[Embolization of splenic artery aneurysms: Treatment of choice. About a case and review of the literature]. / Embolisation des anévrysmes de l'artère splénique : traitement de choix. À propos d'un cas et revue de la littérature.

Splenic artery aneurysms constitute 60% of digestive artery aneurysms. They are often discovered incidentally and by imaging. Currently, endovascular treatment is considered the first-line treatment, as it is less invasive with less morbidity and mortality than surgery. An aggressive approach in their management is certainly justified because the overall mortality of ruptured splenic aneurysms is 25%. False splenic aneurysms have a greater potential for rupture than true aneurysms because they grow faster. Endovascular treatment is generally indicated for aneurysms larger than 2cm or with an increase in size of more than 0.5cm/year. Embolization is rarely associated with an infarction of the spleen due to the good supply of short gastric vessels. Embolization is performed using different materials including coils, which can be used alone or with other embolic agents. Post-embolization syndrome can be seen with persistent pain, fever and other systemic symptoms. Endovascular treatment compared to open surgery is associated with better quality of life and appears to be the most cost-effective strategy. Endovascular treatment and especially coil embolization are starting to be the standard treatment. Surgical and laparoscopic treatment are reserved for ruptured aneurysms which are burdened with significant mortality, especially in pregnant women. We report the case of a 66-year-old female patient in whom a splenic artery aneurysm was discovered incidentally during an ultrasound for an ovarian cyst.

Update of inflammatory proliferative retinopathy: Ischemia, hypoxia and angiogenesis.

Diabetic retinopathy (DR) and retinopathy of prematurity (ROP) present two examples of proliferative retinopathy, characterized by the same stages of progression; ischemia of the retinal vessels, leads to hypoxia and to correct the problem there is the setting up of uncontrolled angiogenesis, which subsequently causes blindness or even detachment of the retina. The difference is the following; that DR initiated by the metabolic complications that are due to hyperglycemia, and ROP is induced by overexposure of the neonatal retina to oxygen. In this review, we will demonstrate the physiopathological mechanism of the two forms of proliferative retinopathy DR and ROP, in particular the role of the CD40/CD40L axis and IL-1 on vascular complications and onset of inflammation of the retina, the implications of their effects on the onset of pathogenic angiogenesis, thus understanding the link between platelets and retinal ischemia. In addition, what are the therapeutic targets that could slow its progression?

Rituximab for sight-threatening refractory pediatric Vogt-Koyanagi-Harada disease.

Rituximab was trialed in a refractory Vogt-Koyanagi-Harada disease (VKH). A 10-year-old girl with panuveitis recalcitrant to treatment, including corticosteroids, was diagnosed with VKH 20 months later. Following rituximab at 0, 1, 6, and 18 months, response was favorable after the second dose, usual life activity resumed after the third dose (uveitis was inactivated and vision improved), and eyes stabilized 9 months after the fourth dose. Rituximab is effective in the treatment and long-term control of advanced, pediatric VKH.

Immunohistochemical and genetic exploration of incompatible A blood group antigen expression in invasive micropapillary breast carcinoma: A case report.

INTRODUCTION: Invasive Micropapillary Carcinoma (IMPC) of the breast is a relatively rare subtype of invasive ductal carcinoma and represents the most inherently aggressive form. Expression of incompatible blood group A antigen in cancer of type O patients has been reported in several types of cancer, however, the biosynthetic mechanism and the genetic basis remain unclear until today. The aim of the present case report study was to evaluate the expression of incompatible blood group A antigen and to identify the genetic basis of this expression in IMPC of the breast. MATERIAL AND METHODS: One patient blood group O with Invasive Micropapillary Carcinoma was screened at Pathology Department of University Hospital CHU Ibn Rochd, Casablanca. ABH antigens expression was assessed by immunohistochemistry. ABO genotyping was performed by allele specific primers PCR-ASP and Exon 6 of ABO gene was sequenced with Sanger method. RESULTS: H antigen was expressed in endothelial and epithelial cells of normal tissue. However, H antigen expression was lost in both invasive micropapillary carcinomas. A antigen was expressed in IMPC with approximately 80% of positive cells. Tumor DNA was genotyped as heterozygous A/O. In normal DNA, we identified a single frameshift deletion c.320delA p.(Glu107Glyfs*12), which is removed from tumor DNA. CONCLUSION: Our findings suggest that incompatible A antigen expression in IMPC is due to glycosyltransferase A encoded by an A allele which is derived from O allele with a deletion at the position 320.

