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Biomedical subjects

J Andresen

Publications and source records attributed to J Andresen.

At least 19 recordsLinked to original sources

Standardised work-up programme for fever of unknown origin and contribution of magnetic resonance imaging for the diagnosis of hidden systemic vasculitis.

BACKGROUND: Fever of unknown origin (FUO) is a diagnostic challenge. Rheumatologists are often in charge of patients with FUO because the vasculitides, especially, are potential and common causes of FUO. OBJECTIVE: To evaluate the value of a standardised investigation to identify the cause of FUO. METHODS: A standardised work-up programme for patients with FUO was started at the beginning of September 1999. The rate of identified causes of FUO was compared between all patients with FUO admitted to a tertiary care centre of rheumatology between January 1996 and August 1999 (control group) and September 1999 and January 2003 (work-up group). In January 2002 magnetic resonance imaging (MRI) was added to the investigation. RESULTS: 67 patients with FUO were identified--32 before and 35 after institution of the work-up programme. Before implementation 25% of all patients with FUO remained undiagnosed, after implementation 37%. After institution of the investigation the percentage of patients with vasculitides increased significantly from 6% (n = 2) to 26% (n = 9, p = 0.047, Fisher's exact test). This increase could be attributed to the addition of MRI in 2002. When all patients with FUO before 2002 (n = 55) and thereafter (n = 12) were compared the prevalence of systemic vasculitis increased from 11% (n = 6) to 42% (n = 5, p = 0.021). CONCLUSION: Implementation of a standardised work-up programme for FUO did not improve the overall rate of diagnosis. Addition of MRI significantly increased the diagnosis of systemic vasculitis as the underlying cause of FUO. MRI should be included in the investigation of patients with FUO when vasculitis is suspected.

Adult↗

The effects of granulocyte colony-stimulating factor and neutrophil recruitment on the pulmonary chemokine response to intratracheal endotoxin.

Although G-CSF has been shown to increase neutrophil (polymorphonuclear leukocyte, PMN) recruitment into the lung during pulmonary infection, relatively little is known about the local chemokine profiles associated with this enhanced PMN delivery. We investigated the effects of G-CSF and PMN recruitment on the pulmonary chemokine response to intratracheal LPS. Rats pretreated twice daily for 2 days with an s.c. injection of G-CSF (50 microg/kg) were sacrificed at either 90 min or 4 h after intratracheal LPS (100 microg) challenge. Pulmonary recruitment of PMNs was not observed at 90 min post LPS challenge. Macrophage inflammatory protein-2 (MIP-2) and cytokine-induced neutrophil chemoattractant (CINC) concentrations in bronchoalveolar lavage (BAL) fluid were similar in animals pretreated with or without G-CSF at this time. G-CSF pretreatment enhanced pulmonary recruitment of PMNs (5-fold) and greatly reduced MIP-2 and CINC levels in BAL fluid at 4 h after LPS challenge. In vitro, the presence of MIP-2 and CINC after LPS stimulation of alveolar macrophages was decreased by coculturing with circulating PMNs but not G-CSF. G-CSF had no direct effect on LPS-induced MIP-2 and CINC mRNA expression by alveolar macrophages. Pulmonary recruited PMNs showed a significant increase in cell-associated MIP-2 and CINC. Cell-associated MIP-2 and CINC of circulating PMNs were markedly increased after exposure of these cells to the BAL fluid of LPS-challenged lungs. These data suggest that recruited PMNs are important cells in modulating the local chemokine response. G-CSF augments PMN recruitment and, thereby, lowers local chemokine levels, which may be one mechanism resulting in the subsidence of the host proinflammatory response.

Animals↗

Impact of attachment styles on dream recall and dream content: a test of the attachment hypothesis of REM sleep.

We tested the hypothesis (McNamara 1996; Zborowski and McNamara 1998) that dream recall and dream content would pattern with interpersonal attachment styles. In study I, college student volunteers were assessed on measures of attachment, dream recall, dream content and other psychologic measures. Results showed that participants who were classified as 'high' on an 'insecure attachment' scale were significantly more likely to (a) report a dream, (b) dream 'frequently', and (c) evidence more intense images that contextualize strong emotions in their dreams as compared with participants who scored low on the insecure attachment scale. In study II, 76 community dwelling elderly volunteers completed measures of attachment, and dream recall. Participants whose attachment style was classified as 'preoccupied' were significantly more likely to report a dream and to report dreams with higher mean number of words per dream as compared with participants classified as 'securely' attached or as 'avoidant' or as 'dismissing.' Dream recall was lowest for the avoidant subjects and highest for the preoccupied subjects. These data support the view that rapid eye movement (REM) sleep and/or dreaming function, in part, to promote attachment.

