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PubMed2003

Anatomy of ilioinguinal and iliohypogastric nerves in relation to trocar placement and low transverse incisions.

OBJECTIVE: The purpose of this study was to map the course of the ilioinguinal and iliohypogastric nerves. STUDY DESIGN: The courses of iliohypogastric and ilioinguinal nerves from 11 fresh frozen cadavers were mapped from their lateral emergence on the anterior abdominal wall to their midline termination in reference to fixed bony landmarks. Bivariate fit ellipses were generated for each nerve and compared with sites of standard abdominal surgical incisions. RESULTS: Thirteen iliohypogastric and 16 ilioinguinal nerves were identified and mapped. On average, the proximal end of the ilioinguinal nerve entered the abdominal wall 3.1 cm medial and 3.7 cm inferior to the anterior superior iliac spine, then followed a linear course to terminate 2.7 cm lateral to the midline and 1.7 cm superior to pubic symphysis. The iliohypogastric nerve entered the abdominal wall on average 2.1 cm medial and 0.9 cm inferior to the anterior superior iliac spine, which followed a linear course to terminate 3.7 cm lateral to the midline and 5.2 cm superior to pubic symphysis. CONCLUSION: Abdominal wall surgical sites below the level of the anterior superior iliac spine have the potential for ilioinguinal or iliohypogastric injury.

Abdominal Wall↗

PubMed1999

Segmental colonic transit after oral 67Ga-citrate in healthy subjects and those with chronic idiopathic constipation.

UNLABELLED: Measurement of segmental colonic transit is important in the assessment of patients with severe constipation. 111In-diethylenetriamine pentaacetic acid (DTPA) has been established as the tracer of choice for these studies, but it is expensive and not readily available. 67Ga-citrate is an inexpensive tracer and when given orally is not absorbed from the bowel. It was compared with 111In-DTPA in colonic transit studies in nonconstipated control subjects and then in patients with idiopathic constipation. METHODS: Studies were performed after oral administration of 3 MBq (81 microCi) 67Ga-citrate or 4 MBq (108 microCi) 111In-DTPA in solution. Serial abdominal images were performed up to 96 h postinjection, and computer data were generated from geometric mean images of segmental retention of tracer, mean activity profiles and a colonic tracer half-clearance time. RESULTS: There were no differences in segmental retention of either tracer or in mean activity profiles between control subjects and constipated patients. Results in constipated subjects were significantly different from those in controls. The mean half-clearance times of tracer for control subjects were 28.8 h for 67Ga-citrate and 29.9 h for 111In-DTPA in control subjects and 75.0 h for 67Ga-citrate and 70.8 h for 111In-DTPA in constipated patients. CONCLUSION: Oral 67Ga-citrate can be used as a safe alternative to 111In-DTPA for accurate measurement of segmental colonic transit.

Administration, Oral↗

PubMed2004

Registration of biplane angiography and intravascular ultrasound for 3D vessel reconstruction.

UNLABELLED: If planned and applied correctly, intra-vascular brachytherapy (IVB) can significantly reduce the risk of restenosis after interventional treatment of stenotic arteries. OBJECTIVES: In order to facilitate computer-based IVB planning, a three-dimensional reconstruction of the stenotic artery based on intravascular ultrasound (IVUS) sequences is desirable. METHODS: To attain a 3D reconstruction, the frames of the IVUS sequence are properly aligned in space and completed with additional intermediate frames generated by interpolation. The alignment procedure uses additional information that is obtained from biplane X-ray angiography performed simultaneously during the capturing of the IVUS sequence. After IVUS images and biplane angiography data are acquired from the patient, the vessel-wall borders and the IVUS catheter are detected by an active contour algorithm. Next, the twist between adjacent IVUS frames is determined by a sequential triangulation method combined with stochastic analysis. RESULTS: The above procedure results in a 3D volume-model of the vessel, which also contains information from the IVUS modality. This data is sufficient for computer-based intravascular brachytherapy planning. CONCLUSION: The proposed methodology can be used to improve the current state-of-the-art IVB treatment planning by enabling computerized dosage computations on a highly accurate 3D model.

