Different steroids co-regulate long-term expansion versus terminal differentiation in primary human erythroid progenitors

Outgrowth, long-term self-renewal, and terminal maturation of human erythroid progenitors derived from umbilical cord blood in serum-free medium can be modulated by steroid hormones. Homogeneous erythroid cultures, as characterized by flow cytometry and dependence on a specific mixture of physiologic proliferation factors, were obtained within 8 days from a starting population of mature and immature mononuclear cells. Due to previous results in mouse and chicken erythroblasts, the proliferation-promoting effect of glucocorticoids was not unexpected. Surprisingly, however, androgen had a positive effect on the sustained expansion of human female but not male erythroid progenitors. Under optimal conditions, sustained proliferation of erythroid progenitors resulted in a more than 10(9)-fold expansion within 60 days. Terminal erythroid maturation was significantly improved by adding human serum and thyroid hormone (3,5,3'-triiodothyronine [T3]) to the differentiation medium. This resulted in highly synchronous differentiation of the cells toward enucleated erythrocytes within 6 days, accompanied by massive size decrease and hemoglobin accumulation to levels comparable to those in peripheral blood erythrocytes. Thus, obviously, different ligand-activated nuclear hormone receptors massively influence the decision between self-renewal and terminal maturation in the human erythroid compartment.     

Usefulness of acoustic cardiography to resolve ambiguous values of B-type natriuretic Peptide levels in patients with suspected heart failure

B-type natriuretic peptide (BNP) levels are helpful to diagnose left ventricular (LV) systolic and/or diastolic dysfunction. BNP levels that are only moderately increased have limited diagnostic ability, and an additional test to resolve this problem would be desirable. The hypothesis that acquiring combined electrocardiographic and electronic cardiac acoustical data can improve the detection of LV dysfunction in patients with nondiagnostic values of BNP was tested. Both BNP and combined 12-lead electrocardiograms with electronic heart sound (acoustic cardiographic) recordings were obtained from 164 outpatients referred for echocardiographic evaluation for suspected heart failure. Acoustic cardiographic parameters included the third heart sound (S(3)) and percentage of electromechanical activation time, measured as the interval from onset of the Q wave of the electrocardiogram to the first heart sound (S(1)) and expressed as a proportion of the cardiac cycle. Sixty-nine of 164 patients (42%) had BNP values in the "gray zone" of 100 to 500 pg/ml. Sensitivity and specificity for LV dysfunction of BNP in the gray zone were 55% and 75%, with a positive likelihood ratio of 2.3. The use of acoustic cardiographic parameters in these 69 patients increased sensitivity and specificity to 69% and 100%, with a corresponding positive likelihood ratio of 69. In conclusion, easily obtainable acoustic cardiographic data substantially improved the diagnostic evaluation of patients with nondiagnostic BNP values and therefore can increase the confidence with which physicians diagnose and treat LV dysfunction.     

Human adult bone marrow mesenchymal stem cells repair experimental conduction block in rat cardiomyocyte cultures.

OBJECTIVES: We evaluated whether human adult bone marrow-derived mesenchymal stem cells (hMSCs) could repair an experimentally induced conduction block in cardiomyocyte cultures. BACKGROUND: Autologous stem cell therapy is a novel treatment option for patients with heart disease. However, detailed electrophysiological characterization of hMSCs is still lacking. METHODS: Neonatal rat cardiomyocytes were seeded on multi-electrode arrays. After 48 h, abrasion of a 200- to 450-microm-wide channel caused conduction block. Next, we applied adult hMSCs (hMSC group, n = 8), human skeletal myoblasts (myoblast group, n = 7), rat cardiac fibroblasts (fibroblast group, n = 7), or no cells (control group, n = 7) in a channel-crossing pattern. Cross-channel electrical conduction was analyzed after 24 and 48 h. Intracellular action potentials of hMSCs and cardiomyocytes were recorded. Immunostaining for connexins and intercellular dye transfer (calcein) assessed the presence of functional gap junctions. RESULTS: After creation of conduction block, two asynchronously beating fields of cardiomyocytes were present. Application of hMSCs restored synchronization between the two fields in five of eight cultures after 24 h. Conduction velocity across hMSCs (0.9 +/- 0.4 cm/s) was approximately 11-fold slower than across cardiomyocytes (10.4 +/- 5.8 cm/s). No resynchronization occurred in the myoblast, fibroblast, or control group. Intracellular action potential recordings indicated that conduction across the channel presumably occurred by electrotonic impulse propagation. Connexin-43 was present along regions of hMSC-to-cardiomyocyte contact, but not along regions of cardiomyocyte-to-myoblast or cardiomyocyte-to-fibroblast contact. Calcein transfer from cardiomyocytes to hMSCs was observed within 24 h after co-culture initiation. CONCLUSIONS: Human mesenchymal stem cells are able to repair conduction block in cardiomyocyte cultures, probably through connexin-mediated coupling.     

