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Biomedical subjects

E Rubinstein

Publications and source records attributed to E Rubinstein.

At least 109 records · Page 6Linked to original sources
PubMed1995

Severe necrotizing soft-tissue infections: report of 22 cases.

Twenty-two cases of severe necrotizing soft-tissue infections (SNSTIs), seen by the infectious disease service from 1983 to 1988 in a community teaching hospital, are described and compared with previously reported series. Clinical findings were distinguishable from cellulitis at the time of surgery in only 45% of the patients who had either necrosis, crepitus, vesicle or bullae, and/or an abnormal air pattern on x-ray studies. Patients with "cellulitis" were not less sick than patients with "necrosis" findings (ie, presence of shock, leukocytosis with left shift, fever, or anion gap). Despite the fact that all but one of the patients were seen by the infectious disease service preoperatively, and 55% underwent surgical intervention within 48 hours of admission, patient mortality (18%) was not better than some reported in earlier series. However, the epidemiology of SNSTI was different: in our series there were more diabetic patients (64%) and fewer postsurgical infections (14%). Among the diabetic patients, SNSTI developed more frequently at a site not related to peripheral vasculopathy or neuropathy. Abdominal wall involvement was 10 times more likely be diagnosed as cellulitis (5/8 vs 2/14 with involvement elsewhere, P < 0.02).

Adult↗
PubMed1994

CD9 antigen is an accessory subunit of the VLA integrin complexes.

The CD9 antigen is a cell surface glycoprotein of unknown function which belongs to the tetraspans family. We demonstrate here, by precipitation, Western blotting and co-capping experiments, that this molecule is associated with a large fraction of beta 1 integrins in two cell lines, the pre-B cell line NALM-6 and the megakaryocytic cell line HEL. In HEL cells, CD9 antigen is only associated with VLA-4. In contrast, in NALM-6 cells, CD9 antigen is associated with both VLA-4 and VLA-5. On the other hand, only the beta 1 chain is co-precipitated with the CD9 antigen in transfected L cells. These data show that the CD9 antigen is associated with the beta 1 chain rather than with a particular integrin. CD9 monoclonal antibodies (mAb) did not modify the binding of HEL and NALM-6 cells to fibronectin, laminin or collagen. The association of CD9 antigen to VLA integrins is strengthened by the fact that both CD9 and anti-VLA mAb induce aggregation of the two cell lines and inhibit their migration in Transwell chambers. Because the aggregating effect, but not the inhibition of migration, is observed in CEM or CD9-transfected CEM cells, these two effects are likely to be mediated by different mechanisms.

Amino Acid Sequence↗
PubMed1994

Treatment of severe infections caused by penicillin-resistant pneumococci. Role of third generation cephalosporins.

Penicillin resistance occurred soon after the discovery of penicillin, first in the test tube and subsequently in patients. The prevalence of invasive pneumococcal disease has been estimated to be as high as 15-18/100,000 in the elderly population and even higher in AIDS patients, children and the very old. While prevention with pneumococcal vaccine seems the most reasonable solution, under-utilization of the vaccine and an increase in the number of immuno-compromised individuals has limited the success of this approach. Streptococcus pneumoniae is conventionally classified as penicillin-susceptible (MIC < 0.125 mg/l), penicillin-intermediate (MIC 0.125-1.0 mg/l) and penicillin-resistant (MIC > or = 2 mg/l). In many countries, penicillin resistance in pneumococci is on the increase and in some areas penicillin intermediate and resistant isolates reach 60%. As a consequence, a switch of therapy from penicillin to other agents is mandatory in infections caused by penicillin-resistant strains. Benzyl-penicillin, however, can be used for most infections caused by penicillin-intermediate and all infections caused by penicillin-sensitive strains. Third generation cephalosporins, and in particular cefotaxime, are an optional alternative, particularly in view of their low MICs against penicillin-susceptible and -intermediate and some penicillin-resistant strains, and the easily achievable therapeutic concentrations in serum, pulmonary tissues and other compartments in which pneumococcal infections occur. Third generation cephalosporins have a high safety record and can be administered to children, pregnant women and the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefotaxime↗
PubMed1994

Human live anthrax vaccine in the former USSR.

