Comparison of nasal valve dysfunction treatment outcomes for temperature-controlled radiofrequency and functional rhinoplasty surgery: a systematic review and meta-analyses.

BACKGROUND: Nasal valve dysfunction (NVD) is a substantial contributor to nasal airway obstruction. Minimally-invasive temp-erature-controlled radiofrequency (TCRF) treatment of the nasal valve is available and comparison with surgical techniques is warranted. METHODOLOGY: Databases: Medline (PubMed), Embase, Cochrane Library. POPULATION: adults with preprocedural nasal obstruction symptom evaluation (NOSE) score ≥45. Treatment effects were derived from a random effects model and reported as weighted mean difference in NOSE score between baseline; 3, 6, and 12 months postprocedure. RESULTS: Of 2529 initial articles, 5 studies describing TCRF treatment and 63 studies describing functional rhinoplasty were included. Pooled effect sizes for TCRF treatment and functional rhinoplasty were comparable in all analyses. CONCLUSIONS: TCRF treatment of the internal nasal valve for NVD was associated with sustained effects comparable to functional rhinoplasty addressing the nasal valve only, rhinoplasty without concomitant turbinate treatment, and all rhinoplasty.

Lumbar Puncture: Creation and Resident Acceptance of a Low-Cost, Durable, Reusable Fluoroscopic Phantom with a Fluid-Filled Spinal Canal for Training at an Academic Program.

Simulation-based medical training provides learners a method to develop technical skills without exposing patients to harm. Although fluoroscopic phantoms are already adopted in some areas of radiology, this has historically not been for lumbar puncture. Commercially available phantoms are expensive. We report a cost-effective, accessible solution by creation of an inexpensive phantom for resident training to perform fluoroscopically guided lumbar puncture, as well as instructions on how to make a phantom for residency education. An anthropomorphic ballistics-gel phantom that contains a plastic lumbar vertebral column and simulated CSF space was created. Radiology residents with minimum or no experience with fluoroscopically guided lumbar punctures were given a brief education and practiced fluoroscopically guided lumbar punctures on the phantom. A survey from the residents was then done. The phantom was qualitatively quite durable and deemed adequate for educational purposes. All the residents surveyed expressed the desire to have this phantom available and it increased comfort, knowledge, and perceived likelihood of success. Few articles have been published that focused on low-cost phantom creation for fluoroscopic-procedure training. This study supports the benefits of using phantoms for fluoroscopic training as well as step-by-step instructions for creation of this phantom. The residents responded positively and felt more confident in their fluoroscopically guided techniques. The ability to make a long-term training device for resident education would be inexpensive and relatively easy to implement in academic programs.

Evidence for episodic acidification effects on migrating Atlantic salmon Salmo salar smolts.

Field studies were conducted to determine levels of gill aluminium as an index of acidification effects on migrating Atlantic salmon Salmo salar smolts in the north-eastern U.S.A. along mainstem river migration corridors in several major river basins. Smolts emigrating from the Connecticut River, where most (but not all) tributaries were well buffered, had low or undetectable levels of gill aluminium and high gill Na(+) /K(+) -ATPase (NKA) activity. In contrast, smolts emigrating from the upper Merrimack River basin where most tributaries are characterized by low pH and high inorganic aluminium had consistently elevated gill aluminium and lower gill NKA activity, which may explain the low adult return rates of S. salar stocked into the upper Merrimack catchment. In the Sheepscot, Narraguagus and Penobscot Rivers in Maine, river and year-specific effects on gill aluminium were detected that appeared to be driven by underlying geology and high spring discharge. The results indicate that episodic acidification is affecting S. salar smolts in poorly buffered streams in New England and may help explain variation in S. salar survival and abundance among rivers and among years, with implications for the conservation and recovery of S. salar in the north-eastern U.S.A. These results suggest that the physiological condition of outmigrating smolts may serve as a large-scale sentinel of landscape-level recovery of atmospheric pollution in this and other parts of the North Atlantic region.

Migratory patterns of hatchery and stream-reared Atlantic salmon Salmo salar smolts in the Connecticut River, U.S.A.

