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Biomedical subjects

J Ritter

Publications and source records attributed to J Ritter.

At least 19 recordsLinked to original sources

Favorable outcome of B-cell acute lymphoblastic leukemia in childhood: a report of three consecutive studies of the BFM group.

In 1981 the BFM group introduced a new treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL). A cytoreductive prephase (prednisone/cyclophosphamide) was followed by eight 5-day courses of chemotherapy. Fractionated cyclophosphamide, methotrexate (MTX) 0.5 g/m2 (24-hour infusion), and MTX intrathecally were administered at each course and cytosine arabinoside (ARA-C)/teniposide (VM-26) was given alternately with doxorubicin. In study ALL-BFM-83, central nervous system (CNS) chemotherapy was intensified by adding dexamethasone, while MTX/ARA-C was administered intraventricularly. Therapy duration was reduced to six courses. In study ALL-BFM-86, MTX 0.5 g/m2 was replaced by high-dose (HD) MTX, 5 g/m2 (24-hour infusion), and MTX/ARA-C/prednisolone intrathecal therapy was introduced. Doses of ARA-C and VM-26 were increased and fractionated, cyclophosphamide was partially replaced by ifosfamide, and vincristine was added. CNS irradiation was 24 Gy for prevention and 30 Gy for overt disease in studies ALL-BFM-81 and -83, but was omitted in ALL-BFM-86. In all, 87 patients were enrolled, 22 (8 CNS-positive) in study All-BFM-81, 24 (7 CNS-positive) in study ALL-BFM-83, and 41 (0 CNS-positive) in study ALL-BFM-86. The estimated 5-year duration of event-free survival (EFS) was 43% in study ALL-BFM 81, 50% in study ALL-BFM-83, and 78% in study ALL-BFM-86 (minimal follow-up, 25 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 bone marrow (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. We conclude that an intensive, short-pulse therapy delivered within a 4-month period is highly effective in the treatment of B-ALL. In addition to fractionated cyclophosphamide/ifosfamide, a 24-hour infusion of HD MTX 5 g/m2 in conjunction with an i.th. therapy is an important component for prevention of both systemic and CNS relapses. CNS irradiation is not needed for CNS-negative patients.

Adolescent

(Sub)periosteal Ewing's sarcoma of bone.

Ewing's sarcoma is a small malignant round-cell tumour that arises from mesenchymal cells, predominantly in the medullary cavity of bone. In exceptional cases it originates in the soft tissues and subsequently invades the underlying bone. A (sub) periosteal origin of Ewing's sarcoma is a very rare condition: only a few cases have been published so far. Three cases of (sub)periosteal Ewing's sarcoma, having received neoadjuvant chemotherapy and radiation therapy as well as wide excision, are reported.

Adolescent

Invasive aspergillosis complicating induction chemotherapy of childhood leukaemia.

Two children with acute leukaemia developed histologically confirmed invasive aspergillosis within 2 weeks after onset of polychemotherapy. One child had received only prednisone and one pulse of vincristine and daunorubicin before. This child showed classical roentgenographic signs of aspergilloma following an upper pulmonary lobe infiltration. The second patient developed caecal aspergillosis obscured by clinical signs of appendicitis. He died of disseminated aspergillosis several weeks later in spite of systemic antifungal therapy. Both case reports illustrate that the possibility of invasive aspergillosis must also be expected in young patients soon after onset of induction chemotherapy.

Aspergillosis

Paraparesis secondary to a spinal mass as the presenting feature of erythroleukaemia in a 10-month-old child.

Severe neurological impairment as the first symptom of acute leukaemia is a rather uncommon finding. We report the case of a 10-month-old infant who presented with acute paralysis of the lower extremities due to cord compression by an epidural tumour composed of malignant erythrocyte precursor cells. Diagnosis of erythroleukaemia (EL) was made by needle biopsy of the spinal epidural mass and confirmed by bone marrow aspiration. Antileukaemic treatment in combination with radiotherapy to the epidural tumour led to haematological remission and neurological recovery with disappearance of the mass lesion as demonstrated by MRI. However, haematological relapse occurred with death of the patient 7 months after diagnosis. This is the first reported case of EL presenting with paraparesis due to an epidural tumour. The clinical symptoms, results of cytogenetic and immunological studies and the clinical course are described.

Biopsy, Needle

[Dynamic MR tomography in the diagnosis of inflammatory and tumorous space-occupying lesions of the musculoskeletal system].

