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Biomedical subjects

M A Sande

Publications and source records attributed to M A Sande.

At least 163 records · Page 9Linked to original sources
PubMed1982

Factors influencing the pathogenesis and prevention of infective endocarditis.

It seems appropriate in a symposium dedicated to the examination of septicemia, that one of the topics for discussion should be the examination of the factors which allow circulating bacteria to adhere to intracardiac or vascular endothelium. In the last 10-12 years our understanding of the pathogenesis of this disease has increased markedly. This can be attributed to a large extent to the development by Dr Freedman and hist colleagues at Yale of reproducible, simple, inexpensive animal model of infective endocarditis. The purpose of this discussion will by to summarize studies aimed at helping to explain why bacteria stick to cardiac valves, what forms the stimulus for vegetation propagation, and some new idea for possible prevention of this event.

Adhesiveness↗
PubMed1982

Cerebrospinal fluid prognostic indices in experimental pneumococcal meningitis.

The prognostic value of initial and sequential determinations of quantitative bacterial concentrations, leukocytes, glucose, lactate, lactic acid dehydrogenase, and creatine phosphokinase in CSF was examined in rabbits with experimental pneumococcal meningitis while they were receiving equivalent, rapidly bactericidal antibiotic therapy. The following mean CSF variables correlated with death due to meningitis: (1) an early (day 1) high bacterial titer and lactate concentration with simultaneous low leukocyte count and glucose level and (2) late (day 3) elevated lactate and lactic acid dehydrogenase levels and leukocyte count. A high concentration of bacteria inoculated into the CSF and a high plasma glucose level also adversely influenced prognosis. Careful analysis of these variables may identify high-risk patients with pneumococcal meningitis and ultimately may be useful in gauging the therapeutic response.

Animals↗
PubMed1981

A multivariate approach to prognostication in experimental bacterial meningitis.

Known concentrations of type III pneumococci were inoculated into eighty-one rabbits by cisternal puncture. Antibiotic therapy was started the following day. Aliquots of cerebrospinal fluid (CSF) and plasma were sampled on day one immediately before therapy was started and at regular intervals thereafter for up to eight days. Samples were analyzed for glucose, lactate, lactic dehydrogenase, and creatine kinase in various combinations. Leukocyte counts were performed on all CSF specimens. The timing of the specimens proved critical to the prognostic utility of the analyses performed. Day two plasma glucose was the most important single measurement for prognostication. Day one values for CSF glucose, lactate, and leukocyte count were also important. Substantial gains in prognostic accuracy were achieved when clinical laboratory measurements were used in combination by discriminant function analysis.

Animals↗
PubMed1981

Moxalactam and cefazolin: comparative pharmacokinetics in normal subjects.

Moxalactam, a new beta-lactam antibiotic with a wide in vitro spectrum of activity, was compared with cefazolin after intravenous and intramuscular administration of 1.0 g in a double-blind crossover design in 21 adult male subjects with normal renal function. Serum samples were obtained at 0.5, 1, 2, 3, 4, 6, 8, and 12 h, and urine was collected at 0 to 2, 2 to 4, 4 to 6, 6 to 8, and 8 to 12 h after dosing. Intravenous kinetics were described by a linear two-compartment model. For moxalactam, the drug clearance and volume of distribution were larger (115.2 versus 75.9 ml/min per 70 kg, P = 0.001, and 0.44 versus 0.19 liter/kg, P less than 0.001, respectively), and the t1/2beta was longer (3.47 versus 2.18 h, P = 0.01), with correspondingly smaller area under the curve (151 versus 236 h x mg/ml, P = 0.003) and lower serum concentration at 30 min (62 versus 106 micrograms/ml, P = 0.003) than cefazolin. Intramuscular kinetics were similar and were well described by a single-compartment model. Urinary recovery was essentially identical for both drugs: 55 to 75% in 8 h. Consistent departures from the two-compartment model for moxalactam (not noted for cefazolin) suggested enterohepatic recirculation of moxalactam. Both drugs were well tolerated, and no adverse reactions were noted.

