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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

Immunoglobulin A autoantibodies against transglutaminase 2 in the small intestinal mucosa predict forthcoming coeliac disease.

BACKGROUND: Reliable markers of early developing coeliac diseases are needed. Coeliac autoantibodies in the serum or Marsh I inflammation may be indicators of subsequent coeliac disease. AIM: To investigate whether determination of intestinal transglutaminase 2-targeted autoantibody deposits would detect early developing coeliac disease better than previous methods. METHODS: The study investigated patients previously excluded for coeliac disease: 25 had positive serum coeliac autoantibodies (endomysial), 25 antibody-negative had Marsh I, and 25 antibody-negative had Marsh 0 finding. Seven (median) years after baseline investigation, new coeliac cases were recorded, and small bowel biopsy was offered to the rest of the patients. Serum and intestinal coeliac autoantibodies and intraepithelial lymphocytes were assessed as indicators of developing coeliac disease. RESULTS: Seventeen patients had developed coeliac disease: 13 in the autoantibody-positive group, three in the Marsh I group and one in the Marsh 0 group. At baseline, intestinal coeliac autoantibody deposits had a sensitivity and specificity of 93% and 93% in detecting subsequent coeliac disease, CD3+ 59% and 57%, gammadelta+ 76% and 60%, and villous tip intraepithelial lymphocytes 88% and 71%, respectively. CONCLUSIONS: Endomysial antibodies with normal histology indicates early developing coeliac disease. Transglutaminase 2-targeted intestinal autoantibody deposits proved the best predictor of subsequent coeliac disease.

Adolescent↗

Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.

BACKGROUND: Some patients with untreated coeliac disease are negative for serum endomysial autoantibodies (EmA) targeted against transglutaminase 2 (TG2). AIMS: To evaluate the clinical and histological features of EmA-negative coeliac disease, and to examine whether EmA-equivalent autoantibodies against TG2 can be seen in the small-bowel mucosa when absent in serum. PATIENTS: Serum EmA was studied in 177 biopsy-proved specimens from adult patients with coeliac disease. 20 patients with intestinal diseases served as non-coeliac controls; three had autoimmune enteropathy with villous atrophy. METHODS: Clinical manifestations, small-bowel mucosal morphology, intraepithelial inflammation and TG2-specific extracellular immunoglobulin A (IgA) deposits were investigated in both serum EmA-negative and EmA-positive patients. RESULTS: 22 patients with IgA-competent coeliac disease were negative for serum EmA. Three of these had small-bowel lymphoma. Patients with EmA-negative coeliac disease were older, had abdominal symptoms more often, and the density of gammadelta+ intraepithelial lymphocytes in their intestinal mucosa was lower than in EmA-positive patients; otherwise the histology was similar. All serum EmA-negative patients with coeliac disease, but none of the disease controls, had gluten-dependent mucosal IgA deposits alongside TG2 in the small-bowel mucosal specimens. In vivo deposited IgA was shown to be TG2-specific by its ability to bind recombinant TG2. CONCLUSIONS: Negative serum EmA might be associated with advanced coeliac disease. TG2-targeted autoantibodies were deposited in the small-bowel mucosa even when absent in serum. This finding can be used in the diagnosis of seronegative coeliac disease when the histology is equivocal. It may also be helpful in the differential diagnosis between autoimmune enteropathy and coeliac disease.

Adolescent↗

No GIST-type c-kit gain of function mutations in neuroblastic tumours.

AIMS: Neuroblastic tumours (NTs) have been shown to respond to imatinib treatment in vivo and in vitro, possibly via inactivating the c-kit receptor. The purpose of this study was to identify gastrointestinal stromal tumour (GIST)-type c-kit gene associated mutations in exons 9, 11, 13, and 17 in NTs to recognise a subset of tumours that would probably respond to imatinib treatment. METHODS: Expression of the c-kit protein was detected immunohistochemically in a total of 37 archival paraffin wax embedded NTs using polyclonal rabbit antihuman c-kit antibody. After immunohistochemistry, c-kit gene associated chromosomal mutations in all cases of NT were detected with denaturing high performance liquid chromatography (HPLC). RESULTS: Denaturing HLPC analysis did not reveal GIST-type mutations in four immunohistochemically detected c-kit positive or in 33 c-kit negative NTs. CONCLUSIONS: c-kit receptor expression and GIST-type c-kit gene mutations are rare events in NTs. Oncogenic activation of c-kit in NTs presumably differs from that of GISTs, which may influence their responsiveness to imatinib treatment. Whether c-kit has an essential role in the pathogenesis of NTs remains to be investigated.

