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.

Familial polythelia over three generations with polymastia in the youngest girl.

UNLABELLED: Supernumerary nipples or polythelia are developmental abnormalities located along the embryonic mammary lines. It is the most common form of accessory breast tissue malformation and usually occurs sporadically but familial aggregation has been reported. Polythelia has been reported in association with congenital malformations, in particular with renal anomalies. Polymastia in female patients has been reported to manifest usually during pregnancy or lactation. We report on a pedigree with six cases of polythelia over three generations and one case of polythelia and polymastia in the youngest member of this family. The girl (11 years old ) had in addition to six supernumerary nipples, an accessory breast gland located under the normal left breast. No other congenital malformations could be detected. This girl will remain under follow-up until the end of puberty when the accessory breast gland will be removed. Manifestation of polymastia during puberty rarely has been reported. CONCLUSION: Polymastia may appear with familial polythelia even without renal anomalies.

Fibrinolytic activity and postoperative salvaged untreated blood for autologous transfusion in major orthopaedic surgery.

OBJECTIVE: To evaluate the fibrinolytic activity in a closed surgical wound, in postoperatively drained blood, and during autologous transfusion. DESIGN: Prospective study. SETTING: National hospital, Norway. PATIENTS: 9 patients operated on for thoracic scoliosis. MAIN OUTCOME MEASURE: Concentrations of plasmin/antiplasmin (PAP), alpha2-antiplasmin, and D-dimers in drained, arterial, and mixed venous blood before, during, and after infusion of 10 ml/kg body weight of postoperatively drained, untreated blood. RESULTS: In drained blood the concentration of alpha2-antiplasmin was 31% of the preoperative arterial control value. Together with the increased concentrations of PAP to 18076 microg/L and D-dimers to 126 mg/L, this indicates extensive fibrinolytic activity in the closed wound. The postoperative autologous transfusion of drained, untreated blood increased the concentration of PAP from 507 to 2453 microg/L and of D-dimer from 0.7 mg/L to 15.3 mg/L in systemic blood. CONCLUSION: The systemic concentration of fibrin(ogen) degradation products, indicated by D-dimers, after recirculation of drained, untreated blood might impair coagulation. The extensive activation of plasmin might exhaust available alpha2-antiplasmin in the wound and result in postoperative rebleeding.

Effects of different suckling systems on milk production, udder health, reproduction, calf growth and some behavioural aspects in high producing dairy cows - a review.

This article discusses the consequences of different suckling systems in the industrial countries for the milk production, udder health, reproduction and behaviour of high producing dairy cows and the effects on the gain, health and behaviour of the calves. The suckling systems are divided into three different categories depending on the purpose and duration of the suckling period. Long-term suckling with or without additional milking covering the period where the calf has a nutritional need for milk, and short-term suckling, where cow and calf are kept together in the colostrum period only.Long-term suckling without additional milking in early lactation can in some situations stimulate the subsequent milk production to a greater extent than milking alone. No clear or significant differences can be found between restricted and free suckling systems. Most experiments show that suckling decreases the risk of mastitis in the suckling period and in some cases even for some time after the suckling has been terminated. Suckling and milking during the same period is not advantageous in production turns because of a very poor ejection of milk. Long-term suckling can increase the post-partum interval until first heat, in some cases until the end of the suckling period. However, as the cows appear to be more fertile, the net effect on reproduction is small. The suckled calves are usually healthy with a high daily gain. Short-term suckling have more advantages than disadvantages on production, health and behaviour of both the cow and the calf compared to an immediate separation after birth.

Multiple intestinal stenoses and peripheral gangrene: a combination of two rare surgical complications in a child with Kawasaki disease.

Kawasaki disease (KD) often presents with a challenging variety of clinical symptoms. Severe gastrointestinal complications are rare and mainly appear as pseudo-obstruction. However, the authors report the unique case of a 4-month-old girl with KD suffering from a mechanical ileus. The optimal timing of surgery presented a dilemma, because she received lytic treatment for gangrenes of both her hands and feet and additionally had large coronary artery aneurysms. Finally laparotomy had to be performed while the patient was on an anticoagulant medication, and it showed a 30-cm-long jejunal segment with multiple filiforme stenoses, requiring resection and anastomosis. The postoperative course was uneventful regarding the abdominal situation; however, the left hand and left foot remained gangrenous and had to be amputated. In patients with KD, not only pseudo-obstruction, but irreversible intestinal obliteration has to be encountered. This combination of intestinal stenosis and acral gangrene has not been described before. J Pediatr Surg 36:651-653.

Tissue factor antigen and activity in serum of postoperatively shed blood used for autologous transfusion.

Orthopaedic surgery involves extensive dissection of connective and richly vascularised tissues rich in tissue factor (TF). It was, therefore, of interest to quantify the amount of TF antigen and activity in postoperatively drained, unwashed wound blood collected for the purpose of autologous transfusion. In nine young patients subjected to surgery for idiopathic thoracic scoliosis, samples were drawn postoperatively from collected shed blood, a pulmonary artery catheter and a radial arterial cannula prior to, during and after reinfusion of shed blood (10 ml/kg body weight), and analysed for TF antigen and activity. Preoperative arterial control samples contained 128 pg/ml TF antigen compared with 40 pg/ml postoperatively. During reinfusion of drained blood, arterial TF concentration rose to 96 pg/ml and dropped to 64 pg/ml after infusion. Arterial and mixed venous blood did not differ significantly in TF levels. Serum from drained blood contained high concentrations of TF antigen (773 pg/ml), but no TF activity was detected. It is concluded that the high concentrations of TF antigen in serum from postoperatively drained blood collected for autologous transfusion are devoid of procoagulant activity. The TF antigen in plasma of drained blood is suggested to be a soluble, proteolysed TF-apoprotein or a TF complex inactivated by the TF pathway inhibitor (TFPI).

