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Biomedical subjects

A Reiter

Publications and source records attributed to A Reiter.

196 records · Page 11Linked to original sources

[Modification of bone quality by extreme physical stress. Bone density measurements in high-performance athletes using dual-energy x-ray absorptiometry].

The treatment of osteoporosis is still controversial. Rehabilitation programs which stress strengthening exercises as well as impact loading activities increase the bone mass. On the other side activity level early in life has not been proven to correlate with increased bone mineral content later in life. Little is known on the influence of high performance sports on the bone density especially in athletes with high demands on weight bearing of the spine. In (n = 40) internationally top ranked high performance athletes of different disciplines (n = 28 weight-lifters, n = 6 sports-boxers and n = 6 bicycle-racers) bone density measurements of the lumbar spine and the left hip were performed. The measurements were carried out by dual-photonabsorptiometry (DEXA; QDR 2000, Siemens) and evaluated by an interactive software-programme (Hologic Inc.). The results were compared to the measurements of 21 age-matched male control individuals. In the high performance weight lifters there was an increase of bone density compared to the control individuals of 23% in the Ward's triangle (p < 0.01). The sports-boxers had an increase up to 17% (lumbar spine), 9% (hip) and 7% (Wards' triangle). In the third athletes group (Tour de France-bikers) BMD was decreased 10% in the lumbar spine, 14% in the hip and 17% in the Wards' triangle. Our results show that training programs stressing axial loads of the skeletal system may lead to an increase of BMD in the spine and the hip of young individuals. Other authors findings, that the BMD of endurance athletes may decrease, is confirmed. Nevertheless the bikers BMD-loss of 10 to 17% was surprisingly high.

Absorptiometry, Photon↗

[Periprosthetic mineral density in cement-free hip replacement arthroplasty].

SUBJECT: We analysed the periprosthetic bone mineral density (BMD) in a prospective longitudinal study over two years after operation and in a separate cross-sectional study more than five years after implantation of cementless total hip arthroplasty (CLS-stem, Mecron threaded acetabular cup) by using dual-energy X-ray absorptiometry (DEXA). MATERIALS AND METHODS: In n = 53 patients (29 women, 24 men) we analysed the periprosthetic BMD prospectively in certain periods. All patients had an uncomplicated postoperative course and good clinical outcome (Merle d'Aubigne score > 12). In the cross-sectional study we analysed 23 patients (13 women, 10 men). Regions of Interest (ROI) were defined according to Gruen et al. for the periprosthetic femur and to De Lee and Charnley for the periprosthetic acetabulum. RESULTS: BMD significantly decreases in the periprosthetic femur as well as in the periprosthetic acetabulum during the first three months. In men BMD reaches its lowest values between six months (femur) and one year (acetabulum) after operation and then increases to 96.2% at the femur and 93.8% at the acetabulum. In women BMD decreases during the entire follow-up to 89.4% at the periprosthetic femur and 80.0% at the periprosthetic acetabulum. In the proximal zones 1 and 7 of the femur and the cranial-medial zone II of the acetabulum we observed the highest decrease of mineralisation. More than five years after implantation of the prosthesis BMD in the femur showed only little changes. On the other side BMD around the threaded acetabular cup significantly decreased to 67.4% in women and 79.1% in men. CONCLUSION: The results reflect the different stress on the periprosthetic bone after implantation of the prosthesis and fit to earlier reported good clinical results of the CLS-stem and to increased loosening rate of threaded acetabular cups after five years. Analysing changes of mineralisation in cementless total hip arthroplasty DEXA together with the analization scheme according to Gruen at the femur and to De Lee and Charnley at the acetabulum is a useful method and has been reliable in clinical practise.

Absorptiometry, Photon↗

Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group.

