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Biomedical subjects

E H Freimer

Publications and source records attributed to E H Freimer.

At least 19 recordsLinked to original sources
PubMed1992

Detection of antibiotic-induced platelet dysfunction in whole blood using flow cytometry.

Using flow cytometry and activation-dependent monoclonal antibodies, we have developed a technique based on forward angle-light scatter (FALS) and immunofluorescence that simultaneously detects human platelet activation, secretion, and aggregation in whole blood. To detect the effects of cefotetan and latamoxef, both of which contain an N-MTT side chain, and of free N-MTT and cefoxitin, which does not contain the N-MTT side chain, on platelet activation and secretion, platelets were stained by the indirect method using a murine-produced platelet specific activation-dependent monoclonal antibody, S12, and a goat anti-mouse IgG fluorescein-conjugated antibody. S12 binds to a 140kd alpha granule membrane protein (GMP-140) that is expressed during secretion. Single parameter, 256 channel, log integrated green fluorescence histograms were generated, and negative and positive fluorescent populations were defined. Latamoxef and cefotetan reduced the number of platelets expressing S12 by more than 43%. In contrast, cefoxitin reduced the number of platelets expressing S12 by only 13.5%. The inhibition of GMP-140 expression per platelet was calculated by converting the log data to linear fluorescence intensity. Latamoxef and cefotetan inhibited expression of GMP-140 by 88% and 87% respectively. Free N-MTT inhibited its expression by 68%. In contrast cefoxitin reduced GMP-140 expression per platelet by only 45%.

Adenosine Diphosphate↗
PubMed1988

Rupture of a pulmonary artery mycotic aneurysm associated with candidal endocarditis.

Candidal endocarditis can develop if candidemia occurs during Swan-Ganz catheterization. Candida endocarditis may persist for many months and is fatal unless the infected valve is resected. Herein is reported the first case of rupture of a mycotic pulmonary artery aneurysm caused by chronic candidal endocarditis. The endocarditis followed Swan-Ganz catheterization and aneurysm progressed despite appropriate medical and surgical therapy.

Amphotericin B↗
PubMed1988

Pharmacokinetics of imipenem-cilastatin in patients with renal insufficiency undergoing continuous ambulatory peritoneal dialysis.

In six patients with end-stage renal disease, a single bolus of imipenem-cilastatin (500 mg each) was given either intravenously or intraperitoneally in a randomized crossover protocol such that each patient received the drug by both routes at a 2- to 3-week interval. Drug levels in plasma and the peritoneal dialysis fluid were analyzed at frequent intervals, and various pharmacokinetic variables were calculated for a one-compartment open model. Data obtained in the present study suggest that while no significant difference in peak plasma levels or volume of distribution were noted, the following variables were significantly different for imipenem as compared with cilastatin: elimination half-life, total plasma clearance, area under the concentration-time curve, and percent drug excretion in the peritoneal dialysis fluid. The elimination half-life of imipenem (3.28 h) or cilastatin (8.84 h) in our patients was in the same range as observed in patients with minimal renal function undergoing hemodialysis. The dose of imipenem-cilastatin should be reduced appropriately in patients with end-stage renal disease undergoing peritoneal dialysis.

Cilastatin↗
PubMed1987

Cefotetan-induced disulfiram-type reactions and hypoprothrombinemia.

A double-blind, placebo-controlled study in eight healthy male volunteers was conducted to study possible disulfiram-type reactions and hypoprothrombinemia associated with cefotetan administration. Three doses of cefotetan (2 g) or of placebo were administered at 12-h intervals. Ethanol (0.5 g/kg of total body weight) was ingested 1 h after the third dose. Blood ethanol, serum acetaldehyde, and prothrombin times were measured throughout the study. Heart rate, blood pressure, and clinical signs as well as symptoms suggestive of a disulfiram-type reaction were also noted. Five of eight volunteers that received cefotetan showed significant flushing. A significant increase in heart rate also was noted. No change in mean arterial pressure was observed during the cefotetan phase, and no one experienced nausea or vomiting. No statistical differences were observed between phases with respect to ethanol area under the time-concentration curve, elimination rate, or serum acetaldehyde concentrations. A slight but statistically significant increase in prothrombin time also was observed with cefotetan. This study suggests that patients receiving cefotetan might be at risk to develop disulfiram-type reactions and hypoprothrombinemia.

Acetaldehyde↗
PubMed1985

Treatment of skin and soft tissue infections with imipenem/cilastatin.

Ninety-eight adult patients with skin and soft tissue infections caused by a variety of bacterial pathogens were treated with imipenem/cilastatin (71), cefazolin (21), or moxalactam (six) at three medical centers. Favorable clinical responses were observed in 87 of the 90 evaluable cases (97 percent). Most etiologic pathogens were eradicated during treatment including five of seven which demonstrated in vitro resistance to the therapeutic agent. Strains that persisted during treatment were not associated with therapeutic failure except in one cefazolin-treated patient who was infected with Bacteroides fragilis. All three drugs were well tolerated and no specific patterns of adverse reactions were observed.

Adult↗
PubMed1985

Pathogenesis and treatment of endocarditis.

The rabbit model has been invaluable for in vivo studies in the pathogenesis and treatment of bacterial endocarditis. Both of the features of the mature bacterial vegetations in this rabbit model, i.e., absence of phagocytosis and decreased metabolic activity, provide evidence to support the concept that a rapidly bactericidal antimicrobial agent provides the optimal approach to the successful treatment of endocarditis. Imipenem, a carbapenem with a very broad spectrum of in vitro activity, has been shown to be rapidly bactericidal in animals and highly effective in the treatment of experimental bacterial endocarditis. In addition, twenty-six patients with endocarditis, caused largely by Staphylococcus aureus, have been successfully treated with imipenem/cilastatin.

