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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 199 records · Page 11Linked to original sources
PubMed1978

Candida albicans endocarditis: ultrastructural studies of vegetation formation.

Candida albicans endocarditis was established in rabbits after transaortic catherization. Within 30 to 90 min after infection, C. albicans was observed by scanning electron microscopy on the valve surface. The organisms were predominantly associated with host deposits of erythrocytes, phagocytes, platelets, and fibrinous-appearing material, which collectively appeared on the valve surface in response to trauma. Within 48 h after infection, vegetations composed of these same host components were observed on the heart valves, although Candida cells were not demonstrable on the valve or vegetation surface. When the vegetations were examined by transmission electron microscopy, Candida blastospores were only observed within phagocytic cells (predominantly monocytes) enmeshed within the vegetation matrix. Many of the intracellular organisms were undergoing degradation, as evidenced by a reduction in electron density of the cell wall. Other fungi had highly electron-dense cell walls and germ tubes. Phagocytic cells containing germinating Candida were highly vacuolated and were observed at various stages of cell lysis. After 7 days of infection, the vegetation contained a dense meshwork of fibrin and Candida pseudohyphae with 10(8) to 10(9) colony-forming units/g of vegetation. The mature vegetation was devoid of phagocytic cells and continued to grow until the death of the animal.

Animals↗
PubMed1978

Diagnosis of pneumococcal pneumonia by antigen detection in sputum.

Pneumococcal polysaccharide was detected by counterimmunoelectrophoresis in the sputum of 20 of 26 (77%) adults with community-acquired pneumonia and a positive sputum culture for Streptococcus pneumoniae. The test was negative in 29 pneumonia patients with negative sputum culture for S. pneumoniae. Pneumococcal antigen was also detected in the sputum of six of nine adults with chronic bronchitis and a positive sputum culture, but was not detected in expectorated respiratory secretions of 22 pneumococcal carriers with colds. Pneumococcal antigen could also be detected in sputum by immunodiffusion; antigen titers varied from 1:2 to 1:256. These results strongly suggest that the detection of pneumococcal antigen in respiratory tract secretions indicates infection caused by S. pneumoniae.

Adult↗
PubMed1978

Bacterial adherence in the pathogenesis of endocarditis. Interaction of bacterial dextran, platelets, and fibrin.

The role of dextran in the pathogenesis of bacterial endocarditis was investigated by studying the adherence of dextran producing oral streptococci to the constituents of nonbacterial thrombotic endocarditis (NBTE) in vitro and in vivo. The adherence of Streptococcus sanguis to fibrin and platelets was determined in an in vitro assay system simulating nonbacterial thrombotic endocarditis. Adherence was increased when the organisms were grown in sucrose-supplemented media (adherence ratio X 10(4), 177 +/- 6 in 5% sucrose vs. 140 +/- 7 in 0.5% sucrose, P less than 0.001), and decreased by incubating the organisms in dextranase (adherence ratio X 10(4), 117 +/- 16, P less than 0.001), an effect which was nullified by heat inactivating this enzyme (adherence ratio X 10(4), 192 +/- 7, P less than 0.001). The amount of dextran produced in broth by three different oral streptococci correlated directly with the adherence observed to fibrin and a fibrin-platelet matrix in vitro (P less than 0.001). These organisms adhered more readily to a fibrin-platelet matrix than to fibrin alone (adherence ratio X 10(4), 455 +/- 30 vs. 177 +/- 6, respectively, P less than 0.001). The role of dextran formation was also examined in vivo in rabbits with preexisting NBTE. After injection of 10(7) S. sanguis, 12 of 17 animals developed endocarditis. In contrast, when the organisms were pretreated with dextranase (an enzyme that removes dextran from the bacterial cell surface), the same inoculum resulted in endocarditis in only 5 of 19 animals (P less than 0.05). In addition, a fresh strain of S. sanguis that produced high levels of dextran (1,220 +/- 50 microgram/ml) and adhered avidly to fibrin (adherence ratio X 10(4), 220 +/- 11) produced endocarditis in 12 of 18 rabbits after injection of 10(7) organisms. Another isolate of the same strain that had been passed repeatedly in the laboratory produced less dextran (400 +/- 30 microgram/ml), adhered poorly to fibrin (adherence ratio X 10(4), 140 +/- 7), and produced endocarditis in only 3 of 14 rabbits under identical conditions (P less than 0.05). This study demonstrates that dextran production is important in the adherence of oral streptococci to the constituents of NBTE and may play a role in the pathogenesis of bacterial endocarditis by oral streptococci.

Animals↗
PubMed1978

The need for controlled clinical studies in antimicrobial therapy.

In recent years in-vitro and in-vivo studies have greatly advanced our understanding of the action of antimicrobial agents and have opened new potential avenues for treatment of infectious diseases. Unfortunately, little interest or financial support has been available to test these observations in rigid, controlled clinical studies. New regimens have thus been used without proof of increased efficacy of reduced toxicity over old regimens. Carefully controlled clinical trials are particularly needed to evaluate the efficacy, toxicity, and cost of newly developed regimens in the therapy of chronic bacterial and fungal infections.

