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Many evidences show that elevated plasma levels of uric acid (UA) are associated to the increased risk of developing athero-thrombotic cardiovascular events. Hyperuricemia is a risk factors for endothelial dysfunction (ED). ED is involved in the pathophysiology of athero-thrombosis since dysfunctional cells lose their physiological, antithrombotic properties. We have investigated whether UA might promote ED by modulating the TF/TFPI balance finally changing the antithrombotic characteristics of endothelial cells.

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OBJECTIVES: Gynecological manifestation of chronic graft-versus-host disease (cGVHD) has been invariably described in association with its extensive form. We have also observed it in a patient with the limited cGVHD form. DESIGN: We here describe our experience of gynecological complications in a population of 30 women who were followed up in a single center 12-120 months after allogeneic stem cell transplant (allo-SCT) due to hematological malignancies. All of them manifested premature ovarian failure because of the received treatments. RESULTS: Three out of 14 women who were affected by cGVHD developed hematocolpometra after estrogen + progestogen therapy (EPT) introduction, due to uterine and vaginal dystrophy and synecchiae. Extensive cGVHD, including dermal and mucosal localization, was present in two women while the third had only liver involvement. None of our patients had received radiation therapy or had a posttransplant history of infection. Local application of estrogens consistently improved the gynecological complication. However, vaginal synecchiae tended to relapse when local treatment was interrupted, despite no other apparent evidence of active cGVHD. CONCLUSIONS: All women with cGVHD should undergo gynecological examination before introducing EPT, to avoid unpleasant complication as hematocolpometra. Vaginal and cervical synecchiae should be treated with prolonged local treatments, and temporary use of continuous EPT regimens may be preferable in these women. Moreover, close monitoring by pelvic exam and ultrasonography is advisable during the initial cycles to detect any complication caused by possible intrauterine adhesions undetected during the previous gynecological examination.

Comparison of the gene expression repertoire in human hematopoietic progenitors and mature leukocytes led to identification of a transcript expressed in CD34+cells and undetectable in differentiated cells. Sequencing of the cDNA (termed EHZF: early hematopoietic zinc finger) revealed 30 zinc fingers with 96% homology to mouse Evi3, a recently identified gene associated with the retroviral integration site in AKXD-27 B-cell lymphomas. EHZF and Evi3 share high homology with the transcription cofactor OAZ, implicated in the control of olfactory epithelium and B-lymphocyte differentiation and in the bone morphogenic protein (BMP) signal transduction. Here we show that (1) EHZF expression is abundant in human CD34+ progenitors and declines rapidly during cytokine-driven differentiation; (2) significant mRNA levels are found in most acute myelogenous leukemias; (3) in response to BMPs EHZF complexes SMADs 1 and 4, binds to, and enhances the transcriptional activity of, a BMP2/4 responsive element; (4) EHZF inhibits the transcriptional activity of early B-cell factor (EBF), a transcription factor essential for specification of the B-cell lineage. Taken together, our data suggest that EHZF is likely to play a relevant role in the control of human hematopoiesis and might be implicated in the development of hematopoietic malignancies.

Osteoporosis and avascular necrosis (AVN) are long-lasting and debilitating complications of hematopoietic stem cell transplantation (HSCT). We describe the magnitude of bone loss, AVN and impairment in osteogenic cell compartment following autologous (auto) and allogeneic (allo) HSCT, through the retrospective bone damage revaluation of 100 (50 auto- and 50 allo-HSCT) longterm survivors up to 15 years after transplant. Current treatment options for the management of these complications are also outlined. We found that auto- and allo-HSCT recipients show accelerated bone mineral loss and microarchitectural deterioration during the first years after transplant. Bone mass density (BMD) at the lumbar spine, but not at the femur neck, may improve in some patients after HSCT, suggesting more prolonged bone damage in cortical bone. Phalangeal BMD values remained low for even more years, suggesting persistent bone micro-architectural alterations after transplant. The incidence of AVN was higher in allo-HSCT recipients compared to autoHSCT recipients. Steroid treatment length, but not its cumulative dose was associated with a higher incidence of bone loss. Allo-HSCT recipients affected by chronic graft versus host disease seem to be at greater risk of continuous bone loss and AVN development. Reduced BMD and higher incidence of AVN was partly related to a reduced regenerating capacity of the normal marrow osteogenic cell compartment. Our results suggest that all patients after autoHSCT and allo-HSCT should be evaluated for their bone status and treated with anti-resorptive therapy as soonas abnormalities are detected.

Technetium-99m-sestaMIBI is a reliable positive tracer of skeletal lesions in multiple myeloma (MM), while bone scintigraphy by 99mTc-MDP and 67Ga scanning are considered of negligible value. We report the case of a young patient with a 5-year history of light chain MM, which was not eradicated by chemotherapy, radiotherapy, allogeneic bone marrow transplantation, α-interferon and donor lymphocyte infusion. In the final phase of the disease a CT scan showed a 14 cm mediastinal mass (Figure 1A). The neoplastic tissue took up 67Ga more avidly than 99mTc-sesta MIBI (Figures 1B-C), and focal bone lesions showed 67Ga uptake even in areas negative by MIBI scan. The patient died of disease progression in a few months. It seems that a 67Ga scan can identify patients with very aggressive MM.

