of the neck].

Technique of the application of radioactive tracer to the primary tumor and lymphoscintigraphy with use of the stationary and handheld gamma probe was presented. Various types of the used radioactive tracers were characterized. Scintigraphical criteria for sentinel nodes recognition were discussed. Advantages and limitations of the use of lymphoscintigraphy for sentinel nodes detection were described. Necessity of further study to determine feasibility of sentinel nodes radiolocalization in stage N0 in head and neck cancer was pointed out.

Humans↗

The concept of the sentinel lymph node.

Lymphangiograms performed via direct cannulation of lymphatic ducts demonstrate drainage of the lymph into a specific lymph node center, the so-called SLN. Contrast materials such as lipiodol, injected directly into the tissue (e.g., tongue) can demonstrate the SLN. As the neoplastic cells can be carried through the lymphatic ducts, the SLN is the first filter in the lymphatic pathway, and the SLN is indeed the most likely regional node to harbor metastatic carcinoma. The results of these efforts challenged the surgical community worldwide to recognize the importance of the concept of SLN. This concept needs to be inexpensive and easily applied in daily practice. Recently, brilliant investigators have found that using "blue dye" and or radioactive tracers are a resourceful way in identifying SLN and have applied the benefits in their daily practice. Morton [15] using the "blue dye" and Krag [1] using radioactive tracers are pioneers in the application of these concepts in other malignant diseases. The SLN concept today is feasible to apply in the investigation, diagnosis, staging and treatment of almost all solid tumors in human pathology. Numerous elegant reports have proved the validation of the concept [2, 7-9, 11, 12, 16, 17, 20, 21, 26-28].

Coloring Agents↗

[A comparison of three different techniques for measuring glomerular filtration rate].

The clearance of inulin, creatinine and radioactive tracers from the blood may be used to measure glomerular filtration rate (GFR). These techniques, however, are usually invasive and time-consuming. Although the clearance of a radioactive tracer is usually applied in nuclear medicine for the determination of GFR, it is also possible to convert the concentration of the tracer in the kidneys to absolute GFR by means of a regression equation. As this new technique is much faster, we have compared it with the conventional technique. A good correlation was found with the standard radionuclide techniques (r = 0.91), but the reference method was under-estimated on the average by 14 ml/min. The new regression equation derived in our clinic will ensure future accurate GFR measurements within 6 minutes.

Chromium Radioisotopes↗

Measurement of whole body acetate turnover in healthy subjects with stable isotopes.

Colonic fermentation of dietary fibres produces short-chain fatty acids (e.g. acetate, propionate). Measurements of whole body acetate turnover was used in order to estimate the production of colonic short-chain fatty acids in human subjects. However, higher flux rates for acetate have been reported in human studies with stable isotopes as compared to radioactive tracers. The reasons for this discrepancy are unclear. In this study, the stable isotope (1-13C)acetate was used and a method was developed to measure its enrichment in plasma. Variations between and within assays were less than 5%. The standard curve was linear from 0.5% to 10% enrichment. When this tracer was infused for 160 min in six healthy volunteers, acetate turnover was found to be 7.5 +/- 1 mumol kg-1 min-1, which is similar to data reported with radioactive tracers. We assumed that the higher flux rate previously observed with stable isotope tracers was related to differences in the physiological status of the subjects involved in these studies.

Acetates↗

Lymphoscintigraphy and lymphatic mapping for identification of sentinel lymph nodes.

The recently introduced technique of sentinel lymph node dissection (SLND) may replace complete axillary lymph node dissection for axillary staging of early breast cancer. Successful SLND is predicated on meticulous delineation of the lymphatic pathway and sentinel node(s). Currently employed lymphatic mapping materials include vital blue dyes and radioactive tracers. Techniques of intraoperative lymphatic mapping and SLND using dye, tracer, or both have high success rates in the hands of experienced investigators, but their routine and widespread use awaits resolution of questions about the timing, dose, and type of radioactive tracer; the optimal lymphatic mapping technique; indications and contraindications for SLND; and certification of qualified surgeons, pathologists, and nuclear medicine physicians.

