The Effect of Seminal Plasma on the Equine Endometrial Transcriptome.

The establishment of pregnancy involves a fine-tuned balance between protection and tolerance within the maternal immune system, as the female needs to accept a foreign antigen (the semi-allogenic fetus) while still being able to combat pathogens from the uterus. In the horse, the first uterine exposure to paternal antigens is during mating when sperm is introduced to the tissue and draining lymphatics of the uterus. Additionally, it has been suggested that seminal plasma and its proteins within it play an essential role in preparing the female tract for a suitable immunologic environment but this has not been confirmed in the horse. Therefore, the objective of this study was to evaluate the endometrial transcriptome following insemination either with seminal plasma or with reduced seminal plasma. We hypothesised that reduced seminal plasma would alter the endometrial transcriptome and affect transcripts relating to immunotolerance, antigen presentation and embryo growth and development. To do so, six (n = 6) mares were inseminated in a randomised switch-back design over the course of four oestrous cycles. Mares were rectally palpated and scanned via ultrasonography for the detection of a pre-ovulatory follicle (>35 mm) alongside increasing uterine oedema and relaxed cervix, and then treated with one of four treatment groups including (1) 30 mL lactated Ringers solution (LRS; NegCon), (2) 500 × 106 spermatozoa in conjunction with 30 mL seminal plasma (SP+), (3) 30 mL lactated Ringers solution (LRS; wash out) and (4) 500 × 106 spermatozoa with seminal plasma reduced via gradient centrifugation and resuspended in 30 mL LRS (SP-). Human chorionic gonadotropin (hCG) was administered to standardise the time to ovulation and endometrial biopsies were collected 7 days after insemination. RNA was isolated utilising Trizol, and RNA-Seq was performed by Novogene, with 97.79% total mapping and 40 million read depth. p value was set to <0.05. When comparing SP+ to SP-, 158 differentially expressed genes (DEGs) were identified. Biological processes impacted included antigen processing and regulation, cholesterol synthesis, and immune/inflammatory response. Gene ontology (GO) enrichment analysis using DAVID v6.8 revealed that many of these DEGs were involved in biological process such as antigen presentation (HLA-DM beta chain, HLA-DRB, HLA-DQA and RASGRP1), immune cell signalling (CXCL9, CXCL1, DEFB1 and MIP-2B), embryo growth and development (INHA, KLF2, RDH10, LAMA3 and SLC34A2) and embryo metabolism (ABCA1, ABCA2, APOA1, LDL, INSR, IGFBP2 and IGFBP3). Overall, reduction of seminal plasma from the insemination dose impacted the endometrial transcriptome at the time of early embryonic exposure to the uterine environment. Further work is justified to evaluate these alterations impact on embryo maturation, placental development, pregnancy outcome and development of offspring.

Multiscale Friction in Lubricant-Surface Systems for High-Performance Transmissions Under Mild Wear.

The lubricant-surface system is complex in nature and can significantly affect the frictional performance of high-performance transmission systems. The complexity stems from the coupled mechanical and chemical phenomena that occur at the interfacial tooth conjunctions. A combined analytical and precision experimental approach is presented to analyse the salient parameters of the lubricant-surface system. A multiscale procedure comprising topographical measurement, pin-on-disc tribometry, atomic force microscopy in lateral force mode, X-ray photo-electron spectroscopy and continuum contact mechanics analysis under mixed non-Newtonian thermo-elastohydrodynamics is used to describe the formation of a tribo-film, as well as wear and frictional characteristics of the lubricant-surface system. The contribution of chemisorbed and physisorbed bonded tribo-film on the boundary coefficient of friction is ascertained at different physical scales. Therefore, the paper presents a novel multiscale analysis, promoting improved understanding of the complex interactions between mechanisms of friction, wear and surface chemistry.

Effect of patterned polyacrylamide hydrogel on morphology and orientation of cultured NRVMs.