Since the introduction of combined immunosuppressive therapy (IST) into management of aplastic anemia (AA) in childhood response and probability of survival improved. In contrast to bone marrow transplantation (BMT), however, patients after IST are not considered cured as high rates of relapse and development of clonal disease demonstrate. From 11/93 to 9/97 114 children (65 m, 49 f; median age 9.5 y.) from 37 centers in Germany and Austria were registered in the SAA 94 study. 86 patients lacking a matched sibling donor received IST. Most of the patients suffered from very severe (VSAA: PMN < 200/microliter) or severe AA (SAA: PMN < 500/microliter). All patients were treated with combined IST consisting of ALG and Cyclosporin A (CSA). VSAA and SAA patients were additionally treated with G-CSF. Therapy response was evaluated at day 112, after 6, 12 and 18 months. 8/86 patients died, the probability of survival being 87% after 4 years. At d 112 61% of evaluable patients became independent of transfusions (IST response: CR + PR), 13% with normal blood counts (CR). After 6 months 33% showed CR. At 12 and 18 months response improved to 74% resp. 80%, 39% resp. 55% CR. The best response was achieved in the subgroup of VSAA with 90% (PR + CR) and 65% CR after 18 months. 4 patients developed AML 3-19 months after the beginning of IST. In 2/4 pts. an aberrant clone (-7; 5q-) could be detected retrospectively in BM at diagnosis of AA. 3 nonresponders developed chromosomal aberrations (+19; -7, +12; +8) after 4, 12 and 16 months without morphological signs of AML or MDS. Overall 11 relapses occurred at a median time of 12 months (range 5-27 months) after the beginning of IST. 2 of them relapsed under CSA therapy, 2 under tapering of CSA and 7 after cessation of CSA. 7 patients responded again to CSA monotherapy. Overall response rate is 77% with a probability of event free survival (EFS) of 54% after 4 years regarding all complications mentioned as events.

Adolescent↗

Prevention of CNS recurrence in childhood ALL: results with reduced radiotherapy combined with CNS-directed chemotherapy in four consecutive ALL-BFM trials.

BACKGROUND: The introduction of cranial radiotherapy (CRT) has provided efficient control of overt or subclinical meningeosis in acute lymphoblastic leukemia (ALL). Especially due to the long-term toxicity of CRT, reduction or elimination of radiotherapy appeared mandatory after cure rates of more than 70% had been achieved in ALL. The Berlin-Frankfurt-Münster (BFM) Study Group initiated several attempts in certain ALL subgroups to omit or reduce CRT while using more CNS-directed chemotherapy but without extended intrathecal treatment during maintenance therapy. This analysis summarizes the essential results that are in particular relevant because irradiation of the central nervous system (CNS) has been further reduced in the most recent trial ALL-BFM 95. PATIENTS AND METHODS: More than 4000 patients enrolled between 1981 and 1995 in one of the last four ALL-BFM trials have been analyzed to demonstrate the efficiency of intensive systemic and intrathecal chemotherapy with or without reduced CRT in the prevention of CNS relapses. RESULTS: In trial ALL-BFM81, it was shown that only in low-risk (LR) patients preventive radiotherapy can be replaced safely by intermediate dose (0.5 g/m2) methotrexate (MHD-MTX). In intermediate risk (IR) patients this attempt failed: IR pts had 8 times more CNS relapses if treated by MHD-MTX without CRT. In the subsequent trial ALL-BFM 83, all pts received MHD-MTX. IR pts were randomly treated with 12 or 18 Gy of preventive CRT which did not result in a significantly different outcome. The results from the subsequent trial ALL-BFM 86, using a more intensive consolidation with high-dose methotrexate (HD-MTX), demonstrated that the elimination of CRT in low-risk ALL, the reduced CRT of 12 Gy for IR, 18 Gy for medium (MR), and the reduced CRT with 18 Gy for high risk (HR) ALL, respectively, was justified: the incidence of relapses with CNS involvement was reduced to less than 5% (Reiter et al. 1994, Blood 84: 3122). When even less intensive preventive CRT (12 Gy for all medium and high risk patients) was used in trial ALL-BFM 90, the rate of CNS-related relapses was again below 5%. HR patients now treated with more CNS-directed chemotherapy had the lowest rate of CNS-related relapses observed so far in the BFM trials, even though CRT was also reduced to 12 Gy. Patients with T-cell ALL were shown to be protected from CNS recurrence by the combination of CRT (12 Gy) and HD-MTX more effectively than by HD-MTX in consolidation and TIT therapy during maintenance, especially if they presented with high WBC as shown in a joint AIEOP/BFM analysis (Conter et al. 1997, JCO 15: 2786). Patients with overt meningeosis which are characterized by a high leukemic cell load at diagnosis had a rate of recurrences that was comparable to that of patients with high WBC but no CNS disease. CONCLUSION: Low-risk ALL patients can be efficiently prevented from CNS relapse by intensive systemic and intrathecal chemotherapy without CRT. Patients with intermediate or medium risk ALL, including T-cell ALL, did not suffer from more CNS or systemic relapses when CRT was reduced to only 12 Gy. Patients with inadequate response to therapy are at particularly high risk for relapse with CNS involvement. Therefore, more CNS-directed systemic and intrathecal chemotherapy was applied in trial ALL-BFM 90, combined with only 12 Gy cranial irradiation, and improved the control of CNS recurrence. It seems likely that larger subsets of B-precursor ALL can be protected from CNS-related relapse by intensive chemotherapy without extended IT treatment and without CRT. This is being investigated in the ongoing trial ALL-BFM 95.

