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.

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.

Association between residual thyroid carcinoma and diffuse hepatic uptake of 131I following radioiodine ablation in postoperative total thyroidectomy patients.

In patients with differentiated thyroid cancer (DTC) total or near-total thyroidectomy, postoperative 131I ablation, and thyroid suppression therapy are reported to be associated with fewer recurrences than other treatments. Many patients with DTC after total thyroidectomy and radioablation therapy have diffuse hepatic uptake of radioiodine, and its clinical importance is debated. Some investigators report that diffuse liver uptake correlates with uptake in the thyroid bed or the presence of metastatic thyroid cancer somewhere in the body, whereas others note no such correlation. The purpose of this research was to determine the clinical importance of diffuse hepatic uptake of radioiodine after 131I ablative therapy in patients with DTC. We retrospectively reviewed 141 posttherapy scans done in 118 patients with DTC. Patients had had total thyroidectomy and were hypothyroid when serum thyroglobulin (Tg) levels were obtained, and they were treated with 30 to 200 mCi of 131I. Scans were performed 3 to 21 days after radioablation therapy. Information was collected regarding the patients' age and gender, the interval between the ablation therapy and scan, uptake of radioiodine, serum thyroglobulin level, thyroid-stimulating hormone (TSH) level, thyroglobulin antibodies, TNM classification, mortality, and recurrence. Diffuse liver uptake was classified from 0 to 4 depending on hepatic brightness. Radioiodine scans were done to determine whether there was uptake in the thyroid bed or elsewhere. Statistical analyses included analysis of variance and Kaplan-Meier survival analysis. Diffuse hepatic uptake was observed (grades 1-4) in 96.4% of the patients; thus 3.6% had no hepatic uptake. There was no significant association between liver uptake and the uptake in the thyroid bed, the dose of 131I administered for ablation therapy, thyroglobulin levels, age, stage of the disease, presence of local or distant metastases, recurrence, or survival. Diffuse hepatic uptake was therefore not associated with residual normal thyroid or metastases as suggested by some but not all previous investigators.

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.

Metastatic head and neck cancer: role and usefulness of FDG PET in locating occult primary tumors.

PURPOSE: To assess the usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) of the head and neck in locating occult primary lesions in patients with metastatic cervical adenopathy. MATERIALS AND METHODS: Seventeen patients with metastatic cervical adenopathy of unknown primary origin were referred for FDG PET of the head and neck. All patients had undergone correlative anatomic imaging within 1 month of FDG PET. Surgical, clinical, and histopathologic findings were used to assess the performance of FDG PET. RESULTS: Increased apical lung uptake at FDG PET led to a biopsy-proved diagnosis of primary lung cancer in two patients. Of the remaining 15 patients, 10 had a focus of increased activity; directed biopsy of these sites led to confirmation of a primary carcinoma in seven patients. Correlative anatomic imaging failed to demonstrate the primary sites of disease in two of these seven patients. None of the five patients with negative FDG PET studies have manifested evidence of a primary site of disease during follow-up of 8-42 months (mean, 29 months). CONCLUSION: FDG PET allows effective localization of the unknown primary site of origin in metastatic head and neck cancer and can contribute substantially to patient care.

Hypercalcemia in malignant paraganglioma due to parathyroid hormone-related protein.

A 15-year-old boy had hypercalcemia in association with malignant retroperitoneal paraganglioma. He had suppressed circulating levels of intact parathyroid hormone, whereas parathyroid hormone-related protein (PTHrP) immunoreactivity was elevated in plasma. Both the serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were normal. Preoperatively the patient required control of hypercalcemia with intravenous pamidronate therapy. His circulating calcium and PTHrP concentrations became normal after a successful surgical resection of the primary retroperitoneal tumor. To our knowledge, this is the first reported case of elevated PtHrP levels in a patient with paraganglioma which resolved postoperatively.

Clinical utility of positron emission tomography with 18F-fluorodeoxyglucose in detecting residual/recurrent squamous cell carcinoma of the head and neck.

