Racing performance following the laryngeal tie-forward procedure: a case-controlled study.

REASONS FOR PERFORMING STUDY: The laryngeal tie-forward procedure (LTFP) is becoming widely used for correction of dorsal displacement of the soft palate (DDSP) despite the absence of an evidence-based assessment of its efficacy. HYPOTHESES: The LTFP returns racing performance to preoperative baseline levels and to that of matched controls; and post operative laryngohyoid position is associated with post operative performance. DESIGN AND POPULATION: Case-controlled study of racehorses undergoing a LTFP for dorsal displacement of the soft palate at Cornell University between October 2002 and June 2007. METHODS: The presence of at least one post operative start and race earnings ($) were used as outcome variables. Controls were matched by age, breed and sex from the third race prior to surgery. A novel radiographic reference system was used to determine laryngohyoid position pre- and post operatively. Data for definitively and presumptively diagnosed cases were analysed separately. RESULTS: During the study interval, 263 racehorses presented, of which 106 were included in the study; 36 had a definitive diagnosis of DDSP and 70 a presumptive diagnosis. Treated horses were equally likely to race post operatively as controls in the equivalent race. Treated horses had significantly lower earnings in the race before surgery than matched controls. The procedure moved the basihyoid bone dorsally and caudally and the larynx dorsally and rostrally. A more dorsal post operative basihyoid position and more dorsal and less rostral laryngeal position were associated with an increased probability of racing post operatively. CONCLUSIONS: Horses undergoing a LTFP are as likely to race post operatively as matched controls. The procedure restores race earnings to preoperative baseline levels and to those of matched controls. POTENTIAL RELEVANCE: This study provides strong evidence supporting the use of the LTFP in racehorses. Further work is needed to determine the relationship between laryngohyoid conformation and nasopharyngeal stability in horses.

Biodistribution and dosimetry of [(18)F]fluorodeoxyglucose labelled leukocytes in normal human subjects.

SUMMARY: This study was performed in order to assess [(18)F]fluorodeoxyglucose white blood cell ((18)F-FDG WBC) dosimetry in normal human subjects. Using previously reported methods, mixed cell suspensions of autologous leukocytes were prepared from four normal volunteers. Leukocytes were labelled in heparin-saline by incubation with (18)F-FDG at 37 degrees C for 20 min. After washing and resuspension, (18)F-FDG WBCs (225-315 MBq) were administered by intravenous injection. Whole-body imaging was performed at 0.5, 1, 2, 4 and 6 h using a GE Varicam with 511 keV collimation. Blood samples were obtained at corresponding times as well as fractionated urinary collection. Whole-body anterior and posterior images were used for calculation of organ dosimetry. Uptake of (18)F-FDG WBCs occurred predominantly within the reticulo-endothelial system. Plasma activity, urinary excretion (9.9+/-2.3% at 6 h), and brain uptake (1.7+/-0.4%) were consistent with partial elution of (18)F-FDG. Positron emission tomography imaging performed at 5-6 h after injection yielded good quality images of reticulo-endothelial uptake. Whole-body and organ dosimetry for (18)F-FDG WBCs in doses of 225-250 MBq are comparable with reported results for conventional doses of (111)In oxine labelled leukocytes. Further studies of (18)F-FDG WBC as an agent for positron emission tomography imaging of inflammatory disease appear warranted.

Effect of mycobacterial phospholipids on interaction of Mycobacterium tuberculosis with macrophages.

This study demonstrates that pretreatment of macrophages with phosphatidylinositol, of either soya bean or mycobacterial origin, results in a down-regulation of the binding and uptake of Mycobacterium tuberculosis by the phagocytes. We also describe the novel observation that cardiolipin induces an increase in the binding and uptake of M. tuberculosis by macrophages. Neither phospholipid interacts with macrophages via the 2F8 epitope of scavenger receptor A, and treatment of macrophages with either phospholipid results in a down-regulation of CR3 function and tumor necrosis factor alpha production by the phagocyte. We have also shown that the ability of macrophages to interact with mycobacteria is greatly affected by an as yet unidentified product from the interaction of chloroform and polypropylene tubes.

18F-FDG labelling of human leukocytes.

Radiolabelled leukocytes are useful for the imaging of inflammation and infection, and 18F-fluorodeoxyglucose (18F-FDG) is known to concentrate in metabolically active cells. We evaluated the feasibility of leukocyte labelling with 18F-FDG using ACD and heparin anticoagulants at 20 degrees C and 37 degrees C, with and without gentle mixing during incubation. With leukocytes (WBC) harvested from 20 ml blood, studies were performed using 18F-FDG in concentrations of 3.7-74 MBq (0.1-2.0 mCi). 18F-FDG WBC stability in platelet-poor plasma was assessed at 1-4 h. Satisfactory labelling efficiency was achieved with incubation in heparin-saline at 37 degrees C for 30 min (62.7+/-1.6%), and was further enhanced by mixing during incubation (78.1+/-3.9%). Cell labelling was predominantly of granulocytes (78.5+/-1.4%). 18F-FDG WBC was relatively stable in platelet-poor plasma for up to 4 h, and no cell staining was observed in viability studies using trypan blue. These results indicate the feasibility of leukocyte labelling with 18F-FDG, providing an approach that may be useful in PET imaging of inflammation and infection.

