A national propensity score-matched analysis of emergency laparoscopic versus open abdominal surgery.

BACKGROUND: Laparoscopy has been widely adopted in elective abdominal surgery but is still sparsely used in emergency settings. The study investigated the effect of laparoscopic emergency surgery using a population database. METHODS: Data for all patients from December 2013 to November 2018 were retrieved from the NELA national database of emergency laparotomy for England and Wales. Laparoscopically attempted cases were matched 2 : 1 with open cases for propensity score derived from a logistic regression model for surgical approach; included co-variates were age, gender, predicted mortality risk, and diagnostic, procedural and surgeon variables. Groups were compared for mortality. Secondary endpoints were blood loss and duration of hospital stay. RESULTS: Of 116 920 patients considered, 17 040 underwent laparoscopic surgery. The most common procedures were colectomy, adhesiolysis, washout and perforated ulcer repair. Of these, 11 753 were matched exactly to 23 506 patients who had open surgery. Laparoscopically attempted surgery was associated with lower mortality (6.0 versus 9.1 per cent, P < 0.001), blood loss (less than 100 ml, 64.4 versus 52.0 per cent, P < 0.001), and duration of hospital stay (median 8 (i.q.r. 5-14) versus 10 (7-18) days, P < 0.001). Similar trends were seen when comparing only successful laparoscopic cases with open surgery, and also when comparing cases converted to open surgery with open surgery. CONCLUSION: In appropriately selected patients, laparoscopy is associated with superior outcomes compared with open emergency surgery.

Minimally invasive (laparoscopic) surgery has been widely adopted in elective surgery but is sparsely used in emergencies. The study used national data to look at outcomes for patients having laparoscopic or open surgery, and used statistical methods to match patients in each group for critical variables such as type of operation, age and how unwell they were at time of surgery. Laparoscopy was found significantly to improve outcomes with reduced duration of stay in hospital, and lower rates of death after surgery. This suggests laparoscopy should be considered for much wider use than is currently employed.

Myositis and myopathy of sarcoidosis: A case report.

Muscular manifestations of sarcoidosis are commonly found on biopsy but rare on correlated imaging. We present a rare case of a 36-year-old male patient with sarcoid myositis and image findings of active myositis in the lower back and pelvic girdle musculature. This case suggests considering sarcoidosis as a differential diagnosis in the setting of chest findings and new lower back and lower extremity weakness.

Impact of laparoscopic approach in emergency major abdominal surgery: single-centre analysis of 748 consecutive cases.

Background Acute abdominal pathology requiring emergency laparotomy is a common surgical presentation. Despite its widespread implementation in other surgical procedures, laparoscopy, rather than laparotomy, is sparingly used in major emergency surgery. This study reports outcomes and impact of rising use of laparoscopy for a single high-volume district general hospital. Methods Data were retrieved from the prospective National Emergency Laparotomy Audit database for a 30-month period. Patient, procedural, and in-hospital outcome data were collated. Temporal trends were assessed and regression analysis conducted for clinical outcomes. Results A total of 748 consecutive cases were recorded. There was an increasing use of laparoscopy over the study period, with 49% of cases attempted laparoscopically in the final six-month interval. Patients treated laparoscopically were at reduced risk of mortality (odds ratio 0.114, 95% confidence interval 0.024 to 0.550) and experienced reduced length of intensive care stay (regression coefficient ­1.571, 95% confidence interval ­2.625 to ­0.517) in multivariate adjusted analysis. Conclusions Laparoscopy is safe and feasible in a large proportion of cases. It is associated with improved outcomes versus laparotomy.

Effect of delivery method on the efficacy of Salmonella vaccination in chickens.

To investigate whether the efficacy of live vaccines is influenced by the mode of vaccine delivery, a widely-used UK live commercial Salmonella Enteritidis vaccine was delivered to pullet chicks either by spray, in drinking water, or in combination with a bivalent vaccine containing inactivated Salmonella Enteritidis and Salmonella Typhimurium. The birds were subsequently challenged with 10(2) or 10(8) colony-forming units (cfu) of Salmonella Enteritidis through drinking water at either six or 20 weeks of age. Ten days after the challenge, the birds were euthanased and their caecal contents cultured for Salmonella. All of the vaccinated groups contained fewer Salmonella Enteritidis-positive birds than the unvaccinated groups. The 'spray-vaccinated' group contained significantly fewer Salmonella Enteritidis-positive birds than the 'water-vaccinated' group after challenge with 10(8) cfu at 20 weeks. However, there was little or no difference at the other challenge time points between the groups that received vaccine through different modes of delivery.

