A placebo-controlled trial of a proprietary lipid-lowering nutraceutical supplement in the management of dyslipidemia.

There is an ever growing emergence in the popularity of patient-driven care. As this health and wellness model grows, inquiries into diet, lifestyle, and supplemental approaches will continue to become a focal point for the healthcare consumer. Because of this, the aim of this study is to determine the tolerability, and overall effectiveness of a proprietary multi-ingredient lipid-lowering supplement in subjects with dyslipidemia. Forty participants were recruited for a single-center, double-blind randomized, placebocontrolled trial. Study participants were recruited between December 2014 and March 2015. Initial screening included a physical examination, renal and hepatic function, serum lipid, serum electrolytes, complete blood counts, and urine analysis. The 40 participants were randomly assigned to receive either the proprietary multi-ingredient lipid-lowering supplement (PMILLS) n= 20 or placebo n= 20. The trial consisted of a screening visit, a two-week run-in, and a four-month treatment period. Samples were taken at baseline, one month and four months of treatment. Results from the trial showed that the PMILLS significantly reduced total cholesterol (TC), low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C), oxidized LDL (oxLDL), Apo-lipoprotein B, triglycerides (TG), LDL particle number (LDL-P), heart rate, and diastolic blood pressure compared to placebo at one month and four months. The PMILLS significantly increased high density lipoprotein (HDL) particle number (HDL-P), and low density lipoprotein (LDL) particle size from dense type III and IV to larger type I and II LDL particle, compared to placebo at one month and four months. In addition, the PMILLS significantly reduced high sensitivity C-reactive protein (hs-CRP), tumor necrosis alpha (TNF-α), and interleukin 6 (IL-6) within the treatment group from baseline. There were no adverse effects noted in the treatment group after four months of supplementation. The present study demonstrates this PMILLS improves all relevant lipid parameters, such as particle numbers and particles sizes, as well as showing a significant reduction in inflammatory markers linked to cardiovascular health. With such combined changes in lipids, lipid sub-fractions, and inflammation, which are considered among the most effective means of reducing coronary heart disease (CHD), this PMILLS represents a new addition to safe and effective lipid-modifying strategies.

Allergic sensitization is enhanced in early life through toll-like receptor 7 activation.

BACKGROUND: Prospective cohort studies suggest that children hospitalized in early life with severe infections are significantly more likely to develop recurrent wheezing and asthma. OBJECTIVE: Using an inhalational mouse model of allergic airways inflammation, we sought to determine the effect of viral and bacterial-associated molecular patterns on the magnitude of the allergic inflammatory response and whether this effect was age dependent. METHODS: BALB/c mice were sensitized by intranasal administration of endotoxin(low) ovalbumin (OVA) in the absence or presence of viral single-stranded (ss)RNA, lipoteichoic acid or flagellin as neonates (within the first 24 h of life) or as weanlings (4 weeks of age). Mice were challenged four times with OVA at 6 weeks of age and end-points (bronchoalveolar lavage cytology, histology, antigen-specific T and B cell responses) determined at 7 weeks of age. RESULTS: Inhalational sensitization (<24 h or 4 weeks of age) and challenge with OVA induced a mild allergic inflammatory response in the airways as indicated by increased numbers of eosinophils and mucus cells, elevated serum OVA-specific IgG1, and production of T helper 2 (Th2) cytokines. Mice sensitized to endotoxin(low) OVA at birth in the presence of ssRNA or lipoteichoic acid, but not flagellin, showed an increase in the numbers of airway and tissue eosinophils, mucus producing cells and antigen-specific production of IL-13 as compared with mice exposed only to endotoxin(low) OVA. By contrast, all three TLR ligands failed to increase the magnitude of OVA-induced allergic inflammation in mice sensitized as weanlings. CONCLUSIONS: Recognition of distinct microbial-associated patterns in early life may preferentially promote the de novo differentiation of bystander, antigen-specific CD4(+) T cells toward a Th2 phenotype, and promote an asthma-like phenotype upon cognate antigen exposure in later life.

