Hypofractionated radiation therapy for invasive breast cancer: From moderate to extreme protocols

Adjuvant irradiation is the standard treatment after breast conservative surgery. Normofractionated regimen with an overall treatment time of 5 to 6 weeks is often considered as a limiting factor for irradiation compliance. In order to answer this issue, moderate and more recently extreme hypofractionated protocols appeared. We report here oncological outcomes and toxicity of hypofractionated breast irradiation. After defining the frame of moderate and extreme hypofractionated breast irradiations based on overall treatment time, patient selection criteria were listed. According to their levels of proof, the results of moderate and extreme hypofractionated breast irradiation were analysed. Overall treatment time for moderate hypofractionated breast irradiation ranged from 3 to 4 weeks, while for extreme hypofractionated breast irradiation, it was less than 1 week. For moderate hypofractionated breast irradiation, whole breast irradiation was currently performed with or without lymph node irradiation. Moderate hypofractionated breast irradiation has proven to be as safe and as efficient as normofractionated breast irradiation with level IA evidence. For extreme hypofractionated breast irradiation, phase III randomized trials confirmed that accelerated partial breast irradiation was non-inferior in terms of local control compared to normofractionated whole breast irradiation (with external beam radiation therapy and multicatheter brachytherapy), with similar acute and late toxicity. While the use of intraoperative breast irradiation remains under debate, new very accelerated partial breast irradiation (overall treatment time not exceeding 2 days) protocols emerged with encouraging results. Accelerated partial breast irradiation is warranted for extreme hypofractionated breast irradiation and is indicated for low-risk breast cancers. Moderate and extreme hypofractionated breast irradiation regimens are validated and can be routinely proposed according to patient selection criteria.     

Strategies to enhance transductional efficiency of adenoviral-based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie-adenovirus receptor (CAR). We explored CAR-independent transduction to fibroblasts and keratinocytes using a panel of CAR-independent fiber-modified Ads to determine enhancement of infectivity. These fiber-modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV-2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber-modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, alpha upsilon integrin, syndecan-1, and glypican-1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of alpha upsilon integrin, syndecan-1 and glypican-1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan-1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber-modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.     

Experimental arthritis induced by a clinical Mycoplasma fermentans isolate

Background  

Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints.     

氟喹诺酮类药物不良反应168例分析

0 引言 随着氟喹诺酮类药物在临床的广泛应用，有关其应用所致不良反应的报道也日趋增多，我们通过对1990／2003年我院氟喹诺酮类药物不良反应情况报告如下，供临床参考。     

Predicting Stricture in Morbidly Obese Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass: A Logistic Regression Analysis

Gastrojejunostomy stricture after Roux-en-Y gastric bypass occurs in 3 to 27% of morbidly obese patients in the USA. We questioned whether preoperative patient characteristics, including demographic attributes and comorbid disease, might be significant factors in the etiology of stricture. In this study from November 2001 to February 2006 (51 months), at a high-volume bariatric center, of the 1,351 patients who underwent laparoscopic gastric bypass, 92 developed stricture (6.8%). All but two were treated successfully by endoscopic dilation. All patients stopped nonsteroidal anti-inflammatory medications 2 weeks prior to surgery and did not restart them. The operative procedure included the use of a 21-mm transoral circular stapler to create the gastrojejunostomy; the Roux limb was brought retrogastric, retrocolic. In an effort to reduce our center’s stricture rate, late in the study, U-clips used at the gastrojejunostomy were replaced by absorbable sutures, and postoperative H₂ antagonists were added to the treatment protocol. The change to absorbable polyglactin suture proved to be significant, resulting in a lower stricture rate. The addition of H₂ antagonists showed no significant effect. Following the retrospective review of the prospective database, univariate and multivariate logistic regression analyses identified factors associated with the development of stricture. Gastroesophageal reflux disease and age were each shown to be statistically significant independent predictors of stricture following laparoscopic gastric bypass. Presented at the 2006 Annual Meeting of the Society for Surgery of the Alimentary Tract, May 20–24, Los Angeles, CA (poster presentation).     

Microbiology of adult cellulitis

Needle aspiration of cellulitis sites is commonly advocated to assist in the identification of causative organisms. Twenty-five nondiabetic, adult patients with a clinical diagnosis of cellulitis had site aspirations and blood cultures obtained before antibiotic therapy was initiated. Site cultures were positive in 6 of 25 patients. Blood cultures were positive in 4 of 25 patients. All organisms except one (Enterobacter agglomerans) were staphylococci or streptococci. The gram-negative bacilli were not believed to be a pathogen based on the patient's prompt response to nafcillin. In adult patients who do not have complications, the use of needle aspiration was not supported. Empiric treatment of cellulitis aimed at gram-positive cocci appears to be sufficient.     

Distribution and function of cholinergic receptors in the sheep detrusor muscle

The distribution of cholinergic nerve fibres, as well as the characterization of the muscarinic receptors responsible for the contraction, were determined in the detrusor smooth muscle of the sheep. The results obtained demonstrated a rich presence of acetylcholinesterase (AChE)-positive fibres distributed throughout the bladder body forming dense neuromuscular, subepithelial and perivascular plexuses. Furthermore, intramural ganglia containing AChE-positive cell bodies were identified. However, acetylcholine and carbachol induced a dose-dependent contraction of detrusor smooth muscle. The effect observed with carbachol was competitively antagonized by atropine (pA2: 8.94), pirenzepine (pA2: 7.38), AF-DX 116 (pA2: 7.35), 4-DAMP (pA2: 9.26) and hexahydroxiladifenidol (HHSiD) (pA2: 8.49). The pA2 value for pirenzepine is intermediate between M1- and M2-receptors which suggests that this antagonist does not act on M1- or M2-receptors, but that it does on M3-receptors. The pA2 value for AF-DX 116 is consistent with the presence of M2-receptors in this tissue. Moreover, the pA2 values obtained for both 4-DAMP and HHSiD are in agreement with the presence of M3-receptors, due to the lack of effect of pirenzepine on M1-muscarinic receptors. These results indicate the existence of a rich parasympathetic innervation in the sheep detrusor muscle and suggest that its contraction could be mediated by the stimulation of muscarinic receptors belonging to both M3- and M2-subtypes.