Outcome of relapsed or refractory acute B-lymphoblastic leukemia patients and BCR-ABL-positive blast cell crisis of B-lymphoid lineage with extramedullary disease receiving inotuzumab ozogamicin

Acute lymphoblastic leukemia (ALL) can relapse in the extramedullary compartment, with or without medullary involvement. Response to treatment may be individual. We evaluated response to inotuzumab ozogamicin in 31 patients with relapsed/refractory B-ALL with extramedullary disease. Median age was 31 years (range, 19-81). All patients were heavily pretreated, including allogeneic hematopoietic stem cell transplantation (HSCT; n=18). Overall response rate after two cycles of inotuzumab ozogamicin was 84% (complete remission, 55%; partial remission, 29%; resistant disease, 13%; early death, 3%). The median follow-up was 29 months and median overall survival was 12.8 months. One-year and 2-year overall survival rates were 53% (95% CI: 37-76%) and 18% (95% CI: 8-43%), respectively. Age had no impact on overall survival when assessed as a continuous variable or dichotomized at 60 years. Twelve patients proceeded to allogeneic HSCT (complete remission, n=6; partial remission, n=3; resistant disease, n=3). Prior to allogeneic HSCT, eight patients received two or fewer cycles and four patients received three or four cycles of inotuzumab ozogamicin. Sinusoidal obstruction syndrome was reported in three patients, including one after transplantation. Allogeneic HSCT, evaluated as a time-dependent variable, had no impact on overall survival. Inotuzumab ozogamicin seems to be effective as a debulking strategy in relapsed/refractory ALL with extramedullary disease. However, inotuzumab ozogamicin followed by allogeneic HSCT seems not to be effective in maintaining long-term disease control.     

Migration Status, Work Conditions and Health Utilization of Female Sex Workers in Three South African Cities

Intersections between migration and sex work are underexplored in southern Africa, a region with high internal and cross-border population mobility, and HIV prevalence. Sex work often constitutes an important livelihood activity for migrant women. In 2010, sex workers trained as interviewers conducted cross-sectional surveys with 1,653 female sex workers in Johannesburg (Hillbrow and Sandton), Rustenburg and Cape Town. Most (85.3 %) sex workers were migrants (1396/1636): 39.0 % (638/1636) internal and 46.3 % (758/1636) cross-border. Cross-border migrants had higher education levels, predominately worked part-time, mainly at indoor venues, and earned more per client than other groups. They, however, had 41 % lower health service contact (adjusted odds ratio = 0.59; 95 % confidence interval = 0.40–0.86) and less frequent condom use than non-migrants. Police interaction was similar. Cross-border migrants appear more tenacious in certain aspects of sex work, but require increased health service contact. Migrant-sensitive, sex work-specific health care and health education are needed.     

Wireless micro current stimulation – an innovative electrical stimulation method for the treatment of patients with leg and diabetic foot ulcers

Clinical experience with a new electrical stimulation (ES) technique, the wireless micro current stimulation (WMCS), for the treatment of chronic wounds is described. WMCS transfers the current to any surface wound from a distance, by using oxygen's and nitrogen's ability to exchange electrons. We studied 47 patients with hard‐to‐heal wounds. Patients with venous, arterial and mixed leg ulcers were predominant; other aetiologies such as diabetic foot lesions, pressure ulcers, vasculitis and pyoderma were also included. WMCS treatment protocol specified treatment twice or thrice per week, for 45–60 minutes per session, with 1·5 μA current intensity. Standard wound care was applied to all patients, including compression bandages, if necessary. Clear progress of wound healing, even after 2 weeks, was observed in all cases. The mean reduction of the wound surface after WMCS treatment was 95% in 8 weeks. Complete healing was achieved within 3 months for the majority of the cases. No clinical side effects were observed. WMCS technology significantly accelerated wound healing for patients with hard‐to‐heal wounds of different aetiologies. This new therapy offers multiple advantages compared with the previous methods of ES, as it is contactless, free of pain and very easy to use.     

Female sex work and international sport events - no major changes in demand or supply of paid sex during the 2010 Soccer World Cup: a cross-sectional study

ABSTRACT: BACKGROUND: Important unanswered questions remain on the impact of international sporting events on the sex industry. Speculation about increased demand and supply of sex work often generates significant attention, but also additional funding for HIV programmes. This study assessed whether changes occurred in the demand and supply of paid sex during the 2010 Soccer World Cup in South Africa. METHODS: Trained sex worker interviewers conducted face-to-face semi-structured interviews among consenting female sex workers during May-September 2010. Using bivariate analyses we compared supply, demand, sexual risk-taking, and police and health services contact pre-World Cup, to levels during the World Cup and after the event. RESULTS: No increases were detected in indicators of sex work supply, including the proportion of sex workers newly arrived in the city (< 2.5% in each phase) or those recently entering the trade (<= 1.5%). Similarly, demand for sex work, indicated by median number of clients (around 12 per week) and amount charged per transaction ($13) remained similar in the three study periods. Only a third of participants reported observing any change in the sex industry ascribed to the World Cup. Self-reported condom-use with clients remained high across all samples (> 92.4% in all phases). Health-care utilisation decreased non-significantly from the pre- to during World Cup period (62.4% to 57.0%; P = 0.075). Across all periods, about thirty percent of participants had interacted with police in the preceding month, two thirds of whom had negative interactions. CONCLUSIONS: Contrary to public opinion, no major increases were detected in the demand or supply of paid sex during the World Cup. Although the study design employed was unable to select population-based samples, these findings do not support the public concern and media speculation prior to the event, but rather signal a missed opportunity for public health action. Given the media attention on sex work, future sporting events offer strategic opportunities to implement services for sex workers and their clients, especially as health service utilisation might decrease in this period.     

