Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients.

Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases.

Quantitative studies of cutaneous hypersensitivity: the prevalence of epicutaneous flare reactions to allergenic pollen extracts.

The flare reactions produced by epicutaneous tests with 68 undiluted allergenic pollen extracts were measured in 550 allergic patients. Skin test reactions greater than or equal to 2, greater than or equal to 5, greater than or equal to 10, greater than or equal to 20, and greater than or equal to 30 mm in diameter, respectively, were detected in approximately 67%, 22%, 10%, 3%, and 1% of the 34,700 skin tests. With the Kolmogorov-Smirnov difference test, the cumulative frequency of reaction diameters and loge-transformed diameters of all reactions and reactions to individual allergenic extracts differed significantly (p less than or equal to 0.01) from a normal distribution. The ability to identify specific differences between reactions to closely related pollen extracts was evaluated. Specific reactions could be reliably identified with greater than or equal to 10 mm diameter flares. This arbitrary conservative threshold was used to estimate the relative prevalence of positive reactions to each allergenic extract. Seven allergenic extracts elicited the first quartile of all positive reactions. Thirteen, 18, and 30 allergenic extracts, respectively, were needed to elicit the second, third, and fourth quartiles of all positive reactions. Reactions to amphiphilous, as well as anemophilous, pollens were detected. Skin test reactions to grasses were more prevalent than reactions to weeds and trees. The most informative allergenic extracts for the detection of patients who exhibited a positive reaction to any extract were from red fescue-grass pollens, mesquite, short ragweed, red clover, and timothy-grass pollens.

Near-infrared monitoring of cerebral oxygen sufficiency. I. Spectra of cytochrome c oxidase.

Near-infrared (NIR) difference spectra were obtained for oxidized cytochrome c oxidase of isolated mitochondria in vitro and of cerebral tissue in situ observed through scalp and skull. The broad peaks of maximal absorption observed in both were not inconsistent with the customary assignment of an 830 nm peak. However, the ratios of the intensity of the NIR band to that of the visible peak (605 nm), which we found to be identical for in-vitro and in-situ spectra, were consistently and significantly higher than those of the various purified enzyme preparations reported in the literature. In addition the half-band widths of our in-vitro and in-situ preparations were narrower. Haemoglobin spectra in the NIR obtained in clear and in highly light-scattering media showed almost total absence of band distortion in this spectral region, suggesting that the differences observed are not due to scattering effects. Anoxia and the specific oxidase inhibitors, cyanide and carbon monoxide, caused the expected disappearance of the band in both the mitochondria in vitro and the cerebrum in situ. The 830 nm band observed in intact, well-oxygenated animal preparations was therefore identified with the NIR absorption band of oxidized cytochrome c oxidase, notwithstanding the differences with the observations on purified preparations. This points to the possibility of developing instrumentation and techniques for the non-invasive monitoring of the redox state of cytochrome c oxidase as an index to cerebral oxygen sufficiency, i.e. adequate delivery and utilization of oxygen to and by brain tissue.

Observer variability in the pulmonary examination.

Observer variability in the pulmonary examination was assessed by having four blindfolded observers (two medical students and two pulmonary physicians) twice examine 31 patients with abnormal pulmonary findings. Examiners were consistent in the repetitive detection of pulmonary abnormalities in 74-89% of the examinations; conversely, 11-26% of the time they disagreed with themselves. Although pulmonary specialists recorded fewer (55% of observations) abnormal findings than did medical students (74%), they were significantly (p = 0.008) less self-consistent than were the students. There was no clear trend in agreement between examiners (kappa = 0.20-0.49). Each examiner's findings were compared with those of physicians specially trained in pulmonary examination. Dichotomous variables (wheezes, crackles, rubs) were more reliably detected (kappa = 0.30-0.70) than graded variables (tympany, dullness, breath sound intensity), where kappa = 0.16-0.43. The authors suggest that dichotomous variables deserve greatest clinical reliance; that time in training, alone, does not improve clinical performance; and that there is a disconcertingly large amount of inter- and intraobserver disagreement in this fundamental clinical task.

Treatment of allergic rhinitis with a new selective H1 antihistamine: terfenadine.

The effectiveness of 60 mg b.i.d. of a novel antihistamine, terfenadine, was compared with an active control, 4 mg t.i.d. of chlorpheniramine, and placebo in 560 patients with seasonal allergic rhinitis. In contrast to the gradual decrease in seasonal symptoms observed over a 7 day period of study in placebo-treated patients, both antihistamines produced a prompt significant decrease in sneezing and rhinorrhea, and a gradual decrease in nasopharyngeal pruritus. Terfenadine-related sedation did not differ from that produced by the placebo and was less than the sedation produced by the active control.

