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Biomedical subjects

D Lutz

Publications and source records attributed to D Lutz.

At least 37 records · Page 2Linked to original sources
PubMed1996

Allogeneic bone marrow transplantation for acute leukaemia--IGCI experience. International Group for Chemo-Immunotherapy.

From October 1984 to December 1994, 142 patients from six IGCI-BMT centers (78 acute myelogenous leukemia and 64 acute lymphoblastic leukemia) received allogeneic bone marrow from their HLA-identical sibling. The probability of LFS at 60 months is 41% for AML patients and 39% for ALL patients. A better LFS was documented in patients allografted in first CR compared to the patients treated in advanced stage of the disease. The overall relapse rate is 27% for AML patients and 45% for ALL patients. The relapse rate is higher for patients allografted in advanced stage of the disease (47 vs 26% at 60 months for AML and 55 vs 38% at 60 months for ALL). The incidence of moderate to severe acute GVHD is between 45-50% for both AML and ALL patients. Chronic GVHD was documented in 30% of AML patients and 38% of ALL patients. Transplant-related mortality for both AML and ALL is about 25%. Relapse and GVHD with or without infection are the main causes of death. These results confirmed that allogeneic BMT is very effective therapy for patients with acute leukemia, especially for patients transplanted in first CR.

Adolescent↗
PubMed1995

Early detection of minimal residual disease by reverse transcriptase polymerase chain reaction predicts relapse in acute promyelocytic leukemia.

The PML/RAR alpha fusion RNA can be detected in acute promyelocytic leukemia (APL), cytogenetically characterized by the translocation t(15;17). Our study included ten newly diagnosed patients with APL who were investigated during the course of their diseases using reverse transcription polymerase chain reaction (RT-PCR). At diagnosis, aberrant fragments with a size heterogeneity due to alternative spliced products were detected in all patients, we observed breakpoints within bcr3 (short type) in two patients and bcr1 and 2 breakpoints (long type) in eight patients. Treatment consisted of all-trans retinoic acid (ATRA) in all patients; six patients received simultaneous cytostatic therapy during remission induction. At the time of complete hematological remission (CR), only two patients showed a negative RT-PCR result; eight of the ten patients were still PCR positive when nested primers were used. Subsequently, eight patients received consolidation chemotherapy and became PCR negative. Seven of eight patients are in continuous complete remission (median remission duration: 21 months, range: 11+ -26+ months). One patient of the chemotherapy group became PCR positive after 4 months in complete remission and relapsed after 6 months. The remaining two patients who were treated only with ATRA relapsed, received induction chemotherapy, and are in second and third complete remission, respectively. In conclusion. PCR negativity can be achieved only by chemotherapeutic consolidation; patients treated with ATRA alone remain PCR positive. Relapse is always preceded by a positive PCR result. Surprisingly, also patients without measurable PML/RAR alpha-mRNA in sequential analyses after cytostatic treatment became PCR positive and experienced relapse.

Adult↗
PubMed1995

Treatment of chronic lymphocytic leukemia in early and stable phase of the disease: long-term results of a randomized trial.

In 1982 the IGCI CLL cooperative group decided to investigate the usefulness of treating, at diagnosis B-cell chronic lymphocytic leukemia (CLL) in early and stable phase of the disease. From January 1982 to December 1986, 148 patients were randomized either to receive immediate treatment with chlorambucil (CLB) or to defer therapy to the time of progression. The early and stable phase of the disease was defined by a total tumor mass (TTM) score < 9, the absence of anemia or thrombocytopenia and a doubling time > 12 months. The main end-point of the study was survival. At the last evaluation in April 1993, after a median follow-up of 75 months, no significant difference was found in overall survival between early vs. deferred treatment patients from every cause of death as well as from death due to CLL-related causes only. The same results were obtained when the patients in more favorable stages, such as Binet stage A and TTM < 4.5, were considered. Interestingly, the incidence of epithelial cancer was similar in the two groups. Early treatment was associated with a significantly better response and a lower progression rate. From this long-term experience, it can be concluded that immediate chemotherapy with CLB is not beneficial for CLL patients in early and stable phase of the disease in terms of survival.

Aged↗
PubMed1994

I.c.v. infusions of ACPD(1S,3R) attenuate learning in a Morris water maze paradigm.

