Differing effects of breast cancer 1, early onset (BRCA1) and ataxia‐telangiectasia mutated (ATM) mutations on cellular responses to ionizing radiation

Purpose: The ataxia‐telangiectasia mutated (ATM) gene encodes a protein kinase, the activation of which is an early event in the cellular response to ionizing radiation. One of the many substrates of ATM is BRCA1 (breast cancer 1, early onset gene), which has been associated with susceptibility to breast and ovarian cancer, and has been implicated in DNA repair processes. Various cellular responses to radiation were analysed in cells with mutations in ATM or BRCA1 in an attempt to clarify which effects of ATM can be mediated through BRCA1.

Materials and methods: The response to radiation of cells with mutations in ATM or BRCA1 was examined, as were BRCA1‐mutant tumour cells transfected with an exogenous wild‐type BRCA1 allele. Assays included cell‐survival curves, studies of potentially lethal damage repair, measurement of chromosomal aberrations and of G1 arrest, and Western blot analysis of lysates of irradiated cells to determine the phosphorylation of the product of the human Mdm2 gene (HDM2).

Results: Both ATM and BRCA1 mutations were associated with sensitivity to ionizing radiation, deficient repair of potentially lethal damage and markedly increased chromosomal aberrations. A BRCA1‐mutated tumour cell line HCC1937, like ATM mutant cells, did not exhibit a normal G1 arrest but, unlike ATM mutant cells, did exhibit phosphorylation of HDM2. Expression of wild‐type BRCA1 in HCC1937 cells partially restored radioresistance, restored repair of potentially lethal damage and markedly reduced radiation‐induced chromosomal aberrations. G1 arrest, however, was not restored by expression of BRCA1.

Conclusions: The results are consistent with a model in which ATM phosphorylation of BRCA1 regulates DNA repair functions, particularly those involved in potentially lethal damage repair and chromosomal integrity, but not other aspects of the cellular response to radiation such as G1 cell cycle arrest. To the authors' knowledge, this is the first demonstration of the ability of exogenously expressed BRCA1 to restore the ability to perform potentially lethal damage repair and maintain chromosomal integrity in irradiated cells.     

Embolization of high flow arteriovenous malformations: experience with use of superabsorbent polymer microspheres

PURPOSE: To determine efficacy, safety, and requirements for adjunctive embolization or surgery in the treatment of symptomatic arteriovenous malformations (AVMs) with superabsorbent polymer microsphere (SAP-MS) particles. MATERIALS AND METHODS: SAP-MS particles (sodium acrylate and vinyl alcohol copolymer) are nonbiodegradable spheres with a precisely calibrated diameter. SAP-MS particles swell by absorbing fluids and become soft and deformable. Twenty-five patients (16 men, nine women; mean age, 32 y; range 12-66 y) with symptomatic facial (n = 5), upper- (n = 8) and lower- (n = 12) extremity AVMs were treated primarily (n = 23) or preoperatively (n = 2) by transarterial embolization (TAE) treatment with use of SAP-MS particles. Direct puncture embolization (DPE; n = 4) and/or surgical intervention (n = 5; ie, skin graft, resection, or amputation) were required. Surgical specimens from the resected (n = 2) and the amputated (n = 2) patients were evaluated histologically. Follow-up study, including clinical findings and imaging studies, was performed at intervals ranging from 3 months to 1 year. Clinical outcome was evaluated retrospectively, depending on the subjective improvement of symptoms and signs, according to the medical records. RESULTS: Seventy-two TAEs (range, 1-11; mean, 2.8) and 12 DPEs (range, 1-3; mean, 2.4) were performed during the mean follow-up period of 38 months (range, 7-110 mo). Twenty patients (80%) experienced symptom improvement by embolotherapy alone (n = 17) or in combination with surgery (n = 3). One lip and two finger AVMs were totally removed by surgical excision or amputation after TAE treatment. In diffuse upper- (n = 1) and lower- (n = 1) extremity AVMs, the symptoms were uncontrolled. No nerve injury or skin necrosis was observed after TAE treatment with SAP-MS particles. Mucosal necrosis was induced by DPE with ethanol in one patient. Histologically, SAP-MS particles penetrated intralesional vessels and conformed to the vessel lumen, resulting in tight vessel occlusion. Minimal perivascular reaction was observed. CONCLUSION: SAP-MS particles were used safely in TAE treatment of AVM. TAE treatment with use of SAP-MS particles was suitable for certain symptomatic AVMs, but diffuse AVMs remain a challenge and a combination of alternative methods will be necessary for further strategy.     

