Biomedical subjects

J Ritter

Publications and source records attributed to J Ritter.

At least 361 records · Page 20Linked to original sources

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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↗

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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↗

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[Prognosis of children with acute myelocytic leukemia after first relapse].

UNLABELLED: Nearly 40% of children treated within the AML BFM studies experience recurrence of their disease after having achieved remission. In our retrospective analysis we tried to estimate prognosis after relapse in children treated with intensive relapse regimens and studied the impact of prognostic factors for second remission and survival. PATIENTS: 102 patients suffering from first relapse were treated intensively according to the relapse protocols BFM REZ91 and REZ93 or intensive salvage therapy consisting of double induction with high dose Ara-C, mitoxantrone and VP-16. Once in CR, patients continued to receive a 6-week consolidation and either allogeneic or autologous bone marrow transplantation (BMT). RESULTS: Time to relapse was in median 1.1 years, range 0-8 years. Fifty-two of 102 pts. (51%) achieved 2nd remission (CR), 10 (10%) partial remission, 37 (36%) were nonresponders, and 3(3%) died early during salvage therapy. Twenty-seven were still in CR, median 2.5 years, range 0.4-7.0 years, with an overall survival of 21%, SE 5% after 5 years. The response and survival rate was similar in all treatment groups. Fifty patients were transplanted, 43 being in 2nd CR, and 7 with residual blasts. Twenty-seven patients received an allograft: Twenty-one from a matched sibling (MSD), 1 from a haploid and 5 from a matched unrelated donor (MUD); 23 received an autograft. None of the patients transplanted in partial remission survived. Whereas 7 of 16 patients were alive after MSD in 2nd CR, 1 after haploid BMT. Four of 5 patients died after MUD BMT. Multivariate risk factor analysis revealed duration until relapse to be the most important factor for survival after relapse. The maximum risk-ratio was obtained at a threshold value of 1.5 years after diagnosis resulting in a 5-year survival of 10%, SE 5% for early relapse, and 40%, SE 10% for late relapse, p logrank 0.0001. CONCLUSION: Intensive relapse regimens can induce a 2nd CR in half of the patients. Children with late relapse (> 1.5 years after diagnosis) have a realistic chance for longtime survival.

Antineoplastic Combined Chemotherapy Protocols↗

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Medulloblastoma: experience of a single institution.

BACKGROUND: The treatment of medulloblastoma has changed considerably during the last decades. Treatment differences between centers may affect a multicenter analysis. We analyzed data from patients of a single institution gathered over a long period of time. PATIENTS: Between 1968 and 1995, 60 patients with medulloblastoma were treated at the University of Munster. Thirty-six were male, 24-female. The ages ranged between 11 months and 32 years. METHODS: Data were retrospectively analyzed from files. Survival was estimated using the Kaplan Meier method and compared using the logranktest and multivariance analysis. RESULTS: The 5-year survival rate was 37%. This included an early mortality of 20% within the first two months, prior to 1980. Significant single, positive, prognostic factors included: no solid metastases (p = 0.001), age > 10 years (p < 0.002); total resection (p < 0.025); posterior fossa radiation with more than 50 Gy (p = 0.04); and intense chemotherapy (p = 0.02). Male patients did slightly worse (not significant). The three-year event-free survival rate of 16 patients treated after 1991 was 70%. CONCLUSION: The prognosis of medulloblastoma has clearly improved with the reduction of the perioperative mortality, standardized radiotherapy, and the introduction of intense chemotherapy.

Adolescent↗

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Good engraftment of B-cell precursor ALL in NOD-SCID mice.

BACKGROUND: In vivo models for human B cell precursor ALL have been established by transplanting human leukemic cells onto immune-deficient SCID mice. High risk and relapsed leukemias engraft very well in these mice, however, good prognosis pediatric ALL often grow poorly if at all. Recently a new, even more immune-deficient mouse strain has been bred by crossing the scid mutation onto the NOD mouse background. As these NOD-SCID mice have been shown to be better recipients for human myeloid cells the goal of this study was to test these mice as hosts for human acute lymphoblastic leukemia cells. PATIENTS AND METHODS: Bone marrow or peripheral blood cells from/pediatric and one adult patient with B-cell precursor ALL were transplanted onto immune-deficient NOD-SCID mice according to established protocols. MAIN RESULTS: ALL cells from 6 out of the 8 patients (75%) successfully engrafted the NOD-SCID mice and from 4 patients (50%) led to an extensive leukemic infiltration in the murine marrow (> 10%). High level human cell engraftment could be demonstrated by flow cytometry, Southern blot analysis and cytology. By cytology and immunophenotype the leukemia in the mice was indistinguishable from the original leukemia in the patients. The presence of few human eosinophils in the marrow of highly engrafted mice indicates minimal coengraftment of residual normal cells. Development of overt leukemia in the mice after transplantation of cells from different patients varied between 1.5 and 7 months. Interestingly and in contrast to myeloid cells, conditioning of the mice by sublethal irradiation was not necessary for successful engraftment. Limiting dilution experiments with leukemic blasts from one patient showed that as few as 10000 cells were sufficient to transfer the leukemia onto NOD-SCID mice. CONCLUSIONS: NOD-SCID mice are sensitive recipients for human ALL xenografts.