PURPOSE: The use of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) to detect residual/recurrent squamous cell carcinoma of the head and neck has been tested only in small groups of patients. Our purpose, therefore, was to evaluate the ability of this technique to detect the presence of tumor at both primary and nodal sites in a large cohort of patients. METHODS: All patients referred for PET scanning over a 2.5-year period with a question of residual or recurrent squamous cell carcinoma of the head and neck were identified. Thirty-five of 44 patients had sufficient follow-up to be meaningful to our analysis (range, 6-33 months). PET scans were interpreted visually with knowledge of the clinical history and correlative anatomic imaging findings. Detection of disease involving primary and nodal sites was assessed independently. Additionally, because each patient had been referred in an attempt to resolve a specific clinical problem, the usefulness of PET in accurately addressing these questions was assessed. RESULTS: At the primary site, sensitivity and specificity for residual/recurrent disease were 100% and 64%, respectively; for nodal disease, sensitivity and specificity were 93% and 77%, respectively. In helping to resolve the clinical question being asked, the positive predictive value of the test result was 65% and the negative predictive value was 91%. CONCLUSION: The high sensitivity and negative predictive value of PET scanning in our cohort of patients suggest an important role for this technique in the care of patients with suspected residual/recurrent head and neck carcinoma. The lower figures obtained for specificity and positive predictive value reflect the fact that increased FDG uptake may be due to either tumor or inflammation.

Lymphatic regeneration following microvascular limb replantation: a qualitative and quantitative animal study.

Lymphatic regeneration following unilateral hindlimb autotransplantation was studied in 14 Lewis rats using Technetium-99 radiolabeled sulfur colloid (TC-99) lymphoscintigraphy and compared to the lymphatic pattern exhibited in four unoperated control rats. Control animals demonstrate a reproducible flow of lymph along the deep lymphatic system from the foot, draining into the ipsilateral inguinal nodes, and then up to the para-aortic nodes. Following replantation, lymphatic outflow from the replanted limb begins to occur within 3 to 6 days, reaching normal lymphatic clearance within 12 days. However, the pattern of lymphatic flow is ill-defined, relying on multiple small channels of the superficial lymphatic system. In contrast to controls, at 3 hr post TC-99 injection, lymphatic drainage in replanted rats is via the inguinal and axillary nodal regions bilaterally. This abnormal pattern persisted in the replanted animals for the duration of this study, 160 days. It is evident that lymphatic regeneration in this animal model is associated with a rapid return to normal levels of lymphatic clearance via collateral channels within the subcutaneous tissue. The rapidity with which lymphatic drainage is restored, and its localization within the subcutaneous tissue, can explain why replanted tissues and microvascular free flaps seldom develop lymphedema. In addition, the rat hindlimb replantation model may prove useful for studies of the general mechanisms and specific factors responsible for lymphangiogenesis.

Morbid obesity, absorption, neuroticism, and the high risk model of threat perception.

We studied 70 morbidly obese patients, candidates for gastric exclusion surgery. We found that their mean absorption score was significantly lower and that their mean neuroticism score significantly higher than a matched control group. These results are consistent with predictions from the High Risk Model of Threat Perception (Wickramasekera, 1979, 1986, 1988, 1993a). People high in neuroticism are hypothesized to be hypersensitive to threat and, therefore, at greater risk for stress related psychobiological disorders. But if they are also low in absorption, they are hypothesized to have poor conscious perception of psychosocial threats and, therefore, they develop a very restricted range of psychosocial methods of coping with such threats. Consequently, lows may be mainly restricted to behavioral methods of coping like feeding and drinking to self-soothe unconscious aversive emotions associated with autonomic dysregulation and elevated parasympathetic tone. Their skeptical, rational, pragmatic cognitive style drives them to perceive medical surgical solutions to weight gain as more credible than psychosocial weight reduction programs.

The treatment of malignant pheochromocytoma with iodine-131 metaiodobenzylguanidine (131I-MIBG): a comprehensive review of 116 reported patients.

Iodine-131 metaiodobenzylguanidine (131I-MIBG), a radiopharmaceutical agent used for scintigraphic localization of pheochromocytomas, has been employed to treat malignant pheochromocytomas since 1983 in a few specialized centers around the world. We review our clinical experience together with the published experience of 23 other centers in 10 countries, regarding the use of 1311-MIBG for treating patients with malignant adrenal pheochromocytomas or extra-adrenal paragangliomas. There were a total of 116 evaluable patients: 3 were from our current report and another 113 were reported in the literature from 1983 to 1996. A majority of the patients were selected for treatment based upon positive tracer uptake studies. The cumulative dose of 131I-MIBG administered ranged from 96 to 2,322 mCi (3.6 to 85.9 GBq), with a mean (+/-SD) of 490+/-350 mCi (18.1+/-13.0 GBq). The subjects received a mean single therapy dose of 158 mCi (5.8 GBq) and the number of doses administered ranged from 1 to 11, with a mean of 3.3+/-2.2 doses. Initial symptomatic improvement was achieved in 76% of patients, tumor responses in 30%, and hormonal responses in 45%. Five patients had complete tumor and hormonal responses, ranging from 16 to 58 months, which were sustained at the time of reporting. Patients with metastases to soft tissue had more favorable responses to treatment than those with metastases to bone. No difference was noted in the age between the responders and non-responders. Adverse effects, recorded in 41% of the treated patients, were generally mild except for one fatality from bone marrow aplasia. Among 89 patients with follow-up data, 45% of the responders had relapsed with recurrent or progressive disease after a mean interval of 29.3+/-31.1 months (median 19 months). Of patients with an initial response to 1311-MIBG, death was reported in 33% after a mean of 23.2+/-8.1 months (median 22 months) following treatment. Of non-responders, death was reported in 45% after a mean of 14.3+/-8.3 months (median 13 months). In conclusion, this review suggests that 131I-MIBG therapy may be a useful palliative adjunct in selected patients with malignant pheochromocytoma or paraganglioma. Although controlled studies are lacking, our review raises the hope that this therapeutic modality may prolong survival with an occasional sustained complete remission or possible cure.

