Traditional criteria for observation of splenic trauma should be challenged.

Age less than 55 years, normal Glasgow Coma Score (GCS), and absence of hypotension are traditional criteria for the selection of adult patients with blunt splenic trauma for observation. The objective of this study is to challenge these criteria. Two hundred twelve patients who presented with blunt splenic injury between 1992 and 1997 were identified from the Trauma Registry at our Level I trauma center. The patients were divided into three groups: 100 patients (47%) were observed, 108 (51%) underwent immediate splenorrhaphy or splenectomy, and 4 (2%) failed observation. The three groups were compared by participants' ages, GCSs, and histories of hypotension. No statistical differences were noted between the successfully observed patients and those requiring immediate surgery with respect to these criteria. Of the 4 patients who failed observation, all were younger than 55 years, all had a GCS >12, and all were normotensive. Our findings suggest that traditional criteria used to select patients for splenic trauma observation are not absolute indicators and should be liberalized: patients can be successfully observed despite having criteria that, in the past, would have led to immediate operative intervention.

Critical thinking: change during medical school and relationship to performance in clinical clerkships.

The development of critical thinking, the ability to solve problems by assessing evidence using valid inferences, abstractions, and generalizations, is one of the global goals advocated by most medical schools. This study determined changes in critical thinking skills between entry and near the end of the third year of medical school, assessed the predictive ability of a test of critical thinking skills, and assessed the concurrent validity of clerkship components and final grade. The Watson-Glaser Critical Thinking Assessment (WGCTA) was administered to one class of students at entry to medical school and near the end of year 3. Performance data for those students who completed their clinical clerkships on schedule were also recorded. Critical thinking improved modestly but significantly from entry to medical school to near the end of year 3. The ability of a critical thinking test to predict clerkship performance was limited; the correlation between WGCTA total score at entry and the components and final grade of five major clerkships ranged from near 0 to 0.34. The concurrent validity of clerkship components and final grade was also limited; correlations with WGCTA total score near the end of year 3 ranged between 0.08 and 0.49. The correlation between WGCTA total score and United States Medical Licensing Examination Step 2 was higher at year 3 than at medical school entry. Critical thinking skills improve moderately during medical school. Used alone, tests of critical thinking may be of limited value in predicting which students will be successful in clinical clerkships. Clerkship evaluation components and final grade have limited concurrent validity when a test of critical thinking is the criterion.

Effect of external reinforcement on the patency of infrainguinal polytetrafluoroethylene arterial grafts.

BACKGROUND: Expanded polytetrafluoroethylene (PTFE) has been used for infrainguinal revascularization when the saphenous vein is unavailable or unsuitable. Patency rates are, however, decidedly inferior to those with autologous vein, especially when anastomosed distally to the infrageniculate popliteal or tibial arteries. Although there are theoretical advantages to the use of reinforced grafts, the issue of external support for infrainguinal grafts has not been addressed in large clinical trials. Despite the insufficiency of data to support their use, externally supported PTFE grafts are widely used in clinical practice. This study attempts to determine whether or not external reinforcement of PTFE grafts affects patency when the graft crosses a joint in a canine arterial model. STUDY DESIGN: Patency rates of standard PTFE prostheses were compared with those of externally supported PTFE across the hip joint in 19 mongrel dogs. In each animal, one limb was randomly assigned to receive standard PTFE and the other, externally supported PTFE. External iliac-superficial femoral artery grafts were constructed in a standardized fashion. At 12 to 16 weeks after implantation, graft patency was assessed by arteriography. RESULTS: Thirteen animals (26 grafts) underwent angiographic evaluatIon of patency. Overall patency was 42 percent at 84 to 113 days. There was no statistically significant difference in patency between the two graft materials. CONCLUSIONS: Intrinsic factors, rather than the presence or absence or external graft reinforcement, are the most important determinants of graft patency in this model. These data do not support the routine clinical use of externally reinforced PTFE grafts for infrainguinal revascularization.

Incidental Meckel's diverticulectomy in adults.