Adult↗

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Assessment of molecular genetic detection of chromosome translocations in the differential diagnosis of pediatric sarcomas.

BACKGROUND: Recent studies have shown that many types of soft-tissue sarcomas are characterized by specific chromosomal translocations, which are likely to be of etiologic significance. In order to evaluate their diagnostic impact, a panel of 129 sarcomas comprising 78 Ewing's tumors (ET), 19 rhabdomyosarcomas (RMS), 20 neuroblastomas (NB), 9 synovialsarcomas, 2 esthesioneuroblastomas, and 1 desmoplastic small-round-cell tumor (DSRCT) were analysed for the occurrence of the major recurrent translocations, such as t(11;22)(q24;q12), t(21;22)(q22;q12), t(11;22)(p13;q12), t(2;13)(q35;q14), t(1;13)(p36;q14), and t(X;18)(p11;q11). METHODS: Nitrogen-frozen tissue material was analysed by means of Reverse Transcription followed by PCR (Polymerase-Chain Reaction) and nested PCR (RT-PCR). Specificity of the PCR products obtained was confirmed by non-isotopic Southern-Blot analysis with gene-specific probes and/or automated direct sequence analysis. RESULTS: 75 ETs have been shown to carry either a t(11;22) or t(21;22) translocation by identification of chimeric EWS-FLI-1 or EWS-ERG gene-fusion transcripts respectively. 3 ETs were lacking EWS/FLI-1 or EWS-ERG fusion products. 2 of these tumors were shown on review to have unusual morphological features for ETs. 8/19 RMS were initially diagnosed as alveolar RMS. These tumours were shown to carry either a t(2;13) translocation exhibiting chimeric PAX3-FKHR fusion transcripts or a t(1;13) translocation with PAX7-FKHR chimeric gene products. One RMS of the embryonal group also carried a t(1;13) translocation. Reevaluation demonstrated a partly alveolar morphology. In 8/9 synovial sarcomas a t(X;18) translocation was identified. Expression of a EWS-WTI gene-fusion product associated with a t(11;22) translocation was found in the DSRCT. None of these rearrangements were detected in the NBs and 2 esthesioneuroblastomas. CONCLUSIONS: Our results support the concept that the major recurrent translocations are histogenetically specific for a subset of sarcomas. Thus, the detection of tumor type-specific translocations represents an extremely useful diagnostic modality as an adjunct to surgical pathology.

Base Sequence↗

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[Intracellular retention of cytarabine-triphosphate (Ara-CTP) in blasts of children with acute lymphoblastic leukemia. Correlation with clinical course parameters].

BACKGROUND: Cellular uptake and intracellular phosphorylation to the nucleotide cytosine arabinoside-triphosphate (Ara-CTP) is the precondition for the cytostatic effect of cytarabine. The pharmacokinetics of Ara-CTP in leukemic cells was reported to be of clinical importance in adult nonlymphoblastic leukemia. Therefore, the role of intracellular Ara-CTP formation and retention was investigated in blast cells from children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: At the time of diagnosis, peripheral or bone marrow blast cells from 41 children with ALL and 13 with relapsed ALL were incubated in Ara-C containing medium (1 hour, 1 or 3 micrograms/ml) followed by reincubation in Ara-C free medium (3 h). Intracellular Ara CTP formation and Ara-CTP retention were determined. MAIN RESULTS: Ara-CTP formation did not show marked differences between the different immunological subtypes. Ara-CTP retention, however, was significantly lower in T-ALL (37 +/- 15%, n = 8) compared to non-T-ALL (67 +/- 25%, n = 33; p < 0.003). Ara-CTP retention was also significantly different in children with and without persistence of peripheral blast cells after one week of prednison treatment (71 +/- 30%, n = 9 and 53 +/- 19%, n = 21; p = 0.031) as well as in children with and without complete bone marrow remission on day 15 of the ALL-BFM treatment protocol (66 +/- 17%, n = 19 and 43 +/- 18%, n = 11; p = 0.018). Ara-CTP retention was inversely correlated with the risk groups defined by the ALL-BFM treatment protocols (standard 79 +/- 29, intermediate 59 +/- 25, high risk 47 +/- 21%). A trend towards lower Ara-CTP retention was observed in relapsed leukemias (relapsed non-T-ALL 51 +/- 17%, p = 0.061). The difference in the probability of event free survival (following risk group adapted treatment according to ALL-BFM trials) between children with high (> or = 72%; 0.92 +/- 0.08) and low (< 72%: 0.58 +/- 0.15) Ara-CTP retention up to now did not reach statistical significance (p = 0.12). CONCLUSIONS: The more rapid decrease of cellular Ara-CTP in T-cell leukemia and children at higher clinical risk groups provide a pharmacokinetic rationale for prolonged infusion duration as an alternative to the intensification by dose escalation alone.

