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Biomedical subjects

J Andersson

Publications and source records attributed to J Andersson.

At least 127 records · Page 7Linked to original sources
PubMed1998

Phonological representation and speech understanding with cochlear implants in deafened adults.

In the present study cognitive performance in 15 deafened adult cochlear implant candidates was examined and related to level of speech understanding after 12 months of experience with the implant. The implant group performed on par with normal hearing controls in all cognitive tasks used in the study with one exception: Performance was significantly lower in cognitive tasks where use of a phonological representation of sound is a key task-demand. Observations of the implanted individuals' level of speech understanding indicate that only those individuals who, pre-operatively, were in possession of phonological representations comparable to that of normal hearing could follow and understand a speaker that was out of sight. The results are discussed with respect to (a) deterioration in the phonological representation of sounds as a function of absence of external auditory stimulation, and (b) the role of cognitive factors in predicting success in speech understanding with the implant.

Adult↗
PubMed1998

Cytokines in idiopathic thrombocytopenic purpura (ITP).

Most research in idiopathic thrombocytopenic purpura (ITP) has focused on characterization of the autoantibodies directed against platelet antigens resulting in enhanced platelet elimination by macrophages. This report summarizes the current knowledge of cytokine pattern found in individuals with ITP. Serum assessment has demonstrated increased levels of interleukin (IL)-2 and interferon-gamma (IFN-gamma), while IL-4 was significantly decreased. In addition, thrombopoietin (TPO) has been found in normal levels while IL-11 has been reported to be elevated. These data indicate that ITP is associated with a Th1 type of T helper cytokine response, while that of type Th2 is downregulated. Initially, megakaryocytes are found at normal levels in bone-marrow aspirates, explaining the unchanged production of TPO. The increase in IL-11 may be reflected by the increased number of platelets being produced per megakaryocyte. However, there is little information on these events in immunocompetent sites such as bone marrow, spleen and lymph nodes.

Adjuvants, Immunologic↗
PubMed1998

[PET scan in neuro-intensive care and research].

The main objective of neurointensive care is to counteract the development of secondary brain ischemia. The management is focused on preventing, detecting and correcting secondary insults that are likely to produce ischemic brain damage. This requires intensive multimodality monitoring of the brain. There is no reliable technique available for continuous monitoring of cerebral blood flow and therefore intermittent methods have to be used in some cases for objective measurement of cerebral perfusion. PET allows measurements of both cerebral blood flow and metabolism, which is essential for the assessment of the energy metabolic state of the brain tissue. PET may be used to guide therapeutic intervention, to evaluate the effect of treatment, to validate new techniques for monitoring of the brain and to determine the efficacy of potential neuroprotective drugs. The possibilities that PET offers in neurointensive care and research are illustrated. The experiences from the application of PET in the evaluation of pharmacological treatment of increased intracranial pressure in head injured patients and the use of PET in combination with intracerebral microdialys, in an MCA-occlusion-reperfusion primate model and in patients with subarachnoid hemorrhage, to validate intracerebral microdialysis as an instrument for chemical monitoring of the brain during neurointensive care, are reported.

Critical Care↗
PubMed1998

Functional neuroanatomical correlates of electrodermal activity: a positron emission tomographic study.

To reveal areas in the central nervous system of importance for electrodermal control, regional cerebral blood flow (rCBF) was correlated to nonspecific skin conductance fluctuations (NSF) during aversive and nonaversive conditions. Participants viewed a TV screen displaying white noise or snake videotapes presented both with and without electric shocks given to the right hand. H2 15 O positron emission tomography was used to measure rCBF, and the constant voltage technique was used to measure NSF from the left hand. Electrodermal activity was positively related to rCBF in the left primary motor cortex (MI, Brodmann's Area 4) and bilaterally in the anterior (Areas 24 and 32) and posterior cingulate cortex (Area 23). Negative relations were observed bilaterally in the secondary visual cortex (Areas 18 and 19) and the right inferior parietal cortex (Area 39), with a tendency also for the right insular cortex (Areas 13, 15, and 16). Because results from lesion and stimulation studies in humans converge with the present imaging results, we conclude that the cingulum and the motor cortex, in addition to the parietal and possibly the insular cortex, form part of one or several distributed neural network(s) involved in electrodermal control. Because these areas also support anticipation, affect, and locomotion, electrodermal responses seem to reflect cognitively or emotionally mediated motor preparation.

