["How do I do that?" Action provides relatives quick contact with health care].
Explore the source record for details and available documents.
Computer-Assisted Instruction↗
Biomedical subjects
A Olsson
Publications and source records attributed to A Olsson.
[Inventors' school for nurses].
Explore the source record for details and available documents.
Career Choice↗
[Will we learn from Southeast Asia? Enormous wage differences, censorship, strike prohibition, long waiting lists for health care...].
Explore the source record for details and available documents.
Culture↗
Antithrombin III supplementation for patients undergoing PTCA for unstable angina pectoris. A controlled randomized double-blind pilot study.
BACKGROUND: Thrombin activation may be a higher risk for complications and restenosis after percutaneous transluminal coronary angioplasty in unstable patients than in patients with stable angina pectoris. The effects of heparin may be partly counteracted by a decrease in antithrombin (III). The primary objectives of this study were to evaluate whether a subnormal antithrombin level was associated with a hypercoagulable state and to evaluate the effects of antithrombin supplementation, before and after percutaneous transluminal coronary angioplasty, on biochemical signs of coagulation activation. Secondary objectives were to evaluate acute complications and restenosis rate at 3 months. METHODS: In a double-blind pilot study, 50 patients with unstable angina, with ongoing heparin infusion and with subnormal antithrombin levels (< 85%) were randomized to receive antithrombin supplementation or placebo. Treatment targeted to an antithrombin level of 120% was started with a 2h intravenous infusion before the percutaneous transluminal coronary angioplasty and was repeated, if there were further subnormal values, every 12th hour for 48 h. RESULTS: Angiographic success was 20/25 in the antithrombin group and 21/25 in the placebo group (ns). Abrupt closure occurred in two and one patients in the two groups, respectively. Activation of coagulation measured as elevations of prothrombin fragment 1+2, thrombin-antithrombin complexes and fibrin D-dimer was seen 2 days after the procedure. Baseline levels of fibrin D-dimer were 68 +/- 69 micrograms.l-1 in the antithrombin group vs 71 +/- 46 micrograms.l-1 in the placebo group (ns). Two days after percutaneous transluminal coronary angioplasty the levels increased to 135 +/- 103 vs 242 +/- 150 micrograms.l-1, respectively (P < 0.05 between the groups). Restenosis at 3 months occurred in 4/20 antithrombin patients and in 8/21 placebo patients (ns). CONCLUSIONS: In unstable angina patients with heparin treatment and subnormal antithrombin levels, anti-thrombin supplementation resulted in less activation of coagulation and a tendency towards less restenosis.
Angina, Unstable↗
The 14-3-3 protein interacts directly with the C-terminal region of the plant plasma membrane H(+)-ATPase.
Accumulating evidence suggests that 14-3-3 proteins are involved in the regulation of plant plasma membrane H(+)-ATPase activity. However, it is not known whether the 14-3-3 protein interacts directly or indirectly with the H(+)-ATPase. In this study, detergent-solubilized plasma membrane H(+)-ATPase isolated from fusicoccin-treated maize shoots was copurified with the 14-3-3 protein (as determined by protein gel blotting), and the H(+)-ATPase was recovered in an activated state. In the absence of fusicoccin treatment, H(+)-ATPase and the 14-3-3 protein were well separated, and the H(+)-ATPase was recovered in a nonactivated form. Trypsin treatment removed the 10-kD C-terminal region from the H(+)-ATPase as well as the 14-3-3 protein. Using the yeast two-hybrid system, we could show a direct interaction between Arabidopsis 14-3-3 GF14-phi and the last 98 C-terminal amino acids of the Arabidopsis AHA2 plasma membrane H(+)-ATPase. We propose that the 14-3-3 protein is a natural ligand of the plasma membrane H(+)-ATPase, regulating proton pumping by displacing the C-terminal autoinhibitory domain of the H(+)-ATPase.
14-3-3 Proteins↗
Clinical safety of enamel matrix derivative (EMDOGAIN) in the treatment of periodontal defects.
The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN at 1 comparable site. In total, 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery, 56 other samples were taken after one treatment with EMDOGAIN, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of postsurgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months postsurgery, and this difference had increased further at the 3 year follow-up. The 2.5-3 mm increase in attachment and bone level after treatment with EMDOGAIN was of the same magnitude as seen in the studies with split-mouth design aiming for test of effectiveness of EMDOGAIN.
