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Biomedical subjects

K O'Grady

Publications and source records attributed to K O'Grady.

At least 19 recordsLinked to original sources

Using the internet to deliver education on drug safety.

BACKGROUND: Medication administration errors (MAEs) occur in 3-8% of all non-intravenous drug doses given in UK hospitals; higher rates have been reported for intravenous drugs. Educational interventions are often advocated as one way of reducing these rates. However, group education sessions are often not practical. We developed internet-based educational modules on drug safety, and evaluated their effect on MAEs. METHODS: 11 modules were developed on different aspects of drug safety and delivered via commercially available software. All nursing staff on one ward were encouraged to participate. MAEs were identified using observation; the denominator used to calculate MAE rates was the number of opportunities for error. We aimed to observe 56 drug rounds before and after asking staff to complete the package. RESULTS: The 19 nurses who administered drugs on the study ward all agreed to participate. Of these, 12 (63%) nurses completed all 11 modules. Pre-education, 82 (6.9%) errors were identified in 1188 opportunities for error. Afterwards, 66 (5.0%) errors were identified in 1397 opportunities for error (95% confidence interval (CI) for the difference -3.8% to 0%). The MAE rate for non-intravenous drugs was 6.1% pre-education and 4.1% afterwards (95% CI for the difference -3.8% to -0.2%). Most errors with regard to intravenous doses were due to fast administration of bolus injections. CONCLUSIONS: An interactive educational package focusing on patient safety was developed, with a high rate of uptake among nursing staff on the study ward. A reduction in non-intravenous MAEs was observed after the use of the package, but no significant change was seen in the overall error rate.

Administration, Oral↗

The transcript abundance of GmGT-2, a new member of the GT-2 family of transcription factors from soybean, is down-regulated by light in a phytochrome-dependent manner.

A new member of the GT-2 family of transcription factors, GmGT-2, was isolated from soybean while screening a cDNA library with a protein binding site (D1) in the promoter of Aux28, a member of the Aux/IAA family of auxin-responsive genes. GmGT-2 possesses various primary amino acid sequence characteristics common to all GT-2 factors thus far isolated, including sequence identity in the twin trihelix DNA-binding domains. Recombinant GmGT-2 expressed in Escherichia coli binds oligotetramers of both D1 and various GT-boxes. However, unlike other known members of the GT-2 family, GmGT-2 message levels are down-regulated by light in a phytochrome-dependent manner. Evidence is presented that the expression levels of Aux28 mRNA are also down-regulated by phytochrome. These results and other referenced data implicate the possible convergence of phytochrome and auxin signaling pathways.

Amino Acid Sequence↗

A histologic analysis of three-dimensional versus two-dimensional tissue expansion in the porcine model.

OBJECTIVE: Recently, a two-dimensional Silastic Dacron stretching skin device has been developed for scalp reduction surgery. Attached subgaleally, this device stretches skin over time, while avoiding the visible volumetric distention that is typical of three-dimensional tissue expanders. Unlike three-dimensional expanders, the histological changes observed with a two-dimensional stretching device have not been described in the literature. The present study compares the histological effects of two-dimensional and three-dimensional skin tissue expansion in the porcine model. STUDY DESIGN: A university Institutional Review Board-approved study in which 16 domestic piglets were used. The 16 piglets were divided evenly into four cohorts as follows: 1, 1-week control cohort; 2, 1-week experimental cohort; 3, 4-week control cohort; and 4, 4-week experimental cohort. METHODS: Tissue expanders (three-dimensional) and Dacron Silastic tissue stretchers (two-dimensional) were surgically inserted into the lateral skin of 16 domestic pigs. Animals were killed at either 1 or 4 weeks based on group assignment. Light microscopic ocular micrometry and stereological point counting were used to determine the depth of the epidermis, dermis, and subdermal adipose tissue layer; width of the panniculus muscle; diameter of sweat gland follicles; percentage ratio of dermal collagen, blood vessels, and tissue space; and epidermal mitotic index in 100 specimens. One-way ANOVA was used to evaluate statistical differences. RESULTS: Both tissue expanders yielded increased values compared with control subjects, with respect to epidermal, dermal, and fat widths and blood vessel counts, whereas adnexal structures in the panniculus muscle width were unaltered. CONCLUSIONS: Although statistically the two types of expansion produced histologically similar changes, the degree of change varied according to the type of expander that was used and the duration of tissue expansion. Most notably, three-dimensional expansion produced more tissue gain per unit area expanded at both the 1-week and the 4-week time intervals, and early (1-week) two-dimensional tissue expansion stimulated a greater angiogenic response than three-dimensional expansion. These findings will assist the surgeon in understanding the physical changes that occur with these two forms of tissue expansion, as well as the potential clinical advantages and shortcomings of each method.

