In vivo characterization of ischemic small intestine using bioimpedance measurements.

The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia.

A tribute to Cicero Parker Meek.

Cicero Parker Meek (1914-1979) was working as a general practitioner at the Aiken County Hospital in South Carolina, USA, and had a special interest in the treatment of burn patients. The procedure first presented in 1958 by Meek for a device-based expansion of split-skin (micrografting), which was invented before the mesh technique, is a milestone in the history of burns surgery. The method was forgotten until well into the 90s of the last century, and was only readopted and improved by no longer identifiable physicians at the Red Cross Hospital in Beverwijk. The Meek translation procedure was subsequently modified through the innovations of Kreis and Raff. With increased survival of massively burned patients, mesh grafting fell short of requirements. Mesh grafts of 1:9 expansion are difficult to handle and are vulnerable to dislodgement on the wound bed. Kreis and Raff showed in 1994 that 1:9 expanded mesh grafts did not achieve a true 1:9 expansion on the wound surface, in contrast to 1:9 expanded Meek grafts. Thus Meek grafts provided a highly effective autograft expansion in very large burns. Cicero Parker Meek was an exceptional person in the history of burn therapy.

[Osteogenesis imperfecta]. / Osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is the most common genetic disease of bone and is characterized by fragile bones and growth disorders of varying severity. Most cases of OI are inherited autosomal dominant and caused by a mutation in the collagen type I gene. DIAGNOSTICS: Indications for OI are bone fragility, stunted growth, scoliosis, skull deformities, blue sclera, loss of hearing, dentinogenesis imperfecta and increased laxity of ligaments and skin. In most cases it is possible to make a clinical diagnosis but a skin biopsy or genetic testing can be useful; however, negative results for these tests do not exclude OI. THERAPY: Therapy must be carried out in a multidisciplinary team and includes conservative (e.g. physiotherapy, rehabilitation programs and orthopedic aids), operative (e.g. intramedullary stabilization procedures) and pharmaceutical (e.g. biphosphonates and growth hormones) procedures. PROGNOSIS: The prognosis depends on the type of OI and ranges from normal life expectations for type 1 patients up to up to perinatal mortality for type II patients.

Systemic and local cytokine kinetics in musculoskeletal injury: a prospective study in patients with ankylosing spondylitis.

OBJECTIVE: Back surgery in patients with ankylosing spondylitis is a major trauma in individuals with tissue inflammation and joint destruction along the spine; we used surgery in these patients as a model in the study of systemic and local cytokine profiles in complicated trauma situations. MATERIAL AND METHODS: Blood was sampled before, during and after surgery in 10 patients operated on with extending osteotomy of the lumbar spine. Samples of arterial blood and local wound blood were analysed for proinflammatory and anti-inflammatory cytokines. RESULTS: Surgery induced no significant changes in systemic values of TNFalpha and IL-1beta. There were significant increments in systemic values of IL-6, IL-8 and sTNF-R1. A systemic increase in values of IL-10 was only noticed after 24 h. There were increments in local values of TNFalpha at 24 h and in local values of IL-1beta, IL-6, Il-8 and IL-10 at both 4 and 24 h postoperatively. The local values were in general significantly higher than the systemic values. CONCLUSIONS: This study indicates that a major musculoskeletal trauma principally is followed by significant increases in systemic levels of IL-6 with only modest systemic reactions in TNFalpha and IL-1beta, even in patients with an inflammatory disease. However, there are in general significantly increased local levels of IL-1beta, IL-6, IL-8 and IL-10, and our conclusion is that systemic cytokine levels might not reflect local reactions.

Immune modulation after total hip surgery. A prospective ex vivo study.

BACKGROUND: Major trauma affects the immune system, and immunosuppression may render the patients susceptible to septic complications. The purpose of this study was to investigate lipopolysaccharide (LPS)-induced releases of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in whole blood in patients undergoing total hip replacement. METHODS: Seven patients (6 females) who underwent elective total hip replacement were included. Ex vivo LPS-induced releases of TNF-alpha and IL-6 were measured in a whole blood assay at days 1, 6, 9 and 12 postoperatively, using low- and high-dose LPS incubation. At the same time, white blood cell counts were analyzed. RESULTS: The amount of TNF-alpha release was significantly reduced at days 6 and 12. Compared to monocyte counts, TNF-alpha release was significantly decreased also at day 9 in low- and high-dose LPS stimulation. IL-6 in plasma was significantly increased at day 1 and normalized thereafter. There were no differences in LPS-induced IL-6 levels compared to the levels before surgery. CONCLUSION: This in vivo/ex vivo study shows a reduced capacity of whole blood to release LPS-induced TNF-alpha at day 6 through to day 12 after major orthopedic surgery. Attenuated TNF-alpha release may contribute to an increased postoperative susceptibility to gram-negative sepsis.