Animals↗
PubMed1985

Infectious antecedent of immunoblastic lymphoma. Progressive immunosuppression in a patient with lymphogranuloma venereum.

Angioimmunoblastic lymphadenopathy is a nonmalignant disease of unknown etiology often progressing to immunoblastic lymphoma. Immunologic deficiency is evident in these patients as well as in those with various infections found in association with the acquired immune deficiency syndrome (AIDS). This report describes a previously healthy young woman in whom angioimmunoblastic lymphadenopathy developed in association with lymphogranuloma venereum, with progressive loss of immunologic competence. This deterioration paralleled the evolution of angioimmunoblastic lymphadenopathy into a rapidly fatal immunoblastic lymphoma.

Adult↗
PubMed1985

Empirical use of imipenem as the sole antibiotic in the treatment of serious infections.

Seventy-three patients with eighty-five infections were treated with imipenem as the sole antimicrobial agent. Some of these infections were caused by pseudomonads and enterococci resistant to other cephalosporins. The vast majority of the Gram-positive and the Gram-negative bacteria that were isolated had a minimal inhibitory concentration (MIC) of less than 1 mg/l, and all MICs for initial isolates were below the levels of imipenem that were achieved in plasma and other body fluids with a dose of 500 mg every 6 h. The outcomes of 67 infectious episodes were satisfactory, four outcomes were failures and 14 were not evaluable. During the two years of this study, only a few strains of Staphylococcus epidermidis and of Pseudomonas aeruginosa emerged which were resistant to imipenem.

Adolescent↗
PubMed1979

Detection of protein A-like substances on haemolytic streptococci prior to use in mixed reverse passive antiglobulin haemagglutination (MRPAH).

Before mixed reverse passive antiglobulin haemagglutination tests (MRPAH) can be used to measure the class of bacterial antibodies, the bacteria have to be shown to be free of Protein A or Protein A-like substances on their surfaces. Two basic procedures have been examined: haemagglutination of red cells coated with immunoglobulin by the bacteria, and the MRPAH reaction itself to reveal absorption of purified gamma Fc by the bacterial suspension. The use of a purified gamma Fc component has proved successful in providing a sensitive test for the detection of Protein A-like substances on the surface of bacterial. In addition to both the Cowan and Wood strains of Staph, aureus, strains of haemolytic streptococci of groups A, C and G had Protein A-like substances on their surfaces. In contrast, strains of group B and group D, as well as Strep. milleri, had no detectable Protein A-like activity.

Absorption↗
PubMed1978

Oxolinic acid for the treatment of chronic gastrointestinal Shigella carriers.

Two patients were long-term gastrointestinal carriers of Shigella flexneri for 23 mo and 6 mo, respectively. Neither patient responded to oral antibiotics, despite in vitro sensitivity of the bacteria to the antibiotics administered. Oral oxolinic acid produced immediate cessation of the carrier state in both patients, with resolution of minor but persistent physical complaints.

Adult↗
PubMed1976

In vitro evaluation of the new oral cephalosporin cefatrizine: comparison with other cephalosporins.

Cefatrizine (BL-S640), a semisynthetic, orally administered cephalosporin, was found to have an in vitro spectrum of activity comparable to those of four other cephalosporins tested. It is as effective as cephalexin, the other orally administered cephalosporin evaluated, against most species, and it appears to be more effective than cephalexin against many Enterobacter, Haemophilus, and Proteus strains isolated in our hospital. It is not inactivated by the plasmid-determined beta-lactamases of 14 strains of ampicillin-resistant Salmonella typhimurium or the ampicillin resistance determinant of an H. influenza strain from the Center for Disease Control. No synergy was observed between cefatrizine and gentamicin, kanamycin, carbenicillin, or polymyxin when tested against selected strains.

Anti-Bacterial Agents↗
PubMed1976

Tetanus.

While the incidence of clinical tetanus had decreased greatly, efforts to eradicate the disease will depend mainly upon continued stress on prophylaxis. Recent cases demonstrate the need for both continued vigil in prophylaxis and sensitivity to the early signs of the clinical disease. The fundamentals of treatment are: neutralize formed toxin, eradicate Clostridium tetani, debride tissues adequately, control spasm and start immunization. Complications are legion. Mortality is highest in the very young and in the elderly.

Adult↗
PubMed1975

Cell-mediated immunity in systemic lupus erythematosus: alterations with advancing age.

Cell-mediated immunity (CMI) was tested in young patients with systemic lupus erythematosus (SLE) (mean age 30.9 years), in elderly patients with SLE (mean age 70.8 years), and in young and elderly control subjects. Pre-existing CMI as evaluated by skin test response to PPD and mumps antigens and the response of peripheral blood lymphocytes in culture to the mitogen phytohemagglutinin was not significantly different in thefour groups. However, the mean area of induration to Candida antigen was significantly less in both groups of elderly patients, suggesting a diminution of CMI with advancing age. Elderly control subjects and elderly patients with SLE had a significant decrease in incidence and severity of skin-test response when sensitized with 2-4-dinitrochlorobenzene (DNCB), suggesting that the capacity to respond to a new antigen is impaired in the elderly, with and without SLE. Young SLE patients were easily sensitized to DNCB and developed strong skin-test responses to Candida antigen suggesting normal CMI in the young SLE group. SLE is a milder disease in the elderly. If, as seems likely, cell-mediated immune injury is of importance in the pathogenesis of SLE, then these data are consistent with the possibility that an altered state of CMI in the elderly modifies the clinical expression of SLE.

Adult↗