Climate change and the permafrost carbon feedback.

Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. A warming climate can induce environmental changes that accelerate the microbial breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.

Use of near infrared spectroscopy for the rapid low-cost analysis of waste papers and cardboards.

Analytical data and quantitative near infrared (NIR) spectroscopy models for various lignocellulosic components (including Klason lignin and the constituent sugars glucose, xylose, mannose, arabinose, galactose, and rhamnose), ash, and ethanol-soluble extractives were obtained for 53 samples of paper and cardboard. These samples were mostly the type of materials typically found in domestic wastes (e.g. newspapers, printing paper, glossy papers, food packaging). A number of the samples (48) were obtained by separating a sample, after milling, into two particle size fractions. It was found that the fractions containing the smaller particles typically had higher ash and Klason lignin contents and lower glucose and xylose contents than the larger particle size fractions. Nevertheless, all of the sample types had attractive total sugars contents (>50%), indicating that these could be suitable feedstocks for the production of biofuels and chemicals in hydrolysis-based biorefining technologies. NIR models of a high predictive accuracy (R2 of >0.9 for the independent validation set) were obtained for total sugars, glucose, xylose, Klason lignin, and ash, with values for the Root Mean Square Error of Prediction (RMSEP) of 2.36%, 2.64%, 0.56%, 1.98%, and 4.87%, respectively. Good NIR models (R2 of >0.8) were also obtained for mannose, arabinose, and galactose. These results suggest that NIR spectroscopy is a suitable method for the rapid, low-cost, analysis of the major lignocellulosic components of waste paper/cardboard samples.

Practice patterns in flexor tendon repair.

BACKGROUND: There is a considerable volume of literature describing new and supposedly superior methods of flexor tendon repair. AIM: The purpose of this study was to assess the flexor tendon techniques currently used in the Republic of Ireland. METHODS: A postal survey was conducted of all consultant plastic surgeons and consultant orthopaedic surgeons who were members of the Irish Hand Surgery Society. RESULTS: The response rate was 90% (27/30). A simple running peripheral suture was used by 73% (P = 0.03) and the Kessler was the core suture of choice for 68% (P = 0.06). A significant number of respondents use non-absorbable suture materials for core (P = 0.0028) and peripheral suture (P < 0.0001). Seventy-seven percent sutured the flexor sheath where possible (P = 0.009). CONCLUSIONS: Notwithstanding the proposed advantages of newer techniques, it is evident from this study that the two-stranded Kessler core and simple running peripheral suture remains the most popular flexor tendon repair, with sheath closure preferred by the majority of respondents.

The evolution of trauma services at Beaumont Hospital.

OBJECTIVE: To review and examine the epidemiology, severity and management of trauma admissions at the national neurosurgical teaching hospital. METHODS: An extensive audit of volume, type and severity of injury and the management requirements of the trauma population admitted to the hospital. RESULTS: The vast majority of severely injured patients were referred from outside the catchment area of the hospital with only 26% being admitted directly through the Emergency Department. As a consequence, 73% of patients arrived out of normal working hours, which posed problems in providing skilled trauma specialists. CONCLUSIONS: The management of patients with serious injury is complex. The large proportion of patients with critical injuries, some of whom were paediatric, highlighted the need for 24 h cover by senior trauma personnel and the provision of radiology and operating facilities to meet their needs. The inclusion of indicators of alterations in innate or adaptive immune responses may improve the predictive power of severity of injury scores.

Co-immunotherapy with interleukin-2 and taurolidine for progressive metastatic melanoma.

BACKGROUND: Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine potentiates the anti-neoplastic effects of IL-2 while reducing its associated endothelial cell dysfunction in experimental settings. We hypothesized that co-administration of rIL-2 with taurolidine could enhance tolerability without weakening effectiveness. METHODS: Eleven patients with progressive metastatic melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were monitored for the development of toxicities and evidence of response. RESULTS: Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose-reduction. Most toxicities were low-grade. No patient developed VLS. Seven patients died from disease progression. Two had complete clinical and radiological responses to treatment. Two patients remain alive despite evidence of disease progression a mean of 17.5 months after diagnosing metastatic disease. CONCLUSION: Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.

