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Biomedical subjects

K Heinonen

Publications and source records attributed to K Heinonen.

At least 55 records · Page 3Linked to original sources

Isochromosome 12p in two cases of acute myeloid leukaemia without evidence of germ cell tumour.

An isochromosome 12p [i(12p)], typical of germ cell tumours (GCT), has, to date, been observed in 10 cases of acute myeloid leukaemia (AML) or myelodysplastic syndrome, nine of which had concurrent or preceding GCT. We report two i(12p)-positive AML cases without clinical evidence of GCT. One patient with AML-M1 had two i(12p) as the only cytogenetic anomalies. In the other case of AML-M3 with t(15;17)(q22;q11-12) at diagnosis, the i(12p) was clearly a secondary rearrangement since it first appeared at relapse and always accompanied the t(15;17). Our results suggest that i(12p) does not always indicate neoplastic disease of germ cell origin.

Acute Disease↗

Local ventilation for powder handling--combination of local supply and exhaust air.

The performance of a modified local ventilation unit equipped with local supply and exhaust ventilation was evaluated during the manual handling of flour additive powder. The investigation tested five different configurations to study the effects of the exhaust opening location and local supply air on worker exposure. The measurements were done under controlled conditions in a test room. The breathing zone (BZ) dust concentration was measured by gravimetric sampling and real time monitoring. The different local ventilation configurations were also modeled numerically using computational fluid dynamics. Without local ventilation the average BZ dust concentration was 42 mg/m3. With local exhaust only the exposure was reduced below 1 mg/m3. The addition of local supply air further reduced the exposure to below 0.5 mg/m3. The lowest results were achieved by locating two exhaust openings on either side of the contaminant source combined with local supply air. With this configuration the average BZ exposure was only 0.08 mg/m3, a reduction of 99.8%. Numerical simulations also gave useful information about the airflow fields in stationary conditions. However, the worker's exposure was greatly affected by body movements, and this was not possible to simulate numerically. The results of this investigation can be useful when controlling dust exposure in manual powder handling operations.

Air Pollutants, Occupational↗

Hearing loss at the age of 5 years of children born preterm--a matter of definition.

The effect of three common hearing impairment criteria on the prevalence of hearing loss was evaluated in 58 prospectively followed-up 5-year-old children born preterm at < or = 32 weeks of gestation. Audiological assessment was done as part of an extensive neurodevelopmental evaluation at the age of 5 years. With the criterion based on the classification of the World Health Organization (average threshold hearing level > 25 dB at frequencies of 0.5, 1 and 2 kHz, classified according to the less impaired side) there were two preterm children with mild hearing impairment. With Clark's criterion (unilateral average threshold hearing level > 15 dB at frequencies of 0.5, 1 and 2 kHz) eight children had slight hearing impairment; seven of these had conductive hearing problems. With the criterion of a single frequency-specific deficit > 15 dB for 0.25-4 kHz the number of hearing-impaired children was 28 out of 54 (51.9%), most of whom had conductive or unspecified hearing deficits. Moreover, of the four multiply handicapped, retarded children whose pure tone thresholds were not assessed monaurally, three would belong to the hearing-impaired group according to Clark's criterion and four according to the frequency-specific criterion.

Acoustic Impedance Tests↗

Cell lineage involvement of recurrent chromosomal abnormalities in hematologic neoplasms.

