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Biomedical subjects

C Urban

Publications and source records attributed to C Urban.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparison of different methods for separation and ex vivo expansion of cord blood progenitor cells.

Umbilical cord blood is capable of hematopoietic stem cell reconstitution in children. However, the major limitation of cord blood is a relatively low content of pluripotent progenitor cells. Thus, safe engraftment for adolescents and for adults is still not predictable and a technology for ex vivo expansion of umbilical cord blood cells is desirable. In a first step, four different methods of red cell depletion followed by magnetic cell sorting of CD34+ cells were evaluated in this study in order to assess the efficacy and safety of optimal stem cell recovery. A modified two-step Ficoll gradient separation and a hydroxyethyl starch separation tended to produce a better WBC/MNC recovery (median 94.2+/-2.44% vs. 90.2+/-5. 8%) as compared with standard Ficoll gradient separation and a gelatin-based procedure (median 78.35+/-7.1% vs. 67.2+/-5.5%). However, the recovery of CD34+ cells after magnetic cell sorting did not reach a statistically significant difference after the four different methods of red cell depletion, indicating that the recovery of WBC/MNC is not predictably correlated with the recovery of stem cells within these fractions. In a second step, we established three different cytokine combinations by adding the megakaryocyte growth and development factor +/- erythropoietin and granulocyte colony-stimulating factor to a fetal calf serum containing medium with Flt 3, stem cell factor, and interleukin-3. Net expansion of total colony-forming cells 20- to 50-fold and expansion of colony-forming cells after 5 weeks of culture 1.5- to 3-fold were obtained over a period of 7-14 days. These results demonstrate that cord blood stem cells can be expanded substantially in this short-term culture system.

Antigens, CD34↗
PubMed1999

Successful treatment of ceftazidime-resistant Klebsiella pneumoniae ventriculitis with intravenous meropenem and intraventricular polymyxin B: case report and review.

Increasing prevalence of multidrug-resistant gram-negative organisms has led to a rise in clinically significant infections with these organisms and an increasing therapeutic dilemma. We present a case of a neurosurgical patient who developed ventriculoperitoneal shunt-associated ventriculitis due to ceftazidime-resistant Klebsiella pneumoniae susceptible to cefepime, imipenem, meropenem, and polymyxin B only. Successful management was accomplished by removal of the shunt and therapy with systemic meropenem and intraventricular polymyxin B. Rapid cerebrospinal fluid (CSF) sterilization occurred, with CSF bactericidal titers of 1:32 to 1:128. Polymyxin B should be considered as adjunctive therapy for life-threatening multidrug-resistant gram-negative infections. Prior literature on use of intrathecal polymyxin B in therapy for meningitis supports its potential efficacy.

Anti-Bacterial Agents↗
PubMed1999

Clinical characteristics and molecular epidemiology associated with imipenem-resistant Klebsiella pneumoniae.

Eight patients were infected or colonized with imipenem-resistant Klebsiella pneumoniae (IRKP) from December 1994 to November 1995. Initial Klebsiella isolates were susceptible to imipenem but resistant to all cephalosporins, aminoglycosides, and beta-lactam inhibitor combinations. All patients had been in the surgical intensive care unit and had undergone abdominal surgery or tracheostomy during hospitalization. The average age of the patients was 71 years (range, 41-81 years). All patients were treated with imipenem for 5 to 36 days, and IRKP was recovered from each during or after therapy. Pulsed-field gel electrophoresis (PFGE) of the IRKP isolates revealed three distinct clonal patterns. Paired sequential isolates of imipenem-susceptible K. pneumoniae and IRKP from two patients had identical PFGE patterns, suggesting the development of clonal stepwise resistance to imipenem during therapy. Thus, imipenem resistance in Klebsiella may occur when this agent is used for treatment of infection due to ceftazidine- and aminoglycoside-resistant strains.

Adult↗
PubMed1999

Highly efficient induction of protective immunity by a vaccinia virus vector defective in late gene expression.

