3He MR imaging of porcine paranasal sinuses

RATIONALE AND OBJECTIVES: The aim of this study was to test the effectiveness of laser-hyperpolarized helium 3 (3He) as a contrast agent for magnetic resonance (MR) imaging of porcine paranasal sinuses. MATERIALS AND METHODS: Imaging experiments were conducted on the heads of four 50-kg Yorkshire pigs after open sinus surgery was performed. Paranasal sinus MR images were obtained with laser-polarized 3He gas produced through the spin-exchange method. The gas was delivered into the sinuses through two 14-gauge plastic catheters inserted in the nostrils. The 3He MR images were then compared with spatially correlated proton MR images. RESULTS: The porcine paranasal sinuses were adequately depicted by MR imaging with hyperpolarized 3He. The signal intensity of the paranasal sinuses on the 3He MR images was related to the size of the opening joining the sinuses to the nasal cavity and was clearly time dependent. CONCLUSION: Hyperpolarized 3He MR imaging may be particularly useful for identifying the anatomic configuration of the paranasal sinuses, as well as for assessing sinus aeration. Further study of the time-dependence of 3He signal intensity may help increase understanding of gas exchange in the sinuses.     

Breast cancer in men

Most men with breast cancer present with a mass in the breast, the evaluation of which should include a tissue diagnosis. If the presence of invasive cancer is established, adequate local therapy includes total removal of the breast. Most tumors are hormone-receptor positive. In high-risk patients, the use of endocrine adjuvant therapy and/or combined endocrine and chemotherapy should be considered. Patients with estrogen-receptor (ER)-negative disease should be offered chemotherapy. In patients with metastatic disease and ER-positive tumors, initial treatment should be endocrine therapy; systemic chemotherapy should be used in patients who are either hormone-receptor negative or resistant to available endocrine therapies.     

ICH guideline for photostability testing: aspects and directions for use

The ICH guideline Q1B for photostability testing gives guidance on the basic testing protocol required to evaluate the light sensitivity and stability of new drugs and products. The choice of the irradiation method, although complying with the guideline demands, may effect test results. High irradiances may shorten testing times, but can lead to enforcement of photodegradation, which was demonstrated for molsidomine tablets. The exposure to an artificial light source (xenon lamp) was compared and correlated to natural daylight. Suitable testing methods for nifedipine and molsidomine tablets were developed. Deviating from the guideline recommendations, the presentation of powder samples should be done in tiny aluminium pans, facilitating the test procedure, minimising the risk of falsified test results due to improper sampling and improving reproducibility. When using glass dishes for the presentation of tablets to photostability testing, they should be lined by e. g. aluminium foil to avoid influences of light reflected from the sample tray.     

A roundtable discussion of aromatase inhibitors as therapy for breast cancer

This article summarizes the conclusions of a meeting of diverse breast cancer experts who discussed issues, controversies, and new clinical trial results relevant to the use of aromatase inhibitors for treating postmenopausal women with breast cancer. The new generation of aromatase inhibitors (anastrozole, letrozole, exemestane) have largely replaced megestrol acetate as a second-line therapy in postmenopausal women with hormone-responsive advanced breast cancer. In addition, anastrozole and letrozole have been shown to be superior to tamoxifen for first-line therapy. Finally, recent results suggest that anastrozole may be superior to tamoxifen as adjuvant therapy for early stage disease in postmenopausal women with hormone-responsive disease.     

Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials

OBJECTIVE: A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request (symptoms of most concern to patient/caregiver), which may be diluted in change scores of multisymptom scales. METHOD: In the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable data. RESULTS: The most common symptoms identified by parents were tantrums, aggression, and hyperactivity. Interrater reliability was excellent. Mean ratings at endpoint were 2.8 +/- 1.2 on risperidone and 4.5 +/- 1.3 on placebo (p <.001). Ratings were collinear with Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale (primary dimensional measure). Effect size d was 1.4, compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale. Effect sizes varied twofold by symptom category, largest for self-injury (2.11) and tantrums (1.95). CONCLUSIONS: Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior. Rating individualized participant-chosen target symptoms seems a reliable, sensitive, efficient, and consumer-friendly way to assess treatment effect and might have clinical application.     

