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Biomedical subjects

A Reiter

Publications and source records attributed to A Reiter.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effect of probenecid on the distribution and elimination of ciprofloxacin in humans.

OBJECTIVE: Probenecid-sensitive anion transport systems may be involved in distribution and elimination processes of anionic drugs. The aim of this study was to determine the effect of multiple probenecid treatment on the pharmacokinetic disposition of the zwitterionic fluoroquinolone ciprofloxacin in 12 healthy volunteers. METHODS: A single intravenous dose of 200 mg ciprofloxacin was given with and without multiple oral administration of probenecid in a randomized crossover fashion. Serial plasma, urine, saliva, tear, and sweat samples were drawn and analyzed for ciprofloxacin and its 2-aminoethylamino-metabolite (M1) by reversed-phase HPLC. RESULTS: Plasma area under the concentration-time curve and elimination half-life of ciprofloxacin were increased (p < 0.05), and urinary recovery and total and renal clearance decreased (p < 0.05) in the presence of probenecid. Nonrenal clearance and volume of distribution did not differ significantly with and without coadministration of probenecid. Peak plasma concentration, plasma area under the concentration-time curve, and elimination half-life of M1 were increased (p < 0.05) because of the higher amount of M1 formed and the reduced renal clearance (p < 0.05) of the metabolite. Saliva, tear, and sweat exposure were elevated (p < 0.05), but the alterations can be attributed primarily to the different kinetics of ciprofloxacin in plasma. CONCLUSIONS: Coadministration of probenecid altered the renal excretion and hence the plasma concentrations of ciprofloxacin. Metabolite kinetics and distribution into saliva, tears, and sweat were affected accordingly, but there was no direct effect of probenecid on these processes. This type of drug-drug interaction might be of clinical relevance when ciprofloxacin is combined with drugs eliminated by the organic anion transport system in the kidney tubules.

Adult↗
PubMed1995

12q13, a new recurrent breakpoint in acute non-lymphoblastic leukemia.

The karyotypes of 312 successfully analyzed samples of children with acute non-lymphoblastic leukemia (ANLL), which were sent to us by 72 German hospitals, were examined in order to find new recurrent chromosome abnormalities of possible clinical relevance. Whereas most of the patients had one of the specific aberrations of ANLL or a normal karyotype, random numerical or structural changes were found in 61 children (20%). Four of them showed an abnormality involving band 12q13: t(12;17)(q13;q21), t(12;21)(q13;q21), t(2;12)(p13;q13), and t(5;12)(p11;q13). Despite the fact that FAB subtypes were different (M0, M1 M6, AHL), the blasts of all patients were characterized by immaturity and were difficult to classify. The breakpoint 12q13 might be of clinical importance in ANLL, because the four patients in our study, as well as the 21 patients with this aberration found in the literature, had a very poor prognosis.

Child↗
PubMed1995

Variable numbers of BCR-ABL transcripts persist in CML patients who achieve complete cytogenetic remission with interferon-alpha.

A substantial minority of patients with chronic myeloid leukaemia (CML) achieve a complete response to treatment with interferon-alpha (IFN-alpha), defined as the disappearance of Philadelphia chromosome positive metaphases or, for patients who are Philadelphia chromosome negative but BCR-ABL positive, the disappearance of the leukaemic clone as assayed by Southern blot. We have measured the levels of BCR-ABL transcripts in 20 such patients by quantitative PCR. Results were standardized for both quality and quantity of cDNA by quantification of ABL as an internal control. All 20 patients had evidence of residual disease; the median number of transcripts was 750/micrograms RNA (range 10-22,000) and the median BCR-ABL/ABL ratio was 0.17% (range 0.0008-3.6%). Our findings show that CML has not been eradicated in any patient and that the quantity of residual disease in complete responders may vary by as much as four orders of magnitude.

Adult↗
PubMed1995

Absence of G-CSF receptors and absent response to G-CSF in childhood Burkitt's lymphoma and B-ALL cells.

