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Biomedical subjects

R Fekety

Publications and source records attributed to R Fekety.

At least 73 records · Page 4Linked to original sources
PubMed1980

Mucosal damage mediated by clostridial toxin in experimental clindamycin-associated colitis.

A toxin produced by Clostridium difficile has been implicated in the pathogenesis of antibiotic-associated colitis in humans and experimental animals. This study was undertaken in order to define the sequential evolution of caecal mucosal lesions in the hamster and to relate those lesions directly to the clostridial toxin. Sterile filtrates from a culture of C. difficile and from caecal contents of clindamycin-treated hamsters were studied with respect to their effects on the caecal mucosa and on cultured cell monolayers. The toxic filtrates both produced cellular swelling in vitro, and appeared to have a similar cytotoxic effect on caecal epithelial cells in vivo. Cellular damage was followed by extensive epithelial desquamation and the evolution of an acute pseudomembranous typhlitis. The pathogenetic sequence produced by the filtrates was identical with that previously described after direct clindamycin treatment. These findings demonstrate that intraluminal clostridial toxin can mediate development of the characteristic antibiotic-associated mucosal lesions.

Animals↗
PubMed1980

Suppression of immune response in mice by navy bean lectin.

A cluster of cases of Hodgkin's disease was observed in a small town which contained a large navy bean elevator. In previous investigations a lectin was isolated from the navy beans and lymphocytes from town residents were shown to be sensitized to this lectin. Mice were exposed to 15 weekly injections of navy bean lectin. Splenic lymphocytes from injected mice incorporated greater amounts of thymidine than did controls when incubated with the lectin. Cell-mediated immunity as measured by a Concanavalin A dose-response curve was significantly suppressed (p < 0.01) in the injected mice. Long term studies are needed to see if the decreased Concanavalin A response in the mice chronically stimulated with navy bean lectin will predispose to lymphoreticular malignancies.

Animals↗
PubMed1979

Clindamycin-induced colitis.

The hamster model of enterocolitis after the administration of clindamycin was used to study various drugs used in treatment of the disease in humans. Current evidence strongly suggests toxigenic, clindamycin-resistant Clostridium difficile is a cause of the disease in hamster and man. This organism is susceptible to vancomycin and metronidazole, and the disease could be prevented in the hamster so long as the antibiotics were given orally. A fatal colitis almost invariably ensued once they were discontinued. Administration of cholestyramine significantly prolonged survival of hamsters, but did not pervent death or colitis. Corticosteroids or atropine-diphenoxylate (Lomotil) did not alter the disease. The hamster model may be useful in studying other kinds of treatment of this disease.

Animals↗
PubMed1979

Cell-mediated immune responses in sporotrichosis.

Cell-mediated immunity (CMI) was evaluated in five patients with cutaneous sporotrichosis and six patients with systemic sporotrichosis. Whereas patients with cutaneous disease showed normal CMI, the patients with systemic disease had significant abnormalities in CMI. Most patients exhibited responses to a sporothrix antigen, measured either in conventional assays of lymphocyte transformation or in preincubation assays. Two patients with protracted illnesses and continued abnormalities in CMI were treated with transfer factor and showed improvement in parameters of CMI and control of their disease.

Adolescent↗
PubMed1979

Etiology of tetracycline-associated pseudomembranous colitis in hamsters.

Tetracyclines were implicated in the 1950s in induction of protracted diarrhea and pseudomembranous colitis. Because the pathogenetic mechanism of these illnesses has been questioned recently, we studied tetracycline in hamster models of antibiotic-associated colitis. Orogastric administration of tetracycline caused diarrhea and death, with evidence of hemorrhagic typhlitis. Filtrates of cecal contents were toxic when inoculated into normal hamsters and cell culture monolayers, and toxicity was neutralized with Clostridium sordellii antitoxin. Tetracycline-resistant C. difficile was cultured from stools of these hamsters, but Staphylococcus aureus was not isolated. The value of tetracycline for treatment or prevention of clindamycin-induced colitis in hamsters was also studied, and it was found that daily orogastric administration of tetracycline was poorly protective against clindamycin-induced colitis.

