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Biomedical subjects

W R Wilson

Publications and source records attributed to W R Wilson.

At least 253 records · Page 14Linked to original sources

Synergy of imipenem or penicillin G and aminoglycosides against enterococci isolated from patients with infective endocarditis.

We tested the synergistic activity of imipenem (formerly imipemide, N-formimidoyl thienamycin, or MK 0787) (20 micrograms/ml) or penicillin (20 micrograms/ml) in combination with increasing concentrations of either streptomycin (5, 10, and 20 micrograms/ml) against 13 strains of streptomycin-susceptible enterococci or gentamicin (1, 3, and 5 micrograms/ml) against 13 strains of streptomycin-susceptible enterococci and 7 strains of streptomycin-resistant enterococci. At 24 h, penicillin together with each increment in streptomycin concentration resulted in a significant increase (P less than 0.001) in killing of streptomycin-susceptible enterococci compared with imipenem and the corresponding concentration of streptomycin. Similarly, at 24 h, the magnitude of killing of streptomycin-susceptible enterococci by a combination of penicillin plus each increment of gentamicin concentration was significantly greater (P less than 0.001) than that of the combination of imipenem and the corresponding concentration of gentamicin. Against streptomycin-resistant enterococci, penicillin together with each increment of gentamicin concentration killed significantly more enterococci (P less than 0.02) than did the combination of imipenem and the corresponding concentration of gentamicin. When combined with an aminoglycoside, the synergistic activity in vitro against enterococci of imipenem was significantly less than that of penicillin.

Aminoglycosides↗

Analysis of Pneumocystis carinii cysts with a fluorescence-activated cell sorter.

Human sera from Pneumocystis carinii-infected patients and specific rabbit antisera have antibodies against the cyst form of the organism. Lung tissue concentrations from cortisone-treated C3H/HeN mice and six open lung biopsy-positive patients were centrifuged and suspended, and immunofluorescent staining was done. We utilized the fluorescence-activated cell sorter to analyze and sort P. carinii cysts from lung homogenates into a morphologically distinct population. A quantitative basis was used for the definition of the cyst population by displaying the frequency of cells as a function of parameter (fluorescence intensity and light scatter) expression. In 14 of 15 histogram analyses, P. carinii-infected homogenates were differentiated from normal- and bacterial-control homogenates. The parameter range of light scatter (size) was 2 to 8 micron, and the fluorescence intensity was greater than a threshold based on the histogram profile.

Animals↗

Comparison of the dexamethasone suppression test and the cortisol suppression index.

Among 50 inpatients, the sensitivity and specificity of the dexamethasone suppression test (DST) were 51.7% and 85.7%, respectively. For the cortisol suppression index they were 10.3% and 91% at 8:00 a.m. and 51.7% and 57.1% at 4:00 p.m. Thus, the cortisol suppression index does not appear to be an adequate substitute for the DST.

Adolescent↗

Treatment of streptomycin-susceptible and streptomycin-resistant enterococcal endocarditis.

Fifty-six patients with enterococcal endocarditis received 4 weeks of antimicrobial therapy with penicillin G and streptomycin (36 patients) or, if infections were streptomycin resistant, penicillin and gentamicin (20 patients). Compared with patients who had symptoms for less than 3 months, patients with symptoms for more than 3 months had a higher relapse rate (0% versus 44%; p less than 0.001) and mortality (2.5% versus 25%; p less than 0.001). Patients with mitral valve endocarditis had a significantly higher relapse rate (25%) than patients with aortic valve infections (0%) (p less than 0.01). Gentamicin-associated nephrotoxicity was more frequent (p less than 0.001) among patients treated with greater than 3 mg/kg d of gentamicin than among those treated with 3 mg or less (100% versus 20%). Relapse and mortality rates did not differ significantly between patients treated with low-dose or high-dose gentamicin regimens. Patients who have had symptoms of enterococcal endocarditis for more than 3 months or patients with mitral valve infection should receive at least 6 weeks of antimicrobial therapy, but patients without these high-risk factors can be treated for 4 weeks.

Adult↗

Why treat sudden hearing loss.

Recent laboratory and clinical studies provide increasing evidence that idiopathic sudden hearing loss can be effectively treated. First, corticosteroid therapy has been shown to be efficacious in restoring hearing in patients with moderate hearing losses. Second, studies of cochlear blood flow and perilymphatic oxygen tension indicate that positive modifications in PO2 can be obtained with 5% CO2 and 95% O2. Future clinical trials are likely to show that improved oxygenation of the cochlea will have a positive effect upon hearing recovery. Third, patients with a clear history of perilymph fistulas are managed by middle ear exploration and repair.

Adult↗

Synthesis, antitumor activity, and DNA binding properties of a new derivative of amsacrine, N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino) phenylamino]-4-acridinecarboxamide.