Adult↗

The Danish National Birth Cohort--its background, structure and aim.

BACKGROUND: It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view, and diseases such as cardiovascular morbidity, cancer, mental illnesses, asthma, and allergy may all have component causes that act early in life. Exposures in this period, which influence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. METHODS: To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better suited for this kind of research than most other countries because of their population-based registers on diseases, demography and social conditions, linkable at the individual level by means of the unique ID-number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. Participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore, a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000. a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this.

Cohort Studies↗

Cultural competence and health care: Japanese, Korean, and Indian patients in the United States.

Cultural competence requires sensitivity to the diverse ethnic, religious, and cultural expectations of patients in our health care system. In the increasingly multicultural world of the city hospital, patients will benefit from increased cultural competency on the part of health care providers. This study interviews Japanese, Korean, and Indian immigrants to the United States, showing that these individuals hold vastly different expectations concerning: 1) when to seek medical assistance; 2) the role of the doctor in the community; 3) the role of the patient and the patient's family in conversations with the medical specialist; 4) the roles of doctors versus nurses; 5) issues of privacy and disclosure to patient and family; 6) organ donation; and 7) end-of-life care. The paper concludes with immigrants' views on what would make their medical experience in the United States more comfortable, and hence, potentially more beneficial to their mental and physical health.

Anecdotes as Topic↗

Single axon analysis of pulvinocortical connections to several visual areas in the macaque.

The pulvinar nucleus is a major source of input to visual cortical areas, but many important facts are still unknown concerning the organization of pulvinocortical (PC) connections and their possible interactions with other connectional systems. In order to address some of these questions, we labeled PC connections by extracellular injections of biotinylated dextran amine into the lateral pulvinar of two monkeys, and analyzed 25 individual axons in several extrastriate areas by serial section reconstruction. This approach yielded four results: (1) in all extrastriate areas examined (V2, V3, V4, and middle temporal area [MT]/V5), PC axons consistently have 2-6 multiple, spatially distributed arbors; (2) in each area, there is a small number of larger caliber axons, possibly originating from a subpopulation of calbindin-positive giant projection neurons in the pulvinar; (3) as previously reported by others, most terminations in extrastriate areas are concentrated in layer 3, but they can occur in other layers (layers 4,5,6, and, occasionally, layer 1) as collaterals of a single axon; in addition, (4) the size of individual arbors and of the terminal field as a whole varies with cortical area. In areas V2 and V3, there is typically a single principal arbor (0.25-0.50 mm in diameter) and several smaller arbors. In area V4, the principal arbor is larger (2.0- to 2.5-mm-wide), but in area MT/V5, the arbors tend to be smaller (0.15 mm in diameter). Size differences might result from specializations of the target areas, or may be more related to the particular injection site and how this projects to individual cortical areas. Feedforward cortical axons, except in area V2, have multiple arbors, but these do not show any obvious size progression. Thus, in areas V2, V3, and especially V4, PC fields are larger than those of cortical axons, but in MT/V5 they are smaller. Terminal specializations of PC connections tend to be larger than those of corticocortical, but the projection foci are less dense. Further work is necessary to determine the differential interactions within and between systems, and how these might result in the complex patterns of suppression and enhancement, postulated as gating mechanisms in cortical attentional effects, or in different states of arousal.

Animals↗

Brain lesions in preterms: origin, consequences and compensation.

