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Biomedical subjects

J L Doppman

Publications and source records attributed to J L Doppman.

At least 199 records · Page 11Linked to original sources

Angiographic ablation of parathyroid adenomas: lessons from a 10-year experience.

Angiographic ablation of parathyroid adenomas with ionic contrast material was performed in 24 patients with persistent hyperparathyroidism who had undergone at least one prior unsuccessful surgical resection; 23 had mediastinal adenomas. The success rate was 83% at 1 month after ablation and 71% at both 5 and 9 years. Ablation was successful in 85% of the patients in whom the catheter could be wedged into the artery feeding the adenoma. Long-term success was achieved in 89% of the patients in whom contrast enhancement persisted in the adenoma on computed tomographic scans obtained 24 hours later. Acute complications were seen only in patients with glands supplied by the inferior or superior thyroid arteries. Long-term complications were limited to permanent hypocalcemia, present in 8% of patients. Even if unsuccessful for ablation, the procedure may provide localization and does not preclude surgical resection. It is recommended for most patients with persistent hyperparathyroidism and mediastinal adenomas, especially adenomas supplied by the internal thoracic artery.

Adenoma↗

Hepatic metastasis detection: comparison of three CT contrast enhancement methods.

A prospective, blinded comparison of three methods of hepatic contrast enhancement in computed tomography (CT) was conducted in 15 patients with colorectal carcinoma metastatic to the liver. Arterial portography (AP-CT) was performed with injection of contrast material into the superior mesenteric artery during CT. Delayed scanning (DS-CT) was performed 4 hours after intravascular administration of contrast material (mean dose, 280 mL). CT with an ethiodized oil emulsion (EOE-CT) was performed 1 hour after slow intravenous infusion of the emulsion. All patients underwent laparotomy following imaging studies. A lesion-by-lesion analysis of 56 metastases showed no significant differences in sensitivity (AP-CT, 77%; DS-CT, 83%; EOE-CT, 82%), but the false-positive rate for AP-CT was significantly higher than that for DS-CT (P less than .001) or EOE-CT (P less than .01). False-positive rates for EOE-CT and DS-CT were not significantly different. The predictive value of a positive test was 63% for AP-CT, 90% for DS-CT, and 81% for EOE-CT. AP-CT does not appear to be clinically useful for detection of hepatic metastases because of the high false-positive rate. No difference could be demonstrated between DS-CT and EOE-CT. DS-CT is a valuable method for hepatic contrast enhancement.

Adult↗

Magnetic resonance imaging of spinal arteriovenous malformations.

Magnetic resonance imaging (MRI) was performed on 12 patients with spinal arteriovenous malformations (AVM's). Six lesions were intramedullary, five were dural, and one was in a posterior extramedullary location. Serpentine filling defects similar to the classic myelographic findings were demonstrated within the high-signal cerebrospinal fluid on T2-weighted coronal scans. The intramedullary nidus was identified by MRI as an area of low-signal intensity within the cord in all six intramedullary AVM's. Neither the dural nor the posterior extramedullary lesions showed intramedullary components. It is concluded that MRI may noninvasively provide the initial diagnosis of a spinal AVM and distinguish intramedullary from dural and extramedullary lesions.

Adolescent↗

A reproducible model of metastatic brain and ocular tumor by hematogenous inoculation of the VX2 tumor in rabbits.

A metastatic brain-tumor model has been developed in rabbits by infusing the VX2 carcinoma into the internal carotid artery to simulate hematogenous dissemination of tumor. In a series of 25 New Zealand White rabbits, multiple metastases arose in the hemisphere of 24 (96%) and in the eye of 22 (92%); in all instances ocular metastases were ipsilateral to the site of infusion. Ocular metastases were visible in the anterior chamber in 80% of animals 3 to 12 days after the infusion of VX2 tumor cell suspension. All rabbits deteriorated neurologically or died by Day 15 after the inoculation. Multiple metastases were demonstrated by magnetic resonance imaging as early as 5 to 7 days after infusion of the tumor cells and were confirmed at autopsy. This technique models hematogenous metastases to the brain and eye and is useful in evaluating the response of metastases to chemotherapy and radiation therapy directed to the brain and eye.

Animals↗

Carotid artery mixing with diastole-phased pulsed drug infusion.