Algorithms↗

PubMed1995

The estimation of administered activity of krypton-81m for lung ventilation studies.

Measurement or estimation of the activity of krypton-81m administered to a patient during lung ventilation imaging is difficult, due to the short half-life and continuous delivery via pipework, and no satisfactory method exists. Calculations based on generator activity have the disadvantages that this activity may not be accurately known and that not all activity eluted is inhaled by the patient. The aim of this study was to develop a simple method for estimating the administered activity from the number of counts in each patient image. A formula based on the ratio of counts in 81mKr and technetium-99m lung ventilation and perfusion images was developed and reduced so that administered activity could be directly calculated from the total 81mKr counts, the 99mTc count rate, the administered activity of 99mTc and a constant representing the ratio of counts expected from equal activities of each radioisotope. The formula allows a direct calculation from the image acquisition data following an initial set of experimental work to establish the constant for a particular gamma camera and collimator system.

Administration, Inhalation↗

PubMed1986

Thallium myocardial perfusion scintigraphy: influence of perfusion, scatter, and photon energy on the detection of lesions.

Experimental studies have been made of lesion detectability in myocardial perfusion studies using thallium-201. A series of images (AP view) was generated mathematically. Images were simulated with 100k, 200k, and 300k counts for the complete image and either non- or half-perfused lesions (lesion volume 1-6 1/2% of total myocardial volume). In addition thallium images were generated excluding scatter; images were also generated with a radiopharmaceutical using 140, 184 and 296 keV, assuming the biological distribution of thallium. All images were interpreted by seven observers. Count density did not affect the true-positive fraction of the interpretations. However, the false-positive fraction decreased significantly when count density increased. Lesions located far from the camera were detected worst. The intraobserved variability was largest for interpretation of these regions. Small lesions were poorly detected. Perfusion of lesions significantly affected their detection, independent of the count density, lesion volume, and lesion location. Scatter did not affect the detection of lesions. No significant difference was found when the performance of the observers was compared for 80 keV and 140 keV. The use of 184-keV and 296-keV photons resulted in a lower detection rate probably because of the use of a high energy collimator.

Coronary Circulation↗

PubMed1997

Adenosine thallium-201 tomography in evaluation of graft patency late after coronary artery bypass graft surgery.

OBJECTIVES: We sought to ascertain the utility of adenosine thallium-201 tomography for assessing graft stenoses late after coronary artery bypass graft surgery. BACKGROUND: Although pharmacologic perfusion imaging has been increasingly used in the assessment of patients with coronary artery disease, the value of this stress modality for detecting coronary artery bypass graft stenosis late after surgery is unknown. METHODS: We studied 109 patients who underwent both adenosine thallium-201 tomography and coronary angiography at 6.7 +/- 4.8 (mean +/- SD) years after coronary artery bypass graft surgery. Adenosine thallium-201 tomography was assessed quantitatively by computer-generated polar maps of the myocardial thallium-201 activity. RESULTS: On coronary angiography, significant graft stenoses were present in 68 patients, 65 of whom had a corresponding perfusion defect as shown by thallium-201 tomography (sensitivity 96%). Significant stenoses were present in 107 (37.8%) of 283 grafts. The overall specificity by quantitative tomography was 61%. Seventy percent of the apparently false positive perfusion defects could be explained on the basis of unbypassed native disease or by the presence of fixed defects in patients with previous myocardial infarction. CONCLUSIONS: Thus, results of adenosine thallium-201 tomography are nearly always abnormal in patients with late coronary graft stenosis. Most of the false positive defects appear to be due to either unbypassed native disease or a previous myocardial infarction.

Adenosine↗

PubMedDate not supplied

From conventional to stealth liposomes: a new frontier in cancer chemotherapy.

Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes ("pure lipid approach") were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called "stealth liposomes" because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less myelotoxic than doxorubicin. Typical forms of toxicity associated to it are acute infusion reaction, mucositis and palmar plantar erythrodysesthesia, which occur especially at high doses or short dosing intervals. Active and cell targeted liposomes can be obtained by attaching some antigen-directed monoclonal antibodies (Moab or Moab fragments) or small proteins and molecules (folate, epidermal growth factor, transferrin) to the distal end of polyethylene glycol in pegylated liposomal doxorubicin. The most promising therapeutic application of liposomes is as non-viral vector agents in gene therapy, characterized by the use of cationic phospholipids complexed with the negatively charged DNA plasmid. The use of liposome formulations in local-regional anticancer therapy is also discussed. Finally, pegylated liposomal doxorubicin containing radionuclides are used in clinical trials as tumor-imaging agents or in positron emission tomography.

Animals↗

PubMed2005

Familial biventricular myocardial noncompaction associated with Ebstein's malformation.

BACKGROUND: Noncompaction of the ventricular myocardium is a rare congenital cardiomyopathy characterized by numerous excessively prominent trabeculations and deep intertrabecular recesses. Noncompaction of the ventricular myocardium is most often an isolated cardiac malformation presenting as a sporadic disease. Associated cardiac anomalies are present in some patients. We report a family with three adult males from consecutive generations having a biventricular form of noncompaction of the myocardium. Two of the patients have an associated Ebstein's malformation of the tricuspid valve. METHODS: Clinical evaluation and follow-up, electrocardiography, echocardiography, heart catheterization, coronary angiography, contrast cineventriculography, and magnetic resonance imaging. RESULTS AND CONCLUSIONS: The association of noncompaction of the ventricular myocardium and Ebstein's malformation has not been reported so far. We believe that both defects were caused by a developmental arrest of the right ventricular myocardium. Echocardiography is the diagnostic modality of choice in patients and in the male relatives, irrespective of their clinical status. Thromboembolic events, cardiac rhythm disorders and heart failure mandate treatment. Anticoagulation treatment and implantation of cardioverter-defibrillator pacemaker have to be strongly considered in these patients.

Abnormalities, Multiple↗

PubMedDate not supplied

In vitro system to estimate renal brush border enzyme-mediated cleavage of Peptide linkages for designing radiolabeled antibody fragments of low renal radioactivity levels.

Renal localization of radiolabeled antibody fragments presents a problem in targeted imaging and radiotherapy. We recently reported that Fab fragments labeled with 3'-[(131)I]iodohippuryl N(epsilon)-maleoyl-l-lysine (HML) demonstrated markedly low renal radioactivity levels from early postinjection in mice. Previous studies suggested that low renal radioactivity levels were attributable to cleavage of the glycyl-lysine sequence in HML by the action of renal brush border enzymes, followed by urinary excretion of the resulting m-iodohippuric acid. In this study, an in vitro system using brush border membrane vesicles (BBMVs) isolated from the rat kidney cortex was developed to estimate renal brush border enzyme(s)-mediated cleavage of the peptide linkage. Low molecular weight HML derivatives, 3'-[(125)I]iodohippuryl l-lysine (HL), 3'-[(125)I]iodohippuryl N(epsilon)-tert-butoxycarbonyl-l-lysine (HBL), and their d-amino acid counterparts, were synthesized and incubated in BBMVs. Both [(125)I]HL and [(125)I]HBL generated m-[(125)I]iodohippuric acid after incubation in BBMVs at 37 degrees C while the latter liberated significantly higher amounts of the metabolite. [(125)I]d-HL and [(125)I]d-HBL failed to release the metabolite under similar conditions. The liberation of m-[(125)I]iodohippric acid from [(125)I]HL was significantly facilitated or completely inhibited by the addition of an activator or an inhibitor for carboxypeptidase M. The release of m-[(125)I]iodohippuric acid from [(125)I]HBL increased by the addition of the activator, whereas the inhibitor partially inhibited the release of the metabolite from [(125)I]HBL. The BBMV-mediated release of m-[(125)I]iodohippuric acid from [(125)I]HBL was not impaired by the addition of inhibitors for neutral endopeptidase or renal dipeptidase. These findings showed that the glycyl-l-lysine sequence in HML would be recognized and cleaved by metalloenzymes and nonmetalloenzymes on the renal brush border even when iodine was incorporated into a benzene ring and the N(epsilon)-amine residue of lysine was chemically modified, which supported the hypothesis that low renal radioactivity levels of HML-conjugated Fab fragments would be attributed to the release of m-iodohippuric acid by renal brush border enzymes. This study suggested that this in vitro system using BBMVs would be useful to estimate radiolabeling reagents of antibody fragments or peptides designed to reduce renal radioactivity with a variety of radionuclides.

