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Biomedical subjects

D Baron

Publications and source records attributed to D Baron.

At least 73 records · Page 4Linked to original sources
PubMed1994

Pharmacokinetics, toxicity, and efficacy of liposomal capreomycin in disseminated Mycobacterium avium beige mouse model.

Capreomycin was incorporated into multilamellar vesicles of pure dipalmitoylphosphatidylcholine. The pharmacokinetics and nephrotoxicity of capreomycin in the free and liposomal forms were studied in normal mice. The efficacies of the two forms were evaluated by using the Mycobacterium avium complex beige mouse model. Approximately 10(7) viable M. avium cells were injected intravenously. Seven days later, treatment with either liposomal or free capreomycin at 60 or 120 mg/kg of body weight was administered daily for 5 days. Mice were sacrificed 5 days after the end of treatment, and the viable bacteria in liver, spleen, lungs, and blood were counted. After 5 days of treatment with dosages of 60 or 120 mg/kg/day, the level of blood urea nitrogen increased in the group treated with free capreomycin but not in the group treated with liposomal capreomycin. After intravenous injection of 120 mg/kg, liposomes enhanced the diffusion of capreomycin in the spleen, lungs, and kidneys and increased the half-life in serum. The 120-mg/kg dose of liposomal capreomycin significantly reduced the number of viable mycobacteria in the liver, spleen, and blood compared with those in the controls. Although these results are promising, further studies are needed to assess the efficacy of liposomal capreomycin for the treatment of M. avium complex infections.

Animals↗
PubMed1994

[Hemiplegia and contralateral multiple aseptic osteonecrosis].

A patient who received treatment for acute myelogenous leukemia (chemotherapy, irradiation, corticosteroid therapy) developed cerebral radionecrosis with hemiplegia (treated by corticosteroids) then multiple foci of osteonecrosis on the nonparalyzed side. The mechanisms which may have prevented osteonecrosis from occurring on the side of the hemiplegia are discussed.

Adult↗
PubMed1993

[Acute ethyl alcohol intoxication].

Excessive intake of ethyl alcohol leads to acute intoxication and necessitates the same management as other forms of intoxication. Diagnosis is based on clinical examination, medical history and course. Determination of alcohol level in the expired air is of limited interest. If low or absent, it should direct clinical investigation toward a disorder having similar symptoms; if high, it does not necessarily explain the clinical picture. The severity of the intoxication must always be assessed carefully. Severity is linked either to a complication of acute alcohol intoxication (coma, inhalation, pneumopathy), or to an associated disorder, observed in 50% of the patients (cranial trauma, drug intoxication). Means of treatment and patient management are simple and well established.

Alcoholic Intoxication↗
PubMed1993

Folding trends in a flexible peptide: two-dimensional NMR study of deltorphin-I, a delta selective opioid heptapeptide.

Deltorphin-I, H-Tyr-(D)ala-Phe-Asp-Val-Val-Gly-NH2 and dermenkephalin, H-Tyr-(D)met-Phe-His-Leu-Met-Asp-NH2 are 2 members of small but growing family of D-amino acid containing opioid peptides isolated from the frog skin. Both peptides exhibit high affinity and selectivity for the delta-opioid receptor. Two-dimensional NMR study of deltorphin-I in DMSO-d6 revealed a close conformational homology with dermenkephalin. However, the temperature dependency of NOE correlations issued from Val5 and Val6 of deltorphin-I reflects a high intrinsic flexibility of the carboxyend. Whereas most of the JN alpha coupling constants and interresidue alpha N NOE effects were compatible with an extended structure, some sequential NOEs together with several medium and long range correlations involving Tyr1, Val6 and Asp4 may reflect an equilibrium mixture of extended and folded conformers in which the C- and the N-terminal parts of deltorphin-I are in close proximity. Finally, g- is the preferential conformer in the side chain of Phe3 in both deltorphin-I and dermenkephalin.

Amino Acid Sequence↗
PubMed1993

Quantitative two-dimensional NMR study of dermenkephalin, a highly potent and selective delta-opioid peptide.