Are posttherapy radioiodine scans informative and do they influence subsequent therapy of patients with differentiated thyroid cancer?

UNLABELLED: Posttherapy scans (PTS) with a gamma camera are typically used after therapeutic doses of 131I to visualize metastases that may not be seen with lower dose diagnostic scans. During a 16-month period, we studied 81 patients (64 with papillary thyroid cancer and 17 with follicular thyroid cancer), who had both a diagnostic whole-body scan (131I dose 3 mCi) and a PTS. A total of 117 PTS were evaluated. At the time of PTS, clinical or radiologic evidence of metastatic or residual disease was present in 68 patients (84%). The anatomic sites of known disease included, neck (63), mediastinum (23), lung (35), bone (14), trachea (16), esophagus (5), and brain (2). PTS showed focal areas of abnormal uptake not seen in diagnostic scans in 15 scans (13%). Areas with abnormal new uptake included: neck (5), lung (5), mediastinum (4), bone (2), and adrenal (1). In 7 patients (9%) the PTS results impacted future decisions regarding plans for subsequent diagnostic scanning and 131I therapy or changed the patient's risk group category. IN CONCLUSION: (1) 13% of 117 PTS demonstrated abnormal foci of 131I uptake not seen on pretherapy scans and (2) PTS changed management strategy in 9% of the studied patients.

Biodistribution of radiolabeled adenosylcobalamin in patients diagnosed with various malignancies.

OBJECTIVE: To study the biodistribution of a vitamin B12 analog, indium In 111-labeled diethylenetriaminepentaacetate adenosylcobalamin (In 111 DAC), in patients recently diagnosed as having primary or recurrent malignancy. PATIENTS AND METHODS: Thirty patients (14 women and 16 men) with radiographically or clinically diagnosed breast, lung, colon, sarcomatous, thyroid, or central nervous system malignancies were studied prior to definitive surgery or biopsy. A maximum of 650 microCi (2.2 microg) of In 111 DAC was administered intravenously. Vitamin B12 and folate levels were determined prior to injection. Serum clearance and urinary and stool excretion of the tracer were measured. Images were routinely obtained at 0.5, 3 to 5, and 20 to 24 hours after injection. Biodistribution of In 111 DAC was determined by computer analysis of regions of interest. RESULTS: Serum T1/2 clearance was 7 minutes. Average urinary and stool excretion of the injected dose over 24 hours was 26.1% and 0.4%, respectively. The greatest focal uptake of In 111 DAC occurred in the liver and spleen, followed by the nasal cavity and salivary and lacrimal glands. The average tumor uptake of the injected dose was 2% at 30 minutes and 1.5% at 24 hours. High-grade primary and metastatic breast, lung, colon, thyroid, and sarcomatous malignancies were all imaged at 3 to 5 hours after injection. Central nervous system tumors and advanced metastatic prostate cancer were best identified at 24 hours. Mammographically occult, palpable, and nonpalpable breast cancers were delineated by In 111 DAC. Low-grade malignancies as well as early skeletal metastatic disease were not effectively imaged by the vitamin B12 tracer. Patients with elevated baseline vitamin B12 or those concurrently taking corticosteroids appeared to have optimal visualization of their malignancies. CONCLUSION: Vitamin B12 may be a useful vehicle for delivering diagnostic and therapeutic agents to various malignancies. Further evaluation of cobalamin analogs and their interaction with transport proteins and cellular receptors within malignant tissue and infection is warranted.

Evaluation of macroaggregated albumin particle sizes for use in pulmonary shunt patient studies.

OBJECTIVE: To assess commercial macroaggregated albumin (MAA) reagent kits for compliance with particle-size parameters needed for proper clinical evaluation of pulmonary shunts (right-to-left). DESIGN: Comparative trial. SETTING: Nuclear pharmacy (laboratory setting). PATIENTS AND OTHER PARTICIPANTS: Not applicable. INTERVENTIONS: Minimally, 90% of the particles contained within an MAA reagent kit should be within the 10 to 90 microns range with minimal variation in particle size distribution and as few small particles (i.e., < 10 microns) as possible. Five separate vials from five commercial brands of MAA reagent kits were obtained, and 500 to 517 particles were analyzed for each sample. An additional study was performed on one of the MAA reagent kit brands, using five vials from each of five different lot numbers to determine the variability between lots. MAIN OUTCOME MEASURES: Long axis (maximum, micron), short axis (minimum, micron), and the area (micron 2) of each MAA particle. RESULTS: One MAA brand had the lowest percentage of unacceptable MAA particle sizes and maintained consistent particle sizes between vials. However, the same MAA reagent kit brand showed that only two of five lots had a low percentage of MAA particle sizes below the 10-micron limit. CONCLUSION: Particle sizes varied among the five different brands of MAA reagent kits, as did different lots of the best-performing kit. This variability in particle sizes may affect the accuracy and reproducibility of pulmonary shunt patient studies.