Amino Acid Sequence↗

PubMed2006

Transgenerational effects of radiation and chemicals in mice and humans.

Parental exposure of mice to radiation and chemicals causes a variety of adverse effects (e.g., tumors, congenital malformations and embryonic deaths) in the progeny and the tumor-susceptibility phenotype is transmissible beyond the first post-radiation generation. The induced rates of tumors were 100-fold higher than those known for mouse specific locus mutations. There were clear strain differences in the types of naturally-occurring and induced tumors and most of the latter were malignant. Another important finding was that germ-line exposure elicited very weak tumorigenic responses, but caused persistent hypersensitivity in the offspring for the subsequent development of cancer by the postnatal environment. Activations of oncogenes, ras, mos, abl, etc. and mutations in tumor suppressor genes such as p53 were also detected in specific tumors in cancer-prone descendants. However, the majority of tumors observed in the progeny were those commonly observed in the strains that were used and oncogene activations were rarely observed in these tumors. It can be hypothesized that genetic instability modifies tumor occurrence in a transgenerational manner, but so far no links could be established between chromosomal and molecular changes and transmissible tumor risks. Our data are consistent with the hypothesis that cumulative changes in many normal but cancer-related genes affecting immunological, biochemical and physiological functions may slightly elevate the incidence of tumors or fasten the tumor development. This hypothesis is supported by our GeneChip analyses which showed suppression and/or over-expression of many such genes in the offspring of mice exposed to radiation. In humans, a higher risk of leukemia and birth defects has been reported in the children of fathers who had been exposed to radionuclides in the nuclear reprocessing plants and to diagnostic radiation. These findings have not been supported in the children of atomic bomb survivors in Hiroshima and Nagasaki, who were exposed to higher doses of atomic radiation. However, it will be important to follow the human subjects, especially for adult type cancers and chronic diseases throughout their lives to determine whether the mouse studies can predict human responses.

Abnormalities, Drug-Induced↗

PubMed2001

Insulin receptor antibodies inhibit insulin uptake by the liver: in vivo 123I-insulin scintigraphic scanning and in vitro characterization in autoimmune hypoglycemia.

BACKGROUND: Insulin receptor antibodies can induce severe hypoglycemia or insulin resistance in rare autoimmune syndromes. In vitro properties of these antibodies occasionally explain the clinical features of the syndrome, but direct evidence of their in vivo activity is poor. We studied a 58-year-old male with rheumatoid arthritis who presented with hypoglycemic coma. METHODS AND RESULTS: Antibodies were detected by inhibition of 125I-insulin binding to human insulin receptor-3T3 cells by the patient's serum. By immunofluorescence, they were immunoglobulin G of all four subclasses, immunoprecipitated insulin receptors from biotin-labeled cells, and triggered phosphorylation of the beta subunit of the insulin receptor. Insulin binding on the patient's red blood cells was markedly reduced. A biodistribution study after intravenous 123I-Tyr A14 insulin showed a marked inhibition of tracer uptake by the liver, reaching 10% of the injected dose (controls, mean +/- SD, 21.1 +/- 1.7%; n = 10). Time activity curves generated on the liver and on the heart were parallel, with a T1/2 of 11.5 minutes for both, suggesting that no specific uptake occurred in the liver, where tracer activity represented only the blood pool. Clearance of insulin from the blood was indeed slower than in controls and mainly occurred through the kidneys. Analysis of plasma 123I-insulin immunoreactivity and trichloroacetic acid precipitate showed that insulin degradation did not occur as in normal controls. CONCLUSIONS: In this patient with hypoglycemic syndrome, insulin receptor antibodies with in vitro insulin-like activity are capable of blocking in vivo the access of insulin to the liver receptor compartment, as directly demonstrated by the markedly altered biodistribution of intravenously injected 123I-insulin.

