[Metal Debris with Cobalt Intoxication and Heart Damage as a THA Complication]. / Kovový oter s otravou kobaltem a poskozením srdce jako komplikace TEP kycelního kloubu.

Total hip replacement is currently a standard orthopaedic procedure. A number of complications caused by wear of the articulating parts of the endoprosthesis were described in the past. In recent years, there have been reports of systemic manifestations of metal components wear, leading to the development of chronic metal poisoning and organ damage. Our case report documents two cases of heart damage, resulting in heart failure with the need for heart transplantation, caused by metal poisoning originating from a failed THA.

Safety and Efficacy of Immunoadsorption in Heart Transplantation Program.

BACKGROUND: Antibody-mediated rejection (AMR) is a serious complication of organ transplantation, and its treatment is complex. The aim of this study was to assess immunoadsorption (IA) for treatment-immunized patients before heart transplantation (HTX) and as the first step of AMR treatment after HTX. METHODS: The cohort consisted of 10 patients (8 men, 2 women; age range, 20-57 years). For 3 of these patients, IA was included in the desensitization protocol before HTX; for 7 patients, IA was the first step of the treatment protocol. One patient underwent IA before and after HTX. RESULTS: A comparison of values before IA and after the last procedure showed a decrease in immunoglobulin subgroups (G, M, and A). In patients before HTX, a decline was noted in panel reactive antibodies. After HTX, IA procedures led to a significant decrease in donor-specific antibody (DSA) class I; DSA class II fell in 6 of 7 patients, with 51% falling below the detection limit. CONCLUSIONS: IA in patients during HTX is safe procedure for reducing DSA. The removal of antibodies is the first step in comprehensive treatment and must be followed by a procedure that prevents their further development.

Danon disease: a focus on processing of the novel LAMP2 mutation and comments on the beneficial use of peripheral white blood cells in the diagnosis of LAMP2 deficiency.

Danon disease (DD) is a monogenic X-linked disorder characterized by cardiomyopathy, skeletal myopathy and variable degrees of intellectual disability. DD develops due to mutations in the gene encoding lysosomal-associated membrane protein 2 (LAMP2). We report on a family exhibiting the clinical phenotype comprising of hypertrophic cardiomyopathy and ventricular pre-excitation, myopia and mild myopathy in two male patients and cardiomyopathy and myopia in a female patient. The diagnosis of DD in this family was based on the assessment of the clinical phenotypes and the absence of LAMP2 in skeletal and/or cardiac muscle biopsy specimens. Sequence analysis of the LAMP2 gene and its mRNA revealed a novel LAMP2 mutation (c.940delG) in all three patients. Approximately 25% of the female patient's cardiomyocytes were LAMP2 positive apparently due to the unfavorable skewing of X chromosome inactivation. We further performed qualitative LAMP2 immunohistochemistry on peripheral white blood cells using the smear technique and revealed the absence of LAMP2 in the male patients. LAMP2 expression was further assessed in granulocytes, CD4+ and CD8+ T lymphocytes, CD20+ B lymphocytes, CD14+ monocytes and CD56+ natural killer cells by quantitative polychromatic flow cytometry. Whereas the male DD patients lacked LAMP2 in all WBC populations, the female patient expressed LAMP2 in 15.1% and 12.8% of monocytes and granulocytes, respectively. LAMP2 expression ratiometrics of highly vs. weakly expressing WBC populations discriminated the DD patients from the healthy controls. WBCs are thus suitable for initial LAMP2 expression testing when DD is a differential diagnostic option. Moreover, flow cytometry represents a quantitative method to assess the skewing of LAMP2 expression in female heterozygotes. Because LAMP2 is a major protein constituent of the membranes of a number of lysosome-related organelles, we also tested the exocytic capacity of the lytic granules from CD8+ T lymphocytes in the patient samples. The degranulation triggered by a specific stimulus (anti-CD3 antibody) was normal. Therefore, this process can be considered LAMP2 independent in human T cells. The c.940delG mutation results in a putatively truncated protein (p.A314QfsX32), which lacks the transmembrane domain and the cytosolic tail of the wild-type LAMP2. We tested whether this variant becomes exocytosed because of a failure in targeting to late endosomes/lysosomes. Western blotting of cardiac muscle, WBCs and cultured skin fibroblasts (and their culture media) showed no intra- or extracellular truncated LAMP2. By comparing the expression pattern and intracellular targeting in cultured skin fibroblasts of normal LAMP2 isoforms (A, B and C) tagged with green fluorescent protein (GFP) and the A314Qfs32-GFP fusion, we found that the A314Qfs32-GFP protein is not even expressed. These observations suggest that the truncated protein is unstable and is co-translationally or early post-translationally degraded.

Long-term efficacy and safety of conversion to tacrolimus in heart transplant recipients with ongoing or recurrent acute cellular rejection.

Despite the widespread use of potent immunosuppressive drugs, such as cyclosporin A and mycophenolate mofetil, ongoing and recurrent cellular rejection remain a common problem after heart transplantation. We aimed to describe the long-term effects of conversion from cyclosporine A to tacrolimus in patients with ongoing and recurrent cellular rejection. This was a single-centre retrospective analysis of 17 heart transplant recipients who were switched from cyclosporine A to tacrolimus due to ongoing (5 patients) or recurrent cellular rejection (12 patients). We studied long-term efficacy and safety of this approach. 167 endomyocardial biopsies were performed during a mean follow-up of 69.1 +/- 12.7 months. Thirteen biopsies (7.8%) in eight patients (47%) revealed higher grades of acute cellular rejection (Banff 2). However, they were not hemodynamically significant and did not require intravenous antirejection therapy. The mean rejection score was reduced significantly. Conversion to tacrolimus was tolerated in 82% pts without any significant side effects during a long-term follow-up. In conclusion, the conversion to tacrolimus in heart transplant recipients with ongoing or recurrent acute cellular rejection was safe and effective also during a long-term follow-up.