Confronting the use of placebos for pain.
What do you do when a physician's order conflicts with your role as patient advocate? Here's how one nurse initiated a policy change that put an end to the unethical use of placebos.
Biomedical subjects
Publications and source records attributed to A E Fox.
What do you do when a physician's order conflicts with your role as patient advocate? Here's how one nurse initiated a policy change that put an end to the unethical use of placebos.
Motilin, pentagastrin and substance P (SP), injected intra-arterially into the canine gastric corpus in vivo increased the amplitude of contractions by an action dependent on activation of cholinergic nerves; i.e. atropine or tetrodotoxin (TTX) completely blocked the responses to motilin and pentagastrin and increased the ED50 of SP. TTX and atropine were not equally effective in increasing the ED50 for SP in vivo and the effect of combining them depended on the order of their addition. Both were much more effective than the SP analog D-Pro2, D-Trp7,9 SP (DSP) which appeared to be a weak antagonist of actions dependent on neural activity. In strips from the same region in vitro no receptors dependent on cholinergic nerve activation could be demonstrated for any peptide; i.e., all were atropine- and TTX-insensitive. Motilin, as expected in the absence of such receptors caused no contractile response in vitro. SP, also as predicted, caused contractions suggesting that a smooth muscle receptor, independent of nerve activation was present. However contrary to expectation pentagastrin induced an atropine and TTX-insensitive increase in the amplitude and frequency of contractions. These results show that 1) the most sensitive sites of action of a number of excitatory peptides depend on cholinergic nerve function in vivo; 2) such sites or the nerve activity on which they depend cannot be demonstrated in vitro; 3) SP has an additional site of action on smooth muscle demonstrable in vivo and in vitro, but motilin does not; 4) pentagastrin has only an action dependent on nerve function in vivo, but manifests an action independent of nerve function in vitro. We conclude that sites and mechanisms of action of peptides cannot be assumed to be identical in vivo and in vitro. Actions dependent on nerves are often lost in vitro and not all smooth muscle actions can be demonstrated in vivo.
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Oxisuran, 2-([methylsulfinyl]acetyl)pyridine, has previously been shown to selectively suppress cell-mediated immunity, as measured by prolongation of allograft survival, without inhibition of humoral immunity. In the present investigation, the influence of this compound on lymphoid cell transfer of delayed hypersensitivity was studied. In actively sensitized animals, including endotoxin-sensitized mice and rabbits, ovalbumin-, dinitrochlorobenzene-, and dinitrofluorobenzene-sensitive guinea pigs, or tuberculin-sensitive rats, daily treatment during the interval just preceding the elicitation and expression of the hypersensitivity was most inhibitory. In both endotoxin-sensitive mice and ovalbumin-sensitive guinea pigs, treatment of the sensitized cell donor just prior to lymphoid cell harvest and transfer resulted in inhibition of the expression of the hypersensitivity in untreated recipients. Approximately 10(4) fewer specifically sensitized lymphoid cells, but not fewer viable cells, were present in passively transferred cell preparations. In contrast, treatment of the lymphoid cell recipient in the same experimental model did not influence the expression of the transferred hypersensitivity. The results suggest that oxisuran may influence an as yet undefined event prior to the expression of a cell-mediated hypersensitivity response in sensitized animals.
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A Boivin preparation of Brucella abortus, unlike common enterobacterial endotoxins, failed to depress water intake or increase numbers of hemolysin-producing spleen cells in mice, or to cause delayed inflammatory reactions in rabbit skin. Reactivity to the B. abortus endotoxin was found only in animals which were previously given the endotoxin with, but not necessarily in, complete Freund's adjuvant. Previous treatment with the endotoxin in saline or with only the adjuvant was ineffective. Sensitization appeared within 10 days and waned after 5 weeks. Passive sensitization was obtained with sensitized donor spleen cells but not with serum. Serum antibody titers did not correlate with the appearance and disappearance of sensitization.
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Fox, Alfred E. (Warner-Lambert Research Institute, Morris Plains, N.J.), George L. Evans, Frank J. Turner, Benjamin S. Schwartz, and Ansel Blaustein. Stimulation of nonspecific resistance to infection by a crude cell wall preparation from Myocobacterium phlei. J. Bacteriol. 92:1-5. 1966.-Exposure of large quantities of viable Mycobacterium phlei to attrition in a colloid mill resulted in 90 to 95% disruption of the organisms. Isolation of the crude cell wall preparation was accomplished by centrifugation of the broken cells at 10,000 x g, resuspension of the sediment, and repeated centrifugation at 1,000 x g to remove intact cells. Single oral or parenteral doses of the cell wall preparation increased the resistance of mice and guinea pigs to experimental infection with Salmonella enteritidis, and of mice to Staphylococcus aureus, for prolonged periods after administration. Histological examination of the organs of mice treated orally or intraperitoneally revealed a lymphoid hyperplasia of the spleen and a Kupffer cell proliferation of the liver. The preparation was nontoxic to mice by the oral route at doses up to 5,000 mg/kg, and the intraperitoneal ld(50) was approximately 680 mg/kg.
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