BACKGROUND: Incidental Meckel's diverticulectomy has been advocated by some surgeons because of the lower associated morbidity and mortality in this setting than when resection is indicated. Others have argued that the low risk of complication occurrence does not justify prophylactic removal. The issue remains controversial. METHODS: Medical records of all adults undergoing Meckel's diverticulectomy at four acute care hospitals during the 5-year period 1989 through 1993 were retrospectively reviewed. Decision analysis was used to determine relative risks for incidental resection compared to indicated resection for a complication. RESULTS: Ninety patients underwent incidental diverticulectomy. Morbidity was 2% and mortality 0%. Four patients underwent resection for a complication of their diverticulum. Morbidity and mortality were each 0%. Combining these results with previously reported results and using decision analysis, the conditional probabilities of producing surgical morbidity or mortality in the adult population at risk by only resecting symptomatic diverticula are 0.2% and 0.04%, respectively. The comparable risks for resecting all incidentally discovered diverticula are 4.6% and 0.2%. CONCLUSIONS: Incidental diverticulectomy in adults should be abandoned.

Acquired intracranial herniations: MR imaging findings.

Many of the pathologic processes that increase intracerebral mass may eventually cause brain herniation. It is important to recognize brain herniation, as it can often produce the presenting clinical signs and symptoms and is often the cause of serious neurologic sequelae or death.

Assessment of a surgical pattern recognition examination.

BACKGROUND: Recent cognitive research in medicine has demonstrated that expert diagnosticians solve many clinical problems through "pattern recognition" rather than deductive reasoning strategies. Development of the ability to recognize and diagnose common surgical problems is a critical objective of undergraduate surgical education. A surgical pattern recognition examination (PAT) was developed to assess surgical diagnosis recognition in clerkship students. METHODS: Surgical faculty selected 18 diagnoses for 20 possible presenting complaints (eg, leg pain, soft tissue mass). A distinctive patient description was written for each diagnosis. An examination of 200 items was compiled covering 20 presenting complaints. RESULTS: The PAT was administered to clerkship students during the 1992-1993 academic year (n = 77). PAT scores ranged from 33% to 90% with a mean of 65% (SD = 12.7). PAT scores correlated highly with the National Board of Medical Examiners (NBME) Surgery Subject Examination (SSE) scores. The validity of the examination was assessed by a speeded administration of the exam to surgical house staff. Senior residents scored significantly higher than junior residents (mean 82% versus 63%, P = 0.004). Performance on the PAT was significantly affected by the order of the student rotation in the academic year (P = 0.02) while performance on the NBME SSE was not (P = 0.40), which is consistent with diagnostic ability improving with clinical experience. CONCLUSIONS: The surgical PAT examination is a new, reliable, and valid method for assessing diagnostic ability in third-year students.

Are stereotaxic breast biopsies adequate?

BACKGROUND: Stereotaxic core breast biopsy (SCBB) has been proposed as a cost-effective and reliable method of evaluating mammographic lesions. This study evaluates an initial experience with SCBB and assesses the adequacy of the biopsy specimens obtained. METHODS: Two hundred forty-one SCBB were performed on 221 patients during 13 months by four radiologists. Mammograms were assigned a suspicion index on a scale of 1 to 5. One pathologist performed a blinded retrospective review of all SCBB specimens and assigned an adequacy score based on the quality and amount of the tissue present. RESULTS: The majority of SCBB were ordered by general surgeons (67%). A suspicion index score of 3 was assigned to 74% of lesion specimens. Twelve percent of specimens were malignant. Overall SCBB adequacy (score > or = 2) was 77%. Adequacy was present in 74% of benign biopsy specimens as compared with 100% of malignant specimens (p < 0.005). Only 62% of specimens reported as benign without specific features were adequate. There were no differences in adequacy between individual radiologists or during the study period. CONCLUSIONS: SCBB is largely used by surgeons to assess indeterminate mammographic lesions. One of four benign specimens was inadequate. Benign SCBB specimens must be interpreted with caution.

Assessment of a pattern-recognition examination in a clinical clerkship.