Animals↗
PubMed1979

Cerebrospinal fluid lymphocyte transformations in meningitis.

Cerebrospinal fluid lymphocytes from 13 patients with nonsuppurative meningitis were cultured with antigens derived from Mycobacterium tuberculosis, Sporotrichum schenckii, and herpes simplex. When CSF lymphocytes from five patients with infections associated with these organisms were incubated with "correct" antigen there was increased incorporation of thymidine. The levels were higher than those seen when the cells were incubated with different antigens or when CSF lymphocytes from patients with other causes for their meningitis were cultured with these antigens. A compartmentalization of antigen-specific cells was suggested as CSF lymphocytes had greater stimulation than did peripheral blood lymphocytes from the same patient when incubated with the correct antigen. Transformational assays of CSF lymphocytes may provide a valuable diagnostic aid in certain cases of chronic meningitis.

Adolescent↗
PubMed1979

Abnormal lymphocyte responses in residents of a town with a cluster of Hodgkin's disease.

A time-space aggregate of Hodgkin's disease was observed in a small town. A large elevator for the storage of navy beans was located in the residential area of the town. Lymphocytes of town residents compared to those of non-residents showed increased levels of transformations when challenged with extracts of navy beans. A phytohaemagglutinin from navy beans with the ability to stimulate lymphocytes was isolated and characterized. A hypothesis concerning a connection between this cluster of Hodgkin's disease and the abnormal lymphocyte responses to navy-bean phytohaemagglutinin is discussed.

Adolescent↗
PubMed1979

Prevention of clindamycin-induced colitis in hamsters by Clostridium sordellii antitoxin.

Toxins produced by Clostridium difficile have been implicated in the etiology of antibiotic-induced colitis. Clostridium difficile antitoxin is not available, but recent studies have shown that toxins present in the feces of patients with this disease are neutralized by Clostridium sordellii antitoxin. We found that C. sordellii antitoxin neutralized toxins produced in broth cultures of either C. sordellii or C. difficile and that passive immunization with C. sordellii antitoxin before challenge with clindamycin prevented colitis in hamsters. Significantly fewer antitoxin-treated animals than unimmunized controls developed diarrhea and died with hemorrhagic colitis. Administration of 300 U of antitoxin parenterally either on the day of challenge with clindamycin or 24 hr later provided significant protection (25% mortality vs. 100% mortality in controls, P less than 0.01). None of eight animals given antitoxin (300 U) both on the day of challenge and 24 hr later died. Filtrates prepared from cecal contents of dead or killed hamsters were tested for toxicity by intraperitoneal injection into hamsters and by addition to monolayers of monkey kidney cells. Fecal filtrates from antitoxin-protected animals were not toxic in these assays, but filtrates from control animals were uniformly toxic. Passive immunization against clostridial toxins was protective against clindamycin-associated colitis in this model. This finding further substantiates the importance of these toxins in the pathogenesis of antibiotic-induced colitis.

Animals↗
PubMed1978

Clindamycin-induced enterocolitis in hamsters.

A lethal enterocolitis was induced in hamsters by oral or parenteral administration of clindamycin in amounts comparable to those used in treatment of humans. The intestinal lesions were characterized histologically as an acute inflammatory reaction with pseudomembrane formation and resembled the lesions seen in humans with antibiotic-induced colitis. Results of quantitative stool cultures showed the numbers of Peptostreptococcus and Corynebacterium decreased in animals with colitis after challenge with 100 mg of clindamycin/kg, while numbers of Escherichia coli, Streptococcus faecalis, and clindamycin-resistant Clostridium sordellii and Clostridium difficile increased. Bacteria were not seen within the intestinal lesions. Viruses were not isolated from hamsters with colitis. Although the pathogenesis of this syndrome is not completely established, the evidence is consistent with the hypothesis that the disease is caused by clostridial toxins and that the production of these toxins by organisms within the intestines is enhanced by the effects of clindamycin upon the bowel flora.

Administration, Oral↗
PubMed1978

Cell-mediated immunity in diabetes mellitus.