Breast Neoplasms↗

[Drainage of the radioactive lymphotropic tracers 198 Au-colloid and 99m Tc-sulfur-colloid from the orbit in rabbits (author's transl)].

In order to investigate lymph drainage from the retrobulbar space colloid solutions (198Au-colloid and 99mTc-sulfur-colloid) were injected into the right retrobulbar space of 31 rabbits. The distribution of radioactivity was measured in vitro after dissection with a sodium iodine crystal well counter and in some animals in vivo with the Gamma camera. More than 90% of the applied activity of either colloid solution was found in some animals up to the eighth day post injection in the retrobulbar space and in the liver. The remaining activity was recovered mainly from the regional lymph nodes, due to its smaller particle size higher values were registered in the experiments with 198Au than in those with 99mTc. The highest concentrations with up to 4,6% of the activity were observed in the deep cervical lymph nodes on both sides. Minor concentrations of activity were found ipsilateral in the superficial cervical and mandibular lymph nodes. Furthermore, small but significant activities were demonstrated in the optic nerves as well as in the contralateral retrobulbar space. The present data clearly substantiate the existence of lymph drainage, although a slow one, from the retrobulbar space. Moreover they indicate a reverse prelymphatic-lymphatic flow toward the optic nerves and the contralateral retrobulbar space. These results are of importance in the discussions of lymphostatic ophthalmopathy. The clinical application of this method is desirable; however, at present it is not yet practicable without further studies.

Animals↗

Methods for the Measurement of a Bacterial Enzyme Activity in Cell Lysates and Extracts.

The kinetic characteristics and regulation of aspartate carbamoyltransferase activity were studied in lysates and cell extracts of Helicobacter pylori by three diffirent methods. Nuclear magnetic resonance spectroscopy, radioactive tracer analysis, and spectrophotometry were employed in conjunction to identify the properties of the enzyme activity and to validate the results obtained with each assay. NMR spectroscopy was the most direct method to provide proof of ACTase activity; radioactive tracer analysis was the most sensitive technique and a microtitre-based colorimetric assay was the most cost-and time-efficient for large scale analyses. Freeze-thawing was adopted as the preferred method for cell lysis in studying enzyme activity in situ. This study showed the benefits of employing several different complementary methods to investigate bacterial enzyme activity.

Journal Article↗

[Resorption and incorporation of radioactive-labeled amino acids during the administration of various protein carriers in rats. 2. Uptake of radioactivity by tissues of the gastrointestinal tract after intragastric administration of 14C-L-U-leucine and 3H-glycine].

Male Albino rats (weighing 90-100 gms) were fed ad libitum for 14 days with limited periods of access to food. Powdered whole egg (V), fish meal (F), yeats (H), and gelatine (10% protein in dry matter) used as protein sources. Additionally, one group of rats received a protein-free (e). Radioactive tracers were administered by intragastric infusion of 25 mu Ci 3H glycine and 5 mu Ci 14C L-leucine per 100 gm of body weight 2 hrs after the feeding of 2 gm of the experimental diet per 100 gms of body weight. The level of uptake of radioactive tracers from the different sections of the gastro-intestinal tract was measurels of 3H and 14C labelling in intestinal tissues were observed 3 hrs and 7 hrs after infusion. The level of 14C labelling was found to be negatively correlated and the level of 3H labelling was positively correlated with the biological value of the diet. Intestinal tissues are capable of storing considerable amounts of 14C radioactivity. So, 72 hrs after infusion, the following levels of 14C radioactivity (expressed as percentage of the total dose of radioactivity) were found in tissues of the gastro-intestinal tract: whole egg: 8.4%, fish meal: 9.6%, yeast: 13.1%, gelatine: 14.9%; protein-free diet; 14.2%. The quotients correlating the levels of radioactivity from the intestinal contents with that found in the intestinal wall suggest that the walls of the small intestine possess a high capacity for absorption. At all times of radioactive measurements the walls of the small intestine were found to contain higher levels of both 14C and 3H radioactivity than the contents of small intestine.

