Inter-cycle and inter-observer variability of the antral follicle count in routine clinical practice

Antral follicle count (AFC) is a reliable predictor of ovarian response to stimulation and its inter-cycle and inter-observer variability has been extensively studied on in vitro fertilization (IVF), mostly in highly selected populations within studies not originally designed for this purpose. In this retrospective cohort study, we assess the inter-cycle variation of AFC in a setting similar to that of the daily practice. We included only patients undergoing mild stimulation for intrauterine insemination (IUI). One hundred and forty-eight patients had two (62 patients, group A), three (49 patients, group B) or four (37 patients, group C) IUI cycles and AFC was measured on early follicular phase of each cycle by one of the members of the medical team within daily practice. Intra-class correlation coefficients were used to estimate variability. Inter-cycle variability rendered ICCs above 0.70 in all groups improving along with the number of cycles [Group A ICC 0.78 (95%CI 0.66–0.86), Group B ICC 0.87 (95%CI 0.80–0.92) and Group C ICC 0.91 (95%CI 0.85–0.95)]. Inter-observer variability showed a high degree of concordance with ICCs above 0.95. We provide the closest approximation to real inter-cycle and inter-observer AFC variability expected in routine clinical practice.     

In vivo cellular reactions to different biomaterials—Physiological and pathological aspects and their consequences

Biomaterials are widely used in guided bone regeneration (GBR) and guided tissue regeneration (GTR). After application, there is an interaction between the host immune system and the implanted biomaterial, leading to a biomaterial-specific cellular reaction. The present review focuses on cellular reactions to numerous biomaterials in vivo with consideration of different implantation models and microenvironments in different species, such as subcutaneous implantation in mice and rats, a muscle model in goats and a femur model in rabbits. Additionally, cellular reactions to different biomaterials in various clinical indications within the oro-maxillofacial surgical field were considered. Two types of cellular reactions were observed. There was a physiological reaction with the induction of only mononuclear cells and a pathological reaction with the induction of multinucleated giant cells (MNGCs). Attention was directed to the frequently observed MNGCs and consequences of their appearance within the implantation region. MNGCs have different subtypes. Therefore, the present review addresses the different morphological phenotypes observed within the biomaterial implantation bed and discusses the critical role of MNGCs, their subtypes and their precursors as well as comparing the characteristics and differences between biomaterial-related MNGCs and osteoclasts. Polymeric biomaterials that only induced mononuclear cells underwent integration and maintained their integrity, while polymeric biomaterials that induced MNGCs underwent disintegration with material breakdown and loss of integrity. Hence, there is a question regarding whether our attention should be directed to alternative biological concepts, in combination with biomaterials that induce a physiological mononuclear cellular reaction to optimize biomaterial-based tissue regeneration.     

Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment

1,4-Dioxane is found in consumer products and is used as a solvent in manufacturing. Studies in rodents show liver tumors to be consistently reported after chronic oral exposure. However, there were differences in the reporting of non-neoplastic lesions in the livers of rats and mice. In order to clarify these differences, a reread of mouse liver slides from the 1978 NCI bioassay on 1,4-dioxane in drinking water was conducted. This reread clearly identified dose-related non-neoplastic changes in the liver; specifically, a dose-related increase in the hypertrophic response of hepatocytes, followed by necrosis, inflammation and hyperplastic hepatocellular foci. 1,4-Dioxane does not cause point mutations, DNA repair, or initiation. However, it appears to promote tumors and stimulate DNA synthesis. Using EPA Guidelines (2005), the weight of the evidence suggests that 1,4-dioxane causes liver tumors in rats and mice through cytotoxicity followed by regenerative hyperplasia. Specific key events in this mode of action are identified. A Reference Dose (RfD) of 0.05 mg/kg day is proposed to protect against regenerative liver hyperplasia based on a benchmark dose (BMD) approach. Based on this RfD, a maximum contaminant level goal of 350 μg/L is proposed using a default relative source contribution for water of 20%.     

Development of a Magnetic Resonance-Compatible Galvanic Skin Response Measurement System Using Optic Signal

The purpose of the current study is to develop a magnetic resonance (MR)-compatible galvanic skin response (GSR) measurement system that can measure the GSR signal during MR image acquisition. If GSR signals are measured simultaneously with the acquisition of MR images, there can be a mutual interference effect. The present system was designed to block noises caused by the main magnetic field, the gradient magnetic field, and the radio frequency (RF) pulse when MR images are acquired. To minimize the distortion of MR images, the GSR measurement system was shielded. Especially, this system used analog, not digital, elements in order to remove any possible effects on MR images. An RF-interference-free optical data link using the pulse-width modulation technique was adopted in order to transmit GSR signals measured inside the MR room. The experiment verified that a reliable GSR signal can be obtained without deteriorating the MR image. It is expected that this system can be used for diverse medical and neuroscience studies.     

