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Biomedical subjects

D Holmgren

Publications and source records attributed to D Holmgren.

At least 19 recordsLinked to original sources

Limits on spin-independent interactions of weakly interacting massive particles with nucleons from the two-tower run of the cryogenic dark matter search.

We report new results from the Cryogenic Dark Matter Search (CDMS II) at the Soudan Underground Laboratory. Two towers, each consisting of six detectors, were operated for 74.5 live days, giving spectrum-weighted exposures of 34 (12) kg d for the Ge (Si) targets after cuts, averaged over recoil energies 10-100 keV for a weakly interacting massive particle (WIMP) mass of 60 GeV/c2. A blind analysis was conducted, incorporating improved techniques for rejecting surface events. No WIMP signal exceeding expected backgrounds was observed. When combined with our previous results from Soudan, the 90% C.L. upper limit on the spin-independent WIMP-nucleon cross section is 1.6 x 10(-43) cm2 from Ge and 3 x 10(-42) cm2 from Si, for a WIMP mass of 60 GeV/c2. The combined limit from Ge (Si) is a factor of 2.5 (10) lower than our previous results and constrains predictions of supersymmetric models.

Journal Article↗

Transplanted children's experiences of daily living: children's narratives about their lives following transplantation.

Transplantation is often an appropriate choice of treatment for children with end-stage renal, liver, heart or lung disease. Over the last decade, mortality and morbidity figures have been relatively stable and quality of life fairly good in children who have undergone organ transplantation. Few studies however, have focused on the experiences of transplantation from the child's perspective. The child's view is an important factor when evaluating the 'true' outcome and quality of life after transplantation. The aim of the present study was to illuminate the meaning of transplanted children's experiences of daily living. Unstructured interviews were carried out with 18 children and adolescents, aged 4-18 yr, who had undergone organ transplantation. Their narratives were transcribed and interpreted using a phenomenologic-hermeneutic method inspired by the philosophy of Ricoeur. Two main themes emerged: Being satisfied with life, with the themes: being able to live a normal life; someone who cares; coping with one's new life; and being dissatisfied with life, with the themes: not being able to live a normal life; lacking someone who cares; not being respected; existential thoughts. Most of the children and adolescents were of the opinion that they lived a normal life while the rest strived to achieve a normal life. Social support and mental support were of great importance and, when lacking, had negative consequences. Multi-disciplinary co-operation between healthcare professionals and between the healthcare system, the school and the family is crucial in order to optimize the outcome and quality of life after organ transplantation in children.

Activities of Daily Living↗

First results from the Cryogenic Dark Matter Search in the Soudan Underground Laboratory.

We report the first results from a search for weakly interacting massive particles (WIMPs) in the Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory. Four Ge and two Si detectors were operated for 52.6 live days, providing 19.4 kg d of Ge net exposure after cuts for recoil energies between 10 and 100 keV. A blind analysis was performed using only calibration data to define the energy threshold and selection criteria for nuclear-recoil candidates. Using the standard dark-matter halo and nuclear-physics WIMP model, these data set the world's lowest exclusion limits on the coherent WIMP-nucleon scalar cross section for all WIMP masses above 15 GeV/c2, ruling out a significant range of neutralino supersymmetric models. The minimum of this limit curve at the 90% C.L. is 4 x 10(-43) cm2 at a WIMP mass of 60 GeV/c2.

Journal Article↗

Increased left ventricular mass in obese adolescents.

AIMS: An increase of left ventricular mass (LVM) has been reported in obese adolescents in previous studies using echocardiography. The aim of our study was to determine the extent of the increase in LVM and correlation to other risk factors using cardiac magnetic resonance imaging in obese and lean adolescents. METHODS AND RESULTS: Nineteen obese and 20 lean adolescents were recruited. Following resting blood pressure measurements and blood sampling for insulin, triglycerides, and cholesterol levels, all subjects underwent cardiac magnetic resonance examination to assess LVM. LVM adjusted for body height was 16% greater in obese compared to lean adolescents (median 66 g/m, p = 0.0042). Obese subjects had higher resting systolic blood pressures than controls (median 115 vs. 110 mmHg, p = 0.0077) and higher fasting triglyceride and insulin levels. HDL-cholesterol levels were lower in the obese group compared with the lean group. CONCLUSIONS: Obese adolescents had a higher LVM than age-matched lean subjects, which correlated mainly with body mass index and systolic blood pressure. These findings add to the established cardiovascular risk profile of obese adolescents.

