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H Hagberg

Publications and source records attributed to H Hagberg.

At least 73 records · Page 4Linked to original sources
PubMed1997

The calpain proteolytic system in neonatal hypoxic-ischemia.

Neonatal rats were subjected to transient cerebral hypoxic-ischemia (HI, unilateral occlusion of the common carotid artery +7.70% O2 for 100 min) and allowed to recover for up to 14 days. Calpain caseinolytic activity was found to increase in both hemispheres for at least 20 hr. Hypoxic exposure per se increased the activity of calpains, more pronounced in a membrane-associated fraction, probably through interaction with cellular components, whereas HI introduced a loss of activity, most likely through consumption and loss of proteases. Consecutive tissue sections were stained with antibodies against calpastatin, 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). 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. The cytosolic fraction (CF) and the membrane and microsomal fraction (MMF) of cortical tissue were subjected to Western blotting and stained with antibodies against calpain, calpastatin and the 150-kDa breakdown product of alpha-fodrin (FBDP). 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 translocation of calpains coincided with the appearance of FBDP in the ipsilateral, HI 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 were found in the contralateral, undamaged hemisphere, despite translocation of calpains in both hemispheres, a prerequisite for calpain activation. This discrepancy may be related to changes in the endogenous inhibitor, calpastatin. Calpastatin protein was found to decrease during and shortly after HI in the ipsilateral, but not the contralateral, hemisphere. The inhibitory activity of calpastatin also tended to decrease after HI, indicating that a reduction of calpastatin may be necessary for extensive calpain activation to occur. The mRNA of m-calpain increased in the HI hemisphere 48 hr after the insult (167%, p < 0.001), a time point when the protein was also increased. In summary, our findings indicate that calpains are activated during HI and in the early phase of reperfusion after HI, preceding neuronal death.

Animals↗
PubMed1997

Is MK-801 neuroprotection mediated by systemic hypothermia in the immature rat?

Hypothermia after hypoxia-ischaemia (HI) confounds the interpretation of the effects of neuroprotective drug intervention. The effect of 0.5 mg/kg of dizocilpine (MK-801) administered after HI on rectal temperature at 2-36 h and on brain damage 2 weeks after the insult was evaluated in the immature rat. In pups kept at an ambient temperature of 21 degrees C, MK-801 lowered the temperature by 1.1 degrees C and reduced the brain damage by 45%. In pups held at an ambient temperature of 33 degrees C, MK-801 treatment afforded a 34% reduction of brain damage without lowering the rectal temperature. In conclusion, the neuroprotection offered by MK-801 does not depend on systemic hypothermia in this model.

Animals↗
PubMed1997

Brain injury after hypoxia-ischemia in newborn rats: relationship to extracellular levels of excitatory amino acids and cysteine.

The aim of this study was to follow extracellular concentrations of excitatory amino acids (EAAs) and cysteine during neonatal hypoxia-ischemia (HI) and reflow and to relate these events to the extent of brain damage evaluated 6 h after the insult. Rat pups (PND 7-10) were subjected to unilateral ligation of the common carotid artery and exposed to hypoxia (7.7% O2). Extracellular amino acids were sampled during HI and for 6 h of reperfusion with microdialysis and the levels were correlated with the extent of brain damage at the site of probe placement. The concentrations of glutamate, aspartate and cysteine increased transiently during HI (15 x, 6 x and 3 x, respectively) in the extracellular space and returned to normal or remained slightly elevated during reperfusion. Changes of EAAs and cysteine were similar during HI in the infarcted, undamaged and border-zone regions. During reperfusion the concentrations of glutamate, aspartate and cysteine were higher in infarcted and border-zone areas compared to undamaged tissue. In neonatal rats, the extracellular levels of EAAs during HI do not correspond to the extent of brain injury whereas the EAA concentrations during reflow are related to the extent of infarction.

Analysis of Variance↗
PubMed1997

Neonatal cerebral hypoxia-ischemia: the effect of adenosine receptor antagonists.

