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Biomedical subjects

J Silva

Publications and source records attributed to J Silva.

At least 19 recordsLinked to original sources

Cohort study of Michigan residents exposed to polybrominated biphenyls: epidemiologic and immunologic findings.

Polybrominated biphenyls (PBB) were dispersed widely in Michigan by a 1973 shipping accident in which PBB was introduced into cattle feed. Human exposure resulted principally from ingestion of contaminated dairy food products. To determine whether PBB exposure has or will cause acute or chronic illness, a prospective cohort study of 4545 persons has been undertaken. Three exposure groups were sought; all persons living on PBB-quarantined farms; persons who had received food directly from such farms; workers (and their families) engaged in PBB manufacture. Enrollment rates were 95.6, 95.1 and 78.0%. Also enrolled were 725 persons with low-level PBB exposure. All were queried concerning 17 symptoms and conditions related possibly to PBB. Venous blood was drawn on 3639 and analyzed for PBB by gas chromatography. Mean serum PBB levels were 26.9 ppb in quarantined farm families, 17.1 in recipients, 43.0 ppb in workers, and 3.4 ppb in the low exposure groups. No associations were found between serum PBB levels and symptom prevalence rates. To evaluate peripheral lymphocyte function, T and B cell quantitation and in vitro responses to 3 nonspecific mitogens were studied in 34 persons with highest PBB levels (mean, 787 ppb), and in 56 with low values (mean, 2.8 ppb). No statistically significant differences in lymphocyte number or function were noted.

Adolescent

Herpetic whitlow: herpetic infections of the digits.

Ten cases of herpes simplex infections of a digit were observed during a 3 year period. The diagnosis was confirmed in seven cases by culture or tests of serum antibodies. In three cases the clinical characteristics were sufficient to suggest the diagnosis. Medical and dental personnel are particularly prone to develop this affliction; their occupations are a frequent clue to the diagnosis. Nonsurgical treatment of this self-limited entity is recommended.

Adult

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

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

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

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

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

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

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

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

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

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

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