A study of molecular adsorption of a cationic surfactant on complex surfaces with atomic force microscopy.

The study of molecular adsorption on solid surfaces is of broad interest. However, so far the study has been restricted to idealized flat smooth rigid surfaces which are rarely the case in real world applications. Here we describe a study of molecular adsorption on a complex surface of the submicron fibers of a fibrous membrane of regenerated cellulose in aqueous media. We use a cationic surfactant, cetyltrimethylammonium chloride (CTAC), as the adsorbing molecule. We study the equilibrium adsorption of CTAC molecules on the same area of the fibers by sequentially immersing the membrane in pure water, 1 mM and then a 20 mM solution of CTAC. Atomic force microscopy (AFM) is applied to study the adsorption. The force-volume mode is used to record the force-deformation curves of the adsorbed molecules on the fiber surface. We suggest a model to separate the forces due to the adsorbed molecules from the elastic deformation of the fiber. Interestingly, knowledge of the surface geometry is not required in this model provided the surface is made of elastically homogeneous material. Different models are investigated to estimate the amount of the adsorbed molecules based on the obtained force curves. The exponential steric repulsion model fits the force data the best. The amount of the adsorbed surfactant molecules and its dependence on the concentration are found to be reasonable compared to the data previously measured by means of Raman scattering done on a flat surface of silica.

Inflammatory cytokines interleukin-6 and oncostatin m induce plasminogen activator inhibitor-1 in human adipose tissue.

BACKGROUND: Adipose tissue is a prominent source of plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of plasminogen activation. Increased PAI-1 expression acts as a cardiovascular risk factor, and plasma levels of PAI-1 strongly correlate with body mass index (BMI). Elevated serum levels of interleukin-6 (IL-6), an inflammatory cytokine and a member of the glycoprotein 130 (gp130) ligand family, are found in obese patients and might indicate low-grade systemic inflammation. Another gp130 ligand, oncostatin M (OSM), upregulates PAI-1 in cardiac myocytes, astrocytes, and endothelial cells. We used tissue explants and primary cultures of preadipocytes and adipocytes from human subcutaneous and visceral adipose tissue to investigate whether IL-6 and OSM affect PAI-1 expression in fat. METHODS AND RESULTS: Human subcutaneous and visceral adipose tissue responded to treatment with IL-6 and OSM with a significant increase in PAI-1 production. Human preadipocytes were isolated from subcutaneous and visceral adipose tissue. Adipocyte differentiation was induced by hormone supplementation. All cell types expressed receptors for IL-6 and OSM and produced up to 12-fold increased levels of PAI-1 protein and up to 9-fold increased levels of PAI-1 mRNA on stimulation with IL-6 and OSM. AG-490, a janus kinase/signal transducer and activator of transcription inhibitor, abolished the OSM-dependent PAI-1 induction almost completely. CONCLUSIONS: We have for the first time established a link between the gp130 ligands, the proinflammatory mediators IL-6 and OSM, and the expression of PAI-1 in human adipose tissue. Thus, we speculate that IL-6 and OSM, by upregulating PAI-1 in adipose tissue, can contribute to the increased cardiovascular risk of obese patients.

No evidence for a direct role of Helicobacter pylori and Mycoplasma pneumoniae in carotid artery atherosclerosis.

BACKGROUND: That infections with certain pathogens, by initiating an inflammatory response, may contribute to the development of atherosclerosis is suggested by clinical and experimental evidence. AIM: To analyse atherosclerotic plaques of the carotid artery, samples of apparently healthy greater saphenous veins and circulating leucocytes from the same individual patients for the presence of Helicobacter pylori and Mycoplasma pneumoniae. METHODS: Samples from 36 patients undergoing carotid endarterectomy for symptomatic carotid artery stenosis were analysed by polymerase chain reaction for the presence of DNA specific for H. pylori and M. pneumoniae. IgG antibody titres against H. pylori and M pneumoniae and plasma levels of soluble E-selectin, soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 were determined. RESULTS: M. pneumoniae-specific DNA was detected in the atherosclerotic plaques of 13 of 36 (36.1%) patients, in the saphenous veins of 9 of 36 (25%) patients and in the leucocytes of 27 of 36 (75%) patients. No salient association was observed between the presence of M. pneumoniae-specific DNA in leucocytes and atherosclerotic plaques or veins. A marked correlation between the presence of M. pneumoniae in the respective specimens and the studied inflammatory markers or the presence of anti-M. pneumoniae antibodies was not observed. H. pylori-specific DNA could not be detected in the specimens tested. CONCLUSIONS: The absence of H. pylori and the random distribution of M. pneumoniae in tissue samples obtained from patients with symptomatic carotid artery stenosis do not support a role for these pathogens in the development of atherosclerosis due to a direct interaction of the bacteria with the vasculature.