PURPOSE: To develop a pattern-recognition examination (called PAT) for use in assessing surgical clerkship students. METHOD: The PAT was developed in 1992-93 by the surgery faculty at the Wright State University School of Medicine. The top 30 diagnoses of patients seen by clerkship students in 1991-92 were identified, and possible presenting complaints were selected for each diagnosis. Then for each complaint faculty selected 18 common or catastrophic diagnoses, and a distinctive patient description was written for each diagnosis. An examination of 200 items was compiled covering 20 presenting complaints, each with a set of ten patient descriptions and 18 diagnoses from which to choose the most likely diagnosis. Scoring was by the percentage of correct responses. The PAT was given to 77 students during the 1992-93 clerkship along with other forms of evaluation. The PAT was also administered to 18 surgical residents. RESULTS: The students' mean score on the PAT was 65%, SD, 12.7. Split-half reliability was high (Spearman-Brown r = .91). The students' PAT performances correlated strongly with other cued-response testing formats, e.g., rs = .79, PAT versus the surgery subject examination of the National Board of Medical Examiners. Moderate correlations with essay scores (r = .49) and preceptors' ratings (r = .49) were found. The residents' PAT performances were significantly higher for senior than junior residents (82% versus 63%, p = .004). CONCLUSION: Utilizing this examination format, it is possible to locally develop a reliable examination that is grounded in the actual clinical problems seen by clerkship students and that assesses more than factual recall.

Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury.

Pulmonary toxicity from asbestos may be due in part to oxidant-mediated mechanisms. The purpose of this study was to determine whether alveolar macrophages (AM) contribute to asbestos-induced alveolar epithelial cell injury by oxidant-dependent mechanisms similar to that previously described for polymorphonuclear leukocytes (PMN). We assessed 51Cr release from cultured rat alveolar epithelial cells (RAEC) and transformed human pulmonary epithelial-like cell lines (rat L2 and human WI-26: HPEC). Amosite asbestos caused dose-dependent injury to both RAEC and L2 cells after an 18-h incubation period. Rat PMN increased asbestos-induced injury to RAEC (11 vs. 20% 51Cr release). In contrast, rat AM diminished asbestos-induced injury to RAEC and L2 cells by 60-80%. Human monocytes cultured for 72 h also attenuated asbestos-induced HPEC damage. Asbestos stimulated more H2O2 release from PMN than from AM isolated from the same rats (5.3 +/- 0.6 vs. 0.3 +/- 0.1 nmol x 10(6) cells-1 x 2h-1). The protective effect of rat AM, as opposed to PMN, was not due to differences in asbestos-induced toxicity to each cell type, since > 90% of AM and PMN were nonviable after 18 h. Transmission electron microscopy demonstrated comparable uptake of asbestos by AM and PMN after a 2-h incubation period. However, after an 18-h exposure period, the PMN were completely lysed, whereas over 90% of the AM contained fibers, despite morphologic evidence of cytotoxicity. These results demonstrate that AM, unlike PMN, can reduce alveolar epithelial cell injury in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of chest radiography for pericardial effusion.

OBJECTIVES: This study was designed to determine the diagnostic value of chest radiography for pericardial effusion. BACKGROUND: Pericardial effusions may cause life-threatening cardiac complications, yet they are often difficult to diagnose. METHODS: In a blinded manner, we reviewed the chest radiographs of 83 patients with echocardiographically diagnosed pericardial effusions (5 large, 18 moderate, 60 small) and those of 17 control subjects without effusions. We examined four radiographic signs: an enlarged cardiac silhouette, a pericardial fat stripe, a predominant left-sided pleural effusion and an increase in transverse cardiac diameter compared with the diameter on a previous chest radiograph. RESULTS: An enlarged cardiac silhouette was moderately sensitive (71%) but not specific (41%) for pericardial effusion. A pericardial fat stripe, a predominant left-sided pleural effusion and an increase in transverse cardiac diameter were all specific (94%, 100% and 80%, respectively) but not sensitive (12%, 20% and 46%, respectively). A predominant left-sided pleural effusion was associated with pericardial effusions of all sizes (odds ratio = 1.3, 95% confidence interval [CI] = 1.0-1.6, p = 0.04) and with large and moderate pericardial effusions alone (odds ratio = 7.7, 95% CI = 2.5-24.0, p = 0.0004). In contrast, a pericardial fat stripe was associated only with large and moderate pericardial effusions (odds ratio = 3.3, 95% CI = 0.9-12.0, p = 0.07), and an enlarged cardiac silhouette and an increase in cardiac diameter were not associated with pericardial effusion at all. CONCLUSIONS: A predominant left-sided pleural effusion and a pericardial fat stripe are chest radiographic signs that are suggestive, but not diagnostic, of pericardial effusion. Because these signs cannot reliably confirm or exclude the presence of pericardial effusion, we conclude that chest radiography is poorly diagnostic of this condition.