The timing of downstream migration and detection rates of hatchery-reared Atlantic salmon Salmo salar smolts and stream-reared smolts (stocked 2 years earlier as fry) were examined in the Connecticut River (U.S.A.) using passive integrated transponder (PIT) tags implanted into fish and then detected at a downstream fish bypass collection facility at Turners Falls, MA (river length 192 km). In two successive years, hatchery-reared smolts were released in mid-April and early May at two sites: the West River (river length 241 km) or the Passumpsic (river length 450 km). Hatchery-reared smolts released higher in the catchment arrived 7 to 14 days later and had significantly lower detection rates than smolts stocked lower in the catchment. Hatchery-reared smolts released 3 weeks apart at the same location were detected downstream at similar times, indicating that early-release smolts had a lower average speed after release and longer residence time. The size and gill Na(+) /K(+) -ATPase (NKA) activity of smolts at the time of release were significantly greater for detected fish (those that survived and migrated) than for those that were not detected. Stream-reared pre-smolts (>11·5 cm) from four tributaries (length 261-551 km) were tagged in autumn and detected during smolt migration the following spring. Stream-reared smolts higher in the catchment arrived later and had significantly lower detection rates. The results indicate that both hatchery and stream-reared smolts from the upper catchment will arrive at the mouth of the river later and experience higher overall mortality than fish from lower reaches, and that both size and gill NKA activity are related to survival during downstream migration.

Captured streams and springs in combined sewers: a review of the evidence, consequences and opportunities.

Captured streams and springs may be flowing in combined sewers, increasing clean baseflow in pipes and wastewater treatment works (WwTWs), reducing pipe capacity and increasing treatment costs. The UK water industry is aware of this in principle, but there has been no explicit discussion of this in the published literature, nor have there been any known attempts to manage it. Instead, the current focus is on the similar intrusion of groundwater infiltration through pipe cracks and joints. We have conducted a thorough review of literature and international case studies to investigate stream and spring capture, finding several examples with convincing evidence that this occurs. We identify three modes of entry: capture by conversion, capture by interception, and direct spring capture. Methods to identify and quantify capture are limited, but the experience in Zurich suggests that it contributed 7-16% of the baseflow reaching WwTWs. There are negative impacts for the water industry in capital and operational expenditure, as well as environmental and social impacts of loss of urban streams. For a typical WwTW (Esholt, Bradford) with 16% of baseflow from captured streams and springs, we conservatively estimate annual costs of £ 2 million to £ 7 million. A detailed case study from Zurich is considered that has successfully separated captured baseflow into daylighted streams through the urban area, with multiple economic, environmental and social benefits. We conclude that there is a strong case for the UK water industry to consider captured streams and springs, quantify them, and assess the merits of managing them.

Endocrine regulation of prolactin cell function and modulation of osmoreception in the Mozambique tilapia.

Prolactin (PRL) cells of the Mozambique tilapia, Oreochromis mossambicus, are osmoreceptors by virtue of their intrinsic osmosensitivity coupled with their ability to directly regulate hydromineral homeostasis through the actions of PRL. Layered upon this fundamental osmotic reflex is an array of endocrine control of PRL synthesis and secretion. Consistent with its role in fresh water (FW) osmoregulation, PRL release in tilapia increases as extracellular osmolality decreases. The hyposmotically-induced release of PRL can be enhanced or attenuated by a variety of hormones. Prolactin release has been shown to be stimulated by gonadotropin-releasing hormone (GnRH), 17-ß-estradiol (E2), testosterone (T), thyrotropin-releasing hormone (TRH), atrial natriuretic peptide (ANP), brain-natriuretic peptide (BNP), C-type natriuretic peptide (CNP), ventricular natriuretic peptide (VNP), PRL-releasing peptide (PrRP), angiotensin II (ANG II), leptin, insulin-like growth factors (IGFs), ghrelin, and inhibited by somatostatin (SS), urotensin-II (U-II), dopamine, cortisol, ouabain and vasoactive intestinal peptide (VIP). This review is aimed at providing an overview of the hypothalamic and extra-hypothalamic hormones that regulate PRL release in euryhaline Mozambique tilapia, particularly in the context on how they may modulate osmoreception, and mediate the multifunctional actions of PRL. Also considered are the signal transduction pathways through which these secretagogues regulate PRL cell function.

Physicochemical properties of pH-controlled polyion complex (PIC) micelles of poly(acrylic acid)-based double hydrophilic block copolymers and various polyamines.

