High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Cell Phone Internet Access,Online Sexual Solicitation,Partner Seeking,and Sexual Risk Behavior Among Adolescents

Archives of Sexual Behavior - Online partner seeking is associated with sexual risk behavior among young adults (specifically men who have sex with men), but this association has yet to be explored...     

Cyberbullying Perpetration and Victimization Among Middle-School Students

Objectives. We examined correlations between gender, race, sexual identity, and technology use, and patterns of cyberbullying experiences and behaviors among middle-school students.Methods. We collected a probability sample of 1285 students alongside the 2012 Youth Risk Behavior Survey in Los Angeles Unified School District middle schools. We used logistic regressions to assess the correlates of being a cyberbully perpetrator, victim, and perpetrator–victim (i.e., bidirectional cyberbullying behavior).Results. In this sample, 6.6% reported being a cyberbully victim, 5.0% reported being a perpetrator, and 4.3% reported being a perpetrator–victim. Cyberbullying behavior frequently occurred on Facebook or via text messaging. Cyberbully perpetrators, victims, and perpetrators–victims all were more likely to report using the Internet for at least 3 hours per day. Sexual-minority students and students who texted at least 50 times per day were more likely to report cyberbullying victimization. Girls were more likely to report being perpetrators–victims.Conclusions. Cyberbullying interventions should account for gender and sexual identity, as well as the possible benefits of educational interventions for intensive Internet users and frequent texters.Cyberbullying is the “willful and repeated harm inflicted [on another] through the use of computers, cell phones, or other electronic devices.”1^(p5) Among 6th- through 10th-grade students nationally, 4% reported being cyberbullying perpetrators, 5% reported being a victim of cyberbullying, and 5% reported being perpetrators–victims (meaning that they have both perpetrated and been victimized by cyberbullying) during the previous 2 months.2 Among middle-school students in the southeastern and northwestern United States, a nonprobability sample of 3767 students by Kowalski and Limber3 found that 11% reported being a victim of cyberbullying, 4% were cyberbullying perpetrators, and 7% were perpetrators–victims during the previous 2 months. Cyberbullying may be more insidious than traditional bullying, because cyberbullying can quickly reach wide audiences (e.g., e-mails sent to an entire school), can be perpetrated anonymously, and is not bound to in-person interactions.4,5 Although cyberbullying has garnered widespread media attention, to our knowledge, no previous study has explored correlates of cyberbullying with a representative probability sample in an urban middle-school sample.Cyberbullying is associated with a host of health and behavioral health consequences. Research has suggested that cyberbullying may have a greater effect on depression and suicidal ideation than traditional offline bullying.6 Both perpetration and victimization are associated with mental health consequences, including lower self-esteem,7 recent depressive symptoms,5,8,9 and suicidal ideation.5,8,10 Cyberbullying perpetrators are more likely to have problems with their behavior, peer relationships, and emotions, and are less likely to be prosocial than their peers who are neither cyberbullying perpetrators nor victims of cyberbullying.11 Specifically, female cyberbullying perpetrators express greater anxiety and depression than their female peers who are not cyberbullying perpetrators.12 Cyberbullying victimization is also strongly associated with substance use, violent behavior, and risky sexual behavior among high-school students.10Cyberbullying disproportionately affects youths who are already vulnerable to mental health and behavioral health disparities, including members of sexual minorities (i.e., gay, lesbian, bisexual), girls, and racial and ethnic minorities. More than half of sexual-minority middle- and high-school students nationally report being a cyberbully victim during the previous year, with almost one fifth reporting often or frequent victimization.13 Female students are significantly more likely to be cyberbully perpetrators–victims than their male peers.9,14 Studies have reported that male students are significantly more likely to be cyberbullying perpetrators2,15 and significantly less likely to be cyberbully victims.2,6,9 Middle-school boys are more likely to cyberbully others because of their race, sexual identity, or both.16 African American students are more likely to be cyberbully perpetrators and Hispanic students are more likely to be cyberbully perpetrators–victims than their White peers.2Cyberbullying may occur across a variety of technology platforms, and the specific qualities of each platform may affect how cyberbullying is perpetrated and experienced. Earlier studies suggested that instant messaging, chat rooms, and message boards were the most common mediums for middle-school students who experienced cyberbullying.3,17 More recently, youths have migrated to social media platforms such as Facebook,18–20 necessitating an examination of cyberbullying across more contemporary and emerging platforms for youth interaction.More frequent use of technology has also been associated with cyberbullying. Students who use the Internet for at least 3 hours per day and those who use instant messaging and Web cams are significantly more likely to have been cyberbully victims at least 7 times during the previous year.17 Frequent Internet users are significantly more likely to be cyberbully perpetrators, victims, and perpetrators–victims.14Research has shown that even though cyberbullying takes place in a virtual space, most cyberbullying perpetrators know their victims and vice versa. Moreover, 73% of victims reported being “pretty sure” or “totally sure” about the identity of their cyberbully, with 51% of cyberbullying perpetrators identified as a classmate, 43% as someone who they only knew online, and 20% as an in-person, nonclassmate relation.17 Cyberbullying perpetrators of middle-school victims were most often a classmate or a stranger; cyberbullying perpetrators most often reported that they cyberbullied classmates, friends, and strangers.3This study expanded previous work with high-school samples2 and nonprobability samples of middle-school students3,17 to explore the role of sexual identity, gender, race, and technology use patterns in a random sample of urban middle-school students in Los Angeles County, California. The study focused on demographic characteristics including sexual identity, patterns of technology use (i.e., frequency of Internet use, texting, parental rules regarding Internet use), and platforms on which middle-school students experience cyberbullying (i.e., Facebook, Twitter, e-mail, text messaging) to inform interventions to disrupt this maladaptive behavior and help protect early adolescents from the consequences of cyberbullying.     

