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Biomedical subjects

John F Fraser

Publications and source records attributed to John F Fraser.

17 recordsLinked to original sources
PubMed2006

Electrical impedance tomography in extremely prematurely born infants and during high frequency oscillatory ventilation analyzed in the frequency domain.

Functional electrical impedance tomography (EIT) measures relative impedance change that occurs in the chest during a distinct observation period and an EIT image describing regional relative impedance change is generated. Analysis of such an EIT image may be erroneous because it is based on an impedance signal that has several components. Most of the change in relative impedance in the chest is caused by air movement but other physiological events such as cardiac activity change in end expiratory level or pressure swings originating from a ventilator circuit can influence the impedance signal. We obtained EIT images and signals in spontaneously breathing healthy adults, in extremely prematurely born infants on continuous positive airway pressure and in ventilated sheep on conventional mechanical or high frequency oscillatory ventilation (HFOV). Data were analyzed in the frequency domain and results presented after band pass filtering within the frequency range of the physiological event of interest. Band pass filtering of EIT data is necessary in premature infants and on HFOV to differentiate and eliminate relative impedance changes caused by physiological events other than the one of interest.

Adult↗
PubMed2006

A porcine deep dermal partial thickness burn model with hypertrophic scarring.

We developed a reproducible model of deep dermal partial thickness burn injury in juvenile Large White pigs. The contact burn is created using water at 92 degrees C for 15s in a bottle with the bottom replaced with plastic wrap. The depth of injury was determined by a histopathologist who examined tissue sections 2 and 6 days after injury in a blinded manner. Upon creation, the circular wound area developed white eschar and a hyperaemic zone around the wound border. Animals were kept for 6 weeks or 99 days to examine the wound healing process. The wounds took between 3 and 5 weeks for complete re-epithelialisation. Most wounds developed contracted, purple, hypertrophic scars. On measurement, the thickness of the burned skin was approximately 1.8 times that of the control skin at week 6 and approximately 2.2 times thicker than control skin at 99 days after injury. We have developed various methods to assess healing wounds, including digital photographic analysis, depth of organising granulation tissue, immunohistochemistry, electron microscopy and tensiometry. Immunohistochemistry and electron microscopy showed that our porcine hypertrophic scar appears similar to human hypertrophic scarring. The development of this model allows us to test and compare different treatments on burn wounds.

Animals↗
PubMed2006

Effect of smoke inhalation on viscoelastic properties and ventilation distribution in sheep.

Smoke inhalation injuries are the leading cause of mortality from burn injury. Airway obstruction due to mucus plugging and bronchoconstriction can cause severe ventilation inhomogeneity and worsen hypoxia. Studies describing changes of viscoelastic characteristics of the lung after smoke inhalation are missing. We present results of a new smoke inhalation device in sheep and describe pathophysiological changes after smoke exposure. Fifteen female Merino ewes were anesthetized and intubated. Baseline data using electrical impedance tomography and multiple-breath inert-gas washout were obtained by measuring ventilation distribution, functional residual capacity, lung clearance index, dynamic compliance, and stress index. Ten sheep were exposed to standardized cotton smoke insufflations and five sheep to sham smoke insufflations. Measured carboxyhemoglobin before inhalation was 3.87 +/- 0.28% and 5 min after smoke was 61.5 +/- 2.1%, range 50-69.4% (P < 0.001). Two hours after smoke functional residual capacity decreased from 1,773 +/- 226 to 1,006 +/- 129 ml and lung clearance index increased from 10.4 +/- 0.4 to 14.2 +/- 0.9. Dynamic compliance decreased from 56.6 +/- 5.5 to 32.8 +/- 3.2 ml/cmH(2)O. Stress index increased from 0.994 +/- 0.009 to 1.081 +/- 0.011 (P < 0.01) (all means +/- SE, P < 0.05). Electrical impedance tomography showed a shift of ventilation from the dependent to the independent lung after smoke exposure. No significant change was seen in the sham group. Smoke inhalation caused immediate onset in pulmonary dysfunction and significant ventilation inhomogeneity. The smoke inhalation device as presented may be useful for interventional studies.

