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.     

Analysis of the measurement precision of arterial lumen and wall areas using high-resolution MRI.

High-resolution MRI may be used to monitor the progression of human carotid atherosclerosis by measuring the lumen and wall area changes over time. The purpose of this study was to analyze the precision of quantitative measurements of lumen and wall areas. Two independent MR scans near the carotid bifurcation were conducted on eight patients within 2 weeks. The error of lumen area measurement was 6. 2%, 9.2%, and 9.7% for T(1), proton density, and T(2)-weighted images, respectively, and the error of wall area measurement was 10. 8%, 10.9%, and 12.0%. The precision of area measurement correlates strongly with image quality.     

FLT3 receptor expression on the surface of normal and malignant human hematopoietic cells

FLT3 ligand is a hematopoietic growth factor that plays a key role in growth of primitive hematopoietic cells. FLT3 receptor mRNA is found in early hematopoietic progenitors and in human myeloid leukemia blasts. Much less is known about the surface expression of FLT3 receptor on human hematopoietic cells. Using human 125I-FLT3 ligand, we have identified and characterized surface FLT3 receptors on normal and malignant human hematopoietic cells and cell lines. Our results showed that surface display of FLT3 receptor was greatest in fresh myeloid leukemia blast cells and myeloid leukemia cell lines. Erythroleukemic and megakaryocytic leukemia cell lines (n = 5) bound little to no 125I- FLT3 ligand. Scatchard analysis of 125I-FLT3 ligand binding data shows that three myeloid leukemia cell lines, ML-1, AML-193, and HL-60, as well as normal human marrow mononuclear cells, exhibit high affinity FLT3 receptors. Crosslinking of 125I-FLT3 ligand to FLT3 receptors on the surface of ML-1 myeloid leukemia cells indicates that the FLT3 ligand. The rates of FLT3 ligand internalization and degradation were determined by binding 125I-FLT3 ligand to ML-1 cells and acid stripping to distinguish surface bound from internalized ligand. Internalized 125I-FLT3 ligand was detected within 5 minutes after binding to ML-1 cells. In addition, we evaluated the effect of FLT3 ligand on megakaryocytic colony growth and nuclear endoreduplication, alone or in the presence of thrombopoietin. FLT3 ligand did not promote colony forming unit megakaryocyte (CFU-Meg) colony growth or megakaryocyte nuclear maturation, nor did FLT3 ligand augment the effects of thrombopoietin on these measures of megakaryopoiesis. These data indicate that the FLT3 receptor shares several characteristics with the c-kit receptor including dimerization and rapid internalization. However, the more restricted cellular distribution of the FLT3 receptor may target the effects of FLT3 ligand to primitive hematopoietic cells and to myeloid and lymphoid progenitor cells, in contrast to the pleiotropic effects of the c-kit receptor ligand, stem cell factor.     

Stem cell factor modulates avidity of alpha 4 beta 1 and alpha 5 beta 1 integrins expressed on hematopoietic cell lines

Interactions between hematopoietic cells and bone marrow (BM) stroma, composed of extracellular matrix and stromal cells, are crucial for hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoiesis. Integrins facilitate these interactions by mediating adherence of hematopoietic cells to both the extracellular matrix and stromal cells. Marrow stromal cells secrete a variety of growth factors, including stem cell factor (SCF). Because treatment with SCF in vivo mobilizes primitive hematopoietic cells from the BM, we investigated the effect of the growth factor SCF of hematopoietic cell adhesion. These studies show that SCF modulates adhesive function in a dose- and time-dependent manner, but does not modulate expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 in the SCF- responsive cell line MO7E. Treatment of MO7E cells with SCF (200 ng/mL) produced a transient increase in adherence to cytokine-activated human umbilical vein endothelial cells (HUVECs) or to vascular cell adhesion molecule 1 (VCAM-1)-transfected Chinese hamster ovary (CHO) cells with peak adhesion at 30 minutes and return to baseline by 60 to 90 minutes. This increase in adhesion was paralleled by increased binding of the beta 1 activation-dependent monoclonal antibody (MoAb) 15/7, as determined by flow cytometry. However, prolonged incubation of MO7E with SCF induced a marked decrease in integrin-mediated adherence, with maximal inhibition by 24 hours. No change in expression of integrins, as determined by flow cytometry, was observed with short- or long-term incubation with SCF. SCF-treated cells were still able to respond to phorbol esters and to the activating beta 1 MoAb 8A2 with increased adherence, but not to the level seen in control cells. This suggests that a subpopulation of expressed alpha 4 beta 1 and alpha 5 beta 1 integrins is disengaged by prolonged incubation with SCF.     

Protein A adsorption of acute myelogenous leukemia serum induces in vitro blast lysis

We studied cytotoxic activity of acute myelogenous leukemia (AML) sera for AML blasts before and after immunoadsorption with Staphylococcus aureus, Cowan I (SAC), which contains protein A. We found in vitro that incubation with treated AML sera reduced viability to 42.7% of control (p less than 0.01) for autologous and 21.0% of control (p less than 0.01) for allogeneic blasts. Normal peripheral blood cells were not killed by treated AML sera. Wood 46 strain of Staphylococcus aureus, which does not contain protein A, did not significantly reduce AML blast viability (94.8%, p greater than 0.4), while Sepharose-bound protein A reduced viability to 63.8% (p less than 0.01). Cytotoxicity does not appear to be complement-mediated, byt cytotoxic activity is trypsin-sensitive and is contained in the immunoglobulin fraction. This model for study of the tumoricidal action of protein A adsorption should be useful for predicting utility of plasma adsorption as a therapeutic adjunct in the future.     

Sarcoidosis: correlation of extent of disease at CT with clinical, functional, and radiographic findings

Computed tomography (CT) was compared with chest radiography in the assessment of disease severity in 27 patients with sarcoidosis. The CT scans and radiographs were each read twice by two independent observers. Disease extent was assessed on CT scans by visual scoring (0%-100% involvement of the lung parenchyma) and on radiographs by using an adaptation of the International Labour Office classification. The severity of parenchymal changes on the CT scan and on the radiograph was significantly correlated with the severity of dyspnea (r = .61 and .58, respectively; P less than .001), diffusing capacity (r = -.62 and -.52, P less than .01), and vital capacity (r = -.49 and -.51, P less than .01). Patients with predominantly irregular opacities had more severe dyspnea and lower lung volumes than patients with predominantly nodular opacities (P less than .05). The authors conclude that in patients with sarcoidosis, the radiographic and CT assessments of disease severity show similar correlation with clinical and functional impairment.