Adolescent↗

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[Flow cytometric characterization of maturation processes and primitive stem cell population in pre-B-cell ALL in childhood].

Bone marrow and peripheral blood from children with acute lymphoblastic leukemia was analyzed by flow cytometry to assess leukemic cell differentiation and to characterize the profile of cell surface marker expression on rare CD34+ cell populations. The goal of this study was to determine if patterns of cell surface antigens could be identified on CD34+ subpopulations which may allow distinction between normal and leukemic stem cells. Expression of the progenitor cell antigen CD34 on leukemic blasts was very heterogeneous and varied between 0.5 and 100% in 20 patients analyzed in this study. In cALL and pre-B-ALL, a variable percentage of the leukemic cells coexpressed CD20 in addition to CD10. Only in one case, differentiation characteristic for normal B cell development with coordinated downregulation of CD10 with increasing expression of CD20 was observed. By analysing 5 x 10(6)-1 x 10(6) cells, a CD34+ cell population could be identified in 8 out of 8 patients which did not express CD19 and comprised less than 0.1% of all bone marrow or peripheral blood cells. Within this population, there was differentiation from primitive CD34-CD38- to more mature CD34+CD38+ cells. In 4 of these patients, an additional CD34+ population with low expression of CD19 (CD34+CD19lo) was detected. The lack of CD45 expression on the leukemic cells of 2 patients was used as a marker for the leukemic cell clone. In both patients, the CD34+CD19- cells did express CD45 while CD34+CD19lo/+ cells were CD45 negative. This suggests that the CD34+CD19lo cells were part of the leukemic clone and that the CD34+CD38-CD19- cells may represent residual normal primitive hematopoietic cells. In conclusion, flow cytometry allowed identification of primitive CD34+ cell populations in children with ALL, which can now be functionally characterized by transplantation onto immune-deficient mice.

Animals↗

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[Prognosis of children with chronic myeloid leukemia: a retrospective analysis of 75 patients].

UNLABELLED: As the probability of survival of patients with chronic myelocytic leukemia (CML) gradually decreases over a period of 10 years, long-term follow-up is mandatory. Between 1977 and 1994, 68 children and adolescents between 1.0 and 18 years of age with CML in chronic phase and 7 presenting with blast crisis at diagnosis were reported to the study center in Münster. The Philadelphia-chromosome and/or BCR/ABL rearrangement could be detected in 66 children. The 4 Philadelphia-negative patients and 5 patients without karyotyping fulfilled the morphological criteria of CML. Clinical symptoms and hematological findings at presentations were similar to adult patients. THERAPY: Until 1985 chemotherapy consisted predominantly in busulfan (BU), later in hydroxyurea (HU) or a combination of both and since 1987 increasingly in HU plus interferon-alpha. 47 patients (6 in blast crisis) were allografted once or twice (n = 4) (27 HLA-identical, 16 unrelated, 4 haplo-identical) within 2.3-135 months (median 12 months) after diagnosis. RESULTS: 38 of 75 patients (3 in blast crisis at diagnosis) were alive after a median follow-up of 5.5 years. The probability of 12 years survival was 27%, SE 9% for patients in chronic phase. All deaths (n = 19) were leukemia-related in the 27 non-transplanted children. A comparison of survival for patients with or without bone-marrow transplantation (BMT) showed a significant difference in favour of the BMT-group (42%, SE 13% vs. 10%, SE 8%, p log-rank 0.003). The probability of survival increased to 62%, SE 10%, if patients transplanted later than 3 years after diagnosis were excluded. Only few patients (4/39 with information about the cause of death = 10%) died due to recurrent CML after BMT. CONCLUSION: Our data confirm the unfavourable outcome of CML in pediatric patients if treated with chemotherapy alone. With early BMT high cure rates can be achieved. If transplant-related mortality which in our patient group was 21% (8/39) can be reduced, even a higher cure rate appear realistic for the future.