Analysis of most hematologic neoplasms indicates the involvement of one or more cell lineages in the bone marrow and/or the blood but rules out the involvement of all lineages in any one neoplasm. It is important to detect lineage involvement in order to clarify which stem cells are involved in leukemia, to predict prognosis, and to select appropriate treatment. Our aim was to study the cell lineage involvement of some of the recurrent chromosomal abnormalities seen in hematological neoplasms. The direct morphology-antibody-chromosomes (MAC) method was used. The deletion 20q in myeloproliferative diseases (MPD), the deletion of 5q and t(1;7) in myelodysplastic syndromes (MDS), and t(3;3) in acute myeloid leukemia subtype M7 (AML-M7) were seen in all or at least in two myeloid lineages. These were interpreted as stem cell abnormalities. Deletion 13q in MPD, t(8;21) in AML-M2 and t(15;17) in AML-M3 were seen in granulocytic lineages only; t(14;18) in non-Hodgkin's lymphoma and trisomy 12 as the sole abnormality in chronic lymphocytic leukemia (B-CLL) were seen only in immunoglobulin light chain clonal B cells; inversion 14 in T-CLL was seen only in T cells, whereas t(15;14) in acute lymphocytic leukemia with eosinophilia (ALL-EO) was seen in lymphoid stem cells but not in mature granulocytes or lymphocytes. Additional abnormalities (in addition to the Philadelphia chromosome) in chronic myeloid leukemia (CML) were seen in all myeloid cell lineages and also in mature granulocytes, B cells, and large granular lymphocytes. Abnormalities in Hodgkin's disease were restricted to CD30-positive Reed-Sternberg cells. Trisomy 8 and monosomy 7 are abnormalities that may be present in either stem cells or any of the single cell lineages.

Blast Crisis↗

Multiple karyotypic abnormalities in three cases of small cell variant of T-cell prolymphocytic leukemia.

Cytogenetic, clinical, and laboratory findings of three patients with a small cell variant of T-cell prolymphocytic leukemia (T-PLL) are presented. Immunophenotypic studies of the morphologically typical small cell variant prolymphocytes showed a mature helper T-cell phenotype (CD4+CD8-) in one patient and a common thymocyte phenotype (CD4+ CD8+) in two other patients. The cytogenetic analysis revealed complex karyotypes with several structural aberrations in the peripheral blood lymphocytes of all three patients. In all cases chromosome 14 was affected with the breakpoint at 14q11. Inversion (14) and isochromosome 8q, often reported as an additional aberration in T-PLL, were detected in two of the patients. In two patients a translocation of the short arm of chromosome 12 was also seen. The T-cell receptor beta-chain gene showed a clonal rearrangement in all three patients, whereas no rearrangements were detected in the immunoglobulin genes. The survival of the patients ranged from 10 weeks to 48 months. The association between cytogenetic, clinical, and laboratory data is discussed.

Adult↗

Cell lineage involvement in four patients with myelodysplastic syndrome and t(1;7) or trisomy 8 studied by simultaneous immunophenotyping and fluorescence in situ hybridization.

Four patients with myelodysplastic syndrome (MDS), one with t(1;7) and three with trisomy 8, were studied by immunophenotyping and fluorescence in situ hybridization (FISH) to assess cell lineage involvement. The t(1;7) was detected using a biotin-labeled chromosome 1 centromere-specific DNA probe. This aberration was present in CD34-positive stem cells, the erythroid cell lineage (GPA+), and the granulocytic/monocytic (CD13+ and CD64+) cell lineages. We were not able to demonstrate the abnormality in the lymphoid cell lineages. In the patients with trisomy 8, the aberration was detected with chromosome 8 centromere-specific DNA probe or by chromosome in situ suppression hybridization (CISS) with a chromosome 8-specific library probe. The trisomy was detected in stem cells, erythroid precursor cells, megakaryocytes, and granulocytes/monocytes. In these MDS patients, the chromosome aberrations appear to occur only in cells of myeloid lineage.

Aged↗

Analysis of phenotype and genotype of individual cells in neoplasms.

The authors describe a combination technique enabling detection of in situ hybridization (ISH) signals from chromosome-specific probes in interphase or mitotic cells that still retain the alkaline phosphatase antialkaline phosphatase (APAAP) or Sudan black B (SBB) staining reactions (simultaneous detection) or have been first classified morphologically and then by APAAP or SBB. The technique can be used on cell suspensions, in situ cultures and tissue sections. Examples from leukemias (chronic lymphocytic, myeloid, and acute myeloid leukemia) and solid tumors (chondromyxoid fibroma and glioblastoma) illustrate the potential of the technique in investigation of cancer tissue heterogeneity. In leukemias, it can be used to study cell lineage involvement, stem cells, and minimal residual disease, as well as to monitor therapy. In solid tumors, it can be used to identify neoplastic areas of tissue and to track the site of origin of neoplastic cells. Finally, it can be used to study the significance of chromosome abnormalities in carcinogenesis.

