Consensus guidelines on analgesia and sedation in dying intensive care unit patients

Background

Intensivists must provide enough analgesia and sedation to ensure dying patients receive good palliative care. However, if it is perceived that too much is given, they risk prosecution for committing euthanasia. The goal of this study is to develop consensus guidelines on analgesia and sedation in dying intensive care unit patients that help distinguish palliative care from euthanasia.

Methods

Using the Delphi technique, panelists rated levels of agreement with statements describing how analgesics and sedatives should be given to dying ICU patients and how palliative care should be distinguished from euthanasia. Participants were drawn from 3 panels: 1) Canadian Academic Adult Intensive Care Fellowship program directors and Intensive Care division chiefs (N = 9); 2) Deputy chief provincial coroners (N = 5); 3) Validation panel of Intensivists attending the Canadian Critical Care Trials Group meeting (N = 12).

Results

After three Delphi rounds, consensus was achieved on 16 statements encompassing the role of palliative care in the intensive care unit, the management of pain and suffering, current areas of controversy, and ways of improving palliative care in the ICU.

Conclusion

Consensus guidelines were developed to guide the administration of analgesics and sedatives to dying ICU patients and to help distinguish palliative care from euthanasia.     

Silent adenoma subtype 3 of the pituitary--immunohistochemical and ultrastructural classification: a review of 29 cases

The silent adenoma subtype 3 (SAS-3) of undetermined cellular derivation is a seemingly nonfunctioning aggressive pituitary tumor with a high recurrence rate. At the time of diagnosis SAS-3s are macro- or giant adenomas particularly aggressive in young individuals, especially women. They are usually associated with mild hyperprolactinemia and are unremarkable by histology. Immunohistochemistry, demonstrating scattered immunoreactivity mostly for GH, PRL, TSH, and alpha-subunit, is not diagnostic. Presently, only TEM permits conclusive diagnosis. Ultrastructurally, the large polar adenoma cells contain abundant RER, masses of SER, extensive multipolar Golgi apparatus, and unevenly clustered mitochondria, displaced by RER and SER, which may show close spatial relationship to RER. Cell membranes often form plexiform interdigitations. Nuclear pleomorphism and nuclear inclusions are common. The 100- to 200-nm secretory granules accumulate heavily in cell processes, which is a hallmark of glycoprotein hormone cell differentiation. The endothelial cells may contain tubuloreticular inclusions. Complete surgical removal of the large often invasive tumors is difficult necessitating postoperative treatment. SAS-3 is sensitive to conventional radiation. Some tumors express somatostatin receptors and respond well to somatostatin analogues, offering long-term control in patients with residual tumor. Possible derivation of SAS-3 from rostral thyrotrophs, a cell type presently known in rodents is contemplated.     

Expression of nonclassical MHC class Ib genes: comparison of regulatory elements

Peptide binding proteins of the major histocompatibility complex consist of the "classical" class Ia and "nonclassical" class Ib genes. The gene organization and structure/function relationship of the various exons comprising class I proteins are very similar among the class Ia and class Ib genes. Although the tissue-specific patterns of expression of these two gene families are overlapping, many class Ib genes are distinguished by relative low abundance and/or limited tissue distribution. Further, many of the class Ib genes serve specialized roles in immune responses. Given that the coding sequences of the class Ia and class Ib genes are highly homologous we sought to examine the promoter regions of the various class Ib genes by comparison to the well characterized promoter elements regulating expression of the class Ia genes. This analysis revealed a surprising complexity of promoter structures among all class I genes and few instances of conservation of class Ia promoter regulatory elements among the class Ib genes.     

Regional differences in the compaction of chromatin in human G0/G1 interphase nuclei

The large-scale structure of chromatin corresponding to G- and R-bands in human G₀/G₁ interphase nuclei was compared. Fluorescence in situ hybridization (FISH) was used to measure the interphase distance between 42 pairs of probes separated by 0.1–1.5Mbp. The probe pairs were derived from 21q22.2 and Xp21.3, G-band positive regions, and from 4p16.3, 6p21.3, and Xq28, R-band positive regions. Distributions of measured interphase distances in all regions approximated a Rayleigh distribution, suggesting that the chromatin follows a random-walk path over this range. A linear correlation of mean-square interphase distance and genomic separation, also indicative of random-walk folding, was observed in all regions. The slope of the correlation observed using probes from G-band regions was systematically lower than that from R-band regions. The difference in the slope between Xp21.3 and Xq28 was particularly striking and was observed in normal fibroblast cells, fixed alternatively with methanol and acetic acid or paraformaldehyde, and HeLa cells. These results demonstrate regional differences in large-scale chromosome structure during interphase, with the more openly configured chromatin corresponding to R-bands.This revised version was published online in November 2005 with corrections to the Cover Date.     

