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Aerosol penetration and mucociliary transport in the healthy human lung. Effect of low serum theophylline levels.

The effect of theophylline on the penetration of an inhaled radioaerosol in the lung, bronchial clearance, and tracheal mucociliary transport rate (TMTR) was investigated in 13 healthy volunteers. Following a randomized, double-blind, crossover protocol, subjects ingested 4 mg/kg twice daily of theophylline or placebo for three days which resulted in stable, low therapeutic serum levels. Aerosol penetration, assessed by the skew of the initial distribution of lung radioactivity, was more peripheral (p less than 0.025) with theophylline, indicating bronchodilation that was not detectable by standard pulmonary function tests. The TMTR increased in ten of 13 subjects after theophylline, but not to a significant level. Bronchial clearance was not significantly different with theophylline despite the longer clearance pathway created by the increased peripheral aerosol deposition. This finding suggests that mucus transport rates in the intrapulmonary airways were increased by theophylline.

Adult↗

Synthesis and Crystal Structure of a New Type of Ionic Technetium(V) Dioxo Phosphine Complexes, [Tc(O)(2)(PR(3))(3)](+). Reactions with Pyridine and Crystal Structures of trans,cis,cis-[Tc(O)(2)(PR(3))(2)(py)(2)](+) Compounds.

New ionic technetium complexes of the type [TcO(2)(PR(3))(3)](+) have been synthesized from the reaction of [TcO(4)](-) with the phosphine in methanol. The crystal structures of two crystallographic forms of [TcO(2)(PEt(3))(3)](BPh(4)) were determined. The first form is monoclinic, space group P2(1)/n with a = 14.353(3) Å, b = 11.731(2) Å, c = 26.478(6) Å, beta = 101.22(1) degrees, and Z = 4. The second form is also monoclinic, space group P2(1)/c with a = 10.043(3) Å, b = 21.122(4), c = 20.994(5) Å, beta = 97.43(2) degrees, and Z = 4. [TcO(2)(PPr(3))(3)](BPh(4)) belongs to the monoclinic C2/c space group with a = 34.097(7) Å, b = 16.944(4) Å, c = 19.033(4) Å, beta = 102.99(1) degrees, and Z = 8. The geometry around the Tc atom is a trigonal bipyramid with the two oxo ligands in the trigonal plane. The Tc-O bond distances are between 1.707(4) and 1.726(3) Å, while the Tc-P bonds vary from 2.507(2) to 2.528(2) Å for the axial ligands and between 2.395(1) and 2.403(1) Å for the equatorial bond. The O-Tc-O angles are in the range 141.5(2)-143.4(2) degrees. The reaction of these complexes with pyridine produced trans,cis, cis-[Tc(O)(2)(PR(3))(2)(py)(2)](+) (py = pyridine). [Tc(O)(2)(PMe(3))(2)(py)(2)](BPh(4)) is monoclinic, space group P2(1)/c with a = 30.346(8) Å, b = 12.865(4) Å, c = 21.464(9) Å, beta = 110.35(2) degrees, and Z = 8, while [Tc(O)(2)(PEt(3))(2)(py)(2)](BPh(4)) is monoclinic, space group P2(1)/c with a = 10.594(6) Å, b = 19.921(7) Å, c = 21.306(10) Å, beta = 95.31(5) degrees, and Z = 4. The geometry around the Tc atom is a distorted octahedron with the oxo ligands located in trans positions to each other, while the phosphine and the pyridine ligands are cis to each other.

Journal Article↗

Technetium complexes with triazacyclononane.

[NBu4][TcOCl4] reacts with ethylene glycol and 1,4,7-triazacyclononane (tacn) in MeOH under the formation of the deep-blue oxotechnetium(V) cation [TcO(OC2H4O)(tacn)]+, which can readily be oxidized by air to give the stable technetium(VII) compound [TcO3(tacn)]+. The reaction with aqueous HCl results in reduction and the formation of the cationic technetium(III) complex [TcCl2(OH2)(tacn)]Cl. The products were isolated in crystalline form and studied spectroscopically and by X-ray diffraction.

Journal Article↗

Chronic post-traumatic osteomyelitis of the lower extremity: comparison of magnetic resonance imaging and combined bone scintigraphy/immunoscintigraphy with radiolabelled monoclonal antigranulocyte antibodies.

