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Biomedical subjects

U M Saarinen

Publications and source records attributed to U M Saarinen.

At least 19 recordsLinked to original sources

Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old.

Atopic diseases constitute a common health problem. For infants at hereditary risk, prophylaxis of atopy has been sought in elimination diets and other preventive measures. We followed up healthy infants during their first year, and then at ages 1, 3, 5, 10, and 17 years to determine the effect on atopic disease of breastfeeding. Of the initial 236 infants, 150 completed the follow-up, which included history taking, physical examination, and laboratory tests for allergy. The subjects were divided into three groups: prolonged (> 6 months), intermediate (1-6 months), and short or no (< 1 month) breastfeeding. The prevalence of manifest atopy throughout follow-up was highest in the group who had little or no breastfeeding (p < 0.05, analysis of variance and covariance with repeated measures [ANOVA]). Prevalence of eczema at ages 1 and 3 years was lowest (p = 0.03, ANOVA) in the prolonged breastfeeding group, prevalence of food allergy was highest in the little or no groups (p = 0.02, ANOVA) at 1-3 years, and respiratory allergy was also most prevalent in the latter group (p = 0.01, ANOVA) having risen to 65% at 17 years of age. Prevalences in the prolonged, intermediate, and little or no groups at age 17 were 42 (95% CI 31-52)%, 36 (28-44)%, and 65 (56-74)% (p = 0.02, trend test) for atopy, respectively, and 8 (6-10)%, 23 (21-25)%, and 54 (52-56)% (p = 0.0001, trend test) for substantial atopy. We conclude that breastfeeding is prophylactic against atopic disease--including atopic eczema, food allergy, and respiratory allergy--throughout childhood and adolescence.

Adolescent

Reemphasis on leukocyte transfusions: induction of myeloid marrow recovery in critically ill neutropenic children with cancer.

Neutropenia is the major factor predisposing to sepsis in cancer patients, and its duration is important for survival. We administered leukocyte transfusions (LT) to 10 children suffering from documented life-threatening infections during profound, prolonged neutropenia. Nine had acute leukemia, and one had aplastic anemia; three were bone marrow transplant recipients. These 10 were the only patients in our unit who received LT during the past 7 years. The median leukocyte dose was 0.6 x 10(9)/kg in total. Instead of leukapheresis products, we used pooled buffy coats from random donors, with a high relative content of lymphocytes and especially T lymphocytes. The leukocyte concentrates were irradiated with 15 Gy. In all 10 patients, we observed prompt and sustained myeloid marrow recovery following LT. Such an effect of LT has never been described before. We hypothesize that in the internal milieu of these aplastic patients the transfused leukocytes were stimulated to secrete cytokines, the result being a cascade-like phenomenon and stimulation and proliferation of the patient's own bone marrow cells. The bone marrow-stimulating effect of LT merits further study.

Acute Disease

Allogeneic bone marrow transplantation in children: single institution experience from 1974 to 1992.

At the Children's Hospital, University of Helsinki, Finland, bone marrow transplantations have been performed since 1974. Between 1974 and 1992, 62 children received allogeneic bone marrow grafts. Median patient age was 9.3 years. Thirty-two patients had ALL, 13 AML and 11 had severe aplastic anemia (SAA). Graft failure occurred in 4 of the 62 patients. The overall long-term survival rate was 47%. Relapse of leukemia was the most common cause of death, especially in patients with ALL transplanted in second or later remission. Deaths during the first 2 months after transplant have decreased with time. In a small country such as Finland, it is important to centralize the experience of allogeneic BMTs, particularly for pediatric patients.

Anemia, Aplastic

Cardiopulmonary evaluation of exercise tolerance after chest irradiation and anticancer chemotherapy in children and adolescents.

OBJECTIVE: The aim of the study was to evaluate the cardiopulmonary exercise tolerance in children and adolescents after chest irradiation and anticancer chemotherapy. METHODS: We studied 30 subjectively asymptomatic patients aged 8 to 25 years treated for pediatric malignancies with chest irradiation (XRT) +/- chemotherapy. The median interval since XRT was 7 (range, 2 to 13) years. The median XRT dose for mediastinum and/or lungs was 2550 (range, 1000 to 5100) cGy. The median cumulative dose of anthracyclines was 250 (range, 0 to 480) mg/m2. Cardiac function and exercise tolerance were evaluated by electrocardiography, echocardiography, radionuclide cineangiography, and exercise test with gas exchange analysis. RESULTS: The patients differed from normal controls in systolic indices of myocardial function. In echocardiography, the left ventricular contractility was abnormal in 14/30 patients. In radionuclide cineangiography, the left ventricular ejection fraction was subnormal in 6/30 patients, and in 9/30 patients the rise in ejection fraction during exercise was inadequate (< 5%). In exercise testing, the mean (+/- SD) maximum workload attained was 2.7 (+/- 0.7) watts/kg, and the mean (+/- SD) maximum oxygen consumption was 35.4 (+/- 9.7) mL/min/kg. Both variables were < 80% of predicted values in 11 patients. CONCLUSIONS: XRT and anticancer chemotherapy very often lead to late cardiopulmonary toxicity and impaired exercise tolerance. Although in most cases this toxicity seemed to be mild and subclinical, the long-term clinical sequels merit further evaluation.

