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Biomedical subjects

T C Sorrell

Publications and source records attributed to T C Sorrell.

At least 91 records · Page 5Linked to original sources

Disseminated candidiasis: evidence of a distinctive syndrome in heroin abusers.

Seven young men developed similar manifestations of disseminated candidiasis after a single episode of intravenous heroin abuse. Sequential development of lesions of the eye, skin, and bone or costal cartilage was noted within 10 days after injection. Skin lesions were confined to the scalp and other hair bearing areas. Candida albicans was cultured readily from affected skin and costal cartilage. Histological examination of scalp biopsy specimens showed infiltration of hair follicles with chronic inflammatory cells and C albicans. Pseudohyphas of C albicans were also identified in and around hair shafts. The skin, skeletal, and small eye lesions resolved on systemic treatment with 1 g amphotericin B plus flucytosine. Pars plana vitrectomy plus local instillation of amphotericin B cured progressive chorioretinitis. These features may represent a distinctive syndrome of disseminated candidiasis in heroin abusers. Systemic antifungal treatment is curative in most cases.

Candidiasis↗

Host defences in the upper genital tract of the female: studies in a murine system.

Mechanical and cellular factors which maintain sterility in the fallopian tube were studied in virgin, BALB/c mice. Quantitative cultures of homogenates from ovary/periovarian sac, fallopian tube and uterine horn were obtained at various times after intratubal injection of 6 X 10(7) Escherichia coli (E. coli) by micropuncture. Immediately post-injection, significantly higher bacterial counts were obtained from fallopian tube than from uterine horn, indicating a functional barrier at the uterotubal junction. Viable E. coli were usually absent from the genital tract within 7 days. Reduction in bacterial counts was significant at 24 h post-injection. Ligation of the uterine horn and/or induction of leucopenia prior to injection were associated with decreased bacterial clearance at 24 h. Histology of samples from normal, injected mice revealed marked polymorphonuclear leucocyte (PMNL) infiltration in response to E. coli, confirmed by quantitation of intralumenal PMNL. By 72 h post-injection, viable E. coli and PMNL containing phagocytosed particles were prominent in vaginal washings. No inflammatory response was elicited in leucopenic mice. We conclude that clearance of E. coli from the fallopian tube depends primarily on excretion through the lower genital tract and PMNL-associated bacterial activity.

Animals↗

In-vitro effects of vancomycin, rifampicin, and fusidic acid, alone and in combination, against methicillin-resistant Staphylococcus aureus.

Minimal inhibitory and minimal bactericidal concentrations were determined for eighteen methicillin-resistant Staphylococcus aureus isolates, the majority also resistant to gentamicin, obtained from the blood of bacteraemic patients. Fifty per cent of organisms had a greater than four-fold difference in M.I.C. and M.B.C. for vancomycin, 83% for rifampicin, and 89% for fusidic acid. In-vitro effects of two-drug combinations of vancomycin, rifampicin, and fusidic acid demonstrated neither synergy nor antagonism when measured by a checkerboard dilution technique. The relevance of these findings to choice of therapy of serious infection due to methicillin-gentamicin resistant Staph. aureus is yet to be determined.

Culture Media↗

Neurological toxicity associated with vidarabine (adenine arabinoside) therapy.

Disorientation, myoclonic jerks, generalised rigidity and tremor developed in a young woman while on treatment with vidarabine for disseminated cutaneous varicella. Residua were still present 11 months later. She had normal renal function and was being treated with relatively low dose vidarabine therapy. A possible drug interaction with allopurinol is described.

Adult↗

Susceptibility of Campylobacter jejuni to twenty-three antimicrobial agents.