Distinctive roles of PKC delta isozyme in platelet function.

Platelet activation is a complex balance of positive and negative signaling pathways. Several protein kinase C (PKC) isoforms are expressed in human platelets. They are a major regulator of platelet granule secretion, activation and aggregation activity. One of those isoforms is the PKCδ isozyme, it has a central yet complex role in platelets such as opposite signaling functions depending on the nature of the agonist, it concentration and pathway. In fact, it has been shown that PKCδ has an overall negative influence on platelet function in response to collagen, while, following PAR stimulation, PKCδ has a positive effect on platelet function. Understanding the crucial role of PKCδ in platelet functions is recently emerging in the literature, therefore, further investigations should shed light into its specific role in hemostasis. In this review, we focus on the different roles of PKCδ in platelet activation, aggregation and thrombus formation.

ABO blood groups in relation to breast carcinoma incidence and associated prognostic factors in Moroccan women.

The association between blood groups ABO and different types of diseases was established in several previous studies. Our aim was to seek the possible association between the ABO blood group and breast cancer-associated prognostic factors. The Chi-squared analytic test was used to compare phenotypic ABO distribution among Moroccan blood donors and 442 cases of women suffering from breast carcinoma with archived files in Maternity Ward of University Hospital C.H.U Ibn Rochd between 2008 and 2011. High incidence of breast carcinoma was observed in blood type B patients (p < 0.05). Blood type B was associated with breast carcinomas overexpressing human epidermal growth factor receptor HER2 (p < 0.05) and high risk of cancer at age over 70 years (p < 0.001). Blood type A was associated with high risk of cancer among women younger than 35 years old. Blood type A and AB were associated with high incidence of lymph node metastasis (p < 0.05). Multivariate analysis has shown correlation between O blood type and estrogen receptor-positive tumor. Patients with blood group A, B, and AB were more likely to develop aggressive breast carcinoma. Further follow-up studies are necessary to clarify the role of ABH antigens in the progression of breast carcinoma.

Association of inflammatory cytokine gene polymorphisms with inflammatory bowel disease in a Moroccan cohort.

The purpose of this study was to investigate whether common variants in inflammatory and immune response genes influence inflammatory bowel disease (IBD) risk among Moroccan patients. Using a candidate gene approach, 10 single-nucleotide polymorphisms mapping on six genes (MIF_rs755622, TNFA_rs1800629, IL6_rs2069840, IL6R_rs2228145, IL6ST_rs2228044, IL17A (rs2275913, rs4711998, rs7747909, rs8193036, rs3819024)) were assessed in 510 subjects grouped in 199 IBD and 311 healthy controls. Genotyping was performed with the TaqMan allelic discrimination technology. The results were analyzed using PLINK software. The frequency of allele A for TNFA rs1800629 was significantly higher in ulcerative colitis (UC) patients compared with controls (30.16 vs 16.72%; P=0.0005; odds ratio (OR)=2.15; 95% confidence interval (CI)=1.39-3.32). Statistically significant association to UC was also found under dominant AA+AG vs GG (OR=1.85, 95% CI=1.07-3.21; P=0.02) and recessive models (OR=8.38; 95% CI=2.86-24.53; P=0.0001). In the same way, an association of TNFA rs1800629 variant was observed with IBD under recessive model AA vs AG+GG (OR=4.10; 95% CI=1.56-10.76; P=0.004). No evidence of significant associations was found for the remaining investigated polymorphisms. Our data suggest that TNFA gene promoter polymorphism participates in determining IBD susceptibility in Moroccan patients.

PKCs in thrombus formation.

The protein kinase C (PKC) family has been implicated in several physiological processes regulating platelet activation. Each isoform of PKC expressed on platelets, may have a positive and/or negative role depending on the nature and concentration of the agonist. Mice lacking PKCα show much reduced thrombus formation in vivo, while PKCθ(-/-) showed inhibition of aggregation in response to PAR4. On the other hand, PKCδ by associating with Fyn, inhibits platelet aggregation. In addition, PKCß by interacting with its receptor RACK1 has been implicated in the primary phases of signaling via the αIIbß3 and finally PKCɛ appears to be involved in platelet function downstream GPVI. The present review discusses the latest observations relevant to the role of individual PKC isoforms in platelet activation and thrombus formation.

