Biomedical subjects

K Nilsson

Publications and source records attributed to K Nilsson.

At least 73 records · Page 4Linked to original sources

PubMed1999

Postoperative nausea and vomiting in children using patient-controlled analgesia: the effect of prophylactic intravenous dixyrazine.

BACKGROUND: Although patient-controlled analgesia (PCA) with morphine provides a high degree of satisfactory postoperative analgesia in children, it is often associated with a high incidence of postoperative nausea and vomiting (PONV). Our aim in this study was to evaluate the prophylactic effect of dixyrazine, a phenothiazine with proven anti-emetic properties. METHODS: The incidence of nausea and vomiting was studied in 60 children using PCA after major surgery. The patients were randomised to receive either dixyrazine 0.25 mg kg-1 or placebo on the induction of anaesthesia in a double-blind, placebo-controlled design. The anaesthetic technique was standardised. The PCA pump was programmed to deliver bolus doses of morphine of 20 micrograms kg-1 with a continuous background infusion of 8-10 micrograms kg-1 h-1. Nausea, vomiting, sedation and pain scores were noted every 3 h for a period of 24 h. RESULTS: The morphine consumption of morphine was the same in both groups. During the stay in the recovery room the incidence of vomiting was 3% in the dixyrazine group compared to 30% in the placebo group (P < 0.05). On the ward, 57% versus 83% of the children vomited (P < 0.05). Rescue antiemetics were significantly lower, 30%, in the dixyrazine group compared to 60% in the placebo group (P < 0.05). Higher sedation scores were recorded for the dixyrazine group in the recovery room. No other adverse effects were found. CONCLUSION: A significant number of children using PCA with morphine after major surgery experience PONV. Although prophylactic dixyrazine reduces the incidence and severity of vomiting, the incidence still remains high.

Adolescent↗

PubMed1999

Topical wound anaesthesia in children--a temporary postoperative pain relief.

BACKGROUND: Administration of local anaesthetics into the surgical wound may modulate pain at the peripheral level. A previous study in adults has shown good analgesic effects of topical lidocaine in wounds after herniorrhaphy. METHODS: Postoperative pain relief after topical administration of 10% lidocaine aerosol in the surgical wound was investigated in a randomised, double-blind study in children undergoing inguinal hernia repair. Forty-four patients aged between 9 months and 11 years were randomised into three groups. One group received active treatment with a lidocaine aerosol 2.5-4.7 mg kg-1, one group received a placebo aerosol and one control group was untreated. Postoperative pain was evaluated by nurse assessment, self-assessment and wound palpation 0, 1, 4 and 12 h after arrival in the recovery room. RESULTS: After 1 h the incidence of pain, as estimated by behavioural assessment and self-assessment, was significantly reduced in the lidocaine group in comparison to the placebo group, but not in comparison to the control group. The reaction on wound palpation was significantly reduced in the lidocaine group compared to both the placebo and control groups. At 0, 4 and 12 h no significant differences between the groups were observed. Plasma lidocaine concentrations were measured in six patients. Maximum individual concentrations were low, ranging from 0.17 to 0.86 microgram ml-1. CONCLUSION: A very short and clinically insignificant pain relief is obtained following the administration of a lidocaine aerosol in the surgical wound. A low pain level in this model may limit the possibility to detect an effect of lidocaine.

Administration, Topical↗

PubMed1999

Intraoperative glucose administration influences respiratory quotient during paediatric anaesthesia.

