Experimental animal model and RNA interference: a promising association for bladder cancer research

Animal models are at the centre of laboratory bladder cancer (BC) research and at the same time, the bridge to the clinic. A new and very promising therapeutical approach is to silence abnormally up-regulated genes in cancer, through small interfering RNA (siRNA) molecules. Therapeutic use and success of siRNAs will largely depend on their efficient and safe in vivo delivery and on avoiding accidental off-target effects. Intravesical siRNA is a strategy which may be the best deliver option to surperficial BC like intravesical immunotherapy. Its direct action might allow a continuous intracellular exposure to effective siRNA concentrations. While the procedure of transurethral siRNA administration is promising for BC research allowing detection of new targets in BC therapy, the optimal intravesical carrier and the best target(s) to siRNA are to be determined.     

Effects of the use of oral contraceptives on hip and knee kinematics in healthy women during anterior stair descent

Purpose

Our aim was to evaluate the effects of the use of oral contraceptives (OC) on the hip and knee kinematics of healthy women during anterior stair descent.

Methods

Forty volunteers aged from 18 to 26 years were divided into two groups: 1—Group of women who had used OC for at least 3 months prior to evaluation (n = 20) and 2—Group of women who did not use OC (n = 20). The knee flexion/extension and abduction/adduction, hip flexion/extension, abduction/adduction and medial/lateral rotation excursions (degrees) were calculated for the dominant (supporting) limb during anterior stair descent. T tests for independent samples were used to compare the kinematic differences between the groups (α = 0.05).

Results

No significant difference was verified between the groups regarding the maximum excursion of knee flexion (n.s.) and abduction (n.s.) or hip flexion (n.s.), adduction (n.s.) and medial rotation (n.s.). When considering the knee flexion at 50°, no significant difference was verified between the groups regarding the excursion of knee abduction (n.s.) or hip flexion (n.s.) adduction (n.s.) and medial/lateral rotation (n.s.).

Conclusion

These results suggest that the use of OC does not influence the hip and knee kinematics during anterior stair descent. Therefore, the role of this medication as a protective factor against anterior cruciate ligament injuries remains questionable.

Level of evidence

III.     

Prognosis in patients with left bundle branch block and normal dipyridamole thallium-201 scintigraphy

Background  The presence of complete left bundle branch block (LBBB) is commonly associated with a poorer prognosis, especially in patients with coronary artery disease (CAD). In the general population with suspected CAD and normal intraventricular conduction, a normal dipyridamole-thallium scintigraphy is a strong marker of a favorable outcome. Objective  Our objective was to assess the prognosis in patients with LBBB and a normal dipyridamole thallium-201 scintigram. Population and methods  Patients with complete LBBB and normal myocardial perfusion on dipyridamole SPECT thallium-201 scintigraphy performed in our center for suspected CAD between 1988 and 1995 were monitored for clinical events. Results  Sixty-nine patients (36 women and 33 men) with a mean age of 59 years (range 56 to 61) were monitored for a mean period of 33 months (range 25 to 35). During this period, 4 patients had unstable angina, 2 of whom underwent myocardial revascularization. There were no deaths or myocardial infarction. All events occurred at least 2 years after the thallium-201 scintigraphy. Conclusion  The presence of a normal myocardial perfusion with dipyridamole thallium-201 scintigraphy in this group of patients with suspected CAD and LBBB was associated with a very good prognosis, a low rate of clinical events occurring only 2 years after the myocardial scintigraphy, and no hard events.     

