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K Heinonen

Publications and source records attributed to K Heinonen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinically symptomatic central venous catheter-related deep venous thrombosis in newborns.

The objective of this study was to evaluate the incidence of clinically symptomatic central venous catheter (CVC)-related deep venous thrombosis (DVT) in newborns and small infants and to try to identify clinical and genetic risk factors for catheter-related DVT among children with thrombotic complications. CVC was inserted in 44 consecutive infants (age range 0-90 d) during the period January 1990 to December 1995 in the neonatal intensive care unit (NICU) of Kuopio University Hospital in Kuopio. The symptoms of DVT were: syndrome of superior vena cava in 2, swelling at the CVC puncture site in 6 and repeated CVC obstructions in 2. The formation of DVT was verified by venography. Children with DVT (n = 10) had 26 (10-365, in total 623) catheter days compared with 9 d (1-155, in total 591) in patients without DVT (n = 26) (p < 0.005). The median (range) number of days from catheter insertion to diagnosis of DVT was 19 (7-210). CVC had to be removed from 11 (25%) children due to various complications. There was no DVT-related mortality. A positive family history with thromboembolic episodes at a young age was found in 3 of 10 families with a child suffering CVC-related DVT. The levels of coagulation inhibitors were evaluated at the age of 9-69 mo in all 10 (23%) children with CVC-related DVT. We detected no deficiencies in protein S, protein C or antithrombin III. One child was heterozygous for the point mutation (R506Q) in the factor V gene known to cause activated protein C resistance (APCR). We conclude that newborns with CVC are at great risk of DVT and that the aetiology of DVT can rarely be identified via measurements of coagulation inhibitors.

Blood Coagulation Disorders↗
PubMed1999

Comparison between low- and standard-dose ACTH tests in premature infants at risk for chronic lung disease.

In order to find a sensitive method to evaluate adrenocortical function in premature infants, we compared low- (0.5 microg/1.73 m(2)) and standard-dose (250 microg/1.73 m(2)) adrenocorticotropin tests (LD- and SD-ACTH) in 12 very-low-birth-weight infants before and 2 days after the end of dexamethasone therapy (duration 9-14 days) for chronic lung disease. Basal serum cortisol levels were inappropriately low in several infants already before dexamethasone therapy (median 190, range 60-357 nmol/l). The 95% confidence intervals of mean serum cortisol levels at 20 min were equal in LD- and SD-ACTH, while at 60 min, the low-dose gave a clearly lower response than the standard-dose test. The LD-ACTH can be used in premature infants as in older children and adults, but the criteria for adrenocortical insufficiency need to be defined.

Adrenocorticotropic Hormone↗
PubMed1999

Comparative genomic hybridization and conventional cytogenetic analyses in childhood acute myeloid leukemia.

Comparative genomic hybridization (CGH) analysis was performed on bone marrow specimens from 19 children with acute myeloid leukemia (AML) at diagnosis. The results of CGH were compared to those of conventional cytogenetic analysis. The most common CGH aberrations were gains of whole chromosomes 6 and 8, both of which appeared three times. Two losses were seen twice; losses of whole chromosomes 7 and X. The CGH findings were concordant with the results of conventional karyotyping. CGH did not add new information to the karyotypes. Since no high-level amplification was found among the samples and standard karyotyping was highly successful, we do not advocate routine use of CGH in the diagnostic evaluation of childhood AML.

Acute Disease↗
PubMed1998

Effects of intrauterine growth retardation and prematurity on spirometric flow values and lung volumes at school age in twin pairs.

