Expression of latent hematopoietic progenitor cells in cultures of newborn and adult baboon liver

The anatomic site of hematopoiesis changes during fetal development from the yolk sac to the liver and finally to the marrow. Factors controlling this switch in the site of hematopoiesis are unknown. We assayed erythroid colony (CFU-E) and erythroid burst (BFU-E) formation in fetal, newborn, and adult baboon liver and marrow to determine the growth requirements of primate hematopoietic progenitor cells from different anatomic sites and developmental stages. We cocultured fetal, newborn, and adult liver and marrow nonadherent cells with adherent cells from these organs to assess the role adherent cells may play in determining the site of hematopoiesis. Fetal liver, fetal marrow, newborn marrow, and adult marrow cultures formed CFU-E and BFU-E colonies in vitro. In contrast, newborn and adult liver cell cultures very rarely formed colonies. However, when newborn or adult liver nonadherent cells were cocultured with marrow adherent cells, CFU-E and BFU-E colonies were detected. The colonies that formed in the newborn and adult liver cultures were derived from the liver and not from the marrow cells or peripheral blood trapped in the liver. These data suggest that in contrast to fetal liver, newborn and adult liver may not be hematopoietic organs in normal primates in vivo because of changes in the growth requirements of hematopoietic progenitor cells present in these organs.     

Similarity and differences in elderly patients with fixed airflow obstruction by asthma and by chronic obstructive pulmonary disease

BACKGROUND: Epidemiologic studies have demonstrated that elderly patients with fixed airflow obstruction can be affected by asthma or chronic obstructive pulmonary disease (COPD). METHODS: We studied 49 consecutive elderly outpatients, presenting fixed airflow obstruction, by clinical history (smoking), pulmonary function tests, blood gas analysis, and induced sputum. RESULTS: The age was not different in patients with COPD (n=28) and asthma (n=21) (70.2+/-3.9 years vs. 69.6+/-3.7 years), also the degree of fixed airflow obstruction was similar (FEV1: 58.3+/-1.5% vs. 59.0+/-1.4% of predicted). Patients with asthma had significantly more eosinophils in peripheral blood (0.43+/-0.05x10(-3)microL vs. 0.27+/-0.1x10(-3)microL, P<0.0001), and in induced sputum (5.0% [(p25th and p75th) 5.0-6.0%] vs. 1.0% [(p25th and p75th) 0.01-1.0%]; P<0.0001), as well as serum ECP (18.6+/-4.9ng/mL vs. 7.7+/-4.7ng/mL, P<0.0001) and ECP in the induced sputum (31.6+/-2.9ng/mL vs. 5.6+/-4.9ng/mL, P<0.0001). Finally, in induced sputum the eosinophils EG2+ were higher in patients with asthma than in patients with COPD (40.5 [(p25th and p75th) 39.3-44.3] MFI vs. 3.9 [(p25th and p75th) 0-11.4] MFI, P<0.0001). They also had significantly higher diffusing capacity, and a greater reversibility to steroids, after 14-day course of therapy, whereas the reversibility to 400microg of salbutamol was similar. CONCLUSION: Despite similar fixed airflow obstruction, elderly patients with asthma have distinct characteristics compared with patients with COPD.     

Granulocyte/macrophage progenitor cells from peripheral blood and bone marrow differ in their response to prostaglandin E1

Prostaglandins of the E series (PGE) inhibit proliferation of normal bone marrow granulocyte/macrophage progenitors (CFU-GM). Circulating CFU-GM are known to differ from marrow CFU-GM in many characteristics, and in the present study, we compared the effect of PGE1 on circulating and bone marrow progenitors in normals and in patients with chronic myelogenous leukemia (CML). PGE1 caused a dose-dependent inhibition of normal marrow CFU-GM. Circulating CFU-GM were inhibited only at concentrations of 10(-5) mol/L or greater, and progenitor proliferation was, in fact, significantly stimulated at PGE1 concentrations between 10(-8) and 10(-6) mol/L. Bone marrow CFU-GM from patients with CML were inhibited in a manner similar to that of normal bone marrow. Circulating cells from patients with CML were, however, less sensitive to PGE1 inhibition than CML bone marrow cells and demonstrated a pattern intermediate between normal circulating and normal marrow progenitors. These studies suggest that peripheral blood and bone marrow contain different progenitor cell populations.     

