Eighteen years of heart transplantation--a single center experience

The best option for the treatment of a failing heart is heart transplantation. The transplantation program at the University Hospital Center Rebro Zagreb started in 1988. To the best of our knowledge this is the first retrospective study on cardiac transplantation in Croatia looking into survival following heart transplantation. Between 1988 and 2006, we performed 81 heart transplantations at the University Hospital Center Rebro Zagreb. Our study focused on the last ten years after establishment of the Department of cardiac surgery as a separate institution. There were thirteen different hospitals throughout Croatia, which contributed to the donor network. Average age of the heart recipient was 48+/-11.8 years (range 14-72), and average age of the heart donor was 34+/-10.7 years (range 14-56). There were more women among the heart donors (34%) then among the heart recipients (18%). During the first ten years, from 1988-1998, the average number of cardiac transplantations was 3 per year In the period from 1998-2006, average number of cardiac transplantations increased to 6 per year. The average thirty-day mortality for the last nine years was 27%. It declined from 30% and 40% in 1998 and 1999, respectively down to 0% in the last two years. Average age of the patients who died was 50+/-6.5years (range 44-62) and did not significantly differ from those who survived. The donor network has grown up to fourteen different hospitals throughout Croatia. The limiting factor in cardiac transplant surgery is the number of available donors. Therefore in attempt to form a good transplant program it is crucial to form an efficient donor network. The number of performed cardiac transplantations is expected to rise until it reaches the number of available donors. With advances in operative technique and postoperative management--immunosuppressive therapy we have observed a remarkable drop in the early operative mortality in the studied period.     

Injuries in racket sports among Slovenian players

On the sample of 83 top Slovenian athletes we have studied the frequency of injuries among table tennis, tennis and badminton players, types of injuries and severity of injuries--the latter based on data of players absences from training and/or competition processes. The most liable parts to injuries are shoulder girdle (17.27%), spine (16.55%) and ankle (15.83%), while foot (10.07%) and wrist (12.23%) are slightly less liable to injuries. The most frequent injuries in racket sports pertain to muscle tissues. According to this data, the majority of injuries occur halfway through a training session or a competition event, mostly during a competition season. The injuries primarily pertain to muscle tissues; these are followed by joint and tendon injuries. There are no differences between male and female players. Compared to other racket sports players, table tennis players suffer from fewer injuries.     

Conjunctival amelanotic melanoma--a case report

Conjunctival melanoma is a relatively rare malignancy. It is presented as pigmented nodule in any area of conjunctiva, amelanotic tumors are pink with smooth appearance. The authors describe an amelanotic melanoma of the conjunctiva in an 82-year-old female patient. Cytological, histopathological and immunohistochemical studies revealed an invasive amelanotic melanoma exhibiting S-100 and MART-1 positivity. The patient undervent surgical and chemotherapy treatment and three years after the initial treatment is in the terminal stage of metastatic disease. Absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is crucial for early recognition and appropriate management.     

Non-Invasive Detection of Early Retinal Neuronal Degeneration by Ultrahigh Resolution Optical Coherence Tomography

Optical coherence tomography (OCT) has revolutionises the diagnosis of retinal disease based on the detection of microscopic rather than subcellular changes in retinal anatomy. However, currently the technique is limited to the detection of microscopic rather than subcellular changes in retinal anatomy. However, coherence based imaging is extremely sensitive to both changes in optical contrast and cellular events at the micrometer scale, and can generate subtle changes in the spectral content of the OCT image. Here we test the hypothesis that OCT image speckle (image texture) contains information regarding otherwise unresolvable features such as organelle changes arising in the early stages of neuronal degeneration. Using ultrahigh resolution (UHR) OCT imaging at 800 nm (spectral width 140 nm) we developed a robust method of OCT image analyses, based on spatial wavelet and texture-based parameterisation of the image speckle pattern. For the first time we show that this approach allows the non-invasive detection and quantification of early apoptotic changes in neurons within 30 min of neuronal trauma sufficient to result in apoptosis. We show a positive correlation between immunofluorescent labelling of mitochondria (a potential source of changes in cellular optical contrast) with changes in the texture of the OCT images of cultured neurons. Moreover, similar changes in optical contrast were also seen in the retinal ganglion cell- inner plexiform layer in retinal explants following optic nerve transection. The optical clarity of the explants was maintained throughout in the absence of histologically detectable change. Our data suggest that UHR OCT can be used for the non-invasive quantitative assessment of neuronal health, with a particular application to the assessment of early retinal disease.     

Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)

Introduction

Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin''s lymphoma in a real-life clinical setting.

Methods

Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.

Results

A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician''s visual analogue scale; mean improvement from baseline of 12.1 mm).

Conclusions

Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.     

Antibodies recognizing Mycobacterium avium paratuberculosis epitopes cross-react with the beta-cell antigen ZnT8 in Sardinian type 1 diabetic patients

The environmental factors at play in the pathogenesis of type 1 diabetes (T1D) remain enigmatic. Mycobacterium avium subspecies paratuberculosis (MAP) is transmitted from dairy herds to humans through food contamination. MAP causes an asymptomatic infection that is highly prevalent in Sardinian T1D patients compared with type 2 diabetes (T2D) and healthy controls. Moreover, MAP elicits humoral responses against several mycobacterial proteins. We asked whether antibodies (Abs) against one of these proteins, namely MAP3865c, which displays a sequence homology with the β-cell protein zinc transporter 8 (ZnT8) could be cross-reactive with ZnT8 epitopes. To this end, Ab responses against MAP3865c were analyzed in Sardinian T1D, T2D and healthy subjects using an enzymatic immunoassay. Abs against MAP3865c recognized two immunodominant transmembrane epitopes in 52-65% of T1D patients, but only in 5-7% of T2D and 3-5% of healthy controls. There was a linear correlation between titers of anti-MAP3865c and anti-ZnT8 Abs targeting these two homologous epitopes, and pre-incubation of sera with ZnT8 epitope peptides blocked binding to the corresponding MAP3865c peptides. These results demonstrate that Abs recognizing MAP3865c epitopes cross-react with ZnT8, possibly underlying a molecular mimicry mechanism, which may precipitate T1D in MAP-infected individuals.     

The Raf-1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments.

Using immobilized GST-Raf-1 as bait, we have isolated the intermediate filament protein vimentin as a Raf-1-associated protein. Vimentin coimmunoprecipitated and colocalized with Raf-1 in fibroblasts. Vimentin was not a Raf-1 substrate, but was phosphorylated by Raf-1-associated vimentin kinases. We provide evidence for at least two Raf-1-associated vimentin kinases and identified one as casein kinase 2. They are regulated by Raf-1, since the activation status of Raf-1 correlated with the phosphorylation of vimentin. Vimentin phosphorylation by Raf-1 preparations interfered with its polymerization in vitro. A subset of tryptic vimentin phosphopeptides induced by Raf-1 in vitro matched the vimentin phosphopeptides isolated from v-raf-transfected cells labeled with orthophosphoric acid, indicating that Raf-1 also induces vimentin phosphorylation in intact cells. In NIH 3T3 fibroblasts, the selective activation of an estrogen-regulated Raf-1 mutant induced a rearrangement and depolymerization of the reticular vimentin scaffold similar to the changes elicited by serum treatment. The rearrangement of the vimentin network occurred independently of the MEK/ERK pathway. These data identify a new branch point in Raf-1 signaling, which links Raf-1 to changes in the cytoskeletal architecture.