Changes in receptor location affect the ability of oxytocin to stimulate proliferative growth in prostate epithelial cells.

In normal prostate cells, cell membrane receptors are located within signalling microdomains called caveolae. During cancer progression, caveolae are lost and sequestered receptors move out onto lipid rafts. The aim of this study was to investigate whether a change in the localisation of receptors out of caveolae and onto the cell membrane increased cell proliferation invitro, and to determine whether this is related to changes in the cell signalling pathways. Normal human prostate epithelial cells (PrEC) and androgen-independent (PC3) cancer cells were cultured with 10nM dihydrotestosterone (DHT). The effects of oxytocin (OT) and gonadal steroids on proliferation were assessed using the MTS assay. Androgen receptor (AR) and oxytocin receptor (OTR) expression was identified by immunofluorescence and quantified by western blot. OTR and lipid raft staining was determined using Pearson's correlation coefficient. Protein-protein interactions were detected and the cell signalling pathways identified. Treatment with OT did not affect the proliferation of PrEC. In PC3 cells, OT or androgen alone increased cell proliferation, but together had no effect. In normal cells, OTR localised to the membrane and AR localised to the nucleus, whereas in malignant cells both OTR and AR were identified in the cell membrane. Colocalisation of OTR and AR increased following treatment with androgens. Significantly fewer OTR/AR protein-protein interactions were seen in PrEC. With OT treatment, several cell signalling pathways were activated. Movement of OTR out of caveolae onto lipid rafts is accompanied by activation of alternative signal transduction pathways involved in stimulating increased cell proliferation.

Health-related Quality of Life (HR-QOL) and Chronic Health Conditions in Survivors of Childhood Acute Myeloid Leukemia (AML) with Down Syndrome (DS): A Report From the Children's Oncology Group.

Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. In total, 26 individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77 to 10.9 y) and median age at interview of 15 years (range, 8.3 to 27.6 y). Participants with DS and AML were compared with AML survivors without DS whose caregiver completed a HR-QOL survey (CHQ-PF50). In total, 77% of survivors with DS reported ≥1 chronic health condition compared with 50% of AML survivors without DS (P=0.07). Mean physical and psychosocial QOL scores for children with DS and AML were statistically lower than the population mean, though not discrepant from AML survivors without DS. Although the overall prevalence of chronic health conditions in survivors with DS is higher than in survivors without DS, prior studies of children with DS have reported similarly high rates of chronic health conditions, suggesting that AML therapy may not substantially increase this risk.

High Incidence of Veno-Occlusive Disease With Myeloablative Chemotherapy Following Craniospinal Irradiation in Children With Newly Diagnosed High-Risk CNS Embryonal Tumors: A Report From the Children's Oncology Group (CCG-99702).

BACKGROUND: The outcomes with high-risk central nervous system (CNS) embryonal tumors remain relatively poor despite aggressive treatment. The purposes of this study using postirradiation myeloablative chemotherapy with autologous hematopoietic stem cell rescue (ASCR) were to document feasibility and describe toxicities of the regimen, establish the appropriate dose of thiotepa, and estimate the overall survival (OS) and event-free survival (EFS). PROCEDURE: The Children's Cancer Group conducted this pilot study in children and adolescents with CNS embryonal tumors. The treatment consisted of induction chemotherapy to mobilize hematopoietic stem cells, chemoradiotherapy, and myeloablative consolidation chemotherapy with ASCR. RESULTS: The study accrued 25 subjects in 40 months and was closed early due to toxicity, namely, veno-occlusive disease (VOD) of the liver, more recently termed sinusoidal obstructive syndrome (SOS). Of 24 eligible subjects, three of 11 (27%) receiving thiotepa Dose Level 1 (150 mg/m(2) /day × 3 days) and three of 12 (25%) receiving de-escalated Dose Level 0 (100 mg/m(2) /day × 3 days) experienced VOD/SOS. One additional subject experienced toxic death attributed to septic shock; postmortem examination revealed clinically undiagnosed VOD/SOS. The 2-year EFS and OS were 54 ± 10% and 71 ± 9%, respectively. The 5-year EFS and OS were 46 ± 11% and 50 ± 11%. CONCLUSIONS: The treatment regimen was deemed to have an unacceptable rate of VOD/SOS. There was complete recovery in all six cases. The overall therapeutic strategy using a regimen less likely to cause VOD/SOS may merit further evaluation for the highest risk patients.