Effects of extrathoracic airway obstruction on intrathoracic pressure and pulmonary artery pressure in exercising horses.

OBJECTIVE: To determine whether dorsal displacement of the soft palate (DDSP) results in pulmonary artery hypertension and leads to increases in transmural pulmonary artery pressure (TPAP); to determine whether pulmonary hypertension can be prevented by prior administration of furosemide; and to determine whether tracheostomy reduces pulmonary hypertension. ANIMALS: 7 healthy horses. PROCEDURE: Horses were subjected to 3 conditions (control conditions, conditions after induction of DDSP, and conditions after tracheostomy). Horses were evaluated during exercise after being given saline (0.9% NaCl) solution or furosemide. RESULTS: Controlling for drug, horse, and speed of treadmill, DDSP-induced increase in intrathoracic pressure was associated with a significant increase in minimum (36 mm Hg), mean (82 mm Hg), and maximum (141 mm Hg) pulmonary artery pressure, compared with values for control horses (30, 75, and 132 mm Hg, respectively). Increases in pulmonary artery pressure did not induce concomitant increases in TPAP. Tracheostomy led to a significant reduction of minimum (53 mm Hg), and mean (79 mm Hg) TPAP pressure, compared with values for control horses (56 and 83 mm Hg, respectively). When adjusted for horse, speed of treadmill, and type of obstruction, all aspects of the pulmonary artery and TPAP curves were significantly decreased after administration of furosemide, compared with those for horses given saline (0.9% NaCl) solution. CONCLUSIONS: DDSP was associated with increases in pulmonary artery pressure but not with increases in TPAP. CLINICAL RELEVANCE: Expiratory obstructions such as DDSP are likely to result in pulmonary hypertension during strenuous exercise, but may not have a role in the pathogenesis of exercise-induced pulmonary hemorrhage.

Nonopsonic and opsonic association of Mycobacterium tuberculosis with resident alveolar macrophages is inefficient.

The association of Mycobacterium tuberculosis with alveolar macrophages (Mphi) in a serum-free environment is a crucial first step in the pathogenesis of this facultative intracellular pathogen. We present data demonstrating that freshly explanted alveolar Mphi do not efficiently bind M. tuberculosis in a serum-free system, although a small subpopulation of these Mphi (10-15%) can bind mycobacteria. In contrast, almost 100% of a peritoneal Mphi population bind mycobacteria under the same conditions. The poor binding of mycobacteria by alveolar Mphi does not reflect a general inability to associate with particles; binding and ingestion of latex beads and zymosan particles were comparable with that seen with peritoneal Mphi. Resident alveolar Mphi did not efficiently bind mycobacteria in the presence of serum and expressed poorly several Mphi surface receptors, including CR3. Furthermore, we demonstrate that bovine surfactant protein A does not enhance the association of M. tuberculosis with alveolar Mphi. Differentiation of alveolar Mphi in vitro resulted in increased expression of Mphi surface receptors and an increased capacity to bind mycobacteria in the presence and absence of serum. Evidence is presented that opsonic binding of M. tuberculosis by differentiated alveolar Mphi is mediated by complement and CR3, and that the poor binding by resident alveolar Mphi is due to their poor expression of CR3. The receptor mediating nonopsonic binding of M. tuberculosis to differentiated alveolar Mphi was not unequivocally identified in this study, but could also be CR3.

Effects of airway obstruction on transmural pulmonary artery pressure in exercising horses.

OBJECTIVE: To determine whether laryngeal hemiplegia would increase transmural pulmonary artery pressure (TPAP). ANIMALS: 6 horses. DESIGN: Horses were studied under 5 conditions: control conditions, after induction of left laryngeal hemiplegia, during obstruction of the left nostril, after placement of an instrumented tracheostomy, and after placement of an open tracheostomy. Horses were evaluated after being given saline solution and after being given furosemide. PROCEDURES: Horses were exercised on a high speed treadmill, using a maximum speed of 13 m/s. During each exercise, airway pressures, airflow, esophageal and pulmonary artery pressures, and blood gas partial pressures were measured. RESULTS: When adjusted for horse, speed, and obstruction condition, mean TPAP (pulmonary artery pressure-esophageal pressure) and minimum TPAP were significantly lower after administration of furosemide than after administration of saline solution. In horses given saline solution, respiratory obstruction that increased intrapleural pressure significantly increased mean TPAP, and respiratory obstruction that decreased intrapleural pressure significantly decreased minimum TPAP. CONCLUSIONS: Changes in intrapleural pressure appear to play an important role in pulmonary artery pressure and TPAP. CLINICAL RELEVANCE: Because induction of laryngeal hemiplegia did not increase TPAP, laryngeal hemiplegia is unlikely to contribute to development of exercise-induced pulmonary hemorrhage.

