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Biomedical subjects

L R Freedman

Publications and source records attributed to L R Freedman.

14 recordsLinked to original sources
PubMed1992

Evaluation of new anti-infective drugs for the treatment of infective endocarditis. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines describe the design and implementation of clinical trials to assess the safety and efficacy of anti-infective drugs for the treatment of infective endocarditis. Identification and enrollment of patients in clinical trials is based on a modification of traditional criteria. To accrue a sufficient number of patients, only those with streptococcal or staphylococcal endocarditis should be included in studies. Results of treatment with approved drugs allow for projection of expected bacteriologic cure rates and survival rates. Prospective randomized, double-blind studies are recommended. These guidelines are based on the premise that future protocols may include shorter courses of therapy, combinations of drugs, or progression from parenteral to oral therapy. Clinical response is judged as cure, failure, or indeterminate; there is no "improved" category. Microbiologic response is categorized as eradication, persistence, or relapse. When a patient has shown no clinical evidence of active disease for a protracted period, there may be no need to perform a posttreatment blood culture; for such patients, the microbiologic response is termed presumptive eradication. Several months of follow-up may be necessary to detect late relapses.

Anti-Infective Agents↗
PubMed1991

Preclinical profile of the anticonvulsant remacemide and its enantiomers in the rat.

Studies conducted by Fisons Pharmaceuticals and the Antiepileptic Drug Development Program (ADD Program) of the Epilepsy Branch (NINDS, NIH) revealed that 'remacemide' (FPL 12924, formerly PR 934-423) was effective orally in the prevention of maximal electroshock seizures (MES) in rats. In this context (-)stereoisomer (FPL 14145) was of equal potency to the racemate (remacemide), while the (+)stereoisomer (FPL 14144) was 54% less potent. With respect to neurotoxicity, remacemide and its enantiomers possessed more favorable therapeutic indices than phenobarbital and valproate and less favorable indices than phenytoin and carbamazepine. The duration of protection of rats in the MES test at the ED50 or 3 x ED50 of remacemide and the (+)isomer was better or on par with the best reference compounds, phenytoin and phenobarbital. After subchronic administration of either the ED50 or the ED97 of remacemide, no tolerance developed in the hexobarbital sleep test, however, the activities of 3 hepatic microsomal enzymes were elevated. In naive rats high doses of remacemide or its (-)isomer and low doses of phenobarbital caused an increase in spontaneous motor activity. Alternatively, motor activity was depressed subsequent to high doses of phenobarbital and phenytoin. Remacemide was inactive against pentylenetetrazol and 'kindling' seizures. It was without effect in 5 electrophysiological tests (evoked responses, recurrent inhibition, long-term potentiation, penicillin-induced discharge rate and veratridine-induced depolarization) employing the in vitro hippocampal slice technique. Moreover, remacemide failed to demonstrate potent binding in vitro to neuronal L-glutamate, gamma-amino-butyrate A, adenosine A1, benzodiazepine, N-methyl-D-aspartate (strychnine-insensitive glycine and ion channel subsites) or muscarinic receptors. In conclusion, remacemide specifically prevents seizures elicited by MES, an action predicting utility in patients with generalized tonic/clonic convulsions.

Acetamides↗
PubMed1979

Experimental endocarditis: prophylaxis of Candida albicans infections by 5-fluorocytosine in rabbits.

The prevention of Candida endocarditis in the rabbit was easily accomplished with a single intramuscular injection of 75 mg of 5-FC (A predominantly fungistatic agent) per kg either 40 min before, or at the same time as, the intravenous challenge with Candida albicans. Renal infarcts were observed more often in rabbits with infected valvular vegetations than in control rabbits with sterile endocarditis. The prophylactic effect of 5-FC is greater in aortic vegetations than in the kidneys. This may be related to differences in the pathophysiology of infection and the pharmacokinetics of 5-FC in the two areas.

Animals↗
PubMed1979

Streptococcal infection of endocardial and other intravascular vegetations in rabbits: natural history and effect of dexamethasone.