Staphylococcus intermedius in canine gingiva and canine-inflicted human wound infections: laboratory characterization of a newly recognized zoonotic pathogen.

Staphylococcal gingival flora was characterized in cultures from 135 dogs. Staphylococcus intermedius was isolated in 39% of the cultures, S. aureus was isolated in 10%, and both were isolated in 2.0%. S. aureus was isolated more often from dogs of working breeds with weights of greater than 40 lb (ca. 18 kg) and with outdoor habitats than was S. intermedius, which was associated with dogs of nonworking breeds with weights of less than 40 lb and indoor habitats. S. intermedius was distinguished from S. aureus by the following characteristics: coagulation of rabbit plasma at 4 h (26 versus 100%, respectively), hemolysis of sheep blood at 24 h (30 versus 79%, respectively), and mannitol fermentation at 24 h (4 versus 93%, respectively). A clear separation of the two species was apparent only with the acetoin (modified Voges-Proskauer) reaction (100% of the S. aureus isolates versus 0% of the S. intermedius isolates) and beta-galactosidase activity on the API Staph-Ident strip (0% of the S. aureus isolates and 100% of the S. intermedius isolates). Susceptibilities of S. intermedius and S. aureus were 72 and 7%, respectively, to penicillin G, and 100% of both species to oxacillin. Fourteen previously collected strains of coagulase-positive staphylococci from infected canine-inflicted human wounds were reanalyzed; 3 of 14 (21%) isolates were S. intermedius. We conclude that S. intermedius is a common canine gingival flora and is responsible for some canine-inflicted human wound infections, thus representing a newly recognized zoonotic pathogen.     

Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex

Numerous spironolactone bodies have been detected in the zona glomerulosa cells of the adrenal cortex of a 36-year-old spironolactone-treated woman whose non-tumorous right adrenal gland was removed surgically because of primary hyperaldosteronism. Electron microscopy revealed spherical laminated whorls which consisted of a central core composed of an amorphous electron-dense material surrounded by numerous smooth-walled concentric membranes. Continuous with and deriving from the endoplasmic reticulum, they were present in viable cells and were not associated with ultrastructural features indicating cellular injury. Cytoplasmic inclusions similar to spironolactone bodies can be detected in other organs after the administration of various compounds. Thus, they can be regarded as neither specific to spironolactone treatment nor exclusively inducible in the zona glomerulosa of the adrenal cortex.     

Expression of nonclassical MHC class Ib genes

Peptide binding proteins of the major histocompatibility complex consist of the “classical” class Ia and “nonclassical” class Ib genes. The gene organization and structure/function relationship of the various exons comprising class I proteins are very similar among the class Ia and class Ib genes. Although the tissue-specific patterns of expression of these two gene families are overlapping, many class Ib genes are distinguished by relative low abundance and/or limited tissue distribution. Further, many of the class Ib genes serve specialized roles in immune responses. Given that the coding sequences of the class Ia and class Ib genes are highly homologous we sought to examine the promoter regions of the various class Ib genes by comparison to the well characterized promoter elements regulating expression of the class Ia genes. This analysis revealed a surprising complexity of promoter structures among all class I genes and few instances of conservation of class Ia promoter regulatory elements among the class Ib genes.     

Inhibitory interaction in the cat's lateral geniculate nucleus

Summary Spike activities of optic tract fibers and corresponding relay cells were recorded simultaneously in layers A and A₁ of the dorsal lateral geniculate nucleus of the cat. Light stimuli of various diameters were shone into the receptive field center of these unit pairs and their input/output ratios were determined. An increase of the stimulus size leads to an impairment of the input/output ratio in on-center and off-center relay cells. This suppressive effect has approximately the same latency as the excitatory response.Intracellular recordings suggest that the inhibitory effect of the surround is due to a postsynaptic process. Inhibitory postsynaptic potentials occur during and — under certain stimulus conditions —before the excitatory response. The short latency of these IPSPs suggests that they result from the activity of adjacent units with the same RF characteristics as the recorded neuron. This inhibitory input is not restricted to the RF periphery but may also be activated by stimulation within the RF center. Most neurons are also inhibited by units with antagonistic center responses.During the period of this research Ernst Pöppel held a training grant of the Stiftung Volkswagenwerk, Az. 11 1015.