The anatomy of the hip abductor muscles.

The anatomy of the hip abductors has not been comprehensively examined, yet is important to understanding function and pathology in the gluteal region. For example, pathology of the hip abductor muscle-tendon complexes can cause greater trochanteric pain syndrome, and may be associated with gluteal atrophy and fatty infiltration. The purpose of this study was to investigate the detailed morphology of gluteus medius (GMed), gluteus minimus (GMin), and tensor fascia lata (TFL), and determine whether the muscles comprised anatomical compartments. The gluteal region from 12 cadavers was dissected and data collected on attachment sites, volume, fascicular and tendinous anatomy, and innervation. Three sites of GMed origin were identified (gluteal fossa, gluteal aponeurosis, and posteroinferior edge of the iliac crest) and the distal tendon had lateral and posterior parts. GMed was the largest in volume (27.6 ± 11.6 cm(3); GMin 14.1 ± 11.1 cm(3); TFL 1.8 ± 0.8 cm(3)). Fascicles of GMin originated from the gluteal fossa, inserting onto the deep surface of its distal tendon and the hip joint capsule. TFL was encapsulated in the fascia lata, having no bony attachment. Primary innervation patterns varied for GMed, with three or four branches supplying different regions of muscle. Distinct secondary nerve branches entered four regions of GMin; no differential innervation was observed for TFL. On the basis of architectural parameters and innervation, GMed, and GMin each comprise of four compartments but TFL is a homogenous muscle. It is anticipated that these data will be useful for future clinical and functional studies of the hip abductors.

Health conditions and quality of life in survivors of childhood acute myeloid leukemia comparing post remission chemotherapy to BMT: a report from the children's oncology group.

BACKGROUND: Therapy for childhood acute myeloid leukemia (AML) has historically included chemotherapy with or without autologous bone marrow transplant (autoBMT) or allogeneic hematopoietic stem cell transplantation (alloBMT). We sought to compare health-related quality-of-life (HRQOL) outcomes between these treatment groups. PROCEDURE: Five-year survivors of AML diagnosed before age 21 and enrolled and treated from 1979 to 1995 on one of 4 national protocols were interviewed. These survivors or proxy caregivers completed a health questionnaire and an HRQOL measure. RESULTS: Of 180 survivors, 100 were treated with chemotherapy only, 26 with chemotherapy followed by autoBMT, and 54 with chemotherapy followed by alloBMT. Median age at interview was 20 years (range 8-39). Twenty-one percent reported a severe or life-threatening chronic health condition (chemotherapy-only 16% vs. autoBMT 21% vs. alloBMT 33%; P = 0.02 for chemotherapy-only vs. alloBMT). Nearly all (95%) reported excellent, very good or good health. Reports of cancer-related pain and anxiety did not vary between groups. HRQOL scores among 136 participants ≥14 years of age were similar among groups and to the normative population, though alloBMT survivors had a lower physical mean summary score (49.1 alloBMT vs. 52.2 chemotherapy-only; P = 0.03). Multivariate analyses showed the presence of severe chronic health conditions to be a strong predictor of physical but not mental mean summary scores. CONCLUSIONS: Overall HRQOL scores were similar among treatment groups, although survivors reporting more health conditions or cancer-related pain had diminished HRQOL. Attention to chronic health conditions and management of cancer-related pain may improve QOL.

Hip abductor muscle volume in women with lateral hip pain: a case-controlled study.

UNLABELLED: Pathology of the hip abductor muscles and their associated tendons is implicated in the aetiology of lateral hip pain (LHP). Muscle atrophy is an important factor to consider in the diagnosis of this condition as it could result in reduced muscle volume and associated decreases in strength. PURPOSE: (1) To estimate the volumes of the gluteus medius (GMed), gluteus minimus (GMin) and tensor fascia lata (TFL) muscles, and (2) to examine pathological changes of the soft tissues in the vicinity of the hip joint, in women with and without LHP. METHODS: Twenty female participants (10 with LHP and 10 age-matched controls) underwent magnetic resonance imaging. Two radiologists reviewed the images for signs of pathological changes. Hip abductor muscle volumes were estimated using cross-sectional areas and Cavalieri's method. Differences in volume between sides, study groups and the three muscles were assessed. RESULTS: The volume of GMed was the largest (292.5 ± 33.3 cm3), followed by GMin (82.1 ± 12.1 cm3), then TFL (49.7 ± 18.9 cm3). No differences were evident in the volumes of the hip abductor muscles in individuals with LHP when compared to age- and sex-matched controls (GMed, p = 0.30; GMin, p = 0.40; TFL, p = 0.90). Pathology of the soft tissues was not specific to the symptomatic hips. CONCLUSIONS: Novel muscle volume data are presented for GMed, GMin and TFL in the context of LHP. Further research is needed to determine if symptom severity and duration have an impact on the extent of muscle atrophy in this population.

