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Biomedical subjects

H Hagberg

Publications and source records attributed to H Hagberg.

At least 91 records · Page 5Linked to original sources
PubMed1996

Elevated serum levels of soluble ICAM-1 in non-Hodgkin's lymphomas correlate with tumour burden, disease activity and other prognostic markers.

The serum levels of soluble ICAM-1 (CD54) were significantly elevated in patients with non-Hodgkin's lymphomas (NHL, n=127) and hairy cell leukaemia (HCL, n=15) compared with healthy controls (n=31). In high-grade malignant NHL (n=79) the sICAM-1 levels correlated with the tumour mass as reflected in the Ann Arbor staging system but not with bulky disease. Further, the sICAM-1 levels correlated with disease activity as reflected by the presence of B symptoms and with other known prognostic markers. In particular serum thymidine kinase (sTK). In patients with low-grade malignant NHL (n=48) a trend towards higher serum levels of sICAM-1 was found in patients with advanced stage and B symptoms. In both low and high-grade malignant NHL, elevated levels of sICAM-1 were associated with poorer overall and disease-free survival. The present results indicated that sICAM-1 levels have a prognostic power equal to that of other serum markers claimed to be of prognostic value in NHL, namely serum lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), beta-2-microglobulin (beta2m), serum thymidine kinase (sTK), albumin and orosomucoid. The cellular origin and the possible interactions between soluble and surface ICAM-1 and its ligands needs further exploration.

Adult↗
PubMed1996

A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy.

BACKGROUND: There are few randomised studies comparing anti-emetic drugs for the prevention of nausea and vomiting in patients treated with fractionated radiotherapy. The aim of the study was to compare the anti-emetic efficacy of 8 mg dose ondansetron twice a day with placebo. MATERIALS AND METHODS: One hundred eleven patients who were to commence a course of 10 or more daily fractionated radiotherapy including the abdomen were included in the study. The patients recorded daily emesis, nausea and bowel habit and graded weekly symptoms of nausea, vomiting, diarrhoea and lack of appetite. The EORTC C30 questionnaire was completed. RESULTS: 67% of patients given ondansetron had complete control of emesis compared with 45% of patients with placebo (P < 0.05). The number of emetic episodes recorded on the worst day was 1.4 for the ondansetron group and 3.1 for the placebo group (P < 0.01). Patients given ondansetron had fewer days with emesis and nausea compared with placebo (P < 0.05). The mean sum score of patients weekly grading of symptoms showed that the ondansetron group had less inconvenience than the placebo group (P < 0.05). This difference persisted during the first three weeks, but not thereafter. Similarly, some quality of life measures showed significant differences in favour of the ondansetron group. More patients (n = 13) withdrew due to lack of efficacy in the placebo group compared with patients (n = 8) in the ondansetron group. CONCLUSIONS: The present study illustrates that prophylactic anti-emetic administration of ondansetron is effective in preventing nausea and vomiting in patients undergoing fractionated radiotherapy of the abdomen.

Abdomen↗
PubMed1996

NMDA Receptor-dependent increase of cerebral glucose utilization after hypoxia-ischemia in the immature rat.

Post-treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 reduces hypoxic-ischemic brain injury in immature animals. To elucidate possible mechanisms, cerebral glucose utilization (CMRglc) and cerebral blood flow (CBF) were measured 1-5 h after hypoxia-ischemia and administration of MK-801 in 7-day-old rats. After 100 min of unilateral hypoxia-ischemia, half of the pups were injected with MK-801. CMRglc was assessed by the [14C]deoxyglucose (2-DG) method. The brains were analyzed either by autoradiography or for energy metabolites and chromatographic separation of 2-DG-6-phosphate and 2-DG. CBF was measured by the autoradiographic [14C]iodoantipyrine method. Mean CMRglc in the cerebral cortex was increased ipsilaterally after hypoxia-ischemia to 15 +/- 3.3 mumol 100 g-1 min-1 (p < 0.01) and areas with CMRglc > 20 mumol 100 g-1 min-1 amounted to 8.0 +/- 7.7 mm2 in the ipsilateral hemisphere compared with 1.2 +/- 1.6 mm2 contralaterally (p < 0.001). Treatment with MK-801 decreased CMRglc bilaterally (p < 0.05) and reduced ipsilateral areas with increased CMRglc by 64% (p < 0.01). CBF was unaltered after hypoxia-ischemia and by MK-801 treatment. In conclusion, regional glucose hyperutilization in the parietal cortex after hypoxia-ischemia was attenuated by MK-801; this may have relevance to the neuroprotective effect of NMDA-receptor antagonists in this model.