Early production of thymic stromal lymphopoietin precedes infiltration of dendritic cells expressing its receptor in allergen-induced late phase cutaneous responses in atopic subjects.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is an interleukin (IL)-7-like cytokine that triggers dendritic cell-mediated T helper (Th)2 inflammatory responses through a receptor consisting of a heterodimer of the IL-7 receptor alpha (IL-7Ralpha) chain and the TSLP receptor (TSLPR), which resembles the cytokine receptor common gamma chain. Dendritic cells activated by TSLP prime development of CD4(+) T cells into Th2 cells contributing to the pathogenesis of allergic inflammation. We hypothesized that allergen exposure induces expression of TSLP and results in recruitment of TSLPR bearing cells in the cutaneous allergen-induced late-phase reaction (LPR) in atopic subjects. METHODS: Skin biopsies were obtained from atopic subjects (n = 9) at various times after cutaneous allergen challenge. In situ hybridization and immunohistochemistry were used to determine TSLP mRNA expression and to measure infiltration of TSLPR(+) DC in skin LPR. RT-PCR and flow cytometry were employed to analyse TSLPR expression on isolated blood DC. RESULTS: Allergen-induced skin TSLP expression occurred as early as 1 h after allergen challenge, whereas TSLPR(+) and CD11c(+) cells infiltrated relatively late (24-48 h). The majority of TSLPR(+) cells were DC co-expressing blood DC antigen-1 (BDCA-1) or BDCA-2. Freshly isolated blood DC expressed both TSLPR and IL-7Ralpha chains. Maturation and stimulation with TSLP or polyriboinosinic-polyribocytidylic acid in vitro upregulated the expression of both TSLPR and IL-7Ralpha chains in DC but not in chemoattractant receptor-homologous molecule expressed on Th2 cells(+) CD4(+) T cells. CONCLUSION: The data suggest that TSLP plays a role in augmenting, through DC recruitment and activation, the development of Th2-type T cells in allergic inflammation.

Holocene El Niño-Southern Oscillation variability reflected in subtropical Australian precipitation.

The La Niña and El Niño phases of the El Niño-Southern Oscillation (ENSO) have major impacts on regional rainfall patterns around the globe, with substantial environmental, societal and economic implications. Long-term perspectives on ENSO behaviour, under changing background conditions, are essential to anticipating how ENSO phases may respond under future climate scenarios. Here, we derive a 7700-year, quantitative precipitation record using carbon isotope ratios from a single species of leaf preserved in lake sediments from subtropical eastern Australia. We find a generally wet (more La Niña-like) mid-Holocene that shifted towards drier and more variable climates after 3200 cal. yr BP, primarily driven by increasing frequency and strength of the El Niño phase. Climate model simulations implicate a progressive orbitally-driven weakening of the Pacific Walker Circulation as contributing to this change. At centennial scales, high rainfall characterised the Little Ice Age (~1450-1850 CE) in subtropical eastern Australia, contrasting with oceanic proxies that suggest El Niño-like conditions prevail during this period. Our data provide a new western Pacific perspective on Holocene ENSO variability and highlight the need to address ENSO reconstruction with a geographically diverse network of sites to characterise how both ENSO, and its impacts, vary in a changing climate.

Poverty and the extent of child obesity in Canada, Norway and the United States.

The goal of this paper is to compare the extent of child obesity in Canada, Norway and the United States. As child poverty is an important correlate of child obesity, we wish to examine the potential role of international differences in child poverty in explaining international differences in the extent of child obesity. We use three representative microdata surveys containing parental reports of child height and weight collected in the mid-1990s in Canada, Norway and the US. We calculate both the prevalence and proportional severity of child obesity for 6-11-year-old children in each country, and represent the 'extent' of obesity diagrammatically. Differences in patterns of child poverty are similarly depicted. Obesity extent is also compared for poor and non-poor children in Canada and the US. Finally, child obesity in the three countries is compared using only non-poor children where we find that the extent of child obesity is much lower in Norway than in Canada or the US. The pattern apparent for obesity is remarkably similar to that found for child poverty. In Canada and especially in the US, we find a much greater extent of obesity for poor than non-poor children. However, when we compare only non-poor children in the three countries, although the magnitude of difference is smaller, it remains clear that Norwegian children are much less likely to be obese. Policy and research directed towards reducing the extent of child obesity in both Canada and the US should pay particular attention to issues of child poverty.

Short term urinary catheter policies following urogenital surgery in adults.