Adolescent↗

Impaired renal function and tumor lysis syndrome in pediatric patients with non-Hodgkin's lymphoma and B-ALL. Observations from the BFM-trials.

OBJECTIVE: Tumor lysis syndrome and renal failure remain important complications early in the course of therapy for pediatric Non-Hodgkin's lymphoma (NHL), frequently leading to therapeutic alterations. In the presented series, children with NHL and tumor lysis syndrome are retrospectively analysed regarding clinical features of acute renal failure and its implications on therapy. PATIENTS AND METHODS: From 4/1990 to 10/1997, 1192 patients diagnosed of any form of NHL have been registered in the NHL-BFM trials. 63 of these patients were reported to have suffered from impaired renal function and/or tumor lysis syndrome before or during initial treatment. Clinical data of these patients were analysed regarding diagnosis, stage, tumor mass, therapy and complications. RESULTS: 62 of 63 patients with impaired renal function and/or tumor lysis syndrome were diagnosed of Burkitt's lymphoma or B-ALL; 58 (92%) of these patients had advanced stages of disease and high LDH-levels (> 500 U/l). 43 of 63 patients had already signs of impaired renal function at admission. Hyperuricemia was the commonest cause of impaired renal function. Renal infiltration or enlargement was observed in 27 of 63 patients. 6 patients were diagnosed of urinary tract obstruction. 25 patients required hemodialysis. Despite improved renal function before administration of MTX, 21 of 63 patients suffered from protracted MTX-elimination during the first course of therapy. 7 of 63 patients (11%) with tumor lysis syndrome died of sepsis after the first course of therapy, another two patients died within 48 hours of therapy due to electrolyte imbalances. CONCLUSIONS: In pediatric NHL-patients, Burkitt's lymphoma and B-ALL appear to be the commonest cause of metabolic complications early in chemotherapy. Patients with advanced stages and large tumor mass are at high risk for renal failure. Impaired renal function predisposes patients to further complications and toxic death. Prophylactic use of urate-oxidase in all patients with advanced stage NHL might limit the incidence of tumor lysis syndrome. Prospective studies on renal function prior to and during therapy are required in order to develop a clinical profile reliably detecting patients at risk for developing renal failure and subsequent complications.

Acute Kidney Injury↗

[Detection of translocation t(8;14)(q24;132) in pediatric Burkitt's lymphomas using "long distance" polymerase chain reaction: a new method for diagnosis of Burkitt's lymphomas].

The pediatric Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of B- or T-cell origin. Approximately half of them are characterized as Burkitt's lymphomas. Typically, one of the reciprocal translocations t(8;14)(q24;q32), t(2;8)(p11;q24) or t(8;22)(q24;q11) is seen in the tumor cell, each involving the protooncogene c-myc on chromosome 8. Characteristically, in most patients the translocation occurs between the distal end of the long arm on chromosome 8 (c-myc) and chromosome 14 (immunoglobulin heavy chain locus, IgH). The breakpoint regions are distributed over a wide range of more than 10 Kb on chr. 8 and over several hundred Kb on chr. 14. With standard-PCR, fragments can only be amplified to a size of about 2 Kb. The development of PCR-applications to generate long products up to 20 Kb now allows a detection of these breakpoints. Several primer pairs from different regions of the IgH-gene and the c-myc-gene were tested in each patient. Until now, 20 patients with Burkitt's Lymphoma or B-ALL characterized by L3 morphology were examined. All patients were treated according the protocols of the NHL-BFM '90 or '95 study. In 11/20 patients, recombinations between chromosomes 8 and 14 could be detected with our primer pairs. In serial dilutions of DNA from malignant cells in DNA from healthy controls, sensitivities of one malignant cell in 2 x 10(4) normal cells could be obtained. This method will now allow us to characterize the involved breakpoints more exactly and to analyze patient samples (blood, bone marrow, aphereses products and residual tumors) during or after therapy for the existence of minimal residual tumor cells.

