Upper extremity deep venous thrombosis

Upper extremity deep venous thrombosis (UEDVT) makes up approximately 1-4% of all episodes of deep venous thrombosis (DVT). Risk factors for UEDVT include central venous catheterization, strenuous upper extremity exercise or anatomic abnormalities causing venous compression, inherited thrombophilia, and acquired hypercoagulable states including pregnancy, oral contraceptive use, and cancer. Unexplained or recurrent UEDVT should prompt a search for inherited hypercoagulable states or underlying malignancy. Clinical presentations include arm, neck, and shoulder pain; edema; skin discoloration; tenderness; and venous distension. Because UEDVT is frequently asymptomatic until complications ensue, a high index of suspicion is required for patients with one or more risk factors for thrombosis. Pulmonary embolism and post-thrombotic syndrome are the most common sequelae of UEDVT. Early detection and treatment of UEDVT decrease complications, morbidity, and mortality. Compressive ultrasonography is an effective and economical means of confirming the clinical diagnosis in most patients. Traditional anticoagulant therapy of UEDVT is giving way to a multimodal approach involving transcatheter thrombolytic therapy followed by a minimum of 3 months of warfarin sodium anticoagulant therapy, venous decompression as needed, and balloon angioplasty with stenting for treatment of residual stricture. Low-dose anticoagulant therapy can safely and effectively mitigate the increased risk of UEDVT associated with the use of central venous catheters.     

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas,ANRS HC‐13 lympho‐C study

Hepatitis C virus (HCV) infection increases the risk of B‐cell non‐Hodgkin lymphomas (B‐NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC‐13 Lympho‐C study aimed at a better understanding of the impact of AT on HCV associated B‐NHL. This multicentric study enrolled 116 HCV‐positive patients with B‐NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n = 45 (39%), diffuse large B‐cell lymphoma (DLBCL) n = 45 (39%), and other types n = 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P = 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P = 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P = 0.42). Three‐year overall survival (OS) and progression‐free survival were 78% 95%CI [63–88] and 64% [48–76], respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P = 0.05) and in the subgroup of MZL patients only (P = 0.04). Our data support that AT improves the outcomes of HCV‐associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [ clinicalTrials.gov Identification number NCT01545544] Am. J. Hematol. 90:197–203, 2015. © 2014 Wiley Periodicals, Inc.     

Regression of established subcutaneous B16‐F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway

Please cite this paper as: Regression of established subcutaneous B16‐F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway. Experimental Dermatology 2009. Abstract: Novel treatment modalities, including gene therapy, are needed for patients with advanced melanoma. We evaluated whether the gef gene, a suicide gene from Escherichia coli, had a significant cytotoxic impact on melanoma in vivo. First, we used a non‐viral gene delivery approach (pcDNA3.1/gef) to study the inhibition of melanoma cells (B16‐F10) proliferation in vitro. Secondly, we used direct intra‐tumoral injection of pcDNA3.1/gef complexed with jetPEI to deliver gef cDNA to rapidly growing murine melanomas. We demonstrated that gef gene not only has an antiproliferative effect on B16‐F10 cells in vitro, but also induces an important decrease in melanoma tumor volume (77.7% in 8 days) in vivo. Interestingly, after gef gene treatment, melanoma showed apoptosis activation associated with the mitochondrial pathway, suggesting that the induction of this death mechanism may be an effective strategy for its treatment. Our in vivo results indicate that gef gene might become a suitable therapeutic strategy for patients with advanced melanoma.     

An unusual chromosome 22q11 deletion associated with an apparent complementary ring chromosome in a phenotypically normal woman

We report an unusual chromosome 22q11 deletion associated with an apparent complementary ring chromosome in a phenotypically normal woman with a family medical history of 22q11 deletion. Using peripheral blood samples, conventional karyotyping, Fluorescence In Situ Hybridization (FISH) analysis on metaphase spreads and oligo array-based comparative genomic hybridization (oligo array-CGH) were performed. After conventional cytogenetic examination, the chromosome formula was as follows: 47,XX,+r(?)[16]/46,XX[6]. The FISH analysis revealed that this patient had a rearranged chromosome 22 with decreased centromeric fluorescence intensity and deletion of the 22q11.2 locus. She also had a supernumerary ring chromosome composed of an alpha-satellite centromere of 22 origin and 22q11.2 locus. The oligo array-CGH profile showed a deletion of approximately 4.18?Mb on chromosome 22 with a log 2 intensity ratio mean deviation of the deleted region of about -0.29. The 22q11 deletion associated with a complementary ring chromosome described in our patient could be consistent with a centromere misdivision mechanism, with one chromosomal break occurring in the alpha-satellite array and a second one in the 22q11 locus, a mechanism which has recently been referred to as the McClintock mechanism.     

