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Biomedical subjects

D Baron

Publications and source records attributed to D Baron.

At least 19 recordsLinked to original sources

[Catalytic antibodies].

Catalytic antibodies (catabs) are currently produced by three different methods, by the generation of monoclonal antibodies against transition-state analogs of chemical reactions, by the gene technological establishment of a huge library of antigen binding sites, and by the transplantation of catalytic motifs into the antigen binding site. In addition, catabs can be further refined by chemical modification and in vitro mutagenesis. Disadvantages of the new technology are the mostly empirical production of catabs, the low affinity, and the slow turnover rate. Advantages are the immense variability of the antigen binding site and the potential of general applicability of the technology due to the conserved structure of the antigen binding site.

Animals

Identification of factors affecting in vivo aminoglycoside activity in an experimental model of gram-negative endocarditis.

Aminoglycoside bactericidal activity during the first 24 h of treatment probably is a determining parameter in the prognosis of severe gram-negative infections in immunocompromised patients. To identify the predictive factors involved in the definition of the best therapeutic regimen for Enterobacter cloacae and Serratia marcescens infections, we studied different gentamicin, tobramycin, and amikacin regimens by using an experimental model of rabbit endocarditis. Two factors appear to play an important role in predicting in vivo efficacy: (i) the level of in vivo bactericidal activity, which can differ widely from one aminoglycoside to another for the same bacterial strain and from one strain to another of the same species, and (ii) the critical serum drug concentration (CSC, in milligrams per liter), defined as the lowest serum antibiotic concentration capable of producing a significant CFU reduction (P less than 0.05) in endocarditis vegetations 24 h after the beginning of a continuous infusion. Stepwise regression analysis showed that for gentamicin and S. marcescens, the area under the concentration-time curve above the CSC and then the time above the CSC are the determining parameters for efficacy (R = 0.69; F = 13.5; P = 0.001), whereas for amikacin and S. marcescens, the time above the CSC and then the area under the concentration-time curve above the CSC predict efficacy (R = 0.74; F = 24.0; P = 0.0001). The lowest CSC is that of amikacin (about 8 mg/liter); those of gentamicin and tobramycin are about 15 mg/liter. In severe S. marcescens infections, intermittent amikacin dosing offers excellent bactericidal activity within the first 24 h.

Amikacin

[Peripheral erosive arthritis in pustulosis palmoplantaris. Apropos of 3 cases].

Three cases of pustulosis palmoplantaris with erosive arthritis are reported. There were two females (aged 53 and 59 years) and one male (aged 39 years). Skin lesions preceded joint lesions in every case (by 2 years, several weeks, and 1 year, respectively). Joints involved were one wrist in two patients and both hips in one patient. Inflammatory joint pain occurred concomitantly with an exacerbation of the skin disease. In two cases, an upper respiratory tract infection preceded the joint manifestations by a few days. Synovial fluid from affected joints was obtained in all three cases and found to be sterile. In the two patients who had histologic studies of skin lesion biopsy specimens, unilocular non-spongiform lesions suggestive of nonpsoriasic disease were found. Erythrocyte sedimentation rate and C-reactive protein levels were raised in every case. HLA groups were [A2, A19, B12, B27], [A2, A9, B12, B19, B27, Dr4, Dr6], and [A2, A19, B12, B13, Dr7, Dr8]. All three patients were given a nonsteroidal antiinflammatory agent. Despite this therapy, destruction of the wrist occurred in both females and bilateral hip destruction required bilateral total hip replacement in the male. The rapidity with which joint destruction occurred suggested infectious disease, especially due to a saprophytic organism. Virtually all previously reported pustulosis palmoplantaris patients with bone and joint manifestations had arthralgia or non-destructive arthritis in appendicular joints, whereas bone and joint destruction has been described in axial structures.

Adult

[Post-traumatic osteoid osteoma. Apropos of 2 cases and review of the literature].

Two cases of osteoid osteoma which became clinically apparent after a prolonged silent period are reported. One was located in the tibia in a 30-year-old female and the other in the femur in a 26-year-old male. Both developed after a surgical procedure, at the site of the operation; one was located on the track of an internal fixation screw. Diagnosis was delayed despite the suggestive timing of the pain; isotopic scanning, CT scan and angiography provided suggestive data and diagnosis was confirmed by histologic studies. A review of the literature found 13 other cases meeting the following criteria: initial trauma, silent period, suggestive pain, discovery of an osteoid osteoma at the site of the trauma, and recovery following surgical treatment. The role of the trauma is discussed.

Adult

[Systemic urticaria, sclerosing osteopathy, monoclonal gammopathy (Schnitzler syndrome). Apropos of a case].

