Role for animal models in understanding essential fatty acid deficiency in cystic fibrosis.

Essential fatty acid deficiency has been observed in most patients with Cystic Fibrosis (CF); however, pancreatic supplementation does not restore the deficiency, suggesting a different pathology independent of the pancreas. At this time, the underlying pathological mechanisms are largely unknown. Essential fatty acids are obtained from the diet and processed by organs including the liver and intestine, two organs significantly impacted by mutations in the cystic fibrosis transmembrane conductance regulator gene (Cftr). There are several CF animal models in a variety of species that have been developed to investigate molecular mechanisms associated with the CF phenotype. Specifically, global and systemic mutations in Cftr which mimic genotypic changes identified in CF patients have been generated in mice, rats, sheep, pigs and ferrets. These mutations produce CFTR proteins with a gating defect, trafficking defect, or an absent or inactive CFTR channel. Essential fatty acids are critical to CFTR function, with a bidirectional relationship between CFTR and essential fatty acids proposed. Currently, there are limited analyses on the essential fatty acid status in most of these animal models. Of interest, in the mouse model, essential fatty acid status is dependent on the genotype and resultant phenotype of the mouse. Future investigations should identify an optimal animal model that has most of the phenotypic changes associated with CF including the essential fatty acid deficiencies, which can be used in the development of therapeutics.

Hemolysis Following Intraoperative Cell Salvage Replacement in a Scoliosis Patient With Sickle Cell Trait: A Case Report.

MINI: Intraoperative cell salvage (ICS) is used to reduce blood loss in scoliosis spinal fusion. We report one case of hemolysis induced acute renal failure following ICS. This is the first reported case of acute renal failure associated with hemolysis following ICS in a scoliosis patient with sickle cell trait. STUDY DESIGN: Case report. OBJECTIVE: To describe a novel presentation of acute renal failure associated with hemolysis after intraoperative cell salvage (ICS) in a neuromuscular scoliosis patient with sickle cell trait (SCT). SUMMARY OF BACKGROUND DATA: Hemolysis-associated acute renal failure after ICS in patients with SCT has not been previously reported. Sickle cell disease is regarded as a relative contraindication for ICS due to the risk of red blood cell sickling in the hypoxic cell saver reservoir. A previous case series demonstrated successful ICS reinfusion after elective caesarean section in two patients with SCT. However, a decision to not reinfuse ICS collected blood due to increased sickling after blood processing was reported in general surgery. METHODS: A 14-year-old female with Group I neuromuscular scoliosis underwent a navigated T3-S1posterior spinal instrumentation fusion. Three hundred milliliters of blood collected by ICS was reinfused intraoperatively along with two units of packed red blood cells. RESULTS: Postoperatively, the patient had delayed emergence from the general anesthetic and gross hematuria was observed in the urinary catheter bag. The patient was transferred to the intensive care unit and was treated successfully for hemolysis-induced renal failure. CONCLUSION: Given the potential seriousness of hemolysis-associated acute renal failure associated with ICS, we recommend against the use of ICS in patients with SCT. LEVEL OF EVIDENCE: 5.

Comparison of cast materials for the treatment of congenital idiopathic clubfoot using the Ponseti method: a prospective randomized controlled trial.

BACKGROUND: The Ponseti method of congenital idiopathic clubfoot correction has traditionally specified plaster of Paris (POP) as the cast material of choice; however, there are negative aspects to using POP. We sought to determine the influence of cast material (POP v. semirigid fibreglass [SRF]) on clubfoot correction using the Ponseti method. METHODS: Patients were randomized to POP or SRF before undergoing the Ponseti method. The primary outcome measure was the number of casts required for clubfoot correction. Secondary outcome measures included the number of casts by severity, ease of cast removal, need for Achilles tenotomy, brace compliance, deformity relapse, need for repeat casting and need for ancillary surgical procedures. RESULTS: We enrolled 30 patients: 12 randomized to POP and 18 to SRF. There was no difference in the number of casts required for clubfoot correction between the groups (p = 0.13). According to parents, removal of POP was more difficult (p < 0.001), more time consuming (p < 0.001) and required more than 1 method (p < 0.001). At a final follow-up of 30.8 months, the mean times to deformity relapse requiring repeat casting, surgery or both were 18.7 and 16.4 months for the SRF and POP groups, respectively. CONCLUSION: There was no significant difference in the number of casts required for correction of clubfoot between the 2 materials, but SRF resulted in a more favourable parental experience, which cannot be ignored as it may have a positive impact on psychological well-being despite the increased cost associated.

