BACKGROUND: A study was undertaken to investigate whether granulocyte-colony-stimulating factor (G-CSF) injection in lower adipose tissue-containing sites (arms and legs) would result in a lower exposure and reduced stem cell collection efficiency compared with injection into abdominal skin.
STUDY DESIGN AND METHODS: We completed a prospective randomized study to determine the efficacy and tolerability of different injection sites for patients with multiple myeloma or lymphoma undergoing stem cell mobilization and apheresis. Primary endpoints were the number of CD34+ cells collected and the number of days of apheresis. Forty patients were randomly assigned to receive cytokine injections in their abdomen (Group A) or extremities (Group B). Randomization was stratified based on diagnosis (myeloma, n = 29 vs. lymphoma, n = 11), age, and mobilization strategy and balanced across demographic factors and body mass index.
RESULTS: Thirty-five subjects were evaluable for the primary endpoint: 18 in Group A and 17 in Group B. One evaluable subject in each group failed to collect a minimum dose of at least 2.0 × 106 CD34+ cells/kg. The mean numbers of CD34+ cells (±SD) collected were not different between Groups A and B (9.15 × 106 ± 4.7 × 106/kg vs. 9.85 × 106 ± 5 × 106/kg, respectively; p = NS) after a median of 2 days of apheresis. Adverse events were not different between the two groups.
CONCLUSION: The site of G-CSF administration does not affect the number of CD34+ cells collected by apheresis or the duration of apheresis needed to reach the target cell dose.
Purpose: In the United States, stillbirths (fetal deaths ≥ 20 weeks' gestation) are now more common than infant deaths. Nationally available data are limited, and little is known about women's experiences around the time of a loss. The Pregnancy Risk Assessment Monitoring System (PRAMS), a state-based survey of women with a recent live birth, could be expanded to include women who experienced a stillbirth. We aimed to determine whether women with a recent stillbirth would be amenable to a PRAMS-like survey.
Methods: Eligible women were Georgia residents aged ≥18 years with a reported stillbirth from December 1, 2012-February 28, 2013 identified through fetal death certificates. Women received a handwritten sympathy card, followed by a mailed questionnaire about their health and experiences around the time of the loss. Nonresponders received two additional mailings and up to three phone calls.
Results: During the study period, 149 eligible women had a reported stillbirth. Forty-nine (33%) women responded. Excluding women with invalid contact information (n = 26) yields an adjusted response rate of 40%. Response differed by race and/or ethnicity, but not by fetal, delivery, or other maternal characteristics.
Conclusions: Women appear willing to respond to a survey regarding a recent stillbirth. Further studies of the expansion of PRAMS to include stillbirth are warranted.
Tubulocystic carcinoma (TC) is a rare primary renal tumor that has been recently described in the pathology literature. Formerly termed low-grade collecting duct carcinoma, further molecular analysis has shown TC to be a distinct entity that is separate from the more aggressive collecting duct carcinoma. Previous series have described the microscopic and immunohistochemical features of this tumor. We describe the natural history of this tumor in a patient who was followed with active surveillance for several years and then underwent partial nephrectomy. Long-term follow-up has shown no evidence of disease. A review of the pertinent literature is performed.
Background: We compared the relationship between sodium (Na) intake and blood pressure when Na intake was estimated from first- and second-morning spot urine samples using the INTERSALT (International Study on Salt and Blood Pressure) formula, versus directly measured 24-hour samples. Methods and Results: We collected 24-hour urine and first- and second-morning voids of 383 participants in coastal Bangladesh for 2 visits. We measured participants’ blood pressure using an Omron® HEM–907 monitor. To assess the shape of the relationship between urinary Na and blood pressure, we created restricted cubic spline plots adjusted for age, sex, body mass index, smoking and alcohol consumption, physical activities, religion, sleep hours, and household wealth. To assess multicollinearity, we reported variance inflation factors, tolerances, and Leamer's and Klein's statistics following linear regression models. The mean daily urinary Na was 122 (SD 26) mmol/d for the first; 122 (SD 27) mmol/d for the second; and 134 (SD 70) mmol/d for the 24-hour samples. The restricted cubic spline plots illustrated no association between first-morning urinary Na and systolic blood pressure until the 90th percentile distribution followed by a downward relationship; a nonlinear inverse-V-shaped relationship between second-morning urinary Na and systolic blood pressure; and a monotonic upward relationship between 24-hour urinary Na and systolic blood pressure. We found no evidence of multicollinearity for the 24-hour urinary Na model. Conclusions: The urinary Na and systolic blood pressure relationship varied for 3 urinary Na measurements. Twenty-four-hour urinary Na captured more variability of Na intake compared with spot urine samples, and its regression models were not affected by multicollinearity.
