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Biomedical subjects

E Rubinstein

Publications and source records attributed to E Rubinstein.

At least 163 records · Page 9Linked to original sources

Kaposi's sarcoma in immunosuppression. Possibly the result of a dual viral infection.

Kaposi's sarcoma of the gingiva and skin developed in an HIV-negative renal transplant patient while he was receiving cyclosporine therapy. The Kaposi's sarcoma developed shortly after the patient had an acute infection with cytomegalovirus (CMV). Electron microscopy of the tumor's established cell line showed two types of virus-like particles. CMV DNA was identifiable in the cell line whereas infectious CMV could be isolated only after repeated passages (only after 3 months of culture). The other virus could not be identified, but did not appear to be either HIV or papilloma virus. The patient's tumor regressed after the discontinuation of cyclosporine therapy and the recovery from the acute CMV infection.

Adult↗

Pefloxacin efficacy in gram-negative bacillary meningitis.

Sixteen patients with acute meningitis caused by Gram-negative bacteria were treated with pefloxacin intravenously. The age range of the patient group was six months to 85 years with a mean age of 40 years; three patients were children. In all but two patients meningitis was a complication of neurosurgical operations and fourteen of the sixteen had received prior therapy which was not successful. The causative organisms were: Pseudomonas aeruginosa (5), Acinetobacter calcoaceticus (4), Klebsiella pneumoniae (3), Enterobacter cloacae (2), Citrobacter diversus (1) and Salmonella group C (1). Pefloxacin was administered intravenously 800 mg twice a day to the adult patients (mean dosage of 21( +/- 6.7) mg/kg body weight) for a mean period ( +/- S.D.) of 11( +/- 4) days. The mean cerebrospinal fluid concentration of pefloxacin was 8.8( +/- 5.0) mg/l which was 54% of the mean peak serum concentration (16.3( +/- 8.8]. The mean MIC and MBC of the causative organisms were 1.1( +/- 1.2) mg/l and 1.64( +/- 1.2) mg/l. Thirteen patients (87%) were cured or clinically improved and twelve (80%) were bacteriologically cured. One patient failed, another patient had reinfection and one was not assessable. No side effects were observed. In the present study pefloxacin offered an efficacious and safe treatment of Gram-negative meningitis following failure of other antibiotic therapy.

Adolescent↗

Pefloxacin versus ceftazidime in therapy of soft tissue infections in compromised patients.

Soft tissue infections in compromised patients are frequently caused by Gram-negative organisms and particularly by Pseudomonas aeruginosa. These pathogens are effectively eradicated by pefloxacin as well as by ceftazidime. The effectiveness and safety of these two agents were compared in a prospective randomized study in 67 patients with soft tissue infections. Underlying conditions included malignant diseases, diabetes mellitus and chronic renal failure. The infections included: post operative infection, septic foot, soft tissue abscess and cellulitis. Thirty-three patients were treated with intravenous ceftazidime for a mean duration of ten days. More than half the 34 patients given pefloxacin were treated only orally for a mean period of 13 days. The clinical and bacteriological outcomes were similar in both groups. There was clinical cure or improvement in 26 pefloxacin cases and in 23 ceftazidime cases, failure in six pefloxacin cases and in seven ceftazidime and relapse in two pefloxacin and in three ceftazidime patients. The bacteriological responses were eradication in 23 pefloxacin cases and in 22 ceftazidime cases, persistence in five pefloxacin cases and in six ceftazidime cases, relapse in one pefloxacin case and in none of the ceftazidime group, reinfection in four pefloxacin cases and in three ceftazidime cases and there was one unassessed patient in the pefloxacin group and two in the ceftazidime group. Nausea and vomiting occurred in three patients and elevation of liver enzymes in another patient; all side effects were observed only in the pefloxacin treated patients. These results suggest that oral pefloxacin could offer an alternative to intravenous ceftazidime in half the compromised patients with tissue infections. However, adverse reactions due to pefloxacin administration should be watched for during such therapy.

