Biomedical subjects

R Vogler

Publications and source records attributed to R Vogler.

17 recordsLinked to original sources

PubMed2001

1Alpha,25-dihydroxyvitamin D3 protects human keratinocytes from apoptosis by the formation of sphingosine-1-phosphate.

Owing to its ability to induce growth arrest and differentiation of keratinocytes, 1alpha,25-dihydroxyvitamin D3 and its analogs are useful for the treatment of hyperproliferative skin diseases, such as psoriasis vulgaris. It has been implicated that the 1alpha,25-dihydroxyvitamin D3-induced differentiation of keratinocytes is mediated, at least in part, by the formation of ceramides; however, ceramides have also been identified to induce apoptosis in many cells, including keratinocytes. Therefore, it was of interest to investigate the influence of 1alpha,25-dihydroxyvitamin D3 on apoptosis in keratinocytes. Most interestingly, physiological concentrations of 1alpha,25-dihydroxyvitamin D3 did not induce apoptosis in keratinocytes, despite the formation of ceramides. Moreover, 1alpha,25-dihydroxyvitamin D3 appeared cytoprotective and made keratinocytes resistant to apoptosis induced by ceramides, ultraviolet irradiation, or tumor necrosis factor-alpha. The cytoprotective effect was accompanied by the formation of the sphingolipid breakdown product sphingosine-1-phosphate, which prevented apoptosis in analogy to 1alpha,25-dihydroxyvitamin D3. The effect of 1alpha,25-dihydroxyvitamin D3 was specific as the almost inactive precursor cholecalciferol neither induced sphingosine-1-phosphate formation nor prevented cells from apoptosis. Besides this, the cytoprotective aptitude of 1alpha,25-dihydroxyvitamin D3 was completely abolished by the sphingosine kinase inhibitor N,N-dimethylsphingosine, which blocked sphingosine-1-phosphate formation. Moreover, sphingosine-1-phosphate was able to restore the cytoprotective effect of 1alpha,25-dihydroxyvitamin D3 in the presence of N,N-dimethylsphingosine. Taken together, here we report for the first time that 1alpha,25-dihydroxyvitamin D3 protects keratinocytes from apoptosis and additionally this cytoprotection is mediated via the formation of sphingosine-1-phosphate.

Apoptosis↗

PubMed1997

Long-term follow-up of three randomized trials comparing idarubicin and daunorubicin as induction therapies for patients with untreated acute myeloid leukemia.

BACKGROUND: Most clinical trials for acute leukemia have reported results after 2-3 years of follow-up. Comparisons between the original data and longer-term follow-up data may be of interest, particularly with regard to promising new therapies. METHODS: In 1996, survival data were updated from three prospective, randomized comparisons of idarubicin and daunorubicin that began in 1984 and 1985. These were trials of the Memorial Sloan-Kettering Cancer Center (MSKCC), the U.S. Multicenter Study Group, and the Southeastern Cancer Study Group (SEG). The original results of these trials were reported in 1991 and 1992. RESULTS: The original results of the SEG trial demonstrated no significant difference between idarubicin and daunorubicin. The updated survival analysis showed similar results. The MSKCC trial revealed a significant advantage of idarubicin compared with daunorubicin in both the original and the updated analyses. The U.S. Multicenter trial found a significant difference favoring idarubicin in the original analysis, but the difference was not significant in the updated analysis. CONCLUSIONS: It is essential that the median length of follow-up be clearly stated in any clinical trial. When the results obtained with a particularly promising new drug or procedure are presented early in the course of study (within 1-2 years), the investigators should strongly consider a repeat evaluation after an additional 3-5 years of follow-up.

Acute Disease↗

PubMed1997

Guidelines for selecting outcome measures: lifestyle modification for stage 1 hypertension.

Lifestyle modification is the recommended intervention for stage 1 hypertension. Advanced practice nurses are well positioned to guide lifestyle modification, and they are well prepared to measure outcomes related to the intervention. Selection of an appropriate outcome measure begins with matching the measure to the intervention. Matching is reliant on identification of the system of ideas and the research database guiding the intervention. This article proposes guidelines for selecting an outcome measure for use with individuals in practice settings. The guidelines are then applied in the selection of an outcome measure for lifestyle modification in stage 1 hypertension.

Guidelines as Topic↗

PubMed1995

Dural cavernous angioma: MR features.

The imaging features of a cavernous angioma, which originated from the meninges, are presented. The patient harbored a second cavernous angioma within the brain parenchyma. Cavernous angioma should be included in the differential diagnosis of dural lesions, especially when other cavernous angiomas are present.

Adult↗

PubMed1993

Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia.

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1 beta genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1 beta gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy.

Aged↗

PubMed1993

Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study.

In an effort to determine if cell cycle active agents are augmented when given after non-cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone. Patients whose bone marrow did not show significant cytoreduction received 5-azacytidine. Twenty-seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission. A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5-azacytidine. Relapsed patients had a higher CR rate (36%) than refractory patients (15%). Nausea, vomiting, and stomatitis were common but rarely severe. The median duration of remission was 3.7 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes. In this patient population, there was no evidence that 5-azacytidine given after mitoxantrone increased the complete remission rate.