Acoustic Stimulation↗
PubMed1998

Diving response and apneic time in humans.

The aim of this study was to compare apneic time with the human diving response, defined as heart rate (HR) reduction and reduced skin blood flow, in groups with varying degrees of breath-hold diving experience. Apneic time and HR reduction at apneas in air and apneas with face immersion in cold water were thus recorded in nine groups. Skin capillary blood flow was recorded in six of the groups. All subjects received the same information on maximizing apneic duration, and no information about their progress during the apneas. The longest apneas and the most pronounced cardiovascular adjustments were found in the young, trained divers. It was found that apneic time was significantly correlated to HR reduction among the nine groups (r = 0.94, P < 0.001), and to skin capillary blood flow reduction among the six groups where the parameter was measured (r = 0.82, P < 0.05). The correlation between HR reduction and skin capillary blood flow reduction was also significant (r = 0.85, P < 0.05). When the difference in HR reduction and apneic time between apneas in air and apneas with face immersion were compared in the nine groups, it was found that all groups reacted with a more pronounced HR reduction during apneas with face immersion. All groups without prior breath-hold diving experience were found to perform shorter apneas with face immersion than apneas in air, or apneas of the same duration in both conditions, which has been reported in other studies. However, in all groups with diving experience, the apneic time was prolonged during apneas with face immersion. The results of this study suggest an oxygen-conserving effect of the diving response in trained apneic divers.

Adult↗
PubMed1998

Arterial oxygen desaturation during apnea in humans.

We studied the effect of the human diving response, defined as bradycardia and reduced peripheral blood flow, on arterial hemoglobin desaturation. We induced a diving response of different magnitudes by using apnea in air and apnea with face immersion. Each of 21 subjects performed five apneas in air and five apneas with face immersion in 10 degrees C water. Periods of apnea in both conditions were of the same duration in any individual subject (average: 126.4 s) and the order of air and water was equally distributed among subjects. Heart rate, skin capillary blood flow, arterial blood pressure, arterial hemoglobin oxygen saturation during apneas, and end-tidal fractions of CO2 after apneas were recorded with non-invasive methods. The bradycardia and capillary blood flow reduction during apnea in air (7.8 and 37.7% change from control, respectively) were significantly potentiated by face immersion (13.6 and 55.9%, respectively). Arterial hemoglobin desaturated more during apnea in air (2.7%) compared to during apnea with face immersion (1.4%). We conclude that the potentiation of the human diving response with face immersion in cold water leads to a smaller decrease in arterial hemoglobin saturation, which may reflect an oxygen-conserving effect.

Adolescent↗
PubMed1997

Interstitial pneumonitis in bone marrow transplant recipients is associated with local production of TH2-type cytokines and lack of T cell-mediated cytotoxicity.