Adolescent↗

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[Acute myeloid leukemia in children with Down syndrome].

Forty-four children, aged between 0.4 and 16.2 years (median 2.0 years) with Down's syndrome and acute myelogenous leukemia (AML) including subacute megakaryoblastic leukemia (M7) were diagnosed between 1980 and 1986 (group 1, n = 16) or between 1987 and 1992 (group 2, n = 28). The leukemic blasts from Down's syndrome patients often proved difficult to classify. In group 1 the most frequent diagnoses were FAB M5 (6 pts.), M6 (3 pts.), in 3 patients the morphological diagnosis of M7 can retrospectively be assumed. In group 2, 15 of 28 patients were classified as M7, in 3 patients based on morphology alone, and in the other 12 patients confirmed by immunophenotyping or biopsy. The other children in group 2 were classified as: FAB M0 (3 pts.), M1 (1 pt.), M4 (2 pts.), M5 (2 pts.), M6 (4 pts.), M6/M7 (1 pt.). Initially, the latter and 10 of the patients with M7 presented with < 30% of blasts in the bone marrow. Karyotyping in 12 of 13 children frequently revealed numeric abnormalities, particularly trisomies involving chromosomes 8 (n = 6), 11 (n = 3), 21 (n = 3) and 14 (n = 1) in addition to the constitutional + 21c. Six patients in group 1 received no specific treatment, while 10 children were treated according to the protocols AML-BFM-78 or -83. Four of them are still alive for more than 5 years, two others died from infections in remission after 1.0 and 3.8 years. Fourteen of the 28 patients in group 2 did not receive any chemotherapy (10 with M7), and subsequently died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

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[Osteosarcoma in 2 siblings. A case report].

With a brother and sister, osteosarcoma developed at the age of 11 and 14 respectively. With both there was no previous retinoblastoma or other bone disease with a proclivity to develop osteosarcoma. We discuss possible explanations for familial aggregation of osteosarcoma, citing external or genetic factors. We suggest that it is the retinoblastoma gene RB and the tumor suppressor gene p53 which play an important part in the development of osteosarcoma.

Adolescent↗

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[Reducing radiation dosage to 20-30 Gy in combined chemo-/radiotherapy of Hodgkin's disease in childhood. A report of the cooperative DAL-HD-87 therapy study].

UNLABELLED: The main objective of the multicenter study DAL-HD-87 was to evaluate for the involved-field irradiation a dose reduction by 5 Gy compared with the precursor studies HD-82 and HD-85. Moreover, the decisional strategy for selective laparotomy developed on the basis of retrospective analyses in study HD-82 was to be tested in a prospective design. Chemotherapy in group 1 (stages I, IIA) consisted in 2 OPA cycles (vincristine, prednisone, adriamycin). Group 2 (stages IIEA, IIB, IIIA) received 2 x OPA + 2 x COP(P), and group 3 (stages IIEB, IIIB, IV) 2 x OPPA (with procarbacine) + 4 x COP(P). For the subsequent radiotherapy, doses of 30, 25, and 20 Gy respectively were applied in the 3 groups. Fields with incomplete lymphoma regression were to receive an additional boost of 5-10 Gy. -Exploratory laparotomy was considered indicated in the event of abnormal findings in abdominal CT/ultrasonography and/or enlargement of lymph nodes at the pulmonary hilus. RESULTS: From Dec. 1986 to Sept. 1990, 204 pts from 51 centres were enrolled in the study. 196 were evaluable. 109 pts (55.6%) were laparotomized, 58 (29.6%) splenectomized. The accuracy for the prediction of an abdominal involvement was 72.3% in case of abnormal findings in abdominal CT/ultrasound but only 36.4% in case of enlarged lymph nodes at the pulmonary hilus without abdominal abnormalities. 91.2% of the removed spleens were proven involved. -2 out of 196 pts suffered progression under treatment, and 22 relapsed (as of 1 Jan, 1994). 6 pts died, 4 of whom succumbed to Hodgkin's disease, and 2 to intercurrent infections. 2 pts in first remission developed a secondary malignancy, namely 1 malignant histiocytoma in radiation field and 1 ANLL. Another patient developed a thyroid carcinoma following salvage therapy for a relapse. The probabilities of event-free survival (EFS) and survival after 7 years are for the total group: 85% and 97%, in group 1: 84% and 99%, in group 2: 82% and 93%, and group 3: 89% and 95%. Comparison with the precursor studies HD-82 and HD-85 reveals that the dose reduction in radiotherapy has not affected the results. Differences in EFS are exclusively correlated with changes in chemotherapy.

