Progressive resistance training and nutrition in renal failure.

Nutrition and exercise are an integral part of the medical management of many chronic and complex conditions. They are interrelated and share many common metabolic pathways that may affect disease processes and their management. In nephrology, nutritional interventions have been relatively well studied and are recommended in many evidence-based clinical practice guidelines for managing people with chronic kidney disease (CKD). Over the past 20 years, growing evidence has suggested that aerobic exercise interventions are efficacious, and that the rationale for progressive resistance training (PRT) is strong, particularly in this population, despite a more limited evidence base to date. In the small number of clinical trials that have included patients with CKD, PRT programs have proved safe, feasible to administer, and efficacious. They have been shown to improve clinical, physical, and functional outcomes.     

The Distally Based Sural Artery Flap for Ankle and Foot Coverage

The sural artery flap is a distally based fasciocutaneous flap that has many advantages to offer for coverage in the foot and ankle area. It has the largest arc of rotation of all the regional flaps and does not require sacrifice of any major artery, and moderate-to-large-sized defects can be covered adequately. The dissection technique is simple, and donor site morbidity is minimal. We report our experience with 17 cases. Age range was from 13 to 56 years. Ten (59%) defects were posttraumatic, 3 (17%) were related to reconstructive surgery of the foot or tendon Achilles', 2 (11%) resulted from tumor resection, and 1 each were from infection and gunshot wound. The smallest flap was 6 x 4 cm and the largest was 15 x 12 cm, with the average size being 11 x 7.5 cm. In 5 cases, the donor site was closed primarily, and in other cases, split-thickness skin graft was needed. The short saphenous vein was included in the pedicle in all cases. There was no incidence of complete flap necrosis. Follow-up ranged from 3 to 30 months. Two cases (12%) developed partial superficial necrosis. In 1 case, there was partial wound dehiscence that needed debridement and repair. Another case had postoperative discharge, which subsided after removal of the calcaneal plate. None of the patients complained of any functional problem related to loss of sensation along the lateral border of the foot. The sural island flap is a reliable, safe, and easy method of providing soft tissue coverage in the area of the foot and ankle.     

Effect of once-daily fluticasone furoate nasal spray on nasal symptoms in adults and adolescents with perennial allergic rhinitis.

BACKGROUND: Intranasal corticosteroids are recommended as first-line therapy for the treatment of allergic rhinitis. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of allergic rhinitis. OBJECTIVE: To compare the efficacy and safety of intranasal fluticasone furoate with those of vehicle placebo nasal spray in adult and adolescent patients with perennial allergic rhinitis (PAR). METHODS: After screening (7-14 days), patients 12 years and older with confirmed PAR were randomized to receive fluticasone furoate, 110 microg once daily, or placebo once daily intranasally for 4 weeks in this double-blind, multicenter study. The primary end point was mean change from baseline during the entire treatment period in daily reflective total nasal symptom score (rTNSS), recorded on diary cards by patients, using a 4-point categorical scale. RESULTS: The mean reduction from baseline during the treatment period in daily rTNSS was significantly greater in fluticasone furoate recipients than in placebo recipients (P = .005). This finding was supported by significantly greater mean reductions in morning rTNSS and evening rTNSS (P = .004 and P = .011, respectively). A significantly greater mean reduction in instantaneous morning predose TNSS with fluticasone furoate compared with placebo (P = .006) confirmed the efficacy of once-daily administration. Fluticasone furoate was also significantly more effective than placebo in overall response to therapy (P = .005). CONCLUSIONS: Fluticasone furoate nasal spray, 110 microg once daily, effectively relieved nasal symptoms of PAR in adults and adolescents 12 years and older.     

Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.     