Clinical impact of drug-eluting stents in changing referral practices for coronary surgical revascularization in a tertiary care center

BACKGROUND: The long-term benefits of angioplasty are limited by the occurrence of restenosis. Drug-eluting stents with a projected restenosis rate of close to 0% are soon to become available. The short- and long-term consequences of this advance to the cardiac surgical volume remain unclear. METHODS: A total of 196 consecutive coronary angiograms and medical records of patients referred for coronary bypass surgery were reviewed. Considering the hypothetical premise of having drug-eluting stents with a near zero restenosis rate, we reviewed each case to determine if surgical revascularization was still the preferred option for revascularization. RESULTS: The mean age was 60 (+/-10.6) years. Seventy-two percent of patients were male. Considering the availability of drug-eluting stents 154 (79%) would still have been sent to surgery, representing a 21% decrease in the number of surgical revascularizations. Angiographic characteristics predicting coronary bypass revascularization were the presence of chronic total occlusion (odds ratio [OR]: 9.1; confidence interval [CI]: 2.1 to 39), left main coronary artery stenosis (OR: 9.6; CI: 1.27 to 73), and need for valvular surgery (OR: 7.38; CI: 1.3 to 157). The most common predictors of a change in clinical management from surgical to percutaneous revascularization if drug-eluting stents were available were diffuse coronary narrowing (OR: 15.78), restenotic lesions (OR: 27.86), and small coronary arteries (OR: 26). CONCLUSIONS: Drug-eluting stents may have a significant impact on cardiac surgery volume (approximately a 21% decrease in our center). It may also direct patients with small vessels, diffuse narrowing, or restenotic lesions and diabetic patients to percutaneous therapy.     

COL1A1 Sp1-binding site polymorphism as a risk factor for genital prolapse

The objective of this study was to verify the possible association between the Sp1-binding site polymorphism and genital prolapse. A case–control study was conducted in 107 patients with stages III and IV genital prolapse. The control group included 209 women with stages 0 and I. The polymorphism of type I collagen Sp1-binding site was identified by amplification of the first intron of the COL1A1 gene. We did not find differences in the prevalence of the GT and TT genotypes between the groups (p = 0.34), even when we grouped patients with at least one polymorphic allele (GT and TT) and compared them with patients without the polymorphic allele (GG; p = 0.17) The presence of at least one vaginal delivery, family history for prolapse, and macrosomatic fetus were independent risk factors for prolapse. In conclusion, the COL1A1 Sp1-binding site was not significantly associated with genital prolapse among our study subjects.     

Hepatitis C Virus Infection After Renal Transplantation

Hepatitis C virus (HCV) infection is the main cause of liver disease after renal transplantation. Most patients have seroconverted on dialysis to positive RNA. The viral load increases during immunosuppressive therapy. The risk of developing chronic liver disease is related to the histopathologic findings, duration and severity of the disease, immunosuppression, and transplantation time. Hepatitis C virus infection can predict onset, of proteinuria and diabetes. We studied 868 patients who received renal transplants between (1987 and 2006), of whom 18.7% were seropositive for HCV. We observed a higher rate of HCV-seropositive patients related to the duration of hemodialysis therapy. Of the HCV seropositive patients, 77% had received renal allografts before 1998. There was no difference between the sexes; however, the HCV positive patients were younger. Polymerase chain reaction tests results were positive in 91.6% of the patients with HCV antibodies. The prevalence of diabetes was greater among HCV positive patients, as was as the persistence of proteinuria. Cryoglobulins were positive in 30.8%. The incidence of acute rejection episodes in the first year was similar between groups. Of the HCV-positive patients, 80.2% were treated with cyclosporine, most patients continued this therapy throughout the study. We observed no significant difference in mortality end graft survival rate between the two groups. However, renal function differed significantly at some points during the evolution of the clinical course. Renal transplantation is still the best treatment option in patients with chronic renal disease.     

Immediate skin-sparing mastectomy reconstruction with deep inferior epigastric perforator (DIEP) flap. Technical aspects and outcome

