Experience with gestational surrogacy as a treatment for sterility resulting from hysterectomy

A retrospective study was carried out to assess the potential of 16 hysterectomized women to achieve surrogate pregnancies. A total of 11 patients completed 16 cycles of assisted conception treatment incorporating in-vitro fertilization and gestational surrogacy. Three other women failed to respond to ovulation induction while two more patients produced few oocytes which also failed to fertilize. Six host mothers became pregnant thereby giving a pregnancy rate of 37.5% (6/16) per patient and embryo transfer and 27.3% (6/22) per cycle of treatment commenced. Two women later miscarried, three have given birth to twins and the remaining host has delivered a male infant. The commissioning mother's age was closely related to occurrence and continuation of pregnancy in the host. Hysterectomized women demonstrate varying patterns of response to assisted conception treatment but gestational surrogacy generally appears to be a feasible option especially in younger patients.      

Intraoperative planning and evaluation of permanent prostate brachytherapy: Report of the American Brachytherapy Society

Purpose: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP).

Methods and Materials: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique.

Results: The ABS proposes the following terminology in regard to prostate planning process: • Preplanning—Creation of a plan a few days or weeks before the implant procedure. • Intraoperative planning—Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. • Intraoperative preplanning—Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. • Interactive planning—Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. • Dynamic dose calculation—Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints.

Conclusion: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.     

Prediction of Long‐Term Outcomes of Catheter Ablation of Persistent Atrial Fibrillation by Parameters of Preablation DC Cardioversion

Prediction of Long‐Term Outcomes of Catheter Ablation of Persistent Atrial Fibrillation. Aim: It has been demonstrated that atrial fibrillation (AF) frequently recurred after cardioversion (CV) using direct current (DC) or radiofrequency catheter ablation (RFCA) in patients with persistent (PeAF) or longstanding persistent AF (LPAF). We hypothesized that the atrial substrate impeding successful CV would also produce difficulty in catheter ablation, and therefore, the outcomes of RFCA for PeAF and LPAF could be predicted by the parameters determined at the time of DC CV. Method: From 2006 to 2009, 94 patients with PeAF and LPAF who had undergone elective DC CV before RFCA were studied. The parameters associated with DC CV, including number of shocks, cumulative energy adjusted, highest energy adjusted, with or without intravenous amiodarone use, and other clinical parameters were assessed. Result: Thirty‐two out of the 94 patients (34%) experienced AF recurrence during the follow‐up of 19.8 ± 12.3 months after RFCA. The average time to recurrence of AF after RFCA was 9.2 ± 3.2 months. Of the 62 patients, 29 patients (31%) remained sinus rhythm (SR) without antiarrhythmic drug (AAD). The patients who maintained SR had smaller body mass index (BMI) (P = 0.048), shorter duration of AF (P = 0.012), and lower prevalence of diabetes mellitus (P = 0.023) compared with patients in whom AF recurred. Total number of shocks, total energy, and highest shock energy during CV were lower (P < 0.001, P = 0.002, P = 0.048, respectively) in patients with SR during the follow‐up. The outcome in patients who used amiodarone IV prior to CV, however, was not different from that in those who did not use amiodarone IV. Conclusion: DC energy parameters for successful CV before RFCA were useful to predict the long‐term outcome after RFCA in patients with PeAF and LPAF. The presence of the atrial substrate making DC CV difficult might reflect atrial substrate that subsequently related to the recurrence of AF after RFCA in chronic AF. These DC energy parameters may be related to the chronicity or electroanatomical remodeling of AF. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1165–1170, November 2012)     

Is Pursuit of Termination of Atrial Fibrillation During Catheter Ablation of Great Value in Patients with Longstanding Persistent Atrial Fibrillation?

Termination of Atrial Fibrillation During Catheter Ablation Predicts Better Outcome . Background: The reliable endpoint for ablation of longstanding persistent atrial fibrillation (LPAF) has not been clearly established. Methods and Results: This study included 140 patients who underwent catheter ablation for drug‐refractory LPAF. A stepwise ablation approach included circumferential pulmonary vein isolation followed by left atrial and right atrial complex fractionated electrogram‐guided ablation. Atrial fibrillation (AF) was terminated by radiofrequency application during catheter ablation in 95 patients (67.9%). Among them, 33 patients (23.6%) converted to sinus rhythm directly, whereas 62 patients (44.3%) via atrial tachycardias (ATs). Patients in whom AF terminated during the index procedure had a lower recurrence rate of atrial arrhythmia than patients in whom AF did not terminate (45.3% vs 68.9%, P = 0.009, follow‐up 18.7 ± 7.6 months). Among patients in whom AF terminated, there was no significant difference in recurrence rate according to the termination mode, whether converted to AT or not (P = NS). However, patients who converted to AT had a higher recurrence rate of AT (54.8% vs 81%; P = 0.016). Multivariable logistic regression analysis demonstrated that termination of AF during ablation (HR 0.440; 95% CI: 0.200–0.969, P = 0.041) and structural heart disease (HR 2.633; 95% CI: 1.211–5.723; P = 0.015) were significant independent factors predicting the recurrence of atrial arrhythmia. Conclusions: Termination of AF during catheter ablation is associated with a better clinical outcome in patients with LPAF. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1051‐1058, October 2012)     