Twenty-nine high-risk preterm born children, from a cohort with cerebral blood flow (CBF) measurements in the first 2 d of life, were examined prospectively at the age of 5.5-7 y neurologically, neuropsychologically and by magnetic resonance imaging (MRI). They were compared to 57 control children in terms of neurology and neuropsychology. Abnormal MRI was found in 19 children. Low oxygen delivery to the brain was found in 63% of them, in contrast to 12.5% in those with normal MRI, indicating neonatal hypoxia-ischemia as an important factor. The MRI abnormalities were mainly periventricular lesions (n = 19), especially periventricular leucomalacia (PVL, n = 17). Three of the very preterm children had severe cerebellar atrophy in addition to relatively mild periventricular abnormalities. MRI showed specific morphological correlates for the major disabilities, e.g. spastic CP (involvement of motor tracts), mental retardation (bilateral extensive white matter reduction or cerebellar atrophy) and severe visual impairment (severe optic radiation involvement). A morphological correlate for minor disabilities, i.e. functional variations in motor performance or intelligence, was not found, with the exception that symptoms of attention deficit hyperactivity disorder were related to mild MRI abnormalities. This could mean that with respect to cognitive functions, mild or unilateral periventricular MRI lesions could be compensated. However, as among preterms without mental retardation (n = 19), IQ was generally and significantly lower than in the control group; other, more chronic pathogenetic factors, not detectable by MRI alone, may play a role.

Attention Deficit Disorder with Hyperactivity↗

The striatum in a putative cerebral network activated by verbal awareness in normals and in ADHD children.

The aim of the present study was to evaluate the striatum's involvement in verbal awareness (semantic processing and supra-modal attention) in normals and children with attention deficit hyperactivity disorder (ADHD). Our previous finding of striatal hypoperfusion in ADHD at rest, supports our prediction that the striatum will also show reduced activation in response to tasks requiring verbal awareness. Regional cerebral blood flow (rCBF) was studied with the Xenon133 SPECT method in 12 boys with ADHD and six normal controls. The experimental controls included: (1) White Noise, (2) Passive Listening to a series of animal names, and (3) Detection of Targets ("dangerous animals") from the same series of animal names. The conditions were selected to isolate the semantic processing (Passive Listening - White Noise) and supra-modal attention components (Detection of Targets - Passive Listening of verbal awareness). ADHD children had decreased rCBF in the right striatum when compared to normals (mean difference from grand mean of each subject 8.06 ml/100 g/min vs 14.16 ml/100 g/min, p < 0.05). Factor analysis of the rCBF data revealed high factor I loadings for the frontal and striatal regions, which, in conjunction with the nature of the experimental conditions supported the inference that factor I mediated verbal awareness. Factor scores, which summarized the activity of all of the regions of interest (ROI's) on factor I, were differentially affected by the language component of the experimental tasks. Function scores were derived from factor I for the anterior cingulum and infero-frontal regions to evaluate their respective involvement in supra-modal attention and semantic processing. Function scores were also developed for the striatum, because of its central location and potential role in ADHD. The anterior cingulum was activated by supra-modal attention. The infero-frontal and the striatal regions were both activated by the language demands of the tasks. However, the striatum demonstrated reduced function scores (p < 0.05) in ADHD for all tasks. Our finding that the anterior gyrus cinguli were activated by supramodal attention and that the infero-frontal and striatal regions were activated by semantic processing supports the involvement of these ROI's in verbal awareness. Furthermore, the depressed functional contribution of the striatum to verbal awareness in ADHD children is consistent with and helps to explain their reduced cognitive control over behaviour and mental function.

Journal Article↗

[Long-term prognosis in febrile convulsions with and without prophylaxis].

This is a long-term follow-up of occurrence of epilepsy, neurological, motor, intellectual, cognitive, and scholastic achievements in a cohort of children with febrile convulsions (n = 289), randomized in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures). At follow-up the two groups were of almost identical age (14.0 vs. 14.1 years), body weight (58.2 vs. 57.2 kg), height (168.2 vs. 167.7 cm) and head circumference (55.9 vs. 56.2 cm). The neurological examination, fine and gross motor development on Stott motor test, intellectual performance on the Wechsler Intelligence Scale for Children verbal IQ (105 vs. 105), performance IQ (114 vs. 111) and full scale IQ (110 vs. 108). cognitive abilities on an neuropsychological test battery, including short and long term, auditory and visual memory, visuomotor tempo, computer reaction time, reading test, scholastic achievements and the occurrence of subsequent epilepsy were also very similar. Children with simple and complex febrile convulsions had the same benign outcome. The long term prognosis in terms of subsequent epilepsy, neurological, motor, intellectual, cognitive, and scholastic ability was not influenced by the type of treatment applied in early childhood. Preventing new febrile convulsions appears no better in the long run than abbreviating them.