Adult↗

Ureaplasma urealyticum infection associated with acute respiratory insufficiency and death in premature infants.

The incidence and outcome of Ureaplasma urealyticum infection were studied in 98 infants born before 34 weeks of gestational age. Infection was defined as the presence of one or more isolations of U. urealyticum in samples obtained from trachea, blood, cerebrospinal fluid, or postmortem brain or lung biopsies. Forty-seven infants were infected. Intact amniotic membranes had no protective effect against infection; intrauterine U. urealyticum infection was detected in 19 infants who were born by cesarean section with intact amniotic membranes. Respiratory distress syndrome, the need for assisted ventilation, severe respiratory insufficiency, and death were significantly more common among infected than among noninfected infants. Our results suggest that U. urealyticum infection is associated with an unfavorable short-term outcome in preterm infants.

Humans↗

Dexamethasone treatment in preterm infants at risk for bronchopulmonary dysplasia.

A randomised double blind placebo controlled study was conducted to determine whether a one week course of dexamethasone could reduce the severity of bronchopulmonary dysplasia in preterm infants without compromising their adrenal function. Forty one infants with a mean birth weight of 880 g and a gestational age of 27 weeks who were ventilator dependent at 10 days of age were enrolled. At the age of 28 days pulmonary outcome was significantly better in the girls treated with dexamethasone but not in all infants. There was no difference between the groups in the long term outcome, except for a shorter duration of supplemental oxygen in dexamethasone treated female infants. After the one week dexamethasone treatment there was a significant but short lived suppression of the basal cortisol concentrations and the adrenal response to corticotrophin (ACTH). No serious side effects were observed. It is concluded that early one week dexamethasone treatment improves short term pulmonary outcome in premature infants, but there is no clear evidence of long term benefits.

Bronchopulmonary Dysplasia↗

Ureaplasma urealyticum cultured from brain tissue of preterm twins who died of intraventricular hemorrhage.

We present a case of premature twins, born at 24 weeks of gestation. Both infants died of intraventricular hemorrhage, aged 1 and 3 days, respectively. Ureaplasma urealyticum was isolated from brain tissue obtained at the autopsy of both infants. Our observations lend additional evidence of the role of U. urealyticum as a central nervous system pathogen in premature infants.

Brain↗

Genomic hypomethylation in human chronic lymphocytic leukemia.

DNA samples from patients with chronic lymphocytic (CLL), chronic myelocytic (CML), acute myelocytic (AML), and acute lymphocytic leukemia (ALL), as well as samples from patients with multiple myeloma (MM) and healthy volunteers, were analyzed for their genomic methylation status using Hpa II and Msp I digestions followed by a simple gel electrophoresis and ethidium bromide staining. A densitometric method was developed to measure more accurately the extent of methylation in genomic DNA samples and the results were confirmed by high-performance liquid chromatography (HPLC) analysis of hydrolyzed DNA. Southern analysis with ornithine decarboxylase (ODC) gene probe was also employed, and the levels of ODC mRNA were determined with the aid of polymerase chain reaction (PCR). The results indicated that a general genomic hypomethylation was present in almost all of the samples obtained from patients with B-cell CLL. This hypomethylation was most striking among the patients who were freshly diagnosed and among untreated chronic patients. CML appeared to be a heterogenous group, comprising patients with normal methylation status in addition to patients with slight hypomethylation. Patients with ALL, AML, or MM did not show any signs of DNA methylation changes in comparison to healthy volunteers. Although all analyzed samples from patients with B-CLL showed hypomethylation of ODC sequences, little correlation existed between the mRNA levels and the extent of hypomethylation of ODC gene.

Chromatography, High Pressure Liquid↗

Hydrops fetalis associated with Ureaplasma urealyticum.

