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Objective: Adolescents and young adults (AYA) with sickle cell disease (SCD) experience high rates of acute care utilization and increased morbidity. At this high-risk time, they also face the need to transition from pediatric to adult services, which, if poorly coordinated, adds to heightened morbidity and acute care utilization. The study objective was to characterize the feasibility, acceptability, and short-term efficacy of a protocolized transition navigator (TN) intervention in AYA with SCD., Methods: We developed a protocolized TN intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, and to provide disease and pain management education and skills to AYAs with SCD., Results: Ninety-three percent (56/60) of enrolled individuals completed the intervention. Participation in the TN program was associated with significant improvement in mean transition readiness scores (3.58-4.15, P < .0001), disease knowledge scale (8.91-10.13, P < .0001), Adolescent Medication Barriers Scale (40.05-35.39, P = .003) and confidence in both disease (22.5-23.96, P = .048) and pain management (25.07-26.61, P = .003) for youth with SCD., Conclusion: The TN intervention was acceptable to youth with SCD, feasible to implement at an urban academic medical center, and addressed barriers to transition identified by the youth. Longer-term assessment is needed to determine if the TN intervention improved successful transfer to and retention in adult care., (Copyright © 2021 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to explore current orthodontic residents' demographics, their opinions on their residency and plans for the future and highlight secular changes since past surveys., Methods: An anonymous 39-item institutional review board-approved survey was implemented at the 2018 Graduate Orthodontic Resident Program using an online survey tool and portable devices. Questions fit 3 categories: program, future goals, and demographics. Responses were analyzed to determine frequencies, means, and cross tabulations. Analyses of variance and chi-square were applied with significance defined as P <0.05., Results: Of the 489 attendees, 76% completed the survey; most were female (51%), white (60%), U.S. citizens (85%), single (63%), and very satisfied with their programs (54%). Tuition costs varied, but 18% of respondents paid >$80,000 annually. Orthodontic and total educational debts were significantly correlated (r = 0.704) and averaged $137,706 ± $127,380 and $323,071 ± $266,510, respectively. These debts were significantly lower (P <0.0001) for respondents with stipends. Debts influenced the decision of where to work in the future for 62% of respondents and were a source of anxiety for 72% of respondents. Educational debts were significantly positively associated with anxiety levels (P <0.0001)., Conclusions: This survey provided current information on orthodontic residents' opinions, plans, and demographics. Comparisons with previous surveys showed increases in the number of female respondents, tuition costs, and educational debts and decreases in stipends. Orthodontics may be approaching a "bubble market" where the financial benefits do not outweigh specialty education costs., (Copyright © 2020 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: Activation of the phosphoinisitide-3 kinase (PI3K) pathway through mutation and constitutive upregulation has been described in renal cell carcinoma (RCC), making it an attractive target for therapeutic intervention. We performed a randomized phase II study in vascular endothelial growth factor (VEGF) therapy refractory patients to determine whether MK-2206, an allosteric inhibitor of AKT, was more efficacious than the mammalian target of rapamycin inhibitor everolimus., Patients and Methods: A total of 43 patients were randomized in a 2:1 distribution, with 29 patients assigned to the MK-2206 arm and 14 to the everolimus arm. Progression-free survival (PFS) was the primary endpoint., Results: The trial was closed at the first futility analysis with an observed PFS of 3.68 months in the MK-2206 arm and 5.98 months in the everolimus arm. Dichotomous response rate profiles were seen in the MK-2206 arm with one complete response and three partial responses in the MK-2206 arm versus none in the everolimus arm. On the other hand, progressive disease was best response in 44.8% of MK2206 versus 14.3% of everolimus-treated patients. MK-2206 induced significantly more rash and pruritis than everolimus, and dose reduction occurred in 37.9% of MK-2206 versus 21.4% of everolimus-treated patients. Genomic analysis revealed that 57.1% of the patients in the PD group had either deleterious TP53 mutations or ATM mutations or deletions. In contrast, none of the patients in the non-PD group had TP53 or ATM defects. No predictive marker for response was observed in this small dataset., Conclusions: Dichotomous outcomes are observed when VEGF therapy refractory patients are treated with MK-2206, and MK-2206 does not demonstrate superiority to everolimus. Additionally, mutations in DNA repair genes are associated with early disease progression, indicating that dysregulation of DNA repair is associated with a more aggressive tumor phenotype in RCC., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: KRAS mutations in NSCLC are associated with a lack of response to epidermal growth factor receptor inhibitors. Selumetinib (AZD6244; ARRY-142886) is an oral selective MEK kinase inhibitor of the Ras/Raf/MEK/ERK pathway., Patients and Methods: Advanced nonsmall-cell lung cancer (NSCLC) patients failing one to two prior regimens underwent KRAS profiling. KRAS wild-type patients were randomized to erlotinib (150 mg daily) or a combination of selumetinib (150 mg daily) with erlotinib (100 mg daily). KRAS mutant patients were randomized to selumetinib (75 mg b.i.d.) or the combination. The primary end points were progression-free survival (PFS) for the KRAS wild-type cohort and objective response rate (ORR) for the KRAS mutant cohort. Biomarker studies of ERK phosphorylation and immune subsets were carried out., Results: From March 2010 to May 2013, 89 patients were screened; 41 KRAS mutant and 38 KRAS wild-type patients were enrolled. Median PFS in the KRAS wild-type arm was 2.4 months [95% confidence interval (CI) 1.3-3.7] for erlotinib alone and 2.1 months (95% CI 1.8-5.1) for the combination. The ORR in the KRAS mutant group was 0% (95% CI 0.0% to 33.6%) for selumetinib alone and 10% (95% CI 2.1% to 26.3%) for the combination. Combination therapy resulted in increased toxicities, requiring dose reductions (56%) and discontinuation (8%). Programmed cell death-1 expression on regulatory T cells (Tregs), Tim-3 on CD8+ T cells and Th17 levels were associated with PFS and overall survival in patients receiving selumetinib., Conclusions: This study failed to show improvement in ORR or PFS with combination therapy of selumetinib and erlotinib over monotherapy in KRAS mutant and KRAS wild-type advanced NSCLC. The association of immune subsets and immune checkpoint receptor expression with selumetinib may warrant further studies., (© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Kaposi sarcoma-associated herpesvirus (KSHV) is a principal causative agent of primary effusion lymphoma (PEL) with a poor prognosis in immunocompromised patients. However, it still lacks effective treatment which urgently requires the identification of novel therapeutic targets for PEL. Here, we report that the hepatocyte growth factor (HGF)/c-MET pathway is highly activated by KSHV in vitro and in vivo. The selective c-MET inhibitor, PF-2341066, can induce PEL apoptosis through cell cycle arrest and DNA damage, and suppress tumor progression in a xenograft murine model. By using microarray analysis, we identify many novel genes that are potentially controlled by HGF/c-MET within PEL cells. One of the downstream candidates, ribonucleoside-diphosphate reductase subunit M2 (RRM2), also displays the promising therapeutic value for PEL treatment. Our findings provide the framework for development of HGF/c-MET-focused therapy and implementation of clinical trials for PEL patients.