Anticonvulsants↗

Phase 1 safety trial of Filgrastim (r-metHuG-CSF) in non-neutropenic patients with severe community-acquired pneumonia.

The objectives of the present study were to: (1) evaluate the safety of Filgrastim therapy in non-neutropenic patients with severe community-acquired pneumonia; (2) determine the absolute neutrophil count (ANC) response to various dosages of Filgrastim in non-neutropenic patients with active infection; and (3) describe the impact of therapy with Filgrastim in combination with antibiotics on selected pneumonia-related clinical parameters. The study design was an open-label, dose-ranging, clinical trial, set in the General Clinical Research Unit of a large, public community hospital. The study population consisted of 30 patients who had presented to the Emergency Department with severe, community-acquired pneumonia. One of five dosages (75, 150, 300, 450 or 600 micrograms day-1) of Filgrastim (r-metHuG-CSF) was given subcutaneously daily for 10 days, until discharge or until the absolute neutrophil count > 75 x 10(9) l(-1), whichever was earlier. Vital signs, pulse oximetry, arterial blood gases, daily complete blood counts with differential, serum chemistries, coagulation profiles, electrocardiograms, chest radiographs, plasma G-CSF concentrations and duration of hospitalization were measured. There was no evidence of Filgrastim-related lung injury or evidence of extra-pulmonary toxicity. There was no apparent dose-response effect of Filgrastim on pneumonia-related clinical variables. Dosages of Filgrastim between 150 and 600 micrograms day-1 had similar effects on increasing the ANC. Filgrastim appeared to be safe in non-neutropenic patients with severe, community-acquired pneumonia when given in dosages of 75-600 micrograms day-1 in combination with appropriate antibiotic therapy. Further study is needed to determine the effect of Filgrastim on morbidity, mortality and duration of symptoms in this patient population.

Adult↗

Long term outcome of prophylaxis for febrile convulsions.

A cohort of 289 children with febrile convulsions who had been randomised in early childhood to either intermittent prophylaxis (diazepam at fever) or no prophylaxis (diazepam at seizures) was followed up 12 years later. The study focused on the occurrence of epilepsy and on neurological, motor, intellectual, cognitive, and scholastic achievements in the cohort. At follow up the two groups were of almost identical age (14.0 v 14.1 years), body weight (58.2 v 57.2 kg), height (168.2 v 167.7 cm), and head circumference (55.9 v 56.2 cm). The occurrence of epilepsy (0.7% v 0.8%), neurological examination, fine and gross motor development on the Stott motor test, intellectual performance on the Wechsler intelligence scale for children verbal IQ (105 v 105), performance IQ (114 v 111), and full scale IQ (110 v 108), cognitive abilities on a neuropsychological test battery, including short and long term, auditory and visual memory, visuomotor tempo, computer reaction time, reading test, and scholastic achievement were also very similar. Children with simple and complex febrile convulsions had the same benign outcome. The long term prognosis in terms of subsequent epilepsy, neurological, motor, intellectual, cognitive, and scholastic ability was not influenced by the type of treatment applied in early childhood. Preventing new febrile convulsions appears no better in the long run than abbreviating them.

Adolescent↗

Personal decisionmaking styles and long-term care choices.

To learn more about how older people make decisions about long-term care (LTC), in-depth interviews were conducted with 63 elderly individuals and 56 of their relatives to obtain information on the decisionmaking process. This qualitative research showed that LTC decisionmaking does not always follow typical consumer decisionmaking models, in which a consumer seeks a product or service, selects among the alternatives, and assesses the choice. Further, the interviews yielded four long-term care decisionmaking styles among older adults related to their degree of planning or not planning. This study underscores the need to develop tailored communications for older people and their families aimed at encouraging appropriate and cost-effective use of LTC services.

Activities of Daily Living↗

Brain magnetic resonance imaging in children with optimally controlled hyperphenylalaninaemia.

