Interferon levels in human pulmonary tumors are lower than plasma levels.

It is uncertain whether interferon levels in the interstitial fluid of tumors are equivalent to interferon plasma levels and we have investigated this problem in human pulmonary tumors by infusing human recombinant interferon alpha A and natural interferon Beta for about three hours before surgery. By determining the hematocrit and hemoglobin content it was possible to calculate interferon values (International Units/g wet tissue) present in the interstitial fluid of tumor and lung samples, simultaneously. In 14 patients (epidermoids, n = 9 and adenocarcinomas, n = 5) interferon levels in tumor and "normal" lung expressed as percentages of interferon plasma levels were: 9.5 +/- 3.9 and 29.8 +/- 6.9 for recombinant interferon alpha A and 3.1 +/- 0.4 and 10.1 +/- 2.4 for natural interferon Beta, respectively. Differences for both interferons are statistically significant (p less than 0.05). To our knowledge these are the first data indicating that interferon levels in pulmonary tumor interstitial fluid are markedly lower than those in normal lung although they do not clarify the main factor responsible for the decrease, they explain at least in part the negligible therapeutic activity of interferons in these tumors and emphasize the need for new approaches for improving the therapeutic index of interferons.

Early diagnosis of adult respiratory distress syndrome: an experimental model of complement-mediated pulmonary injury.

This article presents an experimental model of pulmonary injury resembling subclinical human adult respiratory distress syndrome (ARDS) mediated by leukocytes. The activation of complement was prolonged by an intraperitoneal injection of a suspension of zymosan in paraffin. The first step in the development of the disease was an accumulation of polymorphonuclear leukocytes in the lungs. No significant changes were observed on chest radiographs or computed tomograms and the pathophysiologic changes were only minimal in spite of the characteristic structural changes. The criteria currently used for the diagnosis of ARDS are not sensitive enough to detect the subclinical phase of the disease.

The diagnostic and prognostic value of cardiac Troponin T in bypass surgery.

BACKGROUND: The purpose of this study was to verify the utility of serum Troponin T (TnT) in the diagnosis of myocardial damage after coronary surgery performed using different methods of myocardial protection. The prognostic value of TnT peak for a poor postoperative course was also investigated. METHODS: Forty-three patients were enrolled and randomised in 2 group: Group A (n. 22) receiving warm blood cardioplegia and Group B (n. 21) receiving cold blood cardioplegia. According to TnT peak levels 3 subgroups were identified: Subgroup 1 (TnT peak < than 1 ng/ml); Subgroup 2 (TnT peak between 1 and 3 ng/ml), Subgroup 3 (TnT peak >3 ng/ml). A comparison with the standard criteria for diagnosis of myocardial ischemia was performed for each subgroup of patients. A 12 months follow-up for the patients of subgroups 1 and 2 was also completed in order to evaluate the prognostic value of a higher TnT peak. RESULTS: The overall patients subdivision in subgroup 1, 2 and 3 was 20 (46.5%), 14 (32.5%) and 9 (20.9%) respectively with no statistical difference for Group A or B. Only 7 of the patients of subgroup 3 (87%) matched the WHO diagnostic criteria for myocardial infarction. At the overall follow-up, 2 (14.28%) patients of subgroup 2, and 4 (20.0%) of subgroup 3, revealed a residual ischemia at the ECG-stress test even if none of these needed reoperation. CONCLUSIONS: Our data confirmed the high sensitivity and specificity of TnT measurement in the diagnosis of myocardial infarction and minor myocardial damage. This study, however, failed to show any statistically significant difference of the TnT peak when using different strategies of myocardial protection. The late prognostic value of the TnT increase in the early post-operative course has to be confirmed from a further study.

[Continuous blood gas monitoring in intensive care units]. / Mesure en continu des gaz du sang en unité de soins intensifs.

The measurement of O2 and CO2 transport in the arterial and venous mixed blood constitutes the intersection between haemodynamic data and expiratory-inspiratory gases. The arterial-venous difference in O2 (a-v-DO2) and the venous arterial difference in CO2 (v-a-DCO2) calculated from the data of PA, PO2, PCO2 (read by an ABL4 Radiometer) revealed a close correlation with a a-v-DO2 measured directly by means of the LEXO2 (r = 0.99) or with VCO2 measured in expired gases by a capnograph (r = 0.99). In heart surgery the "on-line" monitoring of VCO2, a-v-DO2 and related parameters (REE = Resting Energy Expenditure) in the operating room and in ICU by means of a PDMS (Patients Data Management System) provides very useful information which, when integrated with haemodynamic parameters, allows a better understanding and better care of critical patients.