A comparison of in vivo catalysis by creatine kinase in avian skeletal muscles with different fibre composition.

The maximum activity of creatine kinase in vitro is similar in the pectoralis major muscle of the chicken and the duck. However, the flux (phosphocreatine to ATP) as measured by 31P saturation transfer NMR in vivo is almost 2-fold higher in the duck. This apparent discrepancy can be accounted for by the differences in the cytosolic free ADP concentrations in resting muscle.

Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers.

BACKGROUND: Endothelial dysfunction initiated by monocyte-endothelial interactions has previously been observed in many vasculopathies, including chronic cigarette smoking. Taurine, a semiessential amino acid, and vitamin C, a naturally occurring antioxidant, have previously been shown to have endothelial protective effects when exposed to proinflammatory insults. Therefore, we hypothesized that taurine and vitamin C would restore endothelial function in young smokers by modifying monocyte-endothelial interactions. METHODS AND RESULTS: Endothelial-dependent vasodilatation was assessed in vivo using duplex ultrasonography, and monocyte-endothelial interactions were assessed in vitro using endothelial cell culture (human umbilical vein endothelial cells [HUVECs]) with monocyte-conditioned medium (MCM). Endothelial-dependent vasodilatation was significantly impaired in young smokers compared with nonsmokers. Pretreatment of young smokers for 5 days with 2 g/d vitamin C and, more significantly, with 1.5 g/d taurine attenuated this response. MCM taken from smokers impaired the release of nitric oxide and increased the levels of endothelin-1 release from HUVECs. When HUVECs were cultured with MCM from smokers who had been treated with taurine, the levels of nitric oxide and endothelin-1 returned toward control levels. This was attributed to an upregulation in endothelial nitric oxide synthase expression. CONCLUSIONS: These observations suggest that taurine supplementation has a beneficial impact on macrovascular endothelial function, and an investigation of its effect on altered endothelial function in dyslipidemic states is warranted.

Transcription factors in melanocyte development: distinct roles for Pax-3 and Mitf.

A transgenic mouse model was used to examine the roles of the murine transcription factors Pax-3 and Mitf in melanocyte development. Transgenic mice expressing beta-galactosidase from the dopachrome tautomerase (Dct) promoter were generated and found to express the transgene in developing melanoblasts as early as embryonic day (E) 9.5. These mice express the transgene in a pattern characteristic of endogenous Dct expression. Transgenic mice were intercrossed with two murine coat color mutants, Splotch (Sp), containing a mutation in the murine Pax3 gene, and Mitf(mi), with a mutation in the basic-helix-loop-helix-leucine zipper gene Mitf. Transgenic heterozygous mutant animals were crossed to generate transgenic embryos for analysis. Examination of beta-galactosidase-expressing melanoblasts in mutant embryos reveals that Mitf is required in vivo for survival of melanoblasts up to the migration staging area in neural crest development. Examination of Mitf(mi)/+ embryos shows that there are diminished numbers of melanoblasts in the heterozygous state early in melanocyte development, consistent with a gene dosage-dependent effect upon cell survival. However, quantification and analysis of melanoblast growth during the migratory phase suggests that melanoblasts then increase in number more rapidly in the heterozygous embryo. In contrast to Mitf(mi)/Mitf(mi) embryos, Sp/Sp embryos exhibit melanoblasts that have migrated to characteristic locations along the melanoblast migratory pathway, but are greatly reduced in number compared to control littermates. Together, these results support a model for melanocyte development whereby Pax3 is required to expand a pool of committed melanoblasts or restricted progenitor cells early in development, whereas Mitf facilitates survival of the melanoblast in a gene dosage-dependent manner within and immediately after emigration from the dorsal neural tube, and may also directly or indirectly affect the rate at which melanoblast number increases during dorsolateral pathway migration.