An obstetric dilemma may have been a persistent characteristic of human evolution, in which the bipedal female's pelvis is barely large enough to accommodate the birth of a large-brained neonate. Evidence in the archaeological record for mortality risk associated with childbirth is rare, especially among highly mobile, immediate return hunter-gatherer populations. This research explores the idea that if excess mortality is associated with first pregnancy, females will outnumber males among young adult skeletons. The sample is of 246 skeletons (119 males, 127 females) representing Later Stone Age (LSA) foragers of the South African Cape. Young adults are distinguished through incomplete maturation of the medial clavicle, iliac crest and vertebral bodies. With 26 women and 14 men in the young category, a higher mortality risk for women is suggested, particularly in the Southern Cape region. Body size does not distinguish mortality groups; there is evidence of a dietary protein difference between young and older women from the Southern Cape. Possible increased mortality associated with first parturition may have been linked to morphological or energetic challenges, or a combination of both. Exploration of the sex ratio among young adult skeletons provides a tool for exploring the antiquity of an important evolutionary factor., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study was conducted to determine the incidence of early stasis in radioembolization using resin yttrium-90 (Y-90) microspheres, to evaluate potential contributing factors, and to review initial imaging outcomes., Methods: Patients in whom early stasis occurred were compared with those in whom complete delivery was achieved for tumour type and vascularity, tumour : normal liver ratio (T : N ratio) at technetium-99m-macroaggregated albumin (Tc-99m-MAA) angiography, previous intra-arterial therapy, and infusion site (left, right or whole liver). Tumour response was evaluated at 3 months and defined according to whether a partial response and stable disease versus progressive disease were demonstrated., Results: A total of 71 patients underwent 128 Y-90 infusions in which 26 (20.3%) stasis events occurred. Hypervascular and hypovascular tumours had similar rates of stasis (17.4% versus 27.8%; P = NS). The mean ± standard deviation T : N ratio was 3.03 ± 1.54 and 3.66 ± 2.79 in patients with and without stasis, respectively (P = NS). Stasis occurred in 14 of 81 (17.3%) and 12 of 47 (25.5%) infusions following previous intra-arterial therapy and in therapy-naïve territories, respectively (P = NS). Early stasis occurred in 15 of 41 (36.6%) left, 10 of 65 (15.4%) right and one of 22 (4.5%) whole liver infusions (P < 0.001). Rates of partial response and stable disease were similar in the stasis (88.3%) and non-stasis (76.0%) groups (P = NS)., Conclusions: Early stasis occurred in approximately 20% of infusions with similar incidences in hyper- and hypovascular tumours. Whole-liver therapy reduced the incidence of stasis. Stasis did not appear to affect initial imaging outcomes., (© 2013 International Hepato-Pancreato-Biliary Association.)