Adult↗
PubMed1981

Pharmacokinetics of cefoperazone in normal volunteers and subjects with renal insufficiency.

We examined the pharmacokinetics of the new beta-lactam agent, cefoperazone, in normal and functionally anephric dialysis subjects with normal liver function. All subjects received 3 g of cefoperazone intravenously, and serial serum and urine samples were taken thereafter for up to 36 h. The serum levels, volume of distribution (0.22 liter/kg, normal; 0.19 liter/kg; dialysis), beta half-life (2.07 h, normal; 2.03 h, dialysis), and total body clearance (96.2 ml/min, normal; 92.9 ml/ min, dialysis) were all not significantly different between the two groups. Cefoperazone may be administered without adjustment of dose for any degree of renal dysfunction to patients with normal hepatic function.

Adult↗
PubMed1981

Bacterial adhesion in the pathogenesis of infective endocarditis. Effect of subinhibitory antibiotic concentrations on streptococcal adhesion in vitro and the development of endocarditis in rabbits.

Bacterial adhesion to the constituents of nonbacterial thrombotic endocarditis (NBTE) is important in the pathogenesis of endocarditis. Subinhibitory concentrations (subMIC) of some antibiotics decrease bacterial adhesion to epithelial cells in vitro. We utilized an in vitro assay system to study the effect of subMIC of various antibiotics on streptococcal adhesion to a fibrin-platelet matrix (simulating NBTE). The results were (a) bacterial adhesion of Streptococcus sanguis and Streptococcus faecalis to NBTE was significantly reduced by vancomycin, penicillin, tetracycline, chloramphenicol and streptomycin (P less than 0.01 vs. controls) but not rifampin or trimethoprimsulfametrole; (b) the effect was dose-dependent and increased with duration of exposure to antibiotic; (c) reduction in bacterial adhesion did not correlate with altered retention by hydrophobic-interaction chromatography. This reduction in adhesion correlated with a diminished capacity of subMIC exposed Streptococcus sanguis (1/4 vancomycin minimum inhibitory concentration (MIC) X 4 h) to produce endocarditis in vivo. After intravenous inoculation of 10(6) colony-forming units of preincubated organisms into rabbits with traumatized aortic valves, 6 of 22 developed endocarditis vs. 17 of 22 controls (P = 0.03). These results may be relevant to prophylaxis of endocarditis since exposure of bacteria to subMIC of various antibiotics may reduce bacterial adherence both, to mucosal surfaces, and to damaged cardiac valves.

Animals↗
PubMed1980

Multiple use of disposable insulin syringe-needle units.

Fourteen insulin-dependent diabetics were asked to use their insulin syringe-needle units three times in succession to determine the efficacy and safety of this practice. The mean duration of time each patient participated in the study was 20.4 weeks, and a total of 2,000 injections were taken. No signs of infections at the injection site were observed. Multiple use of disposable insulin syringe-needle units appears to be safe and cost beneficial.

Adult↗
PubMed1980

Experimental endocarditis in calf after tricuspid valve replacement.

A calf model for reproducible, prosthetic tricuspid valve endocarditis was developed using Staphylococcus aureus. The course of late prosthetic valve endocarditis was characterized as a fulminant disease when untreated with antibiotics. The earliest sign of a colonized valve prosthesis was an elevation of body temperature, which correlated with occurrence of positive blood cultures. The dose required to colonize an endothelialized tricuspid prosthetic valve in the calf model was 10(7) to 10(8) S. aureus organisms. In the model for late prosthetic valve endocarditis, silver-allantoin-heparin (SAH) treatment of the prosthetic valve gave no protection from inoculums of 10(8) S. aureus injected 60 days after operation. SAH treatment may be beneficial in early stages of prosthetic valve endocarditis, but this requires further study. Simultaneous cultures from the right atrium, the right ventricle, and the aorta of 2 animals showed that there was a 1,000- to 10,000-fold decrease in the bacterial titers across the combined pulmonary and systemic capillary beds. Bacterial titers drawn from the jugular vein had a 46% false negative result, and positive cultures from the external jugular vein showed only 1.3 S. aureus organisms per milliliter of blood. These bacteriological findings point out the risks of depending on sampling from the peripheral venous system when culturing for right heart endocarditis.

