Biomedical subjects

J Schindler

Publications and source records attributed to J Schindler.

At least 37 records · Page 2Linked to original sources

PubMed1996

A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma.

IgG-HD37-SMPT-dgA is a deglycosylated ricin A chain (dgA)-containing immunotoxin (IT) prepared by conjugating the monoclonal murine (MoAb) anti-CD19 antibody, HD37, to dgA using the heterobifunctional hindered disulfide linker, N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT). In this report, we have used two regimens for the administration of IgG-HD37-SMPT-dgA to patients with non-Hodgkin's lymphoma (NHL) in two concomitant phase I trials. One trial examined four intermittent bolus infusions administered at 48-hour intervals. The other studied a continuous infusion (CI) administered over the same 8-day period. In the intermittent bolus regimen, the maximum tolerated dose (MTD) was 16 mg/m2/8 d and the dose-limiting toxicity (DLT) consisted of vascular leak syndrome (VLS), aphasia, and evidence of rhabdomyolysis encountered at 24 mg/m2/8 d. Using the CI regimen, the MTD was defined by VLS at 19.2 mg/m2/8 d. At the MTD of both regimens, a novel toxicity, consisting of acrocyanosis with reversible superficial distal digital skin necrosis in the absence of overt evidence of systemic vasculitis, occurred in 3 patients. Of 23 evaluable patients on the bolus schedule, there was 1 persisting complete response (CR; > 40 months) and 1 partial response (PR). Of 9 evaluable patients on the continuous infusion regimen, there was 1 PR. Pharmacokinetic parameters for the bolus regimen at the MTD showed a mean maximum serum concentration (Cmax) of 1,209 +/- 430 ng/mL, with a median T1/2 beta for all courses of 18.2 hours (range, 10.0 to 80.0 hours), a volume of distribution (Vd) of 10.9 L (range, 3.1 to 34.5 L), and a clearance (CL) of 0.45 L/h (range, 0.13 to 2.3 L/h). For the CI regimen at MTD, the mean Cmax was 963 +/- 473 ng/mL, with a median T1/2 beta for all courses of 22.8 hours (range, 24.1 to 30.6 hours), a Vd of 9.4 L (range, 4.4 to 19.5 L), and a CL of 0.32 L/h (range, 0.12 to 0.55 L/h). Twenty-five percent of the patients on the bolus infusion regimen and 30% on the CI regimen made antibody against mouse Ig (HAMA) and/or ricin A chain antibody (HARA). We conclude that this IT can be administered safely and that both regimens achieve comparable peak serum concentrations at the MTD; these concentrations are similar to those achieved previously using other regimens with IgG-dgA ITs at their respective MTDs. Thus, toxicity is related to the serum level of the IT and does not differ with different targeting MoAbs.

Adult↗

PubMed1996

Carriage of antibiotic-resistant Streptococcus pneumoniae by children in eastern and central Europe--a multicenter study with use of standardized methods.

With use of standardized techniques, a study of nasopharyngeal pneumococcal carriage in children in six Central and Eastern European cities was undertaken during the winter of 1993-1994. Nasopharyngeal swab specimens were collected from 954 children (predominantly under the age of 5 years) who were hospitalized or attending outpatient clinics or day-care centers. Susceptibility of isolates was determined by disk diffusion (on Mueller-Hinton agar with 5% sheep blood). Disks containing 1 micrograms of oxacillin were used to screen for susceptibility to penicillin G. Pneumococci were recovered from 258 (27.0%) of the 954 children. A variety of strains were recovered, and most penicillin-resistant strains were ŕesistant to multiple agents. Minimum inhibitory concentrations of penicillin for selected resistant strains were 0.125-8 micrograms/mL. Resistance to penicillin was common in strains from Bulgaria, Romania, and Slovakia. Resistance to erythromycin and chloramphenicol occurred in Bulgarian and Romanian strains. Strains from Poland were all susceptible to penicillin, but many were resistant to tetracycline. Resistance to trimethoprim-sulfamethoxazole was common in Bulgarian, Romanian, and Slovak strains. Czech and Russian strains were predominantly susceptible to antibiotics. Most resistant strains were of serotypes 6, 14, 19, and 23.