We recently demonstrated that patterned Parylene C films could be effectively used as a mask for directly copolymerizing proteins on polyacrylamide hydrogel (PAm). In this work, we have proved the applicability of this technique for studying the effect such platforms render on neonatal rat ventricular myocytes (NRVMs). Firstly, we have characterised topographically and mechanically the scaffolds in liquid at the nano-scale level. We thus establish that such platforms have physical properties that closely mimics the in vivo extracellular environment of cells. We have then studied the cell morphology and physiology by comparing cultures on flat uniformly-covered and collagen-patterned scaffolds. We show that micro-patterns promote the elongation of cells along the principal axis of the ridges coated with collagen. In several cases, cells also tend to create bridges across the grooves. We have finally studied cell contraction, monitoring Ca2+ cycling at a certain stimulation. Cells seeded on patterned scaffolds present significant responses in comparison to the isotropic ones.

Electrospun aniline-tetramer-co-polycaprolactone fibres for conductive, biodegradable scaffolds.

Conjugated polymers have been proposed as promising materials for scaffolds in tissue engineering applications. The restricted processability and biodegradability of conjugated polymers limit their use for biomedical applications however. Here we synthesised a block-co-polymer of aniline tetramer and PCL (AT-PCL), and processed it into fibrous non-woven scaffolds by electrospinning. We showed that fibronectin (Fn) adhesion was dependant on the AT-PCL oxidative state, with a reduced Fn unfolding length on doped membranes. Furthermore, we demonstrated the cytocompatibility and potential of these membranes to support the growth and osteogenic differentiation of MC3T3-E1 over 21 days.

Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells.

Glucocorticoids are effective anti-inflammatory and immunosuppressive agents, but their use is often associated with debilitating side effects such as glucocorticoid-induced osteoporosis. Newly developed glucocorticoid analogues such as the so-called dissociated glucocorticoids are potent immunosuppressants and have the potential for fewer side effects. The effects of these new analogues on osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in osteoblastic cells have not been studied. OPG and RANKL are osteoblast-derived proteins pivotal to the regulation of bone mass. RANKL stimulates bone resorption by increasing osteoclast differentiation, activation and survival. OPG is the decoy receptor for RANKL and thus inhibits bone resorption. Here, we show that dexamethasone, prednisolone, deflazacort and the dissociated glucocorticoids, RU24858, RU40066, RU24782, AL438-F1 and ZK216348 significantly inhibit OPG production in two human osteoblastic cell lines (MG63 and hFOB). The potency for OPG inhibition was ligand and cell-type specific. In both cell types, dexamethasone and prednisolone were the most potent ligands inhibiting OPG production with IC(50)s of approximately 0.1 nM and 10 nM respectively. In MG63 cells, deflazacort and the RU compounds were the next most potent ligands followed by AL438-F1 and ZK216348. In hFOB cells, however, the RU compounds were the least potent ligands with an IC(50) 74 times higher than in MG63 cells. In contrast, the level of maximum inhibition or effectiveness of OPG inhibition did not vary between cell types but did vary according to the ligand. Dexamethasone, prednisolone, deflazacort and the RU compounds all inhibited OPG production by a maximum of approximately 70-80%, whereas AL438-F1 and ZK 216348 inhibited OPG production by a maximum of only 40-50% at 1 microM. All of the dissociated glucocorticoids and deflazacort were poor stimulators of RANKL gene expression stimulating by only approximately 1-3-fold compared to 7-fold by prednisolone. These data demonstrate that deflazacort and the dissociated glucocorticoids are weak stimulators of the RANKL:OPG ratio compared to prednisolone. Therefore, these compounds have the potential to cause less bone loss than that seen with prednisolone, though this was not investigated here.

Analysis of calcitonin gene-related peptide-like immunoreactivity in the cat dorsal spinal cord and dorsal root ganglia provide evidence for a multisegmental projection of nociceptive C-fiber primary afferents.

