[Research ethics within care/nursing--protection for whom and for what?].
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Ethics Committees↗
Biomedical subjects
A Nyström
Publications and source records attributed to A Nyström.
Contrast sensitivity after implantation of diffractive bifocal and monofocal intraocular lenses.
PURPOSE: To compare contrast sensitivity (CS) after implantation of a diffractive bifocal intraocular lens (IOL) and a monofocal IOL of similar design. SETTING: Seven European centers. METHODS: In this randomized, prospective study, CS was tested 5 months after cataract and IOL implantation surgery in 115 patients with a diffractive bifocal IOL and 106 patients with a monofocal IOL. It was also tested in a subgroup of 38 patients who had bilateral implantation of a diffractive bifocal IOL. Contrast sensitivity was tested using the Vision Contrast Test System (VCTS). RESULTS: In patients with a best corrected visual acuity (BCVA) of 1.0 or better, the CS at all spatial frequencies (1.5 to 18 cycles/degree), both at distance and near, was slightly lower in the bifocal IOL group than in the monofocal group. Mean values were within the normal range. In patients with a BCVA of less than 1.0, the CS was lower and the difference between the bifocal and monofocal groups was less. In patients with bilateral bifocal IOLs, CS was better when tested bilaterally than when testing the better eye alone. Pupil size affected the results to a small degree. Contrast sensitivity appeared to improve over time after implantation of a diffractive bifocal IOL. CONCLUSIONS: In patients with cataract and no other eye pathology, the diffractive bifocal IOL with slightly reduce the CS at all spatial frequencies. In those with reduced visual acuity after cataract surgery, CS will be reduced accordingly. In this situation, the reduction from the diffractive bifocal optic would be minor.
Aged↗
Cold intolerance is not more common or disabling after digital replantation than after other treatment of compound digital injuries.
Cold intolerance is a common reason for disability after hand injury. In this study of posttraumatic cold intolerance, 20 patients with a history of digital replantation were matched with 20 control subjects who had not undergone replantation. The incidence and intensity of cold-related symptoms among patients in the two groups was investigated through the use of individual interviews and a grading scale for self-assessment of symptoms. The analysis of data indicates that although the pattern of symptoms may vary, the condition is neither more common nor more disabling among those who have undergone digital replantation. Cold intolerance after digital replantation seems, therefore, to be defined by the initial trauma and not by the subsequent reconstructive surgery.
Adult↗
Inhibitory effect of piracetam on platelet-rich thrombus formation in an animal model.
Intravenous administration of piracetam to hamsters reduced the formation of a platelet-rich venous thrombus induced by a standardised crush injury, in a dose-dependent fashion with an IC50 of 68 +/- 8 mg/kg. 200 mg/kg piracetam also significantly reduced in vivo thrombus formation in rats. However, in vitro aggregation of rat platelets was only inhibited with piracetam-concentrations at least 10-fold higher than plasma concentrations (6.2 +/- 1.1 mM) obtained in the treated animals. No effects were seen on clotting tests. In vitro human platelet aggregation, induced by a variety of agonists, was inhibited by piracetam, with IC50's of 25-60 mM. The broad inhibition spectrum could be explained by the capacity of piracetam to prevent fibrinogen binding to activated human platelets. Ex vivo aggregations and bleeding times were only minimally affected after administration of 400 mg/kg piracetam i.v. to healthy male volunteers, resulting in peak plasma levels of 5.8 +/- 0.3 mM. A possible antiplatelet effect of piracetam could be due to the documented beneficial effect on red blood cell deformability leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations were needed to prevent stirring-induced "spontaneous" platelet aggregation in human whole blood. It is concluded that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall itself must therefore be taken into consideration.
Animals↗
Pattern recognition in post-traumatic cold intolerance.
