Ethics roundtable debate: Patients and surrogates want 'everything done' – what does 'everything' mean?

Highly complex and specialized care plans sometimes overwhelm the comprehension of patients and families. Many optimistic surrogates of critically ill patients err on the side of desiring that everything be done but with a nebulous idea of what 'everything' entails. Physicians must work closely to educate surrogates as to the benefits versus the risks of treatment. Our roundtable experts ponder the question of whether providers possess the authority to interpret unilaterally the nature of requests for everything.     

Postnatal maturation of mast cell subpopulations in the rat respiratory tract.

The distribution and enumeration of mast cell subpopulations within the respiratory tract of a high- and low-Ige responder rat strain was determined during postnatal development. Mast cells were identified in adjacent sections by the alcian blue (AB)/safranin (SAF) staining sequence, or using immunoperoxidase to detect the rat mast cell proteinases I (RMCPI) or II (RMCPII). At birth both mucosal mast cells (MMC) and connective tissue mast cells (CTMC) were represented in very low numbers at distinct locations throughout the respiratory tract. The total number of mast cells increased with age. MMC (AB+/RMCPII+ mast cells) were the predominant phenotype in the epithelium and lamina propria of the trachea and the major conducting airways of the lung in all age groups. In contrast, CTMC (AB+/RPMCPI+ and SAF+/RMCPI+ mast cells) predominated in the submucosa of the trachea and major conducting airways as well as in the parenchyma and visceral pleura of the peripheral lung. Both phenotypes co-exist in similar proportions in peribronchial adventitial tissue and adventitia surrounding large blood vessels in neonates as well as adults. In rats the tracheal epithelium is densely populated by MMC from around the time of weaning (3 weeks) and a small but generalized increase in the number of MMC at all sites within the respiratory tract is noted from this time. This increase in MMC frequency in tissue sections with increasing age is mirrored by the levels of circulating serum RMCPII. The number of bone marrow-derived MMC also increased with increasing age prior to weaning, with a significant drop (P less than 0.01) at 4 weeks of age before returning to the peak numbers in 3-week-old rats. The high-IgE responder Brown Norwegian (BN) rat strain constitutively produces significantly more IgE than the low-IgE responder White albino Glaxo (WAG) strain (P less than 0.001) at all ages studied. In contrast, only minor differences between the number and distribution of mast cells in the two strains were observed.     

Characterization of a P1-deficient strain of Streptococcus mutans that expresses the SpaA protein of Streptococcus sobrinus.

The Streptococcus sobrinus SpaA protein and the Streptococcus mutans P1 protein share 66% sequence homology at the amino acid level. To determine if the SpaA protein can be expressed in S. mutans and functionally replace the P1 protein, the spaA gene of S. sobrinus 6715 was isolated from plasmid pX1303 and inserted into the Escherichia coli-Streptococcus shuttle vector pVA838. The resulting plasmid pX1600 was transformed into the P1-deficient strain S. mutans 834 that has defects in saliva-mediated aggregation and in the ability to adhere to saliva-coated hydroxyapatite surfaces. Western blot (immunoblot) analysis of cellular protein fractions of S. mutans 834 (pX1600) detected in mutanolysin-solubilized cell walls a major protein of 210 kDa with an electrophoretic mobility similar to that of S. sobrinus SpaA protein and a minor 210-kDa protein and a major 64-kDa protein in the extracellular protein fraction. Analysis of virulence traits showed that expression of SpaA protein by S. mutans 834(pX1600) cells had restored the ability of the S. mutans 834 cells to aggregate in the presence of saliva or salivary agglutinin but not to adhere to saliva-coated hydroxyapatite. This cell aggregation was inhibited specifically by antisera to S. sobrinus SpaA protein. These results indicate that SpaA plays a role in the virulence of S. sobrinus by specifically interacting with fluid-phase salivary agglutinin to mediate cell aggregation.     

Cellular fatty acid composition of Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus.

Strains of Actinobacillus actinomycetemcomitans isolated from deep pockets of patients with juvenile periodontitis were analyzed for their content of cellular fatty acids. Oral Haemophilus strains, morphologically and biochemically similar to Haemophilus aphrophilus, were also examined for their content of cellular fatty acids. The extractable lipids of the actinobacilli represented approximately 10% of the cell dry weight, with the bound lipids representing 2 to 5%. The major fatty acids consisted of myristic (C14:0) and palmitic (C16:0) acids and a C16:1 acid, possibly palmitoleic acid, accounting for 21, 35, and 31% of the total extractable fatty acids, respectively. Haemophilus strains had a similar cellular fatty acid content.     

Streptococcus mutans Genes That Code for Extracellular Proteins in Escherichia coli K-12

Chromosomal DNA from Streptococcus mutans 6715 (serotype g) was cloned into Escherichia coli K-12 by using the cosmid pJC74 cloning vector and a bacteriophage λ in vitro packaging system. Rabbit antiserum against S. mutans extracellular proteins was used for immunological screening of the clone bank. Twenty-one clones produced weak to strong precipitin bands around the colonies, but only after the λ c1857 prophage was induced by being heated to lyse the E. coli cells. None of the clones expressed enzyme activity for several known S. mutans extracellular enzymes. One of these clones contained a 45-kilobase recombinant plasmid designated pYA721. An 8.5-kilobase fragment of S. mutans DNA from pYA721 was isolated and recloned into the BamHI restriction site of the plasmid vector pACYC184 to construct pYA726. pYA726 contained all, or nearly all, of the gene for a surface protein antigen (the spaA protein) of S. mutans 6715. This was deduced from immunological studies in which extracts of cells harboring pYA726 reacted with antisera against both purified 6715 spaA protein (about 210,000 daltons) and the immunologically similar antigen I/II of serotype c strains of S. mutans. In addition, the S. mutans spaA protein was found to possess at least one antigenic determinant not present on the protein specified by pYA726. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of E. coli clone extracts revealed that pYA726 produced a polypeptide with a molecular mass of about 180,000 daltons which was predominantly found in the periplasmic space of E. coli cells. Antisera to the spaA protein of S. mutans reacted with extracellular protein from representative strains of S. mutans serotypes a, c, d, e, f, and g, but not b.     

Immune complexes in early arthritis. L Detection of immune complexes before rheumatoid arthritis is definite

Fifty-three patients with early arthritis were studied longitudinally for up to 3 years. During this time, 24 developed sufficient features for definite rheumatoid arthritis (RA) to be diagnosed. The other (arthralgia patients) differed from the RA patients as, in the majority, C-reactive protein and ESR were normal and anti-nuclear antibodies or rheumatoid factors were rarely found. Moreover, in time their signs and symptoms improved or disappeared. Circulating immune complexes were detected in both groups of patients by the platelet aggregation test whereas complexes detected by abnormal Clq-binding activity were found mainly in the RA patients. Platelet-aggregating complexes were usually present in the first samples studied and disappeared in the arthralgia patients with recovery from their symptoms. In the RA patients, Clq-binding complexes appeared simultaneously or later than platelet-aggregating complexes but both tests were positive several months before RA could be diagnosed. These results suggest that immune complexes are one of the first immunological abnormalities to appear in patients with arthritis. Although the constituent antigen and antibody of complexes detected by either test are unknown, their possible nature is discussed.