Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.     

The Variants in the 3′ Untranslated Region of the Matrix Metalloproteinase 9 Gene as Modulators of Treatment Outcome in Children with Asthma

Purpose

The maintaining of asthma control is difficult due to high variability in response to therapy among patients. Since matrix metalloproteinase 9 (MMP9) is implicated in inflammation and remodeling of asthmatic airways, it could be associated with adequate response to asthma therapy. The aim of this study was to investigate whether variants in 3′ end of the MMP9 gene are associated with clinical phenotype and responsiveness to treatment in children with asthma.

Methods

The study included 127 asthmatic children from Slovenia. Variants in the 3′ end of the MMP9 gene were analyzed by direct DNA sequencing and the obtained results were correlated with clinical parameters.

Results

Two variants were detected, rs13925 and rs20544. For the variant rs20544, statistically significant difference in airway hyperresponsiveness (p?=?0.011) and asthma control (p?=?0.049) between genotypes was found. Patients with TT genotype had lower airway sensitivity, and after 12 months of treatment showed significant improvement in Asthma Control Test (ACT) scores compared to CC and CT genotype. For the variant rs13925, the association with lung function was observed. The carriers of A allele showed noticeable improvement of lung function after the first 6 months of treatment in comparison to the carriers of G allele (p?=?0.046).

Conclusion

The main finding of our study is the association of MMP9 genotypes rs20544 TT and rs13925 AA and AG with better asthma control, and indirectly better response to treatment. Based on these results, MMP9 deserves further research as a potential predictive biomarker for asthma.

     

Molecular Mechanism of the t(14;18)—A Model for Lymphoid-Specific Chromosomal Translocations

The chromosomal translocation t(14;18) occurs during early B-cell development and juxtaposes the immunoglobulin heavy chain locus (IgH) with the bcl-2 oncogene. Several factors contribute to the translocation mechanism: (1) The rearrangement of the chromosome 14 DH and JH translocation partners has typical features of V(D)J-recombinase-mediated joining with N-segment addition. (2) The bcl-2 major (mbr) and minor (mcr) breakpoint regions as well as their IgH reciprocal counterparts contain recombinatorial sequences related to chi or the minisatellite-core which bind at least one common DNA-binding protein (bp45). Similar elements are found at the breakpoints of other lymphoid-specific translocations like the t(11;14), t(2;8) or the t(4;11). (3) Structural analysis of the bcl-2 mbr indicates that this region may adopt alternative DNA-configurations which can promote recombination and is cleaved by an endogenous nuclease present in early B-cells. The present data suggest that V(D)J-recombinase as well as chi/minisatellite-core mediated recombination contribute to the mechanism and make the t(14;18) a model system for lymphoid-specific reciprocal translocations.     

Evaluation of a 3-week hospital rehabilitation of patients with rheumatoid arthritis

Essential for evaluation of disease activity and functional disability in rheumatoid arthritis is to monitor the disease course by the outcome measures, which show quality of care i.e. efficacy of drugs, physical therapy and rehabilitation. To assess disease activity in 21 days hospital rehabilitation we chose Disease Activity Score (DAS). Functional disability was measured by Health Assessment Questionnary (HAQ). The measures were noted at arrival and admission and we found statistically significant decrease in values of DAS (t = 5,836; p < 0.01) and HAQ (h = 16.26; p < 0.05), but without clinically valid criteria for improvement. The conclusions are: these measures are not appropriate for assessment of efficacy for a short therm hospital rehabilitation, because DAS is measure which primary shows activity of inflammatory process, and HAQ as a long term measure is not sensitive enough for the assessment of short term rehabilitation.     

Cathepsin L in glioma progression: comparison with cathepsin B

OBJECTIVE: Lysosomal cysteine cathepsins have been implicated in tumor progression. This study is aimed to reveal differential expression and compare the prognostic significance of cathepsins B and L in glioma patients. METHODS: The histological slides of 82 patients with primary astrocytic tumors were reviewed. We evaluated the immunostaining of the cathepsins in tumor and endothelial cells. RESULTS: Cathepsins B and L stained positive in 98 and 88% of cases, respectively. The total score was significantly higher in malignant than in benign tumors, both for cathepsin B (p<0.001) and for cathepsin L (p<0.01). The IHC score in endothelial cells in the malignant group was significantly higher only for cathepsin B (p<0.0001). Survival analysis indicated that in contrast to the prognostic significance of total cathepsin B and endothelial cells associated cathepsin B for shorter patients' survival, the prognostic role of cathepsin L was not confirmed. CONCLUSION: Cathepsin L is preferentially expressed in tumor cells, increasing with glioma progression, but is not significantly associated with new vasculature of glioblastoma. In contrast to cathepsin B, cathepsin L has no prognostic impact, suggesting different roles of the two cathepsins in glioma progression.     