Cognitive function after coronary bypass surgery: effect of decreased cerebral blood flow.

The effect of regional cerebral blood flow during coronary bypass surgery on performance on the Mini-Mental State Examination was studied in 14 patients. No association between lowered regional cerebral blood flow and cognitive scores was found.

Plasma Lp(a) levels are increased in patients with chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease resulting from the thromboembolic obstruction of the segmental and/or large size pulmonary arteries, subsequently leading to pulmonary arterial hypertension. Incomplete resolution of acute pulmonary emboli and thrombus organization are believed to be important for the development of the disease. Primary pulmonary hypertension (PPH) is a further disease that at present is poorly understood but shows a clinical picture similar to CTEPH. Since lipoprotein(a) [Lp(a)]. a genetically determined risk factor for atherosclerosis and thrombosis, has been found increased in plasma of patients with deep vein thrombosis and pulmonary embolism, we measured plasma Lp(a) levels in 40 patients with CTEPH and 50 patients with PPH and compared them to 50 matched controls. The median for Lp(a) plasma levels was significantly higher in CTEPH patients (26.6 mg/dl) than in PPH patients (9.6 mg/dl) and controls (7.2 mg/dl). Increased plasma Lp(a) could, therefore. play a significant role in the mechanisms of ongoing thrombosis and thrombus organization in CTEPH, while its possible role in PPH can be limited to a small number of patients.

Impairment of the plasmin activation system in primary pulmonary hypertension: evidence for gender differences.

Primary pulmonary hypertension (PPH) is a rare disorder, with marked in-situ thrombosis of small pulmonary vessels occurring primarily in adult women. We investigated whether differences in the plasmin- and thrombin activation system are associated with the predominate affection of females. Plasma levels of plasminogen activator inhibitor type 1 (PAI-1), tissue-type plasminogen activator (t-PA), fibrinogen, thrombin-antithrombin (TAT) complexes, and prothrombin fragments (F1.2) were measured at baseline and after standardized venous occlusion (VO) in patients with PPH (24 female, 9 male). At baseline, females showed significant higher TAT levels (p = 0.05), higher t-PA antigen levels (p = 0.01) and higher fibrinogen levels (p = 0.03) with positive correlation to mean pulmonary artery pressure (mPAP), as well as nonsignificant lower t-PA activity, higher PAI-1 antigen and activity and F1.2 levels. After VO, females showed a significantly blunted increase in t-PA antigen (p = 0.01) and t-PA activity (p = 0.001), correlating with mPAP, as well as increased PAI-1 activity (p = 0.05). We hypothesize, that the observed presence of gender differences in the plasmin- and thrombin activation system in PPH leading to an antifibrinolytic/prothrombotic state might, in part, explain the female predominant incidence of this disease.

Treatment of malignant disease in trachea and main-stem bronchi by carbon dioxide laser.

The use of the carbon dioxide laser to remove intraluminal malignant lesions of the trachea and main-stem bronchi is described. Forty-three patients, 30 men and 13 women from 23 to 79 years of age, have received from one to three laser treatments to provide an improved airway with relief of major respiratory tract obstruction. There has been one intraoperative death and there have been three immediate postoperative deaths. Improvement in respiratory status has been accomplished in all surviving patients and has persisted for from 1 to 36 months. The carbon dioxide laser treatment does not cure cancer but does provide an improved airway with low risk so that other treatment can be used. A major advantage of this form of treatment is decreased bleeding and the ability to provide an improved airway. The disadvantages are the necessity for general anesthesia and expense of the equipment.

