Intraoperative radiotherapy (IORT) is an option for patients with localized breast recurrences after previous external-beam radiotherapy

Background  

For patients suffering of recurrent breast cancer within the irradiated breast, generally mastectomy is recommended. The normal tissue tolerance does not permit a second full-dose course of radiotherapy to the entire breast after a second breast-conserving surgery (BCS). A novel option is to treat these patients with partial breast irradiation (PBI). This approach is based on the hypothesis that re-irradiation of a limited volume will be effective and result in an acceptable frequency of side effects. The following report presents a single center experience with intraoperative radiotherapy (IORT) during excision of recurrent breast cancer in the previously irradiated breast.     

Disruption of ROCK1 gene attenuates cardiac dilation and improves contractile function in pathological cardiac hypertrophy

The development of left ventricular cardiomyocyte hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response. However, persistent stress eventually leads to dilated heart failure, which is a common cause of heart failure in human hypertensive and valvular heart disease. We have recently reported that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) homozygous knockout mice exhibited reduced cardiac fibrosis and cardiomyocyte apoptosis, while displaying a preserved compensatory hypertrophic response to pressure overload. In this study, we have tested the effects of ROCK1 deficiency on cardiac hypertrophy, dilation, and dysfunction. We have shown that ROCK1 deletion attenuated left ventricular dilation and contractile dysfunction, but not hypertrophy, in a transgenic model of Gαq overexpression-induced hypertrophy which represents a well-characterized and highly relevant genetic mouse model of pathological hypertrophy. Although the development of cardiomyocyte hypertrophy was not affected, ROCK1 deletion in Gαq mice resulted in a concentric hypertrophic phenotype associated with reduced induction of hypertrophic markers indicating that ROCK1 deletion could favorably modify hypertrophy without inhibiting it. Furthermore, ROCK1 deletion also improved contractile response to β-adrenergic stimulation in Gαq transgenic mice. Consistent with this observation, ROCK1 deletion prevented down-regulation of type V/VI adenylyl cyclase expression, which is associated with the impaired β-adrenergic signaling in Gαq mice. The present study establishes for the first time a role for ROCK1 in cardiac dilation and contractile dysfunction.     

No early signs of atherosclerotic alterations in carriers of inherited thrombophilia

BackgroundCongenital thrombophilia is a risk factor for venous thromboembolism (VTE). Whether it is associated with increased risk of arterial disease is today a matter of debate. We aimed to look for early signs of atherosclerotic alterations in carriers of inherited thrombophilic alterations (ITA).MethodsBetween January 2006 and September 2008 ultrasonography assessment of the carotid arteries with measurement of intima-media thickness (IMT), and determination of the ankle/brachial pressure index (ABI), was performed in: a) 161 carriers of ITA (deficiency of antithrombin, protein C or S, factor V Leiden or prothrombin G20210A mutations), 84 of whom with previous VTE, and b) 180 subjects without ITA, matched for age, sex and previous VTE. All subjects were < 66 year old.ResultsCarotid plaques were found in 8 subjects [3 (1.9%) with ITA]. Increased IMT values (> 1 mm) were detected in 6 subjects with and 1 without thrombophilia (p = 0.055). The prevalence of IMT values > 90^th percentile was not different in subjects with/without thrombophilia (15.2% vs 11.6%, p = 0.416). At multivariate analysis only age was significantly associated with increased odds ratios for IMT values > 90^th percentile. No subjects had abnormal (< 0.9) ABI values.ConclusionsThe present study, the first to investigate the presence of atherosclerotic markers in relatively young subjects with inherited thrombophilia, did not find a particular prevalence of signs of early atherosclerotic markers in these subjects.     

Women's Experiences of Participating in the Magpie Trial: A Postal Survey in the United Kingdom

Background: The Magpie Trial compared magnesium sulfate with placebo for women with preeclampsia. The objective of this study was to explore women's views and experiences of participating in the Magpie Trial in the United Kingdom. Methods: Postal questionnaires were sent to 771 women participants in the Magpie Trial to assess long‐term health of UK women and children. The questionnaire included three questions exploring women's experience of participating in the trial: (a) If time suddenly went backward, and you had to do it all over again, would you agree to participate in the Magpie Trial? (b) Please tell us if there was anything about the Magpie Trial that you think could have been done better; and (c) Please tell us if there was anything about the Magpie Trial, or your experience of joining the trial, that you think was particularly good. Results: Overall, 619 of the 771 women who were sent questionnaires returned them. In response to the three questions: (a) 58 percent (356) of women responded “definitely yes,” 27 percent (169) “probably yes,” 4 percent (23) “probably no,” 5 percent (33) “definitely no,” and 5 percent (34) “not sure.” No clear evidence was shown of a relationship with allocated treatment, although women who responded “probably or definitely no” were more likely to have had side effects from trial treatment. (b) Although 44 percent of women stated that nothing could have been done better, free text suggestions related to content of recruitment information, and its timing, and wanting to know treatment allocation and trial results. c) Women were generally extremely positive about being followed up and receiving trial results. Conclusions: Women were largely positive about participation in the trial and its follow‐up, but still reported ways they believed the study could have been improved, such as more information, given earlier, which also has implications for clinical care.     