CONTEXTE: La méthode de Ponseti pour la correction du pied bot congénital idiopathique a de tout temps spécifié l'utilisation du plâtre de Paris comme matériau de choix; il y a toutefois certains inconvénients associés au plâtre de Paris. Nous avons voulu déterminer l'influence du matériau utilisé (plâtre de Paris c. fibre de verre semi-rigide) sur la correction du pied bot selon la méthode de Ponseti. MÉTHODES: Les patients ont été assignés aléatoirement soit au plâtre de Paris soit à la fibre de verre semi-rigide en vue de l'intervention de Ponseti. Le principal paramètre mesuré était le nombre de plâtres requis pour corriger le pied bot. Les paramètres secondaires incluaient le nombre de plâtres en fonction de la gravité, la facilité de retrait du plâtre, la nécessité de sectionner le tendon d'Achille, le port assidu de l'attelle, le retour de la difformité, la nécessité d'autres plâtres et interventions chirurgicales auxiliaires. RÉSULTATS: Nous avons inscrit 30 patients : 12 ont été assignés au plâtre de Paris et 18 à la fibre de verre. On n'a noté aucune différence entre les groupes quant au nombre de plâtres requis pour la correction du pied bot (p = 0,13). Selon les parents, le retrait du plâtre de Paris était plus difficile p < 0,001), prenait plus de temps (p < 0,001) et nécessitait le recours à plus d'une méthode (p < 0,001). Au moment du dernier suivi à 30,8 mois, les intervalles moyens avant un retour de la difformité nécessitant la pose d'un autre plâtre et/ou une chirurgie ont été de 18,7 et 16,4 mois dans les groupes traités au moyen de la fibre de verre semi-rigide et du plâtre de Paris, respectivement.. CONCLUSION: On n'a noté aucune différence significative entre les 2 matériaux quant au nombre de plâtres requis pour corriger le pied bot, mais la fibre de verre a donné lieu à une expérience plus agréable pour les parents, ce qui ne peut être ignoré en raison de l'impact potentiellement positif sur le bien-être psychologique, et ce, malgré un coût plus élevé.

Volume-of-interest cone-beam CT using a 2.35 MV beam generated with a carbon target.

PURPOSE: This is a proof-of-concept study addressing volume of interest (VOI) cone beam CT (CBCT) imaging using an x-ray beam produced by 2.35 MeV electrons incident on a carbon linear accelerator target. Methodology is presented relevant to VOI CBCT image acquisition and reconstruction. Sample image data are given to demonstrate and compare two approaches to minimizing artifacts arising from reconstruction with truncated projections. Dosimetric measurements quantify the potential dose reduction of VOI acquisition relative to full-field CBCT. The dependence of contrast-to-noise ratio (CNR) on VOI dimension is investigated. METHODS: A paradigm is presented linking the treatment planning process with the imaging technique, allowing definition of an imaging VOI to be tailored to the geometry of the patient. Missing data in truncated projection images are completed using a priori information in the form of digitally reconstructed radiographs (DRRs) generated from the planning CT set. This method is compared to a simpler technique of extrapolating truncated projection data prior to reconstruction. The utility of these approaches is shown through imaging of a geometric phantom and the head-and-neck section of a lamb. The total scatter factor of the 2.35 MV∕carbon beam on field size is measured and compared to a standard therapeutic beam to estimate the comparative dose reduction inside the VOI. Thermoluminescent dosimeters and Gafchromic film measurements are used to compare the imaging dose distributions for the 2.35 MV∕carbon beam between VOI and full-field techniques. The dependence of CNR on VOI dimension is measured for VOIs ranging from 4 to 15 cm diameter. RESULTS: Without compensating for missing data outside of truncated projections prior to reconstruction, pronounced boundary artifacts are present, in three dimensions, within 2-3 cm of the edges of the VOI. These artifacts, as well as cupping inside the VOI, can be reduced substantially using either the DRR filling or extrapolation techniques presented. Compared to 6 MV, the 2.35 MV∕carbon beam shows a substantially greater dependence of total scatter factor on field size, indicating a comparative advantage of the VOI approach when combined with the low-Z target beam. Dosimetric measurements in the anthropomorphic head phantom demonstrate a dose reduction by up to 15% and 75% inside and outside of the VOI, respectively, compared to full-field imaging. For the 2.35 MV∕carbon beam, CNR was shown to be approximately invariant with VOI dimension for bone and lung objects. CONCLUSIONS: The low-Z target, VOI CBCT technique appears to be feasible and combines the desirable characteristics of the low-Z target beam with regard to CNR, with the capacity to localize the imaging dose to the anatomy relevant to the image guidance task.

Silver deposition and tissue staining associated with wound dressings containing silver.

Argyria is the general term used to denote a clinical condition in which excessive administration and deposition of silver causes a permanent irreversible gray-blue discoloration of the skin or mucous membranes. The amount of discoloration usually depends on the route of silver delivery (ie, oral or topical administration) along with the body's ability to absorb and excrete the administered silver compound. Argyria is accepted as a rare dermatosis but once silver particles are deposited, they remain immobile and may accumulate during the aging process. Topical application of silver salts (eg, silver nitrate solution) may lead to transient skin staining. To investigate their potential to cause skin staining, two silver-containing dressings (Hydrofiber and nanocrystalline) were applied to human skin samples taken from electively amputated lower limbs. The potential for skin discoloration was assayed using atomic absorption spectroscopy. When the dressings were hydrated with water, a significantly higher amount of silver was released from the nanocrystalline dressing compared to the Hydrofiber dressing (P <0.005), which resulted in approximately 30 times more silver deposition. In contrast, when saline was used as the hydration medium, the release rates were low for both dressings and not significantly different (silver deposition was minimal). Controlling the amount of silver released from silver-containing dressings should help reduce excessive deposition of silver into wound tissue and minimize skin staining.