Intrinsic and extrinsic regulation of the proliferation and differentiation of cells in the rodent rostral migratory stream

An overriding principle of development is that neurons become permanently postmitotic once they initiate differentiation. Work in our laboratory, however, has provided evidence for a population of progenitor cells in mammalian forebrain that express properties of differentiated neurons, even though they continue to divide. These neuronal progenitor cells are situated in the rostral migratory stream (RMS), which extends from a specialized portion of the subventricular zone surrounding the anterior tip of the lateral ventricle, referred to as the SVZa, to the middle of the olfactory bulb. As SVZa-derived cells migrate to the olfactory bulb, they undergo cell division, and they never deviate from the RMS. Once they reach their final destinations, they become terminally postmitotic interneurons. This Mini-Review concerns findings from our recent experiments designed to reveal the intrinsic and extrinsic mechanisms governing the proliferation and differentiation of the unique SVZa neuronal progenitor cells. We have investigated the role(s) of cell cycle regulatory proteins, in particular, the cell cycle inhibitor p19(INK4d), in the control of SVZa cell proliferation. Several studies have indicated that cells withdraw from the cell cycle once they express p19(INK4d). To begin to investigate whether p19(INK4d)(+) SVZa-derived cells are postmitotic, we analyzed the pattern of p19(INK4d) expression by the cells of the RMS. A pronounced gradient of p19(INK4d) expression was demonstrated; progressively more cells are p19(INK4d) immunoreactive as the olfactory bulb is approached. In addition, the capacity of p19(INK4d)(+) cells to incorporate bromodeoxyuridine was investigated. From the results of these studies, we conclude that SVZa cells in the RMS can successively down-regulate their expression of p19(INK4d) as they migrate and that they repeatedly exit and reenter the cell cycle while en route to the olfactory bulb. These studies led us to investigate whether bone morphogenetic proteins (BMPs) are involved in the regulation of SVZa cell proliferation and p19(INK4d) expression, because, elsewhere in the CNS, BMPs modulate cell proliferation and influence cell fate decisions. To determine the effects of BMP signaling on SVZa cell proliferation and differentiation, we altered the expression of the BMP receptor Ia (BMPR-Ia) using retrovirally mediated gene transfer. The cells in the SVZa encoding the wild-type BMPR-Ia exit the cell cycle and do not appear to migrate through the RMS. Conversely, both within the SVZa and along the RMS, the majority of SVZa-derived cells encoding a dominant-negative BMPR-Ia gene do not express p19(INK4d). These findings indicate that p19(INK4d) expression is suppressed when BMP signaling is inhibited. Furthermore, SVZa-derived cells with both augmented and inhibited BMP signaling retain their neuronal commitment. Collectively, these studies have revealed that SVZa cell proliferation and differentiation is under the control of several interacting intrinsic and extrinsic factors.     

Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain.

Throughout life, the anterior part of the postnatal rodent subventricular zone (SVZa), surrounding the lateral ventricles, contains a prolific source of neuronal progenitor cells that retain their capacity to concurrently generate neurons and migrate along the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into interneurons. This study was designed to determine whether the SVZ and RMS of the postnatal primate also harbor a specialized population of neuronal progenitors with the capacity to divide while they migrate. In order to reveal the spatial-temporal changes in the distribution and composition of the neuronal progenitor cells in the primate SVZ and RMS, seven rhesus monkeys, ranging in age from 2 days to 8 years, were given a single injection of the cell proliferation marker bromodeoxyuridine (BrdU) 3 h before they were perfused. The phenotypic identity of the BrdU(+) cells was revealed by double labeling sagittal sections with cell type-specific markers. From birth onward the distribution of BrdU(+) cells with a neuronal phenotype is extensive and largely overlapping with that of the rodent. Similar to the rodent brain the neuronal progenitors are most numerous in neonates. The BrdU(+) neurons in the primate forebrain extend lateral and ventral to the lateral ventricle and all along the RMS. The cytoarchitectonic arrangement and appearance of the neuronal progenitor cells is quite varied in the primate compared to the rodent; in some locations the cells are aligned in parallel arrays resembling the neuronal chains of the adult rodent RMS, whereas in other positions the cells have a homogeneous "honeycomb" arrangement. The chains are progressively more pervasive in older primates. Akin to the RMS of adult rodents, in the primate SVZ and RMS the astrocytes often form long tubes enveloping the chains of neuronal progenitors. Our study demonstrates that the primate forebrain, similar to the rodent forebrain, harbors a specialized population of mitotically active neuronal progenitor cells that undergo extensive rearrangements while continuing to proliferate throughout life.