A long-period radio transient active for three decades.

Several long-period radio transients have recently been discovered, with strongly polarized coherent radio pulses appearing on timescales between tens to thousands of seconds1,2. In some cases, the radio pulses have been interpreted as coming from rotating neutron stars with extremely strong magnetic fields, known as magnetars; the origin of other, occasionally periodic and less-well-sampled radio transients is still debated3. Coherent periodic radio emission is usually explained by rotating dipolar magnetic fields and pair-production mechanisms, but such models do not easily predict radio emission from such slowly rotating neutron stars and maintain it for extended times. On the other hand, highly magnetic isolated white dwarfs would be expected to have long spin periodicities, but periodic coherent radio emission has not yet been directly detected from these sources. Here we report observations of a long-period (21 min) radio transient, which we have labelled GPM J1839-10. The pulses vary in brightness by two orders of magnitude, last between 30 and 300 s and have quasiperiodic substructure. The observations prompted a search of radio archives and we found that the source has been repeating since at least 1988. The archival data enabled constraint of the period derivative to <3.6 × 10-13 s s-1, which is at the very limit of any classical theoretical model that predicts dipolar radio emission from an isolated neutron star.

Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase.

Hemoglobin and myoglobin are a major source of dietary iron in man. Heme, separated from these hemoproteins by intraluminal proteolysis, is absorbed intact by the intestinal mucosa. The absorbed heme is cleaved in the mucosal cell releasing inorganic iron. Although this mucosal heme-splitting activity initially was ascribed to xanthine oxidase, we investigated the possibility that it is catalyzed by microsomal heme oxygenase, an enzyme which converts heme to bilirubin, CO, and inorganic iron. Microsomes prepared from rat intestinal mucosa contain enzymatic activity similar to that of heme oxygenase in liver and spleen. The intestinal enzyme requires NADPH; is completely inhibited by 50% CO; and produces bilirubin IX-alpha, identified spectrophotometrically and chromatographically. Moreover, duodenal heme oxygenase was shown to release inorganic (55)Fe from (55)Fe-heme. Along the intestinal tract, enzyme activity was found to be highest in the duodenum where hemoglobin iron absorption is reported to be most active. Furthermore, when rats were made iron deficient, duodenal heme oxygenase activity and hemoglobin-iron absorption rose to a comparable extent. Upon iron repletion of iron-deficient animals, duodenal enzyme activity returned towards control values. In contrast to heme oxygenase, duodenal xanthine oxidase activity fell sharply in iron deficiency and rose towards base line upon iron repletion. Our findings suggest that mucosal heme oxygenase catalyzes the cleavage of heme absorbed in the intestinal mucosa and thus plays an important role in the absorption of hemoglobin iron. The mechanisms controlling this intestinal enzyme activity and the enzyme's role in the overall regulation of hemoglobin-iron absorption remain to be defined.

Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies.

We have examined the distribution of radiolabeled liposomes in tumor-bearing mice after i.v. injection. Two mouse tumors (B16 melanoma, J6456 lymphoma) and a human tumor (LS174T colon carcinoma) inoculated i.m., s.c., or in the hind footpad were used in these studies. When various liposome compositions with a mean vesicle diameter of approximately 100 nm were compared using a radiolabel of gallium-67-deferoxamine, optimal tumor localization was obtained with liposomes containing a phosphatidylcholine of high phase-transition temperature and a small molar fraction of monosialoganglioside or hydrogenated phosphatidylinositol (HPI). At 24 h after injection, average values of tumor uptake higher than 10% of the injected dose per g and liver-to-tumor ratios close to 1 were reproducibly obtained. Increasing the molar fraction of HPI from 9% to 41% of the total phospholipid resulted in enhancement of liver uptake and decrease of tumor uptake. Methodological aspects that influence vesicle size appear to affect significantly liposome localization in the tumor. However, varying the phospholipid dose within a 10-fold range caused only minor changes in the percent of injected dose recovered in the tumor. A high uptake by tumors was also observed using other radiolabels [[3H]inulin and indium-111-labeled bleomycin (111In-Bleo)] in monosialoganglioside- and HPI-containing liposomes. In the case of 111In-Bleo, encapsulation in liposomes resulted in approximately 20- to 40-fold increase in tumor accumulation of the radiolabel at 24 h after injection. The marked localization of liposomes in the mouse footpad inoculated with tumor as opposed to the contralateral mock-injected footpad was also documented by imaging experiments with gallium-67-deferoxamine and 111In-Bleo-labeled liposomes. These results support the contention that some glycolipid-containing liposomes previously shown to have long circulating half-lives accumulate significantly in a variety of tumors and are promising tools for the delivery of anti-tumor agents.