This study was undertaken to investigate whether the white-matter changes on MRI and the EEG abnormalities detectable in treated adolescents and adults with hyperphenylalaninaemia (HPA) can be detected in younger children on an optimally controlled diet. The study included 17 children, 7-12 years of age, with HPA. The MRI of five healthy children were included in the blind evaluation of the MR images. According to mutation genotype and dietary tolerance of phenylalanine, 9 patients have severe HPA and 8 have moderate HPA, all requiring dietary treatment. Mild white-matter hyperintensity was detected in 1 of the 5 healthy children and in 10 of 17 patients. EEG was abnormal in 2 patients. This group of children was compared with a previously reported group of adolescents with HPA who had been treated according to the same dietary regimen. MRI changes and EEG abnormalities were significantly less frequent in the group of children than in the group of adolescents. It is suggested that the more frequent MRI changes and EEG abnormalities seen in adolescents are related to the fact that a relaxation of the dietary treatment after the age of 8 years is often accepted.

Adolescent↗

Increasing Enterobacter bacteremia in pediatric patients.

Thirty-two episodes of Enterobacter bacteremia were identified in 30 patients at Children's Hospital of Michigan between September, 1989, and November, 1992. Fifty-six percent of the episodes were nosocomial. Enterobacter accounted for 14% of all nosocomial bacteremias and was the most common Gram-negative organism causing such infections. Enterobacter cloacae was the most commonly isolated species (72%). Twenty-nine (97%) patients had underlying risk factors for infection, including central venous catheters in 22. The susceptibility pattern of 46 Enterobacter isolates from blood during the same study period showed high resistance to extended spectrum penicillins and third generation cephalosporins but low resistance to aminoglycosides and trimethoprim-sulfamethoxazole (TMP/SMX). Resistance to third generation cephalosporins increased throughout the study period and was higher in patients who had received these agents during the previous month. In situations where there is a high frequency of Gram-negative bacteremias with organisms resistant to third generation cephalosporins, we suggest that initial therapy be a combination of a beta-lactam agent and an aminoglycoside or TMP/SMX.

Anti-Bacterial Agents↗

Granulocyte colony-stimulating factor crosses the placenta and stimulates fetal rat granulopoiesis.

We studied the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration to pregnant rats upon fetal and neonatal myelopoiesis. Pregnant rats were treated with rhG-CSF twice daily for 2, 4, and 6 days before parturition. rhG-CSF crossed the placenta and reached peak fetal serum concentrations 4 hours after administration. Peak fetal serum levels were 1,000-fold lower than levels detected in the dam. Hematopoietic effects of rhG-CSF were assessed by cytologic analysis of the newborn blood, spleen, bone marrow, thymus, and liver. White blood cell counts were increased twofold to fourfold in newborns. This increase was due to circulating numbers of polymorphonuclear cells (PMN). rhG-CSF induced a myeloid hyperplasia in the newborn marrow consisting of immature and mature myeloid cells in the day-2 and day-4 treated pups. Bone marrow of pups treated for 6 days contained mostly hyper-segmented PMN with little or no increase in myeloid precursors. An increase in the number of postmitotic (PMN, bands, and metamyelocytes) and mitotic (promyeloblasts, myeloblasts, and metamyeloblasts) myeloid cells in the spleen of neonates was observed. No change was detected in splenic lymphocytes or monocytes. No effect of rhG-CSF was noted in the newborn liver or thymus. These results demonstrate that maternally administered rhG-CSF crosses the placenta and specifically induces bone marrow and spleen myelopoiesis in the fetus and neonate. The significant myelopoietic effects of rhG-CSF at low concentrations in the fetus suggest an exquisite degree of developmental sensitivity to this cytokine and may provide enhanced defense mechanisms to the neonate.

Animals↗

Recombinant methionyl human granulocyte colony-stimulating factor for the prevention and treatment of non-neutropenic infectious diseases.

Recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, hereafter G-CSF) has been demonstrated in clinical trials to be effective in correcting iatrogenic neutropenia by stimulating the production of neutrophils. Not surprisingly, G-CSF has also been found to induce neutrophilia in non-neutropenic hosts. Experimental data suggest that G-CSF leads to the enhancement of neutrophil function. Endogenous G-CSF levels are elevated over a broad spectrum of serious infectious diseases, suggesting the clinical importance of G-CSF in these settings. These findings have stimulated research on the use of G-CSF alone or as an adjunct to conventional antimicrobial therapy in a number of non-neutropenic animal models of infections. In total these studies suggest that G-CSF may be useful in the prevention or therapy of infections in both non-neutropenic and neutropenic clinical settings.

Animals↗