BACKGROUND: Interstitial pneumonitis, especially associated with cytomegalovirus (CMV) infection, is a serious complication after bone marrow transplantation (BMT), with a high fatality rate despite adequate antiviral treatment. The aim of this study was to elucidate the local immunopathogenesis of interstitial pneumonitis caused by CMV or other agents in BMT recipients. METHODS: Cryopreserved lung tissue obtained from 12 patients with interstitial pneumonitis following BMT was analyzed for cytokine production at the single-cell level using a cytokine-specific monoclonal antibody and immunohistochemical technique. Cytokine production in individual cells was analyzed using monoclonal antibodies to 23 different human cytokines: interleukin (IL)-1 to IL-13, tumor necrosis factor (TNF)-alpha, TNF-beta, interferon-gamma (IFNgamma), granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and transforming growth factor (TGF)-beta1 to 3. RESULTS: Marrow transplant patients with interstitial pneumonia had increased numbers of infiltrating alveolar macrophages, CD3+, CD4+ T cells, and CD40+ B cells and significantly increased numbers of IL-4-, IL-10-, IL-1-, TGF-beta1-, TGF-beta2-, and TGF-beta3-producing cells than controls. IL-2-, IFN-gamma-, and TNF-beta-producing cells were undetectable in most patients with CMV pneumonitis (n=7). Neither perforin-positive CD8+ T lymphocytes nor up-regulation of the apoptotic pathway was detected in lung tissue from patients with interstitial pneumonia. In contrast, extensive local production of IgA, IgG, and IgM was demonstrated in all patients. Intracellular and extensive extracellular deposition of CD68, the L-1 antigen synthesized in CD14+ macrophages, was found. CONCLUSIONS: The cytokine profile suggested that Th1-type cytokine production was absent, whereas production of Th2-type cytokines was significantly up-regulated. Interstitial pneumonitis in BMT recipients with fatal outcome (11/12 patients) was associated with dysregulation in the local cytokine network notable for a predominant Th2 immune response with minimal or absent T cell-mediated cytotoxicity.

Adult↗
PubMed1997

Reduced activity in the extrastriate visual cortex of individuals with strabismic amblyopia.

In order to examine the relationship between reduced visual acuity in human strabismic amblyopia and the cortical activation pattern, we studied, by use of positron emission tomography (PET) and the H2(15)O bolus technique, changes in the regional cerebral blood flow (rCBF) induced by monocular visual stimulation of 8 individuals with this disorder. Individual amblyopic thresholds for monocular detection of the checkerboard pattern were employed as stimuli for both eyes during PET scans. Statistical analysis of subtracted images showed significant increases in rCBF (P < 0.05) by the stimulation of the sound eye localized bilaterally to Brodmann's areas (BAs) 17-19. The cortical response evoked by the amblyopic eye was significantly reduced (P < 0.05) in the ipsilateral BAs 18, 19. These results suggest that the reduction in contrast sensitivity (pattern vision) in amblyopia is coupled with deactivation in identifiable regions of occipital visual areas, including ipsilateral BAs 18,19.

Adult↗
PubMed1997

An example of idiotypic mimicry.

We have evaluated the impact of transgenic immunoglobulin (TGIg) expression on endogenous antibody repertoires. The transgenic system was chosen as to allow for normal recombination of endogenous Ig genes, secretion of TGIg from early development on, and distinguishing the TGIg from endogenous Ig by several serological markers on the C and V regions of the molecules. The transgenic construct encodes a complete anti-(4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NP) antibody molecule carrying a well-defined idiotype, bearing a lambda 1 light chain and a chimeric heavy chain encoded by a human alpha 2 C region devoid of its membrane exon, and the murine B1.8 VDJ-region. Endogenous antibody repertoires were analyzed in mitogen-driven limiting dilution cultures, in single-cell assays for naturally activated Ig-secreting cells, and in hybridomas derived by direct fusion of spleen cells from unmanipulated animals. The results show that a very high frequency of splenic resting B cells and plasma cells in transgenic animals produce IgM with B1.8-cross-reactive idiotypes. This was confirmed by hybridoma analysis which also established that the levels of transgene expression and of idiotype-positive IgM production by the same cell are not correlated. The affinities of idiotype-positive endogenous Ig varied, but were generally several orders of magnitude lower than the transgene-encoded idiotype. V regions from idiotype-cross-reactive IgM heavy chains showed marked diversity in sequences that were all different from the transgenic B1.8. These results are compatible with idiotypic mimicry resulting from intercellular selection based on degenerate, whole V region reactivities.

