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Biomedical subjects

J Silva

Publications and source records attributed to J Silva.

At least 253 records · Page 14Linked to original sources
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

Disseminated gonococcal infections (DGI).

Neisseria gonorrhoeae infects superficial membranes of the eyes, oropharynx, genital tract, and rectum prior to dissemination. Gonococcal isolates cultured from patients with disseminated gonococcal infections (DGI) show resistance to serum bacteriolysis, are very sensitive to penicillin, and have characteristic growth requirements for certain amino acids. DGI is characterized by recurrent chills and fever, polyarthralgias and/or polyarthritis (with effusions), and skin lesions. The skin manifestations of DGI include vesicopustules, hemorrhagic bullae, and petechiae. These lesions are found over the juxta-articular areas of the hands (extensor surfaces) or the feet (dorsal aspects). Focal and disseminated gonococcal infections are now treated with several types of penicillin regimens, tetracycline, or spectinomycin.

Anti-Bacterial Agents↗
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

Demonstration of specific cell-mediated anti-tumor immunity in lung cancer to autologous tissue extracts.

Cell-mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 microliter) lymphocyte proliferation (LP) assay. Positive lymphoproleferative responses were observed with cryopreserved intact mitomycin-C-treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 microgram or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti-tumor immunity.

Adenocarcinoma↗
PubMed1978

Abnormalities of in vitro lymphocyte response to mitogens in diabetic children during acute ketoacidosis.

Cell-mediated immunity was evaluated in 11 children with diabetes mellitus; six children were evaluated during ketoacidosis and five were evaluated with ketonuria in the absence of acidosis. Five of the six ketoacidotic children had at least one positive delayed-hypersensitivity skin test. Lymphocytes from two ketoacidotic patients were unresponsive to phytohemagglutinin and pokeweed mitogen, and lymphocytes from these two patients plus a third patient were unresponsive to concanavalin A. Lymphocytes from all six patients responded to these three mitogens after one week of therapy. In the five diabetic children without ketoacidosis, lymphocyte responses were normal to all three mitogens. Similarly, the addition of glucose to normal plasma did not alter the lymphocyte transformations of three healthy nondiabetic controls. These data suggest that cell-mediated immunity may be transiently defective in children with acute diabetic ketoacidosis.

Acute Disease↗
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↗
PubMed1978

Abnormalities of lymphocyte transformations in women with condylomata acuminata.

The cellular immunity of 16 women with recalcitrant condylomata acuminata was investigated with an in vitro assay of antigen-induced lymphocyte transformations. Results were compared to those of 24 age-matched controls. Lymphocyte transformation responses (in counts per minute) for women with condylomata were much lower than controls for phytohemagglutinin-P, 32,285 and 60,015, (P less than .001); for concanavallin A, 28,664 and 58,605, (P less than .001); and for pokeweed mitogen, 34,941 and 73,394 (P less than .0001). No significant differences in lymphocyte transformations were noted between the 2 groups to Candida or streptokinase-streptodornase antigens. Immunosuppressive diseases, recurrent infections, and intraepithelial neoplasms of the genital tract were more frequent in the group of women with condylomata, and this seems to clinically substantiate the depressions noted in their in vitro cellular immunity. A refractory course of condyloma acuminatum in some women may be a reflection of an underlying state of immunosuppression.

Adolescent↗
PubMed1978

A cluster of Hodgkin's disease in a small community: evidence for environmental factors.

A cluster of Hodgkin's disease (HD) cases occurred in a small rural town of 1250 people. Ten cases of HD and three cases of non-Hodgkin's lymphoma were identified within or linked to this town since 1954. This town therefore had an average annual incidence and mortality for HD of 29.3 and 16.7 cases per 100,000 population, respectively. Most cases of HD demonstrated case-contact associations, and a distinct geographic distribution. The data suggested that there was an environmental agent responsible for the elevated rates of HD. One unique aspect of this cluster is that this town has only one industry, a large grain elevator. The cases closely surrounded this elevator. We postulate that residents of the town are subject to chronic immune stimulation from mitogenic substances in this environment. These agents may alter immunity in the residents of this community and predispose them to acquiring HD.

Adolescent↗