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D Lutz

Publications and source records attributed to D Lutz.

At least 19 recordsLinked to original sources

The rapid formation of a large rotating disk galaxy three billion years after the Big Bang.

Observations and theoretical simulations have established a framework for galaxy formation and evolution in the young Universe. Galaxies formed as baryonic gas cooled at the centres of collapsing dark-matter haloes; mergers of haloes and galaxies then led to the hierarchical build-up of galaxy mass. It remains unclear, however, over what timescales galaxies were assembled and when and how bulges and disks--the primary components of present-day galaxies--were formed. It is also puzzling that the most massive galaxies were more abundant and were forming stars more rapidly at early epochs than expected from models. Here we report high-angular-resolution observations of a representative luminous star-forming galaxy when the Universe was only 20% of its current age. A large and massive rotating protodisk is channelling gas towards a growing central stellar bulge hosting an accreting massive black hole. The high surface densities of gas, the high rate of star formation and the moderately young stellar ages suggest rapid assembly, fragmentation and conversion to stars of an initially very gas-rich protodisk, with no obvious evidence for a major merger.

Journal Article↗

[Item response theory and its application in neurology. Measurement of activity limitations in neurologic patients].

This article is concerned with the measurement of activity limitations in neurologic patients and with the application of the item response theory (IRT), especially the Rasch analysis, in analyzing activity ratings. Activity limitations of 166 patients with different neurologic disorders (e.g., stroke, traumatic brain injury) were assessed with the Functional Independence Measure (FIM) during their stay in a rehabilitation hospital. Data analysis was performed with the Rasch model, which allows testing the psychometric qualities of the FIM. Results indicate that the FIM has good psychometric qualities. However, results also show that the 18 FIM items define two statistically and clinically different indicators. Thirteen items define disability in motor functions. Five items define disability in cognitive functions. Separate analyses of the two scales help to improve the psychometric quality of the FIM.

Activities of Daily Living↗

Diffuse large B-cell lymphomas with plasmablastic/plasmacytoid features are associated with TP53 deletions and poor clinical outcome.

To define reproducible criteria for subgroups of diffuse large B-cell lymphomas (DLBCL), including lymphomas with plasmablastic/plasmacytoid features (PB/PC-Fs), we investigated 66 DLBCL; the samples were categorized as either centroblastic (CB), immunoblastic (IB) or PB/PC-F applying standardized morphologic criteria. Blinded specimens were reviewed by three independent pathologists. The final consensus classification included 44 CB (67%), seven IB (10%) and 15 PB/PC-F (23%). The interobserver agreement between two centers (Vienna, Würzburg) was 93.5%. Most PB/PC-F were CD20+, cIgM+, MUM-1+, CD138+/-, bcl-6-, corresponding to an activated B-cell phenotype. Immunoglobulin-V(H) gene mutation analysis was consistent with a germinal or postgerminal center-cell origin. By fluorescence in situ hybridization analysis, 11/13 (85%) PB/PC-F had a monoallelic TP53 deletion. The pretreatment characteristics of patients with PB/PC-F included a tendency for more B symptoms, extranodal disease and a higher IPI. Importantly, PB/PC-F were resistant to standard chemotherapy (complete remission rate 47%, relapse rate 71%) and even autologous stem-cell transplantation. The median overall survival (OS) (14 months, P<0.002) and disease-free survival (6 months, P=0.02) were significantly shorter compared to patients with CB and IB. The OS difference was pronounced within the low and low-intermediate IPI risk group (P<0.001). Our data indicate a strong association of plasmablastic/plasmacytoid morphology with TP53 deletions, poor response to chemotherapy and short survival.

Adult↗

A randomized study comparing interferon (IFN alpha) plus low-dose cytarabine and interferon plus hydroxyurea (HU) in early chronic-phase chronic myeloid leukemia (CML).

This multicenter randomized phase III study was designed to compare the efficacy and toxicity of IFN alpha-2c (3.5 MU/d) in combination with either araC (10 mg/m(2) d1-10) or hydroxyurea (HU: 25 mg/kg per day) in newly diagnosed CML patients. A total of 114 patients were randomized. Following a median observation period of 36 (range 1-73) months the major cytogenetic response rates were 25 and 27% and the 4-year survival probabilities 62.5 and 63% for the araC and HU group, respectively. While the overall toxicity profile was comparable between both groups, patients in the HU arm exhibited a slightly higher degree of WHO grades 3 and 4 non-hematological toxicities.