Adult↗

PubMed1993

Long-term outcome of patients with acute myelogenous leukemia: the role of maintenance therapy, consolidation therapy and the predictive value of two in vitro assays.

Three successive strategies used to treat acute myelogenous leukemia (AML) patients who entered complete remission are compared with respect to their long term efficacy (> 5 years). Additionally, the ability of two in vitro assays to identify patients who would be long term remitters was assessed. With respect to the proportion of patients in long term remission, 5 years of maintenance therapy, intensive consolidation therapy plus 3 years of additional therapy, and 4 courses of consolidation therapy produced equivalent results with 18 to 22% of patients in remission at 7 years. Patients whose leukemia cells retained high levels of cytosine arabinoside triphosphate (araCTP) and who received maintenance therapy were less likely to experience early relapse than comparably treated patients whose leukemia cells failed to retain araCTP. The failure of leukemia cells to clone in vitro was also associated with a lower early relapse rate for patients who received maintenance therapy. Neither the ability of leukemia cells to retain araCTP nor their ability to clone in vitro were of prognostic significance for patients treated with 4 courses of intensive consolidation therapy.

Arabinofuranosylcytosine Triphosphate↗

PubMed1992

Relationship of [3H]Ara-C incorporation and response to therapy with high-dose Ara-C in AML patients: a Leukemia Intergroup study.

Pretherapy bone marrow (BM) aspirates of 143 patients with acute myeloid leukemia (AML) were incubated simultaneously with bromodeoxyuridine (BrdU) and tritiated cytosine arabinoside ([3H]Ara-C) to determine the labeling index (LI) and extent of [3H]Ara-C incorporation. Of 143 AML patients, 121 received high-dose Ara-C (HDAra-C) as a single agent for induction therapy (55 newly diagnosed, 66 in first relapse), whereas 22 received HDAra-C plus mAMSA. The data demonstrate that a subset of patients who will fail HDAra-C remission induction therapy because of drug-resistant disease can be prospectively identified on the basis of the low amount of Ara-C incorporated by their leukemia cells.

Acute Disease↗

PubMed1991

The treatment of patients with newly diagnosed poor prognosis acute myelogenous leukaemia: response to treatment and treatment failure.

The failure of poor prognosis patients with newly diagnosed AML to enter remission is usually due to two phenomena: a high mortality rate and resistance of the leukaemia to chemotherapy. We conducted a pilot study of a regimen designed to overcome these two types of treatment failure. Patients were carefully selected for therapy on the basis of their likelihood of surviving. Chemotherapy consisted of high dose cytosine arabinoside (HDaraC) with the doses modified on the basis of patient age so as to reduce the risk of toxicity. Finally, daunorubicin was administered only to those patients for whom HDaraC was not likely to produce sufficient antileukaemia effects to produce a remission. The median patient age was 67 years and 69/88 (78%) patients had a history of preleukaemia and/or toxic exposure. Only 11/84 (13%) patients died during remission induction therapy and 40/84 (48%) entered CR. Patients with only one risk factor had a higher CR rate than those with more than one risk factor (56% v. 30%, P = 0.02) and also had longer durations (222 d v. 113.5 d, P = 0.035). Two types of resistance to chemotherapy were observed: 'classical resistance' (the failure of chemotherapy to produce substantial killing of leukaemia cells) and the rapid regrowth of leukaemia cells subsequent to a level of cytoreduction which otherwise would have been sufficient to produce a CR.

Aged↗

PubMed1990

MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia.

The expression of the MDR1 gene was studied by Northern blot analysis in leukaemic cell specimens obtained from 74 patients with acute myelogenous leukaemia (AML). No relationship was found between MDR1 RNA levels and FAB type of leukaemia or patient age. Transcript levels tended to be highest in the leukaemic cells of patients with a history of toxic exposure or preleukaemia compared with 'standard risk' patients at diagnosis but the differences were not significant (P = 0.07). Patients whose leukaemic cells contained high MDR1 transcript levels were difficult to induce into remission and, if remission was induced, the remissions were short. Hence high levels of MDR1 expression may explain, at least in part, the ineffectiveness of anthracycline antibiotic containing treatment regimens in some patients with AML.

Adolescent↗

PubMed1986

Limited efficacy of a four-day course of high-dose cytosine arabinoside in the treatment of poor-risk patients with acute nonlymphocytic leukemia.

High-dose cytosine arabinoside therapy was administered to 29 patients with poor-prognosis acute nonlymphocytic leukemia. In an attempt to reduce toxicity, therapy was divided into an initial 4-day course of therapy, followed by a 3-day course of the marrow aspirate examined 1 week after the end of treatment contained substantial numbers of leukemic cells. Of the 29 patients, 5 entered complete remission, 2 of them after the initial 4-day course of therapy. The toxicity of split-course therapy was the same as that of conventional 6-day high-dose cytosine arabinoside therapy. This study demonstrates that the modification of high-dose cytosine arabinoside therapy used in this study failed to reduce toxicity and produced a lower remission rate than that obtained with the 6-day course of therapy.