3T3 Cells↗

PubMedDate not supplied

Synthesis and characterization of a novel chitosan-gelatin bioconjugate with fluorescence emission.

Polysaccharide-protein conjugations have generated increasing interests for biomedical applications in recent years. A naturally occurring cross-linking reagent, genipin, which has been used in herbal medicine, was employed to cross-link chitosan and gelatin for the preparation of a novel chitosan-gelatin conjugate. The primary amine groups on chitosan and gelatin were covalently linked with genipin, leading to the formation of a chitosan-gelatin conjugate with nitrogen-containing heterocycle units, the pyrindine-like derivatives. The FT-IR and UV-vis studies revealed that chitosan could react with genipin via a nucleophilic ring-opening reaction to construct more sufficient and extensive cross-link networks, as compared with its gelatin counterpart. The UV-vis absorption properties of the chitosan-gelatin conjugates were strongly related to the chitosan-to-gelatin weight ratio in the compositions. It is worth noting that the conjugation process endows the special emission properties of the chitosan-gelatin conjugates, which depends on the cross-linking reaction and the formation of hydrogen bonding involved chitosan-gelatin complex. Fluorescence quenching or enhancement was observed from the chitosan-gelatin conjugates upon coordinated with a wide variety of heavy metal ions (Ag+, Cu2+, Fe2+, and Co2+). This study also examined the possibility of covalent coupling the capture chelator (chitosan) with bioactive protein (e.g., albumin, alpha-globulin, and fibrinogen) to create fluorescence emission. These findings may provide a novel way to deliver therapeutic radionuclides for immuno-targeting purposes in the future.

Adjuvants, Immunologic↗

PubMedDate not supplied

Evaluation of basis function and linear least squares methods for generating parametric blood flow images using 15O-water and Positron Emission Tomography.

PURPOSE: Parametric analysis of (15)O-water positron emission tomography (PET) studies allows determination of blood flow (BF), perfusable tissue fraction (PTF), and volume of distribution (V (d)) with high spatial resolution. In this paper the performance of basis function and linear least squares methods for generating parametric flow data were evaluated. PROCEDURES: Monte Carlo simulations were performed using typical perfusion values for brain, tumor, and heart. Clinical evaluation was performed using seven cerebral and 10 myocardial (15)O-water PET studies. Basis function (BFM), linear least squares (LLS), and generalized linear least squares (GLLS) methods were used to calculate BF, PTF, or V(d). RESULTS: Monte Carlo simulations and human studies showed that, for low BF values (<1 ml/min(-1)ml(-1), BF, PTF, and V(d) were calculated with accuracies better than 5% for all methods tested. For high BF (>2 ml/min(-1)ml(-1)), use of BFM provided more accurate V(d) compared with (G)LLS. CONCLUSIONS: In general, BFM provided the most accurate estimates of BF, PTF, and V(d).

Brain↗

PubMed1999

Hereditary renal amyloidosis associated with variant lysozyme in a large English family.

