Tricuspid Incompetence Following Permanent Pacemaker Implantation

Aim: Severe tricuspid insufficiency (TI) after permanent pacemaker implantation (PPI) has been described in small series of patients, though its incidence is not known.
Methods: We retrospectively analyzed the data of 545 patients who underwent PPI and had Doppler echocardiograms performed before and after the procedure. We excluded 135 patients who had ≥moderate TI on the 1st Doppler echocardiogram.
Results: Group 1 included 75 patients (18.3%) who had a >2 grades worsening of TI, and group 2 included 335 patients (82%) with <2 grade increase in TI after PPI. Patients in group 1 were 77 ± 7 years of age, versus 72 ± 10 years in group 2 (P < 0.001). There was no difference in left ventricular size and function. The TI gradient before PPI was higher in group 2 (25 ± 13 mmHg versus 19 ± 12 mmHg [P < 0.001]), though within the normal range in both groups. The mitral E/A ratio was 0.98 in group 1 versus 1.42 in group 2 (P < 0.001). The systolic TI gradient after implantation was 42 ± 12 mmHg in group 1, versus 33 ± 8 mmHg in group 2 (P < 0.001).
Conclusion: Worsening of TI after PPI was not rare and was observed more often in older patients, with abnormal LV relaxation and who developed pulmonary hypertension after the procedure.     

MALIGNANT MELANOMA IN TURNER'S SYNDROME

A 45-year-old woman presented with a 2-week history of weakness with rapidly progressing abdominal distention. Two weeks previously she had an abdominal ultrasound that showed no evidence of ascites or malignant changes.
The patient was known to suffer from Turner's syn-drome 45XO/46XX and Hashimoto's thyroiditis for which she was treated with L-thyroxine. She also had numerous nevi, some of which were biopsied recently and interpreted as having no malignant features.
On admission, the patient complained of weakness and abdominal discomfort. She was of short stature and was pale. Her secondary sexual characteristics were fully devel-oped. Many pigmented nevi were scattered over her skin, without clinical signs of malignant transformation. Fundo-scopy showed no signs of malignancy in the choroid layer. The abdomen was tense and edematous. Breast examina-tion was normal. An ECG and chest x-rays were also within normal limits. Computerized tomography showed a large amount of fluid with small masses spreading in the peri-toneal cavity. Aspiration of the abdominal fluid revealed ma-lignant cells that stained positively with S-100, melanoma-specific antigens, and with Masson-Fontana (Fig. 1).     

Heparanase induces tissue factor expression in vascular endothelial and cancer cells

BACKGROUND: Over-expression of tissue factor (TF) and activation of the coagulation system are common in cancer patients. Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate chains on cell surfaces and in the extracellular matrix, activity that closely correlates with cell invasion, angiogenesis and tumor metastasis. The study was undertaken to investigate the involvement of heparanase in TF expression. METHODS: Tumor-derived cell lines were transfected with heparanase cDNA and TF expression was examined. The effect of exogenous addition of active and inactive heparanase on TF expression and activity was studied in tumor cell lines and primary human umbilical vein endothelial cells. TF expression was also explored in heparanase over-expressing transgenic (Tg) mice. Blast cells were collected from acute leukemia patients and TF and heparanase expression levels were analyzed. RESULTS: Over-expression of heparanase in tumor-derived cell lines resulted in a 2-fold increase in TF expression levels, and a similar trend was observed in heparanase Tg mice in vivo. Likewise, exogenous addition of heparanase to endothelial or tumor-derived cells resulted in enhanced TF expression and activity. Interestingly, TF expression was also induced in response to enzymatically inactive heparanase, suggesting that this effect was independent of heparanase enzymatic activity. The regulatory effect of heparanase on TF expression involved activation of the p38 signaling pathway. A positive correlation between TF expression levels and heparanase activity was found in blasts collected from 22 acute leukemia patients. CONCLUSIONS: Our results indicate that in addition to its well-known function as an enzyme paving a way for invading cells, heparanase also participates in the regulation of TF gene expression and its related coagulation pathways.