Changes in caveolae, caveolin, and polymerase 1 and transcript release factor (PTRF) expression in prostate cancer progression.

BACKGROUND: Caveolae are specialized invaginations in the cell membrane involved in the regulation of cell transport and signal transduction. The aims of this study were to investigate the number of caveolae and expression of caveolae-associated proteins, caveolin-1 and -2, and polymerase 1 and transcript release factor (PTRF) with development of prostate cancer. METHODS: Transmission electron microscopy was used to investigate the number of caveolae in normal human prostate stromal, epithelial cells, and androgen-dependent (LNCaP) and androgen-independent (PC3) cancer cell lines. Surgical tissue was obtained from patients with benign prostatic hyperplasia (BPH), well-differentiated and poorly differentiated prostate cancer. Caveolin-1, caveolin-2, and PTRF expression was identified by immunohistochemistry in tissue samples and quantified by Western blot analysis in cell lines. RESULTS: Caveolae were identified in normal epithelial and stromal prostate cells. The number of caveolae was significantly reduced in LNCaP and PC3 cells (P < 0.0001). PTRF was localized to stromal and epithelial cells in tissue from patients with BPH and in normal stromal and epithelial cells in vitro. PTRF expression was significantly decreased in LNCaP and PC3 cells and also in cancer tissue. In prostate tissue, caveolin-1 and -2 expression appeared to increase in prostate cancer. Caveolin-1 and -2 expression was decreased in LNCaP cells but caveolin-2 expression was significantly increased in PC3 cells compared to normal epithelial cells. CONCLUSIONS: This study demonstrates that changes in the cell membrane involving loss of caveolae and PTRF expression occur with the development of prostate cancer. These changes are accompanied by an up-regulation of caveolin-2.

Health and risk behaviors in survivors of childhood acute myeloid leukemia: a report from the Children's Oncology Group.

BACKGROUND: Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks. PROCEDURES: Participants were diagnosed with AML at <21 years of age and survived > or =5 years following diagnosis. All underwent chemotherapy alone or followed by autologous BMT (chemo +/- autoBMT) or underwent allogeneic BMT (alloBMT) if an HLA-matched related donor was available. Survivors completed a health questionnaire and a Youth Risk Behavior Survey (YRBS). RESULTS: Of eligible survivors, 117 were > or =18 years of age and completed a YRBS. Survivors were a mean age of 10 years at diagnosis and 24 years at interview. Of the substance exposures assessed by YRBS, tobacco, alcohol, and marijuana were most common. Twenty-two percent (22%) had smoked cigarettes in the last 30 days. One-quarter (25%) reported binge drinking in the last month. None of these exposures varied by treatment group. Less than 10% of survivors reported cocaine, heroin, or methamphetamine use. Men were more likely to report high substance exposure (P = 0.004). Sadness/suicidality score was associated with cancer-related anxiety (P = 0.006) and multiple health conditions (P = 0.006). CONCLUSIONS: This analysis reveals exposure to tobacco, alcohol, and marijuana in young adults with few differences based on treatment received. Survivors with cancer-related anxiety or multiple health conditions were more likely to report sadness/hopelessness.

Social outcomes in the Childhood Cancer Survivor Study cohort.

Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.

Use of continuous positive airway pressure in the acute management of laryngeal paralysis in a cat.

Continuous positive airway pressure (CPAP) has been is used widely in humans to manage obstructive sleep apnoea syndrome, but it has not been widely used in animals. A brachycephalic cat, with previously undiagnosed laryngeal paralysis, that developed acute upper respiratory tract obstruction on recovery from anaesthesia, is presented. The condition was managed by CPAP, delivered via a facial mask.

A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: a Children's Oncology Group study.