The physicochemical properties of polyion complex (PIC) micelles were investigated in order to characterize the cores constituted of electrostatic complexes of two oppositely charged polyelectrolytes. The pH-sensitive micelles were obtained with double hydrophilic block copolymers containing a poly(acrylic acid) block linked to a modified poly(ethylene oxide) block and various polyamines (polylysine, linear and branched polyethyleneimine, polyvinylpyridine, and polyallylamine). The pH range of micellization in which both components are ionized was determined for each polyamine. The resulting PIC micelles were characterized using dynamic light scattering and small-angle X-ray scattering experiments (SAXS). The PIC micelles presented a core-corona nanostructure with variable polymer density contrasts between the core and the corona, as revealed by the analysis of the SAXS curves. It was shown that PIC micelle cores constituted by polyacrylate chains and polyamines were more or less dense depending on the nature of the polyamine. It was also determined that the density of the cores of the PIC micelles depended strongly on the nature of the polyamine. These homogeneous cores were surrounded by a large hairy corona of hydrated polyethylene oxide block chains. Auramine O (AO) was successfully entrapped in the PIC micelles, and its fluorescence properties were used to get more insight on the core properties. Fluorescence data confirmed that the cores of such micelles are quite compact and that their microviscosity depended on the nature of the polyamine. The results obtained on these core-shell micelles allow contemplating a wide range of applications in which the AO probe would be replaced by various cationic drugs or other similarly charged species to form drug nanocarriers or new functional nanodevices.

Switching of Na+, K+-ATPase isoforms by salinity and prolactin in the gill of a cichlid fish.

We identified and investigated the changes in expression of two gill Na(+), K(+)-ATPase α-subunit isoforms (α-1a and α-1b) in relationship with salinity acclimation in a cichlid fish, Mozambique tilapia. Transfer of freshwater (FW)-acclimated fish to seawater (SW) resulted in a marked reduction in α-1a expression within 24 h and a significant increase in α-1b expression with maximum levels attained 7 days after the transfer. In contrast, transfer of SW-acclimated fish to FW induced a marked increase in α-1a expression within 2 days, while α-1b expression decreased significantly after 14 days. Hypophysectomy resulted in a virtual shutdown of α-1a mRNA expression in both FW- and SW-acclimated fish, whereas no significant effect was observed in α-1b expression. Replacement therapy by ovine prolactin (oPrl) fully restored α-1a expression in FW-acclimated fish, while cortisol had a modest, but significant, stimulatory effect on α-1a expression. In hypophysectomized fish in SW, replacement therapy with oPrl alone or in combination with cortisol resulted in a marked increase in α-1a mRNA to levels far exceeding those observed in sham-operated fish. Expression of α-1b mRNA was unaffected by hormone treatment either in FW-acclimated fish or in SW-acclimated fish. The mRNA expression of fxyd-11, a regulatory Na(+), K(+)-ATPase subunit, was transiently enhanced during both FW and SW acclimation. In hypophysectomized fish in FW, oPrl and cortisol stimulated fxyd-11 expression in a synergistic manner. The clear Prl dependence of gill α-1a expression may partially explain the importance of this hormone to hyperosmoregulation in this species.

Transcriptional activity and biological effects of mammalian estrogen receptor ligands on three hepatic estrogen receptors in Mozambique tilapia.

Like other fish species, Mozambique tilapia has three forms of estrogen receptor, ERα, ERß1, and ERß2. A primary function of 17ß-estradiol (E(2)) in oviparous species is the hepatic induction of the yolk precursor protein, vitellogenin (Vg). To characterize the roles of ERs in Vg production, transactivation assays and an in vivo study were carried out utilizing agonists for mammalian ERα and ERß, and an antagonist for mammalian ERα, propyl-pyrazole-triol (PPT), diarylpropionitrile (DPN), and methyl-piperidino-pyrazole (MPP), respectively. ERα was more sensitive and responsive to PPT than ERß1 or ERß2 in transactivation assays. All ER isoforms indicated equivalent responsiveness to DPN compared with E(2), although sensitivity to DPN was lower. MPP exhibited antagonistic action on transactivation of all ER isoforms and reduced the E(2) effect on Vg and ERα 48h post-injection. DPN increased ERα and Vg expression and plasma Vg post-injection, whereas PPT was without effect; DPN seems to stimulate Vg production through activation of ERα. The ligand binding domain of all tilapia ER forms shares only 60-65% amino acid identity with human ERα and ERß. This, together with our results, clearly indicates that agonistic or antagonistic characteristics of PPT, DPN and MPP cannot be extrapolated from mammalian to piscine ERs.

Acute salinity challenges in Mozambique and Nile tilapia: differential responses of plasma prolactin, growth hormone and branchial expression of ion transporters.