Adolescent↗

[Concept and interim result of the ALL-BFM 90 therapy study in treatment of acute lymphoblastic leukemia in children and adolescents: the significance of initial therapy response in blood and bone marrow].

In the ongoing trial ALL-BFM 90 for the treatment of childhood non-B cell acute lymphoblastic leukemia (ALL) 1468 unselected patients (pts) were enrolled from 84 centers in Germany and Switzerland from 4/90 to 12/93. Based on the results of the previous trial ALL/NHL-BFM 86 this treatment program focused especially on therapy modifications for average (MRG) and high risk (HRG) pts, on the evaluation of therapy response for prognosis, and on the identification of high risk pts by molecular genetics. For average risk pts consolidation therapy was intensified by the addition of L-asparaginase (L-ASP) on a randomized basis. In HRG induction and consolidation therapy was modified by introduction of early intensification elements that had proved to be effective in relapsed pts. This patient group was randomized for the evaluation of the effects of G-CSF administered in the intervals between the intensification elements. Distribution of the 1376 eligible pts into the three treatment arms SRG (standard risk), MRG, and HRG was as expected (17 pts not yet assigned): 385 pts (28.0%), 834 pts (60.6%), and 140 pts (10.2%), respectively. Treatment consisted of the 8-drug induction (Protocol I), consolidation (Protocol M), reinduction (Protocol II), and maintenance therapy (total therapy duration 24 months). The drug doses and combinations were only slightly modified compared to the previous study ALL-BFM 86 with the exception of the randomized L-ASP containing arm MRG-2 (Protocol M-A) and group HRG. Preventive cranial irradiation was reduced to 12 Gy and applied to MRG and HRG pts only. As in study ALL-BFM 86, the initial response to a 7-day exposure to prednisone and to the first intrathecal injection of MTX at diagnosis was evaluated at day 8 of treatment with regard to blast count in peripheral blood (PB). In addition, pts were now investigated for the presence of blasts in the bone marrow (BM) at day 15 of treatment to compare the prognostic power of both response parameters. Identification of translocation t(9; 22) and/or BCR-ABL rearrangement characterized a small subgroup of pts that were not detected by poor initial therapy response. These pts were enrolled in HRG for more intensive treatment including allogeneic bone marrow transplantation (BMT). After a median observation time of 22 months, the overall probability for event-free survival (p-EFS) is 82 +/- 2%. 11 pts (0.8%) died before complete remission (CR) was achieved, 15 pts (1.1%) died while in CR for reasons other than relapse.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphomas in children and adolescents. Part 1: Classification and allocation to strategic therapy groups. BIF study group].

