Evaluation of neural damage in Duchenne muscular dystrophy patients.

The presence of non-progressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy (DMD). Concurrently, the amyloid beta peptide (Aß42) protein has been associated with changes in memory and cognitive functions. Also, it has been shown that different subtypes of neural stem/progenitor cells (CD 34, CD 45, nestin) are involved in the innate repair of plasticity mechanisms by the injured brain, in which Nerve Growth Factor (NGF) acts as chemotactic agents to recruit such cells. Accordingly, the present study investigated levels of CD 34, CD 45, nestin and NGF in an attempt to investigate makers of neural regeneration in DMD. Neural damage was assayed in terms of Aß42. Results showed that Aß42 (21.9 ± 6.7 vs. 12.13 ± 4.5) was significantly increased among DMD patients compared to controls. NGF (165.8 ± 72 vs. 89.8 ± 35.9) and mononuclear cells expressing nestin (18.9 ± 6 vs. 9 ± 4), CD 45 (64 ± 5.4 vs. 53.3 ± 5.2) and CD34 (75 ± 6.2 vs. 60 ± 4.8) were significantly increased among DMD patients compared to controls. In conclusion cognitive function decline in DMD patients is associated with increased levels of Aß42, which is suggested to be the cause of brain damage in such patients. The significant increase plasma NFG and in the number of mononuclear cells bearing CD34, CD45 and nestin indicates that regeneration is an ongoing process in these patients. However, this regeneration cannot counterbalance the damage induced by dystrophine mutation and increased Aß42.

Schistosomal hepatic fibrosis and the interferon gamma receptor: a linkage analysis using single-nucleotide polymorphic markers.

A minority of individuals infected with the parasite Schistosoma mansoni develops hepatic fibrosis. HLA studies in Egypt and a candidate gene search in a Sudanese population indicate that the host's genetics contribute to disease susceptibility. In an Egyptian community, 32.7% of individuals 11 years and older had significant fibrosis by WHO ultrasound criteria. Linkage to 10 candidate genes was tested using 89 affected sibling pairs from 40 pedigrees in this community. The candidates included genes that initiate fibrosis, participate in collagen synthesis, or control collagen degradation. Two to four single-nucleotide polymorphisms (SNPs) were genotyped per locus, and 188 individuals were genotyped at 48 markers. Model-free modified Haseman-Elston analysis identified linkage to a SNP in the interferon gamma receptor locus (P=0.000001). There was also weak evidence for linkage to the interleukin 13-4 region and tissue growth factor beta 1.

Measuring morbidity in schistosomiasis mansoni: relationship between image pattern, portal vein diameter and portal branch thickness in large-scale surveys using new WHO coding guidelines for ultrasound in schistosomiasis.

OBJECTIVE: World Health Organization consensus meetings on 'Ultrasound in Schistosomiasis' in 1996 and 1997 anticipated further challenges in the global implementation of a standardized protocol for morbidity assessment in schistosomiasis mansoni. We evaluated the performance of the qualitative and quantitative components of the new Niamey criteria. METHOD: Use of the Niamey protocol among 3954 subjects in two linked, cross-sectional ultrasound surveys of Schistosoma mansoni-endemic populations in Egypt and Kenya. RESULTS: There were significant differences between Egyptian and Kenyan sites in prevalence and age distribution of S. mansoni-related hepatic fibrosis (36%vs. 3%, P < 0.001). Protocol image pattern scoring could be performed quickly and was stable to interobserver variation. However, there were unintended but systematic differences between study sites in the measurement of portal vein diameter (PVD) and wall thickness. By Niamey criteria, a high prevalence of portal dilation was scored for normal Egyptian subjects, which reduced the predictive value of image pattern for portal hypertension. Using alternative height-indexing of PVD, image pattern plus PVD findings predicted 15% of Egyptians and 2.5% of Kenyans were at risk for variceal bleeding, whereas locally derived PVD norms estimated 25% of Egyptians and 12% of Kenyans to be at possible risk. CONCLUSION: Niamey scoring criteria performed acceptably as a relative grading system for disease in schistosomiasis mansoni, but failed to account fully for site-to-site variation in test performance and morbidity prevalence. Consequently, standardized image pattern scoring appears to provide the most useful tool for detection and comparison of S. mansoni-associated morbidity in large-scale surveys.

Population-based differences in Schistosoma mansoni- and hepatitis C-induced disease.

Two populations with differing histories of Schistosoma mansoni and hepatitis C infection were compared directly for severity of disease and extent of comorbidity. Demographic, parasitologic, and ultrasound surveys were conducted on 2038 Egyptians and on 2120 Kenyans. Hepatitis B and C serologies and transaminase levels were obtained from a subset at each site. Despite significantly lower prevalence and intensity of infection, Egyptians had a higher prevalence of severe schistosomal fibrosis than Kenyans (36.8% vs. 4.6%). Hepatitis C infection was 3 times more prevalent among Egyptians, and evidence of hepatocellular damage was significantly greater among Egyptians. There was no interaction between S. mansoni infection or disease and the prevalence or severity of hepatitis C. For both infections, the intensity or prevalence of infection was a poor predictor of morbidity. The prevalence of disease in the Egyptian population from different pathogens suggests a generalized susceptibility to inflammatory liver disease.