Acute leukemia associated with the t(4;11) chromosome rearrangement: ultrastructural and immunologic characteristics

The acute leukemia associated with the t(4;11) chromosome rearrangement is characterized by relatively consistent clinical features: occurrence primarily in young individuals, hyperleukocytosis, and poor response to therapy. This study describes the morphological, ultrastructural, and immunologic characteristics of the leukemic cells from ten patients with this type of leukemia. The morphological features of the leukemic blasts vary from lymphoid-appearing to monocytic. Ultrastructurally and cytochemically, some of the lymphoid-appearing blasts possess features of myeloid origin. The immunologic phenotype is characteristically E- SIg- CALLA- BA-1- BA-2+ HLA-DR+ and TdT+. These findings suggest that the t(4;11)-associated acute leukemia represents a proliferation of an early myeloid progenitor cell.     

Clinical results of a novel wide beam reconstruction method for shortening scan time of Tc-99m cardiac SPECT perfusion studies.

BACKGROUND: Newly developed reconstruction algorithms enable the acquisition of images at half of the scan time while maintaining image quality. The purpose of this investigation was to evaluate a novel wide beam reconstruction (WBR) method developed by UltraSPECT for decreasing scan times and to compare it with filtered backprojection (FBP), which is the technique routinely used. METHODS AND RESULTS: Phantom and clinical studies were performed. Hot and cold sphere and cardiac phantom acquisitions were reconstructed via WBR, FBP, and ordered-subsets expectation maximization. Fifty patients were prospectively studied by use of both a standard and a short protocol. The short protocol was performed first on 29 of 50 patients via 8-frame gated technetium 99m stress single photon emission computed tomography and low-energy high-resolution collimators. Stress Tc-99m studies (30-45 mCi) were scanned for 20 seconds per frame. For the short protocol, all parameters remained constant except for the time per frame, which was reduced by 50% on Tc-99m studies. All resting Tc-99m scans (36/50 patients) were processed with FBP for the standard full-scan time studies and with WBR for the short scan studies. The images were interpreted by use of a 17-segment model and 5-degree severity score, and the perfusion and functional variables were determined. Distributions including mean, median, and interquartile ranges were examined for all variables. The differences (FBP - WBR) were computed for all variables and were examined by use of nonparametric signed rank tests to determine whether the median difference was 0. The absolute value of the difference was also examined. Spearman rank-order correlation, a nonparametric measure of association, was used for the 2 methods to determine significant correlations between variables. The hot and cold sphere phantom studies demonstrated that WBR had improved contrast recovery and slightly better background uniformity than did the ordered-subsets expectation maximization. The cardiac phantom studies performed with attenuating medium and background activity showed that the half-scan time images processed with WBR had better contrast recovery and background uniformity than did the full-scan time FBP reconstruction. In the clinical studies, highly significant correlations were observed between WBR and FBP for functional as well as perfusion variables (P < .0001). The summed stress score, summed rest scores, and summed difference score were not statistically different for FBP and WBR (P > .05). Left ventricular volumes had a high correlation coefficient but were significantly larger with FBP than with WBR. CONCLUSION: Our study results suggest that cardiac single photon emission computed tomography perfusion studies may be performed with the WBR algorithm using half of the scan time without compromising qualitative or quantitative imaging results.     

Reappraisal of Partial Ileal Bypass for the Treatment of Familial Hypercholesterolemia

Eleven patients with heterozygous familial hypercholesterolemia (type IIa) were treated by partial ileal bypass. Postoperatively, mean total cholesterol levels fell by 26% at 1 month, and then rose steadily to 20% below preoperative levels of 20-24 months. The rise in cholesterol levels was due in part to an increase in high density lipoprotein (HDL) cholesterol with a resultant improvement in the HDL:LDL ratio (LDL, low density lipoprotein). Five patients had refractory hypercholesterolemia and were treated with lovastatin. One of them was treated with a combination of lovastatin and LDL-apheresis. All patients experienced diarrhea which improved with time, but two patients required reversal of their bypass for intractable gas bloat syndrome. Each received lovastatin to control recrudescence of hypercholesterolamia following reversal. Ten patients are alive and well, but one patient died after a myocardial infarction 55 months postoperatively. The advent of lovastatin and other HMG COA reductase inhibitors is likely to decrease the use of partial ileal bypass to treat familial hypercholesterolemia.     

