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Biomedical subjects

W R Wilson

Publications and source records attributed to W R Wilson.

At least 199 records · Page 11Linked to original sources
PubMed1989

Prospective randomized comparison of mezlocillin therapy alone with combined ampicillin and gentamicin therapy for patients with cholangitis.

Forty-six patients with cholangitis were randomized to receive therapy with mezlocillin sodium (24 patients) or a combination of ampicillin sodium--gentamicin sulfate (22 patients). The biliary concentration of mezlocillin was 112 times higher than that of ampicillin and 778 times higher than that of gentamicin. The ratio of the concentration in serum or bile over the minimum inhibitory concentration against aerobic gram-negative bacilli (therapeutic index) was higher for mezlocillin than for either ampicillin or gentamicin. Twenty (83%) of 24 patients were cured following mezlocillin therapy compared with 9 (41%) of 22 patients after ampicillin-gentamicin therapy. The 3 patients with superinfection were in the ampicillin-gentamicin arm of the study. Fewer toxic or adverse effects occurred in association with mezlocillin treatment than with ampicillin-gentamicin treatment. Mezlocillin therapy was more effective, less toxic, and less expensive than treatment with ampicillin and gentamicin for patients with cholangitis.

Adult↗
PubMed1988

Mechanism of resistance of non-cycling mammalian cells to 4'-[9-acridinylamino]methanesulphon-m-anisidide: role of DNA topoisomerase II in log- and plateau-phase CHO cells.

CHO-AA8 cells were used as a model system to study the role of DNA topoisomerase II in the resistance of non-cycling cells to amsacrine. Plateau-phase AA8 cells have previously been shown to be resistant to amsacrine and to contain fewer DNA breaks than log-phase cells after drug treatment (Robbie, M.A., Baguley, B.C., Denny, W.A., Gavin, J.R. and Wilson, W.R. (1988) Cancer Res., in press). The phage P4-unknotting activity of nuclear extracts decreased 2-fold when AA8 cells entered into the non-cycling state, but there was no difference in sensitivity to amsacrine between log- and plateau-phase nuclear extracts. Drug stimulation of protein-DNA complex formation was similar in whole cells, isolated nuclei and nuclear extracts from either log- or plateau-phase cells. However, stimulation of complex formation in cells, nuclei or nuclear extracts was approx. 4-fold lower in plateau-phase than in log-phase. The data presented suggested that drug-enzyme interaction was altered in plateau-phase cells.

Amsacrine↗
PubMed1988

Mechanism of resistance of noncycling mammalian cells to 4'-(9-acridinylamino)methanesulfon-m-anisidide: comparison of uptake, metabolism, and DNA breakage in log- and plateau-phase Chinese hamster fibroblast cell cultures.

Resistance of noncycling cells to amsacrine (m-AMSA) has been widely reported and may limit the activity of this drug against solid tumors. The biochemical mechanism(s) for this resistance have been investigated using spontaneously transformed Chinese hamster fibroblasts (AA8 cells, a subline of Chinese hamster ovary-cells) in log- and plateau-phase spinner cultures. In early plateau phase most cells entered a growth-arrested state with a G1-G0 DNA content and showed a marked decrease in sensitivity to cytotoxicity induced by a 1-h exposure to m-AMSA or to its solid tumor-active analogue, CI-921. Studies with radiolabeled m-AMSA established that similar levels of drug were accumulated by log- and plateau-phase cells and that there was no significant drug metabolism in either of these cultures after 1 h. However, marked differences in sensitivity to m-AMSA-induced DNA breakage were observed using a fluorescence assay for DNA unwinding (Kanter P.M., and Schwartz, H.S., Mol. Pharmacol., 22: 145-151, 1982). Changes in sensitivity to DNA breakage occurred in parallel with changes in sensitivity to m-AMSA-induced cell killing. DNA breaks disappeared rapidly after drug removal (half-time approximately 4 min), suggesting that these lesions were probably mediated by DNA topoisomerase II. Resistance to m-AMSA may therefore be associated with changes in topoisomerase II activity in noncycling cells.

Amsacrine↗
PubMed1988

The Child Care Activities Scale and Parental Role Preference Scale.

The Child Care Activities Scale (CCAS) and Parental Role Preference Scale (PRPS) were developed to measure parental involvement in four domains of child care: direct care, indirect care, amount of sole responsibility, and play. The CCAS measures level of involvement of each parent in 21 child care activities. The 12-item PRPS is intended to discriminate among how much parents ideally would like to participate, and how much they actually do participate in child care. The psychometric properties of both scales are presented using data from two studies. Recommendations for the future use of the scales are given.

Adult↗
PubMed1988

Invasive procedures in the diagnosis of pneumonia.