BACKGROUND: Two kindreds with hereditary systemic amyloidosis caused by the first two mutations to be described in the human lysozyme gene were discovered recently and study of the variant lysozyme has been powerfully informative about mechanisms of amyloid fibrillogenesis. However, the clinical manifestations in these families, additional members of which have lately been identified, have not previously been reported in detail. METHODS: The proband presented with proteinuria aged 50 and a family history of amyloidosis, and underwent renal biopsy, whole-body serum amyloid P component (SAP) scintigraphy, and sequencing of the lysozyme gene. Her family history and the phenotype of hereditary lysozyme amyloidosis were thoroughly documented and compared with the presentation and natural history of all other known patients with this condition. RESULTS: The proband belonged to an extended English family other members of which were known to have hereditary lysozyme amyloidosis. Those with amyloid in previous generations presented with renal involvement, frequently developed complications due to gastrointestinal amyloid, and died before age 60. All amyloid deposits were composed of lysozyme and complete concordance was established between amyloid and heterozygosity for a point mutation in the lysozyme gene, encoding the previously reported Asp67His substitution in the mature protein. CONCLUSION: The phenotype, reported for the first time in this extended kindred, contrasts with that of an apparently unrelated family carrying the same mutation who presented with spontaneous hepatic haemorrhage and rupture, and with the manifestations in a family with the lysozyme Ile56Thr variant who presented with dermal petechiae before proceeding to fatal visceral amyloidosis. A remarkably wide spectrum of disease can be caused by the same amyloid fibril protein, although renal involvement predominates in all cases except those dying of hepatic rupture.

Amyloidosis↗

PubMed1998

The use of radiopharmaceuticals as an effective toxicologic technique for studying nephrotoxicity of drugs: cyclosporine-A.

The concept of altered biologic behavior of administered radiopharmaceuticals is used routinely in clinical nuclear medicine to increase the sensitivity of diagnosis, monitor the efficacy of chemotherapeutic drugs and radiation treatment, and determine injury caused by a drug whose effect has exceeded its therapeutic value. In this study, cyclosporine-A (CsA) an immunosuppressant drug known to cause nephrotoxicity due to tubular impairment and Tc-99m MAG-3, a renal imaging radiopharmaceutical secreted by the tubules have been used in animal models to establish a method for investigating the nephrotoxicity of drugs. New Zealand rabbits and Wistar rats were used. The rabbits and rats were treated with 30 mg/kg of CsA for 4 and 28 consecutive days respectively. Plasma creatinine and urea were measured and renogram studies were performed in the rabbits prior to and on 1, 4, 8, 11 and 15 days after treatment with CsA. For the renogram, the rabbits were given an intravenous bolus injection of 44.4 MBq (1.5 mCi) of Tc-99m MAG-3. The Tmax, T1/2, TTHM and uptake slope of the Tc-99m MAG-3 were calculated. Each rat was injected intravenously with 185 MBq (5 mCi) of Tc-99m MAG-3, killed 3 min later, the kidneys removed and 20 mm frozen sections made. Autoradiograms were generated from the frozen sections. Creatinine and urea levels were also measured in the rats. There was no consistent difference in creatinine and urea levels between control and CsA treated rabbits and rats. However, for the rabbit, on day 1 or 4 after treatment, there was significant increase in the values of Tmax, T1/2, TTHM and uptake slope between the control and CsA treated animals, indicating intrarenal vasoconstriction and delayed transit of Tc-99m MAG-3 from the parenchyma to the collecting system. This delay is dramatically shown in the tissue autoradiograms of the rats. The results are consistent with reported nephrotoxicity of CsA using other techniques. The results of this study, therefore, indicate that the concept of altered biologic behavior of Tc-99m MAG-3 can be used effectively as a toxicologic method for studying nephrotoxicity of drugs as exemplified by CsA.

Animals↗

PubMed1988

Simplified assessment of fine aerosol distribution in human airways.

