Reducing risks in blood transfusion: process and outcome.

The last decade has seen substantial improvements in the provision of safe "infection-free' blood for patients in many countries. This has resulted from the combined effects of better donor education, selection, testing and exclusion processes. The residual risk of infection with HBsAg attributable to laboratory error is less than 0.1/ 100,000 (1/750,000). The risk for HIV remains to be quantified but may approach this figure. With such low risks it will be difficult to provide statistical evidence that further improvements in the process of selection, testing or exclusion will have an impact on reducing risk from either agent. Over the same time, less progress has been made reducing risk to the recipient attributable to problems in the clinical supply process, i.e. getting the right blood, to the right person, at the right place, at the right time. Uniform definitions of terminology defining blood donation characteristics, together with the sharing of performance data are essential if we are to make national and international comparison of the risks that patients face when they receive a transfusion. Equally, the use of agreed definitions, and the sharing of data on the clinical outcomes of transfusion can provide the key to better prescribing based on evidence of actual risks and benefits.

Xanthine oxidase promotes neutrophil sequestration but not injury in hyperoxic lungs.

Neutrophil accumulation in alveolar spaces is a conspicuous finding in hyperoxia-exposed lungs. We hypothesized that xanthine oxidase (XO)-derived oxidants contribute to retention of neutrophils in hyperoxic lungs. Rats were subjected to normobaric hyperoxia (100% O2) for 48 h, and lungs were assessed for neutrophil sequestration (morphometry and lavage cell counts) and injury (lavage albumin levels and lung weights). In rats exposed to hyperoxia, we found increased (P < 0.05) lung neutrophil retention, lavage albumin levels, and lung weights compared with normoxia-exposed control rats. Suppression of XO activity by pretreatment with allopurinol decreased (P < 0.05) lung neutrophil retention but increased (P < 0.05) lavage albumin concentrations and lung weights in hyperoxic rats. Allopurinol treatment had no effect (P > 0.05) on the numbers of macrophages or lymphocytes recoverable by lung lavage. Depletion of XO activity by an independent method, tungsten feeding, also decreased (P < 0.05) lung lavage neutrophil counts and increased (P < 0.05) lavage albumin concentrations. We conclude that XO may be involved in lung neutrophil retention but not lung injury during exposure to hyperoxia.

Lung injury after experimental smoke inhalation: particle-associated changes in alveolar macrophages.

The role of smoke particles in the pathogenesis of smoke inhalation lung injury is enigmatic. We report an experimental model that facilitates study of this issue. Mice were exposed over a 30-min period to smoke released from a flexible polyurethane foam, heated at 400 degrees C. The smoke was initially rich in spherical, isocyanate-containing particles of respirable sizes. Respirations were labored at the end of the exposure and worsened with time and were accompanied by increases in lung water. Bronchoalveolar lavage revealed a significant reduction in the total number of alveolar macrophages in the fluid recovered from the lungs as early as 2 hr after exposure. Macrophage cytoplasm contained numerous smoke particles and decreased numbers of lysosomal-like granules, and the nuclei were often pyknotic. The same recovered lavage fluid contained numerous smoke particles, free lysosomal-like granules, cytoplasmic and nuclear debris, and significant increases in the soluble activity of both the lysosomal marker enzyme and total protein. These findings indicate that there was cell breakdown, including macrophages. Free-radical isocyanates are toxic compounds, and we suggest that after being phagocytized these compounds contribute to the breakdown of macrophages. A pathogenic relationship between these macrophage changes and the acute lung injury can next be explored in this model.

Foreign-body pulmonary embolism.

