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Biomedical subjects

M Dan

Publications and source records attributed to M Dan.

At least 19 recordsLinked to original sources
PubMed2000

Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.

BACKGROUND: Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. METHODS: We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. RESULTS: Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. INTERPRETATION: Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h(-1) kg(-1).

APACHE↗
PubMed2000

Pseudomembranous colitis: report of a severe case with unusual clinical signs in a young nurse.

We describe the case of a young and otherwise healthy nurse who developed pseudomembranous colitis ten days after receiving oral clindamycin for dental infection. Her clinical course was particularly stormy and was characterized by severe diarrhea and vomiting, profuse ascites, pleural effusion, abdominal tenderness, peritoneal irritation, and systemic toxicity. The Clostridium difficile assay was negative on two occasions. Features compatible with pseudomembranous colitis were seen at sigmoidoscopy, and the diagnosis was confirmed by biopsies.

Adult↗
PubMed2000

Bioethical issues related to continuous renal replacement therapy in intensive care patients.

OBJECTIVE: To examine the ethical approach of intensivists and nephrologists to continuous renal replacement therapy (CRRT). DESIGN: A questionnaire. SETTING: The First International Course on Critical Care Nephrology. PARTICIPANTS: The participants in the course (around 500). RESULTS: Most participants think that establishing ethical criteria for managing CRRT is a medical task, as clinicians have adequate criteria for defining futility. However, many responders would grant the request of starting futile CRRT or would maintain it if requested by the family. Only 55% believe that informed consent is necessary for initiating CRRT; one out of four would start or maintain unwanted life-saving CRRT. In case of lack of equipment, the majority would select the patients, excluding the worst one or on a "first-come, first-served" basis. Withholding and withdrawing are regarded differently by most responders. Again, most think that every vital support should be withdrawn when futile, but practical and psychological aspects still influence the final decision. Responders think that ethics critical care committees can help in the management of ethical problems in ICU. CONCLUSIONS: Our results show that several ethical questions are still unsolved and that practical and psychological aspects of the treatment process can be stronger than bioethical principles.

Attitude of Health Personnel↗
PubMed2000

Dependence of single-bubble sonoluminescence on ambient pressure

Kondic et al.'s theory makes several specific predictions on the dependence of single-bubble sonoluminescence (SBSL) on ambient pressure. We have carried out experiments to verify these predictions for air bubbles in a water-glycerine mixture at about 17.5 kHz. The results show an increase in SBSL with reduced ambient pressure down to a critical value below which SBSL is extinguished. The results are all in good agreement with Kondic et al.'s theory and are also compatible with the dissociation hypothesis of Lohse et al.

Journal Article↗
PubMed2000

Role of alcohol dehydrogenase E (ADHE) in the energy metabolism of Giardia lamblia.

Two hammerhead ribozymes flanked by Giardia lamblia alcohol dehydrogenase E (ADHE) antisense RNA fragments, ARzS and ARzL, were designed, synthesized and found capable of cleaving an ADHE mRNA fragment at the anticipated position in vitro. The ribozymes were then electroporated into Giardia trophozoites and expressed via the giardiavirus-mediated RNA expression system. Expression of the ribozyme with two short antisense arms, ARzS, was stabilized under puromycin selection and demonstrated a 33% reduction in ADHE mRNA and 25% decrease in NAD+-dependent ADH activity in the transfectants. Expression of ARzL, the ribozyme with two long antisense arms, cannot be enriched under puromycin without killing the transfected cells, probably due to excessive depletion of ADHE. Without the drug selection, however, transient expression of ARzL 20-40 h after electroporation resulted in an 83.7% loss of ADHE mRNA and an 84.5% reduction in ADH activity in the transfected cells. When the ribozyme moiety was removed from ARzL, the latter retained some of its in vivo activity of lowering ADHE mRNA and ADH activity, suggesting that inhibition of ADHE gene expression in Giardia can be accomplished by the antisense RNA alone, albeit less efficiently. The ADHE deficient transfectant demonstrated relatively poorer anaerobic growth but grew more vigorously than the wild type under aerobic conditions, suggesting that the role of ADHE in providing NAD+ through anaerobic reduction of acetyl-CoA to ethanol could be replaced by a yet unidentified aerobic enzyme(s) in Giardia. The close association consistently observed between the levels of ADHE mRNA and ADH activity in transfected Giardia cells suggests that ADHE could be the only functional alcohol dehydrogenase in Giaradia. One other Giardia gene encoding a putative Class III ADH, GIADH3, was identified and cloned, but no Class III ADH activity could be detected in Giardia by the conventional enzyme assays. This gene is thus probably unexpressed in Giardia trophozoite.

