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Biomedical subjects

R Scherrer

Publications and source records attributed to R Scherrer.

At least 19 recordsLinked to original sources

Evaluation of a total hematology analysis system (Sysmex HS-430). Benefits for large laboratories by reducing manual work load and optimizing screening efficacy for pathologic samples.

In this study, the authors evaluated a closed tube total hematology analysis system, Sysmex HS-430 (HS), which consists of two automated hematology analyzers, Sysmex NE-8000, the reticulocyte analyzer, Sysmex R-3000, and a slide preparation unit integrated in an automated sample transport system (TOA Medical Electronics, Kobe, Japan). The suitability of the system was compared with a conventional hematology system (CS) consisting of two single standing Coulter STKS analyzers (Hialeah, FL), one automated reticulocyte counter Sysmex R-1000, and the manual blood smear preparation. Evaluation was performed following the concept suggested by the Austrian-German societies for Clinical Chemistry and Laboratory Medicine that includes the evaluation of personnel supply. Eight consecutive series with a total of 4,896 samples were analyzed on both systems. Evaluation revealed that the analysis time per series was 238 minutes on the HS-430 and 359 minutes on the CS. The mean analyzer down times because of technical reasons were 36 minutes on the HS and 32 minutes on the CS. The down time because of "nontechnical" reasons was 31 minutes on the HS-430, but 173 minutes on the CS, which was mainly because of discontinuous sample loading of analyzers of the CS. The average direct technical time effort for complete blood cell count (CBC) analyses, reticulocyte counts, and blood smear preparations per series was 23 minutes on the HS and 245 minutes on the CS. In summary, these data show that an automated system like the HS-430 saves 222 minutes of manual activities arising in a large routine hematology laboratory with a mean throughout of 612 samples per day. Furthermore, the system improves intralaboratory turnaround times, avoids human errors by automated sample identification, and guarantees more safety for laboratory staff by minimizing the contact with potential biohazards.

Blood Cell Count↗

PCR-monitoring of minimal residual leukaemia after conventional chemotherapy and bone marrow transplantation in BCR-ABL-positive acute lymphoblastic leukaemia.

We report the results of consecutive tests in nine BCR-ABL-positive ALL patients by one-step and two-step (nested primer) reverse transcriptase-polymerase chain reaction (RT-PCR). Six patients could be tested in complete haematological remission (CHR). One patient remained one-step positive; four patients became one-step negative, but remained two-step positive; only one patient became two-step negative. In five patients the haematological relapse was preceded by one-step positivity by 1.5-5 weeks. In two patients who received autologous BMT in CHR, BCR-ABL was still detectable by two-step PCR, whereas allogeneic BMT was able to transiently reduce BCR-ABL below the two-step detection level. Our results show that one-step combined with two-step RT-PCR analysis gives valuable information about the efficacy of treatment and the dynamics of the leukaemic clone.

Adult↗

High efficacy of the German multicenter ALL (GMALL) protocol for treatment of adult acute lymphoblastic leukemia (ALL)--a single-institution study.

Sixty-one consecutive patients with acute lymphoblastic leukemia (ALL) (B-ALL excluded) were treated with the protocol described by Hoelzer et al. [15]. The complete remission (CR) rate was 85% (52/61 patients). Three patients died during induction therapy; six patients were refractory to treatment. The median duration of continuous complete remission (CCR), disease-free survival (DFS), and overall survival was 41.5, 41.4, and 40.8 months, respectively. At 5 years the probability of CCR was 49%, of DFS 43.5%, and of overall survival 41.6%. In the univariate analysis older age (> 35 years, p = 0.01), bcr-abl positivity (p = 0.007), and time to CR (> 4 weeks, p = 0.05) were significantly unfavorable prognostic factors. In the multivariate analysis only age (p = 0.006) and time to CR (p = 0.02) remained significant. Thus, our data confirm the high efficacy of this treatment regimen with regard to CR rate and remission duration.

Adolescent↗

Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL).

Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 micrograms/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/microliters at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/microliters) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/microliters) in G-CSF-treated patients compared with controls (1880/microliters). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85%) G-CSF patients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.

