Osteonecrosis in paediatric patients with acute lymphoblastic leukaemia treated on Co-ALL-07-03 trial: a single centre analysis.

BACKGROUND: Osteonecroses (ON) are a serious problem after anti-leukaemic treatment in childhood and critically depend on treatment intensity. We analysed ON incidence, risk factors and outcome in patients (pts) from our institution treated according to the CoALL 07-03 trial. METHODS: Between 01.09.2003 and 31.12.2009, 124 children aged 1-18 years were treated, 22 pts with ON (ARCO I-IV) were assessed by retrospective chart review. Follow-up data were collected as of March 2013. RESULTS: 5-year cumulative incidence of ON grade I-IV was 25%. Median age at ALL diagnosis with vs. without ON was 11 years vs. 4.4 years. In logistic multivariate regression analysis, age was the only independent risk factor for ON (p<0.01). 90.9% of the pts with ON presented with ≥2 bilaterally affected joints, most frequent the weight-bearing joints (95.5%). 77.2% developed ON ≥°III acc. to ARCO. 36.4% underwent core decompression, one patient bilateral total hip arthroplasty. As of March 2013, 12 pts still presented with ON-induced symptoms. DISCUSSION: Our data suggest an overall high incidence of ON in pts treated according to trial CoALL 07-03. Cumulative steroid dose in trial CoALL 07-03 was small, thus, the high CI might be triggered by other treatment-related and study population based risk factors. CONCLUSION: ON are a serious problem concerning long-term sequelae with major impact on activities of daily living. Further prospective evaluation is urgently needed to develop risk-adapted diagnostic strategies and preventive and interventional approaches for high-risk pts.

Longitudinal patterns of psychological distress in adult survivors of childhood cancer.

BACKGROUND: This study investigated longitudinal patterns of psychological distress in adult survivors of childhood cancer. METHODS: Participants included 4569 adult survivors in the Childhood Cancer Survivor Study Cohort (CCSS) who completed the Brief Symptom Inventory-18 on three occasions between 1994 and 2010. Longitudinal latent class analysis was used to identify discrete classes of psychological distress. Predictors of class membership were examined through logistic regression modelling with odds ratios (ORs) and 95% confidence intervals (CIs) reported. RESULTS: Survivors were a median of 39 years of age and 30 years from diagnosis at the most recent follow-up. Most survivors reported few or no symptoms of distress over time, although subsets of survivors reported persistently elevated (depression: 8.9%; anxiety: 4.8%; somatisation: 7.2%) or significant increases in distress symptoms over the follow-up period (depression: 10.2%; anxiety: 11.8%; somatisation: 13.0%). Increasing distress symptoms were predicted by survivor perception of worsening physical health over time (depression: OR=3.3; 95% CI=2.4-4.5; anxiety: OR=3.0; 95% CI=2.2-4.0; somatisation: OR=5.3; 95% CI=3.9-7.4). Persistent distress symptoms were also predicted by survivor perception of worsening physical health over time, as well as by worsening pain and ending analgesic use. CONCLUSION: Subgroups of adult survivors are at-risk for chronic distress or significant increases in distress decades following their original cancer diagnosis. Routine screening of psychological distress in adult survivors of childhood cancer is warranted, especially for survivors who experience physical health morbidities.

Effect of regular sauna on epidermal barrier function and stratum corneum water-holding capacity in vivo in humans: a controlled study.

During the last few years, sauna has become the epitome of wellness. Besides studies in general medicine evaluating the health benefit of sauna, e.g. on the cardiovascular system, no systematic study regarding skin physiology has been published. The present exploratory study was intended to analyse the effect of regular Finnish sauna on skin physiology. The effect of regular sauna bathing was assessed with non-invasive instruments: stratum corneum water-holding capacity, skin redness, transepidermal water loss and surface skin pH were analysed in 41 healthy volunteers, aged 20-49 years, in a group with regular sauna exposure compared to a control group with no regular sauna exposure. A more stable epidermal barrier function, an increase in stratum corneum hydration, a faster recovery of both elevated water loss and skin pH after exposure to 2 x 15 min sauna at 80 degrees C could be demonstrated in volunteers with regular sauna. Heart beat rate and ionic concentration in sweat as well as epidermal blood perfusion showed a training effect under regular sauna. A decrease in casual skin sebum content on the skin surface of the forehead was observed in these volunteers. The present data suggest a protective effect of regular sauna on skin physiology, especially surface pH and stratum corneum water-holding capacity.