BACKGROUND: Oxidation of carbohydrates and fat yields respiratory quotients (RQ) of 1.0 and 0.7 respectively. Maintained or increased blood glucose concentrations are usually seen during paediatric anaesthesia and surgery even without glucose administration. The aim of the present study was to evaluate whether an intraoperative glucose infusion influences the RQ as an indication of a different metabolic preference in comparison to a glucose-free fluid regime. METHODS: Eighteen children between 0.5 and 24 months of age were studied during anaesthesia with controlled ventilation, oxygen in air, isoflurane, thiopentone, atracurium and fentanyl. Oxygen consumption and carbon dioxide production were measured using indirect calorimetry All children received Ringer acetate as needed; in addition, nine children were given glucose 10%, 3 ml.kg-1.h-1, corresponding to 300 mg.kg-1.h-1. Blood samples for analyses of glucose, lactate, free fatty acids and ketones were taken before and during surgery. RESULTS: RQ was significantly higher in the children given glucose 0.92 +/- 0.08, compared to 0.81 +/- 0.06 in the children without glucose (P < 0.01). Oxygen consumption tended to be higher, although not significantly so, in patients without glucose infusion. Energy expenditure was 1.70 +/- 0.29 kcal.kg-1.h-1, without significant group differences. Higher blood glucose concentrations during surgery were found in the children given glucose. CONCLUSIONS: Our results indicate a higher glucose oxidation rate in patients given glucose during surgery.

Anesthesia↗

PubMed1999

The potential of human mast cell progenitors to differentiate into mature mast cells remains after prolonged culture with flt3 ligand, interleukin-3 or granulocyte-macrophage colony stimulating factor.

Stem cell factor (SCF) plays a key role in the development of mast cells from haemopoietic progenitor cells. In this study we have investigated the effect of the early acting haemopoietic cytokines flt3 ligand (FL), IL-3 and GM-CSF on the SCF-dependent differentiation of mast cells from cord blood mononuclear cells. By using delayed addition of SCF, we examined the potential of mast cell progenitors to keep their capacity to differentiate into mast cells after exposure to factors signalling differentiation into other lineages. Culture with either cytokine for 3 weeks before transfer to SCF-containing medium resulted in the development of mast cells in all cultures. The appearance of mast cells was attenuated when the cells had been in culture with IL-3 or GM-CSF prior to culture in SCF, compared to cultures exposed to SCF alone for 7 weeks. However, a proportion of the cells had not lost the capacity to develop into mast cells. In contrast, in cultures initiated with FL and transferred to medium containing SCF, the same amount of mast cells developed as in the SCF cultures. Thus, cells committed to the mast cell lineage appear to be resistant to the lineage directives of IL-3 and GM-CSF and keep their potential to differentiate into mature mast cells.

Adjuvants, Immunologic↗

PubMed1999

Staphylococcus aureus Cowan strain 1 activation of B-chronic lymphocytic leukaemia cells augments the response to CD40 stimulation.

The signals involved in regulating the proliferation, differentiation and survival of B-chronic lymphocytic leukemia (B-CLL) cells are fully understood. B-CLL cells have been found to respond poorly to various activation signals and only after successful Epstein-Barr virus (EBV) transformation has it been possible to maintain such cells in long-term cultures. In this work we describe a new method to activate and induce proliferation in B-CLL cells and to maintain such cells in long-term culture for longer than 1 month. We used a combination of protocols in an attempt to mimic some of the signals of a thymus-dependent immune response. The B-CLL cells were first activated with Staphylococcus aureus Cowan strain 1 (SAC) particles plus thioredoxin (Trx), followed by stimulation with interleukin (IL)-2 + Trx. This treatment primed the cells for further stimulation with anti-CD40 monoclonal antibody (MoAb) presented on irradiated CD32L cells (the CD40-system) or soluble CD40 Ligand, and a combination of Trx and cytokines (IL-4 + IL-10), which allowed the cells to be maintained for up to 1 month with preserved viability and a variable rate of proliferation. However, induced proliferation of the B-CLL cells was limited to approximately 1 month, suggesting that additional signals are required to facilitate further proliferation.

Burkitt Lymphoma↗

PubMed1999

Nebulization of drugs in a nasal CPAP system.

Aerosolized drugs have been used in infants for the treatment of respiratory distress syndrome and bronchopulmonary dysplasia (beta-agonists, steroids and surfactant) and bronchiolitis due to respiratory syncytial virus (epinephrine and ribavirin). Controlled clinical trials have, however, produced conflicting results, probably due in part to problems with the transportation of the aerosol from the nebulizer to the bronchioli. We have modified a nasal continuous positive airway pressure (CPAP) system permitting an aerosol to flow through a canal to the nasal prongs and into the airways of the infant. It has been used successfully for the administration of epinephrine, salbutamol, budesonide, acetylcysteine, natural surfactant and ribavirin to sick infants. The modified nasal CPAP system is a simple, safe, cost-efficient and baby-friendly system for respiratory support and drug treatment, which can be used in future trials of aerosolized drugs.

