A second case of Gerstmann-Sträussler-Scheinker disease linked to the G131V mutation in the prion protein gene in a Dutch patient

A rare case of Gerstmann-Str?ussler-Scheinker disease in a 36-year-old Dutch man is reported. The clinical phenotype was characterized by slowly progressive cognitive decline, later followed by ataxia and parkinsonism. Neuropathologic findings consisted of numerous amyloid plaques in the cerebellum, which showed positive staining for the abnormal prion protein (PrP(Sc)). In addition, there were tau accumulations around numerous amyloid deposits in the cerebral cortex, striatum, hippocampal formation, and midbrain. There was no spongiform degeneration. Western blot analysis showed the co-occurrence of 2 distinct abnormal prion protein species comprising an unglycosylated, protease-resistant fragment of approximately 8 kd, which was found to be truncated at both N- and C-terminal ends by epitope mapping, and a detergent-insoluble but protease-sensitive form of full-length PrP(Sc). Sequence analysis disclosed a mutation at codon 131 of the prion protein gene (PRNP), resulting in a valine-for-glycine substitution (G131V). The patient was heterozygous at the polymorphic codon 129 and carried the mutation on the methionine allele. To our knowledge, this is the second family worldwide in which this mutation has been identified. Gerstmann-Str?ussler-Scheinker disease should be considered in patients with a clinical diagnosis of familial frontotemporal dementia.     

Autoimmune pancreatocholangitis: a series of ten patients

BACKGROUND: During a 10-year period we observed 10 patients who suffered from an inflammatory-fibrosing disease mimicking pancreatic carcinoma and primary sclerosing cholangitis (PSC). METHODS: A review of the presenting features, the clinical course and the relevant literature. RESULTS: Ten male patients (mean age 55 years) presented with weight loss, jaundice and pruritus. Pancreatic cancer was suggested by imaging studies, which showed focal or generalized pancreatic enlargement and compression of the distal common bile duct. Cholangiography also demonstrated intrahepatic biliary stenoses consistent with sclerosing cholangitis. None had evidence of IBD. Exocrine pancreatic insufficiency was found in six cases and diabetes in four. Pancreatic histology (n=3) showed fibrosis and extensive inflammatory infiltrates. Immunosuppressive treatment was instituted in five patients. Clinical and biochemical remission occurred in three; in one other patient, previously documented intrahepatic biliary strictures had disappeared after 3 months. One patient had concomitant Sj?gren's disease. The clinical features, pancreatic involvement, age at presentation, absence of IBD and response to steroids all plead against a diagnosis of "classical" PSC. The natural course of the disease was highly variable. Thirty-five comparable cases, with a largest series of three, have been reported in the literature. The disease has been associated with Sj?gren's disease, retroperitoneal fibrosis and other fibrosing conditions, and may be a manifestation of a systemic fibro-inflammatory disorder. CONCLUSION: Autoimmune pancreatocholangitis is a distinct inflammatory disorder involving the pancreas and biliary tree. The disease may mimick pancreatic carcinoma and PSC and responds to immunosuppressives.     

Treatment with leuprolide acetate and hormonal add-back for up to 10 years in stage IV endometriosis patients with chronic pelvic pain

This pilot study examined the effect of a low-dose E and pulsed progestogen hormone therapy (HT) regimen for add-back during long-term GnRH-agonist therapy on bone mineral density (BMD) in five patients with stage IV endometriosis. Bone mineral density was stable after initiation of HT for the entire follow-up period (up to 10 years). One patient stopped her treatment on two occasions to conceive and was successful each time with delivery of a normal baby. No patient had return of pelvic pain after HT add-back.     

Interaction of Nepsilon(carboxymethyl)lysine- and methylglyoxal-modified albumin with endothelial cells and macrophages. Splice variants of RAGE may limit the responsiveness of human endothelial cells to AGEs

In diabetes mellitus an increased risk exists for vascular complications. A role for advanced glycation endproducts (AGEs) in the acceleration of vascular disease has been suggested. Nepsilon-(carboxymethyl)lysine (CML)- and methylglyoxal (MGO)-modified proteins have been identified as major AGEs. The interaction of these AGEs with the human endothelial cells and macrophages was studied. Changes in adhesion molecule expression, i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin were determined by cell-bound Elisa on human endothelial cells after incubation with CML-modified albumin and MGO-modified albumin. The presence of the full-length receptor of AGEs (RAGE) and splice variants of RAGE was determined by specific RT-PCR. In addition, binding studies were performed with CML- and MGO-modified albumin to endothelial cells and P388D1 macrophages. We demonstrated that CML-albumin or MGO-albumin did not induce activation of endothelial cells as measured by the expression of adhesion molecules, while, under the same conditions, TNF-alpha did. No specific binding of CML-albumin and MGO-albumin on these cells was found. In contrast to endothelial cells, a specific binding of MGO-albumin to P388D1 macrophages was demonstrated, which could be competed by ligands of scavenger receptors. In human umbilical vein and microvascular endothelial cells we found the N-truncated and C-truncated splice variants of RAGE. In conclusion, under our experimental conditions no CML- or MGO-albumin-induced increase in adhesion molecule expression was found on endothelial cells. In agreement with this, no binding of these AGEs was found to endothelial cells. The existence of splice variants of RAGE in endothelial cells might explain the lack of interaction of extracellular AGEs with these cells.     

Management of small soft-tissue sarcoma of the extremity in adults.

To determine the significance of small (< or = 5 cm in diameter) soft-tissue sarcoma of the extremity, 174 adult patients were identified from information that had been entered prospectively into a database of 1742 patients between July 1982 and December 1990. Median follow-up was 48 months. The majority of tumors were high grade (n = 114; 66%). Local recurrence (n = 17) was seen in patients with both high-grade (11%) and low-grade tumors (7%). Distant metastases were seen in 7% of high-grade tumors and in no low-grade tumors. The overall 5-year survival rate was 94% for all patients. Grade, depth, location, type of operation, and sex did not affect 5-year survival or local recurrence-free survival. Neither postoperative adjuvant chemotherapy nor radiation therapy resulted in superior 5-year survival or local recurrence-free survival when compared with no postoperative treatment. The prognosis of these lesions is favorable, and no additional prognostic factors were identified. Inclusion of these patients into adjuvant therapy trials examining survival is inappropriate.     

Hemorrhage simulating tumor growth in malignant fibrous histiocytoma at MR imaging.

During the course of preoperative chemotherapy for treatment of malignant fibrous histiocytoma of the lower extremity, the mass in three patients was found to be enlarged at physical examination. Magnetic resonance (MR) imaging demonstrated, and subsequent pathologic examination of resected specimens proved, that the enlargement was caused by extensive hemorrhage within the masses, rather than by tumor growth. MR imaging can demonstrate this phenomenon well, particularly on T1-weighted images.