Technetium-99m-MAG3 renal studies in spinal cord injury patients: normal range, reproducibility, and change as a function of duration and level of injury

The normal range, reproducibility, and change as a function of duration and level of injury for Tc-99m-MAG3 renal studies were quantitated in spinal cord injury (SCI) patients. METHODS: Five SCI patients without evidence of renal disease in each of four groups: less than 2 months, 2-12 months, 1-2 years, and greater than 2 years from time of injury, were each studied twice. There were at least two patients with paraplegia and two with tetraplegia in each group. Renal clearance (camera based method), percent function in each kidney, time of peak renal parenchymal activity, and half time of parenchymal activity following the peak were evaluated. The peak and half times were determined with regions of interest (ROIs) over the entire kidney and over just the cortex. All results were compared to normal ranges previously established in normal subjects of the same age range using the same methodology. RESULTS: Renal clearance in the less than 2 month SCI patients was not significantly different from normal subjects in either paraplegic or in tetraplegic individuals. However, clearance in tetraplegics was increased by 28.5% at 2-12 month, increased by 50.6% at 1-2 years, and decreased by 25.9% at greater than 2 years compared to normal subjects (all P < 0.02). Clearance in those with paraplegia showed a similar, but less marked, trend (P = NS). The time of peak parenchymal activity when measured with cortical ROIs did not vary among patient groups or level of injury, but was increased compared to normal subjects (P < 0.05). The percent function in each kidney and half time following the peak were symmetrical, did not differ among patient groups or with level of injury, and did not differ from normal subjects. The parenchymal peak time was significantly shorter with cortical rather than renal ROIs in all patient groups (P < 0.05). In serial studies in the same patient the percent standard deviation in total renal clearance was less than between single studies in different patients, but the decrease was significant for only the right kidney (P < 0.03), and the decrease was not as great as in normal subjects. In addition, the percent standard deviation for percent function in each kidney was significantly less than the percent standard deviations in single studies (P < 0.02). There were no significant differences between intra- and interpatient studies for any other parameter. CONCLUSION: We conclude that: (1) renal clearance measured with Tc-99m-MAG3 in tetraplegic patients increases significantly during the first 2 years following injury and decreases significantly thereafter; there is a similar, but much less marked, trend in paraplegics, (2) parenchymal peak times with cortical ROIs occur later for SCI patients than for normal subjects, and (3) there is more intrapatient variation in total renal clearance and percent renal clearance on a side in SCI patients than in normal subjects suggesting that it may be harder to study SCI patients reproducibly. These findings should be taken into account when performing and interpreting Tc-99m-MAG3 renal studies in SCI patients.     

Cervical lymph node metastatic patterns of squamous carcinomas in the upper aerodigestive tract

We report a patient with medial medullary infarction who showed deep sensory impairment as his prominent neurological manifestation. A 54-year-old man with a history of hypertension was admitted to our hospital with numbness of the bilateral upper and lower extremities, followed by dysarthria and right hemiparesis. Physical examination revealed no abnormalities except for high blood pressure. He hiccuped continuously. On neurological examination, he exhibited dysarthria, mild dysphagia and right hemiparesis without facial or lingual paresis. Sensitivity to light touch and pinprick was normal, but sensitivity to vibration and joint position was severely decreased in the bilateral upper and lower extremities, predominantly in the lower extremities and on the right side in the upper extremities. He had been treated with antiedema agents and thromboxane synthetase inhibitor. His hiccups stopped within two weeks, and his right hemiparesis gradually improved within one month. However, his deep sensory impairments remained prominent. Blood examinations disclosed positive lupus anticoagulant. MRI showed bilateral infarction at the medial portion of the upper medulla oblongata, extending to both pyramids, especially on the left. Somatosensory evoked potentials (SEP) after median nerve stimulation showed P14 and the later components with prolonged latency. No SEP were recorded after posterior tibial nerve stimulation. The latency of P14 was well correlated with the severity of deep sensory impairments in the upper extremities. Neurological manifestations of our patient are not typical of medial medullary infarction, and are informative about the functional anatomy of the deep sensory tract in the medulla oblongata. We discuss the relation of the intractable hiccups to the bilateral medial medullary lesions, and emphasize the importance of lupus anticoagulant as one of the risk factors in brainstem infarction.     