Adolescent↗

Clinical signs of heart failure are associated with increased levels of natriuretic peptide types B and A in children with congenital heart defects or cardiomyopathy.

AIM: To study whether natriuretic peptide types B (BNP) and A (ANP) reflect clinical signs of heart failure (CSHF) in children with congenital heart defects or cardiomyopathy resulting in different types of haemodynamic situations, such as pressure overload in coarctation of the aorta (CoA), volume overload in ventricular septal defect (VSD) or systolic dysfunction in dilated cardiomyopathy (DCM). METHODS: Blood samples for plasma P-BNP and P-ANP were taken before procedures during regular investigation from 26 children (9 CoA, 11 VSD and 6 DCM). The ordinary paediatric cardiologist performed the cardiac evaluation and the data were retrieved from medical charts. CSHF was considered positive if two of the following criteria were fulfilled: reduced physical capacity, feeding disorders, dyspnoea, tachypnoea, hepatomegaly and oedema. The statistical methods were non-parametric. RESULTS: 0/9 children with CoA, 5/11 with VSD and 6/6 with DCM had CSHF. In children with CSHF, P-BNP and P-ANP were higher, 263 ng l(-1) (range 47.5-1300) and 303 ng l(-1) (range 168-466), than in those without CSHF, 12.3 ng l(-1) (range 4.8-30.8) and 42.9 ng l(-1) (range 13.7-189), respectively (p < 0.001, Mann-Whitney U-test), irrespective of the diagnosis. The same relationship was also found in the group of children with VSD. CONCLUSION: Plasma levels of ANP and BNP increase in children with CSHF. This increase is seen irrespective of whether it is due to systolic dysfunction, as in children with DCM, or to a volume overload with a normal systolic function, as in children with VSD.

Adolescent↗

Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings.

AIMS: To determine the frequency of cardiomyopathy in children with mitochondrial disease and describe their clinical course, prognosis and cardiological manifestations. METHODS AND RESULTS: Of 301 children with CNS and neuromuscular disease referred to our institution in 1984 to 1999, 101 had mitochondrial disease. Seventeen patients had cardiomyopathy, diagnosed by echo-Doppler investigations, all of the hypertrophic, non-obstructive type. The onset of symptomatic mitochondrial disease ranged from birth to 10 years of age. Eight children had cytochrome-c oxidase deficiency, while the remaining nine had various defects. Cardiomyopathy was diagnosed from birth to 27 years. Left ventricular posterior wall and septal thickness were both increased: z-scores +4.6+/-2.6 and +4.3+/-1.6 (mean+/-SD), respectively. The left ventricular diastolic diameter z-score, +1.3+/-3.4, and fractional shortening, 24+/-13%, displayed marked variations. Nine patients developed heart failure. Eleven patients with cardiomyopathy died, including all eight with cytochrome-c oxidase deficiency, and one patient underwent a heart transplantation. Mortality in children with mitochondrial disease was higher in those with cardiomyopathy (71%) than those without (26%) (P<0.001). CONCLUSIONS: In children with mitochondrial disease, cardiomyopathy was common (17%) and was associated with increased mortality. The prognosis for children with cytochrome-c oxidase deficiency and cardiomyopathy appeared to be particularly unfavorable.

Adolescent↗

Reversal of protein-losing enteropathy in a child with Fontan circulation is correlated with central venous pressure after heart transplantation.

We report on the reversal of protein-losing enteropathy (PLE) after heart transplantation (HTx) in a 10-yr-old boy with Fontan circulation, previously treated unsuccessfully with heparin for several months. The protein loss continued immediately after the Tx. During the following month, however, a gradual decrease in protein loss was observed, which correlated with a decrease in the inferior vena cava (IVC) pressure. The patient is doing well with a normal serum albumin level and a normal IVC pressure, 2 yr after Tx.

Blood Pressure↗

Transcutaneous-PO2 monitoring for detection of exercise-induced right-to-left shunts in children with congenital heart defects: a case report.