Environment and illness in the Calchaquí Valley (Salta, Argentina): phytotherapy for osteo-articular and cardio-circulatory diseases

The aim of this work is to analyze and discuss the phytotherapy employed for two kinds of diseases, osteo-articular and cardio-circulatory, among the inhabitants of Molinos (Calchaquí Valley, Salta Province, Northwestern Argentina). These diseases take their origin in certain environmental conditions as well as the rural activities characteristic of the zone. The observations and interviews conducted among "medicos campesinos" (traditional healers) and the general population provided valuable information concerning the relationship between man and his environment, as it relates to health-illness processes. As a result of our research, we present a chart of the 25 recorded diseases and the 42 plant species employed in their therapy, considering the organs used, the ways of preparation and administration, as well as the geographic origin.     

Comparison of optic nerve head measurements obtained by optical coherence tomography and confocal scanning laser ophthalmoscopy

PURPOSE: To evaluate the relationship between optic nerve head (ONH) measurements generated by optical coherence tomography (OCT; versions 2 and 3) and confocal scanning laser ophthalmoscopy (CSLO) and to compare the association between OCT and CSLO ONH measurements with glaucoma disease status, as determined by clinical evaluation and perimetry. DESIGN: Cross-sectional study. METHODS: In a prospective study in the glaucoma service of an academic department of ophthalmology, 159 eyes (97 subjects) and 77 eyes (44 subjects) were recruited in two separate periods. All subjects were scanned with a CSLO device. Subjects tested within the first period of recruitment were scanned with OCT version 2 and in the second period with OCT version 3. The main outcome measure was the correlation between automatic and manually defined OCT ONH measurements and the correlation of CSLO and OCT ONH measurements between devices and with glaucoma disease status. RESULTS: A high correlation was found between ONH measurements obtained by the automatic determination of ONH margin and those obtained by manual tracing of the disk margin (r =.93 to.98). Optical coherence tomography and CSLO ONH measurements were highly correlated. Optical coherence tomography-measured mean disk area was significantly larger than that measured by CSLO, as were all other disk size-related parameters. The areas under the receiver operator characteristic (AROC) curves for the associations between CSLO and OCT ONH measurements and clinical diagnosis were found to be similar and in the range of 0.47 to 0.79 for both devices. CONCLUSIONS: Automated OCT ONH measurements correlate highly with those obtained by manual tracing of disk margin. Optical coherence tomography and CSLO ONH analyses are highly correlated and have similar associations with glaucoma disease status.     

Early increases in transglutaminase activity and polyamine levels in a Mallory-Denk body mouse model

Rodents treated with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) are a model of two hepatic toxic manifestations: porphyria and the appearance of hepatic cytoplasmic protein aggregates (Mallory-Denk Bodies, MDBs). MDBs are induced after long-term DDC feeding, consist primarily of keratins 8 and 18, and contain glutamine-lysine cross-links generated by transglutaminases (TGs). TGs are Ca²⁺-dependent enzymes which catalyze the formation of covalent bonds between proteins and between proteins and polyamines. The aim of the current study was to investigate the time-course of TG hepatic activity in CF1 male mice either acutely or chronically treated with DDC and to correlate this activity with polyamine and porphyrin levels. On day 3 of the treatment, statistically significant increases in TG activity (75%), porphyrin content (6740%) and spermidine levels (73%) were observed. Although not statistically significant, at this time point putrescine levels showed an increase of 52%. The highest TG activity was observed on day 30 (522%), while porphyrin levels were still gradually increasing by day 45 (37,000%). From day 7 of the treatment and until the end of the experiment, putrescine levels remained increased (781%). Spermine levels were not affected by the treatment. The DDC-induced increases in putrescine and spermidine levels herein reported seem to be an early event contributing to the stimulation of liver TG activity, and thus to the promotion of cross-linking reactions between keratin proteins. This in turn would contribute to the formation of protein aggregates, which would lead to the appearance of MDBs. Due to the pro-oxidant and antioxidant properties of polyamines, it is possible to speculate that putrescine and spermidine may also participate at several levels in the oxidative stress processes associated with MDB formation.     

青光眼视网膜神经纤维层厚度的光学相干断层扫描纵向评估

目的：纵向评估光学相干断层扫描（OCT）视盘周围神经纤维层厚度测量，并将这些检查与临床状态和自动视野计检查作横向比较。 方法：对参与前瞻性纵向研究的青光眼或疑似青光眼患者64只眼（37例）作回顾性评估。所有参与者每6个月作一次全面的临床评估、视野检查和OCT。视野进展按可重复性测量的视野平均偏差至少比基线降低2dB，OCT进展按可重复性测量视网膜神经纤维层平均厚度至少变薄20pro。 结果：每个患者在中位值为4．7年的随访中有5个可使用的OCT扫描。青光眼和疑似青光眼患者之间视网膜神经纤维层厚度线性回归斜度的差异对所有变量均不显著；然而，Kaplan-Meier生存曲线分析显示视野比OCT测量有较高的进展率。在随访期间66％的眼是稳定的。22％只有OCT进展，9％单有视野平均偏差进展。3％视野和OCT都有进展。 结论：OCT比全自动视野计对辨别青光眼进展有更大的可能性。这可能反映OCT的敏感性或在常规方法发现之前其真实损害就能被OCT发现。