Aerosols↗

PubMed1999

Induction of differentiation in U-937 and NB4 cells is associated with inhibition of tissue factor production.

Tissue factor (TF) production is under strict control in mature monocytic cells. However, constitutive expression of TF can be found in myelomonocytic cells and in haematopoietic cells arrested at an early stage of differentiation. In this paper we show that TF expression is down-regulated during the monocyte/granulocyte differentiation process, using the human monoblastic U-937 and the acute promyelocytic leukaemia NB4 cell lines as models. Expression of TF mRNA, protein and procoagulant activity (PCA) was constitutively high in untreated cells. Exposure of U-937 cells to 1alpha,25-dihydroxycholecalciferol (VitD3) and all-trans retinoic acid (ATRA) resulted in down-regulation of TF expression and PCA. In NB4 cells induction by ATRA, but not VitD3, resulted in the down-regulation of TF expression and PCA. Consistent with this, induction of terminal differentiation, as confirmed by the expression of differentiation associated antigens and cell cycle arrest, was inversely correlated to TF expression in U-937 and NB4 cells. Moreover, terminally differentiated U-937 cells retained the capacity to respond to inflammatory mediators, i.e. lipopolysaccharide and interferon-gamma, by a rapid increase in TF expression. In conclusion, we show that not only ATRA but also VitD3 is a potent suppressor of monocytic TF expression and thus might have potential clinical use for the treatment of coagulopathies.

Cell Cycle↗

PubMed1999

Rickettsia helvetica in Ixodes ricinus ticks in Sweden.

In the present study further characterization of the amplified sequence of the citrate synthase gene of the spotted fever group Rickettsia isolated from Ixodes ricinus ticks in Sweden showed that it has 100% homology with the deposited sequence of the citrate synthase gene of Rickettsia helvetica. The restriction fragment length polymorphism (RFLP) pattern of an amplified 382-bp product of the citrate synthase sequence, defined by primers RpCS877 and RpCS1258, yielded fragments for our isolate that could be visualized as a double band that migrated at approximately 44 bp, another double band at 85 bp, and a single band at nearly 120 bp after digestion with the restriction enzyme AluI. When calculating a theoretical PCR-RFLP pattern of the sequence of the citrate synthase gene of R. helvetica from the known positions where the AluI enzyme cuts, we arrived at the same pattern that was obtained for our isolate, a pattern distinctly different from the previously published PCR-RFLP pattern for R. helvetica. Investigation of 125 living I. ricinus ticks showed a higher prevalence of rickettsial DNA in these ticks than we had found in an earlier study. Rickettsial DNA was detected by amplification of the 16S rRNA gene, for which a seminested primer system consisting of two oligonucleotide primer pairs was used. Of the 125 ticks, some were pooled, giving a total of 82 tick samples, of which 20 were found to be positive for the rickettsial DNA gene investigated. When considering the fact that some of the positive samples were pooled, the minimum possible prevalence in these ticks was 20 of 125 (16%) and the maximum possible prevalence was 46 of 125 (36.8%). These prevalence estimates conform to those of other studies of spotted fever group rickettsiae in hard ticks in Europe.

Animals↗

PubMed1999

Jugular bulb temperature compared with non-invasive temperatures and cerebral arteriovenous oxygen saturation differences during open heart surgery.