Systemic and local cytokine patterns during total hip surgery.

OBJECTIVE: Increased levels of inflammatory cytokines have been described in musculoskeletal injury. Total hip replacement is major musculoskeletal surgery, and in the present study this operation was used to investigate systemic and local cytokine patterns during musculoskeletal trauma. MATERIAL AND METHODS: Blood was sampled before, during and after surgery in 10 patients given total hip replacement. Samples of arterial blood and local blood from the femoral canal were analysed for proinflammatory and anti-inflammatory cytokines. RESULTS: Surgery induced significant increases in arterial and local levels of interleukin 6 (IL-6) (p = 0.000, respectively) with the highest levels at 4 h after operation. There were significantly higher local levels of IL-6 than arterial levels. Interleukin 1beta (IL-1beta) was not significantly influenced by surgery at any time (p = 0.800 and 0.300 for local and arterial levels, respectively), nor was tumour necrosis factor alpha (TNFalpha) (p = 0.375 and 0.547 for local and arterial levels, respectively). Local levels were higher than arterial levels for IL-1beta and for TNFalpha. At the end of the operation, local levels of interleukin 10 (IL-10) were significantly reduced (p = 0.036), while surgery did not influence the arterial levels of IL-10 (p = 0.235). There were no significant differences in local and arterial levels of IL-10 (p = 0.558). CONCLUSIONS: The study indicates that a major musculoskeletal operation on otherwise healthy patients is associated with fairly modest reactions of inflammation, both systemically and locally.

Reduced capacity of whole blood leucocytes to express tumour necrosis factor-alpha and interleukin-10 following major orthopaedic surgery.

BACKGROUND: Severe trauma is a challenge to the immune response and may cause reduced immune capacity. As a marker of decreased cellular activity, studies with ex vivo lipopolysaccharide (LPS) stimulation of whole blood or isolated mononuclear cells from injured patients have revealed reduced production of inflammatory cytokines. To gain further insight into immune alterations in orthopaedic surgery, we studied LPS-induced tumour necrosis factor (TNF)-alpha and interleukin (IL)-10 in whole blood of patients during peri- and postoperative phases of total hip replacement. METHODS: Four females and 3 males undergoing elective total hip replacement were included in the study. Ex vivo LPS-induced TNF-alpha and IL-10 were measured in a whole blood assay before, during and at 1 and 6 days after operation. In addition, the counts of white blood cells were determined. RESULTS: During the operation, there were significant reductions in the number of monocytes, but at day 1 and 6 after surgery, there were significant increases as compared to the levels before surgery. The capacity of whole blood to express TNF-alpha and IL-10 did not change significantly during the operation and the following postoperative day. At day 6, however, there were significant reductions in expression of both TNF-alpha and IL-10 as compared to the levels before the operation. In relation to the values of monocytes, there was a significant reduction in the expression of TNF-alpha also at day 1 after operation. CONCLUSION: Our data indicate that in the course of at least 6 days after a major orthopaedic trauma, there is suppression of the whole blood capacity to express the inflammatory cytokine TNF-alpha and the anti-inflammatory cytokine IL-10 when exposed to LPS. During this time, then, the patient is particular susceptible to septic complications.

Iteroparous reproduction strategies and population dynamics.

Asymptotic relationships between a class of continuous partial differential equation population models and a class of discrete matrix equations are derived for iteroparous populations. First, the governing equations are presented for the dynamics of an individual with juvenile and adult life stages. The organisms reproduce after maturation, as determined by the juvenile period, and at specific equidistant ages, which are determined by the iteroparous reproductive period. A discrete population matrix model is constructed that utilizes the reproductive information and a density-dependent mortality function. Mortality in the period between two reproductive events is assumed to be a continuous process where the death rate for the adults is a function of the number of adults and environmental conditions. The asymptotic dynamic behaviour of the discrete population model is related to the steady-state solution of the continuous-time formulation. Conclusions include that there can be a lack of convergence to the steady-state age distribution in discrete event reproduction models. The iteroparous vital ratio (the ratio between the maximal age and the reproductive period) is fundamental to determining this convergence. When the vital ratio is rational, an equivalent discrete-time model for the population can be derived whose asymptotic dynamics are periodic and when there are a finite number of founder cohorts, the number of cohorts remains finite. When the ratio is an irrational number, effectively there is convergence to the steady-state age distribution. With a finite number of founder cohorts, the number of cohorts becomes countably infinite. The matrix model is useful to clarify numerical results for population models with continuous densities as well as delta measure age distribution. The applicability in ecotoxicology of the population matrix model formulation for iteroparous populations is discussed.