Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood

Refractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory cytopenia of childhood. (The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered at clinicaltrials.gov identifiers 00499070 and 00662090, respectively).     

Diagnostic Value of Chest Radiographs in Bedridden Patients Suspected of Having Pneumonia

Objectives

To assess the diagnostic value of the chest radiograph for the diagnosis of pneumonia in bedridden patients, using non-contrast-enhanced high-resolution chest computed tomography (CT) as the gold standard.

Methods

We prospectively evaluated bedridden patients hospitalized with moderate to high clinical probability of pneumonia. Chest radiographs were interpreted in a blinded fashion by 3 observers and classified as definite, normal, or uncertain for pneumonia. Chest CT was obtained within 12 hours of chest radiograph. We applied Bayesian analysis to assess the accuracy of chest radiograph in the diagnosis of pneumonia.

Results

In a 5-month period, 58 patients were evaluated, 31 (53%) were female. Their chest radiographs were interpreted as negative, uncertain, or positive for pneumonia in 31 (53%), 15 (26%), and 12 (21%) patients, respectively, while CT confirmed pneumonia in 11 (35%), 10 (67%), and in 10 (83%). The sensitivity of the chest radiograph to diagnose pneumonia was 65%, the specificity was 93%, the positive and negative predictive values were, respectively, 83% and 65%, while the overall accuracy was 69% (95% confidence interval, 50%-79%).

Conclusions

In bedridden patients with suspected pneumonia, a normal chest radiograph does not rule out the diagnosis, hence, a chest CT scan might provide valuable diagnostic information.     

A novel sustained-release clotrimazole varnish for local treatment of oral candidiasis

The use of dental varnish for therapeutic purposes has been reported for fluoride or antibacterial drugs. Our objectives were to develop a sustained-release varnish containing an antifungal drug (clotrimazole) for topical application and to evaluate the release rate of the drug in human saliva in comparison with an available commercial troche and their acceptance by healthy volunteers. Following in vitro optimization of the release rate from the varnish, we have embarked on a crossover comparative study assessing the oral sensations and pharmacokinetics of a 10-mg clotrimazole oral troche versus a 10-mg sustained-release clotrimazole varnish in 14 human volunteers over a period of 5 h. Saliva samples were assessed for clotrimazole concentration by high performance liquid chromatography analysis. The volunteers’ evaluation of the varnish and troche (taste, other sensory changes, convenience, and oral suitability) were recorded. At all time points, salivary clotrimazole concentrations were higher, and the terminal half-life was significantly prolonged in the varnish group in comparison to the control group. This can be attributed to continuous release of clotrimazole from the varnish formulation. The duration of the drug over the minimal inhibitory concentration, following application of the varnish, was more than threefold longer than following administration of the troche. The developed sustained-release varnish can be applied in patients at a lower frequency than troches, thus, achieving higher patient compliance and efficacy. This novel varnish application can serve as the basis for a new treatment approach to oral candidiasis, a very common chronic opportunistic infection with improved clinical outcome.     

Identification of 3′UTR region implicated in tau mRNA stabilization in neuronal cells

Tau, a neuronal microtuble-associated protein (MAP) plays an important role in the formation and maintenance of neuronal polarity. Tau mRNA is a stable message and exhibits a relatively long half-life in neuronal cells. The regulation of mRNA stability is a crucial determinant in controlling mRNA steady-state levels in neuronal cells and thereby influences gene expression. The half-lives of specific mRNAs may be dependent on specific sequences located at their 3′untranslated region (UTR), which in turn, may be recognized by tissue-specific proteins. To identify the sequence elements involved in tau mRNA stabilization, selected regions of the 3′UTR were subcloned downstream to c-fos reporter mRNA or to the coding region of the tau mRNA. Using stably transfected neuronal cells, we have demonstrated that a fragment of 240 bp (H fragment) located in the 3′UTR can stabilize c-fos and tau mRNAs. Analysis of stably transfected cells indicated that the transfected tau mRNAs are associated with the microtubules of neuronal cells, suggesting that this association may play a role in tau mRNA stabilization. This step may be a prerequisite in the multistep process leading to the subcellular localization of tau mRNA in neuronal cells.     

Lung coin lesions due to Echinococcal disease (2004:7b)

European Radiology -     

Quantitative imaging in late TBI. Part II: cognition and work after closed and penetrating head injury: a report of the Vietnam head injury study

Context : Functional outcome in relation to CT findings in traumatic brain injured (TBI) patients is not well established in relation to cognitive and vocational outcome.

Objective : To investigate the possible correlation between relatively simple quantitative radiological measurements and cognitive and vocational outcome.

Design : Retrospective analysis of quantitative assessment of CT studies in relation to post-injury cognitive changes and vocational outcome.

Setting : US Army Medical Centre.

Patients : 74 penetrating head injured (PHI) and 37 closed head injured (CHI) Vietnam war veterans.

Outcome measures : The Armed Forces Qualification Test (AFQT); Disability score; Return to work.

Results : Total brain volume loss, third ventricle width (3VW), ventricular score (VS), and septumcaudate distance (SCD) were significantly related to cognitive change and return to work in PHI patients. Volume loss and 3VW were the most valuable radiologic predictors of outcome in multivariate linear and logistic regression models for both CHI and PHI.

Conclusion : 3VW on late CT scans following traumatic brain injury is a powerful predictor of overall long-term cognitive outcomes and potential for return to work.     

Epidural haematoma: Computerized tomography (CT) parameters in 19 patients

Between the years 1984 to 1989, 624 urgent brain CT examinations were performed for head-trauma patients in the Tel-Aviv Medical Center. In 19 patients, epidural haematomas were diagnosed. Different radiological parameters were discussed such as homogeneity of the haematoma, midline shift, ventricular collapse, obliteration of the perimesencephalic cistern and the presence of additional brain damage.     

Brain metastases of malignant melanoma in interferon complete responders: clinical and radiological observations

Summary Three patients with metastatic malignant melanoma, 2 of whom were males with primary lesion on the shoulder, and a female with primary lesion on the ankle, with Clark's level III–IV, completely responded to interferon-DTIC, but failed in the brain. Radiologically, all the lesions were peripheral in location, and none showed any bleeding tendency. Clinically, these lesions seemed to be resistant to radiotherapy, chemotherapy or steroid treatment, and were the cause of death after a very short survival period. Interferon apparently is inactive against melanoma brain metastases, but does cause CNS symptoms. Because CNS metastases are sometimes the sole site of clinical relapse, and are frequently disabling, prophylactic cranial irradiation (PCI) needs to be studied in high risk patients.