The etiology of respiratory infections can be elusive despite the recent advances in diagnostic technology. Thereby, the clinician needs a systematic approach for a definitive early diagnosis. This review presents the pros and cons of various invasive procedures in order to select the most appropriate diagnostic method. Expectorated sputum, the important initial step in community-acquired pneumonia, is unreliable in complex pneumonias, mainly because of colonization of the oropharynx. Even though blood cultures are frequently negative, they provide a precise diagnosis and should be obtained in undiagnosed pneumonias. Transtracheal needle aspiration has few false-negative results. However, its use has decreased because of the high frequency of false-positive cultures and risk of serious complications. Bronchoscopy provides direct access to both the bronchi and parenchyma for visualization and sampling. Plugged telescoping catheter brush, used safely in different clinical settings, has good sensitivity in identifying the pathogen, but the specificity varies with the underlying status of the patient. Because of upper airway contamination, bronchial washings are only slightly better than expectorated sputum. A newer technique, transbronchial needle aspiration, is, thus far, no improvement over the plugged telescoping catheter brush. In the immunosuppressed patient, bronchoalveolar lavage has excellent diagnostic accuracy for opportunistic infections. The accuracy increases with the addition of transbronchial biopsy. Transthoracic needle aspiration gives decisive information with low false-positive results. With the ultrathin needle, the complications decrease. Renewed interest in thoracoscopy-guided biopsy has demonstrated a high diagnostic accuracy with low complication rate. One procedure, a combination, or improvements of these procedures may reduce the need for open lung biopsy. Nevertheless, an open lung biopsy furnishes the best specimen for making a histological and microbiological diagnosis, although controversy exists regarding any improvement in survival rates.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis with ciprofloxacin or vancomycin alone or in combination with rifampin.

Therapy with vancomycin alone or ciprofloxacin alone did not significantly reduce the number of methicillin-resistant Staphylococcus aureus (MRSA) in bone in rats with experimental osteomyelitis, compared with the number in control rats. Treatment with rifampin significantly (p less than 0.01) decreased the number of MRSA per gram of bone compared with the number in control animals. There was no significant difference in the results of therapy with rifampin compared with the results obtained with the combination of vancomycin plus rifampin. The combination of ciprofloxacin plus rifampin was the most effective regimen for the treatment of MRSA experimental osteomyelitis and the results of therapy were significantly (p less than 0.01) superior to those following treatment with rifampin alone or the combination of vancomycin and rifampin. Following cessation of antimicrobial therapy, significant (p less than 0.01) regrowth of MRSA in bone occurred in animals treated with rifampin alone or ciprofloxacin plus rifampin. The emergence of resistance of MRSA during treatment occurred in two rats treated with rifampin alone and in one treated with rifampin plus vancomycin.

Animals↗
PubMed1987

Toluidine blue staining of the esophagus. A useful adjunct in the panendoscopic evaluation of patients with squamous cell carcinoma of the head and neck.

Carcinoma of the esophagus has a much higher incidence among patients with squamous cell carcinoma of the head and neck than among the population at large. Esophageal cancer has a low cure rate, and the possibility for increased survival can be enhanced primarily through early detection. Toluidine blue has proved to be effective in demonstrating early malignant lesions that would not be detectable otherwise. A technique has been developed for toluidine blue staining of the esophagus during panendoscopy. In this initial series of 18 patients with squamous cell carcinoma of the upper aerodigestive tract, we found a 17% incidence of early carcinoma of the esophagus. We believe this technique to be an important adjunct to the evaluation of these patients at high risk for esophageal carcinoma.

Biopsy↗
PubMed1987

Comparison of in vivo and in vitro drug sensitivities of Lewis lung carcinoma and P388 leukaemia to analogues of amsacrine.

The activity of several clinical agents (5-fluorouracil, methotrexate, adriamycin, daunorubicin, mitoxantrone and amsacrine) and of a number of analogues of amsacrine, including the 4-methyl,5-(N-methyl)carboxamide derivative (CI-921) which is at present in clinical trial, has been compared in vivo against Lewis lung carcinoma (LL) and P388 leukaemia in mice, and against corresponding cell lines in cell culture. All derivatives were active against i.p. inoculated P388 leukaemia whereas only some were active against i.v. inoculated LL cells. The relative in vitro activities in the two cell lines, as measured by growth inhibition (IC50) assays, varied from equitoxic to 26-fold more active with P388 cells than with LL cells. The in vivo activity of these drugs against i.v. inoculated LL relative to i.p. inoculated P388 could be predicted with a high degree of significance from the ratio of in vitro activities in the 2 cell lines. However, this correlation did not appear to reflect cell line selectivity alone, since, when P388 cells were inoculated i.v. rather than i.p., drug sensitivity closely matched that of the LL tumour. This observation suggests a dominant role for pharmacological variables in determining the in vivo activity of amsacrine analogues, and underlines the importance of standardising tumour site in the determination of antitumour spectrum. Nevertheless, the correlation of selective in vitro toxicity for cultured LL cells with high activity against remotely implanted tumours demonstrates the utility of in vitro tests in identifying amsacrine analogues with improved clinical potential.

