Empty iron stores in children and young adults--the diagnostic accuracy of MCV, MCH, and MCHC.

INTRODUCTION: Erythrocyte mean cell volume (MCV) is used clinically to classify anemia, and normal values may be used to exclude iron deficiency. We have studied the diagnostic accuracy of MCV and the related measures mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) in diagnosing empty iron stores in children and young adults. METHODS: Diagnostic accuracy of MCV, MCH, and MCHC was studied by ROC curve analysis in 6443 ambulant patients aged 0.5-25 years, of which 476 were anemic. In all patients, blood hemoglobin, MCV, MCH, and serum ferritin were measured in specimens sampled at the same time. MCHC was calculated as MCH divided by MCV. The gold standard of empty iron stores was s-ferritin <10, 15, or 20 µg/L. The cutoff limit of MCV giving 90% sensitivity in diagnosing serum ferritin <15 µg/L was constructed using quantile regression. RESULTS: Generally, MCH was slightly more accurate than MCV and MCHC. In the whole study population, the area under the ROC curve was 0.68-0.93 for MCV, 0.73-0.96 for MCH, and 0.68-0.87 for MCHC; and 0.70-0.86, 0.71-0.89, and 0.68-0.88, respectively, in the anemic subpopulation. At the cutoff limits of MCV giving a sensitivity of 90% at all ages in anemic patients, the specificity was about 50%. CONCLUSION: Mean cell hemoglobin, MCH, and MCHC are only moderately accurate in diagnosing empty iron stores in children and young adults, and normal values of these tests do not exclude empty iron stores in anemic patients.

Compliance with European guidelines for diagnostic mammography in a decentralized health-care setting.

PURPOSE: To evaluate the compliance of Danish mammography clinics with requirements concerning organization, activity volume, and assessment procedures from two European guidelines for quality assurance in diagnostic mammography (EUSOMA and EUREF). MATERIAL AND METHODS: We used individual records on all diagnostic mammographies performed in Denmark in 2000, and questionnaires given to Danish mammography clinics in 2000, 2002, and 2004. RESULTS: The study showed a marked centralization of the diagnostic activity from 2000 to 2004 to a smaller number of public breast assessment centers with full multidisciplinary breast assessment. However, a relatively large number of these centers did not comply with the activity volume requirement of 2000 mammograms per clinic per year. The number of private diagnostic mammography clinics performing basic diagnostic mammography has remained fairly stable in the period 2000 to 2004. Compared with public breast assessment centers, the private diagnostic mammography clinics had a lower compliance with activity volume requirements. CONCLUSION: A marked proportion of Danish public breast assessment centers operate with less than optimal activity volume, suggesting that further centralization would be appropriate. The situation in private diagnostic mammography clinics may cause concern, as our study showed that the majority of these clinics did not meet the activity volume requirements.

Concordance of information in parallel electronic and paper based patient records.

OBJECTIVE: to evaluate the results of parallel use of both paper based and electronic patient records with respect to concordance of corresponding information in two continuously updated versions of the same records. DESIGN: retrospective evaluation of patient records, comparing documentation in electronic and paper based patient records. SETTING: Department of Neurology in a Norwegian university hospital using paper based and electronic patient records in parallel during migration towards completely electronic patient records. MATERIAL: electronic and paper based patient records of 90 randomly selected patients visiting the department between 1 November 1997 and 30 April 1999. RESULTS: seven percent of the electronic documents were significantly different in some way from the corresponding paper documents. About 4-13% of the documents in the electronic record were missing; one percent were missing from the paper record. CONCLUSION: parallel use of electronic and paper based patient records has resulted in inconsistencies between the record systems in our setting. Documentation is missing in both the electronic and paperbased records. When implementing electronic record systems intended to operate in parallel with paperbased systems, focus should be on securing the validity of all versions of the record.

Constitutive STAT3-activation in Sezary syndrome: tyrphostin AG490 inhibits STAT3-activation, interleukin-2 receptor expression and growth of leukemic Sezary cells.