Thrombomodulin: tumour biology and prognostic implications.

BACKGROUND: Thrombomodulin (TM) is an endothelial receptor that exerts anti-coagulant, anti-fibrinolytic, and anti-inflammatory activity by inhibiting thrombin and cellular adhesion. There is growing evidence that TM plays a role in tumour behaviour. METHODS: The electronic literature (1966-2004) was reviewed with a specific focus on tumour biology. RESULTS: TM is expressed on both the endothelium and tumour cells in several cancers. Loss of expression denotes a more malignant profile with poorer prognosis. Loss of TM is mediated by hypoxia, endotoxin, and various cytokines, while up-regulation can be achieved by pharmacological manipulation (e.g. pentoxyfylline and statins). CONCLUSION: Originally described as an endothelial anticoagulant, TM plays a key role in tumour biology and prognostics, and provides a potential therapeutic target in impeding cancer spread.

Development and transferability of a cost-effective laparoscopic camera navigation simulator.

BACKGROUND: Laparoscopic camera navigation (LCN) is vital for the successful performance of laparoscopic operations, yet little time is spent on training. This study aimed to develop an inexpensive LCN simulator, to design a structured curriculum, and to determine the transferability of skills acquired. METHODS: In this study, 0 degrees and 30 degrees LCN simulators were developed for use on a videotrainer platform. Transferability was tested by enrolling 20 medical students in an institutional review board-approved, randomized, controlled, blinded protocol. Subjects viewed a video tutorial and were pretested in LCN on a porcine Nissen model. Procedures were videotaped and the LCN performance was scored by a blinded rater according to the number of standardized verbal cues required and the percentage of time an optimal surgical view (%OSV) was obtained. Procedure time also was recorded. Subjects were stratified and randomized. The trained group practiced on the LCN simulator until competency was demonstrated. The control group received no training. Both groups were posttested on the porcine Nissen model. RESULTS: The constructed simulators required 35 man hours for development, cost $25 per board for materials, and proved to be durable. The trained group demonstrated significant improvement in verbal cues (p = 0.001), %OSV (p < 0.001), and procedure time (p = 0.001), whereas the control group showed improvement only in verbal cues (p < 0.02). At posttesting, the training group demonstrated significantly better scores for verbal cues (2.1 vs 8.0; p = 0.02) and %OSV (64% vs 45% p = 0.01) than the control group. CONCLUSION: These data suggest that the LCN simulator is cost effective and provides trainees with skills that translate to the operating room.

Characterization of novel akermanite:poly-ϵ-caprolactone scaffolds for human adipose-derived stem cells bone tissue engineering.

In this study, three different akermanite:poly-ϵ-caprolactone (PCL) composite scaffolds (wt%: 75:25, 50:50, 25:75) were characterized in terms of structure, compression strength, degradation rate and in vitro biocompatibility to human adipose-derived stem cells (hASC). Pure ceramic scaffolds [CellCeram™, custom-made, 40:60 wt%; ß-tricalcium phosphate (ß-TCP):hydroxyapatite (HA); and akermanite] and PCL scaffolds served as experimental controls. Compared to ceramic scaffolds, the authors hypothesized that optimal akermanite:PCL composites would have improved compression strength and comparable biocompatibility to hASC. Electron microscopy analysis revealed that PCL-containing scaffolds had the highest porosity but CellCeram™ had the greatest pore size. In general, compression strength in PCL-containing scaffolds was greater than in ceramic scaffolds. PCL-containing scaffolds were also more stable in culture than ceramic scaffolds. Nonetheless, mass losses after 21 days were observed in all scaffold types. Reduced hASC metabolic activity and increased cell detachment were observed after acute exposure to akermanite:PCL extracts (wt%: 75:25, 50:50). Among the PCL-containing scaffolds, hASC cultured for 21 days on akermanite:PCL (wt%: 75:25) discs displayed the highest viability, increased expression of osteogenic markers (alkaline phosphatase and osteocalcin) and lowest IL-6 expression. Together, the results indicate that akermanite:PCL composites may have appropriate mechanical and biocompatibility properties for use as bone tissue scaffolds.