Avoidance of gastroduodenal toxicity in patients receiving hepatic arterial 5-fluoro-2'-deoxyuridine.

Gastroduodenal inflammation and ulceration have been frequently observed in patients receiving continuous hepatic arterial infusions of 5-fluoro-2'-deoxyuridine (FUDR) for liver malignancy. Thirty-five patients with metastatic colon cancer received hepatic arterial FUDR administered with implanted infusion pumps. At surgery, particular care was taken to identify and divide those vessels arising from the hepatic arteries distal to the point of cannulation that supplied the superior border of the distal stomach and proximal duodenum. None of the patients developed signs or symptoms of gastritis or ulcer attributable to chemotherapy. We contend that gastritis and ulcer in patients receiving hepatic arterial FUDR are due to misperfusion of drug into the upper gastrointestinal tract and that these complications can be largely avoided by use of appropriate surgical techniques.

Determination of the bromide space in man by fluorescent excitation analysis of oral bromine.

The bromide dilutional volume determined by intravenous administration of 82Br has been compared with the corresponding volume determined by oral administration of stable bromide in 11 patients with various medical disorders. Stable bromide was assayed by fluorescent excitation analysis using a 109Cd source and a lithium-drifted silicon detector. The average deviation between the fluorescent and the radiobromide dilutional volumes was 4.2% with a standard deviation of +/- 8.5%. This substantiates both the accuracy of the fluorescent excitation method as applied to this tracer and the validity of utilizing oral tracer administration in comparison with intravenous administration. The derived estimates of extracellular fluid volume averaged 28.7% of body weight in the entire group of 11 patients and 25.8% in the 4 normal subjects included in the group. Evaluation of the extracellular fluid space utilizing fluorescent excitation of stable bromide permits high statistical accuracy of sample measurement with great simplicity compared with current chemical methods and with avoidance of the patient radiation exposure associated with 82Br.

Comparison of Ga-67 citrate images obtained with rectilinear scanner and large-field Anger camera.

Two methods for Ga-67 citrate imaging were compared on 20 patients. Scans were performed using approximately equal procedure time with two instruments: (A) a dual 5-in. rectilinear scanner with medium-energy collimator, with a single window spanning both the 93-keV and the 185-keV spectral peaks; and (B) a large-field (15-in. diam) Anger camera equipped with moving table, medium-energy collimator, and three windows covering the 93-keV, 185-keV, and 300-keV peaks separately. Sixteen abnormal sites and 24 normal sites were selected for comparison. Each site was evaluated by four physicians experienced in interpreting Ga-67 citrate images. The observers performed significantly better using the images obtained with the large-field camera (three windows) than with the dual 5-in. scanner (single window).

Neuroblastoma imaging using a combined CT scanner-scintillation camera and 131I-MIBG.