Cell surface expression of c-kit receptors by childhood acute myeloid leukemia blasts is not of prognostic value: a report from the Childrens Cancer Group

The prognostic significance of c-kit receptor expression on leukemic blast cells was determined in 122 children with acute myeloid leukemia (AML) entered onto Childrens Cancer Group protocol 213. Clinical and laboratory characteristics as well as outcome were analyzed according to the percentage of blast cells expressing c-kit receptors and the relative number of c-kit receptors per cell as determined by indirect immunofluorescence. c-kit receptor expression was strongly associated with the expression of the CD34 antigen. However, contrary to findings in adult patients with AML, c-kit receptor expression by childhood AML blast cells was not predictive of a poor response to therapy.     

Development of an in vivo model of human multiple myeloma bone disease

Osteolytic bone destruction and its complications, bone pain, pathologic fractures, and hypercalcemia, are a major source of morbidity and mortality in patients with multiple myeloma. The bone destruction in multiple myeloma is due to increased osteoclast (OCL) activity and decreased bone formation in areas of bone adjacent to myeloma cells. The mechanisms underlying osteolysis in multiple myeloma in vivo are unclear. We used a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses IgG kappa, as a model for human multiple myeloma, SCID mice were irradiated with 400 rads and mice were injected either with 10(6) ARH-77 cells intravenously (ARH-77 mice) or vehicle 24 hours after irradiation. Development of bone disease was assessed by blood ionized calcium levels, x-rays, and histology. All ARH-77, but none of control mice that survived irradiation, developed hind limb paralysis 28 to 35 days after injection and developed hypercalcemia (1.35 to 1.46 mmol/L) a mean of 5 days after becoming paraplegic. Lytic bone lesions were detected using x-rays in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Controls or ARH-77 mice, after developing hypercalcemia, were then killed and bone marrow plasma from the long bones were obtained, concentrated, and assayed for bone-resorbing activity. Bone marrow plasma from ARH-77 mice induced significant bone resorption in the fetal rat long bone resorption assay when compared with controls (percentage of total 45Ca released = 35% +/- 4% v 11% +/- 1%). Histologic examination of tissues from the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen and marked infiltration in vertebrae and long bones, with loss of bony trabeculae and increased OCL numbers. Interestingly, cultures of ARH-77 mouse bone marrow for early OCL precursors (colony-forming unit-granulocyte- macrophage [CFU-GM]) showed a threefold increase in CFU-GM from ARH-77 marrow versus controls (185 +/- 32 v 40 +/- 3 per 2 x 10(5) cell plated). Bone-resorbing human and murine cytokines such as interleukin- 6 (IL-6), IL-1 alpha or beta, TGF-alpha, lymphotoxin, and TNF alpha were not significantly increased in ARH-77 mouse sera or marrow plasma, compared with control mice, although ARH-77 cells produce IL-6 and lymphotoxin in vitro. Conditioned media from ARH-77 cells induced significant bone resorption in the fetal rat long bone resorption assay when compared with untreated media (percentage of total 45Ca released = 22% +/- 2% v 11% +/- 1%). This effect was not blocked by anti-IL-6 or antilymphotoxin (percentage of total 45Ca released = 19% +/- 1% and 22% +/- 1%, respectively). Thus, we have developed a model of human multiple myeloma bone disease that should be very useful to dissect the pathogenesis of the bone destruction in multiple myeloma.     

Regulation of hematopoiesis II: the role of polyamine inhibition on helper or suppressor influences of the thymus

We have previously suggested in murine model systems, that two cell subpopulations with differing proliferative capacity, from the thymus, modify the growth of erythroid progenitor cells in vitro. In order to further characterize these populations, we have specifically inhibited polyamine biosynthesis; this pathway is essential for the process of cell replication. Thus, alpha-difluoromethyl ornithine (DFMO) was used to block the conversion of ornithine to putrescine, the first and rate- limiting step in polyamine biosynthesis. We observed a threefold increase in hematopoietic progenitors (CFU-S and CFU-E) from bone marrow in animals treated with DFMO. We further examined the effect of DFMO on accessory "helper" and "suppressor" cells from the thymus and observed an increase in helper activity with an elimination of suppressor activity. All of these effects of DFMO were specific for inhibition of polyamine biosynthesis, since simultaneous addition of the depleted biosynthetic product, putrescine, restored suppressor activity. We conclude that polyamine biosynthesis is required acutely for accessory cell regulation of hematopoiesis.     