In vitro evaluation of neutrophil viability after exposure to a hypotonic medium.

Separation techniques for radiolabelled leukocytes have inherent problems with contaminants (e.g. platelets and erythrocytes). Hypotonic lysis methods can eliminate the erythrocytes, but the question of neutrophil viability after an exposure to a hypotonic solution (i.e. sterile water) remains. Ficoll/ hypaque two-density gradient separation was performed on donor whole blood to obtain a pure neutrophil suspension. A timed sequence of water exposure was done for 5-100 s on the neutrophil preparations. The viability of these preparations was evaluated using flow cytometry and chemotaxis. The trypan blue staining method was used to document cell death. With water exposures ranging up to 100 s, 2.04 +/- 1.80% neutrophils exhibited cellular degradation by flow cytometry, and all samples demonstrated viable neutrophils by chemotaxis and trypan blue staining. The hypotonic medium exposure times for leukocyte separations should be less than 30 s for neutrophils to retain their viability by these in vitro techniques.

Effects of generator eluate age on the radiochemical purity of fractionated 99Tcm-MAG3.

The fractionation of US mercaptoacetyltriglycene (MAG3) cold kits provides an economical way of preparing 99Tcm-MAG3. However, our nuclear pharmacy noted that fractionated 99Tcm-MAG3 kits sometimes failed radiochemical purity (RCP) testing (i.e. RCP < 90%) when a 99Tcm eluate of older age was used. The purpose of this study was to evaluate the effects of eluate age on the radiochemical purity of fractionated 99Tcm-MAG3 kits. Each of four US MAG3 cold kits was initially diluted with 10 ml N2-purged 0.9% NaCl solution and subdivided into 10 aliquots of 1 ml MAG3 solution and overlayered with N2. The 40 fractionated MAG3 vials were immediately frozen at -20 degrees C for storage. Fractionated MAG3 kits were reconstituted with 1 ml of approximately 111 GBq 99Tcm eluate from a long-ingrowth generator (i.e. > or = 72 h) every hour during the 6 h post-elution period. The RCP of each 99Tcm-MAG3 preparation was determined using the recommended Sep-Pak C18 column chromatography 1, 2, 3, 4, 5 and 6 h post-reconstitution. All fractionated MAG3 kits prepared with 99Tcm eluates 4 h post-elution or less maintained an average RCP value of 96.3 +/- 2.5% (n = 144) throughout the 6 h evaluation period following preparation. However, 99Tcm eluates 5 and 6 h post-elution resulted in kit failure rates of 16.7% (1/6) with RCP = 89.3%, and 50% (3/6) with RCP = 88.2, 83.9 and 87.1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility of fractionating MAG3 cold kit for cost reduction.

99Tcm-MAG3 is the first 99Tcm-labelled radiopharmaceutical with a renal clearance similar to that of 131I-OIH. The cost of a unit dose of 99Tcm-MAG3 is comparatively less expensive than the cost of a combined 99Tcm-DTPA and 131I-OIH study dose. However, this cost-saving is dramatically reduced when only a few doses are withdrawn from a 99Tcm-MAG3 kit. Our goal in this study was to subdivide the MAG3 kit into fractions to reduce expense. By dissolving the lyophilized ingredients of MAG3 kits with either 5 or 10 ml N2-purged normal saline, the resultant liquid was divided into 1-ml aliquot vials filled with N2. The MAG3 aliquot vials were then frozen at -70 degrees C for future use. The radiochemical purity (RCP) of each vial was evaluated using the recommended Sep-Pak C18 column chromatography at different time periods. Over the entire 28-day evaluation period, the average RCP of the 5:1 dilution MAG3 vials after reconstitution with 3.7 GBq 99Tcm was maintained at 95.6 +/- 2.7% (n = 100) for 6 h, whereas the 10:1 fractionation MAG3 kits after labelling with 740 MBq 99Tcm showed an average RCP value of 98.4 +/- 2.1% (n = 100) for 6 h. Based upon these results, it is concluded that the fractionation of MAG3 kits and frozen storage in an N2 atmosphere not only maintains the stability of MAG3 but also provides a cost-effective method for using 99Tcm-MAG3.