Human natriuretic factor in cirrhotic patients undergoing orthotopic liver transplantation

We measured the plasma levels of atrial natriuretic factor (ANF) during orthotopic liver transplantation (OLT) in eight adult patients with cirrhosis and ascites. The aim of this study was to determine whether significant differences in ANF concentration may be detected during the individual phases of OLT and to correlate these changes with hemodynamics. In each patient a hemodynamic assessment was achieved using a Swan-Ganz fiber optic catheter for continuous monitoring of cardiac output (CO), systemic vascular resistance index (SVRI), right filling pressure as assessed by central venous pressure (CVP), and left filling pressure by means of pulmonary arterial wedge pressure (PAWP). During reperfusion a clear-cut increase in ANF values was observed (P<0.05). Concurrently, an increase in CVP (P<0.05) and a decrease in SVRI were observed without any significant increase in diuresis. These data suggest that ANF might play a role in the development of the reperfusion syndrome.     

Exposure levels of asthmatic children to allergens, endotoxins, and serine proteases in a tropical environment.

A cross-sectional study was conducted in Bayamón, Puerto Rico, to identify and quantify indoor allergens, serine proteases, and bacterial endotoxin present in homes of asthmatic children. A total of 126 dust samples from houses were obtained from the entire mattress and bedside floor. Most of the patients had detectable levels of mite, cockroach, cat, and dog allergens. Mold allergens were found only in bedside floor dust samples. Mouse allergens were not detected. Forty-two percent, 36.5%, and 1.8% of the patients demonstrated exposures to sensitizing levels of mite, Bla g 1 and cat allergens, respectively. The percentage of patients exposed to high levels of allergens capable of triggering asthma symptoms was 33.3% and 26.4% for mite and Bla g 1 allergens. Only dog allergen, bacterial endotoxin, elastase, and trypsin were associated with asthma symptoms. Eighty-nine percent of the asthmatic children were exposed to endotoxin concentrations greater than 100 EU/mg dust, and more than half of the patients were exposed to high levels of serine proteases. Our study indicates that indoor concentrations of allergens traditionally associated with asthma symptoms and severity may not be applicable in tropical environments and highly ventilated households. In fact, in the study population, endotoxins, dog allergen, and serine proteases may play a dominant role in the induction of asthma symptoms.     

Endothelial differentiation of hematopoietic stem and progenitor cells from patients with multiple myeloma.

PURPOSE: Vasculogenesis is a physiologic process typical of fetal development in which new blood vessels develop from undifferentiated precursors (or angioblasts). In tumors, near angiogenesis, vasculogenesis contributes to the formation of the microvascular plexus that is important for diffusion. Here, we show that hematopoietic stem and progenitor cells (HSPC) of multiple myeloma (MM) patients are able to differentiate into cells with endothelial phenotype on exposure to angiogenic cytokines. EXPERIMENTAL DESIGN: Circulating HSPCs were purified with an anti-CD133 antibody from patients with newly diagnosed MM before autologous transplantation and exposed to vascular endothelial growth factor (VEGF), fibroblast growth factor-2 and insulin-like growth factor in a 3-week culture. RESULTS: HSPCs gradually lost CD133 expression and acquired VEGF receptor-2, factor VIII-related antigen, and vascular endothelial-cadherin expression. The expression pattern overlapped with paired MM endothelial cells (MMEC). During culture, cells adhered to fibronectin, spread, and acquired an endothelial cell shape. Differentiated HSPCs also became capillarogenic in the Matrigel assay with maximal activity at the third week of culture. Bone marrow biopsies revealed HSPCs inside the neovessel wall in patients with MM but not in those with monoclonal gammopathy of undetermined significance. CONCLUSIONS: In patients with MM, but not in those with monoclonal gammopathy of undetermined significance, HSPCs contribute to the neovessel wall building together with MMECs. Therefore, besides angiogenesis, HSPC-linked vasculogenesis contributes to neovascularization in MM patients. Tentatively, we hypothesize that in HSPC cultures a multipotent cell population expressing low VEGF receptor-2 levels corresponds to the endothelial progenitor cell precursor and seems to be the MMEC precursor.     