Adult↗

Prognostic value of tumour cell detection in peripheral blood of breast cancer patients.

To investigate the prognostic value of tumour cells in peripheral blood (pB) of breast cancer (BC) patients, pB samples from 143 patients with benign lesions of the breast and from 467 BC patients were tested via a nested RT-PCR assay for mammaglobin mRNA. No sample from patients with benign lesions of the breast was found to be mammaglobin positive in contrast to 5/310 (2%) BC patients with no evidence of disease (NED) and 46/157 (29%) patients with metastatic disease (MD). Two hundred and eighteen BC patients with NED were followed for at least 12 months. All five mammaglobin-positive BC patients relapsed 1-13 months after first examination of positive pB samples in contrast to 27/213 (13%) patients without detectable tumour cells in pB. Fifty-nine BC patients with MD were tested for mammaglobin expression in pB at the time of first diagnosis of MD; 20 of them (34%) were mammaglobin positive. Patients were followed for a median of 19 months (2-51 months). During this time, 19/59 (32%) died due to tumour progression. In Kaplan-Meier survival analysis, BC patients with mammaglobin-negative pB samples at time of diagnosis of MD lived significantly longer than mammaglobin-positive patients (log-rank test: P = 0.0013). In addition, mammaglobin was an independent prognostic parameter and the difference reached significance in univariate as well as in multivariate analysis (P < 0.01). We conclude that the presence of tumour cells in pB of BC patients is of prognostic value.

Adult↗

Statistical validation of the mammaglobin-nested RT-PCR assay for tumor cell detection in blood of breast cancer patients.

A stochastic model was developed to validate the results obtained with the mammaglobin-nested RT-PCR assay for tumor cell detection in peripheral blood of breast cancer patients. Since the assay consists of four PCR setups per peripheral blood sample, the probabilities for receiving 0, 1, 2, 3, or 4 positive setups were calculated. In this model, samples with just 500 mammaglobin mRNA molecules are highly probable to result in at least three positive setups, whereas lower quantities shift the probabilities towards one or two positive setups. In the clinical trial, samples with one or two mammaglobin positive setups were detected in 6/143 (4%) patients with benign lesions of the breast, in 41/310 (13%) breast cancer patients with no evidence of disease and in 39/157 (25%) breast cancer patients with metastatic disease. On the contrary, no sample from patients with benign lesions of the breast resulted in three or four positive setups, but 5/310 (2%) breast cancer patients with no evidence of disease and 46/157 (29%) with metastatic disease. These results correspond with the model: an increased number of tumor cells in peripheral blood lead to a higher amount of mammaglobin mRNA molecules, and these samples may result in at least three positive setups. Samples with three orfour positive setups were mainly derived from breast cancer patients with metastatic disease and only occasionally from patients with no evidence of disease. On account of these results, samples with at least three positive setups are of prognostic value and regarded as tumor cell positive.

Breast Neoplasms↗

[Detection of mammaglobin mRNA as a marker for circulating tumor cells in breast carcinoma].

Mammaglobin (hMAM) has been shown to be a marker for the detection of circulating tumor cells in the peripheral blood (pB) of breast cancer (BC) patients via a nested RT-PCR assay. 286 samples from BC patients were classified into four defined clinical subgroups: prior to and after surgery (pre, post), no evidence of disease (NED) and metastatic disease (MD). hMAM mRNA expression was detected in 2/46 pre (4%), 2/24 post (8%), 4/135 NED (3%) and 35/81 MD (43%) patients. 68 BC patients with NED and negative for hMAM mRNA in their pB were repeatedly tested for at least 6 months. Fifteen of these patients relapsed. Eight of them were hMAM-positive, 5 at time of relapse, one patient 13 months before and two patients 10 and 17 months after relapse was diagnosed. 7/15 BC patients relapsed within 24 months, 5 of them were hMAM-positive versus 3 of 8 patients with later relapses. On the basis of these preliminary results we conclude that tumor cells can be detected via hMAM nested RT-PCR in the pB of BC patients and that hMAM could be a marker for early relapse.