The expression of the granulocyte colony-stimulating factor (G-CSF) receptor in childhood Burkitt's lymphoma (BL) cells, and the mitogenic effect of G-CSF on these cells, was studied in a panel of 13 Epstein-Barr virus (EBV) positive and negative BL cell lines derived from nine children. G-CSF receptor mRNA expression was investigated by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Binding of G-CSF to BL cell lines was measured by chemical crosslinking of 125I-G-CSF, and proliferation by thymidine incorporation. Inducibility of the G-CSF receptor was studied by stimulation with interleukin-1 beta, tumour necrosis factor-alpha, Staphylococcus aureus Cowan A, anti-human IgM, phorbol myristate acetate, calcium ionophore A23187, and by infection in vitro by immortalizing and non-immortalizing strains of EBV. BL cell lines, unstimulated or stimulated by biological reagents or EBV infection, did not bind radioionated G-CSF in crosslinking experiments. No stimulation by recombinant human G-CSF was observed in 3H-thymidine incorporation assays. No G-CSF receptor mRNA was detected by Northern blot analysis or RT-PCR in BL cell lines. It is concluded that G-CSF plays no direct stimulatory role in the growth of these malignant B-cells, making a deleterious influence of G-CSF in the clinical treatment situation unlikely.

Adolescent↗
PubMed1995

Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage--a report of the Berlin-Frankfurt-Münster Group.

PURPOSE: To prove the efficacy of a treatment stratified according to histology for children with non-Hodgkin's lymphoma (NHL), including acute B-cell leukemia (B-ALL). PATIENTS AND METHODS: From October 1986 to March 1990, 302 assessable patients, 0.6 to 17.8 years of age, with newly diagnosed NHL were enrolled onto study ALL/NHL-BFM 86. Fifty percent of patients had Burkitt-type lymphomas, including B-ALL; 24% had lymphoblastic lymphoma; 18% had diffuse large-cell lymphoma; and 8% had an NHL not further classified. Therapy group B included Burkitt's-type lymphomas, B-ALL, and most large-cell lymphomas including Ki-1 anaplastic large-cell lymphoma. Patients with stage I and II disease resected received three, while all others received six, 5-day therapy courses (dexamethasone, methotrexate [MTX] 0.5 g/m2 [5 g/m2 for stage IV and B-ALL], and intrathecal [IT] therapy in each course, plus ifosfamide, cytarabine, and etoposide alternating with cyclophosphamide and doxorubicin). Therapy for group non-B patients (lymphoblastic lymphoma and pleomorphic T-cell lymphoma [PTCL]) consisted of a Berlin-Frankfurt-Münster (BFM) acute lymphoblastic leukemia protocol, including cranial irradiation for advanced stage. Local therapy was restricted to patients with incomplete tumor regression. RESULTS: The probabilities of event-free survival (pEFS) at 7 years were 80% +/- 2% for the whole group, 81% +/- 3% for group B (n = 225), and 78% +/- 5% for group non-B (n = 77) with a follow-up duration of 3.6 to 7 years (median 5 years). Treatment results were comparable between NHL subtypes, except for PTCL, in which three of four patients suffered from relapse. Local disease manifestations were the most frequent site of failure. CONCLUSION: This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.

Adolescent↗
PubMed1995

[Quantitative follow-up of callus distraction with dual-energy roentgen absorptiometry (DEXA)].

With dual-energy X-ray absorptiometry (DEXA), bone mineralization during and after limb-lengthening procedures with unilateral fixators can be monitored quantitatively and precisely with low radiation exposure. We measured prospectively the bone mineral density (BMD) in the newly formed callus, in the bone adjacent to the callus and in the proximal femur in 21 patients with leg lengthening of the femur and/or tibia with unilateral external fixators. Mineralization showed a typical course with a peak value of 0.365 +/- 0.196 g/cm2 (30.9% of the first value) at 6-8 weeks after the beginning of distraction and a minimum value at the time of maximum distraction. In the consolidation period BMD in the distraction gap increased to 1.020 +/- 0.234 g/cm2 (87%) at the time of fixation removal. BMD in the regenerated bone increased faster in regions of interest (ROIs) opposite the fixator compared to ROIs near it. Dynamization of the fixation device led to a 13% increase in mineralization velocity (VBMD). On the other hand, dynamization caused more homogeneous regeneration equalizing VBMD in the different ROIs as well. BMD in the proximal femur of the leg operated on decreased to 67% and in the contralateral leg to 87% of the preoperative value. We consider DEXA to provide a precise and quantitative assessment of callus and bone mineralization during limb lengthening with unilateral fixators. Since we are well aware of the limitation of the technique. DEXA helps to understand what is happening in limb-lengthening procedures by providing quantitative values.