Asbestos-induced injury to cultured human pulmonary epithelial-like cells: role of neutrophil elastase.

The mechanisms responsible for asbestos-induced pulmonary epithelial cell cytotoxicity, especially oxidant-independent mechanisms, are not established. We determined whether human polymorphonuclear leukocyte (PMN) proteases contribute to asbestos-induced damage to human pulmonary epithelial-like cells (PECs) assessed using an in vitro chromium-51 release assay. Serine antiproteases, phenylmethylsulfonyl fluoride and alpha 1-antitrypsin, each ameliorated PEC injury induced by amosite asbestos and PMNs. A role for a specific proteinase, human neutrophil elastase (HNE), is supported by the facts that (1) asbestos increased HNE release assessed by an enzyme-linked immunosorbent assay technique (1.7 +/- 0.5 vs. 2.8 +/- 0.5 micrograms/ml; P < .025), (2) purified HNE or porcine pancreatic elastase (PPE) each alone caused PEC detachment, (3) asbestos plus either HNE or PPE caused PEC lysis similar to that mediated by asbestos and PMNs, and (4) cationic agents released from PMNs were unlikely to be involved because polyanions did not ameliorate injury resulting from asbestos and PMNs. Compared to elastase, cathepsin G caused less PEC detachment and negligible augmentation in asbestos-induced PEC lysis. Asbestos increased the association of 125I-labeled elastase with PECs nearly 50-fold compared with PPE alone (14.4% vs. 0.3%, respectively; P < .01) and nearly 10-fold compared with another particle, opsonized zymosan. We conclude that PMN-derived proteases, especially elastase, may contribute to asbestos-induced lung damage by augmenting pulmonary epithelial cell injury.

Adjunctive vasodilator therapy in the treatment of murine ischemia.

Potent vasoconstrictors such as angiotensin II and vasopressin have been implicated as mediators of persistent vasoconstriction after reversible superior mesenteric artery (SMA) occlusion. Neither captopril (CAP), an angiotensin-converting enzyme (ACE) inhibitor, nor papaverine (PAP), a vasodilator, has proven effective in reversing this vasoconstriction when employed singly. The present study examined the combined effect of these agents in reducing mortality in a murine model of acute mesenteric ischemia. The SMAs of 106 adult male Sprague-Dawley rats were totally occluded for 85 minutes. Test agents were given intravenously at reperfusion over a 90-minute period. Survival rates were assessed at 48 hours. CAP was given as a single bolus (0.3 mg/kg) and PAP (0.5 mg/kg/h) as an infusion. Aortic and SMA blood flows were measured pretreatment and posttreatment in a separate group of 19 animals treated with CAP and PAP as single agents. chi 2 analysis and analysis of variance were used to test differences with p < or = 0.05 accepted as significant. PAP alone as an adjunct resulted in a significant increase in 48-hour survival (57% versus 19%, p < or = 0.005). PAP in combination with CAP produced the best outcome in this model (87% versus 19%, p < or = 0.005). Aortic blood flow decreased, whereas SMA blood flow increased after treatment both with CAP and with PAP, but not significantly. The combination of an intravenously administered vasodilator with either glucagon or an ACE inhibitor was the most effective adjunctive therapy in this mesenteric ischemia model. There was no evidence that an inotropic effect, rather than SMA vasodilation, was the responsible mechanism of action.

