Selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period (Br J Surg 2006; 93: 489-497).
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Biomedical subjects
Publications and source records attributed to P E Watkins.
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This study allowed the development of an in vitro model of a high-energy ballistic fracture. Direct fractures are more heavily contaminated than indirect fractures, and the spread of contamination is more extensive than examination of the wounds, particularly the entry wounds, would suggest. The major spread of contamination is along tissue planes, and we would recommend that these are thoroughly lavaged in the management of the fracture. The fracture site is heavily contaminated, with endosteal spread in direct fractures. However, there appears to be relatively little bony contamination beyond the fracture site.
The management of open fractures requires excision of all devitalised tissues, both bony and soft tissue, and failure to do so is likely to increase the risk of infection. This study evaluated the applicability of laser Doppler flowmetry for the objective evaluation of fracture fragment viability in an experimental open ballistic fracture over a period of 12 h. The results indicate that this technique could not be used to distinguish between vascularised and non-vascularised fragments at any time, and did not aid the surgeon in their decision making at the time of wound excision. Subjective evaluation, based upon the degree of soft tissue attachment of fragments, was a far better indicator of fragment vascularity, although it had a relatively low specificity. There remains the need for education and training for trauma surgeons in the evaluation of fragment viability to ensure adequate wound excision as part of fracture management.
An ovine model was developed to study the outcome following intramedullary nailing of a heavily contaminated fracture. Animals in the control group received no treatment directed at controlling infection, whereas those in the treatment group received wound debridement, lavage and the use of appropriate systemic antibiotics. Despite this, infection developed at the osteotomy site and along the entire length of the implant in all animals in both groups. It was felt that standard methods of wound management might be inadequate when applied at the time of intramedullary nailing since the spread of contamination following the use of reamers was demonstrated in all animals. Results from this study support the clinical impression that heavily contaminated fractures should not be treated by primary intramedullary nailing.
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Primary thoracic blast injury causes a triad of bradycardia, hypotension and apnoea mediated in part via a vagal reflex. Blast casualties may also suffer blood loss, and the response to progressive simple haemorrhage is biphasic: an initial tachycardia followed by a vagally mediated reflex bradycardia which can be attenuated by micro opioid agonists. The aims of this study were to determine the effects of thoracic blast injury on the response to subsequent haemorrhage, and the effects of morphine, administered after blast, on the response to blood loss. Male Wistar rats, terminally anaesthetised with alphadolone-alphaxolone (19-21 mg x kg(-1) h(-1) I.V.), were allocated randomly to one of three groups: Group I, sham blast; Group II, thoracic blast; Group III, thoracic blast plus morphine (0.5 mg x kg(-1) I.V. given 5 min after blast). Blast (Groups II and III) resulted in significant (P < 0.05, ANOVA) bradycardia, hypotension and apnoea. Sham blast (Group I) had no effect. Ten minutes later, haemorrhage (40 % of the estimated total blood volume (BV)) in Group I produced a biphasic response comprising a tachycardia followed by a peak bradycardia after the loss of 33 % BV. Arterial blood pressure did not fall significantly until the loss of 13.3 % BV. In Group II the haemorrhage-induced tachycardia was absent and the bradycardia was augmented: peak bradycardia was seen after the loss of 23 % BV. Mean arterial blood pressure (MBP) began to fall as soon as haemorrhage commenced and was significant after the loss of 10 % BV. Morphine (Group III) prevented the haemorrhage-induced bradycardia and delayed the significant fall in MBP until the loss of 30 % BV. It is concluded that the response to thoracic blast injury augments the depressor response to haemorrhage while morphine attenuates this response.
An animal model was used to study the pathogenesis of pin track infection. The roles of fluid accumulation around the pin/bone interface and mechanical loosening of the pin were specifically studied. In addition, the spread of bacteria in relation to the clinical appearance of the pin track was assessed. This study demonstrated that fluid accumulation around the interface is an important factor in the spread of infection from the superficial wound track to the medulla of the bone. Spread occurs despite the absence of mechanical pin loosening, and can occur before any clinical features of infection are apparent.