UNLABELLED: High-dose administration of 131I-metaiodobenzylguanidine (131I-MIBG) continues to be a promising treatment for neuroblastoma. However, currently used methods of estimating 131I-MIBG uptake in vivo may be too inaccurate to properly monitor patient radiation exposure doses. To improve localization and uptake measurements over currently practiced techniques, we evaluated different methodologies that take advantage of the correlated patient data available from a combined CT-scintillation camera imaging system. METHODS: Serial CT and radionuclide scans of three patients were obtained on a combined imaging system. SPECT images were reconstructed using both filtered backprojection and maximum-likelihood expectation maximization (MLEM). Volumes of interest (VOIs) were defined on anatomic images and automatically correlated to spatial volumes in reconstructed SPECT images. Several radionuclide quantification methods were then compared. First, the mean reconstructed values within coregistered SPECT VOIs were estimated from MLEM reconstructed images. Next, we assumed that reconstructed activity in SPECT voxels were linear combinations of activities present in individual objects, weighted by geometric factors derived from CT images. After calculating the weight factors by modeling the SPECT imaging process with anatomically defined VOIs, least-squares fitting was used to estimate the activities within lesion volumes. We also estimated the lesion activities directly from planar radionuclide images of the patients using similar linearity assumptions. Finally, for comparison, lesion activities were estimated using a standard conjugate view method. RESULTS: Activities were quantified from three patients having a total of six lesions with volumes ranging from 0.67 to 117 mL. Methods that used CT data to quantify lesion activities gave similar results for planar and tomographic radionuclide data. Estimating activity directly from mean VOI values in MLEM-reconstructed images alone consistently provided estimates lower than CT-aided methods because of the limited spatial resolution of SPECT. Values obtained with conjugate views produced differences up to fivefold in comparison with CT-aided methods. CONCLUSION: These results show that anatomic information available from coregistered CT images may improve in vivo localization and measurement of 131I-MIBG uptake in tumors.

Prevention of ischemia-induced myocardial platelet deposition by exogenous prostacyclin.

The antithrombotic effects of prostacyclin infusion on myocardial platelet deposition were studied in a canine model during and after global ischemia. Eleven isolated heart preparations were subjected to 1 hour of cardioplegic arrest under moderate hypothermia (27 degrees to 28 degrees C), including a control group (n = 7) and a prostacyclin-treated group (n = 4). The hearts of four other dogs were continuously perfused for 180 minutes. Platelet deposition was measured at 15 minute intervals throughout the 3 hour study. Serial full-thickness myocardial biopsy specimens were analyzed for activity of 111In-labeled platelets with 99mTc-labeled erythrocyte correction for tissue blood content. The pattern of platelet distribution was determined by scintiscans of each heart, taken with a gamma camera at the end of the 60 minute reperfusion period. Substantial myocardial platelet deposition was found in the control hearts after ischemia but not in the prostacyclin-treated group (p less than 0.05). Furthermore, prostacyclin infusion had a significant disaggregatory effect on intracoronary platelet deposits when the precardioplegic and postcardioplegic biopsy specimens were analyzed (p less than 0.05). Three hours of continuous perfusion did not increase tissue 111In-labeled platelet activity. Ex vivo images showed platelet deposition to be a diffuse patchy process with significantly more 111In activity in the endocardium than in the epicardium after global ischemia (p less than 0.05). These data show the potent antithrombotic properties of prostacyclin in preventing and disaggregating ischemia-induced intracoronary platelet deposition during and after cardioplegic arrest.

Noncontrast and contrast enhanced MR imaging in the evaluation of partial ureteral obstruction: an experimental study in the micropig.

Twelve Yucatan micropigs (3 controls; 3 sham-operated; 6 with unilateral obstruction) were studied to assess the value of noncontrast and contrast-enhanced (Gadolinium-DTPA) magnetic resonance (MR) imaging in the evaluation of partial ureteral obstruction. MR findings were correlated with findings of quantitative (Tc-99m-DMSA) scintigraphy, and histology. On noncontrast T1-weighted images, the normal porcine kidney demonstrated good corticomedullary contrast (CMC = 16.8% +/- 5.0). Five minutes after administration of Gd-DTPA, there was enhancement of the renal cortex (+24.4% and medulla (+46.2%), and CMC was no longer discernible. Enhancement of the urine within the collecting system (+119.1%) was also observed. The obstructed kidneys demonstrated marked thinning of the renal parenchyma and decreased signal intensity on noncontrast T1- and T2-weighted images (P less than 0.01). Urine in the dilated collecting system did not differ significantly from urine in controls except in the three animals with urinary tract infection (P less than 0.05). Five minutes following injection of Gd-DTPA, there was enhancement of the renal parenchyma in all kidneys. Excretion was seen in three pigs and no excretion in two. Thus, useful information can be obtained in partial ureteral obstruction from both pre-contrast and Gd-DTPA-enhanced MR images of the kidney.

