Treatment trial with recombinant human erythropoietin in children with congenital hypoplastic anemia.
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Biomedical subjects
Publications and source records attributed to A Jobke.
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An intensive 7-day combination chemotherapy protocol was designed to reinduce children with early bone marrow relapse of acute lymphoblastic leukemia (less than 6 months after the end of or during preceding treatment). This aggressive approach seemed to be justified for a group of patients who were at the highest risk for ultimate treatment failure. In all, 38 children were enrolled for study. The ratio of male (median age, 10 years) to female (median age, 13 years) subjects was 27:11. Thirty patients were treated for their first relapse and eight for their second or subsequent relapse. Isolated bone marrow involvement was present in 24 cases. All patients had received heavy pretreatment including anthracyclines with cumulative doses of between 120 and 240 mg/m2. 22 of these patients, achieved complete remission, ten did not respond to therapy, and six died from the toxicity of the protocol. Cardiac failure was the cause of death in one child (after additional radiotherapy for a mediastinal mass). No further clinical manifestation of cardiomyopathy could be observed. The other five patients died from hemorrhages or infectious complications. The main side effects were fever, gastrointestinal problems, stomatitis, and severe bone marrow aplasia lasting for about 2 weeks with nadirs of platelets and white blood count around days 10-14. The remission rate of 60% was acceptable, though not satisfactory. Only four children survived disease-free for 13+, 14+, 20+, and 22+ months after diagnosis of relapse.
During l-Asparaginase (l-Asp) treatment the development of specific antibodies of IgG isotype is frequently observed. In most instances elevated IgG antibodies to l-Asp activate the complement system and induce allergic reactions following l-Asp infusion. However, in some cases no adverse reactions and no activation of complement are noticed, despite the presence of elevated anti-l-Asp levels. We studied the development of specific IgG antibodies to l-Asp in different subclasses in 12 children who had produced high levels of specific IgG. Results showed that all patients had elevated levels of IgG1. In 5 cases we were able to demonstrate the development of specific IgG3 antibodies and in 1 case of IgG4 antibody. Patients with high levels of IgG3 (above 100 AU) had the highest risk for subsequent anaphylaxis. Thus, subclass-specific determination of antibodies to l-Asparaginase might improve the estimation of the risk of anaphylaxis prior to 1-Asp infusions.
2 boys aged 4 and 6 1/2 years and a 1 1/2-year-old girl in whom persistent EBV-infections developed are described. Serological investigations showed a markedly increased IgG-antibody titer against the virus-capsid antigen (VCA-IgG). Furthermore there was a persistence of anti-early-antigen-antibodies (anti-EA-antibodies) resp. VCA-IgA indicating a chronic infection. The observation period was 1 to 4 years. Cellular immunity in these children was depressed. They show the typical clinical symptoms of infectious mononucleosis; additionally they often suffer from other infectious diseases.
Two children aged 3 and 11 years are described in whom a combined autoimmune neutro-and thrombocytopenia developed in association with pronounced cell-membrane bound IgG. These latter antibodies were detected by the unlabelled immunoperoxidase (PAP) method. Prednisone therapy proved to be beneficial.
A 3-year-old child presented with vague abdominal pain, fever, leucocytosis and elevation of alkaline phosphatase. Ultrasonography revealed a space occupying process within the extrahepatic bile ducts surrounded by fluid. Various densities (between 15-25 Hounsfield units) were measured in this intrabiliary tumor by computed tomography.
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In a cooperative adjuvant chemotherapy study of osteosarcoma (COSS-80), 192 patients were registered from December 1979 to March 1982. Forty-one patients have been excluded from study because of their nonadjuvant situation, therapy-limiting clinical conditions, or inadequate diagnosis. One hundred and fifty-one patients have been randomized to receive either the drug combination bleomycin + cyclophosphamide + dactinomycin (BCD) or cisplatinum (CPL) within a course of sequential multidrug chemotherapy including adriamycin (ADR) and high dose methotrexate (HDMTX). After exclusion of 51 patients with some deviation in history and/or management 100 selected patients were randomized once more to receive in addition or not fibroblast interferon after preoperative chemotherapy and surgical removal of the primary tumor. Patients were stratified for age and sex and for site and extension of tumor as well in both randomizations. Median follow up is now 12 (1-16) months. The expected 2-year disease free survival (DFS) rate of the total doubly randomized group is 78% and of the single randomized group 76%. No difference could be discerned between recombined groups receiving BCD vs CPL or interferon vs no interferon. The effect of preoperative chemotherapy on the tumor was evaluated clinically and by histopathologic grading; 66/85 (78%) patients were judged clinically as responders with pathohistologic verification of this finding in 71% of these cases. No adverse effect arose from delaying definite surgery for preoperative chemotherapy, but initial application of chemotherapy as well as planning, preparing, and performing of the surgical procedure have been facilitated. The majority of patients received some kind of limb-salvage treatment without local recurrences so far. A statistically insignificant but intriguing tendency for a slightly higher incidence of pulmonary metastases after resection as opposed to amputation could be detected. Similar to observations in the previous study COSS-77.