Aerobiosis↗
PubMed2000

Inhibition of pyruvate-ferredoxin oxidoreductase gene expression in Giardia lamblia by a virus-mediated hammerhead ribozyme.

Giardia lamblia is a primitive eukaryotic microorganism that derives its metabolic energy primarily from anaerobic glycolysis. In trophozoites, pyruvate-ferredoxin oxidoreductase (PFOR) converts pyruvate to acetyl-CoA with the transfer of a pair of electrons to ferredoxin, which can then reduce metronidazole and activate it into a potent antigiardiasis agent. It is unclear, however, whether this anaerobic disposal of electrons is essential for the energy metabolism in Giardia. In the present study, cDNAs encoding hammerhead ribozyme flanked with various lengths of antisense PFOR RNA were cloned into a viral vector pC631pac derived from the genome of giardiavirus (GLV). RNA transcripts of the plasmids showed high cleavage activities on PFOR mRNA in vitro. They were introduced into GLV-infected G. lamblia trophozoites by electroporation and stablized in the transfected cells via serial passages under puromycin selection. PFOR mRNA and enzyme activity in the transfected cells were decreased by 46-60% with the ribozyme PRzS flanked with 20 nt PFOR antisense RNA on each arm and by 69-80% with the ribozyme PRzL flanked with 600 and 1500 nt PFOR antisense RNA. PRzS without the inserted ribozyme or ribozyme flanked with alcohol dehydrogenase E antisense RNA showed no effect on PFOR mRNA and activity. The ribozyme-transfected cells demonstrated significantly enhanced resistance to metronidazole and grew equally well under anaerobic and aerobic conditions. In contrast, the wild-type cells grew slightly better anaerobically than the transfectants but did not grow at all in aerobic conditions. Thus, the reduced PFOR expression enables Giardia to grow under molecular oxygen and the presence of PFOR enhances the anaerobic growth of Giardia with an increased susceptibility towards metronidazole. In addition, this study demonstrated for the first time the feasibility of using a viral RNA vector to express a ribozyme targeted at a specific mRNA in G. lamblia to reduce the expression of a specific gene.

Animals↗
PubMed2000

Adsorption in sepsis.

The pathophysiology of sepsis offers a highly complicated scenario. In sepsis, endotoxin or other gram-positive-derived products induce a complex and dynamic cellular response, giving rise to several mediators known to be relevant in the pathogenesis of septic shock such as specific mediators, substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of translational or transductional pathways, and precursor molecules. In this review, we delve into some new concepts stemming up from the use of sorbents in continuous plasma filtration. Nonspecific simultaneous removal of several mediators of the inflammatory cascade have led to improved outcomes in animal models of septic shock and to improved hemodynamics in a pilot clinical study. It seems of great importance to explore all possible treatment techniques that may have a direct impact on circulating mediators of sepsis and that also may interfere with the imbalance between proinflammatory and anti-inflammatory substances in the critically ill patient with multiple organ failure. In this view, the application of sorbents appears to open new and interesting therapeutic options. The search for innovative treatments specifically targeted to the special needs of the critically ill patients seems therefore more important than the attempt to adjust concepts and technologies that are normally applied to patients with chronic renal failure.