Animal Nutritional Physiological Phenomena↗

Fluorescein-labeled dextran concentration is increased in BAL fluid after ANTU-induced edema in rats.

Several methodologies have been developed to assess alveolocapillary membrane permeability in acute lung injury. The purpose of this study was to determine the reliability of FITC-dextran compared with radioactive tracers to assess lung permeability alterations. After intraperitoneal administration of alpha-naphthylthiourea (ANTU, 50 mg/kg) or DMSO-ANTU vehicle, the animals were euthanized and their lungs were studied in an isolated-lung preparation. FITC-dextran or radiolabeled tracers were added to the perfusate. At 2 h the bronchoalveolar lavage (BAL) fluid from the ANTU group showed a significantly greater amount of fluorescence in the supernatant after centrifugation of BAL fluid compared with the DMSO group. Consistent results were observed with the radioactive tracers: there was an increase in extravascular albumin space and extravascular lung water compared with the control group. No cleavage of the FITC from the dextran molecule was evident by chromatography comparing samples recovered from the BAL fluid to the pure FITC-dextran molecule. In conclusion, measurement of FITC-dextran in the supernatant of BAL fluid after intravascular administration is a reliable method of assessing lung permeability changes in vivo and ex vivo.

Animals↗

Colon submucosal microdialysis: a novel in vivo approach in barrier function assessment - a pilot study in rats.

During shock, prognosis of a patient depends largely on intestinal barrier function. The potency of gut epithelium to represent an obstacle to toxins is determined by the blood supply. All established methods of mucosal function determination necessitate the functional involvement of bloodstream. Microdialysis allows monitoring of extracellular substances in the gut submucosa, but its potential use for gut barrier integrity assessment is unknown. Twelve rats underwent perfusion of the descending colon either with 20 % ethanol or control medium (vehicle). Both media contained equal amounts of a radioactive tracer substance ((51)Cr-EDTA). Mucosal permeability for (51)Cr-EDTA was assessed by microdialysate to luminal perfusate activity ratios. Sampling was performed using the colon submucosal microdialysis technique. The group subjected to ethanol treatment had profound macro- and microscopical alterations in perfused colonic segment associated with a significant increase in tracer permeability during ethanol exposure (2.354+/-0.298 % for ethanol as opposed to 0.209+/-0.102 % for control group, p 0.01), which remained elevated for 60 min after cessation of ethanol administration (3.352+/-0.188 % for ethanol compared to 0.140+/-0.0838 % for the control group, p 0.001). Submucosal microdialysis with radioactive tracer substance can be considered a feasible and advantageous alternative of gut barrier function estimation. Parallel monitoring of local tissue chemistry with this method remains a challenge in the future.

Animals↗

Effect of concentration and hyaluronidase on albumin diffusion across rabbit mesentery.

OBJECTIVE: To measure the diffusion coefficient of albumin through rabbit mesentery using the steady-state flux of radioactive tracer 125I-albumin. The effect of albumin concentration and testicular hyaluronidase were also studied. METHODS: Mesenteric tissue was bonded between two plates, exposing a 7 mm diameter surface, with two chambers on either side. One chamber was filled with a test solution of albumin containing the radioactive tracer and the other with lactated Ringer solution. The solutions in both chambers were stirred with small magnetic cylinders. The chamber filled with lactated Ringer solution was placed in a well-type NaI(Tl) detector, and the radiation emitted from the tracer that diffused across the mesentery was monitored continuously for 9 hours. The diffusion coefficient (D) was calculated using Fick's law of diffusion. The diffusion coefficient was measured at albumin concentration differences (delta C) between approximately 0 and 10 g/dL. The diffusion coefficient was also measured with testicular hyaluronidase at three different albumin-concentration differences. RESULTS: The diffusion coefficient increased significantly (P < 0.0001) approximately three-fold from a mean value of 2.2 x 10(-8) +/- 1.2 x 10(-8) (SD) cm2/s at 0-0.5 g/dL delta C to 5.9 x 10(-8) +/- 1.1 x 10(-8) (SD) cm2/s at 10 g/dL delta C. The values are much less than the free diffusion coefficient of albumin (6 x 10(-7) cm2/s). Testicular hyaluronidase added to the albumin solution decreased D by approximately 60%, but did not eliminate the increase in D with delta C. CONCLUSIONS: The increase in D with delta C and the reduced D with hyaluronidase were attributed to a reduced albumin-excluded volume caused by an interaction between albumin and hyaluronan. Further studies are required to define this interaction.

