Comparison of hematopoietic progenitor cells in human umbilical cord blood collected from neonatal infants who are small and appropriate for gestational age

BACKGROUND: Cord blood has been used for transplantation. The purpose of this study was to compare numbers of hematopoietic progenitors in cord blood collected from neonatal infants who are small for their gestational age and those who are normal. STUDY DESIGN AND METHODS: Sixteen pregnant women diagnosed with intrauterine growth restriction were prospectively identified. Cord blood was collected at delivery. Fourteen cord blood samples were obtained from gestational age-matched, appropriately grown newborns. In vitro assays for hematopoietic progenitors were performed and results of the two compared. Comparisons were also made with numbers of hematopoietic progenitor cells previously found by this laboratory in samples collected with the possibility of use for transplantation. RESULTS: Gestational age, the women's pregnancy and delivery histories, maternal risk factors for intrauterine growth restriction, maternal age, delivery method, umbilical cord blood gases, and 5-minute Apgar scores were similar in the two groups. Newborns who were small for their gestational age had significantly lower birth weights and longer stays in the neonatal intensive care unit with no evidence for viral infections in the immediate neonatal period. The mean number of progenitors per collection of cord blood in the small newborns was about half that per collection from appropriately grown newborns, but in most cases, these differences were not significant in the two groups, and many numbers in the small newborns fell within the range associated with successfully engrafting cord blood collections. CONCLUSION: Hematopoietic progenitor cells in the small newborns may be adequate for transplantation purposes in many cases. Their possible use in this context should, however, involve careful consideration of the numbers of progenitors collected as well as of possible viral or other contamination.     

Human umbilical vein endothelial cells display high-affinity c-kit receptors and produce a soluble form of the c-kit receptor

Stem cell factor (SCF) is a hematopoietic growth factor produced by fibroblasts and endothelial cells that stimulates the growth of primitive hematopoietic cells. SCF triggers cell growth by binding to the c-kit receptor. Because endothelial cells can respond to certain hematopoietic growth factors, we tested human umbilical vein endothelial cells for display of the c-kit receptor and examined the effect of SCF on endothelial cell proliferation, adhesion molecule expression, and production of tissue factor. Quantitative binding experiments with 125I-SCF showed both high-affinity (Kd = 42 pmol/L) and low-affinity (Kd = 1.7 nmol/L) c-kit receptors. There were approximately 1,100 high-affinity c-kit receptors, and 5,400 low- affinity c-kit receptors per endothelial cell. Enzyme immunoassays showed that endothelial cells released soluble c-kit receptor and SCF. The transmembrane form of SCF was detected by indirect immunofluorescence analysis using monoclonal or polyclonal anti-SCF receptor antibodies. The addition of SCF (100 ng/mL) did not alter endothelial cell proliferation over a 7-day period. Similarly, there was no change in the release of tissue factor or expression of inducible endothelial adhesion molecules (intercellular adhesion molecule-1, endothelial-leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1) measured by enzyme-linked immunosorbant assay at 4 and 24 hours after SCF addition. The neutralizing anti-c-kit receptor monoclonal antibody SR-1 blocked binding of 125I-SCF to the c- kit receptor by 98% but did not alter endothelial cell proliferation or adhesion-molecule expression. c-kit receptors were also detected on adult endothelial cells lining small blood vessels in normal human lymph nodes. These data indicate that normal human endothelial cells produce SCF and show high-affinity c-kit receptors that have the capacity to dimerize. The lack of response to exogenous SCF may be because of intracellular activation of the c-kit receptor via autocrine production of SCF. Alternatively, SCF and c-kit may play a role other than stimulation of proliferation, adhesion-molecule display, or tissue factor production by endothelial cells. The production of soluble c-kit receptors by normal human endothelial cells may serve to regulate the bioactivity of SCF within the bone marrow microenvironment.     

The use of multiattribute decision models in evaluating triptan treatment options in migraine

Background The physician treating patients with migraine is now able to choose from among seven triptans–almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. Objective To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method–TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)–can be applied to evaluate the currently available triptans. Methods In an example application, summary data from a recent meta–analysis of 53 published and unpublished placebo–controlled trials of the oral triptans were combined in TOPSIS models with computer–generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta–analysis, and uncertainty was assessed based on the confidence intervals from the meta–analysis. Results When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. Conclusion Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan.     

