Distribution of HLA-B27 and its alleles in patients with reactive arthritis and with ankylosing spondylitis in Tunisia

The purpose of the present study is to investigate the frequency of HLA-B27 and its alleles in reactive arthritis (ReA) and in ankylosing spondylitis (AS) in Tunisia. HLA-B27 alleles were typed by PCR amplification with sequence-specific primers. We studied 17 patients with ReA associated with urethritis or with gastrointestinal infection; 42 HLA-B27-positive patients with AS and 100 healthy controls. Eleven ReA patients (67.7%) were HLA-B27 positive. There was an increased frequencies of HLA-B27 (P = 7.76 × 10⁻¹², OR = 59.30) and a moderate increase of HLA-B51 (P = 0.015; OR = 4.91) alleles in ReA patients when compared with healthy controls. Four B27 subtypes were identified: B*2702, 05, 09 and B*2712. The distribution of these alleles in the ReA patients was 37.5% for B*2702 and B*2705. Only these two subtypes were detected in 18 (42.8%) and 24 (57.1%), respectively, of the AS patients. B*2709 and B*2712 were relatively rare in ReA patients and were identified in one case each. Our results showed a restricted number of HLA-B27 subtypes associated with ReA and AS. B*2702 and 2705 were common in ReA and AS patients.     

MRI measures and progression of cognitive decline in nondemented elderly attending a memory clinic

OBJECTIVE: To investigate whether MRI-based volumes of whole brain, medial temporal lobe and white matter hyperintensities (WMH) predict progression of cognitive decline in a sample of nondemented elderly. METHODS: Thirty-seven nondemented elderly attending a memory clinic and 28 elderly controls participated in this follow-up study. The average follow-up period was 1.8 years. Cognitive function was measured at baseline and follow-up with the Cambridge Cognitive Examination (CAMCOG). Baseline Magnetic Resonance Imaging (MRI) provided quantitative measures of whole brain, medial temporal lobe and WMH. Linear mixed models controlled for age and sex were used to assess the independent associations between MRI measures, baseline cognition, and annual decline in cognition. RESULTS: Medial temporal lobe volume was independently associated with baseline CAMCOG score (p < 0.01), whereas whole brain volume (p < 0.01) and WMH (p < 0.05) were associated with annual decline in CAMCOG score. CONCLUSIONS: These data suggest that regional damage to the medial temporal lobes underlies initial mild cognitive impairment, whereas more global brain changes, such as whole brain atrophy and WMH, contribute to further progression of cognitive decline.     

Akt: a potential target for thyroid cancer therapy

Thyroid cancer is a heterogeneous disorder characterized by gene mutations that activate signaling pathways, and also by abnormalities in tumor suppressor genes and cell cycle proteins. Activation of the Akt/PKB signaling pathway appears to be an important event in thyroid tumorigenesis and, perhaps, in tumor progression too. Akt is activated in Cowden's syndrome through inactivation of PTEN, a negative regulator of Akt. Cowden's syndrome is an autosomal dominant multiorgan hamartoma syndrome characterized by benign and malignant thyroid tumors, breast cancers, and colon cancers. In addition, the Akt pathway appears to be activated in a significant proportion of sporadic thyroid cancers through activation of growth factor pathways by thyroid oncogenes and/or receptor overexpression. Disruption of PI3-kinase activity pharmacologically or disruption of Akt signaling using dominant negative cDNA expression have demonstrated salutary effects on several cancer models in vitro. Therefore, Akt represents an attractive target for pharmaceutical development for a variety of malignancies, including thyroid cancer.     

Multisequence magnetic resonance imaging study of neuropsychiatric systemic lupus erythematosus

OBJECTIVE: To investigate the relationship between magnetization transfer imaging (MTI), diffusion-weighted imaging (DWI), proton magnetic resonance spectroscopy (H-MRS), and T2 relaxometry findings in patients with primary neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: The study group consisted of 24 female patients (mean age 36 years [range 23-65]) who had had a variety of neuropsychiatric symptoms that were judged to be due to NPSLE according to the criteria of the American College of Rheumatology. Patients with current active disease were excluded from participation. Quantitative MTI, DWI, H-MRS, and T2 relaxometry data were acquired in all patients, and the correlation coefficients were calculated. RESULTS: MTI results reflecting a decrease in homogeneity of cerebral parenchyma correlated significantly with H-MRS results representing axonal damage. MTI results also correlated significantly with DWI results reflecting increased diffusivity in the cerebral parenchyma. Finally, MTI results reflecting decreased cerebral homogeneity correlated significantly with increased T2 relaxation time, associated with either edema or gliosis. Increased T2 relaxation time correlated significantly with DWI results reflecting increased diffusivity. With the exception of the correlation between H-MRS and MTI findings, there was no significant correlation between H-MRS results and any other parameter. CONCLUSION: The selected study parameters represent different biologic features in the human brain and can be informative with regard to different pathologic processes in NPSLE. The demonstrated associations between MTI, DWI, H-MRS, and T2 data in patients with a history of NPSLE suggest that there is one pathogenesis and/or common neuropathologic outcome in NPSLE despite differences in clinical presentation.     