Anti-Bacterial Agents↗
PubMed1978

Factors influencing the penetration of antimicrobial agents into the cerebrospinal fluid of experimental animals.

Successful therapy of bacterial meningitis is dependent upon achieving adequate antibacterial activity in the CSF. The percent penetration (CSF concentration/serum concentration X 100) of various antimicrobial agents was determined in a rabbit model of bacterial meningitis. The percent penetration of the penicillin and cephalosporin derivatives was found to vary inversely with the protein binding of the respective drugs. Esterification of ampicillin increased its lipid solubility and likewise increased the penetration into the CSF. Probenecid competitively inhibits the active transport efflux of various organic acids from the CSF and increased the CSF concentrations of penicillin and cephalosporin derivatives. The percent penetration of all drugs was increased in the presence of the inflamed meninges.

Animals↗
PubMed1977

Cefamandole and ampicillin therapy in experimental Haemophilus influenzae meningitis.

Cefamandole and ampicillin were compared in the therapy of experimental Haemophilus influenzae meningitis in rabbits. Three dosages of each drug were administered as a continuous intravenous infusion for 8 hr to 24 infected animals. Samples of serum and cerebrospinal fluid (CSF) were obtained at 0, 4, and 8 hr for determination of antibiotic concentrations and bacterial titers in CSF. Serum levels of cefamandole were higher, but CSF concentrations of both antibiotics were similar. With the 60-mg/kg per hr dose, the mean serum level was 106 +/- 61 mug/ml for cefamandole and 58 +/- 32 mug/ml for ampicillin (P less than 0.05). With this dosage the mean level in CSF was 7.3 +/- 8.4 mug/ml for cefamandole and 9.5 +/- 5.4 mug/ml for ampicillin (P = 0.26). The percentage penetration ([concentration in CSF/concentration in serum] X 100%) was higher for ampicillin (mean, 18.8% +/- 8.9%) than for cefamandole (mean, 5.6% +/- 3.8%) with all dosages tested (P less than 0.001). The rate of bacterial killing in vivo during therapy was similar with both drugs. The efficacy of cefamandole and ampicillin given intramuscularly for five days (250 mg every 8 hr) was examined in 42 rabbits. Twelve of 14 untreated control rabbits died within 24-72 hr of inoculation. In contrast, 11 of 14 rabbits treated with cafamandole and 10 of 14 rabbits treated with ampicillin were cured of their infections. Cefamandole compared favorably with ampicillin in the therapy of experimental H. influenzae meningitis.

Ampicillin↗
PubMed1977

In vitro antibiotic susceptibility of salmonellae.

In vitro antibiotic susceptibilities were determined for 101 strains of salmonellae. Resistance to chloramphenicol and ampicillin was low. Cefamandole was active against the majority of strains and deserves further evaluation.

Ampicillin↗
PubMed1977

Comparative pharmacology of cefaclor and cephalexin.

Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 +/- 0.55 (standard deviation [SD]) mug/ml compared with 9.43 +/- 2.36 mug/ml for cephalexin (P < 0.01). The half-lives were 0.58 +/- 0.07 (SD) h and 0.80 +/- 0.12 (SD) h, and elimination constants were 1.22 +/- 0.15 and 0.88 +/- 0.13 h(-1) for cefaclor and cephalexin, respectively (P < 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated.

Adult↗
PubMed1977

In vitro susceptibility studies with cefaclor and cephalexin.

The in vitro activity of cefaclor and cephalexin against clinical isolates of four bacterial genera was compared. Both agents had a similar range of activity, but cefaclor was significantly more active by weight than cephalexin for most isolates tested.

Bacteria↗
PubMed1977

Experimental Candida albicans endocarditis: characterization of the disease and response to therapy.

Endocarditis caused by Candida albicans was induced in rabbits after insertion of a catheter across the aortic valve. The mean survival time of 34 rabbits was 26 days. Only 7% of temperature recordings taken were elevated. Candida was recovered from only 9% of blood cultures taken. Precipitating and agglutinating serum antibody was detected after 12 days of infection. Antibody titers rose progressively until death in rabbits with endocarditis, whereas titers peaked early and subsequently decreased in animals that received an intravenous injection of C. albicans without precatheterization. Three groups of rabbits were treated for 6 days with amphotericin B, 5-fluorocytosine, or the two durgs in combination. Amphotericin B alone reduced the mean titer of organisms from log10 8.79 +/- 1.46 to log 10 3.1 +/- 1.9 colony-forming units/g. 5-Fluorocytosine was less effective (mean titer after 6 days of therapy was log10 7.4 +/- 0.33 colony-forming units/g). The addition of 5-fluorocytosine to amphotericin B did not increase the rate at which Candida cells were eradicated from the vegetations. These in vivo results corrleated with the failure to demonstrate an increased rate of fungicidal activity in vitro with the two drugs.

