The diagnostic and surgical management of a multifocal calcifiyng epithelial odontogenic tumor in the mandible and maxilla associated with a squamous odontogenic tumor: first reported case in the literature

The calcifiyng epithelial odontogenic tumor (CEOT) and the squamous odontogenic tumor (SOT) are rare and benign odontogenic tumors that affect the jaw. This article describes the diagnostic and surgical management of a multifocal CEOT in the mandible and maxilla associated with an SOT. This case is the first to demonstrate that there may be a multifocal variant of CEOT associated with an SOT that has not been previously recognized. Clinical, radiographic, and histologic signs are reported. Treatment modality, oral rehabilitation, and long-term follow-up are shown. Because of the rarity of this kind of simultaneous pathologic association, it is of paramount, and indeed obvious, importance to prospective reviewers that published reports are produced meticulously, including all clinically, radiographically, and histologically relevant data.     

Integrated implementation of programs targeting neglected tropical diseases through preventive chemotherapy: identifying best practices to roll out programs at national scale

In 2006 the U.S. Agency for International Development (USAID) established the Neglected Tropical Disease (NTD) Control Program to support national governments in developing successful, cost-efficient NTD programs that integrate disease-specific programs into coordinated national initiatives, in accord with the World Health Organization recommendations. A 3-stage "roll-out package" has been developed for effectively integrating and scaling up such programs to full-national scale. Stage-1 lays the groundwork-identifying NTD leadership within the Ministry of Health, conducting a national Situation Analysis, formulating a multiyear Plan of Action, and undertaking a funding gap analysis. Stage-2 focuses on scaling up the integrated NTD program-convening national stakeholder meetings, developing annual work plans, carrying out disease mapping, and establishing monitoring and evaluation activities. Stage-3 aims at ensuring effective management-identifying clear roles and responsibilities for partners, and creating a central coordinating mechanism. Assessment and reassessment of these complex NTD programs that target literally billions of people are essential to establish "best practice" strategies for long-term public health success.     

Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation

Hairy cell leukemia (HCL) is a distinct clinicopathologic entity that responds well to purine analogs but is sometimes difficult to differentiate from HCL-like disorders (e.g., splenic marginal zone lymphoma and HCL variant). We recently identified the BRAF-V600E mutation as the disease-defining genetic event in HCL. In this study, we describe a new, simple, and inexpensive test for genetics-based diagnosis of HCL in whole-blood samples that detects BRAF-V600E through a sensitive allele-specific PCR qualitative assay followed by agarose-gel electrophoresis. This approach detected BRAF-V600E in all 123 leukemic HCL samples investigated containing as few as 0.1% leukemic cells. BRAF-V600E was detected at different time points during the disease course, even after therapy, pointing to its pivotal role in HCL pathogenesis and maintenance of the leukemic clone. Conversely, 115 non-HCL chronic B-cell neoplasms, including 79 HCL-like disorders, were invariably negative for BRAF-V600E. This molecular assay is a powerful tool for improving the diagnostic accuracy in HCL.     

Hyperparathyroidism can be useful in the identification of primary aldosteronism due to aldosterone-producing adenoma

Type 1 diabetes triggers protein kinase C (PKC)-dependent NADPH oxidase activation in the renal medullary thick ascending limb (mTAL), resulting in accelerated superoxide production. As acute exposure to superoxide stimulates NaCl transport by the mTAL, we hypothesized that diabetes increases mTAL Na(+) transport through PKC-dependent and NADPH oxidase-dependent mechanisms. An O(2)-sensitive fluoroprobe was used to measure O(2) consumption by mTALs from rats with streptozotocin-induced diabetes and sham rats. In sham mTALs, total O(2) consumption was evident as a 0.34±0.03 U change in normalized relative fluorescence (ΔNRF)/min per mg protein. Ouabain (2 mmol/L) reduced O(2) consumption by 69±4% and 500 μmol/L furosemide reduced O(2) consumption by 58±8%. Total O(2) consumption was accelerated in mTAL from diabetic rats (0.74±0.07 ΔNRF/min/mg protein; P<0.05 versus sham), reflecting increases in ouabain- and furosemide-sensitive O(2) consumption. NADPH oxidase inhibition (100 μmol/L apocynin) reduced furosemide-sensitive O(2) consumption by mTAL from diabetic rats to values not different from sham. The PKC inhibitor calphostin C (1 μmol/L) or the PKCα/β inhibitor G?6976 (1 μmol/L) decreased furosemide-sensitive O(2) consumption in both groups, achieving values that did not differ between sham and diabetic. PKCβ inhibition had no effect in either group. Similar inhibitory patterns were evident with regard to ouabain-sensitive O(2) consumption. We conclude that NADPH oxidase and PKC (primarily PKCα) contribute to an increase in O(2) consumption by the mTAL during type 1 diabetes through effects on the ouabain-sensitive Na(+)-K(+)-ATPase and furosemide-sensitive Na(+)-K(+)-2Cl(-) cotransporter that are primarily responsible for active transport Na(+) reabsorption by this nephron segment.     