A 65 years old man has been suffering from the upper limbs and legs for 2 years. Bone pain was associated with a non pruritic chronic urticaria and fever. Bone scintigraphy showed lesions of the lower limbs. X rays showed only one sclerotic bone lesion. Immunoelectrophoretic analysis showed an IgM kappa monoclonal gammapathy. Bone marrow aspirate and bone marrow biopsy were normal. The association of chronic urticaria, bone pain and macroglobulinemia has been first reported by L. Schnitzler. Seventeen other cases have been reported in the literature. The pathogenesis of the syndrome is unknown although anti-interleukin 1 alpha autoantibodies were found in several cases (8 out of 13).

Aged

Pharmacokinetics of norfloxacin in the elderly.

9 elderly and 9 younger adult patients, with proven post-operative lower urinary tract infection were treated with 400 mg of norfloxacin twice daily for 5 days. Pharmacokinetics of norfloxacin were measured on days 1 and 5. Compared to the younger adult patients, the elderly showed a decreased creatinine clearance and, following the last dose on day 5, an increased maximum plasma concentration of norfloxacin, an increased area under the concentration-time curve and a decreased total body clearance of norfloxacin. These results confirm that in elderly, as in younger adult patients, the pharmacokinetics of norfloxacin can be described by a linear model and accumulation of the drug during repetitive multiple doses is predictable. The differences between the two groups cannot be considered as clinically significant so that no dose change would be required in elderly patients within the range of creatinine clearance studied.

Age Factors

Impact of dosage schedule on the efficacy of gentamicin, tobramycin, or amikacin in an experimental model of Serratia marcescens endocarditis: in vitro-in vivo correlation.

Aminoglycosides are usually considered to be concentration-dependent antibiotics and to have similar pharmacodynamic and pharmacokinetic properties. To verify the equivalent activity of the aminoglycosides on a susceptible strain, we tested the killing rate of three aminoglycosides (gentamicin, tobramycin, and amikacin) on one strain of Serratia marcescens both in vitro and in vivo by using a rabbit model of left-ventricle endocarditis. Despite, similar MICs, the time-kill curve of gentamicin was consistently better than those of amikacin and tobramycin, whatever the concentration of each antibiotic used (1, 2, 4, 8, 16, or 32 mg/liter), after a 5-h incubation. The in vivo bacterial reduction in the vegetations was measured 24 h after administration of an intravenous 48-mg/kg bolus of each antibiotic or at the end of a 24-h continuous intravenous infusion of the same dose. Gentamicin was significantly more effective when administered as a bolus than when administered as a continuous infusion (2.8 +/- 0.2 versus 6.4 +/- 1.5 log10 CFU/g of vegetation, respectively; P less than 0.01), whereas amikacin was more effective as a continuous infusion than as a bolus injection (3.6 +/- 2.0 versus 7.5 +/- 1.3 log10 CFU/g of vegetation, respectively; P less than 0.01). Tobramycin was not very effective, whatever the dosage tested (approximately 6.5 to 7 log10 CFU/g). These results suggest that concentration-dependent bactericidal activities, both in vitro and in vivo, may vary greatly among aminoglycosides despite similar MICs.

Amikacin

Washed human platelets prevent ischemia-reperfusion edema in isolated rabbit lungs.

Washed human platelets prevent edema formation in isolated rabbit lungs infused with xanthine oxidase, an enzyme that injures endothelial membranes by generating extracellular oxidants. We hypothesized that platelets would similarly preserve membrane permeability in isolated lungs exposed to ischemia-reperfusion injury, a model that perturbs endothelial cells by the generation of intracellular oxidants. Isolated perfused rabbit lungs (IPL) were exposed to warm ischemia-reperfusion to cause lung edema. The infusion of washed human platelets (1.05 +/- 0.02 x 10(10) cells) prevented edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, histological edema, and preservation of paraendothelial cell tight junctions. Inhibition of the platelet glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, dehydroepiandrosterone, or 1-chloro-2,4-dinitrobenzene interfered with platelet protective effects. In contrast, inhibition of platelet catalase with aminotriazole and H2O2 had no effect on platelet protection. Lung tissue malonyldialdehyde concentrations were similar in isolated lungs exposed to ischemia-reperfusion with or without the infusion of platelets. These results indicate that platelet attenuation of ischemia-reperfusion lung edema depends on platelet glutathione redox cycle antioxidants but not platelet catalase.

Animals

Group psychotherapy for HIV-seropositive patients with major depression.

Patients were recruited from the UCLA AIDS Research Center who had previously been referred to psychiatry for participation in an open-label pilot treating patients with major depression with fluoxetine. They chose to participate in group therapy for continuing distress in coping with their HIV-seropositive status, dissolution of their support system, "accepting patienthood," and on being placed on an experimental medical protocol. The group was a closed, twenty-session, homogeneous (for patient characteristics), psychoeducational, supportive, and cognitively oriented psychotherapy group. We found this to be a successful intervention in helping patients manage HIV illness and in providing the coping skills and social support necessary to function at home, work, and in their interaction with their health care providers.