Antineoplastic Agents↗

The siblings of childhood cancer patients need early support: a follow up study over the first year.

BACKGROUND AND METHODS: In a 1 year follow up study, we assessed the life situation of 33 siblings of childhood cancer patients and 357 healthy controls. The hypothesis was that siblings have more behavioural and health related problems just after the cancer diagnosis. Validated assessment methods were used. RESULTS: Siblings below school age tended to have conduct problems, psychosomatic problems, and a mixed group of other behavioural problems, when assessed 3 months after the cancer diagnosis. These symptoms became less evident during follow up. Among the school aged siblings, however, conduct problems, learning problems, psychosomatic problems, impulsive-hyperactive symptoms, and other behavioural symptoms remained unchanged during follow up. In their self assessments, the school aged siblings showed both state and trait anxiety more often than controls at the first assessment, but later these symptoms settled to the same level as the controls. The overall Children's Depression Inventory (CDI) depression scores did not show differences between the study groups. CONCLUSIONS: The ratings of the parents were in keeping with the self assessment of the school aged siblings only in a few aspects; the emphasis of findings can be changed when proxies are used. The siblings have symptoms and adverse feelings which probably could be relieved by targeted, early information about the illness, and possibly by group discussions or activities, soon after the cancer diagnosis. In order to obtain necessary support for the siblings with educational problems, school personnel need to be informed about the sibling distress.

Adolescent↗

The life situation of parents over the first year after their child's cancer diagnosis.

AIM: To evaluate the impact of childhood cancer on the life of the parents. METHOD: A 1-y follow-up study, with two time points for questionnaires, was completed in 21 out of 26 eligible families, and there were 46 control families matched by mothers' educational status. RESULTS: Half of the mothers worked outside home during the first year of their child's illness. The perceived amount of lost family income was high during the first few months. The attitudes of the parents were fairly positive as their family life and spouse relations were concerned. Feelings of being under strain or stressed were, by the mothers, described as intolerable in the beginning. However, standardized anxiety assessment failed to show an increase in feelings of anxiety. Own health was rated significantly negative by cancer parents. CONCLUSIONS: Despite good family relationships, a need for supportive measures exists, especially during the first few months, and in-depth interviews by psychologists or special nurses might be a way of finding out possible anxiety. The perceived feelings of own health may also be an indicator of the level of distress. Parent support groups could also do more to offer opportunities of physical activities for the parents, not merely disease-related information and group discussions.

Adaptation, Psychological↗

Childhood cancer patients at school.

The aim of this study was to assess the school-related problems of childhood cancer patients. A cross-sectional questionnaire study for school-aged children with extracranial malignancies, in the area of Turku University Hospital serving around 1000000 people. Siblings, healthy pupils and teachers were studied as controls. 43 patients responded. None of the patients or controls was placed in special educational programmes. However, 30.8% of the patients, 15.7% of the controls and 3.7% of the siblings had required extra tutoring. The patients' results differed statistically from both the siblings' (P=0.022) and the controls' (P=0.041) results. The school marks in mathematics (P=0.05) and in foreign languages (P=0.06) tended to be worse for the patients than for the healthy controls. Bullying was reported by 31.7% of the patients, 10.9% of controls (P=0.0012) and 8.3% of the siblings (P=0.056). The biggest problem faced by the cancer patients was bullying-the patients reported approximately 3 times as much bullying as the healthy children did. It seems that there are still several aspects which need to be reconsidered when these children return to school or start their school-life as survivors of childhood cancer. Some proposals are presented.

Absenteeism↗

Induced leukemia and antineoplastic agent carmustine cause permanent changes in craniofacial growth of immature rats.