Adsorption↗
PubMed2000

Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula neritina in 1982 and is currently undergoing evaluation in a number of malignancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymphoma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h continuous infusion every 2 weeks at a dose of 120 microg/m2 per course. Patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion. The dose of vincristine was escalated in groups of three patients as follows: level 1, 0.5 mg/m2; level 2, 1.0 mg/m2; and level 3, 1.4 mg/m2 with vincristine doses capped at 2.0 mg for all patients. Bryostatin 1 alone resulted in one complete remission and two partial remissions. Nine patients received sequential treatment with bryostatin 1 and vincristine. The addition of vincristine at a dose of 2 mg was feasible and caused the expected dose-related sensory neuropathy. Phenotypic analysis by flow cytometric analysis on pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed up-regulation in the coexpression of CD11c/ CD22 on CD20+ B cells in two of four CLL patients studied, which is consistent with in vitro findings of differentiation of CLL cells to a hairy cell phenotype.

Adult↗
PubMed1999

Value of radiation therapy in the management of chemoresistant intermediate grade non-Hodgkin's lymphoma.

The purpose of this study was to evaluate the probability and extent of response to radiation therapy in patients with chemotherapy-resistant intermediate grade non-Hodgkin's lymphoma. Thirty-five patients with chemotherapy-resistant non-Hodgkin's lymphoma received local radiation therapy after initial treatment with at least six cycles of systemic chemotherapy. There were 17 men and 18 women in our study. Ages ranged from 15 to 68 years, median age was 42 years. Chemotherapy resistance was defined as relapse after initial chemotherapy (11 patients) or failure to achieve complete remission (partial response in 18 patients, stable disease in 1 patient, and disease progression in 5 patients). Radiation doses were between 1,980-5,040 cGy (median dose of 3,200 cGy). Treatment outcome was evaluated with respect to any subsequent relapse either within or outside the irradiated region. The 2-year actuarial survival was 65%. The cumulative incidence of isolated local failure and any local failure at 2 years were 33% and 54%, respectively. Tumors that responded to initial chemotherapy had a better local control probability than tumors that did not respond. The 2-year actuarial local failure rates for these two groups were 51% and 83%, respectively (P = 0.01). There was a trend for improved local control with radiation doses > or = 3,960 cGy, suggesting the presence of a dose-control relationship. The rate of disease progression within an irradiated region in patients with intermediate grade non-Hodgkin's lymphoma that relapsed after or failed to respond completely to full course chemotherapy was substantially higher than the historical in-field failure rates when radiation therapy was used as the sole modality of treatment. Prior response to initial chemotherapy was a predicting factor for local control following radiation therapy.

Adolescent↗
PubMed1999

Maternal infectious morbidity following multiple courses of betamethasone.

OBJECTIVE: the beneficial effects of antepartum corticosteroids on the reduction of morbidity and mortality in the premature neonate have been amply demonstrated. The NIH consensus statement has, therefore, endorsed their use in women at risk from pre-term delivery between 24 and 34 weeks gestation. Patients at persistent risk of pre-term delivery nay receive multiple weekly courses. However, increased susceptibility to infection is a well-recognized complication of prolonged high-dose steroid therapy. We examined infectious morbidity among women exposed to three or more courses of betamethasone. METHODS AND OUTCOMES MEASURES: thirty-seven patients at risk of pre-term delivery who received three or more courses of betamethasone (median = 6: range 3-10) and 74 normal controls, matched for maternal age, route of delivery, and year of delivery were included in the study. Data on medical care provided to study and control patients between 24 weeks gestation and 6 weeks postpartum were retrieved from centralized medical records. Incidences and types of infections were compared by Chi-square and Fisher's exact test, as appropriate. Only infections diagnosed at least 1 week after betamethasone therapy was initiated were included. Patients with pre-existing conditions predisposing to infectious morbidity were excluded. RESULTS: twenty-four of 37 patients (64.8%) exposed to betamethasone vs. 13 of 74 (17.5%) controls developed infectious diseases (P < 0.001). Symptomatic lower urinary tract infections occurred in 13 of 37 (35.1%) and two of 74 (2.7%) in the study and control groups, respectively (P < 0.001). Serious bacterial infections were found in nine of 37 (24.3%) vs. none of 74 (0%) patients, respectively (P < 0.001). These included sepsis (n=2), pneumonia (n=4), pyelonephritis (n=2), and cholangitis (n=1). Eight of nine serious infections occurred in patients exposed to five or more weekly courses of betamethasone. Postpartum endometritis related to Caesarean delivery was found in five of 37 patients (13.5%) vs. seven of 74 (9.4%), respectively (P=NS). CONCLUSIONS: Three or more courses of antepartum betamethasone in women at risk of pre-term delivery are associated with substantial infectious maternal morbidity. The excess morbidity consisted mainly of bacterial infections, some of which were associated with systemic and potentially life-threatening infections.