Adolescent

Recombinant human granulocyte-macrophage colony-stimulating factor in children with chemotherapy-induced neutropenia.

Twenty children 1-17 (median, 5.5) years of age received GM-CSF during chemotherapy-induced neutropenia at the dose of 5 micrograms/kg/day, continued until the absolute neutrophil count (ANC) exceeded 500 x 10(6)/liter. Twelve children with solid tumors received GM-CSF after courses of conventional chemotherapy (VP-16 + ifosfamide or "6 in 1"). One course followed by GM-CSF was compared to identical courses without GM-CSF in the same patients. Eight children with recurrent/poor risk malignancies received GM-CSF after marrow-ablative therapy and autologous bone marrow transplantation (ABMT). Their engraftment data were compared to matched historical controls. In both groups GM-CSF accelerated myeloid recovery, which was preceded by the appearance of immature myeloid elements in bone marrow. The ANC levels of 200, 500, and 1,000 x 10(6)/liter were exceeded 2, 3 (P < 0.05), and 6 (P < 0.005) days earlier with GM-CSF in the conventional chemotherapy group, and 6, 10 (P < 0.05), and 9 days earlier in the ABMT group, as compared to the controls. All adverse effects observed were mild, including skin rashes, nasal stuffiness, general achiness, nausea, and fever. We conclude that GM-CSF is well tolerated in children and accelerates myeloid recovery in chemotherapy-induced neutropenia.

Adolescent

Cytokine and acute-phase reactant levels in serum of children with cancer admitted for fever and neutropenia.

Serum concentrations of tumor necrosis factor-alpha (TNF alpha), interleukin (IL)-1 beta, IL-6, and the acute-phase reactants C-reactive protein (CRP) and serum amyloid A (SAA) were measured on admission in 46 neutropenic children with cancer in 81 episodes of fever. The aim was to find out whether any of these variables would differentiate true bacteremia from fever due to other causes. In most episodes serum concentrations of TNF alpha and IL-1 beta were elevated. IL-6 was detectable in 68%, but the serum concentration was elevated in only 15%. SAA proved to be more sensitive than CRP for the early detection of bacteremia. However, not even SAA was sufficiently accurate at the individual level. We conclude that the cytokine and acute-phase protein levels found were related to the febrile response but did not correlate with documented bacterial etiology.

Acute-Phase Proteins

Bone marrow fractionation by the haemonetics system: reduction of red cell mass before marrow freezing, with special reference to pediatric marrow volumes.

For purposes of freezing autologous marrow or transplants of allogeneic marrow with major ABO blood group incompatibility, 54 freshly harvested bone marrows from children of 7-65 kg of weight were depleted of their red cells with the Haemonetics V50 system. The marrow volumes ranged from 230 to 1,145 ml, with 17 small (200-399 ml), 18 intermediate (400-799 ml) and 19 large (800-1,200 ml) volumes. After processing, the median recoveries were: volume 24%, red cell mass 18%, and nucleated cells 75%. In the small marrow volume group, a good nucleated cell recovery was achieved at the expense of red cell depletion. The colony-forming units, granulocytes-macrophages (CFU-GM) were normal after thawing of processed, cryopreserved marrows, and good engraftment of both allogeneic and autologous marrows were achieved. We conclude that marrow processing with the Haemonetics V50 system results in adequate red cell depletion and good nucleated cell recovery without open-air contact of marrow or excessive time consumption. For small marrow volumes, however, the red cell depletion was suboptimal, and a bowl size smaller than 125 ml is desirable for pediatric use.

Adolescent

Cell-surface ganglioside GD2 in the immunohistochemical detection and differential diagnosis of neuroblastoma.