Awake renal transplantation; a realistic alternative to general anesthesia.

A 63-year-old man with profound phobia of general anesthesia recently underwent successful renal transplantation in our unit under combined spinal-epidural anesthesia (CSEA). We believe that although this is not a novel technique, it is a realistic option for renal transplantation in patients in whom general anesthesia is not feasible. The use of CSEA for surgery below the umbilicus and its postoperative pain management has increased in popularity in recent years. Its use in renal transplantation is not widely reported; however, available articles suggest that it is a safe and useful alternative to general anesthesia, with no significant difference in anesthesia or surgical time, surgical conditions, hemodynamic stability, or early postoperative renal function. The procedure was performed with no alteration to the surgical technique usually adopted by the surgeon. The patient had a largely uneventful postoperative recovery, with good pain control and no significant complications. He has achieved good stable renal function, with a serum creatinine concentration of 105 mumol/L at 6 months (preoperative serum creatinine concentration, 832 mumol/L). We believe this case demonstrates that CSEA is a practical option for renal transplantation in the United Kingdom, and would recommend CSEA as a useful alternative to general anesthesia in patients with this type of phobia. Careful preoperative planning, patient selection, and consideration of a contingency plan meant that surgically the procedure proceeded as standard, with good results. Because of the success of this case, a second patient with phobia of general anesthesia has recently been placed on the regional transplantation waiting list.

Hybrid cells formed by fusion of Epstein-Barr virus-associated B-lymphoblastoid cells and either marrow-derived or solid tumour-derived cell lines display different co-stimulatory phenotypes and abilities to activate allogeneic T-cell responses in vitro.

A panel of stable cell hybrids was generated by fusing a range of marrow-derived and solid tumour-derived human cell lines with the B-lymphoblastoid cell lines, HMy2 or KR4, and expression of immunologically relevant accessory and co-stimulatory molecules, and ability to stimulate allogeneic T-cell responses in vitro was investigated. Hybrid cell lines generated from three marrow-derived tumour cells consistently expressed both MHC class I and class II molecules, a range of accessory and T-cell co-stimulatory ligand molecules, including CD80 and CD86, and directly stimulated markedly enhanced T-cell proliferative responses in vitro, as compared with the parent tumour cell lines. The responses were blocked by addition of CTLA4-Ig fusion protein to the cultures, indicating a role of CD28/B7 interaction in induction of T-cell activation. By contrast, hybrid cells derived from three solid tumours only expressed MHC class II when the parent tumour cell line expressed MHC class II and consistently failed to express CD80 or CD86. These hybrid cells also stimulated greater T-cell proliferative responses in vitro than the parent tumour cell lines, although effective co-stimulation depended on the presence of responder non-T cells in the cultures. The expression of co-stimulatory ligand molecules and ability to directly stimulate strong allogeneic T-cell responses correlated with the EBV latency type of the hybrid cells. These data suggest that phenotypic and functional differences in fusion cells of professional antigen- presenting cells and tumour cells arise as a result of the parent tumour cell type.

The effectiveness of protective clothing in the reduction of potential DNA contamination of the scene of crime.

The use of ultra-sensitive low copy number (LCN) DNA typing allows the analysis of picogram amounts of DNA. Trace evidence accidentally left at a scene of crime (SOC) by the investigating team may be inadvertently collected and analysed, potentially leading to spurious evidence being introduced into the criminal investigation. A series of experiments were undertaken to determine the extent to which an investigator could contribute to any DNA contamination of a scene of crime under different simulated activities. Further, the degree to which any contamination was reduced by the use of commercially available protective clothing was demonstrated. Precautions that should routinely be taken at a scene of crime to reduce the risk of DNA contamination are recommended.