AIDS-Related Complex

[Fixation of Indium111-labeled antifibrin monoclonal antibody on the vegetation in endocarditis: evaluation in a rabbit model].

The uptake of a 111In labelled antifibrin antibody was studied in left ventricle endocarditis on a rabbit model. The immunospecificity of the antibody for the cardiac vegetations is favorable, exhibiting an uptake at least 4 times that of blood, or myocardium. A planar scintigraphy of the opened left ventricle showed a radionuclide imaging of vegetations, according to anatomical lesions. The use of antifibrin monoclonal antibodies could prove helpful to improve the specificity of valvular lesions visualized by echocardiography, or to detect the small vegetations at the early stage of acute endocarditis.

Animals

Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease.

The potential advantage of using 111In-antifibrin (111In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before 111In-AF injection). All patients had contrast venography (considered as the gold standard) and 111In-AF scintigraphy within 24 hr. Two to 3 mCi of 111In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of 111In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive 111In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of 111In-AF for diagnosing DVT.

Antibodies, Monoclonal

[Industrial production of monoclonal antibodies].

Murine monoclonal antibodies (mabs) are produced in either mouse ascites or bioreactors (spinner culture, stirred-tank reactor, airlift reactor, hollow-fiber reactor). Human mabs are produced solely in bioreactors. Encapsulation represents a special technology. Hybridoma cells have to be adapted prior to growth in bioreactors. Of crucial importance is the construction of over-producing cell lines by cell- and gene-technological methods. Manipulated cell lines often produce modified mabs.

Animals

[Monoclonal antibodies and mediators--immunologic tumor therapy].

Immunological tumor therapy includes the use of interferons, interleukins, tumor necrosis factor, and monoclonal antibodies. Clinical tests performed on about 20 types of solid tumors and 10 types of leukemias and lymphomas showed rather limited success. In many cases the side effects are considerable, resulting in the interruption or cessation of therapy. Improvements can be achieved by gene technology. Only the interferons have been approved as official drugs to treat cancer.

Antibodies, Monoclonal

[Study of incidence and risk factors of nosocomial urinary tract infection in patients with indwelling urinary catheter in intensive care units].

A prospective study was carried out in a medical and surgical ICU to determine the incidence of nosocomial urinary tract infection (NUTI) and to identify the most important risk factors. Over a 6 month period, 180 patients were included. All had an indwelling catheter. Six risk factors were studied: age, sex, illness (medical, surgical, trauma), hospital or extra-hospital origin, simplified acute physiology score and length of bladder catheterization. Forty three patients developed a NUTI. Length of bladder catheterization was the only significant different risk factor in infected and non-infected patients. Kaplan Meir analysis was used to determine time to development of NUTI. The risk rose from 19% for 5 day long catheterization to 50% for 14 day long catheterization.

Adult

Pharmacokinetics of teicoplanin in burn patients.

The pharmacokinetics of teicoplanin were studied in 21 adult burn patients and in 5 healthy controls. All subjects were given a single dose of teicoplanin, 10 mg/kg i.v. The pharmacokinetic parameters of teicoplanin were calculated using a tri-exponential model. Three parameters were investigated--burn surface area, creatinine clearance and time of administration after injury (3 days, 8-10 days and 15-20 days respectively). The elimination half-life was not significantly different between the control group (47 +/- 6 hours), the group with a burn surface area greater than 40% (64 +/- 38 hours), and the group with a burn surface area of 25-30% (44 +/- 15 hours). Trough serum concentrations at 12 hours were consistently less than 8 mg/l in all groups. There was some degree of correlation between creatinine clearance and renal clearance of teicoplanin (p = 0.03; r = 0.44). However, there was no correlation between burn surface area and creatinine clearance, or between the time of administration and creatinine clearance. Non-renal clearance of teicoplanin was unaffected by a large burn surface area. The conclusions from this study are as follows. Burn surface area and time of administration after injury are not predictive factors for the determination of an appropriate dose regimen. Trough serum concentrations at 12 hours emphasize the need for a further intravenous bolus. Burn patients with a high creatinine clearance (greater than 140 ml/min) should be carefully monitored.

Adult

[Comparative study of two protocols of antibiotic prophylaxis in endoscopic urologic surgery].

We report an open, prospective, randomized and double-blind study which compared two groups of patients without preoperative bacteriuria, undergoing transurethral urologic surgery. A first group received cefazoline 3 g perioperatively and a second group a single preoperative dose of cefotiam 1 g. A hundred patients were included in each group which were well matched on all essential characteristics, risk factors, surgery, anesthesia and postoperative temperature. The incidence of postoperative infection (bacteriemia and bacteriuria) was the same in both groups (16%). It is concluded that in transurethral urologic surgery performed in patients without preoperative bacteriuria, 1 preoperative dose cefotiam is as efficacious as 3 perioperative doses cefazoline.

Aged