UNLABELLED: A 2-y-old boy with scimitar syndrome underwent surgery involving the redirection of partial anomalous pulmonary venous return to the left atrium. Heart catheterization after the operation did not reveal any significant intra-cardiac shunts. An exercise test performed at the age of 10 y revealed a reduction in working capacity. At the age of 12 y, the patient became unconscious and experienced seizures during heavy physical exercise. EEG and Holter ECG examinations were normal. In a second exercise test, a fall in transcutaneous PO2 was demonstrated at the start of the test. A new heart catheterization revealed communication between the inferior vena cava and the left atrium owing to a misplaced patch. No right-to-left shunt was found at rest, probably as a result of drainage of the inferior vena cava to the superior vena cava by the azygous vein. An exercise test after re-operation revealed normal conditions. CONCLUSION: Haemodynamic studies during heart catheterization in children are usually performed at rest. This could result in exercise-induced right-to-left-shunts being overlooked. The use of PtcO2 monitoring during exercise tests is a non-invasive means of exposing these shunts.

Blood Gas Monitoring, Transcutaneous↗

Failure of treatment with cephalexin for Lyme disease.

CONTEXT: Lyme disease typically presents with a skin lesion called erythema migrans (EM), which though often distinctive in appearance may be confused with cellulitis. The first-generation cephalosporin, cephalexin monohydrate, is effective for treating bacterial cellulitis but has not been recommended or studied for treating Lyme disease because of poor in vitro activity. OBJECTIVE: To describe the outcome of patients with EM who were treated with cephalexin. PATIENTS AND METHODS: Patients presenting with EM to the Lyme Disease Diagnostic Center in Westchester, NY (May 1992-September 1997). A 2-mm punch biopsy specimen of the leading edge of the EM lesion and/or blood was cultured for Borrelia burgdorferi. RESULTS: Eleven (2.8%) of 393 study patients had been initially treated with cephalexin prior to our evaluation; 9 (82%) were originally diagnosed with cellulitis. Cephalexin was administered for 8.6 days (range, 2-21 days) prior to presentation. All 11 patients had clinical evidence of disease progression, including 8 whose rash enlarged, 2 who developed seventh-nerve palsy (1 with new EM lesions), and 1 who developed new EM lesions. Borrelia burgdorferi grew in cultures from 5 patients despite a mean of 9.8 days of treatment with cephalexin (range, 5-21 days). CONCLUSION: Cephalexin should not be used to treat early Lyme disease and should be prescribed with caution during the summer months for patients believed to have cellulitis in locations where Lyme disease is endemic.

Adult↗

Increase in size of the pulmonary autograft after the Ross operation in children: growth or dilation?

OBJECTIVE: We sought to assess growth properties of the pulmonary autograft after the Ross operation in children. METHODS: Eight infants with critical aortic stenosis who underwent the Ross operation early in life (median age, 6.4 months) were followed up regarding the possible growth of the autograft. The pulmonary autograft was measured repeatedly by echocardiography during the follow-up, ranging from 6 months to 7 years (median, 5.2 years). Twelve normal children who served as control subjects were similarly followed from 3.9 to 5.8 years (median, 4.9 years). RESULTS: Somatic growth during the follow-up period was significant and was reflected in a doubling of the body surface area, which increased from 0.33 +/- 0.14 m(2) to 0.74 +/- 0.21 m(2). The proximal part of the autograft increased from 13.6 +/- 3.6 mm to 23.3 +/- 3.7 mm (mean +/- SD) and the distal part from 10.5 +/- 2.5 mm to 15.9 +/- 2.8 mm. Growth pattern of the autograft was analyzed by relating measured diameters to predicted normal diameters (ie, Z values). During the first year after the operation, the mean Z value of the proximal autograft increased from 0.2 to 2.2, indicating a more rapid increase than the predicted increase and was also significantly higher than that of the control group (P =.01). After the first year, Z-value changes in patients and control subjects were very similar. CONCLUSIONS: We thus conclude that the pulmonary autograft in the aortic position after the Ross operation does increase in size and that the pattern of this increase is suggestive of passive dilation in the early postoperative period, followed by normal active growth.

Aortic Valve Stenosis↗

Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms.

UNLABELLED: Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. CONCLUSIONS: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition.

Administration, Inhalation↗

Thoracic organ transplantation in children. The Sahlgrenska University Hospital experience.