Adolescent↗

Hypergranular acute lymphoblastic leukemia (ALL). Report of a case and review of the literature.

We report a case of adult acute lymphoblastic leukemia (ALL) with myeloid-like hypergranulation of blast cells. Like most of the "granular" ALLs described in the literature, the blast cells had L2 morphology and exhibited a common-ALL immunologic phenotype. The clinical findings at diagnosis were unremarkable. Cytogenetic analysis showed a 46XY karyotype. Molecular genetic analysis revealed T-cell receptor (TCR) gamma and immunoglobulin heavy chain rearrangements; no rearrangement was found at the TCR beta gene locus. The polymerase chain reaction (PCR) for the BCR-ABL translocation was negative. The clinical course of the patient was uncomplicated. On standard ALL treatment protocol he achieved complete remission (CR) within 4 weeks, and he is currently disease free 8 months after diagnosis. The case contributes well-documented data to the characterization of adult "granular" ALL, with special regard to changes at the molecular genetic level.

Adult↗

Type beta transforming growth factors promote interleukin-3 (IL-3)-dependent differentiation of human basophils but inhibit IL-3-dependent differentiation of human eosinophils.

Basophils and eosinophils share a common differentiation pathway. Factors regulating terminal commitment toward one cell type, however, have so far not been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both human eosinophils and basophils. In the present study, the effects of various recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils and basophils were studied in a bone marrow (BM) suspension culture system (normal donors, n = 13). We found that type beta transforming growth factors (TGFs) lead to a significant increase in the absolute numbers of basophils in BM cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4 +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and formation of eosinophil cationic protein in the same culture system. The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system. Type beta TGFs as well as the IFNs failed to directly induce differentiation of human basophils or eosinophils in the absence of other growth factors. Together, these results show that type beta TGFs and IFNs are potent regulators of cytokine-dependent growth and differentiation of human allergic effector cells.

Antibodies, Monoclonal↗

Detection of circulating endogenous interleukin-3 in extensive chronic graft-versus-host disease.

Recent data suggest that activated immune cells and their products are involved in the initiation and progression of graft-versus-host disease (GVHD). To test whether the production of endogenous interleukin-3 (IL-3), a product of activated immune cells, might be an indicator of disease activity in GVHD, we analysed sera of 61 bone marrow transplant (BMT) recipients for IL-3 levels by using an enzyme linked immunosorbent assay. Measurable levels (greater than 25 pg/ml) of endogenous IL-3 were detected in a significant subgroup (5/16 patients, 31.25%) of allograft recipients suffering from extensive chronic GVHD, but not in patients with limited chronic GVHD (n = 6) or in those without signs of chronic GVHD (n = 17). In IL-3 positive patients, IL-3 levels were not associated with pathologic conditions (such as infectious disease) other than GVHD. IL-3 levels were undetectable in disease-free phases preceding severe chronic GVHD. Lower levels of IL-3 were measured in chronic GVHD patients during extensive disease while on high dose steroid medication compared with before and/or after (p less than 0.02). IL-3 was also detected in a small group (2/17) of patients suffering from acute GVHD. IL-3 could neither be detected in syngeneic (n = 3) nor autologous (n = 7) BMT recipients nor in the vast majority (99/100) of healthy controls. Together, measurable amounts of IL-3 are produced in a significant subgroup of patients suffering from extensive chronic GVHD.

Adolescent↗

MDR1 gene expression and treatment outcome in acute myeloid leukemia.

To prospectively assess the role of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML), levels of MDR1 RNA in blast cells were determined at diagnosis and correlated with treatment outcome in 63 patients. MDR1 RNA levels were negative in 29% and positive in 71% of the patients. The complete remission rate in response to induction chemotherapy was 89% for MDR1 RNA-negative patients and 53% for MDR1 RNA-positive patients (P = .008). Expression of the MDR1 gene was observed in most patients who died early or had resistant disease. Kaplan-Meier curves revealed a decrease in both disease-free survival and overall survival of patients with detectable MDR1 gene expression compared with the disease-free survival and overall survival of MDR1 RNA-negative patients (P = .029 and P = .009, respectively). These data indicate that MDR1 gene expression is an unfavorable prognostic factor and suggest that multidrug resistance is important in AML.