Flavopiridol is a protein bound, cytotoxic, cyclin-dependent kinase inhibitor. Flavopiridol given by 1-hour bolus at 50 mg/m(2) daily 3 times followed by cytosine arabinoside and mitoxantrone (FLAM) is active in adults with poor-risk acute leukemias. A pharmacologically derived "hybrid" schedule (30-minute bolus followed by 4-hour infusion) of flavopiridol was more effective than bolus administration in refractory chronic lymphocytic leukemia. Our phase 1 trial "hybrid FLAM" in 55 adults with relapsed/refractory acute leukemias began at a total flavopiridol dose of 50 mg/m(2) per day 3 times (20-mg/m(2) bolus, 30-mg/m(2) infusion). Dose-limiting toxicity occurred at level 6 (30-mg/m(2) bolus, 70-mg/m(2) infusion) with tumor lysis, hyperbilirubinemia, and mucositis. Death occurred in 5 patients (9%). Complete remission occurred in 22 (40%) across all doses. Overall and disease-free survivals for complete remission patients are more than 60% at more than 2 years. Pharmacokinetics demonstrated a dose-response for total and unbound plasma flavopiridol unrelated to total protein, albumin, peripheral blast count, or toxicity. Pharmacodynamically, flavopiridol inhibited mRNAs of multiple cell cycle regulators, but with uniform increases in bcl-2. "Hybrid FLAM" is active in relapsed/refractory acute leukemias, with a recommended "hybrid" dose of bolus 30 mg/m(2) followed by infusion of 60 mg/m(2) daily for 3 days. This clinical trial is registered at www.clinicaltrials.gov as #NCT00470197.

Follicle selection is associated with an increase in the expression of vascular endothelial growth factor (VEGF) and its receptors in granulosa cells, however, the roles of VEGF in regulating the function of these or other non-endothelial cells in the ovary have not been explored in detail. The current study used bovine cell cultures to investigate potential roles of VEGF in the regulation of granulosa cell function during follicle development. Granulosa cells were obtained from morphologically healthy follicles 4 to 8 mm or 9 to 14 mm in diameter (corresponding to diameters before and after the establishment of dominance, respectively, during a bovine follicular wave) and exposed to a range of VEGF concentrations (1 to 100 ng/mL) encompassing concentrations found naturally in bovine dominant follicles. A concentration of VEGF of 1 ng/mL induced significant proliferation of granulosa cells from 4- to 8-mm follicles (P=0.024) and increased the proliferative response of these cells to follicle-stimulating hormone (FSH; P=0.045); whereas higher doses of VEGF had no effect on proliferation (P=0.9). Treatment with VEGF induced an overall increase in mean extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation (P=0.02). In contrast, VEGF, alone or in combination with FSH, had no effect on expression of the steroidogenic enzyme, CYP11A1, by cells from 4- to 8-mm follicles (P=0.9). Granulosa cells from 9- to 14-mm follicles responded to 1 ng/mL VEGF with an increase in expression of the ovulation-associated gene, PTGS2 (P=0.003) but higher VEGF doses had no effect (P=0.9). The PTGS2 response to 1 ng/mL VEGF was similar to that induced by treatment with luteinizing hormone (LH). Interestingly, the stimulatory effects of LH on ERK1/2 phosphorylation (P=0.003) and PTGS2 expression (P<0.01) in granulosa cells from 9- to 14-mm follicles were abolished (P=0.2) by specific chemical inhibition of VEGF receptor 2 (VEGFR2). These results suggest novel and important roles of VEGF and its receptor, VEGFR2, in mediating and/or enhancing the effects of gonadotropins in granulosa cells., (Copyright 2009. Published by Elsevier Inc.)

