A phase I/II study of sequential interleukin-3 and granulocyte- macrophage colony-stimulating factor in myelodysplastic syndromes

In this phase I/II study, 9 patients with myelodysplastic syndromes (MDS) were treated with interleukin-3 (IL-3) followed by granulocyte- macrophage colony-stimulating factor (GM-CSF). Each treatment cycle was 28 days long and administered as follows: 1 microgram/kg/d IL-3 on days 1 through 7 and 3 micrograms/kg/d GM-CSF for days 8 through 21, followed by a 7-day rest period. IL-3 dose escalations were planned, but the dose of GM-CSF was fixed. Three patients had refractory anemia, 4 had refractory anemia with ringed sideroblasts, and 2 had refractory anemia with excess blasts. Six patients were dependent on red blood cell transfusions, 1 on platelet transfusions, and 2 on both. The absolute neutrophil count improved in 7 (77%) patients and the platelet count improved in 3 (33%) patients during therapy. Hemoglobin levels were unchanged. A clinically relevant response was seen in only 1 patient with thrombocytopenia, and he received five cycles of therapy. The neutrophil count decreased in 2 patients and the platelet count decreased in 4 patients during treatment. The toxicity of the treatment was significant. In the first cohort of 3 patients, 1 patient developed supraventricular tachycardia and congestive heart failure. In the second group, 1 patient developed progressive granulocytopenia and died of gram-negative septicemia. Because of the disparate toxicity, 3 more patients were treated at the same dose level. One of these experienced a high fever and bone pain requiring hospitalization. Because of these adverse effects, the IL-3 dose was not escalated and all patients received 1 microgram/kg/d for 7 days. We believe that sequential therapy with IL-3 and GM-CSF at these dose levels causes unacceptable toxicity in patients with MDS. The major toxic events occurred during weeks 4 and 5 after starting treatment and may have been primarily caused by GM-CSF therapy. Although neutrophil counts improve in most patients, the effect on red blood cells and platelets is minimal. At present, this form of therapy remains problematic and appears to have a limited potential in the management of MDS.     

Degenerative lumbar disk disease: pitfalls and usefulness of MR imaging in detection of vacuum phenomenon

Magnetic resonance (MR) images of the lumbar spine from 150 patients were retrospectively reviewed. In 14 of these patients, at 18 disk levels, a vacuum phenomenon (VP) had been identified on plain radiographs and/or computed tomographic scans. The MR imaging appearance of these gas collections in 17 disks was an area without signal, best seen on spin-echo sequences with short repetition time and echo time in the sagittal view. MR imaging precisely located the VP in the anulus fibrosus, the nucleus pulposus, and Schmorl nodes. In all but one case, degeneration of the disk was complete and associated with adjacent changes in vertebral bone. Pitfalls of MR imaging detection of VP included chemical shift artifact, calcifications, and tears without gas in the disk.     

Percutaneous spermatic vein occlusion: evaluation of sclerosing agents in experimental animals

The 5%-20% rate of recurrence of testicular varicoceles after embolotherapy has been a persistent clinical problem. Three sclerosing agents--sodium tetradecyl sulfate 3%, absolute ethanol, and 100 degrees C contrast material--were evaluated in canine spermatic veins for degree and durability of venous occlusion. Pathologic examination for perivenous, pulmonary, and neural changes was performed. Both sodium tetradecyl sulfate and absolute ethanol were effective sclerosants, but sodium tetradecyl sulfate was technically easier to use. The use of a sclerosant in conjunction with balloons or coils is the safest, most effective technique for occluding variococeles and minimizing postembolotherapy recurrences.     

Chemical Nature of the Interaction between Macrophage Fusion Factor and Macrophage Membranes

Giant-cell formation induced by macrophage fusion factor (MFF) was not altered after pretreatment of macrophages with trypsin, chymotrypsin, pronase, neuraminidase, phospholipase C, or phospholipase D. Pretreatment of macrophages with either alpha-mannosidase or alpha-glucosidase completely inhibited giant-cell development, without altering macrophage viability. No alteration of giant-cell formation was observed when 0.1 M of L-fucose, N-acetyl-glucosamine, D-arabinose, D-xylose, melibiose, D-glucose, D-galactose, alpha-lactose, sucrose, D-fructose, or maltose was present during incubation of macrophages with MFF. Giant-cell formation was abolished when 0.1 M alpha-D-mannose was present during macrophage incubation with MFF. These results suggest that the protein moiety of MFF recognizes a specific receptor site on the macrophage membrane, one that is different from those described for other lymphokines and contains alpha-mannose.     

Multiple sclerosis: gadolinium enhancement in MR imaging

Magnetic resonance (MR) images--both nonenhanced and enhanced with gadolinium DTPA/dimeglumine (Gd)--were compared with high-iodine (88.1 g I) computed tomographic (HICT) scans in demonstrating lesions in 15 patients known to have multiple sclerosis (MS). T1-weighted, mixed (T1, proton density, and T2), and T2-weighted MR pulse sequences were used. More than 20 lesions in each of 14 patients were demonstrated by pre-Gd mixed images and T2WI. Nine patients had clinical symptoms of active disease. Gd-enhanced T1WI showed at least one lesion that appeared to correspond with newly reported symptoms or signs. In addition, three clinically stable patients showed enhancement. Enhancement was best seen on 3-minute T1WI. HICT scans showed enhancement in four of the nine patients with active disease and in none of five clinically stable patients. Gd-enhanced MR imaging appears to be more sensitive than HICT in the detection of the transient abnormalities of the blood-brain barrier that occur in patients with active MS and appears capable of distinguishing active lesions that may correspond to the anatomic regions responsible for abnormal clinical findings.     

Gamma Probe Radioguided Parathyroid Forearm Surgery in Recurrent Hyperparathyroidism

A case is described of a successful radioguided forearm graft parathyroidectomy. This is the first report of both pre-operative diagnostic and successful intra-operative localisation during a single procedure, of autologous transplanted parathyroid tissue.