Comparing clerkship sites in a community-based medical school by evaluating students' undergraduate and postgraduate performances.

BACKGROUND: Studies have generally found clinical training sites within the same clerkship to be comparable regarding students' performances--by using undergraduate measures in individual clerkships at medical schools with university hospitals. The present study examined performance comparability among sites within two clerkships in a community-based medical school and used both undergraduate and postgraduate measures. METHOD: The participants were the 349 graduates from the classes of 1988-1991 at Wright State University School of Medicine who took an internal medicine clerkship (332 of the graduates, in five principal combinations of sites) and a general surgery clerkship (349 at six sites). The undergraduate measures were final percent scores for the clerkships and subtest and total scores on the National Board of Medical Examiners (NBME) Part II examination. The postgraduate measures were supervisors' ratings from the first year of residency (210 graduates) and total score on the NBME Part III (212). Univariate analysis of variance and Tukey's multiple-range test were used for the comparisons. RESULTS: The only statistically significant difference among sites was for the medicine clerkship and involved only one undergraduate measure, the clerkship score (and the differences were slight, less than four percentage points). CONCLUSION: Virtually no differences in the students' performances on the undergraduate and postgraduate measures were found among sites for the two clerkships.

Characterization of unintegrated retroviral DNA with long terminal repeat-associated cell-derived inserts.

We have used a replication-competent shuttle vector based on the genome of Rous sarcoma virus to characterize genomic rearrangements that occur during retrovirus replication. The strategy involved cloning circular DNA that was generated during an acute infection. While analyzing a class of retroviral DNA clones that are greater than full length, we found several clones which had acquired nonviral inserts in positions adjacent to the long terminal repeats (LTRs). There appear to be two distinct mechanisms leading to the incorporation of cellular sequences into these clones. Three of the molecules contain a cell-derived insert at the circle junction site between two LTR units. Two of these molecules appear to be the results of abortive integration attempts, because of which, in each case, one of the LTRs is missing 2 bases at its junction with the cell-derived insert. In the third clone, pNO220, the cellular sequences are flanked by an inappropriately placed copy of the tRNA primer-binding site on one side and a partial copy of the U3 sequence as part of the LTR on the other side. A fourth molecule we characterized, pMD96, has a single LTR with a U5-bounded deletion of viral sequences spanning gag and pol, with cell-derived sequences inserted at the site of the deletion; its origin may be related mechanistically to pNO220. Sequence analysis indicates that all of the cellular inserts were derived from the cell line used for the acute infection rather than from sequences carried into the cell as part of the virus particle. Northern (RNA) analysis of cellular RNA demonstrated that the cell-derived sequences of two clones, pNO220 and pMD96, were expressed as polyadenylated RNA in uninfected cells. One mechanism for the joining of viral and cellular sequences suggested by the structures of pNO220 and pMD96 is recombination occurring during viral DNA synthesis, with cellular RNA serving as the template for the acquisition of cellular sequences.

Serum promotes asbestos-induced injury to human pulmonary epithelial cells.

Asbestos exposure causes chronic interstitial pulmonary fibrosis. Injury to human pulmonary epithelial cells (HPEC) is speculated to precede the fibrotic response. We investigated whether asbestos, either alone or in conjunction with serum, injured cultured HPEC as assessed in a standard chromium 51 release assay. Amosite asbestos in serum-free media induced modest HPEC injury (9.4% +/- 3.3% Cr release), which was significantly enhanced (2.7-fold) in the presence of serum (25.5% +/- 4% Cr release). HPEC cytotoxicity was both asbestos and serum dose-dependent. Additionally, we demonstrated that, compared with HPEC injury induced by asbestos plus serum, (1) heat-decomplemented serum or serum fractions of a wide range of molecular weights were equipotent to fresh serum, (2) catalase, superoxide dismutase, or dimethylthiourea was not protective, (3) 3-aminobenzamide, which prevents oxidant-induced adenosine triphosphate depletion by inhibiting poly-adenosine diphosphate-ribose polymerase, afforded significant protection (32% decrease in HPEC injury), and (4) deferoxamine-treated asbestos was significantly less toxic to HPEC compared with untreated asbestos, causing a 57% decrease in HPEC cytotoxicity. Electron microscopic studies revealed that, compared with buffer, serum increased the amount of amosite asbestos along the surface and inside HPEC. Thus, amosite asbestos is cytotoxic to cultured HPEC and serum promotes this injurious effect by augmenting the interaction of asbestos with HPEC. These data suggest that this effect may occur by increasing intracellular oxidant stress mediated in part by the iron in asbestos.