Hospital emergency rooms and children's health care attitudes.

OBJECTIVE: To assess attitudes of children requiring hospital emergency room (ER) treatment for trauma injuries 5 years afterward to evaluate the long-term effect of treatment distress. For comparison, health care attitudes of a large random sample of children were assessed. METHOD: Children (N = 139, 7-19 years old) recruited from the ER completed a health care attitude questionnaire. Comparable schoolchildren (N = 1,300) completed the same questionnaire, with the addition of a few questions asking about hospital contact. The ER-recruited group was part of a 5-year follow-up study, and at the time of initial recruitment, their parents had rated their children's degree of distress at both the time of injury and of ER treatment on a 6-point scale. RESULTS: For the ER-recruited sample, the degree of distress during ER treatment did not seem to have longterm effects on children's attitudes. For the random sample, contact with the ER, especially for a trauma injury, was related to children liking the ER more. CONCLUSIONS: Although other research has shown that aversive medical experiences may negatively affect children's attitudes, these findings suggest that the nature of the medical contact is important in how children interpret medically induced pain, which is related to their attitudes.

Basal release of nitric oxide and its interaction with endothelin-1 on single vessel hydraulic permeability.

BACKGROUND: Both endothelin-1 (ET-1) and nitric oxide (NO) are released by the endothelium and are implicated in modulating the permeability of the endothelial barrier. The present study was designed to examine the interaction between ET-1 and NO and its influence on microvascular permeability as well as the role of NO in maintaining microvascular permeability. To isolate the direct effect of ET-1 and NO, experiments were conducted under conditions where hydraulic and oncotic pressures were controlled. METHODS: Postcapillary venules in the rat mesentery were perfused in situ and paired measurements of hydraulic permeability (Lp) obtained using the modified Landis micro-occlusion method. The effect of basal endogenous NO was tested by measuring the effects of perfusion with the NO synthase inhibitor Nw-nitro-L-arginine-methyl-ester (L-NAME) (100 micromol/L) on Lp (n = 6). In addition, Lp measured after a 15-minute perfusion with L-NAME (100 micromol/L) was compared with measures of Lp obtained after perfusion with a combined mixture of L-NAME (100 micromol/L) and ET-1 (80 pmol/L) (n = 6). RESULTS: Units for Lp are mean +/- SE x 10(-8) cm x sec(-1) x cm H2O(-1). Under basal conditions, in the absence of exogenous ET-1, NO synthase inhibition led to a significant increase in Lp from 5.7 +/- 0.5 to 9.8 +/- 1.4 (p = 0.02). Compared with L-NAME alone, ET-1 + L-NAME significantly decreased Lp from 10.3 +/- 0.8 to 5.7 +/- 0.6 (p = 0.006). CONCLUSION: Constitutive release of NO from the microvascular endothelium plays a role in maintaining a basal level of microvascular permeability. Decreases in microvascular permeability seen with the administration of ET-1 are not mediated via the release of NO. These findings suggest important roles for ET-1 and NO in maintaining and modulating microvascular permeability.

Gliding flight: drag and torque of a hawk and a falcon with straight and turned heads, and a lower value for the parasite drag coefficient.