Gene therapy of the central nervous system: General considerations on viral vectors for gene transfer into the brain

The last decade has nourished strong doubts on the beneficial prospects of gene therapy for curing fatal diseases. However, this climate of reservation is currently being transcended by the publication of several successful clinical protocols, restoring confidence in the appropriateness of therapeutic gene transfer. A strong sign of this present enthusiasm for gene therapy by clinicians and industrials is the market approval of the therapeutic viral vector Glybera, the first commercial product in Europe of this class of drug. This new field of medicine is particularly attractive when considering therapies for a number of neurological disorders, most of which are desperately waiting for a satisfactory treatment. The central nervous system is indeed a very compliant organ where gene transfer can be stable and successful if provided through an appropriate strategy. The purpose of this review is to present the characteristics of the most efficient virus-derived vectors used by researchers and clinicians to genetically modify particular cell types or whole regions of the brain. In addition, we discuss major issues regarding side effects, such as genotoxicity and immune response associated to the use of these vectors.     

Low-dose hypersensitivity after fractionated low-dose irradiation in vitro

Purpose : It was demonstrated previously that some radioresistant tumour cell lines respond to decreasing single, low radiation doses by becoming increasingly radiosensitive. This paper reports the response of four radioresistant human glioma cell lines to multiple low-dose radiation exposures given at various intervals. Three of the cell lines (T98G, U87, A7) were proven already to show low-dose hyper-radiosensitivity (HRS) after single low doses; the fourth, U373, does not show HRS after acute doses. Materials and methods : Clonogenic cell-survival measurements were made in vitro using the Dynamic Microscopic Image Processing Scanner (DMIPS) or Cell Sorter (CS) following exposure to 240kVp X-rays one or more times. Results : A consistent, time-dependent hypersensitive response to a second, or subsequent, dose was observed in the cell lines that demonstrated HRS. This time-dependent change in radiosensitivity did not occur in the radioresistant cell line that did not show HRS (U373). In one cell line that demonstrated strong HRS, T98G, a similar time-dependent hypersensitive response was also seen when the cells were irradiated whilst held in the G1-phase of the cell cycle. In this same cell line, significantly increased cell kill was demonstrated when three very low doses (0.4 Gy) were given per day, 4 h apart, for 5 days, compared with the same total dose given as once-daily 1.2Gy fractions. Conclusions : These data demonstrate the possibility that a multipledose per day, low-dose per fraction regimen, termed 'ultrafractionation', could produce increased tumour cell kill in radioresistant tumours compared with the same total dose given as conventional-sized 2 Gy fractions.     

Declining Coronary Heart Disease Mortality in Iceland: Contribution by Incidence,Recurrence and Case Fatality Rate

Objective : To analyse to what extent the recent decline in coronary heart disease mortality in Iceland is due to changes in incidence, recurrence and case fatality rates. Design : A countrywide registration of myocardial infarction (MI) in people aged 25-74 was performed in Iceland during 1981-1999 according to the MONICA protocol. Possible cases were found by review of all hospital discharge records, autopsy records and death certificates. Results : MI death rate declined by 63% in males and 51% in females, most in the youngest age groups in men (86%) and least in the oldest (49%). In women there was not a significant difference in age groups. Overall the age-adjusted reduction in MI death rate was 55.4% in both sexes combined; of this 23.1% was due to incidence reduction, 22.8% to recurrence reduction and 11.6% to case fatality reduction. In the youngest age groups the decline in incidence contributed most to the decline in MI death rate (62% in men and 71% in women), but thereafter the decline in case fatality in men. In the older age groups decline in recurrence rate has greater weight. Conclusion : The recent decline in MI mortality under the age of 75 years in Iceland is due to reduction in incidence and recurrence rate by about 40% each and to reduction in case fatality by 20%.     

中药口服并穴位贴敷联合腹腔、静脉双途径化疗治疗晚期卵巢癌合并腹水临床研究

目的:观察双途径化疗(以顺铂为主的PT方案静脉滴注配合腹腔顺铂灌注)联合中药穴位贴敷及口服自拟健脾生血汤治疗晚期卵巢癌并发腹水的临床疗效。方法:以62例晚期卵巢癌合并腹水的患者为研究对象,随机分为治疗组和对照组,各31例,治疗组予以双途径化疗+中药穴位贴敷+健脾生血汤口服,对照组单纯予以双途径化疗,连续治疗6个周期,观察两组患者腹水变化情况及血CA125、白细胞、血红蛋白、红细胞水平。结果:对照组有效率51.61%,治疗组有效率83.87%,两组比较,差异有统计学意义(P0.05);治疗后对照组血清CA125为(36.22±12.71)U·m L~(-1),治疗组血清CA125为(23.85±13.06)U·m L~(-1),两组比较,差异有统计学意义(P0.05);治疗后对照组白细胞为(3.65±1.12)×109L~(-1),血红蛋白为(88.62±7.63)g·L~(-1),红细胞为(3.23±0.44)×10~(12)L~(-1),治疗组白细胞为(6.83±1.70)×109L~(-1),血红蛋白为(115.15±10.39)g·L~(-1),红细胞为(5.63±1.42)×10~(12)L~(-1),两组比较,差异有统计学意义(P0.05)。结论:静脉、腹腔双途径化疗结合中药穴位贴敷及自拟健脾生血汤口服,可使晚期卵巢癌合并腹水患者的腹水明显减少,改善化疗引起的骨髓抑制,提高临床疗效。