Biomedical subjects
Publications and source records attributed to S T Donta.
Two Streptococcus bovis isolates obtained from patients with endocarditis were found to be tolerant to penicillin and other cell wall active agents. By time-kill analysis, penicillin and streptomycin acted synergistically against these strains. The existence of tolerant S. bovis strains should be considered when initially choosing antibiotics for the treatment of serious S. bovis infections.
Eighty-three serum specimens from 24 patients infected with Candida albicans were examined for circulating Candida protein antigens with the Candida Detection System (CAND-TEC; Ramco Laboratories, Inc., Houston, Tex.). The medical records of each patient were reviewed for clinical evidence of Candida colonization or disease, predisposing factors for infection, underlying illness, the presence of a contaminated indwelling venous catheter, intravenous amphotericin B therapy, and outcome. Forty-nine serum specimens with antigen titers of 1:2 or less were obtained either from colonized patients or at a time when disseminated disease was not yet clinically suspected. Except for five specimens from two colonized patients, one with a contaminated arterial line, the other specimens with titers of 1:8 or greater (n = 14) were obtained from patients who had been clinically diagnosed and treated for disseminated candidiasis. Serum specimens with titers of 1:4 were often from patients with deep-seated candidal infection but were not uniformly diagnostic; in this situation additional specimens should be tested for Candida antigen titers. Only 1 of 24 serum specimens from patients with no evidence of C. albicans infection had a Candida protein antigen titer of 1:8. With a 1:8 or greater titer as a criterion for dissemination, the sensitivity of the CAND-TEC system was 71%, with a specificity of 98%. If the 1:8 titer for the colonized patient with a contaminated arterial line is not considered a false-positive result, the CAND-TEC sensitivity was 83%. The latex agglutination assay appears to be a useful, rapid, and noninvasive means of laboratory diagnosis of systemic candidiasis. The recovery of C. albicans from at least three body sites may also be a useful predictor of disseminated disease.
We describe four patients with Mycobacterium marinum infections who did not respond to two- to six-week courses of therapy with tetracycline, minocycline, and doxycycline. All four patients had prompt responses to therapy with either rifampin alone (two patients) or rifampin in combination with ethambutol. Results of antimicrobial sensitivity tests may be helpful in guiding therapy. Rifampin may be the drug of choice for treatment of these infections.
Patients receiving gentamicin or tobramycin were studied to determine whether there were differences in the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) between the two groups. The average daily increases in NAG excretion were significantly higher in the group receiving gentamicin. In individual patients, the best correlation with nephrotoxicity was with high initial rates of NAG excretion. If abnormally high initial rates of increase can serve as a prognosticator of nephrotoxicity, it may be possible to alter aminoglycoside therapy and to avoid renal damage.
We have discussed the basic principles of pharmacokinetics and convective solute removal in the context of each other. Clinical observations appear to follow the theoretical expectations. For practical purposes plasma and plasma water are not different. In the calculation of drug sieving, venous samples do not contribute enough to warrant their extra costs. We recommend that drug removal in hemofiltration be expressed by the sieving coefficient, UF/A. Drug sieving data in humans undergoing CAVH are tabulated. Recommendations for supplemental dosing are discussed which are applicable to any clinical setting.
C difficile produces two toxins, each of which is cytotoxic and lethal to animals [1]. Whether one or both of the toxins is responsible for pseudomembranous colitis in humans is unknown. C difficile is rarely found in the intestinal tracts of healthy adults, and then only in relatively low numbers. The same numbers of C difficile found in adults with pseudomembranous colitis may be present in infants with no obvious adverse effects [3]. The primary cytotoxin of C difficile, toxin B, may also be found in these infants, but the presence of toxin A, which causes intestinal fluid accumulation and mucosal necrosis in hamsters, has not been demonstrated [3]. However, an ELISA developed in our laboratory has been used to detect toxin A in fecal specimens from adults with pseudomembranous colitis [1]. Using this assay, we attempted to determine whether this toxin might be found in hospitalized infants with no obvious gastrointestinal distress. Ten of the 21 infants tested had toxin A in their feces. No infant had toxin A in the absence of toxin B. This is not surprising, because both toxins are produced in about the same ratio in vitro by all strains of C difficile we have tested [1]. In general, those specimens with high titers of toxin B had correspondingly high concentrations of toxin A. The infant with the highest titers of both toxin A and B was the eight-month-old infant with a clinical diagnosis of antibiotic-associated colitis. The other nine infants with toxin A had no enteric symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
The binding of iodinated cholera and Escherichia coli (LT) enterotoxins to Y1 mouse adrenal cells was studied by using saturation analysis (Scatchard). Each toxin bound to Y1 cells with similar affinity [KA = (1.5--2.0) x 10(9)M-1], but there appeared to be twice as many receptor sites per cell for E. coli toxin (approximately 4 x 10(5). Despite the increased binding of E. coli toxin, Y1 cells respond sooner to, and to smaller concentrations of, cholera toxin. The binding of each toxin was inhibited competitively by both toxins, although twice as much E. coli toxin was required to inhibit 50% of the binding of cholera toxin as was needed for either homologous inhibition or the inhibition of E. coli toxin binding by cholera toxin. The B subunits of both toxins were equally effective in competing for the binding of both iodinated toxins. Whereas the A subunits of both toxins had little or no effect on the binding of E. coli toxin, they consistently inhibited 20--40% of the binding of cholera toxin to cells. These results suggest that there are receptor loci on cells for the A subunit and that conformational differences exist between the two toxins that might explain the greater sensitivity of Y1 cells to cholera toxin. A model is suggested in which cholera toxin exhibits a greater degree of multivalent ligand binding than does the E coli toxin, resulting in a more favorable situation for apposition of the A subunit to its receptor or for its insertion into the membrane.