The Impact of Persistent Leukoencephalopathy on Brain White Matter Microstructure in Long-Term Survivors of Acute Lymphoblastic Leukemia Treated with Chemotherapy Only.

BACKGROUND AND PURPOSE: Survivors of acute lymphoblastic leukemia are at risk for neurocognitive deficits and leukoencephalopathy. We performed a longitudinal assessment of leukoencephalopathy and its associations with long-term brain microstructural white matter integrity and neurocognitive outcomes in survivors of childhood acute lymphoblastic leukemia treated on a modern chemotherapy-only protocol. MATERIALS AND METHODS: One hundred seventy-three survivors of acute lymphoblastic leukemia (49% female), treated on a chemotherapy-only protocol, underwent brain MR imaging during active therapy and repeat imaging and neurocognitive testing at follow-up (median, 13.5 years of age; interquartile range, 10.7-17.6 years; median time since diagnosis, 7.5 years; interquartile range, 6.3-9.1 years). Persistence of leukoencephalopathy was examined in relation to demographic and treatment data and to brain DTI in major fiber tracts and neurocognitive testing at follow-up. RESULTS: Leukoencephalopathy was found in 52 of 173 long-term survivors (30.0%) and persisted in 41 of 52 (78.8%) who developed it during therapy. DTI parameters were associated with leukoencephalopathy in multiple brain regions, including the corona radiata (fractional anisotropy, P = .001; mean diffusivity, P < .001), superior longitudinal fasciculi (fractional anisotropy, P = .02; mean diffusivity, P < .001), and superior fronto-occipital fasciculi (fractional anisotropy, P = .006; mean diffusivity, P < .001). Mean diffusivity was associated with neurocognitive impairment including in the genu of the corpus callosum (P = .04), corona radiata (P = .02), and superior fronto-occipital fasciculi (P = .02). CONCLUSIONS: Leukoencephalopathy during active therapy and neurocognitive impairment at long-term follow-up are associated with microstructural white matter integrity. DTI may be more sensitive than standard MR imaging for detection of clinically consequential white matter abnormalities in childhood acute lymphoblastic leukemia survivors treated with chemotherapy and in children undergoing treatment.

Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study.

PURPOSE: This study compared measured physical performance, health-related quality of life (HRQOL), and social role attainment between extremity sarcoma survivors and controls, and evaluated associations between disease and treatment exposures, health conditions, and performance measures. METHODS: Survivors of extremity sarcoma from the St. Jude Lifetime cohort and controls frequency matched by age-, sex-, and race completed physical performance testing and questionnaires. Survivors with Z-scores on outcome measures ≤ -2.0 SD (compared to controls) were categorized with severe impairment/limitation. RESULTS: Among 206 survivors (52.4 % male median age 36 years (range 19-65)), 37 % had low relative lean mass, 9.7 % had an ejection fraction <50 %, 51.5 % had diffusion capacity for carbon monoxide <75 %, 27.7 % had sensory and 25.2 % motor neuropathy, and 78.2 % had musculoskeletal complications. Severe impairments/limitations were present among ≥25 % of survivors on fitness, balance, and physical HRQOL measures, and among ≥15 % on strength and activity of daily living measures. Lower extremity tumor location (OR 8.23, 95 % CI 2.54-26.67, P value 0.0004) and amputation (OR 8.07, 95 % CI 3.06-21.27, P value <0.0001) were associated with poor fitness. Poor fitness was associated with increased odds of scoring <40 on the SF-36 physical component summary (OR 4.83, 95 % CI 1.95-11.99, P value 0.001) and role-physical subscale (OR 3.34, 95 % CI 1.33-8.43, P value 0.01). Survivors and controls had similar rates of marriage, independent living, employment, and college attendance. CONCLUSIONS: Extremity sarcoma survivors experience high rates of physical impairment and report lower than expected physical HRQOL. However, they are as likely as peers to be married, live independently, be employed, and attend college. IMPLICATIONS FOR CANCER SURVIVORS: Follow-up for extremity sarcoma survivors should include assessment of need for further orthopedic care and rehabilitation to address cardiopulmonary and musculoskeletal health.

Simple reaction time event-related potentials: effects of alcohol and diazepam.