Experiments were designed to study the natural history of infection in different parts of the vascular system. Sterile vegetations were produced in rabbits by placing catheters in the inferior vena cava, tricuspid or aortic valves, and thoracic or abdominal aorta and then were infected by the intravenous inoculation of Streptococcus sanguis. At 1 day after bacterial challenge, all VEGS were infected, mean bacterial densities being highest in the VEGS of the aortic and tricuspid valves. By 14 days, there was a significant decrease in the mean bacterial density in all VEGS except for the aortic valve: the VEGS of the inferior vena cava and abdominal aorta were sterile, as were half of those of the thoracic aorta. There were no deaths except for animals with aortic valve infection. Dexamethasone inhibited the sterilization of the thoracic aorta VEGS, but was without effect on aortic valve VEGS, 5 mm distant. Sterilization of tricuspid valve VEGS after catheter removal was also inhibited by dexamethasone. Thus, there are host defense mechanisms which lead to the sterilization of infections everywhere in the vascular system except in the left side of the heart, and these mechanisms, as yet undefined, are inhibited by dexamethasone.

Animals↗
PubMed1978

[Recent developments in the field of infectious diseases].

A résumé is presented of recent developments in the field of infectious diseases of particular interest of practising physicians. Examples are given to illustrate recent discoveries concerning the frequent misuse of antibiotics, the problem of infections developing in hospitalized patients, the biology of microbial infection, the etiology of well-known illnesses, new infectious diseases, and the development of vaccines. It is evident that the rate at which new and important information is evident that the rate at which new and important information is being reported demands particular effort in medical school teaching to ensure that students learn how to acquire and evaluate new information as well as how to discard ideas which are no longer valid.

Anti-Bacterial Agents↗
PubMed1978

[The role of prevention of infectious diseases in health maintenance].

The prophylaxis of infectious diseases is one of the triumphs of medical science. In examining the role and the responsibility of the physician in this activity the author emphasizes the importance of fundamental research (in the laboratory and the clinic), the need to employ prophylactic measures which are known to be effective, and, finally, the obligation of individual physicians and organized medicine to assume responsibility for problems which extend beyond their national boundaries. The encouragement of preventive medicine depends, among other factors, upon the development of a strong personal relationship between patient and physician. The current system for the remuneration of physicians hinders this relationship instead of promoting it.

Anti-Bacterial Agents↗
PubMed1975

[Proceedings: Experimental endocarditis. Experimental basis and prophylaxis].

A simple model has been developed for the production of bacterial endocarditis in rabbits. The principle depends on the insertion of a polyethylene catheter into the venous or arterial system so that the tip rests in the heart cavity in which endocarditis is to be established. After catheter placement, intravenous injection of any one of a variety of microorganisms regularly produces infective endocarditis. The characteristics of the infection in rabbits are similar to those observed in infective endocarditis in man. The production of streptococcus viridans infections in previously immunized animals leads to the development of diffuse glomerulonephritis. Translating antibiotic doses on a weight basis, prophylactic antibiotic treatment programs recommended in man have been shown to be ineffective in rabbits. If the activity of antibiotics in this model infection in rabbits can be assumed to be comparable to that in man, it is necessary that we reconsider the currently accepted recommendation for prophylaxis and treatment of infective endocarditis in man.

Animals↗
PubMed1975

Diffuse glomerulonephritis in rabbits with Streptococcus viridans endocarditis.

Intravenous administration of live microorganisms to rabitts with cardiac catheters produces an experimental model of infective endocarditis. Despite the development of infected valvular vegetations, positive blood cultures, splenomegaly, and focal embolic renallesions, glomerulonephritis has not been found in these animals. In the present study, acute diffuse proliferative glomerulonephritis, featuring endothelial and mesangial proliferation, capillary occlusion, and leukocytic infiltration was produced in rabbits immunized withthe infecting agent prior to the establishment of left sided alpha-streptococcal endocarditis. Controls receiving immunization alone, immunization and sterileendocarditis, or infective endocarditis alone did not develop diffuse glomerulonephritis. Electron microscopic findings of occasional subendothelial electron-dense deposits and immunofluorescence deposition of IgG and C3 in a peripheral granular capillary pattern were consistent with an immune complex type nephritis. Decreased serum complement levels were demonstrated in those animals developing diffuse glomerulonephritis, and some animals developed circulating rheumatoid factor. In view of the morphologic findings and the necessity of preimmunization for development of glomerular changes, it is concluded that immune mechanisms play a role in the diffuse glomerulonephritis associated with this model of infective endocarditis.

Animals↗