BACKGROUND: Urinary catheterisation (by the urethral or suprapubic routes) is common following urogenital surgery. There is no consensus on how to minimize complications and practice varies. OBJECTIVES: To establish the optimal way to manage urinary catheters following urogenital surgery in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised trials register (searched 30 May 2005) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised trials were identified. Studies were excluded if they were not randomised or quasi-randomised trials of adults being catheterised following urogenital surgery. DATA COLLECTION AND ANALYSIS: Data collection was performed independently by two of the review authors and cross-checked. Where data might have been collected but not reported, clarification was sought from the trialists. MAIN RESULTS: Thirty nine randomised trials were identified for inclusion in the review. They were generally small and of poor or moderate quality reporting data on only few outcomes. Confidence intervals were all wide. USING A URINARY CATHETER VERSUS NOT USING ONE: The data from five trials were heterogeneous but tended to indicate a higher risk of (re)catheterisation if a catheter was not used postoperatively. The data gave only an imprecise estimate of any difference in urinary tract infection. URETHRAL CATHETERISATION VERSUS SUPRAPUBIC CATHETERISATION: In six trials, a greater number of people needed to be recatheterised if a urethral catheter rather than a suprapubic one was used following surgery (RR 3.66, 95% CI 1.41 to 9.49). SHORTER POSTOPERATIVE DURATION OF CATHETER USE VERSUS LONGER DURATION: In 11 trials, the seven trials with data suggested fewer urinary tract infections when a catheter was removed earlier (for example 1 versus 3 days, RR 0.50, 95% CI 0.29 to 0.87) with no pattern in respect of catheterisation. CLAMP AND RELEASE POLICIES BEFORE CATHETER REMOVAL VERSUS IMMEDIATE CATHETER REMOVAL: In a single small trial, the clamp-and-release group showed a significantly greater incidence of urinary tract infections (RR 4.00, 95% 1.55 to 10.29) and a delay in return to normal voiding (RR 2.50, 95% CI 1.16 to 5.39). AUTHORS' CONCLUSIONS: Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

In-vitro dynamic micro-probing and the mechanical properties of human prostate tissues.

In vitro macro- and micro-indentation test systems have been designed to measure the dynamic micro-mechanical properties of human prostate tissues at actuation frequencies between 5 Hz and 30 Hz, and 0.5 Hz and 20 Hz, respectively. The development of in vitro test systems was aimed at assessing the capacity of such an in vivo medical probe to provide information useful for the diagnosis of various prostate diseases. The macro-indentation test system is an established one, which we have used to determine structure-property relationships in human and canine prostate tissues and here we use it to validate a newly-developed micro-indentation test system using a tissue phantom. Mechanical testing was also carried out on sections of prostate tissue harvested from cystectomy and radical prostatectomy, diagnosed with bladder cancer and benign prostatic hyperplasia. Dynamic probing under displacement control was carried at pre-strains between 5% and 8% for macro-probing and at 5% pre-strain for micro-probing, and the general effect of pre-strain on the dynamic mechanical properties (described by the amplitude ratio between stress and strain, and the phase lag between strain and stress) of phantom and prostate tissues is presented. Specific point probing on epithelial and stromal histological components was also carried out showing a significant difference between the amplitude ratios of epithelial and stromal components for actuation frequencies exceeding 5 Hz. However, no significant difference was found between phase lags for epithelial and stromal tissues.

Cognitive and academic functioning in survivors of pediatric bone marrow transplantation.

PURPOSE: To evaluate cognitive and academic functioning in survivors of pediatric bone marrow transplants (BMTs) at 1 and 3 years after a BMT. PATIENTS AND METHODS: In a prospective, longitudinal design, patients underwent a comprehensive battery of neurocognitive measures before admission for transplantation and at 1, 3, and 5 years after a BMT. This article describes a cohort of 102 survivors with follow-up data available for 1 year after a BMT, including 54 survivors with follow-up available for 3 years. This represents the largest cohort of pediatric BMT survivors yet reported in a prospective study. RESULTS: In the cohort as a whole, there were no significant changes on global measures of intelligence (intelligence quotient [IQ]) and academic achievement at either 1 or 3 years after a BMT, despite adequate power to detect an IQ change of three points or greater. Likewise, performance on specific tests of neuropsychologic function remained stable. No significant differences were observed between patients whose conditioning regimen included total-body irradiation (TBI) and those whose did not. The primary predictor of neurocognitive outcome was patient age, with younger patients more likely to show declines over time. The subset of patients who were less than 3 years of age at the time of transplantation seemed to be particularly vulnerable to cognitive sequelae. CONCLUSION: The use of BMTs with or without TBI entails minimal risk of late neurocognitive sequelae in patients who are 6 years of age or older at the time of transplantation. However, patients who are less than 6 years of age at the time of transplantation, and particularly those less than 3 years of age, seem to be at some risk of cognitive declines.

Late effects of treatment in survivors of childhood acute myeloid leukemia.