Interleukin-2 (IL-2) is a growth factor which upon binding to high-affinity receptors (IL-2Ralphabetagamma) triggers mitogenesis in T cells. IL-2Ralpha expression is restricted to T cells which have recently encountered antigen, and in healthy individuals the majority (>95%) of peripheral T cells are IL-2Ralpha negative. An aberrant expression of IL-2Ralpha has recently been described in cutaneous T-cell lymphoma (CTCL). Here, we study the regulation of IL-2Ralpha expression and STATs in a tumor cell line obtained from peripheral blood from a patient with Sezary syndrome (SS), a leukemic variant of CTCL. We show that (1) STAT3 (a transcription factor known to regulate IL-2Ralpha transcription) is constitutively tyrosine-phosphorylated in SS tumor cells, but not in non-malignant T cells; (2) STAT3 binds constitutively to a STAT-binding sequence in the promotor of the IL-2Ralpha gene; (3) the Janus kinase inhibitor, tyrphostine AG490, inhibits STAT3 activation, STAT3 DNA binding, and IL-2Ralpha mRNA and protein expression in parallel; and (4) tyrphostine AG490 inhibits IL-2 driven mitogenesis and triggers apoptosis in SS tumor cells. In conclusion, we provide the first example of a constitutive STAT3 activation in SS tumor cells. Moreover, our findings suggest that STAT3 activation might play an important role in the constitutive IL-2Ralpha expression, survival, and growth of malignant SS cells.

STAT3-mediated constitutive expression of SOCS-3 in cutaneous T-cell lymphoma.

A characteristic feature of neoplastic transformation is the loss of external control by cytokines and extracellular matrix of cellular differentiation, migration, and mitogenesis. Because suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that an aberrant SOCS expression plays a role in neoplastic transformation. This study reports on a constitutive SOCS-3 expression in cutaneous T-cell lymphoma (CTCL) cell lines. SOCS-3 protein is constitutively expressed in tumor cell lines (but not in nonmalignant T cells) obtained from affected skin from a patient with mycosis fungoides (MF) and from peripheral blood from a patient with Sezary syndrome (SS). In contrast, constitutive SOCS-3 expression is not found in the leukemic Jurkat T-cell line, the MOLT-4 acute lymphoblastic leukemia cell line, and the monocytic leukemic cell line U937. Expression of SOCS-3 coincides with a constitutive activation of STAT3 in CTCL tumor cells, and stable transfection of CTCL tumor cells with a dominant negative STAT3 strongly inhibits SOCS-3 expression, whereas transfection with wild-type STAT3 does not. Moreover, the reduced SOCS-3 expression in cells transfected with the dominant negative STAT3 is associated with an increased sensitivity to interferon-alpha (IFN-alpha). In conclusion, evidence is provided for a constitutive SOCS-3 expression in cancer cells obtained from patients with CTCL. Moreover, the findings indicate that the aberrant expression of SOCS-3 is mediated by a constitutive activation of STAT3 in CTCL cells and affects the IFN-alpha sensitivity of these cells. (Blood. 2001;97:1056-1062)

Intersegmental sagittal motion in the lower cervical spine and discogenic spondylosis: a preliminary study.

OBJECTIVE: The object of this investigation was to identify any correlation between discogenic spondylosis and the type of motion (normal, hypomobility, hypermobility, paradoxical motion) found in the sagittal plane of the intervertebral motion units of the lower cervical spine. DESIGN AND SETTING: A case control study was performed from the files of 100 patients (ages 15-73) with cervical spine-related symptomatology at the Anglo-European College of Chiropractic Clinic. PATIENTS: The cases were randomly selected from a cohort of patients with normal radiographic anatomy who attended the clinic from 1987-1990 and were known to have cervical spine neutral, flexion and extension lateral radiographs taken. MAIN OUTCOME MEASURES: Extended chi 2 was used to test the observed data. RESULTS: The findings from both the flexion and extension films suggested that intervertebral motion units with and without varying severities of discogenic spondylosis did differ with respect to the type of motion exhibited there (flexion: chi 2 = 39.399, p < .001; extension: chi 2 = 45.7424, p < .001). Intervertebral motion units which had discogenic spondylosis had a greater likelihood of exhibiting motion abnormalities (flexion: chi 2 = 5.665, p < .01; extension: chi 2 = 6.178, p < .01), and all types of motion seemed to be dependent on its severity (flexion: chi 2 = 16.464, p < .01; extension: chi 2 = 15.954, p < .02). In general, normal motion occurred approximately 60% of the time when there was absent or mild discogenic spondylosis and decreased precipitously as moderate and severe amounts of discogenic spondylosis appeared. In global cervical flexion, when there was either little or no discogenic spondylosis and abnormal motion was present, intersegmental hypermobility was predominant. Hypomobility became predominant overall as moderate and severe discogenic spondylosis was found. In global cervical extension, for all severities of discogenic spondylosis when there was abnormal motion, intersegmental hypomobility was predominant. Also of note was the presence of paradoxical motion, which occurred in 11% of the intervertebral motion units without discogenic spondylosis [usually at the C7-T1 intervertebral motion unit (86%)]. CONCLUSIONS: From the data it can be concluded that there are trends which occur with differing amounts of discogenic spondylosis when considering intersegmental cervical sagittal motion. However, additional detailed study is required to corroborate the findings and determine what their clinical significance is.