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Biomedical subjects

K Holm

Publications and source records attributed to K Holm.

At least 19 recordsLinked to original sources
PubMed2006

Oats in the treatment of childhood coeliac disease: a 2-year controlled trial and a long-term clinical follow-up study.

BACKGROUND: The exclusion of oats from the diet in coeliac disease is controversial. AIM: To study the long-term safety of oats in the treatment of children with coeliac disease. METHODS: Altogether 32 children with coeliac disease were enrolled in a 2-year controlled trial. Twenty-three children in remission were randomized either to oats or gluten challenge; when small bowel histological relapse was evident after gluten challenge, a gluten-free diet including oats was started. Furthermore, nine newly detected coeliac patients adopted an oat-containing gluten-free diet. Small bowel mucosal morphology, CD3+, alphabeta+ and gammadelta+ intraepithelial lymphocytes, human leucocyte antigen (HLA) DR expression and coeliac serology were determined. After the trial, the children were allowed to eat oats freely; follow-up was extended up to 7 years. RESULTS: In coeliac children in remission, oats had no detrimental effect on intestinal histology or serology during the 2-year trial. In contrast, the gluten-challenge group relapsed after 3-12 months. Complete recovery from the disease was accomplished in all relapsed and newly detected patients on an oat-containing gluten-free diet. After the trial, 86% of the children preferred to consume oats and they all remained in remission. CONCLUSION: In most children with coeliac disease, long-term consumption of oats is well tolerated, and it does not result in small bowel mucosal deterioration or immune activation.

Adolescent↗
PubMed2006

Pubertal development in Danish children: comparison of recent European and US data.

Two recent epidemiological studies (PROS and NHANES III) from the USA noted earlier sexual maturation in girls, leading to increased attention internationally to the age at onset of puberty. We studied the timing of puberty in a large cohort of healthy Danish children in order to evaluate differences between USA and Denmark, as well as to look for possible secular trends in pubertal development. Healthy Caucasian children from public schools in Denmark participated in the study which was carried out in 1991-1993. A total number of 826 boys and 1,100 girls (aged 6.0-19.9 years) were included, and pubertal stages were assessed by clinical examination according to methods of Tanner. In boys testicular volume was determined using an orchidometer. We found that age at breast development 2 (B2) was 10.88 years, and mean menarcheal age was 13.42 years. Girls with body mass index (BMI) above the median had significantly earlier puberty (age at B2 10.42 years) compared with girls with BMI below the median (age at B2 11.24 years, p < 0.0001). Similarly, menarcheal age was significantly lower in girls with BMI above the median compared with girls with BMI below the median (13.12 vs. 13.70 years, p = 0.0012). In Danish boys we found that age at genital stage 2 (G2) was 11.83 years. Both sexes were significantly taller compared with data from 1964, but timing of pubertal maturation seemed unaltered. Finally, puberty occurred much later in Denmark compared with recent data from USA. We could not detect any downwards secular trend in the timing of puberty in Denmark between 1964 and 1991-1993 as seen in the US. Obesity certainly plays a role in the timing of puberty, but the marked differences between Denmark and USA cannot be attributed exclusively to differences in BMI. A possible role of other factors like genetic polymorphisms, nutrition, physical activity or endocrine disrupting chemicals must therefore also be considered. Therefore, we believe it is crucial to monitor the pubertal development closely in Denmark in the coming decades.

Adolescent↗
PubMed2004

Enhanced local immune response in children with prolonged gastrointestinal symptoms.

AIM: Recently, we reported typical endoscopic findings and an increment in gammadelta+ T cells in the foregut among children with food-sensitive enteropathy other than coeliac disease. To find out the extend to which the upregulation of the local immune response might explain gastrointestinal (GI) complaints of the foregut, we sought to examine by the increment in gammadelta+ T cells a I-y consecutive series of children referred for recurrent GI complaints to a tertiary-level hospital. METHODS: A 1-y cohort of 102 children scheduled for gastroduodenoscopy were examined for mucosal histology and the densities of CD3+, alphabeta+ and alphabeta+ T-cell subsets from mid-duodenal specimens. The final diagnostic categories were used in analysing the data. RESULTS: Fifteen subjects showed villous atrophy and a high gammadelta+ T-cell density; the finding being compatible with coeliac disease (CD). At the other extreme, 20 subjects in whom diagnostic GI diseases were ruled out showed low densities and served as controls. The subjects reporting GI symptoms after an open food challenge with milk and/or cereals (n = 18) as well as children remitting with a milk- or cereal-eliminating diet but not responding to a challenge (n = 23) also expressed significantly higher densities of gammadelta+ T cells than the controls. In all, 45 of 102 children could be considered to have an elevated gamma6+ T-cell density as an indication of locally activated immune response. Lack of villous architecture and lymphonodular hyperplasia of the duodenal bulb as an endoscopic finding and atopic dermatitis but not the presence of DQ2 alleles showed a close association with these increased densities. CONCLUSION: Considering that an elevated incidence of gammadelta+ T cells is an indication of mucosal response against luminal antigens, up to half the children with prolonged GI symptoms have immune mediated disorder; CD and food allergy being the most obvious clinical entities.