Lung volumes and pulmonary expiratory flow values were investigated in 67 children from multiple pregnancies (30 twins, one set of triplets, one set of quadruplets) at the age of 7-15 years. At birth, 30 of 67 children (44%) had intrauterine growth retardation (IUGR, birth weight <-2 SD or birth weight difference between twin-pairs >1.3 SD). The median gestational age was 35 weeks (range, 28-38 weeks), and the median birth weight was 2,050 g (800-3,150 g). Lung functions were measured with a heated pneumotachograph. Data were standardized using height-based reference equations. No differences were found in lung volumes between children with IUGR and those children who had normal birth weight. Gestational age did not correlate with either airway flow rates or lung volumes. Maximum mid-expiratory flow (FEF50) did not correlate with standardized birth weight or with gestational age. In discordant twin pairs, the IUGR twins had significantly lower FEF50 than their normal birth weight counterparts (p=0.03, Z=-2.13). In the whole study group (67 children), children with IUGR had significantly lower FEF50 than children with normal birth weight (p=0.04; CI, 0.3-19.9). We propose that IUGR has the most pronounced effect on the growth of airways, and no detectable influence on lung volumes. This study confirms the crucial effect of appropriate intrauterine growth on subsequent growth on pulmonary airways.

Birth Weight↗
PubMed1998

Clinical characteristics of patients with de novo acute myeloid leukaemia and isolated trisomy 11: a Cancer and Leukemia Group B study.

Isolated trisomy 11 is the third most common sole trisomy in de novo acute myeloid leukaemia (AML). However, only 49 cases have been published, and for only a fraction of these cases has full description of clinical and haematological features been provided. As a result, little is known about the clinical characteristics of de novo AML patients with solitary trisomy 11. We have identified 13 patients (0.9%) with isolated trisomy 11 among a total of 1496 consecutive adult patients successfully karyotyped as part of a prospective Cancer and Leukemia Group B (CALGB) cytogenetic study (CALGB 8461). Nine patients (69%) were over the age of 60 (range 29-73 years). Eight patients (62%) were diagnosed with AML of FAB M2 subtype, three patients (23%) had FAB M1 AML and one patient each had AML of FAB M0 and M7, respectively. Seven patients (54%) had high, >100 x 10(9)/l, platelet counts (median 102 x 10(9)/l; range 17-207 x 10(9)/l). All patients received CALGB induction therapy with standard doses of cytarabine and daunorubicin. Six patients (46%) achieved a complete remission (CR). The median CR duration was 17.5 months (range 8.7-49.8). Only one patient, who underwent bone marrow transplantation in first CR, continues in initial CR. The median survival was 14.3 months (range 0.5-50.7); only one patient survives. We conclude that de novo AML with isolated trisomy 11 is predominantly associated with older age, M2 and M1 FAB subtypes, high platelet count and few long-term disease-free survivals, although it is currently unknown whether isolated trisomy 11 constitutes an independent prognostic factor.

Adult↗
PubMed1998

Determinants of bone mineral density in prematurely born children aged 6-7 years.

The aim of this study was to assess the long-term effects of prematurity and growth during the first year on bone mineralization in prematurely born children. The study group consisted of 38 prematurely born Finnish children (17M, 21F) examined at the age of 6-7 y. After birth, all children were fed with banked human milk until discharge from hospital. Thereafter, 27 children were partially breastfed until the age of 5-7 months. Infants with gestational age (GA) < or = 33 weeks (n = 25) received calcium 45-50 mg/100 kcal, phosphorus 40-45 mg/100 kcal, vitamin A 1000 IU/d, vitamin C 2 mg/d and vitamin D 400 IU/d until 2.5 kg. Infants born > 33 weeks received only vitamin D 400 IU/d. Bone mineral density (BMD) and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry (DXA) of the lumbar spine (L2-L4) at 6-7 y of age. At examination, all children had normal height and weight. BMD values were within the confidence interval of the Finnish reference values. In regression analysis bone area, present weight, GA and weight at 1 y were the most significant factors explaining 77.1% of the variance of BMC. After adjusting for other independent variables the prematurely born children who were thinner at 1 y of age subsequently had higher BMC values when examined at the age of 6-7 y. This study shows that growth patterns during the first year of life have long-term effects on bone mineralization.