Adipose Tissue↗

Modulation of mechanical properties in multiple-component tissue adhesives.

In vitro, ex vivo, and in vivo studies were performed to investigate the effect of mixing upon the mechanical properties of a two-component tissue adhesive. The hypothesis investigated was that a more complete mixing of the two components would yield an increase in the mechanical performance of the adhesive. This in turn would be demonstrated by improved outcomes in models of clinical sealant application. In vitro stereological analysis of tissue adhesive mixed and delivered by several different applicators demonstrated variation in the amount of mixing provided by each type of delivery system. Ex vivo tensile adhesive strength showed that there was a correlation between the amount of mixing and bonding strength; that is, more thorough mixing demonstrated higher adhesive strength. No significant difference was seen, however, between the different applicator types and impact on in vivo dermal incisional closure strength. There was a correlation, though, in amount of mixing and in vivo hemostasis. In a rabbit spleen incision model, a more thoroughly mixed sealant corresponded with a decrease in time to obtain complete hemostasis, as well as less sealant used. The effects of mixing on tissue-adhesive mechanical performance were influenced somewhat by the amount of mixing provided by the applicator. This effect, however, was dependent upon the sealant formulation and the type of in vivo application.

Animals↗

Mandibular reconstruction using bone morphogenetic protein 2: long-term follow-up in a canine model.

OBJECTIVE: To determine the degree of bone resorption and stability of 3-cm, full-thickness canine mandibular defects reconstructed with recombinant human bone morphogenetic protein 2 (rhBMP-2) and a bioerodible particle carrier followed for 30 months after reconstruction. STUDY DESIGN: Nine dogs, divided into three groups, underwent reconstruction of surgically created 3-cm, full-thickness defects of the body of the mandible. METHODS: Mandibular reconstruction was performed via a combined intraoral and extraoral approach. Using standard plating techniques, a unilateral full-thickness, 3-cm defect was created in the body of the mandible. After stabilizing the defects with titanium reconstruction plates, test implants composed of rhBMP-2 and poly(lactide-co-glycolide) bioerodible particles were placed in the mandibular defects of six animals. Reconstruction plates were removed from test animals at 10 weeks. Three short-term test animals were sacrificed 3 months after reconstruction. Three long-term test animals were sacrificed 30 months after reconstruction to determine the degree of resorption and long-term stability of the rhBMP-2-induced bone. Control implants (carrier without rhBMP-2) were used in three animals and were sacrificed at 3 months. At 9 months, long-term animals were advanced to a solid diet. Masticatory function and body weight were monitored periodically to assess diet tolerance. Roentgenographic photodensitometry was performed on serial dental roentgenograms of the reconstructed segments to determine bone density and the degree of bone resorption over 30 months. After sacrifice, reconstructed segments were harvested and embedded in plastic for histological analysis and histomorphometry to determine the percentage of the defect replaced by mineralized bone (area density) and degree of resorption from 3 to 30 months after reconstruction. The main outcome measures were bone density and bone height determined from serial roentgenograms and percentage of the reconstructed segment replaced by mineralized bone (area density) determined from histomorphometry. RESULTS: Control animals without rhBMP-2 showed no evidence of bone formation across the defect. Histological examination revealed good bone formation in two of three of the short-term test animals with a mean area density of 41.0%. The long-term test animals treated with rhBMP-2 demonstrated good bone formation that was comparable to that of normal host bone by 3 months. The roentgenographic photodensity measurements stabilized at 5 months without evidence of persistent bone resorption. The height of the reconstructed segment (rhBMP-2-induced bone) initially decreased, then stabilized by 11 months after reconstruction with no indication of resorption or failure. Histological examination of the long-term test animals revealed good bone formation across the mandibular defects. However, there were localized areas of thinning of the cortical bone as compared with the short-term test animals sacrificed at 3 months. Histological examination verified the loss of height of the bone in the reconstructed segments. The area density (mean) of the long-term test animals was 56.5%. Despite the decrease in height of the induced bone, there was an increase in area density of the bone over time. CONCLUSIONS: This study demonstrated that rhBMP-2 in a bioerodible particle carrier induced new host bone formation across critical-size mandibular defects. The newly formed bone successfully integrated with existing host bone creating a stable union capable of withstanding the forces of masticatory function in a canine. There was some evidence of early bone resorption (thinning of the cortical bone and decrease in height) in the rhBMP-2-induced bone. The rhBMP-2-induced bone stabilized by 11 months after reconstruction and no further resorption was noted. The percentage of area of the defect replaced by rhBMP-2-induced bone (area density) increased over 30 months. (ABSTRACT TRUNCATED)