Adult↗

Detection of circulating mammary carcinoma cells in the peripheral blood of breast cancer patients via a nested reverse transcriptase polymerase chain reaction assay for mammaglobin mRNA.

PURPOSE: According to current medical research, mammaglobin (hMAM) is expressed exclusively in the mammary glands of adult women and in mammary tumor cell lines. Therefore, we examined hMAM expression as a marker for the detection of carcinoma cells in the peripheral blood of patients with breast cancer (BC). PATIENTS AND METHODS: Blood samples obtained from 114 BC patients at the various stages of their disease and from 68 individuals without BC were screened for hMAM mRNA by a nested reverse transcriptase polymerase chain reaction (RT-PCR) assay. RESULTS: The assay exhibited a calculated analytical limit of one tumor cell per 10(6) to 10(7) WBCs. None of the samples from peripheral blood of 27 healthy individuals were positive, whereas 29 (25%) of 114 samples from BC patients were positive for hMAM mRNA. hMAM mRNA expression was detected in five (28%) of 18 BC patients at diagnosis, in three (6%) of 53 with no evidence of disease, and in 21 (49%) of 43 with metastatic disease. These results correlate with patients' carcinoembryonic antigen (CEA) plasma level and, to some extent, with estrogen receptor status. Two of 41 samples from patients with malignancies other than BC were also positive. CONCLUSION: In contrast to healthy volunteers, hMAM transcripts were detected in the peripheral blood of BC patients. The percentage of positivity relates to the clinical stages of disease, CEA plasma level, and estrogen receptor status. Aberrant hMAM expression might occur occasionally in malignancies other than BC. The clinical relevance of hMAM RT-PCR-based tumor cell detection in the peripheral blood of BC patients should be further evaluated in prospective studies.

Adult↗

Telemedicine in the emergency department: a randomized controlled trial.

Emergency physicians and nurses were trained in telemedicine techniques in two emergency departments, one rural (low volume) and one suburban (high volume). Fifteen patient complaints were selected as appropriate for the study. Of 122 patients who met the inclusion criteria, 104 (85%) consented to participate. They were randomized to control and experimental groups. The suburban emergency physician diagnosed and treated the control patients. Experimental patients presenting to the high-volume emergency department were evaluated and treated by the telemedicine nurse in person and the rural emergency physician via the telemedicine link. Immediately before discharge all telemedicine patients were re-evaluated by the suburban emergency physician. Data collected on each patient included: diagnosis; treatment; 72 h return visits; need for additional care; and satisfaction of patient, physicians and nurses. There were no significant differences (P > 0.05) for occurrence of 72 h return visits, need for additional care or overall patient satisfaction. The average patient throughput time (from admission to discharge) was 106 min for the telemedicine group and 117 min for the control group. Telemedicine was a satisfactory technique for the chosen group of patients in the emergency department and was acceptable to the participants.

Emergency Service, Hospital↗

Synergistic interactions between ampakines and antipsychotic drugs.

Tests were made for interactions between antipsychotic drugs and compounds that enhance synaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-type glutamate receptors ("ampakines"). Typical and atypical antipsychotic drugs decreased methamphetamine-induced hyperactivity in rats; the effects of near or even subthreshold doses of the antipsychotics were greatly enhanced by the ampakines. Interactions between the ampakine CX516 and low doses of different antipsychotics were generally additive and often synergistic. The ampakine did not exacerbate neuroleptic-induced catalepsy, indicating that the interaction between the different pharmacological classes was selective. These results suggest that positive modulators of cortical glutamatergic systems may be useful adjuncts in treating schizophrenia.

Animals↗

A randomized controlled trial of telemedicine in an emergency department.