Administration, Oral↗

Ofloxacin and the gastrointestinal tract: a potential role in the treatment of bacterial enteritis.

Ofloxacin is highly active against most pathogens causing bacterial enteritis. High faecal levels are achieved readily following a single oral dose and may persist for up to five days despite partial binding by faeces. In addition, adequate ofloxacin levels persist in pancreatic secretions and bile for 12 to 14 h following oral administration. Clinical data from various centres demonstrate a prompt response when ofloxacin is administered once-daily for shigellosis, salmonellosis and various other enteric pathogens. These theoretical observations and clinical data suggest a potential for once-daily oral ofloxacin therapy for bacterial diarrhoea.

Administration, Oral↗

Relapse of rickettsial Mediterranean spotted fever and murine typhus after treatment with chloramphenicol.

In the years 1975-1984, 132 patients with rickettsial Mediterranean spotted fever and murine typhus were treated with chloramphenicol or tetracycline. Among the 24 patients who received chloramphenicol ten relapsed and one failed to respond at all. None of the 108 recipients of tetracycline suffered a relapse. It appears that tetracycline should serve as first-line therapy in several rickettsial diseases.

Chloramphenicol↗

The effect of ciprofloxacin and pefloxacin on bone marrow engraftment in the spleen of mice.

In order to investigate the in-vivo effect of ciprofloxacin and pefloxacin on bone marrow engraftment in mice, irradiated mice were transplanted with bone marrow graft (5 x 10(5) cells/mouse) obtained from syngeneic mice. Three groups of mice (30 mice in each) received a bone marrow graft incubated for 1 h with ciprofloxacin at concentrations of 0.5, 5 and 50 mg/l. Six additional groups (30 mice in each) were treated twice daily after transplantation with intra-peritoneal injections of ciprofloxacin in dosages of 25, 50 and 100 mg/kg/24 h or pefloxacin in dosages of 10 and 100 mg/kg/24 h. Evaluation of bone marrow engraftment was performed in animals injected with I125 Iodo-deoxyuridine (0.5 mu Ci/mouse) by radioactive counting of the entire spleen and also by counting visible colonies on the spleen surface. The results of this study demonstrate a statistically significant depression of bone marrow graft uptake (P less than 0.05, student t-test) in mice treated twice daily with ciprofloxacin in dosage of 100 mg/kg/24 h, a concentration far beyond the therapeutic range.

Animals↗

The lack of long-term suppressive effect of ciprofloxacin on murine bone marrow.

In order to investigate the long-term effect of therapy with ciprofloxacin on haemopoietic cells, we administered ciprofloxacin orally in a daily dosage of 150 mg/kg/day in three divided doses for 11 days to syngeneic mice. A control group of mice was treated with saline. On the second, sixth, tenth and sixteenth day of ciprofloxacin therapy complete blood counts (cbc) and determination of haemopoietic progenitor cells (cfu-gm) from the tibial and femoral bone marrow were performed and followed by the transplantation of the bone marrow into lethally irradiated syngeneic mice. Bone marrow engraftment was evaluated ten days following transplantation by counting the visible colonies formed on the spleen surface (cfu-s) and by measuring the incorporation of 125I by the spleen and by the femurs of the transplanted mice. The results revealed that there was no statistical significance between the control and the ciprofloxacin treated mice in cbc, cfu-gm and cfu-s parameters. It is concluded that the suppressive effect of ciprofloxacin on haemopoietic cells appears only with very high concentrations of ciprofloxacin and is short-term and reversible.

Animals↗

The pharmacokinetics and therapeutic efficacy of fleroxacin and pefloxacin in a rat abscess model.