Raptors - falcons, hawks and eagles in this study - such as peregrine falcons (Falco peregrinus) that attack distant prey from high-speed dives face a paradox. Anatomical and behavioral measurements show that raptors of many species must turn their heads approximately 40 degrees to one side to see the prey straight ahead with maximum visual acuity, yet turning the head would presumably slow their diving speed by increasing aerodynamic drag. This paper investigates the aerodynamic drag part of this paradox by measuring the drag and torque on wingless model bodies of a peregrine falcon and a red-tailed hawk (Buteo jamaicensis) with straight and turned heads in a wind tunnel at a speed of 11.7 m s(-)(1). With a turned head, drag increased more than 50 %, and torque developed that tended to yaw the model towards the direction in which the head pointed. Mathematical models for the drag required to prevent yawing showed that the total drag could plausibly more than double with head-turning. Thus, the presumption about increased drag in the paradox is correct. The relationships between drag, head angle and torque developed here are prerequisites to the explanation of how a raptor could avoid the paradox by holding its head straight and flying along a spiral path that keeps its line of sight for maximum acuity pointed sideways at the prey. Although the spiral path to the prey is longer than the straight path, the raptor's higher speed can theoretically compensate for the difference in distances; and wild peregrines do indeed approach prey by flying along curved paths that resemble spirals. In addition to providing data that explain the paradox, this paper reports the lowest drag coefficients yet measured for raptor bodies (0.11 for the peregrine and 0.12 for the red-tailed hawk) when the body models with straight heads were set to pitch and yaw angles for minimum drag. These values are markedly lower than value of the parasite drag coefficient (C(D,par)) of 0.18 previously used for calculating the gliding performance of a peregrine. The accuracy with which drag coefficients measured on wingless bird bodies in a wind tunnel represent the C(D,par) of a living bird is unknown. Another method for determining C(D,par) selects values that improve the fit between speeds predicted by mathematical models and those observed in living birds. This method yields lower values for C(D,par) (0.05-0.07) than wind tunnel measurements, and the present study suggests a value of 0.1 for raptors as a compromise.

The deep fovea, sideways vision and spiral flight paths in raptors.

Raptors - falcons, hawks and eagles in this study - have two regions of the retina in each eye that are specialized for acute vision: the deep fovea and the shallow fovea. The line of sight of the deep fovea points forwards and approximately 45 degrees to the right or left of the head axis, while that of the shallow fovea also points forwards but approximately 15 degrees to the right or left of the head axis. The anatomy of the foveae suggests that the deep fovea has the higher acuity. Several species of raptors in this study repeatedly moved their heads among three positions while looking at an object: straight, with the head axis pointing towards the object; or sideways to the right or left, with the head axis pointing approximately 40 degrees to the side of the object. Since raptors do not rotate their eyes noticeably in the sockets, these movements presumably cause the image of the object to fall on the shallow and deep foveae. The movements occurred approximately every 2 s on average in hawks and falcons, and approximately every 5 s in bald eagles. The proportion of time that the raptors spent looking straight or sideways at an object depended on how far away the object was. At a distances closer than 8 m, they spent more time looking at the object straight, but as the distance increased to 21 m, they spent more time looking at it sideways. At distances of 40 m or more, raptors looked sideways at the object 80 % or more of the time. This dependence of head position on distance suggests that raptors use their more acute sideways vision to look at distant objects and sacrifice acuity for stereoscopic binocular vision to look at close objects. Having their most acute vision towards the side causes a conflict in raptors such as falcons, which dive at prey from great distances at high speeds: at a speed of 70 m s(-)(1), turning their head sideways to view the prey straight ahead with high visual acuity may increase aerodynamic drag by a factor of 2 or more and slow the raptor down. Raptors could resolve this conflict by diving along a logarithmic spiral path with their head straight and one eye looking sideways at the prey, rather than following the straight path to the prey with their head turned sideways. Although the spiral path is longer than the straight path, a mathematical model for an 'ideal falcon' shows that the falcon could reach the prey more quickly along the spiral path because the speed advantage of a straight head more than compensates for the longer path.

Curved flight paths and sideways vision in peregrine falcons (Falco peregrinus).

When diving at prey straight ahead from great distances at high speeds, a peregrine has a conflict between vision and aerodynamics: it must turn its head approximately 40 degrees to one side to see the prey with maximum visual acuity at the deep fovea of one eye, but the head in this position increases aerodynamic drag and slows the falcon down. The falcon could resolve this conflict by holding its head straight and flying along a logarithmic spiral path that keeps the line of sight of the deep fovea pointed sideways at the prey. Wild peregrines, observed with binoculars, telescopes and a tracking device, did approach prey the size of American robins (Turdus migratorius) and smaller birds from distances of up to 1500 m by holding their heads straight and flying along curved paths that resembled the logarithmic spiral.

Basal release of endothelin-1 and the influence of the ETB receptor on single vessel hydraulic permeability.

