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Biomedical subjects

T Linden

Publications and source records attributed to T Linden.

At least 19 recordsLinked to original sources
PubMed2005

Visual neglect and cognitive impairment in elderly patients late after stroke.

OBJECTIVES: To investigate the prevalence of visual neglect and its relationship to cognitive impairment and dementia in elderly stroke patients 20 months after stroke. METHODS: Of 243 stroke patients aged 70-91 years, 149 underwent neuropsychiatric testing, 138 with the Star Cancellation Test for visual neglect. RESULTS: Fifteen per cent (n = 21) had visual neglect, 9% (n = 12) severe and 9% (n = 12) lateralized. Cognitive impairments were twice as common in patients with neglect as in patients without it and threefold more common when the neglect was severe. Neglect was related to apraxia, impaired visual field, and a previous stroke. Severe neglect was related to dementia, amnesia and impaired visual field. CONCLUSIONS: Chronic neglect is common after stroke in elderly patients. So are cognitive impairments, especially in those with neglect. This calls for high alertness to impairments in spatial attention when treating patients with dementia and other cognitive impairments.

Aged↗
PubMed2001

Glucose degradation products in peritoneal dialysis fluids: how they can be avoided.

OBJECTIVES: A patient on peritoneal dialysis (PD) uses 3-7 tons of PD fluid every year. The result is considerable stress on the peritoneal tissue. Aspects of PD fluids that have been considered responsible for bioincompatibility are low pH, high osmolality, high glucose and lactate concentrations, and the presence of glucose degradation products (GDPs). However, the relative importance of each factor in PD fluid has so far not been investigated. Discovering their relative importance was the aim of the present study. METHODS: Two main methods for investigating biocompatibility were used in this study: cytotoxicity measured as in vitro inhibition of cell growth, and in vitro AGE formation measured as albumin-linked fluorescence. RESULTS: The two most important factors for determining in vitro bioincompatibility of PD fluids were the presence of GDPs, which caused both severe cytotoxicity and strong AGE promotion, and low pH, which induced severe cytotoxicity. CONCLUSIONS: The biocompatibility of PD fluids can be monitored through fairly simple in vitro methods such as cell proliferation and AGE formation. Bioincompatibility of PD fluids is caused mainly by the presence of GDPs and low pH. These findings correlate well with known clinical bioincompatibility.

Animals↗
PubMed2000

Carcinoma in situ of the breast: correlation of histopathology to immunohistochemical markers and DNA ploidy.

In a consecutive and unselected series of 178 cases of carcinoma in situ of the breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2, and p53), and DNA ploidy was investigated, in order to discriminate biologically different groups. In DCIS, significant correlation was shown between large nuclear size and comedonecrosis, both of which showed also strong association to DNA aneuploidy, high proliferation activity, low steroid receptor content, and overexpression of c-erbB-2 and p53 factors that may indicate an aggressive behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA diploid with low proliferation, and no cases showed overexpression of c-erbB-2 and p53. Heterogeneity with respect to the investigated parameters was also a frequent finding that may reflect a development complexity. In IC, comparison of the DCIS and the invasive component showed similar patterns. No significant differences were shown between DCIS without and with invasion. This may indicate that none of the investigated parameters on its own are essential for the event of invasion.

Biomarkers, Tumor↗
PubMed2000

The feasibility of telemedicine for orthopaedic outpatient clinics--a randomized controlled trial.

We investigated the use of videoconferencing in the examination of orthopaedic outpatients. A consecutive sample of orthopaedic outpatients was randomized to examination either via videoconferencing (n = 76) while attending a primary-care unit or at a conventional hospital outpatient clinic 160 km away (n = 69). Videoconferencing was found to be feasible and the equipment functioned well technically. There were somewhat more problems in examining the telemedicine patients than the clinic patients. The two patient groups were equally satisfied with the specialist service. The telemedicine patients were more willing to have their next visit by videoconferencing than the conventional patients. Videoconferencing between primary and secondary care can be used in the examination of orthopaedic patients whenever no demanding imaging technology is needed.

Ambulatory Care↗
PubMed2000

Biological significance of reducing glucose degradation products in peritoneal dialysis fluids.

