Biomedical subjects

L Eriksson

Publications and source records attributed to L Eriksson.

At least 109 records · Page 6Linked to original sources

PubMed1994

18F-labelled vesamicol derivatives: syntheses and preliminary in vivo small animal positron emission tomography evaluation.

As possible presynaptic tracers for cholinergic function in humans, three 18F-labelled vesamicol analogs were synthesized for use in positron emission tomography (PET): cis-[18F]-4-fluoromethylvesamicol (FMV), [18F]-N-fluoroacetamidobenzovesamicol (FAA) and [18F]-N-ethyl-N-fluoroacetamidobenzovesamicol (NEFA). Radiolabelling was accomplished using [18F]fluoride and the corresponding tosylates, the syntheses of which are also described. Yields were on the order of 40-60, 5 and 40-60%, respectively. Dynamic studies of the biodistribution in rats of [18F]FAA and [18F]NEFA using PET were compared with those previously reported for [18F]FMV. Due to probable rapid metabolism, [18F]FAA was considered unsuitable as a ligand for in vivo imaging. [18F]NEFA, similar to [18F]FAA, displayed a more moderate cerebral uptake than that of [18F]FMV (2 vs 20-30%). Pretreatment with vesamicol blocked the cerebral uptake, indicating a specific interaction with the vesamicol binding site. The biodistribution of high specific activity [18F]NEFA with time could be described with a three-compartmental model. The evaluation of [18F]NEFA as a tracer for cholinergic function is currently being pursued in monkeys and humans.

Animals↗

PubMed1994

Methodological aspects of brain activation studies: cerebral blood flow determined with [15O]butanol and positron emission tomography.

In this methodological study, a procedure for measuring regional CBF (rCBF) with positron emission tomography and 15O-labelled tracers is optimized. Four healthy volunteers were subjected to eight studies with use of [15O]butanol as a tracer: four times while reading aloud and four times while reading silently from a phonologically balanced list of single words. The gain from these repeated intra-individual studies of the same activation state (fractionation) was demonstrated in terms of noise-equivalent counts in a phantom study. A computerized brain atlas was used to reformat the images to a common anatomical representation, thereby minimizing the effects of inter- and intra-individual anatomical and positional variations. This allowed the formation of inter- and intra-individual average subtraction images with error estimates. Differences between the two activation states were detected with use of an exploratory significance map based on a paired Student's t test. The results compared well with Friston's method of determining levels of statistical significance. No difference was obtained when comparing results from rCBF images and images generated from measurement of uptake of the tracer. The paradigm chosen for activation was shown to yield a constant activation level during the repeated measurements (i.e., no habituation).

Brain↗

PubMed1994

The relationship between DNA content and centromere content in micronucleated mouse bone marrow erythrocytes analysed by flow cytometry and fluorescent in situ hybridization.

A fixation method for mouse bone marrow erythrocytes was developed which allows both flow cytometric enumeration of micronucleated polychromatic erythrocytes (MPCEs) and detection of centromeres using fluorescent in situ hybridization (FISH) with a mouse gamma satellite probe on flow-sorted MPCEs. Male CBA mice were treated with clastogens or spindle poisons: X-irradiation (XR; 0.5 Gy), cyclophosphamide (CPA; 80 mg/kg), vincristine sulphate (VCR; 0.125 mg/kg) and colchicine (COL; 1 mg/kg). At 30 and 50 h after treatment bone marrow suspensions were prepared and subsequently analysed by flow cytometry to enumerate and determine the DNA content of induced MPCEs. The mean DNA content in MPCEs was found to be higher after treatments with the two aneugens, VCR and COL, than with the two clastogens, CPA and XR. The mean DNA content of MPCEs was positively correlated with the mean proportion of micronuclei (MN) containing centromeres, indicating that determination of the mean DNA content alone can give information about the mechanism of MN induction. When the MPCEs induced with VCR were outsorted according to four classes of increasing DNA content and the presence or absence of centromeres was determined with FISH, it was found that only the class with the lowest DNA content (0.8-1.7% of the diploid DNA content) had a low proportion (< 20%) of centromere-containing micronuclei while in the three classes with higher DNA content (1.7-10.2% of the diploid DNA content) > 80% of the MN had centromeres. This was in contrast to the results from treatments with CPA where the proportion of centromere-containing MN did not increase with increasing DNA content.

Animals↗

PubMed1994

Urge to scratch represented in the human cerebral cortex during itch.