BACKGROUND: Endothelin-1 (ET-1) has a direct permeability decreasing effect on the microvasculature. The present study was designed to test the hypothesis that this effect is mediated via the endothelin B (ETB) receptor located on the microvascular endothelium and to determine whether basal microvascular permeability is dependent on constitutive release of ET-1. To isolate the direct effect of ET-1, experiments were conducted under conditions in which hydraulic and oncotic pressures were controlled. METHODS: Postcapillary venules in the rat mesentery were perfused in situ, and paired measurements of hydraulic permeability (Lp) were obtained using the modified Landis micro-occlusion method. Lp measured after a 15-minute perfusion with the ETB receptor blocker BQ-788 (1 micromol/L) was compared with measures of Lp obtained after perfusion with a combined mixture of BQ-788 and ET-1 (80 pmol/L) (n = 6). In addition, the effect of basal endogenous ET-1 was tested by measuring the effects of BQ-788 perfusion on Lp (n = 6). RESULTS: Units for Lp are mean +/- SE x 10(-8) cm x s(-1) cm H2O(-1). ETB receptor blockade prevented any decrease in Lp induced by ET-1 (BQ-788 alone = 7.9 +/- 0.7; BQ-788 + ET-1 = 8.2 +/- 0.8;p = 0.5). Under basal conditions and in the absence of exogenous ET-1, ETB receptor blockade led to a significant increase in Lp from 6.8 +/- 0.9 to 9.7 +/- 1.2 (p = 0.001). CONCLUSION: Decreases in microvascular permeability in single postcapillary venules after the administration of ET-1 are mediated via the ETB receptor. Constitutive release of ET-1 from the microvascular endothelium also plays a role in maintaining basal levels of permeability. These findings suggest important roles for ET-1 in maintaining and modulating microvascular permeability.

T-cell telomere length maintained in HIV-infected long-term survivors.

BACKGROUND AND METHODS: We have used the erosion of telomeric DNA as a measure of cellular division to study the replicative history of isolated T-lymphocyte subpopulations from a group of HIV-infected long-term survivors and age-matched healthy controls. RESULTS: In keeping with previous studies, we found that CD45RO+ (memory) T-cells showed greater telomere erosion than CD45RA+ (naive) T-cells. We did not, however, find any significant differences in the telomere lengths of isolated CD4+, CD8+, CD45RA+ or CD45RO+ T-cells between HIV-infected long-term survivors and age-matched controls. Further, we found no evidence of telomerase activation in T-cells from the HIV-infected groups to account for the lack of telomere erosion. CONCLUSIONS: Our data show no evidence, through telomere shortening, of clonal exhaustion or replicative senescence due to an increased rate of immune cell turnover in HIV-infected long-term survivors.

Human antigen-presenting cell/tumour cell hybrids stimulate strong allogeneic responses and present tumour-associated antigens to cytotoxic T cells in vitro.

Most tumours do not stimulate effective antitumour immune responses in vivo. In order to enhance the immunogenicity of human tumour cells, we fused a variety of tumour cell lines with an Epstein-Barr virus transformed B-lymphoblastoid cell line (EBV B-LCL) in vitro, to produce stable hybrid cells. Hybrid cell lines showed a marked increase in their ability to stimulate primary allogeneic T-cell responses in vitro, as compared with the parent tumour cells. The hybrid cells induced proliferation of naive (CD45RA+) as well as memory (CD45RO+) T lymphocytes, and both CD4+ and CD8+ subpopulations of T cells were directly stimulated. The stimulatory hybrids expressed human leucocyte antigen (HLA) class I and II, and a wide range of surface accessory molecules, including the T-cell co-stimulatory ligand molecules CD40, CD80 (B7.1) and CD86 (B7.2), the expression of which was required for optimal stimulation of T-cell responses. Fusion of the EBVB-LCL with a melanoma cell line (518.A2) yielded hybrid cells that expressed the melanoma-associated antigens MAGE-1 and MAGE-3, and presented these antigens to antigen-specific, HLA class I-restricted cytotoxic T-lymphocyte clones with greater efficiency than the parent melanoma cell line. These findings suggest that the generation of human antigen-presenting cell/tumour cell hybrids offers promise as an approach to cancer immunotherapy.

Direct actions of endothelin-1 on single vessel hydraulic permeability.