Cardiovascular parameters after acute myocardial infarction and streptokinase administration in patients receiving coronary artery bypass grafts.

In 16 patients requiring coronary artery bypass grafting (10 control and 6 streptokinase patients), we compared the preoperative, operative, and postoperative cardiovascular parameters. Streptokinase patients had an acute myocardial infarction and attempted reperfusion with streptokinase before coronary artery bypass grafting. One patient failed to recannalize with streptokinase and one patient had reocclusion after withdrawal of heparin necessitating coronary artery bypass grafting. Examination of hemodynamic parameters revealed a lower preoperative mean blood pressure and an elevated pulmonary artery wedge pressure in streptokinase patients. The elevated pulmonary artery wedge pressure persisted through the postoperative period of observation. These results indicate that only minor differences exist between control and streptokinase patients. Emergency and elective coronary artery bypass grafting can be safely performed in patients treated with streptokinase for acute myocardial infarction without associated cardiogenic shock.

Interruption of the aortic arch: experience in 17 infants.

Between April, 1965, and August, 1982, 17 children ranging in age from 2 days to 4 years were identified as having interruption of the aortic arch and operated on at our institution. There were eight type A interruptions, eight type B interruptions, and one type C interruption. Associated intracardiac anomalies were present in all but 3 patients. These 3 children, who all had type A interruption, underwent repair by mobilization of the aorta and end-to-end reconstruction. The other 14 children had initial palliative operations. The 2 patients in Group 1 had type A interruption with associated ventricular septal defect (VSD), and underwent subclavian artery-aorta anastomosis. In Group 2, the palliative procedure consisted of placement of a Dacron tube graft in 1 patient with type A interruption and associated VSD, and placement of a polytetrafluoroethylene (PTFE) graft, division of the patent ductus arteriosus, and banding of the pulmonary arteries in 11 patients--2 with type A, 8 with type B, and 1 with type C interruption. Ten children (71%) survived initial palliation, 1 of the 2 in Group 1 and 9 of the 12 in Group 2. In Group 2, 5 children had interruption of the aortic arch (4, type B; 1, type C) with associated VSD; among the 4 who survived palliation, 3 subsequently have had successful closure of the VSD and 1 is awaiting closure. Among the patients who had palliative procedures, there are 6 long-term survivors (43%). In the total series, there are 9 long-term survivors (53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of combined digoxin and dopamine administration in postoperative patients with cardiac dysfunction.

In 10 patients with postoperative cardiac dysfunction which required dopamine for inotropic and hemodynamic support, we observed the cardiovascular effects of short-term digoxin administration. The average dosage of dopamine was 7.45 micrograms/kg per minute and was maintained while the patients were given 1 mg of digoxin over 8 hours. The dosage of dopamine was then tapered over the next 4 hours. We observed a significant increase in the cardiac index (4 hours) and a reduction in the heart rate (8 hours) before the dopamine dosage was reduced. After a reduction in dopamine dosage to 2.28 micrograms/kg per minute, these effects persisted. No significant changes were noted in systemic vascular resistance or pulmonary artery diastolic pressure during digoxin administration. These results indicate that the inotropic effects of dopamine and digoxin are additive when given in combination and that digoxin can be used to significantly reduce the dopamine dosage in patients with postoperative cardiac failure. Thus, the combination of an acute inotropic agent, dopamine, and a chronic inotropic agent, digoxin, appears to be clinically useful in postoperative cardiac dysfunction.

Surgical treatment of pericarditis in the dialysis patient.

Eighteen patients with pericarditis complicating chronic renal failure who were unresponsive to medical therapy underwent surgical decompression of the pericardium for either pericardial tamponade [16] or constrictive pericarditis [2]. There was one perioperative death and minimal morbidity. Preoperative pericardiocentesis in nine patients afforded only temporary relief in most of the patients and caused a life-threatening pericardial tamponade in one patient. Creation of a pericardial window through a left anterior thoracotomy was the procedure of choice in patients without signs of constrictive pericarditis or posterior loculated effusions and had excellent long-term results. We recommend early surgical treatment of uremic pericarditis in all patients with hemodynamic instability, enlarging pericardial effusion, or effusion that is unresponsive to intensive medical therapy.