Implant sepsis. due to previous external fixator pin track infection, is the most common complication of secondary intramedullary (IM) nailing of the tibia. We have developed an animal model, which allows different treatment methods to be studied. Using an established ovine model of a pin track infection, Staphylococcus aureus was used to infect the external fixator pins, two weeks prior to reamed IM nailing. In the control group, the animals were killed at a mean of 10.5 days following nailing, when widespread infection was evident, with septic arthritis, abscess formation, and infection of the entire length of the tibia in all six animals. In the treatment group, before IM nailing, the pin sites were debrided, and both local and systemic antibiotics were administered. All surgical wounds healed without evidence of infection, 4 of the 6 animals survived for 28 days, and bacteria were only isolated from 1 of the 6 implants. Treatment was successful at reducing, but not eliminating, infection after secondary nailing.
BACKGROUND: The mortality rate from sepsis has improved little over the past two decades. One reason for this has been the use of flawed or inappropriate experimental models in preclinical sepsis studies. METHODS: A literature review of animal models of sepsis was performed following a Medline search based on the following medical subject headings: disease models, endotoxin, inflammation, peritonitis and sepsis. Additional references were identified from the papers identified in the search. RESULTS AND CONCLUSION: Many animal models of sepsis have been described but none has proved to be superior. Extrapolation of results from endotoxicosis or bacterial infusion models should be regarded with caution. Peritonitis models should be accepted as the 'gold standard' but the use of appropriate virulent bacterial species needs to be ensured. A standardized panel of animal models for the preclinical assessment of immunomodulatory agents should be established, including at least one immuno- suppressed model to simulate the immunocompromised patient with sepsis. A uniform and valid definition of sepsis applicable to both small and large animal species is required.
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Blast injuries represent a problem for civilian and military populations. Primary thoracic blast injury causes a triad of bradycardia, hypotension and apnoea. The objective of this study was to investigate the reflex nature of this response and its modulation by vagotomy or administration of atropine. The study was conducted on terminally anaesthetised (alphadolone/alphaxalone, 18-24 mg x kg x h(-1), I.V.) male Wistar rats randomly allocated to the groups indicated below. Blast injuries were produced with compressed air while sham blast involved the sound of a blast only. Primary blast injury to the thorax resulted in a bradycardia (measured as an increase in the interval between beats, or heart period (HP) to 489 +/- 37 ms from 133 +/- 3 ms with a latency of onset of 4.3 +/- 0.3 s, mean +/- S.E.M.), hypotension (fall in mean arterial blood pressure (MBP) from 128.1 +/- 3.7 mmHg to 34.8 +/- 4.1 mmHg, latency of onset 2.0 +/- 0.1 s) and apnoea lasting 28.3 +/- 2.3 s. Sham blast had no effect. The bradycardia and apnoea following thoracic blast were abolished by cervical vagotomy while the hypotension was attenuated. Atropine (0.3 mg x kg(-1), I.V.) caused a significant reduction in the bradycardia (HP increasing from 124 +/- 3 ms to 142 +/- 4 ms) but did not modulate either the hypotension or apnoea. It is concluded that a reflex involving the vagus nerve mediates the bradycardia, apnoea and a component of the hypotension associated with thoracic blast. The pattern of this response is similar to effects that follow stimulation of the pulmonary afferent C-fibres.
We used laser Doppler flowmetry (LDF) to measure flux in cortical bone fragments as a method of determining their vascular status and viability. In an experimental tibial osteotomy measurements of flux were made from specific cortical sites both before and after osteotomy. Flux levels fell rapidly in non-vascularised fragments and remained significantly reduced throughout the experiment. By contrast, those in vascularised fragments were significantly reduced one and two hours after the osteotomy but then increased. From three hours after the osteotomy there was no significant difference in flux levels between the vascularised fragments and proximal bone stock. We conclude that measurement of bone flux by LDF may have a role in the objective evaluation of the viability of bone fragments, but that further studies are required to validate the technique before its adoption in the management of the injured patient.