Acute effects of alcohol and diazepam on reaction time (RT) and event-related potential (ERP) measures were examined in 108 healthy male volunteers. The subjects engaged in a simple RT task at two levels of stimulus intensity during baseline and treatment sessions. Lower stimulus intensity produced increased RT's, increased ERP peak latencies, and suppression of peak amplitudes. Moderate and high doses of alcohol, and high doses of diazepam produced increased RT's. Alcohol suppressed P100 and N100 amplitudes, while diazepam suppressed P100 amplitudes only. P100 amplitudes were correlated to RT's under baseline and treatment conditions. These results were taken as evidence for impaired stimulus detection during alcohol and diazepam intoxication, with both drugs influencing sensory-perceptual processes and alcohol alone influencing the degree of attentiveness.

The influence of alcohol and sleep deprivation on stimulus evaluation.

The effects of alcohol and sleep deprivation on choice reaction time (RT) as a function of stimulus intensity, stimulus quality, and response compatibility were investigated. Fifty-four male subjects were assigned to one of three levels of alcohol (0.00, 0.07, or 0.10 BAC), and one of two levels of sleep deprivation (0 or 24 h). Stimulus intensity, stimulus quality, and response compatibility were varied (high or low), with RTs identified according to time on task. Significant main effects of each of the stimulus variables were present in baseline analysis, with low-level conditions producing longer RTs. Alcohol produced an overall slowing of RT. The combination of both treatments led to larger increases in RT for low stimulus quality. Sleep deprivation increased RT for high stimulus intensity. Alcohol increased RT for low stimulus intensity, but only when subjects were not sleep deprived. These results imply higher risk with degraded stimulus conditions, e.g., driving in settings of low visibility or at night.

[Therapy motivation of young prisoners]. / Therapiemotivation junger Strafgefangener.

OBJECTIVES: Therapy adherence was examined within a sample of 145 imprisoned male juveniles with regard to factors of influence, structure and predictability. METHODS: Predictors included biographic data, expectations with regard to therapy, personality traits (measured with the FPI-R) and psychological impairment (investigated by means of the Symptom Checklist). Therapy adherence as a criterion can be divided into the following dimensions: affliction, dissatisfaction, requests for change and help, and expectations of success. RESULTS: Within the sample a clear impairment of biographical and psychological data, as well as of personality traits was found. Values were average for expectations regarding therapy and therapy adherence, while two thirds of the sample were willing to undergo treatment during imprisonment. CONCLUSIONS: Therapy adherence proved to be a one-dimensional construct, best predicted by emotional instability, followed by the symptom score, expectations regarding therapy and inhibition. Dividing the entire sample into subgroups, significant differences were found mainly for psychological test data and less so for the construct of therapy adherence.

Cognitive outcomes following contemporary treatment without cranial irradiation for childhood acute lymphoblastic leukemia.

BACKGROUND: Treatment of acute lymphoblastic leukemia (ALL) has included the use of prophylactic cranial irradiation in up to 20% of children with high-risk disease despite known cognitive risks of this treatment modality. METHODS: Patients enrolled on the St Jude ALL Total Therapy Study XV, which omitted prophylactic cranial irradiation in all patients, were assessed 120 weeks after completion of consolidation therapy (n = 243) using a comprehensive cognitive battery. χ(2) analysis was used to compare the percentage of below-average performers among the entire ALL patient group to the expected rate based on the normative sample. Univariate logistic regression was used to estimate the effect of intensity of chemotherapy (treatment arm), age at diagnosis, and sex on the probability of below-average performance. All statistical tests were two-sided. RESULTS: Overall, the ALL group had a statistically significantly higher risk for below-average performance on a measure of sustained attention (67.31% more than 1 SD below the normative mean for omission errors, P < .001) but not on measures of intellectual functioning, academic skills, or memory. Patients given higher intensity chemotherapy were at greater risk for below-average performance compared with those given lower intensity therapy on measures of processing speed (27.14% vs 6.25%, P = .009) and academic abilities (Math Reasoning: 18.60% vs 3.90%, P = .008; Word Reading: 20.00% vs 2.60%, P = .007; Spelling: 27.91% vs 3.90%, P = .001) and had higher parent-reported hyperactivity (23.00% vs 9.84%, P = .018) and learning problems (35.00% vs 16.39%, P = .005). Neither age at diagnosis nor sex was associated with risk for below-average cognitive performance. CONCLUSIONS: Omitting cranial irradiation may help preserve global cognitive abilities, but treatment with chemotherapy alone is not without risks. Caregiver education and development of interventions should address both early attention deficits and cognitive late effects.