BACKGROUND: An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS: Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS: Ninety-seven patients with a median age of 11.2 years (range, 3.2-21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for >or=4 courses (range, 4-25 courses). The median number of courses received was 2 (range, 1-25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6-month progression-free survival rate (+/-standard deviation) was 14%+/-6% for HGG, 6%+/-6% for MB/PNET and 3%+/-3% for BSG. CONCLUSIONS: Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies.

Phase 2 study of temozolomide in children and adolescents with recurrent central nervous system tumors: a report from the Children's Oncology Group.

BACKGROUND: Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors. METHODS: Temozolomide was administered orally as monthly 5-day courses at doses of 200 mg/m(2)/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m(2)/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles. RESULTS: The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors. Notably, 41% of patients with low-grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity was infrequent. CONCLUSIONS: Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low-grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy.

The effects of oestrogen receptors alpha and beta on testicular cell number and steroidogenesis in mice.

Oestrogen plays an important role in testicular function. This study used mice null for oestrogen receptor alpha (ER alpha) or beta (ER beta) to investigate which receptor mediates the effects of oestrogen within the testis. Groups of ER alpha knockout mice (alpha ERKO) and ER beta knockout mice (beta ERKO) and wild-type littermates (n=5-8) were killed at 11 weeks post partum. One testis was fixed in Bouin's fluid for stereology and the other frozen for testosterone measurement. Trunk blood was collected for testosterone RIA. The optical disector combined with the fractionator methodology was used to estimate Leydig, Sertoli and germ cell numbers. At all times, the knockout animals were compared with their wild-type littermates. The physical disector quantified cells stained immunohistochemically for the apoptotic marker active caspase-3 and Hoechst staining was used to identify nuclear fragmentation. The mean Leydig cell volume was measured using the point sampled intercept method. The Leydig cell number per testis was significantly increased in beta ERKO mice but not in alpha ERKO mice. Plasma and testicular testosterone concentrations were increased in alpha ERKO mice but no changes were observed in beta ERKO mice. Hypertrophic Leydig cell changes were observed in alpha ERKO mice, and a decreased mean cell volume was seen in beta ERKO mice. No difference in Sertoli cell number per testis was observed in any of the groups. The spermatogonial cell number per testis was increased in beta ERKO mice. Immunohistochemistry identified increased numbers of active caspase-3-labelled germ cells per testis in alpha ERKO mice but not beta ERKO mice. Hoechst staining supported these findings. There was significant germ cell loss in alpha ERKO mice. This study suggests that ER beta may be involved in regulation of Leydig cell proliferation and testosterone production in the adult mouse testis.

Determinants of passive hip range of motion in adult Greyhounds.

OBJECTIVE: To determine the ranges of normal pelvic limb range of motion in adult Greyhound dogs, and to explore which factors influence hip range of motion in a population bred to meet the specific demands of racing. Design A cross-sectional study design. METHOD: Thirty-two dogs (17 male and 15 female) 13 to 81 months old were randomly selected from a local pool of 160 Greyhounds. Goniometric measurements of hip, stifle and hock range of motion were recorded in triplicate. Signalment information collected included sex, weight and age of each Greyhound. The outcome factors for the study were range of hip flexion and hip extension. The theorised exposures, age, sex, weight, racing history and hock and stifle range of motion, were modelled against the outcome variables by linear regression analysis. RESULTS: Male dogs were significantly heavier (P < 0.001) and older (P < 0.002) than female dogs. Mean hip flexion was 71.75 degrees and mean hip extension 128.10 degrees. The determinants of hip flexion were sex (P = 0.008) and range of stifle flexion (P = 0.002). Race training did not influence the range of hip flexion in the sample. Determinants of hip extension included range of stifle extension (P = 0.015), history of race training (P = 0.004) and hock flexion. The mean hip extension of raced Greyhounds was 134.95 degrees compared with 121.25 degrees for unraced Greyhounds (mean difference -13.70, 95% confidence interval -18.12, -9.29; P < 0.001). CONCLUSIONS: This study has reported isolated pelvic limb joint range of motion in the racing Greyhound. Hip range of motion was affected by stifle range of motion, sex and race training. Dogs that had received race training had greater flexibility, possibly due to training having an active stretching role on muscles, tendons and other structures limiting the hip range of motion.

Phase I trial and pharmacokinetic study of pemetrexed in children with refractory solid tumors: the Children's Oncology Group.