Anemia of the Belgrade rat: evidence for defective membrane transport of iron

The mechanisms underlying the impaired utilization of transferrin-bound iron by erythroid cells in the anemia of the Belgrade laboratory rat were investigated using reticulocytes from homozygous anemic animals and transferrin labeled with 59Fe and 125I. The results were compared with those obtained using reticulocytes from phenylhydrazine-treated rats and iron-deficient rats. Each step in the iron uptake mechanism was investigated, ie, transferrin-receptor interaction, transferrin endocytosis, iron release from transferrin, and transferrin exocytosis. Although there were quantitative differences, no fundamental difference was found in any of the abovementioned aspects of cellular function when the reticulocytes from Belgrade rats were compared with those from iron-deficient animals. The basic defect in the Belgrade reticulocytes must therefore reside in subsequent steps in iron uptake, after it is released from transferrin within endocytotic vesicles, ie, in the mechanism by which it is transferred across the lining membrane of the vesicles into the cell cytosol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reticulocyte ghosts extracts demonstrated a prominent protein band of mol wt 69,000 that was absent or present only in low concentration extracts from the other two types of reticulocytes. This may be a result of the genetic defect.     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.     

Acceptability of Smartphone Application-Based HIV Prevention Among Young Men Who Have Sex With Men

Young men who have sex with men (YMSM) are increasingly using mobile smartphone applications (“apps”), such as Grindr, to meet sex partners. A probability sample of 195 Grindr-using YMSM in Southern California were administered an anonymous online survey to assess patterns of and motivations for Grindr use in order to inform development and tailoring of smartphone-based HIV prevention for YMSM. The number one reason for using Grindr (29 %) was to meet “hook ups.” Among those participants who used both Grindr and online dating sites, a statistically significantly greater percentage used online dating sites for “hook ups” (42 %) compared to Grindr (30 %). Seventy percent of YMSM expressed a willingness to participate in a smartphone app-based HIV prevention program. Development and testing of smartphone apps for HIV prevention delivery has the potential to engage YMSM in HIV prevention programming, which can be tailored based on use patterns and motivations for use.