The minimal incidence of pulmonary foreign-body embolism in a general pediatric pathology experience was ascertained by reviewing autopsy records, and the true incidence of pulmonary foreign-body embolism was determined by studying lung sections from 64 autopsies of patients who had undergone cardiac procedures. Seventeen cases of embolism were reported from 370 autopsies, an incidence of 4.6%. The true incidence of pulmonary foreign-body embolism was found to be 21.9% in the cardiac surgical autopsies and the minimal incidence was 5.1% in patients who had other types of surgery. No patients other than those having surgical procedures had embolism. Hair was found to be the embolic material in 35% of cases. Embolic lesions were characterized, staged, and correlated with clinical data. The pathogenesis of this condition is unclear, but it probably involves contamination of surgical materials with particulate matter.

Effects of smoke inhalation on surfactant phospholipids and phospholipase A2 activity in the mouse lung.

The effects of smoke inhalation on the pulmonary surfactant system were examined in mice exposed for 30 minutes to smoke generated from the burning of polyurethane foam. At 8 or 12 hours after exposure, surfactants were isolated separately from lung lavage (extracellular surfactant) and residual lung tissue (intracellular surfactant) for phospholipid analysis. Calcium-dependent phospholipase A2 (PLA2) was measured on a microsomal fraction prepared from the tissue homogenate. Smoke inhalation produced a twofold increase in extracellular surfactant total phospholipid. While there was no change in the total phospholipid or phosphatidylcholine (PC) content of the intracellular surfactant, smoke inhalation significantly decreased the disaturated species of PC (DSPC). The specific activity of PLA2 was reduced by more than 50% in both groups of exposed mice. Smoke inhalation appears to result in selective depletion of the DSPC of intracellular surfactant and PLA2 involved in its synthesis. This depletion may be compensated for by increased secretion or slower breakdown of the material present in the extracellular compartment.

Use of a fluid dispensing apparatus for bronchoalveolar lavage in mice.

The volume of the mouse lung is small, so bronchoalveolar lavage (BAL) in mice is generally performed with 1 ml syringes to infuse smaller volumes of fluid. Multiple infusions are required to obtain enough recovered fluid for multiple analyses. This paper introduces the use of one type of a simple fluid dispensing apparatus as an infusion device. It proved to be a faster and a less tedious method than the syringe infusion method. The results of studies in normal mice using both infusion techniques showed no differences between the two with respect to the recovery of cells and protein and to differential leukocyte counts. Thus, the results obtained with this device can be compared with those previously obtained with syringes.

Anitschkow nuclear structure: a study of pediatric hearts.

Anitschkow nuclear structures are commonly found in hearts of children who have died of various disorders. The peculiar chromatin pattern, as shown by immunohistochemical methods, occurs in striated muscle cells, histiocytes, Schwann cells, nondescript mesenchymal cells of the heart, and, rarely, cells outside of the heart. They are most abundant in the atrioventricular valves and in valve rings of premature infants. The histogenesis and significance of these unique nuclei are unknown, but their association with hypoxia and their similarity to forms seen in cell division suggest that the presence of increased numbers of Anitschkow nuclear structures may be a response to cardiac injury.

Development of a rational blood-ordering policy for obstetrics and gynaecology.

The relation between quantities of blood ordered to cover obstetrical and gynaecological diagnoses and quantities actually used was studied over a period of 3 months in one Scottish hospital. It appeared that the amount of blood ordered as 'cover' for many operative procedures and for patients under observation was, in many instances, uneconomic. On the basis of this a 'maximum surgical blood-ordering schedule' has been proposed which would reduce the amount of blood cross-matched as 'cover' by 65%. Review of the circumstances of all transfusions given over the study period suggested that adoption of the proposed schedule would not be detrimental to patient study.

Antiviral effects of aphidicolin, a new antibiotic produced by Cephalosporium aphidicola.

Aphidicolin is an antibiotic of novel structure produced by the mold Cephalosporium aphidicola. It is a potent inhibitor of cellular deoxyribonucleic acid synthesis, and it also strongly inhibits the growth of herpes simplex virus both in tissue culture and in the rabbit eye. Aphidicolin is active against iododeoxyuridine-resistant herpes virus, and does not itself readily induce the formation of drug-resistant strains of herpesvirus.