Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Fluorescein-labeled naloxone binding to mu opioid receptors on live Chinese hamster ovary cells using confocal fluorescent microscopy

A general method of confocal laser scanning microscopy was used to demonstrate specific binding of fluorescein-labeled naloxone (FNAL, 10-50 nM) to stably transfected mu opioid receptors on live Chinese hamster ovary cells. Nonspecific binding was visually indistinguishable from autofluorescence in cells with intact cell membranes. Fluorescent labeling of cell perimeters, not present in control nontransfected cells, reversed in transfected cells upon washout of FNAL or following the addition of either unlabeled naloxone (25 microM) or the mu specific antagonist CTOP (1 microM). The addition of the delta and kappa specific agonists DPDPE (1 microM) and U50488 (1 microM), respectively, failed to reverse the labeling. Further evidence of specific binding was obtained from kinetic experiments, where it was observed that only transfected cells showed a time-dependent exponential change in fluorescence that permitted estimation of association and dissociation binding rate constants of (5.8+/-0.5, mean+/-S.E.M.)x10(5) M(-1) s(-1) and (3.3+/-0.6)x10(-3) s(-1), respectively and a kinetically derived dissociation constant of 5.7+/-1.4 nM. These estimates were comparable to those obtained under similar conditions in radioligand binding experiments using [3H]-naloxone.     

Computer-Based Intensity Measurement Assists Pathologists in Scoring Phosphatase and Tensin Homolog Immunohistochemistry — Clinical Associations in NSCLC Patients of the European Thoracic Oncology Platform Lungscape Cohort

Introduction

Phosphatase and tensin homolog (PTEN) loss is frequently observed in NSCLC and associated with both phosphoinositide 3-kinase activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable readout, but lacks standardized staining protocol and cutoff value.

Circulating serum xenoestrogens and mammographic breast density

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; P_trend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; P_trend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.     

Comparing single‐target and multitarget approaches for postoperative circulating tumour DNA detection in stage II–III colorectal cancer patients

Circulating tumour DNA (ctDNA) detection for postoperative risk stratification in cancer patients has great clinical potential. However, low ctDNA abundances complicates detection. Multitarget (MT) detection strategies have been developed to increase sensitivity. Yet, empirical evidence supporting performance gains of MT vs. single‐target (ST) strategies in a postoperative setting is limited. We compared ctDNA detection in 379 paired plasma samples from 112 stage II–III colorectal cancer patients by ST digital PCR and MT sequencing of 16 patient‐specific variants. The strategies exhibited good concordance (90%, Cohen''s Kappa 0.79), with highly correlated ctDNA quantifications (Pearson r = 0.985). A difference was observed in ctDNA detection preoperatively (ST 72/92, MT 88/92). However, no difference was observed immediately after surgery in recurrence (ST 11/22, MT 10/22) or nonrecurrence (both 2/34) patients. In serial samples, detection was similar within recurrence (ST 13/16, MT 14/16) and nonrecurrence (ST 3/49, MT 1/49) patients. Both approaches yielded similar lead times to standard‐of‐care radiology (ST 4.0 months, MT 4.1 months). Our findings do not support significant performance gains of the MT strategy over the ST strategy for postoperative ctDNA detection.     

蓣知子皂甙IV的结构

从木通科木通属植物白木通[Akebia trifoliata(Thunb.)Koidz.var.australis(Diels)Rehd]种子的乙醇提取物中以硅胶层析等方法得四种三萜皂甙。其中甙IV是新天然产物,命名为蓣知子皂甙IV(yuzhiziosideIV)。根据化学和光谱分析,确定甙IV的结构为3-O-β-D-吡喃木糖基-(1→2)-a-L-吡喃阿拉伯糖齐墩果酸-28-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖酯甙。另外皂甙B(I)、皂甙C(II)和皂甙D(III)为已知物。这些化合物在白木通种子中均是首次得到。     

Comparison of dose requirement,serum erythropoietin and blood pressure following intravenous and subcutaneous erythropoietin treatment of dialysis patients IV and SC erythropoietin

Objective: The purpose of the study was to investigate the effect of route of administration of erythropoietin (EPO) on the dose requirement in dialysis patients after intravenous (IV) and subcutaneous (SC) therapy. Methods: The study was performed as a single centre, prospective, open, combined parallel and cross-over study of 50 dialysis patients, consecutively randomised to IV or SC treatment with EPO. The initial dose was 40 U⋅kg⁻¹ 3-times weekly, adjusted to increase haemoglobin (Hgb) from a median 5.3 mmol⋅l⁻¹ to a target of haemoglobin 6.5–7.5 mmol⋅l⁻¹. After reaching the target level, the haemoglobin was maintained for 4 months (Period 1). Then IV and SC treatment was switched for a further 4 months (Period 2). The study included high risk patients. The adjustment period was completed by 38 patients, Period one by 32 patients (IV/SC = 15/17; male/female = 19/13; age = 54 (24– 71) y), and Period two by 22 patients. Results: No significant difference was found between the two groups in the reticulocyte response, the rate of Hgb increase (IV 0.7 versus SC 0.5, mmol⋅l⁻¹⋅ month⁻¹), time to reach target level (IV 43 versus SC 60 days), or total EPO dose per increase in haemoglobin to target level (IV 663 versus SC 946 (U⋅kg⁻¹) per (mmol Hgb⋅l⁻¹). The overall median maintenance dose during the last month of the two four month periods was 105 (range IV 51–336) U⋅kg⁻¹⋅w⁻¹ and SC 104 (range 21–321) U⋅kg⁻¹⋅w⁻¹. Trough serum EPO levels were significantly higher during SC treatment. The blood pressure did not change significantly from the base level after either route of administration; start 133/80 versus 143/80 mmHg, target 127/78 versus 154/85 mmHg, and maintenance period 140/84 versus 142/85 mmHg. Thus, three-times weekly IV or SC EPO did not differ significantly in efficacy or in the effect on blood pressure in dialysis patients. Received: 13 June 1995/Accepted in revised form: 30 October 1995     

Ultra-micro samples can be used for mRNA quantification of lung cancer biomarkers

Background Isolating sufficient material for molecular testing remains challenging in non-small cell lung cancer (NSCLC). The use of new ultra-microsamples (uMS) is proven sufficient for DNA and mRNA detection, but whether uMS are useful for quantifying mRNA expression is unknown. We investigated if uMS from lung cancer patients can be used to generate quantitative data on mRNA expression. Methods uMS were collected from primary tumors and lymph nodes from patients suspected of having lung cancer. mRNA was isolated, reverse-transcribed into cDNA and quantified with quantitative PCR assays for hepatocyte growth factor receptor (MET), hepatocyte growth factor (HGF), epidermal growth factor receptor (EGFR) and amphiregulin (AREG) mRNA. The fraction of tumor cells to normal cells was estimated in each sample. Results MET, HGF, EGFR, and AREG expression were evaluated in 90 samples (30 containing cancer cells and 60 without cancer cells). MET and EGFR expression were negligible in samples without cancer cells. In samples containing cancer cells, MET and EGFR could be quantified in 13 samples each. Adjustment for tumor-cell fraction made it possible to obtain a quantitative result for the tumor-cell mRNA expression of MET and EGFR. In contrast, AREG and HGF were expressed in samples without tumor cells. These samples were used to establish the AREG and HGF mRNA expression in normal cells. Seven out of 14?AR-positive and two out of eight HGF-positive samples with tumor cells were above a cut-off of the mean?+?2SD established in samples without tumor cells. Conclusion We demonstrate that uMS contain high-quality mRNA, and quantitative studies can be performed when the tumor-cell fraction is considered.