Adult↗
PubMed1999

Comparison of ex-vivo serum bactericidal activity of cefepime, ceftazidime and cloxacillin against Staphylococcus aureus.

Cefepime (1 g), ceftazidime (1 g), and cloxacillin (2 g) were administered intravenously to 10 volunteers each. After infusion of a single dose over 30 min, blood samples were obtained at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 h (for ceftazidime at 0.5 and 4 h) after dosing. Drug levels were determined by the bioassay method. Serum bactericidal activity against five clinical isolates of cloxacillin-susceptible Staphylococcus aureus were determined by the microdilution method according to the National Committee for Clinical Laboratory Standards guidelines. The mean peak serum level was 76.88 +/- 24.71 mg/L for cefepime, 42.8 +/- 15.98 mL/L for ceftazidime, and 92.81 +/- 24.7 mg/L for cloxacillin. Concentrations of cefepime were detected during the whole testing period (mean trough level, 1.43 +/- 0.9 mg/L at 12 h), whereas concentrations of cloxacillin were measurable up to 5 h after administration (mean trough level, 0.90 +/- 0.97 mg/L). The mean peak reciprocal bactericidal titers were 29.41 for cefepime, 5.6 for ceftazidime, and 377 for cloxacillin. Effective bactericidal titers were detected as long as 5 h for cefepime (approximately 40% of the dosing interval) and 3 h for cloxacillin (at least 50% of the dosing interval). For ceftazidime, serum bactericidal activity was markedly lower compared with that of cefepime. Although cefepime has demonstrated an improved antistaphylococcal bactericidal activity compared with ceftazidime, it was somewhat lower than that of cloxacillin.

Adult↗
PubMed1999

Rectal colonization with vancomycin-resistant enterococci among high-risk patients in an Israeli hospital.

The prevalence of rectal carriage of vancomycin-resistant enterococci (VRE) in two high-risk populations--61 patients admitted to ICU and 92 patients on renal dialysis--was studied longitudinally over a period of six months in a 650-bed general hospital. ICU patients were swabbed weekly and dialysis patients monthly. Enterococcal isolates were fully identified using the ATB identification system, and MICs were determined according to the NCCLS recommendations. Enterococci were isolated in 52 (83.6%) ICU patients and 86 (93.4%) dialysis patients. VRE were recovered at least once in 14 (27%) ICU patients and four (4.8%) dialysis patients. All VRE isolates (MIC of vancomycin > or = 256 micrograms/mL) were resistant to teicoplanin (MIC > or = 32 micrograms/mL; vanA phenotype), 87.5% were ampicillin-resistant, and 92% showed high-level resistance to gentamicin; 88% were E. faecium. The main risk factors for acquisition of VRE included duration of hospitalization in the six months preceding entry into the study and during the survey (P = 0.009 and 0.007 respectively, for ICU patients), and duration of antibiotic administration (P = 0.005, for ICU patients). The impact of vancomycin was most prominent (P = 0.005 for receipt and 0.06 for duration of administration, in ICU patients). Six of the 18 VRE carriers developed bacteraemia, six isolates being vancomycin-susceptible and one vancomycin-resistant (one patient had both). In this study, the first in Israel, a low rectal carriage rate occurred in renal dialysis patients and antibiotic use was the most important risk factor for VRE colonization.