Absorptiometry, Photon↗
PubMed1998

Clinical relevance of Ureaplasma urealyticum colonization in preterm infants.

A cohort of 78 infants of gestational age less than 34 weeks was examined for Ureaplasma urealyticum colonization and neonatal morbidity. Ureaplasma urealyticum was cultured from nasopharyngeal, endotracheal and blood-culture samples. A child was considered as being colonized if any sample was positive. The children with perinatal U. urealyticum colonization (n = 11; 14%) differed from those with no colonization (n = 67) in two important aspects: (i) they had higher leucocyte counts on the first (18.6 vs 12.4 10(9)) and the second (29.0 vs 15.4 10(9)) days of life (p = 0.01, both days); and (ii) they more often needed high-frequency oscillatory ventilation (45% vs 13%, p = 0.02). This study showed that U. urealyticum colonization is associated with signs of the host defence response together with symptoms of respiratory tract involvement suggesting the pathogenicity of U. urealyticum in premature infants.

Exudates and Transudates↗
PubMed1998

DNA copy number changes in childhood acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVE: Comparative genomic hybridization (CGH) allows the study of DNA copy number changes in a single hybridization from tumor DNA without any cell culture. Three reports of childhood acute lymphoblastic leukemia (ALL) studied by CGH have been published so far, with somewhat discrepant results. In the present study we performed CGH analysis on 36 patients with childhood ALL. The results were compared to those reported earlier on 157 cases. DESIGN AND METHODS: DNA was extracted from bone marrow specimens from 36 patients with childhood ALL. The tumor and reference DNAs were labeled with fluorescein-isothiocyanate conjugated dCTP and dUTP, and Texas red-conjugated dCTP and dUTP. The hybridizations were analyzed using the ISIS digital image analysis system. RESULTS: The most commonly gained chromosomes were X (42%), 4 (31%), 6 (31%), 10 (36%), 14 (28%) and 18 (33%), and the most common losses were at 9p22-pter (6%) and 12p13-pter (14%). INTERPRETATION AND CONCLUSIONS: The pattern of gains of DNA sequences was very similar in the four reports, but the 9p and 12p deletions were observed only in the present study and one previous report. Our review of the results of 193 patients studied so far shows that the success rate using CGH was close to 100%, whereas cytogenetic analysis failed to reveal any information in 21 patients (11%). Furthermore, in 69 (36%) out of 193 patients CGH gave additional information to the banding analysis. CGH should, therefore, be used to supplement standard cytogenetics in the analysis of childhood ALL patients.

Adolescent↗
PubMed1997

Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study.

Following reports of childhood acute myeloid leukemia (AML) showing that patients with t(9; 11)(p22; q23) have a better prognosis than those with translocations between 11q23 and other chromosomes, we compared response to therapy and survival of 24 adult de novo AML patients with t(9; 11) with those of 23 patients with other 11q23 translocations [t(11q23)]. Apart from a higher proportion of French-American-British (FAB) M5 subtype in the t(9; 11) group (83% v 43%, P = .006), the patients with t(9; 11) did not differ significantly from patients with t(11q23) in terms of their presenting clinical or hematologic features. Patients with t(9; 11) more frequently had an extra chromosome(s) 8 or 8q as secondary abnormalities (46% v 9%, P = .008). All patients received standard cytarabine and daunorubicin induction therapy, and most of them also received cytarabine-based intensification treatment. Two patients, both with t(9; 11), underwent bone marrow transplantation (BMT) in first complete remission (CR). Nineteen patients (79%) with t(9; 11) and 13 (57%) with t(11q23) achieved a CR (P = .13). The clinical outcome of patients with t(9; 11) was significantly better: the median CR duration was 10.7 versus 8.9 months (P = .02), median event-free survival was 6.2 versus 2.2 months (P = .009), and median survival was 13.2 versus 7.7 months (P = .009). All patients with t(11q23) have died, whereas seven (29%) patients with t(9; 11) remain alive in first CR. Seven of eight patients with t(9; 11) who received postremission regimens with cytarabine at a dose of 100 (four patients) or 400 mg/m2 (2 patients) or who did not receive postremission therapy (2 patients) have relapsed. In contrast, 7 (64%) of 11 patients who received intensive postremission chemotherapy with high-dose cytarabine (at a dose 3 g/m2) (5 patients), or underwent BMT (2 patients) remain in continuous CR. We conclude that the outcome of adults with de novo AML and t(9; 11) is more favorable than that of adults with other 11q23 translocations; this is especially true for t(9; 11) patients who receive intensive postremission therapy.