The functional role of metabotropic glutamate receptors is beginning to be understood. Cognitive effects of metabotropic receptor activation were examined in the present study in a Morris water maze following intraventricular (i.c.v.) infusions of ACPD(1S,3R). I.c.v. infusions of ACPD substantially increased the amount of time animals took to find a hidden platform in a water maze. Current results demonstrate that subtoxic doses of ACPD can produce in vivo effects with functional significance. Spatial learning abilities are impaired following activation of metabotropic receptors with ACPD(1S,3R). Negative implications are provided for the use of cognitive enhancing compounds that stimulate metabotropic glutamate receptors.

Analysis of Variance↗
PubMed1993

Potassium channel openers stimulate DNA synthesis in mouse epidermal keratinocyte and whole hair follicle cultures.

We have conducted studies using primary mouse epidermal keratinocyte and whole hair follicle cultures to investigate the mechanism of the hypertrichotic activity of potassium channel openers. In a time course study, the extent of stimulation of epidermal keratinocyte DNA synthesis by minoxidil increased as the rate of DNA synthesis in control cultures declined. Minoxidil stimulation of DNA synthesis in 7-day cultures required prolonged (> 1 day) exposure to the agent. Pinacidil and diazoxide also stimulated DNA synthesis in mouse epidermal keratinocyte cultures. In addition, minoxidil, pinacidil, diazoxide, and cromakalim stimulated DNA synthesis in whole-organ cultures of mouse hair follicles. These results suggest that potassium channel openers retard the loss of proliferative activity of differentiating keratinocytes and support the hypothesis that these agents stimulate hair growth through a direct effect on hair follicles.

Animals↗
PubMed1993

Bioavailability and pharmacokinetics of a new isosorbide dinitrate spray preparation in healthy volunteers.

In the course of this study the bioavailability and pharmacokinetic profile of a newly developed 2.5 mg (per valve release) oral isosorbide dinitrate (ISDN, CAS 87-33-2) spray preparation (Isoket Spray) were determined and compared with the results for an already marketed reference spray preparation following single application. For this purpose, the test and reference spray were examined in 18 healthy volunteers according to a randomized 2-way cross-over design. Blood samples were collected during 12 h p.a. and plasma concentrations of ISDN and its metabolites isosorbide-2-mononitrate (IS-2-MN) and isosorbide-5-mononitrate (IS-5-MN) were quantified by a GC-method. Both sprays showed mean maximum concentrations of ISDN in plasma of nearly 18 ng/ml about 7 min after drug intake with arithmetic mean values for the areas under the curve AUC0-12 of 7.01 (test spray) and 7.30 h.ng/ml (reference spray). For the metabolic products IS-2-MN and IS-5-MN (values for the reference spray in brackets) the corresponding maximum concentrations were 4.15 (4.21) ng/ml and 16.1 (15.9) ng/ml, respectively, and for the areas under the curve AUC0-12 values of 9.75 (9.92) h.ng/ml for IS-2-MN and 104.3 (99.7) h.ng/ml for IS-5-MN in the mean were calculated. Statistical evaluation of all pharmacokinetic parameters revealed bioequivalence between the two preparations. Typical side-effects known and described under isosorbide dinitrate therapy were also observed in this study.

Adolescent↗
PubMed1993

[Interferon-alpha therapy in chronic myeloid leukemia].

In 1983 was for the first time reported that natural interferon-alpha (IFN-alpha) has a cytoreductive effect when used for treatment of chronic myelogenic leukemia (CML). The following studies using natural as well as recombinant IFN-alpha preparations confirmed the high remission rates with this therapy (70% CR and more than 30% cytogenetic responses) in patients with CML. Flu-like symptoms are recorded in more than 90% of the patients in the initial therapy phase. IFN-alpha seems to have no activity in patients in accelerated phase or blast crisis. High doses of IFN, i.e. more than 4,000,000 per day, achieve high response rates. Responses correlate with risk factors. New possibilities for improvement of therapy results with IFN are the combinations of IFN with other therapy modalities or concepts such as chemotherapy and/or bone marrow transplantation.