Adolescent↗

Hepatic and splenic abscesses--a common complication of intensive chemotherapy of acute myeloid leukemia (AML). A prospective study.

In order to determine the frequency of hepatosplenic abscesses in AML patients during chemotherapy and to evaluate the clinical and laboratory characteristics of this complication we performed a prospective study over a 28-month period. Fifty-five consecutive patients with de novo AML or relapse who received intensive chemotherapy underwent regular ultrasound examinations. In 16 patients (29.1%) hepatic and/or splenic abscesses were detected sonographically. Histopathological evidence for abscess formation was obtained in five of these 16 patients. In three patients granulation tissue and in one patient necrotizing granulomas were found. Causative micro-organisms were proven in only three patients: Candida hyphae were demonstrated in one patient, gram-positive cocci in another. Bacteria and fungi were seen in the tissue specimen of the third patient. Patients with hepatosplenic abscesses had significantly prolonged fever after neutrophil recovery but did not differ from patients without abscesses in any other laboratory or clinical features. Due to the absence of specific alerting clinical and laboratory signs and symptoms of hepatosplenic abscesses, routine ultrasound examination is required for detection of this complication. The presence of hepatic and/or splenic abscesses does not necessarily worsen the prognosis, but it may influence the decision on further chemotherapy and antimicrobial treatment.

Abscess↗

Histologic tumor regression grades in squamous cell carcinoma of the head and neck after preoperative radiochemotherapy.

Forty-one patients with Stage III and IV squamous cell carcinomas (SCC) of the head and neck were treated preoperatively with mitomycin C and 5-fluorouracil and concomitant radiotherapy. Operation specimen were examined histologically, the percentage of vital tumor cells and devitalized tumor cells were graduated. The grade of regression was classified according to a four-stage scale. Tumor regression was elevated as good (Grades 1, 2) and bad (3, 4) response to combined preoperative therapy. After a follow-up of 18 to 30 months, 14 of 41 patients have experienced a locoregional recurrence; all these patients were bad responders (Grades 3, 4) to preoperative radiochemotherapy. There was a statistically significant correlation between tumor regression grade and probability of survival (P less than 0.001). The authors conclude that the prognosis of patients with pretreated SCC of head and neck depends on the histologic grade of tumor regression.

Adult↗

Conditional impairment of cell division and altered lethality in hipA mutants of Escherichia coli K-12.

Mutations in hipA, a gene of Escherichia coli K-12, greatly reduce the lethality of selective inhibition of peptidoglycan synthesis. These mutations have also been found to reduce the lethality that accompanies either selective inhibition of DNA synthesis or heat shock of strains defective in htpR. In addition, the mutant alleles of hipA are responsible for a reversible cold-sensitive block in cell division and synthesis of macromolecules, particularly peptidoglycan. Recombination between the chromosome of hipA mutants and plasmids containing noncomplementing fragments of hipA+ revealed that the mutations responsible for both cold sensitivity and reduced lethality were probably identical and, in any case, lay within the first 360 base pairs of the coding region of hipA, probably within the first 50 base pairs. We suggest that the pleiotropic effects of mutations in hipA reflect the involvement of this gene in cell division.

Alleles↗

[The Mantoux test using Berna and Copenhagen tuberculins in comparison with the epicutaneous Mérieux Monotest in adults].

New infection with tuberculosis is a risk for hospital patients, and it would therefore be desirable to evaluate the proportion of converters by a simple epicutaneous test. It is also known that reactions to Mantoux tests of different manufacturers may vary widely. Simultaneous tuberculin skin tests with tuberculin Berna, tuberculin Kopenhagen and Monotest Mérieux have been compared in 81 geriatric patients and 54 young volunteers. Monotest Mérieux and Mantoux test with tuberculin Berna were administered in 222 additional patients, and it was therefore possible to compare a Monotest and a tuberculin test in a total of 357 patients. There was no statistically significant difference between the two Mantoux tests. An unexpectedly high false positive rate was found with Monotest. The reasons for this are discussed. The two products used in Switzerland today are equivalent. Positive reactions to Monotest need confirmations by Mantoux test.

