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Biomedical subjects

T T Salmi

Publications and source records attributed to T T Salmi.

At least 19 recordsLinked to original sources

Recovery of blood B-lymphocytes and serum immunoglobulins after chemotherapy for childhood acute lymphoblastic leukemia.

Recovery of humoral immunity after cessation of chemotherapy for childhood acute lymphoblastic leukemia (ALL) was investigated by determining blood leukocyte, lymphocyte and B-lymphocyte, and serum immunoglobulin (Ig) levels and IgG subclasses at 0, 1, 3, 6, 9, and 12 months after cessation of chemotherapy for ALL in 14 patients. Blood B-lymphocytes were analyzed with the use of flow cytometry and monoclonal CD20 antibody. At cessation of chemotherapy, the amount of blood B-lymphocytes was subnormal in most patients but increased to normal levels in 1 month after therapy was discontinued. The recovery of serum Ig, which reflect B-cell function, was slower, but occurred by 6 months after therapy was discontinued in most patients. The authors conclude that by 6 months after cessation of chemotherapy for ALL, a sufficiently functioning immune system by these parameters is established and that prophylactic antibiotics can be withdrawn and immunizations started.

Adolescent

Wolman disease: morphological, clinical and genetic studies on the first Scandinavian cases.

On the Aland Islands, a 1-month-old girl was diagnosed as having Wolman disease. The diagnosis was confirmed neurochemically; a decreased activity of acid lipase was noted in the proband and her parents had typical carrier values. This is the first Scandinavian case reported. The skin biopsy revealed cytoplasmic accumulations identical to those noted in two sibs who highly probably had Wolman disease during the 1950s. Both these sibs died at the age of about 3 months and presented a heavy accumulation of lipid material in lymph nodes, spleen, adrenal glands, liver, gut, and also some pathological alterations in other organs. Electron microscopic findings from deparaffinized samples showed cytoplasmic accumulation of lipid material similar to that noted in Wolman disease. Genealogical analyses revealed that the index families had ancestors from the same restricted area and also common ancestors during the 17th century. The parents of the two affected sibs were born on a small island and were related in many different ways. On the basis of genealogical studies and other genetic investigations performed, the importance of founder and drift effect for manifestations of rare hereditary disorder in isolates is stressed.

Consanguinity

Superior treatment results in females with high-risk acute lymphoblastic leukemia in childhood.

In this population-based study, 808 children aged 1-15 years from Denmark, Finland, Iceland, Norway and Sweden, were diagnosed between July 1981 and June 1986 as suffering from non-B-cell acute lymphoblastic leukemia (ALL). The total population was 4.5 million children. Remission was achieved in 770/808 of the patients (95%). No sex difference in the remission rate was observed. The event free survival (EFS) at 102 months was 0.47 for males and 0.62 for females (p less than 0.001). There was no difference in EFS between males and females with standard-risk (0.58 and 0.60) or intermediate-risk (0.47 and 0.60) ALL, respectively. The EFS for females with high-risk ALL (0.68) was superior to that of males with high-risk ALL (0.31). Cox multivariant analysis showed that white blood cell count, sex, age and thrombocyte count were significant prognostic factors in all children. The intensified treatment according to the prognostic factors used in this study led to equal EFS for females with ALL from all risk groups. Males with high-risk ALL, however, did not benefit from the intensified treatment.

Age Factors

Expression of L-myc and N-myc proto-oncogenes in human leukemias and leukemia cell lines.

The myc proto-oncogenes encode nuclear phosphoproteins, which are believed to participate in the control of cell proliferation and differentiation. Deregulated expression of c-myc has been implicated in several human hematopoietic malignancies. We have studied the expression and mRNA processing of human L-myc, N-myc, and c-myc genes in a panel of human leukemias, leukemia cell lines, and normal hematopoietic cells. L-myc mRNA was expressed in three acute myeloid leukemias (AML) studied and in several myeloid leukemia cell lines. Only low expression levels were observed in adult bone marrow and in fetal spleen and thymus. The K562 and Dami leukemia cell lines showed a unique pattern of L-myc mRNA processing, with approximately 40% of L-myc mRNA lacking exon III and intron I. N-myc was expressed in five of six AML cases studied, in one of nine acute lymphocytic leukemia (ALL) cases, and in several leukemia cell lines, while c-myc mRNA was detected in all leukemias and leukemia cell lines studied. Coexpression of all three myc genes was observed in Dami and MOLT-4 cell lines and in two AMLs, and either L-myc or N-myc was coexpressed with c-myc in several other cases. These results show that in addition to c-myc, the L-myc and N-myc genes are expressed in some human leukemias and leukemia cell lines, and suggest a lack of mutually exclusive cross-regulation of the myc genes in human leukemia cells.