Animals↗
PubMed2006

An advanced expiratory circuit for the recovery of perfluorocarbon liquid from non-saturated perfluorocarbon vapour during partial liquid ventilation: an experimental model.

BACKGROUND: The loss of perfluorocarbon (PFC) vapour in the expired gases during partial liquid ventilation should be minimized both to prevent perfluorocarbon vapour entering the atmosphere and to re-use the recovered PFC liquid. Using a substantially modified design of our previously described condenser, we aimed to determine how much perfluorocarbon liquid could be recovered from gases containing PFC and water vapour, at concentrations found during partial liquid ventilation, and to determine if the amount recovered differed with background flow rate (at flow rates suitable for use in neonates). METHODS: The expiratory line of a standard ventilator circuit set-up was mimicked, with the addition of two condensers. Perfluorocarbon (30 mL of FC-77) and water vapour, at concentrations found during partial liquid ventilation, were passed through the circuit at a number of flow rates and the percentage recovery of the liquids measured. RESULTS: From 14.2 mL (47%) to 27.3 mL (91%) of the infused 30 mL of FC-77 was recovered at the flow rates studied. Significantly higher FC-77 recovery was obtained at lower flow rates (ANOVA with Bonferroni's multiple comparison test, p < 0.0001). As a percentage of the theoretical maximum recovery, 64 to 95% of the FC-77 was recovered. Statistically significantly less FC-77 was recovered at 5 Lmin(-1) (ANOVA with Bonferroni's multiple comparison test, p < 0.0001). Amounts of perfluorocarbon vapour recovered were 47%, 50%, 81% and 91% at flow rates of 10, 5, 2 and 1 Lmin(-1), respectively. CONCLUSION: Using two condensers in series 47% to 91% of perfluorocarbon liquid can be recovered, from gases containing perfluorocarbon and water vapour, at concentrations found during partial liquid ventilation.

Chemical Fractionation↗
PubMed2006

Recombinant human activated protein C improves pulmonary function in ovine acute lung injury resulting from smoke inhalation and sepsis.

OBJECTIVE: To investigate the effects of recombinant human activated protein C (rhAPC) on pulmonary function in acute lung injury (ALI) resulting from smoke inhalation in association with a bacterial challenge. DESIGN: Prospective, randomized, controlled, experimental animal study with repeated measurements. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Eighteen sheep (37.2 +/- 1.0 kg) were operatively prepared and randomly allocated to either the sham, control, or rhAPC group (n = 6 each). After a tracheotomy had been performed, ALI was produced in the control and rhAPC group by insufflation of 4 sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live Pseudomonas aeruginosa bacteria (containing 2-5 x 10(11) colony forming units) was instilled into the lungs according to an established protocol. The sham group received only the vehicle, i.e., 4 sets of 12 breaths of room air and instillation of 30 mL normal saline. The sheep were studied in the awake state for 24 hrs and were ventilated with 100% oxygen. RhAPC (24 mug/kg/hr) was intravenously administered. The infusion was initiated 1 hr post-injury and lasted until the end of the experiment. The animals were resuscitated with Ringer's lactate solution to maintain constant pulmonary artery occlusion pressure. MEASUREMENTS AND MAIN RESULTS: In comparison with nontreatment in controls, the infusion of rhAPC significantly attenuated the fall in Pao2/Fio2 ratio (control group values were 521 +/- 22 at baseline [BL], 72 +/- 5 at 12 hrs, and 74 +/- 7 at 24 hrs, vs. rhAPC group values of 541 +/- 12 at BL, 151 +/- 29 at 12 hours [p < .05 vs. control], and 118 +/- 20 at 24 hrs), and significantly reduced the increase in pulmonary microvascular shunt fraction (Qs/Qt; control group at BL, 0.14 +/- 0.02, and at 24 hrs, 0.65 +/- 0.08; rhAPC group at BL, 0.24 +/- 0.04, and at 24 hrs, 0.45 +/- 0.02 [p < .05 vs. control]) and the increase in peak airway pressure (mbar; control group at BL, 20 +/- 1, and at 24 hrs, 36 +/- 4; rhAPC group at BL, 21 +/- 1, and at 24 hrs, 28 +/- 2 [p < .05 vs. control]). In addition, rhAPC limited the increase in lung 3-nitrotyrosine (after 24 hrs [%]: sham, 7 +/- 2; control, 17 +/- 1; rhAPC, 12 +/- 1 [p < .05 vs. control]), a reliable indicator of tissue injury. However, rhAPC failed to prevent lung edema formation. RhAPC-treated sheep showed no difference in activated clotting time or platelet count but exhibited less fibrin degradation products (1/6 animals) than did controls (4/6 animals). CONCLUSIONS: Recombinant human activated protein C attenuated ALI after smoke inhalation and bacterial challenge in sheep, without bleeding complications.