Recent studies have suggested that calcitonin gene-related peptide (CGRP) can be used as a marker for a subpopulation of nociceptive primary afferents. Consequently, CGRP-immunoreactive (CGRP-IR) primary afferents have been reported to project many segments rostral to their segment of entry and to send collaterals into the superficial and deep laminae of the dorsal horn. This study reports that some CGRP-IR primary afferents of sacral origin project rostral through the ipsilateral lumbar enlargement in the cat. The ultrastructure of these multisegmentally projecting primary afferent axons and terminals identified in a partially denervated cat was examined and compared to the ultrastructure of CGRP-IR afferents from an intact cat. Retrograde transport of wheatgerm agglutinin-colloidal gold injected into the cat L4 spinal cord resulted in labeling of primary afferent cell bodies in the ipsilateral L4-S1 dorsal root ganglia (DRG). Analysis of every fourth section through the ipsilateral S1 DRG revealed as many as 1,000 retrogradely labeled neuronal cell bodies. One third of these cell bodies were double labeled for CGRP-like immunoreactivity. The number of single- and double-labeled cells increased in ganglia closer to the injection site (L4-L7). At the ultrastructural level, in the lumbosacral dorsal spinal cord of a normal cat, most CGRP-IR axons were unmyelinated, while the rest were small myelinated axons. In both the superficial dorsal horn and lamina V, CGRP-IR varicosities were dome shaped, scallop shaped, or elongated. The CGRP-IR varicosities contained small agranular vesicles and frequently a few dense core vesicles. These labeled varicosities formed asymmetric synapses on unlabeled dendritic spines, shafts, or neuronal somata. One cat received multiple unilateral dorsal rhizotomies (S1-L4) and an ipsilateral hemisection (mid L4). CGRP-IR axons and terminals were found within each of the rhizotomized segments, although their density was greatly reduced compared to that in the intact animals. In Lissauer's tract the majority (greater than 90%) of CGRP-IR fibers were unmyelinated. In laminae I and V, the remaining CGRP-IR varicosities were mainly the dome-shaped varicosities morphologically similar to those observed in the normal spinal cords. They contained small agranular vesicles and a few dense core vesicles and formed asymmetric synapses on unlabeled dendritic shafts and spines. These data demonstrate that unmyelinated, presumably C-fiber nociceptive primary afferents and some small myelinated A-delta nociceptive primary afferents of sacral origin project rostral through the cat lumbar enlargement and make synaptic connections in both the superficial and deep laminae of the cat dorsal spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of transfusion of emboli and aged plasma on pulmonary capillary permeability.

The effects of transfusion of whole blood clot emboli and aged citrated platelet-poor plasma on pulmonary capillary permeability were investigated in anesthetized sheep by continuous collection of pulmonary lymph. Changes in lymph flow and lymph-to-plasma ratios (CL/CP) for albumin and globulin were utilized to detect changes in permeability. Infusion of 0.5 cc/kg of finely (less than or equal to 1 mm) diced autologous whole blood clot resulted in a 170% increase in lymph flow over control with no change in CL/CP for albumin or globulin. Infusion of 1 cc/kg of autologous clot increased lymph flow 180% over control and increased CL/CP for albumin and globulin. Infusion of homologous platelet-poor plasma caused greater increases in lymph flow without changes in CL/CP. Changes in each of these three groups were consistent with increased permeability. Balloon occlusion of one main pulmonary artery was induced without a fall in cardiac output and resulted in no change in lymph flow of CL/CP despite a rise in pulmonary vascular resistance (PVR). Femoral arteriovenous fistulas were created to increase cardiac output, but no change in lymph flow or CL/CP occurred. The results in these latter two experiments suggest that increased perfusion per unit lung capillary bed or increased PVR were not primarily responsible for the changes observed in the emboli-treated and plasma-infused animals. Since both emboli and aged platelet-poor plasma increased pulmonary capillary permeability, the permeability increasing factor appears to be humoral in origin. Similar humoral factors may be important in the pathogenesis of the adult respiratory distress syndrome in man.

Management of acid-peptic esophageal strictures.

Eighty-nine patients with benign acid-peptic strictures of the esophagus were evaluated. Of these, 56 patients were treated by dilatation and medical therapy, whereas 33 underwent operative therapy because medical therapy failed. Three patients, all psychotic and having post-emetic strictures, required resection of the stricture and a colon interposition. Twenty-nine patients underwent a Belsey or Nissen fundoplication combined with esophageal dilatation. Fourteen of 29 had an associated vagotomy and 15 did not. Two patients of this 29 had a poor result, one of whom had a post-emetic stricture. Although the patients having a concurrent vagotomy and pyloroplasty had the more severe disease,there was no significant difference between the results in the two groups. It is concluded that most patients with such esophageal strictures may be adequately treated without resecting the stricture and that the routine addition of a vagotomy and drainage procedure is probably not indicated.

Influence of histologic type on survival after curative resection for undifferentiated lung cancer.