Adult↗
Pharmacokinetics, toxicity, side effects, receptor affinities and in vitro radiosensitizing effects of the novel metoclopramide formulations, sensamide and neu-sensamide.
Metoclopramide is a drug which has experienced worldwide use in the clinic for over 30 years as an antiemetic. Recently, it has also been shown to possess radio- and chemosensitizing properties in both animal tumour models and humans at the higher dose of 2 mg/kg. Two new metoclopramide formulations are being clinically developed and they differ mainly in whether the pH of their formulations are acidic (pH 2.5-3.5) or neutral (pH 6.5-7.0). Here we report that intramuscular administration of neutral metoclopramide is about 100% bioavailable, safer and with reduced side effects compared to acidic metoclopramide delivered by intramuscular injection to rats within the dose range of 3.5 to 14 mg/kg. The intramuscular administration of metoclopramide was also about 100% bioavailable compared to the intravenous route of administration. Furthermore, neutral metoclopramide had significantly decreased affinity for dopamine D2 receptors and increased affinity for 5-hydroxytryptamine, receptors, but the radiosensitizing potency was the same, when compared to equimolar concentrations of acidic metoclopramide. Taken together these data support the continued development of neutral metoclopramide for high dose intramuscular administration of metoclopramide for future clinical use as both an antiemetic and radiosensitizer.
Animals↗
[Decubitus prevention in theory and practice--a study structure with the VIPS model].
The aim of this paper is to demonstrate that the VIPS-model, a model for nursing documentation, can be used as a tool and as a structure for analyzing and categorizing literature and emprical data. The usefulness of the model is demonstrated with data from a study concerning nursing interventions to prevent decubitus.
Clinical Nursing Research↗
Sulfatide-induced L-selectin activation generates intracellular oxygen radicals in human neutrophils: modulation by extracellular adenosine.
The sulfated form of galactocerebrosides (sulfatides) have recently been established as ligands for L-selectin. In this study we show that exposure of human neutrophils to sulfatides induces a transient generation of oxygen radicals, revealed by the luminol-enhanced chemiluminescence (CL) technique. The CL response was mainly located intracellularly, and was dependent on sulfation of the galactose ring, since non-sulfated galactocerebrosides had no effect. Sulfatides also dramatically amplified the CL response triggered by the chemotactic peptide formylmethionyl-leucyl-phenylalanine (fMLP). This effect was primarily due to an increased (up to 10-fold) intracellular generation of oxygen metabolites. Removal or blocking of L-selectin with chymotrypsin and monoclonal antibodies, respectively, markedly reduced the effects of sulfatides. Furthermore, sulfatides amplified the CL response triggered by ionomycin, whereas the response induced by phorbol-12-myristate-13-acetate was slightly reduced. The tyrosine kinase inhibitor, genistein, markedly inhibited the oxygen radical production induced by sulfatides, and totally abolished the potentiating effects of sulfatides in fMLP- and ionomycin-stimulated neutrophils. Sulfatides also triggered a transient rise in the intracellular free calcium concentration, [Ca2+]i. Consequently, L-selectin activation through sulfatides appear to affect oxidase activity through a Ca(2+)-dependent pathway involving tyrosine phosphorylation. Adenosine is an anti-inflammatory agent predominately released from the vascular endothelium which might suppress an inappropriate activation of the oxidase during L-selectin-mediated rolling of neutrophils. Indeed, we found that adenosine inhibited the oxidative burst induced by sulfatides, mainly by attenuating the intracellular generation of oxygen radicals. However, 10-100 times higher concentration of exogenous adenosine was required to inhibit the CL response induced by sulfatides to the same extent as the adenosine-mediated inhibition of the fMLP-induced response. This difference in sensitivity to adenosine could be explained by various expression of extracellular adenosine deaminase (ADA), since we found that the ADA-inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) markedly reduced the oxygen radical production caused by sulfatides and almost totally abolished the potentiating effects of sulfatides on the fMLP-induced respiratory burst. In contrary, EHNA only slightly reduced the fMLP-triggered CL response. We suggest that the initial activation of L-selectin prepare the neutrophil for an effective microbicidal activity in the extravascular space. This process might be dependent on a L-selectin-mediated increase in the expression and activity of ADA, which locally reduces the extracellular level of adenosine.
Adenosine↗
Hypochlorous acid/N-chloramines are naturally produced DNA repair inhibitors.