Animals↗

Fibrin sealant for treatment of cerebrospinal fluid leaks.

OBJECTIVE: Persistent cerebrospinal fluid leaks in the human population are rarely found in otherwise healthy individuals, but occur in patients with comorbid illnesses. These leaks are frequently resistant to dural suturing or closure of the defect site with connective tissue, cartilage, or plastic materials. In this study, fibrin sealant (ViGuard Fibrin Sealant was used to adhere muscle grafts to surgically created dural defects to close cerebrospinal fluid leaks in chinchillas. Histologic evaluation of the defect sites were conducted to assess healing and tissue response in the test and control groups. METHOD: In 20 chinchillas, after a skin incision, a 6 mm X 6 mm window was created in the right superior bulla exposing the underlying bony tegmen. Using a microcutting burr, a 3 mm X 3 mm area of tegmen was drilled out and the exposed dura was resected to create a large cerebrospinal fluid (CSF) leak. In the control group (n = 10), a small muscle graft from the surrounding tissue was placed into the defect site. In the test group (n = 10), the muscle graft was glued into the defect with ViGuard Fibrin Sealant. Bulla and skin were then closed. All animals were killed at 3 weeks into the experiment, and tissue was harvested for histologic examination. SETTING: The Department of Otolaryngology, Head and Neck Surgery Research Laboratory. University of Illinois, Chicago. RESULTS: Three weeks after surgery in the test group the tegmen defects were found to be closed by bone or connective tissue or both. Meninges had regrown, and the underlying brain appeared histologically normal. There was no evidence of CSF leak, toxicity, infection or other deleterious tissue reactions. In the control group, again the meningeal and bony tegmen defects were seen to be closed by connective tissue or bone or both. Brain tissues appeared histologically normal. There was no evidence of CSF leak, toxicity, or other deleterious tissue reactions. One animal of the test group died of unknown causes. On autopsy, no signs of meningitis or encephalitis could be detected and the cause of death was unapparent. CONCLUSION: Fibrin Sealant, made from pooled donor blood and treated with viral elimination procedures, was found in combination with muscle grafts to securely close induced CSF leaks in the chinchilla model. Inflammation, infection, or toxic reactions were not observed. We believe that ViGuard Fibrin Sealant has stronger bonding power compared with available autologous fibrin tissue adhesives.

Animals↗

The effect of platelet-derived growth factor on tracheal wound healing.

In order to evaluate a new method for the direct application of a polypeptide growth factor to injured tracheal epithelium and to determine the effect of topical platelet-derived growth factor (PDGF) on tracheal wound healing, a controlled animal study was designed using six adult beagle dogs. Four 2x1 cm mucosal defects were created in the tracheal lumen of each dog for a total of 24 experimental sites. Twelve wounds were treated with PDGF in a collagen-fibrin composite tissue adhesive (CTA) carrier. Eight sites received CTA alone and four were left untreated. Healing was assessed by endoscopic exam on post-operative days 4, 7, 10, 14, 17 and 21. The animals were sacrificed on day 21 and the tracheas were harvested for histological examination of the experimental sites and adjacent unwounded trachea. By 21 days, complete healing of all sites was observed endoscopically. Wounds treated with CTA or PDGF-CTA healed at a faster rate than control sites. The PDGF-CTA treated wounds demonstrated excessive granulation tissue formation. Histological examination demonstrated a higher percentage of wound coverage with ciliated epithelium most similar to normal trachea in the PDGF treated wounds. CTA is effective as a carrier for the direct delivery of a growth factor to injured tracheal epithelium. The application of CTA or PDGF-CTA results in a more rapid rate of tracheal wound healing as compared with control wounds. PDGF-CTA led to increased acute local inflammatory changes but was associated with a structurally more normal respiratory epithelium after healing. Physiological studies are necessary to determine the functional significance of these findings.