Vaccinia viruses defective in the essential gene coding for the enzyme uracil DNA glycosylase (UDG) do not undergo DNA replication and do not express late genes in wild-type cells. A UDG-deficient vaccinia virus vector carrying the tick-borne encephalitis (TBE) virus prM/E gene, termed vD4-prME, was constructed, and its potential as a vaccine vector was evaluated. High-level expression of the prM/E antigens could be demonstrated in infected complementing cells, and moderate levels were found under noncomplementing conditions. The vD4-prME vector was used to vaccinate mice; animals receiving single vaccination doses as low as 10(4) PFU were fully protected against challenge with high doses of virulent TBE virus. Single vaccination doses of 10(3) PFU were sufficient to induce significant neutralizing antibody titers. With the corresponding replicating virus, doses at least 10-fold higher were needed to achieve protection. The data indicate that late gene expression of the vaccine vector is not required for successful vaccination; early vaccinia virus gene expression induces a potent protective immune response. The new vaccinia virus-based defective vectors are therefore promising live vaccines for prophylaxis and cancer immunotherapy.

Animals↗
PubMed1998

Characterization of Turbid Colloidal Suspensions Using Light Scattering Techniques Combined with Cross-Correlation Methods.

The ability to characterize colloidal suspensions by means of dynamic light scattering is in general limited to systems with negligible contributions from multiple scattering. For larger particle sizes with high scattering contrast this immediately limits the technique to very low concentrations. A promising solution of this problem is to suppress multiple scattering in dynamic light scattering experiments using cross-correlation schemes. Based on these considerations we have constructed a so-called 3D cross-correlation experiment with which we are able to characterize extremely turbid suspensions. We have measured monomodal and bimodal suspensions of latex particles of relatively high volume fraction. The results show clearly that we are able to measure the dynamic structure factor in concentrated polydisperse suspensions with dynamic light scattering. Combining static and dynamic light scattering measurements for characterizing turbid suspensions the single scattering particle form factor and also the static structure factor can be evaluated. We demonstrate that the implementation of a 3D cross-correlation scheme is a powerful method in suppressing multiple scattering contributions in light scattering experiments and opens a wide field of characterization of colloidal dispersions with high turbidity without having to resort to high dilution. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella.

CONTEXT: Resistance to most or all cephalosporin antibiotics in Klebsiella species has developed in many European and North American hospitals during the past 2 decades. OBJECTIVE: To determine if restriction of use of the cephalosporin class of antibiotics would reduce the incidence of patient infection or colonization by cephalosporin-resistant Klebsiella. DESIGN: A before-after comparative 2-year trial. SETTING: A 500-bed, university-affiliated community hospital in Queens, NY. PATIENTS: All adult medical and surgical hospital inpatients. INTERVENTION: A new antibiotic guideline excluded the use of cephalosporins except for pediatric infection, single-dose surgical prophylaxis, acute bacterial meningitis, spontaneous bacterial peritonitis, and outpatient gonococcal infection. All other cephalosporin use required prior approval by the infectious disease section. MAIN OUTCOME MEASURE: Incidence of patient infection or colonization by ceftazidime-resistant Klebsiella during 1995 (control period) compared with 1996 (intervention period). RESULTS: An 80.1% reduction in hospital-wide cephalosporin use occurred in 1996 compared with 1995. This was accompanied by a 44.0% reduction in the incidence of ceftazidime-resistant Klebsiella infection and colonization throughout the medical center (P<.01), a 70.9% reduction within all intensive care units (P<.001), and an 87.5% reduction within the surgical intensive care unit (P<.001). A concomitant 68.7% increase in the incidence of imipenem-resistant Pseudomonas aeruginosa occurred throughout the medical center (P<.01). All such isolates except one were susceptible to other antibiotics. CONCLUSION: Extensive cephalosporin class restriction significantly reduced nosocomial, plasmid-mediated, cephalosporin-resistant Klebsiella infection and colonization. This occurred at the price of increased imipenem resistance in P aeruginosa, which remained susceptible to other agents. Thus, an overall reduction in multiply-resistant pathogens was achieved within 1 year.

Adult↗
PubMed1998

"Emergency hepatectomy" in a 16-month-old boy with a hepatoblastoma, severe cytomegalovirus-induced pancytopenia, and intractable diarrhea.

