Conjugated linoleic acid and the control of cancer and obesity

The effects of conjugated linoleic acid (CLA) in animals are reviewed. In most of the CLA preparations that have been investigated to date for biological activity, two CLA isomers are present in about equal concentrations: cis-9,trans-11 CLA, and trans-10,cis-12 CLA. The occurrence of these isomers in foods and their production by rumen microorganisms are discussed. Potential mechanisms of action as regards the effects of CLA on cancer and body composition are reviewed, including recent evidence that body composition changes are produced by the trans-10,cis-12 CLA isomer. Evidence is presented indicating that CLA may modulate cellular response to tumor necrosis factor-alpha (TNF- alpha). The mechanistic implications of this finding are considered.      

Altered white matter diffusion anisotropy in normal and preterm infants at term‐equivalent age

To investigate white matter (WM) development, voxelwise analyses of diffusion tensor MRI (DTMRI) data, acquired from 12 very preterm and 11 preterm infants with gestational ages (GA) ranging from 25 to 29 and 29 to 32 weeks, respectively, and 10 newborn normal term infants were performed. T₂ relaxation measures were also generated to assess brain water content. Compared with newborn term infants, very preterm infants were found to possess reduced fractional anisotropy (FA) within the frontal lobe, and a number of anterior and posterior commissural pathways. Preterm infants possessed reduced FA mainly within the posterior regions of the corpus callosum. Unexpectedly, we observed significantly reduced FA and increased T₂ within a number of corticospinal projections in the newborn term infants compared to the preterm groups. This finding may reflect increased water concentration and/or a lowering of FA due to the presence of crossing interhemispheric WM projections. These findings indicate that care should be taken when interpreting FA indices without knowledge of the possible effects of water concentration in the newborn infant brain. Magn Reson Med 60:761–767, 2008. © 2008 Wiley‐Liss, Inc.     

Atopy in parents of children dying with sudden infant death syndrome

36 parents of infants who had died suddenly did not differ in frequency of atopic symptoms, immediate skin tests, IgE, IgE antibody, immunoglobulin G, A, and M, or yeast opsonisation, from 36 matched controls, although atopy was common (about half had atopy in both groups.     

Value of cystography in urinary tract infections

Fifty-one children with a bacteriologically proven urinary tract infection had both an intravenous urogram (IVU) and a micturating cystogram. The IVU was normal in 35. Only 6 of these children showed reflux in the cystogram, affecting 7 of the 70 ureters at risk. Since reflux on its own does not cause renal damage, which occurs only with super-added infection, detection of reflux is not important providing the urine is kept sterile. We suggest that cystography be deferred providing the IVU is normal until recurrent infections occur while under hospital care, and, with this policy this unpleasant and sometimes hazardous investigation could be avoided in many children with a single urinary tract infection.     

Randomized phase II – study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer – PARC: study protocol [ISRCTN56652283]

Background

Pancreatic cancer is the fourth commonest cause of death from cancer in men and women. Advantages in surgical techniques, radiation therapy techniques, chemotherapeutic regimes, and different combined-modality approaches have yielded only a modest impact on the prognosis of patients with pancreatic cancer. Thus there is clearly a need for additional strategies. One approach involves using the identification of a number of molecular targets that may be responsible for the resistance of cancer cells to radiation or to other cytotoxic agents. As such, these molecular determinants may serve as targets for augmentation of the radiotherapy or chemotherapy response. Of these, the epidermal growth factor receptor (EGFR) has been a molecular target of considerable interest and investigation, and there has been a tremendous surge of interest in pursuing targeted therapy of cancers via inhibition of the EGFR.

Methods/design

The PARC study is designed as an open, controlled, prospective, randomized phase II trial. Patients in study arm A will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine infusions weekly over 4 weeks. Patients in study arm B will be treated with chemoradiation using intensity modulated radiation therapy (IMRT) combined with gemcitabine and simultaneous cetuximab infusions. After chemoradiation the patients receive gemcitabine weekly over 4 weeks and cetuximab infusions over 12 weeks. A total of 66 patients with locally advanced adenocarcinoma of the pancreas will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patient's enrolment.

