Patients' recollections of therapeutic paralysis in the intensive care unit.

BACKGROUND: Neuromuscular blocking agents used for therapeutic purposes, such as facilitating mechanical ventilation and relieving life-threatening agitation, paralyze patients but leave them fully conscious. Aggressive sedation or analgesia is necessary to reduce awareness, relieve fear, produce comfort, decrease anxiety, induce unconsciousness, and minimize possible complications such as posttraumatic stress syndrome. Little information is available on the extent to which patients experience awareness during therapeutic paralysis. OBJECTIVES: To determine and describe the remembered experiences of critical care patients who were given neuromuscular blocking agents and sedatives and/or analgesics to facilitate mechanical ventilation, improve hemodynamic stability, and improve oxygenation. METHODS: A phenomenological approach with in-depth interviews with 11 patients was used. Data were analyzed by using the constant comparative approach. RESULTS: A total of 4 themes and 3 subthemes were identified. The first theme was back and forth between reality and the unreal, between life and death; the subtheme was having weird dreams. The second theme was loss of control; the 2 subthemes were (1) fighting or being tied down and (2) being scared. The third theme was almost dying, and the fourth theme was feeling cared for. CONCLUSIONS: Patients can remember having both negative and positive experiences during neuromuscular blockade. Steps to improve the experiences of patients receiving neuromuscular blockers include improving assessment parameters, developing and using sedation/analgesia guidelines, and investing in quality improvement programs to provide assessment of awareness during therapeutic paralysis and follow-up and referral as necessary. Ways to decrease the use of neuromuscular blockers would also be useful.     

ENDOTHELIN RECEPTORS IN RAT ADRENAL GLAND VISUALIZED BY QUANTITATIVE AUTORADIOGRAPHY

1. The radioligand [125I]-endothelin was used to map receptors for endothelin in rat adrenal gland using in vitro autoradiography and computerized densitometry. 2. In the adrenal, a high density of binding was found in the adrenal medulla (binding affinity constant 0.18 +/- 0.11 X 10(9)M-1) and zona glomerulosa (binding affinity constant 0.18 +/- 0.07 X 10(9)M-1). Binding was low to undetectable in the zona fasciculata and zona reticularis. Unrelated peptides did not displace endothelin. 3. These results provide evidence of endothelin receptor distribution in adrenal gland and suggest that endothelin might exert multiple actions in the adrenal gland on catecholamine and aldosterone biosynthesis and secretion.     

In vivo and in vitro studies of the site of inhibitory action of omeprazole on adrenocortical steroidogenesis

Summary The site of omeprazole inhibition of adrenal steroidogenesis has been sought in vivo by analyzing the patterns of urinary steroid metabolite excretion after 6 days of treatment with placebo/omeprazole.Excretion rates of androsterone, aetiocholanolone, dehydroepiandrosterone, 11 hydroxyandrosterone, tetrahydrocortisone, tetrahydrocortisol and cortolone were reduced, indicating a block at an early step in steroidogenesis, possibly cholesterol side-chain cleavage. In vitro studies have confirmed this finding by measuring conversion of added precursors to cortisol in isolated bovine adrenocortical cells. Cortisol synthesis from added 20 hydroxycholesterol was inhibited by 83% in the presence of 100 µg omeprazole/ml. Conversion from pregnenolone and progesterone and their 17 hydroxylated derivatives was inhibited by 20–40% whereas cortisol production from added 11 deoxycortisol was not affected.These data suggest that omeprazole primarily inhibits cholesterol cleavage and does not inhibit 3 hydroxysteroid dehydrogenase, 17 hydroxylase or 11 hydroxylation; 21 hydroxylase activity may be marginally attenuated.     

A cAMP-activated chloride channel in the plasma membrane of cultured human gastric cells (HGT-1)

Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl^– conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl^–149 mmol/ 1 in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (–0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl^– conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a –21 mV shift of their reversal potential when bath Cl^– was decreased from 149 mmol/l to 53 mmol/l (calculated Cl^–:cation permeability ratio 171), and (iii) were highly sensitive to the Cl^– channel blocker diphenylamine-2-carboxylic acid (DPC, 10^–3 mol/l). This cAMP-activated Cl^– channel bears many similarities to other Cl^– channels within intestinal epithalia, and may represent the apical Cl^– channel operating in HCl-secreting gastric parietal cells.     

Genetic analysis and attribution of microbial forensics evidence

Because of the availability of pathogenic microorganisms and the relatively low cost of preparing and disseminating bioweapons, there is a continuing threat of biocrime and bioterrorism. Thus, enhanced capabilities are needed that enable the full and robust forensic exploitation and interpretation of microbial evidence from acts of bioterrorism or biocrimes. To respond to the need, greater resources and efforts are being applied to the burgeoning field of microbial forensics. Microbial forensics focuses on the characterization, analysis and interpretation of evidence for attributional purposes from a bioterrorism act, biocrime, hoax or inadvertent agent release. To enhance attribution capabilities, a major component of microbial forensics is the analysis of nucleic acids to associate or eliminate putative samples. The degree that attribution can be addressed depends on the context of the case, the available knowledge of the genetics, phylogeny, and ecology of the target microorganism, and technologies applied. The types of genetic markers and features that can impact statistical inferences of microbial forensic evidence include: single nucleotide polymorphisms, repetitive sequences, insertions and deletions, mobile elements, pathogenicity islands, virulence and resistance genes, house keeping genes, structural genes, whole genome sequences, asexual and sexual reproduction, horizontal gene transfer, conjugation, transduction, lysogeny, gene conversion, recombination, gene duplication, rearrangements, and mutational hotspots. Nucleic acid based typing technologies include: PCR, real-time PCR, MLST, MLVA, whole genome sequencing, and microarrays.     

NK cells developing in vitro from fetal mouse progenitors express at least one member of the Ly49 family that is acquired in a time-dependent and stochastic manner independently of CD94 and NKG2

NK cells developing in vitro from fetal progenitors in the presence of IL-2 are phenotypically and functionally indistinguishable from mature adult NK cells, with the exception that they generally lack surface expression of any of the Ly49 molecules that have previously been examined. Using two recently developed anti-Ly49 mAb, we show here that most of these NK cells in fact express high levels of at least one previously uncharacterized member of the Ly49 family, most likely Ly49E. Detailed kinetic and clonal analysis revealed that these Ly49 molecules were acquired in a progressive and stochastic manner independently of CD94 and NKG2. CD94 and NKG2 were both expressed early in NK cell development, sometimes in the absence of NK1.1, with CD94 invariably being expressed at two different levels. IL-4 differentially inhibited the expression of CD94 and Ly49 receptors, but had little or no effect on the expression of NKRP1 molecules.