Human mononuclear leukocytes (HML) respond to oxidative DNA damage by activation of ADP ribosylation and initiation of DNA repair synthesis (i.e. unscheduled DNA synthesis, UDS), whereas neutrophils do not. When neutrophils are added to HML cultures in ratios up to 4:1 ADP ribosylation becomes inhibited to approximately 50-60%. The ability of neutrophils to inhibit HML ADP ribosylation was shown to be dependent on H2O2, chloride ions and myeloperoxidase, which in turn are factors known to govern HOCl and N-chloramine production by phagocytic cells. HOCl and a model N-chloramine, chloramine T, were shown to give a dose-dependent inhibition of DNA repair using four independent estimates, namely ADP ribosylation, UDS and the repair of DNA strand breaks estimated by nucleoid sedimentation and alkaline elution profiles. All the DNA repair measurements used on HML were inhibited approximately 70-80% by 100 microM doses of HOCl or chloramine T, which was considered a biologically relevant dose because: (i) viable neutrophils equal in concentration to those found in blood could easily produce 100 microM levels in short-term culture; (ii) 100 microM doses of these agents were not acutely cytotoxic judged by trypan blue stained cells after 30-60 min exposure and under the conditions used for assay, but yet they abolished 86-95% of the growth response of HML to phytohemagglutinin.
Adenosine Diphosphate Ribose↗
Hypophosphatasia affecting the permanent dentition.
Reports on dental abnormalities in connection with hypophosphatasia almost exclusively describe changes in primary teeth. A 23-year-old man with hypophosphatasia, first diagnosed at the age of 8 months, is described; histologically and radiographically verified signs of the condition were present in the permanent dentition. The findings included a reduced level of the marginal alveolar bone supporting the upper central incisors, which had to be extracted. The molars displayed large coronal pulp chambers. Histologically, the upper incisors demonstrated abnormal root cementum, with areas of dentin resorption, as well as disturbances of the mineralization of the coronal dentin. The patient also had signs of abnormal root resorption of molars. The potential involvement of permanent teeth puts children with hypophosphatasia at risk of developing oral complications during adolescent and adult life.
Adult↗
Wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits transcytosis in polarized epithelial cells.
Wortmannin, an inhibitor of phosphoinositide 3-kinase, inhibits both basolateral to apical and apical to basolateral transcytosis of ricin in Fisher rat thyroid (FRT) cells by 50% at 100 nM in a continuous transcytosis assay. In MDCK cells, a similar effect of wortmannin on basolateral to apical transcytosis of ricin was found, whereas apical to basolateral transcytosis was inhibited to a lesser degree. Transcytosis of dimeric IgA in MDCK cells expressing the polymeric immunoglobulin receptor was also reduced to 50% of controls, suggesting that wortmannin inhibits membrane translocation rather than sorting of specific proteins in the transcytotic pathway. This effect of wortmannin is selective, however, in that endocytosis at the basolateral domain and recycling at both the basolateral and apical membrane domains are unaffected, and apical endocytosis and apical secretion are only moderately reduced. We have shown previously that cAMP stimulates a late stage in basolateral to apical transcytosis in MDCK cells through activation of protein kinase A (Hansen, S. H., and Casanova, J.E. (1994) J. Cell Biol. 126, 677-687). Elevation of cellular cAMP still induced a 100% increase in transcytosis in wortmannin-treated cells, but transcytosis was no longer increased when compared to cells which received no drugs. In contrast, in experiments using a 17 degrees C block to accumulate ricin internalized from the basolateral surface in the apical compartment of MDCK cells, wortmannin had little effect on the stimulation of transcytosis by activators of protein kinase A observed under these conditions. The data thus suggest the existence of a wortmannin-sensitive step in the transcytotic pathway, positioned after endocytosis but prior to translocation into the protein kinase A-sensitive apical compartment, implying a role for phosphoinositide 3-kinase in an intermediate step in transcytosis in polarized epithelial cells.
Androstadienes↗
Progress in identifying clinical relevance of inhibition, stimulation and measurements of poly ADP-ribosylation.