Animals↗
PubMed1996

Glial fibrillary acidic protein is increased in the cerebrospinal fluid of preterm infants with abnormal neurological findings.

Glial fibrillary acidic protein (GFAP) is the structural protein of the intermediate filament of astroglia. The aims of the present study were to examine GFAP in the cerebrospinal fluid (CSF) of preterm infants at different postmenstrual ages and to evaluate the potential of GFAP to predict abnormal neurodevelopmental outcome. GFAP increased in correlation with postmenstrual age in preterm infants (n = 17) and full-term infants (n = 9). The levels were five times higher in preterm infants (n = 10) with an abnormal neonatal course and/or an abnormal neurological outcome than in healthy preterm infants. The positive predictive value of a GFAP higher than the 98th percentile of normal infants was 69%, while a GFAP level below this limit invariable predicted a good outcome. Simultaneously analysed noradrenaline, hypoxanthine and glutamate did not differ between the groups. We conclude that CSF GFAP increases with maturity and that CSF GFAP appears to be a promising marker for perinatal brain damage.

Biomarkers↗
PubMed1996

Impact of reoxygenation with oxygen and air on the extent of the brain damage after hypoxia-ischaemia in neonatal rats.

Brain damage after hypoxia-ischaemia develops partly during the state of reoxygenation. The generation of free oxygen radicals is considered to be one possible mechanism. In order to evaluate the role of hyperoxygenation, a comparison was made between reoxygenation with pure oxygen and with air after hypoxia-ischaemia in a rat model of unilateral cerebral hemisphere damage. Brain damage was induced in 7-day-old rats. The animals were treated during reoxygenation with either 100% oxygen for 0.5 h or air. The extent of the brain damage was determined at 3 weeks of age by weighing the left and right hemispheres separately. No significant difference in weight deficit of the hemispheres was seen in the oxygen-treated group (15.5%, median) compared to the air-treated group (25.0%). Reoxygenation with pure oxygen after hypoxia-ischaemia in neonatal rats does not cause increased brain damage compared with reoxygenation with room air.

Air↗
PubMed1996

Effects of the 21-amino steroid tirilazad mesylate (U-74006F) on brain damage and edema after perinatal hypoxia-ischemia in the rat.

Using 7-d-old rat pups, the neuroprotective efficacy of the lipid peroxidation inhibitor tirilazad mesylate (U-74006F) was tested in a model of perinatal hypoxic-ischemic (HI) brain damage. The experimental protocol was divided into five parts: 1) pre- plus post-HI treatment or 2) only post-HI treatment with tirilazad (7.5 mg/kg intraperitoneally) or vehicle with evaluation of hemispheric weight deficit 14 d after the insult; 3) post-HI treatment with tirilazad or vehicle with histopathologic evaluation 14 d after the insult; 4) pre- plus post-HI treatment; or 5) posthypoxic treatment with tirilazad or vehicle with evaluation of brain edema 20 h after the insult. In the pre- plus post-HI treatment group, the mean left hemispheric weight deficit was 20.7% +/- 17.8 (mean +/- SD) in tirilazad-treated rats and 27.5% +/- 20.4 in vehicle-treated rats (p = 0.032). Corresponding values for the post-HI treated animals were 19.6% +/- 16.0 and 28.6% +/- 15.4 (p = 0.043). Histopathologic injury assessed as pathology score on a scale of 0-5 was less extensive in tirilazad-treated animals compared with controls (p = 0.038). There was a significant increase in water content in the HI hemisphere compared with the contralateral (hypoxic) hemispheres in tirilazad- and vehicle-treated animals. This increase of water content in the HI hemispheres did not differ between tirilazad- and vehicle-treated animals. The lipid peroxidation inhibitor tirilazad administered after perinatal HI reduced brain damage by 30%, but no effect was found on early postinsult edema.