Bone Marrow↗
PubMed1993

[A questionnaire suitable for general practice for detection of the health status and quality of life of patients with hemato-oncologic diseases: psychometric properties. The Study G "Quality of Life" of the International Society for Chemo- and Immunotherapy (I.G.C.I.)].

In the evaluation of therapeutic measures it is important to consider the consequences of the proposed treatment on the subjective quality of health and the subjective quality of life. Since no adequate instrument existed to provide such assessments, a short, theoretically based questionnaire was developed and psychometrically tested. The construction phase was based on data of 104 adults with haemato-oncological diseases, leading to the design of a questionnaire which was tested using data of a further 292 patients. The validity of the "questionnaire for attitudes towards quality of health and quality of life" was assessed by comparing it with physicians' ratings and by correlation with the results of an extensive questionnaire. The reliability was satisfactory; the questionnaire met with high acceptance by patients, physicians and health care personnel. It complies with the requirements of clinical trials where the objective is to measure quality of health and quality of life.

Adaptation, Psychological↗
PubMed1992

Indications for the presence of antibodies cross-reactive with HTLV-I/II, but not HIV, in patients with myelodysplastic syndrome.

Serological evidence is presented for the fact that patients with the myelodysplastic syndrome exhibit a statistically significant reactivity in confirmatory assays for antibodies to human T-lymphotropic viruses types I and II (HTLV-I/II). This antibody reactivity, evident by indirect immunofluorescence and Western blot, was not confined to HTLV core antigens but extended to native and recombinant envelope glycoproteins. The effect was also observed in cases of acute myeloic leukemia, albeit to a lesser degree. It was essentially absent from patients with chronic myeloic leukemia or lymphocytic leukemias and healthy or multitransfused controls. No antibodies to human immunodeficiency viruses types 1 or 2 were detected in any of the specimens. The investigated clinical population had no known risk factor for retroviral infection other than a history of multiple platelet transfusions, and none of the specimens was seropositive for HTLV-I or HTLV-II according to recommended criteria. The cause of this cross-reactivity remains to be determined.

Antibodies, Viral↗
PubMed1992

Remission may continue after termination of rIFN alpha-2b treatment for essential thrombocythemia.

Essential thrombocythemia, a myeloproliferative disorder of clonal origin, is often associated with various clinical manifestations resulting from thromboembolic or hemorrhagic complications. The long-established successful method of treatment with cytotoxic agents or radioactive phosphorus has recently been superseded by interferon alpha. We treated 14 symptomatic patients with 5 x 10(6) IU recombinant interferon alpha-2b s.c. daily. 12/14 pts responded within 14-75 days. When platelet counts decreased to below 450 g/l the frequency of administration was reduced stepwise. 7 patients remained in CR during this reduction phase and treatment was stopped in 5 pts after 12-32 months. Until now, 3 of them are still in continuous good PR without any drug therapy and free of symptoms for 3+, 19+ and 36+ months. Continuous response during maintenance was associated with age, initial platelet count and time required to reduce platelet counts to less than 450 g/l.

Adult↗
PubMed1992

Childhood acute lymphoblastic leukemia immunophenotypes and their prognostic significance: experience of the IGCI-study in 389 children. International Society for Chemo-immunotherapy (IGCI-Vienna) Cooperative Group.

The prognostic significance of immunophenotype and other features including sex, age, anaemia, WBC, FAB type, and PAS staining were analysed in a group of 389 children newly diagnosed as acute lymphoblastic leukemia (ALL) and treated according to the BFM 1981/1983 protocol. The CR rate was higher (82-94%) in immunophenotypic subgroups defined as 'non-B' compared with B-ALL (54%). The probability of being in CCR at the end of follow up was 0.68 (median. observation, 3 years). Using the stepwise Cox regression analysis the following independent factors predictive of duration of CCR were selected (relative risk in brackets): 1. WBC (> 25G/1:< 25G/1 = 2.0, P = 0.0008), 2. age (> 10y:2-10y = 1.3, P = 0.04), 3. CALLA positivity (neg.:posit. = 2.4, P = 0.04), 4. CALLA within B-cell progenitor ALL (pre;preB,Calla-:Calla+ = 1.7, P = 0.007). T-ALL appeared to have a worse prognosis than U-ALL and B-progenitor derived ALL but it did not retain independent prognostic significance in multivariate analysis.

Adolescent↗