Albumins↗

Ion permeability of rabbit intestinal brush border membrane vesicles.

The ion permeability of rabbit jejunal brush border membrane vesicles was studied by measuring unidirectional fluxes with radioactive tracers and bi-ionic diffusion potentials with the potential-sensitive fluorescent dye, diS-C3-(5). Tracer measurements provide estimates of the absolute magnitudes of permeability coefficients, while fluorescence measurements provide estimates of relative and absolute ion permeabilities. The magnitudes of the permeability coefficients for Na+, K+, Rb+, and Br- were approximately 5 nanoliters/(mg protein X sec) or 10(-5) cm/sec as determined by radioactive tracer measurements. The apparent selectivity sequence, relative to Na+, as determined by bi-ionic potential measurements was: F-, isethionate, gluconate, choline (less than 0.1) less than Na+(1.0) less than Cl-(1.5) = NO-3(1.5) less than Br-(2.3) less than K+(2.4) less than Rb+(2.5) less than Cs+(2.6) less than Li+(3.9) less than NH+4(12) less than I-(40). The origin of this selectivity sequence and its relationship to the ion permeability of the brush border membrane in the intact epithelium are discussed.

Animals↗

[Acupuncture meridians demythified. Contribution of radiotracer methodology].

Radioactive trajectories can be visualized by injecting a radioactive tracer, technetium 99 m, at the site of acupuncture points. To determine the exact nature of these trajectories we performed several experiments on healthy volunteers, and our results may be summarized as follows. The target organs of technetium 99 m, and notably the thyroid gland, were always visualized. The circulating radioactivity, visible on scintiscans and confirmed by venous blood counts, was not negligible. The radioactive trajectories we observed were often divided at their starting point and did not extend along the whole length of the acupuncture meridians they might have made visible. The radioactive trajectories disappeared after venous blockade to reappear when the blockade was lifted. Finally, the radioactive trajectories obtained were very similar after injection at the acupuncture point and at a control point. These findings indicate a lymphatic and venous drainage of the radioactive tracer at the site of injection followed by transportation through the veins, rather than visualization of acupuncture meridians as suggested by some authors.

Acupuncture Therapy↗

Synthesis of rhodopsin and opsin in vitro.

Isolated bovine retinas have been used to study the synthesis of rhodopsin and the renewal of photoreceptor rod outer segments. Both leucine and glucosamine served as radioactive tracers to follow rhodopsin synthesis. In both cases the rod outer segment preparations contained large amounts of labeled macromolecules chromatographically distinct from rhodopsin, the latter representing only about 10% of the high molecular weight labeled material. However, electrophoresis on polyacrylamide gels with sodium dodecyl sulfate indicated that as much as 60-68% of the radioactivity coincided with opsin, the apoprotein of rhodopsin. Treatment of labeled rod outer segments with 9-cis-retinal caused much of the non-rhodopsin label to be converted to isorhodopsin. After such treatment the fraction of the label in visual pigment rose from about 10 to 51% with leucine as the radioactive tracer and to 78% with glucosamine. Similar treatment of bleached outer segments labeled with leucine gave identical results with complete regeneration of isorhodopsin (lambda max 487 nm) which then accounted for 56% of the labeled macromolecules. No such conversion occurred in controls lacking 9-cis-retinal. Both 9-cis- and 11-cis-retinal were effective but all-trans-retinal was ineffective in producing the conversion. Under in vitro conditions opsin appears to be accumulated in the outer segment prior to the addition of retinal.