A 16-month-old boy presented with massive abdominal enlargement. Magnetic resonance imaging (MRI) revealed a liver tumor measuring 11 x 11 x 10 cm. Pulmonary metastases were detected by chest computed tomography. The diagnosis of a hepatoblastoma was made from the patient's age, the location of the tumor, and marked elevation of alpha1-fetoprotein (AFP). Chemotherapy according to the German Cooperative Pediatric Liver Tumor Study HB-94 was started, leading to a rapid and dramatic decrease in AFP levels. Despite an excellent response to chemotherapy, however, the abdominal distension increased. On a second MRI scan the tumor was unchanged in size, showing large areas of necrosis and cystic transformation. In addition, the patient acquired a cytomegalovirus infection with intractable diarrhea and severe pancytopenia. Since the patient's clinical course had worsened, the decision was made to alleviate the life-threatening tumor compression by an extended right hepatic lobectomy despite platelet-transfusion dependence and a white blood cell (WBC) count of only 300/microliter. Postoperative necrosis of the common bile duct necessitated a secondary resection with Roux-en-Y hepaticojejunostomy. The boy recovered quickly, and the white blood and platelet counts increased to normal values immediately after the first surgery so that chemotherapy could be finished after the postoperative recovery period. He is now in good condition without evidence of local or metastatic disease 1 year after the primary diagnosis.

Cytomegalovirus Infections↗
PubMed1998

Synchronous radiochemotherapy in unfavorable brain tumors of children and young adults.

The prognosis of patients with incompletely resected malignant brain tumors is almost fatal. In an attempt to improve the outcome of children and young adults with unfavorable brain tumors an intensive multimodal therapeutic strategy was developed combining simultaneous (hyper)fractionated external beam irradiation and conventional adjuvant chemotherapy after initial surgery. 17 patients aged between 2.10 and 25.11 years were entered into the study. 16/17 patients were treated according to the German/Austrian Pediatric Brain Tumor Study Group multicenter trial HIT '91. They are not protocol patients of this HIT '91 trial. Induction chemotherapy consisted of 2 courses of ifosfamide (3 g/m2/d) on days 1-3, etoposide (150 mg/m2/d) on days 4-6, methotrexate (5 g/m2) on days 15 and 22, cisplatin (40 mg/m2/d) and cytarabine (400 mg/m2/d) on days 29-31. Three weeks after the last dose of cisplatin/cytarabine the second course of chemotherapy was started. The last patient entered into the study received a modified therapy containing ifosfamide, cisplatin and etoposide. Synchronously at a median of 12 days after initiation of chemotherapy 12/17 patients received local radiotherapy (6000-7040 cGy) to the brain and 5/17 patients craniospinal irradiation (3520 cGy with a tumor boost of 1400-2000 cGy). 4-6 weeks after completion of the second course of chemotherapy maintenance therapy was started with carmustine (CCNU) (75 mg/m2) and carboplatin (400 mg/m2) each on day 1 and vincristine (1.5 mg/m2) on day 1, 8, 15. This course was repeated eight times every six weeks. 9/17 patients are alive at a median follow-up of 25 months (range 5-50) with 4 complete remissions, 2 partial remissions and 1 stable disease lasting 42+ months. Two patients, who initially had stable disease, progressed, but are still alive at 31+ and 41+ months after diagnosis. Median progression-free survival and median overall survival is 19 and 36 months, respectively. Hematologic and methotrexate-induced toxicity were severe and resulted in one therapy-related death. However, radiotherapy concomitant to chemotherapy appears to be an effective method of treatment for brain tumors with poor prognosis, though toxicity is severe in some cases.

Adolescent↗
PubMed1998

Unrelated 5/6-locus matched umbilical cord blood transplantation in a 23-month-old child with hemophagocytic lymphohistiocytosis.

