102,042 research outputs found
Natural history and outcome in systemic AA amyloidosis
No full textBACKGROUND:Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious complication of many chronic inflammatory disorders. Little is known about the natural history of AA amyloidosis or its response to treatment.METHODS:We evaluated clinical features, organ function, and survival among 374 patients with AA amyloidosis who were followed for a median of 86 months. The SAA concentration was measured serially, and the amyloid burden was estimated with the use of whole-body serum amyloid P component scintigraphy. Therapy for inflammatory diseases was administered to suppress the production of SAA.RESULTS:Median survival after diagnosis was 133 months; renal dysfunction was the predominant disease manifestation. Mortality, amyloid burden, and renal prognosis all significantly correlated with the SAA concentration during follow-up. The risk of death was 17.7 times as high among patients with SAA concentrations in the highest eighth, or octile, (greater/equal 155 mg per liter) as among those with concentrations in the lowest octile (< 4 mg per liter); and the risk of death was four times as high in the next-to-lowest octile (4 to 9 mg per liter). The median SAA concentration during follow-up was 6 mg per liter in patients in whom renal function improved and 28 mg per liter in those in whom it deteriorated (P < 0.001). Amyloid deposits regressed in 60% of patients who had a median SAA concentration of less than 10 mg per liter, and survival among these patients was superior to survival among those in whom amyloid deposits did not regress (P=0.04).CONCLUSIONS:The effects of renal dysfunction dominate the course of AA amyloidosis, which is associated with a relatively favorable outcome in patients with SAA concentrations that remain in the low-normal range (< 4 mg per liter)
Eprodisate for the treatment of renal disease in AA amyloidosis
No full textBackground: Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the kidney causes progressive deterioration in renal function. Eprodisate is a member of a new class of compounds designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues.
Methods: We performed a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of eprodisate in patients with AA amyloidosis and kidney involvement. We randomly assigned 183 patients from 27 centers to receive eprodisate or placebo for 24 months. The primary composite end point was an assessment of renal function or death. Disease was classified as worsened if any one of the following occurred: doubling of the serum creatinine level, reduction in creatinine clearance by 50% or more, progression to end-stage renal disease, or death.
Results: At 24 months, disease was worsened in 24 of 89 patients who received eprodisate (27%) and 38 of 94 patients given placebo (40%, P=0.06); the hazard ratio for worsening disease with eprodisate treatment was 0.58 (95% confidence interval, 0.37 to 0.93; P=0.02). The mean rates of decline in creatinine clearance were 10.9 and 15.6 ml per minute per 1.73 m2 of body-surface area per year in the eprodisate and the placebo groups, respectively (P=0.02). The drug had no significant effect on progression to end-stage renal disease (hazard ratio, 0.54; P=0.20) or risk of death (hazard ratio, 0.95; P=0.94). The incidence of adverse events was similar in the two groups.
Conclusions: Eprodisate slows the decline of renal function in AA amyloidosis
Aa aa (4/4 C)
No full textLaulun sanat: Aa, aa, aa, aa, aa, aa, aa, aa, Aa, aa, aa, aa, A, aa, aa, aa
AA-deficient <i>sfx</i> mice had decreased articular cartilage.
No full text(A) Representative sections of articular cartilage from control sfx/+ mice and AA-deficient sfx/sfx mice stained with Safranin-O. Articular cartilage was quantitated using the OsteoMeasure software, and sfx/sfx mice had less articular cartilage area (B) and width (C) at the femur and tibia. OARSI scores (D) are shown for sfx/+ and sfx/sfx mice. Results are presented as mean ± SEM. *P t-test), n = 6 per group.</p
Renal AA-amyloidosis in intravenous drug users - a role for HIV-infection?
No full textBackground: Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades.
Methods: Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany.
Results: Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1--2 years.