Absorptiometry, Photon↗
PubMed1994

Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86.

In trial ALL-BFM 86, the largest multicenter trial of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight-drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD-cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety-eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

Adolescent↗
PubMed1994

Therapy of B-cell acute lymphoblastic leukaemia in childhood: the BFM experience.

In 1981 the BFM group introduced a new treatment strategy for B-ALL based on two alternating 5-day courses of chemotherapy delivered in short intervals up to a total of eight. The therapy courses were composed of fractionated cyclophosphamide, MTX 0.5 g/m2 (24-h infusion), i.t. MTX therapy, and ara-C/VM26 alternating with doxorubicin. The development of the therapy strategies during the subsequent two studies was characterized by shortening treatment duration from eight to six courses, and intensification of CNS chemotherapy in study ALL-BFM-83, and the introduction of HD-MTX (5 g/m2, 24-h infusion) in study ALL-BFM-86. In study ALL-BFM-81, CNS therapy consisted of ID-MTX in combination with i.t. MTX and RX. CNS-positive patients received complete neuroaxis irradiation. In study ALL-BFM-83, CNS chemotherapy was intensified by adding dexamethasone, while MTX/ara-C were administered intraventricularly. Spinal irradiation for CNS-positive patients was omitted. In study ALL-BFM-86, i.t. MTX/ara-C/prednisolone therapy was introduced in combination with HD-MTX but the intraventricular route of drug administration was no longer used. Radiotherapy was omitted completely. In all, 87 patients were enrolled, 22 (eight CNS positive) in study ALL-BFM-81, 24 (seven CNS positive) in study ALL-BFM-83, and 41 (none CNS positive) in study ALL-BFM-86. The estimated 5-year duration of EFS was 40% in study ALL-BFM-81, 50% in study ALL-BFM-83, and 78% in study ALL-BFM-86 (minimal follow-up 36 months). Nineteen of 24 relapses occurred while on therapy or shortly thereafter. In study ALL-BFM-81, the CNS was the most frequent site of failure. In ALL-BFM-83 there were no isolated CNS relapses but more BM relapses occurred. In ALL-BFM-86 localized manifestations were the predominant site of failure, no isolated BM relapses occurred, and only one CNS relapse was diagnosed. No single parameter exerted a consistent influence on outcome with one exception. The presence of residual disease after the first two courses was correlated with an increased risk of therapy failure. Our conclusions from the three studies are listed below. An intensive, short-pulse therapy delivered within a 4 month period is highly effective in the treatment of B-ALL. Prolonged therapy duration is of no value. In addition to fractionated cyclophosphamide-ifosfamide, a 24-h infusion of HD-MTX5 g/m2 in conjunction with an i.t. therapy is a very important component for prevention of both systemic and CNS relapses.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1994

The role of initial laparotomy and second-look surgery in the treatment of abdominal B-cell non-Hodgkin's lymphoma of childhood. A report of the BFM Group.

The aim of this study was to determine the role of surgery in the treatment of abdominal B-cell non-Hodgkin's lymphomas (B-NHL) in children. We analyzed the effect of surgical variables of initial laparotomy and second-look surgery on event-free survival (EFS) of 177 patients with abdominal B-NHL enrolled into the three consecutive multicenter trials NHL-BFM 81, NHL-BFM 83, and NHL-BFM 86. The therapy regimen was comparable in all 3 trials as well as the overall outcome of the patients. Patients with stage II and complete resection received 3 courses of therapy (4 in trial NHL-BFM 81), patients with stage II not resected, stage III, and stage IV received 6 courses of therapy (8 in trial NHL-BFM 81). An initial laparotomy was performed in 161 patients, in 59 of them as an urgent procedure. Complete resection of the abdominal primary was performed in 43 patients, 40 of them had a localized bowel tumor. The probability of EFS (pEFS) at 5 years is 95%, 69%, 62%, and 67% for patients with complete resection, subtotal resection (n = 36), partial resection (n = 21), or biopsy only (n = 61), respectively. Complete resection was achieved in 30 out of 40 patients with stage II, but only in 12 of 113 and 1 of 24 patients with stage III and IV, respectively. pEFS at 5 years according to stage and completeness of resection is as follows: stage II complete resected 97%; stage II not complete resected 100%; stage III/IV complete resected 92%; stage III/IV not complete resected 63%.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Neoplasms↗
PubMed1994

Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias.