The history of the development and use of the Soviet live spore human anthrax vaccine is described. Results of mass field trials on this vaccine following administration by scarification, by subcutaneous injection route or by aerosol exposure are presented. For the immunological assessment of these vaccinations a skin test with an original product 'Anthraxin' was used.

Anthrax↗
PubMed1994

How interleukin-2 can affect human fibroblasts behaviour.

The alpha and beta chains of the Interleukin 2 receptor (IL2R alpha and IL2R beta) were detected at the surface of cultured fibroblastic cells by flow cytometry, using monoclonal antibodies (mAbs) directed against the IL2R alpha and the IL2R beta. These cells bound FITC-IL2 and this binding was inhibited by an excess of cold ligand and by mAbs recognizing the IL2 binding sites of the alpha and beta chains. Internalisation studies show that the fibroblastic IL2R/IL2 complex is internalized at 37 degrees C. By Northern Blot analysis we detected the presence of specific transcripts for the IL2R alpha and IL2R beta genes. Finally, the addition of exogenous IL2 specifically modified the surface expression of different antigens involved in the process of immunosurveillance. Indeed, IL2, at concentrations affecting the high affinity IL2R, caused the down regulation of ICAM-1 protein. IL2 also decreased the surface expression of the class I and class II HLA. By contrast, the use of IL2 concentrations which saturate the intermediate affinity IL2R beta caused the up regulation of the surface expression of the ICAM-1 protein. ICAM-1 is the natural ligand for the LFA-1 integrin expressed at the surface of lymphoid cells. ICAM-1/LFA-1 interactions favour homotypic and heterotypic cell-cell adhesion. Since human fibroblasts express an LFA-1 like molecule, we propose that in these cells IL2 can modify homotypic and heterotypic interactions acting on the surface expression of ICAM-1 protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Line↗
PubMed1994

The intestinal elimination of ciprofloxacin in the rat.

The transepithelial intestinal elimination of ciprofloxacin was studied in a rat model. Two jejunal and one ileal segment, along with their intact blood supplies, were isolated and continuously perfused. Following a single parenteral administration of 25 mg/kg ciprofloxacin, the drug in amounts of 1.97 +/- 0.70, 1.88 +/- 0.99, and 1.44 +/- 0.77 micrograms/cm2 of mucosal surface was recovered over 90 min from the proximal and distal jejunal loops and the ileal loop, respectively, reaching a calculated fraction of 6%-7% of the dose eliminated in the entire small intestine. The rate of intestinal elimination related linearly to the parenteral dose. In the proximal jejunum, however, doses > 25 mg/kg were not accompanied by a concomitant increase in the eliminated fraction, suggesting a saturable transport process. Parenterally administered probenecid, amoxicillin, and nifedipine and changes ranging from 6.0 to 8.5 in the pH of the perfusates did not alter transepithelial elimination. This pathway of elimination of ciprofloxacin may play an important role in curing intestinal infections.

Amoxicillin↗
PubMed1994

Efficacy of combinations of doxycycline and rifampicin in the therapy of experimental mouse brucellosis.

Mice infected with Brucella melitensis were treated with doxycycline and rifampicin in daily dosages of: 1.5, 3 and 6 mg/kg separately and in combination, for a period of 14 days. Doxycycline alone in all dosages did not result in a cure rate superior to controls. A significant reduction in the viable count of B. melitensis recovered from the spleens of mice (which was the criterion for cure) was achieved with 6 and 3 mg/kg/day of doxycycline. Rifampicin at a dose of 6 mg/kg/day gave significantly better cure rates and reduction of mean viable counts of B. melitensis than untreated controls or doxycycline in similar doses. Low dose therapy with rifampicin (1.5 and 3 mg/kg) resulted in a further reduction in viable counts from spleens but with a cure rate no better than untreated animals. Rifampicin was more potent than doxycycline in all low dose regimens. When rifampicin was given in combination with doxycycline, the effect observed was similar to that of rifampicin alone. No synergy between rifampicin and doxycycline was demonstrable in the mouse model of brucellosis.

Animals↗
PubMed1994

The use of fluoroquinolones in neutropenic patients--analysis of adverse effects.