In 216 inflammatory and tumorous lesions of bone and soft tissue, dynamic Gd-DTPA enhanced MR imaging was performed. For that purpose, 12 FLASH sequences (TR = 40 ms/TE = 10 ms/NSA = 2/flip angle = 90 degrees) were acquired within 4 minutes; and Gd-DTPA bolus injection was administered following the first sequence. Slopes from the signal intensity curves were calculated. Estimated slopes allowed an assessment of the malignant potential of a lesion with an accuracy of 88%. Further more, a reliable differentiation between vital and necrotic tissue and between tumour and peritumoral edema was reliably possible. With this technique, response of malignant tumours to preoperative chemotherapy was correctly predicted in 83% of the cases. No differentiation of inflammatory from tumorous lesions was possible.

Bone Neoplasms

Relevance of the quantitative detection of HIV proviral sequences in PBMC of infected individuals.

Changes in HIV replication during progression of HIV infection were assessed by estimation of the number of peripheral blood mononuclear cells (PBMC) harboring HIV proviral sequences. Samples from 23 patients at different stages of HIV infection were analyzed by quantitative polymerase chain reaction (PCR) using GAG primers. HIV titers in PBMC were also determined by serial dilutions of cells in coculture with phytohemagglutinin-activated normal PBMC. A positive correlation was observed between the number of HIV DNA copies and the HIV titer in PBMC. The PCR test was more sensitive than the coculture technique. The number of HIV copies detected by PCR ranged from 50 to 10,500 per 10(6) PBMC: assuming one copy per cell this implies a frequency of proviral HIV-containing cells of one per 100 to one per 20,000 mononuclear cells. The mean number of HIV DNA sequences in PBMC was significantly lower in asymptomatic patients than in AIDS patients and patients with AIDS-related complex (ARC). In patients who progressed from asymptomatic infection to AIDS, the number of HIV DNA copies in PBMC rose, indicating an increase of HIV replication. These results show that the number of infected PBMC increases during clinical progression. However, some asymptomatic patients had a higher number of HIV DNA copies in their PBMCs suggesting that increased HIV replication precedes the appearance of clinical symptoms.

DNA, Viral

Canine systemic lupus erythematosus. II: Antinuclear antibodies.

The frequency and the specificities of antinuclear antibodies (ANAb) were studied in dogs with systemic lupus erythematosus (SLE) and compared to those found in normal dogs and in dogs with various infectious diseases. Whole ANAb were detected by immunofluorescence. Anti-double-stranded DNA Ab were found in only 2% of SLE dogs, whereas anti-single-stranded DNA Ab were present in 21.4% of SLE dogs and in 26.8% of dogs with infectious disease. Antihistone Ab were frequently observed in SLE dogs (71%) and are essentially directed against trypsin-resistant epitopes of H3, H4 and H2A. The Western blots of nuclear extracts of HeLa cells were recognized mainly by type 1 Ab (30%, reacting with bands of 43, 36, 35, 34, 30 and 27 kDa) and by anti-Sm Ab (12%) associated with anti-RNP Ab. Anti-SSA and anti-SSB Ab were rare.

Animals

[Role of herpes virus simplex and cytomegalovirus as cofactors of papillomavirus in dysplastic and cancerous lesions of the uterine cervix].

Human papillomaviruses (HPV) play an important role in cervical carcinogenesis but are probably not the only factors. To assess the role of HPV 6 and 11, of herpes simplex virus (HSV) and of cytomegalovirus (CMV) as cofactors for HPV 16 and HPV 18, we used polymerase chain reaction (PCR). The genomes of these six viruses was searched for in cervical biopsies, inbred in paraffin, from 22 normal cervices, 21 low grade cervical intraepithelial neoplasia (CIN), 21 high grade CIN and 20 squamous cancers. HPV 16 DNA had the highest prevalence in cervical lesions. Its frequency reached 24% in low grade CIN, 57% in high grade CIN, 50% in cancers and 9% in normal cervices. The simultaneous presence of HPV 16 and/or HPV 18 DNA and CMV and/or HSV DNA was significantly more frequent in high grade CIN and cancers than in normal cervices. On the other hand the presence of HPV 16 and/or HPV 18 DNA in samples lacking the other viral genomes did not significantly differ between the groups. Consequently the disease-viral infection relation was not apparent when these two "potentially oncogenic" HPV are isolated without coinfection by HSV or CMV. Our results are in agreement with the hypothesis of the role of herpesviruses as cofactors in cervical carcinogenesis. These viruses may disturb the control mechanisms of cellular growth and differentiation in HPV infected cells.

Adult

[Rhabdomyosarcoma: differential diagnosis of cutaneous tumors in childhood].