Limited information is available about the correlation between cerebral temperature and routine temperature measurements during cardiopulmonary bypass in infants. Nasopharyngeal, tympanic membrane and rectal temperatures were compared with jugular bulb temperature in ten infants operated on with moderate or deep hypothermia. The cerebral arteriovenous saturation differences were correlated with the temperatures at the four measurement sites. The jugular bulb and nasopharyngeal temperatures showed the most rapid response during cooling and rewarming. The tympanic temperature response varied in an unpredictable way. Rectal temperature, which was the target for rewarming, lagged behind during both cooling and rewarming. Overwarming at the end of cardiopulmonary bypass, seen as jugular bulb and nasopharyngeal temperatures exceeding 38 degrees C, was common after deep hypothermia. A high correlation was found between the cerebral arteriovenous oxygen saturation differences and the jugular bulb temperature (r = 0.81) and the nasopharyngeal and the tympanic temperature (r = 0.79), whereas the correlation with rectal temperature was weaker (0.66).

Body Temperature↗

PubMed1999

Open heart surgery; pump prime effects and cerebral arteriovenous differences in glucose, lactate and ketones.

This study included 17 young children, who were operated with cardioplumonary bypass for congenital heart defects and were cooled to 20 degrees C or 25 degrees C. No glucose, except for the pump prime solution, was administered during surgery. Samples of arterial blood, cerebral venous blood from the jugular bulb and mixed venous blood from the bypass circuit were obtained and analysed for concentrations of glucose, lactate and ketones as well as oxygen saturation. The prime content of lactate significantly contributed to the arterial lactate concentrations, which together with the cerebral arteriovenous (A-V) lactate differences remained elevated throughout the bypass period. The prime content of glucose had less influence on the arterial concentrations and these did not increase until the rewarming period, when indications of gluconeogenesis from lactate were found. Arterial ketone concentrations also increased during rewarming in parallel with significant cerebral uptake of ketones. The lowest cerebral A-V glucose, lactate and oxygen saturation differences were found at the target minimum temperature and this effect was significantly more pronounced in the patients cooled to 20 degrees C.

Analysis of Variance↗

PubMed1998

Fas/APO-1 (CD95)-mediated apoptosis is activated by interferon-gamma and interferon- in interleukin-6 (IL-6)-dependent and IL-6-independent multiple myeloma cell lines.

A poor response to Fas-induced apoptosis is evident in some multiple myeloma (MM) cell lines and primary cells. In this study, we have examined the possibility to increase the sensitivity to Fas-induced apoptosis by pretreatment of MM cells with interferon-gamma (IFN-gamma) or interferon-alpha (IFN-alpha). Both IFN-gamma and IFN-alpha markedly increased the Fas-induced apoptosis in all cell lines tested (U-266-1970, U-266-1984, and U-1958). In the U-266-1970 and U-1958 cell lines, pretreatment with either IFN-gamma or IFN-alpha also inhibited proliferation in a dose-dependent manner. In contrast, IFN-gamma activation of the Fas death pathway in the U-266-1984 cells was not accompanied by growth inhibition. Incubation with the IFNs increased the Fas antigen expression in one of three cell lines but did not alter the expression of Bcl-2 or Bax. The IFNs are important regulators of growth and survival in MM cells. Our results suggest that activation of Fas-mediated apoptosis is a novel mechanism by which the IFNs exert inhibitory effects on MM cells.

Apoptosis↗

PubMed1998

Blood dendritic cells from myeloma patients are not infected with Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8).

In recent studies, the sequence of Kaposi's sarcoma-associated herpes virus (KSHV) or human herpes virus-8 (HHV-8) was detected in dendritic cells (DC) of patients with multiple myeloma (MM). A concern was raised whether there is an causal association between the viral infection and development of these tumors. In the present study, we have examined DC generated from blood adherent cells from 8 Swedish MM patients at different clinical stages and 2 patients with monoclonal gammopathy of undetermined significance. In addition, 6 myeloma cell lines and bone marrow cells from 2 MM patients were also studied. By polymerase chain reaction (PCR), including nested PCR, no virus DNA was demonstrable in the patients' DC or in myeloma cell lines or fresh bone marrow cells. Moreover, no antibody against KSHV was found in the serum of these 10 patients. Thus, our results indicate that blood-derived DC of MM patients in Sweden usually are not infected with KSHV/HHV-8. This study also suggests that KSHV/HHV-8 is not regularly associated with MM and consequently does not play a primary role in the pathogenesis of these tumors.