Focal injury to the brain or retina is a frequent complication of drug delivery to the internal carotid artery (ICA) and may be due to poor mixing of the drug with blood at the infusion site. Rhesus monkeys were studied to determine whether phased drug delivery during diastole from a modified pulsatile angiographic injector would improve drug mixing in vivo. A radiolabeled flow tracer, carbon-14-iodoantipyrine (14C-IAP), was injected into the ICA of three monkeys in 80-msec pulses, each ending at least 50 msec before the end of local diastole. Local isotope concentration in the brain was determined by quantitative autoradiography. The ratio of highest to lowest concentration was 1.86 +/- 0.26 (mean +/- standard deviation) in the frontoparietal cortex, 1.65 +/- 0.42 in the frontoparietal white matter, 1.89 +/- 0.28 in the temporal cortex, and 1.39 +/- 0.17 in the basal ganglia. These results were similar to recordings in three control animals that received intravenous 14C-IAP to demonstrate complete drug mixing (1.37 +/- 0.12, 1.41 +/- 0.11, 1.70 +/- 0.08, 1.22 +/- 0.24, respectively), and contrasted to findings in five animals which received continuous intracarotid infusions to demonstrate standard ICA drug delivery (4.54 +/- 2.07, 2.94 +/- 1.45, 5.43 +/- 3.57, 3.60 +/- 2.90, respectively). Pulsed intra-arterial infusion during diastole provides a technically simple method for improving intravascular drug mixing, and results in drug delivery to tissue capillaries that is proportional to blood flow.

Animals↗

Uniformity of intracarotid drug distribution with diastole-phased pulsed infusion.

Drug streaming has been implicated in the development of focal necrotic lesions in perfused tissues following intracarotid chemotherapy of brain tumors at low infusion rates. The narrow infusate path characteristic of streaming within laminar blood flow is not observed at high infusion rates such as are typical in contrast injection for angiography. By periodically pulsing the infusate at a high rate, the mechanisms of rapid mixing can be exploited while retaining the practicality of low average infusion rates. This in vitro study demonstrates the effects of the pulse-controlling parameters and the catheter characteristics and placement on mixing effectiveness. An internal carotid artery model including eight cerebral branches was infused with dye through various indwelling catheters, and individual branch effluents were collected and analyzed spectrophotometrically for dye concentration. While catheter placement dominates the factors that control infusate distribution, judicious selection of the pulse parameters can alleviate that dependence. A primary advantage is gained by phasing the pulse to occur during that period of the cardiac cycle when the blood flow is lowest at the injection site. The data clearly showed that diastole-phased pulsed infusions are highly effective in producing a uniform infusate distribution at low average infusion rates.

Carotid Arteries↗

Spinal arteriovenous malformations: a comparison of dural arteriovenous fistulas and intradural AVM's in 81 patients.

The medical records and arteriograms of 81 patients with spinal arteriovenous malformations (AVM's) were reviewed, and the vascular lesions were classified as dural arteriovenous (AV) fistulas or intradural AVM's. Intradural AVM's were further classified as intramedullary AVM's (juvenile and glomus types) and direct AV fistulas, which were extramedullary or intramedullary in location. Dural AV fistulas were defined as being supplied by a dural artery and draining into spinal veins via an AV shunt in the intervertebral foramen. Intramedullary AVM's were defined as having the AV shunt contained at least partially within the cord or pia and receiving arterial supply by medullary arteries. Of the 81 patients, 27 (33%) had dural AV fistulas and 54 (67%) had intradural AVM's. Several dissimilarities in clinical and radiographic findings of the two subgroups were evident. The patients with intramedullary AVM's were younger; the age at onset of symptoms averaged 27 years compared to 49 years for dural AV fistulas. The most common initial symptom associated with dural AV fistulas was steadily progressive paresis, whereas hemorrhage was the most common presenting symptom in cases of intramedullary lesions. No patients with dural AV fistulas had subarachnoid hemorrhage. Activity exacerbated symptoms more frequently in patients with dural lesions. Associated vascular anomalies occurred only in cases of intradural AVM's. In 96% of the dural lesions the AV nidus was in the low thoracic or lumbar region; in only 15% did the intercostal or lumbar arteries supplying the AVM also provide a medullary artery which supplied the spinal cord. In contrast, most intradural AVM's (84%) were in the cervical or thoracic segments of the spinal cord and all of them were supplied by medullary arteries. Transit of contrast medium through the intradural AVM's was rapid in 80% of cases, suggesting high-flow lesions. Forty-four percent of the patients with AVM's of the spinal cord had associated saccular arterial or venous spinal aneurysms. No dural AV fistulas displayed these characteristics. A good outcome occurred in 88% of patients with dural AV fistulas after nidus obliteration, while 49% of patients with intramedullary AVM's did well after surgery or embolization. These findings suggest that dural and intradural AVM's differ in etiology (acquired vs. congenital) and that they have different pathophysiology, radiographic findings, clinical presentation, and response to treatment.