The harmful effects of ventricular distention during postischemic reperfusion.

To assess the effects of left ventricular distention during the early reperfusion period following ischemic arrest, 16 canine heart preparations were subjected to 45 minutes of hypothermic (27 degree C) cardioplegic arrest and normothermic reperfusion. Isovolumic left ventricular developed pressure and rate of rise of left ventricular pressure (dp/dt) were measured with an intraventricular balloon; endocardial/epicardial flow ratios were determined with microspheres; and myocardial gas tensions were monitored with mass spectrometry. During early reperfusion, Group 1 hearts (n = 8) were not distended (end-diastolic pressure = 0). Group 2 hearts (n = 8) were subjected to an enddiastolic pressure of 20 mm Hg for the initial 15 minutes of reperfusion. Group 2 hearts demonstrated impaired subendocardial blood flow after 5 minutes of reflow (0.75 +/- 0.06 vs 0.96 +/- 0.04, endocardial/epicardial flow rates, Group 2 vs Group 1) and persistent elevation of intramyocardial carbon dioxide (CO2) tension (68 +/- 4 vs 51 +/- 4 mm Hg, Group 2 vs Group 1). In addition, postischemic ventricular function was significantly worse in Group 2 hearts (60 +/- 7 vs 79 +/- 3% of control dP/dt, Group 2 vs Group 1, and 53 +/- 6 vs 81 +/- 5% of control left ventricular developed pressure, Group 2 vs Group 1). These data demonstrate that even mild distention during early reperfusion can result in reduced subendocardial perfusion and delayed washout of tissue CO2. Although myocardial blood flow and CO2 tension subsequently returned to normal in the distended hearts, left ventricular performance remained significantly depressed. This injury can occur clinically in nonvented hearts prior to the resumption of effective ventricular contraction.

Comparison of the effects of left ventricular distention during cardioplegic-induced ischemic arrest and ventricular fibrillation.

To evaluate the role of left ventricular distention in the pathophysiology of myocardial injury during cardiac surgery, 40 isolated, perfused feline hearts were subjected to 1 hour of either hypothermic potassium arrest (groups 1, 2 and 3) or 1 hour of hypothermic ventricular fibrilation (groups 4 and 5). During this period, intracavitary left ventricular pressure was maintained at 0 mm Hg in groups 1 and 4, at 30 mm Hg in groups 2 and 5 and 45 mm Hg in group 3. After either reperfusion of defibrillation, myocardial gas tensions, left ventricular function, coronary blood flow, the ration of endocardial to epicardial blood flow, and myocardial water content were measured to evaluate the degree of myocardial injury incurred. In addition, structural changes in the myocardium were assessed using light and electron microscopy. No differences in these parameters were seen in hearts that underwent ischemic arrest, regardless of the presence or absence of significant left ventricular distention. In fibrillating hearts, however, dilatation decreased ventricular performance, impaired subendocaridal blood flow and elevated myocardial CO2 tensions. These results suggest that left ventricular distention per se is not harmful during periods of ischemia. During periods of ventricular fibrillation, howevr, distention produces impaired subendocardial blood flow, resulting increased ischemia and decreased recovery of ventricular performance.

Effect of multiple-dose potassium cardioplegia on myocardial ischemia, return of ventricular function, and ultrastructural preservation.

To evaluate the myocardial protection afforded by multiple-dose versus single-dose administration of potassium cardioplegic solution, we studied 24 isolated feline hearts before, during, and after 1 hour of ischemic arrest. Intramyocardial gas tensions, ventricular function, histologic preservation, and postischemic myocardial edema were compared in hearts maintained at 27 degrees C during the ischemic period. Equal groups of hearts received no infusion of cardioplegic solution, a single dose of potassium solution at the onset of ischemia, or multiple infusions of the cardioplegic solution throughout the arrest period. During ischemia, single-dose cardioplegic administration resulted in less accumulation of myocardial carbon dioxide (Pmco2) than did hypothermia alone, reflecting a reduction in metabolic activity during ischemia. The fact that multiple-dose cardioplegia further reduced Pmco2 accumulation suggests an intermittent washout of metabolic end products. During reperfusion, hearts protected by multidose cardioplegia demonstrated superior preservation of ventricular performance compared to hearts protected by single-dose cardioplegia or hypothermia alone. In addition, multiple infusions of the cardioplegic solution resulted in optimal structural preservation in both light and electron microscope studies.