OBJECTIVE: A retrospective study of the validity of combined bone scintigraphy (BS) and immunoscintigraphy (IS) using (99m)Tc-labelled murine antigranulocyte antibodies (MAB) and magnetic resonance imaging (MRI) in chronic posttraumatic osteomyelitis. DESIGN AND PATIENTS: The results of MRI and combined BS/IS of 19 lesions in 18 patients (13 men, 5 women; mean age 45 years, range 27-65 years) were independently evaluated by two radiologists and one nuclear medicine physician with regard to bone infection activity and extent. The patient group was a highly selective collection of clinical cases: the average number of operations conducted because of relapsing infection was eight (range 2-27), the average time interval between the last surgical intervention and the present study was 6.5 years (range 3 months to 39 years), and from the first operation was 14 years (range 1.5-42 years). Interobserver agreement on MRI was measured by kappa statistics. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for MRI and the nuclear medicine studies. RESULTS: For MRI/nuclear medicine, a sensitivity of 100%/77%, a specificity of 60%/50%, an accuracy of 79%/61%, a PPV of 69%/58% and a NPV of 100%/71% were calculated. Four MR examinations were false positives because of postsurgical granulation tissue. A high degree of interobserver agreement was found on MRI (kappa=0.88). A low-grade infection was missed on two scintigrams, while four were false positive because of ectopic haematopoietic bone marrow, and in one examination the anatomical distortion resulted in an inaccurate assignment of the uptake leading to false positive findings. Image analysis was frequently hindered by susceptibility artefacts due to residual abrasions of metallic implants after removal of orthopaedic devices (15/18 patients); this led to limited assessment in 17% (3/18 patients). CONCLUSION: Acute activity in a chronic osteomyelitis can be excluded with high probability if the MRI findings are negative. In the first postoperative year fibrovascular scar cannot be distinguished accurately from reactivated infection on MRI and scintigraphy may improve the accuracy of diagnosis. MRI is more sensitive in low-grade infection during the later course than combined BS/IS. Scintigraphic errors due to ectopic, peripheral, haematopoietic bone marrow can be corrected by MRI.

Adult↗

Effects of vinyl chloride on liver function of exposed workers, evaluated by measurements of plasma clearance of the 99mTc-N-2,4-dimethylacetanilido-iminodiacetate complex.

In 77 males exposed occupationally to vinyl chloride (VC), the plasma clearance (Cl) of 99mTc-N(2,4-dimethylacetanilido)iminodiacetate ('HEPIDA' complex) was determined. The results were juxtaposed with a scaled assessment of liver parenchyma performance based upon clinical examination and a series of biochemical tests. Detection of the diagnosable damage of liver parenchyma by means of the reduced clearance was sensitive (90%) at the reasonable specificity of 74%. Probability of exclusion of liver damage in patients with the clearance above 240 ml min-1 1.73 m-2 amounted to 92%. There was a significant correlation between degree of exposure to VC and the frequency of low clearance values. It appears that the periodic determination of the 99mTc-HEPIDA clearance in workers exposed to VC allows the assessment of incipient liver damage and signals the need for prophylactic measures.

Adult↗

Regional deposition and retention of particles in shallow, inhaled boluses: effect of lung volume.

The regional deposition of particles in boluses delivered to shallow lung depths and their subsequent retention in the airways may depend on the lung volume at which the boluses are delivered. To evaluate the effect of end-inspiratory lung volume on aerosol bolus delivery, we had healthy subjects inhale radiolabeled, monodisperse aerosol (99mTc-iron oxide, 3.5-microm mass median aerodynamic diameter) boluses (40 ml) to a volumetric front depth of 70 ml into the lung at lung volumes of 50, 70, and 85% of total lung capacity (TLC) end inhalation. By gamma camera analysis, we found significantly greater deposition in the left (L) vs. right (R) lungs at the 70 and 85% TLC end inhalation; ratio of deposition in L to R lung, normalized to L-to-R ratio of lung volume (mean L/R), was 1.60 +/- 0.45 (SD) and 1. 96 +/- 0.72, respectively (P < 0.001 for comparison to 1.0) for posterior images. However, at 50% TLC, L/R was 1.23 +/- 0.37, not significantly different from 1.0. These data suggest that the L and R lungs may be expanding nonuniformly at higher lung volumes. On the other hand, subsequent retention of deposited particles at 2 and 24 h postdeposition was independent of L/R at the various lung volumes. Thus asymmetric bolus ventilation for these very shallow boluses does not lead to significant increases in peripheral alveolar deposition. These data may prove useful for 1) designing aerosol delivery techniques to target bronchial airways and 2) understanding airway retention of inhaled particles.

Adult↗

Extravascular lung water to blood volume ratios as measures of permeability in sepsis-induced ALI/ARDS.