On the basis of the experience acquired from more than 350 thoracic organ transplantations in adults, the outcome of thoracic organ transplantations in the paediatric age group (0-17 years of age) performed consecutively from 1989 to 1998 at our centre was reviewed. Heart transplantation was performed in 27 patients, heart-lung in 6 and bilateral lung transplantation in 2 patients. The preoperative diagnosis included dilated cardiomyopathy in 17 patients, congenital heart defects in 8, hypertrophic cardiomyopathy in 2, cystic fibrosis in 1 and secondary and primary pulmonary hypertension in 5 and 2 patients, respectively. The median age at transplantation and the follow-up period were 12.7, range 0.3-18.2, and 4, range 0.1-9.2 years, respectively. No early deaths occurred after heart transplantation, but one patient died of coronary artery disease 4.8 years after transplantation. One early death occurred one week after heart-lung transplantation as a result of bleeding complications, and another patient died of obliterative bronchiolitis and pulmonary infection 2.5 years after surgery. The remaining patients are alive and have been functionally rehabilitated. In conclusion, despite a relatively small centre volume, paediatric thoracic organ transplantations can be performed with good short- and medium-term survival and good functional status can be achieved by deriving knowledge and experience from transplantations in adults and by collaboration between the various professionals involved in the caring process.

Adolescent↗

Immunotherapy in children with allergic asthma: effect on bronchial hyperreactivity and pharmacotherapy.

BACKGROUND: Immunotherapy has been shown to reduce allergen sensitivity to allergens such as cat and dust mite. The aim of this study was to investigate the effect of cat or dust mite immunotherapy on bronchial hyperreactivity and the need for inhaled corticosteroids in children with asthma, cat or dust mite allergy, and hay fever. SUBJECTS: Twenty-nine children, 7 to 16 years old, completed the 3-year study. They were randomly allocated to receive cat/dust mite or placebo and birch/timothy immunotherapy. METHODS: Before immunotherapy was begun and then once each year, bronchial histamine challenges were performed. Bronchial allergen challenge with the perennial allergen was done before and after the 3-year study. Pharmacotherapy was given according to a standardized protocol. RESULTS: PC20 allergen increased significantly in both the active immunotherapy group (P <.001) and in the placebo-pollen group (P <.05). PC20 histamine increased continuously in the active immunotherapy group (P <.05 and P =.002 after 1 and 3 years, respectively) and had also increased after 3 years in the placebo-pollen group (P <.05). The difference between the 2 groups was significant for PC20 allergen (P =.001) but not for PC20 histamine. There was no significant change in the dose of inhaled budesonide needed for symptom control in either of the groups. CONCLUSION: Pollen immunotherapy combined with inhaled corticosteroids results in improvement of both cat/dust mite bronchial sensitivity and hyperresponsiveness to histamine. The combination of cat or dust mite, pollen immunotherapy, and inhaled budesonide enhances this improvement. Cat immunotherapy also induces cat allergen tolerance.

Adolescent↗

Histamine provocation in young, awake children with bronchial asthma, using a fall in oxygenation as the only indicator of a bronchial reaction.

Bronchial provocation with histamine was performed in 11 boys and 6 girls, age range 2.7-7.4 y, with unspecific respiratory symptoms or bronchial asthma, using a fall in oxygenation as the only indicator of a bronchial reaction. In addition to transcutaneous oxygen tension (tcPO2), transcutaneous carbon dioxide tension (tcPCO2) was continuously monitored during the provocation procedure in order to identify possible changes in ventilation. A fall of 20% or more in the tcPO2 below a "floating" baseline value, defined as the highest tcPO2 value between the inhalations of histamine up to that point, was regarded as indicating a significant bronchial reaction. One child was excluded from the study because of an "early, false-positive" reaction due to hyperventilation during the inhalation, verified by a decrease in the tcPCO2 followed by a compensatory period of hypoventilation, resulting in a fall of more than 15% in the tcPO2 after the inhalation of saline. In the vast majority of the children, however, the tcPO2 values remained stable during the first dose stages of saline and histamine, with either a gradual fall immediately before or a distinct fall in conjunction with the reaction. The mean reaction concentration was significantly lower in the group of children with clinical asthma, 0.74 mg/ml, compared with the group of children with unspecific respiratory symptoms, 2.00 mg/ml (p = 0.03). In conclusion, a 20% fall in the tcPO2 can be used as the only indicator of a bronchial reaction during bronchial provocation tests in young, awake children. Changes in ventilation evaluated by monitoring tcPCO2, makes it possible to distinguish between a fall in oxygen tension due to an early, "false" reaction as a result of hypoventilation and a "true" bronchial reaction.

Age Factors↗

Association of specific subtypes of Borrelia burgdorferi with hematogenous dissemination in early Lyme disease.