Agglutinins↗
PubMed1977

Comparison of four aminoglycoside antibiotics in the therapy of experimental E. coli meningitis.

Tobramycin, sisomicin, and amikacin were compared with gentamicin in the therapy of experimental E. coli meningitis in rabbits. Meningitis was produced in 40 animals by intracisternal injection of 10(5) E. coli. Three dosages of each antibiotic were administered intravenously over 8 hours. Serum and CSF samples were obtained at 0,2,4,6, and 8 hours for determination of aminoglycoside concentrations and CSF bacteria counts. The four aminoglycosides demonstrated comparable penetration into the CSF. The mean percent penetration (CSF conc./serum conc. X 100%) with the three dosages was 10 to 50% for gentamicin, 8 to 23% for tobramycin, 6 to 16% for sisomicin, and 11 to 23% for amikacin. This variation in penetration reflected individual differences in each dosage group and the increase in percent penetration that was observed during therapy. Sisomicin and gentamicin were consistently bactericidal in vivo. Mean CSF bacterial titers gentamicin were consistently bactericidal in vivo. Mean CSF bacterial titers decreased 3.07 logs in rabbits treated with sisomicin and 2.44 logs in animals treated with gentamicin. Even through CSF concentrations were comparable, the group treated with tobramycin demonstrated only a 0.64 log decrease and the amikacin group had a 0.45 log increase in mean CSF titers. The bactericidal effect of sisomicin appeared to be more rapid than that of gentamicin. During the first 2 hours of therapy CSF titers declined 1.02 logs in animals treated with sisomicin as compared to 0.37 log in animals receiving gentamicin even though gentamicin concentrations were higher (mean 7.4 vs. 4.1 gm./ml.). Sisomicin also demonstrated greater bactericidal activity than the other aminoglycosides in normal CSF in vitro. The results of this study suggest that sisomicin may be of value in the therapy of E. coli meningitis.

Amikacin↗
PubMed1977

Otitis media: a review.

We have presented recommendations for diagnosis and management of otitis media in children based on a comprehensive review of the pertinent medical literature. For an entity that is so common, there still remain amazingly large numbers of areas of controversy. We have also attempted to stress the importance of appropriate therapy and adequate followup as being very important in the management of otitis media. Newer concepts, particularly the use of the impedance bridge tympanogram, have been mentioned. With all the above background information in mind and with considerations for what is practical for the patient and the medical community, we would recommend the following as the acceptable minimal care for patients with otitis media. When the diagnosis of the acute otitis media is made on the basis of physical findings of myringitis, and/or middle ear fluid, and/or rupture of the tympanic membrane, the following treatment course is advisable: Neonates Culture of middle ear fluid if possible. Ampicillin 200 mg/kg/day intramuscularly. Gentamicin 3/5mg/kg/day intramuscularly. Hospitalize and treat until well and for minimum of seven days. Observe closely for meningitis and other infections and drug toxicity. These should be handled only by physicians experienced in dealing with patients in this age range. Appropriate work-up for septicemia should precede treatment. Switch to specific antibiotic when cultures and sensitivity available. Children. From 2 months to 6 years of age: Ampicillin 50mg/kg/day. Decongestant (if desired). Administer for ten days. Every patient with otorrhea, severe otitis and those not clinically well should be seen for followup ten to 14 days later. They should have a minimum of otologic evaluation including drum mobility. In persistent cases, audiometry and otologic referral are necessary. If patient is allergic to penicillin, erythromycin at 20mg/lb/day may be used. Trimethoprim sulfa may hold promise in the future. Tetracycline is never indicated in this age range because of side effects and high relapse rate secondary to resistant organisms. Patients above 6 years of age: Penicillin pheyoxymethyl 250 mg every six hours for ten days. Decongestant (if desired). Followup and penicillin allergy as above.

Adenoidectomy↗
PubMed1976

Ampicillin and an ester in experimental Hemophilus influenzae meningitis.

A new methoxymethyl ester of hetacillin is highly lipid-soluble, a property which was expected to enhance its penetration into the central nervous system (CNS). We compared the penetration of the ester and ampicillin into the cerebrospinal fluid (CSF) of normal rabbits and those with experimental Hemophilus influenzae meningitis. In normal rabbits treated by constant intravenous infusion, mean per cent penetration (see article) of the ester was four times as great as that of ampicillin (6.6 +/- 3.7% against 1.6 +/- 1.9%), and the difference in CSF drug levels attained was accentuated when bolus IV infusion was used. Drug concentration in brain tissue was three times as great in a rabbit treated with the ester (0.79 mug/gm against 0.26 mug/gm). In rabbits with meningitis, the ester again achieved higher CSF concentrations. Per cent penetration into CSF in infected rabbits was 23% for the ester and 13% for ampicillin. Bactericidal activity of the drugs was comparable; over 8 hr of treatment both drugs significantly reduced the CSF bacterial titers of infected animals. Our data demonstrated that the ester enters the CSF and CNS in higher concentration than ampicillin, with no loss in bactericidal activity.

Ampicillin↗