Animals↗
PubMed1996

Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxia-ischemia in neonatal rats.

The effect of hypoxia-ischemia (HI) on IL-1, and IL-6 bioactivity in relation to expression of IL-1 alpha, IL-1 beta, and IL-6 mRNA was studied, and the neuroprotective efficacy of IL-1 receptor antagonist (IL-1ra) was evaluated in neonatal rats. HI was induced in 7-d-old rats by unilateral carotid artery ligation and hypoxia for 70-100 min. Animals were killed at different time points up to 14 d after HI, and brains were analyzed for IL-1 and IL-6 bioactivity using bioassays and for mRNA for IL-1 alpha, IL-1 beta, and IL-6 with reverse transcription followed by a polymerase chain reaction. In separate animals, IL-1ra was administered intracerebrally before or after HI, and the extent of brain injury was assessed 14 d after HI. A transient increase of IL-1 bioactivity occurred after HI, reaching a peak at 6 h of recovery. IL-1 beta mRNA followed a similar time course but attained maximum expression at 3 h. IL-6 bioactivity and mRNA were also stimulated by HI and followed a similar time course as IL-1. Pretreatment with IL-1ra reduced HI brain damage from 54.4 +/- 9.3 to 41.4 +/- 10.0% (p < or = 0.01), and IL-1ra posttreatment increased the proportion of animals devoid of brain injury (40%) compared with vehicle-treated controls (13%) (p < or = 0.05). In conclusion, a transient activation of IL-1 and IL-6 occurred after HI, and IL-1ra reduced HI brain injury to a moderate degree.

Animals↗
PubMed1996

Methyl-GAG, ifosfamide, methotrexate and etoposide (MIME) as salvage therapy for non-Hodgkin's lymphomas: a Swedish national prospective study. Swedish Lymphoma Study Group.

One hundred and two patients with recurrent or refractory non-Hodgkin's lymphoma (NHL) were treated with MIME (methyl-GAG, ifosfamide, methotrexate, etoposide) in accordance with a prospective protocol. Of 75 patients with high-grade malignant NHL (median age 57 years, range 21-79), 15 patients (20%) obtained a complete response (CR) and 27 patients (36%) a partial remission (PR), giving an overall response rate of 56%. The remissions were usually short when not consolidated with ABMT or radiotherapy. The probability of progression-free survival after 2 years was 13%, and the cause-specific survival was 23%. Of 27 patients with low-grade NHL (median age 46 years, range 37-86), 7% had a CR and 37% a PR giving a response rate of 44%. The remissions were again usually short when not consolidated, and the probability of progression-free survival at two years was 11%, and the cause-specific survival 26%. The main toxicity was hematological with septicemia in 20% of the patients and other severe infections in 19%. Fifteen patients (11 high-grade NHL and 4 low-grade NHL) were consolidated with high-dose therapy followed by ABMT, of whom 6 are in continuous CR. We conclude that MIME can induce remissions in NHL patients, and that the remission rates are comparable with those of many other salvage regimens. The remissions are, however, generally of short duration and need consolidation. There was considerable toxicity therefore patients not suitable for ABMT preferably should be treated with less toxic salvage regimens.