A cervical lymph node enlarged since 3 weeks was to be removed in a 12-year-old boy, whose only complaint was slight fatigue. Routine screening revealed hypercalcemia of 7.3-8.1 mval/l. This rose to 9.2 mval/l despite furosemide-induced high fluid turnover and prednisone while diagnostic evaluation proceeded. Serum phosphate was low consistently. Malignancy, vitamin D-intoxication, immobilisation and familial conditions could be ruled out as causes. Highly elevated serum-parathormone levels inspite of hypercalcemia, and ultrasonography of the neck were the most helpful evidence of a parathyroid adenoma. Calcitonin was effective in lowering serum-calcium to 6-7 mval/l preoperatively.
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The increasing importance of radiotherapy in tumor of childhood demands the investigation and consideration of the psychological aspects of this afflicting therapy. In this paper the results obtained by questioning and observing 28 children of different ages, their parents, attendants and employees of several radiological departments are discussed. As the children's fantasies and the resulting anxieties and reactions are depending on the respective intellectual and emotional developmental stage detailed proposals concerning the preparation and performance of radiation in toddlers, school children and adolescents are presented.
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Among twelve patients with homozygous alpha1-antitrypsin deficiency (Pi-type Z), five cases of infantile liver disease were diagnosed. The course of the disease was extremely variable; only one patient died of liver cirrhosis at the age of fourteen. In four cases the clinical, biochemical and histological (2 cases) findings became normal over a follow-up period of one to fifteen years. The results of these observations demonstrate that in alpha1-antitrypsin deficiency even when associated with proven liver disease the prognosis need not be unfavorable.
Rabbit splenic capsular strips contract in response to angiotensin II and simultaneously release prostaglandins E and F into the bath fluid. Contractions, though not sustained, and prostaglandin release are dependent on the concentrations of angiotensin II. Addition of indometacin to the bath fluid inhibits prostaglandin release and potentiates the angiotensin II-induced contractions. Similarly, 5,8,11,14-eicosatetraynoic acid, another blocker of prostaglandin synthesis, potentiates contractions elicited by angiotensin II. Exogenous prostaglandin E1 (300 ng/ml) tends to decrease angiotensin II-induced contractions, while prostaglandin E2 (300 ng/ml) as well as prostaglandin F2alpha (300 ng/ml) significantly increase the contractions produced by angiotensin II. The prostaglandin endoperoxide analogues (15S)-hydroxy-9alpha,11alpha-(epoxymethano)prosta-5Z,13 E-dienoic acid and (15S)-hydroxy-11alpha,9alpha-(epoxymethano)-prosta-5Z,13 E-dienoic acid in concentrations of 300 ng/ml are either without effect or weak smooth muscle stimulants of their own, but do not influence the effect of angiotensin II. By the simultaneous use of sensitive and specific radioimmunoassays for prostaglandins E1 and E2 the prostaglandin E-like substance released by the rabbit splenic capsular strips was found to resemble serologically much more the dienoic prostaglandin E2 than prostaglandin E1. The potentation of the effect of angiotensin II by indometacin and 5,8,11,14-eicosatetraynoic acid might be caused by inhibition of synthesis of prostaglandins or related compounds in the splenic tissue. However, an undefined sensitizing effect of indometacin and 5,8,11,14-eicosatetraynoic acid, not related to their effect on prostaglandin synthetase, on the smooth muscle preparation cannot be excluded.
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Increasing concentrations of angiotensin I and different perfusion rates were used to study the conversion of angiotensin I in guinea-pig and rat lungs. Even the highest concentration used (32.0 muM), which is a thousand times higher than that which occurs in vivo, was unable to saturate the converting system indicating the enormous capacity of this system. SQ 20881 proved to be a reversible inhibitor of the converting system. Its effect on the angiotensin I conversion was greater in guinea-pig lungs than in rat lungs (ID50 was 40.0 nM in guinea-pig lung and above 360.0 nM in rat lungs at a substrate concentration of 38.6 nM).