Allogeneic marrow transplantation for myelodysplastic syndrome with advanced disease morphology: a phase II study of busulfan, cyclophosphamide, and total-body irradiation and analysis of prognostic factors

PURPOSE: To determine if an intensive preparative regimen of busulfan (BU), cyclophosphamide (CY), and total-body irradiation (TBI) could improve outcome after marrow transplantation for advanced morphology myelodysplasia (refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEB-T], and chronic myelomonocytic leukemia [CMML]) compared with that obtained with conventional CY/TBI and to analyze prognostic factors for transplantation for myelodysplasia. PATIENTS AND METHODS: A phase II study was conducted of 31 patients (median age, 41 years) treated with BU (7 mg/kg), CY (50 mg/kg), TBI (12 Gy), and human leukocyte antigen (HLA)-matched (n = 23) or -mismatched (n = 2) related or unrelated donor (n = 6) marrow transplantation. Results were compared with 44 historical control patients treated with CY (120 mg/kg) and TBI. RESULTS: The 3-year actuarial disease-free survival (DFS) rate was similar for the BU/CY/TBI group and the CY/TBI group (23% v 30%, P = .6), but there were trends toward lower relapse rates (28% v 54%, P = .27) and higher nonrelapse mortality rates (68% v 36%, P = .12) among the current patients compared with historical controls. Multivariate analysis showed that a normal karyotype pretransplant and the use of methotrexate as part of posttransplant immunosuppression were associated with improved survival and reduced nonrelapse mortality. Univariate analysis showed significant differences in relapse rates based on marrow source (57% for HLA genotypically matched marrow v 18% for all others, P = .04) and on disease morphology (66% for RAEB-T v 38% for RAEB and CMML, P = .05). CONCLUSION: Patients with advanced morphology myelodysplasia tolerated the intensified BU/CY/TBI preparative regimen and reduced posttransplant immunosuppression poorly. Novel transplant procedures are needed to reduce relapse rates without increasing nonrelapse mortality rates. In addition, transplantation before progression to RAEB-T, if possible, may reduce the risk of relapse.     

Mechanism-based design of prolactin receptor antagonists

The mechanism of action of two forms of the prolactin (PRL) receptor was studied using analogs of human growth hormone (hGH). At low concentrations (approximately 1 pM), hGH binds and stimulates proliferation of Nb2 cells containing the 391-residue PRL receptor as well as murine lymphoid FDC-P1 cells transfected with the 591-residue hPRL receptor. However, at high concentrations (approximately 70 microM) hGH inhibits proliferation of both these cell lines. Such a "bell-shaped" hormone response curve was observed for hGH stimulation of the hGH receptor (Fuh, G., Cunningham, B.C., Fukunaga, R., Nagata, S., Goeddel, D. V., and Wells, J.A. (1992) Science 256, 1677-1680) and is consistent with the sequential formation of an active hormone-(receptor)2 complex in which hGH binds through a first site (Site 1) to a first receptor and then through a second site (Site 2) to a second receptor. By analogy to hGH activation of the hGH receptor, we find that hGH variants that are mutated in Site 1 or Site 2 are greatly reduced as agonists. Similarly, only Site 2 mutants are potent antagonists of either hGH or hPRL stimulated cell proliferation. These and other data support the notion that hGH and hPRL activate the PRL receptor by sequential dimerization and provide a rational basis for the design of potent antagonists to the prolactin receptor.     

Interhemispheric subdural hematoma in adults: case reports and a review of the literature

The interhemispheric subdural hematoma is a relatively uncommon type of subdural hematoma, especially seen in patients with blood clotting disturbances. When its mass becomes sufficiently large, specific neurological abnormalities such as hemiparesis and signs of the falx syndrome are seen. Treatment can consist of conservative observation or craniotomy and is dictated by the clinical course. Conservative management is the treatment of choice for patients without disturbances of consciousness and for patients with stable clinical conditions. Surgical treatment is necessary in patients with progressive deterioration. Three case reports are presented, as well as a review of 64 cases described in the literature. The salient aspects of this clinical entity are discussed.     

Fibromuscular dysplasia of the internal carotid artery associated with alpha1-antitrypsin deficiency

OBJECTIVE: A deficiency of alpha1-antitrypsin has been implicated in the development of various disorders affecting medium-sized arteries, including intracranial aneurysms, cervicocephalic arterial dissections, and fibromuscular dysplasia (FMD). We performed alpha1-antitrypsin phenotyping in three consecutive patients who underwent bypass surgery for FMD of the extracranial internal carotid artery to test the hypothesis that alpha1-antitrypsin deficiency is a genetic risk factor for the development of FMD. METHODS: The study population consisted of three women (aged 37, 49, and 53 years, respectively) who had bilateral internal carotid artery stenosis caused by FMD. The indications for surgery included ocular or cerebral ischemic symptoms in two patients and progressive stenosis in one patient. The diagnosis of FMD was confirmed by histological examination of the resected segment of artery. The alpha1-antitrypsin phenotype was determined by isoelectric focusing in polyacrylamide gels. RESULTS: Two of the three patients had a heterozygous alpha1-antitrypsin deficiency (PiMZ phenotype). Pathological examination of the resected arterial segment showed typical medial FMD with focal intimal fibroplasia in both patients with the PiMZ phenotype. CONCLUSION: These findings suggest that a heterozygous alpha1-antitrypsin deficiency may be a genetic risk factor for the development of FMD of the internal carotid artery.