The subjective symptoms called "post-traumatic cold intolerance" were analysed in a study of 40 patients with a history of digital trauma (amputation, neurovascular laceration, or comminuted fracture requiring surgical reconstruction). The patients were individually interviewed to obtain detailed information about perception of each symptom as well as the pattern of symptoms of post-traumatic cold intolerance. The study confirmed the high incidence of the condition and its potentially disabling nature. Although the individual symptoms described by the patients have a limited number of categories, the subjective expression of cold intolerance is too varied to allow an adequate definition or assessment to be based on any single symptom or group of symptoms.
Adult↗
A technique to investigate mural thrombus formation in small arteries and veins: I. Comparative morphometric and histological analysis.
Numerous clinically relevant animal models exist for thrombosis studies. Few of these are suitable for both arteries and veins. In this investigation, an established venous thrombosis model was adapted through minimal technical adjustments to allow also the study of arterial thrombosis. A standardized subintimal crush injury was performed to carotid arteries or femoral veins of hamsters. Thrombus volumes were then quantified by direct morphometric measurements from serial microscopic sections or by on-line image analysis of light intensity changes from transilluminated vessels. The platelet-rich mural thrombus, which was established within minutes of the trauma, disintegrated during the observation period. The life cycle of the thrombus was different in arteries and veins, but significant linear correlation (p < 0.01) was found in both types of vessel between thrombus volumes measured by the two techniques. The model can consequently be used for comparative in vivo thrombosis studies in small (approximately 1-mm) arteries and veins.
Animals↗
A technique to investigate microvascular mural thrombus formation in arteries and veins: II. Effects of aspirin, heparin, r-hirudin, and G-4120.
After a standardized trauma to carotid arteries or femoral veins of hamsters, the antithrombotic effects of two antiplatelet agents (aspirin and the glycoprotein IIb/IIIa antagonist G4120) and two anticoagulants (heparin and the direct thrombin inhibitor r-hirudin) were studied in vivo. The thrombus area volume was assessed by image analysis of the transilluminated experimental vessels. Heparin, r-hirudin, and G-4120 demonstrated a dose-dependent complete inhibition of arterial and venous thrombosis. In contrast, the antithrombotic effect of aspirin was only partial in both vessel types. A significant correlation between activated partial thromboplastin time (aPTT) at the end of the experiments and the antithrombotic effect was observed with the anticoagulant agents. However, only r-hirudin inhibited thrombus formation at a therapeutical prolongation of aPTT, while heparin required supratherapeutical amounts to achieve the same inhibition. The data confirm that the inhibition of aspirin, heparin, r-hirudin, and G-4120 on the formation of platelet-rich thrombi is independent of the blood flow rate.
Animals↗
A historical review of hemostasis, thrombosis, and antithrombotic therapy.
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Animals↗
Comparison of a diffractive bifocal and a monofocal intraocular lens.
PURPOSE: To compare a Pharmacia diffractive bifocal intraocular lens (IOL) with a monofocal lens of the same design without the diffractive grating. SETTING: Multicenter study. METHODS: This randomized, prospective study comprised 70 patients with a monofocal IOL and 79 with a diffractive bifocal IOL. Follow-up was 5 to 6 months. Near and distance visual acuities, contract sensitivity, patient satisfaction, and spectacle use were evaluated. RESULTS: All patients achieved a best corrected visual acuity of 0.5 or better; 80% in the monofocal and 71% in the bifocal group had a best corrected visual acuity of 1.0 or better. Without correction, 93% of the bifocal and 9% of the monofocal group could read J3 or better. With distance correction, 99% and 4%, respectively, could read J3 or better. Contrast sensitivity was slightly lower in the bifocal group at distance and near for all spatial frequencies. In the bifocal group, 46% never used spectacles for near tasks. Overall satisfaction was rated good by 86% of the monofocal and 85% of the bifocal group. CONCLUSIONS: The diffractive bifocal IOL performed well at distance and near. Patients who no longer require spectacles will benefit significantly from a bifocal IOL, but many with a bifocal IOL in one eye will require spectacles for the fellow eye.