The penetration, pharmacokinetics and therapeutic efficacy of fleroxacin and pefloxacin were investigated in a rat abscess model. Abscesses were induced by implanting a dialysis tube unit contaminated with Serratia marcescens in the subcutaneous tissue. Simultaneous serum, interstitial fluid (IF) and abscess fluid concentrations of the investigated antibiotics were measured 24 and 96 h after implantation. The concentrations were determined at various time intervals after the last intramuscular administration of each drug (20 mg/kg). Peak fleroxacin and pefloxacin concentrations in the serum of the infected animals were 14.6 +/- 4.7 mg/l and 13 +/- 2.9 mg/l respectively, peak fleroxacin and pefloxacin abscess fluid concentrations after 24 h were 12.3 +/- 2.5 mg/l and 8.9 +/- 2.2 mg/l, respectively (85% and 68% of peak serum concentrations). Abscess fluid concentrations at 96 h were: fleroxacin 4.7 +/- 2.6 mg/l and pefloxacin 4.5 +/- 1.7 mg/l. Both antimicrobials persisted significantly longer in the abscess fluid than in serum. Both drugs failed to sterilize the abscesses following a single administration; however after four consecutive administrations all abscesses became sterile. We conclude that fleroxacin and pefloxacin may be suitable for the therapy of closed space infections caused by susceptible micro-organisms.

Abscess↗

[The central nervous system and neuroendocrine system in the regulation of the immune response].

There is at present a clear trend in the study of psychoneuroimmunoregulatory events. Different experimental models have demonstrated: a) the participation of stress, psychosocial factors and the central nervous system in the regulation of the immune response; b) an extensive innervation by the autonomic nervous system of the lymphatic organs; c) the presence of receptors for the neuroendocrine mediators in the mononuclear peripheral cells; d) the activity of neuropeptides, hormones and neurotransmitters in lymphocyte activation and function; e) the production of neuroendocrine substances by lymphocytes; f) the existence of feedback pathways in the immune system. In our laboratory we have contributed to these studies with the description of: a) the regulatory activity of different neuroendocrine substances on interferon-gamma production; b) the characterization of the immune regulation exercised by the muscarinic cholinergic system; c) the in vitro activity of the indoleamines, serotonin and melatonin on the immune response, and the production of these indoleamines by lymphocytes and monocytes, thus establishing a model of paracrine regulation.

Adrenal Cortex Hormones↗

N-ras dependent revertant phenotype in human HT1080 fibrosarcoma cells is associated with loss of proliferation within normal tissues and expression of an adult membrane antigenic phenotype.

To investigate how the activated N-ras oncogene contributes to the tumorigenic potential of malignant human fibrosarcoma HT1080 cells we analysed the behavior of the parental cell line and of two flat revertants (1c and 10a) in an organ culture assay for invasion. In this assay the two revertants retain the ability of HT1080 cells to migrate within the chick cardiac muscle but lose the capacity to proliferate and to replace the normal tissue. Moreover the reversion of tumorigenic potential is associated with an evolution from an oncofoetal membrane antigenic pattern towards expression of a normal adult phenotype. Both the 4F2 antigen, which is implicated in the control of HT1080 cell proliferation, and heterodimers of the two chains (alpha and beta) of the IL2 receptor (IL2-R) are expressed in embryonic and HT1080 cells, but not in normal adult fibroblasts or in the revertant cell lines. For the first time in a non-lymphoid environment, we have detected a complex between the two IL2-R chains, together with a new species of mRNA (2.8 kB) from the IL2-R alpha gene. The behavior of these membrane markers strengthens the hypothesis that HT1080 cells may represent a block in the differentiation pathway of fibroblastic cells.

Antigens, Surface↗

Pefloxacin treatment of meningitis caused by gram-negative bacteria.

Ten patients with acute meningitis caused by gram-negative bacteria were treated with pefloxacin intravenously for a mean period of 10 days. Eight patients responded clinically to pefloxacin treatment, and the causative organisms were eradicated from the cerebrospinal fluid in 9 of the 10 patients. Pefloxacin may offer a new, efficacious, and safe therapy for gram-negative meningitis.

Acute Disease↗

The intravitreal penetration of ceftriaxone in man following systemic administration.