Dermenkephalin, H-Tyr-(D)Met-Phe-His-Leu-Met-Asp-NH2, a highly potent and selective delta-opioid peptide isolated from frog skin, was studied in DMSO-d6 solution by two-dimensional nmr spectroscopy, including the determination of NH temperature coefficients, the evaluation of 3J coupling constants from phase-sensitive correlated spectroscopy (COSY) and the volumes of nuclear Overhauser effect (NOE) correlations. The two-dimensional NOE spectroscopy (NOESY) spectrum of dermenkephalin revealed sequential, medium-, and long-range effects. To put this information on a quantitative basis, special attention was devoted to J cross-peak suppression, quantification of the NOE volumes and analysis of the overlaps, normalization of the NOEs against diagonal peaks and H beta beta' geminal interactions. Although most of the dihedral angles deduced from the 3JN alpha coupling constants together with several Ni alpha i and alpha iNi+1 NOEs pointed to a partially extended peptide backbone, several NiNi+1 NOEs and beta iNi+1 interactions argued in favor of a folded structure. Moreover, several long-range correlations of strong intensities were found that supported a close spatial proximity between the side chains of D-Met2 and Met6, Tyr1 and His4, Tyr1 and Asp7, and His4 and the C-terminal amide group. In Phe, the g- rotamer in the side chain is deduced from the 3J alpha beta coupling constants and alpha beta and N beta NOE correlations. Whereas the amide proton dependency was not indicative of stable hydrogen bonds, the nonuniform values of the temperature coefficient may reflect an equilibrium mixture of folded and extended conformers. The overall data should provide realistic starting models for energy minimization and modelization studies.

Amino Acid Sequence↗
PubMed1993

Detection of lung and bone infection with anti-granulocyte monoclonal antibody BW 250/183 radiolabelled with 99Tcm.

Twenty-four patients with suspected infection (eight bone, 16 lung) were studied using monoclonal antibody BW250/183 which recognizes epitopes present on the surface of granulocytes. Bronchofibroscopic samples (microbiological studies and alveolar cell counts) were obtained from 14/16 patients with lung disease. Bronchofibroscopy isolated a micro-organism nine times. In two other cases, the diagnosis of infection was based on clinical course data. Infection was confirmed by surgical biopsy in the eight patients with bone pathology. Scans were performed 2 and 24 h after injection of 1 mg BW 250/183 labelled with 99Tcm. For lung disease, immunoscintigraphy was positive six times (five true positive, one false positive) and negative 10 times (six false negative, four true negative). Immunoscintigraphy was false negative when the lung infection was not systematized or no granulocytes were mobilized in the infectious site. Immunoscintigraphy was falsely positive when noninfectious lung disease mobilized granulocytes. It was positive in all patients with bone infection. Images recorded at 24 h had better sensitivity (five false negative) than those at 2 h (eight false negative).

Bone Diseases↗
PubMed1993

Lung distribution and pharmacokinetics of aerosolized tobramycin.

Aminoglycosides are commonly used in the treatment of nosocomial pneumonia in association with beta-lactams. Unfortunately, penetration of intravenously administered aminoglycosides into the lung tissue remains low. In animal models, aerosolization of these drugs provides high lung concentrations and low serum levels. Three-hundred milligrams of tobramycin and 1 ml of 99mTc-DTPA were administered via a pneumatic nebulizer to five healthy volunteers and to five mechanically ventilated patients. Lung scintigraphy was then performed, and plasma and urine pharmacokinetics were studied. In a second group of patients undergoing thoracic surgery, 300 mg of tobramycin alone were administered in the same way; a fragment of healthy lung was then removed, and tobramycin was measured. In the first group, the scintigraphy showed radioactivity distribution in the whole lungs both in healthy volunteers and in ventilated patients. Urine samples contained 5.5% of the initial amount of tobramycin. The mean serum half-life of tobramycin was 8.96 h in healthy volunteers and 11.23 h in ventilated patients. In the second group, mean lung tissue concentrations were 5.5 and 3.61 micrograms/g, respectively, 4 and 12 h after nebulization, respectively. Aerosolization of tobramycin thus produced high lung concentrations and low serum levels.

Aerosols↗
PubMed1993

[Osteoporosis during pregnancy. 4 cases].

Osteoporosis of pregnancy is an infrequent condition of unclear pathogenesis. We report four new cases. Mean age of patients was 28 years; diffuse bone loss was seen on pre-pregnancy roentgenograms in two patients. Two patients were primiparas. In all four cases, acute spinal pain led to the discovery of vertebral crush fractures and diffuse osteopenia predominating in the spine and pelvis. Urinary calcium was low in one case. Our cases and a review of the literature demonstrate that diffuse osteopenia exists prior to the pregnancy and becomes symptomatic during childbearing as a result of additional mechanical stresses with or without concomitant vitamin D deficiency and/or heparin therapy.

Adult↗
PubMed1993

[Inflammatory Gorham disease].

The case of a 48-year old female with massive osteolysis since the age of 13 years is reported. She had inflammatory flares which resolved spontaneously or after a transient discharge of lymph.

Female↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1992

[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↗