A simplified, data-constrained approach to estimate the permafrost carbon-climate feedback.

We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (γ sensitivity) of -14 to -19 Pg C °C(-1) on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.

Cell-density-dependent regulation of expression and glycosylation of dopachrome tautomerase/tyrosinase-related protein-2.

The expression of the dopachrome tautomerase gene (Dct) and its protein product, tyrosinase-related protein-2, was studied in the cultured, phorbol-ester-dependent murine melanocyte cell line melan-a. Increased cell density was found to stimulate Dct expression both in cells stably transfected with a Dct promoter-lacZ construct and endogenously in nontransfected cells. Increased Dct expression under these conditions corresponds to increased tyrosinase-related protein-2 production. Tyrosinase-related protein-2 was found to exist in two distinct glycoforms with different endoglycosidase sensitivities. Density-dependent expression of tyrosinase-related protein-2 was independent of time of cell growth, cell proliferation, and soluble factors, implying that cell-cell contact is the important determinant governing increased Dct expression under these conditions. Tyrp1 gene expression and tyrosinase-related protein-1 production were also induced under similar conditions. The results show that cell-cell contact between melanocytes induces a coordinated response at both transcriptional and nontranscriptional levels that induces production of the tyrosinase-related proteins that have a significant role in melanization.

Efflux of 6-deoxy-D-glucose from Plasmodium falciparum-infected erythrocytes via two saturable carriers.

Glucose transport in human erythrocytes infected with the malaria parasite, Plasmodium falciparum, has been studied using 6-deoxy-D-glucose (6DOG) as a non-metabolised glucose analogue. Inhibition studies using cytochalasin B, a powerful inhibitor of the erythrocyte glucose transporter, GLUT1, indicate that in the infected red blood cell (IRBC), glucose is transported via a saturable carrier. However, inhibition is not as complete as in the uninfected erythrocyte. The synergistic inhibition effect of 6DOG entry by niflumic acid, an inhibitor of the non-specific malaria-induced pore, in the presence of cytochalasin B suggests that some glucose may also enter the infected erythrocytes through the pore, if entry via the carrier is blocked. The time course of 6DOG efflux from infected erythrocytes in the presence of cytochalasin B did not follow simple first-order kinetics. To elucidate the kinetic mechanism of 6DOG efflux from the infected erythrocytes, the concentration dependence of efflux was determined. Eight two-compartment kinetic models were simulated, involving first-order pore diffusion and carrier-mediated saturable diffusion in two systems, one ductless and one assuming the existence of a parasitophorous duct. The only two models showing reasonable fits to the efflux data each involve two saturable carriers. It is likely that one of the saturable carriers is associated with the parasite itself. Evidence that the parasite carrier has different inhibitor sensitivities from that of GLUT1 is presented.

The effect of two novel analogues of antimycin A on oxygen consumption and survival of filarial nematodes in vitro.

The effects of two novel analogues of antimycin A (BWA466C and BWA728C) on filarial oxygen consumption, energy generation and survival were investigated in vitro. For comparison, incubations were performed with a range of mitochondrial respiration inhibitors. All compounds tested (rotenone, antimycin A, KCN, oligomycin, CCCP, rafoxanide, BWA466C and BWA728C) inhibited oxygen uptake. The two analogues were less potent than antimycin A at impairing respiration of either filariae or beef heart submitochondrial particles. However, the two compounds affected motility and were lethal in vitro. Although the analogues affected oxygen uptake similarly to antimycin A itself, the levels of ATP were significantly lower than those noted in the presence of antimycin A. Glucose consumption and lactate output were markedly reduced by BWA466C and BWA728C. Glucose transport (measured as 2-deoxy-[2,6-3H]glucose) was reduced after treatment with BWA728C. It is likely that a combination of the effects on glucose transport and inhibition of oxidative pathways of carbohydrate metabolism may lead to worm death in vitro.