One of the goals of the study NHL-BFM 90 was to investigate the distribution and prognosis of the different subtypes of Non-Hodgkin's Lymphoma (NHL) in children and adolescents according to histological, cytomorphological and immunological characteristics. From 4/1990 to 12/1992, 346 patients (pts) (84 females, 262 males) were enrolled (median age: 9.1 years; range: 0.8-17.9 years). Histology was available from 290 pts (84%), cytomorphology from 155 (44%), and immunophenotyping from 245 (70%). Cases with L1 oder L2 cytomorphology according to the French-American-British Classification were classified as lymphoblastic lymphoma and those with L3 cytomorphology as Burkitt-Type lymphoma or acute B-cell leukemia (B-ALL) if a histological classification was not available. By means of the combined analysis of all three diagnostic criterias the classification of the NHL according to the updated Kiel-classification was possible in 312 cases: 49% were classified as Burkitt-type-lymphoma (incl. B-ALL), 22% als lymphoblastic lymphoma, 10% as large cell anaplastic lymphoma (LCAL), 6% as centroblastic lymphoma, only few cases were classified as NHL of other subtypes, 3 pts (1%) suffered from low grade malignant lymphomas, and in 34 pts (10%) the NHL was not further classified. Patients were stratified according to NHL-subentities in 3 branches (Non-B-NHL, B-NHL, LCAL) of different treatment modalities. The estimated probability of a 3-year event free survival (pEFS) was 88 +/- 2% for the whole group (follow up 7 to 40 months, median 23 months) while pEFS of different subtypes was: lymphoblastic lymphoma: 91 +/- 4%; Burkitt-type-lymphoma/B-ALL: 90 +/- 2%; centroblastic lymphoma: 94 +/- 6%, LCAL: 88 +/- 6%. We conclude that the stratification of treatment modalities in study NHL-BFM 90 according to biological entities provided patients of different NHL-subtypes an equal chance to survive event free. The efficacy of the treatment strategy for rare subtypes, however, is not evaluable yet.

Adolescent↗

[NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphomas in children and adolescents. Part 2: An intermediate term analysis of the non-B-NHL therapy group. BFM Study group].

The goals of study NHL-BFM 90 for the therapy group Non-B NHL are to prospectively evaluate the dynamic of tumor regression and the persistence of a residual mass after induction therapy for its prognostic impact. Patients (pts) of stages I and II receive induction composed of prednisone, vincristine (VCR), daunorubicin, L-asparaginase (L-ASP), cyclophosphamide (CP), cytarabine (ARA-C), 6-mercaptopurine (6-MP) and intrathecally (i.th.) methotrexate (MTX), followed by consolidation (6-MP,MTX 5 g/m2 x 4, MTX i.th.), and maintenance up to 24 months. Pts of stages III and IV receive additionally reinduction (Dexamethasone, VCR, doxorubicin, L-ASP, CP, ARA-C, 6-thioguanine, MTX i.th.) and cranial irradiation. Pts with < 70% tumor regression at day 33 of induction receive an intensified chemotherapy. Pts with > 70% tumor regression at day 33 but a persistent mass at the end of induction have a surgical resection. Pts with a completely necrotic residual mass continue with consolidation therapy. Pts with active residual lymphoma receive an intensified chemotherapy. No local radiotherapy is given. From 4/1990 to 12/1992, 80 pts were registered; 71 pts are evaluable for response. The distribution of stages is as follows: 6, 1, 47, 17 pts of stage I, II, III, IV, respectively. The probability of event free survival at 3 years is 87 +/- 4% for the whole group (median observation time 21 months). 66 pts are evaluable for the dynamic of response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphoma in children and adolescents. Part 3: An intermediate term analysis of the B-NHL/B-ALL].

The aims of trial NHL-BFM 90 for patients (pts) suffering from B-cell neoplasms are to prove whether: 1. Treatment for pts with complete resection can be reduced from 3 to 2 therapy courses; 2. Results for pts of stage III with large abdominal tumors can be improved by high dose (HD) chemotherapy; 3. Survival for pts with incomplete initial response can be improved by therapy intensification; 4. Intraventricularly applied CNS chemotherapy can improve the outcome for CNS positive pts. Therapy is stratified into 3 branches. Branch 1: completely resected; branch 2: not resected, extra-abdominal localization only or abdominal localization and LDH < 500 U/l; branch 3: abdominal localization and LDH > or = 500 U/l, and all pts with BM or/and CNS involvement or multifocal bone disease. A 5-day prephase is followed by 2 (R1), 4 (R2), 6 (R3) therapy courses composed of dexamethasone (DEXA), methotrexate (MTX) 5 g/m2/24 h (in branch R1, 500 mg/m2), MTX/Cytarabine (ARA-C)/prednisolone (PRED) i.th., vincristine (not in branch R1), ifosfamide alternating with cyclophosphamide, ARA-C/etoposide (VP16) alternating with doxorubicin. CNS pos. pts receive MTX/ARA-C/PRED applied intraventricularly. Pts with incomplete response after 2 courses receive an intensification (DEXA, Vindesine, HD-ARA-C, VP16, and MTX/ARA-C/PRED i.th.). Pts with viable tumor after the intensified course receive mega-dose chemotherapy with autologous BM rescue (aBMT). From 4/1990 to 12/1992, 228 pts were registered; 212 pts are evaluable for response. The probability of event free survival (pEFS) at 3 years is 89 +/- 2% for the whole group, 97 +/- 3% for pts of branch R1 (n = 32), 99 +/- 1% for patients of branch R2 (n = 87), and 77 +/- 4% for patients of branch R3 (n = 94) (median observation time 21 months). 7 pts of branch R3 died early due to infections. 15 pts failed therapy (one pt each in branch R1, and R2, 13 pts in branch R3). pEFS for pts with stage III abdominal disease and LDH > or = 500 U/l is 80 +/- 6 as compared to 53 +/- 8% in the preceding studies (p < .02). Of 13 evaluable pts with CNS disease 3 died early of infection, however none suffered from relapse. Only 1 of 22 pts of branch R2 who had residual tumors after 2 therapy courses suffered from progress in contrast to 9 of 33 such pts of branch R3. Only 2 pts had viable tumor after the intensification course CC. They received aBMT, both are in CCR.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Imaging methods in diagnosis of cerebrovascular complications with L-asparaginase therapy].