OBJECTIVES: The purpose of the present study was to investigate the possible effects of untreated terminal leukemia on craniofacial growth (Study I), and also the effects of the antineoplastic agent carmustine on craniofacial growth in both leukemic and healthy rats (Study II). MATERIAL: A total of 367 inbred Piebald variegated rats was used. METHOD: Transmission of leukemic cells was carried out intraperitoneally at 30 days of age, and without treatment (Study I), the rats reached the terminal phase within 17 +/- 1 days. Rats with induced leukemia was cured with 10 mg/kg carmustine (BCNU) given on days 6 and 13 following cell transmission (Study II), the rats remaining in remission until they were killed at 100 days of age. Final weight was recorded and 12 craniofacial dimensions and tibial length were measured with a digital sliding caliper. RESULTS: The results showed that the effect of untreated terminal rat leukemia (Study I) on craniofacial growth differed between the genders. Male rats showed clearly reduced dimensions of facial structures and also retarded general body growth, whereas females showed differences mainly in general body growth. The effect of cured leukemia (Study II) as such was minor, while BCNU had a strong and permanent reducing effect on both craniofacial and general body growth in both genders. CONCLUSION: We suggest that the results in Study I came both from a direct effect of leukemia and an indirect effect of untreated terminal leukemia through malnutrition. The alkylating agent BCNU seemed to be the main cause of permanent craniofacial and general growth retardation in Study II.

Analysis of Variance↗

Amifostine protects against early but not late toxic effects of doxorubicin in infant rats.

The improved prognosis and increased expected lifetime among long-term survivors of childhood malignancies have made these patients especially sensitiveto the late toxicity of cancer therapy and prone to secondary malignancies. Recently, new strategies aiming to protect against cancer treatment toxicity have been developed, including the drug amifostine (Ethyol), which is suggested to protect normal tissues from the toxic effects of radiation and cytotoxic agents. In the present study, the possible protective effect of amifostine against toxicity induced by a single injection of doxorubicin (3 mg/kg) in immature rats was evaluated. Specifically, we evaluated the protection against long-term toxicity and the effects of amifostine on growing immature tissues. Amifostine (50-200 mg/kg) given 15 min before doxorubicin had a significant protective effect against doxorubicin-induced early alopecia in young rats. Significant protection against cataract formation was obtained by the use of low-dose amifostine (50 mg/kg). However, amifostine did not protect young rats against the late toxic effect of doxoubicin on linear growth, body weight, plasma leptin levels, and heart or testicular tissue. Worrisome, and in contrast to earlier studies in adult rats, an increased doxorubicin toxicity actually was observed and mortality was increased when the higher doses of amifostine (100-200 mg/kg) were used. The present results suggest that more data from growing immature animal models are needed to analyze the safety of amifostine treatment and its mechanisms of action before wider clinical use of this drug in pediatric cancer patients is recommended.

Age Factors↗

Cognitive functions of adolescent childhood cancer survivors assessed by event-related potentials.

BACKGROUND: Neurophysiological methods were applied to examine subtle central nervous system (CNS) adverse effects for adolescent childhood cancer survivors. We analyzed auditory event-related potentials (ERPs)-P300 and MMN/P3a complex-to find out whether there was impaired attention orientation in asymptomatic cancer survivors, and whether these ERP methods could be used as more objective tools in detecting those survivors who might need academic testing. Previous clinical studies of P300 have focused on leukemia survivors. MMN for cancer survivors has not been reported. PROCEDURE: The subjects were survivors of childhood leukemia (n=11) and solid tumors (n=8), as well as healthy controls (n=10). The mean age was 15.5 years for survivors and 15.9 years for controls. Pure sine-wave tones (500 and 553 Hz, 100 ms) were used as stimuli in an oddball paradigm. The ERPs to frequency change were measured. MMN recordings were performed in a passive non-attended situation where the subject was watching a voiceless video cartoon. P300 was produced thereafter, but in an active attend situation, by the same auditory oddball paradigm as MMN. RESULTS: A significant difference was detected between the groups for the latency of P300 at electrodes Cz (P = 0.03) and C4 (P = 0.05). The cancer survivors had prolonged P300 latencies as an indication of prolonged short-term memory processing. The area and latency parameters of MMN did not differ significantly between the study groups, but in cancer survivors, the area and the mean amplitude of the subsequent P3a wave were diminished. The results indicate that the discrimination process was not as easy for the survivors as for the controls. However, it seems that in cancer survivors the basic mechanism starting attention shift to novel stimuli is not impaired. CONCLUSIONS: These results indicate that it is important to carefully evaluate the proper methods for the teaching of children who are survivors of malignancies. The auditory information may not always lead to the best possible learning results.

