Exhaled nitric oxide levels in atopic children: relation to specific allergic sensitisation,AHR, and respiratory symptoms

BACKGROUND: Exhaled nitric oxide (eNO), which has been proposed as a measure of airway inflammation, is increased in atopic subjects. This raises the question of whether eNO provides any additional information about airway inflammation in asthmatic subjects, other than as a marker for atopy. A study was undertaken to determine whether eNO levels in a population of atopic children are associated with sensitisation or natural exposure to specific allergens, and to examine the relationship between eNO, airway responsiveness, and current respiratory symptoms. METHODS: Exhaled NO and airway responsiveness to histamine were measured in winter and in summer in 235 children aged 8-14 years who had been classified as atopic by skin prick testing. Current respiratory symptoms, defined as wheeze or cough during the month preceding the test, were measured by a parent completed questionnaire. Airway hyperresponsiveness (AHR) was defined as a dose response ratio (DRR) of >8.1 (% fall in forced expiratory volume in 1 second (FEV(1))/micromol + 3). RESULTS: Sensitisation to house dust mite was associated with raised eNO levels in winter while sensitisation to Cladosporium was associated with raised eNO levels in both winter and summer. Grass pollen sensitisation was not associated with raised eNO levels in either season. Exhaled NO correlated significantly with DRR histamine (r=0.43, p<0.001) independently of whether the children had current symptoms or not. In children with current wheeze, those with AHR had eNO levels 1.53 (95% CI 1.41 to 1.66) times higher than those without AHR (p=0.006). Neither DRR (p=1.0) nor eNO levels (p=0.92) differed significantly between children with or without persistent dry cough in the absence of wheeze. CONCLUSIONS: In atopic children, raised eNO levels are associated with sensitisation to perennial allergens, but not to seasonal allergens such as grass pollen. In this population, an increase in eNO is associated with AHR and current wheezing, suggesting that eNO is more than just a marker for atopy.     

PEG “Rescue”: a practical NOTES technique

Dislodged percutaneous endoscopic gastrostomy (PEG) tubes occur commonly and may require urgent surgical intervention in a susceptible patient population. Natural orifice translumenal endoscopic surgery (NOTES) may facilitate PEG rescue and avoid the morbidity associated with contemporary surgical techniques. We report a case of a dislodged PEG tube in the early post-operative period with evidence of incomplete gastrocutaneous tract formation and intra-abdominal leakage. Bedside transgastric NOTES exploration facilitated peritoneoscopy, evacuation of intra-abdominal fluid, and re-establishment of the PEG tube through the original gastrotomy tract. Tube feeds were resumed and postoperative contrast fluoroscopy demonstrated no intra-abdominal leakage from the replaced PEG tube. No postoperative complications related to the NOTES procedure were noted at 30 days of follow-up. PEG rescue represents a unique, practical, and empowering application of the burgeoning experience of NOTES. Electronic Supplementary Material The online version of this article (doi: ) contains supplementary material, which is available to authorized users     

Patient satisfaction with dermal fillers and effect on utilization of invasive aesthetic treatment modalities at a university-based cosmetic center

The use of noninvasive facial rejuvenation measures has increased even in difficult economic times. We present a 10-year retrospective patient satisfaction survey to obtain a comprehensive long-term review of our patients' experience and satisfaction with dermal filler therapy. Dermal filler use in our practice has increased. The majority of patients treated with dermal fillers underwent serial treatments with very few complications. Of patients who had invasive procedures performed, 75% continued dermal filler treatment. Patients (67%) treated with dermal fillers reported that they also had invasive facial aesthetic procedures performed. Patients (89%) reported that they would recommend dermal fillers to their peers. We found that dermal filler therapy is a noninvasive procedure that can be used as a tool to promote and increase the rate of definitive facial rejuvenation via invasive procedures in a plastic surgical practice with high patient satisfaction.     

Duplex-guided infrainguinal balloon angioplasty and stenting. A 4-year experience

AIM: The traditional technique of infrainguinal arterial balloon angioplasties involves the use of fluoroscopy and contrast material. We performed these procedures under duplex guidance to eliminate radiation exposure and avoid nephrotoxic effect of contrast. METHODS: Over the last four years, 274 patients (59% males) with a mean age of 74+/-9 years (range 42-97 years) had a total of 360 attempted balloon angioplasties of the superficial femoral (SFA) and/or popliteal arteries under duplex guidance. Cannulation of common femoral artery, manipulation of the guidewire across the stenoses and/or occlusions of the SFA and/or popliteal artery, and balloon dilation were achieved with duplex guidance alone. Infrapopliteal angioplasties of 80 arteries were attempted in 54 cases (15% of all cases). RESULTS: Overall technical success for femoral-popliteal segment was 95% (342/360 cases) and 96% (77/80 cases) for infrapopliteal segment. CONCLUSION: Duplex guided balloon angioplasty and stent placement appears to be a safe and effective technique for treatment of femoral-popliteal and infrapopliteal arterial occlusive disease.     

Negative pressure wound therapy

Negative pressure wound therapy has become an increasingly important part of wound management. Over the last decade, numerous uses for this method of wound management have been reported, ranging from acute and chronic wounds, to closure of open sternal and abdominal wounds, to assistance with skin grafts. The biophysics behind the success of this treatment largely have focused on increased wound blood flow, increased granulation tissue formation, decreased bacterial counts, and stimulation of wound healing pathways through shear stress mechanisms. The overall success of negative pressure wound therapy has led to a multitude of clinical applications, which are discussed in this article.     