The expression of the disialoganglioside GD2 was analyzed in 67 solid tumors and normal tissues from children by using the GD2-specific murine monoclonal antibody 3A7 and the indirect immunoperoxidase method. GD2 was expressed in all of 28 neuroblastomas and was most abundant in stroma-poor tumors. In differentiating stroma-rich neuroblastomas, neuroblastic clusters, neurofibrils, and most ganglion-like cells were positive, whereas Schwann's-cell stroma did not express GD2. In ganglioneuromas, only a few ganglion-like cells showed GD2, whereas all other structures were negative. Scattered foci of ganglioside GD2 also were found in some non-neuronal tumors, such as rhabdomyosarcomas and osteosarcomas, but not in lymphomas, Askin tumors, or most Wilms' tumors. The monoclonal antibody 3A7 is a useful aid in the immunohistochemical diagnosis of neuroblastoma. In addition, the intense cell surface staining of neuroblastoma cells by this reagent makes it potentially useful for detecting residual neuroblastoma in bone marrow samples and lymph node biopsies.

Antibodies, Monoclonal

Recurrent disseminated retinoblastoma treated by high-dose chemotherapy, total body irradiation, and autologous bone marrow rescue.

A case of recurrent, disseminated retinoblastoma is presented. The primary intraocular tumor, a metastatic mass at recurrence, and the tumor cells infiltrating bone marrow were all positive for the anti-GD2 monoclonal antibody (Mab) 3A7. Indirect immunofluorescence using the monoclonal antibody 3A7 was an effective method of detecting residual disease in the marrow. After remission was achieved by conventional therapy, the patient underwent autologous bone marrow transplantation (ABMT). The preparative regimen consisted of VP-16, cisplatinum, high-dose melphalan, and total body irradiation. The autologous marrow inoculum was clean of tumor cells at the detection level of 1:10,000. The transplant course was uneventful, and the patient is well and disease-free 17 months after ABMT. We conclude that high-dose chemotherapy and total body irradiation in an ABMT setting is feasible and a potentially curative approach to disseminated retinoblastoma.

Antibodies, Monoclonal

Percutaneous needle biopsy preceding preoperative chemotherapy in the management of massive renal tumors in children.

While the National Wilms' Tumor Study (NWTS) Group in the United States puts an emphasis on accurate staging and histology before any therapy is given for Wilms' tumor, the International Society of Pediatric Oncology (SIOP) in Europe focuses on preoperative therapy and safer surgery. Our current approach combines the benefits of both policies in the management of massive renal tumors in children. In seven consecutive patients we first obtained a percutaneous posterior needle biopsy to obtain adequate tissue for histology, and proceeded with preoperative chemotherapy with vincristine and dactinomycin until tumor shrinkage was sufficient. Tumor removals were feasible and uneventful. At the time of operation, two tumors were found to be totally or almost totally necrotic. In the others, which still included viable tumor, the histology corresponded well to the needle biopsy findings. One case with unfavorable histology and one with rhabdoid sarcoma would have been missed and given suboptimal therapy without the primary needle biopsy. As possible biopsy-related complications, subcapsular intratumoral bleeding was recognized in two patients. We conclude that percutaneous posterior needle biopsy is safe and yields definite, detailed histology in massive renal tumors in children. Preoperative chemotherapy facilitates surgery in these patients.

Antineoplastic Combined Chemotherapy Protocols

Characteristics and outcome of acute infection with hepatitis B virus in children with cancer.

After an outbreak of hepatitis B virus (HBV) infection in a unit of pediatric oncology, the clinical outcome and HBV markers were followed in 1 child with chronic and 10 children with acute HBV infection for 12 months. Four children had acute hepatitis with jaundice whereas 7 of the infections were subclinical. Ten children had antecedent malignancies and 1 had aplastic anemia. Four patients died of causes unrelated to the hepatitis after periods of 2, 4, 8 and 10 months. All 3 children who were not immunosuppressed at the time of contracting the HBV infection quickly turned negative for hepatitis B surface antigen (HBsAg), whereas only 2 of 8 patients who were immunosuppressed by chemotherapy eventually became HBsAg-negative. The latter 8 patients were also hepatitis B e antigen (HBeAg)-positive. Two of them quickly cleared HBeAg, but 6 remained HBeAg-positive throughout the follow-up. In 6 of 9 patients HBsAg was also detected in saliva. These results suggest that children who are receiving anticancer chemotherapy have an increased risk of remaining HBeAg-positive and secreting HBsAg and possibly HBV in their saliva, which makes them particularly infective.