Impact of viability and scar tissue on response to cardiac resynchronization therapy in ischaemic heart failure patients.

AIMS: At present, 20-30% of patients do not respond to cardiac resynchronization therapy (CRT). In this study, the relation between the extent of viable myocardium and scar tissue vs. response to CRT was evaluated. In addition, the presence of scar tissue in the left ventricular (LV) lead position was specifically related to response to CRT. METHODS AND RESULTS: A total of 51 consecutive patients with ischaemic heart failure and substantial LV dyssynchrony undergoing CRT were included. All patients underwent gated SPECT before CRT implantation to determine the extent of scar tissue and viable myocardium. Clinical and echocardiographic parameters were assessed at baseline and after 6 months of CRT. The results demonstrated direct relations between the response to CRT and the extent of viable myocardium and scar tissue. In addition, the 15 patients (29%) with transmural scar tissue (< 50% tracer activity) in the region of the LV pacing lead showed no improvement after 6 months of CRT. CONCLUSION: The extent of scar tissue and viable myocardium were directly related to the response to CRT. Furthermore, scar tissue in the LV pacing lead region may prohibit response to CRT. Evaluation for viability and scar tissue may be considered in the selection process for CRT.     

Detection of mesenteric ischemia by means of endoscopic visible light spectroscopy after luminal feeding

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Performance of questionnaires aimed at detecting sleep disorders in patients attending a hypertension center

Introduction: Hypertension (HT) and obstructive sleep apnea-hypopnea syndrome (OSA) are prevalent and frequently related pathologies. The predictive value of screening questionnaires in cardiovascular settings is not totally clear and could be useful to select candidates for the sleep test.

Materials and Methods: We performed a prospective study in adults with suspected HT referred to a day-care hospital. Epworth Sleepiness Scale (ESS), Berlin, and STOP-BANG (SBQ) questionnaire were checked against data from home-based respiratory polygraphy (RP). We calculated sensitivity (S) and specificity (Sp), positive and negative predictive values (PPV and NPV), and the area under the ROC curve (AUC-ROC) for each questionnaire and their combinations.

Results: We analyzed 382 patients; 234 men (61.3%) and 148 women, mean age: 54.5 ± 13.7 years, body mass index (BMI): 33.1 ± 7.8 kg/m², ESS: 7.4 ± 4.7. Seventy-eight percent had an apnea-hypopnea index (AHI) >5 events per hour (eV/h) and 58% presented >15 eV/h (mean: 17.5 ± 9.3 eV/h). With regard to clinically significant OSA (AHI > 15 eV/h), 5 SBQ components showed S: 100% (CI: 97–100) and Sp: 98% (CI: 95–99) with a NPV of 100, a PPV of 97.8, and an AUC-ROC of 0.90 (p < 0.0001). ESS > 10 + high-risk Berlin did not perform as effectively.

Conclusion: In a population of HT patients, SBQ > 5 performed better at identifying patients with >15 eV/hour with a high discrimination power.     