Control of beef heart submitochondrial particle-catalyzed Pi goes to and comes from ATP exchange by nucleotides and the ATPase inhibitor protein.

F1I, the specific ATPase inhibitor protein, and the chromium(III) analogs of ATP and ADP, CrATP and CrADP, were used to study the inhibition of Pi goes to and comes from ATP exchange reaction catalyzed by beef heart submitochondrial particles. F1I was found to be an uncompetitive inhibitor of the exchange reaction. CrATP and CrADP, both competitive inhibitors of ATP hydrolysis in isolated F1 (Schuster, S. M., Ebel, R. E., and Lardy, H. A. (1975) ARch. Biochem. Biophys. 171, 656-661) were shown to be competitive and noncompetitive inhibitors of Pi goes to and comes from ATP exchange, respectively. Dual inhibitor studies were done using combinations of F1I and the chromium nucleotides, or the nucleotide analogs in combination. All cases show sets of intersecting Dixon plots indicative of interacting inhibitors. Upward curvature is also evident on some of the plots. This phenomenon was explained using the concept of multiple synergistic binding of the inhibitors. Binding mechanisms and their relevant kinetic equations were postulated to explain the results of the dual inhibitor studies. They support the notion that in addition to the catalytic site, there are two types of regulatory binding sites on F1, one specific for nucleotides and one specific for F1I. When one of these sites is occupied, other sites are either opened or other inhibitors become more potent.

A comparison of indices of premorbid intelligence in clinical populations.

Estimation of premorbid intelligence using the regression formula developed by Barona et al. (1984) was compared with prorated IQ's based on the higher of the Vocabulary or Picture Completion subtests from the WAIS-R. Actual and predicted premorbid IQ's of 50 brain-damaged patients were compared to those of 35 non-brain-damaged patient controls equated on age and education. For both groups, the Barona et al. (1984) formula produced mean IQ's close to 100, though greatly restricted the range. The prorated IQ's tended to be over-estimated in the patient control group, but not the brain-damaged group. Compared with the regression based formula, the distribution of these prorated IQ's was more consistent with the WAIS-R standardization sample.

Interpretive significance of variability of performance on neuropsychological tests.

The interpretive significance of variability of performance on neuropsychological measures was investigated in groups of brain-damaged and non-brain-damaged subjects. The 39 brain-damaged subjects were matched on Full Scale IQ and age with 39 non-brain-damages subjects. The two groups failed to differ on a measure of level of performance, but did differ on variability of performance. The results were interpreted as providing support for the clinical utility of measures of variability of performance and indicating the need for additional investigation of such measures.

Simple reaction time event-related potentials: effects of alcohol and sleep deprivation.

The effects of two levels of alcohol intoxication and 30 hr of sleep deprivation on visual event-related potential (ERP) waveforms concomitant to simple reaction time (RT) were examined in 54 normal male subjects. In a previous study, we reported that alcohol and sleep deprivation each increased RT. At a 0.05 breath alcohol concentration (BAC), the combined treatments produced an additive increase in RT, whereas at a 0.08 BAC the combined treatments produced no increase beyond that seen with each alone. In this study we present the ERP findings. Sleep deprivation alone increased the latency of a 150 msec negative component (N1) of the ERP. Alcohol increased the latency of a 250 msec negative component (N2), but only in the absence of sleep deprivation. Furthermore, this increased latency of N2 was correlated with RT measures. These results suggested that sleep deprivation slowed initial stimulus detection, whereas alcohol slowed later processing and response activation.

The treatment of mentally disordered offenders: a national survey of psychiatrists.

A nationwide (U.S.) survey of major public mental hospitals treating patients who are incompetent for trial, not guilty by reason of insanity, mentally disordered sex offenders, or mentally ill inmates was conducted. Responses were received from 71 percent of the 115 facilities surveyed. Respondents were the directors of psychiatry from the respective facilities. The pattern of treatments delivered generally appeared clinically appropriate. However, behavioral and cognitive-behavioral treatments were reported infrequently, even in areas in which they would be particularly useful.

Further validation of constructs from the selective reminding test.

The Selective Reminding Test (SRT) partitions recall into three classes. Short-Term Recall (STR), Random Long-Term Recall (RLTR), and Consistent Long-Term Recall (CLTR). Examination of conditional probabilities of delayed recall or recognition of individual words as a function of their memory status at the end of a standard 12-word, 12-trial test showed that Buschke's (1973) operational definitions of STR, RLTR, and CLTR have excellent predictive validity.