Amino Acid Sequence↗
PubMed1997

Structure and expression of the c-Myc/Pvt 1 megagene locus.

A chromosomal translocation (Tx) that interrupts the transcription of either c-Myc or Pvt 1 is the principal lesion in many B cell malignancies including Burkitt's Lymphoma (BL), AIDs-NHL, mouse plasmacytoma (Pct) and possibly multiple myeloma (MM). There is a restriction associated with this Tx such that only the immunoglobulin (Ig) heavy chain gene is found juxtaposed to c-Myc and only the Ig light chain gene is found juxtaposed to Pvt 1. Over the past several years, our laboratory has been instrumental in the elucidation of the structure of the mouse Pvt 1 locus as a means of understanding the relationship between these two divergent Txs which, nevertheless, produce indistinguishable disease phenotypes. In the mouse, we have identified a uniform Pvt1/Ig Ck fusion product which is consistently found in all tumors harboring Pvt 1 associated Txs. We have recently constructed transgenic mice harboring a translocated Pvt 1/Ck segment in order to determine whether 1). these mice produce the Pvt 1/Ck fusion product 2). these mice are immunocompromised and 3). these mice develop tumors of a B cell origin.

Amino Acid Sequence↗
PubMed1997

Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis.

Bacterial infections, especially cholangitis, are still common complications after liver transplantation (LTx). During recent years, multiresistant enterococci have become a nosocomial problem in transplant units. The present prospective study on 26 patients, including 24 patients with chronic liver disease, demonstrated that enterococci were the predominant micro-organism involved in post-LTx bacterial infections. They were cultured in the feces and in other sites of 10 out of 13 (77%) patients who underwent extensive examinations. Ampicillin-resistant Enterococcus faecium strains were isolated in urine or feces of 2 of the 13 patients prior to LTx. Similarly, resistance to ampicillin and gentamicin, the empirically used antibiotics for patients with fever of unknown origin, was found in E. faecium strains in 3 and 2 patients, respectively. Moreover, multiresistant E. faecium and E. faecalis strains were demonstrated in 46% of the patients in the postoperative period (3 months). However, no vancomycin-resistant enterococci were isolated. The use of antibiotics within 4 months prior to LTx significantly increased the risk of developing ampicillin-resistant bacteria at the time of LTx and of infections with bacteria of enteric origin after LTx (P = 0.03 and 0.01, respectively). We conclude that stool and urine cultures performed prior to LTX may be useful for selecting prophylactic antibiotic regimens.

Adult↗
PubMed1997

Do organic solvents induce changes in the dopaminergic system? Positron emission tomography studies of occupationally exposed subjects.

OBJECTIVES: The objective of this study was to test the hypothesis that long-term occupational exposure to organic solvents may effect the levels and turnover of dopamine in man. METHODS: A study was performed on 17 patients with neuropsychiatric symptoms due to occupational solvent exposure, and 11 healthy non-exposed male volunteers (controls). Positron emission tomography (PET) was used to assess striatal dopaminergic function, using L-[11C]DOPA, [11C]nomifensine and [11C]raclopride as tracers. RESULTS: The rate of dopamine synthesis was significantly increased among subjects with occupational exposure to organic solvents compared with non-exposed controls. After controlling for the difference in age between exposed and controls, the effect of solvent exposure became less apparent and was reduced from +32% (P = 0.009) to +25% (P = 0.07). There were no differences with regard to the binding of [11C]nomifensine. Patients with and without the diagnosis of toxic encephalopathy did not differ with regard to their putaminal uptake of L-[11C]DOPA, [11C]nomifensine and [11C]raclopride. CONCLUSION: The data support the hypothesis that long-term exposure to organic solvents may increase the rate of dopamine synthesis in the brain without affecting the number of presynaptic terminals or postsynaptic dopamine receptors.