A primary role for kinin B1 receptor in inflammation, organ damage, and lethal thrombosis in a rat model of septic shock in diabetes.

Diabetes mellitus and septic shock increase the incidence of mortality by thrombosis. Although kinin B1 receptor (B1R) is involved in both pathologies, its role in platelet function and thrombosis remains unknown. This study investigates the expression, the inflammatory, and pro-thrombotic effects of B1R in a model of septic shock in diabetic rats. Sprague-Dawley rats were made diabetic with streptozotocin (STZ) (65 mg/kg, i.p.). Four days later, control and STZ-diabetic rats were injected with lipopolysaccharide (LPS) (2 mg/kg, i.p.) or the vehicle. B1R antagonist (SSR240612, 10 mg/kg by gavage) was given either acutely (12 and 24 h prior to endpoint analysis) or daily for up to 7 days. Moreover, a 7-day treatment was given either with cyclooxygenase (COX)-2 inhibitor (niflumic acid, 5 mg/kg, i.p.), non-selective COX-1 and COX-2 inhibitor (indomethacin, 10 mg/kg, i.p.), non-selective nitric oxide synthase (NOS) inhibitor (L-NAME, 50 mg/kg by gavage), iNOS inhibitor (1400W, 5 mg/kg, i.p.), or heparin (100 IU/kg, s.c.). The following endpoints were measured: edema and vascular permeability (Evans blue dye), B1R expression (qRT-PCR, western blot, flow cytometry), aggregation in platelet-rich plasma (optical aggregometry), and organ damage (histology). Rats treated with STZ, LPS, and STZ plus LPS showed significant increases in edema and vascular permeability (heart, kidney, lung, and liver) and increased expression of B1R in heart and kidney (mRNA) and platelets (protein). Lethal septic shock induced by LPS was enhanced in STZ-diabetic rats and was associated with lung and kidney damage, including platelet micro-aggregate formation. SSR240612 prevented all these abnormalities as well as STZ-induced hyperglycemia and LPS-induced hyperthermia. Similarly to SSR240612, blockade of iNOS and COX-2 improved survival. Data provide the first evidence that kinin B1R plays a primary role in lethal thrombosis in a rat model of septic shock in diabetes. Pharmacological rescue was made possible with B1R antagonism or by inhibition of iNOS and COX-2, which may act as downstream mechanisms.

[Clinical presentation of Moroccan cases with Alzheimer's disease]. / Présentation clinique de cas marocains atteints de la maladie d'Alzheimer.

INTRODUCTION: The diagnostic approach for Alzheimer's disease is based on the presence of cerebral atrophy combined with the score of the mini-examination of the mental state. In this context, this study was conducted to assess the correlation between imaging and neuropsychological testing for cases of early-onset and late-onset Alzheimer's disease. AIM OF THE STUDY: Analysis of the clinical and paraclinical aspects of Moroccan cases with Alzheimer's disease. METHODS: Seventeen sporadic cases and 8 family cases were seen at the memory clinic of the Neurology Department of the University of Casablanca Ibn Rochd Hospital. A family history was obtained through a clinical interview of the patient and a yes or no self-reporting questionnaire from the guardian or other family member. The disease was considered familial if at least one additional first degree relative suffered from early-onset AD-type dementia. All patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Written consent was obtained from the patients and their guardians prior to the study. RESULTS: In our study of 25 individuals, the observed mean age of AD patients was 64.52 ± 9.30 and we observed a slight female predominance (56% versus 44%). In addition, we found a prevalence of AD of approximately 20%, increasing with age, in the population below 60 years of age. Approximately half of our patients (48%) had a score lower than 10 and were affected by severe insanity, while 28% were affected by moderate severe insanity and 24% were light to moderately insane. Twenty-five patients underwent neuroimaging, 18 of whom were assessed by MRI, while 7 were assessed by CT. All patients had hippocampal atrophy, which progressed to affect others brain regions. The blood tests showed no abnormalities in the 25 enrolled AD cases. DISCUSSION: Age is undoubtedly the main risk factor for AD; this is also the true for our cases where advanced age was responsible for the exponential increase of the disease's frequency; it reached a peak in the age group of 60-69 years. The AD diagnosis approach is based on the presence of cerebral atrophy combined with the score of the mini-examination of the mental state (MMSE). In our study, in addition to the MMSE, depending on the level of education, the clinician used other tests that do not necessarily require a level of education such as the BEC96, visual short-term or digital memory assessment, work memory assessment, language assessment test (DO80) and apraxia. Neuropsychological examination of the cases with a score of less than 10 showed severe cognitive impairment. The cases presented memory and language impairments, aphasia, visual spatial disorientation, decreased autonomy, executive dysfunction and praxis deficits, all major causes of severe dementia. Neuroimaging revealed hippocampal and cortical atrophy. Correlated with the other studies that aimed to establish links between brain alterations and neuropsychological disorders, we can conclude that a higher level of atrophy reflects a decrease in neuropsychological performance.