The 4-(N-methylcarboxamido)-5-methyl derivative of amsacrine (NSC 249 992) has been synthesized as part of a program aimed at optimizing solid tumor activity in this series. Physicochemical studies of this analogue (N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino) phenylamino]-4-acridinecarboxamide; NSC 343 499) indicate a slightly increased lipophilicity (estimated log p = 1.10), a decreased acridine base strength (pKa 6.40), and a 16-fold-higher association constant for double-stranded calf thymus DNA (Ka 2.1 X 10(6) M-1 at 0.01 ionic strength). Like amsacrine, the drug binds to DNA by intercalation. Inhibition of cell growth has been monitored by continuous drug exposure assays with a variety of rodent and human cell lines. The concentration for 50% inhibition varied from 6.7 nM (T-47D, a human breast carcinoma line) to 800 nM (P388/ADR, a murine cell line resistant to Adriamycin). N-5-Dimethyl-9-[(2-methoxy-4-methylsulfonylamino) phenylamino]-4-acridinecarboxamide was cytotoxic at growth-inhibitory concentrations and also induced cell cycle arrest in the G2 phase. It was active against P388 leukemia following administration by p.o., i.v., or i.p. routes, and it was superior to amsacrine, daunorubicin, and Adriamycin. It was curative towards i.v.-injected Lewis lung tumor in a proportion of animals when treatment was started on Day 1 or Day 5 after tumor inoculation. It also produced highly significant life extensions against advanced tumors (treatment starting Day 9 after i.v. inoculation or on Day 8 after s.c. inoculation) and was comparable to cyclophosphamide in its effectiveness. It is a candidate drug for clinical trial.

Aminoacridines↗

Comparison of the mutagenic and clastogenic activity of amsacrine and other DNA-intercalating drugs in cultured V79 Chinese hamster cells.

The acridine derivative amsacrine (m-AMSA) is used clinically for the treatment of acute leukemias. The mutagenic activity of this drug has been evaluated at the 6-thioguanine (6-TG) and ouabain resistance loci in cultured Chinese hamster fibroblasts (V79-171b cell line). m-AMSA was found to have weak but significant mutagenic activity at the 6-TG but not at the ouabain resistance locus, after either 1- or 45-hr exposures at concentrations causing up to 90% cell kill. Two other intercalating agents with antitumor activity, Adriamycin and actinomycin D, provided essentially identical results. All three drugs were potent inducers of micronuclei in V79-171b cells, indicating high clastogenic activity. For these intercalating agents, the yield of 6-TG-resistant mutants was approximately 100-fold lower than that for ethyl methanesulfonate after exposures causing equivalent toxicity or equivalent chromosome breakage. The acridine half-mustard ICR-191 resembled ethyl methanesulfonate rather than the other intercalating agents in providing a high yield of 6-TG-resistant mutants relative to its clastogenic activity. The tumor-inactive intercalator 9-aminoacridine demonstrated only low clastogenic activity with a lack of significant mutagenic activity at toxic concentrations. These results suggest that, for m-AMSA, Adriamycin, and actinomycin D, both cell killing and mutagenesis could be direct consequences of chromosome breakage, while 9-aminoacridine may kill cells by a different mechanism. In view of its mutagenic and clastogenic activity at clinically achievable exposures and the similarity of its genotoxic properties to Adriamycin, m-AMSA should be considered a potential carcinogen.

Aminoacridines↗

Auditory brain-stem responses in infants with Down's syndrome.

Auditory brain-stem responses to clicks were recorded from 38 infants with Down's syndrome at the ages of 3, 6, and 12 months in an attempt to delineate age-dependent and intensity-dependent latency changes in this population. Comparisons were made with 35 normally developing infants at the same age levels. Significant wave V latency differences were observed between groups for both age and intensity, with the group with Down's syndrome showing, in general, shorter absolute wave V latency values across age and steeper latency functions across intensity. The implications of this study are as follows: (1) latency-intensity curves for normally developing infants will not serve adequately as normative values for infants with Down's syndrome, particularly at the age of 12 months, and (2) cochlear function in infants with Down's syndrome may differ from normal infants by the age of 12 months.

Acoustic Stimulation↗

Divergent activity of derivatives of amsacrine (m-AMSA) towards Lewis lung carcinoma and P388 leukaemia in mice.