Aged↗
PubMed1999

Concentration and bactericidal activity of fusidic acid and cloxacillin in serum and synovial fluid.

Fusidic acid and cloxacillin were studied in patients who underwent joint aspiration for noninfectious disorders. Nine patients were given oral 500 mg fusidic acid tid for 72 h, the last dose being given 4, 8 or 12 h before the joint aspiration. Cloxacillin was administered in a single 2 g iv dose to 9 patients, 0.5, 4 or 8 h before the aspiration. Bactericidal activity was determined against five isolates each of methicillin-susceptible and methicillin-resistant Staphylococcus aureus. Satisfactory activity (> or = 1:3) was detected in the serum in patients who received fusidic acid, while in the synovial fluids titres reflected borderline effectiveness (c. 1:2). Despite drug concentrations and excellent MICs, fusidic acid demonstrated markedly lower inhibitory and bactericidal activity against S. aureus than did cloxacillin.

Adult↗
PubMed1999

Expression of membrane-associated macrophage colony-stimulating factor (M-CSF) in Hodgkin's disease and other hematologic malignancies.

We have identified a membrane-bound form of M-CSF (m-M-CSF) from an established human leukemic J6-1 cell line. To further understand its biological significance, we studied the expression of this membrane-associated growth factor in the lymph nodes of lymphoma patients and bone marrow smears from patients with hematologic diseases by immunohistochemical staining using anti-M-CSF MAb. We detected a high incidence of m-M-CSF expression in 75% (9/12) of the lymph node sections from patients with Hodgkin's Disease (HD). The antigens were detected primarily in large clusters of mononuclear Hodgkin's cells and the extracellular matrix (EM) surrounding them. In one HD patient with abundant multinucleated Reed-Sternberg (R-S) cells, all of them were intensely stained with anti-M-CSF MAb. In non-Hodgkin's lymphomas (NHL), the incidence (17.6 %) of m-M-CSF expression was lower (3/17). Yet, no m-M-CSF antigens were detected in the lymph nodes from six cases of non-hematologic malignancies and other diseases. A high response also was detected in bone marrow smears obtained from patients with hematologic malignancies, which include myeloid leukemias (32.5%), lymphomas with bone marrow metastasis (50%) and myelodysplastic syndromes (MDS) (37.5 %). By comparison, only 6.8 % of bone marrow smears from non-malignant hematologic diseases and 2.7% of lymphoid leukemias showed positive staining with anti-M-CSF MAb. Our results showed that high expression of m-M-CSF antigens is linked to some types of lymphomas, especially HD. and myeloid leukemias, and may play a role in the development of these hematologic malignancies.

Adult↗
PubMed1999

Present and future options in continuous renal replacement therapies of sepsis and MOF.

Conventional continuous extracorporeal treatments such as hemofiltration and hemodiafiltration have not achieved significant reduction in cytokine plasma levels, in spite of their increasing popularity mainly related to the unnecessary fluid restriction thereby rendering adequate caloric intake possible (Actualités Nephrologiques, 1994). This is mainly due to reduced filtration, to saturability of the adsorption-related phenomena and to the absence of a convective mass transfer. New approaches have been more recently introduced. The concept of blood purification has been applied in some new innovative techniques that use non-selective or selective sorbents. We will focus on the criteria used by others and us to assess the efficiency in vitro and in animal models of sepsis of more recently introduced non-selective and selective devices. Among the innovative techniques, modalities aimed at the plasma treatment will receive emphasis. These modalities that are based on plasma filtration with the use of different sorbents. The preliminary results obtained from ongoing clinical trials will be presented. We will also expand on the technical, biological and clinical aspects that should be addressed in order to establish a new modality as innovative in the treatment of sepsis.

Hemofiltration↗