Peripheral administration of the melanocortin-4 receptor antagonist NBI-12i ameliorates uremia-associated cachexia in mice

We have recently shown that genetic or pharmacological blockade of the melanocortin-4 receptor (MC4-R) attenuates uremia-associated cachexia. However, the potential clinical utility of this approach has been limited by the need to deliver a peptide MC4-R antagonist into the ventricles of the brain. NBI-12i is a recently developed small molecule MC4-R antagonist, with high affinity and selectivity that penetrates the central nervous system after peripheral administration. We tested whether NBI-12i would also be effective in attenuating uremia-associated cachexia in a mouse model. Intraperitoneal administration of NBI-12i stimulated food intake and weight gain in uremic mice. Furthermore, NBI-12i-treated uremic mice gained lean body mass, fat mass, and had a lower basal metabolic rate compared to vehicle-treated and diet-supplemented uremic mice, which lost both lean body mass and fat mass and had an increase in basal metabolic rate. We found that NBI-12i normalizes the expression of uncoupling protein, which is normally upregulated in uremic mice, and we speculate that this may contribute to the drug's protective effect. These data underscore the importance of melanocortin signaling in the pathogenesis of uremia-associated cachexia and demonstrate the potential of peripheral administration of MC4-R antagonists as a novel therapeutic approach.     

The effect of dutasteride on the peripheral and transition zones of the prostate and the value of the transition zone index in predicting treatment response

PURPOSE: We determined the effects of dutasteride on transition and peripheral zone volume, and the clinical value of the transition zone index in men with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 2,802 men 50 years or older with diagnosed benign prostatic hyperplasia, American Urological Association symptom index score 12 or greater, total prostate volume 30 cc or greater, prostate specific antigen 1.5 ng/ml or greater and 10 ng/ml or less, and peak urinary flow rate 15 ml per second or less were randomized to receive 0.5 mg dutasteride daily or placebo for 2 years. Total prostate and transition zone volume was measured with transrectal ultrasound at baseline and 4 times during the 2-year period. Peripheral zone volume (total prostate volume minus transition zone volume) and the transition zone index (transition zone volume/total prostate volume) were calculated. Patients were stratified into tertiles according to baseline total prostate and transition zone volume, and the transition zone index. RESULTS: At 24 months dutasteride significantly decreased total prostate volume from baseline (p <0.0001). There were similar decreases in transition and peripheral zone volume (approximately 25%). In men receiving placebo high baseline total prostate and transition zone volume, and transition zone index were associated with poor 2-year outcomes, ie a low peak urinary flow rate, high American Urological Association symptom index scores, and an increased frequency of acute urinary retention and benign prostatic hyperplasia related surgery. Improvements in outcomes with dutasteride vs placebo were greatest in men with the highest baseline total prostate and transition zone volume, and transition zone index. In men with low (30 to less than 42 cc) and intermediate (42 to less than 58 cc) baseline total prostate volume the benefits of dutasteride therapy were only significant in the intermediate (0.4 to less than 0.55) and high (0.55 to less than 1.0) transition zone index tertiles. CONCLUSIONS: Total prostate and transition zone volume, and the transition zone index are directly related to benign prostatic hyperplasia progression. The transition zone index may add value to transition zone volume alone for predicting outcomes. Dutasteride decreased transition and peripheral zone volume equally, supporting a known therapeutic role in benign prostatic hyperplasia and a possible preventive role in prostate cancer.     

Clinical significance of isolated v lesions in paediatric renal transplant biopsies: muscular arteries required to refute the diagnosis of acute rejection

Intimal vascular lesions are considered features of acute T‐cell‐mediated rejection yet can occur in the absence of tubulointerstitial inflammation, termed isolated ‘v’ lesions. The clinical significance of these lesions is unclear. The diagnosis requires a biopsy with the presence of arteries. The frequency of adequate biopsies was analysed in 89 renal transplant biopsies from 57 paediatric renal allograft recipients, and the incidence of isolated endarteritis was determined. 60 (67%) biopsies contained an artery and of these, isolated ‘v’ lesions occurred in 6 (10%). 5 (83%) biopsies with isolated ‘v’ lesions were associated with positive DSA, suggesting that these lesions may represent acute antibody‐mediated rejection. Patients with vessel‐negative biopsies had an increased decline in eGFR (median ?20.5, IQR ?24.4 to 1.2 ml/min/1.73 m² vs. ?9.6, IQR ?78.7 to ?6.8 ml/min/1.73 m²; P = 0.01). Patients with vessel‐negative biopsies were more likely to have repeat biopsy for ongoing allograft dysfunction, (25.0% vs. 2.4%; P < 0.01). The data suggest that isolated ‘v’ lesions are more common than previously thought. A significant proportion of biopsies classified as ‘normal’ or ‘borderline change’ in the absence of a large vessel may represent undiagnosed acute rejection. This may result in suboptimal therapy with possible adverse effects on renal outcome.     

Target detection: Magnetic resonance imaging-ultrasound fusion–guided prostate biopsy

Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance.     

Efficacy and safety of prolonged‐release tacrolimus in stable pediatric allograft recipients converted from immediate‐release tacrolimus – a Phase 2, open‐label,single‐arm,one‐way crossover study

There are limited clinical data regarding prolonged‐release tacrolimus (PR‐T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR‐T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate‐release tacrolimus (IR‐T), on a 1:1 mg total‐daily‐dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy‐confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole‐blood trough levels (target 3.5–15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6–17.7% of patients across follow‐up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug‐related treatment‐emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR‐T to PR‐T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.