Cytokine modulation in experimental endotoxemia: characterization of an ex vivo whole blood model.

A new model was developed to study cytokine regulation and modulation in whole blood ex vivo. The model is characterized by stable leukocyte counts and high leukocyte viability throughout the experimental period. Oxygen consumption per time decreased slowly, whereas carbon dioxide partial pressure increased accordingly throughout the experiment. In this model, the anti-inflammatory effects of recombinant human (rh) interleukin (IL)-4, rhIL-10 and rhIL-13 on lipopolysaccharide (LPS) stimulated (10 ng/ml) leukocytes were examined and compared by measuring their ability to inhibit the release and mRNA levels of tumor necrosis factor (TNF)alpha, IL-6 and IL-1beta. rhIL-10 potently inhibited the release of TNF-alpha, IL-6 and IL-1beta in a potent and dose-dependent manner, but did not influence the mRNA levels of these cytokines in CD14-positive cells. Also, rhIL-4 and rhIL-13 inhibited the release of IL-6 and IL-1beta in a potent and dose-dependent manner, however, stronger maximal inhibition of IL-1beta (85%) than of IL-6 (60%) was obtained. In contrast, rhIL-4 and rhIL-13 seemed to have both stimulatory and inhibitory effects on plasma values of TNF-alpha. The effects of 10 ng/ml LPS showed to be signalling through the CD14 receptor, since blood treated with a monoclonal anti-CD14 antibody did not produce any TNF-alpha. The whole blood model described in this study is in our opinion a useful tool for investigating immunomodulating effects on a mixed white blood cell population.

Fibrinogen, fibrin and its degradation products in drained blood after major orthopaedic surgery.

The aim of this study was to evaluate the fibrinogen enzymatic conversion in blood collected postoperatively from a surgical wound. Ten otherwise healthy patients (aged 11-28 years) in need of surgical treatment for thoracic scoliosis were included in the study. Arterial blood preoperatively and at wound closure were compared with samples of drained blood from the wound at closure and from a collection system for autologous transfusion 2.8 +/- 1.1 h later. There was a decrease in the fibrinogen content in arterial blood from 2.17 +/- 0.35 g/l to 1.23 +/- 0.42 g/l, which followed a 40% haemodilution estimated from the blood loss of 1.6 +/- 0.9 l during the operation. Drained blood contained high concentrations of D-dimer (85 +/- 53 mg/l from the wound and 121 +/- 47 mg/l from the collection system), but no clottable fibrinogen. The Western immunoblots all visualized the same patterns; in drained blood there were split-products mainly from cross-linked fibrin, in contrast to arterial blood which contained only normal fibrinogen. This indicates a strong fibrinolysis in the surgical wound after closure, with concentrations of fibrin degradation products that may impair local coagulation, and if infused, might interfere with general haemostasis.

Inflammatory cytokines and their receptors in arterial and mixed venous blood before, during and after infusion of drained untreated blood.

Wound blood for postoperative autologous transfusion is drained through an area of damaged tissue, the surgical wound, and contains inflammatory mediators. The inflammatory cytokines interleukin-1-beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) and their modulators interleukin-1-receptor antagonist (IL-1Ra), interleukin 6 soluble receptor (IL-6sR), soluble tumour necrosis factor receptor 1 (sTNF-R1) and interleukin 10 (IL-10), together with white cell count (WCC) and white cell differential count were measured in arterial and mixed venous blood before, during and after infusion of postoperatively drained untreated blood in nine patients operated for thoracic scoliosis. We found a transient increase in IL-6, an increase in TNF-RI, an increase in IL-8 with granulocytosis and a decrease in IL-10 in the systemic circulation. The increase in IL-6 was higher in mixed venous than in arterial blood.

Complement activation and increased systemic and pulmonary vascular resistance indices during infusion of postoperatively drained untreated blood.

In nine healthy young patients, operated on for thoracic scoliosis, a pulmonary artery catheter was inserted for the study of haemodynamic variables and blood sampling during autologous transfusion of postoperatively drained blood. At 1-3 h after wound closure, 10 ml kg/body weight of drained untreated blood from the wound was collected and recirculated over a l-h period. The concentration of the complement activation product, C3bc, increased from a mean of 5.4 (SD 1.5) AU ml-1 before infusion to 11.1 (3.9) AU ml-1 during infusion and then returned to 7.8 (2.8) AU ml-1 after infusion. The concentration of the terminal complement complex (TCC) increased from 0.5 (0.2) to 1.3 (0.5) AU ml-1 and was reduced to 0.7 (0.3) AU ml-1 after infusion. Only TCC exceeded the reference values which are 14 AU ml-1 for C3bc and 1.0 AU ml-1 for TCC. Pulmonary vascular resistance index concomitantly increased from a mean of 130 (SD 52) to 195 (88) dyn s cm-5 m-2 and was reduced to 170 (86) dyn s cm-5 m-2 after infusion. Systemic vascular resistance index increased from a mean of 1238 (SD 403) to 1349 (473) dyn s cm-5 m-2 and returned to 1196 (401) dyn s cm-5 m-2 after infusion. White blood cell count (WCC) increased from 14.4 (4.3) x 10(9) litre-1 before infusion to 17.8 (7.2) x 10(9) litre-1 during and after infusion. No change in platelet count during infusion was observed. There were no differences in WCC or platelet count between mixed venous or peripheral arterial blood. Pulmonary and systemic vascular resistance indices may be influenced by activated complement in drained untreated blood when it is recirculated.