Adult↗
PubMed1996

High-grade non-Hodgkin's lymphoma stage I. A retrospective study of treatment, outcome and prognostic factors in 213 patients.

In a retrospective study of 213 patients with high-grade non-Hodgkin's lymphomas clinical stage I, diagnosed 1985-1990, pretreatment prognostic variables and result of treatment were analysed. The median age of the patients was 67 years. Treatment consisted of radiotherapy in 61%, chemotherapy (10%) chemotherapy followed by radiotherapy (23%) and surgery alone (5%) of the patients. Complete response was achieved in 89% of the patients with estimated relapse-free survival at 5 years of 73%. Relative 5-year survival of all patients was 73%. After chemotherapy followed by radiotherapy the relapse rate was 15% compared with 29% after radiotherapy only. The 5-year relative survival differed between 58% and 74% in the treatment groups. Age, sex, nodal versus extranodal lymphoma, systemic symptoms, bulk of tumor and level of serum lactic dehydrogenase (s-LDH) were analysed as prognostic factors. In multivariate variate analysis, only age 65 years or older and elevated s-LDH were significant independent adverse prognostic factors.

Aged↗
PubMed1995

Degradation of fodrin and MAP 2 after neonatal cerebral hypoxic-ischemia.

Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral occlusion of the common carotid artery + 7.70% O2 for 100 min) and allowed to recover for 3 h, 24 h, 2 days or 14 days. Consecutive tissue sections were stained with antibodies against alpha-fodrin, the 150 kDa breakdown product of alpha-fodrin (FBDP, marker of calpain proteolysis) or microtubule associated protein 2 (MAP 2, marker of dendrosomatic neuronal injury). Cortical tissue pieces were subjected to Western blotting using the antibody against the FBDP. Areas with brain injury displayed a distinct loss of MAP 2 which clearly delineated the infarct. FBDP accumulated in injured and borderline regions ipsilaterally and a less conspicuous, transient increase in FBDP also occurred in the contralateral hemisphere, especially in the white matter. A reciprocal staining pattern could be seen in the cerebral cortex, i.e. loss of MAP 2 and accumulation of FBDP, most pronounced 14 days after the insult. Fodrin and MAP 2 are known calpain substrates, and degradation of these proteins preceded neuronal degeneration, indicating that these proteases may be involved in the early events triggering the cascades leading to neuronal death.

Animals↗
PubMed1995

Fodrin degradation and subcellular distribution of calpains after neonatal rat cerebral hypoxic-ischemia.

Neonatal rats were subjected to transient cerebral hypoxic-ischemia (unilateral occlusion of the common carotid artery + 7.70% O2 for 100 min). Ipsi-and contralateral parietal cerebral cortex was assayed with Western blotting for fodrin breakdown product (FBDP). Calpain immunoreactivity was assayed in the cytosolic fraction (CF) and the membrane and microsomal fraction (MMF). Calpain immunoreactivity decreased bilaterally in the CF during the insult (62-68% of controls) and remained significantly lower during early recovery, whereas the MMF showed no significant changes. This relative redistribution of calpains coincided with the appearance of FBDP in the left, ipsilateral hemisphere, displaying a significantly higher level of FBDP from immediately after the insult until at least 1 day of recovery (204-292% of controls). No significant changes in FBDP could be detected in the right, contralateral hemisphere, indicating that although redistribution of calpains occurred, hypoxia per se did not suffice to initiate fodrin degradation in this model of neonatal hypoxic-ischemia.

Animals↗
PubMed1995

Microglia activation after neonatal hypoxic-ischemia.