The effects of nonselective (theophylline), A1-(DPCPX) or A2A-selective (SCH 58261) adenosine receptor antagonists administered before or after neonatal hypoxia-ischemia (HI) were studied on the extent of brain injury in 7-day-old rats evaluated after 14 days. A possible effect of theophylline (20 mg/kg) on expression of immediate early genes was studied with in situ hybridization. Theophylline (20, 30 or 60 mg/kg) given prior to HI reduced brain damage by 48% (P < 0.001), 36% (P < 0.01) and 34% (P < 0.05), respectively, compared to control rats. This effect was not explained by changes in temperature, cerebral blood flow, blood gas/acid base status or blood glucose during the insult. Theophylline enhanced the upregulation of c-fos and NFGI-A during reperfusion but did not prevent the decrease in adenosine A1 receptor mRNA. Posttreatment with SCH 58261 (0.2 or 2 mg/kg) reduced brain damage by 19% (P < 0.05) and 14% (NS), respectively, compared to control rats which was unrelated to the core temperature. DPCPX (2 or 10 mg/kg) had no effect on the development of brain injury. In conclusion, nonselective and A2A adenosine receptor antagonists reduced brain injury in a model of HI in immature animals.

Animals↗
PubMed1997

Potential advantages of protons over conventional radiation beams for paraspinal tumours.

BACKGROUND AND PURPOSE: Conformal treatment planning with megavoltage X-rays and protons was studied in an attempt to determine if there are advantage of boost therapy with protons instead of X-rays for a patient with a tumour growing around the cervical spinal cord. MATERIALS AND METHODS: A patient with a Ewing sarcoma was selected for the model study. The proton boost plan was realised with a six beam patched technique. Several X-ray boost techniques were planned, some not yet practically realisable. The techniques giving the best dose distributions and the best tumour control probabilities in the absence of significant late toxicity were looked for. The boost techniques were added to two large lateral X-ray beams covering the planning target volume (PTV) and the main risk organ, the spinal cord. The evaluation was made with two biological models, i.e. the tumour control probability (TCP) model, proposed by Webb and Nahum (Webb, S. and Nahum, A.E. A model for calculating tumour control probability in radiotherapy including the effect of inhomogeneous distributions of dose and clonogenic cell density. Phys. Med. Biol. 38: 653-666, 1993), and the normal tissue complication probability (NTCP) model, first derived by Lyman (Lyman, J.T. Complication probability as assessed from dose-volume histograms. Radiat. Res. 104: s13-s19, 1985). RESULTS: The comparison showed small but clear advantages of protons for the boost. At 1% NTCP in the spinal cord, the calculated TCP was on average 5% higher. However, depending on the values of the parameters chosen in the biological models, the gain for protons varied from 0-10%. The smallest gains were seen in radiosensitive tumours for which the TCP was close to 100% with any of the techniques and in radioresistant tumours for which neither technique resulted in any appreciable probability of local cure. CONCLUSION: Protons appear to have therapeutic advantages over conventional radiotherapy in tumours with relatively high radiosensitivity situated close to the spinal cord.

Adult↗
PubMed1997

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia.

Hypercalcaemia is an important cause of morbidity in malignant disease. We studied the efficacy and safety of intravenous ibandronate (a new, potent bisphosphonate) in a multicentre study of 147 patients with severe cancer-associated hypercalcaemia which had been resistant to treatment with rehydration alone. Of 131 randomized patients who were eligible for evaluation, 45 were allocated to receive 2 mg ibandronate, 44 patients to receive 4 mg and 42 patients to receive 6 mg. Serum calcium values fell progressively in each group from day 2, reaching a nadir at day 5, and in some patients normocalcaemia was maintained for up to 36 days after treatment. The 2-mg dose was significantly less effective than the 4-mg or 6-mg dose in correcting hypercalcaemia, as the number of patients who achieved serum calcium values below 2.7 mM after treatment was 50% in the 2-mg group compared with 75.6% in the 4-mg group and 77.4% in the 6-mg group (P < 0.05; 2 mg vs others). In a logistic regression analysis, three factors were found to predict response; ibandronate dose (higher doses were more effective), severity of presenting hypercalcaemia (severe hypercalcaemia was associated with less complete response) and tumour type (patients with breast carcinoma and haematological tumours responded better than those with other tumours). Ibandronate was generally well tolerated and no serious drug-related adverse events were observed. We conclude that ibandronate is a safe, well tolerated and effective treatment for cancer-associated hypercalcaemia, which should prove a useful addition to the current range of therapies available to treat this condition.

Bone Resorption↗
PubMed1997

Assessment of suspected bone metastases. CT with and without clinical information compared to CT-guided bone biopsy.

