Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

Central regulation of intestinal basal and stimulated water and ion transport by endogenous opiates in dogs

The influence of intracerebroventricular (ICV) vs intravenous (IV) administration of (D-Ala2, Met5) enkephalinamide (Dalamide) on normal and stimulated (cholera toxin) jejunal fluxes of water, Na+, and K+ were investigated in dogs prepared with a Thiry-Vella (TV) loop. Intestinal transport in the TV loop and concomitant transit time were measured during an infusion (2 ml/min) of an isotonic electrolyte solution alone, or containing 0.4 micrograms/ml of cholera toxin (CT). Basal net water absorption was slightly, but significantly (P less than 0.05), increased during an ICV infusion of Dalamide at 0.5 ng/kg/min, while the secretory effects of cholera toxin were markedly reduced by nearly 75%. Similar effects were observed for Na+ and K+ movement. In contrast, Dalamide infused intravenously at a five times higher dose, ie, 2.5 ng/kg/min did not affect the control and CT-stimulated water and electrolyte movements. The jejunal loop transit times were halved during CT infusion. Similar values were observed under Dalamide ICV administration as well as during a five times higher dose of Dalamide administered intravenously. It was concluded that (1) Dalamide administered into the CNS, but not peripherally, increased the absorption of water, Na+, and K+, causing a net reduction in their secretion induced by cholera toxin; and (2) these effects did not result from changes in transit time. These results also suggest that Met-enkephalin can act in the brain to affect the intestinal transport of water and electrolytes in dogs.     

Integration of local inputs in visual cortex

In mammalian visual cortex, local connections are ubiquitous, extensively linking adjacent neurons of all types. In this study, optical maps of intrinsic signals and responses from single neurons were obtained from the same region of cat visual cortex while the effectiveness of the local cortical circuitry was altered by focally disinhibiting neurons within a column of known orientation preference. Maps of intrinsic signals indicated that local connections provide strong and functional subthreshold inputs to neighboring columns of other orientation preferences, altering the observed orientation preference to that of the disinhibited column. However, measuring the suprathreshold response using single-cell recordings revealed only mild changes of preferred orientation over the affected region. Because strongly tuned subthreshold inputs from cortex only marginally affect the tuning of a cortical cell's output, it is concluded that local cortical inputs are integrated weakly compared to geniculate inputs. Such circuitry potentially allows for the normalization of responses across a wide range of input activity through local averaging.      

VALIDATION OF A SUBENDOCARDIAL ISCHAEMIC SHEEP MODEL BY INTRACORONARY FLUORESCENT MICROSPHERES

1. We evaluated the use of non-radioactive fluorescent-labelled microspheres (FM) for the measurement of regional myocardial blood flow (RMBF) in an ischaemic sheep model. 2. Injection of FM directly into the coronary artery was compared with left atrial injection. There was a good correlation in the measurement of RMBF between these two injection methods (r = 0.92; n= 107 data points). Injection into the coronary artery requires less FM (one twentieth of that required by atrial injection) and is more economical. 3. The use of a fluorescent technique without filtering myocardial tissue was investigated. Calibration curves from the fluorescence plus myocardial tissue samples were similar to those of the pure fluorescence samples and both showed a linear relationship between fluorescent intensity and the number of microspheres (r > 0.97). These results indicate that the extraction of six fluorescent dyes (blue-green, yellow-green, green, orange, red and crimson) directly from the aqueous solution using ethyl acetate is effective. 4. A subendocardial ischaemic model was produced by partially occluding the circumflex artery (CxA) with concomitant left atrium (LA) pacing. During ischaemia, the endocardium/epicardium (Endo/Epi) flow ratios in the ischaemic area changed from 1.04 ± 0.12 to 0.47 ± 0.17 (P < 0.05; CxA injection) and from 1.08 ± 0.12 to 0.51 ± 0.05 (P < 0.05; LA injection). The ratio in the non-ischaemic area remained unchanged (1.12 ± 0.26 to 1.01 ± 0.22; not significant). 5. RMBF calculation using coronary inflow as the reference flow was also compared with that using the traditional method. We found that, in this study in which a non-filtering technique was applied, using coronary inflow as the reference flow was superior to the conventional distal sampling method.