Our laboratory, in collaboration with Oxigene Inc, has been involved in identifying commercially feasible clinical applications of measurement or modulation of ADP-ribosylation as a core technology. For this purpose a pivotal regulatory role for ADP-ribosylation in the repair of DNA lesions leading to cytotoxic as well as mutagenic events has been hypothesized. A new class of DNA repair inhibitors, the N-substituted benzamides, has been identified which can react with radiation to produce reactive intermediates that oxidize thiol amino acids. Their proposed mechanisms of action are two-fold: ie they can interact with radiation: i) to directly enhance DNA damage; and ii) to react with thiols in the zinc finger DNA binding domain of poly ADP-ribosyl transferase to inhibit DNA repair and thereby increase DNA damage. Sensamide, a clinically relevant formulation of metoclopramide which is an N-substituted benzamide, has indicated enhancement of tumor response and survival in patients with inoperable squamous cell carcinoma of the lung when it was administered as a radiosensitizer in a phase I/II trial and compared to historical controls. A mechanism of endogenous regulation of human mononuclear leucocyte ADP-ribosylation has been identified to be HOCl/N-chloramine production via the oxidative burst of phagocytes. HOCl/N-chloramines are potent oxidants of thiol-containing proteins. Quantitative estimation of N-chloramine sensitive plasma thiols has been identified as an effective surrogate measure of leucocyte poly ADPRT.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
A phase I/II evaluation of metoclopramide as a radiosensitiser in patients with inoperable squamous cell carcinoma of the lung.
The feasibility of administering metoclopramide (MCA) as a radiosensitizer has been evaluated in 23 patients with a pathological or cytological diagnosis of a squamous cell carcinoma of the lung, clinically evaluated as inoperable. All patients received 40-60 Gy radiotherapy fractionated into 1.8 Gy fractions 5 times per week (Monday-Friday). Two MCA treatment regimens were used: (i) MCA at 2 mg/kg administered by intravenous-infusion 1-2 h prior to radiotherapy 3 times per week (Monday, Wednesday, Friday); and (ii) MCA at 1 mg/kg administered by intravenous infusion 1-2 h prior to radiotherapy 5 times per week (Monday-Friday). 11 of the 23 patients treated with radiotherapy and MCA had none to mild pneumonitis or fibrosis and another 8 of the 23 had moderate levels. No patient had their therapy interrupted due to radiation-related side-effects. The MCA-related side-effects were as expected, i.e. 78% of the patients experienced sedation/tiredness and 48% expressed restlessness/anxiety symptoms. Both the total dose and serum levels of MCA were significantly associated to the MCA side-effect profile. Tumour response, duration of tumour response and survival were significantly positively correlated to the total and weekly doses of MCA administered to the patients during their radiotherapy treatment. These favourable phase II data have justified the initiation of a phase II/III randomised multicentred trial being carried out in Europe to evaluate MCA as a radiosensitiser.
Aged↗
In vivo tumor measurement of DNA damage, DNA repair and NAD pools as indicators of radiosensitization by metoclopramide.
Metoclopramide (MCA), a N-substituted benzamide, causes DNA strand breaks and inhibits DNA repair in vitro and sensitizes radiation and chemotherapeutic drugs in human squamous cell carcinomas when xenographed into nude mice or in a rat glioma model. Here we report on the evaluation of the mechanism behind the radiosensitizing effects of MCA. DNA damage was measured in vivo in a CBA-mouse tumor line (A12B3, sarcoma tumor) by using both alkaline elution and nucleoid sedimentation analysis of cell suspensions prepared from either resected tumor, spleen tissues or whole blood samples. The amount of DNA damage caused by radiation alone, measured 30 min after the irradiation was started, was dose dependent up to 18 Gy in all tissues. The radiation-induced DNA damage in tumor tissue was elevated compared to radiation alone in the presence of MCA, but the level was not higher at 18 Gy compared to 6 Gy in the presence of MCA, and it was still not fully repaired 12 h after irradiation. HPLC analysis of the NAD pools in tumor tissue after DNA damage induction showed a delay in the recovery of the NAD pools (presumably due to the presence of still unrepaired DNA) after exposure to MCA (2 mg/kg) + radiation (6 Gy) compared to tumors exposed to radiation (6 Gy) only, which were fully restored after 48 h. These data confirm earlier published in vitro data on MCA as an inducer of DNA damage and an effector of DNA repair. In addition, the in vivo measurement of radiation-induced DNA damage and DNA repair using the nucleoid sedimentation and alkaline elution assays together with NAD pool determinations may prove to be effective intermediate endpoints in the evaluation of drugs as potential radiosensitizers.