Airway Obstruction↗
PubMed2006

Successful use of recombinant factor VII in massive hemoptysis due to community-acquired pneumonia.

Recombinant activated factor VII (rFVIIa) is a powerful hemostatic agent developed for use in hemophilia. It has been used increasingly in life-threatening hemorrhage in a variety of other settings in which conventional medical or surgical therapy is unsuccessful. This report describes the successful use of rFVIIa for pulmonary hemorrhage due to a focal bleeding source in a regional hospital where bronchial artery embolization or surgery were not available. rFVIIa may be a useful temporizing measure in the unstable patient with pulmonary hemorrhage without coagulopathic bleeding when conventional treatment is not immediately available.

Bronchography↗
PubMed2006

Heparin-induced thrombocytopenia without thrombosis: an evidence-based review of current literature.

BACKGROUND AND AIM: There has been a recent change in the management guidelines for patients with heparin-induced thrombocytopenia with the addition of a recommendation to commence parenteral anticoagulation in patients with isolated HIT without evidence of thrombosis. We assessed the evidence supporting this recommendation, to answer the following questions: in a patient with isolated HIT, should alternative anticoagulation be commenced, what alternative agent should be used, what is the recommended duration of anticoagulation, and when should warfarin be used? METHODS: We searched MEDLINE (using keywords "heparin-induced thrombocytopenia", "heparin induced thrombocytopaenia", "HIT" and "HITTS") and PubMed (using MeSH terms "thrombocytopenia" and "heparin") from 1966 to 2006 and selected articles for further assessment according to specified criteria. RESULTS: We assessed 12 non-randomised studies, five large case series and multiple small case series. CONCLUSION: Although patients with isolated HIT are at considerable risk of new thrombosis, there is limited evidence to support or reject the use of non-heparin anticoagulation in this group. Non-randomised, historically controlled trials support the use of lepirudin and argatroban; evidence favouring danaparoid is limited to large case series and one retrospective observational study. Duration of parenteral anticoagulation and warfarin use are guided by consensus opinion alone.

Anticoagulants↗
PubMed2004

An in vitro study of the anti-microbial efficacy of a 1% silver sulphadiazine and 0.2% chlorhexidine digluconate cream, 1% silver sulphadiazine cream and a silver coated dressing.

UNLABELLED: Burn sepsis is a leading cause of mortality and morbidity in patients with major burns. The use of topical anti-microbial agents has helped improve the survival in these patients. There are a number of anti-microbials available, one of which, Silvazine (1% silver sulphadiazine (SSD) and 0.2% chlorhexidine digluconate), is used only in Australasia. No study, in vitro or clinical, had compared Silvazine with the new dressing Acticoat. This study compared the anti-microbial activity of Silvazine, Acticoat and 1% silver sulphadiazine (Flamazine) against eight common burn wound pathogens. METHODS: Each organism was prepared as a suspension. A 10 microl inoculum of the chosen bacterial isolate (representing approximately between 10(4) and 10(5) total bacteria) was added to each of four vials, followed by samples of each dressing and a control. The broths were then incubated and 10 microl loops removed at specified intervals and transferred onto Horse Blood Agar. These plates were then incubated for 18 hours and a colony count was performed. RESULTS: The data demonstrates that the combination of 1% SSD and 0.2% chlorhexidine digluconate (Silvazine) results in the most effective killing of all bacteria. SSD and Acticoat had similar efficacies against a number of isolates, but Acticoat seemed only bacteriostatic against E. faecalis and methicillin-resistant Staphylococcus aureus. Viable quantities of Enterobacter cloacae and Proteus mirabilis remained at 24h. CONCLUSION: The combination of 1% SSD and 0.2% chlorhexidine digluconate (Silvazine) is a more effective anti-microbial against a number of burn wound pathogens in this in vitro study. A clinical study of its in vivo anti-microbial efficacy is required.

