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Biomedical subjects

J Schindler

Publications and source records attributed to J Schindler.

At least 19 recordsLinked to original sources

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

[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

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

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

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

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

[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

[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

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

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

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

Plasma glutamate--a prognostic marker of cancer and of other immunodeficiency syndromes?

Elevated plasma levels of glutamate (GLU) have been reported to occur in patients with malignancies and other immunodeficiency syndromes (IDS). To evaluate, whether GLU is useful as prognostic indicator, the plasma concentrations were determined in patients with colorectal carcinoma (CRC), with breast cancer (BRC), and with HIV-infection (HIV). The results were correlated with the disease-stages, and compared with data obtained from patients with benign diseases of the same organ, as well as from sex-matched healthy volunteers. GLU concentrations (volunteers: 27.4 +/- 17.6 mumol/l) were elevated in all BRC patients (range of mean values: 53.5-83.2 mumol/l), in CRC patients with T2-T4-tumours (means: 46.8-85.9), and in HIV+ patients of stage WR 5, 6 (means: 53.9-69.7 mumol/l). All CRC- and BRC-patients with metastases showed highly significant elevations of GLU concentrations (p less than 0.001), but there were no direct correlations between disease stages and GLU levels. Pre-operative patients with benign diseases (diverticulitis, adenoma = GID; and mastopathy = MTP) showed increased GLU levels, which were comparable to those of the tumour patients. The glutamine/GLU ratios (volunteers: 19.3 +/- 15.0) were decreased only in HIV-WR 6 (7.6 +/- 2.1), and BRC-stage 4 (8.0 +/- 1.7). From these results we deduce that the plasma GLU concentrations do not allow a discrimination either between patients with malignancies and without, and between persons of different disease stages.

Aged

[Dosimetric studies of 192Ir line sources and the mathematical presentation of the dose distribution].

The dose distribution of a "line-shaped" 192Ir-source was measured in 1,152 measuring points in a water phantom. Using regression analysis the analytical description of dose distribution was obtained. Accomplished comparison measurings with a solid phantom of miramide in 45 measuring points show that the dose distribution can be reproduced well by solid phantom measurings. Taking an ideal line source distribution as a basis, the r-dependence of correction factor, obtained by regression analysis, refers to a dispersion effect. The angle-dependent deviation of dose distribution from the ideal line source can be described by cos-terms with the single and double angle between line source axis and measuring point.

Brachytherapy

[A standard code for naming microbes].

The author suggests a code for communication and processing of data which involves the formation of code names, in particular of microorganisms. These code is reached after agreement, made compulsory and then strictly respected. The principle for the formation of the code is relative comprehensibility, simplicity and orientation on a given area of application. The generation of the code is made by a computer.

Information Systems

Plasma amino acid pattern of patients with HIV infection.

We measured the free amino acids in plasma of 58 patients with HIV infection and in six persons in the risk group. The HIV+ patients had significantly increased concentrations of arginine, phenylalanine, and glutamate in comparison with both age- and sex-matched controls and the members of the risk group. Glutamate concentrations increased only in an advanced stage of the disease (WR 5 and 6 of the Walter Reed staging classification), whereas arginine and phenylalanine increased independently of the stage. There was no correlation between the amino acid concentrations and the number of T4 and T8 lymphocytes, the sedimentation rate, and the existence or absence of Kaposi's sarcoma. The amino acid pattern of HIV-infected persons is similar to that of cancer patients or those with other immune deficiencies.

Acquired Immunodeficiency Syndrome

Interferon gamma in rheumatoid arthritis--a double blind study comparing human recombinant interferon gamma with placebo.

A double blind trial comparing recominant interferon gamma (IFN gamma) with placebo in rheumatoid arthritis is presented. Twenty-six patients entered the study and 22 completed the 6-month period. IFN gamma was administered subcutaneously as was placebo; the 1st week, patients treated with the active compound received a daily subcutaneous injection of 100 micrograms of IFN gamma and for the following 23 weeks the schedule was decreased to 2 injections of 100 micrograms every week. No serious side effects were observed. After Week 24 the group treated with the active compound showed a significant decrease of the joint tenderness score and the placebo group showed a significant increase of the number of subcutaneous nodules. All other variables shifted in favour of the active compound but not significantly. More double blind trials with a larger number of patients and using other treatment schedules or other routes of administration are required.

Arthritis, Rheumatoid