UNLABELLED: Carbohydrates are not stable when exposed to energy; they degrade into new molecules. In peritoneal dialysis (PD) fluids, degradation of glucose occurs during the heat sterilization procedure. The biological consequences of this degradation are side effects such as impaired proliferation and impaired host defense mechanisms, demonstrated in vitro for a great variety of cells. Several highly toxic compounds--such as formaldehyde and 3-deoxyglucosone--have been identified in PD fluids. Carbonyl compounds, apart from being cytotoxic, are also well-known promoters of irreversible advanced glycation end-products (AGEs), which might participate in the long-term remodeling of the peritoneal membrane. Various approaches can be used to reduce the formation of glucose degradation products (GDPs) during heat sterilization. Some examples are shortening the sterilization time, lowering the pH, removing catalyzing substances, and increasing glucose concentration. The latter three factors are employed in the multi-compartment bag with a separate chamber containing pure glucose at high concentration and low pH. Gambrosol trio, a PD fluid produced in this way, shows reduced cytotoxicity, normalized host defense reactions, less AGE formation, and reduced concentrations of formaldehyde and 3-deoxyglucosone. Moreover, in the clinical situation, the fluid turns out to be more biocompatible for the patient, causing less mesothelial cell damage, which in the long term could lead to a more intact peritoneal membrane. CONCLUSION: Glucose degradation products in heat-sterilized fluids for peritoneal dialysis are cytotoxic, promote AGE formation, and cause negative side effects for the patient. Using improved and well-controlled manufacturing processes, it is possible to produce sterile PD fluids with glucose as the osmotic agent but without the negative side effects related to GDPs.

Cells, Cultured↗
PubMed1999

Visualizing two-component protein diffusion in porous adsorbents by confocal scanning laser microscopy.

The use of confocal scanning laser microscopy (CSLM) has recently been described for the visualization of intraparticle protein profiles during single-protein finite bath uptake experiments. By coupling of fluorescent molecules to proteins the penetration of porous media by labeled macromolecules could be detected by scanning single adsorbent particles for fluorescence emission after laser excitation. Thus the internal protein distribution profile, which is a central element in modeling of protein transport in porous adsorbents, became experimentally accessible. Results from the simultaneous visualization of two proteins by this technology are shown here. The use of two different fluorescent dyes for protein labeling and two independent detectors in the CSLM allowed for the first time ever the direct observation of a two-component diffusion process within a porous stationary phase. The finite bath uptake of human immunoglobulin G (hIgG) and bovine serum albumin (BSA) to two different ion exchange adsorbents (SP Sepharose Fast Flow and Source 30S) and to an affinity adsorbent (Protein A Sepharose) was measured using Cy5 and Oregon Green as labels. Single adsorbent particles were scanned for intensity distribution of fluorescence emission from the two fluorophors. The intraparticle profiles obtained from the confocal images were translated into a relative protein concentration thus allowing the calculation of protein uptake kinetics from direct measurement in the stationary phase. The confocal technique may prove to be a very powerful means of data generation for modeling of multi-component mass transfer phenomena in protein adsorption.

Adsorption↗
PubMed1999

Intramedullary nailing of humeral shaft fractures. A retrospective study of 126 cases.

Antegrade intramedullary nailing with four different implants was used in 126 humeral shaft fractures. There were 74 acute fractures, 17 pathologic fractures, 16 fractures malaligned in a hanging cast or brace, 15 fractures with delayed union and 4 fractures that were nailed after failed open reduction and internal fixation. The nonunion rate was 21/95 after primary operation, and after reoperations 14/95. Distraction of the fracture was a significant cause of nonunion, but not type of fracture, localization, implant, and delay between injury and surgery. Shoulder joint function was significantly impaired in 25/67 patients. The patients regarded the result as good or satisfactory in 41/67 of the cases who were followed mean 3 (0.5-10) years. We conclude that antegrade intramedullary nailing of humeral shaft fractures leads to a substantial risk of non-union and impairment of shoulder function. It can be recommended as primary treatment only when nonoperative treatment is likely to fail.

Adolescent↗
PubMed1998

Activation of gadd153 expression through transient cerebral ischemia: evidence that ischemia causes endoplasmic reticulum dysfunction.