Thermotolerance attenuates ischemia-reperfusion induced renal injury and increased expression of ICAM-1.

Thermotolerance describes the process in which hyperthermia induces a transient resistance of the stressed cells to subsequent episodes of oxidative stress. The aims of this study were first, to assess the effect of ischemia-reperfusion (IR) injury on renal function and the expression of the ICAM-1 receptor and MHC antigens, and second, to evaluate the protective effects of thermotolerance on IR induced renal injury and its potential for decreasing allograft rejection, by decreasing alloantigen expression. Sprague-Dawley rats were randomized into three groups: control, IR, and hyperthermia + IR (HIR) (n=8 per group). Thermotolerance was induced 18 hr prior to IR by increasing the core body temperature to 41 degrees C+/-0.5 degrees C for 15 min. After left uninephrectomy, IR was induced by clamping the right renal pedicle for 45 min, followed by 2 hr reperfusion. Myeloperoxidase (MPO) activity was used as an indicator of renal neutrophil influx. Kidney edema was assessed using the weight difference between left and right kidneys. Renal function was evaluated by measuring serum creatinine and urea 2 hr following clamp removal. Immunocytochemistry was used to measure expression of ICAM-1 and MHC antigen. Renal function was significantly impaired by IR with serum creatinine and urea levels of 131.5+/-5.01 microM and 11.2+/-0.71 mM, respectively, compared with controls of 67.9+/-5.11 microM and 8.1+/-0.36 mM, P<0.005 in both cases. Renal function was preserved in the HIR group, serum creatinine (84.8+/-8.58 microM) and urea (9.0+/-0.52 mM) were comparable to that of controls. Renal endothelium was activated in the IR group compared with controls, with increased ICAM-1, and tubular epithelium showed increased class II MHC expression. This up-regulation was prevented by prior induction of thermotolerance. Endothelial permeability was increased in the IR group with MPO activity of 0.8+/-0.08 units/g tissue--twice that of control levels P<0.05--and a marked increase in organ edema. Thermotolerance preserved endothelial barrier function. Thermotolerance may prevent IR injury by preventing endothelium activation and has the potential to modify allograft rejection by decreasing expression of ICAM-1, an important T cell receptor, and class II MHC.

A 31P-NMR study of the acute effects of altered beta-adrenoceptor stimulation on the bioenergetics of skeletal muscle during contraction.

The effects of acute administration of a beta-adrenoceptor agonist (isoprenaline) or antagonist (propranolol) on skeletal muscle contraction and metabolism in the rat have been studied in vivo using 31P-nuclear magnetic resonance spectroscopy and conventional metabolite analysis. In resting muscle, isoprenaline caused a three-fold increase in cyclic AMP concentration, whereas propranolol decreased cyclic AMP concentration by 40%. Isometric contraction of gastrocnemius muscle at a frequency of 4 Hz was caused by supramaximal sciatic nerve stimulation. Altered beta-adrenoceptor stimulation had no effect on contractile performance at any time during the 30 min stimulation period. During the initial stimulation period (0-4 min) intracellular pH decreased to significantly lower values in the isoprenaline-treated animals (6.24 +/- 0.03) compared to either the control (6.44 +/- 0.08) or propranolol-treated (6.42 +/- 0.08) groups. During the subsequent stimulation period (after 15-30 min stimulation at 4 Hz), pH recovered in all experimental groups to values greater than 6.90 and phosphocreatine concentration achieved a constant level at 35-40% of resting values. Calculation of free ADP concentrations using 31P-NMR determined metabolite concentrations and the creatine phosphokinase equilibrium showed that at similar tension development, [ADP]free varied between the three experimental groups; with the lowest (47 +/- 4 microM) and highest (73 +/- 4 microM) values being calculated for the beta-adrenoceptor agonist- and antagonist-treated groups respectively. Upon termination of stimulation, recovery of phosphocreatine concentration to pre-stimulation values was rapid and similar in all experimental groups. However, gastrocnemius muscle ATP concentration, determined by 31P-NMR and analysis of freeze-clamped muscle, was lower in the isoprenaline-treated group. This study has shown that although altered beta-adrenoceptor stimulation had no effect on contractile performance, significant changes in muscle metabolism were observed in vivo; these effects are discussed with respect to the role of beta-adrenoceptors in skeletal muscle.