Discussion

The primary objective of this study is to evaluate the feasibility and the toxicity profile of trimodal therapy in pancreatic adenocarcinoma with chemoradiation therapy with gemcitabine and intensity modulated radiation therapy (IMRT) and EGFR-targeted therapy using cetuximab and to compare between two different methods of cetuximab treatment schedules (concomitant versus concomitant and sequential cetuximab treatment). Secondary objectives are to determine the role and the mechanism of cetuximab in patient's chemoradiation regimen, the response rate, the potential of this combined modality treatment to concert locally advanced lesions to potentially resectable lesions, the time to progression interval and the quality of life.     

Expanding the therapeutic repertoire of epidermal growth factor receptor blockade: radiosensitization

Expression of epidermal growth factor receptor (EGFR) has been associated with radioresistance in cancer. Moreover, tumour cell recovery after irradiation paradoxically occurs, in part, as a result of activation of EGFR signalling by such treatment. A recent article by Huang, Li, Armstrong and Harari provides strong rationale for considering the anti-EGFR agent ZD1839 ('Iressa') as a radiosensitizing strategy. With the use of several in vitro and xenograft models of human squamous cell head and neck carcinoma, ZD1939 was shown to markedly improve radiotherapeutic response, with superior tumour inhibition and delayed tumour regrowth. Mechanisms underlying this effect included anti-proliferative and pro-apoptotic activity, with significant perturbation of tumour angiogenesis.     

The multifaceted roles of nitric oxide in cancer

The roles of nitric oxide (NO) in numerous disease states have generated considerable discussion over the past several years. NO has been labeled as the causative agent in different pathophysiological mechanisms, yet appears to protect against various chemical species such as those generated under oxidative stress. Similarly, NO appears to exert a dichotomy of effects within the multistage model of cancer. Chronic inflammation can lead to the production of chemical intermediates, among them NO, which in turn can mediate damage to DNA. Yet, NO also appears to be critical for the tumoricidal activity of the immune system. Furthermore, NO can also have a multitude of effects on other aspects of tumor biology, including angiogenesis and metastasis. This report will discuss how the chemistry of NO may impact the initiation and progression stages of cancer.      

Treatment of respiratory failure in an infant with bronchopulmonary dysplasia infected with respiratory syncytial virus using inhaled nitric oxide and high frequency ventilation

A 2-month-old, former 28-week premature infant with brochopulmonary dysplasia infected with respiratory syncytial virus was treated with nitric oxide and high frequency oscillatory ventilation after conventional therapy failed. Nitric oxide and high frequency oscillatory ventilation rapidly improved oxygenation allowing recovery without the need for extracorporeal membrane oxygenation. This treatment regimen should be considered as an option in high-risk infants with respiratory syncytial virus infection who meet extracorporeal membrane oxygenation criteria.     

Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis

Mutations in three different genes of phosphorylase kinase (Phk) subunits, PHKA2, PHKB and PHKG2, can give rise to glycogen storage disease of the liver. The autosomal-recessive, liver-specific variant of Phk deficiency is caused by mutations in the gene encoding the testis/liver isoform of the catalytic gamma subunit, PHKG2. To facilitate mutation detection and to improve our understanding of the molecular evolution of Phk subunit isoforms, we have determined the structure of the human PHKG2 gene. The gene extends over 9.5 kilonucleotides and is divided into 10 exons; positions of introns are highly conserved between PHKG2 and the gene of the muscle isoform of the gamma subunit, PHKG1. The beginning of intron 2 harbors a highly informative GGT/GT microsatellite repeat, the first polymorphic marker in the PHKG2 gene at human chromosome 16p11.2-p12.1. Employing the gene sequence, we have identified homozygous translation-terminating mutations, 277delC and Arg44ter, in the two published cases of liver Phk deficiency who developed cirrhosis in childhood. As liver Phk deficiency is generally a benign condition and progression to cirrhosis is very rare, this finding suggests that PHKG2 mutations are associated with an increased cirrhosis risk.      

55例主动脉窦瘤的外科治疗

目的：探讨先天性动脉窦瘤（ＣＡＳＶ）的外科治疗方法。方法：对５５例动脉窦行外科治疗,其中窦瘤切除修补术２２例（４０％）,窦瘤切除加房、室间事缺损修补２５例（４２％）,窦瘤切除加主动脉成形３例,窦瘤切除修补加主动脉瓣置换５例。结果：全组手术死亡２例,其中１例死于手术后急性肾功衰竭,另１例死于手术后纵隔感染致心脏大出血,余患者均痊愈出院,结论：心脏超声（ＵＣＧ）具有确诊和手术指导意义。窦瘤的破裂对心功