Acute Disease

High-dose thiotepa with autologous bone marrow rescue in pediatric solid tumors.

High-dose thiotepa was given as a single agent at a total dose of 1125 mg/m2 with autologous bone marrow rescue to nine patients with recurrent/refractory/poor risk pediatric malignancies (primitive neuroepithelial tumor (PNET), two; neuroblastoma, one; Wilms' tumor, one; osteosarcoma, one; Ewing's sarcoma one, Hodgkin's disease one, high-grade glioma, two). The response rate in these heavily pretreated patients was 71% (five out of seven evaluable patients) including two complete responses (Wilms', glioma), three partial responses (osteosarcoma, Ewing's sarcoma, Hodgkin's disease), and two with stable disease (PNET, glioma). The median duration of response was 2.5 months. The extramedullary toxicity was acceptable with symptoms mainly of skin and gastrointestinal tract. The data indicate that high-dose thiotepa is effective in several types of recurrent pediatric solid tumors, and merits further evaluation in combination regimens.

Adolescent

Skeletal muscle wasting and protein-energy malnutrition in children with a newly diagnosed acute leukemia.

The changes in skeletal muscle mass of 14 children with newly diagnosed acute leukemia were studied during the first 24 weeks of antileukemia therapy. A muscle index was calculated from the femoral quadriceps muscle thickness, measured by using an ultrasound method, and from the body surface area. Serum albumin concentration was used as a biochemical indicator of protein status. Some children had muscle wasting before diagnosis. The highest degree of muscle wasting developed by 4 to 6 weeks with an average of 27% decrease of the muscle index. Because of simultaneous increase of adipose tissue (average, 33% at 6 weeks and 37% at 12 weeks), the relative body weight or the limb circumferences did not decrease. Muscle mass recovery occurred within the next 6 months. Our data emphasize that changes in the relative body weight or limb circumferences do not reveal nutritional protein depletion and muscle wasting that occurs in children with newly diagnosed acute leukemia.

Adipose Tissue

Tumor necrosis factor in children with malignancies.

We measured serum tumor necrosis factor alpha (TNF) concentrations by a double-antibody radioimmunoassay method, with a detection level of 10 ng/liter, in 32 children with malignancies. Seventeen had acute lymphoblastic leukemia, 4 had acute nonlymphocytic leukemia, and 11 had solid tumors. At the diagnosis of malignant disease, 30 of the 32 patients had elevated serum TNF levels ranging up to 450 ng/liter. After complete remission status was achieved, 2-6 months from the diagnosis, the TNF levels were within the range of 130 healthy children who served as the reference group. Most of them had TNF levels below the detection limit. We consider the upper limit of normal to be 40 ng/liter. We conclude that elevated serum TNF concentration may be of potential significance in the diagnosis and follow-up of children with malignant diseases.

Adolescent

Effective prophylaxis against platelet refractoriness in multitransfused patients by use of leukocyte-free blood components.

Development of permanent platelet refractoriness is a major problem in multitransfused patients with diseases such as leukemia, aplastic anemia, or pediatric solid tumors. We tried to prevent alloimmunization in these patients by systematic use of leukocyte-free blood components with less than one million of contaminating leukocytes per unit of platelets or red cells. Our study group comprised 26 patients with a minimum of 10 platelet transfusions per patient. These patients were compared with a historical reference group of 21 patients who had received standard blood products. In the leukocyte-free group none developed platelet refractoriness, in contrast to the reference group where 11 of the 21 patients became refractory to random platelets. The median corrected platelet increment for random pooled platelets was significantly higher in the leukocyte-free group compared with the reference group. The increasing number of transfusions did not correlate with the development of platelet refractoriness; instead we propose that the lower limit of antigenic exposure is important. We conclude that systematic use of leukocyte-free blood components effectively prevents development of platelet refractoriness and contributes to optimal supportive care of children with cancer.

Blood Platelets

High-dose thiotepa with autologous bone marrow rescue in recurrent malignant oligodendroglioma: a case report.

High-dose thiotepa with autologous bone marrow rescue is a new and promising treatment modality in several kinds of solid tumors. We used this regimen in a pediatric patient who had the third recurrence of his malignant oligodendroglioma of brain that developed during '8 in 1' chemotherapy. We achieved complete response after a total dose of 1125 mg/m2 of intravenous thiotepa. Good penetration into the CNS renders thiotepa potentially useful for chemosensitive brain tumors, and one course of high-dose thiotepa can be administered with acceptable toxicity by utilizing autologous bone marrow rescue.

Bone Marrow Transplantation