Congenital neutropenias include a heterogenous group of diseases characterized by a decrease in circulating neutrophils. In phase I/II/III studies in patients with severe congenital and cyclic neutropenia, treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) resulted in a rise in the absolute neutrophil counts (ANC) and a reduction in infections. We report the effects of long-term safety of subcutaneous r-metHuG-CSF administration in 54 patients (congenital n = 44. cyclic n = 10) treated for 4-6 years. A sustained ANC response was seen in 40/44 severe congenital neutropenia patients and 10/10 cyclic neutropenia patients. Two patients required an increase of > 25% in dose to maintain a clinical response; one patient became refractory to therapy. A significant decrease in the incidence of severe infections and the need for intravenous antibiotics was noted. Significant adverse events noted which may or may not be related to therapy included: osteopenia (n = 15), splenomegaly (n = 12), hypersplenism (n = 1), vasculitis (n = 2), glomerulonephritis (n = 1), BM fibrosis (n = 2), MDS/leukaemia (n = 3), and transient inverted chromosome 5q with excess blasts (n = 1). R-metHuG-CSF has been well tolerated in the majority of patients and resulted in a long-term improvement in their clinical status.

Adolescent↗
PubMed1994

Successful treatment strategy for Ki-1 anaplastic large-cell lymphoma of childhood: a prospective analysis of 62 patients enrolled in three consecutive Berlin-Frankfurt-Munster group studies.

PURPOSE: To prove prospectively the efficacy of a short-pulse chemotherapy for treatment of Ki-1 anaplastic large-cell lymphoma (ALCL) of childhood. PATIENTS AND METHODS: From October 1983 to December 1992, 62 patients (median age, 9.7 years) with newly diagnosed Ki-1 ALCL were enrolled onto Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Munster (NHL-BFM) studies 83, 86, and 90. The most frequent immunophenotype was T cell. Ki-1 ALCL differed from other subsets of NHL of childhood by the more frequent involvement of bone, soft tissue, and skin, and by the lack of bone marrow (BM) disease. A 5-day prephase course (prednisone/cyclophosphamide) was followed by two different 5-day courses of chemotherapy: course A consisted of dexamethasone, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), intrathecal chemotherapy, ifosfamide, cytarabine (Ara-C), and etoposide (VP-16); course B consisted of cyclophosphamide and doxorubicin instead of ifosfamide, and Ara-C/VP-16, respectively. Treatment was stratified into three branches. Branch 1 (stage I and stage II resected) received three courses; branch 2 (stage II not resected, stage III), six courses; and branch 3 (stage IV), six intensified courses containing MTX 5 g/m2, and Ara-C 2 g/m2. Local radiotherapy was not performed. RESULTS: Four patients failed to enter remission, and one died of infection. Seven patients relapsed within 9 months after diagnosis; two patients had isolated local relapses, but BM and CNS were never involved. Fifty patients have been in first continuous complete remission (CR) for 0.6 to 9.7 years (median, 2.5), and 56 are alive. The probabilities for survival and event-free survival (EFS) at 9 years are 83% +/- 7% (SE) and 81% +/- 5%. Skin involvement was the only negative prognostic parameter. CONCLUSION: Short-pulse chemotherapy over 2 to 5 months without local therapy modalities is effective in the treatment of Ki-1 ALCL.

Adolescent↗
PubMed1994

Immunophenotypic features of childhood and adult acute lymphoblastic leukemia (ALL): experience of the German Multicentre Trials ALL-BFM and GMALL.