Magnetic resonance imaging detection of an experimental pulmonary perfusion deficit using a macromolecular contrast agent. Polylysine-gadolinium-DTPA40.

RATIONALE AND OBJECTIVES: This study was designed to evaluate the potential of a blood-pool magnetic resonance (MR) contrast agent, polylysine-gadolinium-DTPA40 (polylysine-Gd-DTPA40) for detecting pulmonary perfusion defects. MATERIALS AND METHODS: Pulmonary emboli were induced in 10 rats by venous injection of 0.2 mL of air. Axial spin-echo images were acquired (TR = 800 mseconds; TE = 6 mseconds) before and after air injection and serially after the administration of polylysine-Gd-DTPA40. The embolism model was confirmed by scintigraphy using 99mTc-macroaggregated albumin. RESULTS: Signal intensity differences between normal and embolized lungs before and after the air injection were less than 25%. After polylysine-Gd-DTPA40 administration, signal intensity of the perfused lung increased more than 200%, whereas the embolized lung increased by only 25%. Signal intensities of the perfused lung remained stable for 1 hour, whereas signal intensities of the embolized lung gradually increased for 20 minutes as the air embolus dissolved. CONCLUSION: Magnetic resonance imaging (MRI) enhanced with a macromolecular blood-pool contrast agent can be used to detect acute pulmonary embolism in a confirmed animal model.

Rapid, contrast-enhanced, diuretic magnetic resonance imaging of unilateral partial ureteral obstruction. An experimental study in micropigs.

The value of rapid, contrast-enhanced, diuretic magnetic resonance (MR) imaging (using ferrioxamine B and furosemide) in demonstrating partial unilateral ureteral obstruction and the potential of such MR imaging in differentiating obstructive from nonobstructive hydronephrosis was assessed in six micropigs. MR imaging (0.35 Tesla, partial-flip technique with repetition time [TR] of 125 milliseconds, echo-delay time [TE] of 20 milliseconds, and flip angle of 70 degrees) was performed before, and at 5, 12, and 19 days after partial ureteral obstruction. Additionally, MR images were acquired 5, 12, and 19 days after release of obstruction. The diuretic was injected 10 minutes after the contrast medium. MR findings were correlated with results from nuclear scintigraphy (99mTc-DMSA uptake). MR images provided good morphologic detail from which renal size, parenchymal thickness, and degree of hydronephrosis could be determined. Contrast medium allowed assessment of cortical uptake and urinary excretion. The course of cortical signal enhancement best characterized the difference between obstructive and nonobstructive hydronephrosis. Normal kidneys and kidneys with nonobstructive hydronephrosis showed progressive decrease in cortical signal enhancement (-11.7% within 40 minutes) after furosemide injection. The kidneys with obstructive hydronephrosis demonstrated a plateau of signal enhancement without decrease (-0.7% within 40 minutes). These results demonstrate the utility of rapid contrast-enhancing, diuretic MR imaging in differentiating obstructive from nonobstructive hydronephrosis.

Imaging characteristics of a small germanium camera.

A high purity germanium gamma-camera has been developed and is currently being evaluated. This camera incorporates unique performance parameters such as a 2 mm full-width spatial response function with rejection of multiple-scatter in the detector, a 2.2% FWHM energy resolution for 99 mTc, a 180 nsec paralyzable dead-time, and a 2 mu sec non-paralyzable dead-time. Imaging studies demonstrate the superior capabilities of this instrument.

An automated fluorescent excitation analysis system for medical applications.

The use of stable tracers assayed by x-ray fluorescent excitation analysis has proven advantageous over other stable or radioisotopic techniques in a number of clinical and investigative situations. An automated fluorescent excitation analysis system for medical application has developed. Its design parameters and performance are described.

Total hepatic arterial perfusion after occlusion of variant lobar vessels: implications for hepatic arterial chemotherapy.

