[Toward others medications?].
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Biomedical subjects
Publications and source records attributed to M Senft.
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Use of modified fluid gelatins as a plasma expander is of interest in human clinical medicine due to osmotic pressure similarities with plasma proteins. However, adverse reactions such as urticaria, edema, and/or anaphylactic shock occur and can lead to diagnostic problems. In addition, mechanisms of these reactions are poorly understood. We report three cases of anaphylactic shock studied by skin tests and, for the first time, in vitro leukocyte histamine release (LHR). Intradermal skin tests were significantly positive for concentrations of 1:1000 to 1:10 of the commercial preparation used before the reaction in each patient. Thirty control subjects were negative even for the undiluted preparation. Positive LHR was obtained from patients' leukocytes washed and then incubated in Tris-albumin Ca++ Mg++ buffer with serial dilutions of fluid gelatins; controls were negative. Addition of D2O (50%) caused significant increase of LHR in patients but had no effect on controls. In conclusion, skin tests and LHR might be valuable in diagnosis of patients reactive to gelatins. Furthermore, these findings suggest release of mediators from mast cells or basophils, but discrimination between immunologic and idiosyncratic pharmacologic mechanism was not obtained.
The mechanisms of anaphylactic reactions to muscle relaxants under general anesthesia are not completely understood. Extending an earlier study, we report 41 cases of anaphylactic shock investigated by intradermal skin tests with muscle relaxants (suxamethonium, pancuronium, gallamine, nortoxiferine), in vitro leukocyte histamine release, and Prausnitz-Küstner tests. Intradermal tests were significantly positive at concentrations ranging from 10 to 10(5) times less than those in controls. Reproducibility tested for suxamethonium at a 1-year interval in five patients was good. Histamine release induced by muscle relaxants in Tris-albumin-Ca++-Mg++ buffer showed positive results in 8/25 instances and was inhibited by antigen excess in seven cases. Addition of 50% deuterium oxide (D2O) caused significant increase of histamine release in positive cases and induced release in all five negative cases studied. Muscle relaxant-induced histamine release was inhibited by in vitro anti-IgE leukocyte desensitization. The mean maximal histamine release dropped from 58.2% +/- 9.7 to 5.8% +/- 2 (p less than 0.01). Similarly, leukocyte desensitization also inhibited histamine release induced by anti-IgE but not by formyl-L-methionyl-L-leucyl-L-phenylalanine or poly-L-arginine. Prausnitz-Küstner tests were positive in five out of 21 cases studied and became negative after heat inactivation. These results confirm the usefulness of intradermal skin tests in diagnosis of patients' reaction to muscle relaxants and suggest an IgE-mediated rather than an idiosyncratic mechanism.
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Assimilation of lipid nutrients depends on the efficiency of emulsified fat hydrolysis by digestive lipases. As shown in vitro, the activity of preduodenal and pancreatic lipases is governed by the physicochemical properties of emulsions. Thus the aim of this study was to evaluate in the rat how emulsions are digested and assimilated depending on their droplet size or solute composition. Fasted rats were intragastrically tube fed emulsions with different median droplet sizes (0.6 microns, fine; 22 microns, coarse) or solute composition (0.8 microns, complex fine) containing 14C-triolein and 3H-cholesterol. Two and 5 hours after feeding, fat-droplet size was measured in gastric and duodenal contents, and lipids were radioactively quantified in different compartments. In the stomach, the droplet size of the fine emulsions significantly increased to values (13 microns to 24 microns) comparable with those of the coarse emulsion (35 microns to 36 microns). In the duodenum, the droplet sizes of the three emulsions were in the range of 14 microns to 33 microns. After 2 hours, gastric triglyceride hydrolysis was significantly higher with the fine than with the coarse emulsion and was lower with the complex fine emulsion. Gastric emptying of fat was significantly different, with the following decreasing order: coarse, fine, and complex fine emulsion. In the small intestine, the fine and coarse emulsions were processed comparably, whereas the assimilation of the fine complex emulsion was significantly delayed. Calculations indicate that ingested fatty acids were distributed in the peripheral tissues at different rates with the same decreasing order. The fate of a lipophilic nutrient, cholesterol, was also markedly altered by the type of emulsion. These data support the concept that tube-fed emulsions with different droplet sizes and solute composition are digested differently and thus are metabolized differently.