The responses of Mozambique and Nile tilapia acclimated to fresh water (FW) and brackish water (BW; 17 per thousand) were compared following acute salinity challenges. In both species, plasma osmolality increased to above 450 mOsm by 2h after transfer from FW to seawater (SW); these increases in osmolality were accompanied by unexpected increases in plasma prolactin (PRL). Likewise, PRL receptor gene expression in the gill also increased in both species. In Nile tilapia, hyperosmotic transfers (FW to BW and SW) resulted in increased plasma growth hormone (GH) and in branchial GH receptor gene expression, responses that were absent in Mozambique tilapia. Branchial gene expression of osmotic stress transcription factor 1 (OSTF1) increased in both species following transfer from FW to SW, whereas transfer from BW to SW induced OSTF1 expression only in the Nile tilapia. Branchial expression of Na(+)/Cl(-) cotransporter was higher in FW in both species than in BW. Branchial gene expression of Na(+)/K(+)/2Cl(-) cotransporter (NKCC) increased after transfer from BW to SW in Mozambique tilapia, whereas expression was reduced in the Nile tilapia following the same transfer. The difference in the SW adaptability of these species may be related to a limited capacity of Nile tilapia to up-regulate NKCC gene expression, which is likely to be an essential component in the recruitment of SW-type chloride cells. The differential responses of GH and OSTF1 may also be associated with the disparate SW adaptability of these two tilapiine species.

Analytical modelling of fringe and core biodegradation in groundwater plumes.

Biodegradation can be divided into two categories depending on the location at which it occurs within the plume: degradation at the plume fringes, and degradation in the interior (core). Available analytical solutions are limited to the consideration of either fringe or core degradation, which in turn limits the applicability of these solutions. Here, a new analytical approach to modelling plumes with both fringe and core degradation is presented. The approach relies on the use of readily available analytical solutions for solute transport. Using a well-known solution for three-dimensional solute transport from a planar source, an approximate solution is derived for the maximum plume length at steady-state conditions. This is verified through the use of a numerical solution. The solution suggests that the parameters controlling the plume length are: (i) the size of the contaminant source, (ii) electron acceptor to electron donor ratio, (iii) transverse dispersivities and (iv) the ratio between degradation rate constant and velocity (lambda/v). The latter term provides a simple check on the relative weights of transport to core degradation and can be used to estimate the importance of core degradation in the overall plume attenuation. The well-documented Bemidji field site has both fringe and core degradation. The new combined degradation model estimates the length of the plume with 10 m of the observed length; core only and fringe only solutions overestimate the length by more than a factor of 2.

Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50 percent of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease.

Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

Neuropeptide-stimulated cell migration in prostate cancer cells is mediated by RhoA kinase signaling and inhibited by neutral endopeptidase.

The neuropeptides bombesin and endothelin-1 stimulate prostate cancer (PC) cell migration and invasion (J Clin Invest, 2000; 106: 1399-1407). The intracellular signaling pathways that direct this cell movement are not well delineated. The monomeric GTPase RhoA is required for migration in several cell types including neutrophils, monocytes and fibroblasts. We demonstrate that bombesin-stimulated PC cell migration occurs via the heterotrimeric G-protein-coupled receptors (G-protein) G alpha 13 subunit leading to activation of RhoA, and Rho-associated coiled-coil forming protein kinase (ROCK). Using siRNA to suppress expression of the three known G-protein alpha-subunit-associated RhoA guanine nucleotide exchange factors (GEFs), we also show that two of these RhoA GEFs, PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), link bombesin receptors to RhoA in a non-redundant manner in PC cells. We next show that focal adhesion kinase, which activates PDZ-RhoGEF and LARG, is required for bombesin-stimulated RhoA activation. Neutral endopeptidase (NEP) is expressed on normal prostate epithelium whereas loss of NEP expression contributes to PC progression. We also demonstrate that NEP inhibits neuropeptide activation of RhoA. Together, these results establish a contiguous signaling pathway from the bombesin receptor to ROCK in PC cells, and they implicate NEP as a major regulator of neuropeptide-stimulated RhoA in these cells. This work also identifies members of this signaling pathway as potential targets for rational pharmacologic manipulation of neuropeptide-stimulated migration of PC cells.

Psychiatric and neuropsychological characterization of Pallister-Hall syndrome.

