Glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction has been proposed as a mechanism underlying psychosis. D-cycloserine, a partial agonist at the glycine site of the NMDA receptor, enhances learning in animal models, although tachyphylaxis develops with repeated dosing. Once-weekly dosing of D-cycloserine produces persistent improvement when combined with cognitive behavioral therapy (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a learning deficit, characterized by the failure to use contradictory evidence to modify the belief. CBT techniques have been developed with modest success to facilitate such reality-testing (or new learning) in delusional beliefs. The current study evaluated whether D-cycloserine could potentiate beneficial effects of CBT on delusional severity. Twenty-one outpatients with schizophrenia or schizoaffective disorder and moderately severe delusions were randomized in a double-blind cross-over design to receive a single-dose of either D-cycloserine 50mg or placebo in a counterbalanced order on two consecutive weeks 1-hour prior to a CBT intervention involving training in the generation of alternative beliefs. Assessments were completed at baseline, 7 days following the first study drug administration and 7 days following the second study drug administration. Contrary to prediction, there was no significant D-cycloserine treatment effect on delusional distress or severity as measured by the SAPS or PSYRATS. An unexpected finding was an order effect, whereby subjects who received D-cycloserine first had significantly reduced delusional severity, distress, and belief conviction on PSYRATS compared to subjects who received placebo first. However, this finding is consistent with animal models in which D-cycloserine enhances learning only when accompanying the first exposure to training.

Purpose

To evaluate clinical outcomes of frozen-thawed embryo transfer cycles when one or two blastocysts are transferred.

Methods

Retrospective chart review

Results

Two hundred forty-three frozen blastocyst transfer (FBT) cycles were analyzed. Clinical pregnancy rate (50.4% vs. 34.7%), live birth rate (45.8% vs. 30.6%), and twin live birth rate (19.3% vs. 0) were significantly higher in the double versus single FBT group, respectively (p < 0.05). Prior fresh cycle success with same-cohort embryos did not predict outcome of FBT cycle. When the fresh cycle was unsuccessful, there still was a significant increase in twinning when two frozen-thawed blastocysts were transferred.

Conclusions

Transferring two blastocysts during an FBT cycle resulted in higher live birth and twin live birth rates. Single FBT provided acceptable pregnancy rates for couples seeking to avoid a multiple pregnancy or for those having a single blastocyst stored. Interestingly, the outcome of fresh cycle with same-cohort embryos did not influence the outcome of frozen-thawed cycle.

Purpose

To evaluate pregnancy rate (PR) and live birth rate (LBR) after freezing pronuclear (PN) embryos for two purposes: to reduce the risk of ovarian hyperstimulation syndrome (OHSS) and to bank embryos for cancer patients anticipating gametotoxic chemotherapy/radiotherapy.

Methods

Data from 3,621 consecutive IVF cycles were retrospectively analyzed. PN freezing was offered to patients at risk for OHSS and for those wishing to preserve fertility prior to cancer therapy. Primary outcomes evaluated were PR and LBR. Outcomes were compared to patients who underwent fresh embryo transfer (ET) in 2006.

Results

Sixty-six patients froze PN embryos. Thirty-eight were at risk for OHSS. The LBR was 34.3% after one transfer, and 51.4% after a mean of 1.4 transfers. Twenty-eight cancer patients froze embryos. The LBR was 16.7% after one transfer and 25.0% after a mean of 1.5 transfers. The LBR was 35.5% for patients who underwent fresh ET.

Conclusion

PN freezing with delayed ET is an effective tool for achieving pregnancy for patients at risk of OHSS and for cancer patients wishing to preserve fertility.