Although breast reconstruction with deep inferior epigastric perforator (DIEP) flap is a well-described technique, few publications have specifically reported the technical aspects and the outcome following skin-sparing mastectomy (SSM). The aim of this study is to analyse the feasibility of its immediate application and to describe the operative planning, outcome and complications after SSM. 27 patients underwent 30 DIEP flap breast reconstructions with all immediate and 3 bilateral. Mean time of follow-up was 29 months. Breast skin, DIEP Flap and donor-site complications were evaluated. Information on patient satisfaction was collected. 70% had tumors measuring 2 cm or less (T1) and 74% were stage 0 and I according to American Joint Committee on Cancer. Breast skin complications occurred in 7.4%, all represented by small areas of skin necrosis. Partial losses were observed in two (7.4%) patients (less than 15% of total area) and total DIEP loss in 1 (3.7%). Donor-site complications represented by bulging occurred in only one patient (3.7%). The majority of patients were either very satisfied or satisfied. One local recurrence was observed. All complications except 2 were treated by a conservative approach. The DIEP flap is a reliable technique for SSM reconstruction. Success depends on patient selection, coordinated planning with the oncologic surgeon and careful intraoperative and postoperative management. The main advantage is that patients can safely undergo dual procedures with the added aesthetic benefits in breast and abdominal donor site.     

Superficial femoral artery recanalization with self-expanding nitinol stents: long-term follow-up results.

PURPOSE: Since long-term patency and device integrity of nitinol stents in SFA lesions are not well studied, we examined clinical outcome, patency and device integrity after stenting long lesions using a standardized implantation technique. METHODS: Between 2001 and 2006, 59 patients (74 lesions) were treated with the same nitinol self-expandable stent (Zilver, Cook, USA) and technique for SFA recanalization. Clinical charts and imaging were retrospectively reviewed for patency (primary and assisted-primary), and device integrity. RESULTS: Patients were 74.5 (10.9) years old (range 49 to 93), 64% male, 42% diabetic, 62% hypertensive and 67% current or former smokers. Lesions were 23% TASC B, 16% TASC C, or 61% TASC D. Mean recanalization length was 19 cm (range 3 to 53). Mean number of stents per patient was 2.8 (total 210). Mean follow-up time was 2.4 years (range 3 days to 4.8 years). Kaplan-Meier estimates for primary patency rates were 90%, 78%, 74%, 69%, and 69% at 1, 2, 3, 4 and 4.8 years, respectively. Ten restenoses at a mean of 500 (388) days (1-1251 days) were successfully recanalized. The assisted primary patency rates were 96%, 90%, 90%, 90% and 90% at 1, 2, 3, 4 and 5 years, respectively. Six complete occlusions could not be reverted by a second recanalization procedure, and were treated by surgical bypass (1 case), amputation (3 cases), or medical management (2 cases). One (1.04%) Class II stent fracture was noted. CONCLUSIONS: SFA recanalization with a standardized implantation technique and nitinol stents provides good long-term primary and assisted-primary patency.     

Linking the Disabilities of Arm, Shoulder, and Hand to the International Classification of Functioning, Disability, and Health.

The objective of this study was to explore whether the items from a specific outcome measure, that is, Disabilities of the Arm, Shoulder, and Hand (DASH), for quantifying limb symptoms and functions in musculoskeletal disorders fit into the framework of the International Classification of Functioning, Disability and Health (ICF). All DASH items were compared to the ICF according to eight linking rules. Two groups of researchers performed the linking independently, and the results were compared by correlation. The 30 DASH items and four items from the optional modules were linked to 63 ICF categories and 11 chapters: 15 categories belong to the ICF body functions component and 48 to the activities and participation component. There were no items coded under the components body structure or environmental factors. Kappa index showed an agreement of 0.73 (p<0.001). The results showed that the content of the DASH does link well with the ICF framework. Clinicians and researchers must attend to the fact that certain domains and categories from the ICF are not covered by the DASH. Limitations of the instrument may be overcome by simultaneously using other instruments that address the intended content.     

hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Background The aim of this study was to search for mutations in the humanmutS homolog 2 (hMSH2) and humanmutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC). Methods The families were grouped according to the following clinical criteria: Amsterdam I or II; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing. Results Ten mutations were detected (10 of 25 [40%]); of nine different mutations, seven were novel. ThehMLH1 gene had a higher mutation detection rate thanhMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in thehMLH1 gene and four in thehMSH2 gene. Conclusions ThehMLH1 gene had a higher mutation detection rate thanhMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.