Open peritoneal management in murine peritonitis.

Open management of the peritoneal cavity with mesh insert in severe peritonitis has been the subject of favorable clinical reports. The present study was undertaken to develop an animal model suitable for investigation of this technique. Peritonitis was induced in anesthetized rats using the technique of cecal puncture following nonobstructing cecal ligation. A pilot study with this technique did not result in either intestinal distention or edema. Therefore, distal ileal ligation was added to duplicate the clinical findings associated with diffuse peritonitis. Twenty animals treated in this manner underwent standard abdominal wall closure and were simply observed for 96 hours. This produced a 15 per cent mortality at 24 hours, 65 per cent at 48 hours, 70 per cent at 72 hours, and 80 per cent at 96 hours. A second group underwent sham laparotomy only (n = 5) with a resultant 100 per cent survival. Based on these preliminary findings, two study groups were defined. Animals in both groups had cecal ligation and puncture and ileal ligation performed. Group I (n = 22) animals underwent re-laparotomy 24 hours later with primary fascial closure, while group II (n = 23) animals underwent re-laparotomy at 24 hours with placement of a standardized Dexon mesh insert covered by a superficial polyethylene film to prevent fluid loss. No animals received antibiotics. Cumulative mortalities in group I were 77, 90, 90, and 90 per cent at 24, 48, 72, and 96 hours after reoperation. In group II mortalities were found to be 48, 57, 61, and 70 per cent at 24, 48, 72, and 96 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphonuclear leukocyte- and Pseudomonas aeruginosa-induced damage to a human pulmonary epithelial cell line.

Polymorphonuclear leukocytes (PMNL) or Pseudomonas aeruginosa can damage the lung, but the manner in which they interact to induce toxicity is unclear. An in vitro model of the pulmonary epithelium was used to investigate interactions of PMNL and P. aeruginosa on epithelial cytotoxicity. A low inoculum of P. aeruginosa (10(7) bacteria) was minimally toxic to the epithelial cells (lysis = 9.0 +/- 2.9, detachment = 3.5 +/- 1.4). The addition of PMNL to the low inoculum markedly increased damage to the epithelial cells (lysis = 18.1 +/- 3.9, detachment = 17.6 +/- 3.6). Both the bacterium and a low-molecular-weight exoproduct were able to induce PMNL-mediated damage to epithelial cells. The damage was inhibited by serum or the addition of alpha 1 antiprotease but not by antioxidants. A larger inoculum of P. aeruginosa (10(9) bacteria) was directly toxic to the pulmonary cells (lysis = 44.8 +/- 4.1, detachment = 7.6 +/- 0.7). The damage was mediated by a heat-labile bacterial exoproduct. Pulmonary epithelial damage following pseudomonal infections may be related to either neutrophil or bacterial activity depending on the bacterial inoculum.

The interaction of asbestos and neutrophils injures cultured human pulmonary epithelial cells: role of hydrogen peroxide.