Different therapeutic modalities for treatment of melasma

Background Chemical peels and topical depigmenting agents have become a popular modality in the treatment of melasma. Aims To compare the clinical efficacy of trichloroacetic acid peel 20%vs. Jessner’s solution peel vs. the topical mixture of hydroquinone 2% and kojic acid. Patients and methods Forty five patients with melasma were randomly assigned into three groups of fifteen patients each. Group A received Jessner’s solution peel, group B received trichloroacetic acid peel 20%, and group C received topical hydroquinone 2% and kojic acid. All patients were seen in follow‐up period after 16 weeks; clinical evaluation using Melasma Area and Severity Index (MASI) score and photography were recorded before and after treatment and after 16 weeks. Results There was a decrease in MASI score in all three groups after treatment and after follow‐up period but after treatment MASI score was statistically significantly lower in group A than group C (P = 0.01), and it was also statistically significantly lower in group B than group C (P < 0.001) but there was no statistically significant difference between groups A and B. After the follow‐up period, MASI score was statistically significantly lower in group A than group C (P < 0.001), statistically significantly lower in group B than group C (P < 0.001), and statistically significantly lower in group B than group A (P = 0.035). The statistical analysis was done through one‐way anova followed by least significant difference (LSD). Conclusion Trichloroacetic acid 20% showed better results than Jessner’s solution as peeling agent and hydroquinone 2% with kojic acid as a topical agent in the treatment of melasma.     

The evolution of mammaplasty

Mammaplasty is now a very common operation. However, it took nearly a century from the first attempts to the latest evolution of techniques improving safety and providing long-lasting results and minimal scarring. As with any surgical technique, it has pitfalls and complications, but a good knowledge of anatomy and rigorous operative technique makes it possible to obtain excellent results in the majority of cases.     

Effectiveness and safety of ultrasound-guided foam sclerotherapy for recurrent varicose veins: immediate results.

PURPOSE: To evaluate the effectiveness and safety of ultrasound-guided foam sclerotherapy in treating recurrent varicose veins. METHODS: Between July 2003 and January 2005, 38 outpatients (25 women; median age 59 years, interquartile range 53.5-66.0) with recurrent varicose veins in 45 legs were treated. Ultrasound was used to identify sites of reflux. The Tessari method was used to produce foam using 3% sodium tetradecyl sulphate; up to 6 mL of foam was injected per session under ultrasound control. Results are shown as median (interquartile range). RESULTS: A single sclerotherapy session was adequate in 26 (58%) legs. In 87% of all legs, complete elimination of both varicose veins and all reflux points was achieved. A positive association between the amount of injected foam and CEAP class (r=0.45, p=0.002) and venous clinical severity score (r=0.37, p=0.012) was found. There was a trend for more sclerotherapy sessions [median 2 (1-2)] in legs with incomplete saphenofemoral junction/ great saphenous vein (GSV) ligation or accessory GSV (n=16) to achieve varicose vein ablation versus legs with other primary sites of reflux [median 1 (1-2), p=0.12]. There were no instances of deep vein thrombosis or systemic complications; superficial thrombophlebitis occurred in 6 (8.2%) of the 73 injection sessions. Legs with proximal reflux due to previous incomplete ligation or fed by an incompetent pelvic vein experienced superficial thrombophlebitis more frequently (4/12, 33%) than legs without proximal reflux [1/33 (3%); OR 16, 95% CI 1.6-164, p=0.014]. CONCLUSION: In most patients, ultrasound-guided foam sclerotherapy is a safe treatment for recurrent varicose veins, with an excellent immediate result. However, the presence of proximal reflux may decrease the immediate results and predispose to superficial thrombophlebitis.     