Aged↗
Antithrombotic effects of thrombolytic agents in a platelet-rich femoral vein thrombosis model in the hamster.
BACKGROUND: The extent and mechanism of the antithrombotic properties of fibrin-selective and non-fibrin-selective thrombolytic agents have not yet been established. METHODS AND RESULTS: The antithrombotic, thrombolytic, fibrinogenolytic, and pharmacokinetic properties of the following substances were determined in hamsters in the absence of conjunctive anticoagulant or antiplatelet therapy: recombinant tissue-type plasminogen activator (rTPA), recombinant single-chain urokinase-type plasminogen activator (rscu-PA), two-chain urokinase-type plasminogen activator (UK), with a rTPA deletion mutant lacking amino acids 6 to 173 and a mutation N184E (K2Pt), a rTPA/rscu-PA chimeric plasminogen activator consisting of amino acids 1 to 3 and 87 to 274 of rTPA and amino acids 138 to 411 of rscu-PA (K1K2Pu), streptokinase (SK), and recombinant staphylokinase (STAR). The anti-thrombotic effect, defined as the intravenous dose required to reduce mural thrombus formation to 50% in a platelet-mediated femoral vein thrombosis model in the hamster, was 6 +/- 1, 5 +/- 2, 1 +/- 0.05, 2.5 +/- 0.2, 0.02 +/- 0.002, 1 +/- 0.09, and 2 +/- 0.3 mg/kg (mean +/- SEM), respectively. The amounts, given as intravenous infusion over 60 minutes that induced 50% clot lysis in a hamster pulmonary embolism model, were 0.18 +/- 0.03, 1.1 +/- 0.05, 0.9 +/- 0.13, 0.34 +/- 0.03, 0.04 +/- 0.003, 0.05 +/- 0.005, and 0.04 +/- 0.001 mg/kg, respectively, indicating that for most thrombolytic agents the antithrombotic dose is much higher than their thrombolytic dose. The fibrinogen levels, measured 40 minutes after bolus injection, were reduced to 50% of baseline with 3.1 +/- 0.2, 2.5 +/- 0.3, 1.2 +/- 0.08, 2.0 +/- 0.14, 1.7 +/- 0.65, 0.54 +/- 0.03, and 1.2 +/- 0.11 mg/kg, respectively. Mean residence times following intravenous bolus injection were: 18 +/- 1, 14 +/- 1, 100 +/- 10, 80 +/- 2, 20 +/- 3, and 34 +/- 5 minutes for rTPA, rscu-PA, K2Pt, K1K2Pu, SK, and STAR, respectively. Regression analysis revealed a significant correlation of the antithrombotic effect with the fibrinogen breakdown (P = .006) but not with the thrombolytic potency or with the mean residence time. CONCLUSIONS: These observations support the hypothesis that thrombolytic therapy with fibrinogen-sparing agents requires the conjunctive use of anticoagulant and/or antiplatelet agents.
Animals↗
Monoallelic expression of IGF2 at the human fetal/maternal boundary.
IGF2 is expressed in both placental and decidual tissues, enabling an analysis of the parental imprinting over the fetomaternal boundary. Evidence is provided that IGF2 is monoallelically expressed in both placenta and pregnant, as well as nonpregnant, endometrium. These observations suggest that the maternally derived IGF2 allele is inactivated during germline transmission. Comparison of promoter usage in decidua and placental samples shows that the P3 promoter appears to regulated independently of the others. These observations are discussed with respect to current models of IGF2 imprinting and the hypothesized conflict of parental reproductive interests which bears on the phenomenon of parental imprinting.
Alleles↗
Intraoperative thrombolytic treatment of microarterial occlusion by selective rt-PA infusion.