To investigate whether genetic diversity of Borrelia burgdorferi sensu stricto may affect the occurrence of hematogenous dissemination, 104 untreated adults with erythema migrans from a Lyme disease diagnostic center in Westchester County, New York, were studied. Cultured skin isolates were classified into 3 groups by a polymerase chain reaction amplification and restriction fragment length polymorphism (RFLP) method. A highly significant association between infecting RFLP type in skin and the presence of spirochetemia was found (P<.001). The same association existed for the presence of multiple erythema migrans lesions (P=.045), providing clinical corroboration that hematogenous dissemination is related to the genetic subtype of B. burgdorferi sensu stricto. There were no significant associations between RFLP type and seropositivity or clinical symptoms and signs except for a history of fever and chills (P=.033). These results suggest that specific genetic subtypes of B. burgdorferi sensu stricto influence disease pathogenesis. Infection with different subtypes of B. burgdorferi sensu stricto may help to explain differences in the clinical presentation of patients with Lyme disease.

Adult↗

Clinical and laboratory spectrum of culture-proven human granulocytic ehrlichiosis: comparison with culture-negative cases.

We describe the clinical and laboratory manifestations of human granulocytic ehrlichiosis (HGE) in eight patients for whom cultures were positive for the HGE agent and compare them with 15 patients for whom cultures were negative but who fulfilled a modified New York State Surveillance definition for HGE. Polymerase chain reaction analysis was positive in 8 (100%) of 8 culture-positive cases vs. 3 (20%) of 15 culture-negative cases (P < .001), morulae were detected in 7 (100%) of 7 culture-positive cases in which tests were performed vs. 0 of 15 culture-negative cases (P < .001), and a fourfold change in antibody titer was demonstrated in 6 (75%) of 8 culture-positive cases vs. 9 (69%) of 13 culture-negative cases (P = not significant). Patients for whom cultures were positive had higher mean oral temperatures +/- SD at presentation than did patients for whom cultures were negative (38.6 degrees C +/- 0.7 degree C vs. 37.2 degrees C +/- 0.8 degree C, respectively; P = .002). Other symptoms and signs were not significantly different between the two groups. Multivariate analysis revealed that the lymphocyte count at presentation was significantly lower in culture-positive cases than in culture-negative cases. Clinical response to treatment was similar in the two groups. Culture confirmation of HGE is the gold standard for defining the sensitivity and specificity of other diagnostic tests presently being developed.

Adult↗

Aortic valve replacement with a pulmonary autograft in infants with critical aortic stenosis.

Seven patients with critical aortic stenosis underwent aortic valve replacement with a pulmonary autograft (the Ross operation) between the ages of 5 weeks and 9 months. The operation was considered mandatory for survival because of continued severe heart failure or valve avulsion. Six of the patients had undergone unsuccessful previous palliations, such as commissurotomy, balloon dilation, and transventricular valvotomy, performed singly (n = 1) or in combination (n = 5). The other patient with a severely hypoplastic aortic valve ring underwent the Ross procedure as a primary operation. Two operative deaths occurred. In both cases severe endocardial fibroelastosis was detected at autopsy. One late death 1 year after the operation resulted from progressive hypertrophic cardiomyopathy and pulmonary hypertension. The rest of the patients are doing well, without medications. Apart from trivial regurgitation in two patients, the pulmonary autograft is performing well.

Aortic Valve↗

Influence of breathing pattern on transcutaneous oxygen and carbon dioxide tension during histamine provocation in children with bronchial asthma.

The influence of the breathing pattern on transcutaneous blood gases was evaluated in 18 boys and 8 girls 7-18 years of age, with bronchial asthma, during bronchial provocation with histamine-HCl. Transcutaneous oxygen tension (tcPO2), carbon dioxide tension (tcPCO2) and the breathing pattern assessed by the transthoracic impedance technique were continuously monitored during the provocation. At reaction, when the fall in the forced expiratory volume in 1 s (FEV1) was 20% or more, the tcPO2 fell by 15% or more below the baseline in 22/26 and by 20% or more in 14/26 children. In some children, a marked fall in the tcPO2 was already noted after the saline inhalation and the first histamine dose steps without simultaneous changes in the FEV1. This early fall in the tcPO2 correlated to changes in the breathing pattern and was interpreted as a sign of compensatory hypoventilation secondary to the hyperventilation observed during the inhalations. We conclude that transcutaneous oxygen tension can be used as an indicator of a bronchial reaction during bronchial provocation tests in children only if one takes account of the fact that the breathing pattern during the inhalation of the challenge compound per se has an effect on the oxygen tension.

Administration, Inhalation↗