Undifferentiated carcinoma of the lung carries a worse prognosis overall than other cell type, but it is unclear whether these tumors represent a homogeneous group with uniformly poor survival. This study identifies certain histologic subtypes of large cell and small cell undifferentiated carcinoma which have a better prognosis after curative resection than other similarly treated undifferentiated carcinomas. From 1947 through 1975, a total of 2,352 patients with lung cancer were admitted to one hospital. Follow-up to death was available in 98%. Pathological material was reviewed from 1,979 cases by a team of three pathologists during a single 6 month period without knowledge of clinical outcome. Curative resection was carried out in 632, with 170 (27%) 5 year survivors. Small cell cancer occurred in 481 patients and nine (1.6%) survived 5 years. Curative resections were performed in 34 with polygonal small cell carcinoma, 20 with normal lymph nodes and 14 with diseased lymph nodes. Seven survived 5 years (21%), six of 20 with normal and one of 14 with diseases lymph nodes. Eleven with nonpolygonal small cell carcinoma (eight oat cell, three fusiform) (five normal, six diseases nodes) underwent curative resection, with no survivors. Large cell carcinoma occurred in 151 and 19 survived 5 years. Curative resection was performed in 24 having large cell carcinoma with stratification (16 normal, eight diseased nodes), and 12 (50%) survived 5 years. In 26 with nonstratified large cell carcinoma undergoing curative resection (18 normal, eight diseases nodes); six (23%) survived 5 years (chi 2 = 4.06 p less than 0.05). Thus patients with resectable polygonal small cell carcinoma appear to have a better prognosis than those with nonpolygonal small cell carcinoma, and their prognosis approaches that of all patients with resectable lung cancer. Patients having resectable large cell carcinoma with stratification have a significantly better prognosis than those with nonstratified large cell carcinoma. Patients with these subtypes should therefore not be denied an attempt at curative resection because of the diagnosis of undifferentiated lung cancer.

Prevention of acute pulmonary edema during isolated perfusion for 24 hours.

Fifty-nine canine lungs were perfused with cryoprecipitated plasma, silica gel fraction, or modified silica gel fraction (MSGF) af different perfusate pressures for periods up to 24 hours under hypothermic conditions. High perfusate pressures accounted for all poor perfusion results. The use of MSGF at a low perfusate pressure protected all the lungs from the appearance of pulmonary edema during perfusion, and the morphology was consistently maintained for 24 hours.

Aberrant left pulmonary artery presenting as a right paratracheal mass in an adult.

Aberrant left pulmonary artery, or pulmonary sling, is a rare variation of the pulmonary vasculature, with only one previous report of the condition being recognized in an adult. In this report a second case recognized de novo in an adult is presented. Both of these adults were evaluated because of right paratracheal masses which required differentiation from pulmonary malignancies. The barium swallow shows a characteristic indentation of the anterior esophageal wall and the lateral tomogram demonstrates absence of the left pulmonary artery from its normal position in the left hilum. The pulmonary arteriogram is diagnostic and allows avoidance of more invasive diagnostic measures.

National survey of the pattern of care for carcinoma of the lung.

A national survey of the patterns of care for carcinoma of the lung sponsored by the Commission on Cancer of the American College of Surgeons has documented continuing changes in epidemiology, treatment, and outcome. The project consisted of a long-term study of 15,219 patients whose diagnosis was made in 1981 and a short-term study of 19,074 patients whose diagnosis was made in 1986. The male/female incidence ratios have continued to decrease and the decrease has moved into the older age groups. Although the percentage of adenocarcinoma is increasing at the expense of squamous carcinoma, the latter is still the most prevalent histologic type. The accuracy of percutaneous needle biopsy and transbronchial biopsy of lung nodules reported from this group of 941 hospitals was high and equal to that reported by single institutions. The percentage of patients having a resection did not increase from 1981 to 1986, but for smaller lesions a move was apparent toward more lung-sparing resections. Little change has occurred in the use of adjuvant radiotherapy, particularly in stage III disease, where approximately 50% of the patients received postoperative irradiation. An improvement in the overall 5-year survival when compared with Surveillance, Epidemiology, and End Results data was noted. Whether this is a true improvement in survival or is the result of selection because of an unrecognized change in the pattern of care for patients with a carcinoma of the lung is unknown.

Temporal trends in survival after surgical resection of localized non-small cell lung cancer.