Supportive social relationships, including a positive patient-practitioner relationship, have been associated with positive health outcomes. Using the data from a randomized controlled trial (RCT) undertaken in the Boston area of the United States, this study sought to identify baseline factors predictive of patients' response to an experimentally applied supportive patient-practitioner relationship. To sort through the hundreds of potential attributes affecting the patient-practitioner relationship, we applied a false discovery rate method borrowed from the field of genomics and bioinformatics. To our knowledge such a method has not previously been applied to generate hypotheses from clinical trial data. In a previous RCT, our team investigated the effect of the patient-practitioner relationship on symptom improvement in patients with irritable bowel syndrome (IBS). Data were collected on a sample of 289 individuals with IBS using a three-week, single blind, three arm, randomized controlled design. We found that a supportive patient-practitioner relationship significantly improved symptomatology and quality of life. A complex, multi-level measurement package was used to prospectively measure change and identify factors associated with improvement. Using a local false discovery rate procedure, we examined the association of 452 baseline subject variables with sensitivity to treatment. Out of 452 variables, only two baseline factors, reclusiveness, and previous trial experience increased sensitivity to the supportive patient-practitioner relationship. A third variable, additional opportunity during the study for subjects to discuss their illness through experiential interview, was associated with improved outcomes among subjects who did not receive the supportive patient-practitioner relationship. The few variables associated with differential benefit suggest that a patient-centered supportive patient-practitioner relationship may be beneficial for most patients. This may be especially important for reclusive individuals. Within the context of our study, additional study attention in the form of repeated experiential interviews compensated for a lack of positive patient-practitioner support. A supportive patient-practitioner relationship may also help overcome low provider expectations for subjects with previous trial experience. These results converge with the results of the parent trial, implicating the importance of the social world in healing.

While the prognosis of patients with glioblastoma (GBM) remains poor despite recent therapeutic advances, variable survival times suggest wide variation in tumor biology and an opportunity for stratified intervention. We used volumetric analysis and morphometrics to measure the spatial relationship between subventricular zone (SVZ) proximity and survival in a cohort of 39 newly diagnosed GBM patients. We collected T2-weighted and gadolinium-enhanced T1-weighted magnetic resonance images (MRI) at pre-operative, post-operative, pre-radiation therapy, and post-radiation therapy time points, measured tumor volumes and distances to the SVZ, and collected clinical data. Univariate and multivariate Cox regression showed that tumors involving the SVZ and tumor growth rate during radiation therapy were independent predictors of shorter progression-free and overall survival. These results suggest that GBMs in close proximity to the ependymal surface of the ventricles convey a worse prognosis-an observation that may be useful for stratifying treatment.

Electronic supplementary material

The online version of this article (doi:10.1007/s11060-010-0477-1) contains supplementary material, which is available to authorized users.

Adults with β thalassemia major frequently have low BMD, fractures, and bone pain. The purpose of this study was to determine the prevalence of low BMD, fractures, and bone pain in all thalassemia syndromes in childhood, adolescence, and adulthood, associations of BMD with fractures and bone pain, and etiology of bone disease in thalassemia. Patients of all thalassemia syndromes in the Thalassemia Clinical Research Network, ≥6 yr of age, with no preexisting medical condition affecting bone mass or requiring steroids, participated. We measured spine and femur BMD and whole body BMC by DXA and assessed vertebral abnormalities by morphometric X-ray absorptiometry (MXA). Medical history by interview and review of medical records, physical examinations, and blood and urine collections were performed. Three hundred sixty-one subjects, 49% male, with a mean age of 23.2 yr (range, 6.1–75 yr), were studied. Spine and femur BMD Z-scores < −2 occurred in 46% and 25% of participants, respectively. Greater age, lower weight, hypogonadism, and increased bone turnover were strong independent predictors of low bone mass regardless of thalassemia syndrome. Peak bone mass was suboptimal. Thirty-six percent of patients had a history of fractures, and 34% reported bone pain. BMD was negatively associated with fractures but not with bone pain. Nine percent of participants had uniformly decreased height of several vertebrae by MXA, which was associated with the use of iron chelator deferoxamine before 6 yr of age. In patients with thalassemia, low BMD and fractures occur frequently and independently of the particular syndrome. Peak bone mass is suboptimal. Low BMD is associated with hypogonadism, increased bone turnover, and an increased risk for fractures.