PURPOSE: To evaluate the role of CT with and without clinical information as compared to CT-guided bone biopsy in the assessment of suspected bone metastases. MATERIAL AND METHODS: The study comprised 51 consecutive patients with suspected bone metastases who had undergone CT-guided bone biopsies with an eccentric drill system. CT of the targets, clinical information, and histopathology were scored separately as malignant, uncertain or benign. The results of CT alone and CT in combination with clinical information were compared to the results of histopathology. RESULTS: Histopathology diagnosed 45/51 lesions (88%), 23 as malignant and 22 as benign. CT correctly depicted 17 of these 23 malignant lesions. The remaining 6 malignant lesions were CT-scored as uncertain (n = 5) or benign (n = 1). CT correctly depicted only 3 of the 22 benign lesions. The remaining 19 benign lesions were CT-scored as malignant (n = 2) or uncertain (n = 17). When uncertain CT scores were combined with clinical scores, the true-positive and true-negative results for malignancy increased from 44% to 82%. CONCLUSION: In most cases, CT in combination with clinical information gives enough information about the nature-malignant or benign-of a skeletal lesion. In uncertain cases, diagnostic accuracy can be improved by means of CT-guided bone biopsy.

Adolescent↗
PubMed1997

Occupation and occupational exposure to UV light as risk factors for hairy cell leukaemia evaluated in a case-control study.

To investigate the role of occupation as a risk factor for hairy cell leukaemia a case-control study on 121 male, hairy cell leukaemia (HCL) patients, and 484 controls matched for age and sex, was conducted. We found significantly elevated risk for HCL among building painters (OR, 5.7; 95% CI, 1.6-20.8; based on six cases and four controls) and construction workers (OR, 3.3; CI, 1.2-9.2; based on seven cases and eight controls). Farming has been suggested as a risk factor in HCL. In this investigation farmers had an OR of 1.2 (CI, 0.6-2.3) and farm workers an OR of 1.5 (CI, 0.8-2.8). However, having ever worked in farming yielded an OR of 1.8 (CI, 1.1-2.9). Having grown up mainly in a rural area gave an OR of 1.4 (CI, 0.9-2.4). UV light has been suggested as a risk factor for non-Hodgkin's lymphoma (NHL). To evaluate the impact of UV exposure, classification of occupations as indoor, outdoor or mixed indoor/outdoor was made. Outdoor and mixed outdoor/indoor work yielded ORs of 2.3 (1.0-4.9) and 1.6 (1.0-2.5), respectively. When the effect of outdoor/indoor or mixed indoor/outdoor work was analysed using a scoring system the OR was 2.0 (CI, 0.9-4.4) for farmers compared with 0.8 (CI, 0.3-1.9) among non-farmers in the highest scoring group. There was no clear correlation between socioeconomic status as defined by the Swedish Socio-Economic Classification (SEI), and the risk of HCL. As many comparisons were made, the possibility of associations occurring by chance can not be excluded.

Adult↗
PubMed1997

Fetal fibronectin, endotoxin, bacterial vaginosis and cervical length as predictors of preterm birth and neonatal morbidity in twin pregnancies.

OBJECTIVE: To evaluate the predictive values of fetal fibronectin, bacterial vaginosis, endotoxin and cervical length for preterm birth (< 35 and < 37 weeks) and neonatal morbidity in twin pregnancies. PARTICIPANTS: One-hundred and twenty-one women with twin pregnancies recruited into a prospective longitudinal study at three antenatal clinics in the southwest of Sweden. METHODS: Cervical or vaginal fluid was sampled and determined for fetal fibronectin (> or = 0.05 microgram/mL was used as cutoff), endotoxin (> or = 100 pg/mL) and bacterial vaginosis (presence of clue cells) at two week intervals from 24 to 34 weeks of gestation. The cervical length was measured with transvaginal sonography at the same time intervals. MAIN OUTCOME MEASURES: Occurrence of preterm birth (< 35 and < 37 weeks of gestation) and neonatal morbidity. RESULTS: All positive fetal fibronectin samples obtained at screening between 24 and 34 weeks predicted birth < 35 weeks (RR 18.0; 95% CI 2.2-145.9). A positive fetal fibronectin at 28 weeks of gestation predicted delivery < 35 weeks (RR 6.3; 95% CI 2.6-15.1) with a sensitivity, specificity, positive and negative predictive value of 50.0, 92.0, 62.5 and 87.3%, respectively. An independent association between fetal fibronectin at 28 weeks and preterm birth (< 35 weeks) was verified with logistic regression (P = 0.03). A positive fetal fibronectin at 28 weeks of gestation predicted neonatal morbidity (RR 5.1; 95% CI 2.4-11.0) and a longer period of care at the neonatal intensive care unit. The predictive power of cervical sonography was generally low but cervical length (cutoff < or = 33 mm) measured at 28 weeks of gestation was significantly associated with birth < 37 weeks (RR 2.2; 95% CI 1.1-4.2). The presence of endotoxin correlated to bacterial vaginosis, but these tests were not significantly related to preterm birth or neonatal morbidity. CONCLUSIONS: Fetal fibronectin predicted preterm birth and neonatal morbidity in twin pregnancies. The predictive value of cervical length determinations was low. Endotoxin and bacterial vaginosis had no predictive power for preterm delivery in this study.