Lung cancer after heart transplantation: a 17-year experience

Background

The effects of heart transplantation on lung cancer incidence in heart transplant recipients are unclear.

Methods

In an observational study, we retrospectively reviewed the charts of all patients undergoing heart transplantation at our institution from July 1982 to July 1999. Data on lung cancer incidence, risk factors, treatment, and outcome were collected.

Results

Five hundred seventy-two patients (mean age, 50 ± 11 years; range, 18 to 73) were considered at risk for lung cancer. Of these, 324 (57%) had a more than 20 pack-year history of smoking before transplantation. Lung cancer developed in 2 patients 1 year or less after transplantation and in 8 patients more than 1 year after transplantation (incidence, 2.2 per 1,000 patients per year of follow-up). Non-small cell lung cancer was diagnosed in all cases. Median survival was 10.8 months (range, 2 to 37.5). Routine annual chest radiographs after transplantation enabled early diagnosis in 5 cases (stages Ia and IIa), which correlated with better mean survival (28.1 months [range, 19 to 37.5] versus 5.1 months [range, 2 to 10.8]; p = 0.0002).

Conclusions

The incidence of lung cancer in our population of heart transplant recipients appears to be no higher than in nontransplant populations with similar risk factors (ie, smoking and age). Routine radiographic imaging of transplant recipients may allow earlier detection of lung cancer and thus offer a survival benefit.     

Quality and efficacy of a telecolposcopy programme

We tested the performance of telecolposcopy in the diagnosis of various squamous intraepithelial lesions. There were three groups of physicians: Group 1 consisted of 15 gynaecologists who were not trained in colposcopy; Group 2 consisted of six experienced colposcopists (specialists); Group 3 was a supervising team consisting of three experts (colposcopists with more than 15 years of colposcopy experience). The first group took colpophotographs during gynaecological examinations and used a Web browser to compare them with examples from a database of colposcopy findings. Group 2 made their own diagnoses independently. Then the supervising team examined the findings from all 250 patients and made diagnoses that could be considered the 'gold standard'. The findings were identical for Groups 1 and 2 in 219 cases, i.e. an inter-observer agreement of 88%; Cohen's kappa was 0.81. The findings were identical for Groups 1 and 3 in 208 cases, i.e. an inter-observer agreement of 83%; Cohen's kappa was 0.74. The findings were identical for Groups 2 and 3 in 239 cases, i.e. an inter-observer agreement of 96%; Cohen's kappa was 0.93. There was high inter-observer agreement between all participants. However, there were also significant differences in some cases. In the cases of suspected invasive carcinoma, the results showed a significant difference (chi2=4.8, P< 0.005) because gynaecologists from Group 1 were not sure of their diagnosis and they wanted to obtain a second opinion by referring the decision to a higher level.     

Phlegmonous gastritis in a patient with rheumatoid arthritis

Phlegmonous gastritis is an acute infection of the stomach wall by pyogenic bacteria. It represents an extremely rare disease with a fulminating course and a high mortality rate. A precise lifetime diagnosis is generally unsuccessful. The inflammation, most often caused by alpha-hemolytic streptococci, is most frequently expressed in patients who are more susceptible to infection. Among these are elderly patients, women, patients with chronic gastritis, chronic peptic ulcer, hepatic cirrhosis and decreased immune tolerance, T-cell leukemia, patients with a low socio-economic status and alcoholics. In our paper we are describing the case of a 66-year old female patient, who had received many years of treatment for rheumatoid arthritis. She died due to phlegmonous gastritis, which was only established post-mortem. The authors share the opinion that the occurrence of the phlegmonous form of gastritis was influenced significantly by the treatment with nonsteroidal antirheumatics and corticosteroids, which she had received for many years and also immediately prior to the complication.