Acute Disease↗
PubMed1997

Ultrasonic and magnetic resonance imaging of fetal sacrococcygeal teratoma.

OBJECTIVE: To evaluate ultrasonic and magnetic resonance imaging (MRI) and Doppler examination in fetal sacrococcygeal teratoma (SCT), in respect to the postnatal findings and histological type of the tumor. STUDY DESIGN: Nine pregnancies complicated by histologically mature fetal sacrococcygeal teratoma in four cases and by immature/malignant teratoma in five cases. Transabdominal ultrasonic imaging and Doppler velocity waveforms were recorded during the second or last trimester in all cases, first trimester ultrasound examination was carried out in six cases and last trimester MRI in five cases. These findings were compared with postnatal and operative findings of the children. RESULTS: Ultrasound examination did not reveal intrapelvic parts of SCT, but this was possible by MRI. Velocity waveforms of the tumor arteries were similar in all histological types and the resistance index varied from 60 to 70. The mean gestational age at antepartal diagnosis was 25.2 weeks. Large tumor size with relatively large proportion of solid components was often recognized in cases with malignant/immature histology. CONCLUSIONS: Antepartal MRI is useful for examination of fetal SCT, but reliable differentiation of mature and immature SCT is not possible antepartally.

Female↗
PubMed1997

Risk factors for community-acquired pneumonia in children: a population-based case-control study.

Risk factors for community-acquired pneumonia were studied by collecting data from all pneumonia patients (n = 201) in a defined child population between 3 months and 15 years of age during a surveillance period of 12 months, and from randomly selected healthy controls under 15 years of age (n = 250) from the same area. A structured questionnaire was used, with 409 (176 patients and 233 controls) families responding in total. The chi-square test, and the univariate and multivariate logistic regression analyses were used. The confounding effects of gender, age and place of acquisition were standardized, and the possible interactions between these variables and each individual risk factor were calculated. In the risk factor analysis, the responders were classified into 2 age groups: under 5 years and 5-14 years of age. In children under 5 years of age the significant risk factors were a history of recurrent respiratory infections during the past year [odds ratio (OR) 5.5], a history of wheezing episodes (OR 5.3), and a history of otitis media and tympanocentesis before the age of 2 years (OR 3.6). In the older children, the significant risk factors were a history of recurrent respiratory infections during the previous year (OR 3.0), and a history of wheezing periods at any age (OR 2.1). To sum up, a susceptibility to respiratory infections was found to be significantly associated with community-acquired pneumonia, and no interactions with age, gender or place of acquisition were significant. This trend was reflected by a history of wheezing and that of acute otitis media.

Case-Control Studies↗
PubMed1997

Clinical significance of cytogenetics in acute myeloid leukemia.

Cytogenetic studies of acute myeloid leukemia (AML) have revealed that the majority of patients display acquired chromosome aberrations. Numerous recurrent karyotypic aberrations have been and continue to be discovered in AML. Cytogenetic studies have paved the way for molecular analyses that have identified genes involved in the process of leukemogenesis. Moreover, chromosome aberrations, regardless of whether they have been molecularly characterized or not, have been shown to constitute tumor markers of diagnostic and prognostic value. This review presents current information on cytogenetic findings in AML, and correlations between karyotype and clinical features and outcome of de novo AML.

