Familial Mediterranean fever (FMF)-response to TNF-blockers used for treatment of FMF patients with concurrent inflammatory diseases

ObjectiveFamilial Mediterranean fever (FMF) is the most common interleukin 1 (IL-1)-driven monogenic autoinflammatory disease. Yet published data also suggest that tumor necrosis factor (TNF) may have a role in the pathogenesis of FMF and may serve as a target for treatment. In the present study we evaluate this hypothesis.MethodsTo this goal, we studied the incidental effect on FMF of TNF-directed treatment, administered to colchicine-refractory FMF patients for the management of a concurrent inflammatory disease. The rates of FMF patients and of treatments with complete or nearly complete FMF response were determined, based on the number of FMF attacks during TNF-blocker exposures. The possible effect of various FMF and non-FMF features on the outcome was determined using comparative analysis. Patients were identified and data were retrieved using electronic files from the FMF clinic.ResultsTwenty-six patients were identified, each receiving ≥ 1 of four TNF-blockers for a mean duration of 27.6 ± 16.4 months. The TNF-blockers were found to induce complete or nearly complete FMF response in 10 (38.5%) of the patients, and in 13 of 50 (26%) exposures. No clinical, genetic, demographic, or therapeutic feature could predict which FMF patient would respond favorably to TNF-blocker therapy.ConclusionThis study suggests that TNF-blockers may be beneficial for a small proportion of colchicine-resistant FMF patients.     

About ISAM: Its Inception and Promises

Abstract

Faith-based substance abuse rehabilitation programs provide residential treatment for many substance abusers. To determine key governing concepts of such programs, we conducted semi-structured interviews with sample of eleven clinical and administrative staff referred to us by program directors at six, Evangelical Christian, faith-based, residential rehabilitation programs representing two large, nationwide networks. Qualitative analysis using grounded theory methods examined how spirituality is incorporated into treatment and elicited key theories of addiction and recovery. Although containing comprehensive secular components, the core activities are strongly rooted in a Christian belief system that informs their understanding of addiction and recovery and drives the treatment format. These governing conceptions, that addiction stems from attempts to fill a spiritual void through substance use and recovery through salvation and a long-term relationship with God, provide an explicit, theory-driven model upon which they base their core treatment activities. Knowledge of these core concepts and practices should be helpful to clinicians in considering referrals to faith-based recovery programs.     

Portal vein thrombosis in a patient with Turner’s syndrome: A case report

This work aimed at reporting a case of Turner’s syndrome with portal vein thrombosis and elevated levels of factor VIII and von Willebrand factor. A 14-year-old Libyan girl was admitted for evaluation of infantilism and pallor; meanwhile, she was found to be of short stature, with webbing of the neck. Chromosomal studies showed monosomy pattern Turner’s syndrome (45XO). Abdominal ultrasound displayed a hugely enlarged spleen. Computed tomography (CT) imaging of the abdomen revealed portal vein thrombosis and dilated venous collaterals in porta hepatis. Thrombophilia screening demonstrated elevated levels of factor VIII (207 IU dl^–1) and von Willebrand factor (450 IU dl^–1). It was concluded that this was a case report on the unusual finding of portal vein thrombosis in a patient with Turner’s syndrome in whom high levels of factor VIII and von Willebrand factor were found. Detailed molecular epidemiological study is recommended to clarify this finding and its underlying factors.     

Gastric cancer and Helicobacter Pylori infection in the Eastern Libya: A descriptive epidemiological study

Background and study aimsThe aim of this study was to determine the pattern of histologically-proven gastric cancer in Eastern Libya and explore its association with Helicobacter pylori infection.Patients and methodsThe registries of the Departments of Histopathology, Faculty of Medicine, Benghazi University and Oncology, Al-Jomhoria Hospital, Benghazi, were reviewed for cases with primary gastrointestinal cancer from January 2000 to December 2002 (sole Histopathology and Oncology Departments in Eastern Libya). Slides of hematoxylin and eosin stain of gastric cancer patients were re-stained to detect H. pylori. The American Joint Committee on Cancer Tumor, Node, Metastasis staging was used for clinical and pathologic staging. Gastric cancer biopsy materials were classified into intestinal or diffuse type according to Lauren criteria.ResultsOne hundred and fourteen cases of gastric cancer were diagnosed. Tumor stages were: 2 (14%), 3 (21%), 4 (57%) and unknown (8%). Most common site of involvement was the antrum (48%). Diffuse adenocarcinoma occurred in 56 patients (49.1%), intestinal adenocarcinoma in 46 (40.4%) and malignant gastric lymphoma in 12 (10.5%). The overall frequency of H. pylori infection was 63.2% (72/114), more frequent in intestinal adenocarcinoma (71.7%) and malignant lymphoma (66.6%) than diffuse adenocarcinoma (55.3%). The frequency of gastric cancer increased throughout the three years of study.ConclusionThe majority of the patients were diagnosed in locally advanced or metastatic stage. Clearly more efforts need to be given to early detection. We showed a stronger association of H. pylori infection with intestinal type gastric adenocarcinoma and malignant lymphoma than diffuse adenocarcinoma suggesting that H. pylori infection is the most probable causal factor of gastric cancer in this part of Libya.     

Age Progression of Neuropathological Markers in the Brain of the Chilean Rodent Octodon degus,a Natural Model of Alzheimer's Disease

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the leading cause of age‐related dementia worldwide. Several models for AD have been developed to provide information regarding the initial changes that lead to degeneration. Transgenic mouse models recapitulate many, but not all, of the features of AD, most likely because of the high complexity of the pathology. In this context, the validation of a wild‐type animal model of AD that mimics the neuropathological and behavioral abnormalities is necessary. In previous studies, we have reported that the Chilean rodent Octodon degus could represent a natural model for AD. In the present work, we further describe the age‐related neurodegeneration observed in the O. degus brain. We report some histopathological markers associated with the onset progression of AD, such as glial activation, increase in oxidative stress markers, neuronal apoptosis and the expression of the peroxisome proliferative‐activated receptor γ coactivator‐1α (PGC‐1α). With these results, we suggest that the O. degus could represent a new model for AD research and a powerful tool in the search for therapeutic strategies against AD.     

Changes in Cathepsin D and Beclin-1 mRNA and protein expression by the excitotoxin quinolinic acid in human astrocytes and neurons

Quinolinic acid (QUIN) is an excitotoxin that has been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD). While QUIN has been shown to induce neuronal and astrocytic apoptosis as well as excitotoxic cell death, other mechanisms such as autophagy remain unexplored. We investigated the role of Cathepsin D (CatD) and Beclin-1 (Bc1) in QUIN-treated primary human astrocytes and neurons. We demonstrated that the expression patterns of CatD, a lysosomal aspartic protease associated with autophagy, are increased at 24 h after QUIN treatment. However, unlike CatD, the expression patterns of Bc1, a tumour suppressor protein, are significantly reduced at 24 h after QUIN treatment in both brain cell types. Furthermore, we showed that the NMDA ion channel blockers, MK801, can attenuate QUIN-induced changes CatD and Bc1 expression in both astrocytes and neurons. Taken together, these results suggest that induction of deficits in CatD and Bc1 is a significant mechanism for QUIN toxicity in glial and neuronal cells. Maintenance of autophagy may play a crucial role in neuroprotection in the setting of AD.