Primary rhabdomyosarcoma can arise in the skin, but there are few reports on this common childhood malignancy in the dermatological literature. We report on a male infant with a cutaneous tumour growing on the right nasal bridge since his 10th week of life. Clinically the tumour mimicked pilomatrixoma. Histological and immunohistological examination of the skin tumour and of subsequent lymph node metastases revealed rhabdomyosarcoma of the alveolar growth pattern. Our patient died at the age of 4 years of disseminated organ metastases.

Biomarkers, Tumor

Acute myelogenous leukaemia in children under 2 years--experiences of the West German AML studies BFM-78, -83 and -87. AML-BFM Study Group.

Clinical, morphological, immunological, cytogenetical and prognostic features of 84 children under 2 years of age with AML in studies AML-BFM-78, -83 and -87 were retrospectively analysed. There was a high incidence of acute monoblastic leukaemia (FAB M5) (41 patients--49%) and acute megakaryoblastic leukaemia (FAB M7) (study AML-BFM-87: five patients--13%) in this age group. Acute monoblastic leukaemia was associated with hepatosplenomegaly, extramedullary organ manifestations and chromosomal abnormalities involving 11q23. The probability of an 11-year event-free survival of all patients under 2 years of the three studies combined was 39% (SD 6%). While the event-free survival rates of patients aged 2 years and older could be improved in studies AML-BFM-83 and -87 compared with study AML-BFM-78, overall prognosis in children under 2 years in the three consecutive studies remained unchanged. The event-free survival rate of children with acute monoblastic leukaemia in both age groups was comparable (7 yr-EFS (AML-BFM-83 and -87): much less than 2 years--43% (SD 9%), =/much greater than 2 years--33% (SD 9%); P much greater than 0.5). This also applied to other risk groups. In conclusion, taking the high incidence of acute monoblastic and megakaryoblastic leukaemia in children under 2 years into account, no significant differences between children under 2 years or older children concerning response to therapy and overall prognosis could be evaluated.

Antineoplastic Combined Chemotherapy Protocols

HIV detection in culture of peripheral blood mononuclear cells: a relevant in vitro correlate of the antiviral effect of ZDV in vivo.

To better assess the antiviral effect of zidovudine (ZDV) in vivo and understand its limitations, we have studied human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cell (PBMC) cultures from 25 ZDV-treated patients and 20 untreated controls. Three months after initiation of therapy, 9 of the 25 treated cases became negative for HIV isolation (36%). Untreated cases never converted to a negative culture. In patients treated by ZDV and who remained culture positive, the kinetics of HIV replication in PBMC culture was found to vary with time. A statistically significant delay in the production of HIV in PBMC cultures from treated cases could be demonstrated after 3 months of ZDV therapy, when compared with untreated patients. By contrast, in such untreated patients the time required to reach the peak of reverse transcriptase activity in culture decreased during the follow-up period. These changes of in vitro HIV replication kinetics as well as the change to negative culture during ZDV therapy probably reflected the reduction of the number of infected cells in vivo. These results as well as the decrease of p24 antigenemia do indicate that ZDV indeed inhibits HIV replication in vivo. However, the effect of ZDV on HIV replication kinetics in PBMC fails to reach significance at 6 months, suggesting that the antiviral effect of ZDV may decrease over time. Our results suggest that ZDV is most effective when the intensity of HIV replication in vivo is still low.

Cells, Cultured

Redesigned nursing practice: a case management model for critical care.

Changes within the health care system necessitate changes in nursing practice. Given the financial environment and the need to balance the cost/quality equation, case management will become increasingly important and has the potential to become the predominant care delivery system of the 1990s. This transition represents a tremendous opportunity for nursing. The CCM role offers many potential advantages and benefits for individual nurses and the profession as a whole. Nurses practicing as case managers have the opportunity to function in a highly professional, independent manner with a great deal of interdisciplinary collaboration. In addition to the challenges and satisfactions of the work itself, the nurse case manager may also enjoy a higher salary and more scheduling control and flexibility. The broader advantages of case management include its benefits to patients and institutions and its fit with current trends in the health care environment. Nurse case managers manage hospital systems to produce optimal clinical outcomes for patients in the shortest time using as few resources as possible. This approach to care delivery places nurses in a position to demonstrate the tremendous contribution they can make to achieving the institution's goal of delivering high-quality, cost-effective care. Thus, case management fits extremely well with current trends in health care financing and outcome measurement. The model described in this article illustrates one approach to implementing these important concepts in a critical care setting.

Clinical Protocols

Treatment results of three consecutive German childhood AML trials: BFM-78, -83, and -87. AML-BFM-Group.