Twenty-three antimicrobial agents, including 4 new broadspectrum beta-lactam antibiotics were tested against 50 clinical isolates of Campylobacter jejuni. The activity of metabolites of metronidazole and tinidazole was also tested. Minimum inhibitory concentrations (MIC) were determined by agar dilution. beta-lactamase production was detected by a chromogenic cephalosporin method. All strains were susceptible to erythromycin, clindamycin, chloramphenicol, furazolidone, aminoglycosides (including gentamicin), cefotaxime and NF-thienamycin. All isolates were resistant to penicillin, cephalothin, cefoperazone, vancomycin, rifampicin and trimethoprim; beta-lactamase was detected in 2% of isolates. Some strains were resistant and others sensitive to the other drugs tested, which included ampicillin, moxalactum tetracycline, metronidazole and tinidazole. The 'hydroxy' metabolites of metronidazole and tinidazole were more active than the parent compounds.

Anti-Bacterial Agents↗

Vancomycin therapy for methicillin-resistant Staphylococcus aureus.

Ten patients with bacteremia due to methicillin-resistant Staphylococcus aureus were treated with vancomycin. These patients were compared with matched controls, nine bacteremic patients with methicillin-sensitive S. aureus, and one patient with penicillin-sensitive S. aureus. Controls were treated with a penicillin. There were no significant differences in time to defervescence, metastatic infections, relapse, mortality, need for surgical drainage, or duration of therapy. Fifteen of 19 episodes of serious methicillin-resistant S. aureus infection responded to vancomycin. Severe toxic effects included tinnitus, neutropenia, rash, and possible nephrotoxicity. Tolerance (a minimal bactericidal concentration to minimal inhibitory concentration ratio of at least 32), but not a minimal bactericidal concentration of at least 32 mg/L, correlated with therapeutic failure (respectively, p = 0.04 and p = 0.11, Fisher's exact test). Bacteremic infections due to methicillin-resistant and methicillin-sensitive S. aureus cause similar morbidity and mortality. Vancomycin is effective but potentially toxic therapy for most serious infections due to methicillin-resistant S. aureus. In-vitro tests may not predict therapeutic efficacy.

Dose-Response Relationship, Drug↗

Antimicrobial therapy of postpartum endomyometritis. I. Comparative susceptibility of mezlocillin and other antibiotics to genital anaerobic bacteria.

The in vitro activity of mezlocillin, a new ureidopenicillin, against 377 obligate anaerobes from the female genital tract, was studied by an agar dilution technique. Mezlocillin demonstrated broad-spectrum activity against all genital obligate anaerobes, with a geometric mean minimum inhibitory concentration (MIC) of 4.2 microgram/ml, and inhibited 84% of B. fragilis and 99% of all isolates at 64 microgram of the antibiotic per milliliter. At readily attainable serum concentrations, mezlocillin inhibited significantly more isolates than cefoxitin (p less than 0.0005), ampicillin (p less than 0.0005), penicillin G (p less than 0.005), and clindamycin (p less than 0.025); its activity was comparable to that of carbenicillin and chloramphenicol. Mezlocillin was significantly more active than ampicillin (p less than 0.025), penicillin G (p less than 0.025), and clindamycin (p less than 0.05) against Bacteroides species other than B. fragilis and B. melaninogenicus.

Ampicillin↗

Antimicrobial therapy of postpartum endomyometritis. II. Prospective, randomized trial of mezlocillin versus ampicillin.

Seventy patients with postpartum endomyometritis were treated with either intravenous mezlocillin (16 gm/day) or ampicillin (8 gm/day) in a prospective, randomized, double-blind comparison. Endocervical dilatation was routinely performed. Clindamycin (2 gm/day) was added if patients failed to improve within 48 hours of beginning therapy. Pretreatment clinical and microbiologic profiles were comparable in the two groups. Bacteremia was documented in 21 patients (30%). Anaerobic cocci and Bacteroides spp. (non-B. fragilis) comprised 19 of 29 (65%) blood isolates. Thirty of 33 mezlocillin-treated patients (91%) and 30 of 37 ampicillin-treated patients (81%) responded to initial therapy (P greater than 0.4). Resolution was noted after the addition of clindamycin in all ten nonresponders; two of these patients also required surgical wound debridement. Objective parameters of clinical response were not significantly different in the two treatment groups. Side effects of mezlocillin therapy were minimal. We conclude that mezlocillin and ampicillin are equally effective and safe for therapy of postpartum endomyometritis. That mezlocillin was not superior to ampicillin, despite expanded activity against B. fragilis and members of Enterobacteriaceae, suggests that these pathogens are less important than was previously considered in postpartum endomyometritis.