Pallister-Hall syndrome (PHS) is a rare, single-gene, malformation syndrome that includes central polydactyly, hypothalamic hamartoma, bifid epiglottis, endocrine dysfunction, and other anomalies. The syndrome has variable clinical manifestations and is inherited in an autosomal dominant pattern. We sought to determine whether psychiatric disorders and/or neuropsychological impairment were characteristic of PHS. We prospectively conducted systematic neuropsychiatric evaluations with 19 PHS subjects ranging in age from 7 to 75 years. The evaluation included detailed clinical interviews, clinician-rated and self-report instruments, and a battery of neuropsychological tests. Seven of 14 adult PHS subjects met diagnostic criteria for at least one DSM-IV Axis I disorder. Three additional subjects demonstrated developmental delays and/or neuropsychological deficits on formal neuropsychological testing. However, we found no characteristic psychiatric phenotype associated with PHS, and the frequency of each of the diagnoses observed in these subjects was not different from that expected in this size sample. The overall frequency of psychiatric findings among all patients with PHS cannot be compared to point prevalence estimates of psychiatric disease in the general population because of biased ascertainment. This limitation is inherent to the study of behavioral phenotypes in rare disorders. The general issue of psychiatric evaluation of rare genetic syndromes is discussed in light of this negative result.

Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property.

The aim of this study is to determine the feasibility of loading biologically active molecules into templated mesoporous silica (MCM 41). This material shows an important mesoporosity associated to hexagonally organized channels, a narrow pore size distribution and a large surface area. Ibuprofen was selected as a model molecule since it is a well documented and much used anti-inflammatory drug. Furthermore, it has a lipophilic character and its molecular size is suitable for inclusion within the mesopores of the MCM 41 material. In order to load ibuprofen within the mesopores, adsorption experiments using various solvents or successive impregnations with solutions of ibuprofen in ethanol were performed. At each step of the loading process, the pore filling was characterized by nitrogen adsorption experiments and by X-ray diffraction. The impregnation procedure results in a significant improvement of the amount of ibuprofen loaded into MCM 41. The in vitro drug release was investigated with simulated biological fluids (gastric and intestinal). Hundred percent release is observed at the end of the in vitro experiment.

Prioritisation of abstraction boreholes at risk from chlorinated solvent contamination on the UK Permo-Triassic Sandstone aquifer using a GIS.

A 250 km2 area of the Permo-Triassic Sandstone aquifer in the West Midlands of England, UK, was selected as a test region for the development of a geographic information system (GIS)-based risk assessment methodology that incorporates contaminant source, groundwater vulnerability and groundwater abstraction catchment elements in order to prioritise areas and boreholes potentially at risk from chlorinated solvent pollution on a regional scale. Factors incorporated in the vulnerability assessment include the nature of soils, presence or absence of superficial or glacial deposits, fault density and depth to water table. ARCVIEW GIS was employed with a simple ranking system from which the derived vulnerability assessment index was combined with current chlorinated solvent user industry data and source protection zone components. Results indicate the presence of high-risk areas in urban locations where locally dense distributions of chlorinated solvent user industries combine with high vulnerability aquifers within the catchment of supply boreholes. Ranking of catchment-specific risk reveals the abstraction points under greatest stress. The proposed methodology has applications as a regional-scale initial screening tool to guide site selection for regulatory inspections and assist in prioritising monitoring strategies for existing boreholes. Future developments will provide guidance for locating new urban boreholes in areas of lowest risk.

Strategic management of non-point source pollution from sewage sludge.

In the UK, the recycling of sewage sludge to land is expected to double by 2006 but the security of this route is threatened by environmental concerns and health scares. Strategic investment is needed to ensure sustainable and secure sludge recycling outlets. At present, the security of this landbank for sludge recycling is determined by legislation relating to nutrient rather than potentially toxic elements (PTEs) applications to land--especially the environmental risk linked to soil phosphorus (P) saturation. We believe that not all land has an equal risk of contributing nutrients derived from applications to land to receiving waters. We are currently investigating whether it is possible to minimise nutrient loss by applying sludge to land outside Critical Source Areas (CSAs) regardless of soil P Index status. Research is underway to develop a predictive and spatially-sensitive, semi-distributed model of critical thresholds for sludge application that goes beyond traditional "end-of-pipe" or "edge-of-field" modelling, to include hydrological flow paths and delivery mechanisms to receiving waters from non-point sources at the catchment scale.

Preparation and characterization of siliceous material using liposomes as template.

Material synthesis using unilamellar liposomes with a high sol-gel temperature transition phase as a template leads to a new silica material.