Animals↗

The determination of amino acid pool sizes and turnover rates by gas chromatographic mass spectrometric analysis of stable isotope enrichment.

Gas chromatography mass spectrometry has been used to determine the 15N enrichment of plasma glycine of rabbits at various times following the intravenous administration of 15N-glycine. These data were used to prepare isotope enrichment time decay curves for eleven individual animals. The slopes and intercepts of least squares lines that describe the decay curves were considerably more accurately than those reported in similar studies employing radioactive tracers. Individual glycine pool sizes (13.8-37.4 micronmoles per 100 g body wt), turnovers rates (2.66-3.36 pools h-1) and flux (50.4-99.7 micronmoles h-1 per 100 g body wt) were estimated from these parameters in a group of animals and compared with the literature values. These results demonstrate that low risk non-radioactive stable isotopes can be substituted for radioactive tracers in studies of human amino acid metabolism, with considerable saving in time and without loss in accuracy, when gas chromatography mass spectrometry is used to determine plasma amino acid and stable isotope enrichment.

Animals↗

Hystero-salpingo scintigraphy: a routine investigation in sterile women?

Based on the spontaneous migration of radioactive tracer from the posterior vaginal fornix to the ovaries and peritoneal cavity, several attempts were made to assess hystero-salpingo scintigraphy (HSS). The low acceptance rate by sterile women of routine investigation of tubal function may be due to a fear of radiation exposure and unpleasant examination procedures. Our protocol for HSS adopts a low dose of radioactive tracer (0.2-0.3 mCi), a defined mode of application (between the external and internal os of the cervical canal) and a short imaging time (60 min). From 1990 to 1992, we investigated 60 fallopian tubes in 32 sterile women by HSS, hystero-salpingography (HSG) and/or chromopertubation during laparoscopy (LPSC). The results of HSG and HSS corresponded in 15 of 49 fallopian tubes, LPSC and HSS in 9 of 24. None of the 32 patients had become pregnant naturally during the average observation period of 17 months. Two patients became pregnant after in-vitro fertilization. HSS, performed according to our protocol, causes less pain and results in a lower dose of radiation than HSG (about 50%). It is well accepted by patients and is easy to perform. As an investigation of tubal function, HSS may serve as an additional examination technique in cases of presumed tubal sterility.

Adult↗

Early renal changes in 45 degrees HDT rats.

BACKGROUND: Both microgravity and simulated microgravity models, such as the 45HDT (45 degrees head-down tilt), cause a redistribution of body fluids indicating a possible adaptive process to the microgravity stressor. Understanding the physiological processes that occur in microgravity is a first step to developing countermeasures to stop its harmful effects, i.e., (edema, motion sickness) during long-term space flights. HYPOTHESIS: Because of the kidneys' functional role in the regulation of fluid volume in the body, it plays a key role in the body's adaptation to microgravity. METHODS: Rats were injected intramuscularly with a radioactive tracer and then lightly anesthetized in order to facilitate their placement in the 45HDT position. They were then placed in the 45HDT position using a specially designed ramp (45HDT group) or prone position (control group) for an experimental time period of 1 h. During this period, the 99mTc-DTPA (technetium-labeled diethylenepentaacetate, MW=492 amu, physical half-life of 6.02 h) radioactive tracer clearance rate was determined by measuring gamma counts per minute. The kidneys were then fixed and sectioned for electron microscopy. A point counting method was used to quantitate intracellular spaces of the kidney proximal tubules. RESULTS: 45HDT animals show a significantly (p=0.0001) increased area in the interstitial space of the proximal tubules. CONCLUSIONS: There are significant changes in the kidneys during a 1 h exposure to a simulated microgravity environment that consist primarily of anatomical alterations in the kidney proximal tubules. The kidneys also appear to respond differently to the initial periods of head-down tilt.

Adaptation, Physiological↗