Background: We studied the clinical characteristics and outcomes of patients undergoing pneumonectomy after preoperative concurrent chemoradiation for non-small cell lung cancer., Methods: Clinical records of patients with non-small cell lung cancer who underwent pneumonectomy at our institution between 1995 and 2005 after preoperative concurrent chemoradiation were reviewed retrospectively., Results: Twenty-nine patients underwent pneumonectomy after preoperative concurrent chemoradiation. Of the 21 men and 8 women who were treated, 1 had stage IIB (T3N0M0) and the remainder had stage IIIA or IIIB non-small cell lung cancer. Mean patient age at surgery was 53.4 years. There were 15 right pneumonectomies, of which 2 were for pancoast tumors. All patients received concurrent preoperative chemoradiation. Mean total radiation dose was 61.1 Gy. All patients went on to have complete (R0) resection by pneumonectomy. Pathologic complete response was found in 16 patients (55.2%). All patients were discharged alive from the hospital after pneumonectomy. Median hospital length of stay was 5 days (mean 8.6). Ninety-day mortality after surgery was 3.4% (n = 1). Recurrences have been found in 11 patients (38%), including brain metastases (n = 6), bone metastases (n = 4), liver metastases (n = 2), and cervical lymph node metastases (n = 2). One patient had a contralateral new primary lung cancer develop 70 months after undergoing pneumonectomy. Estimated 5-year disease-free survival is 48%. Median survival time has not been reached., Conclusions: Pneumonectomy can be performed safely after preoperative concurrent chemoradiation, even with high-dose radiation. The frequency of disease recurrence in the brain underscores the need to evaluate the role of prophylactic cranial radiation in non-small cell lung cancer., (2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

New tools are needed for managing celiac sprue, a lifelong immune disease of the small intestine. Ongoing drug trials are also prompting a search for noninvasive biomarkers of gluten-induced intestinal change. We have synthesized and characterized noninflammatory gluten peptide analogs in which key Gln residues are replaced by Asn or His. Like their proinflammatory counterparts, these biomarkers are resistant to gastrointestinal proteases, susceptible to glutenases, and permeable across enterocyte barriers. Unlike gluten peptides, however, they are not appreciably recognized by transglutaminase, HLA-DQ2, or disease-specific T cells. In vitro and animal studies show that the biomarkers can detect intestinal permeability changes as well as glutenase-catalyzed gastric detoxification of gluten. Accordingly, controlled clinical studies are warranted to evaluate the use of these peptides as probes for abnormal intestinal permeability in celiac patients and for glutenase efficacy in clinical trials and practice.

Background: We have previously demonstrated that high-dose chemoradiotherapy followed by resection for patients selected on the basis of mediastinal sterilization was feasible and resulted in excellent outcomes. This study was designed to determine the ability to intensify our prior approach utilizing hyperfractionated radiation and more aggressive consolidative chemotherapy., Methods: Patients with documented stage IIIA/B nonsmall-cell lung cancer, performance status 0 to 2, and adequate organ function were eligible. A phase I portion utilized escalating doses of carboplatin and vinorelbine, commencing with areas under the curve of 1 and 5 mg/m(2), respectively, and concurrent 69.6 Gy hyperfractionated radiotherapy. A phase II portion utilized the identical radiotherapy with carboplatin/vinorelbine at the maximum tolerated dose established in phase I. Patients for whom mediastinal nodal clearance was demonstrated underwent resection. All patients were to receive consolidation chemotherapy consisting of carboplatin/vinorelbine for three cycles, followed by docetaxel for three cycles. Prophylactic cranial irradiation was offered to patients after completion of therapy., Results: Forty-seven patients participated in the study (33 IIIA, 14 IIIB; 15 men, 32 women; median age, 56 years). The maximum tolerated dose for concurrent carboplatin/vinorelbine and hyperfractionated radiotherapy was established at areas under the curve of 1 and 10 mg/m(2), respectively. Twenty-eight patients completed trimodality treatment including surgery. Median survival time for the entire study cohort (n = 47) is 29.6 months, and it is 55.8 months for patients with mediastinal clearance who underwent resection (n = 28)., Conclusions: Surgical resection of locally advanced stage IIIA and IIIB nonsmall-cell lung cancer after induction hyperfractionated radiation and concurrent chemotherapy is safe and well tolerated. Whether this approach is superior to less aggressive therapy is uncertain and will require comparative studies.