Brain↗
PubMed1997

Ribavirin therapy in bone marrow transplant recipients with viral respiratory tract infections.

Treatment with ribavirin was instituted in 12 allogeneic and one autologous bone marrow transplant (BMT) recipients with proven respiratory syncytial virus (RSV), influenza B virus or parainfluenza virus infections. RSV was diagnosed in six cases, influenza B virus in four and parainfluenza virus in three patients. Ribavirin was given orally or intravenously (15-20 mg/kg/day in three divided doses) and in nine cases with the addition of ribavirin inhalations (6 g/day). Three patients required ventilator support. Three out of seven patients with pneumonia, including one patient with RSV who developed pulmonary infiltrates 10 days after the start of therapy, died despite treatment with ribavirin (two RSV, one influenza B). Multiple etiological agents were found in the fatal cases. The clinical condition improved in 10 of 13 patients during therapy. No serious adverse effects of systemic ribavirin were noticed. Two patients had reversible signs of hemolysis but only one patients required more erythrocyte transfusions than expected after BMT. Obstructive respiratory distress was often observed (6/9 patients receiving ribavirin inhalation therapy), which resulted in discontinuation of aerosolized therapy in four cases. Time to engraftment (WBC < 0.2 x 10(9)/l) did not differ from other non-treated BMT patients. We conclude that ribavirin is well tolerated both orally and intravenously and it may, if instituted before development of hypoxia, reduce morbidity and mortality of RSV, influenza B and parainfluenza in this group of patients.

Administration, Oral↗
PubMed1997

Targeted suppression of cytokine production in monocytes but not in T lymphocytes by a tetravalent guanylhydrazone (CNI-1493).

Image analysis was used to study the cytokine-inhibitory effect of the nitric oxide inhibitor tetravalent guanylhydrazone (CNI-1493) in individual immunocytochemically stained human peripheral blood mononuclear cells (PBMC). CNI-1493 inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-8 production whether or not LPS stimulation was enhanced by interferon (IFN)-gamma priming. Addition of TNF-alpha to CNI-1493-exposed LPS-stimulated cells partially restored the incidence of IL-1alpha-, IL-1beta-, and IL-8-producing cells. TNF-alpha production induced by costimulation by ligation of CD3 and CD28 was inhibited by CNI-1493 in monocytes but not in T lymphocytes. The prevalence of IL-2-, IFN-gamma-, and TNF-beta-producing T cells was not reduced by CNI-1493. Phorbol ester and ionomycin activation also resulted in a CNI-1493 -induced inhibition of TNF-alpha in monocytes but resistant production of TNF-alpha, IL-2, and IFN-gamma by T cells. Thus, CNI-1493 preferentially inhibited synthesis of proinflammatory cytokines in monocytes.

Cells, Cultured↗
PubMed1997

Differential sensitivity of B lymphocyte populations to IgM receptor ligation is determined by local factors.

Ligation of surface IgM on B cells responding to lipopolysaccharide (LPS) suppresses terminal differentiation and high-rate Ig secretion with no effect on proliferation. As shown here, different B cell populations show characteristic mean values of ligand concentration required for 50% inhibition, with Gaussian distributions of sensitivity to IgM receptor ligation that reflect cellular heterogeneity of 'al-or-none' inhibitions in single cells. Differential sensitivity of B cell populations to IgM ligation seems to be locally determined by the cellular environment and unrelated to the 'maturity' of the responding cells. Thus, while long-lived peritoneal B cells are 3- to 5-fold more resistant than splenic B cells, there is no difference in sensitivity between short- and long-lived B cells in the spleen. Furthermore, while B cells in bone marrow and spleen differ in sensitivity by two orders of magnitude, B cells differentiated in vitro from bone marrow pre-B cells are as resistant as splenic B cells. Moreover, bone marrow cell culture supernatants restore a high level of sensitivity in such cell populations. Differential sensitivity to IgM receptor ligation is reproduced by multivalent nominal antigen, in cell populations that show identical dose-response inhibition curves to direct activation of protein kinase C by phorbol esters. We conclude that the level of sensitivity to IgM ligation is independent of the life span or maturity of the B cell, but differentially regulated in vivo by putative tissue factors.