Cell-mediated immunity was evaluated in patients with diabetes mellitus by delayed hypersensitivity skin tests and in vitro lymphocyte transformations. Only 44% of diabetic patients had skin test reactivity to Candida antigen, compared with 88% of normal controls (P < 0.001). Insulin-dependent diabetic (IDD) patients had abnormally low lymphocyte transformation responses to phytohemagglutinin, concanavalin A, and streptokinase-streptodornase (P < 0.05). This defect was not corrected by culturing the cells in nondiabetic plasma. IDD patients with persistent hyperglycemia (fasting serum glucose level, >200 mg/dl) had lower levels of transformation than did IDD patients with fasting serum glucose levels less than 150 mg/dl. Lymphocytes from two IDD patients with poor lymphocyte transformation responses had marked improvement in response to phytohemagglutinin when the lymphocytes were cultured after a preincubation period designed to deplete cultures of suppressor activity. Seven IDD patients were studied serially over 12 months. Lymphocyte transformation responses in four of these patients improved coincidentally with a change in the level of fasting hyperglycemia from >200 to <150 mg/dl. The other three IDD patients with consistent fasting serum glucose levels of >200 mg/dl had poor lymphocyte transformation responses. Diabetic patients have demonstrable defects in lymphocyte function which improved in a small number of patients with reduction in the level of fasting hyperglycemia.

Adolescent↗
PubMed1978

Gastrointestinal and systemic toxicity of fecal extracts from hamsters with clindamycin-induced colitis.

The production of toxic substances by intestinal bacteria is one pathogenic mechanism proposed for antibiotic-associated colitis. We demonstrated the presence of a toxic substance(s) in the feces of hamsters developing clindamycin-induced enterocolitis. Suspensions derived from cecal contents of clindamycin-treated animals induced a hemorrhagic ileocecitis and death within 2 to 4 days after being given orogastrically to hamsters. Intraperitoneal injection of sterile filtrates of these suspensions produced an exudative peritonitis, intraabdominal hemorrhages, and death of 80 to 100% of hamsters within 1 day. These effects were not seen with intraperitoneal injection of clindamycin or endotoxin, only small amounts of which were present in the filtrate. Incubation of the filtrate in vitro with polyvalent clostridial antitoxin neuralized its toxicity. In vitro incubation of the filtrate with normal equine serum did not reduce its in vivo toxicity. The toxic substance(s) contained in the filtrate was heat-labile and produced morphological changes in Y-1 adrenal cell cultures characteristic of heat-labile enterotoxins. Cecal filtrates obtained from saline-treated animals produced none of these effects. These preliminary studies suggest that enterotoxin-like substances, possibly produced by clostridia, may play an important role in the pathogenesis of clindamycin-induced colitis in the hamster.

Animals↗
PubMed1975

Quantitative nitro blue tetrazolium test in febrile patients. Correlation with diagnosis and bacterial activity of leukocytes.

The quantitative nitro blue tetrazolium (NBT) test did not show increased NBT reduction in bacterial infections as frequently as has been reported with the qualitative NBT test in untreated infections. Lower than normal values were seen in septic shock and bacterial endocarditis, and normal results were seen in most other bacterial infections. Increased NBT reduction was seen with reticulum cell sarcoma, Hodgkin disease, postoperative wound infections, and upper respiratory tract infections. Thus, the quantitative NBT was of little use in diagnosis of acute infections. The correlation between quantitative tests and tests of bactericidal capacity of leukocytes was poor. These data suggest that NBT reduction and bactericidal activity are dissociative events within phagocytes. Patients with low NBT results usually had bactericidal activity within normal limits.

Adult↗
PubMedDate not supplied

Antibiotic-associated colitis: effects of antibiotics on Clostridium difficile and the disease in hamsters.