Adult↗

Microincineration and elemental X-ray microanalysis of single Bacillus cereus T spores.

Single whole spores of bacillus cereus T were analyzed by scanning electron microscopy and electron microprobe X-ray microanalysis before and after high-temperature (600 degrees C) ashing in air. High-temperature ashing consisted of a centripetal oxidation of the spore surface combined with pyrolysis of the spore's interior. Ashing of single spores produced a compact central ash particle, mimicking the much larger unashed spore body in outline but containing craterlike microregions, and a peripheral thin ash film. Ashing mostly eliminated the spore's organic matrix; however, ash residues still gave residual carbon-characteristic X-ray counts. Ashing of single spores produced a two-, five-, and six-fold increase of potassium, magnesium, and calcium X-ray intensities, respectively. Iron, although low in actual counts, became detectable after ashing. Phosphorus characteristic X-rays were decreased by 41% after ashing, while volatilization lowered sodium and manganese X-ray intensities by over 80%. High-temperature ashing enhanced element-characteristic X-ray intensities of the non-volatilizable mineral(ized) elements of spores by compacting them into ash residues, more so than by simply abolishing their organic matrix. Microincineration appears a generally useful preconcentration technique for elemental detection and localization in X-ray microanalysis.

Bacillus cereus↗

Structure, partial elemental composition, and size of Thiopedia rosea cells and platelets.

The phototrophic purple sulfur bacterium Thiopedia rosea forms multicellular, gas-vacuolate, regular, flat aggregates (platelets, sheets) held together by slime. Platelets found in eutrophic water consisted of slime (85% of the total wet volume) and 16 cells, while the gas-filled vacuole occupied 44% of the volume of a single wet cell. Individual platelet cells contained central spindle-shaped gas vesicles (which together constitute the cell's gas vacuole), intracytoplasmic membrane vesicles (chromatophores), and peripheral sulfur globules. Cells were surrounded by a Gram-negative type cell envelope and were connected to neighboring cells of the same platelet by mostly unstructured slime. Cells contained detectable amounts of magnesium, phosphorus, sulfur, and potassium as determined by wavelength-dispersive X-ray microanalysis. The large size and relatively low slime density of the platelet, as well as the flat shape, could greatly decrease platelet sedimentation and so stabilize the position of T. rosea within its water column.

Electron Probe Microanalysis↗

Isolation and characterization of anti-rotavirus immunoglobulins secreted by cloned hybridoma cell lines.

Five monoclonal hybridoma cell lines secreting antibodies against bovine rotavirus have been produced and four of them characterized by immunostaining of structural polypeptides electrophoretically transferred on to nitrocellulose sheets. Three hybridomas appeared to be directed against the major structural polypeptide (VP39) of the virion. These three monoclonals cross-reacted with the major polypeptide of simian rotavirus and human rotavirus. A fourth hybridoma appeared to react specifically with the high-molecular weight external polypeptide (VP89) and its cleavage products. A cross-reaction was observed with human Wa strain but not with SA11. The fifth hybridoma, even though reacting in an immunofluorescent test, did not show any reactivity by immunostaining. None of the monoclonals neutralized the infectivity of bovine rotavirus.

Antibodies, Monoclonal↗

Interaction of bisulfite with unsaturated fatty acids.

Sodium bisulfite reacted with unsaturated fatty acids, significantly increasing their polarity as determined by behavior on silica gel thin-layer chromatography. The ultraviolet absorption spectra of unsaturated fatty acids (due to the presence of double bonds) were abolished as a result of the reaction. Fatty acids containing more than one double bond (arachidonate, linolinate, and linoleate) reacted more rapidly with bisulfite than did oleate. When arachidonate double bonds were titrated with bisulfite there was a much larger spectral decrease with the first equivalent of bisulfite added than with each subsequent addition. Vitamin E, vitamin E nicotinate, and butylated hydroxytoluene significantly inhibited the reaction of bisulfite with unsaturated fatty acids. It is suggested that the reaction of bisulfite with unsaturated fatty acids may be a mechanism of SO2 toxicity.

Antioxidants↗