Adult↗

Pneumonia with bacteraemia due to Escherichia coli.

Pneumonia due to Escherichia coli (E. coli) has a reported mortality of up to 70 per cent. Most infections are associated with underlying disease, and follow bacteraemia from a genitourinary or gastrointestinal source. This report describes two patients with bacteraemic E. coli pneumonia, presumed secondary to aspiration of E. coli from the oropharynx. Both patients presented a rapidly progressive illness with hypotension. Response of the pneumonia to early, appropriate antimicrobial therapy, was complete. Our cases are discussed with particular reference to clinical features of the infection and choice of antimicrobial therapy.

Cefoxitin↗

A rapid slid coagglutination test-an alternative to the fluorescent antibody test for the identification of Neisseria gonorrhoeae.

The Phadebact(R) Gonococcus Test, a slide coagglutination test, was compared with the Difco fluorescent antibody test for the identification of Neisseria gonorrhoeae isolated from 18- to 24-hour primary plates. A total of 316 morphologically characteristic, oxidase-positive, Gram-negative diplococci were tested. Altogether 298 isolates were identified definitively as N. gonorrhoeae by a rapid carbohydrate utilisation test; 287 of the 298 isolates of N. gonorrhoeae were identified by the coagglutination test, a sensitivity of 96%. The sensitivity of the fluorescent antibody test was 85% (254 of 298 isolates). False-positive results due to cross-reactions with non-gonococcal Neisseria were uncommon (1 of 18 non-gonococcal isolates in the coagglutination test, a specificity of 94%; 2 of 18 in the fluorescent antibody test, a specificity of 88%). None of the 14 other contaminant organisms seen frequently on primary isolation media gave positive reactions. Interpretation of the coagglutination test proved to be difficult initially. Thirty-two (10%) coagglutination tests had to be repeated; 3 of the 32 (1% of the total isolates tested) remained uninterpretable.

Agglutination Tests↗

Host defenses in acute pelvic inflammatory disease. I. Bacterial clearance in the murine uterus and oviduct.

Bacterial clearance in the uterine horn and oviduct as a host defense in acute pelvic inflammatory disease was studied in 8- to 12-week-old virgin Balb/c mice. Quantitative cultures of organ homogenates were determined at various intervals following intrauterine injection of a standard inoculum of E. coli by micropuncture technique. The effect of uterine horn ligation and of estrus cycle of inoculated mice was evaluated also. Mean bacterial counts in the uterine horn were significantly higher than in the contiguous oviduct (p less than 0.005), suggesting a barrier function of the uterotubal junction for bacterial passage into the oviduct. Our data suggest a protective role for the uterotubal junction, and demonstrate the influence of uterine obstruction and estrus cycle on bacterial clearance of the oviduct.

Animals↗

Mechanism of nonspecific macrophage-mediated cytotoxicity: evidence for lack of dependence upon oxygen.

Peritoneal macrophages elicited in C3H/HJ mice by the i.p. injection of Corynebacterium parvum were cytotoxic to allogeneic virus-transformed fibroblasts in vitro. Cytotoxicity was demonstrated in a morphologic (plaque) assay, and quantitated by measuring macrophage-mediated inhibition of incorporation of 3H-thymidine by the target cells. The cytotoxic effect was well established by 6 hr of macrophage-fibroblast interaction, and was retained in cultures from which the supernatant was removed before the addition of 3H-thymidine. Cytotoxic activity of macrophages diminished rapidly after 22 hr of cultivation in vitro. Maximal cytotoxic effect could be prolonged by addition of C. parvum, 50 microgram/ml to macrophage monolayers preincubated in vitro for 22 hr. It could neither be retained nor regenerated when C. parvum was added to monolayers greater than 22-hr old. C. parvum-activated macrophages, grown under anaerobic conditions for 8 hr, retained the ability to phagocytize heat-killed Candida albicans and to exclude trypan blue dye. There was a small but significant reduction in the ability of macrophages to inhibit 3H-thymidine incorporation by target fibroblasts under anaerobic conditions. The cytotoxic effect of activated macrophages in air was not altered by the presence of catalase and was enhanced by enzymatically active superoxide dismutase. We conclude that the processes involved in macrophage-mediated cytotoxicity against allogeneic fibroblasts in this system are largely independent of oxygen.