Conclusions: AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU
The Burden of Cardiovascular Risk in Chronic Kidney Disease and Dialysis Patients (Cardiorenal Syndrome Type 4)
No full textType 4 cardiorenal syndrome is a growing societal problem as the aging population, with increasing incidence of chronic kidney disease (CKD), diabetes, obesity, hypertension, and other cardiovascular risks, leads to higher numbers of individuals suffering the complications of this bidirectional disorder. In this review, the immense burden of cardiovascular risk faced by patients on dialysis, as well as lesser degrees of CKD, will be examined, with emphasis on rates of acute coronary syndrome/coronary insufficiency, congestive heart failure/left ventricular hypertrophy, and cardiac arrhythmia/sudden cardiac death. Copyright (C) 2011 S. Karger AG, Base
AA-deficient <i>sfx</i> mice had less trabecular bone at the femoral primary and secondary spongiosa.
No full textRepresentative microCT images of (A) primary and (B) secondary spongiosa from control sfx/+ mice and AA-deficient sfx/sfx mice. Scans were quantitated by (C) bone volume adjusted for tissue volume (BV/TV), (D) trabecular number, (E) trabecular thickness, and (F) trabecular separation. Results are presented as mean ± SEM. *P t-test), n = 6 per group.</p
Extracorporeal blood purification in sepsis and sepsis-related acute kidney injury
No full textSepsis-related acute kidney injury (AKI) is an important complicating feature of sepsis, and is associated with greater complexity of care and higher mortality. Until recently, AKI lacked a standard, widely accepted definition, rendering it difficult to compare previously published strategies to prevent, recognize and treat this entity. Recently, the RIFLE classification of AKI has been developed, and confirmed in observational studies to be associated with subsequent morbidity and mortality. The management of sepsis-related AKI is evolving with new basic discoveries and ongoing translational clinical research, and will likely include nephroprotective strategies to protect kidneys in patients at risk, early recognition and amelioration of renal damage and pharmacological interventions to minimize injury and promote recovery. Furthermore, extracorporeal blood purification (EBP) has an important role to play, not only in the replacement of certain aspects of renal organ function such as acid -base/el ectrolyte homeostasis and extracellular fluid volume, but also in an immunomodulatory fashion. As a therapy that has the potential to influence the course of disease in sepsis, EBP in sepsis and sepsis-related AKI is the subject of this review. Copyright (c) 2008 S. Karger AG, Basel
Association between AA-NAT gene polymorphism and reproductive performance in sheep
No full textAbstract Arylalkylamine N-acetyltransferase (AA-NAT) is critical enzyme
in Melatonin (MLT) biosynthesis for MLT regulating the animal seasonal
breeding. In this study, DNA sequencing methods were applied to detect
the polymorphisms of the AA-NAT gene in 179 Chinese sheep belonging to
two non-seasonal reproduction breeds and two seasonal reproduction
breeds. One mutation at exon 3 (NM_001009461:c.486A > G) was firstly
described at the sheep AA-NAT locus. Hence, we described the SmaI
PCR-RFLP method for detecting EX3 486A > G mutation, frequencies of
the AA-NAT-G allele varied from 0.871 to 0.908 in two non-seasonal
reproduction breeds and 0.517 to 0.578 in two seasonal reproduction
breeds. The associations of SmaI polymorphism with estrus traits was
analyzed in non-seasonal reproduction breeds sheep and seasonal
reproduction breeds sheep, the significant statistical results were
found between them, the GG genotype frequencies was higher in
non-seasonal reproduction breeds (p < 0.001), while, the GA genotype
frequencies was higher in seasonal reproduction breeds (p < 0.05).
Hence, the EX3 486A > G mutation could facilitate association
analysis and serve as a genetic marker for Chinese sheep breeding and
genetics
AA-amylodosis, cat.
No full textCongo red stain. a) Liver. A diffuse moderate amount of red stained amyloid (arrows) displaces the hepatocellular cords, sometimes isolating the hepatocytes. Inset: apple-green birefringence under polarized light. b) Spleen. Red stained amorphous material (amyloid, asterisks) is observed in the interstitium and around arteries (arrows). Inset: apple-green birefringence under polarized light. c) Kidney. The glomerular tuft is expanded by a large amount of Congo red-stained amorphous material (asterisk) consistent with amyloid, which is also present around a proximal arteriole (arrowhead) and along the Bowman’s capsule (arrows). Insets: Apple-green birefringence under polarized light is evident in a glomerulus (upper inset) and around tubules (lower inset). Histologic pictures of AA-amyloidosis-negative liver, spleen, and kidney is reported in S3 Fig.</p
- …