The expression of the gene encoding the C/EBP-homologous protein (CHOP), which is also known as growth arrest and DNA-damage-inducible gene 153 (gadd153), has been shown to be specifically activated under conditions that disturb the functioning of the endoplasmic reticulum (ER). To investigate a possible role of ER dysfunction in the pathological process of ischemic cell damage, we studied ischemia-induced changes in gadd153 expression using quantitative PCR. Transient cerebral ischemia was produced in rats by four-vessel occlusion. In the hippocampus, ischemia induced a pronounced increase in gadd153 mRNA levels, peaking at 8 h of recovery (6.4-fold increase, p<0.01), whereas changes in the cortex were less marked (non-significant increase). To elucidate the possible mechanism underlying this activation process, gadd153 mRNA levels were also evaluated in primary neuronal cell cultures under two different conditions, both leading to a depletion of ER calcium pools in the presence or absence of an increase in cytoplasmic calcium activity. The first procedure, exposure to thapsigargin, an irreversible inhibitor of ER Ca2+-ATPase, caused a marked increase in gadd153 mRNA levels both in cortical and hippocampal neurons, peaking at 12-18 h after treatment. The second procedure, immersion of cells in calcium free medium supplemented with EGTA, caused only a transient increase in gadd153 mRNA levels, peaking at 6 h of recovery, indicating that a depletion of ER calcium stores in the absence of an increase in cytoplasmic calcium activity is sufficient to activate neuronal gadd153 expression. The results imply that transient cerebral ischemia disturbs the functioning of the ER and that these pathological changes are more pronounced in the hippocampus compared to the cortex.

Animals↗
PubMed1998

Role of calcium in the activation of erp72 and heme oxygenase-1 expression on depletion of endoplasmic reticulum calcium stores in rat neuronal cell culture.

Endoplasmic reticulum (ER) calcium pool depletion was induced by 30 min exposure of primary neuronal cells to thapsigargin (Tg), an irreversible inhibitor of ER Ca2+-ATPase. Twelve hours later, erp72 and heme oxygenase-1 (HO-1) mRNA levels were quantified by PCR. Protein synthesis was also measured. Transient Tg exposure of neurons induced a marked rise in mRNA levels (7-fold and a 21-fold increase in erp72 and HO-1 mRNA levels; P < 0.001). Loading of neurons with the calcium chelator 1,2-bis(o-Aminophenoxy)ethane-N,N,N',N'-tetra(acetoxymethyl)ester (BAPTA-AM) prior to thapsigargin treatment had only a minor effect on the Tg-induced rise in gene expression. This small inhibitory effect may result from the severe suppression of protein synthesis caused by BAPTA-AM. The results suggest that the increase in stress gene expression induced by exposure of neurons to Tg is triggered by a decrease in ER calcium activity and not by the corresponding increase in cytoplasmic calcium activity.

Animals↗
PubMed1998

Effects of transient cerebral ischemia on hsp40 mRNA levels in rat brain.

Rats were subjected to transient cerebral ischemia by four-vessel occlusion of 30 min duration, followed by 2, 4, 8 or 24 h of recovery. Total RNA was isolated from the cerebral cortex and hippocampus, and reverse transcribed into cDNA. Hsp40 mRNA levels of samples were evaluated by quantitative PCR. Transient cerebral ischemia caused a marked increase in hsp40 mRNA levels to about 250% and 500% of control in the cortex and hippocampus respectively. Since hsp40 exerts a critical regulatory function in the HSC70/HSP70 ATPase cycle, an ischemia-induced rise of hsp40 mRNA levels could mark the onset of the recovery process after transient ischemia. On the other hand, the inhibitory action of hsp40 on P58 (a protein that activates protein synthesis by blocking the interferon-induced double-stranded RNA-activated protein kinase PKR) implies that the rise in hsp40 expression may equally well contribute to the post-ischemic suppression of protein synthesis.

Adenosine Triphosphatases↗
PubMed1998

Erp72 expression activated by transient cerebral ischemia or disturbance of neuronal endoplasmic reticulum calcium stores.

Stress-induced activation of the expression of the endoplasmic reticulum (ER)-resident chaperon and member of the protein disulfide isomerase family erp72 was studied after transient cerebral ischemia in vivo using the four-vessel occlusion method and experimental depletion of ER calcium stores in primary neuronal cell cultures. After 8 days in vitro, neurons were exposed to thapsigargin (Tg), an irreversible inhibitor of ER Ca2+-ATPase, or the Tg solvent DMSO. In separate experiments neurons were pre-loaded with the cell-permeant calcium chelator BAPTA-AM before Tg exposure. Stress-induced changes in erp72 expression were analysed by quantitative PCR. Transient cerebral ischemia produced a significant increase in erp72 mRNA levels which rose to about 200% of control (hippocampus) or 300% of control (cortex). After depletion of ER calcium stores neuronal erp72 mRNA levels rose markedly, peaking at 12 h of recovery. Counteracting the Tg-induced rise in cytoplasmic calcium activity by preloading cells with the chelator BAPTA-AM did not influence erp72 expression significantly, suggesting that the activation of erp72 expression resulted from the depletion of ER calcium stores and not from the corresponding increase in cytoplasmic calcium activity. An activation of erp72 expression is indicative of a disturbance of ER function. The results of the present study therefore provide evidence to support the notion that transient cerebral ischemia induces disturbances of neuronal ER function, probably through a depletion of ER calcium stores.

