Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia

Elevated numbers of primitive Philadelphia chromosome-positive (Ph+) progenitors, including long-term culture-initiating cells (LTC-IC) as well as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which focused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent and occasionally exclusive presence of circulating normal (Ph-) LTC-IC, often at levels above those seen for LTC-IC in the blood of normal individuals. The presence of detectable numbers of circulating Ph- LTC-IC was independent of the fact that the same peripheral blood samples also contained elevated numbers of predominantly or exclusively Ph+ CFC. Interestingly, both the Ph+ and Ph- LTC-IC in these samples were CD34+CD71- and variably CD38- and Thy-1+, as previously documented for LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1 expression was useful for discriminating between Ph+ and Ph- LTC-IC in mixed populations. Nevertheless, an association of these phenotypes with LTC- IC function did allow highly enriched (> 5% pure) suspensions of either Ph+ or Ph- LTC-IC to be obtained from selected samples of CML blood in which the initial LTC-IC population was either predominantly Ph+ or Ph- , respectively. These findings suggest that the mechanisms causing mobilization of leukemic stem cells in untreated CML patients may affect their normal counterparts. They also indicate a possible new source of autologous cells for the support of intensive therapy of CML patients. Finally, they provide a method for obtaining the most highly purified populations of Ph+ LTC-IC described to date. This method should be useful for further analyses of the molecular activities of these very primitive neoplastic cells.     

Comparison of population activity in the dorsal premotor cortex and putamen during the learning of arbitrary visuomotor mappings

A previous study found that as monkeys learned novel mappings between visual cues and responses, neuronal activity patterns evolved at approximately the same time in both the dorsal premotor cortex (PMd) and the putamen. Here we report that, in both regions, the population activity for novel mappings came to resemble that for familiar ones as learning progressed. Both regions showed activity differences on trials with correct responses versus those with incorrect ones. In addition to these common features, we observed two noteworthy differences between PMd and putamen activity during learning. After a response choice had been made, but prior to feedback about the correctness of that choice (reward or nonreward), the putamen showed a sustained activity increase in activity, whereas PMd did not. Also in the putamen, this prereward activity was highly selective for the specific visuomotor mapping that had just been performed, and this selectivity was maintained until the time of the reward. After performance reached an asymptote, the degree of this selectivity decreased markedly to the level typical for familiar visuomotor mappings. These findings support the hypothesis that neurons in the striatum play a pivotal role in associative learning. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Abnormalities of iron metabolism and erythropoiesis in vitamin E- deficient rabbits

Rabbits fed a vitamin E-deficient diet developed severe muscular dystrophy in 3-4 wk, but they did not become anemic. Nevertheless, reticulocyte counts increased in deficient rabbits (3.2%) compared to control rabbits (0.9%), and erythroid hyperplasia was evident in the bone marrow. Comparing deficient rabbits to controls, the plasma iron concentration was lower (134.4 versus 206.6 microgram/dl); the TIBC was higher (335.9 versus 228.3 microgram/dl); the whole blood protoporphyrin concentration was higher (131.6 versus 81.7 microgram/dl); and the total iron content was lower in spleen (71 versus 153 microgram), higher in skeletal muscle (4956 versus 3054 microgram), and unchanged in bone marrow, liver, and heart. Studies of iron absorption and excretion using 59Fe showed no abnormalities in deficient rabbits. There were abnormalities of ferrokinetics, however. The half-time of disappearance of 59Fe was shorter (100.6 versus 169.4 min), the plasma iron turnover was greater (1.25 versus 0.95 mg/dl blood/day), and the reappearance of 59Fe in circulating erythrocytes at day 9 was greater (77.2% versus 57.2%) in deficient rabbits. Anemia induced by phlebotomy accentuated the abnormal iron metabolism of deficient rabbits, and the animals were unable to correct the anemia. These findings show that vitamin E deficiency in rabbits causes abnormal erythropoiesis associated with abnormal iron metabolism and sequestration of iron in skeletal muscle.     

CORRELATION BETWEEN THE NUMBER OF MITOTIC FIGURES AND THE PERCENTAGE OF Ki67-POSITIVE CELLS IN NON-HODGKIN’S LYMPHOMAS

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The impact of longitudinal intestinal lengthening and tailoring on liver function in short bowel syndrome.