We characterized homogeneity of bronchopulmonary distribution of a 0.9% saline aerosol with a mass median aerodynamic diameter (MMAD) of 1.12 micron (sigma g = 2.04) labeled with [99mTc]sulfur colloid in nine normal subjects and nine patients with asthma. Aerosol distribution was quantified from frequency distribution histograms generated from Anger camera scans. Skew (a measure of histogram asymmetry) and kurtosis (a measure of histogram range) were significantly elevated (p less than 0.05) in the asthma patients with 0.68 +/- 0.30 and 2.62 +/- 0.81, respectively, compared with 0.39 +/- 0.12 and 1.89 +/- 0.18, respectively, in the normal subjects. Skew and kurtosis were significantly correlated with baseline forced expiratory volume in 1 sec (FEV1, an index of airway obstruction) with rs = -0.4799 (p less than 0.05) and -0.5929 (p less than 0.01), respectively. Skew and kurtosis were also significantly correlated with mucociliary clearance after approximately 90 min (an index of large, central airway deposition) with rs = 0.6801 and 0.6373, respectively (p less than 0.01). This simplified method of analysis does not require additional study days or procedures and facilitates the detection of airflow obstruction in asthma.

Adult↗

PubMed1978

Dynamic renal transplant imaging with Tc-99m DTPA (Sn) supplemented by a transplant perfusion index in the management of renal transplants.

We have performed 955 studies on 152 patients with 167 renal transplants. Images were recorded following bolus injection of 12-15 mCi Tc-99m DTPA (Sn). The data were stored on a computer and analyzed by generation of region-of-interest curves from (a) the iliac artery distal to the transplant, (b) the kidney, and (c) a background area. A perfusion index was adopted: formula see text. In 276 studies the patient clearly had acute tubular necrosis (ATN), rejection, or a normal kidney on retrospective analysis. The normal perfusion index has a value below 150, and it increases with falling perfusion, such as is seen in rejection and in renal-artery stenosis. The use of this index in addition to sequential images and changes in the region-of-interest curves usually allows separation of rejection from ATN and, particularly, rejection from normals. When serial studies are performed, the separation of rejecting from nonrejecting transplants is excellent, although renal-artery stenosis may cause similar changes in perfusion.

Acute Kidney Injury↗

PubMed2003

Radiolabeling of avidin with very high specific activity for internal radiation therapy of intraperitoneally disseminated tumors.

PURPOSE: For the effective internal radiation therapy of i.p. disseminated tumors, we developed avidin (Av)-dendrimer-chelate complex, which can be labeled with indium-111, emitting Auger and conversion electrons, with very high specific activity, and we studied its internalization, biodistribution, and therapeutic effect in nude mice with i.p. tumors. EXPERIMENTAL DESIGN: Generation 4 dendrimer (G4) was biotinylated and conjugated with 52 1B4M chelates. (111)In-G4-bt was mixed with Av to form (111)In-G4-Av complex. (111)In-G4-Av was incubated with ovarian cancer cells (SHIN-3), and the rate of internalization of the radiolabel into SHIN-3 cells was followed. (111)In-G4-Av was i.p. injected into nude mice that had i.p. disseminated SHIN-3 tumors, and the biodistribution was determined. Nude mice bearing i.p. disseminated tumors received i.p. injection of (111)In-G4-Av (9.25 or 18.5 MBq x 2, with a 1-week interval) and were followed for the formation of malignant ascites. RESULTS: Av could be labeled with (111)In with specific activity as high as 37 GBq/mg. More than 75% of the radioactivity was internalized 24 h after binding to cancer cells. (111)In-G4-Av accumulated rapidly and highly in the i.p. tumors (128.20% injected dose/gram of tissue at 2 h, 114.91% injected dose/gram of tissue at 24 h for unsaturated compound) with high tumor:background ratios. Treatment with a high dose of (111)In-G4-bt-Av was tolerable and showed dose-dependent therapeutic effect. CONCLUSIONS: G4-Av complex, which could be labeled with (111)In with very high specific activity and showed efficient internalization into cancer cells and high accumulation to i.p. tumors, appears to be suitable for the internal radiation therapy of i.p. disseminated tumors using metallic radionuclides emitting Auger and conversion electrons.

Animals↗