Potential value of digital radiography. Preliminary observations on the use of dual-energy subtraction in the evaluation of pulmonary nodules.

The radiographic demonstration of calcification in a solitary pulmonary nodule renders the possibility of malignancy extremely unlikely, although rare exceptions have been reported. Conventional roentgenograms and tomograms sometimes provide inconclusive evidence although CT can be highly accurate in both identifying and quantifying calcium content. An alternative method is dual-energy subtraction utilizing scanned projection digital radiography. Forty-one patients with solitary (occasionally multiple) pulmonary nodules were examined with the technique, employing second-generation fan-beam equipment: 28 nodules or masses were noncalcified and 13 calcified. Of the former, 20 were pathologically proved, 16 being malignant and 4 benign (2 granulomas, 2 bronchiectasis); in 3 of the remaining 8, a presumptive diagnosis was reasonably certain (1 granuloma, 2 metastases), while in 5 the diagnosis was not made. In 8 of the 13 calcified lesions, the diagnosis can reasonably be regarded as confirmed as granulomas; 5 are being followed up with that presumptive diagnosis.

The utility of open lung biopsy following lung transplantation.

BACKGROUND: Most pulmonary complications associated with lung transplantation have non-specific clinical characteristics. Furthermore, common diagnostic modalities, including bronchoscopy with transbronchial biopsy (TBB), often do not render a definitive diagnosis. In this study, we reviewed our experience with open lung biopsy (OLB) following lung transplantation, specifically regarding its ability to safely provide clinically relevant information that affects therapeutic decisions. METHODS: From October 1989 to March 2000, 202 patients underwent lung transplantation at our institution. We reviewed the clinical course of the 42 patients who received 48 OLBs. Of these patients, we determined the pre-operative clinical condition, preceding TBB histologic information, OLB histology, treatment changes, and procedural complications as a result of the OLB. RESULTS: A new, clinically unsuspected diagnosis was made in 14 biopsies (29% of all OLB), and all of these resulted in therapy changes. Thirty-two biopsies (67% of all OLB) confirmed our clinical suspicions, and new therapy was initiated in 30 of these patients. Two patients (4% of all OLB) had non-diagnostic OLB. Four biopsies (8% of all OLB), including the 2 non-diagnostic OLBs, did not result in any therapy changes or initiation of new therapy. Complications occurred in 3 patients, all of whom had an air leak for >7 days. CONCLUSION: Open lung biopsy in lung transplant patients renders a new, unsuspected diagnosis in nearly one third of patients and leads to specific, directed therapy in the vast majority of patients. Open-lung biopsy can be performed safely and should be considered when diagnosis is uncertain in clinically deteriorating patients.

Soluble selectins in the pulmonary and systemic circulation in acute cardiogenic and non-cardiogenic pulmonary failure.

OBJECTIVE: Pulmonary endothelial activation caused by high pulmonary capillary pressures may be involved in the pathogenesis of cardiogenic pulmonary edema (CPE). We studied soluble selectins and soluble ICAM-1 as markers of cell activation in the systemic and pulmonary circulation of patients with respiratory failure (RF) due to CPE (RFCPE) as compared to patients with RF due to pulmonary infection (RFPI). SETTING: Cardiovascular Intensive Care Unit at a university hospital. PATIENTS: Twenty patients with RFCPE, 20 patients with RFPI and 17 critically ill patients without RF. INTERVENTIONS: Blood samples were obtained from the arterial and the pulmonary capillary circulation and sE-, sL-, and sP-selectin as well as sICAM-1 were determined. To distinguish between systemic and pulmonary endothelial activation, transpulmonary gradients (concentrationarterial blood - concentrationpulmonary capillary blood) were calculated. RESULTS: Systemic concentration of sL-selectin was lower in patients with RFCPE and RFPI than in patients without RF (RFCPE: 719.0 +/- 243.9 ng/ml, RFPI: 528.5 +/- 220.8 ng/ml, no RF: 882.4 +/- 222.6 ng/ml; P < 0.001). Systemic concentrations of ICAM-1, sE- and sP-selectin were not significantly different between the three groups. Transpulmonary gradients in sE- and sL-selectin were predominantly negative in patients with RFCPE (-3.2 +/- 7.8 ng/ml and -55.4 +/- 116.1 ng/ml, respectively) and RFPI (-2.3 +/- 5.8 ng/ml and -17.6 +/- 40.3 ng/ml, respectively) but were predominantly positive in patients without RF (11.6 +/- 7.2 ng/ml and 66.6 +/- 69.6 ng/ml, respectively), which suggests trapping of sE- and sL-selectin in the pulmonary circulation in the majority of patients with RFPI as well as in the majority of patients with RFCPE. CONCLUSION: Pulmonary endothelial activation occurs during both RFCPE and RFPI. This adds evidence that, besides hydrostatic mechanisms, cell activation occurs during CPE.

Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection.

The role of thromboxane (Tx) in hyperacute rejection of pig lung by human blood was studied in an ex vivo model, wherein lungs from juvenile piglets were perfused with fresh heparinized human blood. In this model, hyperacute lung rejection was characterized by an abrupt rise in pulmonary vascular resistance (PVR; >1 cmH2O x ml(-1) x min) and prolific Tx elaboration (>15 ng/ml) within 5 min and loss of function within 10 min. Although papaverine significantly blunted the rise in PVR (<0.2 cmH2O x ml(-1) x min), Tx production was not inhibited (>20 ng/ml), and florid tracheal edema was usually evident within 20 min. In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx > 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH2O x ml(-1) x min) but also with attenuated increase in lung wet-to-dry ratio and airway edema. In concert, elaboration of histamine and tumor necrosis factor was blunted, and median survival increased >10-fold to 2 h (SQ-30741) and >4 h (OKY-046). Depletion of the pig lung macrophages with dichloromethyl bisphosphonate in liposomes, but not Pall filtration of the human blood or liposomes alone, significantly inhibited Tx elaboration (<0.2 vs. >8 ng/ml for Pall filtration or liposomes) and blunted PVR elevation (<0.3 cmH(2)O x ml(-1) x min) during initial perfusion. C3a and histamine elaboration were inhibited, and median survival was significantly prolonged (>4 h). These findings implicate Tx in the inflammation associated with hyperacute lung rejection and demonstrate that pulmonary intravascular macrophages are critical to its elaboration.

Transthoracic exposure for anterior spinal surgery.

The anterior approach to the vertebral column is used to treat fractures, spinal deformities, and destructive lesions secondary to tumor or infection. The thoracic surgeon, working with orthopedic surgeons and neurosurgeons, is uniquely qualified to provide surgical exposure expediently and assist in postoperative care. Forty-five patients with spinal deformities secondary to trauma (18 patients), congenital anomalies (16 patients), neoplastic disease (7 patients), and inflammation (4 patients) were treated by a transthoracic (37 patients) or thoracoabdominal (10 patients) anterior approach to the vertebral column. Two patients had subsequent operations. Free and vascularized rib grafts were used for stabilization and fusion with good results and few complications (8 patients). These results indicate that interspecialty cooperation results in expedient surgical exposure and good postoperative care.

Use of expanded polytetrafluoroethylene pericardial substitute with ventricular assist devices.

Expanded polytetrafluoroethylene membrane was used to reconstruct the pericardium after ventricular assist device insertion in 7 consecutive patients. One patient remains on support with the membrane in place and 6 have had the membrane removed. The expanded polytetrafluoroethylene membrane protected the device cannulas during repeat sternotomy and expedited the dissection of the heart and great vessels at the time of device removal. Reconstruction of the pericardium with expanded polytetrafluoroethylene membrane is recommended at the time of ventricular assist device insertion.

Management of congenital abnormalities of the donor lung.

Congenital abnormalities were encountered in three donor lungs. A donor tracheal bronchus was incorporated into the right bronchial anastomosis. Anomalous pulmonary venous return of the right upper lobe to the superior vena cava and the left upper lobe to the innominate vein were managed by bridging the anomalous veins to the left atrial cuff with autologous pericardium and donor iliac vein, respectively.