Is PTH a risk factor for cardiovascular calcifications in haemodialysis?

Sir, We read with interest the article in NDT by Coen et al. [1],on the association between serum intact parathyroid hormone(iPTH) levels higher than 600 pg/ml and the severity of coronarycalcifications in haemodialysis (HD) patients. In     

A novel presenilin 1 mutation (V261L) associated with presenile Alzheimer's disease and spastic paraparesis

Background and purpose:  We report a novel mutation in exon 8 of the presenilin 1 (PSEN1) gene (V261L) associated with early-onset autosomal dominant Alzheimer's disease and spastic paraparesis.
Methods and results:  The proband was a woman who developed insidious cognitive decline with predominant memory loss and gait disorder secondary to spasticity at the age of 40. Her brother and her mother had a similar disease in the fifth decade of life. The feature of amnestic presentation with spastic paraparesis is consistent with the majority of mutations in the exon 8 of the PSEN1 1 gene.
Conclusions:  Screening for PSEN1 mutations is especially likely to be productive when directed toward persons with positive family history and with age at onset of under 60.     

Acute renal and hepatic failure due to accidental percutaneous absorption of 1,2-dichlorpropane contained in a commercial paint fixative.

Sir, 1,2-dichloropropane (DCP), a colourless, flammable liquid witha chloroform-like odour, is a volatile organo-halogenated compoundcontained in many commercial chemicals, such as solvents foroils, waxes, resins and glues, degreasing and dry-cleaning fluids,pesticides, lead scavengers for gasoline, and paint fixatives[1]. In the few cases of acute severe 1,2-DCP toxicity reported sofar in humans, toxic damage has involved the kidney, liver,haemostatic system, red blood cells and CNS, but in every instance,intoxication occurred through the inhalatory or oral route [1–3]. Here we describe the case of     

Anti-interleukin 2 receptor monoclonal antibody in the treatment of ongoing acute rejection episodes of human kidney graft--a pilot study

Monoclonal antibodies (MoAbs) against human interleukin 2 receptor (IL-2-R) have been shown to prevent early kidney rejection in animals and humans. We report here the effect of an anti-IL-2-R MoAb (33B3.1) inhibiting IL-2 binding high-affinity sites on activated lymphocytes in 10 declared acute rejection episodes of first cadaveric kidney grafts. Six patients were under cyclosporine treatment only at the time of diagnosis of the rejection. All rejection episodes but one were biopsy-proved cellular rejections. Treatment consisted of intravenous infusions of 33B3.1 at 20 mg/day x 2 days, followed by 10 mg/day for 8 additional days. In case of MoAb ineffectiveness at day 5, anti-IL-2-R MoAb was discontinued and a rescue treatment of corticosteroid boluses (CSb) was given. If not, in all cases corticosteroids (CS) were given (1 mg/kg) at the end of MoAb treatment (day 10) and tapered off thereafter. Two rejection episodes immediately responded to 33B3.1 treatment. During 33B3.1 treatment four other patients had only a stabilization of their blood creatinine concentration, which nevertheless returned to prerejection levels after day 10 when anti-IL-2-R was discontinued and CS administered at 1 mg/kg (no rescue treatment). The four remaining patients had an increase of their blood creatinin levels at day 5 despite 33B3.1 treatment, and their renal function only improved with CSb rescue treatment. One of these patients lost the graft despite rescue treatment, as well as a 9-day course of antithymocyte globulin. Trough levels of MoAb reached a plateau as early as day 2 (approximately 6 micrograms/ml). All patients developed antibodies (IgM and IgG) after day 14. In no instance could unresponsiveness be related to low circulating 33B3.1 trough levels or to early host anti-MoAb immune response (IgM or IgG). We conclude that 33B3.1, known to be effective in preventing early rejection, has only inconsistent and/or incomplete effects on the ongoing rejection process. Our data suggest that once IL-2-dependent clones are expanded in the rejected graft, interference with IL-2/IL-2-R signals does not block the effector mechanisms sustaining acute rejection.