Migraine in childhood and adolescence. A critical study of the diagnostic criteria and of the influence of age on clinical findings

We studied 253 children aged <15 years. Phase 1 included 193 children with migraine (1.1 and 1.2) divided into two groups (<10 and ≥ 10 years). We studied the relationship between age and migraine type, headache characteristics, and associated symptoms of the International Headache Society (IHS) definition. A higher frequency of migraine with aura, pulsatile quality, and unilateral location was observed in older children. In phase 2 we studied 176 children with headache (excluding migraine with aura), comparing diagnostic criteria, definition items, sensitivity, and specificity. The results showed that item B of the definition was the most frequent cause of exclusion in the 1.7 diagnostic group. Compared with Vahlquist and the IHS, the Prensky criteria were the most sensitive. Sensitivity was >70% for pain of moderate/severe intensity, duration between 2 and 48 h, isolated photophobia, isolated phonophobia, and aggravation with physical activity. Specificity was >70%, for nausea, vomiting, phonophobia and photophobia, isolated photophobia, aggravation with physical activity, and isolated phonophobia. Based on three alternative definitions, each modifying one item of the IHS definition, the sensitivity and specificity of these alternative definitions were compared with the "extended" criteria (children with migraine without aura and migrainous disturbance, according to the IHS criteria, grouped together). Exclusion of headache duration increased sensitivity by 10%, compared to restrictive IHS criteria, without decreasing specificity.     

Allogeneic marrow grafting with partially mismatched, unrelated marrow donors

Forty patients with advanced hematologic malignancies or severe aplastic anemia received marrow grafts from partially mismatched, unrelated marrow donors. All patients were administered conventional prophylaxis for acute graft-v-host disease (GVHD) consisting of methotrexate and low-dose glucocorticoids. All but two patients who survived at least 30 days showed durable engraftment. Six patients survive 17+ to 36+ months following transplantation. Severe acute GVHD was seen in 47% of the patients; however, no direct correlation between GVHD and the degree of mismatching could be determined. Fatal infections were seen in 29 patients, and in the majority the infection occurred after the granulocyte count had risen to greater than 500 cells/microL. We conclude that the problems encountered in this pilot study can potentially be solved, and that further studies with this type of marrow grafting are warranted.     

Exploring adaptations to the clinical reasoning cycle for forensic mental health nursing: A qualitative enquiry

Forensic mental health nurses (FMHN) provide care to address the needs of people who have mental illnesses across a range of diverse settings. The Clinical Reasoning Cycle (CRC) has been identified as a potential framework to assist FMHNs; however, adaptations were required to reflect the unique nature of the clinical setting. This study aimed to explore adaptations made to determine suitability prior to implementation in practice. Nominal Group Technique was used to explore suggested adaptations determined from a previous study and reach a consensus on the changes. Fourteen senior nurses from a state-wide Forensic mental Health (FMH) service participated. A consensus was reached for two proposed changes. Data were analysed using thematic analysis. Three main themes were interpreted from the data; FMH adaptations are warranted, the focus of the CRC, and who owns the cycle? Nurses in this study considered the need to include offence and risk issues due to the impact these factors have on the therapeutic relationship and cognitive bias; however, they also identified the need to focus on recovery-oriented care while engaging in clinical reasoning. Nurses in this study also expressed some reluctance for nursing to ‘own' the model, due to concern that ownership may cause division among the team or result in inconsistency in care. However, some participant's suggested the CRC with adaptations assisted FMH nurses to articulate their specialist skills and knowledge to others and highlight the nursing contribution to care. Further work is needed to finalize adaptations with a focus on engaging the consumer carer workforce and interdisciplinary team.