Animals↗

The effect of recombinant human bone morphogenetic protein-2 on the integration of porous hydroxyapatite implants with bone.

To determine if recombinant human bone morphogenetic protein-2 (rhBMP-2) can be adsorbed onto porous ceramic hydroxyapatite (HA) and promote the integration of HA to host bone, 54 subperiosteal pockets were created on the skulls of 19 adult Pasteurella-free white rabbits. Fourteen HA implants were saturated with saline and placed in subperiosteal pockets (control), 22 HA implants were saturated with saline and placed into subperiosteal pockets after burring 1-2 mm of calvarium to expose bleeding cancellous bone, and 18 HA implants were saturated with rhBMP-2 and placed into subperiosteal pockets. The animals were sacrificed at 1 month with examination to determine implant mobility. Histology was used to determine the amount of bone growth into the implant. Of the 14 control sites, 10 implants were found to be freely mobile, five demonstrated host bone resorption, and only one exhibited bone growth into the implant. Of the 22 burred sites, eight were freely mobile and 10 demonstrated bone growth into the implant (p = 0.04). Of the 18 rhBMP-2 sites, only two were freely mobile, none demonstrated host bone resorption, and 16 exhibited bone growth into the implant (p = 0.00002). This study supports the use of porous ceramic HA as a biocompatible, osteoconductive implant material for use in craniomaxillofacial augmentation and reconstruction. It also provides evidence that rhBMP-2 enhances osseointegration, thereby fixing the implant in position against the host-bone interface. In the clinical setting, osseous fixation of the implant should aid in preventing displacement, minimizing host bone resorption, and decreasing the incidence of extrusion.

Animals↗

Use of octyl-2-cyanoacrylate for skin closure in facial plastic surgery.

Octyl-2-cyanoacrylate is a long carbon chain cyanoacrylate derivative that is stronger and more pliable than its shorter chain derivatives. One hundred and eleven patients underwent elective surgical procedures by the same surgeon using either octyl-2-cyanoacrylate or sutures for skin closure at the University of Illinois at Chicago. Most patients underwent excision of benign skin lesions with a mean wound size of 112 mm3. Patients were randomized into either control (vertical mattress suture closure) or test groups (closure with octyl-2-cyanoacrylate). Surgical judgment was used to determine which wounds in each group required application of subcutaneous sutures to relieve tension and aid in skin edge eversion. Generally, full-thickness (through dermis) wounds larger than 1 cm3 required the use of subcutaneous sutures. The time required to close the epidermis with suture (mean, 3 minutes and 47 seconds) was about four times that of octyl-2-cyanoacrylate (mean, 55 seconds). Wounds were evaluated at 5 to 7 days for infection, wound dehiscence, or tissue reaction, and at 90 days using the modified Hollander wound evaluation scale. At 1 year, photographs of the wounds were evaluated by two facial plastic surgeons that graded the cosmetic outcome using a previously validated visual analog scale. There were no instances of wound dehiscence, hematoma, or infection in either group. Results of wound evaluation at 90 days determined by the modified Hollander scal revealed equivalent cosmetic results in both groups. Results of the visual analog scale ratings showed scores of 21.7 +/- 16.3 for the 49 patients treated with octyl-2-cyanoacrylate and 29.2 +/- 17.7 for the 51 control patients treated with sutures. The lower visual analog scale score represented a superior cosmetic outcome at 1 year with the octyl-2-cyanoacrylate as compared with sutures. This difference is statistically significant at p = 0.03. Additionally, patient satisfaction was very high in the group treated with octyl-2-cyanoacrylate.

Adolescent↗

Biophysics of airflow within the airway: a review.