Amino acid absorption and incorporation after hypophysectomy

Uptake of the amino acidsl-glycine,l-leucine,dl-methionine, anddl-ornithine by the small bowel of the rat was enhanced during a 4 to 5 day period following hypophysectomy but was subsequently depressed. Synthesis of small-bowel protein was depressed soon after hypophysectomy. These early effects were independent of the reduced food intake by the hypophysectomized animals.     

Inadequacy of predicted creatinine clearance as guide to chemotherapy

Many chemotherapeutic agents are nephrotoxic and/or excreted via the kidney. Thus, careful evaluation of renal function is important since drug dosages are often lowered in patients with impaired renal function. When the creatinine clearance as calculated by the method of Cockcroft and Gault from the patient's age, weight, and serum creatinine was compared to the measured creatinine clearance in the same patients, the correlation coefficient was low (r = 0.40) and the average difference between the predicted and measured creatinine clearance values was 25.3%. Thus, in our patient population, creatinine clearance calculated by the method of Cockcroft and Gault did not correlate well with measured creatinine clearance and thus was not useful as a clinical tool.     

Duodenal Obstruction by Abdominal Aortic Aneurysms

We report a case of duodenal obstruction caused by an abdominal aortic aneurysm. The duodenum was firmly attached to the lateral wall of the aneurysm by a tough, fibrous band. Duodenal obstruction is a rare presenting complaint in a patient with an abdominal aortic aneurysm. Anatomic features have not been routinely described in previous patients. We propose a mechanism for the cause of this entity and a review of the literature. The treatment of choice is resection of the aneurysm with graft replacement of the aorta.     

Human thrombocytopenia is associated with structural abnormalities of the endothelium that are ameliorated by glucocorticosteroid administration

Capillary fragility is characteristic of severe thrombocytopenia. This mechanical weakness may not be solely accounted for by decreased ability of platelets to repair endothelial breaks. Platelets may have a role in maintaining endothelial hemostasis. This laboratory has demonstrated thinning of capillary endothelium in experimental thrombocytopenia. We now report similar findings in human thrombocytopenia. Capillary endothelium supplying either skin or skeletal muscle was found to have a mean thickness only half that of normal as well as frequent very thinned areas, including some fenestrations. All findings reverted toward normal after four days of prednisone administration at a time the degree of thrombocytopenia was equally severe. These findings are consistent with the hypothesis that platelets are necessary for normal structure and function of endothelial cells and that glucocorticosteroid administration may ameliorate the pathophysiology of thrombocytopenia.     

Identification of the hereditary pyropoikilocytosis carrier state

We evaluated the hematologic, rheologic, and biochemical features of erythrocytes obtained from 10 relatives of a 5-yr-old black female with hereditary pyropoikilocytosis (HPP) and severe hemolytic anemia. Erythrocyte morphology was normal in the father and five other relatives, but ghost mechanical fragility and drug-induced red cell endocytosis were increased, as was the percentage of spectrin dimers noted on 3.2% nondenaturing PAGE of spectrin extracts. Identical changes were also noted in the mother and her sister, whose erythrocytes were elliptocytic and exhibited morphological changes upon heating to 45 degrees-48 degrees C (normal 49 degrees). The two other family members were normal in every respect. SDS-PAGE analysis of membrane proteins demonstrated diminished amounts of spectrin in HPP erythrocytes, but was normal in other family members. A diffuse band (mol wt 575,000-665,000), composed entirely of spectrin, was apparent adjacent to the dimer region on nondenaturing PAGE of spectrin extracts from the propositus, mother, and aunt. In this family, HPP appears to have resulted from compound heterozygosity for two distinct genetic abnormalities (reflected by the differences between elliptocytic and nonelliptocytic carriers). Although the membrane abnormalities in carriers did not result in hemolytic anemia, they were of sufficient magnitude to allow the detection of the carrier state.