Acute Disease↗
PubMed1996

Partial tandem duplication of ALL1 as a recurrent molecular defect in acute myeloid leukemia with trisomy 11.

Gains of a single chromosome are frequent cytogenic findings in human cancer, but no molecular rearrangement has been consistently associated with any trisomy. In acute myeloid leukemia (AML), trisomy 11 (+11) occurring as a sole abnormality is the third most common trisomy. We have shown that the ALL1 gene, located at 11q23, can be rearranged as a result of a partial tandem duplication in two such cases of AML. To test the hypothesis that the partial tandem duplication of ALL1 is the recurrent molecular defect in cases of AML presenting with +11 as a sole cytogenic abnormality, we performed Southern analysis and PCR for defects of ALL1 in 17 cases of AML and one case of myelodysplastic syndrome with +11 or +11q but without cytogenic evidence of a structural abnormality involving 11q23. Twelve cases (67%) had rearrangement of ALL1, including 10 of 11 patients (91%) with +11 as a sole abnormality and 2 of 7 cases (29%) with +11 and other aberrations; all were classified as FAB M1 or M2. In 10 of the 12 cases, material was available for additional characterization; a partial tandem duplication of ALL1 was detected in each of these 10 cases (100%). Four cases demonstrated previously unreported duplications, two of which were detectable only by reverse transcription-PCR. Four patients with the ALL1 duplication also displayed a loss of material from 7q, suggesting an association between these two findings. We conclude that the partial tandem duplication of ALL1 is present in most, if not all, cases of AML with +11 as a sole abnormality, and can be found in cases of AML with +11 or +11q accompanied by other cytogenic abnormalities. The duplication is more prevalent in AML than was recognized previously in part because its size and location vary considerably, requiring a variety of molecular probes for detection. Our finding of the ALL1 duplication as a consistent defect in patients with +11 represents the first identification of a specific gene rearrangement associated with recurrent trisomy in human cancer.

Acute Disease↗
PubMed1996

Biological effects of recombinant human granulocyte colony-stimulating factor in patients with untreated acute myeloid leukemia.

Hematopoietic growth factors are being administered to patients with acute myeloid leukemia (AML) both to shorten the duration of chemotherapy-induced neutropenia and in an attempt to increase cytotoxicity of cell cycle-specific agents. However, limited information is available concerning the effects of growth factors in AML patients. To examine the in vivo effects of recombinant human granulocyte colony-stimulating factor (G-CSF) on AML cells, laboratory studies were performed before and after a 72-hour intravenous infusion of G-CSF (10 micrograms/kg/d) administered to 28 untreated AML patients. Twenty-seven patients (96%) showed increases in at least one of the following parameters after G-CSF: blood blasts, bone marrow (BM) blasts, leukemia cells in S phase or interphase cells with leukemia-specific markers shown by fluorescence in situ hybridization. The median paired change in absolute blast count was +2.7 x 10(9)/L (P = .0001) after G-CSF, as compared with 0.0 during the 72 hours before initiation of G-CSF. The median percentage of BM leukemia cells in S phase increased from 6.0% to 10.7% after G-CSF (median change, %5.9%; P = .009). Interphase BM cells with trisomy 8 or monosomy 7 increased in 6 of 6 patients with these abnormalities (P = .02) with a median percent increase of 47%. Blood neutrophil counts also increased during G-CSF (median paired change, +2.8 x 10(9)/L; P < .0001). Trisomy 8 or monosomy 7 was shown by fluorescence in situ hybridization in post-G-CSF blood neutrophils from 4 of 6 patients but was also present in neutrophils before G-CSF. We conclude that the percentage of leukemia cells in S phase increases and that leukemia cell populations undergo expansion during short-term administration of G-CSF in almost all AML patients.