To test whether modern preoperative staging modalities and perioperative care improve survival after resection of localized non-small cell lung cancer (NSCLC), we retrospectively reviewed outcomes of 454 patients with NSCLC resected from 1947 through 1969 (designated pre-1970 cases), and 540 patients with cancers resected from 1981 through 1994 (designated post-1980 cases). Mean ages, histological subtypes, surgical stages, and types of surgical procedures differed significantly between the two groups. Compared with pre-1970 cases, post-1980 cases were older, had more adenocarcinoma and less squamous cell carcinoma, and had lesser proportions of advanced stage disease. Postoperative (day 30) mortality was significantly higher for resections of localized (stages 1 and 2) NSCLC prior to 1970. For patients surviving at least 30 days after surgery, subsequent survival after resection of localized NSCLC differed minimally between pre-1970 and post-1980 groups. We conclude that perioperative mortality after resection of localized NSCLC improved, but subsequent postoperative survival for these patients did not significantly improve over the 45-year period studied.

Evidence for calcitonin gene-related peptide contacts on a population of lamina I projection neurons.

Using double-labeling techniques, we evaluated small diameter primary afferent input, as indicated by calcitonin gene-related peptide-immunoreactive varicosities, to a population of lamina I projection neurons in the rat lumbar spinal cord. About one third of the lamina I neurons labeled after injections of a retrograde tracer into the region surrounding the brachium conjunctivum received contacts from immunoreactive varicosities. Significantly fewer immunoreactive varicosities were in apposition to fusiform neurons than pyramidal or flattened neurons. A positive correlation was found between the size of the retrogradely labeled neuron and the number of contacts received. This study demonstrates that a known population of nociceptive lamina I neurons received direct input from presumed nociceptive primary afferents.

The impact of phantom CT scanning on surgery for the solitary pulmonary nodule.

A reliable preoperative method to distinguish benign from malignant peripheral solitary pulmonary nodules (SPNs) would be clinically valuable. New techniques using epoxy resin plastic models of the thorax combined with calcium carbonate (phantom) nodules to determine the density of SPN have been proposed as a partial solution to this problem. During the first 3 years that phantom computed tomography (CT) has been available, 50 consecutive patients in whom SPN was discovered on screening chest x-ray film and who were considered to be candidates for surgery were evaluated by this technique. Twenty patients (40%) clearly met the phantom CT criteria for benign nodules (more dense than the phantom nodule, at least 10% of the surface area uniformly calcified, round or oval lesions without spicules, and lesions less than 3.0 cm in diameter) and have been followed up without surgery (no change on periodic screening chest x-ray film or CT for as many as 36 months). Only one of these 20 patients would have met standard x-ray criteria for benign nodules. Thirty patients who had lesions with densities less than the phantom nodule underwent thoracotomy, and in 17 (57%) of these, the lesions were malignant. No patient in this study who had a benign reading on the phantom CT scan had a malignancy at surgery or during follow-up. We conclude that phantom CT scanning is a useful adjunct to standard technique (review of prior screening chest x-ray film) and may prevent unnecessary thoracotomy in a significant percentage of patients with SPN.

The nature of failure of pulmonary adaptation to atelectasis.

The ability of the lung to decrease blood flow to an atelectatic lobe and to increase flow to normal after reinflation was investigated with a model using left lower lobe atelectasis (LLLA) in the dog. The change in the shunt fraction QS/Qt with continuing LLLA was assumed to represent a change in blood flow to the LLL. With LLLA the Qs/Qt rose from 0.112 to 0.172 and then decreased to 0.119 by the end of 2 hours at the rate of -17%/hour. Reversal of atelectasis for varying times demonstrated that the pulmonary vasoconstrictive response persisted for at least 4 hours after reinflation of LLLA. With LLL ischemia for 1 and 2 hours followed by LLLA, Qs/Qt decreased, but at a rate less than the controls, whereas after hemorrhagic shock with venous reinfusion and LLLA, the Qs/Qt did not decrease. When hemorrhagic shock was followed by arterial reinfusion, 60% had a normal response to LLLA; 40% did not. There was no difference in PVR in these two groups. Pulmonary extravascular water in both groups was the same as in controls. Infusion of NE after 3 hours of LLLA caused Qs/Qt to rise from 0.125 to 0.248, comparable to the value immediately after onset of LLLA. EPi had similar results. Catecholamines may restore blood flow to the atelectatic lobe by causing a maximum generalized pulmonary vasocontriction or by overexpansion of the pulmonary blood volume secondary to peripheral vasoconstriction and thereby abolish any differential in pulmonary vascular resistance across the lung. The early hypoxemia of adult respiratory distress syndrome may arise not on the basis of any intrinsic lung pathology but rather as the result of a normal response of the lung to increased catecholamines.

Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. VII. Hemoglobin does not inhibit clearance of Escherichia coli from the peritoneal cavity.

Hemoglobin has been shown to be a potent adjuvant in experimental Escherichia coli peritonitis, although a satisfactory mechanistic rationale is still obscure. Hemoglobin has been thought to impair intraperitoneal neutrophil function, delay clearance of bacteria from the peritoneal cavity by the normal absorptive mechanisms, or directly enhance bacterial growth. Using highly purified stroma-free hemoglobin (SFHgb), we have largely discounted any direct effect of hemoglobin on peritoneal white blood cell function. In the present study, we confirmed that uncontrolled proliferation of bacteria takes place in the presence of hemoglobin in the peritoneal cavity. Nonviable 5-iododeoxyuridine 125I-labelled bacteria were then used to directly study peritoneal clearance kinetics, eliminating the problem of bacterial growth. SFHgb had no influence on the removal of intraperitoneal bacteria. The rate of bloodstream appearance of radiolabel was similar with or without intraperitoneal SFHgb. Thus, SFHgb does not prevent clearance of bacteria from the peritoneal cavity by interfering with normal host clearance mechanisms. SFHgb may act as a bacterial growth adjuvant, either by serving as a bacterial nutrient or by suitably modifying the environment so that extensive bacterial proliferation can occur. The latter hypothesis appears to be an area in which investigation concerning the adjuvant effect of hemoglobin may prove most fruitful.

Decreased hepatic glutathione levels in septic shock. Predisposition of hepatocytes to oxidative stress: an experimental approach.

Intracellular metabolite glutathione, existing in either its reduced (GSH) or oxidized states, is crucial for the protection of any cell against an oxidative stress or injury. Significant depletion of intracellular levels of GSH predisposes cells to an oxidative injury. We have investigated the level of hepatic GSH during the early course of sepsis in a physiologically well-characterized septic-sheep model. Following six hours of sepsis, which was characterized by hypotension, hypoxemia, and granulocytopenia, the level of intrahepatic GSH was significantly reduced compared with baseline levels. There was no reduction after two hours of sepsis. Hepatic GSH levels in control animals were unchanged compared with baseline levels. These findings suggest that the liver may be more susceptible to an oxidative stress in septic patients.

Surgical treatment of duodenal ulcer: a prospective randomized study.

From 1960 to 1980, 344 patients were included in a prospective randomized study for elective surgical treatment of duodenal ulcer disease. Results of vagotomy and pyloroplasty were compared with vagotomy and hemigastrectomy. There were no postoperative deaths, the postoperative complication rates were similar for both groups. Ulcerations recurred in 12% of the vagotomy-pyloroplasty group and in 3% of the vagotomy-hemigastrectomy group (P less than .05). Independent analyses of recurrence were performed for young patients, for alcoholics, and for patients who had obstructions or were bleeding preoperatively. Recurrence rates in these special populations were not found to be significantly different. Eight percent of the vagotomy-pyloroplasty group required reoperations for recurrent ulceration; only 2% of the vagotomy-hemigastrectomy group required reoperation. Postoperative dumping symptoms were significantly more frequent in the vagotomy hemigastrectomy group. Postoperative diarrhea was also more frequent and more severe in the vagotomy-hemigastrectomy group.

Enterococcal sepsis and lung microvascular injury in sheep.

In a common bile duct contamination model, we studied the effect of Streptococcus faecalis compared with Escherichia coli in sheep with chronic lymph fistulas to investigate the role of enterococcus in acute lung injury and acute sepsis. Early pulmonary hypertension in the E coli group was not expressed in the S faecalis group, probably due to a failure of S faecalis to illicit a thromboxane A2 response. In the late period, E coli was associated with significantly greater lung microvascular damage compared with S faecalis. The lack of difference between groups with respect to complement activation suggests the action of chemotactic factors, in addition to complement, mediating granulocyte aggregation, and neutropenia. In this model, S faecalis demonstrated limited pathogenicity as expressed in lung microvascular injury compared with E coli.