A prospective algorithm for the management of air leaks after pulmonary resection.

BACKGROUND: Air leaks (ALs) are a common complication after pulmonary resection, yet there is no consensus on their management. METHODS: An algorithm for the management of chest tubes (CT) and ALs was applied prospectively to 101 consecutive patients who underwent elective pulmonary resection. Air leaks were graded daily as forced expiratory only, expiratory only, inspiratory only, or continuous. All CTs were kept on 20 cm of suction until postoperative day 2 and were then converted to water seal. On postoperative day 3, if both a pneumothorax and AL were present, the CT was placed to 10 cm H2O of suction. If a pneumothorax was present without an AL, the CT was returned to 20 cm H2O of suction. Air leaks that persisted after postoperative day 7 were treated with talc slurry. RESULTS: There were 101 patients (67 men); on postoperative day 1, 26 had ALs and all were expiratory only. Univariable analysis showed a low ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) (p = 0.005), increased age (p = 0.007), increased ratio of residual volume to total lung capacity (RV/TLC) (p = 0.04), increased RV (p = 0.02), and an increased functional residual capacity (FRC) (p = 0.02) to predict the presence of an AL on postoperative day 1. By postoperative day 2, 22 patients had expiratory ALs. After 12 hours of water seal, 13 of the 22 patients' ALs had stopped, and 3 more sealed by the morning of postoperative day 3. However, 2 of the 6 patients whose ALs continued experienced a pneumothorax. Five of the 6 patients with ALs on postoperative day 4 still had ALs on postoperative day 7, and all were treated by talc slurry through the CT. All ALs resolved within 24 hours after talc slurry. CONCLUSIONS: Most ALs after pulmonary resection are expiratory only. A low FEV1/FVC ratio, increased age, increased RV/TLC ratio, increased RV, and an increased FRC were predictors of having an ALs on postoperative day 1. Conversion from suction to water seal is an effective way of sealing expiratory AL, and pneumothorax is rare. If an expiratory AL does not stop by postoperative day 4 it will probably persist until postoperative day 7, and talc slurry may be an effective treatment.

Role of anti-Gal alpha13Gal and anti-platelet antibodies in hyperacute rejection of pig lung by human blood.

BACKGROUND: Previous work has shown that antibodies against porcine antigens are an important trigger of hyperacute lung rejection (HALR). The relative importance of Gal alpha1,3Gal epitopes and other antigens, such as those expressed on pig platelet membranes or lung itself, has not been defined. This study compares the efficiency of three anti-pig antibody depletion strategies, and their efficacy with regard to attenuation of HALR. METHODS: Plasma pooled from three human donors was adsorbed against Gal alpha1,3Gal disaccharide or porcine platelet extract (PPE), or passed through pig lung vasculature. Whole blood reconstituted using adsorbed plasma was then used to perfuse piglet lung, and results were compared with unmodified human blood. RESULTS: Depletion of lung-reactive anti-Gal alpha1-3Gal antibodies was most efficient with the alphaGal column (99% +/- 0.5% vs 87% to 93% +/- 11% for PPE and 92% to 95% +/- 8% for lung, p < 0.01 vs alphaGal column). PPE column tended to be more efficient (77% to 84% +/- 12%) in removing anti-PPE antibodies than pig lung (66% to 70% +/- 14%) or the alphaGal column (56% to 63% +/- 16%, p < 0.05). Lung survival and function with each antibody depletion strategy was improved relative to unmodified controls (mean survival > or = 146 minutes vs 8 minutes for controls). Although alphaGal and lung adsorption yielded more consistent lung protection (survival beyond 2 hours) than did PPE, no approach proved significantly superior. Complement C3a elaboration at 10 minutes was attenuated > 80% by each adsorption strategy, an effect that was most pronounced in the lung adsorption group (95%, p < 0.01). Histamine elaboration was blunted significantly by PPE adsorption but not in other groups (p < 0.05). Platelet but not leukocyte sequestration was decreased with antibody depletion compared with the nondepleted group (44% to 50% vs 82%, p < 0.01). CONCLUSIONS: Each antibody depletion strategy tested significantly prolongs lung xenograft survival and function compared with unmodified human blood, but none was sufficient to reliably prevent HALR. Depletion of antibodies against both alphaGal and additional cell membrane antigens, or control of antibody-independent pathogenic pathways, may be necessary to consistently prevent HALR.