Tumour necrosis factor-alpha increases extravasation of virus particles into tumour tissue by activating the Rho A/Rho kinase pathway

Tumour Necrosis Factor alpha (TNF) is a pleiotropic pro-inflammatory cytokine with known vascular permeabilising activity. It is employed during isolated limb perfusion to enhance delivery of chemotherapeutic drugs into tumour tissue. The use of conditionally-replicating lytic viruses, so called 'oncolytic virotherapy', provides a new approach to cancer treatment that is currently limited by the low efficiency of extravasation of viral particles into tumours. We report here evidence that TNF significantly enhances the delivery of virus particles through the endothelial layer to allow access to tumour cells both in vitro and in vivo. Intravenous administration of TNF resulted in a 3- to 6-fold increase in EL4 tumour uptake of Evans Blue/Albumin, adenovirus and long-circulating polymer coated adenovirus. Interestingly, endothelial permeabilisation could be suppressed in vitro and in vivo by Y-27632, a Rho kinase inhibitor, without inhibiting viral infection. These data indicate that TNF can enhance the delivery of virus particles into tumours through a Rho A/Rho kinase dependent mechanism and may be a valuable strategy for increasing the delivery of oncolytic viruses and other therapeutic agents.     

Animal diseases caused by orbiviruses, Algeria

Antibodies against bluetongue virus were detected in cattle, sheep, goats, and camels in Algeria in 2008. Antibodies against epizootic hemorrhagic disease virus were detected in cattle, but antibodies against African horse sickness virus were not detected in horses and mules. Epizootic hemorrhagic disease in northern Africa poses a major risk for the European Union.     

Giant Trichobezoar of Duodenojejunal Flexure: A Rare Entity

Bezoars are concretions of undigested material in the gastrointestinal tract, most commonly in the stomach. Duodenojejunal localization of bezoars is exceptional. We report a case of a 27-year-old woman who experienced nausea, vomiting and severe abdominal pain for one week. By palpation a mobile and sensitive mass, 15 × 15 cm, was detected, which filled the upper quadrant. Results of gastric endoscopy were normal. X-ray and ultrasonography suggested a bezoar. A laparotomy revealed that the jejunum was fissured by the trichobezoar ball. This trichobezoar mass was totally excised by intestinal resection.

Conclusion:

To our knowledge, this is the first reported case of duodenojejunal fissuration caused by trichobezoar in an adult. Among patients with high subocclusif syndrome, duodenojejunal bezoar should remain a possibility in differential diagnosis.     

Identification of two new mutations in the GPR98 and the PDE6B genes segregating in a Tunisian family

Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous disorder. ARRP could be associated with extraocular manifestations that define specific syndromes such as Usher syndrome (USH) characterized by retinal degeneration and congenital hearing loss (HL). The USH type II (USH2) associates RP and mild-to-moderate HL with preserved vestibular function. At least three genes USH2A, the very large G-protein-coupled receptor, GPR98, and DFNB31 are responsible for USH2 syndrome. Here, we report on the segregation of non-syndromic ARRP and USH2 syndrome in a consanguineous Tunisian family, which was previously used to define USH2B locus. With regard to the co-occurrence of these two different pathologies, clinical and genetic reanalysis of the extended family showed (i) phenotypic heterogeneity within USH2 patients and (ii) excluded linkage to USH2B locus. Indeed, linkage analysis disclosed the cosegregation of the USH2 phenotype with the USH2C locus markers, D5S428 and D5S618, whereas the ARRP perfectly segregates with PDE6B flanking markers D4S3360 and D4S2930. Molecular analysis revealed two new missense mutations, p.Y6044C and p.W807R, occurring in GPR98 and PDE6B genes, respectively. In conclusion, our results show that the USH2B locus at chromosome 3p23-24.2 does not exist, and we therefore withdraw this locus designation. The combination of molecular findings for GPR98 and PDE6B genes enable us to explain the phenotypic heterogeneity and particularly the severe ocular affection first observed in one USH2 patient. This report presents an illustration of how consanguinity could increase familial clustering of multiple hereditary diseases within the same family.