The role of intraoperative radiotherapy (IORT) in the management of patients with pancreatic and periampullary cancer: A single center experience

Background

In spite of the advances in modern surgery, the outcome for patients suffering from pancreatic adenocarcinoma or periampullary adenocarcinoma is still bad. Recently, introperative radiotherapy (IORT) was introduced into the multimodality management approach to improve both tumor control and patient’ survival.

Liposomal Bupivacaine Mixture Has Similar Pain Relief and Significantly Fewer Complications at Less Cost Compared to Indwelling Interscalene Catheter in Total Shoulder Arthroplasty

Background

The efficacy and costs of indwelling interscalene catheter (ISC) and liposomal bupivacaine (LBC), with and without adjunctive medications, in patients with primary shoulder arthroplasty are a source of current debate.

Glargine Insulin Use Versus Continuous Regular Insulin in Diabetic Surgical Noncritically Ill Patients Receiving Parenteral Nutrition: Randomized Controlled Study

Background: Hyperglycemia is a major complication of parenteral nutrition (PN). Guidelines for hyperglycemia management in noncritically ill patients cite basal insulin administration but do not recommend a regimen. The GLUCOSE‐in‐PN study aimed to compare the efficacy of glargine insulin versus continuously infused regular insulin in PN (RI‐in‐PN) to achieve glycemic control in noncritically ill surgical patients with diabetes who were receiving PN. Methods: This prospective randomized open‐label study was conducted at King Faisal Specialist Hospital and Research Centre. Noncritically ill surgical patients with diabetes who were receiving PN were randomized to receive basal glargine insulin or RI‐in‐PN on day 4 of PN support. Mean blood glucose levels were compared on study days 5–9. The percentages of blood glucose measurements at goal were compared between groups. Results: Sixty‐seven PN treatment episodes were analyzed. There were no statistically significant differences in mean glucose levels between groups on any study day (P > .1). Overall glycemic control rates were 52.24% (glargine insulin) and 47.76% (RI‐in‐PN; P = .06). A significantly higher percentage of hyperglycemia was observed on day 5 for glargine insulin versus RI‐in‐PN (22.39% vs 5.97%, P = .0059). Blood glucose measurements indicated 6 hypoglycemic events: 2 for glargine insulin (5.7%) and 4 for RI‐in‐PN (11.4%; P > .1). Conclusion: Both glargine insulin and RI‐in‐PN are effective basal insulin modalities for blood glucose control in noncritically ill surgical patients with diabetes who are receiving PN. Uncontrolled hyperglycemic events occurred more frequently with glargine insulin, and the rate of hypoglycemia was acceptable for both regimens.     

Interleukin-17 (IL-17) Expression Is Reduced during Acute Myocardial Infarction: Role on Chemokine Receptor Expression in Monocytes and Their in Vitro Chemotaxis towards Chemokines

The roles of immune cells and their soluble products during myocardial infarction (MI) are not completely understood. Here, we observed that the percentages of IL-17, but not IL-22, producing cells are reduced in mice splenocytes after developing MI. To correlate this finding with the functional activity of IL-17, we sought to determine its effect on monocytes. In particular, we presumed that this cytokine might affect the chemotaxis of monocytes important for cardiac inflammation and remodeling. We observed that IL-17 tends to reduce the expression of two major chemokine receptors involved in monocyte chemotaxis, namely CCR2 and CXCR4. Further analysis showed that monocytes pretreated with IL-17 have reduced in vitro chemotaxis towards the ligand for CCR2, i.e., MCP-1/CCL2, and the ligand for CXCR4, i.e., SDF-1α/CXCL12. Our results support the possibility that IL-17 may be beneficial in MI, and this could be due to its ability to inhibit the migration of monocytes.