During or immediately following L-asparaginase (L-asp) therapy especially intracranial thromboembolic or hemorrhagic complications due to hemostatic imbalance have been observed. We report about 6 children who had intracranial thrombosis or hemorrhage after 3 to 8 doses of L-asp. Initial symptoms of the cerebral events were similar--seizure, coma, hemiparesis and disorientation. All patients were examined by cerebral computerized tomography (CT) or/and magnetic resonance imaging (MRI). Three patients had a dural sinus thrombosis, one had an intracranial hemorrhage and two a hemorrhagic infarction with typical findings in the cerebral CT or MRI. Two other patients were interpreted as having peripheral thrombosis. They showed nontypical hypodense cortical and subcortical areas without any contrast medium enhancement in CT and hyperintense areas in T2-weighted MRI scan. All patients recovered from neurological symptoms, and showed obvious regression of CT and MRI findings which correlate with the good prognosis of these complications. Both CT and MRI are useful in diagnosis and follow-up of cerebrovascular complications of L-asp therapy. The CT and MRI findings of the reported cases seem to reflect different appearances of the same entity, i.e. thrombosis of venous vessels of different size with or without congestive edema and hemorrhagic complication.

Adolescent↗

Comparative results of two intensive treatment programs for childhood acute lymphoblastic leukemia: The Berlin-Frankfurt-Münster and Dana-Farber Cancer Institute protocols.

We analyzed two of the most successful trials for childhood acute lymphoblastic leukemia, from the Berlin-Frankfurt-Münster group (BFM) and the Dana-Farber Cancer Institute (DFCI), to determine their similarities and differences and suggest ways to improve future treatments. Protocol ALL-BFM 81 (n = 611) was conducted between 1981-1983 in 37 centers in West Germany and Austria; Protocol DFCI 81-01 (n = 286) was conducted between 1981-1985 in seven centers within the United States. The BFM study used a risk score, based on peripheral lymphoblast count, liver size, and spleen size at the time of diagnosis to assign patients into one of the three treatment arms. The DFCI study classified patients into two groups: standard risk patients (age 2-9 years, with white blood count less than 20,000/mm3, and with no T-cell markers, mediastinal mass, nor central nervous system disease), and high risk patients (all others). Both studies involved intensive chemotherapy, although treatment strategies, cumulative drug doses and cranial radiation protocols differed. Study populations in the two trials were comparable with respect to age, sex, white blood count and proportion of patients with T-cell markers at the time of diagnosis. Using DFCI risk group criteria, 37% of BFM and 38% of DFCI patients were classified as standard risk. Median follow-up times were 6.8 years and 6.1 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intermediate dose methotrexate is as effective as high dose methotrexate in preventing isolated testicular relapse in childhood acute lymphoblastic leukemia.