Chronic administration of the oral hypoglycaemic agent diphenyleneiodonium to rats. An animal model of impaired oxidative phosphorylation (mitochondrial myopathy).

Daily subcutaneous administration of the oral hypoglycaemic agent, diphenyleneiodonium at a low dose (1.5 mg/kg body weight) over a 4-5 week period resulted in a normoglycaemic stable animal model of impaired oxidative phosphorylation in the rat. Diphenyleneiodonium specifically inhibits NAD-linked mitochondrial oxidation [Bloxham, Biochem. Soc. Trans. 7, 103 (1979)], and in isolated mitochondrial preparations from heart, soleus and gastrocnemius muscle and liver from treated animals NAD-linked respiration was reduced by 40% or more of mean control values. Brain and kidney mitochondria isolated from the treated group had similar rates of NAD-linked respiration to their respective control values. The activity of NADH-ferricyanide reductase was significantly reduced in all tissues tested, even in the isolated brain and kidney mitochondria where the activity in these tissues was 60-75% of control values. This suggests that at least 40% of Complex I activity must be inhibited before there is a decline in NAD-linked mitochondrial respiration. This paper discusses the use of diphenyleneiodonium as a means of establishing an animal model of the human disease state, termed mitochondrial myopathy.

The effect of laparotomy and laparoscopy on the establishment of spontaneous tumor metastases.

BACKGROUND: Surgical extirpation of solid tumors may be entirely possible, and the consequence of surgical excision is invariably the release of tumor cells into the systemic circulation. The aim of this study was to determine whether laparotomy affects the establishment of spontaneous pulmonary metastases after excision of the primary tumor in a murine flank tumor model and to determine possible underlying immune abnormalities. METHODS: An initial experiment was carried out to compare the development of gross spontaneous pulmonary metastases in the presence of a primary flank tumor and after excision of the tumor in C57/BL6 female mice. Another group of mice had flank tumors excised and were simultaneously randomized to undergo anesthetic only (control), laparoscopy, or laparotomy, after which the subsequent development of pulmonary metastases was determined. Finally, a third experiment entailed determination of natural killer cell (NK) cytotoxicity and the effect of splenic macrophages on NK cytotoxicity at days 1,7, and 14 after tumor excision. RESULTS: Excision of the primary tumor resulted in a significant increase in the number of pulmonary metastases in mice compared with mice that did not have tumors excised (P = .01). Both laparotomy and laparoscopy significantly increased the number of spontaneous pulmonary metastases after tumor excision compared with controls (P < or = .01), and there was also a significant difference between laparotomy and laparoscopy groups (P = .00). NK cytotoxicity was significantly suppressed at all time points after operation in the laparotomy group compared with both the laparoscopy group and the controls (P < or = .01). Suppression occurred after laparoscopy at 24 hours after the procedure compared with controls (P = .00); by day 7 this difference was not significant, but as day 14 there was again a significant suppression (P < or = .03). Splenic macrophages appeared to be a suppressor to natural killer cell cytotoxicity (NKCC) in the corresponding groups and at the corresponding time points. CONCLUSIONS: The differential establishment of spontaneous metastases after tumor excision and laparotomy and, to a lesser extent, laparoscopy results in lowered host antitumor surveillance and may be mediated at least in part by the generation of splenic suppressor cells in the early postoperative period, causing a more marked and prolonged effect after laparotomy than after laparoscopy.