An understanding of the fundamental principles that govern flow through the airway, like anatomy and physiology, is essential for the practising otolaryngologist. Failure to grasp these principles prevents the clinician from understanding why certain things happen clinically and why certain treatments are effective. This review presents the basic concepts of fluid mechanics as applied to the airway, using commonly encountered clinical situations to further illustrate ideas. Since air is a gaseous fluid, a review of the gas laws initiates the reader. Laminar and turbulent flow is discussed as well as the method used to distinguish between the two. Also included is a brief review of the air/liquid interface inside an alveolus, as well as a discussion of airflow through an endotracheal tube.

Airway Obstruction↗

Premenstrual symptoms in general practice patients. Prevalence and treatment.

OBJECTIVE: To examine the rates of premenstrual symptoms in Australian patients, the treatments they had tried for such symptoms, the perceived effectiveness of these treatments, the proportion of women who reported that they had sought help for premenstrual symptoms and whether women perceived the need for additional help in dealing with premenstrual symptoms. Characteristics associated with higher symptom levels and desire for help were examined. STUDY DESIGN: A cross-sectional survey of 310 general practices patients aged 18-45 years and who had reported having had a menstrual period in the previous three months. RESULTS: Between 11% and 32% of women reported severe or extreme changes during the premenstrual phase on each of the 10 symptoms in the short Premenstrual Assessment Form, with the highest rates for affective symptoms. Eighty-five percent of women reported that they had tried treatments for premenstrual symptoms, and many reported having tried multiple treatments. The most commonly tried treatments included pain killers rest, drinking more fluid and exercise, which had been tried by at least one-third of women. When women were asked to nominate up to three treatments they had tried and found most effective, the most commonly mentioned were dietary changes, evening primrose oil, vitamins (including B6) and exercise. Approximately 50% of the women had sought help, most commonly from a general practitioner and 45% reported that they would like more help dealing with premenstrual symptoms. Higher overall symptom scores were associated with a history of endometriosis, a lower education level, not taking oral contraceptives, taking evening primrose oil and taking vitamin B6. CONCLUSION: There is a need to further refine, through evaluation of different approaches, programs and resources, ways to effectively help women who report premenstrual symptoms and would like help to deal with them.

Adolescent↗

Fibroblast growth factor-induced motor end plate regeneration in atrophic muscle.

OBJECTIVE: To determine whether fibroblast growth factor 1 implanted with viable nerve into atrophic muscle will stimulate formation of functional, acetylcholine producing motor end plates. DESIGN: Twelve male Lewis rats underwent predenervation of the hamstring muscle 8 weeks before implantation of the nerve at a site distant from the original motor end plate. Six animals underwent implantation of the tagged nerve ending into atrophic muscle with 50 microgram of fibroblast growth factor 1 in a fibrin adhesive carrier (group 1). Three animals underwent implantation with nerve, fibrin adhesive, and no fibroblast growth factor 1 (group 2); and three animals underwent implantation with fibroblast growth factor 1 and fibrin adhesive with no nerve (group 3). Animals were killed 9 weeks after implantation and nerve and muscle specimens were harvested. MAIN OUTCOME MEASURES: Histoenzymologic methods for acetylcholinesterase and silver impregnation of nerve fibers were performed 9 weeks after fibroblast growth factor 1-fibrin adhesive implantation. Variables included the number of motor end plates per highpower field and motor end plate length. RESULTS: Robust axonal sprouting and formation of multiple motor end plates were found arborized in serial fashion equidistant around the implanted nerve ending. Rare extrasynaptic staining occurred. End plate lengths were significantly shorter in the fibroblast growth factor 1-treated muscles (group 1) than in the specimens without fibroblast growth factor 1 (group 2) (31.2 vs 58.5 micron; P>001, paired t test). The arborization of motor end plates, rare extrasynaptic staining, and shorter end plate lengths seen in group 1 were all consistent with mature motor end plates. Controls (group 3) displayed limited motor end plate formation and extensive extrasynaptic staining typical of denervation. CONCLUSION: This study presents encouraging evidence that fibroblast growth factor 1 with fibrin adhesive carrier can facilitate the reinnervation of atrophied muscle by enhancing the formation or revitalization of motor end plates. Future studies will address muscle function and use of different carrier materials.