Several lines of evidence have clearly indicated that inflammation plays a pivotal role in the development of atherosclerosis and of its thrombotic complications such as acute coronary syndromes or ischemic stroke. Thus, it has been postulated that the use of anti-inflammatory agents might be extremely useful to improve cardiovascular outcome. Recently, increasing attention has been reserved to one of the oldest plant-derived drugs still in use in clinical practice, colchicine that has been used as drug to treat inflammatory diseases such gout or Mediterranean fever. To date, current guidelines of the European Society of Cardiology have included colchicine as first line choice for treatment of acute and recurrent pericarditis. Moreover, several studies have investigated its role in the clinical scenarios of cardiovascular disease including chronic and acute coronary syndromes with promising results. In this review, starting from a description of the mechanism(s) involved behind its anti-inflammatory effects, we give an overview on its potential effects in atherothrombosis and finally present an updated overview of clinical evidence on the role of this drug in cardiovascular disease.

Women undergoing stem cell transplantation (SCT) are mostly young and have more than 90% probability of ovarian failure, which is often permanent. A woman's age, use of radiotherapy and alkylating chemotherapy, and the allogeneic type of transplant are associated with a higher rate of premature ovarian failure and worse residual ovarian function. Premature ovarian failure has serious systemic and psychological effects that may need treatment and should be managed by practitioners trained to treat this particular population of women. Ultrasonographic evidence of ovarian follicles is often associated with a future resumption of cycles, but there are no serum markers to predict the return of ovarian function in these patients. In our center, the rate of ovarian function recovery was 7% after allogeneic SCT and 25% after autologous SCT (P

Background Frequent endocrine disorders have been reported after allogeneic stem-cell transplant, but data on adult survivors of autologous transplants are still scarce. Methods In this prospective study we investigated early (at 3 months) and late (at 12 months) endocrine dysfunctions in 95 consecutive autologous stem-cell transplant recipients (47 men and 48 women) aged 16 to 55 years. The functions of the hypothalamic-pituitary-gonadal/thyroid/adrenal/somatotroph axis were evaluated. Results Three months after the transplant, insulin-like growth factor-1 values were below the normal range in 53 patients (56%); 37 of 40 women (93%) of reproductive age experienced precocious ovarian failure; 39 of 46 men (85%) showed high follicular stimulating hormone, and 17 men (37%) showed low testosterone levels. Adrenal insufficiency occurred in 28 patients (30%) during the peritransplant period after corticosteroid withdrawal. Transient subclinical hyperthyroidism was found in 15 patients (16%). Transient "low T3" syndrome was revealed in 29 patients (31%). Twelve months after the transplant, insulin-like growth factor-1 values were still low in 36 patients (38%). Menstrual cycles resumed in four women; follicular stimulating hormone, luteinizing hormone, and estradiol levels improved in 10 patients. Testosterone was low in only two men (4%). Seminal analysis revealed azoospermia in 32 (91%) of 35 men examined. Subclinical hypothyroidism was found in 11 patients (12%); eight of them had previously received radiotherapy for the upper half of the body. Conclusion This study documents frequent endocrine disorders during the first year after autologous stem-cell transplant. Despite a tendency to improve, in more than half of the cases, the complications persisted for more than 1 year. Therefore, to diagnose and correct early and late endocrine dysfunctions, endocrine screening is required during the first year in all patients undergoing autografting.

BACKGROUND: Ovarian failure is a frequent complication occurring after haematopoietic stem cell transplantion (SCT), which is generally ascribed to radiation treatment and antiblastic alkylating agents. METHODS: Ovarian morphology and function were studied in reproductive age women 12-24 months after allogeneic SCT (n = 23) received from an HLA identical sibling, or autologous SCT (n = 22). Thirteen allo-transplanted women were suffering from chronic graft-versus-host disease (cGVHD). RESULTS: Menstrual cycles recovered in two and four women in the allo- and auto-SCT groups respectively, being associated with younger age and longer period elapsed from transplant. There was no difference in previous use of alkylating agents between allo- and auto-transplantation, while corticosteroid treatment was longer and more recent in the allo-SCT group. Significantly higher gonadotrophin levels and lower estradiol were seen in the combined group of patients than in controls. In allo-transplanted women, androgens were also significantly lower than in controls. Ovarian and uterine volumes were lower in patients than in controls, and in the allo- than in the auto-transplanted women. Within the allo-SCT group, endocrine function and ovarian and uterine volumes were significantly lower in the patients suffering from cGVHD. CONCLUSIONS: Ovarian failure in SCT recipients is likely to be caused principally by myelo-ablative treatments, but the condition of gonadal and androgen insufficiency can be worsened by an altered immunomodulation in allogeneic setting.