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.     

MR susceptometry: an external-phantom method for measuring bulk susceptibility from field-echo phase reconstruction maps

A novel method for estimating the susceptibility of an object by using the magnetic resonance (MR) imaging field distortions in an external-reference water bath next to the object is described. The field measurement was obtained with a phase reconstruction from a gradient-echo acquisition. A field model of an arbitrary object in a static magnetic field was discretely calculated from geometry determined from the magnitude reconstruction. Least-squares estimation yields the susceptibility of the object. Required (and proven) assumptions include validity of superposition, object homogeneity, negligible higher-order field terms, field-model accuracy, geometric-model accuracy, and correlation of gradient-echo phase to field distortion. MR susceptometry estimation of phantoms yielded susceptibility estimates that correlated well with known values (r >.9975). This MR susceptometry method is a first step toward quantitation of iron levels through MR imaging phase information in patients with iron overload.     

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.     

Activity involvement, risk-taking, demographic variables, and other drug use: prediction of trying smokeless tobacco

Four activity participation variables (clubs, sports, church, and parties); two indices of "risk-taking" (preference for risk-taking, getting into trouble at school); three demographic variables (sex, ethnic group, socioeconomic status); and two drug use variables (trial of cigarettes and alcohol) were examined as correlates and prospective predictors of trial of smokeless tobacco in two cohorts of seventh graders in urban Los Angeles. The data were analyzed separately for males and females. Cross-sectional logistic regression analyses indicated that correlates of trying smokeless tobacco among the seventh-grade cohorts or among these same cohorts in the eighth grade (considering those persons who had not tried smokeless tobacco in seventh grade) generally included being white, trying cigarettes, risk-taking, and attending parties. Prospective logistic regression analyses with data from subjects who had not tried smokeless tobacco in the seventh grade indicated that predictors of subsequent trial of it generally included only being white and having tried cigarettes. Sports participation predicted onset only in one cohort of female subjects but not in males. Some activities that have been proposed as being predictive of smokeless tobacco use (e.g., sports participation) are generally irrelevant for a large sample of young adolescents in urban Los Angeles. White male cigarette smokers, regardless of the activities they have engaged in, are most likely to try smokeless tobacco.     

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.     

Alveolar macrophages. VI. Regulation of alveolar macrophage-mediated suppression of lymphocyte proliferation by a putative T cell.

Alveolar macrophages (AM) from normal rats suppressed antigen- or mitogen-stimulated blastogenic responses in cultures of splenic or lymph node lymphocytes, high levels of suppression often being observed when added AM comprised as few 0.6% of the total cells in culture. The efficiency of AM-mediated suppression of spleen cell blastogenesis declined with the age of the spleen cell donors, was severely curtailed by pretreatment of donors with low levels of cyclophosphamide, and was depleted by adult thymectomy coupled with thoracic duct drainage. The suppressive activity of AM was most obvious at high cell density, was unaffected by the presence of indomethacin in the cultures, or by prior X-irradiation of the spleen cells. Fractionation of spleen cells by velocity sedimentation yielded cell populations of greatly varying sensitivities to AM-mediated suppression, from small splenocytes (sedimentation velocity 1.1-2.8 mm/h) which were almost totally refractory to AM-suppression when assayed in isolation from the remainder of the spleen cell population, to larger cells (sedimentation velocity greater than 3.,5 mm/h) exhibiting high levels of sensitivity. Fractionation of spleen cells by glass wool adherence indicated decreased sensitivity to AM-suppression in the effluent population. Examination of the suppressive activity of individual subpopulations of AM separated by velocity sedimentation indicated that the larger macrophages were the most active in vitro. Suppressive activity of this nature was not seen with unstimulated peritoneal macrophages, but was observed when 'activated' peritoneal exudate cells were tested. These data are discussed in terms of a two-cell model for suppression of blastogenesis, the ultimate effector cell being a macrophage, the activity of which is controlled by a long-lived, recirculating lymphocyte, which we have provisionally designated as a T lymphocyte.