1. We used functional positron emission tomography (PET), measuring regional cerebral blood flow (rCBF) as an index of neuronal activity, to investigate the central processing of itch in 10 healthy volunteers subjected to intracutaneous injections of histamine. 2. The study has unraveled a central representation that depicts a motor intention of the urge to scratch contingent on the perception of unpleasant itch. The coactivation of the anterior cingulate cortex (ACC), supplementary motor area (SMA), premotor area (PM), and inferior parietal lobule (IPL) substantiates that the posterior sector of the ACC (Brodmann 24) is related to the sensorial/affectional aspect of the event. The premotor cortical areas (SMA, PM) and the IPL may participate in the preparation of an intended action.

Adult↗

PubMed1994

Influence of medetomidine on acid-base balance and urine excretion in goats.

Seven goats were given medetomidine 5 micrograms/kg as an iv bolus injection. Venous blood samples were taken repeatedly and urine was collected continuously via a catheter up to 7h after the injection. Medetomidine caused deep clinical sedation. Base excess, pH and PCO2 in venous blood rose after medetomidine administration. There were no significant changes in plasma concentrations of sodium, calcium, magnesium, creatinine or osmolality, whereas potassium and bicarbonate concentrations increased, and phosphate and chloride decreased. Medetomidine increased plasma glucose concentration, and in 4 of 7 goats glucose could also be detected in urine. Medetomidine did not influence urine flow rate, free water clearance, bicarbonate and phosphate excretion or pH, but renal chloride, sodium, potassium, calcium, magnesium and creatinine excretion were reduced. The results suggest that the metabolic alkalosis recorded after medetomidine administration is not caused by increased renal acid excretion.

Acid-Base Equilibrium↗

PubMed1994

Intraruminal fluid administration to goats: effects of handling and fluid temperature.

Physiological stress response to intraruminal fluid administration was studied in 5 female goats. The fluid was given through a stomach tube. The water was cold (10 degrees C) or warm (38 degrees C) and in an amount of 7.5-10% of body weight. Plasma concentrations of adrenaline, noradrenaline and cortisol increased significantly after both treatments. Adrenaline and noradrenaline responses were greater and more longlasting after cold water administration, but there was no difference in cortisol response between cold and warm water. Haematocrit and plasma protein concentrations increased also and the effects of cold water lasted longer. Blood pressure showed a sharp rise of short duration and was independent of water temperature. The immediate tachycardiac response was similar with both treatments, but cold water caused an additional peak 15 min later. The cooling did not increase plasma histamine level. The results suggest that stomach intubation and administration of water into the rumen leads to strong activation of hormonal and cardiovascular stress parameters even in goats well adapted to handling. Low temperature of the fluid further heightens the effect. Warming of fluids to near body temperature before their administration is thus recommended.

Animals↗

PubMed1994

Improved cell-mediated immune responses in HIV-1-infected asymptomatic individuals after immunization with envelope glycoprotein gp160.

Strong specific T-cell responses to human immunodeficiency virus type 1 (HIV-1) gp160 were induced by immunization with recombinant gp160 (rgp160). It was given as postinfection vaccination to 40 asymptomatic HIV-1 seropositive patients. The participants received 6 doses of 160 micrograms rgp160 administered intramuscularly at 0, 1, 4, 8, 17, and 26 weeks and were monitored for 1 year. Lymphocyte proliferation was performed by cultivating lymphoid cells in vitro with specific antigens and mitogens. After immunization with gp160, specific T-cell proliferative responses were induced in all 40 patients. One week after the sixth immunization at day 180, a substantially increased response was detected in 98% of the patients, with a mean stimulation index value of 195. Furthermore, proliferative responses were also identified, after immunization, against native gp120 and against a peptide representing the V3 region of gp120. In addition to the HIV-specific T-cell responses, increased reactivity to several other non-HIV antigens, including tetanus toxoid, influenza, measles, and cytomegalovirus, were seen after gp160 vaccination. The responses to CMV and measles were interpreted to represent an improved recall antigen response. Such recall antigen responses were few in matched HIV-infected controls immunized with influenza virus only. All patients initially and repeatedly showed a normal capacity of total T-cell activation, evaluated by the mitogen phytohemagglutinin (PHA). The trend in CD4 counts improved in 30 of 40 patients during the year of follow-up. The frequency of increases of proliferative responses to antigens was associated with a better CD4 trend. Addition of zidovudine for 2 weeks after each immunization had no beneficial effects nor did it prevent induction of immune responses. All patients tolerated the immunizations well, and no systemic adverse effects were noted. This is a phase I trial, and no definitive conclusions regarding clinical efficacy can be reached.