A hydroptic newborn was born at 32 weeks' gestation and at the age of 14 h died of post-asphyxial syndrome. Immunologic causes of hydrops fetalis were excluded, as were anomalies and chromosomal aberrations. Ureaplasma urealyticum was isolated in bronchial secretions, lung tissue and brain tissue of the newborn. Our findings suggest that U. urealyticum infection should be considered in the differential diagnosis of hydrops fetalis.

Brain Diseases↗

Fungal gut colonization with Candida or Pityrosporum sp. and serum Candida antigen in preterm neonates with very low birth weights.

To evaluate the diagnostic value of gut colonization by yeasts and of candida antigen in serum for predicting fungal infection in very premature neonates, faecal and serum samples were obtained biweekly from 27 newborn babies treated at our neonatal intensive care unit. Altogether 82 sets of serum and faecal samples were obtained. 17 babies were followed for > or = 4 weeks. Blood cultures, both by routine and lysis centrifugation techniques, were performed for bacteria and fungi if infection was suspected. All children were given systemic broad-spectrum antibiotic treatment. Five of the children died, all without evidence of fungal infection. No systemic antifungal treatments were given. Quantitative faecal cultures demonstrated Candida albicans in 3 (11%) (10(3)-10(5) colony forming units/g) and Pityrosporum sp. in 8 (30%) of the preterm neonates. Candida antigen in titre 4 was detected in 1/82 serum samples. The child subsequently died with no other evidence of candida infection. In 56 full term neonates treated at the intensive care unit during the same period and tested by 1 set of samples, faecal colonization with Candida sp. was detected in 2 (4%) and with Pityrosporum sp. in 4 (15%). None were positive for candida antigen. Fungal gut colonization did not lead to clinical infection in the preterm neonates studied. The false positivity rate of the candida antigen test was low (0.7%). The predictive value of the test could not be determined in this study group with no systemic fungal infections. The role of pityrosporum as an inducer of neonatal infections remains to be evaluated.

Antigens, Fungal↗

Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium.

Blood coagulation and fibrinolytic inhibitors and the balance between and within the two systems were investigated in 26 normal pregnant women during pregnancy and the puerperium. The concentration of the coagulation inhibitors antithrombin and protein C remained within normal levels, whereas the mean level of free protein S showed a significant decrease from 0.26 U/mL in early pregnancy to 0.14 U/mL in week 35. At the same time, soluble fibrin levels increased from 9.2 to 13.4 nmol/L and thrombin-antithrombin complexes increased from 3.1 to 7.1 micrograms/L; both are indicators of thrombin activity. A concurrent increase in the levels of the fibrinolytic inhibitors plasminogen activator inhibitor-1 and -2 from 7.4 to 37.8 AU/mL and 31 to 160 micrograms/L, respectively, suggests a decrease in fibrinolytic activity. However, the levels of fibrin D-dimer, ie, fibrin split products, also increased in parallel from 91 to 198 micrograms/L, suggesting that fibrinolysis is present. Thus, a balance normally exists, which is probably why thrombotic events are rare during pregnancy.

Adult↗

Pulmonary function and respiratory morbidity in school-age children born prematurely and ventilated for neonatal respiratory insufficiency.

We examined 72 children aged 6-9 years to assess the effects of prematurity and ventilator treatment on subsequent lung function and respiratory morbidity. The preterm study group (n = 42) was divided into children with a history of bronchopulmonary dysplasia (BPD) (n = 10), children who had had neonatal respiratory treatment but no BPD (n = 19), and children without severe neonatal respiratory problems (n = 13). The BPD children as a group had markedly lower specific airway conductance and larger residual volume than did the full-term control group, but there were no significant differences in spirometric measurements. The BPD group also had higher respiratory morbidity requiring hospitalizations, particularly during the first 2 years of life, than did the children in the other study groups. Therefore, BPD may improve but does not disappear as age increases. Non-BPD children who had had ventilator treatment as neonates recovered well and suffered no severe respiratory problems after infancy. Pulmonary function parameters in prematurely born children without neonatal ventilator treatment did not differ from those in the full-term control group. Thus, neonatal lung disease seems to be a more important determinant of abnormal pulmonary function at a later age than is prematurity alone.

Aging↗