PURPOSE: To investigate the incidence of and risk factors for late sequelae of treatment in patients who survived for more than 10 years after the diagnosis of childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: Of 77 survivors (median follow-up duration, 16. 7 years), 44 (group A) had received chemotherapy, 18 (group B) had received chemotherapy and cranial irradiation, and 15 (group C) had received chemotherapy, total-body irradiation, and allogeneic bone marrow transplantation. Late complications, tobacco use, and health insurance status were assessed. RESULTS: Growth abnormalities were found in 51% of survivors, neurocognitive abnormalities in 30%, transfusion-acquired hepatitis in 28%, endocrine abnormalities in 16%, cataracts in 12%, and cardiac abnormalities in 8%. Younger age at the time of diagnosis or initiation of radiation therapy, higher dose of radiation, and treatment in groups B and C were risk factors for the development of academic difficulties and greater decrease in height Z: score. In addition, treatment in group C was a risk factor for a greater decrease in weight Z: score and the development of growth-hormone deficiency, hypothyroidism, hypogonadism, infertility, and cataracts. The estimated cumulative risk of a second malignancy at 20 years after diagnosis was 1.8% (95% confidence interval, 0.3% to 11.8%). Twenty-two patients (29%) were smokers, and 11 (14%) had no medical insurance at the time of last follow-up. CONCLUSION: Late sequelae are common in long-term survivors of childhood AML. Our findings should be useful in defining areas for surveillance of and intervention for late sequelae and in assessing the risk of individual late effects on the basis of age and history of treatment.

A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma.

Transducing and distributing a vector throughout a tumor mass are presently insufficient for effective cancer gene therapy. To overcome these difficulties an adenoviral vector was designed that would replicate specifically in tumor cells. This tumor-specific replication-restricted adenoviral (TSRRA) vector was constructed by requiring that the essential E1A gene be expressed from a tumor-specific promoter, namely, the alpha-fetoprotein (AFP) gene promoter. This promoter was chosen since the AFP gene is highly expressed in 70-80% of patients with hepatocellular carcinoma (HCC) but not in normal adults. HCC is one of the major worldwide causes of cancer death. A vector was constructed (AvE1a04i) and demonstrated to replicate in human AFP-producing HCC cell lines. However, little replication was observed in seven other, non-AFP-producing human cell lines, as well as primary cultures of normal human lung epithelial and endothelial cells. In addition, AvE1a04i was shown to prevent tumor growth of an ex vivo-transduced AFP-expressing HCC cell line but not a non-AFP-expressing cell line. Finally, in situ administration of AvE1a04i into preestablished tumors resulted in a greater than 50% long-term survival rate. This novel TSRRA vector for HCC demonstrated both specificity and efficacy in vitro and in vivo.

Antiangiogenic gene therapy for cancer via systemic administration of adenoviral vectors expressing secretable endostatin.

A growing number of antiangiogenesis strategies have been investigated for the treatment of cancer and other angiogenesis-dependent diseases. One of the most promising strategies is to systemically administer one or more antiangiogenic proteins frequently enough to achieve a sufficient long-term steady state level of the protein(s) to achieve the maximum beneficial effect. However, the utility of this strategy is limited because of many technical difficulties, including obtaining both the quantity and quality of the protein(s) necessary for optimal therapeutic benefit. To overcome these difficulties, we hypothesized that a single administration of a replication-defective adenoviral vector expressing a secretable antiangiogenic protein could achieve an optimal long-term systemic concentration. We constructed a recombinant adenoviral vector, Av3mEndo, which encodes a secretable form of murine endostatin. We demonstrated secretion of endostatin from several cell lines transduced with Av3mEndo. Partially purified endostatin secreted from Av3mEndo-transduced mammalian cells was shown to potently inhibit endothelial cell migration in vitro. A single intravenous administration of Av3mEndo in mice was shown to result in (1) prolonged and elevated levels of circulating endostatin, (2) partial inhibition of VEGF-induced angiogenesis in a VEGF implant angiogenesis model, and (3) prolonged survival and in 25% of mice the complete prevention of tumor growth in a prophylactic human colon/liver metastasis xenograft murine model. These results support our contention that adenoviral vector-mediated expression of an antiangiogenic protein(s) represents an attractive therapeutic approach to cancer and other angiogenesis-dependent diseases.

Characterization of the 5-hydroxytryptamine2A receptor-activated cascade in rat C6 glioma cells.

