Gastrointestinal complications of schistosomiasis.

Schistosomiasis is an important disease in many parts of the world and has affected the course of human history many times over. The parasitic infection is acquired during contact with infected water. A chronic inflammatory response to schistosome eggs, mediated by both cellular and humoral mechanisms, is the root of the pathology seen in schistosomiasis. Hepatosplenic disease results in intrahepatic presinusoidal portal hypertension. The resultant esophageal and gastric varices are an important cause of morbidity and mortality. Standard treatment guidelines for managing varices can be applied to patients with schistosomiasis. Coinfection with viral hepatitis results in liver disease that progresses more rapidly and is more difficult to treat. Intestinal schistosomiasis may be confused with other disease states and can be an important cause of morbidity, especially in heavily infected patients. Diagnosis relies on demonstration of schistosome eggs in feces or tissue. Praziquantel is the treatment of choice. The development of a vaccine for schistosomiasis is an important goal in the attempt to control this disease.

Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1.

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.