A diagnosis of familial hemophagocytic lymphohistiocytosis (FHL) was established in an 18-month-old boy who presented with prolonged fever of unknown origin, severe pancytopenia, hepatosplenomegaly and hypofibrinogenemia. Serum levels of ferritin and soluble interleukin-2 receptor (SIL2R) were highly elevated, and the number of natural killer (NK) cells was markedly decreased. An allogeneic stem cell donor was neither found in the family nor in unrelated donor registries; however, an umbilical cord blood (UCB) donor request revealed a 5/6 HLA-matched UCB. After conditioning with busulphan 16 mg/kg body weight (BW), cyclophosphamide 120 mg/kg BW and etoposide (VP-16) 900 mg/m2 the patient received 19.6 x 10(7)UCB nucleated cells/kg BW. White blood count (WBC) reached 1.0 x 10(9)/l on day +45. Chimerism studies showed full and permanent hematopoietic and lymphopoietic engraftment on day +16. However despite full engraftment the patient still experienced two severe relapses of his disease after stem cell transplantation with the highest ferritin level in the range of 10 3967 microg/l (n = 7-142). NK cell function appeared only 6 months after UCB transplantation followed by a decrease of FHL markers and resolution of disease activity. This clinical outcome indicates that unless competent immunologic engraftment after transplantation is established, FHL is capable of relapsing even if complete three-lineage engraftment is achieved.

Fetal Blood↗
PubMed1998

Discrepancy of clinical, radiographic and histopathologic findings in two children with chronic pulmonary graft-versus-host disease after HLA-identical sibling stem cell transplantation.

We report two children who presented with cough and shortness of breath 7-8 months after a matched sibling stem cell transplant (SCT) for chronic myelogenous leukemia and myelodysplastic syndrome, respectively. Pulmonary function tests (PFTs) revealed severe airways obstruction (AO). However, radiographic investigations showed no serious abnormalities in the early phase and open lung biopsy revealed only mild lymphocytic bronchiolitis and bronchiolitis obliterans consistent with pulmonary graft-versus-host disease (GVHD). Despite administration of bronchodilators and various immunosuppressive agents obstructive lung disease progressed to pulmonary failure in patient 1, whereas stabilization of the clinical course was observed in patient 2. Serial PFTs were the best predictor of the clinical course in contrast to radiographic and histologic findings. It is concluded that PFTs should be performed repeatedly in pediatric patients after allogeneic SCT with the aim of diagnosing GVHD-associated AO in the subclinical phase. Progressive post-transplant AO necessitates prompt initiation of intensive immunosuppressive therapy in order to stop the underlying immunopathologic process even in the absence of severe radiographic and histologic findings.

Adolescent↗
PubMed1998

Mycobacterium tuberculosis specimen contamination revisited: the role of laboratory environmental control in a pseudo-outbreak.

OBJECTIVE: To investigate suspected pseudo-outbreaks of Mycobacterium tuberculosis (MTB) during August 1994 and July 1995 among patients who did not have clinical findings consistent with tuberculosis. DESIGN: Retrospective and prospective surveys of all clinical and laboratory data using standard epidemiological tools and DNA fingerprinting. SETTING: A university-affiliated community hospital. PATIENTS: Those with positive MTB cultures during periods when we noted that the number of MTB positive cultures greatly outnumbered the usual monthly average (retrospective analysis, 1994) and patients with positive MTB cultures without clinical findings consistent with tuberculosis (prospective survey, 1995). RESULTS: Epidemiological and molecular studies revealed specimen cross-contamination in the laboratory due to a faulty exhaust hood. Improvement in laboratory ventilation and change of the implicated hood prevented further specimen contamination. CONCLUSIONS: The identification of positive MTB cultures from patients without clinical evidence of tuberculosis should be a signal to suspect laboratory contamination and implement control measures. These should include a thorough epidemiological investigation, DNA fingerprint analysis, and an environmental inspection.

Bias↗
PubMed1997

Noncytotoxic drug therapy in children with unresectable desmoid tumors.