Adult↗

PubMed1993

Striatal D2/acetylcholine interactions: PET studies of the vesamicol receptor.

The regional cerebral distribution of [18F]NEFA, an aminobenzovesamicol (ABV), was studied in primates with PET. The binding was stereoselective and could be blocked but not displaced with vesamicol. The regional distribution pattern at late times, striatum > cortex > cerebellum, was corroborated by in vitro autoradiography using [3H]ABV and is consistent with known patterns of cholinergic innervation. Pretreatment with sigma 1 or D1 antagonists did not affect the striatal uptake, whereas D2 antagonists markedly augmented the uptake. This is consistent with the known induction of acetylcholine turnover in the striatum in response to D2-receptor blockade and demonstrates that the amount of [18F]-(-)-NEFA incorporated was influenced by the cholinergic activity in the target neurones.

Acetylcholine↗

PubMed1993

5-HT2 and D2 dopamine receptor occupancy in the living human brain. A PET study with risperidone.

It has been suggested that a combined blockade of 5-HT2 and D2 dopamine receptors may be superior to D2 dopamine antagonists alone in the treatment of schizophrenia. Risperidone, which has a high affinity for 5-HT2 and D2 dopamine receptors in vitro, is a new antipsychotic drug that has been developed according to this hypothesis. The aim of this study was to examine if risperidone indeed induces 5-HT2 and D2 dopamine receptor occupancy in vivo in humans. Central receptor occupancy was examined by positron emission tomography (PET) in three healthy men after oral administration of 1 mg risperidone. [11C]N-methylspiperone ([11C]NMSP) was used as a radioligand for determination of 5-HT2 receptor occupancy in the neocortex. Both an equilibrium ratio analysis and a kinetic three-compartmental analysis indicated a 5-HT2 receptor occupancy about 60%. [11C]raclopride was used as a radioligand for determination of D2 dopamine receptor occupancy in the striatum and the calculated occupancy was about 50%. This is the first quantitative determination of 5-HT2 receptor occupancy induced by an antipsychotic drug in the living human brain. The results indicate that 5-HT2 receptor occupancy should be very high at the dose level of 4-10 mg risperidone daily, as suggested for clinical use. Risperidone is thus an appropriate compound for clinical evaluation of the benefit of combined 5-HT2 and D2 dopamine receptor blockade in the treatment of schizophrenia.

Adult↗

PubMed1993

A functional cerebral response to frightening visual stimulation.

The defense reaction, a fundamental reflex in the human behavioral response to threat, is characterized by anxiety and increased activity of the sympathetic nervous system. To study changes in regional cerebral blood flow (rCBF) related to the defense reaction, volunteers with snake phobia were investigated with positron emission tomography. The relative rCBF during phobogenic visual stimulation was increased in the secondary visual cortex but reduced in the hippocampus, orbitofrontal, prefrontal, temporopolar, and posterior cingulate cortex compared with that observed during neutral visual stimulation. The relative rCBF under aversive stimulation was intermediate between phobic and neutral stimulation. The rCBF patterns observed are suggested to represent a functional cerebral correlate to the visually elicited defense reaction and its associated emotions.

Adult↗

PubMed1993

Leukocyte-depleted platelets prepared from pooled buffy coat post-transfusion increment and "in vitro bleeding time" using the Thrombostat 4000/2.

A technique for preparation of platelet concentrate (PC) from pooled buffy coat (BC) is described in this study. The yield of platelets from 4 BCs was 310+/-48x10 9 per unit with a leukocyte content of 21+/-20x10 6 per unit. When a leukocyte removing filter was interconnected, Sepacell 5N and Pall PL-50 filters, no leukocytes could be found in 56 of 59 and in 36 of 37 PCs, with a maximum content of 2.3 and 0.54x10 6 leukocytes per PC, respectively. The platelet yield was 276+/-37 and 279+/-54x10 9 per unit, respectively. The in vitro bleeding time (IVBT), using the Thrombostat 4000/2, corresponded with the corrected count increment in most of 11 thrombocytopenic patients receiving platelet transfusions. However, in two transfusions no correction of IVBT was obtained. This technique offers a new possibility to investigate the functional capacity of transfused platelets.

Bleeding Time↗

PubMed1993

Epidural anaesthesia for caesarean section in a patient with a cerebral artery aneurysm.