Adolescent↗

Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome, and multiple endocrine neoplasia type I: a prospective study.

This study evaluates prospectively the effect of parathyroidectomy on basal acid output (BAO), maximal acid output (MAO), fasting serum gastrin, secretin-stimulated serum gastrin, and sensitivity to antisecretory medication in 10 consecutive patients with primary hyperparathyroidism (PHP), Zollinger-Ellison syndrome (ZES), and multiple endocrine neoplasia type I (MEN-I). After parathyroidectomy, 9 of 10 patients remained normocalcemic, and each had a lower BAO; 6 of 9 no longer had gastric acid hypersecretion (less than 15 mEq/hr). Seven of 9 normocalcemic patients had a lower MAO, and a decrease in fasting serum gastrin. Two patients showed no evidence of ZES, a normal BAO, normal fasting serum gastrin concentration, and a negative secretin response after parathyroidectomy. Parathyroidectomy also reduced the dose of histamine H2-receptor antagonist required to control gastric acid secretion in 60% of patients. After successful parathyroidectomy three patients were studied for drug sensitivity, and each had greater acid inhibition with a given dose of histamine H2-receptor antagonist than preoperatively. One patient remained hypercalcemic after surgery and had no change in BAO, MAO, or gastrin. All patients with postoperative normocalcemia will have a lower BAO, 80% a lower MAO, 80% a decreased fasting serum gastrin, and 33% a negative secretin test. Antisecretory medication dose can be reduced because patients have reduced BAO and increased sensitivity to histamine H2-receptor antagonist. The study supports parathyroidectomy as the initial surgical procedure of choice in patients with PHP, ZES, and MEN-I.

Adult↗

Nuclear magnetic resonance imaging in oncology.

MRI is synonymous with proton imaging. It provides detailed images of gross anatomy and pathology owing to the excellent soft-tissue contrast, signal void of flowing blood, versatile geometry, and freedom from streak artifacts, as well as other advantages summarized in Table 8-2. In the CNS, MRI has emerged as the most sensitive imaging modality in virtually all pathologies--some reservations remaining concerning acute hemorrhage, focal calcifications, and bone detail. Hence, it should be considered the premier noninvasive examination in the evaluation of the cancer patient with any suspicion of CNS pathology. Economics and availability must, of course, be considered when evaluating MR's role relative to CT. MR clearly provides the best means of excluding pathology, particularly in the posterior fossa, and must be considered after a negative CT examination with persistent clinical suspicions. MRI must also be considered in routine surveillance, if the earliest possible detection of metastasis, demyelination, and other pathologies is to be achieved. MRI should be considered in the evaluation of vertebral metastases, spinal cord compression, and back pain because of its ability to depict CSF, spinal cord, disk, and vertebral body as distinct structures and its sensitivity to marrow disease. In the extremities and pelvis, clearer depiction of soft tissues, vessels, and marrow is a proven advantage. Hence, MRI is indicated in the evaluation of prostate/bladder/rectal carcinoma, uterine/cervical carcinoma, soft tissues/bony sarcomas, and bone metastasis/infarction. In the abdomen, MRI's display of the retroperitoneum and sensitivity to liver lesions indicates its use in the evaluation and staging of renal/adrenal carcinoma, retroperitoneal sarcomas, primary liver tumors, and metastases. Moreover, MRI is also indicated in the evaluation of liver or adrenal masses of uncertain histology owing to a limited specificity of the MR signal for adenoma, carcinoma, and hemangioma. In the chest, MRI's advantages are currently limited owing to the excellent quality of CT images of mediastinum and lung parenchyma and the deleterious effects of respiratory motion. MRI's primary indications in the chest are for the distinction of mediastinal and hilar masses from vessels and aneurysms; evaluation of lumenal patency and superior vena cava syndrome; detection and display of pericardial effusion and the relationship of tumor to the pericardium; and evaluation of internal cardiac anatomy, thrombi, and tumor. Because of rapid technological advances, statements concerning MRI's limitations must be guarded.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal Neoplasms↗

Differentiation of adrenal masses by magnetic resonance imaging.