The development of microvascular thrombosis during replantation surgery or free-flap transfer is generally best treated by identification of the problem, vascular revision, and reanastomosis. It is not unique, however, that surgical measures alone are insufficient or undesirable. Pharmacologic adjuncts are widely used for the prevention and sometimes treatment of microvascular thrombosis in surgical practice, but the benefit of thrombolytic agents, effective in dissolving an already established thrombus, is usually considered counterlevered by the fear of uncontrollable bleeding. However, selective infusion of the drug reduces the risk for systemic complications considerably and may therefore be considered in peripheral microvascular reconstruction. The technique was used successfully in a case of digital revascularization, where an arterial thrombosis was dissolved with the use of recombinant tissue plasminogen activator (rt-PA).
Adult↗
Cold induced vasospasm in replanted digits: a comparison between different methods of arterial reconstruction.
Nineteen patients each of whom had had a single digit replanted were examined after replantation. The arterial reconstruction had been done with long grafts (n = 10) or short grafts or no graft (n = 9). The effect of local or whole body cooling on the replanted and uninjured opposite digits was monitored (9-46 months after the replantation), and the patients were given a questionnaire (9-95 months after replantation) designed to explore the development of their cold related symptoms in relation to time. All patients were troubled by cold intolerance, and improvement occurred in only 60% of the cases. Pathological (vasospastic) arterial reactions to cold measured as finger systolic pressure, were less common after replantation with long grafts. Perceived cold intolerance was significantly more pronounced in the group of patients (60%) who had evidence of cold induced arterial spasm in the replanted finger.
Adult↗
Characterisation of a novel series of aprotinin-derived anticoagulants. I. In vitro and pharmacological properties.
Previous investigations have indicated that interference with the initial level of the blood coagulation may lead to effective antithrombotic therapy. Recently a series of potential coagulation inhibitors derived from bovine pancreatic trypsin inhibitor (BPTI, aprotinin) was described. We have determined their inhibition constants, effects on coagulation assays, effects in an in vitro human thrombosis model and pharmacological profiles in hamsters. The aprotinin-derived analogues (4C2, 7L22, 5L15, 6L15, 5L84) showed significantly increased inhibitory activity towards factor Xa, factor VIIa-tissue factor (TF) complex, factor XIa and plasma kallikrein or a combination of them, and a significantly decreased plasmin inhibition as compared to aprotinin. In the coagulation assays, 4C2 and 7L22 mainly inhibited factor Xa, 5L15 and 6L15 inhibited factor VIIa-TF complex and 5L84 inhibited factor Xa, factor VIIa-TF complex and the contact activation. In flow chamber experiments with human blood 7L22, 5L15, 6L15, 5L84 and rTAP significantly inhibited fibrin formation and platelet deposition on extracellular matrix from phorbol ester stimulated human endothelial cells both under high and low shear stress and in the presence of low molecular weight heparin. The pharmacological profiles of the aprotinin analogues and rTAP with a mean residence time of 64 to 140 min were not significantly different. Modification of an aprotinin analogue with PEG (5L15-PEG) resulted in a 10-fold decrease of the inhibition constant for the factor VIIa-TF complex and in a significant prolongation of the secondary half-life, while the initial half-life was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Characterisation of a novel series of aprotinin-derived anticoagulants. II. Comparative antithrombotic effects on primary thrombus formation in vivo.