Immunophenotyping prospectively performed in about 2800 children and adults within the framework of the German multicentre ALL trials revealed marked differences in frequency distribution of immunologic subgroups with a higher incidence of immature B-cell precursor and pre-T/T phenotypic features in adults. Detailed immunophenotypic characterization by applying monoclonal antibodies to lymphoid- and myeloid-associated antigens as well as non-lineage-restricted molecules underlined the diagnostic value of pan-B and pan-T antigens that were expressed in virtually all cases of B-cell precursor (CD19, CD24) or T-cell ALL (cytoplasmic CD3, CD7) for lineage affiliation of leukemic blasts. About 10% of children and 20% of adults disclosed simultaneous expression of lymphoid markers and at least one myeloid-lineage-associated antigen. Our data confirm that immunophenotyping in ALL provides a solid basis for a biologically oriented and reliable classification of this heterogeneous disease.

Adult↗
PubMed1994

Effects of granulocyte colony-stimulating factor in children with severe neutropenia.

In children with all types of severe neutropenia the development of G-CSF for therapeutic use changed the quality of their life dramatically. Missing the most important cells in the defense against bacterial infections the neutrophilic granulocytes, these patients suffered from episodes of severe, often life-threatening bacterial infections. They spent numerous days in hospital, requiring intravenous antibiotic treatment. Recurrence of bacterial infections at the same site led to irreversible tissue damage, for example in the lung, requiring often disabling surgical interventions. In most patients G-CSF treatment induced an increase of blood and tissue neutrophils to a level high enough to guarantee a normal defense against bacterial infections. The quality of life improved substantially in these children. The fact that they have to inject themselves daily does not cause any problems. Overall, taken in consideration all possible adverse events during our short observation period, all patients who responded to G-CSF benefit from this treatment to a degree never considered to be possible before.

Adolescent↗
PubMed1994

[Immunophenotyping of acute lymphatic leukemia: diagnostic aspects and clinical relevance].

During the past two decades immunophenotyping has yielded significant new information regarding the biological heterogeneity of ALL and has provided a solid basis for a biologically oriented and reliable classification of this disease. At present, lineage commitment of acute leukaemias can be achieved in more than 98% of cases by applying a standardized panel of mAbs to pan-B-cell (CD19, cyCD22), pan-T-cell (cyCD3, CD7) and pan-myeloid antigens (CD13, CD33, MPO) that are expressed either on the surface or in the cytoplasm of the earliest progenitors of the respective cell lineage. Further subclassification of ALL based on the analysis of antigens more closely associated with different maturational stages of B- and T-cell lineage has proven useful for the identification of biologically and clinically distinct entities in both B-cell precursor and T-lineage ALL. Immunophenotyping in about 2800 patients recruited for the German multicentre trials has shown that children and adults differ markedly in frequency distribution of immunological subgroups, with a higher adult incidence of immature B-cell precursor (i.e., pre-pre-B ALL) and T-lineage ALL immunophenotypes (i.e., pre-T ALL). Detailed immunological analyses using a broad panel of mAbs have recently documented typical ALL cases inappropriately expressing myeloid antigens (My+ ALL) as well as morphologically/cytochemically defined acute myeloid leukaemia (AML) with lymphoid-associated markers (Ly+ AML). Based on our own results and a critical review of published data, leukaemic blasts in 5-20% of ALL patients disclose My+ ALL, whereas a coexpression, mostly of T-cell-associated antigens, can be identified in 10-25% of AML cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Superior prognosis in combined compared to isolated bone marrow relapses in salvage therapy of childhood acute lymphoblastic leukemia.

Three hundred twenty-six children with bone marrow (BM) relapse of non-B acute lymphoblastic leukemia (ALL) were stratified according to the time of relapse in three consecutive multicenter trials--ALL-REZ BFM 83, 85, and 87. Employing an intensive polychemotherapy regimen, extramedullary involvement appeared to be predictive of superior outcome in both strata as well as in the whole group (probability of 7-year event-free survival (EFS) 42% in combined vs. 15% in isolated BM relapse, P = 0.015). Children with combined BM relapse occurring later than 6 months after completion of front-line therapy reached EFS estimates of 60%. We conclude that results of conventional polychemotherapy with BFM relapse protocols are equivalent to those achieved by bone marrow transplantation in children with late combined BM relapse.

Adolescent↗