BACKGROUND: Antiestrogens and nonsteroidal antiinflammatory drugs have been shown to be effective in adult patients with unresectable or recurrent desmoid tumors. It appears that the growth of these tumors is influenced by estrogen, and that antiestrogen treatment may inhibit further proliferation of tumor cells. Nonsteroidal antiinflammatory drugs are thought to be effective through their interference with prostaglandin metabolism. METHODS: Two children with unresectable desmoid tumors (aggressive fibromatosis) were treated with tamoxifen (1 mg/kg orally, twice daily) and diclofenac (2 mg/kg rectally, twice daily). RESULTS: At last follow-up, tumor regression and growth arrest were maintained for more than 51 months in 1 child with rapidly growing recurrent fibromatosis of the thoracic wall. Another child with an inoperable desmoid tumor of the submandibular region had stable disease since the initiation of treatment. CONCLUSIONS: This is the first report describing this treatment approach in childhood fibromatosis. Combined therapy with endocrine therapy and nonsteroidal antiinflammatory drugs may be a nonaggressive alternative to chemotherapy and radiotherapy in the treatment of children with inoperable desmoid tumors.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Feasibility of peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMNC) separation in children with a body weight below 20 KG.

Nine children from 10 to 76 months (median 28.0), weighing 8.5 to 19.7 kg (median 13.0 kg) underwent peripheral blood stem cell separation (PBSCS) or peripheral blood mononuclear cell separation (PBMNCS), after insertion of a double-lumen central venous catheter (8-10 French). Separations were performed with a continuous flow blood separator (Fen-wall CS 3000 plus), running a specially adopted separation-program. In 7 children (5 with neuroblastoma IV, 1 with multifocal Ewing's sarcoma, and 1 with rhabdomyosarcoma IV), stem cells were mobilized by application of G-CSF at a dosage of 15-27.7 micrograms/kg body weight (median 16.25) subcutaneously following high-dose chemotherapy, according to the disease-related protocols, whereas 2 children had PBMNCS to induce graft vs. leukemia (GvL)-reaction in the HLA-identical sibling suffering from relapsed chronic myelogenous leukemia (CML: n = 1), or chronic myelomonocytic leukemia (CMML: n = 1) after allogeneic BMT. In all cases, the collecting procedure was performed after filling the cell separator with priming solution consisting of 2 U of irradiated and washed packed red cells, 250 ml human albumin, and 0.9% NaCl. In the 7 patients with solid tumors between 0.45 and 62.7 x 10(6) CD-34 positive cells/kg body weight were separated; the patient who had the lowest yield was separated twice after another mobilizing course. Three patients (2 with neuroblastoma IV and 1 with multifocal Ewing's-sarcoma) underwent a double transplantation with 1-3 portions of the collected stem cells within a 5- to 6-week interval. Two children had a rapid engraftment on both peripheral blood stem cell transplantations (PBSCTs). The third child, who had the lowest yield and was separated twice had prompt engraftment at the first PBSCT but delayed and incomplete engraftment at the second PBSCT. One patient after adoptive immunotransfer with PBMNCs for relapsed CML is now 40 months in complete cytogenetic and molecular biological remission, whereas the other patient treated for relapsed CMML did not respond to the PBMNC-transfusion. The results indicate that PBSCS and PBMNCS can be performed in children with a body weight below 20 kg.

Antigens, CD34↗
PubMed1997

Determination of homovanillic acid and vanillylmandelic acid in neuroblastoma screening by stable isotope dilution GC-MS.

A method for the quantitative determination of homovanillic acid (HVA) and vanillylmandelic acid (VMA), two metabolites of catecholamines, is presented. The assay is based on gas chromatography/electron impact mass spectrometry. The preparation of 13C-labeled VMA from [13C6]vanillin is described. Together with purchased deuterated HVA the 13C-labeled VMA is used as an internal standard in stable isotope dilution GC/MS. The method involves elution from soaked filter-papers, determination of creatinine content, extraction of HVA and VMA from eluted and urinary samples and derivatization to the di-and tri(trimethylsilyl) derivatives, respectively. The detection limits were found to be 4.0 pg for HVA and 0.8 pg for VMA. The method was applied to the routine determination of urinary HVA and VMA in a range from 5 to 100 ng HVA and VMA per microgram creatinine. The lower limits of pathological concentrations are set at 35 ng micrograms-1 creatinine for HVA and to 20 ng micrograms-1 creatinine for VMA, which are in close correlation with the values from other methods, but with the main advantage of reducing the amount of questionable or elevated results from 6.7% (high-performance liquid chromatography (HPLC) alone) to 0.9% (HPLC and GC/MS).

Calibration↗