PURPOSE: We report results of a phase I trial and pharmacokinetic study of pemetrexed (LY231514) in children and adolescents with refractory solid tumors. Pemetrexed is a novel antifolate that inhibits multiple enzymes necessary for the biosynthesis of thymidine and purine nucleotides. The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic properties of pemetrexed in children. PATIENTS AND METHODS: Pemetrexed was administered as a 10-minute intravenous infusion every 21 days. Patients received vitamin B12 and folic acid supplementation as well as dexamethasone prophylaxis. Cohorts of three to six children were enrolled at dose levels of 400, 520, 670, 870, 1,130, 1,470, 1,910, and 2,480 mg/m2. Pharmacokinetic studies were performed during the first course of treatment. RESULTS: Thirty-three patients (31 assessable) with a median age of 12 years were enrolled. DLT occurred in one of six patients at 1,470 mg/m2 and two of four patients at 2,480 mg/m2. The MTD was 1,910 mg/m2. The primary DLTs were neutropenia and rash. No objective antitumor responses were seen. Mean plasma clearance, half-life, and steady-state volume of distribution values were 2.3 L/h/m2, 2.5 hours, and 5.4 L/m2, respectively. CONCLUSION: Pemetrexed is well-tolerated in children with refractory solid tumors at doses similar to the MTD in adults. The recommended dose for phase II studies is 1,910 mg/m2 administered every 21 days with dexamethasone, folic acid, and vitamin B12 supplementation.

Long-term morphology of a healing bone-tendon interface: a histological observation in the sheep model.

The purpose of this study was to examine and describe the sequence of events involved in long-term biological reconstruction of a tendon-bone interface following surgical reattachment. Patellar tendon re-attachment in the adult sheep was used to investigate and describe the biological components involved in healing and repair of a tendon enthesis. Light microscopy was used to describe the healing morphology at time intervals of 8, 12, 26, 52 and 104 weeks. By 8 weeks a collagen continuum was observed between the tendon and bone. Over time this fibrous bridge became anchored into the original tissues (tendon and bone), with the resultant enthesis resembling more a fibrous rather than the original fibrocartilagenous enthesis. The associated collagen fibrils between the two tissues gradually changed in morphology over time to reflect the fibres seen in the original tendon tissue. The fibrous tissue of the forming enthesis remained hypercellular when compared with the controls. The resultant long-term morphology may be a reflection of functional adaptation rather than anatomical replication.

Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors who retain ovarian function after completing cancer treatment are at increased risk of developing premature menopause, defined as cessation of menses before age 40 years. However, published data pertaining to the risk and frequency of premature menopause are limited. METHODS: We assessed the incidence of and risk factors for premature menopause in 2819 survivors of childhood cancer who were older than 18 years and were participants in the multicenter Childhood Cancer Survivor Study (CCSS). The comparison group was 1065 female siblings of participants in the CCSS. A multiple Poisson regression model was constructed to determine risk factors for nonsurgical premature menopause. All statistical tests were two-sided. RESULTS: A total of 126 childhood cancer survivors and 33 control siblings developed premature menopause. Of these women, 61 survivors (48%) and 31 siblings (94%) had surgically induced menopause (rate ratio [RR] = 0.8, 95% confidence interval [CI] = 0.52 to 1.23). However, the cumulative incidence of nonsurgical premature menopause was higher for survivors than for siblings (8% versus 0.8%; RR = 13.21, 95% CI = 3.26 to 53.51; P<.001). A multiple Poisson regression model showed that risk factors for nonsurgical premature menopause included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score (based on number of alkylating agents and cumulative dose), and a diagnosis of Hodgkin lymphoma. For survivors who were treated with alkylating agents plus abdominopelvic radiation, the cumulative incidence of nonsurgical premature menopause approached 30%. CONCLUSIONS: The results of this study will facilitate counseling current survivors about their future risk of premature menopause and aid in designing new regimens that seek to diminish late ovarian toxicity.

Pain, sleep disturbance, and fatigue in children with leukemia and their parents: a pilot study.