A case is described of a 30-year-old insulin-dependent diabetic woman who presented at 25 weeks gestation with frontal headache. Contrast tomography revealed an aneurysm of the middle cerebral artery with no evidence of subarachnoid bleeding. Although elective caesarean section at term was planned, it was performed at gestational week 38 due to the onset of vaginal bleeding and premature labour. In contrast to previous reports, the cerebral aneurysm was not managed surgically at the same time as the delivery, but was treated conservatively. An epidural anaesthetic was performed successfully and postoperative analgesia maintained with a continuous infusion of local anaesthetic in the epidural space. Literature is reviewed and advantages of regional versus general anaesthesia are discussed.

Journal Article↗

PubMed1993

Transfusion-associated Serratia marcescens infection: studies of the mechanism of action.

The growth of two strains of Serratia marcescens in blood components was tested in this study. One of the strains had been implicated in the epidemic of transfusion-associated sepsis experienced in Denmark and Sweden in 1991. In whole blood with a final concentration of 100 colony-forming units per mL of S. marcescens, there was an immediate reduction of more than 95 percent of colony-forming units, but no reduction of the bacterial concentration if the blood had been white cell-reduced before inoculation. This is interpreted as an effect due to phagocytosis by white cells and as a lack of bactericidal effect of the plasma. A reduction to 10 percent of the original concentration, observed if the blood had a nominal content of white cells, was most likely due to phagocytosis. White cell reduction by filtration after inoculation further reduced the bacterial concentration of one of the strains tested, but, after a 1-week lag phase, growth accelerated to high concentrations by 6 weeks. In platelet-rich plasma prepared from S. marcescens-inoculated units, abundant growth was found after 24 hours, increasing to very high concentrations (10(12) colony-forming units/mL) during 10-day storage at 22 +/- 2 degrees C. Keeping the whole blood at ambient temperature for 20 hours before preparation of platelet-rich plasma caused only temporary reduction of bacterial concentration in the S. marcescens experiments, but resulted in a complete absence of bacteria in the platelet-rich plasma for 10 days in control experiments performed with Staphylococcus epidermidis.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗

PubMed1993

Decreasing autopsy rate in Sweden reflects changing attitudes among clinicians.

The autopsy rate has declined in the last 20 years in Sweden and is now approximately 30%. Clinical autopsies constitute about 18% and medico-legal autopsies somewhat more than 10%. There is an obvious geographical variation in clinical autopsy rate, whereas the variation in medico-legal autopsy rate is narrower. The difference in autopsy frequency between males and females seemed to be mainly dependent on the higher number of medico-legal autopsies among males. In order to explore the reasons behind the decline in autopsy rate we accomplished a study of the autopsy rate in 1986 and 1991 in three Swedish hospitals of various types and sizes. The hospitals studied were one university hospital and two community hospitals of different sizes. The autopsy rate varied between 0 and 100% among the different departments within these hospitals and also varied considerably between wards within the same department. The number of clinical autopsies declined between 1986 and 1991 in all three hospitals. The fall was greatest in the university hospital and in the larger of the two community hospitals. However, in these two hospitals departments with active research of clinico-pathological relevance maintained or even increased their autopsy rate during this period. The decline in autopsy rate in general and the difference in rate between hospitals, departments and wards could be explained neither by the Autopsy Act of 1976, or by the reluctance of relatives to give consent to the autopsy of a relative. A change in attitude toward and interest in the autopsy activity of clinicians seemed to be the major explanation for the decline of the autopsy.

Adolescent↗

PubMed1993

Tumour-like localized amyloid of the brain is derived from immunoglobulin light chain.

A patient is presented in whom the amyloid component of an intracerebral 'amyloidoma' has been purified and characterized by amino acid sequence analysis. The material originated from an autopsy of a 76-year-old man who 15 years earlier had been operated for an intracerebral 'amyloid tumour'. The tumour had recurred and grown to an almost walnut-sized mass in the right cerebral hemisphere. It was located in the parietal lobe close to the lateral ventricle and had a close connection to the choroid plexus. Histological examination showed large masses of amyloid surrounded by some plasma cells and a few macrophages of the foreign body type. Amino acid sequence analysis of a major fibril subunit protein showed homology with the variable region of a monoclonal lambda immunoglobulin light chain, subgroup III or IV. This shows that the amyloid in the 'tumour' was of AL type and presumably derived from local synthesis by plasma cells.

Aged↗

PubMed1993

Half-strength citrate CPD and new additive solutions for improved blood preservation. I. Studies of six experimental solutions.