Achievement↗

Disturbances in craniofacial morphology in children treated for solid tumors.

Because of increased survival rates in childhood cancer, special interest has been focused on the side-effects of the therapy and the quality of life in long-term survivors. Our aim was to investigate craniofacial growth in children who had received different kinds of antineoplastic therapies for solid tumors. A total of 40 children treated in the Turku University Central Hospital were examined and divided into three different groups. Group 1 comprised 18 children treated for intracranial tumors with cranial irradiation (CRI) and chemotherapy (CT) including alkylating agents. Seven children out of 18 in this group received growth hormone (GH) therapy. In Group 2, 11 children with extracranial solid tumors also received multiagent CT including alkylating agents, but no CRI. Group 3 consisted of 11 children treated for Wilm's tumor with CT, which did not include alkylating agents or CRI. A total of 19 linear and four angular variables from the lateral cephalograms of the subjects were measured. Most deviations in craniofacial structures were found in children treated with combined CRI and multiagent CT. All disturbances were seen in the vertical measurements which were reduced when compared to the matched controls. It seems reasonable to assume that impaired growth following combined radio- and chemotherapy, as well as GH treatment, particularly affects cartilage-mediated growth. However, the deviations seen in the present study were fairly minor and did not usually require clinical consideration.

Antineoplastic Combined Chemotherapy Protocols↗

Cerebral glucose metabolism in survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Cranial radiation therapy (CRT) has been suggested to be a principal factor responsible for long term neurocognitive deficits in survivors of acute lymphoblastic leukemia (ALL). However, neither reduction of the irradiation dose nor the elimination of irradiation entirely appear to have abolished neurocognitive impairment in long term ALL survivors. Positron emission tomography (PET) and [(18)F]-fluorodeoxyglucose (FDG) can be used to quantitate cerebral glucose metabolism, a potential indicator of treatment-induced adverse central nervous system (CNS) effects. The purpose of this study was to assess whether CRT is associated with defects in cerebral glucose metabolism in long term ALL survivors. The authors also studied whether chemotherapy and/or the severity of disease have deleterious effects on glucose metabolism. METHODS: Forty long-term survivors of childhood ALL were studied using FDG PET. All subjects went through an elaborate neurocognitive assessment. In 20 of these children, the prophylactic treatment of the CNS had been CRT combined with methotrexate (MTX), and it was MTX only in the remaining 20 children. RESULTS: No major differences were found in the regional cerebral glucose utilization or in neurocognitive performance between the irradiated and nonirradiated groups. A high leukocyte count at the time of diagnosis was found to be associated inversely with cerebral glucose utilization. CONCLUSIONS: CRT does not appear to affect cerebral glucose metabolism in long term survivors of ALL. By contrast, the association between the leukocyte count and glucose utilization implies that disease severity may be partly responsible for adverse CNS effects in long term survivors of childhood ALL.

Adolescent↗

Granulocyte-macrophage colony-stimulating factor support in therapy of high-risk acute lymphoblastic leukemia in children.

