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.     

Evaluation of the chronic toxicity and oncogenicity of N,N-diethyl-m- toluamide (DEET)

Chronic toxicity and/or oncogenicity studies were conducted in rats, mice, and dogs with the insect repellent DEET. DEET was mixed in the diet and administered to CD rats for two years at concentrations that corresponded to dosage levels of 10, 30 or 100 mg/kg/day for males and 30, 100, or 400 mg/kg/day for females; to CD-1 mice for 18 months at dosage levels of 250, 500, or 1000 mg/kg/day; and to dogs for one year, via gelatin capsules, at dosage levels of 30, 100, or 400 mg/kg/day. In the rodent studies, each group consisted of 60 animals of each sex, and two concurrent independent control groups, each containing 60 animals/sex were included in each study. Each group in the dog study consisted of four male and four female dogs and one control group was included in the study. Treatment-related effects were observed at the highest dose level in all three studies. For rats, the effects included decreases in body weight and food consumption and an increase in serum cholesterol in females only. In mice, the effects observed were decreases in body weight and food consumption in both sexes. The effects observed in dogs included increased incidences of emesis and ptyalism, and levels of transient reduction in hemoglobin and hematocrit, increased alkaline phosphatase (males only), decreased cholesterol, and increased potassium. One male dog in the high-dose group also exhibited ataxia, tremors, abnormal head movements, and/or convulsions on several occasions during the study. The highest no- observed-effect levels (NO-ELs) for rats, mice and dogs were determined to be 100, 500, and 100 mg/kg/day, respectively. No specific target organ toxicity or oncogenicity was observed in any of the studies.      

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