Acute neuropathies after peripheral blood stem cell and bone marrow transplantation

Neuromuscular complications are not uncommon after bone marrow and stem cell transplantation, especially in patients with allogeneic transplantations and graft-versus-host disease. The pathogenesis of these complications remains unclear, but the changes in immune modulation that occur after transplantation are likely to play a key role. We describe 4 patients who developed brachial plexopathy (3 cases) or multiple lumbosacral radiculopathies (1 case) between 5 days and 4 months after autologous peripheral blood stem cell (3 cases) or allogeneic bone marrow transplantation without evidence of graft-versus-host disease (1 case). Infectious, tumor-related, toxic, and metabolic causes were excluded in all cases. Recovery was limited in two cases and nearly complete in the other two patients. Brachial plexopathies and polyradiculopathies are potential complications of peripheral blood stem cell and bone marrow transplantation. It is possible that these disorders may be the result of autoimmune phenomena directed against specific nerve antigens.     

Selectins influence thrombosis in a mouse model of experimental deep venous thrombosis

BACKGROUND: This study characterizes venous thrombosis in the mouse and examines the important role that the adhesion molecules P-selectin and E-selectin and the anti-inflammatory cytokine interleukin-10 (IL-10) play in the thrombotic process. MATERIALS AND METHODS: C57BL/6 (wild-type) mice in a natural history protocol (Phase I) and gene-targeted (KO) mice for P-selectin, E-selectin, P/E-selectin, and IL-10 in a follow-up protocol (Phase II) were studied. Inferior vena caval thrombosis was produced by ligation just below the renal veins, and mice were sacrificed and evaluated at various time points up to 12 days later. RESULTS: Phase I: A significant increase in neutrophils on day 2 and in monocytes on day 6 postthrombosis was found in ligated vs sham animals. An associated significant increase in vein wall P-selectin mRNA (6 h, day 2) and an increase in protein (6 h through day 6) were found, while E-selectin mRNA was significantly increased (day 2 through day 6), with a smaller increase in E-selectin protein. IL-10 mRNA increased significantly later (day 2 through day 9), with the values increasing progressively. A positive correlation existed (r = 0.77) between neutrophils and thrombosis at day 2. PHASE II: The E-selectin and P/E-selectin double-KO mice showed the least thrombus at day 2 vs wild-type clotted mice, P < 0.01. Additionally, P/E-KO mice demonstrated the lowest inflammatory cell extravasation into the vein wall at day 2. CONCLUSIONS: This study demonstrates an acute to chronic inflammatory response in the vein wall associated with venous thrombosis. Inhibition of selectins decreased thrombus formation.     

A novel model of acetaminophen-induced acute hepatic failure in rabbits

BACKGROUND: Few reliable and reproducible animal models of acute hepatic failure exist or conform to the criteria proposed by Terblanche and Hickman (Dig. Dis. Sci. 36: 770, 1991). In this prospective randomized study we describe the selective induction of CYP450 enzymes, depletion of glutathione, and hepatotoxic insult using acetaminophen in the development and characterization of a novel rabbit model of acute hepatic failure. MATERIALS AND METHODS: Male New Zealand white rabbits weighing 3-5 kg were used. After preliminary dose ranging experiments, two groups of New Zealand white (n = 8 in each group) rabbits had CYP450 induction with phenobarbitone (40 mg/kg ip for 5 days) or with 20-methylcholanthrene (80 mg/kg ip). The glutathione synthetase inhibitor buthionine sulfoxime (2 mmol/kg iv) was then administered prior to acetaminophen administration (500 mg/kg sc). Clinical observations were recorded and arterial blood was sampled over 72 h. RESULTS: Grade I-III encephalopathy occurred at 5-12, 12-25, and 28-56 h, respectively, in animals pretreated with 20-methylcholanthrene, but not in the phenobarbitone pretreated group. Mortality was 75% in the 20-methylcholanthrene group compared to 0% in the phenobarbitone group. Blood lactate (P < 0.05), prothrombin time (P < 0.005), aspartate transaminase (P < 0.005), and creatinine (P < 0.05) were higher in the 20-methylcholanthrene group compared to the phenobarbitone group. Histological changes were marked in the 20-methylcholanthrene group with massive coagulative hepatic necrosis compared to minimal histological damage in the phenobarbitone group. CONCLUSION: The induction with 20-methylcholanthrene, glutathione depletion with buthionine sulfoxime, and subcutaneous administration of acetaminophen have led to the development of an animal model that parallels clinical, biochemical, and histological features of human hepatic failure.     

Renal transplantation in patients with Fabry disease

Anderson-Fabry disease (AFd) is a rare X-linked disorder characterized by deficiency of alpha-galactosidase A that leads to systemic accumulation of neutral glycosphingolipids, predominantly globotriaosylceramide (Gb3), in body fluids and visceral tissues, including the kidney. End-stage renal failure is a common manifestation in hemizygous males that often occurs by the third to fourth decade of life. Usually transplanted patients exhibit improvement in clinical symptoms of the disease, probably related to the production of alpha-galactosidase A from the grafted kidney, but mainly related to the increase in Gb3 clearance by the functioning kidney, and increased survival of red cells due to the correction of the uremic status with an evident decrease in the production of Gb3 depending from hemolysis. Several Fabry patients with successful kidney graft survived for 10-15 years and died for cardiovascular complications related to the metabolic disease. The loss of grafted kidney is due to rejection, thrombosis or sepsis. An important issue considering renal transplantation in AFd is the recurrence of the disease in the kidney graft; however, no evidence regarding this possibility has occurred up to now. We report herein the ultrastructural study of the urinary sediment of a 35-year-old male Fabry patient with a severe clinical form of the disease with progression to ESRF at age 29, and submitted to renal transplantation at 33 years. Ultrastructural findings of the urinary sediment documented several cells, probably tubular epithelial cells, with typical accumulation of myelinic bodies resulting from intracellular storage of neutral glycosphingolipids. This morphological evidence arises the problem of the possible recurrence of AFd in the kidney graft in patients with severe phenotype of the metabolic disease.     