Background: Major grades of intraventricular haemorrhage (IVH) are associated with adverse neurodevelopmental sequelae in early childhood but the extent of problems in specific cognitive areas, such as executive function, and the contribution of lesser grades of IVH to neurodevelopmental problems at school age are not well described., Aims: To determine the neuromotor, cognitive and educational outcome of extremely low birthweight (ELBW, birthweight <1000 g) or very preterm (<28 weeks) infants at 8 years of age related to the severity of IVH diagnosed in the newborn period., Design: Regional cohort study., Patients: Consecutive surviving children of either birthweight <1000 g or gestational age <28 weeks born in the state of Victoria in 1991 or 1992., Main Outcome Measures: Neurological impairments and disabilities, cognitive function and academic progress., Results: Of 298 consecutive ELBW/very preterm survivors 270 (90.6%) with cranial ultrasound data were assessed at 8 years of age. Cerebral palsy, poor motor performance and major neurosensory disability were more prevalent with increasing severity of IVH. Cognitive functioning across domains was worse with increasing severity of IVH. Most of the differences were attributable to the few (n=6) survivors who had grade 4 IVH; there were few substantial differences between survivors with lesser grades of IVH., Conclusions: Neurodevelopmental dysfunction at school age in ELBW/very preterm survivors varies little with increasing severity of IVH, with the exception of grade 4 IVH.

Lung cancer is the major cause of cancer-related death in both men and women in the United States. Emerging evidence indicates that there are differences in the pathogenesis and possibly increased susceptibility to lung cancer in women. In addition, considerable data support small, but important differences favoring women in terms of response to therapy and long-term survival after the diagnosis of lung cancer, regardless of histology or stage. These differences in both biology and outcome will be important considerations in the design of future trials of screening and therapy for lung cancer.

Background: Very preterm infants at the borderline of viability, especially those <25 weeks of gestational age, have survived in increasing numbers in recent years, but concerns persist about their long-term outcome and their consumption of scarce hospital resources., Aims: To determine incremental changes in long-term outcome and consumption of resources by very preterm infants in the 1990s., Design: Cohort study., Patients: Consecutive livebirths with gestational ages 23-27 weeks born in the state of Victoria in two discrete eras, 1991-1992 (n=401) and 1997 (n=208), and randomly selected contemporaneous normal birthweight (NBW, birthweight >2499 g) controls (1991-1992 n=265, 1997 n=198)., Main Outcome Measures: Survival, and neurosensory impairments, disabilities and utilities, and consumption of hospital resources to 2 years of age., Results: Compared with 1991-1992, in 1997 more infants were offered intensive care and the survival rate was higher at each week of gestation, and overall (absolute increase in survival 16%; 95% confidence interval, 8%, 24%). The largest increases in the survival and quality-adjusted survival rates were in infants at 23 weeks (31% and 20%, respectively). The incremental resource costs of improving survival and quality-adjusted survival were similar in infants of 23-24 weeks compared with those of 25-27 weeks (e.g., 112 vs. 105 days of assisted ventilation per additional survivor, or 167 vs. 180 days of assisted ventilation per additional quality-adjusted survivor, respectively)., Conclusions: Increased intensive care in the late 1990s for infants at the borderline of viability was associated with improved outcomes, at incremental costs that were not excessive compared with slightly more mature infants.