Anti-Infective Agents, Local↗
PubMed2004

Cytotoxicity of topical antimicrobial agents used in burn wounds in Australasia.

BACKGROUND: Burn sepsis is a leading cause of mortality and morbidity in patients with major burns. The use of topical antimicrobial agents has helped improve the survival of these patients. Silvazine (Sigma Pharmaceuticals, Melbourne, Australia) (1% silver sulphadiazine and 0.2% chlorhexidine digluconate) is used exclusively in Australasia, and there is no published study on its cytotoxicity. This study compared the relative cytotoxicity of Silvazine with 1% silver sulphadiazine (Flamazine (Smith & Nephew Healthcare, Hull, UK)) and a silver-based dressing (Acticoat (Smith & Nephew Healthcare, Hull, UK)). METHODS: Dressings were applied to the centre of culture plates that were then seeded with keratinocytes at an estimated 25% confluence. The plates were incubated for 72 h and culture medium and dressings then removed. Toluidine blue was added to stain the remaining keratinocytes. Following removal of the dye, the plates were photographed under standard conditions and these digital images were analysed using image analysis software. Data was analysed using Student's t-test. RESULTS: In the present study, Silvazine is the most cytotoxic agent. Seventy-two hour exposure to Silvazine in the present study results in almost no keratinocyte survival at all and a highly statistically significant reduction in cell survival relative to control, Acticoat and Flamazine (P<0.001, P<0.01, P<0.01, respectively). Flamazine is associated with a statistically significant reduction in cell numbers relative to control (P<0.05), but is much less cytotoxic than Silvazine (P<0.005). CONCLUSION: In this in-vitro study comparing Acticoat, Silvazine and Flamazine, Silvazine shows an increased cytotoxic effect, relative to control, Flamazine and Acticoat. An in-vivo study is required to determine whether this effect is carried into the clinical setting.

Anti-Infective Agents, Local↗
PubMed2003

The morning after the night before: campfires revisited.

Even eight hours after a campfire has been extinguished with sand, it retains sufficient heat to cause a full-thickness burn with contact of one second. Because extinguishing with sand disguises the danger, this is a particular hazard for children. The only safe way to extinguish a campfire is with water.

Burns↗
PubMed2003

Flammable liquid burns in children.

OBJECTIVES: To document and describe the effects of flammable liquid burns in children. To identify the "at risk" population in order to tailor a burns prevention programme. DESIGN, PATIENTS AND SETTING: Retrospective study with information obtained from the departmental database of children treated at the burns centre at The Royal Children's Hospital, Brisbane between August 1997 and October 2002. MAIN OUTCOME MEASURES: Number and ages of children burned, risk factors contributing to the accident, injuries sustained, treatment required and long-term sequelae. RESULTS: Fifty-nine children sustained flammable liquid burns (median age 10.5 years), with a clear preponderance of males (95%). The median total body surface area burned was 8% (range 0.5-70%). Twenty-seven (46%) of the patients required debridement and grafting. Hypertrophic scars occurred in 56% of the children and contractures in 14%, of which all of the latter required surgical release. Petrol was the causative liquid in the majority (83%) of cases. CONCLUSIONS: The study identified the population most at risk of sustaining flammable liquid burns were young adolescent males. In the majority of cases these injuries were deemed preventable.

Accident Prevention↗
PubMed2002

Campfire burns in children: an Australian experience.