Adult↗
PubMed1997

Hypoxia-ischaemia model in the 7-day-old rat: possibilities and shortcomings.

The Levene model in 7-day-old rats is the most often used model of hypoxia-ischaemia (HI) in immature animals. The rat central nervous system is immature at birth and corresponds neurodevelopmentally to the term human infant during the second postnatal week. The Levene model of HI differs from clinical asphyxia with respect to the unilateral distribution of brain injury and lack of multi-organ dysfunction. Furthermore, it does not allow cardiovascular monitoring or repeated blood sampling. On the other hand, the progressive nature of HI bears many similarities to birth asphyxia with regard to blood flow changes and cellular metabolic derangements. The model is well characterized, easy to carry out and the low cost allows inclusion of a sufficient number of animals for dose-response evaluation of neuroprotective agents. In addition, it provides the unique opportunity of long-term evaluation of neuropathological and functional outcome.

Animals↗
PubMed1997

Magnesium and the N-methyl-D-aspartate receptor antagonist dizocilpine maleate neither increase glucose use nor induce a 72-kilodalton heat shock protein expression in the immature rat brain.

In adult rats N-methyl-D-aspartate receptor (NMDAR) antagonists increase glucose use and induce a 72-kD heat shock protein (HSP72) expression in limbic system areas that later undergo neuronal necrosis, which have limited the clinical development of these drugs. Dizocilpine maleate (MK-801) and magnesium sulfate (MgSO4) reduce hypoxic-ischemic brain injury in immature animals, but the effects on HSP72 expression and glucose use are unknown. Seven-day-old rats received injections of either vehicle (control), 0.5 or 1.0 mg/kg MK-801, or 2 or 4 mmol/kg MgSO4. Glucose utilization was measured with the deoxyglucose method, 30 min, 48 h, and 4 d after injection. HSP72 immunostaining was evaluated 4 or 24 h after injection. Both doses of MK-801 and 4 mmol/kg MgSO4 induced a temporary decrease in glucose use in the posterior cingulate and retrosplenial cortex, the CA1 and CA3 subfields of the hippocampus, the caudoputamen, and the parietal cortex. Doses of 2 mmol/kg MgSO4 did not affect glucose use in any structure. Neuronal HSP72 expression was not found in any drug-treated rats. In conclusion, neither MK-801 nor MgSO4 increased glucose use in the limbic system and did not induce HSP72 expression, suggesting that NMDAR antagonists lack direct neurotoxicity in the immature brain.

Animals↗
PubMed1997

Sensorimotor function and neuropathology five to six weeks after hypoxia-ischemia in seven-day-old rats.

Various therapeutic interventions after hypoxia-ischemia (HI) have been shown to reduce brain injury in the short-term perspective, but it remains uncertain whether such findings are accompanied by long-term functional and structural improvements. HI was induced in 7-d-old rats as follows. The left carotid artery was ligated, and the rat was exposed to 100 min of hypoxia (7.70% oxygen in nitrogen). At postnatal d 42 the rats were assessed using four sensorimotor tests. The results were correlated with the extent of brain damage expressed as volume of deficit of the left hemisphere as percent of the right hemisphere. In the grip-traction test, the time to falling was 2.2 times shorter in the HI animals compared with controls (p < 0.01). Asymmetries of limb-placing and foot-faults (p < 0.001) were detected in HI animals, and the motor function was abnormal in the postural reflex test (p < 0.001). We found a moderate correspondence between functional and neuropathologic outcome (r = 0.842, p < 0.001). A set of four easily performed sensorimotor tests is presented for the long-term evaluation of neurologic function in the 7-d-old rat model of HI.

Animals↗
PubMed1997

[18F] FDG PET in gastric non-Hodgkin's lymphoma.