Pentoxifylline is a phosphodiesterase inhibitor, known to suppress tumour necrosis factor-alpha production and improve cardiopulmonary parameters and survival in animal models of sepsis. Using a porcine model of abdominal trauma resulting from the combined insults of haemorrhage and infection, a randomised placebo-controlled trial was conducted of pentoxifylline (20 mg/kg bolus followed by 20 mg/kg infusion over 1 h) administered in addition to a colloid resuscitation regimen. Female Large White pigs (45-60 kg) were bled 40% of their blood volume and peritonitis was induced using E. coli (O18: K1: H7) in an autoclaved faecal suspension. Animals were resuscitated with either colloid alone (n=5) or colloid plus pentoxifylline (n=5). Pentoxifylline attenuated increases in mean arterial and pulmonary artery pressures and reduced both systemic and pulmonary vascular resistance. It worsened the lactic acidosis associated with 'septic shock' and failed to reduce serum TNF-alpha levels. Pentoxifylline, in the high doses used in this study, does not have a role as an adjunct to resuscitation in this clinically relevant model of trauma.
The physiological responses to either hemorrhage or sepsis have been well documented, however, their simultaneous delivery, as often seen in penetrating trauma, has not been extensively studied. A terminally-anesthetized porcine model of fixed-volume hemorrhage combined with intraperitoneal sepsis was developed. Large White pigs (45-60 kg) were bled 40% of blood volume and peritonitis was induced using an E. coil (O18:K1:H7) culture. Three groups of animals were sequentially studied. Group A (n = 8) received 10(8) bacteria, and Groups B (n = 4) and C (n = 5) received 10(10) organisms. All animals were maintained on a 2.5 mL/kg/h infusion of 0.9% saline. Group C was autotransfused at 1 h. Animals were monitored for up to 24 h. Cardiovascular features of hypovolemia were recorded in all animals. Animals in Group A improved clinically with little microbiological evidence of systemic sepsis. Group B showed rapid cardiovascular collapse, early E. coil-positive blood cultures, and an early rise in serum TNF-alpha levels. Autotransfusion of Group C significantly improved cardiopulmonary parameters, acid-base status, and survival. A reproducible model of hemorrhage and peritonitis, appropriate for abdominal trauma, which allows investigation of resuscitative and pharmacological interventions has been characterized.
Profound physiological changes occur following primary blast exposure but the contribution of cardiac arrhythmias is unknown. Thirteen rats, under intravenous anaesthesia, were exposed to a blast wave directed at the thorax (Group II); 10 other animals underwent abdominal blast (Group III) and nine animals acted as controls (Group I). Animals were monitored before, during and after blast exposure. Group II animals demonstrated apnoea, bradycardia and hypotension. No significant physiological changes were seen in Groups I or III. Group II displayed a variety of ECG disturbances, from ventricular extrasystoles to ventricular fibrillation. All abnormalities reverted to sinus rhythm within minutes except in fatally injured animals. These ECG changes probably result from stress wave injury. Significant disturbances might account for some fatalities following primary blast exposure and may exacerbate the triad of apnoea, bradycardia and hypotension. Such observations may have important consequences for the management of blast casualties.
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We developed an ovine model of an external-fixator pin-tract infection. With use of a novel method of tissue sampling, infection of the medullary canal was confirmed in all (10 of 10) external-fixator pins that were contaminated with Staphylococcus aureus after they were inserted. In addition, all (five of five) adjacent, uncontaminated pins became infected. We demonstrated that pin-tract infection can be difficult to diagnose clinically, despite gross infection of the tract, and that bacteria can spread within the medulla. Three of the infected pins (20%) did not appear clinically infected, were not loose, and were normal on radiographs after 1 week. Staphylococcus aureus was isolated from the medulla around all 15 pin tracts, and nine other organisms were isolated from the tracts. Despite the presence of infection, the majority of the pins remained well fixed in the bone after 2 weeks.