Purpose: To determine whether initiation of on-site dispensing of hormonal contraceptives (oral contraceptive pill, Depo-provera, and Norplant) in six urban school-based health centers reduced time to initial selection, and increased their consistent use among sexually active females., Methods: Participants were sexually active females who received family planning care in a school year before (1994-1995 cohort) or after (1996-1997 cohort) the initiation of on-site dispensing. Data on contraception and sexual behavior were collected at each family planning visit. Cohorts were compared using Student's t-tests and Chi-square tests, analysis of covariance, and logistic regression., Results: About 59% of the 1994-1995 cohort selected hormonal contraceptives at the first or second visit; this increased to 72% of the 1996-1997 cohort (chi(2) = 11.3; p <.001). After adjustment for cohort differences, the 1996-1997 cohort consistently selected hormonal contraceptives a longer period of time, although the difference did not reach statistical significance (adjusted means: 1994-1995 cohort = 73 days, 1996-1997 cohort = 81 days; t = 1.6, p <.10)., Conclusion: Sexually active females receiving family planning care select methods of hormonal contraception sooner and somewhat more consistently when the clinics in their high schools can dispense contraceptives on-site.

A relatively brief course of antenatal glucocorticoids (ACS), given to reduce the severity of respiratory distress syndrome in preterm infants, improves survival and appears to protect against brain damage. In clinical trials as well as observational studies, ACS have been associated with a decreased risk of intraventricular haemorrhage and cerebral palsy. In observational studies a decreased risk of white-matter damage, identified with cranial ultrasound, has been observed. There is some evidence, from observational studies, that repeated courses of ACS (typically given at weekly intervals) can reduce the rate of fetal head growth, and experiments in animals provide further support for this possibility. In contrast to the effects of a brief course of ACS, postnatal glucocorticoids (PCS), given to preterm infants to reduce the severity of chronic lung disease have been associated with an increased risk of neurologic impairment. Available evidence suggests that PCS does not improve survival. Further study is needed of the neurodevelopmental consequences of both multiple courses of ACS, as well as PCS., (Copyright 2002 Elsevier Science Ltd.)

Breast cancer resistance protein (BCRP), an ABC half-transporter, is overexpressed in cancer cell lines selected with doxorubicin/verapamil, topotecan, or mitoxantrone. BCRP-overexpressing cells show cross-resistance to camptothecin derivatives such as irinotecan, SN-38 (the active metabolite of irinotecan), and topotecan. To test whether BCRP confers SN-38 resistance, we selected two SN-38 resistant sublines from PC-6 human small-cell lung cancer cells by SN-38, and then characterized these cells. Compared to PC-6 cells, the resistant sublines PC-6/SN2-5 and PC-6/SN2-5H were approximately 18- and 34-fold resistant, respectively. The intracellular SN-38 accumulation was reduced in the sublines, and BCRP mRNA was overexpressed in proportion to the degree of SN-38 resistance. These findings suggest that BCRP confers SN-38 resistance in the sublines. To confirm this hypothesis, PC-6/SN2-5 cells were transfected with antisense oligonucleotides complementary to portions of BCRP mRNA. The antisense oligonucleotides significantly suppressed BCRP mRNA expression, and enhanced SN-38 sensitivity in the subline. These data indicate that BCRP is directly involved with SN-38 resistance, by efflux transport of SN-38.

Breast cancer resistance protein (BCRP) is a novel member of the adenosine triphosphate-binding cassette superfamily of transport proteins. Transfection and enforced expression of BCRP in drug-sensitive cells confer resistance to mitoxantrone, doxorubicin, daunorubicin, and topotecan. We studied blast cells from 21 acute leukemia patients (20 acute myeloid leukemia, 1 acute lymphocytic leukemia) for the expression of BCRP mRNA using a quantitative reverse-transcription polymerase chain reaction assay. BCRP mRNA expression varied more than 1000-fold among the samples tested, with low or barely detectable expression in half of the samples. Seven samples (33%) had relatively high expression of BCRP mRNA. High expression of BCRP did not correlate strongly with high expression of P-glycoprotein, suggesting that BCRP may cause resistance to certain antileukemic drugs in P-glycoprotein-negative cases. High expression of BCRP mRNA is sufficiently frequent in AML to warrant more extensive investigations to determine the relation of disease subtype and treatment outcome to BCRP expression and function.