The possibility of using [18F] FDG PET for assessment of tumor extension in primary gastric non-Hodgkin's lymphoma (NHL) was studied in 8 patients (6 high-grade and 2 low-grade, one of the MALT type) and in a control group of 7 patients (5 patients with NHL without clinical signs of gastric involvement, 1 patient with NHL and benign gastric ulcer and 1 patient with adenocarcinoma of the stomach). All patients with gastric NHL and the two with benign gastric ulcer and adenocarcinoma, respectively, underwent endoscopy including multiple biopsies for histopathological diagnosis. All patients with high-grade and one of the two with low-grade NHL and the patient with adenocarcinoma displayed high gastric uptake of [18F] FDG corresponding to the pathological findings at endoscopy and/or CT. No pathological tracer uptake was seen in the patient with low-grade gastric NHL of the MALT type. In 6/8 patients with gastric NHL, [18F] FDG PET demonstrated larger tumor extension in the stomach than was found at endoscopy, and there was high tracer uptake in the stomach in two patients who were evaluated as normal on CT. [18F] FDG PET correctly excluded gastric NHL in the patient with a benign gastric ulcer and in the patients with NHL without clinical signs of gastric involvement. Although the experience is as yet limited, [18F] FDG PET affords a novel possibility for evaluation of gastric NHL and would seem valuable as a complement to endoscopy and CT in selected patients, where the technique can yield additional information decisive for the choice of therapy.

Aged↗
PubMed1996

Microglia-astrocyte interactions after cortisone treatment in a neonatal hypoxia-ischemia model.

Microglial and astrocyte responses to glucocorticoid pretreatment in the neonate exposed to hypoxia-ischemia (HI) are largely unknown. The expression of microglial antigens and astrocytic proliferation was compared in neonatal rats exposed to HI with and without cortisone. HI was induced in 7 day old rats. One group of rats received cortisone within 24 h of birth. Immunocytochemical and immunoblot investigations were performed. Monoclonal antibodies (OX18 and OX42) were used for the detection of the major histocompatibility complex (MHC) class I antigens and complement receptor 3 (CR3) respectively. Antibodies directed against glial fibrillary acidic protein (GFAP) and microtubule associated protein II (MAP II) were used to evaluate the extent of brain damage. Cortisone treatment provoked a decline in the number of microglial cells but did not modify GFAP levels in control rats which were not exposed to HI. Neuronal damage was similar in control and cortisone treated rats exposed to HI. There were also similarities in the expression of CR3 antigens on microglia. However microglial cells expressing MHC class I antigens were less prevalent in rats exposed to HI only. Cortisone pretreatment enhanced the expression of MHC class I antigens. Astrocytic proliferation was intense in rats exposed to HI; however in rats treated with cortisone and exposed to HI there was a drastic reduction in astrocytic proliferation. In conclusion it is suggested that microglia which survive cortisone pretreatment become over-activated thereby preventing astrocytic proliferation.

Animals↗
PubMed1996

Development of brain damage after neonatal hypoxia-ischemia: excitatory amino acids and cysteine.

The aim of this study was to investigate the possible role of excitatory amino acids (EAAs) and cysteine in the development of brain damage after hypoxia-ischemia (HI) in neonates. In a rat model of neonatal HI, changes in extracellular (ec) amino acids in cerebral cortex were measured with microdialysis and correlated with the extent of brain damage at the site of probe placement. Extracellular concentrations of glutamate, aspartate and cysteine increased during HI and remained elevated during reperfusion. During HI the pattern of EAA changes was the same in the infarcted, undamaged and border zone regions. During reperfusion, however, the ec concentrations of glutamate, aspartate and cysteine were higher in infarcted and border zone areas compared to undamaged tissue. HI also produced a slight increase of tissue concentration of cysteine and decrease of tissue concentration of glutamate in parietal cortex of the HI hemisphere. The effect of cysteine on brain damage induced by HI and glutamate was also investigated. A subtoxic dose of cysteine potentiated glutamate toxicity in the arcuate nucleus and enhanced brain infarction after HI in neonatal rats. The results show that in neonatal HI the extracellular levels of EAAs during HI are not directly related to brain injury but the EAA levels during reflow predict the extent of infarction. Cysteine increases HI-induced brain injury and potentiates glutamate toxicity in neonatal rats. Speculatively, elevated level of cysteine during reperfusion may participate in the excitotoxic cascade leading to brain injury.

Animals↗
PubMed1996

Treatment of aggressive non-Hodgkin's lymphoma in adults--are we doing any better?

Great improvement in the treatment of patients with aggressive non-Hodgkin's lymphoma (NHL) has been obtained with the introduction of new combination chemotherapy regimens in the 1970s. The hope that there would be further improvement has waned during recent years due to the fact that some controlled studies did not reveal any better results using the new more intensive treatment regimens. This is the reason for the question: are we doing any better?

Adult↗