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 Methods In an example application, summary data from a recent meta–analysis of 53 published and unpublished placebo–controlled trials of the oral triptans were combined in TOPSIS models with computer–generated attribute importance weights representing the entire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.     

Endometrioid carcinoma simultaneously involving the uterus and the fallopian tube: a clinicopathologic study of 13 cases

Although the simultaneous presentation of endometrial and ovarian carcinomas of the endometrioid type is well described, little is known about a similar phenomenon involving the endometrium and fallopian tube (FT). We present the clinicopathologic features of 13 such cases seen in the Department of Pathology at The University of Texas M.D. Anderson Cancer Center over an 8 year period (1995 to 2002). FT tumors that could have represented luminal extension of the endometrial carcinoma or that represented an unequivocal metastasis to the FT were excluded. The patients' ages ranged from 34 to 77 years (median 54). The most common symptom was abnormal uterine/vaginal bleeding (11) and all of the patients were considered overweight or obese (mean body mass index was 41). The size of the endometrial carcinomas ranged from 0.3 to 8 cm. According to the FIGO grading of the endometrial endometrioid carcinomas, the cases were distributed as follows: Grade 1 (3) and Grade 2 (10). In 2 cases, there were also small areas of other histologic types, papillary serous carcinoma (1 case), and papillary endometrial carcinoma of intermediate grade (another case). The size of the fallopian tube carcinomas ranged from 0.2 to 17.5 cm. Seven of these tumors were located in the distal/fimbriated end of the FT. There was bilateral involvement in 2 cases. Three of the FT tumors were in situ. The grades of the fallopian tube carcinomas were as follows: Grade 1 (2), Grade 2 (6), and Grade 3 (2). In situ components were seen in all cases. One fallopian tube carcinoma was mixed with serous carcinoma. In 4 cases, there was also an endometrioid carcinoma involving the ovary, all of them with an intact ovarian capsule. Patients were treated as follows: total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) (4), TAH/BSO/chemotherapy (chemo) (4), TAH/BSO/radiation (3), and TAH/BSO/chemo/radiation (2). Follow-up ranging from 6 to 54 months was available in 10 patients: 1 patient died of disease (at 38 mo), 1 patient is alive with disease (at 9 mo), 7 patients have no evidence of disease (6 to 54 mo), and 1 patient died of metastatic endometrial carcinoma (at 9 mo). Simultaneous endometrioid carcinomas of the uterus and FT are unusual and occur primarily in obese perimenopausal women. The tumors are predominantly well or moderately differentiated with dissimilar endometrial and FT grades. The FT carcinoma is usually unilateral and located at the distal end of the tube.     

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.     

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.