We have investigated the identity and intracellular cascade of responses resulting from activation of the endogenous 5-hydroxytryptamine receptor in the C6 rat glioma cell line. Sequence analysis of reverse transcription-polymerase chain reaction products derived from C6 glioma cell messenger RNA revealed complete homology with a portion of the rat 5-hydroxytryptamine2A receptor. The binding of [3H]ketanserin to cell membranes demonstrated a significant correlation with the 5-hydroxytryptamine2A receptor in rat frontal cortex. On intact cells, 5-hydroxytryptamine stimulated a concentration-dependent increase in phosphatidyl inositide turnover and intracellular [Ca2+] mediated by 5-hydroxytryptamine2A receptors. In whole-cell patch-clamp recordings, 5-hydroxytryptamine induced an outward current mediated predominantly by K+ ions (reversal potential = -80 mV). Using caged molecules containing Ca2+ or inositol 1,4,5-trisphosphate in the patch electrode solution, we found that rapid photolytic release of Ca2+ and particularly inositol 1,4,5-trisphosphate within the cytosol induced an outward current with characteristics similar to those seen after application of 5-hydroxytryptamine. Comparison between differentiated and undifferentiated cells revealed significantly higher receptor density and maximal phosphoinositide response to 5-hydroxytryptamine in undifferentiated cells but the associated rise in [Ca2+]i and activation of an outward current was observed more frequently in differentiated cells. Prolonged exposure of the cells to 5-hydroxytryptamine led to a decrease in all responses and to the down-regulation of receptor number. We conclude that the rat C6 glioma cell expresses a 5-hydroxytryptamine2A receptor identical to that found in rat brain and that stimulation of the receptor in C6 cells leads to the activation of Ca2+ activated K+ channels via phosphoinositide hydrolysis and subsequent rise in cytosolic Ca2+ ion concentration. However, the contrasting effects of differentiation on receptor number and phosphoinositide response to 5-hydroxytryptamine compared to Ca2+ release and conductance change indicate that a complex relationship exists between the component parts of the receptor-activated cascade.

Oral ketamine premedication to alleviate the distress of invasive procedures in pediatric oncology patients.

This study prospectively evaluated the efficacy of oral ketamine in alleviating procedure-related distress in pediatric oncology patients. Ketamine (10 mg/kg) was administered orally to 35 children and adolescents, ranging in age from 14 months to 17 years (mean = 6.5 years). Procedure-related distress was evaluated by using parent/clinician ratings and the Observational Scale of Behavioral Distress (OSBD-R). Eighty-seven percent of children were sedated within 45 minutes. Clinician and parent ratings were similar, with 77% rating procedural distress as low (0 to 3). The OSBD-R scores were low throughout all phases of the study. Although this study was neither randomized nor placebo-controlled, statistical comparison of the OSBD-R scores of the patients who received oral ketamine with those of historical controls (from a study previously performed at the same institution but using intravenous midazolam) showed significantly less distress (P < .001) during the procedure in children who received oral ketamine. Additionally, OSBD-R scores of the patients who received oral ketamine were significantly lower (P < .001) during all phases than those of the saline placebo group in the other study. No cardiorespiratory side effects related to ketamine were noted. The majority of patients showed recovery from sedation within 2 hours following the procedure. In conclusion, oral ketamine effectively alleviated procedure-related distress in pediatric oncology patients.

Psychological response to amniocentesis: I. Mood state and adaptation to pregnancy.

The responses of a group of pregnant women undergoing amniocentesis and control women not having the procedure were studied using objective, self-report measures of mood state, attitudes toward pregnancy, and maternal-fetal attachment. Questionnaires were completed on three occasions: after genetic counseling (time-1), after amniocentesis (time-2), and 1 wk after communication of results (time-3) for amniocentesis subjects, and at comparable points in the pregnancy for control subjects. Amniocentesis and control subjects differed markedly in their pattern of change in anxiety scores over time, with amniocentesis subjects being more anxious than control subjects at time-2 and less anxious at time-3. Results were similar but less pronounced for depression scores, whereas there were smaller differences between groups on measures of anger and confusion. Unusual patterns of mood state changes were seen in the control group, which were related to a history of previous fetal loss. The groups did not differ in their attitudes toward pregnancy, but amniocentesis subjects showed a greater relative increase in attachment to the fetus than did control subjects. Overall, amniocentesis subjects were faring as well or better on every measure taken at time-3 and were showing improvement on all measures. In contrast, control subjects were demonstrating a trend toward increasing mood disturbance. These results suggest that any amniocentesis-related psychological disturbances are only transient and are outweighed by the receipt of normal results, which appear to enhance emotional adaptation to pregnancy.