Animals↗
PubMed1997

Cerebral normoxia in the rhesus monkey during isoflurane- or propofol-induced hypotension and hypocapnia, despite disparate blood-flow patterns. A positron emission tomography study.

BACKGROUND: Due to a few reports of cerebral dysfunction in connection with isoflurane-induced hypotension and concomitant hypocapnia, positron emission tomography (PET) was used to measure cerebral oxygenation and blood flow during similar conditions with isoflurane or propofol. METHODS: The short-lived radionuclide 15O was used for measurement of cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF) and oxygen extraction ratio (OER) regionally in rhesus monkeys during normotensive/normocapnic and hypotensive/hypocapnic conditions, mean arterial pressure 100-110 and 50-65 mmHg and PaCO2 4.4-5.4 and 3.4-4.4 kPa, respectively. Isoflurane or propofol anaesthesia was given (n = 4 in both groups), supported with 70% nitrous oxide and preceded by ketamine anaesthesia (baseline). RESULTS: PET revealed wide variations in CBF between regions during isoflurane anaesthesia, particularly in comparison with propofol anaesthesia, while rCMRO2 decreased globally in a dose-dependent manner during both isoflurane and propofol anaesthesia. The metabolism-flow coupling was intact during propofol but not during isoflurane anaesthesia. Hypotension reduced rCBF, and rOER increased globally with both study drugs when changing from normo- to hypotension. However, this rOER increase was not significant when using PaCO2 as a covariate, and rOER was never above an arbitrary limit for hypoxia of 70%. Thus, hypocapnia, rather than hypotension, was responsible for the somewhat higher rOER measured. CONCLUSION: PET indicated adequate cerebral oxygenation during isoflurane and propofol anaesthesia, despite disparate blood-flow patterns. Hypotension and concomitant moderate hyperventilation reduced rCBF, but did not result in hypoxia.

Anesthesia↗
PubMed1997

A positron emission tomography study of cerebral blood flow and oxygen metabolism in healthy male volunteers anaesthetized with eltanolone.

BACKGROUND: The effects of eltanolone anaesthesia in humans on regional cerebral blood flow, regional cerebral metabolic rate of oxygen and oxygen extraction ratio were to be evaluated using positron emission tomography (PET). METHODS: Six healthy male volunteers were studied. Series of PET-measurements with 15O and H2(15)O were carried out in the awake state (baseline)(n = 6), during eltanolone anaesthesia (n = 5) and during early recovery (n = 5), when the subjects were oriented with respect to person, place and time. Eltanolone was given as a programmed infusion. RESULTS: Cerebral blood flow (rCBF) was reduced in almost all cortex regions studied by 31 +/- 16% (mean +/- SD, P < 0.01). During recovery rCBF increased to 109 +/- 26% of pre-anaesthetic baseline levels (P < 0.01). Eltanolone in the doses administered lowered oxygen metabolism (rCMRO2) by 52 +/- 8% (P < 0.01) in cortex regions. During recovery rCMRO2 increased to 90 +/- 13% of baseline (P < 0.01). The oxygen extraction (OER) in cortical regions decreased by 32 +/- 23% (P < 0.01) during anaesthesia and returned to 82 +/- 10% of baseline (P < 0.01) during recovery. Less reduction in cortical blood flow during eltanolone anaesthesia was seen in the uncus (P < 0.01), though no differences in the depression of oxygen metabolism were seen. Oxygen extraction remained homogeneous throughout the brain. CONCLUSION: Eltanolone anaesthesia was shown to reduce cerebral oxygen metabolism and cerebral blood flow in healthy volunteers. There were no signs of ischaemic effects.

Adult↗