Chemiluminescent substrates for detection of restriction fragment length polymorphism.

Five new enzyme-triggered dioxetane substrates were evaluated for restriction fragment length polymorphism (RFLP) analysis of HaeIII- restricted DNA. Of these, one substrate designated CDP-Star provided unsurpassed sensitivity within one working day without the presence of an enhancer. Far greater sensitivity was obtained from chemiluminescent detection of DNA on MSI neutral membranes than the sensitivity obtained from six day film exposures of 32P labelled insert probes on PALL B membranes, including the detection of most low molecular weight alleles. For nylon membranes better suited for alkaline phosphatase-triggered chemiluminescent detection of DNA, high salt/neutral pH southern transfer conditions were better than alkaline southern transfer conditions.

Radioisotopic evaluation of the thyroid and the parathyroids.

Since the inception of the discipline of nuclear medicine, thyroid evaluation and therapy with radioactive isotopes have remained an important and constant component of thyroidology. Parathyroid scintigraphy with 201Tl/99mTc subtraction has been a more recent and also very useful addition in the assessment of hyperparathyroidism, particularly at reoperation. The radioactive iodine uptake test gives important metabolic information on thyroid function in such diverse disease states as hyperthyroidism, hypothyroidism, the thyroiditides, and thyroid carcinoma. Thyroid scintigraphy is also a key contributor to the assessment of patients with hyperthyroidism or with single versus multiple thyroid nodules, those with a history of head and neck irradiation during childhood, and those requiring diagnostic follow-up studies with 131I after total thyroidectomy for differentiated thyroid carcinoma. Each of these topics is reviewed and expanded on in this article, with a diversity of illustrative scans provided to complement the discussion.

Assessment of in situ renal transplant viability by 31P-MRS: experimental study in canines.

In 14 in situ canine renal transplants, intracellular phosphorus metabolites were evaluated by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), performed using surface coils to investigate the usefulness of this technique for assessing renal viability in situ. Group I control kidneys (n = 5) were autografts, as were Group II (n = 5) kidneys: the latter group were subjected to surgically induced vascular ischemia and thrombosis. Group III kidneys (n = 4) were rejecting allografts. Renal flow and function, as measured by 99mTc-DTPA, and findings on histologic examination were correlated with 31P-MRS spectra. Group I kidneys showed excellent viability on both 99mTc-DTPA studies and biopsy evaluation, and their 31P-MRS-derived ratios of phosphomonoesters/inorganic phosphate (PME/Pi) and adenosine triphosphate/Pi (ATP/Pi) were high (1.32 +/- 0.23 and 0.90 +/- 0.36, respectively). In contrast, Group II kidneys demonstrated poor flow and function, histologic evidence of severe ischemia from venous and arterial thrombosis, and significantly (P < 0.005) less viability than controls, as monitored by 31P-MRS PME/Pi (0.58 +/- 0.30) and ATP/Pi (0.20 +/- 0.13) ratios. Group III kidneys also demonstrated poor flow and function with 99mTc-DTPA, and the associated histologically injury was noted to be caused by accelerated rejection and severe vascular damage. PME/Pi (0.24 +/- 0.22) and ATP/Pi (0.10 +/- 0.01) ratios were also significantly (P < 0.005) less than those in controls, reflecting nonviability. The 31P-MRS-derived PME/Pi and ATP/Pi ratios enable a qualitative noninvasive assessment of blood flow-dependent renal viability, but with currently used localization techniques the differentiation between severe ischemia and severe acute rejection was not possible.

Phe-Met-Arg-Phe-NH2 (FMRFa)-related peptides inhibit Na(+)-Ca2+ exchange in cardiac sarcolemma vesicles.