Atrophy↗
PubMed2003

Serum thyroglobulin as a marker of thyroid neoplasms after childhood cancer.

AIM: To evaluate serum thyroglobulin (Tg) level as a marker of the development of thyroid disease when following individuals who received neck irradiation therapy in childhood. METHODS: In a non-randomized cross-sectional study Tg was assessed in 172 survivors of childhood cancer 10.8 y (1.9-24) median (range) after diagnosis and 7.9 y (0.9-24.3) median (range) after the end of treatment. The patients were divided into two groups: group 1 included 47 patients who had received irradiation to the neck and group 2 included 125 patients who did not receive irradiation to the neck. RESULTS: Patients who had received irradiation to the neck had significantly higher Tg levels compared with those who did not receive neck irradiation: median 14.0 (1.0-189.0) microg/L vs median 8.8, (0.7-112.2) microg/L (p < 0.001). Six out of seven patients with elevated Tg levels (>70 microg/L) had received neck irradiation. Among these six patients, two patients developed secondary differentiated thyroid cancer and two patients developed benign thyroid neoplasms. None of the patients who had normal levels of Tg developed thyroid cancer. CONCLUSION: A high Tg level should be a cause for further investigation in the follow-up of individuals who have received irradiation therapy in childhood.

Acute Disease↗
PubMed2001

Phosphorylation-dependent and -independent functions of p130 cooperate to evoke a sustained G1 block.

The retinoblastoma (pRb)-related p130 pocket protein is a regulator of cell growth and differentiation, and a candidate tumour suppressor. Both pRb and p130 operate through interactions with cellular proteins, including the E2F transcription factors. While such interactions are controlled by phosphorylation of multiple sites of pRb, regulation of p130 remains poorly understood. We now identify 22 in vivo phosphorylation sites of p130, targeted by diverse kinases, and present evidence for three cyclin-dependent kinase 4(6) [Cdk4(6)] specific phosphorylations, which appear critical for controlling the growth-restraining activity of p130. When expressed in U2OS cells, the phosphorylation-deficient mutant p130(Delta)(CDK4), in which the Cdk4 specific sites were mutated to alanine residues, imposed a more sustained G1 arrest than a constitutively active pRb(Delta)(CDK), known to repress all cellular E2F activity. Experiments using p130(Delta)(Cdk4) and another phosphorylation-deficient mutant, p130(PM19A), with 19 phosphorylation sites mutated, revealed that the p130-imposed G1 block reflects cooperative growth-suppressive effects of phosphorylation-regulated E2F binding and phosphorylation-independent sequestration of cyclin E(A)-Cdk2 through the N-terminal cyclin binding motif of p130.

Binding Sites↗
PubMed2001

Bone mass after treatment of malignant lymphoma in childhood.

BACKGROUND: Sex hormone deficiency, growth hormone deficiency, skeletal irradiation, and treatment with corticosteroids or methotrexate may all cause reduction in bone mass after treatment for childhood malignant lymphoma. Previous studies of the bone mass of childhood cancer survivors often lacked adequate local reference data, and survivors of malignant lymphoma were never analyzed separately. PROCEDURE: The bone mass of survivors of childhood Hodgkin disease (n = 23) or non-Hodgkin lymphoma (n = 21) was measured by dual-energy X-ray absorptiometry a median of 11 years after diagnosis (range 2-25). Results were compared with local data on 463 healthy controls. RESULTS: Adjusted for gender and age, the mean whole-body bone mineral content and bone mineral areal density were slightly, but significantly, reduced (0.5 and 0.4 SD lower than predicted). The reduced bone mineral content was associated with a significantly reduced height, whereas the size-adjusted bone mass (bone mineral content for bone area) did not differ significantly from that of controls. Lower height was related to male gender and to cranial, thoracic, and lumbar spine irradiation. Whole-body bone mineral content and bone mineral density were lower in persons treated with lumbar spine irradiation and whole-body bone mineral content was higher in nine women receiving sex hormone replacement therapy or oral contraceptives. Whole-body bone mass was not related to the cumulated doses of corticosteroids or methotrexate. CONCLUSIONS: Eleven years after diagnosis of childhood Hodgkin disease or non-Hodgkin lymphoma, the whole-body bone mass of survivors was only slightly reduced and the size-adjusted bone mass was normal.