Seventeen patients who underwent vitreal surgery received ceftriaxone (Rocephin) 1-2 g intramuscularly at various time intervals before surgery. Specimens of serum and vitreous were assayed for ceftriaxone concentrations both by bioassay and high pressure liquid chromatography. All patients had detectable vitreous (and serum) ceftriaxone concentrations at all time periods. Vitreous ceftriaxone levels at the first 4.5 hr following the administration of the antibiotic ranged from 1.4-19.4 micrograms/ml and averaged 5.9 micrograms/ml. At 12-13 hr following ceftriaxone administration vitreous concentrations were 11.5 (+/- 9.0) micrograms/ml. Ceftriaxone in intramuscular administration could be used as prophylaxis against ceftriaxone-susceptible microorganisms in vitreal surgery. Ceftriaxone is the first antibiotic for which reliable penetration into the vitreous is demonstrable following intramuscular administration.

Adolescent↗

In vitro effects of ciprofloxacin and pefloxacin on growth of normal human hematopoietic progenitor cells and on leukemic cell lines.

The in vitro effect of ciprofloxacin and pefloxacin on growth of normal hematopoietic progenitor cells and on leukemic cell lines was investigated. Ciprofloxacin and pefloxacin caused dose-dependent inhibition of colony formation both from normal bone marrow cells and from the leukemic line K-562 cells. This inhibition exerted by ciprofloxacin and pefloxacin was statistically significant at concentrations of 25 micrograms/ml and above. Ciprofloxacin appeared to be the most potent inhibitor of colony formation among the antimicrobial agents tested. Although the inhibitory effect of pefloxacin on normal hematopoietic stem cells was similar to that of cefazolin and chloramphenicol, the inhibitory effect of pefloxacin on leukemic cells was more prominent than that of cefazolin and chloramphenicol. In a proliferation assay in liquid culture of the cell line HL-60, ciprofloxacin and pefloxacin caused a dose-dependent inhibition of cell proliferation. Both drugs failed to induce cellular differentiation, as assessed by the nitrogen blue tetrazolium dye reduction assay. In therapeutic concentrations no cumulative toxic effect of the combination of ciprofloxacin with cytosine-arabinoside, vincristine, actinomycin D and doxorubicin on colony formation by HL-60 cells was observed. It is concluded that ciprofloxacin does not exert in vitro inhibitory effect on human leukemic cells when assayed at concentrations of less than or equal to 5 micrograms/ml. However, at concentrations of 25 and 50 micrograms/ml of ciprofloxacin alone and in combination with several antineoplastic agents exerts an inhibitory effect on colony formation.

Cell Division↗

Failure of influenza vaccination in the aged.

A cohort of 127 nursing home residents aged 60-98 years were vaccinated during the winter of 1985-86 with the A-Chile 1/83 (C), A-Philippines 2/82 (P), and B-USSR (B) commercial influenza vaccines. Before vaccination 40%, 23%, and 69% were susceptible to influenza Ac, Ap, and B, respectively [hemagglutinin inhibition (H.I.) titer less than 1:40]. One month following initial vaccination, 32 patients [25%] remained unprotected against two or all three vaccine strains. These patients were revaccinated with the same influenza vaccine and followed up. At five months 11%, 19%, and 23% of the initial cohort were still unprotected against Ac, Ap, and B strains, respectively. We conclude that two conventional influenza vaccines administered one month apart leave unprotected 30% of healthy elderly people who are initial influenza vaccine failures.

Aged↗

Antibiotic cost reduction by providing cost information.

Antibiotic cost information was added to the computerized print-out for each patient of microbiology culture results, next to the antibiotic susceptibility list. During the first six months of this addition, the average monthly cost of antibiotics decreased by 16.5% ($7636) compared to the 12 months period preceding the study period. The average antibiotic cost per admission decreased by 15.7% ($1.61) and the average antibiotic cost/hospital day decreased by 10.6% ($0.23). Antibiotic savings were highest in the Department of Obstetrics and Gynaecology (21.7%) and lowest in the Department of Paediatrics (10.8%). Two-thirds of the average savings were initiated by the house-staff and the remainder by infectious disease consultants. The effect of this system on the level of medical care remains to be studied.

Anti-Bacterial Agents↗