Acute Disease↗
PubMed1996

ML-1 cell line lacks a germline MLL locus.

Gene rearrangements involving MLL (also known as ALL1, HRX, or Htrx) are among the most common molecular abnormalities associated with acute leukemia. These leukemias generally have one allele involved in a rearrangement, while the remaining allele is uninvolved and demonstrates a germline MLL configuration. In this study, we describe a leukemic cell line that does not have a germline MLL allele and thus cannot produce a normal MLL gene product. We show that the ML-1 cell line, derived from a patient with acute myeloid leukemia, has one allele involved in a t(6;11)(q27;q23), while the remaining MLL allele is deleted. Cloning of the genomic breakpoints on the derivative(6) and der(11) chromosomes demonstrated a balanced translocation between MLL on chromosome band 11q23 and AF6 on chromosome band 6q27. Sequence analysis of the derivative chromosomes revealed that a 186-bp segment of MLL intron 6, downstream of the breakpoint, had been duplicated, inverted, and inserted between MLL and AF6 on the der(11) chromosome. In light of the fact that ML-1 cells can be induced to differentiate along the granulocyte and macrophage lineages, the finding that ML-1 lacks a germline MLL allele demonstrates that a normal MLL gene is not required for survival, proliferation, or differentiation of this cell line.

Adult↗
PubMed1996

Oestrous synchronisation in Ethiopian highland zebu cattle by means of intravaginal cloprostenole administration.

Two series were used in studying the use of a low dose of intravaginal cloprostenole in oestrous synchronisation of zebu cows. In series I, 39 cows were given 175 mcg of cloprostenole with a plastic catheter in the anterior vagina twice, with a 12-day interval. After treatment, 61.5% of these cows came into heat, were inseminated and 70 days later pregnancies were confirmed in 66.6% of inseminated cows. In series II, intravaginal treatment (40 cows) was compared with intramuscular administration (33 cows) of 500 mcg of cloprostenole. After treatment the cows were checked for silent heat in addition to visible heat. The overall oestrous response, for both visible and silent heat, was 62.6% and 60.6% after the intravaginal and the intramuscular treatments respectively, and there was no statistical difference between the 2 treatments. Unfortunately the pregnancy of the cows could not be checked. Intravaginal administration of 175 mcg of cloprostenole resulted in good oestrous synchronisation and pregnancy rate. For zebu cattle, the oestrous synchronisation response was similar to that reached with 500 mcg of cloprostenole administered intramuscularly.

Administration, Intravaginal↗
PubMed1996

Detection of numerical chromosome abnormalities by FISH in childhood acute lymphoblastic leukemia.

Fluorescence in situ hybridization (FISH) was performed on interphase bone marrow cells to study numerical chromosome abnormalities in childhood acute lymphoblastic leukemia (ALL). Ten patients were selected for this study on the basis of having an extra chromosome 6 in the abnormal clone of the bone marrow at diagnosis. The numerical changes that were detected by FISH with a chromosome 6 specific alpha-satellite DNA probe correlated well with the cytogenetic and clinical data in all patients. Three hybridization signals were seen in 43.8--83.0% of interphase cells in the specimens with a hyperdiploid karyotype. The diagnostic bone marrow sample of the patient with a tetraploid karyotype revealed four signals in 67.0% of cells. Two signals were detected in the majority of the cells in the three nonleukemic control bone marrow samples (97.0--97.7%), assessing the cut-off value of about 1% for trisomy 6. This study demonstrates that FISH analysis is a useful and sensitive tool to screen for the presence of extra chromosomes in interphase cells and is important clinically for evaluating the achievement and maintenance of remission in hyperdiploid childhood ALL. However, to detect structural chromosome aberrations which carry important diagnostic and prognostic information, as seen in our patient with the translocation t(1;19) at diagnosis but not at relapse, conventional cytogenetic analysis should be performed both at diagnosis and at relapse.

Adolescent↗