Poor stability of plasma factor VIII in whole blood and loss of erythrocyte 2,3-bis-phosphoglycerate (BPG) during red cell storage are limitations with systems for blood component preparation in current use. This study presents attempts to improve post-collection storage conditions in both these respects using half-strength citrate CPD solution (0.5CPD) for blood collection, which has been shown by others to improve the stability of factor VIII, and some compositions of hypotonic additive solutions for red cell storage containing citrate, adenine, mannitol, and phosphate. Guanosine was also included in some of the media. The erythrocyte BPG concentration was maintained at a normal level for 3-4 weeks with the best of the tested compositions. Total adenine nucleotide concentration was maintained at the original level for 49 days and adenosine triphosphate for 28 days. Spontaneous storage haemolysis was low, 0.31% (mean) +/- 0.08-0.10% (SD) after 49 days in the two best compositions. The intracellular pH was 0.2-0.3 pH units higher than the extracellular pH at the beginning of storage, but this difference gradually diminished and disappeared after 4-5 weeks. We suggest two likely explanations of the effects: the maintenance of intracellular pH at a level sufficiently high not to impair BPG synthesis until after several weeks of storage, and a sufficient supply of phosphate needed in the synthesis of organic phosphate compounds. The content of citrate was selected such that the total amount supplied to a patient in a massive transfusion, when using a combination of 0.5CPD plasma and red cell suspension, would be smaller than that provided by a transfusion of CPD whole blood.

2,3-Diphosphoglycerate↗

PubMed1993

Half-strength citrate CPD combined with a new additive solution for improved storage of red blood cells suitable for clinical use.

Currently used systems for red blood cell (RBC) collection and storage for transfusion have the disadvantage that the RBC 2,3-bisphosphoglycerate (BPG) concentration is depleted within two weeks of storage, resulting in a left-shift of the oxygen dissociation curve and a temporarily impaired capacity to deliver oxygen. We have studied the effects on red cell metabolism, morphology and in vivo recovery of 49-day storage of RBC, with collection in half-strength citrate CPD (0.5CPD) and storage in an additive solution containing citrate, adenine, mannitol, phosphate and glucose (RAS2). Traditional CPD-SAGM was used for comparison. Component preparation was performed after an initial holding period of the whole blood at ambient temperature for 8 h. The BPG concentration in 0.5CPD-RAS2 RBC was 0.633 +/- 0.120 mol (mol Hb)-1 as compared to 0.454 +/- 0.138 mol (mol Hb)-1 in CPD-SAGM RBC which implied a decrease to 67 and 48% of normal concentration, respectively. The mean RBC BPG concentration was maintained at the initial level for 28 days in the new system but decreased to very low levels within 14 days in the controls. The total adenine nucleotides were well maintained in both systems, adenosine triphosphate slightly better in the new system. Hemolysis after 49 days was 0.35 +/- 0.21% in the new system and 0.72 +/- 0.25% in the controls (p < 0.001). The morphology was better maintained in the new system (p < 0.001). The 24-hour posttransfusion survival of 49-day stored RBC was 78.9 +/- 7.1%. The membrane leakage of sodium and potassium was not significantly different in the two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3-Diphosphoglycerate↗

PubMed1993

Transfusion-transmitted Yersinia enterocolitica infection. Protection through buffy coat removal and failure of the bacteria to grow in platelet-rich or platelet-poor plasma.

In a previous study, removal of white blood cells (WBC), by filtration 5 h after deliberate contamination of whole blood with a type 0:3 strain of Yersinia enterocolitica, was shown to be an effective way of avoiding bacterial growth in red blood cells (RBC) during storage. In the present study the Opti-System technique was used to remove the buffy coat from whole blood, leaving 10-20% of the original number of WBC in the RBC preparation. In one series of experiments, all of 4 units of RBC suspension, from which buffy coats were removed 2 h after inoculation of 112 colony-forming units (cfu) per ml of Y. enterocolitica, became Yersinia-free, while abundant bacterial growth occurred in all of 4 units where RBC suspension and buffy coat had been recombined. In a second series of 10 experiments, with an inoculum of 80 cfu/ml, no growth was found in platelet-poor plasma stored for 42 days at 4 degrees C. Five out of 10 RBC suspensions in SAGM additive solution remained Yersinia-free throughout a 6-week storage period; 4 of these 10 units showing growth of Yersinia after 4 weeks and 5 after 6 weeks. In the buffy coats bacterial growth was found in 1 out of 10 units after 1 week, 4 after 2 weeks, and in all of 10 units after 4 weeks. In 2 control experiments with WBC-reduced RBC inoculated with the same bacterial dose, growth started within 24 h and was abundant after 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