Adolescent↗

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Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients.

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg.d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4+ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving greater than 20 mg/(kg.d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.

AIDS-Related Complex↗

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DNA-analysis of human testicular samples by cytofluorometry.

Germ cells in human testicular samples have been estimated by histology and quantitated by flow cytometry. There is an excellent relationship between the two techniques. These samples were classified histologically as "normal", "reduced number of germ cells" or "no germ cells". A definition of "normalcy" as determined by flow cytometry as having at least 38% of the cells in the haploid state, is proposed. Testicular samples from prepubertal boys with infiltrating leukemic cells often show an increase in the percentage of S-phase cells indicating the presence of tumor. These results indicate the value of flow cytometry in the identification of reproductive and neoplastic disorders.

Adolescent↗

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Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia.

UNLABELLED: Febrile neutropenia in patients who have undergone chemotherapy is usually treated with a combination of broad-spectrum antibiotics. There are no exactly defined protocols for single-agent treatment because a clear definition of low risk febrile neutropenia is lacking. This paper examines the safety and efficacy of once-daily ceftriaxone in 376 cases. MATERIAL AND METHODS: In a prospective observational study carried out between February 1992 and January 1996, 959 febrile episodes at 48 hospitals were recorded. Inclusion criteria were neutropenia (absolute neutrophil count, ANC <1,000/ microl) with fever (>/=38.5 degreesC) or a C-reactive protein concentration >1 mg/dl and suspected infection. Nine hundred and one episodes (acute leukemia n = 396, lymphoma n = 220, solid tumors n = 272 and other disorders n = 13) in 828 patients aged between 1 and 97 years were analyzed, of which 876 episodes were evaluable for response. All patients initially underwent empirical treatment with ceftriaxone (adults: 2 g/day; children: 80 mg/kg/day), either alone (376) or in combination with other agents (525). RESULTS: The mean ANC was 423/ microl (SD +/- 316) and the median duration of neutropenia 10 days. Of the 363 episodes treated initially with ceftriaxone alone, 70.8% responded versus 56.9% in the combination therapy group. The favorable response to the initial monotherapy treatment was explained by a low-risk population in the monotherapy group. A KI >6 (p < 0.0001), ANC >/=500/ microl (p = 0.0001) and a duration of ANC <5 days (p < 0.05) were significantly more frequent in the monotherapy arm and were predictive of lower risk at the commencement of treatment. CONCLUSION: Ceftriaxone is effective in febrile neutropenia. Treatment with ceftriaxone alone was safe and highly effective in low-risk patients. Single-agent regimens appear to be a suitable treatment option in low-risk febrile neutropenia.

Adolescent↗

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Prenatal diagnosis of cystic neuroblastoma.

Cystic adrenal masses are unusual in the fetus. The most common diagnosis for adrenal cyst is hemorrhage. We report 2 cases of cystic neuroblastoma diagnosed prenatally by ultrasound. In each case, diagnosis was confirmed in the neonatal period first by scintigraphy, then by histology. Differential diagnosis and management after delivery are discussed.

Adrenal Gland Neoplasms↗

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Prenatal diagnosis of hepatic hemangioma.

We report the prenatal diagnosis of a hepatic hemangioma presenting as a heterogeneous mass (6 x 5 cm) of the fetal liver, thickly septated with calcifications. Pulsed Doppler confirmed the vascular pattern of the mass. Subsequent postnatal examinations and follow-up have documented the spontaneous regression of this benign tumor. Antenatal diagnosis of fetal liver masses and management after delivery are discussed.

Adult↗

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Cervicography. Does it improve cervical cancer screening?

OBJECTIVE: To compare the reliability of cytology with that of cervicography and with the use of both tests when screening for neoplasia of the cervix and to analyze the causes of false positive and false negative results with both methods. STUDY DESIGN: The results of cytology and cervicography in 1,709 patients (1,447 seen for routine screening, 82 for follow-up after treatment for cervical neoplasia and 180 referred because of cytologic anomalies) were correlated with colpohistologic findings. RESULTS: Cervicography entailed more defective examinations than did cytology (8.9% vs. 0.2%, P < .0001). It was less sensitive (51% vs. 59%, P = .320) and less specific (96% vs. 98%, P = .004). Whatever the clinical criteria (patient's age, parity, pregnancy or history of cervical treatment), the rate of false positives with cervicography was always higher than with cytology, as was the rate of false negatives, except in pregnant women. CONCLUSION: Cervicography does not seem to offer a worthwhile alternative to cytology for cervical screening.

Adolescent↗