Blotting, Northern

Vincristine treatment of acute lymphoblastic leukemia induces transient autonomic cardioneuropathy.

Reduced respiratory sinus arrhythmia, measured as heart rate variability, is a reliable indicator of autonomic nervous dysfunction, reflecting a damage in vagal cardiac control. The authors studied the heart rate variability (HRV) of nine children treated for acute lymphoblastic leukemia during the different phases of cytostatic treatment utilizing heart rate processing techniques with a computer. The indices of HRV as well as the spectral components of heart rate were examined with special relation to vincristine administration. The heart rate variability was significantly reduced during the vincristine induction phases as compared to the consolidation and maintenance phases without vincristine administration. In particular, the respiratory components of the HRV during deep breathing tests were significantly reduced during vincristine treatment. The authors conclude that the measurement of the HRV is a suitable method for monitoring transient autonomic neuropathy, which these results show to be a frequent complication of vincristine treatment.

Adolescent

Radio-iodobenzylguanidine scintigraphy of neuroblastoma: conflicting results, when compared with standard investigations.

Seventy-one patients with neuroblastoma (NB) and 25 patients with other neoplastic or nonneoplastic diseases were studied with MIBG scintigraphy. Sensitivity and specificity at diagnosis were 94% and 88%, respectively. Of 52 patients with NB studied during follow-up, 14 had on one or several occasions conflicting results, when the findings at MIBG scintigraphy were compared to standard investigations (SI: CT scan, bone scan, x-ray, and ultrasound). The correlation of MIBG scintigraphy and SI to clinical outcome were in these 14 patients not significantly different. Adding VMA-excretion measurements did not significantly improve the predictive value of MIBG scintigraphy or SI. Patients with tumor-suspected lesions only at MIBG scintigraphy should be followed closely and the nature of the lesions should be explored through biopsy.

3-Iodobenzylguanidine

The N-myc proto-oncogene and IGF-II growth factor mRNAs are expressed by distinct cells in human fetal kidney and brain.

We studied the expression of the N-myc proto-oncogene and the insulin-like growth factor-II (IGF-II) gene in human fetuses of 16-19 gestational wk. Both genes have specific roles in the growth and differentiation of embryonic tissues, such as the kidney and neural tissue. Since continued expression of N-myc and IGF-II mRNAs is also a characteristic feature of Wilms' tumor, a childhood neoplasm of probable fetal kidney origin, we were particularly interested in the possibility that their expression might be linked or coordinately regulated in the developing kidney. Expression of N-myc mRNA was observed in the brain and in the kidney by Northern hybridization analysis. In in situ hybridization of the kidney, N-myc autoradiographic grains were primarily located over epithelially differentiating mesenchyme while most of the mesenchymal stromal cells showed only a background signal with the N-myc probe. N-myc mRNA was detectable throughout the developing brain with a slight accentuation in the intermediate zone cells in between the subependymal and cortical layers. Thus, even postmitotic neuroepithelial cells of the fetal cerebrum expressed N-myc mRNA. In Northern hybridization, IGF-II mRNA signal was abundant in the kidney but much weaker, though definite, in the brain. The regional distribution of IGF-II mRNA in the kidney was largely complementary to that of N-myc. IGF-II autoradiographic grains were located predominantly over the stromal and blastemal cells with a relative lack of hybridization over the epithelial structures. In the brain, IGF-II mRNA was about two- to threefold more abundant in the subependymal and intermediate layers than in the cortical plate and ependymal zone, respectively. The fetal expression patterns of the N-myc and IGF-II mRNAs are reflected by the types of tumors known to express the corresponding genes during postnatal life such as Wilms' tumor. However, the apparent coexpression of the IGF-II and N-myc genes in immature kidneys occurs largely in distinct cell types.

Autoradiography

A population-based study of children with standard risk acute lymphoblastic leukemia in the five Nordic countries. A follow-up of 230 patients.