Background: Pulmonary resection after high-dose thoracic irradiation is reported to be associated with a high morbidity and mortality, and has been considered to be prohibitive., Methods: We report safe pulmonary resection in 19 consecutive patients receiving neoadjuvant therapy that included greater than 59 Gy thoracic radiation. The mean thoracic radiation dose was 61.8 Gy (range 59.5-66.5) and mean age was 52 years (range 36-72 years). Cell type was adenocarcinoma (6), squamous (7), and other non-small cell lung cancer (NSCLC) (6). Sixteen of 19 patients received concurrent chemotherapy. Median time from end of treatment to surgical resection was 89 days (range 22-258 days). Surgical resection included 13 lobectomies and six pneumonectomies (four right, two left)., Results: A complete pathologic response was seen in 8 of 19 (42%) patients. Three patients required intraoperative transfusion of blood. Mean intensive care unit stay was 2.0 days (range 1-8 days), and mean length of stay (LOS) was 8.0 days (range 3-18 days). There were four postoperative complications; one bronchopulmonary fistula, one subarachnoid-pleural fistula, and 2 patients with prolonged atelectasis. There was no incidence of acute respiratory distress syndrome (ARDS) or operative mortality., Conclusions: Pulmonary resection, including pneumonectomy, after chemotherapy and high-dose thoracic radiation may be performed safely with a low rate of intraoperative and postoperative complications.

Recent studies have shown that human cancer cell lines can be adapted to grow in serum-free, unsupplemented RPMI-1640 (RO) medium. We have developed similar techniques to rapidly identify proteins of interest in serum-free conditioned medium (CM) of human lung cancer cell lines. Classic and variant small cell lung cancer (SCLC) lines were adapted to growth in RO medium. CM from each line was concentrated and fractionated on an anion-exchange column of a fast protein liquid chromatography system. Concentrates of each fraction were loaded onto lanes of minigels of an automated electrophoresis system. Analysis of the chromatograms reveals peaks seen only in CM of the classic SCLC lines. Electrophoretic analysis of the fractions containing these peaks reveal protein bands distinguishing between the subtypes of human SCLC. One protein was purified to homogeneity with subsequent reversed-phase chromatography and identified by protein microsequencing as histone H2B. These automated techniques have general use in the rapid identification of CM proteins associated with the differentiation or progression of the many types of neoplastic cells which can be adapted to growth in RO medium.

Data were obtained from a risk task, the zipwire, in order to examine self-report and heart rate responses of males and females. Using this task, heart rate data demonstrated similar patterns to those found in earlier parachuting studies. ANOVAs demonstrated significant differences between sexes in self-report measures, but no significant differences in heart rate. In addition, examination of the relationships between heart rate and self-report showed a positive correlation for the women, while there was a negative correlation for the men.

Intrauterine devices (IUD's) containing 0, 5, or 10 per cent by weight of progesterone, melengestrol acetate (MGA), norethindrone, norgestrel, medroxyprogesterone acetate, isoxsuprine, or R2323 or wound with fine copper wire were placed in one or both horns of cycling female rats. All the progestins improved retention of the silicone-rubber IUD's to some degree. The effects of these compounds on the estrous cycle, mating, ovulation, fertilization, tubal transport, and implantation varied among the compounds. Effects were local or systemic, depending upon the amount and the drug. Uterine motility studies showed clearly that 5 per cent MGA decreased uterine motility; however, no consistent results could be obtained using the other compounds in the same in vivo system.

This is a report of bilateral partial ruptures of the flexor carpi radialis tendons associated with trapezial osteoarthritis. Splinting for 4 weeks was curative. One of the tendons was exposed 4 months after rupture in conjunction with carpal tunnel release and the abnormal healed tendon was revealed.

Oral human gammaglobulin or placebo was given with each feed during the first week of life to 75 low-birth-weight babies. All were in a nursery where rotavirus was known to be endemic, 25 of the babies excreted rotavirus during the first 2 weeks of life. This group was regarded as the "challenge" group. Gammaglobulin administration was associated with delayed excretion of rotavirus and with milder symptoms of infection. Rotavirus-associated diarrhoea necessitating low-lactose feeds developed in 6 of 11 babies given placebo and 1 of 14 babies given gammaglobulin. Oral human gammaglobulin seems to protect low-birth-weight infants from diarrhoea caused by rotavirus.

A review of all cases of osteoid osteoma of the hand seen by four hand surgeons over the last 10 years was performed. Seven cases were documented. Average follow-up was 28.3 months. Average age of the patients was 21.1 years. Five men and two women participated. Six lesions were in the right and one in the left upper extremity. Delay from presenting symptoms to definitive treatment averaged 13.5 months with a range of 7 to 30 months. Surgical excision was curative in all cases. We concluded that although a very unusual occurrence, osteoid osteoma of the hand should be considered in the differential diagnosis of pain in the hand.