PURPOSE/OBJECTIVES: To determine the feasibility of collecting symptom data at home from school-age children with acute lymphoblastic leukemia (ALL) and from their fathers and mothers and to obtain initial descriptions of pain, sleep disturbance, and fatigue experienced by the family members at home. DESIGN: Prospective and descriptive. SETTING: Children's homes in Oregon and southwestern Washington. SAMPLE: 9 children with ALL (aged 8-16 years), 6 fathers, and 7 mothers. The children received vincristine during the maintenance phase of their outpatient chemotherapy treatments. METHODS: With age-appropriate, paper-and-pencil diaries and wrist actigraphy, data were collected for three days in the families' homes. Families were reminded by telephone to complete their sleep and activity diaries. MAIN RESEARCH VARIABLES: Pain, sleep disturbance, and fatigue in school-age children and their fathers and mothers. FINDINGS: Most of the families who were approached indicated willingness to participate in the study. After receiving outpatient chemotherapy, the children reported pain, sleep disturbance, and fatigue data over three days. Fathers and mothers also reported symptoms. Actigraphy showed children waking more often during the night than mothers or fathers. CONCLUSIONS: Children's pain, sleep disturbance, and fatigue suggest that the symptoms are influencing families' quality of life. Larger studies are needed to examine the symptom patterns and health outcomes of children, fathers, and mothers over the course of chemotherapy. IMPLICATIONS FOR NURSING: Improving sleep and managing pain and fatigue after chemotherapy treatment for children with ALL may improve health outcomes for children and parents.

Toxicity profile of delayed high dose sodium thiosulfate in children treated with carboplatin in conjunction with blood-brain-barrier disruption.

PURPOSE: To assess the safety of delayed high dose intravenous (i.v.) sodium thiosulfate (STS) in a case series of 12 children with malignant brain tumors who were treated with intraarterial (i.a.) carboplatin in conjunction with blood-brain-barrier disruption (BBBD). METHODS: Twelve children ages 17 months-12 years underwent a total of 132 BBBD chemotherapy treatments and also received delayed high dose STS (i.v.). Dose 1 of STS (10-16 g/m(2)) was administered 2 or 4 hr after carboplatin, and a second STS dose was administered 4 hr after dose 1 if the child had impaired baseline hearing. Toxicity data were graded in accordance with the National Cancer Institute Common Toxicity Criteria (Version 2). Audiologic monitoring to evaluate the otoprotective potential of STS was performed on 11 children. Ototoxicity was defined in accordance with the American Speech-Language-Hearing Association (ASHA) criteria. Baseline and end of treatment hearing status were graded using Brock's criteria. RESULTS: Nausea and vomiting were well controlled with anti-emetics administered approximately 30 min prior to STS infusion. Analogous to results in adult patients, there was mild transient hypernatremia and a trend for improved protection from ototoxicity in children who received STS delayed to 4 hr post-treatment versus 2 hr. Tumor responses were seen in heavily pre-treated patients with relatively chemo-resistant tumors, suggesting that STS did not protect the tumor from platinum cytotoxicity. CONCLUSION: High dose STS is well tolerated in children under 12 years of age. Further studies of STS in children are warranted to assess otoprotection and the impact of STS on platinum mediated efficacy.

Sustained engraftment post bone marrow transplant despite anti-platelet antibodies in Glanzmann thrombasthenia.

BACKGROUND: Patients with Glanzmann thrombasthenia (GT) have normal platelet counts but abnormal platelet aggregation and carry the risk of life-threatening bleeding. We report three patients who received bone marrow transplantation (BMT) for type I GT and discuss the risk and management of anti-platelet antibodies. PATIENTS AND RESULTS: Diagnosis of GT was made through abnormal platelet aggregation studies or the absence of GPIIb/IIIa by flow cytometry. All patients had severe bleeding requiring multiple red blood cell transfusions. One patient received an unrelated donor transplant and two received matched sibling donor transplants following conditioning therapy with busulfan, cyclophosphamide, and fludarabine. Two patients developed an anti-platelet antibody, treated in one with intravenous immune globulin (IVIG). Engraftment of white blood cells and platelets was achieved on day +13 to +14 and +17 to +25, respectively. Complete donor chimerism and GPIIb/IIIa+ platelets are sustained at +22 to +30 months post transplant. CONCLUSIONS: In summary, patients with GT and history of severe hemorrhage can be cured with BMT, but the presence of anti-platelet antibodies should be sought and platelet transfusions minimized prior to transplant. IVIG may be helpful in cases of refractory immune thrombocytopenia related to anti-platelet antibodies. Improvement in transplant-related complications with current transplant regimens allows consideration of BMT for life-threatening non-malignant disorders such as GT.