OBJECTIVE: We studied the relationship, and the effect of fluid loading on this, between the ratio of extravascular lung water (EVLW) to intrathoracic/pulmonary blood volumes (ITBV, PBV) and the radionuclide pulmonary leak index (PLI) to protein during sepsis-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). DESIGN AND SETTING: A prospective observational study, in the intensive care unit of a university hospital. PATIENTS: Twenty-two consecutive mechanically ventilated patients with sepsis-related ALI/ARDS from pneumonia (n = 12) or extrapulmonary sources (n = 10), without elevated cardiac filling pressures. INTERVENTION: Crystalloid (1700-1800 ml) or colloid (1000-1800 ml) fluid loading until target filling pressures. MEASUREMENTS AND RESULTS: Protein permeability was assessed noninvasively over the lungs with help of 67Ga-labeled transferrin and 99mTc-labeled red blood cells (Pulmonary leak index, upper limit normal 14.1 x 10(-3)/min) and EVLW and blood volumes by the thermal-dye transpulmonary dilution technique before and after fluid loading. Prior to fluids the pulmonary leak index related to the ratio of EVLW/ITBV and EVLW/PBV (r(s) = 0.46) particularly when the pulmonary leak index was below 100 x 10(-3)/min and in extrapulmonary sepsis (PLI vs. EVLW/PBV r(s) = 0.71). Fluid loading did not alter EVLW, EVLW/ITBV, or EVLW/PBV or the relationship to PLI. CONCLUSION: The data demonstrate that EVLW/ITBV or EVLW/PBV are imperfect measures of increased protein permeability in mechanically ventilated patients with sepsis-induced ALI/ARDS particularly when the PLI is severely increased and during pneumonia, independent of fluid status.

Aged↗

Radioactivity thresholds for sentinel node biopsy in breast cancer.

AIMS: The aim of the present study is to clarify the level of radioactive lymph node should be biopsied after the most radioactive SN is removed. METHODS: SNB using radionuclide was performed in our hospital for 1179 primary breast cancers between April 2000 and October 2005; most (1177/1179) were performed successfully. Our criterion for harvesting SNs is to remove tissue until no radioactive site is present. The level of radioactivity and the order of removal of each lymph node were compared with pathologic results. RESULTS: More than 2 (overall average 1.9) radioactive SNs were biopsied in 686 of 1177 breasts. Cancer positive results were recorded for 142 breasts with multiple SNs. In 142 breasts, 64 showed metastasis to the most radioactive node only, 39 showed metastasis other than the most radioactive node only, and 39 showed the most radioactive node and other radioactive nodes. Moreover, if several other criteria were applied, false-positive cases were increased significantly. CONCLUSIONS: It is necessary to harvest radioactive lymph nodes other than the most radioactive. Moreover, efforts to remove every radioactive lymph node will minimize false-negative results.

Axilla↗

Comparison of labeled MIBG and somatostatin analogs in imaging neuroendocrine tumors.

In 10 patients with histologically proven neuroendocrine tumors (4 carcinoids, 4 pheochromocytomas, 1 medullary thyroid cancer and 1 Merkel tumor) the results of radiolabeled metaiodobenzylguanidine (MIBG) and somatostatin analogs were compared. A total of 24 tumor lesions was detected on standard imaging studies. MIBG scintigraphy correctly localized 12 (50%) of these lesions which were observed in 5 patients (4 with pheochromocytoma and 1 with carcinoid tumor). Scintigraphy using labeled somatostatin analogs correctly localized 21 (87%) lesions which occurred in 8 patients (4 with carcinoid, 2 with pheochromocytoma, 1 with medullary thyroid cancer and 1 with Merkel tumor). Concordant scintigraphic results were obtained in 1 patient with carcinoid and 2 with pheochromocytoma. In conclusion, although this series was limited, our results suggest that MIBG is more accurate than somatostatin analogs in imaging pheochromocytoma. Conversely, somatostatin analogs are more accurate than MIBG in detecting other neuroendocrine tumors such as carcinoids.

3-Iodobenzylguanidine↗

Tc-99m-labeled tropanes as dopamine transporter imaging agents.

The development of novel Tc-9m-labeled tropane derivatives as dopamine transporter imaging agents is reported. A series of neutral and lipophilic conjugated complexes, containing N-(alkylthiolato)-tropane, aminobis(ethylthiolato), and a [99mTc]TcO3+ center core, were prepared and evaluated as central nervous system (CNS) dopamine transporter imaging agents in rats. One of the compounds, [99mTC]technetium, [methyl 3-(4-chlorophenyl)-8-(2-mercaptoethyl-8-azabicyclo [3.2.1]octane-2-carboxylato-S][[2,2'-(methylimino)bis[eth anethiolato]] (2-)-N,S,S']oxo (25), displayed low initial uptake in rat brain (0.1% at 2 min post i.v. injection); the striatal/cerebellar (ST/CB) ratio reached 3.50 at 60 min after an i.v. injection. The specific uptake can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, N-methyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; i.v. 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.0. In contrast, the specific uptake in striatum was not affected by pretreating rats with a noncompeting ligand, haldol (i.v., 1 mg/kg). In vitro autoradiography of rat brain sections exhibited elevated labeling in striatum, major islands of Calleja, and olfactory tubercle regions, where dopamine neurons are known to be concentrated. This series of compounds is the first example of technetium-99m labeled CNS receptor-specific imaging agents and may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS abnormality in conjunction with single photon emission computed tomography.

Animals↗

Modifications of lung clearance mechanisms by acute influenza A infection.

Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity (4.9 +/- 1.9 mm/min) by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

Adult↗