Southern blot patterns, frequencies, and junctional diversity of T-cell receptor-delta gene rearrangements in acute lymphoblastic leukemia

Southern blot analysis of T-cell receptor (TCR)-delta gene rearrangements is useful for diagnostic studies on the clonality of lymphoproliferative diseases. We have developed 18 new TCR-delta gene probes by use of the polymerase chain reaction (PCR) techniques. Application of these probes for detailed analysis of the TCR-delta genes in normal control samples, 138 T-cell acute lymphoblastic leukemias (T-ALL), and 91 precursor B-ALL allowed us to determine the TCR-delta gene restriction map for five restriction enzymes, as well as the Southern blot restriction enzyme patterns of all theoretically possible TCR-delta gene rearrangements. Based on this information, it appeared that 97% of all 213 detected TCR-delta gene rearrangements in our series of ALL could be detected by use of the TCRDJ1 probe and that the majority (76%) of the 213 rearrangements could be identified precisely. In T-ALL, we found a strong preference for the complete rearrangements V delta 1-J delta 1 (33%), V delta 2-J delta 1 (10%), and V delta 3-J delta 1 (7%) and the incomplete rearrangement D delta 2- J delta 1 (11%). In precursor B-ALL, the majority of rearrangements consisted of V delta 2-D delta 3 (72%) and D delta 2-D delta 3 (10%). The junctional diversity of these 6 preferential TCR-delta rearrangements was analyzed and showed an extensive junctional insertion (approximately 30 nucleotides) for complete V delta-J delta rearrangements, whereas incomplete rearrangements had correspondingly smaller junctional regions. The detailed TCR-delta gene restriction map and probes presented here, in combination with the Southern blot patterns of TCR-delta gene rearrangements, are important for TCR-delta gene studies in ALL; all TCR-delta gene rearrangements can be detected and the majority can be identified precisely. Identification of rearrangements is a prerequisite for subsequent PCR analysis of TCR- delta gene junctional regions, eg, for detection of minimal residual disease during follow-up of ALL patients.     

Expression of murine CD38 defines a population of long-term reconstituting hematopoietic stem cells

Using a monoclonal antibody to murine CD38, we showed that a population of adult bone marrow cells that expressed the markers Sca-1 and c-kit but lacked the lineage markers Mac-1, GR-1, B220, IgM, CD3, CD4, CD8 and CD5 could be subdivided by the expression of CD38. We showed that CD38high c-kit+ Sca-1+, linlow/-cells sorted from adult bone marrow cultured with interleukin-3 (IL-3), IL-6, and kit-L produced much larger colonies in liquid culture at a greater frequency than their CD38low/- counterparts. In addition, we found that CD36low/ - cells contained most of the day-12 colony-forming units-spleen (CFU-S) but were not long-term reconstituting cells, whereas the population that expressed higher levels of CD38 contained few, but significant, day-12 CFU-S and virtually all the long-term reconstituting stem cells. Interestingly, the CD38high Sca-1+ c-kit+ linlow/- cells isolated from day-E14.5 fetal liver were also found to be long-term reconstituting stem cells. This is in striking contrast to human hematopoietic progenitors in which the most primitive hematopoietic cells from fetal tissues lack the expression of CD38. Furthermore, because antibodies to CD38 could functionally replace antibodies to Thy-1.1 in a stem cell purification procedure, the use of anti-CD38 may be more generally applicable to the purification of hematopoietic stem cells from mouse strains that do not express the Thy-1.1 allele.     

Cytotoxicity of human umbilical cord blood-derived mesenchymal stem cells against human malignant glioma cells

Background Mesenchymal stem cells (MSCs) represent a potential useful source for cell-based glioma therapies because these cells evidence both orthodox and unorthodox plasticity and also show tropism for cancer. In this study, the authors attempted to access the cytotoxicity of human umbilical cord blood (hUCB)-derived MSCs, with or without cytokine activations against malignant glioma cells. Materials and methods hUCB-derived MSCs were activated by interleukin-2, interleukin-15, granulocyte macrophage colony-stimulating factor, and combinations. The hUCB-derived MSCs and activated hUCB-derived MSCs were effector cells. The cytotoxicity of the unactivated hUCB-derived MSCs and activated hUCB-derived MSCs against the target cells (human malignant glioma cells) was estimated via visual survival cell assays and transwell inserts. Phenotypic changes occurring in these hUCB-derived MSCs before and after cytokine activation were determined via flow cytometry. The secreted proteins from these effector cells were estimated via enzyme-linked immunosorbent assays. Results We noted a significant cytotoxicity of hUCB-derived MSCs against malignant glioma cells. In addition, the hUCB-derived MSCs activated with cytokines evidenced significantly higher cytotoxicity than that observed with unactivated hUCB-derived MSCs. Differentiated immune effectors cells from the hUCB-derived MSCs after cytokine activation were not shown to have increased in number. However, the activated hUCB-derived MSCs secreted more immune response-related proteins (interleukin 4, interferon-γ) than did the unactivated hUCB-derived MSCs. Conclusion The data collected herein confirm for the first time that hUCB-derived MSCs, with or without activation, evidence significant cytotoxicity against human malignant glioma cells, and the immune response-related proteins secreted in this process may perform relevant functions.