[Ultrastructural changes in the saphenous vein removed during aorto-coronary bypass]. / Modifications ultrastructurales de la veine saphène prélevée en cours d'intervention de pontage aorto-coronarien.

In order to observe ultrastructural changes of the saphenous vein before implantation during coronary artery by-pass surgery, 58 fragments from a series of 29 consecutive patients, were studied by means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Two fragments were taken: the first just before the distal anastomosis; the second just before the last anastomosis on the aorta. The vein graft was kept in a finger solution of 10% nitroglycerin. Forced dilatation was avoided. The EM showed areas of early loss of the endothelial layer, not time-related, deposits of fibrin and blood corpuscular elements with muscular contraction in 75% of the examined grafts. From our experience and according to the literature, loss of the endothelial layer, spasm and early platelet and fibrin aggregation, are constant features of the explanted saphenous vein. In clinical practice, we emphasize, in addition to the "no touch technique", the early use of antiplatelet drugs during coronary artery by-pass coronary surgery.

[Anesthesia problems in thoracic and lung surgery; the use of althesin as an alternative solution]. / Problemi di anestesia in chirurgia toracopolmonare; l'impiego dell'althesin come soluzione alternativa.

Cardiocirculatory stability and arterial blood oxygenation represent the major problems in chest and lung surgery. The need to cut ventilation off from one of the lungs, or from a segment of a lung, may lead to dangerous haemodynamic and respiratory changes. The use of neuroleptoanalgesia guarantees marked cardiocirculatory stability but problems arise out of the need to administer high percentage nitrogen protoxide with consequent hypoxaemia. The use of Althesin surmounted this inconvenience and made it possible to keep basic haemodynamic parameters (heart stroke volume, peripheral resistances, lung resistances) and respiratory parameters (partial pressure in O2 and CO2 in the arterial and venous blood) stable.

Inhibition by methylprednisolone of leukocyte-induced pulmonary damage.

BACKGROUND AND METHODS: The purpose of this study was twofold: the development of a chronic model of leukocyte-mediated pulmonary injury and the evaluation of the protective effects of methylprednisolone. Rabbits were inoculated ip with zymosan. Blood gases and circulating leukocytes were evaluated. Survivors were killed on day 10 for microscopic studies and for the evaluation of lung lipid peroxidation through the by-product malondialdehyde. RESULTS: Intraperitoneal zymosan resulted in a marked decrease of Pao2 and circulating leukocytes, and increased cellularity of alveolar septa, interstitial edema, and increased lung malondialdehyde. Pulmonary damage was partially prevented when methylprednisolone was administered before zymosan inoculation, but not when methylprednisolone was given 24 hr later. CONCLUSIONS: The authors conclude that a local nonseptic inflammatory stimulus may provoke remote changes to the lungs and that methylprednisolone may counteract the process only if it is administered before or very early after the onset of inflammation.

Hypermetabolic response after hypothermic cardiopulmonary bypass.

Sixteen patients undergoing hypothermic cardiopulmonary bypass for open heart surgery were studied prospectively. Oxygen consumption and CO2 production showed a marked increase during the first 6 h postoperatively. Consequently, the measured resting energy expenditure was markedly elevated compared to the predicted energy expenditure. This hypermetabolic response occurred simultaneously with maximum spontaneous rewarming after the end of surgical procedures. Ventricular function was low throughout the postoperative period, and no cardiac response to increased energy requirements was recorded. On the contrary, marked increases in arteriovenous oxygen and CO2 difference were observed during the period of highest resting energy expenditure. We conclude that the first hours after hypothermic cardiopulmonary bypass represent the period of highest risk for decompensation. The continuous monitoring of CO2 production is suggested as a useful clinical method to detect postoperative changes in metabolic rate.

[Correlations between membrane and bubble oxygenators in patients treated with or without methylprednisolone. Haemodynamic and metabolic parameters (author's transl)]. / Correlazioni tra ossigenatori a membrana e ossigenatori a bolle in pazienti trattati e non con metilprednisolone. Parametri emodinamici e metabolici.