The inflammatory response following hypoxic-ischemia (HI) in the neonate is largely unknown. Presently, the expression of microglial antigens and the beta-amyloid precursor protein (APP) were studied in relation to a dendrosomatic marker of neuronal injury (microtubule associated protein II; MAP II). HI was induced in 7-day-old rats by the combined unilateral carotid ligation and hypoxia. The pups (n = 23) were perfusion fixed 2-3 h, 24 h, 2-4 days and 14 days after HI and compared to sham-operated controls (n = 6). Antibodies were used for detection of the major histocompatibility complex II (OX-6), major histocompatibility complex I (OX-18) and complement receptor type 3 (OX-42), APP (APP 676-695) and MAP II (monoclonal MAP II) antigens. There was a transient APP expression 2-3 h after HI. A slight increase of microglial antigens (OX-18) was seen in the white matter 2 h after HI followed by a marked increase of OX-18, OX-6, OX-42 antigens 24 h-3-4 days in most injured regions with exception of the thalamus where a delayed (14 days) microglial response was seen. The latter event was parallelled by a delayed loss of MAP II. In conclusion, intense microglial expression occurs after neonatal HI either with an acute or delayed time-course depending on brain region.

Amyloid beta-Protein Precursor↗
PubMed1995

Differential effects of N-methyl-D-aspartate on Ca2+ homeostasis in developing and adult rat striatum: in vivo microdialysis approach.

This in vivo study concerns developmental differences in the sensitivity of striatal neurons to N-methyl-D-aspartate (NMDA). Changes in calcium homeostasis in adult vs immature rats at postnatal days 8-10, evoked by NMDA, were evaluated by measurements of 45Ca efflux and of Ca2+ taurine and phosphoethanolamine concentrations in striatal microdialysates. The efflux of [14C]sucrose was employed in order to measure changes in extracellular space volume. In adult rats the addition of 5 mM NMDA for 20 min to the perfusion medium resulted in a 30-40% increase in 45Ca efflux, and in a 15% increase in [14C]sucrose efflux. Ten minutes after NMDA perfusion, 45Ca and [14C] sucrose efflux returned to the baseline. No significant changes in Ca2+ or amino acid concentrations were observed in the dialysate of the adult rat striatum. NMDA perfusion in the striatum of immature rats initially induced a transient (5 min) increase in the efflux of 45Ca (by 13%) and [14C]sucrose (by 9%). This was followed by a prolonged (lasting 45-50 min) 45% decrease in 45Ca efflux, an 80% reduction of Ca2+ concentration, and increases in taurine and phosphoethanolamine concentrations in the dialysate, whereas [14C]sucrose efflux recovered within 10 min. These data illustrate differences in the NMDA response between developing and adult rat striatum. Only in developing rats did NMDA induce a large and prolonged influx of extracellular calcium to neurons that may explain the enhanced NMDA neurotoxicity in immature rats.

Aging↗
PubMed1995

The cytotoxic activity of Taxol in primary cultures of tumour cells from patients is partly mediated by Cremophor EL.

In patient tumour samples the activity in vitro of Taxol corresponded fairly well to the known clinical activity and Taxol showed low cross-resistance to standard cytotoxic drugs. However, the Taxol solvent Cremophor EL--ethanol was considerably active alone, whereas paclitaxel formulated in ethanol was less active. Taxol thus seems to contain two components active against patient tumour cells in vitro.

Antineoplastic Agents↗
PubMed1995

Neuron specific enolase in asphyxiated newborns: association with encephalopathy and cerebral function monitor trace.

Neuron specific enolase (NSE) in serum and cerebrospinal fluid (CSF) and glutamate in CSF were investigated in the immediate postasphyctic period in 22 term newborn infants. The cerebral function monitor (CFM) pattern was also assessed and hypoxic-ischaemic encephalopathy (HIE) was graded. NSE was significantly increased in the CSF of infants with HIE (median value 25.4 micrograms/l) compared with control infants (10.0 micrograms/l). Infants with the highest concentrations died. NSE in CSF correlated with the degree of asphyxial damage. Glutamate and NSE in CSF did not correlate, presumably due to the different time factors of the release after the insult. NSE in CSF corresponded well with the type of CFM pattern, which was also highly predictive of outcome.

Asphyxia Neonatorum↗