Serotonin syndrome. Presentation of 2 cases and review of the literature.

Serotonin syndrome is an underreported complication of pharmacotherapy that has been relatively ignored in the medical literature. We discuss 2 recent cases seen at our institution and 39 cases described in the English-language literature since 1995. We found that patients with serotonin syndrome most often (74.3%) presented within 24 hours of medication initiation, overdose, or change in dosage. The most common presenting symptoms and signs were confusion, agitation, diaphoresis, tachycardia, myoclonus, and hyperreflexia. The prevalences of hypertension, coma/unresponsiveness, seizures, and death were not as prominent in our study as previously reported, perhaps reflecting earlier recognition and intervention. The most common therapeutic intervention was supportive care alone (48% of patients). The use of 5-hydroxytryptamine (5-HT) antagonists such as cyproheptadine, however, has become more common and might reduce the duration of symptoms. Only 1 death occurred, and most patients (57.5%) had complete resolution of their symptoms within 24 hours of presentation. The increased use of serotonergic agents (alone and in combination) across multiple medical disciplines presents the possibility that the prevalence and clinical significance of this condition will rise in the future. Internists will need to be increasingly aware of and prepared for this pharmacologic complication. Prevention, early recognition of the clinical presentation, identification and removal of the offending agents, supportive care, and specific pharmacologic therapy are all important to the successful management of serotonin syndrome.

Volume changes during contraction of isolated frog muscle fibers.

A microscope objective and electronic imaging system were used to determine how isolated frog skeletal muscle fibers adjust their volume during an isometric tetanus. Cross-sectional area and volume of the middle third of a fiber increased rapidly with the development of active tension, which indicates that contraction produced components of force perpendicular to the long axis. The extreme ends are known to shorten whether or not the middle of a fiber is isometric or stretched. Shortening of the ends may shift water towards the middle, which could account for the volume changes we observed. The cytoskeletal matrices of muscle evidently adjust rapidly during contraction to maintain a dynamic equilibrium between the axial and radial forces that stabilize the whole cell. The Z disks have been shown to expand during active, but not passive, tension development. Z disks might be the elastic elements of the muscle cytoskeleton primarily involved in rapid balancing of the radial components of active force.

Nonuniform volume changes during muscle contraction.

We measured dynamic changes in volume during contraction of live, intact frog skeletal muscle fibers through a high-speed, intensified, digital-imaging microscope. Optical cross-sections along the axis of resting cells were scanned and compared with sections during the plateau of isometric tetanic contractions. Contraction caused an increase in volume of the central third of a cell when axial force was maximum and constant and the central segment was stationary or lengthened slightly. But changes were unequal along a cell and not predicted by a cell's resting area or shape (circularity). Rapid local adjustments in the cytoskeletal evidently keep forces in equilibrium during contraction of living skeletal muscle. These results also show that optical signals may be distorted by nonuniform volume changes during contraction.

Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts.

Because previous work has suggested that NK cells may be important in host resistance against the intracellular parasite Toxoplasma gondii we examined whether human NK cells and lymphokine-activated killer (LAK) cells have activity against trophozoites and cysts of this organism in vitro. A method to radiolabel Toxoplasma trophozoites with 51Cr was developed and direct cytotoxic activity was determined by using modifications of the standard 51Cr release assay. Viability of 51Cr-labeled trophozoites assessed by both methylene blue staining and trypan blue exclusion was greater than 90%. Significantly more 51Cr was released by anti-Toxoplasma antibody and C than by antibody in the absence of C. Incubation of trophozoites with freshly isolated human NK cells or NK cells activated with either rIL-2 or rIFN-alpha did not result in significant release of 51Cr (specific lysis was 0 to 2.3%). In contrast, the average specific lysis of radiolabeled trophozoites by LAK cells was significant (specific lysis was 7.8% +/- 1.1, p less than 0.01). In a series of separate experiments, preincubation of radiolabeled trophozoites with heat-inactivated normal or Toxoplasma antibody-positive human serum increased the cytotoxicity of LAK cells from a mean specific lysis of 15% +/- 4.5 to 39% +/- 8.5, respectively (p less than 0.05), as assessed by 51Cr release. Because previous work has shown that radioisotope release from parasites may be nonspecific, separate experiments were performed to determine the cytotoxicity of LAK cells against antibody-coated trophozoites by using ethidium bromide-acridine orange staining to assess effector cell damage. LAK cells had a mean specific lysis of 51% against antibody-coated trophozoites by ethidium bromide-acridine orange staining. Preincubation with heat-inactivated Toxoplasma-antibody positive human serum did not increase activity of rIL-2-activated NK cells against 51CR-labeled trophozoites. Neither human NK cells (freshly isolated or activated by rIL-2 or rIFN-alpha) nor LAK cells were cytotoxic for purified preparations of cysts of Toxoplasma isolated from the brains of chronically infected mice.

Somatostatin in the idiopathic inflammatory bowel diseases.

To study the effect of mucosal inflammation on tissue concentrations of somatostatin, the distribution and concentration of somatostatin in specimens of normal and abnormal (ulcerative colitis and Crohn's disease) ileum and colon were determined by a specific radioimmunoassay. Each tissue specimen obtained at surgery was separated by microdissection into the mucosa-submucosa and the muscularis externa. Immunoreactive somatostatin was acid-extracted from each layer before measurement. Gel chromatography was used to characterize immunoreactive somatostatin measured by radioimmunoassay; somatostatin-28 was the major immunoreactive species measured in human intestine. In normal colon, concentrations of somatostatin were not related to patient age. Concentrations of immunoreactive somatostatin in the mucosa-submucosa of the descending colon were significantly decreased in ulcerative colitis and in Crohn's colitis, compared with normal colon. There was no apparent relationship between concentrations of somatostatin and the duration of inflammatory bowel disease. However, somatostatin concentrations appeared to be lower in patients with severe colitis than in patients with minimal colitis. The decrease in mucosal-submucosal concentrations of somatostatin is in agreement with previous morphologic studies, which have suggested diminished populations of endocrine cells in ulcerative colitis. The possible role of somatostatin in the colon suggests that further studies of the alteration of this gut peptide may be useful in understanding a component of the pathophysiology of idiopathic inflammatory bowel disease.