Therapeutic potential of adult progenitor cells in cardiovascular disease

Cardiovascular diseases are responsible for high morbidity/mortality rates worldwide. Advances in patient care have significantly reduced deaths from acute myocardial infarction. However, the cardiac remodeling processes induced after ischaemia are responsible for a worsening in the heart condition, which in many cases ends up in failure. In the last decade, a novel therapy based on stem cell transplantation is being intensively studied in animal models and some stem cell types (i.e., skeletal myoblasts and bone marrow-derived cells) are already being tested in clinical trials. A novel stem cell population isolated from the bone marrow, termed multipotent adult progenitor cells was characterised a few years ago by its ability to differentiate, at the single cell level, towards cells derived from the three embryonic germ layers. Later on, other pluripotent cell populations have been also derived from the bone marrow. In this overview, the authors outline different stem cell sources that have been tested for their cardiovascular potential and put the regenerative potential of multipotent adult progenitor cells in animal models of acute and chronic myocardial infarction into perspective.     

Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy? A randomised controlled trial

Please cite this paper as: Stafne S, Salvesen K, Romundstad P, Torjusen I, M?rkved S. Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy? A randomised controlled trial. BJOG 2012;119:1270-1280. Objective To assess whether pregnant women following a general exercise course, including pelvic floor muscle training (PFMT), were less likely to report urinary and anal incontinence in late pregnancy than a group of women receiving standard care. Design A two-armed, two-centred randomised controlled trial. Setting Trondheim University Hospital (St. Olavs Hospital) and Stavanger University Hospital, in Norway. Population A total of 855 women were included in this trial. Methods The intervention was a 12-week exercise programme, including PFMT, conducted between 20 and 36?weeks of gestation. One weekly group session was led by physiotherapists, and home exercises were encouraged at least twice a week. Controls received regular antenatal care. Main outcome measures Self-reported urinary and anal incontinence after the intervention period (at 32-36?weeks of gestation). Results Fewer women in the intervention group reported any weekly urinary incontinence (11 versus 19%, P?=?0.004). Fewer women in the intervention group reported faecal incontinence (3 versus 5%), but this difference was not statistically significant (P?=?0.18). Conclusions The present trial indicates that pregnant women should exercise, and in particular do PFMT, to prevent and treat urinary incontinence in late pregnancy. Thorough instruction is important, and specific pelvic floor muscle exercises should be included in exercise classes for pregnant women. The preventive effect of PFMT on anal incontinence should be explored in future trials.     

Prenatal management and perinatal outcome in giant placental chorioangioma complicated with hydrops fetalis, fetal anemia and maternal mirror syndrome

ABSTRACT: BACKGROUND: Giant placental chorioangiomas have been associated with a number of severe fetal complications and high perinatal mortality. CASE PRESENTATION: We report a case of giant chorioangioma with fetal hydrops, additionally complicated by severe anemia, mild cardiomegaly with hyperdinamic heart circulation and maternal mirror syndrome. Intrauterine blood transfusion and amniodrainage was performed at 29 weeks. Worsening of the fetal and maternal condition prompted us to proceed with delivery at 29[THIN SPACE]+[THIN SPACE]5 weeks. The newborn died 3 hours later due to pulmonary hypoplasia and hemodynamic failure. Maternal course was favourable, mirror syndrome resolved in the second day and the patient was discharged four days following delivery. CONCLUSIONS: In the case described here, fetal condition got worse despite of the anemia correction and amniodrainage. Our outcome raises the issue whether additional intrauterine clinical intervention, as intersticial laser, should have been performed to stop further deterioration of the fetal condition when progressive severe hydrops develops.     

Ventilation response to CO2 and exercise-induced hypoxaemia in master athletes

Exercise-induced hypoxaemia (EIH) in master athletes may be related to a diminished exercise hyper- pnoea. The aim of this study was to determine whether EIH is associated with a change in the sensitivity of the ventilation response to activation of the central chemoreceptors. The ventilation response to CO₂ was measured in nine elderly untrained men (UT) [mean age 66.3 (SEM 3.1) years] and nine master athletes (MA) [mean age 62.7 (SEM 0.8) years] at rest, during moderate exercise (40% maximal oxygen uptake, V˙O_2max), and during strenuous exercise (70% V˙O_2max) using the rebreathing method. Our results showed that the ventilation response to CO₂ did not differ with endurance training and/or exercise, that the threshold of the CO₂ response (Th) increased with exercise (P?0–40: 8.55 (SEM 1.8) vs 3.06 (SEM 1.72) mmHg, P?0–40 and Th during moderate exercise were negatively correlated with arterial O₂ saturation during maximal exercise (r?=?0.50, P<0.05). We concluded therefore that exercise-induced hypoxaemia in master athletes may not be due to a lower ventilation response to CO₂, but may be partly related to a greater increase in Th during moderate exercise.     

Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the pre-ovulatory follicular fluid is associated with development of ovarian hyperstimulation syndrome during ovarian stimulation

Purpose

Investigating whether pre-ovulatory follicular fluid (FF) levels of selected proteins differ between women who do or do not develop severe ovarian hyperstimulation syndrome (OHSS) and evaluate whether they potentially could guide a “freeze-all” strategy.

Methods

FF was collected during a randomized controlled trial comparing OHSS in antagonist versus agonist protocol including 1050 women in their first assisted reproductive technology (ART) cycle during year 2009–2013. The present sub-study is a matched case-control study comparing FF levels of soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, placental growth factor, vascular endothelial growth factor, and angiopoietins 1 and 2 in OHSS cases (n?=?25, severe OHSS, and ≥?15 oocytes), high-risk controls (n?=?25, no OHSS, and ≥?15 oocytes), and low-risk controls (n?=?25, no OHSS, and 5–8 oocytes).

Results

FF level of suPAR differed significantly between the three groups (p?=?0.018) with mean (SD) levels of 2.3 (0.4) μg/L, 2.6 (0.8) μg/L, and 2.8 (0.6) μg/L in OHSS cases, high-risk controls, and low-risk controls, respectively. Receiver operating characteristic curve analysis demonstrated that suPAR levels could predict severe OHSS (AUC 0.678; 95% CI 0.553–0.803) with a sensitivity of 64% and a specificity of 66%. None of the other investigated proteins differed between the three groups or between OHSS cases and combined controls.

Conclusion

The pre-ovulatory FF level of suPAR was significantly lower in women developing severe OHSS, indicating that the plasminogen activator system could be involved in the pathophysiology of OHSS. However, suPAR did not provide a satisfying predictive value for the prediction of OHSS.

     

2′-Deoxycoformycin (pentostatin) in hairy cell leukemia: Response in patients refractory to interferon alpha

Summary Three patients with advanced hairy cell leukemia received low-dose deoxycoformycin treatment after failure to respond to therapy with interferon alpha. Patients 1 and 2 had progressive disease after splenectomy and subsequent treatment with recombinant interferon alpha (for 7 and 3 months, respectively). DCF was administered at 4 mg/m² weekly for 3 weeks, and then once every week for 6 weeks. Patient 1 was in complete remission after 9 weeks of treatment and patient 2 in partial remission with normalization of peripheral blood counts. The third patient, also splenectomized, developed hepatotoxicity after therapy trial with interferon for 24 days and no objective improvement was observed at this stage. She subsequently responded to DCF treatment with improvements in blood counts and bone marrow. This report demonstrates that DCF is highly effective in hairy cell leukemia and non-cross-resistant with interferon alpha.Abbreviations DCF Deoxycoformycin - HCL Hairy cell leukemia