Primary non-Hodgkin's lymphoma of bone: three cases and a short review of the literature

Primary non-Hodgkin's lymphoma of bone (PLB) is a rare entity. We present three new cases and a review of the literature. If PLB is suspected radiologically, the diagnosis must be confirmed by open biopsy. Histopathologically, PLB usually represents diffuse large B-cell lymphoma or lymphoma of the follicular center type. The extent of local disease manifestation, additional skeletal involvement, and the presence or absence of lymphadenopathy is assessed by radiological examination. Localized stages of the disease require involved-field radiotherapy (45-50 Gy) to the entire bone that is affected. Regional lymphatics must also be irradiated. Radiotherapy may be required immediately to prevent pathological fractures. In the few cases of more widespread skeletal or extraskeletal involvement, radiotherapy of the major site of manifestation may be followed by a "watch-and-wait" strategy until progression of the disease becomes apparent. In cases of intermediate or high-grade lymphoma of bone, combined radiochemotherapy is the treatment of choice for all stages. Six to eight cycles of chemotherapy (usually the CHOP regimen) are recommended for remission induction. This is followed by involved-field radiotherapy with 45-50 Gy. High-dose chemotherapy with autologous stem cell support is an option if there is no satisfactory response to conventional chemotherapy, or if early relapse occurs.     

Influence of gender,parity, and caloric load on gastrorectal response in healthy subjects: a barostat study

The gastrocolonic response consists of a prompt increase in colonic tone after a meal. With a barostat and a high compliant air-filled bag, it is possible to measure rectal tone by recording changes in volume at a constant intrabag pressure. The aim of this study was to evaluate the gastrorectal response in males and females as well as the effect of different caloric loads on the gastrorectal response. In 33 volunteers a barostat procedure during basal conditions and after a 600-kcal meal was performed. In 26 volunteers the procedure was repeated with a 1000-kcal meal. A meal response was defined as a decrease in volume of more than 10%. Phasic volume events (PVE) were defined as a 10% decrease in volume of 15–60 sec duration. After a 600-kcal meal, the decrease in volume after 1 hr was 28 ± 7% (mean ± SEM, P < 0.001). A meal response was found in 64% of the subjects. Parous females had a diminished meal response compared with nulliparous females (2 ± 5% and 48 ± 11%, P < 0.001). After the 600-kcal meal, PVEs increased from 3 to 10/hr (P = 0.001). In the 26 subjects, volume decrease was 40 ± 9% after the 1000-kcal meal and 20 ± 7% after the 600-kcal meal (P = 0.28). In the high-calorie meal, 18 subjects (69%) had a response versus 14 (54%) in the low-calorie meal (NS). Enhancing the caloric load of the meal did not increase the amounts of PVEs. In conclusion, a gastrorectal response occurs in 64% of the healthy subjects after a 600-kcal meal. The gastrorectal response can be measured to a similar extent in men and nulliparous women; however, the response is significantly impaired in parous women. This is possibly due to neurogenic damage during childbirth. Increasing the caloric load did not increase the gastrorectal response. Therefore, to study gastrorectal meal response with the barostat, a meal of 600-kcal is sufficient and a correction for parity should be made when results are compared.     

Rheopheresis in patients with ischemic diabetic foot syndrome: results of an open label prospective pilot trial

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis, for extracorporeal hemorheotherapy. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with ischemic diabetic foot syndrome. Eight patients with type 2 diabetes mellitus and non-healing foot ulcers caused by severe ischemic diabetic foot syndrome were treated by a series of seven Rheopheresis sessions in a time span of 11 weeks. Wound healing had not been detectable under conditions of standardized wound care during at least 2 months. Wound status was classified by its morphology, severity and location, according to the criteria of Wagner. Transcutaneous oxygen pressure (tcPO2), laser Doppler flowmetry and vital capillary microscopy were repeatedly performed to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology, endothelial function and inflammatory state were measured in addition to safety parameters. In four patients (baseline Wagner stage 2), Rheopheresis accelerated wound healing of foot ulcers and was associated with an improvement of Wagner stage and a pronounced increase in tcPO2. In two patients (baseline Wagner stage 2), wound healing was unchanged but mean tcPO2 increased, allowing successful minor amputation. Values of tcPO2 remained stable and enhanced for the 3 months follow-up period. In two patients (baseline Wagner stage 4 or 5), no improvements in foot lesions were observed within the treatment period. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.