Animals↗
PubMed1997

DNA ploidy analysis in breast carcinoma. Comparison of unfixed and fixed tissue analyzed by image and flow cytometry.

OBJECTIVE: To form a methodologic basis for DNA analysis of ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) of the breast, including very small lesions, by comparison of flow cytometric (FCM) and image cytometric (ICM) methods for DNA quantitation. STUDY DESIGN: The material consisted of 41 DCIS lesions and 26 ICs. FCM DNA analysis of unfixed, frozen samples were compared to (1) FCM of formalin-fixed, paraffin-embedded tissue; (2) ICM of imprints; and (3) ICM of paraffin-embedded tissue sections. RESULTS: FCM of unfixed tissue showed higher DNA measurement precision and a higher number of DNA nondiploid clones as compared to the other three methods. For the classification of DNA diploid/nondiploid cases, high concordance rates were found between the methods. Discordant cases were predominantly DNA neardiploid by FCM of unfixed tissue but DNA diploid by the other methods. The reproducibility of the DNA index (DI) was best in the interval 1.2 < DI < or = 2.2; it was 74% for FCM of fixed tissue and 79% for ICM of imprints. Clones with DI > 3 were found almost exclusively by ICM of imprints. For ICM of tissue sections, DI could not be reliably estimated. By ICM, contrary to FCM, a combined DNA diploid and nondiploid pattern was found frequently. CONCLUSION: Each of the methods has its own advantages and limitations. If possible, FCM should be combined with ICM. FCM of unfixed tissue is superior to the other methods with respect to precise DI estimation. Alternatively, FCM of fixed tissue and ICM of imprints may both give a reliable estimate of DI. ICM of tissue sections can discriminate DNA diploid from nondiploid clones, except for neardiploid subpopulations, and permits the analysis of very small lesions.

Breast Neoplasms↗
PubMed1989

Binding parameters and concentration modulate formation of complexes between LDL and arterial proteoglycans in serum.

The interactions of LDL with extracellular matrix proteoglycans apparently contribute to the accumulation of apo B-lipoproteins in atherogenesis. Serum LDL forms insoluble complexes with human arterial chondroitin sulfate proteoglycans (CSPG). While the amount of insolubilized LDL varies, serum from survivors of myocardial infarcts and ischaemic subjects shows higher values of CSPG-insolubilized LDL than serum from controls. In this study, we explored the relationship between the formation of LDL-CSPG complexes in serum and some LDL properties, using binding isotherms and characterization of isolated LDL from 12 healthy controls and 12 young myocardial infarct survivors. The amount of LDL insolubilized in serum from solutions of CSPG was found to be a function of the product Bt (total binding) x the amount of serum LDL-cholesterol. Furthermore, the Bt values for the isolated LDL from controls and patients could be predicted with more than 70% certainty by using a multiple regression model which included the cholesterol/protein ratio, protein/triglyceride ratio, isoelectric point and the affinity coefficient of the lipoprotein for CSPG. The results indicate that LDL-CSPG measurements in serum are dependent upon both LDL concentration and structural properties which are related to its tendency to form complexes with arterial CSPG.

Adult↗
PubMed1989

Affinity of LDL to a human arterial proteoglycan among male survivors of myocardial infarction.

In the present study, the hypothesis that the affinity of LDL to arterial proteoglycans might discriminate myocardial infarction patients from controls were tested. The patients were 52 men who had sustained a myocardial infarction at an age of 50 years or less and the controls, selected from a random population sample, were matched to the patients for age and sex. Serum cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and apoB discriminated patients from controls. In addition, LDL reactivity with arterial proteoglycans was significantly higher in patients than in controls. In a multiple regression analysis, with patient or control as the dependent variable, apoB levels, LDL proteoglycan reactivity and serum triglycerides appeared as independent contributors to the regression. These observations indicate that LDL reactivity with arterial proteoglycans is a new, highly significant factor which discriminates between young myocardial infarction patients and controls.