Adult↗

PubMed1998

Relationship between cytotoxic drug response patterns and activity of drug efflux transporters mediating multidrug resistance.

Drug activity patterns in 10 human tumor cell lines representing defined mechanisms of drug resistance, including cell lines with high expression of P-glycoprotein and multidrug resistance associated protein (MRP), have previously been used for prediction of mechanism of drug action. In the present study, this cell line panel was analyzed for cellular accumulation of the fluorescent probe calcein/AM [4'5'-bis(N,N-bis (carboxymethyl) aminomethyl) fluorescein acetoxymethyl ester] and compared with drug response patterns of 20 standard chemotherapeutic drugs. According to degree of correlation with the ability to exclude calcein/AM, topoisomerase II inhibitors and tubulin actives were at the top of the list although the correlations were of lower magnitude than those obtained from the drug response patterns of mechanistically similar drugs. There was a significant relationship between the rank-order of drugs based on correlation with calcein/AM accumulation and Pgp/MRP mediated drug resistance suggesting that compounds being substrates for these pumps were identified. In simulated drug response profiles, the impact of Pgp and MRP expressing cell lines on the mechanistic prediction was found to be marginal. The results indicate that the differential molecular function/expression in the cell line panel may identify drugs interacting with specific biochemical pathways. Furthermore, the presence of cell lines overexpressing drug efflux mechanisms in the panel do not significantly influence the mechanistic predictions.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

A 50-year perspective of a family with chromosome-14-linked Alzheimer's disease.

A Swedish family with two generations suffering from presenile dementia with an unusually severe Alzheimer encephalopathy was first reported in 1946. The hypothesis that the disease was inherited through a dominant gene is strongly supported by the follow-up 50 years later of three additional generations and molecular genetic findings of a novel presenilin-1 gene mutation in the family. The pedigree contains six cases with well-documented dementia in four consecutive generations. The Alzheimer encephalopathy was unusually severe in the three cases studied post-mortem, with a pronounced involvement of the central grey structures, such as the claustrum, the nuclei around the third ventricle, the central thalamic nuclei and the brain stem. There were no vascular lesions and little amyloid angiopathy. All six affected cases showed the typical temporoparietal symptom pattern and other core symptoms of Alzheimer's disease, such as logoclonia, myoclonic twitchings and major motor seizures. Other predominant features were psychomotor slowness, increased muscular tension, a stiff stooped gait and a rapid loss of weight. The symptom pattern is convincingly explained by the consistent and severe involvement of cortical and central grey structures and is probably linked to the presenilin-1 gene mutation.

Alzheimer Disease↗

PubMed1998

Comparison between extradural infusion of ropivacaine or bupivacaine for the prevention of postoperative pain after total knee arthroplasty.

We have compared the analgesia and motor block produced by extradural infusions of ropivacaine and bupivacaine after total knee arthroplasty. Fifty-two patients received 8 ml h1 of either 0.2% ropivacaine or 0.2% bupivacaine by extradural infusion for 24 h after operation. Analgesia was assessed by postoperative visual analogue scale (VAS) and morphine consumption. At rest these were low in both groups; median VAS was 0-13.3 mm for the ropivacaine group and 0-0.5 mm for the bupivacaine group. Over the 24 h of the infusion, the estimated (ropivacaine bupivacaine) difference in wound pain at rest was 5.6 mm (P = 0.017) and on passive movement 11.6 mm (P = 0.016). Median morphine consumption was 30.7 mg in the ropivacaine group and 20.5 mg in the bupivacaine group. In the ropivacaine group, 50% of patients compared with 19% in the bupivacaine group had no motor block 2 h after operation, increasing to 88% for ropivacaine and 56% for bupivacaine by 24 h. Bupivacaine produced significantly more frequent and intense motor block over the 24 h (P = 0.015).

Aged↗

PubMed1998

Demonstration of mast-cell chemotactic activity in nasal lavage fluid: characterization of one chemotaxin as c-kit ligand, stem cell factor.