Animals↗

Molecular characterization of cDNAs encoding low-molecular-weight heat shock proteins of soybean.

Three cDNA clones (GmHSP23.9, GmHSP22.3, and GmHSP22.5) representing three different members of the low-molecular-weight (LMW) heat shock protein (HSP) gene superfamily were isolated and characterized. A fourth cDNA clone, pFS2033, was partially characterized previously as a full-length genomic clone GmHSP22.0. The deduced amino acid sequences of all four cDNA clones have the conserved carboxyl-terminal LMW HSP domain. Sequence and hydropathy analyses of GmHSP22, GmHSP22.3, and GmHSP22.5, representing HSPs in the 20 to 24 kDa range, indicate they contain amino-terminal signal peptides. The mRNAs from GmHSP22, GmHSP22.3, and GmHSP22.5 were preferentially associated in vivo with endoplasmic reticulum (ER)-bound polysomes. GmHSP22 and GmHSP22.5 encode strikingly similar proteins; they are 78% identical and 90% conserved at the amino acid sequence level, and both possess the C-terminal tetrapeptide KDEL which is similar to the consensus ER retention motif KDEL; the encoded polypeptides can be clearly resolved from each other by two-dimensional gel analysis of their hybrid-arrest translation products. GmHSP22.3 is less closely related to GmHSP22 (48% identical and 70% conserved) and GmHSP22.5 (47% identical and 65% conserved). The fourth cDNA clone, GmHSP23.9, encodes a HSP of ca. 24 kDa with an amino terminus that has characteristics of some mitochondrial transit sequences, and in contrast to GmHSP22, GmHSP22.3, and GmHSP22.5, the corresponding mRNA is preferentially associated in vivo with free polysomes. It is proposed that the LMW HSP gene superfamily be expanded to at least six classes to include a mitochondrial class and an additional endomembrane class of LMW HSPs.

Amino Acid Sequence↗

Perceptions of social pathology in the neighborhood and the etiology of narcotic addiction. A retrospective study.

In this study, we examined whether differential perceptions of poor urban neighborhoods may contribute to narcotic addiction in individuals who grow up in these neighborhoods. Three groups of adult males provided retrospective perceptions of the neighborhoods where they lived at ages 12 to 14. The groups, matched on neighborhood, age, and race, were: narcotic addicts, peer controls--a never-addicted control sample of age-11 associates of the addicts, and community controls--a never-addicted control sample of age-11 peers who did not associate with the addicts. Results suggested clear group differences in perceptions of neighborhood deviance, with addicts perceiving the greatest and community controls the least amount of deviance. However, within groups, subjects who lived in more socially deviant areas, as determined by official records, tended to view their neighborhoods as more deviant than did subjects who lived in less deviant neighborhoods.

Adolescent↗

Site-directed mutagenesis of the enhancer region of the 780 gene promoter of T-DNA.

Potential regulatory sequences within the enhancer-like region of the 780 gene promoter (Agrobacterium tumefaciens T-DNA) were identified by site-directed mutagenesis. Transcriptional activity of the mutated promoter was analyzed by S1 nuclease mapping of RNA from crown gall tumors of sunflower incited using a T-DNA-based vector. Variability in expression levels were minimized by the use of an internal reference gene and the pooling of at least 200 tumors per construct tested. This approach identified numerous sequences that influence transcriptional activity in either a positive or negative manner. Eight regions of positive influence and three of negative were identified from analysis of those mutations that exhibited low variability in expression (P < 0.005) and affected activity by at least 20%.

Agrobacterium tumefaciens↗

Surgical tissue adhesives in otolaryngology-head and neck surgery.

The primary surgical tissue adhesives used in otolaryngology-head and neck surgery include the cyanoacrylate derivatives and the fibrin tissue adhesives. The cyanoacrylate derivatives are effective for superficial skin closure. Use of this material below the level of the skin can result in acute and chronic inflammation and tissue necrosis. Fibrin tissue adhesives can be used for wound closure, tissue sealing, and hemostasis. Drawbacks noted with the fibrin tissue adhesives include method of preparation, relatively low binding strength, and variable resorption time. This article discusses the properties, methods of preparation, and clinical indications of the cyanoacrylate derivatives and fibrin tissue adhesives.

Cyanoacrylates↗