Thrombopoietin, but not erythropoietin promotes viability and inhibits apoptosis of multipotent murine hematopoietic progenitor cells in vitro

The recently cloned c-mpl ligand, thrombopoietin (Tpo), has been extensively characterized with regard to its ability to stimulate the growth, development, and ploidy of megakaryocyte progenitor cells and platelet production in vitro and in vivo. Primitive hematopoietic progenitors have been shown to express c-mpl, the receptor for Tpo. In the present study, we show that Tpo efficiently promotes the viability of a subpopulation of Lin-Sca-1+ bone marrow progenitor cells. The ability of Tpo to maintain viable Lin-Sca-1+ progenitors was comparable to that of granulocyte colony-stimulating factor and interleukin-1, whereas stem cell factor (SCF) promoted the viability of a higher number of Lin-Sca-1+ progenitor cells when incubated for 40 hours. However, after prolonged (> 40 hours) preincubation, the viability- promoting effect of Tpo was similar to that of SCF. An increased number of progenitors surviving in response to Tpo had megakaryocyte potential (37%), although almost all of the progenitors produced other myeloid cell lineages as well, suggesting that Tpo acts to promote the viability of multipotent progenitors. The ability of Tpo to promote viability of Lin-Sca-1+ progenitor cells was observed when cells were plated at a concentration of 1 cell per well in fetal calf serum- supplemented and serum-depleted medium. Finally, the DNA strand breakage elongation assay showed that Tpo inhibits apoptosis of Lin-Sca- 1+ bone marrow cells. Thus, Tpo has a potent ability to promote the viability and suppress apoptosis of primitive multipotent progenitor cells.     

Adenosine deaminase activity in protein-energy malnutrition

Cell-mediated immunity (CMI) was evaluated in 69 children with protein-energy malnutrition (PEM) and 20 healthy controls. Significantly decreased responses to purified protein derivative (PPD) ( p < 0.02) and absolute lymphocyte count (ALC) ( p < 0.01) and increased serum adenosine deaminase (ADA) activity ( p < 0.001) were observed in PEM cases compared with the controls. The mean values of ALC and ADA activity in PEM patients were 85.9% and 158.7% of the normal mean, respectively. A significant negative correlation was observed between the two parameters ( r = −0.2765, p < 0.01). The CMI tests were abnormal in all three grades of PEM, except for the response to PPD in grade I, when compared with the controls. No significant differences were found between infected and uninfected PEM cases. Thus, impaired CMI was observed not only in grades II and III but also in grade I PEM patients and the concomitant infection did not affect its status. However, ADA activity demonstrated a more pronounced change than the other tests     

Congenital lobar emphysema

Congenital lobar emphysema, a life-threatening respiratory disorder presenting in infancy is best diagnosed by chest x-ray. Abnormality of bronchial cartilage is one of the suspected aetiological factors. Prompt lobectomy is the treatment of choice as conservative treatment carries an unacceptably high mortality and morbidity. One such patient, a 3-month-old child who underwent successful emergency left upper lobectomy is presented.     

Disposition of cyclophosphamide on two consecutive cycles of treatment in patients with ovarian carcinoma

The disposition of cyclophosphamide was determined in 12 women with ovarian carcinoma receiving cyclophosphamide 500 mg/m2, doxorubicin (adriamycin) 50 mg/m2 and cisplatin 50 mg/m2 during their first and second courses of therapy. Plasma samples were obtained over 24 h following the completion of the cyclophosphamide infusion and assayed for cyclophosphamide by high performance liquid chromatography. The mean disposition of cyclophosphamide conformed to a 2-compartment model with a mean terminal half-life of 7.14 h on the first course and 8.77 h on the second course. Mean area under the plasma concentration versus time curve appeared to increase from 248.8 mg.h/l for the initial course to 282.2 mg.h/l on the second. Mean total body clearance was 2.01 l/h/m2 on the first course and 1.77 l/h/m2 on the second. Volume of distribution on the first and second courses were 15.3 l/m2 and 18.1 l/m2, respectively. These results suggested that cyclophosphamide clearance decreased when given in a bolus fashion every 3 weeks. However, inter-patient and intra-patient variability was large and the differences in the calculated parameters were not statistically significant when the individual patient data was considered. It is concluded that: 1. cyclophosphamide disposition can best be fit by a bi-exponential equation; 2. considerable intra- and interpatient variability in the concentration-time profile will be encountered; 3. cyclophosphamide disposition does not change from the first to the second course. Reasons for the wide variation are proposed.     

High-performance liquid chromatographic measurement of cyclophosphamide in serum

The analysis of cyclophosphamide [N,N-bis(2-chlorethyl)-tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine -2-oxide] by high-performance liquid chromatography using ultraviolet detection is described. The method will enable measurement of serum concentrations of cyclophosphamide over a period of approximately 24 h after a dose of 150 mg, and requires 1 ml of serum. The between-day precision of the assay at concentrations of 0.3, 1.0, and 15.0 mg/L generated coefficients of variation of 11.8, 12.2, and 7.7%, respectively. Percentages of analytical recovery of cyclophosphamide and internal standard (5-ethyl-5-p-tolylbarbituric acid) were 63 and 73%, respectively. Preliminary data providing the half-life for two patients with normal renal function are presented.     

Thyroid function testing in pregnancy and thyroid disease: trimester-specific reference intervals

During pregnancy the thyroid is hyperstimulated, resulting in changes in thyroid hormone concentrations. Accurate assessment of thyroid function during pregnancy is critical, for both the initiation of thyroid hormone therapy, and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. Gestational age-specific reference intervals are now available for thyroid function tests. Knowing the expected normal changes in hormone concentrations throughout pregnancy allows individualized supplementation when necessary.     

Therapeutic drug monitoring of antithyroid drugs in pregnancy: the knowledge gaps

Despite being a common condition in pregnancy, and despite propylthiouracil (PTU) being perceived as safer than methimazole, there are virtually no epidemiological controlled studies on malformation rate an neurobehavioral outcomes with the former. This knowledge gap must be filled to ensure fetal safety.