A prospective study of emergency department telemedicine was carried out at two hospitals in northern New Jersey. One hundred and twenty-two patients met the inclusion criteria. One hundred and four (85%) consented to participate, with 54 being randomized to the telemedicine group and 50 to the control group. Four patients did not complete the protocol. No significant differences were seen between the groups for: occurrence of 72 h emergency department return visits (0% vs 0%); need for additional care (2.3% vs 2.4%); positive patient-physician interaction (98% vs 100%); positive patient-nurse interaction (98% vs 98%); positive overall patient satisfaction (98% vs 95%). The average patient throughput time (time from admission to discharge) for the telemedicine group was 106 min; the average for the control group was 117 min. Telemedicine was found to be a satisfactory technique for pre-selected emergency department patients and was viewed by the physicians as an acceptable method of complementary care.

Emergency Medical Services↗

High dose chlorambucil versus Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone regimen in the treatment of patients with advanced B-cell chronic lymphocytic leukemia. Results of an international multicenter randomized trial. International Society for Chemo-Immunotherapy, Vienna.

BACKGROUND: In recent years, much attention has been paid to the possible efficacy of intensive chemotherapy in the treatment of advanced, progressive B-cell chronic lymphocytic leukemia (CLL) patients. For this reason, the International Society for Chemo-Immunotherapy, Chronic Lymphocytic Leukemia Cooperative Group, has begun a randomized multicenter trial comparing Binet's modified cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen with continuous high dose chlorambucil (HD-CLB). METHODS: During the period January 1987 to May 1993, 228 previously untreated CLL patients from 7 cooperative institutions were randomized to this trial. Advanced and/or progressive disease was defined by high Total Tumor Mass (TTM) score (> 9), and/or short doubling time (DT) (< 12 months), and/or bone marrow failure. The response to therapy was defined by reduction of the initial TTM score. The end points of the trial were response rate, survival, and toxicity. RESULTS: HD-CLB resulted in a higher response rate than CHOP in evaluable cases, with 89.5% overall responses (complete response+partial response) versus 75%, respectively (P < 0.001). At the time of an analysis performed in July 1995 (after a median follow-up period of 37 months), overall survival was also longer in the HD-CLB treatment arm (median survival, 68 months) than in the CHOP treatment arm (median survival, 47 months) (P < 0.005). Toxicity was acceptable and comparable in the two treatment arms. CONCLUSIONS: The current study showed that HD-CLB is an effective and well-tolerated therapeutic option for patients with advanced and/or progressive CLL. Therefore, the authors recommend its wider use, possibly in comparison with and/ or in combination with new therapeutic agents, such as purine analogues.

Aged↗

Bisindolylmaleimide protein-kinase-C inhibitors delay the decline in DNA synthesis in mouse hair follicle organ cultures.

We have used a series of bisindolylmaleimide selective protein-kinase C (PKC) inhibitors to investigate the role of this enzyme in the regulation of cell proliferation in mouse hair follicle organ cultures. Mouse whisker follicles were isolated by microdissection, and rates of DNA synthesis during culture were determined from 3H-thymidine incorporation. The bisindolylmaleimides Ro 31-7549, Ro 31-8161, Ro 31-8425 and Ro 31-8830 inhibit isolated brain PKC with IC50 values of 8-80 nM, are > 60-fold less potent against protein kinase A, and inhibit PKC-mediated protein phosphorylation in platelets with IC50 values in the range 0.25-4.4 microM. These PKC inhibitors were found to increase levels of mouse hair follicle DNA synthesis, with EC50 values in the range 1-4 microM and maximal levels in the range 151-197% of control. Ro 31-7549 had an IC50 value 50-fold lower than that of minoxidil, while the maximal level of DNA synthesis for the PKC inhibitor was 86% higher. Incubation of mouse hair follicles with Ro 31-7549 resulted in a delay of approximately 24 h in the onset of decline in follicular DNA synthesis rates. Ro 31-6045 and Ro 31-7208, bisindolylmaleimides without activity in the platelet PKC assay, did not affect mouse hair follicle DNA synthesis rates. Taken together, these findings show that PKC mediates, at least in part, the rapid loss of proliferative activity that occurs in mouse whisker follicles in culture, and provide further evidence that PKC plays a role as a negative proliferative signal in hair follicles.

Animals↗

All-trans retinoic acid and short-time, high-dose cytarabine in two children with acute promyelocytic leukemia.