Carrier State↗

PubMed1996

[Identification and typing of hospital strains of Acinetobacter calcoaceticus-Acinetobacter baumanni complex].

A collection of 95 strains of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex, isolated between 1991 and 1993 in the Prague Burn Center (BC), was studied. Ninety-one strains were isolated from 43 patients: 50 of them from burnt sites, 22 from endotracheal tube, 13 from urine, 3 from blood and 3 from venous catheter, and 4 strains were isolated from the hospital environment and the nursing staff. The strains were classified by restriction endonuclease fingerprinting of total DNA, plasmid profile analysis, ribotyping, comparison of antibiograms, biotyping and according to epidemiological data, into 31 relatedness groups each of them including 1 to 29 strains, likely to be isolates of the same strain. None of the methods used enabled to distinguish all groups. The importance of the polyphasic approach is emphasized since three multiresistant strains, isolated almost simultaneously in the BC, needed at least two methods to be distinguished (e.g. ribotyping and biotyping). Twenty-eight representative strains of different groups were identified by ribotyping: 18 of them were allocated to genomospecies 2 (A. baumannii), 5 to genomospecies 3 and 5 to genomospecies 13 sensu Tjernberg and Ursing. Only A. baumannii was found to spread among patients. Strains of two multiresistant groups persisted in the BC throughout the period studied and strains of one of these groups were responsible for an outbreak in the autumn of 1993. The methods mentioned above were used to describe 12 multiresistant strains isolated in three hospital wards in other localities. When ribotyped these strains were identified as A. baumannii. The strains of the same origin were identical in their typing profiles while the strains of different origins were easy to differentiate using any of the above methods; nevertheless, 2 of these groups were almost identical to 2 groups of multiresistant strains isolated in the BC.

Acinetobacter↗

PubMed1996

Using HL7 and the World Wide Web for unifying patient data from remote databases.

W3-EMRS is an architecture designed to access clinical data from remote heterogeneous electronic medical record system (EMRS) databases. We describe the technologies used in an experimental implementation of W3-EMRS that concurrently collects data from several sources and presents them in an integrated set of views. After describing some of the organizational constraints, the architectural decision, implementation methodology, and operation of the completed project are discussed.

Computer Communication Networks↗

PubMed1995

Ex vivo purging of allogeneic marrow with L-Leucyl-L-leucine methyl ester. A phase I study.

L-Leucyl-L-leucine methyl ester (LLME) is a lysosomatropic compound that is converted by dipeptidyl peptidase I to metabolites that are membranolytic for cytotoxic T cells, NK cells, and LAK cells. Ex vivo treatment of murine marrow with LLME ameliorates acute graft-versus-host-disease (GVHD), which led to consideration of a clinical study. A phase I study design was initiated to evaluate the effects of ex vivo purging of allogeneic marrow on engraftment, since LLME also suppresses human progenitor cells. All patients received a preparative regimen of cyclophosphamide plus total body irradiation. GVHD prophylaxis consisted of cyclosporine +/- corticosteroids. This study included 19 patients with high risk disease undergoing allogeneic transplantation from an HLA-identical sibling (n = 12) or a partially HLA-matched family donor (n = 7). Marrow mononuclear cells were treated ex vivo in a dosage escalation study with LLME concentrations of 0.25 mM, 0.375 mM, and 0.5 mM. Marrow NK and LAK activities were essentially eliminated at concentrations > or = 0.375 mM LLME. CD8+ cells were also reduced. Granulocyte macrophage colony-forming unit recovery was 3% at 0.5 mM LLME. The median time to an absolute neutrophil count of 500/microliters was 17 days after transplantation (95% confidence interval = 14-18 days). One patient that received marrow treated with 0.5 mM LLME died of secondary graft failure. Complete donor chimerism was documented in each evaluable case. NK recovery was delayed at LLME concentrations > or = 0.375 mM LLME. Grade II/IV GVHD occurred in 4/18 evaluable patients. Ex vivo treatment of human marrow with LLME diminishes NK activity, LAK activity, CD8+ cells, and granulocyte macrophage colony-forming units, but does not totally prevent acute GVHD.