Fifteen isolates of Clostridium difficile from hamsters and human patients were inhibited or killed by low concentrations of metronidazole, vancomycin, penicillin, and ampicillin; the isolates were often reesistant to tetracycline, cephalosporins, trimethoprim-sulfamethoxazole, clindamycin, erythromycin, and aminoglycosides. Antibiotics to which C. difficile was susceptible were able to prevent or postpone the colitis caused by clindamycin in hamsters. Colitis could be produced by treatment of hamsters with any one of these antibiotics. Production of colitis not only involved selection of resistant variants, but in some instances seemed to result from the acquisition of organisms after treatment, their persistence despite treatment, or from subinhibitory cecal concentrations of antibiotic (explainable by either pharmacologic factors or enzymatic inactivation). As in humans, no organisms other than C. difficile have been implicated conclusively as etiologic agents of colitis in hamsters. Our results suggest it may be wise to use isolation precautions for patients with colitis caused by C. difficile.

Animals↗
PubMedDate not supplied

Recent advances in management of bacterial diarrhea.

The number of recognized infectious causes of diarrhea potentially treatable with specific antibiotics has markedly increased within the past ten years. Laboratories are developing and expanding their abilities to deal with these new pathogens. Neither prophylaxis nor specific treatment of diarrhea in travelers is simple, practical, and safe. Although enterotoxigenic Escherichia coli is the most important cause of diarrhea in U.S. travelers to tropical areas, Campylobacter jejuni causes acute diarrhea in persons in the United States about as often as do Salmonella and Shigella. Vibrio parahemolyticus is an important cause of outbreaks of gastroenteritis following ingestion of improperly cooked shellfish; Bacillus cereus is important in outbreaks of diarrhea after ingestion of improperly cooked and stored rice in Chinese restaurants. Although Yersinia enterocolitica is probably an important cause of severe enteritis in the United States, imperfect techniques for its isolation and lack of good serologic tests have hampered recognition of its importance. Practical means for diagnosing antibiotic-associated colitis and the role of Clostridium difficile toxins in this disease are now available. Vancomycin, metronidazole, bacitracin, and cholestyramine are useful in treatment of antibiotic-associated colitis.

Adult↗
PubMedDate not supplied

Rifampin and pseudomembranous colitis.

Isolates of toxigenic Clostridium difficile, the most frequent cause of antibiotic-associated pseudomembranous colitis, are almost always highly susceptible to rifampin. However, resistant isolates exist and have been associated with colitis in both hamsters and humans given rifampin. Rifampin is rarely implicated in the disease in humans; only six cases have been documented, all in elderly patients receiving treatment for tuberculosis. At least three of these patients had liver disease, and all six had also received one or more other antimicrobial agents. The only isolate of C. difficile from these patients that was studied was resistant to rifampin. The colitis was usually mild and responsive to discontinuation of treatment with rifampin or to oral treatment with vancomycin.

Aged↗
PubMedDate not supplied

Inciting and etiologic agents of colitis.

Since 1979, 3,115 stool samples were tested for detection of Clostridium difficile and its cytotoxin; these were obtained from patients who had drug-related diarrhea. Presumed or proven colitis due to C. difficile was diagnosed in 130 patients. Drugs implicated most commonly as causing or associated with the onset of enterocolitis due to C. difficile were ampicillin (38 episodes), cephalosporins (71), clindamycin (36), and the aminoglycosides (45). The hamster model of colitis was employed to explore the role of other inducing agents. Altering the usual diet of hamsters to one with a higher protein content decreased the time to death due to C. difficile cecitis following the administration of cefazolin (10 mg). Several cathartics also were studied for their effect on the lethality of antibiotic-induced cecitis. Daily administrations of castor oil (0.5 ml per day) and vegetable oil (1.0 ml per day) improved survival against lethal doses of clindamycin. Milk of magnesia or mineral oil provided no protection. Four patients with C. difficile colitis induced by therapy with cytotoxic drugs also were identified. Methotrexate induced cecitis when administered orally and daily to hamsters, and C. difficile and its cytotoxin were identified in the hamsters' stools. Death due to methotrexate-induced cecitis was prevented by daily administration of folinic acid or vancomycin. These data demonstrate that a variety of antibiotics, antineoplastic agents, cathartics, and diet changes can induce C. difficile colitis in humans and hamsters.

Animals↗