Novel presenilin mutations within Moroccan patients with Early-Onset Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive brain disorder that causes gradual and irreversible loss of higher brain functions and is the most common cause of dementia in the elderly, as assessed by autopsy and clinical series. Furthermore, it has an annual incidence of approximately 3% in the 65-74-year-old age group. This incidence rate doubles with every increment of 5 years above the age of 65. In Morocco, AD affects almost 30,000 individuals and this number will possibly increase to 75,000 by 2020 (projections of the World Health Organization (WHO)). Genetically, AD is caused by a mutation in one of at least 3 genes: presenilin 1 (PS1), presenilin 2 (PS2) and the amyloid precursor protein (APP). Most cases are late onset and apparently sporadic, most likely as a result of a combination of environmental and non-dominant genetic factors. In Morocco, the genes predisposing individuals to AD and predicting disease incidence remain elusive. The purpose of the present study was to evaluate the genetic contribution of mutations in PS1 and PS2 genes to familial early-onset AD cases and sporadic late-onset AD cases. Seventeen sporadic late-onset AD cases and eight familial early-onset AD cases were seen at the memory clinic of the University of Casablanca Neurology Department. These patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging and laboratory tests. Direct sequencing of each exon in PS1 and PS2 genes was performed on genomic DNA of AD patients. Further, we identified 1 novel frameshift mutation in the PS1 gene and 2 novel frameshift mutations in the PS2 gene. Our mutational analysis reports a correlation between clinical symptoms and genetic factors in our cases of Early-Onset Alzheimer's Disease (EOAD). These putative mutations cosegregate with affected family members suggesting a direct mutagenic effect.

Soluble CD40 ligand impairs the anti-platelet function of peripheral blood angiogenic outgrowth cells via increased production of reactive oxygen species.

Adult peripheral blood angiogenic early outgrowth cells (EOCs), also known as early endothelial progenitor cells, interact with other blood and vascular cells and may regulate atherothrombosis. We have previously shown that endothelial progenitor cells inhibit platelet function and thrombus formation. The CD40L/CD40 axis is a thrombo- inflammatory mediator that affects platelet and endothelial functions. It has been shown that EOCs express CD40, whereas platelets represent the major source of its soluble ligand (sCD40L), which impairs EOC function.We aimed to test the hypothesis that the sCD40L/CD40 axis affects the anti-platelet function of EOCs. Human peripheral blood mononuclear cell-derived EOCs in culture inhibited platelet aggregation. Pre-treatment of EOCs with sCD40L reduced their inhibitory effect on platelet aggregation in a CD40-dependent manner. EOCs viability and release of the anti-aggregating agents, prostacyclin and nitric oxide, were not affected by sCD40L. However, production of reactive oxygen species (ROS) was increased in sCD40L-treated EOCs. Blockade of ROS reversed the effects of sCD40L-treated EOCs on platelet aggregation. This study reveals that the sCD40L/CD40 axis impairs the anti-platelet properties of EOCs through increased production of ROS. These data may explain the link between elevated levels of sCD40L, impaired activity of EOCs and enhanced platelet reactivity, and consequently the occurrence of atherothrombotic disease.