Acute Disease↗

PubMed1995

[Biochemical indicators of Citrobacter sedlakii].

The authors describe eight strains identified biochemically as a new species of C. sedlakii in clinical material, surface water and the cutting surface of a melon. The majority of strains was isolated in the Czech and Slovak Republic.

Citrobacter↗

PubMed1994

[Bacterial resistance to antibiotics in the Czech Republic. The Working Group for Monitoring Resistance in the Czech Republic].

In 1991 the authors made an investigation on the resistance of clinically important bacteria. Seventeen antibiotic centres in the Czech Republic participated in the investigation. The resistance to antibiotics of 32,567 strains of twelve bacterial species isolated from hospitalized patients depends on 1. the type of bacteria and antibiotics, 2. the source (specimen of pathological material) and 3. the locality (hospital). The resistance of Staphylococcus aureus to oxacillin with the exception of one hospital is not more than 6%, in rare instances also resistance to vancomycin was encountered. The frequency of resistance of gram-negative rods to so-called reserve antibiotics (cephalosporins of the third generation, quinolones and amikacin) depends markedly on the type of bacteria, being highest in typical causal agents of hospital infections--Enterobacter cloacae, Serratia marcescens, Providencia rettgeri and Pseudomonas aeruginosa. With the exception of cephalosporins the resistance of gram-negative rods and Pseudomonas aeruginosa isolated from urine is much greater than in strains from other clinical materials. The frequency of resistance in faculty hospitals which concentrate patients with more serious diseases is high, the highest resistance was, however, recorded in the North Bohemian area--in pneumococci against penicillin (13%) and in haemophili against ampicillin (17%). Every hospital is a closed ecological niche with a typical bacterial population and resistance rate. A competent estimate of an adequate and probably effective antibiotic for immediate initiation of treatment of an urgent infection can thus be made only by somebody with close and steady knowledge of the state of resistance in a given hospital.

Bacteria↗

PubMed1994

[Biochemical identification of aeromonads].

To assess the species of the genus Aeromonas in 178 strains isolated from human and animal materials and from the environment (water and hospital environment), examined along with 11 type strains of the best known species, a key was used the basis of which are in addition to biochemical tests defining the genus Aeromonas 12 tests: Voges-Proskauer, lysine decarboxylase, gas from glucose, haemolysis, gluconate oxidation, elastase, arabinose, mannose, saccharose, salicine, esculine hydrolysis, arbutine. Three tests--salicine, esculine hydrolysis, arbutine--differentiate A. hydrophila (2-3 positive) from A. sobria (0-1 positive).

Aeromonas↗

PubMed1993

Dynamics of Bacillus colony growth.

A growing bacterial colony is not an amorphous mass but is a dynamic and differentiated system. It may appear chaotic in the details of its structure but it can be accurately described by simple models for fractal geometry. As Benoit Mandelbrot said: 'Surprise, simple rules can generate rich structures'.

Bacillus↗

PubMed1992

Training the urban health care provider: one department's first steps.

As our country faces a national crisis in health care, few have outlined plans to improve the shortage of primary care physicians. This is especially critical in urban areas where sociocultural impacts on health are large. The Department of Family Practice and Community Medicine at the University of Texas School of Medicine in Houston has begun development of a division of Urban Family Medicine to address the special training needs of the urban family practitioner. Subdivisions that have been formed focus on undergraduate curriculum, graduate educational strategies, service, and research and policy to further develop the training model.

Curriculum↗

PubMed1992

Classification of strains of Pragia fontium, Budvicia aquatica and of Leminorella by whole-cell protein pattern.

SDS PAGE protein patterns of 37 H2S-positive strains of species belonging to the family Enterobacteriaceae including the genera Budvicia (11 strains) and Leminorella (L. grimontii--3 strains, L. richardii--4 strains) were compared with 10 strains of species Pragia fontium. All strains under study form well separated clusters with overall similarity C = .49. Clusters are separated in the range of C = .68-.83. They display high homogeneity, only one strain of Edwardsiella tarda clusters with budviciae. Strains of Pragia form two distinct clusters separated from other genera. Electrophoretograms of two strains which do not group as expected are analyzed and results discussed. Results support evidence that strains designated Pragia fontium deserve independent treatment as a new species.