BACKGROUND: Our purpose was to increase the dose intensity of chemotherapy and reduce the days with neutropenic fever in childhood high-risk (HR) acute lymphoblastic leukemia (ALL) by systematic use of granulocyte-macrophage colony-stimulating factor (GM-CSF). PROCEDURE: All children with HR-ALL in Finland during 1990-1996 were included. Two open-label study groups were formed: 1) 34 children diagnosed between January, 1992, and December, 1996, received seven or nine courses (depending on cranial RT or no cranial RT) of GM-CSF at 5 microg/kg s.c. daily until an absolute neutrophil count (ANC) of 1,000 x 10(6)/liter at scheduled places in the protocol and 2) 80 control children, those diagnosed between January, 1990, and December, 1991, plus all with significant coexpression of myeloid markers, did not receive GM-CSF. RESULTS: Dose intensity increased in patients who received regular GM-CSF support. The intensive phase of therapy, including induction, consolidation courses, and delayed intensification, was 33 days shorter (P < 0.001) in children with seven courses and 26 days shorter (P < 0.01) in those with nine courses of GM-CSF compared to controls. The number of infections during the whole ALL therapy was reduced by use of GM-CSF in children aged >5 years (P < 0.001), but not in those aged <5 years. The mean total duration of intravenous antibiotics per child was 39 days in the GM-CSF group and 48 days in the control group (P < 0. 001). Systematic use of GM-CSF was cost-effective. CONCLUSIONS: Systematic use of GM-CSF improved dose intensity by shortening the intensive treatment period by about 4 weeks. Use of GM-CSF reduced the days for inpatient antibiotics by about 1 week per child, which translates into reduced costs.

Age Factors↗

Catch-up growth and craniofacial dimensions following administration of the antineoplastic agent vincristine to young rats.

Decreased linear growth is a common problem during childhood anticancer therapy. Although catch-up growth may occur, short stature is sometimes permanent. A macroscopic experimental study was performed to investigate the catch-up growth of body and craniofacial structures of growing rats subjected to the antineoplastic agent vincristine. A total of 150 Long-Evans/Turku strain rats were randomly divided into one of two treatment or control groups. A group of 10-d-old rats was given a single s.c. injection of 0.0375 mg/kg vincristine, while another treatment group of 30-d-old rats received three injections of 0.05 mg/kg vincristine. All rats were killed at the age of 100 d. Twelve different craniofacial dimensions, tibia and body length, and final weight were recorded. Female and male groups were analyzed separately. As an expression of catch-up growth, most of the body and craniofacial structures returned to the control level by 100 d of age. A clear sex-dependency was seen in the measurements which remained reduced so that females seemed to catch-up better than males. The timing of the first injection was found to be important for the catch-up growth in the neurocranial area.

Analysis of Variance↗

Military service of male survivors of childhood malignancies.

BACKGROUND: The objective of this study was to assess the eligibility for and the course of compulsory military service of childhood cancer survivors. METHODS: The medical, military recruitment, conscription, and military service data of male Finnish childhood cancer survivors were collected from manually filed records. Inclusion criteria were: survivors born 1977 or earlier, treated for a malignancy between birth and age 15 years, and followed by a pediatrician until at least age 18 years. The documents of 207 survivors from the Pediatric Clinics of Finnish University Hospitals were examined, and 130 of these survivors were considered eligible for military service. Demographic factors, the predictors of fitness for military service, factors associated with service interruption, the attained level of military training, and the health status of conscripts during service were evaluated. Comparisons were made with the Finnish male population of the same age and with conscripts serving at the corresponding time. RESULTS: Approximately 60% of studied survivors were enlisted. Positive predictors of fitness for service were year of birth of 1973 or later (odds ratio [OR], 3.2), height at call-up age of 170-174.9 cm (OR, 3.6), and the man's own positive opinion of his fitness for service (OR, 62.3). Negative predictors were age at diagnosis > or = 11 years (OR, 0.5), central nervous system radiotherapy (OR, 0.3), limb defects (OR, 0.02), and the group of sequelae concerning neurologic, cardiopulmonary, and gastrointestinal systems, or secondary malignancies (OR, 0.3). Survivors interrupted their service more often (20%) (P < 0.001). Leukemia survivors were less likely to interrupt their service (7%) compared with other survivors (P = 0.04). Factors associated with service interruption were: diagnosis (P = 0.04), the man's own opinion of his fitness for service (P = 0.013), surgery (P = 0.003), and height (P = 0.049), weight (P = 0.019), and body mass index (P = 0.035) at the beginning of military service. The attained level of military training was equal to that of controls. The survivors visited the garrison physician less frequently in total (mean, 5.9 times) (P < 0.001), visited because of infections as much as controls, and were off duty more (mean, 11.9 days) (P = 0.012) than controls. CONCLUSIONS: The current study found that childhood cancer survivors were less likely to meet the requirements set for military service in Finland. The causes of rejection usually were obvious, but approximately 30% were rejected merely on the basis of a former cancer diagnosis. However, enlisted survivors coped well with military service if their treatment sequelae were taken into consideration carefully at the time of enlistment. Vocational opportunities within the armed forces might be an appropriate career option even for survivors of childhood malignancies.