Two hundred and thirty children with standard risk acute lymphoblastic leukemia (ALL) were diagnosed during a period of 3 years from July 1, 1981 to June 30, 1984 in the five Nordic countries. Criteria for standard risk ALL were age above 2.0 and below 10 years, WBC less than or equal to 20 x 10(9)/l, no evidence of CNS-involvement, mediastinal mass or T- or B-cell leukemia. The children were treated without prophylactic CNS irradiation, the majority (200 patients) according to two treatment programs. Follow-up of the entire group after a minimum of 30 months showed 64% of the children living in complete continuous remission with a probability of event-free survival of 0.60. The treatment results are not entirely satisfactory and intensification of therapy is required. A subgroup of patients with WBC between 10 and 20 x 10(9)/l and with adverse prognosis was identified, justifying a change of the present criteria for risk grouping.

Adolescent

Luminol-enhanced chemiluminescence of peripheral blood leukocytes as an early indicator of graft take after allogeneic bone marrow transplantation in patients with acute myelogenous leukaemia.

The luminol-enhanced chemiluminescence (CL) of peripheral blood leukocytes was studied daily in five patients with acute myelogenous leukaemia (AML) in first remission, who were undergoing allogeneic bone marrow transplantation (BMT). The CL was measured after stimulation of leukocytes with opsonized zymosan in highly diluted whole blood. All patients had an undetectable CL level on day +7, post BMT, simultaneously with severe pancytopenia caused by the pre-conditioning for BMT. Subsequently, CL started to rise, reaching the maximum level, twice that of healthy controls, on day +11. This preceded the rise of blood leukocytes above 1.0 x 10(9) l.-1 and that of neutrophils above 0.5 x 10(9) l.-1 by 3-14 days, but coincided with the appearance of large unstained cells (LUC; a parameter given by a Technicon H 6000 blood analyzer). One of the patients later had a transient decline of CL. This preceded the fall in white blood count and platelets by 7 days, suggesting marrow suppression. We conclude that in AML the measurement of leukocyte CL is a more sensitive test for prediction of graft take than the conventional blood counts.

Blood Cell Count

Vaccination of children during treatment for leukemia.

Forty-one children receiving maintenance treatment for leukemia were vaccinated with inactivated mumps virus, meningococcal polysaccharide groups A and C and polyvalent pneumococcal polysaccharide vaccines. Antibodies against pneumococcal types 3, 18C, 19F and 23F and against meningococcal groups A and C were measured by radioimmunoassay. Mumps antibodies were determined by complement fixation, hemolysis-in-gel and enzyme-linked immunosorbent assays. The antibody responses tended to be lower than those of healthy age-matched controls. The individual responses were unpredictable; the magnitude of the response correlated neither with the age nor sex of the patient, duration of the chemotherapy nor with the prevaccination antibody concentration. Nevertheless, most patients achieved and even exceeded the geometric mean of the antibody concentrations of the healthy children, considered protective against infection.

Acute Disease

Measles vaccination after exposure to natural measles.

When an extensive measles epidemic broke out in Turku in late 1975, the availability of a previous study on measles vaccination reactions in 442 children permitted a comparative evaluation to be made on reactions to and the efficacy of measles vaccine (Schwartz strain) administered after exposure to natural measles. In a preliminary study, nine children were vaccinated one to 14 days after exposure to natural measles but before prodromal symptoms appeared. Only one of these nine children developed symptoms and signs comparable to those of the natural disease. In five day-care centers the children were vaccinated when five or more children out of 30 to 40 at each center had measles. In only five of 74 exposed children were the signs and symptoms comparable to those of natural measles. No marked differences in signs and symptoms after the vaccinations were observed between the exposed and nonexposed children. It is concluded that vaccination is safe, can usually prevent measles, even when administered after a prolonged interval following exposure to natural disease, and can usually control an epidemic in progress.

Adolescent

Central nervous system involvement in patients with rotavirus gastroenteritis.

Two children with rotavirus gastroenteritis are presented. The first case developed a fatal Reye's syndrome and the other one encephalitis with slow recovery. The rotavirus diagnosis was made in both cases by electron microscopy and a significant rise in antibody titres to Nebraska calf diarrhea virus was seen in one of the two patients.

Antibodies, Viral

[Vaccinations].

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Child Health Services

[Kawasaki disease].

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Child, Preschool

[Acidocillin concentration in middle ear exudate].

Acidocillin levels were determined in the middle ear exudates and serum of patients with acute exudative otitis media after oral administration of the drug. Acidocillin rapidly diffused exudate into the ear and its level in the exudate in 1 hour was 0-1.7 gamma/ml. At the same time the serum levels ranges within 4 to 25 gamma/ml. acidocillin remained longer in the ear exudate than in the serum. In 12 hours 0.2 to 1.3 gamma/ml of acidocillin was still found in the exudates, while there was no antibiotic in the serum.

Adolescent