OBJECTIVES: To document and describe the effects of campfire burns on children. To identify the sources of danger contributing to such injuries, so that a prevention strategy can be devised. DESIGN, PATIENTS AND SETTING: Departmental database and case note review of all children with campfire burns seen at the Burns Unit of a tertiary referral children's hospital between January 1999 and June 2001. MAIN OUTCOME MEASURES: Number and ages of children burned; risk factors contributing to the accidents; injuries sustained; treatment required and long-term sequelae. RESULTS: Thirty-three children, median age 2.5 years, sustained burns, usually to the hands and feet, with eight requiring surgery and the majority requiring some form of scar therapy. Seventy-four percent of the children were burned by hot ashes and coals, usually from the previous night's fire, rather than by open flames. CONCLUSIONS: Campfires cause serious injuries to children. In particular, hot ashes and coals from inadequately extinguished campfires pose the greatest danger. Increasing the awareness of this easily preventable problem amongst campers is intended through a public education campaign.

Accidents↗
PubMed2002

Woodstoves uncovered: a paediatric problem.

OBJECTIVES: To document and describe the effects of woodstove burns in children. To identify how these accidents occur so that a prevention strategy can be devised. DESIGN, PATIENTS AND SETTING: Retrospective departmental database and case note review of all children with woodstove burns seen at the Burns Unit of a Tertiary Referral Children's Hospital between January 1997 and September 2001. MAIN OUTCOME MEASURES: Number and ages of children burned; circumstances of the accidents; injuries sustained; treatment required and long-term sequelae. RESULTS: Eleven children, median age 1.0 year, sustained burns, usually to the hands, of varying thickness. Two children required skin grafting and five required scar therapy. Seven children intentionally placed their hands onto the outside of the stove. In all children, burns occurred despite adult supervision. CONCLUSIONS: Woodstoves are a cause of burns in children. These injuries are associated with significant morbidity and financial costs. Through public education, woodstove burns can easily be prevented utilising simple safety measures.

Accident Prevention↗
PubMedDate not supplied

Deep dermal burn injury results in scarless wound healing in the ovine fetus.

Early to mid-term fetuses heal cutaneous incisional wounds without scars; however, fetal response to burn injury has not been ascertained. We present a fetal model of thermal injury and subsequent analysis of fetal and lamb response to burn injury. A reproducible deep dermal burn injury was created in the fetus by application of water at 66 degrees C for 7 seconds, and at 82 degrees C for 10 seconds to the lamb. Macroscopically, the area of fetal scald was undetectable from day 7 post injury, while all lamb scalds were readily identified and eventually healed with scarring. Using a five-point histopathology scoring system for alteration in tissue morphology, differences were detected between control and scalded skin at all stages in lamb postburn, but no difference was detected in the fetal model after day 7. There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01). This novel model of fetal and lamb response to deep dermal injury indicates that the fetus heals a deep burn injury in a scarless fashion. Further elucidation of this specific fetal process of burn injury repair may lead to improved outcome for patients with burn injury.

Actins↗
PubMedDate not supplied

Collagen in the scarless fetal skin wound: detection with picrosirius-polarization.

Our group has developed an ovine model of deep dermal, partial-thickness burn where the fetus heals scarlessly and the lamb heals with scar. The comparison of collagen structure between these two different mechanisms of healing may elucidate the process of scarless wound healing. Picrosirius staining followed by polarized light microscopy was used to visualize collagen fibers, with digital capture and analysis. Collagen deposition increased with fetal age and the fibers became thicker, changing from green (type III collagen) to yellow/red (type I collagen). The ratio of type III collagen to type I was high in the fetus (166), whereas the lamb had a much lower ratio (0.2). After burn, the ratios of type III to type I collagen did not differ from those in control skin for either fetus or lamb. The fetal tissue maintained normal tissue architecture after burn while the lamb tissue showed irregular collagen organization. In conclusion, the type or amount of collagen does not alter significantly after injury. Tissue architecture differed between fetal and lamb tissue, suggesting that scar development is related to collagen cross-linking or arrangement. This study indicates that healing in the scarless fetal wound is representative of the normal fetal growth pattern, rather than a "response" to burn injury.

Animals↗