Clostridium difficile toxin was detected in the feces of 10.5% of normal newborn infants and 55% of neonates in the intensive care unit. None of the normal infants and less than one-third of those in the NICU had any signs of enteric illness. Vaginal delivery and breast-feeding were associated with increased rates of toxin carriage. Although toxin was not detected during antibiotic therapy, it could be found in 85% of infants two weeks or more, and for at least an additional two months, following exposure to antibiotics.
Two immunologically distinct Clostridium difficile toxins elicited similar morphological changes on cultured cells, although there were differences in both toxin potency and cell sensitivities.
A 22-year-old woman with systemic lupus erythematosus experienced generalized pruritus, shortness of breath, pleuritic chest pain, visual blurring, severe photophobia, a stiff neck, an occipital headache, and a temperature of 39.4 degrees C within one hour after taking sulindac (Clinoril). Findings from a CSF examination disclosed a notable elevation of protein and a polymorphonuclear pleocytosis. All symptoms disappeared within 24 hours. Inhibition of prostaglandin synthesis did not seem to be the mechanism of this adverse reaction, since the patient tolerated aspirin.
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After seeding at subconfluent densities, human adrenocortical adenocarcinoma cells (SW-13) proliferate to form a typical epithelial monolayer upon the culture vessel substratum. Single cells of the confluent monolayer are spontaneously released into the medium, however, where they may remain isolated or reaggregate with other floating cells. In this study, we examined the growth patterns of these cells in culture and analyzed alterations of their most prominent intercellular contact specialization, the gap junction, as cellular relationship changed during growth and development of the cell culture. We report here details of gap junction assembly during cellular aggregation and correlate the apparent endocytosis of gap junctions with the spontaneous release of single cells from the monolayer into the medium.
A partially purified toxin of Clostridium difficile induced similar morphologic changes in three different tissue-cultured mammalian cell lines. The morphologic changes were not associated with biochemical changes indentical to those caused by the enterotoxins of Vibrio cholerae and Escherichia coli. Although the mechanisms responsible for the noncytotoxic morphologic effects remain to be delineated, the toxin appears to exert its effects by directly affecting membrane constituents.
The relationship between creatinine clearance changes during gentamicin therapy and several patient and therapeutic variables was studied in a prospective, multicenter trial. Adult patients in three hospitals who were receiving gentamicin in doses based on lean body weight and creatinine clearance were studied. Pre- and post-therapy serum creatinine measurements were obtained for 62 patients (Group 1); only 45 of the patients had both pre- and post-therapy creatinine clearance measurements (Group 2). Other data collected for correlation with creatinine clearance changes were: body temperature, age, sex, blood pressure, albumin level, previous and concomitant therapy with nephrotoxic drugs, hematocrit, peak and trough gentamicin levels, and duration of therapy. In Group 2 patients, only peak gentamicin level, concomitant therapy, sex, and previous furosemide therapy correlated significantly (p less than or equal to 0.05) with change in creatinine clearance during gentamicin therapy. The first two variables decreased creatinine clearance, the last variable increased creatinine clearance, and women tended to have more of a decrease in clearance than did men. Sex, peak gentamicin level, prior furosemide therapy and concomitant cephalothin therapy explain about 50% of the renal function changes during gentamicin therapy, and should be considered in monitoring gentamicin therapy.
A case of cephalosporin-associated colitis occurred in which a tissue-cultured morphologic-altering activity was demonstrated in the patient's feces during the active episode. Neutralization of the tissue culture activity by antiserum directed against a partially purified toxin of Clostridium difficile provided a more suggestive link between the colitis and this clostridial species.