Allantoin↗
PubMed1980

Pharmacokinetics of moxalactam in subjects with various degrees of renal dysfunction.

We have examined the pharmacokinetics of moxalactam (LY127935) in 36 subjects with various degrees of renal dysfunction. Creatinine clearance (Ccr)/1.73 m2 ranged from zero to 135.8 ml/min. After a 1-g administration of moxalactam intravenously, the volume of distribution was 20.6 /+- 9.5 liters (0.28 liter/kg), and the mean half-life ranged from 3.1 h for subjects with Ccr greater than 65 ml/min to 19.3 h for subjects with Ccr less than 10 ml/min. The moxalactam clearance was closely correlated to Ccr (r = 0.93, P less than 0.0001) and excretion of antibiotic was 73.6 +/- 13% in normal subjects. Renal clearance accounted for 90% of moxalactam clearance in the normal subjects. A dosage schedule for administering moxalactam to patients with various degrees of renal dysfunction is provided.

Adolescent↗
PubMed1980

Detection of circulating antigen in experimental Candida albicans endocarditis by an enzyme-linked immunosorbent assay.

A double-antibody sandwich enzyme-linked immunosorbent assay was developed for the detection of circulating Candida albicans antigen during the course of experimental C. albicans endocarditis. The enzyme-linked immunosorbent assay was positive in 75% of rabbits with polyethylene catheter-induced experimental aortic valve C. albicans endocarditis but was negative in all controls, including catheterized animals that received intravenous Candida or catheterized but uninfected animals, and in rabbits with experimental fungal or bacterial endocarditis of other etiologies. The enzyme-linked immunosorbent assay was much more sensitive than blood culturing or fever determinations in experimental C. albicans endocarditis. This assay is more sensitive than currently available serological techniques, is highly specific, and deserves further study in the diagnosis of invasive, disseminated C. albicans infections, including endocarditis.

Animals↗
PubMed1980

Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone.

Acute bacterial meningitis may be associated with increased intracranial pressure, neurological sequelae such as communicating hydrocephalus, and a slow response to antibiotic therapy. Alterations in cerebrospinal hydrodynamics are at least partially responsible for these complications. Constant, low-flow short-duration manometric infusion studies through a hollow-bore pressure monitoring device in direct continuity with the supracortical subarachnoid space were performed in rabbits with experimental meningitis. Maximal resistance to cerebrospinal fluid (CSF) outflow from the subarachnoid to vascular space was markedly increaed in acute pneumococcal meningitis when compared to control, uninfected animals (6.77 +/- 3.52 vs. 0.26 +/- 0.04 mm Hg/microliter per min, P less than 0.001). Similar elevations (8.93 +/- 4.15 mm Hg/microliter per min were found in experimental Escherichia coli meningitis. Despite eradication of viable bacteria from the CSF by penicillin therapy during the acute stage of pneumococcal meningitis, resistance remained elevated (6.07 +/- 4.68 mm Hg/microliter per min) and had not returned to normal up to 15 d later. Administration of methylprednisolone during the early stages of acute pneumococcal meningitis reduced mean peak outflow resistance towards control values (0.59 mm Hg/microliter per min) and no "rebound" effect was apparent 24 h later. These hydrodynamic alterations in experimental meningitis prevent normal CSF absorption and decrease the ability of the bran to compensate for changes in intracranial volume and pressure.

Animals↗
PubMed1980

Combination antibiotic therapy of bacterial endocarditis.

A penicillin-aminoglycoside regimen is accepted therapy for enterococcal endocarditis, but use of combinations of antibiotics in other forms of bacterial endocarditis is controversial. This review analyzes in-vitro, experimental animal model, and clinical studies of combination "synergistic" antibiotic treatment for enterococcal, viridans streptococcal, staphylococcal, and gram-negative aerobic bacillary endocarditis. Current recommendations for treatment of these entities are discussed.

Aminoglycosides↗