MEF2C deletions and mutations versus duplications: A clinical comparison

5q14.3 deletions including the MEF2C gene have been identified to date using genomic arrays in patients with severe developmental delay or intellectual disability, stereotypic behavior, epilepsy, cerebral malformations and a facial gestalt not really distinctive though characterized by broad and/or high, bulging forehead, upslanting palpebral fissures, flat nasal root and bridge, small, upturned nose, hypotonic small mouth resulting in cupid bow/tented upper lip. MEF2C mutations have been also identified in patients with overlapping phenotype so that it is considered the gene responsible for the 5q14.3 deletion syndrome. To date, one single duplication including MEF2C has been reported in a patient with intellectual disability but its clinical significance remains uncertain also because of the large size of the imbalance. Here we present two further patients with 5q14.3 duplications including MEF2C. Their phenotype indeed suggest the pathogenic effect of the MEF2C duplication although other duplicated genes also brain expressed might contribute to the clinical features. In none of them a clear-cut syndrome can be identified. A comparison between MEF2C deleted/mutated and duplicated patients is also presented.     

Anaemia during pregnancy: impact on birth outcome and infant haemoglobin level during the first 18 months of life

To determine the effect of maternal anaemia on pregnancy outcome and describe its impact on infant haemoglobin level in the first 18 months of life, we conducted a prospective study of 617 pregnant women and their children in Benin. Prevalence of maternal anaemia at delivery was 39.5%, and 61.1% of newborns were anaemic at birth. Maternal anaemia was not associated with low birth weight [OR = 1.2 (0.6-2.2)] or preterm birth [OR = 1.3 (0.7-2.4)], whereas the newborn's anaemia was related to maternal anaemia [OR = 1.8 (1.2-2.5)]. There was no association between an infant's haemoglobin level until 18 months and maternal anaemia. However, malaria attacks during follow-up, male gender and sickle cell trait were all associated with a lower infant haemoglobin level until 18 months, whereas good infant feeding practices and a polygamous family were positively associated with a higher haemoglobin level during the first 18 months of life.     

What Do Cytokine Profiles Tell Us About Subsets of Juvenile Idiopathic Arthritis?

Classification of juvenile idiopathic arthritis is an ongoing process and up to now has been predominantly based on clinical manifestations—mainly number of joints at onset of disease. In the meantime, basic studies have advanced our knowledge regarding the disease pathogenesis. Unfortunately, studies of cytokines and cytokine polymorphisms have not followed the predominantly clinical International League of Associations for Rheumatology classification in that no significant biological differences among the different disease categories have been demonstrated with robust associations. Only systemic-onset disease seems to be quite different from other disease categories with regard to biologic mechanisms; indeed, it now seems closer to autoinflammatory than to classic autoimmune diseases. New players in the immunologic basis of juvenile idiopathic arthritis (eg, interleukin-17 and regulatory T cells) are also discussed in this review.     

Favorable radiological outcome of skeletal Erdheim-Chester disease involvement with anakinra

Erdheim-Chester disease is a rare non-langerhans cell histiocytosis characterized by infiltration of foamy CD68-positive but CD1a-negative macrophages and fibro-inflammatory lesions as retroperitoneal, periureteral areas or bones. Interferon-α therapy has been used as treatment but it had variable efficiency and limited tolerance. More recently, a recombinant form of interleukin-1 receptor antagonist (anakinra) was used with success but no skeletal radiological improvement was recorded. We report here a case of interleukin-1 receptor antagonist in the treatment of refractory bones infiltration in Erdheim-Chester disease. After 1 year of treatment, the positron emission tomography-computed tomography showed an outstanding response of the skeletal involvement with clearly lower and smaller hypermetabolism images.