Bacterial Proteins↗

PubMed1992

Continuous ionography (CIG) in haemodialysis by ion-selective carrier membrane electrodes (ISCME) with solid cement contact for flow-through measurement.

Ion balance is of particular interest for patients maintained on RDT because of the importance of controlling ion movement and ion removal during haemodialysis. Continuous ionography (CIG) was therefore tested for electrolyte monitoring in extracorporeal haemodialysis in vitro and in vivo. The accuracy and stability of the electrodes were examined and various concentrations of potassium in blood, ultrafiltrate and dialysate were evaluated. Ion selective carrier membrane electrodes (ISCME) appeared to be suitable for continuous and simultaneous measurement of ions in blood and dialysis fluid. CIG monitoring of ion movement and ion removal could be the basis for adjusting and computer-managing ion elimination during extracorporeal haemodialysis.

Electrodes↗

PubMed1992

Semiautomatic photometric screening of urine samples for significant bacteriuria with high predictive values.

A simple method for screening urine specimens for significant gramnegative bacteriuria is presented, in which microtitration plates, a vertical-beam photometer used for reading ELISA and an inexpensive microcomputer are employed. The wells of the plate containing brain-heart infusion broth are inoculated with urine. Every hour turbidity is measured and the values are compared with the original ones. The whole examination is terminated in five hours. At the actual prevalence of 0.27, specificity is 0.97, the predictive value of a negative result is 0.97 and false positives 0.03. The method is used for rapid reporting to the ward, and for subsequent differentiated standard cultivation.

Bacteriuria↗

PubMed1991

[Classification of sensitive and resistant strains based on the degree of antibiotic growth inhibition].

The course of growth suppression of sensitive strains depends on the type of antibiotic. Based on the kinetics of the early growth phase in the microculture when the inoculum is relatively concentrated it is possible to divide in the presence of the antibiotic the Gram negative fermenting rods into sensitive and resistant strains already within five hours. Data obtained by automated photometric assessment at selected intervals were processed by the aggregation method using a block distance as the coefficient of similarity. Ampicillin, ticarcillin, gentamicin, tetracycline and colistin readily discriminate sensitive and resistant strains, consistent with the minimal inhibitory concentration. Cefazolin, cefoxitin and chloramphenicol differentiate readily sensitive strains. Slowly growing sensitive strains of Proteus mirabilis and Serratia marcescens may appear to be resistant.

Drug Resistance, Microbial↗

PubMed1991

[The Aeromonas genus].

Aeromonas hydrophila manifested itself since its discovery in 1891 as a pathogen of cold-blooded and warm-blooded animals and man. Aeromonads cause intestinal and non-intestinal disease. The genus Aeromonas comprises: A. hydrophila, A. sorbria, A. caviae, A. veronii, A. schubertii, i.e. mesophilie species and as to psychrophilie immobile species. A. salmonicida and A. media. For warm-blooded animals and man mesophilie motile species are important as pathogens. A. veronii is an ornithine-decarboxylase positive species, A. schubertii is mannitol-negative, A. caviae is non-haemolytic and VP-negative. It is difficult to differentiate. A. hydrophila with aerogenic and anaerogenic strains from A. sobria. Several practical differential diagnostic tests were suggested by Janda et al. and Joseph et al.: hydrolysis of esculine, KCN, arabinose and salicin are usually positive in A. hydrophila, in A. sobria usually negative. Existing species of mesophilie aeromonads, however, do not correspond to some strains which are found. Therefore Arduino et al. divided their aeromonads into DNA-hybridization groups: for A. hydrophila there were 5, for A. caviae 2 and for A. sobria 1 hybridization group. Biochemisal characteristics corresponded to the hybridization groups. For isolation of aeromonads from faeces selective media with ampicillin must be used and possibly enrichment in alkaline peptone water. Evidence of pathogenity factors is similar as in E. coli,: detection of adhesins and enterotoxin or cytotoxin by means of tests commonly used in cholera and E. coli. The types of adhesins are differentiated by means of fucose- galactose- and mannose resistant haemagglutination.(ABSTRACT TRUNCATED AT 250 WORDS)

Aeromonas↗

PubMed1990

In vivo biological response to recombinant interferon-gamma during a phase I dose-response trial in patients with metastatic melanoma.

