[Spontaneous splenic vein rupture complicating liver cirrhosis: an autopsy case report].

A 70-year-old woman, who had hepatitis-C related liver cirrhosis died suddenly. Autopsy showed a massive retroperitoneal hematoma and ruptured splenic vein, as well as densely bloody ascites. This suggested that chronic and unnoticed retroperitoneal leak from the ruptured vein preceded the acute and fatal outcome of the intra-abdominal bleeding. Spontaneous rupture of the splenic vein is rarely reported in liver cirrhosis despite the presence of portal hypertension. This rare association is discussed with a literature review.

[A case of rapid-onset antimitochondrial antibody-positive autoimmune hepatitis possibly triggered by a urinary tract infection].

A 54-year-old woman suffered acute hepatitis after she acquired cystitis. Laboratory results on admission showed: AST 925, ALT 1171, ALP 623, gamma-GTP127 IU/l, T-Bil 5.0 mg/dl, antinuclear antibodies negative, smooth muscle antibodies 80, antimitochondrial antibodies (AMA) 80, antimitochondrial M2 antibody (AMA-M2) 117 index, IgG 2210 mg/dl. She also had HLA-DR4 and HLA-DR8. Histological study of a liver biopsy specimen suggested that she had autoimmune hepatitis rather than primary biliary cirrhosis. When prednisolone was administered, her liver function immediately improved and AMA and AMA-M2 levels fell to 20 and 52 respectively. However when cystitis recurred 4 months later, her liver function worsened. Laboratory findings showed AST 174, ALT 183 IU/l. Upon increasing the dosage of prednisolone, her liver function improved again. After the recurrence of hepatitis, AMA and AMA-M2 levels increased to 320 and 149 respectively. We speculate that the urinary tract infection triggered an autoimmune response and her genetic predisposition also played a crucial role in the process.

Non-secretory multiple myeloma with azurophilic granules and vacuoles: an immunological and ultrastructural study.

Cytoplasmic vacuolation was seen in patients with a variety of plasma cell dyscrasia. We report here a case of leukemic non-secretory multiple myeloma with many azurophilic granules. By electron microscopy, the myeloma cells were found to have a well-developed rough endoplasmic reticulum and a clear Golgi apparatus, and azurophilic granules were identified as phagocytic vacuoles. In addition to myeloma markers, the cells were positive for B cell-associated, myeloid and stem cell markers. The diagnosis is difficult because of its misleading morphology and unusual surface markers. We consider that electron microscopy is useful for the identification of cell lineage in this disorder.

Disappearance of intraglomerular lipoprotein thrombi and marked improvement of nephrotic syndrome by bezafibrate treatment in a patient with lipoprotein glomerulopathy.

Lipoprotein glomerulopathy (LPG) is a hereditary disorder characterized by intraglomerular lipoprotein thrombi and increased serum apolipoprotein (apo) E. Patients with LPG usually manifest with nephrotic syndrome, and some progress to renal failure; however, no effective therapeutic regimen has been established for this disease. We experienced a patient with LPG for whom bezafibrate treatment was very effective. This 30-year-old Japanese woman had nephrotic syndrome and type III hyperlipoproteinemia. Renal biopsy showed markedly dilated capillary lumina containing massive lipoprotein thrombi. Plasma apo E concentration was elevated to twice that of normal controls. She was proved to be a heterozygote of apo E2 Kyoto (Arg25Cys). After 2 years treatment with bezafibrate (400 mg/day), her plasma albumin gradually increased from 2.1 to 4.0 mg/dl, and intraglomerular lipoprotein thrombi disappeared almost completely. Bezafibrate decreased plasma apo E and dramatically increased high density lipoprotein (HDL)-cholesterol. The decrease in apo E was observed mainly in the pre-beta-fraction, not in the alpha fraction. Lipidological analyses of our patient suggest that the origin her lipoprotein thrombi may be mainly from pre-beta-lipoproteins and that HDL might be involved in resolving lipoprotein thrombi. Our case suggests that administration of fibrates such as bezafibrate may be a novel therapeutic strategy for resolving intraglomerular thrombi and improving nephrotic syndrome in patients with LPG.

Long-term support of hematopoiesis by a single stem cell clone in patients with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by clonal blood cells that are deficient in glycosylphosphatidylinositol-anchored proteins because of somatic mutations of the PIG-A gene. Many patients with PNH have more than one PNH clone, but it is unclear whether a single PNH clone remains dominant or minor clones eventually become dominant. Furthermore, it is unknown how many hematopoietic stem cells (HSCs) sustain hematopoiesis and how long a single HSC can support hematopoiesis in humans. To understand dynamics of HSCs, we reanalyzed the PIG-A gene mutations in 9 patients 6 to 10 years after the previous analyses. The proportion of affected peripheral blood polymorphonuclear cells (PMNs) in each patient was highly variable; it increased in 2 (from 50% and 65% to 98% and 97%, respectively), was stable in 4 (changed less than 20%), and diminished in 3 (94%, 99%, and 98% to 33%, 57%, and 43%, respectively) patients. The complexity of these results reflects the high variability of the clinical course of PNH. In all patients, the previously predominant clone was still present and dominant. Therefore, one stem cell clone can sustain hematopoiesis for 6 to 10 years in patients with PNH. Two patients whose affected PMNs decreased because of a decline of the predominant PNH clone and who have been followed up for 24 and 31 years now have an aplastic condition, suggesting that aplasia is a terminal feature of PNH.

Autoimmune pancreatitis successfully treated with ursodeoxycholic acid.

A 51-year-old woman with autoimmune pancreatitis is reported in whom treatment with ursodeoxycholic acid (UDCA) was beneficial. Complaining of epigastric discomfort, she presented with liver dysfunction of the cholestatic type, and diabetes mellitus. Pancreatic imaging revealed a diffuse swelling of the body, an irregular narrowing of the main pancreatic duct, and a terminal stricture of the common bile duct. Histologically, the biopsied pancreas was replaced by fibrous tissue with a small amount of mononuclear cell infiltration. She had anti-carbonic anhydrase-II antibody and anti-lactoferrin antibody. After treatment with UDCA, her liver dysfunction and diabetes mellitus improved and the pancreas size was reduced. Steroid therapy is usually indicated for this disorder, but UDCA may be given as an alternative choice.