High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.     

Antibody to human T-lymphotropic virus type III in wives of hemophiliacs. Evidence for heterosexual transmission

To evaluate the risk of heterosexual transmission of the acquired immunodeficiency syndrome, lymphadenopathy, and infection with human T-lymphotropic virus type III (HTLV-III), we studied 42 hemophiliacs and their wives. By early 1984, 9 of the hemophiliacs had asymptomatic lymphadenopathy and 1 had the acquired immunodeficiency syndrome. Twenty-one hemophiliacs, including all 10 with clinically overt disease, had antibody to HTLV-III. None of the 42 wives had lymphadenopathy or the acquired immunodeficiency syndrome but 2 had HTLV-III antibody. One of these women had evidence of immunologic dysfunction with a markedly reduced T-helper/suppressor cell ratio. The husbands of these 2 women both had HTLV-III antibody, but neither had overt acquired immunodeficiency syndrome-related disease. Thus, as of early 1984, the prevalence of HTLV-III antibody in wives of hemophiliacs seropositive for HTLV-III was 9.5% (2 of 21). We conclude that transmission of HTLV-III occurs between hemophiliacs and their heterosexual partners.     

Two types of muscarinic response to acetylcholine in mammalian cortical neurons.

Applications of acetylcholine (AcCho) to pyramidal cells of guinea pig cingulate cortical slices maintained in vitro result in a short latency inhibition, followed by a prolonged increase in excitability. Cholinergic inhibition is mediated through the rapid excitation of interneurons that utilize the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). This rapid excitation of interneurons is associated with a membrane depolarization and a decrease in neuronal input resistance. In contrast, AcCho-induced excitation of pyramidal cells is due to a direct action that produces a voltage-dependent increase in input resistance. In the experiments reported here, we investigated the possibility that these two responses are mediated by different subclasses of cholinergic receptors. The inhibitory and slow excitatory responses of pyramidal neurons were blocked by muscarinic but not by nicotinic antagonists. Pirenzepine was more effective in blocking the AcCho-induced slow depolarization than in blocking the hyperpolarization of pyramidal neurons. The two responses also varied in their sensitivity to various cholinergic agonists, making it possible to selectively activate either. These data suggest that AcCho may produce two physiologically and pharmacologically distinct muscarinic responses on neocortical neurons: slowly developing voltage-dependent depolarizations associated with an increase in input resistance in pyramidal cells and short-latency depolarizations associated with a decrease in input resistance in presumed GABAergic interneurons.     

Left ventricle: automated segmentation by using myocardial effusion threshold reduction and intravoxel computation at MR imaging

This retrospective analysis of existing patient data had institutional review board approval and was performed in compliance with HIPAA. No informed consent was required. The purpose of the study was to develop and validate an algorithm for automated segmentation of the left ventricular (LV) cavity that accounts for papillary and/or trabecular muscles and partial voxels in cine magnetic resonance (MR) images, an algorithm called LV Myocardial Effusion Threshold Reduction with Intravoxel Computation (LV-METRIC). The algorithm was validated in biologic phantoms, and its results were compared with those of manual tracing, as well as those of a commercial automated segmentation software (MASS [MR Analytical Software System]), in 38 subjects. LV-METRIC accuracy in vitro was 98.7%. Among the 38 subjects studied, LV-METRIC and MASS ejection fraction estimations were highly correlated with manual tracing (R(2) = 0.97 and R(2) = 0.95, respectively). Ventricular volume estimations were smaller with LV-METRIC and larger with MASS than those calculated by using manual tracing, though all results were well correlated (R(2) = 0.99). LV-METRIC volume measurements without partial voxel interpolation were statistically equivalent to manual tracing results (P > .05). LV-METRIC had reduced intraobserver and interobserver variability compared with other methods. MASS required additional manual intervention in 58% of cases, whereas LV-METRIC required no additional corrections. LV-METRIC reliably and reproducibly measured LV volumes. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/248/3/1004/DC1.     

Quantitative MR susceptibility mapping using piece‐wise constant regularized inversion of the magnetic field

Magnetic properties characterized by susceptibility and chemical shift linearly modify the local magnetic field experienced by spins. A piece‐wise constant solution using magnetic resonance imaging is found to the challenging inversion problem from field to magnetic properties. The magnetic field shifts were estimated from MR phase images. The MR magnitude images were segmented into many regions of uniform magnetic properties. Standard linear regression using the calculated magnetic field from each region allowed accurate susceptibility quantification. The technique was experimentally validated on a variety of samples including water, vegetable oil, air, Gadolinium, and superparamagnetic iron oxides. Susceptibility was measured with a precision better than 0.1 ppm, in a range of 10 ppm. In vivo feasibility was shown on the forearm for which soft‐tissue, cortical bone, and bone marrow susceptibility, and chemical shift values in good agreement with literature data were obtained. Magn Reson Med 60:1003–1009, 2008. © 2008 Wiley‐Liss, Inc.     

Active surveillance is superior to radical nephrectomy and equivalent to partial nephrectomy for preserving renal function in patients with small renal masses: Results from the DISSRM registry

Purpose

We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry.

The effects of homocysteine and MTHFR genotype on hip bone loss and fracture risk in elderly women

Summary  Few studies have evaluated the effects of homocysteine and methylenetetrahydrofolate reductase (MTHFR) genotype on age-related bone loss. In our 5-year cohort study with 1,213 women aged 70–85 years, high homocysteine is associated with greater hip bone loss but not fracture risk. The effect of MTHFR genotype on bone density and fracture is weak. Introduction  Previous studies on the effects of homocysteine and MTHFR genotype on bone mineral density (BMD) and osteoporotic fracture risk have shown inconsistent results. Few studies have evaluated their effects on age-related bone loss. We evaluated the effects of homocysteine and MTHFR genotype variation on hip BMD and fracture risk over 5 years in a cohort of 1,213 community-dwelling women aged 70–85 years. Methods  Nutritional intake and prevalent fracture status were assessed at baseline, plasma homocysteine was measured at year 1, and hip dual-energy X-ray absorptiometry (DXA) BMD was measured at years 1 and 5. Clinical incident osteoporotic fractures confirmed by radiographic report were collected throughout the study and the MTHFR gene C677T and A1298C polymorphisms genotyped. Data were analyzed using analysis of covariance and Cox proportional hazard regression. Results  The highest tertile of homocysteine was associated with a greater hip BMD loss over 4 years (−2.8%) compared to the middle (−1.6%) and lowest tertiles (−1.2%) (P < 0.001). This effect remained after adjustment for covariates. There was no effect of homocysteine on fracture prevalence or incidence. MTHFR gene variation was only weakly related to one of the bone outcome measures. Conclusion  In this study population, high homocysteine is associated with greater hip bone loss but not fracture risk.