Absorption of dietary alkylresorcinols in ileal-cannulated pigs and rats

Alkylresorcinols (AR) are amphiphilic 1,3-dihydroxy-5-alkyl phenolic lipids. AR in food are only found in the outer layers of wheat and rye grains, and in whole grains are present at concentrations of 500-1000 microg/g. In wheat and rye, there are five main homologues, differing in the length of the odd-numbered alkyl chain (from seventeen to twenty-five C atoms long). Because AR may be bioactive, and might serve as biomarkers for these cereals, their absorption was investigated in model experiments with pigs and rats. Pigs with a cannula in the terminal ileum were fed four diets containing rye fractions with different levels of AR and the ileal effluents were analysed. The ileal recovery of AR was found to vary between 21 and 40 %, with no major difference between different chain-length homologues. The absorption of AR by rats was investigated by feeding (14)C-labelled heneicosylresorcinol (C21 : 0). Of the total activity, about 34 % was recovered in the urine, showing that the labelled AR was absorbed and metabolised by rats. AR were mostly cleared from rats by 60 h. It is concluded that AR are absorbed in the small intestine of single-stomached animals and excreted in metabolised form in the urine, and might contribute to the nutritional qualities of wholegrain wheat and rye diets.     

大肠癌及癌旁组织中雌激素、孕激素受体的表达及意义

目的 探讨大肠癌与雌激素受体、孕激素受体的关系。方法 用免疫组化ＡＢＣ法对４３例大肠癌及癌旁组织进行雌激素受体（ＥＲ）、孕激素受体（ＰＲ）检测。结果 大肠癌ＥＲ、ＰＲ阳性率分别为８３．７２％和８８．３７％。癌旁粘膜内也检出ＥＲ、ＦＲ其检出率与癌组织部位相比差异有显著性（Ｐ〈０．０１）。与年龄、性别、肿瘤部位、分期及有无转移无关,与肿瘤分化程度亦无关（Ｐ〉０．０５）。结论 大肠癌为性激素依赖性肿瘤;     

Characteristics of rapid rhythms recorded within pulmonary veins during atrial fibrillation

Rapid rhythms often arise in the pulmonary veins during atrial fibrillation (AF). The activation patterns within pulmonary veins during these rapid rhythms are not well described. In 39 patients with paroxysmal AF, ostial recordings were obtained during AF in 110 pulmonary veins with a decapolar distal ring catheter. Pulmonary vein tachycardia (PVT) was defined as a pulmonary vein (PV) rhythm that had a cycle length shorter than at the adjacent left atrium. During AF, PVT was recorded in 93% of PV's, usually in the form of intermittent bursts that had a mean duration of 1,325 +/- 647 ms and mean cycle length of 125 +/- 20 ms. The mean cycle length of continuous PVT's (141 +/- 25) was longer than the mean cycle length of intermittent bursts of PVT (P < 0.05). The intermittent PVT's were associated with a shorter left atrial cycle length than were the continuous PVT's. In 90% of PVTs, complex activation patterns attributable to simultaneous recordings from two or more overlapping fascicles were present at a segment of the pulmonary vein ostium, and the mean cycle length of these recordings was 80 +/- 32 ms. PVT during AF is much more often intermittent than continuous. The relationship between PVT cycle length and left atrial cycle length suggests that PVT's influence the left atrium during AF. PVT must be distinguished from recordings within PV's that have a short cycle length as a result of simultaneous recordings from two or more overlapping fascicles.     

High concordance of parent and teacher attention-deficit/hyperactivity disorder ratings in medicated and unmedicated children with autism spectrum disorders

Abstract Objective: Parent and teacher ratings of core attention-deficit/hyperactivity disorder (ADHD) symptoms, as well as behavioral and emotional problems commonly comorbid with ADHD, were compared in children with autism spectrum disorders (ASD). Method: Participants were 86 children (66 boys; mean: age=9.3 years, intelligence quotient [IQ]=84) who met American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for an ASD on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS). Parent and teacher behavioral ratings were compared on the Conners' Parent and Teacher Rating Scales (CPRS-R; CTRS-R). The degree to which age, ASD subtype, severity of autistic symptomatology, and medication status mediated this relationship was also examined. Results: Significant positive correlations between parent and teacher ratings suggest that a child's core ADHD symptoms-as well as closely related externalizing symptoms-are perceived similarly by parents and teachers. With the exception of oppositional behavior, there was no significant effect of age, gender, ASD subtype, or autism severity on the relationship between parent and teacher ratings. In general, parents rated children as having more severe symptomatology than did teachers. Patterns of parent and teacher ratings were highly correlated, both for children who were receiving medication, and for children who were not. Conclusions: Parents and teachers perceived core symptoms of ADHD and closely-related externalizing problems in a similar manner, but there is less agreement on ratings of internalizing problems (e.g., anxiety). The clinical implication of these findings is that both parents and teachers provide important behavioral information about children with ASD. However, when a clinician is unable to access teacher ratings (e.g., during school vacations), parent ratings can provide a reasonable estimate of the child's functioning in these domains in school. As such, parent ratings can be reliably used to make initial diagnostic and treatment decisions (e.g., medication treatment) regarding ADHD symptoms in children with ASDs.