The fluoroquinolones have been extensively used in the neutropenic patient. When fluoroquinolone monotherapy was used as prophylaxis, frequently for extended periods, the rate of adverse effect of ciprofloxacin (6.9%) ofloxacin (11.6%) and norfloxacin (5.5%) were significantly lower than those of the comparator agents--co-trimoxazole, vancomycin and polymycin. Rash and gastrointestinal upset were the commonest adverse effects associated with the fluoroquinolones. When used as monotherapy for bacterial infections, often intravenously and in high dosages, the cumulative rate of adverse effects caused by the fluoroquinolones (12.6%) was similar to that caused by the comparator agents (10.3%), but significantly higher than reported for non-neutropenic patients (6.4%) and for prophylactic use. The main adverse events were also rashes (15.4%) and gastrointestinal upset (6.1%). When fluoroquinolones were used as therapy of bacterial infections in combination with other agents, the incidence of adverse events was 14.9%, which was similar to the comparator agents (13.5%). Adverse events were also similar except that nephrotoxicity was commonest with comparator combinations (4.0%). The data suggest that fluoroquinolone prophylaxis in neutropenic patients, even for prolonged periods, is safer than the comparator agents, but is associated with more frequent adverse events than in non-neutropenic patients. Fluoroquinolone therapy, frequently with high dosages, is associated with similar rate of adverse events as the comparator agents. When used in combination with the other antibiotics, fluoroquinolones are as safe as the comparator agents.

Animals↗
PubMed1994

Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental gram-negative infections in mice.

Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 polymyxin-susceptible strains tested more susceptible to novobiocin, lowering the MIC of novobiocin eightfold or more. The combination of polymyxin B nonapeptide with novobiocin or with erythromycin administered intraperitoneally in multiple doses synergistically protected mice infected with gram-negative bacteria. This combination may be clinically useful because of the apparent rarity of the acquisition of resistance.

Animals↗
PubMed1994

Intestinal elimination of ciprofloxacin in rabbits.

The intestinal transepithelial elimination of ciprofloxacin was studied in a rabbit model. Jejunal, ileal, and cecal segments along with their intact blood vessels were isolated and perfused, and their contents were collected over a 120-min period following administration of a single parenteral dose of 27 mg of ciprofloxacin per kg of body weight. The intestinal elimination rates of ciprofloxacin were 0.126 +/- 0.084, 0.235 +/- 0.22, and 0.11 +/- 0.084 micrograms.min-1.cm-2 for the jejunal, ileal, and cecal segments, respectively. The calculated fractions of ciprofloxacin eliminated were 3.3 mg from the jejunum and 13.8 mg from the ileum, representing 19% of the administered dose. Additional amounts of 2.5 to 3.7 mg or 4.9 to 7.3% of the administered dose were eliminated from the cecum. Elimination was probably not due to a passive diffusion process but rather due to an active transepithelial transport. This intestinal elimination pattern of ciprofloxacin may explain the unusual activity of the fluoroquinolones in modifying the intestinal flora.

Animals↗
PubMed1994

Surgical excision of meningiomas involving the clivus: preoperative and intraoperative features as predictors of postoperative functional deterioration.

Neurological deterioration is commonly seen after surgical excision of clival meningiomas; however, an understanding of the risk factors associated with postoperative deterioration can lead to improvements in outcome. In 75 patients with clival meningiomas operated on over a 7-year period, the following data were studied; preoperative variables such as presenting Karnofsky scale score, age, sex, and prior operations or radiation therapy. Radiological findings on magnetic resonance imaging or arteriography, such as the development of the arachnoidal cleavage plane between tumor and the brain stem, brainstem edema, tumor size, extent of compression on the brain stem, vascular encasement, and blood supply from the basilar artery were among other data studied. In addition, intraoperative findings such as development of the arachnoid plane, vascular encasement, and the difficulty of dissection were noted. Finally, each patient's neurological and functional statuses were recorded at 1 week postoperatively and at follow-up examinations. Early postoperative functional deterioration occurred in 45 patients (60%) and ranged from mild (30 patients) to severe (three patients). Significant improvement had occurred by the time of follow-up examination in all but four patients; however, permanent postoperative dysfunction was present in 12 patients. Statistical analysis revealed significant correlations between early functional deterioration and preoperative Karnofsky scale scores, male gender, radiological findings of the absence of an arachnoid plane, edema of the brain stem, and arteriographic supply from the basilar artery. Operative features included difficulty with dissection, an absent arachnoidal cleavage plane, and incomplete tumor resection. Permanent functional deterioration was statistically associated with the following: blood supply from the basilar artery, difficulty of dissection, incomplete tumor resection, and early postoperative dysfunction. Logistical regression analysis revealed that the most important risk factor for early postoperative deterioration was tumor size. Patients with large or giant tumors had a 6.7 to 13 times greater risk of functional deterioration, respectively, than patients with small- or medium-sized tumors. Excluding tumor size, the most important factor for permanent deterioration was blood supply from the basilar artery. Patients in this category had a 4.4 times greater risk of permanent functional deterioration. Three stages of tumor relationship to the brainstem arachnoid and pial membranes are proposed. Based on the results of this clinical study of clival meningiomas, suggestions are made for changes in the management strategy of these difficult lesions.