Absorptiometry, Photon↗
PubMed2001

Degree of fatness after allogeneic BMT for childhood leukaemia or lymphoma.

Excess fatness is frequent after childhood ALL treated without BMT. We measured the whole-body percent fat by dual-energy X-ray absorptiometry and the body-mass index (weight/height(2) (kg/m(2)), BMI) in 25 survivors of childhood leukaemia or lymphoma (21 with ALL) who had received TBI and allogeneic BMT a median of 8 years ago (range 4-13). Adjusted for sex and age, the mean BMI was slightly but significantly reduced (0.4 s.d. below predicted) and the whole-body percent fat was significantly increased compared with healthy controls (1.1 s.d. above predicted). Eleven of 25 patients had a percent fat above the 90 percentile of the reference values, which indicates excess fatness. Adjusted for sex and age, a higher percent fat was related to additional cranial irradiation. Controlled for this, the whole-body percent fat seemed to be unrelated to age at BMT, length of follow-up, and previous chemotherapy. Compared with untransplanted ALL survivors treated with cranial irradiation, BMT survivors had significantly reduced BMI but similar whole body percent fat. BMI was a poor measure of body fatness in these patients. In conclusion, survivors of BMT for childhood leukaemia or lymphoma are adipose and slightly underweight and consequently have a substantially reduced lean body mass.

Body Composition↗
PubMed2001

Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the significance of prophylactic cranial irradiation.

OBJECTIVE: Focus on long-term side-effects after cancer therapy in childhood has become of the utmost importance. The hypothalamic-pituitary thyroid (HPT) axis is exposed to irradiation when some children are treated for acute lymphoblastic leukaemia (ALL) with prophylactic cranial irradiation (CIR). Whether this treatment causes hypofunction of the HPT axis remains controversial. DESIGN: We measured plasma levels of total T3 (T3), total T4 (T4) and TSH before stimulation with TRH and plasma levels of TSH, 30 and 150 minutes after stimulation with TRH in 95 patients in first continuous remission of childhood ALL. PATIENTS: Patients diagnosed with ALL before the age of 15 years between 1970 and 1991 and who were in first continuous remission and off treatment for at least one year were studied. The children were aged between 0.5 and 14.8 years (median: 3.9) at diagnosis of ALL. Thyroid function was assessed between 1.2 and 18.3 years (median: 7.6) after completion of therapy. MEASUREMENTS: We measured T4 levels before, and compared TSH levels before and after, stimulation with TRH in patients who were treated with prophylactic CIR (15-24 Gy) (n = 38) (CIR group) with patients who were treated with chemotherapy only (n = 57) (non-CIR group). RESULTS: We found that T3 and T4 levels were normal in all individuals (excluding the women who were on oral contraceptives). The median time from end of treatment to time at follow-up was 9.1 years in the non-CIR group vs. 4.2 years in the CIR group (P < 0.001), and the effect on follow-up time was significant (P = 0.04). It was estimated that just after irradiation, the TSH levels before and 30 and 150 minutes after TRH stimulation was 49% lower in the CIR group; however, after 4.0 years, TSH levels were not significantly different between the two groups. Although within normal limits, the T4 levels were significantly higher in the CIR group compared to the non-CIR group (P = 0.003). It was estimated that, just after the end of treatment, T4 was 19.9% higher in the CIR group. However, in the CIR group, the T4 level decreased significantly over time with -1.5% per year (P = 0.025), while the difference in the non-CIR group was not significant. There was no correlation between T4 and TSH levels and sex, age at diagnosis, age at the end of treatment or age at follow-up. CONCLUSIONS: We conclude that, in our cohort of survivors of childhood ALL, prophylactic cranial irradiation of the central nervous system did not have an adverse effect on hypothalamo-pituitary-thyroid function within a median follow-up time of 8 years.

Adolescent↗
PubMed2001

Obesity in adults and children: a call for action.

Obesity/overweight in adults and children is a worldwide health problem associated with substantial economic burden as measured by paid sick leave, life and disability insurance rates, and obesity-related physician visits and hospital stays. Overweight/obese people experience hypertension, elevated cholesterol, and type 2 diabetes and suffer more joint and mobility problems than people within the normal weight for height range. While there is need to understand individual behaviors that can be modified to promote weight loss and weight maintenance, there is as great a need to consider contextual factors at the societal level that can impede or even sabotage weight control efforts. In every country with improved living standards people will continue to eat too much and engage in too little physical activity. The call for action is for all modernized societies to alter environments and attitudes to support, rather than hinder, healthy dietary intake and being physically active.