We report on two girls, 3 and 13 years old, with acute promyelocytic leukemia (APL) who were successfully treated with all-trans retinoic acid (ATRA) 45 mg/m2/day. "Retinoic acid syndrome" was prevented with short-time treatment of high dose (4 x 1.5 g/m2) cytarabine. This regimen was well tolerated, although both children were critically ill. They achieved a complete remission confirmed by light microscopy, but reverse transcriptase polymerase chain reaction remained positive after ATRA, underlining the need of further chemotherapy.

Adolescent↗

2-Chlorodeoxyadenosine treatment in non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia resistant to conventional chemotherapy: results of a multicentric experience. International Society for Chemo-Immunotherapy.

Among the purine analogs, 2-chlorodeoxyadenosine (2-CDA) is particularly effective for the treatment of hairy cell leukemia and Waldemstrom's macroglobulinemia. Both efficacy and toxicity of 2-CDA were evaluated in previously treated patients affected with chronic lymphoproliferative disorders such as low-grade non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). Thirty cases, mainly refractory, 16 affected with CLL, were included from six centers of the International Society for Chemo-Immunotherapy (IGCI). 2-CDA was administered in a 2 h i.v. infusion for 5-7 days at the standard dose of 0.1 mg/kg/day every 4 weeks. The median number of cycles was 3. Of 30 cases, eight (26.7%) achieved a complete remission (CR), nine (30%) a partial remission (PR), and two (6.7%) a minor response, while five cases (16.6%) did not respond, and six (20%) were considered early deaths. The overall response rate (CR + PR) was 56.7%, with a median response duration of 12 months (range 3-28 +) and a better response in CLL patients. Considering that the majority of patients were heavily pretreated, toxicity was acceptable, with 40% of cases not presenting any toxic effect. The main toxicity consisted in infectious complications. Based on the results of the present study, we confirm that 2-CDA is an effective drug in these lymphoproliferative disorders, suggesting its possible use either alone or in combination, also as first-line therapy.

Adult↗

Development of a regional cohort of very-low-birthweight children at six years: cognitive abilities are associated with neurological disability and social background.

The authors studied the intelligence, memory, visuomotor skills and la nguage of 298 six-year-old children with very low birthweight (VLBW) (less that 1500g). Of 591 VLBW childern born July 1983 to June 1986 within 50km of the centre of Hamburg, Germany, 330 were traceable at age six years and 298 of these were seen by a neuropaediatrician and a psychologist; the other 19 were too severely disabled for psychological assessment with the standardized tests used. The mean memory performance of VLBW children at age six years was below the standard mean in all diagnostic and socio-economic subgroups. As expected, visuomotor development was clearly influenced by neurological but not socio-economic status. Intelligence and language skills were much more closely related to socio-economic background that to neurological morbidity. However, VLBW children with hyperactivity, clumsiness or cerebral palsy differed significantly in intelligence and visuomotor performance from those without neurological symptoms.

Cerebral Palsy↗

Factors influencing the timing of peripheral blood stem cell collection (PBSC).

High-dose conditioning regimens followed by autologous peripheral blood stem cell rescue are frequently used for the treatment of solid tumors and hematological malignancies. In 24 patients up to four peripheral stem cell collections (PBSC) were performed after priming with various chemotherapies and G-CSF (300 micrograms s.c. per day). In 16 patients (group A) more than 2 x 10(6) CD 34 positive cells per kg bodyweight could be collected; fewer were harvested in the remaining eight patients (group B). The amount of collected CD 34 positive cells correlated with the median number of these cells in the peripheral blood at the start of PBSC. The two groups differed both in recovery time after priming-induced cytopenia (4 vs 6 days from nadir) and in the number of WBC (21 x 10(6) mL-1 vs 6.1 x 10(6) mL-1) and platelets (133 x 10(6) mL-1 vs 58 x 10(6) mL-1) reached at first day of PBSC. No difference between the two groups was seen according to age, duration of disease or disease status. However, the intensity of prior treatment was significantly greater in group B than in group A. These observations indicate that the toxicity of previous chemotherapy is the most important factor for the mobilization of sufficient CD 34 positive cells into the peripheral blood.

Adolescent↗