Adult↗
PubMed1994

[Post anthrax vaccine delayed hypersensitivity. II--delayed hypersensitivity in humans vaccinated against anthrax].

To detect cell immunity characterized by delayed postvaccination hypersensitivity to anthrax in man and assess its dynamics, vaccination using unencapsulated live anthrax vaccine was performed in 668 healthy volunteers. Vaccination was performed either by scarification (n = 172), subcutaneous injection (n = 202), or low-dose (n = 202) or high-dose (n = 83) inhalation. The anthraxin intradermal tests were performed in each patient at various times during the year following vaccination (D7, D15, D90, D180, D365). This study confirm that, regardless of the mode of administration, the vaccine induces cell-mediated immunity in man, as determined by positive anthraxine skin test. The incidence of positive tests decreases with time regardless of the mode of vaccination. After one year, the test remained positive in 34.8% of subjects vaccinated by subcutaneous injection, 37.5% vaccinated by low-dose inhalation, 34.2% vaccinated by high-dose inhalation, and 22.4% vaccinated by scarification. These findings are in agreement with those obtained in clinical epidemiological studies documenting the effectiveness of encapsulated live anthrax vaccine in man.

Administration, Inhalation↗
PubMed1994

[Delayed hypersensitivity after anthrax vaccination. I--Study of guinea pigs vaccinated against anthrax].

To evaluate delayed hypersensitivity after anthrax vaccination, an Anthraxin skin test was performed in 682 guinea pigs at various times after immunization with veterinary unencapsulated active anthrax vaccine. Results were compared with those obtained in unimmunized control guinea pigs (n = 216), in guinea pigs that received a non-immunizing dose of live vaccine (n = 183) and in guinea pigs inoculated with inactivated vaccine (n = 120). Anthraxin skin tests were positive in the first postvaccination days. The incidence and intensity of positive tests peaked between two weeks and one month after vaccination and then gradually decreased during the first year. Study of resistance of guinea pigs to an inoculum at a lethal dose of a virulent strain of Bacillus anthracis showed a close correlation between positive tests and resistance. These findings demonstrate development of cell-mediated immunity after anthrax vaccination. The Anthraxin skin test should have practical applications for the production of vaccines and for evaluation of the immune status of vaccinated livestock [corrected].

Animals↗
PubMed1994

Perioperative prophylactic cephazolin in spinal surgery. A double-blind placebo-controlled trial.

We investigated the efficacy of a single dose of 1 g of cephazolin in reducing postoperative infections in patients undergoing 'clean' operations on the lumbar spine. In a double-blind, randomised, trial there were 21 wound or urinary infections in the 71 patients who received placebo and nine in the 70 who received cephazolin (p < 0.05). Nine of the placebo patients (12.7%) developed wound infections (complicated by bacteraemia in two) compared with three (4.3%) in the cephazolin group (p = 0.07). Hospital stay was longer for infected patients than for non-infected patients (p < 0.05). Cephazolin-resistant pathogens were isolated more frequently from patients who received cephazolin than from those who received placebo.

Adolescent↗
PubMed1993

Molecular cloning of the mouse equivalent of CD9 antigen.