INTRODUCTION: Short bowel syndrome is a functional or anatomic loss of major parts of the small bowel leading to severe malnutrition. The limiting factor for the survival of these patients remains parenteral nutrition-related liver damage leading to end-stage liver failure. Longitudinal intestinal lengthening and tailoring (LILT) has been proven to enhance peristalsis, to decrease bacterial overgrowth and to extend the mucosal contact time for the absorption of nutrients. The aim of this study was to show the impact of LILT on the development of parenteral nutrition-related liver damage. PATIENTS AND METHODS: A cohort of 55 patients with short bowel syndrome managed with LILT in our institution between 1987 and 2007 was retrospectively reviewed. LILT was performed at a mean age of 24 months (range 4 - 150 months). Mean follow-up time was 83.76 months (range 5 - 240 months). We obtained reliable data from 31 patients with regard to liver enzymes and function parameters in blood samples before LILT and at the present time. Liver biopsy was performed in 14 patients prior to LILT. RESULTS: Liver enzymes ALAT (mean 121 U/l), ASAT (mean 166 U/l) and bilirubin (mean 2.49 mg/dl) were elevated preoperatively in 27/31 children. After the lengthening procedure, ALAT (mean 50 U/l), ASAT (mean 63 U/l) and bilirubin (mean 1.059 mg/dl) normalized except in 5 of 8 patients who could not be weaned from parenteral nutrition after LILT. Liver function parameters such as the international normal ratio (INR) were slightly elevated in 5/31 patients. Albumin was generally low, probably due to parenteral nutrition. Liver biopsy was performed in 14 patients preoperatively, showing 4 patients with low-grade, 6 patients with intermediate and 4 patients with high-grade fibrosis. End-stage liver disease with cirrhosis was an exclusion criterion for LILT. All patients with liver fibrosis showed a normalization of liver enzymes when they were weaned from parenteral nutrition. But patients with higher grade liver fibrosis tend to develop more complications perioperatively. CONCLUSION: After LILT, all patients with liver fibrosis who could be weaned from parenteral nutrition showed a normalization of liver enzymes. Preoperative liver biopsy is mandatory in order to differentiate reversible liver fibrosis from end-stage liver disease. A higher grade of liver fibrosis and elevated INR has been shown to be a sensitive parameter for peri- and postoperative complications.     

Breast and axillary tissue MR imaging: correlation of signal intensities and relaxation times with pathologic findings

We tested a variety of inversion-recovery (IR) and spin-echo (SE) sequences by imaging the breast masses of 22 patients before surgery and 23 tissue specimens with magnetic resonance (MR) imaging at 0.6 T to determine the most effective pulse sequences to evaluate breast disease. An SE pulse sequence using a long repetition time (TR) of 1,600 msec and a long echo time (TE) of 90 msec was found to be the most sensitive in depicting carcinoma in the excised tissue specimens, with all of the carcinomas (n = 15) demonstrating irregular areas of higher signal intensity (SI) than that of the adjacent fat. However, only five of 11 breast carcinomas present in the preoperative patients produced a higher SI than that produced by fat on the same T2-weighted sequence. Five of the remaining six carcinomas in the preoperative patients appeared as localized distortions of fibroductular architecture on both T2-weighted SE and IR sequences. In axillary tissue specimens, both metastatic carcinoma and hyperplastic lymph nodes produced a high SI on T2-weighted SE sequences. However, metastatic carcinoma had a significantly longer T2 relaxation time than did hyperplastic lymph nodes.     

Did suturing services at Alexandra Health Centre need upgrading?

Due to financial restrictions patients at the Alexandra Health Centre (AHC) were sutured under conditions of cleanliness but not complete asepsis. A study was undertaken in 1987 to determine the need and priority for upgrading suturing services at AHC by determining the rate of wound sepsis after suturing in 348 consecutive patients during 1 month. One hundred and thirty-nine (40%) returned for removal of sutures, of whom 31 (22.3%) were assessed as having septic wounds, 15 (10.8%) with mild sepsis (inflammation only) and 16 (11.5%) severe (pus present). Depending on whether one considers mild or only severe sepsis and how one takes account of the effect of non-responders, the overall sepsis rate is between 4.6% and 22.3%. The only factor found to be a predictor of sepsis was clinically evident wound contamination. A follow-up study, undertaken to investigate the reasons for so many patients not returning to the AHC for removal of sutures, found that most patients removed their sutures at home. The literature is reviewed and the problems in defining sepsis and handling poor response rates are discussed. In all, we recommended that the introduction of complete asepsis should not occur at the expense of other priorities at the AHC.     

Cutaneous events during treatment of chronic inflammatory joint disorders with anti‐tumour necrosis factor alpha: a cross‐sectional study

Background Anti‐tumour necrosis factors (anti‐TNF) are more and more used, but the rate of skin adverse events is not known. Objective The aim was to assess the number of skin infections and other dermatoses in patients treated with anti‐TNFα. Patients and methods One hundred eighty‐seven patients suffering from rheumatoid arthritis or ankylosing spondylitis underwent a dermatological exam. Patients with anti‐TNF were compared with those without this treatment in a prospective transversal study. Results Among them, 59 patients were treated with anti‐TNFα and steroids were prescribed in 100 cases. There was no difference in the prevalence of skin infections or eczema or tumours. Skin drug reactions were observed in six patients. Infections by dermatophytes appear very frequent, approaching 70% in both groups. Conclusions This study shows that skin infections (or other skin diseases) are not more frequent in these patients. No differences were observed in infections (bacterial fungal, parasital or viral), tumours, psoriasis or the manifestations of atopic dermatitis. Nonetheless, a long‐term survey might be interesting, especially about skin tumours.     

Single dose oxazepam has no effect on acetaminophen clearance or metabolism

Summary The metabolism of acetaminophen and oxazepam in humans is mainly dependent on the microsomal capacity for glucuronide conjugation. The clearance of acetaminophen and the formation of metabolites were evaluated in 7 patients before and during concomitant administration of oxazepam 30 mg. The subjects received a single 500 mg dose of acetaminophen i.v. and concentrations in plasma were measured for 360 minutes and in urine for 24 h in order to estimate the production of metabolites. The single therapeutic dose of oxazepam had no effect on the clearance of acetaminophen or on formation of its metabolites.