Considerations in selection and management of patients undergoing valve replacement with glutaraldehyde-fixed porcine bioprotheses.

From November, 1973, through June, 1978, 428 operations in 425 patients were performed for replacement of aortic, mitral, or aortic plus mitral valves, utilizing 277 Hancock and 180 Carpentier-Edwards bioprostheses. Actuarially determined survival at 36 months was similar for all three groups and compared favorably with our experience with the Björk-Shiley prosthesis. Certain patient-related variables influencing late survival were identified by multivariate analysis and included previous operation for congenital heart disease, coronary artery bypass grafting in nonaortic valve replacement, race (black), age at operation, and New York Heart Association Functional Class. A small but definite incidence of thromboembolism occurred in all three groups, again similar to our experience with the Björk-Shiley prosthesis. Multivariate analysis identified four factors influencing risk of thromboembolism: previous cardiac operation, age, double-valve replacement, and rhythm at discharge. Valve degeneraation occurred, primarily in children and young adults. Over the medium term, the porcine bioprosthesis compared favorably with mechanical prostheses in terms of survival, function, and thromboembolism. Certain patient-related variables affecting survival may be modified by earlier surgical intervention.

Factors and their influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass.

In this study we examined the relationship of regional cerebral blood flow (CBF) to mean arterial pressure, systemic blood flow, partial pressure of arterial carbon dioxide (PaCO2), nasopharyngeal temperature, and hemoglobin during hypothermic nonpulsatile cardiopulmonary bypass (CPB). Regional CBF was determined by clearance of xenon 133 in 67 patients undergoing coronary bypass grafting procedures. There was a significant decrease in regional CBF (55% decrease) during CPB, with nasopharyngeal temperature and PaCO2 being the only two significant factors (p less than 0.05). In a subgroup of 10 patients, variation of pump flow between 1.0 and 2.0 L/min/m2 did not significantly affect regional CBF. We conclude that cerebral autoregulation is retained during hypothermic CPB. Under the usual conditions of CPB, variations in flow and pressure are not associated with important physiological or detrimental clinical affects.

Homocysteine plasma levels in young patients with coronary artery disease. Relation to history of acute myocardial infarction and anatomical extent of disease.

Although there is considerable epidemiologic evidence for a relationship between plasma homocysteine (Hcy) levels and cardiovascular disease, not all prospective studies have shown such a relationship. Furthermore, data concerning the role of hyperhomocysteinemia in patients with premature coronary artery disease (CAD) are rare. It was the aim of the study to investigate a possible association between Hcy plasma levels in young patients with the extent of CAD and the history of myocardial infarction (MI). A cohort of 94 patients was examined for conventional risk factors and the history of previous transmural MI. Furthermore, coronary angiography was performed to assess the anatomical extent of vessel disease. Plasma Hcy levels were measured by use of a commercial enzyme-linked immunosorbent assay. Only a history of previous MI was significantly associated with hyperhomocysteinemia. There was no relationship between elevated Hcy levels and the anatomical extent of vessel disease in patients with premature CAD. Our data may indicate that hyperhomocysteinemia represents an independent risk factor for acute coronary thrombosis rather than for the development of coronary sclerosis. Thereby, hyperhomocysteinemia may influence the clinical situation after plaque rupture not only by prothrombotic action but also by favouring endothelial dysfunction and vasospasm.

Carbon dioxide laser therapy.

A carbon dioxide laser coupled with a ventilating bronchoscope has been used to treat 135 patients with symptomatic obstruction of the trachea and main stem bronchi. This laser has the advantages of being controllable and hemostatic, and can be used repetitively. It does not interfere with other modes of treatment such as radiation therapy or chemotherapy.