The CD9 antigen was originally described as a 24 kDa molecule present on B lineage-derived acute lymphoblastic leukemia cells and developing B-lymphocytes. However, platelets express a large amount of CD9 antigen and can be activated by CD9 antibodies. We report here the cloning and sequencing of a cDNA coding for the mouse CD9 antigen. There is 89% homology at amino acid level between the human and mouse CD9 molecules. Most of the differences (19 out of 24) are located in the large putative extracellular domain encoded by exons 5 and 6. CD9 antigen belongs to a new cell surface protein family which includes TAPA1 and the platelet activation antigen CD63. These proteins share common structural features with the CD9 antigen and a similar distribution of the evolutionarily variable region.

Amino Acid Sequence↗
PubMed1993

Human melanoma cells express a functional interleukin-2 receptor.

Flow cytometric analysis reveals that 5 human melanoma cell lines (M14, IGR3, ME1477, JUSO, GLL19) express both alpha and beta chain of the interleukin 2 receptor (IL-2R alpha and IL-2R beta). These chains are able to specifically bind IL-2 and to form high-affinity heterodimers (IL-2R alpha beta). Analysis of poly A+ RNAs by Northern blot reveals the presence of typical transcripts for both the IL-2R alpha gene (3.6 kb) and the IL-2R beta gene (4 kb). Reverse transcription/polymerase chain reaction analysis allowed transcripts for the IL2R gamma (p64) gene to be detected in 3 of these melanoma cell lines (M14, IGR3, ME 1477). Incubation with human recombinant IL-2 modifies in IL-2R alpha+beta+gamma+ (M14) the expression of several surface molecules: down-regulation of ICAM-1, HLA class I and HLA-DR and up-regulation of CD44. IL-2 is also active on IL-2 alpha+beta+gamma- cell lines since it decreases ICAM-1 and HLA class-II expression at the surface of JUSO cells. Down-regulation of ICAM-1, whose expression in melanoma cells is a marker of tumor progression, is detectable within 3 hr in M14 cells and is maximal after 48 hr incubation, at IL-2 concentrations corresponding to the high-affinity heterodimers. This feature is specific since it is partially inhibited by MAbs directed against the IL-2 binding site of the IL-2R alpha (MAR93, 10T14) and IL-2R beta (MiK beta 1, TU27) chains. Our data support the notion of a direct effect of IL-2 on human melanoma cells. Modulation of the expression of surface molecules which is important for the interaction with immunocompetent cells or for tumor progression, could have a role to play during in vivo IL-2 treatment of human melanomas.

Antigens, Neoplasm↗
PubMed1993

Treatment of acute bacterial diarrhea: a multicenter international trial comparing placebo with fleroxacin given as a single dose or once daily for 3 days.

This study was designed to test the efficacy of 400 mg fleroxacin given orally as a single dose or once daily for 3 days against acute bacterial diarrhea. A group of 508 adults with acute diarrhea were entered into a randomized, double-blind, placebo-controlled, multicenter trial. Patients were examined and asked about numbers of liquid stools daily for 3 days and at 5 days after start of treatment. Repeat stool samples were obtained for culture on days 3 and 5 after start of treatment. A total of 332 patients showed stool cultures positive for bacterial pathogens sensitive to fleroxacin and completed their treatments. Patients treated with fleroxacin, both single-dose and 3-day regimens, showed faster clinical improvement than did placebo-treated patients, as shown by earlier cessation of diarrhea (p < 0.001) and reduction in mean number of loose stools per day on days 2, 3, and 5 after start of therapy (p < 0.05). Bacteriologic efficacy was demonstrated by negative stool cultures for initial pathogens on days 3 and 5 after start of therapy in 94% of patients treated with single doses of fleroxacin and in 93% of patients treated with three doses of fleroxacin as compared with 57% of patients treated with placebo (p < 0.001). Patients with cholera, shigellosis, and infections due to Vibrio parahaemolyticus showed both clinical and bacteriologic responses to fleroxacin treatment, whereas patients with salmonellosis showed only bacteriologic responses. The good overall clinical and bacteriologic responses of most patients with acute bacterial diarrhea of fleroxacin indicate that this convenient single-dose therapy should be advantageous for empiric treatment of certain diarrheal illnesses.

Administration, Oral↗