BACKGROUND: There is evidence that endothelin-1 (ET-1) increases extravasation of fluid and protein into vascular beds. The present study was designed to determine the direct effects of ET-1 on hydraulic permeability (Lp) when microvascular hydraulic and oncotic pressures are controlled. METHODS: Postcapillary venules in the rat mesentery were perfused in situ and paired measurements of Lp obtained by using the modified Landis micro-occlusion method. Lp measured after a 15-minute perfusion with Ringer's albumin solution (control) was compared with Lp after a subsequent 15-minute perfusion with one of three treatments: control (n = 4), 8 pM ET-1 (n = 6), or 80 pM ET-1 (n = 6). RESULTS: Baseline L for all vessels averaged (+/- SE) 8.1 +/-0.8 x 10(-8) cm x sec(-10 x cm H2O(-1) and was not significantly different between groups. Perfusion with either control or 8 pM ET-1 did not significantly change the Lp of any of the vessels. Significant decreases in Lp of 40 to 60% were observed in venules perfused with 80 pM ET-1. The average Lp in this group was 9.9 +/- 1.4 during baseline and decreased to 5.0 +/- 0.7 during ET-1 perfusion (p = 0.003). Washout of 80 pM ET-1 for periods of up to 15 minutes did not return Lp to baseline values. CONCLUSION: Low-dose ET-1 did not directly increase Lp in postcapillary venules. ET-1 at 80 pM, however, significantly decreased Lp. These data implicate factors other than a direct permeability-increasing effect in ET-1. At higher concentrations, ET-1 may have a protective effect on endothelial barrier function.

Acute effects of tumor necrosis factor on hydraulic conductivity of mammalian postcapillary venules.

BACKGROUND: Tumor necrosis factor (TNF) is a cytokine that has been implicated in the development of capillary leak in sepsis. METHODS: We examined the direct effects of intraluminally applied TNF on microvessel hydraulic permeability (Lp) in the in situ mesentery of pentobarbital anesthetized female rats. Postcapillary venules were cannulated and perfused with Ringer's solution containing 0.5% albumin and washed erythrocytes. Transcapillary volume flow per unit surface area (Jv/S) was measured by using the modified Landis technique and Lp was calculated from the regression of Jv/S on pressures between 35 and 75 cm H2O. RESULTS: Under control conditions the Lp (mean +/- SE) was 1.06+/-0.08 x 10(-7) cm/(s x cm H2O) (n = 16). Lp was 0.87+/-0.12 x 10(-7) cm/(s x cm H2O) after a 20-minute perfusion with murine recombinant TNF at a concentration of 150 pg/mL (n = 5, p vs. control = 0.3). At a concentration of 10 ng/mL Lp was 1.15+/-0.15 x 10(-7) cm/(s x cm H2O) (n = 7,p vs. control = 0.6). In vessels perfused for 2 hours with TNF at 10 ng/mL, Lp was 0.96+/-0.33 x 10(-7) cm/(s x cm H2O) (n = 4, p = 0.66). At 100 ng/mL, Lp was 2.4+/-0.40 x 10(-7) cm/(s x cm H2O) (n = 7,p = 0.046). CONCLUSION: The acute intraluminal exposure to TNF, in the absence of other circulating factors, does not increase venular hydraulic permeability at concentrations of 150 pg/mL and 10 ng/mL. In vessels exposed at high or supraphysiologic concentrations (100 ng/mL), an acute twofold increase in Lp was demonstrated.

Measurement of microvascular transport parameters of macromolecules in tissues and organs of intact animals.

A critical analysis is presented of two widely used approaches to measurement of microvascular transport of large molecules in intact animals: (1) measurement of lymph flow and macromolecular solute concentration relative to plasma, and (2) tissue accumulation of tracer macromolecules. To demonstrate the advantages and limitations of each method, experimental results which permit direct comparison of the two methodologies are reviewed and analyzed, and sources of error in each pointed out. It is concluded that both approaches are valid under the appropriate conditions: steady state of lymph, initial transient state for tissue uptake. These conditions are mutually exclusive, but complementary. When the requirements for neither lymph collection or tissue accumulation alone can be satisfied experimentally, a combination of the two approaches can yield valid results.