Absenteeism↗
PubMed2001

Characteristics of the trauma recidivist: an exploratory descriptive study.

INTRODUCTION: The purpose of this study was to identify characteristics and perceptions of trauma recidivists. Information obtained from this study will help health care professionals better understand trauma patients and design more effective trauma prevention programs. METHODS: An exploratory descriptive, correlational design was used. A convenience sample of 100 trauma patients entering a midwestern university medical center were studied. A demographic chart review and a personal interview consisting of 29 questions were conducted for each subject. The interview questions sought information regarding high-risk behavior, risk-taking personality traits, safety precautions used, and social, psychological, and environmental factors surrounding the patient's traumatic event. RESULTS: Thirty-six percent of trauma patients studied were recidivists. The recidivist was more likely to be male, younger than 45 years, a member of a racial minority, single, uninsured, and have less than 12 years of education. Behavioral characteristics common to most recidivists included a history of past arrests, illegal drug use, and having witnessed past violent injuries. DISCUSSION: Trauma remains one of the most devastating diseases facing americans. Characteristics of trauma recidivists have been identified, and further research is needed to test possible interventions to curb the unnecessary trauma injuries that occur every day.

Age Distribution↗
PubMed2001

No effect of seasonal variation in training load on immuno-endocrine responses to acute exhaustive exercise.

This study was designed to examine the relationship between seasonal changes in training and competition load, and changes in leukocyte subsets, stress hormones, and interleukin-6 (IL-6) in response to a standardised bout of endurance exercise. In addition, changes in mood states were monitored. Ten male, international Nordic skiers, age 20-29, maximal oxygen uptake 70-82 ml x kg(-1) x min(-1) performed the same incremental treadmill tests to exhaustion at the same time of day (+/-1 h), during the competitive season (in-season HI test) and the recovery season (off-season LO test). The subject filled out a training and competition log (TC score) for three weeks prior to each test and a 65-item Profile of Mood State (POMS) test on arrival at the laboratory. Venous blood for haematological, hormonal, and IL-6 analysis was drawn before and at 0, 15, 30, 60, 120 and 240 min after the test. TC score was more than twice as high during the competitive season (16.0 +/- 3.9) compared to the off-season period (7.0 +/- 4.4). An ANOVA procedure for repeated measures showed no difference in exercise induced changes in concentrations of neutrocytes, lymphocytes, epinephrine, ACTH or cortisol between the in-season HI and off-season LO tests; however, norepinephrine and the IL-6 concentrations were elevated at the in-season HI test compared to the off-season LO test. There were no significant differences in POMS global mood score or sub-scores between the in-season HI and the off-season LO tests. Thus, in a group of elite Nordic skiers, we conclude that a doubling of the training and competition load during the winter season does not alter the leukocyte and stress hormone responses to an incremental exercise test to exhaustion.

Adaptation, Physiological↗
PubMed2000

An AB recombinant and its parental HIV type 1 strains in the area of the former Soviet Union: low requirements for sequence identity in recombination. UNAIDS Virus Isolation Network.

In the former Soviet Union (SU) increasing numbers of HIV-1 infections among injecting drug users (IDU) have been reported, especially in the Ukraine. The main subtype transmitted among the IDUs seems to be subtype A, but limited numbers of subtype B cases have also been reported. In Kaliningrad, Russia, an AB recombinant strain was earlier shown to be responsible for the local outbreak. Here we describe the genetic relationship of HIV-1 strains circulating among IDUs in the former SU. For subtype A and the AB recombinant strains nearly full-length genomes were sequenced, and for one subtype B strain the entire envelope gene was cloned. The relationship between the AB recombinant strain and the subtype A and subtype B strains and the mosaic structure of the recombinant was studied by phylogenetic analysis. Ukrainian A and B strains were shown to be the probable parental viruses of the Kaliningrad AB recombinant strain. In the envelope gene the recombination breakpoint could also be precisely mapped to a region of similarity of only 14 base pairs. This suggests that only short stretches of absolute sequence identity may be needed for efficient RNA recombination between HIV-1 subtypes.

Base Sequence↗
PubMed2000

Bone mass after allogeneic BMT for childhood leukaemia or lymphoma.