Mast cells are known to accumulate in tissue during allergic inflammation. However, the chemotaxins responsible are undefined. Using a modified Boyden chamber and the human mast-cell line HMC-1, we first identified mast-cell chemotactic activity in nasal lavage fluid collected before the pollen season after allergen provocation of allergic patients (n=29) (mean migratory response compared to medium control was 121%, range 85-198%). Mast-cell chemotactic activity was also detected in lavage fluid collected after allergen provocation at the end of a Swedish birch-pollen season from three different treatment groups: topical steroid treatment with budesonide; the topical antihistamine, levocabastine; and placebo. There was no significant difference in mast-cell chemotactic activity between nasal lavage fluid collected from the placebo group (mean=102%), the budesonide-treated group (mean=114%), or the levocabastine group (mean=125%). Stem cell factor (SCF), a known mast-cell chemotaxin, was present in the nasal lavage fluids from all three groups, and correlated with the mast-cell chemotactic activity (r=0.67, P<0.01). The mast-cell chemotactic activity was inhibited (range 5-100%) in some, but not all, nasal lavage fluids by a polyclonal antibody directed against SCF. This report describes the presence of mast-cell chemotactic activity in nasal lavage fluid during an allergic reaction. These findings show that SCF may play a pivotal role in the recruitment of mast cells in allergic rhinitis.

Allergens↗

PubMed1998

An ELISA technique for quantitation of human xenoantibodies binding to pig cells: application in patients with pig kidneys extracorporeally connected to the circulation.

A quantitative ELISA technique for determination of human anti-pig xenoantibody number in serum samples has been established using pig lymphocytes and pig/rabbit erythrocytes as target cells and a pool of serum from human blood group AB donors. The number of low affinity antibodies binding to the cells was determined by quantitation following the use of aqueous washing of the cells and separation of bound and unbound antibodies with the phthalate oil method. The efficiency of different soluble Gal(alpha)1-3Gal-terminating di- and tri-saccharides to inhibit antibody binding was tested and found to vary between 70-90% at a saccharide concentration of 10 mg/ml. The assay was used to evaluate the antibody changes in two patients who, after plasmapheresis treatments, had pig kidneys extracorporeally connected to their blood circulation. The number of anti-pig IgM/IgG antibodies bound to each pig lymphocyte were reduced from 5,600/13,200 to 1,300/3,100 in patient 1 and from 1,200/6,500 to 500/2,100 in patient 2 by three consecutive daily plasmapheresis treatments. Although the lymphocytotoxic titers were reduced to very low levels, the antibody numbers still present in the blood of patient 1 caused a hyperacute rejection of the pig kidney. However, the antibody levels in patient 2 did not cause rejection of this kidney during 15 min perfusion time. A strong anti-pig antibody response 3 weeks after the perfusion experiment was found in patient 1 as shown by 27,600/245,300 IgM/IgG molecules bound to pig lymphocytes corresponding to an increase of lymphocytotoxic titer from 8 to 512. The second patient showed a much weaker immune response with 1,400/19,800 IgM/IgG antibodies corresponding to a lymphocytotoxic titer increase from 8 to 32. The use of this quantitation technique enables more accurate investigation of antibody binding to xenogenic target cells than conventional titration techniques.

Animals↗

PubMed1998

Summary report on the ISOBM TD-6 workshop: analysis of 20 monoclonal antibodies against Sialyl Lewisa and related antigens. Montreux, Switzerland, September 19-24, 1997.

The ISOBM TD-6 Workshop is the first international workshop on monoclonal antibodies against the Sialyl Lewisa (SLea) antigen. Eight research groups participated in a blind study to characterize the epitope binding, relative affinity and performance in immunoradiometric assays, of a panel of 20 monoclonal antibodies. The antibodies were tested against a diverse panel of neoglycoconjugates, purified antigens and human serum pools from gastrointestinal malignancies. Epitope specificities were determined for the majority of antibodies in the panel. Cross-reactivity with related saccharide structures was noted in several antibodies. Overall, the results of the TD-6 Workshop show further development of SLea immunoassays may yield yet more specific assays for the detection and management of gastrointestinal and other malignancies.

Antibodies, Monoclonal↗