Eighty-one adrenal masses in 68 patients were examined with magnetic resonance imaging (MRI). Masses included nonfunctioning adenomas (17), metastases (25), adrenocortical carcinomas (10), and pheochromocytomas (23). T1-weighted pulse sequences depicted the anatomy with a resolution comparable to that of computed tomography (CT). T2-weighted pulse sequences provided some histologic specificity separating nonfunctioning adenomas with low signal-intensity from metastases with intermediate signal-intensity and pheochromocytomas with high signal-intensity. Pheochromocytomas could always be distinguished from other adrenal masses. In 20% of the cases, metastases with low signal-intensity could not be distinguished from nonfunctioning adenomas.

Adenoma↗

Hemiparkinsonism in monkeys after unilateral internal carotid artery infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Infusion of MPTP (0.2-0.8 mg/kg) into the right internal carotid artery of monkeys produces toxin-induced injury to the right nigrostriatal pathway with sparing of other dopaminergic neurones on the infused side and with negligible or little injury to the opposite, untreated side. There are contralateral limb dystonic postures, rigidity, and bradykinesia, but the animals are able to eat and maintain health without drug treatment. Spontaneous motor activity is attended by circling towards the injured side, whereas treatment with L-DOPA/-carbidopa or apomorphine stimulates circling towards the intact side. Dopamine and dopamine metabolite levels are normal in the left caudate and putamen, but markedly depressed on the right (MPTP-treated) side. This animal hemiparkinsonian model will be useful in studies of volitional movement control, drug treatments of Parkinson's disease, and functional efficacy of brain tissue implants.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1.

Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [3H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause.

Adenoma↗

Jet-directed catheter for interventional radiology.

A new catheter of dual lumen construction, suitable for clinical use, is capable of navigating acute vessel branches by selective retrojet fluid thrusts issuing from cowlings built into its distal sidewalls. Conventional radiopaque liquids can be used both to drive the system and to fluoroscopically locate its position relative to the vascular network. In vitro studies have shown the catheter to traverse straight vessels and negotiate difficult lateral turns over short radii in the process of entering progressively smaller branches. In vivo studies have verified these capabilities and suggest a means for embolizing tumors and arteriovenous malformations located at otherwise inaccessible regions. For arterial infusion of drugs to treat tumors, the turbulent jet action is utilized to enhance mixing within the blood stream to overcome the streaming phenomenon common to other catheters. The result is better distribution of the agent and increased opportunity for the drug to reach more of the tumor. The catheter system is undergoing clinical trials.

Angiography↗

Prevention of ocular toxicity of carmustine (BCNU) with supraophthalmic intracarotid infusion.

Intracarotid administration of carmustine (BCNU) is an increasingly accepted therapeutic modality for primary brain tumors. Its beneficial effect on prolonging survival, however, is countered by its frequent delayed complication of retinal toxicity and severe visual loss, which reportedly occurs in approximately 70% of the patients. Since this complication probably results from increased flow of the drug into the ophthalmic artery, the authors have attempted to infuse BCNU via a small intracarotid catheter advanced beyond the origin of the ophthalmic artery. In a series of nine patients (average follow-ups, 10.7 months), the authors were successful in treating six patients with exclusively supraophthalmic infusions. None of these patients developed any ocular toxicity. From the remaining three patients, two patients received one infraophthalmic infusion with no retinal toxicity. The third patient, however, who received three infraophthalmic infusions, developed ipsilateral retinopathy. These results suggest that retinopathic complications of intracarotid BCNU can be avoided if the infusion catheter is advanced beyond the origin of the ophthalmic artery.

Adolescent↗

Aggressive resection of metastatic disease in selected patients with malignant gastrinoma.

Fifteen patients with Zollinger-Ellison syndrome followed at the National Institutes of Health with extensive metastatic disease had an actuarial 5-year survival of 20%. Therefore, in 1982 a prospective study to examine the effect and feasibility of removing all gross tumor in selected patients with extensive metastatic disease was instituted. Five patients with extensive metastatic gastrinoma confined to the abdomen in whom imaging studies suggested the possibility of complete surgical resection were entered into this study and underwent attempted complete surgical resection and chemotherapy with streptozotocin, doxorubicin, and 5-fluorouracil. Median follow-up was 24 months. Surgical resection of all gastrinoma was possible in 4/5 patients attempted. In one patient in whom all gross disease could not be resected, the residual tumor progressed and the patient died 19 months after operation. All four patients with all disease resected appeared to benefit since all of them had a significant reduction in antisecretory medications and are enjoying normal activity and work. Three patients have had no detectable tumor on follow-up, and two of these patients are clinically and biochemically "cured" with normal fasting gastrin levels and negative provocative gastrin tests at 14 and 32 months. Therefore, aggressive resection of metastatic disease in selected patients with malignant gastrinoma is recommended.

Abdominal Neoplasms↗