We studied 64 patients who underwent cardiac surgery. Hemodynamic and metabolic variables-cardiac index (CI), total peripheral resistances (TSR), oxygen consumption and (VO2), urinary output, alveolar-arterial oxygen difference (delta A-a O2) - were related with oxygenator (bubble or membrane oxygenator) and with treatment (with or without methylprednisolone). 31 patients were perfused with membrane oxygenator (MO), 33 with bubble oxygenator (BO), 13 patients MO and 18 patients, BO were treated with methylprednisolone (mps). The analyzed variables were sampled 15 minutes after the start and one to five times during the perfusion. At first data were analyzed in terms of mean values in whole set of time intervals. Only delta A-a O2 showed statistically significant difference between the MO and the BO group (282 +/- 110 versus 361 +/- 82, p less than 0.005). Between nomps-treated and mps-treated patients statistically significant difference were found in TSR (2.134 +/- 362 versus 1.785 +/- 317, p less than 0.005) and in delta A-a O2 (293 +/- 92 versus 355 +/- 108, p less than 0.02). Secondo analysis is concerning time change of variables. The time behaviour of TSR is similar in all groups studied, but a statistically significant lower value was found in mps-treated patients in every time interval. The VO2, in the last time interval, is statistically higher in the mps-treated than in the nomps-treated patients (p less than 0.05) and furthermore, for the same temperature change, the rise of VO2 is higher in the mps-treated (p less than 0.001). The delta A-a O2 shows time increase both in the MO and in the BO group, but the MO patients start from statistically significant lower values than the BO and the behaviours remain parallel for all analyzed time. The results are interpreted and discussed in relation to hemodynamic and metabolic patterns of perfusion as good or bad tissue perfusion.

Total arterial myocardial revascularization without cardiopulmonary bypass.

The risks associated with cardiopulmonary bypass have led to an interest in coronary surgery without the use of such a bypass. Six patients of mean(s.d.) age 62.0(8.0) (range 52-71) years were selected for elective coronary surgery without cardiopulmonary bypass. In five cases a midline sternotomy and in one case a small anterolateral thoracotomy were performed; in the latter case the harvesting of the proximal end of the left internal mammary artery was video-assisted by thoracoscopy. The left internal mammary artery was used in all cases; the right internal mammary artery was used in one case, the radial artery in four, the inferior epigastric artery in two and the right gastroepiploic artery inn one. No patient died or had a stroke. There were no postoperative episodes of low cardiac output syndrome or perioperative myocardial infarction. All patients were extubated within a few hours after surgery. The mean(s.d.) intensive care unit and hospital stays were 1.3(0.5) and 5.0(0.9) days, respectively. Total arterial myocardial revascularization without cardiopulmonary bypass using composite grafts, is a new and promising technique that is feasible with low risks and good early results in selected cases.

Inhibition of CD11-CD18 complex prevents acute lung injury and reduces mortality after peritonitis in rabbits.

Acute lung injury is frequent after severe peritonitis. The aim of this study was to investigate whether inhibition of the adhesion molecule CD11-CD18 on polymorphonuclear leukocytes (PMNs) would have any beneficial effects on pulmonary function and mortality in an animal model reproducing these clinical conditions. Acute peritonitis was induced in 36 rabbits by intraperitoneal injection of zymosan (0.6 g/kg) suspended in mineral oil; 20 were pretreated with a murine-specific IgG2a anti-CD18 monoclonal antibody, 16 (controls) with nonspecific purified murine IgG (1 mg/kg). The animals were followed for 10 d, then killed for histologic examination of the lungs. Blood samples were taken on Days 0, 1, 3, 7, and 10 for red blood cell (RBC), white blood cell (WBC), and platelet counts, pH, PO(2), PCO(2), carbon dioxide content (HCO(3)(-)) measurements, and renal and liver tests. Treatment with the anti-CD18 monoclonal antibody reduced mortality by approximately 40% (p < 0.05). PO(2) was higher in these treated animals than in the control animals throughout the study (p < 0.05 on Day 1, 3, and 10). On Day 1 control animals had significant leukopenia, whereas anti-CD18-treated animals had a moderate increase of the number of circulating WBC compared with baseline values (p < 0.05 between groups). The lungs of the anti-CD18-treated animals showed minor signs of inflammation and PMN infiltration whereas controls had interstitial and intra-alveolar edema and a large number of granulocytes. Quantification of PMNs by morphometry showed that there were constantly less granulocytes in the lungs of the animals treated with the anti-CD18 antibody (p < 0.001). PMN infiltration correlated with the levels of PO(2) (p < 0.001). Lung tissue of anti-CD18-treated rabbits contained less malonyldialdehyde, a by-product of membrane lipid peroxidation by PMN oxygen radicals (950 +/- 120 versus 1,710 +/- 450 pM/mg of protein) and, conversely, more of the antioxidant alpha-tocopherol (136 +/- 22 versus 40 +/- 9 ng/mg of protein), than the control rabbits (p < 0.01). In this particular model of ARDS the monoclonal antibody against the CD11-CD18 complex had a beneficial effect, reducing PMN infiltration and oxygen radical release in the lungs, preventing alveolocapillary membrane damage, improving gas exchange and, finally, significantly reducing mortality.