PURPOSE: We evaluated the influence of three different dosages of methotrexate (MTX) during consolidation on the incidence of testicular relapse in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: One thousand one hundred forty-four boys with newly diagnosed ALL, enrolled in three consecutive trials of the Berlin-Frankfurt-Münster group (ALL-BFM 81, 83, 86), were retrospectively evaluated for the influence of MTX on testicular relapse-free interval. The basic treatment design was similar in all trials. No intravenous MTX was used in trial ALL-BFM 81 in the group who received cranial irradiation (CRT) except for a part of standard risk patients. Four courses of intermediate dose MTX (IDM) (0.5 g/m2) were introduced for all patients in trial ALL-BFM 83 (IDM group), which were replaced by high dose MTX (HDM) (5 g/m2) in trial ALL-BFM 86 (HDM group). The media observation time was > 9 years. RESULTS: The cumulative incidence of isolated testicular relapses was significantly higher in the CRT group as compared to the IDM and HDM groups (6.7% versus 2.5% and 2.3%, p = 0.02 and 0.01). HDM decreased neither the incidence nor the rate of isolated testicular relapses any further. Event-free survival (EFS) for boys was similar between trial ALL-BFM 81 and 86 (64% versus 69%, p = 0.35), but differed significantly between trials ALL-BFM 83 and 86 (61% versus 69%, p = 0.0078). CONCLUSION: The introduction of IDM reduced the incidence of isolated testicular relapses significantly by a factor two, but had no significant influence on overall survival. HDM did not result in a more effective prevention of testicular relapses, but resulted in better systemic control and hence better survival than IDM.

Antimetabolites, Antineoplastic↗

Marker proteins in the particulate fraction of third-trimester amniotic fluid.

The present clinical evaluation of fetal lung maturity relies largely on the determination of the amniotic surfactant phospholipids phosphotidylglycerol, lecithin, and sphingomyelin, but there are many false negatives as well as false positives among diabetics. The use of other components of lung surfactant, namely, the hydrophobic surfactant proteins (SPs) has long been suggested as an alternative to the classical assay, but tests based on the detection of immunoreactive SP-A have not proved superior or supplanted phospholipid ratios as an index. This report investigates the proteins in a fraction of third-trimester human amniotic fluid (the particulate fraction) enriched in the SP complexes that form the surfactant monolayer. The proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis and visualized by silver staining and immunoblotting. Eight proteins are of particular interest. Three novel proteins (termed AFPP-1, AFPP-4, and AFPP-8) and the alpha-fetoprotein/human serum albumin complex (AFPP-7) can be detected throughout the 28- to 38-week gestational window. The protein that is referred to as AFPP-2 could be identified as SP-A on the basis of immunologic cross-reactivity as well as size and charge characteristics. The time course of appearance of AFPP-2 was also followed in patients with Rh isoimmunization syndrome and was found to be the same as that seen for SP-A. The SP-A was detected as at least five major charged isoforms with multiple subisoforms of different molecular weight and can be distinguished from a related set of proteins (AFPP-5) that appear with a different time course but are possible precursors. Two other proteins (AFPP-3, AFPP-6), which are detectable inconsistently bear some similarity to others reported previously but not extensively characterized. These results define both constant and variable proteins of the particulate fraction of the amniotic fluid and indicate that certain protein isoforms are changing throughout the third trimester. These data enhance the possibility of the utilization of these proteins as markers of lung maturity in conditions such as maternal diabetes.

Amniotic Fluid↗

Successful prenatal therapy of thoracic lesions.

Improvements in prenatal imaging techniques now permit in utero treatment of potentially serious lesions. We describe three cases in which decompression of significant space-occupying thoracic lesions resulted in an excellent clinical outcome. The pregnancies were all carried to term after second or early third trimester intervention and resulted in infants with minimal respiratory distress. Cytologic and chemical analysis of the thoracic fluid aspirated in utero provided diagnostic and physiologic information.

Adult↗

[Fatal accidental mixed poisoning of 3 men at the same time].

The case history presented reports on three 30- to 40-years-old men, who were found dead in a party like situation in the living room. The toxicological investigation proved alcohol and THC as well as therapeutic Flunitrazepam- and Pentobarbital levels and toxic 7- Amino-Flunitrazepam concentrations. The background of this surprising scene led up to the conclusion of an accidental death caused by a mixed intoxication.

Accidents↗