Psychological response to amniocentesis: II. Effects of coping style.

Differences in coping style were assessed in a group of women undergoing amniocentesis and a control group not having the procedure. Subjects were divided into two groups according to coping style; "monitors" (information seekers) and "blunters" (information avoiders). In the amniocentesis group, coping style was associated with differences in mood state and change in mood state over time. "Monitors" experienced greater mood disturbance than "blunters" both before and during the procedure, but this effect disappeared after communication of amniocentesis results. Coping style was not associated with differences in maternal attitudes toward pregnancy or maternal-fetal attachment. In the control group, there were no differences between "monitors" and "blunters" on any of the mood state or pregnancy measures. Implications of these findings for providers of genetics services are discussed.

Acute health-related quality of life in children undergoing stem cell transplant: II. Medical and demographic determinants.

Medical and demographic variables were examined as predictors of acute health-related quality of life (HRQL), specifically, somatic distress, mood disturbance and activity levels, during the period of bone marrow transplant (BMT) hospitalization, and the transition phase in the months following hospital discharge. The responses of 153 children undergoing BMT were assessed by both parent report and patient self-report in a prospective longitudinal design. Type of transplant, diagnosis, age, gender, and socio-economic status (SES) were examined as predictor variables of patient outcome. Type of transplant, patient age, and SES emerged as significant determinants of patient response. Children undergoing unrelated donor (MUD) transplants experiencing the highest levels of distress, followed by those undergoing matched-sibling BMT, while those undergoing autologous transplant experienced the lowest levels of distress. Younger patients experienced lower levels of distress and better HRQL than older children and adolescents. Although patients from different SES backgrounds appeared very similar at the time of hospital admission, those from lower SES backgrounds demonstrated greater distress and disturbance in HRQL subsequently, and throughout the first 6 months post BMT. These findings help to target specific subgroups of patients that may be in greater need of preventive interventions or more aggressive supportive care.

Psychological effects of bone marrow transplantation on children and adolescents: preliminary report of a longitudinal study.

The number of pediatric bone marrow transplantation (BMT) survivors is growing rapidly, yet little is known about the long-term neuropsychologic and psychosocial sequelae of this procedure. Using a prospective, longitudinal design, 64 pediatric patients undergoing BMT were evaluated with standardized measures of global intelligence, academic achievement and selected tests of neuropsychologic function. In addition, adjustment was assessed with parent and patient report measures of social competence, behavior problems and self-esteem. Patients were evaluated prior to admission for BMT, and again in the period 6-12 months after BMT. Longitudinal findings are reported on an initial cohort of 25 survivors. Cognitive and neuropsychologic function remained stable during the study period. The few significant changes from baseline which were observed were in the direction of improvement, and may be attributed to practice effects. In contrast, declines were observed in patient social competence, self-esteem and general emotional well-being. BMT conditioning regimens appear not to be associated with significant neuropsychologic impairment in the first year after transplant. However, a longer period of follow-up is necessary before neuropsychologic late-effects can be ruled out. The first year after BMT is characterized by significant psychosocial difficulties for survivors. Adjustment issues may provide a more salient focus of study during this time frame.

Acute health-related quality of life in children undergoing stem cell transplant: I. Descriptive outcomes.

There has been little empirical documentation of the acute effects of bone marrow or stem cell transplant (BMT) on children. In the present study, the responses of 153 children undergoing BMT were assessed in a prospective, longitudinal design. Children were assessed at the time of admission for transplant, then underwent weekly assessments to week +6, followed by monthly assessment to month +6. Data were obtained both by parent report and patient report (for patients age 5 and up) using the BASES scales. The major findings are: (1) children undergoing BMT enter the hospital with an already heightened level of distress (defined by high levels of somatic symptoms and mood disturbance, and low levels of activity) that increases dramatically following conditioning, reaching a peak approximately 1 week following transplant; (2) this increased distress is transient, declining rapidly back to admission levels by week +4 to week +5, followed by a further decline to presumed basal levels by months 4-6; and (3) the trajectories of distress depicted by both parent and child report are remarkably similar, each providing confirmatory support for the validity of the findings. These findings confirm a number of widely held clinical impressions that had not previously been documented empirically, and point to the need for new interventions or more intensive approaches to supportive care aimed at reducing levels of distress during the acute phase of transplant.