Animals↗
Acidic and neutralized metoclopramide formulations sensitize ionizing radiation induced cytotoxicity in a human lung adenocarcinoma xenografted to scid mice.
A neutralized formulation (Neu-Sensamide) of metoclopramide (MCA) has been shown to possess reduced sedative side effects compared with the conventional acidic formulations (Primperan). The acidic formulation of MCA has also been shown to sensitize the effect of ionizing radiation (6-8 Gy) using human squamous cell carcinomas from the head and neck xenografted to nude mice. In the present study, 2 mg MCA/kg body weight 1-3 h before treatment with 1 Gy radiation (single dose) was evaluated in scid mice xenografted with a human lung adenocarcinoma. MCA given alone in acidic or neutralized formulations did not show any effect on tumor growth retardation. However, when combined with radiation, both acidic and neutralized formulations of MCA sensitized the cytotoxic effect of radiation directed against the tumors by increasing tumor doubling time, tumor quadrupling time and specific growth delay, and by decreasing area under growth curve measurements. In addition, there was no statistically significant difference between the two formulations of MCA in the efficacy of sensitizing the cytotoxicity of a single low dose (1 Gy) of radiation.
Adenocarcinoma↗
Computerized evaluation of the peripheral blood flow during maximal vasodilatation in humans using venous occlusion plethysmography.
Forearm blood flow was studied with venous occlusion plethysmography after ischaemic exercise in 10 healthy volunteers and 10 hypertensive patients. The peak blood flow was calculated by three methods: the manual conventional graphic technique and by fitting of a tangent to the inflow curve with the help of a computer. In addition a computer-aided derivation of an exponential curve adapted to the initial part of the inflow curve was used for the calculation of the maximal blood flow. With the two tangential techniques the peak mean blood flow values did not differ significantly and were 58 ml min-1 100 ml-1 tissue while the exponential derivation procedure gave in both groups about 40% higher maximal flow values. The effect of venous occlusion on the linear velocity of the brachial arterial blood flow blood was studied with Ultrasound Doppler Flowmetry. The maximal flow velocity after ischaemic exercise decreased by about 18% during 50 mmHg venous occlusion; the influence of the venous stasis was least during the first heart beats after the onset of the venous occlusion. The effect of the venous stasis was similar but less pronounced in the hypertensive patients. In conclusion, forearm blood flow during maximal vasodilatation is reduced by venous occlusion and the best estimate of the flow is obtained from the earliest part of the venous occlusion inflow curve, as indicated by the use of the computer-aided exponential derivation technique.
Adult↗
Molecular characterization of native and recombinant apolipoprotein A-IMilano dimer. The introduction of an interchain disulfide bridge remarkably alters the physicochemical properties of apolipoprotein A-I.
The disulfide-linked dimer of apolipoprotein A-IMilano (A-IM/A-IM), a natural Arg173-->Cys variant of apoA-I, was purified from carriers' plasma and produced in Escherichia coli. The recombinant A-IM/A-IM is identical to native A-IM/A-IM, by mass spectrometry, SDS-polyacrylamide gel electrophoresis, and isoelectric focusing. Lipid-free A-IM/A-IM undergoes concentration-dependent self-association similar to apoA-I, but at all concentrations apoA-I is more self-associated than A-IM/A-IM. Far-ultraviolet CD spectra of A-IM/A-IM reveal a highly alpha-helical structure predicted to be approximately 65% in the lipid-free and approximately 78% in the lipid-associated states, versus 43 and 73% for apoA-I. A significant loss of alpha-helix occurs below pH 3.5 and above pH 10 in both apoA-I and A-IM/A-IM; A-IM/A-IM constantly shows a higher alpha-helical content than apoA-I over the entire pH range (1.7-12.8), suggesting that hydrophobic forces stabilize the interaction between the two A-IM chains. Indeed, and differently from apoA-I, the alpha-helical content of A-IM/A-IM is minimally affected by solvent ionic strength. The aromatic side chains in both lipid-free and lipid-bound A-IM/A-IM are immobilized in a more asymmetric and hydrophobic environment than in lipid-free apoA-I, the conformation of A-IM/A-IM being instead similar to that achieved by apoA-I following interaction with lipids. The present findings prove that rA-IM/A-IM is structurally identical to the native protein; the conformation of A-IM/A-IM is remarkably different from that of apoA-I, thus possibly explaining some of the peculiar functional properties of the apoA-IMilano dimer.
Amino Acid Sequence↗