Context: Parenting concerns are a major source of distress for patients with advanced cancer. However, validated tools to measure this construct in advanced cancer patients are lacking. Objectives: The Parenting Concerns Questionnaire (PCQ) is the only tool available to assess parenting concerns in cancer patients, yet its psychometric properties have not been fully evaluated. Methods: This cross-sectional Web-based survey of the psychosocial concerns included 211 women with Stage IV solid tumor malignancy who had at least one minor child in the home. Participants completed a battery of questionnaires assessing parenting concerns, health-related quality of life (HRQOL), depression and anxiety symptoms, and sociodemographic and clinical characteristics. Internal consistency was assessed by computing Cronbach's alpha. Convergent validity was evaluated using correlations of the PCQ with anxiety and depression symptom severity and HRQOL. We examined the PCQ's underlying dimensions with confirmatory factor analysis. Results: The mean total PCQ score for the sample was 2.2 (SD, 0.7), corresponding to “a little bit concerned.” Internal consistency was 0.82. The PCQ demonstrated adequate convergent validity with expected correlations with anxiety (r = 0.49) and depression (r = 0.56) symptom severity, and HRQOL (r = −0.61). The original three-factor structure was not fully supported by confirmatory factor analysis. Conclusion: The PCQ assesses a unique aspect of psychological distress in cancer patients. It demonstrated adequate reliability and convergent validity, but its original three-factor structure was not supported in a population of patients with metastatic cancer. The PCQ would benefit from further testing and refinement to enhance its representation of parenting concerns in metastatic cancer.
Aim: Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα deficiency would reduce MAP, by a reduction in vascular contractility. Methods: Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCα mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion. Results: PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls. Conclusion: Together, these data suggest that global deletion of PKCα results in reduced MAP due to decreased vascular contractility.
Retrograde ejaculation (RE) has been reported in humans and animals but RE with subsequent sperm calculi has rarely been reported. This report documents clinical and pathological findings of spontaneous sperm cystolithiasis in four rhesus macaques. While this condition has been associated with repeated electroejaculation, spontaneous sperm cystolithiasis is highly unusual. The animals presented with either stranguria, dysuria, hematuria, distended abdomen or lethargy. Ultrasound examination revealed several hyperechoic masses within the lumen of the urinary bladder. The animals were euthanized due to poor prognosis or study end points. Postmortem examination revealed multiple angular, amorphous, soft to firm, pale yellow to greenish-brown and variably sized calculi in the lumen of the urinary bladder or prostatic/penile urethra. Histologically, the calculi were composed of numerous sperm embedded in abundant brightly eosinophilic matrix. Based on gross and histologic findings, RE associated sperm cystolithiasis was diagnosed, with ulcerative urethritis as the major primary apparent etiology. To the authors' knowledge, this is the first report of four spontaneous cases of sperm cystolithiasis in rhesus macaques.
We compared geographic information system (GIS)- and Census-based approaches for measuring the physical and social neighborhood environment at the census tract-level versus an audit approach on associations with body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Data were used from the 2012-2014 Women and Their Children’s Health (WaTCH) Study (n = 940). Generalized linear models were used to obtain odds ratios (ORs) for BMI (≥30 kg/m2), WC (>88 cm), and WHR (>0.85). Using an audit approach, more adverse neighborhood characteristics were associated with a higher odds of WC (OR: 1.10; 95% confidence interval [CI]: [1.05, 1.15]) and WHR (OR: 1.09; 95% CI: [1.05, 1.14]) after adjustment for age, race/ethnicity, income, and oil spill exposure. There were no significant associations between GIS- and Census-based measures with obesity in adjusted models. Quality aspects of the neighborhood environment captured by audits at the individual-level may be more relevant to obesity than physical or social aspects at the census tract-level.
by
Shan V. Andrews;
Brooke Sheppard;
Gayle C. Windham;
Laura A. Schieve;
Diana E. Schendel;
Lisa A. Croen;
Pankaj Chopra;
Reid S. Alisch;
Craig J. Newschaffer;
Stephen Warren;
Andrew P. Feinberg;
M. Danielle Fallin;
Christine Ladd-Acosta
Background: Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. Methods: DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. Findings: In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 × 10- 7. Seven CpGs showed differences at p < 1 × 10- 5and 48 at 1 × 10- 4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. Conclusions: No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.