Interferon-gamma (IFN gamma), as produced by recombinant DNA technology, has shown a wide range of immunomodulatory activity in vitro and in vivo. Clinical studies have attempted to establish a dose-response relationship to define optimal dosage ranges for induction of effector cell function and host response in patients with cancer. We conducted a randomized trial to test the in vivo biologic activity of five daily dosages ranging from 3 to 3,000 micrograms/m2, administered by daily 2-hour bolus injection or by continuous infusion for 14 days. We demonstrate comparable immunobiologic effects of recombinant IFN gamma (rIFN gamma; Biogen, Inc, Cambridge, MA) administered by these two schedules at the various dosages tested, and have defined a relationship of dose to biologic response over this 3-log10 dose range. Oligo 2'5' adenylate synthetase (2'5'As) induction, natural-killer (NK) cell activity, and T-cell subset distribution (heightened T helper/suppressor ratio) showed the most consistent treatment-associated changes and the greatest immunobiologic effects at dosages of 300 to 1,000 micrograms/m2. Mononuclear cell DR and DQ antigen expression showed no consistent dose-related treatment effect. The relevance of the phenotypic, functional, and enzymologic effects observed in this trial to any clinical antitumor effects of IFN gamma in cancer therapy must now be established.

2',5'-Oligoadenylate Synthetase↗

PubMed1990

Use of IFN-gamma in patients with AIDS.

The tolerance and toxicity of interferon-gamma (IFN-gamma) was assessed in a phase I/II study of 21 patients with acquired immune deficiency syndrome (AIDS). A highly purified preparation of human recombinant E. coli-produced IFN-gamma was given i.v. twice weekly for an 8 week period. Patients were enrolled in the study in groups of four or five; the initial group received an IFN-gamma dose of 0.03 mg/m2 and subsequent groups received higher IFN-gamma doses of 0.3, 1, or 3 mg/m2. Toxicity resulting from IFN-gamma was minimal and the therapy was well tolerated even at the maximum dose (3 mg/m2). No patients developed antibodies that neutralized IFN-gamma. Clinical responses were observed in 3 of 17 patients with Kaposi's sarcoma (KS). A complete clinical response was achieved in one individual and a partial, temporary regression of KS lesions was observed in two other patients. HIV p24 antigen was decreased in plasma samples obtained from six of nine patients with initially detectable HIV protein. These data suggest that IFN-gamma should be considered as a therapeutic agent, possibly with other antivirals, in the treatment of patients with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Beta-2-microglobulin for differentiation between ciclosporin A nephrotoxicity and graft rejection in renal transplant recipients.

The clinical relevance of daily measurement of beta 2-microglobulin in serum and urine was evaluated in 49 patients undergoing renal transplantation. The changes in beta 2-microglobulin levels were compared to standard parameters for assessment of renal function. One hundred episodes of acute deterioration of renal function, clinically diagnosed as rejection, were analyzed retrospectively: (1) In 18 episodes renal malfunction did not respond to methylprednisone but improved immediately upon dose reduction of ciclosporin A, thus indicating a nephrotoxic effect of the drug. In these cases a mean increase of beta 2-microglobulin in urine as high as 7.9 mg/l was observed while serum values decreased. (2) Fifty episodes of apparent rejection (responsive to steroids) were preceded by a 3-day lasting continuous rise of beta 2-microglobulin in serum of up to 3.6 mg/l as a mean with only a moderate elevation in urine. (3) In 13 episodes antirejection treatment could have been avoided as continuously declining laboratory parameters indicated spontaneous improvement of renal function. We conclude that parallel determination of beta 2-microglobulin in serum and urine allows to differentiate between ciclosporin A nephrotoxicity and rejection in 91% of the cases.

Acute Disease↗