The surgical placement of hepatic arterial cannulas, followed by intra-arterial chemotherapy, is a promising technique for the treatment of unresectable hepatic malignancies. Complete perfusion of the liver with drugs is essential, but may be difficult to achieve in some patients with variant arterial anatomy. In 79 patients, we encountered 15 with variant anatomy that precluded standard single or dual cannulation techniques. In 12 patients variant lobar arteries were ligated at surgery. Postoperative transarterial coil occlusion was used in three patients. In each case, the remaining hepatic lobar artery was perfused with a single catheter. Complete bilobar hepatic perfusion was documented by a technetium 99m macroaggregated albumin scan in 13 of 15 (87%) patients. Of patients scanned more than 5 days after occlusion, six of six (100%) had full perfusion of the region supplied by the variant lobar vessels. Postocclusion hepatic arteriography demonstrated translobar collateral vessels that provided perfusion of the region of the occluded variant artery. There was no added morbidity from lobar arterial occlusion and no disparity in tumor response between perfusion by direct cannulation and perfusion by collateral flow. Occlusion of variant hepatic lobar arteries in conjunction with single catheter cannulation to infuse the remaining lobar vessels is a useful technique to provide total hepatic arterial perfusion in patients with variant hepatic arterial anatomy.

Iatrogenic pheochromocytomatosis: a previously unreported result of laparoscopic adrenalectomy.

BACKGROUND: Laparoscopic adrenalectomy is now regarded as the procedure of choice for treatment of small or benign adrenal tumors, including pheochromocytoma. However, long-term outcomes have not been critically assessed. We report here 3 cases of pheochromocytomatosis recurring 3 to 4 years after laparoscopic adrenalectomy. We postulate laparoscopic-induced seeding of tumor as the mechanism of recurrence. METHODS: We retrospectively reviewed the cases of 3 patients with documented biochemical and radiolabeled metaiodobenzylguanidine evidence of recurrent pheochromocytoma after prior presumed curative laparoscopic adrenalectomy. RESULTS: Original pheochromocytomas were 5.5 to 6.5 cm in diameter. At the time of laparoscopic adrenalectomy, tumors were not believed to be malignant, based on clinical or histopathologic data. However, on 3- to 4-year follow-up, each patient developed symptoms, elevated urinary catecholamine levels, and metaiodobenzylguanidine imaging consistent with recurrence. At reoperation, multiple small tumor nodules were found in the adrenal bed near the site of the initial laparoscopic resection. The original operative notes suggested some possible method of local seeding: tumor fragmentation and spillage or excessive tumor manipulation. CONCLUSIONS: Pheochromocytoma recurrence may occur as a result of local spillage of tumor during laparoscopic adrenalectomy. The relative risk of recurrence between open and laparoscopic resection needs to be assessed. Long-term follow-up will continue to be important, regardless of operative approach.

Vessel wall and indium-111-labelled platelet response to carotid endarterectomy.

Postendarterectomy platelet deposition and thrombus formation may play an important role not only in vessel wall healing but also in the small incidence of postoperative cerebral ischemia and postoperative stenosis. A study has been performed using a canine model to investigate the healing response to carotid endarterectomy and the validity of an in vivo indium-111 (In-111) radiotracer technique in the assessment of postendarterectomy deposition of autologous labelled platelets. Sixteen endarterectomized carotid arteries showed uptake of autologous In-111 platelets immediately after infusion, reaching a maximum by 1 hour with little increase at 24 or 48 hours. No uptake was seen in ten control vessels following platelet infusion (P less than 0.05). At autopsy, seven vessels were demonstrated to have In-111 platelet deposition immediately prior to sacrifice of the animals. Postmortem scanning confirmed the localization to the vessel lumens, and microscopy revealed thrombus formation with or without partial endothelialization. Complete reendothelialization had occurred in the vessels that failed to show platelet deposition. Delayed healing was associated with continuing platelet deposition, excessive thrombus formation, and luminal stenosis. Arteriotomy closure with a vein patch altered the healing characteristics of the vessel with segmental thrombus formation over the vein patch. A preliminary study of the postendarterectomy in vivo In-111 platelet response in humans demonstrated platelet deposition that was not influenced by the administration of antiplatelet drugs at currently prescribed levels.