Aortic valve fibroelastomas as an incidental intraoperative transesophageal echocardiographic finding

IMPLICATIONS: We report incidental findings of aortic valve fibroelastomas during routine intraoperative transesophageal echocardiography examination in cardiac surgery. Preoperative echocardiography failed to identify this potentially devastating pathology. The echocardiographic features of this lesion are reviewed, and the importance of diligence and complete examination are emphasized.     

Ferritin concentrations in dried serum spots from capillary and venous blood in children in Sri Lanka: a validation study

BACKGROUND: Assessing iron status continues to be challenging in field situations. Spot methods developed for analyzing ferritin from serum or plasma samples that are spotted and dried on filter paper have been shown to provide reliable and accurate iron-status assessments. However, the spot methods are based on samples from venous serum or plasma and have not been evaluated in field settings. OBJECTIVE: We evaluated the validity of analyzing ferritin to assess iron status by using venous and capillary dried-serum-spot (DSS) samples by the spot method compared with using serum ferritin by the traditional method in a field setting. DESIGN: Venous and capillary blood was obtained from healthy schoolchildren (n = 100; +/- SD age: 8.9 +/- 0.3 y) in Colombo, Sri Lanka. To prepare DSS samples, we aliquoted precisely 20 microL serum per spot on filter paper, air-dried the spots, and placed them in airtight plastic bags until analysis by the spot ferritin method with the use of cellulase from Trichoderma reesei at 2 wk after collection. Venous serum (100 microL) was frozen until ferritin determination by traditional radioimmunoassay. RESULTS: Venous and capillary DSS ferritin values correlated strongly with traditional serum ferritin values (r = 0.88 and 0.86, respectively; P = 0.0001). The geometric means (+/- 1 SD) for venous and capillary DSS ferritin and traditional ferritin were 26.9 (15.3-47.4), 33.9 (20.9-54.8), and 33.1 (18.6-58.8) microg/L, respectively, and were not significantly different. Venous and capillary DSS methods on average (+/- SD) yielded ferritin values that were 5.8 +/- 10.1 microg/L lower and 0.1 +/- 9.4 microg/L higher, respectively, than serum ferritin values obtained with the traditional method. CONCLUSIONS: Capillary and venous DSS methods for analyzing ferritin provide accurate tools for assessing iron status. Furthermore, capillary DSS ferritin is a practical means of detecting iron deficiency in field settings.     

Independent effects of residual renal function and dialysis adequacy on dietary micronutrient intakes in patients receiving continuous ambulatory peritoneal dialysis

BACKGROUND: Dialysis patients are at risk of vitamin and mineral deficiencies, not only because of losses during chronic hemodialysis or peritoneal dialysis but also because of low intakes. OBJECTIVE: The objective was to determine the importance of urea clearance (calculated as K(t)/V) and residual renal function (RRF) in predicting micronutrient intakes in a large cohort of patients receiving continuous ambulatory peritoneal dialysis (CAPD). DESIGN: We conducted a survey of dietary intakes in 242 CAPD patients and divided them into 3 groups according to their weekly urea clearance and RRF: WD group (n = 84), a urea clearance >/= 1.7 and a glomerular filtration rate (GFR) >/= 1 mL x min(-1) x 1.73 m(-2); DD group (n = 71), a urea clearance >/= 1.7 and a GFR < 1 mL x min(-1) x 1.73 m(-2); and ID group (n = 87), a urea clearance < 1.7. RESULTS: Most of the patients had intakes of water-soluble vitamins and minerals that were lower than the recommended dietary allowance; most intakes were significantly higher in the WD group than in the DD and ID groups, except those of niacin and calcium. After age, sex, body weight, and the presence of diabetes were controlled for, total weekly urea clearance and the GFR (but not peritoneal dialysis urea clearance) were significantly associated with intakes of vitamins A and C, the B vitamins, and minerals (calcium, phosphate, iron, and zinc). Low intakes of vitamins and minerals with low RRF and urea clearance were the result of reduced overall food intakes, except for thiamine, vitamin B-6, and folic acid, which were deficient in the diet. CONCLUSIONS: Supplementation with most water-soluble vitamins and minerals, including iron and zinc, should be considered in CAPD patients, especially those with low RRF and low urea clearance. The optimal dose needs to be determined.     

Advanced glycosylation end product quantification: differently produced polyclonal antisera do not share the recognition of epitopes of different nature

Advanced glycosylation end products (AGE) which are probably involved in the pathogenesis of diabetic complications, comprise a series of related chemical structures. Thus different antisera might recognize particular AGE epitopes rather than the complete range of epitopes. To test this hypothesis, two antisera were raised using different immunization techniques and different AGE-carrier proteins as immunogens. The antisera reactivity towards different AGE-proteins under various experimental conditions was compared. Both antisera recognized all AGE-proteins, although with different binding curves. Following pre-incubation with carboxymethyllysine-BSA (CML-BSA) (an oxidation-derived AGE) one antiserum partially retained its reactivity, suggesting recognition of non-oxidation-derived AGE. This result was confirmed both in the cross-reactivity and the preincubation experiments and when the reactivity of the antisera was tested against antigens incubated under oxidative and non-oxidative conditions. These results confirmed the hypothesis that differently produced antisera may not share the recognition of epitopes of different nature and suggest the necessity to adopt a standardized methodology for the production of antisera for an accurate and reproductible determination of the in vivo AGE concentration.