Acute myelogenous leukemia (AML) represents a heterogenous group of leukemias in adults as well as in children. The BFM group initiated 3 consecutive studies on the treatment of this disease. Between December 1978 and April 1991, 543 children under the age of 17 years entered the 3 consecutive multicenter studies, AML-BFM-78 (n = 151), AML-BFM-83 (n = 182), and the still ongoing study AML-BFM-87 (n = 210). The treatment strategy of BFM-78 consisted of an eight week induction/-consolidation regimen employing 7 different drugs together with cranial irradiation, followed by continuous maintenance for two years. The main alteration in the second study BFM-83 was the addition of an intensive 8-day ADE induction course (cytosine arabinoside, daunorubicin, etoposide). In the ongoing trial BFM-87 two courses of HD-ARA-C and etoposide are given after consolidation. CR rates were 80% in trials I and II, and 78% in trial III. The probability of a 4.5-year event-free survival was 35%, SD 4% in study I; 49%, SD 4% in study II, and 45%, SD 4% in study III. The probability of a 4.5-year event-free interval (EFI) was increased from 45%, SD 5% in study I to 61%, SD 4% in study II, it is in the same range in study III (58%, SD 5%). Seven of 10 children which underwent bone marrow transplantation (BMT) in 1. CR are still in first CR after a maximum follow-up time of 3.5 yrs. In summary, the addition of HD-ARA-C together with etoposide given after induction/consolidation treatment did not further reduce the incidence of relapses in childhood AML. So far, the results of study BFM-87 are in the same range than those of study BFM-83.

Adolescent

Urinary excretion of the enantiomers of ifosfamide and its inactive metabolites in children.

The precondition for the antineoplastic effect of ifosfamide (ifo) is the oxidation of the oxazaphosphorine ring system, which contains a chiral centre at the phosphorous atom. This "ring oxidation" leads to the formation of alkylating mustard via several steps. A second metabolic pathway produces the cytostatically inactive metabolites 2- and 3-dechloroethyl-ifosfamide (2-d- and 3-d-ifo). The urinary excretion of the optical isomers of unmetabolised ifo and of 2- and 3-d-ifo, which represents the amount of ifo that has not been activated, was investigated by capillary gas chromatography for 18 treatment cycles in 14 children on various therapeutic schedules. The total cumulative excretion in 12 completely sampled cycles ranged from 27% to 50% of the ifo dose. Between 14% and 34% of the dose could be detected as ifo; 9% to 29%, as 3-d-ifo; and 2% to 8%, as 2-d-ifo. At 24 h after the end of therapy, excretion was nearly complete. Without exception, slightly more R-ifo (53%-61%) than S-ifo was excreted. S-2-d-ifo (50%-73%) was the main 2-d-metabolite. S-3-d-ifo (deriving from R-ifo) predominated in 6 of 14 children and R-3-d-ifo, in 8. Enantiomer-specific excretion increased after the end of infusion (up to 73% for R-ifo and 27% for S-ifo). We demonstrated stereospecific metabolism of ifo in children, with two different patterns of side-chain oxidation being observed. There was no evidence of important stereospecific ring oxidation in most children. A benefit should not be expected from the therapeutic application of pure enantiomers.

Adolescent

Plasma viraemia as a marker of viral replication in HIV-infected individuals.

Two hundred and twenty-eight blood samples from 154 HIV-seropositive subjects were investigated for the presence of HIV in peripheral blood mononuclear cells (PBMC) and plasma (without prior ultracentrifugation or filtration), using normal PBMC as the target for replication. HIV was recovered from PBMC and plasma in 80.5 and 19.5% of the patients, respectively. Plasma viraemia was significantly associated with clinical manifestations of HIV infection, indicating that HIV replication increased as disease progressed. This was confirmed by the statistically significant correlations between plasma viraemia and low CD4 cell counts (P less than 0.01) and low anti-p24 antibody titers (P less than 0.01). On patient follow-up, detection of HIV in plasma was transient. p24 antigenaemia was only detected in 13.6% of cases and was also associated with advanced clinical stages of the disease. When HIV RNA detection by polymerase chain reaction (PCR) was compared with plasma viraemia, HIV RNA was detected in plasma in all symptomatic cases and in 53.8% (seven out of 13) of asymptomatic patients [Centers for Disease Control (CDC) stages II and III], confirming that PCR was far more sensitive than plasma culture. These results indicate that cell-free virus production is associated with the clinical stage of HIV infection and may serve as a marker for disease progression. Detection of HIV RNA by PCR appears to be the most sensitive method to detect viraemia.

AIDS-Related Complex