Asbestos exposure causes diffuse interstitial pulmonary fibrosis. Since alveolar epithelial cell injury is hypothesized to precede the fibrotic response in asbestosis, we investigated whether asbestos, either alone or in conjunction with neutrophils (PMNs), injured cultured human pulmonary epithelial cells (HPECs). HPEC cytotoxicity was assessed with a standard 51chromium release assay after a 16-hour incubation with asbestos and PMNs. Negligible HPEC cytotoxicity was observed after incubation with either amosite asbestos (500 micrograms/ml) or PMNs alone in serum-free media. However, incubation with both asbestos and PMNs caused significant HPEC injury, which was asbestos dose-dependent; causing 25% +/- 4% detachment and 52% +/- 8% 51chromium release with 500 micrograms/ml asbestos. The cytotoxic effects of asbestos plus PMNs were nearly completely attenuated with serum (20%) or catalase (100 micrograms/ml) but were not prevented with scavengers of superoxide anion, hydroxyl radical, or hypochlorous acid. A role for hydrogen peroxide (H2O2) in mediating HPEC injury was also suggested by the demonstration of asbestos-induced generation of H2O2 by PMNs. Furthermore, H2O2 alone (10(-4)mol/L) caused significant HPEC damage. Intimate contact between asbestos-activated PMNs and HPECs was a necessary requirement for PMN-mediated HPEC cytotoxicity. These data suggest that pulmonary epithelial cell injury is mediated in part by H2O2 release from asbestos-activated PMNs as well as intimate contact between the epithelial cell, PMNs, and asbestos.

Contrasting effects of inflammatory stimuli on neutrophil and monocyte adherence to endothelial cells.

Leukocyte adherence to endothelial cells (EC) is an important early event in inflammatory responses, which are often characterized by a predominance of either neutrophils (PMN) or monocytes. However, there is little information concerning the molecular events important in leukocyte adherence to EC. Intracellular activation of protein kinase C and the calcium-second messenger system leads to the stimulation of a number of important functions in PMN and monocytes. We compared the effects of members of these pathways on human PMN and monocyte adherence to cultured bovine aortic EC. We observed that phorbol myristate acetate, phorbol, 12,13-dibutyrate, L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol, and ionomycin each induced significant dose-dependent increases in PMN adherence to EC monolayers. In contrast, similar concentrations of each of these agents induced significant decreases in EC adherence of monocytes enriched by countercurrent centrifugal elutriation. Separate experiments determined that the differences in PMN and monocyte adherence to EC were not related to differences in oxidant production because 1) phorbol myristate acetate and L-alpha-1-oleoyl-2-acetoyl-sn-3-glycerol caused similar marked increases in both PMN and monocyte superoxide anion and hydrogen peroxide production and 2) ionomycin, which had opposing effects on PMN and monocyte adherence, had no effect on PMN and monocyte superoxide anion or hydrogen peroxide release. We conclude that activators of protein kinase C and the Ca-second messenger pathway have opposite effects on PMN and monocyte adherence to EC and that these effects are mediated by O2 radical-independent mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

The pulmonary clearance of smooth and rough strains of Pseudomonas aeruginosa.

Upper airway colonization with rough strains of Pseudomonas is associated with clinical deterioration in patients with cystic fibrosis. These rough strains are less toxic than smooth strains in the burned mouse model and in vitro assays. We measured the 4-h pulmonary clearance of 10(4) and 10(6) rough and smooth Pseudomonas after intrabronchial inoculation. After 10(4) Pseudomonas, rough strains were cleared more efficiently than smooth strains (89 +/- 13% versus 140 +/- 19% of the original inoculum, respectively, p less than 0.05). This was associated with more total bronchoalveolar lavage PMNs after inoculation with rough as compared with smooth Pseudomonas (1.60 +/- 0.38 x 10(5) versus 0.55 +/- 0.09 x 10(5), respectively, p less than 0.05). After inoculation with 10(6) Pseudomonas, rough were cleared less efficiently than smooth Pseudomonas (380 +/- 45% versus 134 +/- 12% of the original inoculum, respectively, p less than 0.05). There was no difference in the BAL PMNs of the animals inoculated with either bacterial strain at this inoculum (8.1 +/- 0.6 x 10(5) and 9.4 +/- 1.0 x 10(5) for the rough and smooth Pseudomonas, respectively). When PMN differences were abolished in C5-deficient mice, 10(4) rough were cleared less efficiently than smooth Pseudomonas. The relatively poor clearance of rough Pseudomonas could not be explained by in vitro differences in PMN killing or BAL toxicity or by intrinsic growth rates.