The molluscan cardioexcitatory tetrapeptide FMRF-amide (Phe-Met-Arg-Phe-NH2) and related peptides inhibit Na(+)-Ca2+ exchange in calf cardiac sarcolemma vesicles. FMRFa itself has a low inhibitory potency (IC50 = 750 microM) which completely resides in its COOH-terminal RFa portion. The physiologically active analog FLRFa is 10-fold more potent (IC50 = 60 microM). Two other substitutions of the Met2 in FMRFa, by either Ile or Lys increase inhibitory potency 7- and 50-fold, respectively. The inhibitory potency increases 300-500-fold if the NH2-terminal Phe1 in FMRFa is substituted by either Val or His (IC50 = 1-2 microM). The inhibitory activity of WnLRFa (IC50 = 40 microM) is lost when either the NH2-terminal amino group is acylated or the NH2-terminal Trp1 is deleted. These data suggest that the COOH-terminal portion is essential for the basic low potency inhibition of Na(+)-Ca2+ exchange, whereas the NH2-terminal portion is important for the potentiation of the inhibitory activity. Although the IC50 values of various peptides range widely (10(-6)-10(-3) M), all of them induce a complete inhibition. The dose-response pattern of the peptide-induced inhibition is identical for the Na(+)-Ca2+ exchange and its partial reaction, the Ca(2+)-Ca2+ exchange. The inhibitory effect is reversible and affects both Nai(or Cai)-dependent 45Ca uptake and Nao-dependent 45Ca efflux, suggesting that the bidirectional movements of ions are altered. A mild pretreatment of vesicles with trypsin augments the Na(+)-Ca2+ exchange 1.5-fold but diminishes the inhibitory potency 3-4-fold, suggesting that the inhibition is mediated by an extravesicular membrane protein. The characteristics of the peptide-induced inhibition resemble the effect of opiates on Na(+)-Ca2+ exchange. FLRFa and dextrorphan (a non-opioid stereoisomer of an opiate agonist) are mutually exclusive inhibitors, suggesting that they may bind to the same site. This putative site lacks the pharmacological properties of opiate receptors and may be located either on the Na(+)-Ca2+ exchanger or at its vicinity. Endogenous analogs of FMRFa may regulate intracellular calcium via Na(+)-Ca2+ exchange.

Differentiation of alveolitis and pulmonary fibrosis with a macromolecular MR imaging contrast agent.

The ability of macromolecular contrast agent (polylysine-[gadopentetate dimeglumine]) to allow differentiation of pulmonary fibrosis and alveolitis at magnetic resonance imaging was investigated. Lung damage was induced by means of left bronchial instillation of 200 micrograms of cadmium chloride. Rats were imaged 3 hours (early alveolitic stage, n = 5), 24 hours (late alveolitic stage, n = 5), and 8 days (fibrotic stage, n = 5) later. Rats imaged 3 hours after cadmium chloride instillation demonstrated a gradually increasing contrast enhancement over 45 minutes (from 314% +/- 110 to 476% +/- 69 over baseline [P less than .01]), indicating a leak of paramagnetic macromolecules from the intravascular into the extravascular spaces. Conversely, lung enhancement remained virtually constant after injection of contrast material in contralateral control lungs and in damaged lungs imaged 24 hours and 8 days after cadmium chloride instillation. Furthermore, the enhancement in the fibrotic lung was lower (170% +/- 50) than that in the alveolitic and control lungs (320% +/- 65 and 298% +/- 61, respectively), indicating a decrease in plasma volume in the fibrotic lung. A macromolecular contrast agent can facilitate the differentiation between the exudative and fibrotic phases of interstitial lung disease.

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.

Comparison of Fe-HBED and Fe-EHPG as hepatobiliary MR contrast agents.

The authors studied the biodisposition and hepatobiliary transport of two potential magnetic resonance imaging contrast agents, the iron (III) chelates of N,N'-bis(2-hydroxybenzyl)ethylene-diamine-N,N'-diacetic acid (HBED) and diastereomeric N,N'-ethylenebis(2-hydroxyphenylglycine) (EHPG). Fecal and urinary excretion (mean +/- standard deviation), respectively, of FE-59 over 7 days in rats given tracer doses of the contrast agents were 67% +/- 2% and 22% +/- 1% for Fe-59-HBED and 22% +/- 2% and 26% +/- 5% for Fe-59-EHPG. In bile duct-cannulated rats given 0.05-mmol/kg doses labeled with Fe-59, 52% +/- 8% of Fe-59 from Fe-59-HBED but only 17% +/- 3% of that from Fe-59-EHPG was excreted into the bile within 90 minutes. Bromosulfophthalein, but not taurocholate or oxyphenonium, was shown to compete with both agents for hepatobiliary transport. Enterohepatic recirculation of both agents was less than 1%.