The bone mass was measured by dual energy X-ray absorptiometry in 25 survivors of childhood leukaemia or lymphoma (21 with ALL) who had received TBI and allogeneic BMT a median of 8 years ago (range 4-13). Results were compared with local data on 463 healthy controls and 95 survivors of childhood ALL treated without BMT. Adjusted for sex and age, the mean whole-body bone mineral content (BMC) and bone mineral areal density were significantly less than in healthy controls (0.8 and 0.5 s.d. less than predicted). The reduced BMC was caused by a significantly reduced height for age, whereas bone area for height and BMC for bone area were similar to controls. Less bone mass tended to be related to additional cranial irradiation and age above 20 years at follow-up. Controlled for this, the whole-body bone mass seemed to be unrelated to previous chemotherapy and endocrine status at follow-up and tended to be only marginally less in BMT patients than in ALL survivors treated without BMT. In conclusion, 8 years after allogeneic BMT for childhood leukaemia or lymphoma, the whole-body bone mass was only slightly reduced and the size-adjusted bone mass (BMC for bone area) was normal. Bone Marrow Transplantation (2000) 25, 191-196.

Adolescent↗
PubMed2000

Children with untreated food allergy express a relative increment in the density of duodenal gammadelta+ T cells.

BACKGROUND: We investigated whether children with food allergy (FA) express increased densities of intraepithelial gammadelta+ T cells similarly to subjects with celiac disease. METHODS: The duodenal specimens taken by gastroduodenoscopy from 20 children with untreated FA, 17 with treated FA, 12 with celiac disease (CD) and 12 controls were studied with monoclonal antibodies and a three-layer peroxidase staining method. RESULTS: The subjects with untreated FA expressed equal densities of total intraepithelial CD3+ and alpha/beta+ T cells, but significantly higher densities of gammadelta+ cells than the subjects currently on an elimination diet for FA or the controls. Accordingly, their gammadelta+/CD3+ ratio was higher. On the other hand, the results differed clearly from CD, where all the three cell populations showed high densities. Another finding that discriminated the subjects with FA from the CD patients was endoscopic examination. Lymphonodular hyperplasia (LNH) of the duodenal bulb with a normal villous pattern was demonstrated in 14 (70%) of the 20 subjects with untreated FA and in 8 (47%) of the 17 with treated FA, but in none of the celiac patients or controls. Surprisingly, the biopsy samples from the subjects with FA showed quite normal histological findings. CONCLUSIONS: According to this preliminary observation, high densities of intraepithelial gammadelta+ T cells and a significantly elevated gammadelta+/CD3+ ratio are associated with untreated FA. If seen LNH in a gastroduodenoscopy and/or increased densities of gammadelta+ T cells in the biopsy specimen, the possibility of gastrointestinal FA should be reliably assessed by a food challenge.

Adolescent↗
PubMed2000

Oocyte donation in women cured of cancer with bone marrow transplantation including total body irradiation in adolescence.

Female survivors of cancer in childhood and adolescence who have been treated with bone marrow transplantation including total body irradiation (TBI) are at high risk of developing ovarian follicular depletion and infertility. The lack of oocytes may be compensated for by oocyte donation but these patients also seem to have a uterine factor. Even though oestrogen replacement therapy is given, the growth of the uterus during adolescence is impaired. To our knowledge there have been no earlier reports of live births after oocyte donation in such patients. We report three cases of oocyte donation in women who, at a young age, were cured of haematological malignancies with bone marrow transplantation including TBI. In adolescence they developed ovarian failure and uterine volumes were assessed by ultrasonography. One woman with a uterus of almost normal size delivered a healthy child in the 37th week of gestation. Another woman with severely diminished uterine volume miscarried in the 17th week of gestation. The third woman has not yet conceived. Pregnancy achieved by oocyte donation is possible despite TBI in adolescence. However, the uterine factor is a concern and complications during pregnancy and preterm birth may be expected in these patients.

Acute Disease↗
PubMed2000

Primary and secondary prevention using lipid-lowering therapies.

The observation that coronary heart disease was greatest in those individuals with the highest cholesterol levels resulted in the development of interventions to lower cholesterol to improve coronary risk status. Some individuals will achieve target lipid levels with diet and lifestyle modification alone. Therefore, diet and lifestyle modification is the preferred initial treatment. For more aggressive management of those who do not respond to diet and lifestyle modification or who have documented coronary heart disease, lipid-lowering drugs, extensively tested in large, multicenter, randomized clinical trials are preferred. Initially, questions arose about adverse effects of lipid-lowering drugs, but continued use has demonstrated that these drugs are both safe and efficacious. The need remains, however, for clinicians to monitor each patient's response to lipid-lowering diets, lifestyle modification efforts, and drugs and evaluate whether beneficial effects outweigh the cost and potential for adverse effects.

Coronary Disease↗