A mouse model of spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease, caused by the expansion of a trinucleotide repeat (TNR) in exon 1 of the androgen receptor (AR) gene. This disorder is characterized by degeneration of motor and sensory neurons, proximal muscular atrophy, and endocrine abnormalities, such as gynecomastia and reduced fertility. We describe the development of a transgenic model of SBMA expressing a full-length human AR (hAR) cDNA carrying 65 (AR(65)) or 120 CAG repeats (AR(120)), with widespread expression driven by the cytomegalovirus promoter. Mice carrying the AR(120) transgene displayed behavioral and motor dysfunction, while mice carrying 65 CAG repeats showed a mild phenotype. Progressive muscle weakness and atrophy was observed in AR(120) mice and was associated with the loss of alpha-motor neurons in the spinal cord. There was no evidence of neurodegeneration in other brain structures. Motor dysfunction was observed in both male and female animals, showing that in SBMA the polyglutamine repeat expansion causes a dominant gain-of-function mutation in the AR. The male mice displayed a progressive reduction in sperm production consistent with testis defects reported in human patients. These mice represent the first model to reproduce the key features of SBMA, making them a useful resource for characterizing disease progression, and for testing therapeutic strategies for both polyglutamine and motor neuron diseases.     

Human leukocyte interferon-α in cream,for the treatment of genital warts in asian women a placebo-controlled,double-blind study

The purpose of this double-blind, placebo-controlled study was to determine and compare the clinical efficacy and tolerance of human leukocyte -interferon (incorporated 2 × 10⁶ IU/g) in hydrophilic cream to cure genital warts. Preselected Asian female patients (n=150) aged 18–40 years (mean 22.5), with the clinical and biopsy-confirmed diagnosis of genital warts (mean 2.64), predominantly flat vaginal condylomas, were randomly allocated to 3 parallel groups. Each patient was given a coded tube containing 80 g placebo/active preparation with a graduated applicator. Patients were instructed to inject 6 g of the either alloted placebo/active cream deep into the vagina thrice a day for 3 consecutive days (group A) or 4 consecutive days (group B) per week, and if not cured the same treatment was extended to 3 more weeks (maximum 4 weeks active treatment). To assess the clinical efficacy patients were examined on a week-to-week basis. A total clearance of warts (biopsy-confirmed) was evaluated as a complete cure. Patients cured during the treatment were spared further treatment and were requested to visit us after 16 weeks for relapse control. As for the remaining patients, empty tubes were collected, and similarly coded replacement tubes were given for further treatment (in total 588 tubes were used). By the end of the treatment 57.2% lesions (227/397) were eliminated in all the groups: 48% patients in group A, 90% patients in group B, and 10% patients in placebo groups taken as completely cured. Of the 150 patients 128 (85.3%) did not complain of any drug-related adverse symptoms. Transitory increase in body temperature (mean 38.4°C), accompanied by headache (14.6%) and generalized itching (6.6%) were the most frequently reported side effects; however, treatment was well tolerated by all the patients, and there were no dropouts. Our findings indicate that clinical efficacy is dose dependent, that is, the results of group B were significantly superior to that of group A (P < 0.05). Of the 49.3% cured patients (74/150) followed up for 6 months (monthly basis) seven had a relapse, and none had reinfection. It is concluded that clinical efficacy of leukocyte interferon-a to cure genital warts is dose dependent. These results further support the view that leukocyte interferon-a incorporated in hydrophilic cream can be considered a reliable, safe, and home-based treatment to cure vulvar and vaginal warts.Abbreviation HPV human papillomavirus     

A novel tissue engineered three-dimensional in vitro colorectal cancer model

The interactions of cancer cells within a solid mass with the surrounding reactive stroma are critical for growth and progression. The surrounding vasculature is recruited into the periphery of the growing tumour to supply cancer cells with nutrients and O₂. This study focuses on developing a novel three-dimensional (3-D) in vitro biomimetic colorectal cancer model using colorectal cancer cells and connective tissue cells. The 3-D model comprises a dense artificial cancer mass, created by partial plastic compression of collagen type I containing HT29 colorectal cancer cells, nested in a non-dense collagen type I gel populated by fibroblasts and/or endothelial cells. HT29 cells within the dense mass proliferate slower than when cultured in a two-dimensional system. These cells form tumour spheroids which invade the surrounding matrix, away from the hypoxic conditions in the core of the construct, measured using real time O₂ probes. This model is also characterized by the release of vascular endothelial growth factor (VEGF) by HT29 cells, mainly at the invading edge of the artificial cancer mass. This characterization is fundamental in establishing a reproducible, complex model that could be used to advance our understanding of cancer pathology and will facilitate therapeutic drug testing.