Prostacyclin production in regions of arterial stenosis.

The effect of abnormal flow dynamics on prostacyclin (PGI2) production by intact endothelium is unknown. To investigate this we studied the effects of graded stenoses on vessel wall PGI2 production in dogs (n = 8) whose femoral and carotid arteries (n = 32) were narrowed by machine-milled clips, producing 1.0 cm segmental stenoses of 25%, 50%, 75%, and 90% diameter reduction. Three dogs were injected with Indium 111-labeled platelets and 12 vessels were scanned for platelet deposition. All stenotic vessels were excised at 6 weeks for histologic study (hematoxylin-eosin section and immunohistochemistry for factor VIII) and PGI2 radioimmunoassay (as the metabolite 6-keto PGF1 alpha). All vessels remained patent with no thrombus formation in any segment. Vessel imaging in platelet-labeled animals showed no significant deposition. Histologic analysis demonstrated an intact endothelial surface in the stenotic segments, confirmed by the demonstration of factor VIII production by these cells. PGI2 production (per unit surface area) by the arterial segments with greater than or equal to 50% stenosis markedly exceeded the PGI2 production by the normal proximal and distal segments (p less than 0.0002) and showed further significantly increased production with increasing degrees of stenosis (p less than 0.00001). The data indicate increased PGI2 production by normal endothelium in regions of arterial stenosis. The mechanism of this increase is unknown, but this endothelial "turn on" effect may serve to inhibit deposition of platelets and thrombus formation in the presence of disordered flow patterns.

Liquid thickness vs. vertical pressure gradient in a model of the pleural space.

In recent studies using relatively noninvasive techniques, the vertical gradient in pleural liquid pressure was 0.2-0.5 cmH2O/cm ht, depending on body position, and pleural liquid pressure closely approximated lung recoil (J. Appl. Physiol. 59: 597-602, 1985). We built a model to discover why the vertical gradient in pleural pressure is less than hydrostatic (1 cmH2O/cm). A long rubber balloon of cylindrical shape was inflated in a plastic cylinder. The "pleural" space between the balloon and cylinder was filled with blue-dyed water. With the cylinder vertical, we measured pleural pressure by a transducer through side taps at 2-cm intervals up the cylinder. The pressure was measured with different amounts of water in the pleural space. With a clear separation between the balloon and the container, the vertical gradient in pleural liquid pressure was hydrostatic. As water was withdrawn from the pleural space, the balloon approached the wall of the container. Over an 8-cm-long midregion of the model where the balloon diameter matched the cylinder diameter, the vertical gradient was not hydrostatic and was virtually absent. In this region, the pleural liquid pressure was uniform and equal to the recoil of the balloon. In this section we could not see any pleural space. By scintillation imaging using 99mTc-diethylenetriamine pentaacetic acid in the water, we estimated the thickness of this flat "costal" pleural space to be approximately 20 microns. Radioactive tracer injected at the top of the pleural space appeared by 24 h at the bottom, which indicated a slow drainage of liquid by gravity.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of abscess in adult polycystic kidney by indium-111 leukocyte scan.

In patients with adult polycystic kidney disease (APKD) infected cysts are difficult to localize with current radiographic techniques, especially those dependent on renal function. Indium-111 leukocyte (In-WBC) imaging is both highly sensitive and effective in detecting and localizing abscesses in patients with renal failure. We report on a patient with APKD and sepsis in whom computed tomography, ultrasound, and physical examination failed to locate the renal abscess, which was found by In-WBC scanning.

Evaluation of oral submucosal blood flow at dental injection sites by radioactive Xenon clearance in beagle dogs.

Oral submucosal blood flow was measured at dental injection sites in anesthetized dogs and compared with subcutaneous blood flow. Blood flow was calculated from the measured half-time for clearance of radioactive xenon dissolved in saline. By this method, oral submucosal blood flow was much greater than subcutaneous blood flow and was comparable in magnitude to values reported for cerebral blood flow. Injection of a solution containing 1:100,000 epinephrine at the mandibular canal produce a delayed clearance of isotope which was three times as long as the clearance time for solutions without epinephrine.