Acute Disease↗

PubMed1986

Prediction of response of patients with acute nonlymphocytic leukaemia to remission induction therapy: use of clinical measurements.

Two hundred patients with acute nonlymphocytic leukaemia received remission induction therapy consisting of cytosine arabinoside and an anthracycline antibiotic. Analysis of the pretherapy characteristics of the patients demonstrated that patient age was the most important factor in determining whether or not the patient would survive remission induction therapy. Assessment of the characteristics of the bone marrow after 6 d of therapy permitted the recognition of patients who were likely to fail to enter remission because of persistent leukaemia. Taken together, these observations demonstrate that it is possible to identify patients for whom conventional chemotherapy is not likely to be of benefit either because it is too intensive or because it is not intensive enough to produce a complete remission.

Acute Disease↗

PubMed1984

Relationship between plasma adriamycin levels and the outcome of remission induction therapy for acute nonlymphocytic leukemia.

Plasma adriamycin and adriamycinol levels were measured in 45 patients with acute nonlymphocytic leukemia 3 h after the drug was administered. A wide range of levels as found. Plasma levels increased after the administration of each of the three daily doses of the drug. High plasma levels were associated with both death during remission induction therapy and, for patients who entered remission, long remissions.

Acute Disease↗

PubMed1984

Relationship between the per cent of marrow cells in S phase and the outcome of remission-induction therapy for acute nonlymphocytic leukaemia.

The relationship between the pretherapy cell cycle characteristics of leukaemic marrow cells and the outcome of remission-induction therapy for acute nonlymphocytic leukaemia was studied in newly diagnosed and relapsed patients who were then treated with either combination chemotherapy consisting of cytosine arabinoside/anthracycline antibiotic +/- 6 thioguanine or with single agent high-dose cytosine arabinoside therapy. The outcome of high-dose cytosine arabinoside therapy was highly dependent upon the per cent of pretherapy cells in S phase with no remissions occurring in patients in whom the 3H-TdR labelling index was less than 6%. In contrast, the outcome of cytosine arabinoside/anthracycline antibiotic therapy was independent of the pretherapy cell cycle characteristics of the leukaemic cells.

Acute Disease↗

PubMed1984

Prediction of response of acute nonlymphocytic leukaemia to therapy with 'high dose' cytosine arabinoside.

The Leukemia Intergroup Study has treated 110 patients with acute nonlymphocytic leukaemia with 'high dose' cytosine arabinoside remission induction therapy and studied the factors which were related to the outcome of therapy. With respect to death during remission induction therapy, only patient age was of prognostic significance. Treatment failure due to resistant leukaemia was associated with a high pretherapy leukaemic cell mass, the presence of few cells in S phase, and insensitivity of DNA synthesis to cytosine arabinoside. If, after 6 d of therapy, more than 40% of the marrow cells were leukaemic, the patient almost invariably failed to enter complete remission because of persistent leukaemia. Simultaneous consideration of the pretherapy labelling index and the per cent abnormal cells in the day 6 marrow permitted a distinction to be made between almost all patients who would enter remission or fail therapy because of persistent leukaemia.

Age Factors↗

PubMed1977

Urinary excretion of the cancer-related glycoprotein EDCl: effect of chemotherapy.

The effect of chemotherapy on the urinary excretion of a cancer-related glycoprotein labeled EDCl, recently isolated from the urine of a patient with acute myelocytic leukemia, has been studied by radioimmunoassay in eight cancer patients who were excreting 200 to 500 mg/day before treatment. In five patients, chemotherapy caused marked clinical improvement, and the glycoprotein disappeared from the urine within 10 days after chemotherapy began. In the two patients with solid tumor who responded to chemotherapy, disappearance of glycoprotein EDCl from the urine preceded clinical improvement by 1 to 2 months. Four of the five responsive patients relapsed within 6 months; in each instance, the glycoprotein reappeared in the urine (greater than 100 mg/day) 2 to 5 weeks before clinical relapse. Three patients were resistant to chemotherapy, and their urinary glycoprotein did not decline during chemotherapy. Measurement of urinary glycoprotein EDCl will be useful in rapidly ascertaining which drug will be effective in a cancer patient and in predicting relapse.

Adolescent↗

PubMedDate not supplied

Developing a nursing doctorate for the 21st century.

Nursing in the next century will reflect changes in the health care system, and although the profession has made great strides in preparing nurse researchers, the current system has a serious gap that must be addressed; that of preparing clinical leaders. The article describes the need for a practice-focused doctoral curriculum that will produce a new type of senior clinician or expert practitioner to fill this gap. The envisioned graduates will be skilled in clinical decision making and information processing and will effect changes at both the micro- and macro-levels of the system. There is a clear future need to expand the number of primary care providers. The faculty required for their education must be doctorally prepared nurses who are themselves clinically proficient. The research and practice doctorates should be differentiated by faculty, the program of studies, resources, and placement/expectation of graduates. The article includes a model curriculum plan.

Clinical Competence↗