Upon vascular damage platelet activation and blood coagulation are initiated. Interference at the initial level of the activation of the coagulation cascade can result in effective inhibition of thrombus formation. The in vivo antithrombotic properties of a series of bovine pancreatic trypsin inhibitor mutants (BPTI, aprotinin) 4C2, 7L22, 5L15, 5L15-PEG, 6L15 and 5L84, as described in the accompanying paper, with a combined inhibitory activity on factor Xa, factor VIIa-tissue factor complex, factor XIa and plasma kallikrein were compared to rTAP, r-hirudin, heparin and enoxaparin in a platelet rich thrombosis model in hamsters. Platelet dependent thrombus deposition was quantified by dedicated image analysis after transillumination of the femoral vein to which a standardised vascular trauma was applied. After increasing intravenous bolus injections all tested agents, except for aprotinin, induced a dose dependent decrease of thrombus formation and a concomitant prolongation of the aPTT. From the linear correlation between these two parameters it was found that 5 out of the 6 tested aprotinin analogues, rTAP and r-hirudin completely inhibited thrombus formation at a therapeutical (2- to 3-fold) aPTT prolongation while 4C2, heparin and enoxaparin only inhibited thrombus formation for 40 to 50 percent at a 2-fold aPTT prolongation. Based on the calculated IC50 values for thrombus formation rTAP was found to be the most active compound in this model. It is concluded that acceptable interference at the initial level of the blood coagulation, e.g. within a therapeutical aPTT prolongation, can significantly inhibit platelet deposition at a site of vascular injury.
Animals↗
Insulin-like growth factor 2 cannot be linked to a familial form of Beckwith-Wiedemann syndrome.
The Beckwith-Wiedemann syndrome (BWS) is characterised by congenital malformations and organomegaly associated with an increased risk for development of childhood neoplasms. Both a sporadic and a familial form have been described in the literature. It has been suggested that duplications or rearrangements of the short arm of chromosome 11 (11p15.5) underlie the aetiology of the disease. This region of chromosome 11 contains the insulin-like growth factor 2 (IGF2) gene, which has been shown to be parentally imprinted in the sporadic form of the BWS with only the active, paternally-derived allele being duplicated. The familial form of BWS, which exhibits a predominantly maternal inheritance, has been suggested to result from a relaxation of IGF2 imprinting. This could render both parental IGF2 alleles active, thereby generating a similar gene dosage as in the sporadic from of the BWS. To address this issue, we used an RNase protection assay based upon a polymorphic region within exon nine of IGF2. We show here that only the paternally-inherited IGF2 allele is transcriptionally active in the index patient of one family with inherited BWS. In addition, highly informative IGF2 DNA markers were used to perform linkage analysis. Since these data ruled out a common maternally-transmitted IGF2 allele in the affected patients, we argue that IGF2 cannot be linked to the hereditary form to the disease.
Alleles↗
Gray-scale sonography in torsion of the testicular appendages.
The reliability of gray-scale ultrasonography in diagnosing torsion of the testicular appendages was studied in a series of 54 boys with acute non-traumatic scrotal pain. All boys were operated upon, and the appendages extirpated irrespective of their appearance at exploration; the final diagnosis was based on histological examination. Forty-two boys had appendicular torsion, 2 had testicular torsion and 10 had other diagnoses. Using the sign of appendicular torsion--an echogenic extratesticular structure situated between the head of the epididymis and the upper pole of the testis--as the criterion, 37 displayed a true positive, 9 a true negative, 3 a false positive and 5 a false negative diagnosis. Thus, the sensitivity was 88%, the specificity 75% and the positive predictive value 93% respectively. The echogenic mass varied in size from 3 to 17 mm in diameter. In 34 of the 42 cases of appendicular torsion extratesticular fluid was present, and 19 patients showed enlargement of the head of the epididymis. It is concluded that gray-scale sonography is an accurate and valuable tool in diagnosing torsion of the testicular appendages.
Adolescent↗
Arterial spasticity and cold intolerance in relation to time after digital replantation.
Cold induced arterial vasospasm was studied in ten patients with single digit replantation, by measuring finger systolic pressure at different finger temperatures. Each patient was examined three times; within 2 weeks of surgery, after 1 year and after 3 years. The replantations were performed using long arterial and venous grafts. Cold-related vasospasm is established during the first year after trauma, and thereafter seems to be persistent. It is concluded that the subjective cold tolerance, which affects all patients after digital amputation regardless of whether replantation is performed or not, is partly due to vasospasm. It is less pronounced in patients without pathological vasospasm in the replanted digit. Cold intolerance is likely to decrease during the first 2 years after replantation, but not to disappear completely.
Adult↗