Anaerobiosis↗

Phenytoin sensitivity in a case of phenytoin-associated Hodgkin's disease.

The case of a patient who developed Hodgkin's disease three years after commencement of therapy with phenytoin is presented. Humoral and cellular immunological capacity were significantly depressed. Phenytoin caused a striking increase in DNA synthesis when lymphocytes were culture in the presence of this drug, in contrast to significant inhibition in the lymphocytes of control subjects. These findings are consistent with the hypothesis that both chronic antigenic stimulation and immunosuppression by phenytoin and involved in the induction of lymphoma.

Adult↗

Depression of immune competence by phenytoin and carbamazepine. Studies in vivo and in vitro.

Depression of one or more parameters of cellular and/or humoral immune responses was found in 60% of general hospital patients treated with phenytoin and 47% of patients treated with carbamazepine. Phenytoin-treated patients failed to manifest delayed hypersensitivity (DHS) reactions to common antigens, and to make antibody to Salmonella typhi and tetanus toxoid. Serum levels of IgA and IgM, DNA synthesis in circulating leucocytes, and phytohaemagglutinin (PHA) induced deoxyribonucleic acid synthesis were also low. Depression of IgA, DHS reactivity and antibody responsiveness to S. typhi were shown to develop after the commencement of phenytoin therapy in a study of eleven patients. The presence of immunological defects was independent of the dosage of drug, its serum concentration, the duration of therapy and the sex of the subject. Studies in vitro provided evidence that immunosuppression was the result of a direct effect of phenytoin on the metabolism of lymphoid cells. Carbamazepine was shown to have a similar but less potent direct effect. Pharmacological concentrations of phenytoin caused a significant depression of DNA synthesis in PHA-stimulated and non-stimulated blood cell cultures in vitro. High concentrations in addition caused depression of cell counts, lymphocyte blastogenesis, ribonucleic acid and protein synthesis. Phenytoin was not cytocidal at concentrations of up to 125 mug/ml. Depression of DNA synthesis by phenytoin was maximal when phenytoin was added within 4-8 hr of the addition of PHA. PHA-induced DNA synthesis was not significantly affected by pre-incubation with phenytoin. In vivo, the presence of immunological defects was not related to phenytoin-induced folic acid deficiency. High concentrations of carbamazepine, but not phenobarbitone or diazepam caused a significant depression of PHA-stimulated DNA synthesis in blood cell cultures. The data show that immunosuppression is a common side-effect of phenytoin therapy, and that lymphoma is rare. They suggest that in the presence of phenytoin-induced immunosuppression another factor, or factors are required to induce the formation of lymphoma.

Adolescent↗

Depression of immunological function in patients treated with phenytoin sodium (sodium diphenylhydantoin).

63 patients on long-term oral therapy with phenytoin sodium (sodium diphenylhydantoin) were screened for abnormalities of immunological function. They were compared with 92 controls and 28 patients with lymphoma. Depression of cellular or humoral immunity, or both, was found in a significant number of phenytoin-treated and lymphoma subjects. Phenytoin therapy was associated with low immunoglobulin A (21%), failure of antibody response to Salmonella typhi antigen (9%), absence of delayed hypersensitivity (D.H.S.) to three common skin-test antigens (22%), and depression of in-vitro lymphocyte transformation by phytohaemagglutinin (27%). Lymphoma patients manifested low IgM (22%), and inability to make antibody to S. typhi (11%) and to tetanus toxoid (21%). D.H.S. was absent in 36%; lymphocyte transformation was depressed in 17%. Abnormal lymphocyte transformation did not correlate with depression of cellular or humoral immunity in either group.

Adolescent↗