Adult↗
PubMed1987

Protective effect of lesion to the glutamatergic cortico-striatal projections on the hypoglycemic nerve cell injury in rat striatum.

In rat striatum severe hypoglycemia causes an irreversible nerve cell injury, which does not become manifest until during the post-insult recovery period. This injury can be ameliorated by lesions of the glutamatergic cortico-striatal pathway, which suggests that an "excitotoxic" effect mediated by the glutamatergic input is the likely cause of the post-hypoglycemic nerve cell destruction. In this paper we further characterize the protective effect of abolishing the glutamatergic innervation to striatum at the ultrastructural level. Two weeks after a unilateral cortical ablation rats were subjected to 30 min of severe hypoglycemia with isoelectric EEG and killed either immediately after the insult or following 60 min of recovery induced by restoring the blood glucose levels. Immediately after the hypoglycemic insult the structure of striatum was similar on both sides (except for the changes attributable to the ablation); i.e., the neurons and their dendrites had pale cytoplasm with condensed mitochondria, sparse RER and pinpoint ribosomes. After 60 min restitution numerous striatal neurons on the non-protected, non-ablated side had turned variably dark and condensed, whereas underneath the ablation they remained similar as immediately after hypoglycemia. This sequence indicates that the most likely cause of nerve cell destruction on the non-protected side is the "excitotoxic" effect mediated by the glutamatergic innervation, which is superimposed on the action of the hypoglycemic insult per se. Furthermore, the primary condensation of neurons and their dendrites indicate existence of another type of acute "excitotoxic" nerve cell injury which differs from the previously described injury characterized by neuronal swelling.

Animals↗
PubMed1985

Completion of Schistosoma mansoni life cycle in thyroidectomized rats and effects of thyroid hormone replacement therapy.

The survival and maturation of Schistosoma mansoni worms was analyzed in normal, thyroidectomized (Thyrox), and hormone-restored Thyrox rats. Restoration therapy was conducted with both T3 and T4; weight gain of treated rats was monitored to assess hormone-replacement efficacy. Worm yields, lengths, and sex-ratios were compared. Egg yields and the capacity of miracidia to hatch from eggs were also analyzed. The results of these studies support the conclusion that the sequence of steps leading to completion of the S. mansoni life cycle are operational in Thyrox rats. Hormone-treated Thyrox rats are restored to the nonpermissive status, although the worms isolated from these rats still differ in certain respects when compared to worms isolated from normal rats.

Animals↗
PubMedDate not supplied

Degradation in peritoneal dialysis fluids may be avoided by using low pH and high glucose concentration.

OBJECTIVE: When glucose is present in a medical fluid, the heat applied during sterilization leads to degradation. The glucose degradation products (GDPs) give rise to bioincompatible reactions in peritoneal dialysis patients. The extent of the degradation depends on a number of factors, such as heating time, temperature, pH, glucose concentration, and catalyzing substances. In the present work, we investigated the influence of pH and concentration in order to determine how to decrease the amounts of GDPs produced. DESIGN: Glucose solutions (1%-60% glucose; pH 1-8) were heat sterilized at 121 degrees C. Ultraviolet (UV) absorption, aldehydes, pH, and inhibition of cell growth (ICG) were used as measures of degradation. RESULTS: Glucose degradation was minimum at an initial pH (prior to sterilization) of around 3.5 and at a high concentration of glucose. There was considerable development of acid degradation products during the sterilization process when the initial pH was high. Two different patterns of development of UV-absorbing degradation products were seen: one below pH 3.5, dominated by the formation of 5-hydroxy-methyl-2-furaldehyde (5-HMF); and one above, dominated by degradation products absorbing at 228 nm. 3-Deoxyglucosone (3-DG) concentration and the portion of 228 nm UV absorbance not caused by 5-HMF were found to relate to the in vitro bioincompatibility measured as ICG; there was no relation between 5-HMF or absorbance at 284 nm and bioincompatibility. CONCLUSION: In order to minimize the development of bioincompatible GDPs in peritoneal dialysis fluids during heat sterilization, pH should be kept around 3.2 and the concentration of glucose should be high. 5-HMF and 284 nm UV absorbance are not reliable as quality measures. 3-DG and the portion of UV absorbance at 228 nm caused by degradation products other than 5-HMF seem to be reliable indicators of bioincompatibility.

Acetaldehyde↗