Amsacrine↗
PubMed1987

Antimicrobial agents in adult patients with renal insufficiency: initial dosage and general recommendations.

The dosage or the time interval of administration (or both) of many antimicrobial agents must be adjusted in anephric patients or those with compromised renal function. Antimicrobial agents that must have adjustment of dosages include most, but not all, of the penicillins and cephalosporins, the aminoglycosides, vancomycin, and trimethoprim-sulfamethoxazole. The maximal doses of these agents generally should be decreased in proportion with the extent of reduction in renal function. The dosage of chloramphenicol, clindamycin, rifampin, nafcillin, and ceftriaxone probably need not be adjusted if hepatic function is essentially normal. The suggested doses are relatively crude guidelines to initial antimicrobial therapy. Serum antimicrobial assays are frequently indicated for accurate adjustment of the dosage, especially with the amino-glycosides. The efficacy of therapy and the possible occurrence of toxicity should be monitored in all patients but particularly in those with renal insufficiency. Recommendations for patients undergoing peritoneal dialysis are not included in this article.

Adult↗
PubMed1987

Tetracyclines, chloramphenicol, erythromycin, and clindamycin.

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and may also be used for gonococcal infections in patients unable to tolerate penicillins. These drugs may cause gastrointestinal irritation, photo-toxic dermatitis, diarrhea, vestibular damage, and hepatotoxicity in pregnant women. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and typhoid fever. The most important toxic effect of chloramphenicol is bone marrow suppression, which can be dose related or idiosyncratic. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious untoward effects associated with the use of erythromycin is low; epigastric distress may occur. Clindamycin is active against Bacteroides fragilis and other anaerobic microorganisms. Pseudomembranous enterocolitis has developed in as many as 10% of patients taking this drug. The use of clindamycin should be discontinued promptly if diarrhea occurs.

Bacterial Infections↗
PubMed1987

Cytokinetic factors in drug resistance of Lewis lung carcinoma: comparison of cells freshly isolated from tumours with cells from exponential and plateau-phase cultures.

The cytotoxic effects of chemotherapeutic drugs on quiescent and actively proliferating cells of a Lewis lung carcinoma (LLTC) cell line have been examined. The sensitivities of cells in plateau-phase and exponentially growing cultures were compared with those of cells recovered from large subcutaneous tumours both immediately after tumour disaggregation and after one or 4 days in culture. Flow cytometric analysis indicated that when cells freshly prepared from tumours were placed into culture, they underwent extensive recruitment into S-phase. Several drugs were less cytotoxic towards both plateau-phase cultured cells and cells freshly isolated from tumours than they were against exponentially growing cells. These included amsacrine, its 4-methyl-5-(N-methyl)carboxamide derivative CI-921, doxorubicin, and nitrogen mustard. In contrast to these drugs, chlorambucil and plasma from cyclophosphamide-treated mice did not show decreased activity against slowly proliferating cells from cultures or tumours relative to cells in an actively proliferating state. The similar sensitivities of plateau-phase cultured cells and cells taken directly from large growing tumours is direct evidence that plateau-phase cultures are a useful approximation to the state of cytokinetic resistance to chemotherapeutic drugs that prevails in solid tumours, although they may not fully reflect the cytokinetic heterogeneity present in tumours.

Amsacrine↗
PubMed1987

Hypoxia-selective radiosensitization of mammalian cells by nitracrine, an electron-affinic DNA intercalator.

The radiosensitizing ability of the 1-nitroacridine nitracrine (NC) is of interest since it is an example of a DNA intercalating agent with an electron-affinic nitro group. NC radiosensitization was evaluated in Chinese hamster ovary cell (AA8) cultures at 4 degrees C in order to suppress the rapid metabolism and potent cytotoxicity of the drug. Under hypoxic conditions, submicromolar concentrations of NC resulted in sensitization (SER = 1.6 at 1 mumol dm-3). Sensitization was also seen under aerobic conditions but a concentration more than 10-fold higher was required. In aerobic cultures NC radiosensitization was independent of whether cells were exposed before and during, or after, irradiation. Postirradiation sensitization was not observed under hypoxic conditions. The time dependence of NC uptake and the development of radiosensitization were similar (maximal at 30 min at 4 degrees C under hypoxia) suggesting that sensitization, unlike cytotoxicity, is due to unmetabolized drug. NC is about 1700 times more potent as a radiosensitizer than misonidazole. This high potency is adequately accounted for by the electron affinity of NC (E(1) value at pH7 of -275 mV versus NHE) and by its accumulation in cells to give intracellular concentrations approximately 30 times greater than in the medium. However, concentrations of free NC appear to be low in AA8 cells, presumably because of DNA binding. If radiosensitization by NC is due to bound rather than free drug, it suggests that intercalated NC can interact very efficiently with DNA target radicals. This is despite a binding ratio in the cell estimated as less than 1 NC molecule/400 base pairs under conditions providing efficient sensitization. This work suggests a new approach in the search for more effective clinical radiosensitizers, and poses questions on the means by which intercalated drugs can interact with DNA damage.