Perinatal HIV infection is characterized by a sustained high-level viremia and a high risk of rapid progression to AIDS, indicating a failure of immunologic containment of the virus. We hypothesized that age-related differences in the specificity or function of HIV-specific T cells may influence HIV RNA levels and clinical outcome following perinatal infection. Here we define the HIV epitopes targeted by 76 pediatric subjects (47 HIV-infected and 29 HIV-exposed but uninfected), and assessed the ability of HIV-specific CD8 and CD4 T cells to degranulate and produce IFNγ, TNFα, and IL-2. No responses were detected among HIV-uninfected infants, while responses among infected subjects increased in magnitude and breadth with age. Gag-specific responses were uncommon during early infancy, and their frequency was significantly lower among children younger than 24 months old (p=0.014). Importantly, Gag responders exhibited significantly lower HIV RNA levels than nonresponders (logVL 5.8 vs. 5.0; p=0.005). Both the total and Gag-specific T cell frequency correlated inversely with viral load after correction for age, whereas no relationship with targeting of other viral proteins was observed. Functional assessment of HIV-specific T cells by multiparameter flow cytometry revealed that polyfunctional CD8 cells were less prevalent in children before 24 months of age, and that HIV-specific CD4 cell responses were of universally low frequency among antiretroviral-naïve children and absent in young infants. These cross-sectional data suggest that qualitative differences in the CD8 response, combined with a deficiency of HIV-specific CD4 cells, may contribute to the inability of young infants to limit replication of HIV.

The basis of the association between asthma and an increased rate of pain among children with sickle cell anemia (SCA) is unclear. To provide evidence for a familial contribution to this observation, we tested the hypothesis that a family history of asthma is associated with an increased pain rate. Using data from the Cooperative Study for Sickle Cell Disease (CSSCD), we identified 211 children with SCA with asthma history of the parents and siblings. A sibling history of asthma was associated with a greater rate of pain (mean rate ratio = 2.48, 95% CI 1.6–4.0; p<0.001) when compared to children without a sibling history of asthma. Parental history of asthma was not associated an increase rate of pain (mean ratio = 1.51, 95% CI 0.92 to 2.62; P=0.12). Further studies are needed to examine genetic and/or environmental risks for asthma as potential contributors to pain in children with SCA.

Increasing atmospheric carbon dioxide is responsible for climate changes that are having widespread effects on biological systems. One of the clearest changes is earlier onset of spring and lengthening of the growing season. We designed the present study to examine the interactive effects of timing of dormancy release of seeds with low and high atmospheric CO2 on biomass, reproduction, and phenology in ragweed plants (Ambrosia artemisiifolia L.), which produce highly allergenic pollen. We released ragweed seeds from dormancy at three 15-day intervals and grew plants in climate-controlled glasshouses at either ambient or 700-ppm CO2 concentrations, placing open-top bags over inflorescences to capture pollen. Measurements of plant height and weight; inflorescence number, weight, and length; and days to anthesis and anthesis date were made on each plant, and whole-plant pollen productivity was estimated from an allometric-based model. Timing and CO2 interacted to influence pollen production. At ambient CO2 levels, the earlier cohort acquired a greater biomass, a higher average weight per inflorescence, and a larger number of inflorescences; flowered earlier; and had 54.8% greater pollen production than did the latest cohort. At high CO2 levels, plants showed greater biomass and reproductive effort compared with those in ambient CO2 but only for later cohorts. In the early cohort, pollen production was similar under ambient and high CO2, but in the middle and late cohorts, high CO2 increased pollen production by 32% and 55%, respectively, compared with ambient CO2 levels. Overall, ragweed pollen production can be expected to increase significantly under predicted future climate conditions.