Neurodevelopmental outcome of hypoglycaemia in healthy, large for gestational age, term newborns

AIMS: To evaluate the effects of transient hypoglycaemia on the first day of life in 75 healthy term large for gestational age (LGA) infants, born to non-diabetic mothers, on their neurodevelopmental outcome at the age of 4 years. METHODS: Screening for hypoglycaemia was performed 1, 3, and 5 hours after birth, and continued if blood glucose levels were low. Treatment with intravenous glucose for hypoglycaemia was started if hypoglycaemia was severe or symptomatic. Patients' development and behaviour was examined at the age of 4 years by the Denver Developmental Scale, a non-verbal intelligence test, and the Child Behaviour Check List. RESULTS: There were no significant differences between children with neonatal normoglycaemia (n = 15) and hypoglycaemia (plasma glucose <2.2 mmol/l 1 hour after birth, or <2.5 mmol/l subsequently; n = 60) in Denver developmental scale scores and child behaviour checklist scores. Although total IQ did not differ between hypoglycaemic and normoglycaemic children, one subscale (reasoning) did (mean difference 9.3, 95% CI 1.3 to 17.2). The correlation between reasoning IQ and neonatal blood glucose levels was weak and not statistically significant. When other definitions for hypoglycaemia were applied, the difference in reasoning IQ was not found. There were no differences in any of the test scores between hypoglycaemic children who had and who had not been treated with intravenous glucose. CONCLUSION: Transient mild hypoglycaemia in healthy, term LGA newborns does not appear to be harmful to psychomotor development at the age of 4 years.     

Pulmonary nodules: detection using magnetic resonance and computed tomography

Detection of pulmonary nodules using spin-echo magnetic resonance (MR) imaging was compared with detection using computed tomography (CT). Of the 25 patients studied independently by two radiologists, no lung nodules were detected in 11 (CT or MR), ten had a single nodule, and four had multiple nodules. The lesions not seen using CT or MR were less than 1.3 cm in diameter. The greater spatial resolution of CT enabled better detection of nodules close to the diaphragm, the pleura, or to each other, whereas the better contrast resolution of MR enabled the detection of several nodules close to blood vessels. With MR, nodules were best seen on images with long repetition times (2.0 sec). Most pulmonary nodules are seen using both CT and MR. CT generally enables the detection of more small nodules than MR does, and some low-density nodules near blood vessels are better displayed using MR.     

Usage of antimicrobial agents in a private primary healthcare setting in South Africa

Objective The aim of this study was to investigate the prescribing of antimicrobials in a private primary healthcare setting in South Africa. Setting A group of private primary healthcare clinics in South Africa. Method A retrospective, drug utilisation study was conducted on nine clinics that were randomly selected from 33 clinics situated in different geographical areas of South Africa, and whose data were electronically available. Data were obtained from the central database of the private primary healthcare provider and extracted for the period January 1, to December 31, 2001. Key findings The study population consisted of the total patient population (n = 83 655) who visited the clinics during this one‐year period. The total number of medicine items prescribed was 515 976 at a total cost of R1 716 319 ($17 163). Of these, antimicrobials represented 18.69% (n = 96 421) of all medicine items prescribed at a cost of R1 045 108 ($10 451) (60.89%). Antimicrobials were prescribed during 72.72% of consultations at the nine clinics during the one‐year period. The antimicrobials most frequently prescribed were penicillins (38.17%) followed by sulphonamides (22.49%), antiprotozoals (9.88%) and tetracyclines (9.34%). The most common diagnoses for which antimicrobials were prescribed were viral influenza, upper respiratory tract infections, hypertension, acute bronchitis, and common cold. Conclusions The high percentage of antimicrobial prescribing obtained in this study could indicate excessive use of antimicrobials in the private primary healthcare setting. The prescribing of antimicrobials in respiratory tract infections could indicate overuse and inappropriate use of these agents. This could have an effect on the health of the patients needing care, and the general budget for healthcare services. It is recommended that further investigations on the prescribing protocols of antimicrobial usage be done.