Adolescent↗

Reemphasis on lymphoblast L2 morphology as a poor prognostic factor in childhood acute lymphoblastic leukemia.

BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), the relationship between lymphoblast L1/L2 morphology and prognosis is controversial. According to some studies L2 morphology is associated with poor prognosis, whereas in others the association disappears after adjustment for other known risk factors. PROCEDURE: We investigated the prognostic importance of lymphoblast L1/L2 morphology in childhood ALL treated with current Nordic ALL protocols in Finland. From the routine bone marrow (BM) aspirate and biopsy slides of 251 children with ALL diagnosed in 1990-1995, the blast cell morphology and early treatment responses were assessed blindly in a central review, using French-American-British (FAB) criteria with the Children's Cancer Group (CCG) modification. RESULTS: L1 morphology (>90% L1) was found in 197 (80%) children and L2 (>/=10% L2) in 49 (20%). Early treatment response was poorer in L2 than in L1: >5% blasts in the marrow on day 15 were seen in 27% of L2 as opposed to 12% of L1 (P = 0.048). The 6-year event-free survival (EFS) in the study population was 75%, 76% in L1 and 70% in L2 (P = 0.34). In the group with white blood cell count (WBC) below 50 x 10(9)/liter at diagnosis, the L2 morphology was associated with inferior survival: 6-year EFS 74% in L2 and 84% in L1 (P = 0.07), with 6-year overall survival (OS) 81% vs. 91% (P = 0.035), respectively. L2 morphology was not associated with any other adverse prognostic factor analyzed. CONCLUSIONS: With the intensive Nordic ALL protocols, lymphoblast L2 morphology is an independent poor prognostic factor, influencing both the early response to treatment and, in the low-WBC group, the ultimate outcome, and should be reemphasized in risk categorization of childhood ALL.

Adolescent↗

Nursing activities and outcomes of care in the assessment, management, and documentation of children's pain.

This study describes how assessment and documentation of children's acute postoperative pain is managed by nurses in university hospitals in Finland. A survey was conducted of 303 nurses working in children's wards of university-affiliated hospitals, and at the same time a retrospective chart review of 50 consecutive cases of operation of acute appendicitis was carried out. Charts were analyzed by content analysis, and the results of the survey are reported with percentage distribution and nonparametric statistical calculations. The results indicate that nurses assess pain mainly by observing the child's behavior and changes in physiology. Pain measurement instruments are rarely used, and nurses do not recognize them. The documentation of pain care is unsystematic and does not support the continuity of care. There is a clear need for development of assessment and documentation practices in the studied hospitals. Future research should look at the postoperative care of pain at home as well as care in non-university-affiliated hospitals.

Adolescent↗

Nurses' knowledge about pharmacological and nonpharmacological pain management in children.

The purpose of this study was to investigate the knowledge base and practices of Finnish nurses in the area of children in pain. The convenience sample consisted of 265 nurses working on children's wards in university hospitals. Data were collected using an instrument designed for the study. The results showed that there remain gaps in the knowledge base of nurses with regard to both pharmacological and nonpharmacological pain management in children. The education and the area of expertise were significant influences on knowledge scores. Nurses used a fairly wide range of nonpharmacological pain alleviation methods but most of these were such that the nurse was in an active role and the child was passive. There is a clear need for further education. Nurses should take a more active role in seeking new information and also should be encouraged to use nonpharmacological methods that let the children be active participants in their own care.

Adult↗