Imported malaria in Kuwait (1985-2000)

BACKGROUND: The objective of this study was to document the status of malaria infection and effect of preventive measures on the epidemiologic profile of imported malaria cases in Kuwait during 1985-2000. METHODS: The study included screening of two groups of individuals for malaria infection by microscopy; (1) all migrant workers from malaria-endemic countries on their first entry to Kuwait; and (2) all suspected malaria cases already residing in the country. The study period was divided into pre-war (1985-1990), postwar (1992-1997) and proactive preventive (1998-2000) periods. During the proactive preventive period, the home countries were also involved in screening for malaria infection in all prospective immigrants to Kuwait. RESULTS: The annual incidence of malaria cases detected during the pre-war, postwar and proactive preventive periods ranged between 465 and 1,229, 654 and 1,379, and 248 and 393, respectively. Plasmodium vivax infection was detected in 71% of the cases and P. falciparum in 27%. The number of malaria cases detected increased to >1,300 after the war during 1992-1993. However, the number of malaria cases dropped significantly to less than 400 during 1998-2000 (p80%) of malaria patients were young male adults between 21 and 40 years of age. The data on drug resistance were not well defined, due to limited testing. CONCLUSION: This study suggests that the proactive preventive program to screen all prospective immigrants for malaria infection in their home countries significantly reduced the numbers of imported infections to <400 cases/year, a drop of 52.6%. In addition, it also identified a group of settled immigrants, the majority of whom were at high risk for acquisition of malaria infection during their visit to home countries. There is an urgent need to target this group for prevention strategies such as education/information and other preventive measures against malaria infection.     

Comparison of two egyptian strains ofSchistosoma mansoni in hamsters

In human infection withSchistosoma mansoni from Beni-Suef, the eggs were encountered more frequently in the urine of patients than in infection withS. mansoni from Giza, where eggs were passed into the stool. A comparative study of the two strains ofS. mansoni from Beni-Suef and Giza has been carried out in golden hamster. Consistent strain differences were observed. The Beni-Suef strain proved to have lower worm recovery and different egg distribution patterns in tissues of infected hamsters. Worms of both sexes of this strain were larger in size and required a longer period to reach maturity. Hence, the prepatent period was prolonged. Significant differences between the two strains were also noted in the number of eggs per worm. A lower mortality rate and a longer survival time were encountered in hamsters infected with the Beni-Suef strain.This work was supported by the Naval Medical Research and Development Command, NMC, NCR, Bethesda, MD. Work Unit No. 3M161102BS10.AA421     

Ventricular shape biomarkers for Alzheimer's disease in clinical MR images

The aim of this work was to identify ventricular shape-based biomarkers in MR images to discriminate between patients with Alzheimer's disease (AD) and healthy elderly. Clinical MR images were collected for 58 patients and 28 age-matched healthy controls. After normalizing all the images the ventricular cerebrospinal fluid was semiautomatically extracted for each subject and an innovative technique for fully automatic shape modeling was applied to generate comparable meshes of all ventricles. The search for potential biomarkers was carried out with repeated permutation tests: results highlighted well-defined areas of the ventricular surface being discriminating features for AD: the left inferior medial temporal horn, the right medial temporal horn (superior and inferior), and the areas close to the left anterior part of the corpus callosum and the head of the right caudate nucleus. The biomarkers were then used as features to build an intelligent machine for AD detection: a Support Vector Machine was trained on AD and healthy subjects and subsequently tested with leave-1-out experiments and validation tests on previously unseen cases. The results showed a sensitivity of 76% for AD, with an overall accuracy of 84%, proving that suitable biomarkers for AD can be detected in clinical MR images.     

Background sodium current underlying respiratory rhythm regularity

Rhythm-generating neural circuits underlying diverse behaviors such as locomotion, sleep states, digestion and respiration play critical roles in our lives. Irregularities in these rhythmic behaviors characterize disease states – thus, it is essential that we identify the ionic and/or cellular mechanisms that are necessary for triggering these rhythmic behaviors on a regular basis. Here, we examine which ionic conductances underlie regular or ‘stable’ respiratory activities, which are proposed to underlie eupnea, or normal quiet breathing. We used a mouse in vitro medullary slice preparation containing the rhythmogenic respiratory neural circuit, called the preBötzinger complex (preBötC), that underlies inspiratory respiratory activity. We varied either [K⁺]_o or [Na⁺]_o, or blocked voltage-gated calcium channels, while recording from synaptically isolated respiratory pacemakers, and examined which of these manipulations resulted in their endogenous bursting becoming more irregular. Of these, lowering [Na⁺]_o increased the irregularity of endogenous bursting by synaptically isolated pacemakers. Lowering [Na⁺]_o also decreased the regularity of fictive eupneic activity generated by the ventral respiratory group (VRG) population and hypoglossal motor output. Voltage clamp data indicate that lowering [Na⁺]_o, in a range that results in irregular population rhythm generation, decreased persistent sodium currents, but not transient sodium currents underlying action potentials. Our data suggest that background sodium currents play a major role in determining the regularity of the fictive eupneic respiratory rhythm.