A series of acridine monosubstituted derivatives of the antitumour agent amsacrine [4'-(9-acridinylamino)methanesulphon-m-anisidide] has been tested for activity against intraperitoneally inoculated P388 leukaemia and intravenously inoculated Lewis lung carcinoma growing in DBA/2J X C57BL/6J mice, and treated using a q4d X 3 intraperitoneal injection schedule. Whereas all derivatives tested exhibited moderate to high activity towards the leukaemia, activity against the lung tumour varied from inactive to curative. Amsacrine itself displayed low but statistically significant activity. Cyclophosphamide and 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) were highly active. 5-Fluorouracil was active but doxorubicin, daunorubicin, ametantrone and mitoxantrone showed no significant activity. Since the Lewis lung carcinoma is responsive to a high proportion of agents active against solid tumours in the clinic, it is concluded that some derivatives of amsacrine could be considerably more active than amsacrine itself against human solid tumours.

Aminoacridines↗

Infective endocarditis--a 25 year overview of diagnosis and therapy.

Diagnosis and management of infective endocarditis have significantly changed in the past 25 years. Improved bacteriologic techniques have allowed detection of cases of infective endocarditis caused by unusual organisms. Bactericidal therapy has become available for patients with gram-negative endocarditis and antimicrobial therapy has improved. Echocardiography has become an important diagnostic and management aid, and cardiac valve replacement has dramatically improved the outlook for many patients.

Anti-Bacterial Agents↗

Microbiological and clinical evaluation of the isolator lysis-centrifugation blood culture tube.

In a controlled evaluation of 6,010 blood cultures, the yield of clinically significant microorganisms was greater from a lysis-centrifugation system (Isolator, Du Pont Co.) than from a nonvented vacuum bottle containing tryptic soy broth with sodium polyanetholesulfonate and CO2 and a vented bottle containing biphasic brain heart infusion medium with sodium polyanetholesulfonate. The Isolator significantly increased the frequency of isolation of Staphylococcus aureus and Candida spp. and significantly decreased the time required for the detection of S. aureus, Pseudomonas aeruginosa, and Candida spp.; however, anaerobic bacteria were recovered significantly more frequently from nonvented bottles with tryptic soy broth, and pneumococci were recovered significantly more frequently from both bottle systems. Contamination of cultures was significantly greater with the Isolator system than with either bottle system. Regardless of the number of blood cultures obtained per septic episode, the Isolator detected microbiologically proven bacteremia or fungemia in a significantly greater number of patients and significantly decreased the time required for detection.

Adult↗

Antibiotic treatment of infective endocarditis.

At least 85% of patients with infective endocarditis can be cured with effective therapy. Streptococci or staphylococci cause 75% of cases of endocarditis. Patients with penicillin-sensitive viridans or nonenterococcal group D streptococcal endocarditis may be treated successfully with aqueous penicillin G alone for four weeks or with combined penicillin and streptomycin for two weeks. Enterococcal endocarditis should be treated for four to six weeks with a combination of aqueous penicillin G together with either streptomycin or gentamicin. Patients with endocarditis caused by Staphylococcus aureus should receive antimicrobial therapy for four to six weeks with a semisynthetic penicillin (nafcillin or oxacillin) or a cephalosporin such as cephalothin or cefazolin. In urgent cases where empiric antimicrobial therapy is necessary before the causative organism is identified, a combination of aqueous penicillin G, nafcillin, and gentamicin is effective therapy.

Anti-Bacterial Agents↗

Viral and epidemiologic studies of idiopathic sudden hearing loss.

The relationship between viral seroconversions and idiopathic sudden hearing loss (ISHL) is studied. Compared with our control group, the incidence of viral seroconversions is greater among ISHL patients, both for single and multiple viral infections. There was a significantly greater number of patients with seroconversions to mumps, rubeola, varicella-zoster, cytomegalovirus, and influenza B. We were unable to find a relationship between viral seroconversion and type or degree of hearing loss, vertigo, or chance for recovery. The incidences of viral conversion and sudden hearing loss track one another closely, suggesting that viral infection is a major cause of ISHL. During this 3-year study in Boston, ISHL was most prevalent in the spring.

Adolescent↗

Endocarditis caused by B fragilis.

A 54-year-old man had had an acute anterior myocardial infarction nine years prior to this hospital admission. Since that time he had been asymptomatic with the exception of occasional episodes of precordial chest pain. The patient died from septic shock on the tenth day after the present admission. On autopsy there was an old myocardial infarct with aneurysmal dilatation of the left ventricle which contained a large thrombus with multiple abscesses. Septic infarcts were also found in the left kidney and the left temporal lobe of the brain.

Bacteroides Infections↗

Traveling toothpicks.

Although most ingested foreign bodies usually pass through the gastrointestinal tract uneventfully, such objects infrequently cause intestinal perforation and may even result in death. Herein we present five cases of gastrointestinal perforation caused by toothpicks. In one of these patients, the toothpick penetrated the inferior vena cava and caused overwhelming bacteremia and death. A major factor that contributes to the inability to identify foreign objects such as toothpicks in food is the wearing of dental plates, which precludes normal palatal sensitivity. Patients should be alerted to the potential hazards associated with the use of toothpicks.

Adult↗