Aminoacridines↗
PubMed1987

In vitro and in vivo studies of streptomycin-resistant, penicillin-susceptible streptococci from patients with infective endocarditis.

The combination of penicillin and streptomycin did not act synergistically in vitro against three streptomycin-resistant strains (MIC, greater than or equal to 1,000 micrograms of streptomycin/ml) of penicillin-susceptible streptococci. Using a model of experimental infective endocarditis, we infected rabbits with a control streptomycin-susceptible strain, with an intermediately streptomycin-resistant strain (MIC, 1,000 micrograms/ml), and with a highly streptomycin-resistant strain (MIC, greater than 32,000 micrograms/ml). Treating animals with a combination of procaine penicillin and streptomycin was more effective (P less than .01) than treating them with procaine penicillin alone only for those animals infected with the control streptomycin-susceptible strain. Treatment with procaine penicillin plus gentamicin was more effective (P less than .01) than treatment with procaine penicillin alone for all three treatment groups and was more effective (P less than .01) than treatment with procaine penicillin and streptomycin for those animals infected with an intermediately or highly streptomycin-resistant strain of streptococci.

Animals↗
PubMed1987

Antimicrobial therapy of streptococcal endocarditis.

The majority of patients with endocarditis caused by viridans streptococci or Streptococcus bovis susceptible to less than or equal to 0.1 mg/l of penicillin may be treated successfully for two weeks with penicillin 20 X 10(6) million units intravenously together with streptomycin 7.5 mg/kg body weight intramuscularly twice daily or gentamicin 1 mg/kg body weight intravenously every 8 h. Patients with nutritionally variant viridans streptococcal endocarditis should be treated for four weeks with penicillin combined with an aminoglycoside in dosages as above, which will require adjustment when renal impairment is present. Patients with enterococcal endocarditis should be treated with penicillin together with an aminoglycoside in dosages as above for four to six weeks. Patient with enterococcal endocarditis with symptoms of infection less than three months in duration or with aortic valve endocarditis may be treated successfully for four weeks with antimicrobial therapy; patients with symptoms of infection longer than three months in duration or with mitral valve infection should receive six weeks of antimicrobial therapy. Patients with enterococcal endocarditis who relapse should be treated for six weeks of antimicrobial therapy.

Drug Therapy, Combination↗
PubMed1987

A prospective randomized trial of the Lazarus-Nelson vs. the standard peritoneal dialysis catheter for peritoneal lavage in blunt abdominal trauma.

One hundred consecutive injured patients with blunt abdominal trauma requiring peritoneal lavage were prospectively randomized to placement of lavage catheters with an open or percutaneous technique. The Lazarus-Nelson catheter, placed by Seldinger wire technique, was compared to a standard dialysis catheter, placed by direct visualization and incision of the peritoneum. Placement of the catheter was consistently faster using the percutaneous method; no difference was noted in time of lavage, volume recovered, or complications. When not contraindicated, the percutaneous technique was widely preferred by study participants.

Abdominal Injuries↗
PubMed1987

In vitro and in vivo activity of ciprofloxacin against enterococci isolated from patients with infective endocarditis.

In vitro activity of ciprofloxacin against 27 strains of enterococci was inoculum dependent. Using inocula of 10(5) to 10(6) or 10(7) to 10(8) CFU of enterococci per ml, the MICs for 50 and 90% of strains tested increased from 1 to greater than or equal to 128 micrograms of ciprofloxacin per ml with the higher inoculum compared with the lower inoculum. The MBC for 50% of strains tested increased from 2 to greater than 128 micrograms/ml and the MBC for 90% of strains tested increased from 8 to greater than 128 micrograms of ciprofloxacin per ml with the lower and higher inocula, respectively. The combination of penicillin-gentamicin was more effective in vitro than the combination of ciprofloxacin-gentamicin against the low or high inoculum of enterococci. Using two strains of enterococci, we studied the efficacy of ciprofloxacin in the treatment of enterococcal experimental endocarditis in rabbits. Ciprofloxacin used alone or combined with gentamicin was significantly less effective (P less than 0.01) than procaine penicillin alone or procaine penicillin combined with gentamicin for the treatment of enterococcal experimental endocarditis. The combination of ciprofloxacin-procaine penicillin was not a more effective therapy than procaine penicillin alone.

Animals↗