Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neurologic symptoms in human shigellosis have often been attributed to Shiga toxin, although its exact role has not been determined. By use of a [3H] thymidine-labeled HeLa cell assay, cytotoxic activity was demonstrated in stool but not cerebrospinal fluid or serum from five patients with shigellosis presenting with seizures or encephalopathy. Bacterial isolates produced 16.0-88.2 CD50 (50% cytotoxic dose) of cytotoxin/mg of protein. The toxin activity in stool and the cytotoxic activity of the isolates were not neutralized by antiserum to purified Shiga toxin. DNA hybridization studies showed that Shigella isolates from these patients lacked the structural genes for Shiga toxin. The cytotoxin produced was also distinct from Shiga-like toxins I and II. Sonicates of the Shigella strains injected intraperitoneally into mice caused lethargy and lethality. The toxin activity was heat-labile and sensitive to trypsin, indicating that its active component is protein. Ultrafiltration and gel filtration chromatography showed a molecular mass of 100-125 kDa. Thus Shiga toxin production is not essential for the development of neurologic manifestations of shigellosis; other toxic products may play a role.
 ...
PMID:The association of Shiga toxin and other cytotoxins with the neurologic manifestations of shigellosis. 232 46

The prevalence, presentation, and outcome of bacteremia due to Shigella and other gram-negative bacteria were determined by review of records of 2,018 inpatients with shigellosis who had their blood cultured in a Bangladeshi hospital in 1976-1983. Shigella bacteremia occurred in 82 (4.1%) patients; other bacteremia occurred in 102 (5.1%) patients. Patients with shigella sepsis more frequently (P less than .02) manifested severe dehydration, abdominal tenderness or ileus, agitation or lethargy, and leukocytosis than did nonbacteremic controls; they developed more frequently (P less than .05) renal failure (26%), leukemoid reaction (22%), thrombocytopenia (20%), and hemolytic-uremic syndrome (6%). The prevalence of all bacteremia was highest in the first year of life. Protein-energy malnutrition was a strong risk factor for shigella sepsis (P less than .01). The fatality rate in shigella bacteremia (21%) was higher (P less than .005) than in nonbacteremic shigellosis (10%) but lower (P less than .001) than in other bacteremia (51%). At highest risk of death from shigella bacteremia (P less than .01) were patients less than one year old, non-breast-fed, malnourished, and afebrile.
 ...
PMID:Shigella septicemia: prevalence, presentation, risk factors, and outcome. 404 31

A nonsurgical rabbit model of enteric Shigella infection was developed for studying the pathogenesis and immunology of shigellosis and for evaluating Shigella vaccine candidates. In this model, rabbits are made susceptible to Shigella infection by a pre-inoculation conditioning procedure consisting of a 36-h nonfeeding period, with 250 mg of tetracycline administered in 250 ml of drinking water, 75 mg of cimetidine given intravenously, and two 15-ml doses of 5% sodium bicarbonate given orally immediately before orogastric administration of the bacterial inoculum. Lastly 2 ml of tincture of opium is administered intraperitoneally. With a virulent strain, Shigella flexneri 2a, the clinical and pathologic characteristics of shigellosis in this rabbit model were studied. Twenty hours after oral inoculation of 10(10) bacteria, all six experimental rabbits developed diarrhea and were lethargic or moribund, whereas the four control rabbits inoculated with sterile broth remained healthy. Histologic examination revealed severe, diffuse, necrotizing ileitis with hemorrhage in experimental rabbits, whereas no lesions were found in the controls. Although the major site of necrosis in this rabbit model was the ileum, as opposed to the colon in humans and nonhuman primates, the histologic morphology of the lesion was the same in the various hosts. Because it is relatively inexpensive and convenient, this model should facilitate study of the pathophysiology and immunology of shigellosis, thereby speeding development of oral vaccines, which can be tested in this animal model.
 ...
PMID:Pathologic study of a rabbit model for shigellosis. 869 22

A juvenile western lowland gorilla (Gorilla gorilla gorilla) experienced recurrent fever, lethargy, diarrhea, and/or arthritis starting at age 6 mo. During an episode at age 15 mo, Shigella sp. was isolated from diarrheic feces. At age 41 mo, reactive arthritis was diagnosed. In addition, the gorilla's growth was retarded. All arthritic attacks were managed symptomatically prior to age 4 yr, at which time a severe episode precipitated the implementation of therapy with sulfasalazine, an arthritis suppressive medication. Examination 27 mo later revealed cessation of progressive joint pathology although the animal exhibited decreased range of motion in most joints. The gorilla has been on sulfasalazine therapy for 4 yr without lameness. Growth has resumed, and there has been no radiographic evidence of progressive joint degeneration. Immunogenetic analysis of whole blood obtained at age 68 mo identified the gorilla major histocompatibility class I allele, Gogo-B*0101, which has limited nucleotide sequence similarity to HLA-B27, an allele associated with postinfection reactive arthritis in humans. Sulfasalazine therapy effectively managed reactive arthritis in this gorilla and should be considered for similarly frequently affected animals. Juvenile gorillas, in populations with a history of clinical shigellosis and/or postdiarrhea arthritis, may benefit from prophylactic sulfasalazine therapy after episodes of bacterial enterocolitis. Sulfasalazine therapy should be considered in all gorillas, juvenile and adult, experiencing confirmed Shigella sp.-associated enterocolitis.
 ...
PMID:Management of reactive arthritis in a juvenile gorilla (Gorilla gorilla gorilla) with long-term sulfasalazine therapy. 1142 3

The importance of an acute encephalopathy associated with nontyphoidal salmonellosis has recently been recognized, but the disease entity has been poorly established. In this study, we describe two encephalopathic patients associated with nontyphoidal salmonellosis. The patients exhibited a rapid evolution of coma after the onset of lethargy or seizure. Fever and diarrhea due to salmonellosis preceded these events. Secondary factors inducing encephalopathies, such as severe dehydration, sepsis, meningitis, electrolyte or metabolic disturbances, acute renal failure, and multiple organ failure, were excluded in the differential diagnosis at the onset of encephalopathic features. These clinical findings and rapid development of encephalopathic features from localized intestinal infection without any significant abnormalities in a variety of blood tests may suggest a toxic etiology. However, endotoxin was not found in serum from both patients. From these results, we conclude that nontyphoidal salmonellosis can cause a toxic encephalopathy syndrome, like shigellosis or verocytotoxin-producing Escherichia coli infection.
 ...
PMID:Acute encephalopathy associated with nontyphoidal salmonellosis. 1145 56