Professional and public attitudes towards unsolicited medical intervention.
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Accidents, Traffic↗
Biomedical subjects
J Pedersen
Publications and source records attributed to J Pedersen.
Pathophysiological mechanisms behind work-related muscle pain syndromes.
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Humans↗
Fin-flicking behaviour: a visual antipredator alarm signal in a characin fish, Hemigrammus erythrozonus.
Glowlight tetras, Hemigrammus erythrozonus, show a conspicuous visual display ('fin flicking') upon detecting a conspecific chemical alarm signal (alarm pheromone). We conducted laboratory studies to test two, nonmutually exclusive hypotheses regarding the function of this behaviour. To test the hypothesis that fin flicking acts as a visual alarm signal to conspecifics, we paired shoals of tetras with a stimulus tetra in an adjacent tank (separated by a one-way mirror) and exposed the stimulus tetras to conspecific skin extract (with alarm pheromone) or swordtail skin extract (which lacks ostariophysan alarm pheromone). Stimulus tetras significantly increased their frequency of fin flicking when exposed to conspecific skin extract, but not to the swordtail skin extract control. The test shoals showed a significant increase in antipredator behaviour in response to fin-flicking stimulus tetras, but not to stimulus tetras that did not fin-flick. To test the hypothesis that fin flicking serves as a predator deterrent, we paired predatory Jack Dempsey cichlids, Cichlasoma octofaciatum, with tetras in adjacent tanks and exposed the tetras to either conspecific or swordtail skin extract. Predators remained further away from the stimulus tetra, took longer to initiate a bite and displayed fewer bites towards tetras that fin-flicked compared with tetras that did not fin-flick. These results support our hypothesis that fin flicking in tetras serves as both a visual alarm signal to conspecifics and a deterring signal to predators, and suggest that individual tetras may reduce their risk of predation by fin flicking upon detecting a predation threat. Copyright 1999 The Association for the Study of Animal Behaviour.
Journal Article↗
Removal of N-terminal polyhistidine tags from recombinant proteins using engineered aminopeptidases.
We have developed a specific and efficient method for complete removal of polyhistidine purification tags (HisTags) from the N-termini of target proteins. The method is based on the use of the aminopeptidase dipeptidyl peptidase I (DPPI), either alone or in combination with glutamine cyclotransferase (GCT) and pyroglutamyl aminopeptidase (PGAP). In both cases, the HisTag is cleaved off by DPPI, which catalyzes a stepwise excision of a wide range of dipeptides from the N-terminus of a peptide chain. Some sequences, however, are resistant to DPPI cleavage and a number of mature proteins have nonsubstrate N-termini which protects them against digestion. For such proteins, HisTags composed of an even number of residues can be cleaved off by treatment with DPPI alone. When the target protein is unprotected against DPPI, a blocking group is generated enzymatically from a glutamine residue inserted between the HisTag and the target protein. A protein with a HisTag-Gln extension is incubated with both DPPI and GCT. As above, the polyhistidine sequence is cleaved off by DPPI, but when the glutamine residue appears in the N-terminus, it is immediately converted into a pyroglutamyl residue by an excess of GCT and further DPPI digestion is prevented. The desired sequence is finally obtained by excision of the pyroglutamyl residue with PGAP. All the enzymes employed can bind to immobilized metal affinity chromatography (IMAC) matrices, and in this paper we demonstrate a simple and highly effective process combining IMAC purification of His-tagged proteins, our aminopeptidase-based method for specific excision of HisTags and use of subtractive IMAC for removing processing enzymes. Typical recoveries were 75-90% for the enzymatic processing and subtractive IMAC. The integrated process holds promises for use in large-scale production of pharmaceutical proteins because of a simple overall design, use of robust and inexpensive matrices, and use of enzymes of either recombinant or plant origin.
Amino Acid Sequence↗
Localized muscle fatigue decreases the acuity of the movement sense in the human shoulder.
PURPOSE: The purpose of this study was to investigate alterations in the movement sense acuity during localized muscle fatigue in the human dominant shoulder. METHODS: Fourteen healthy volunteers (8 males and 6 females) with a mean age 23 +/- 2 yr participated in the study. The subjects' ability to discriminate movement velocity relative to a reference velocity imposed over the dominant shoulder was tested following two experimental conditions: 1) Light exercise (LE), repetitive isokinetic horizontal flexion/extensions at the shoulder, ranging from 85 degrees to 20 degrees relative to the frontal plane, at 10% of maximal voluntary contraction (MVC) and 2) Hard exercise (HE), same movements as in LE, but performing MVC to fatigue. RESULTS: The results showed that subjects had a lower probability of distinguishing between different movement velocities following HE as compared with those during the LE condition (P < 0.001). When genders were compared, female subjects had a lower probability of distinguishing correctly than male subjects (P < 0.001). CONCLUSIONS: The acuity of the movement sense in the dominant shoulder is reduced in the presence of shoulder muscle fatigue. The possible influence of muscle fatigue via peripheral muscle receptors on movement sense is discussed.
Adult↗
Inhibition of nitric oxide synthesis improves left ventricular contractility in neonatal pigs late after cardiopulmonary bypass.
BACKGROUND: Following neonatal open heart surgery a nadir occurs in left ventricular function six to 12 hours after cardiopulmonary bypass. Although initiated by intraoperative events, little is known about the mechanisms involved. OBJECTIVE: To evaluate the involvement of nitric oxide in this late phase dysfunction in piglets. DESIGN: Piglets aged 2 to 3 weeks (4-5 kg) underwent cardiopulmonary bypass (1 h) and cardioplegic arrest (0.5 h) and then remained ventilated with inotropic support. Twelve hours after bypass, while receiving dobutamine (5 microg/kg/min), the left ventricular response to non-selective nitric oxide synthase inhibition (l-N(G)-monomethylarginine (l-NMMA)) was evaluated using load dependent and load independent indices (E(es), the slope of the end systolic pressure-volume relation; M(w), the slope of the stroke work-end diastolic volume relation; [dP/dt(max)](edv), the slope of the dP/dt(max)-end diastolic volume relation), derived from left ventricular pressure-volume loops generated by conductance and microtip pressure catheters. RESULTS: 10 pigs received 7.5 mg l-NMMA intravenously and six of these received two additional doses (37.5 mg and 75 mg). E(es) (mean (SD)) increased with all three doses, from 54.9 (40.1) mm Hg/ml (control) to 86.3 (69.5) at 7.5 mg, 117.9 (65.1) at 37.5 mg, and 119 (80.4) at 75 mg (p < 0.05). At the two highest doses, [dP/dt(max)](edv) increased from 260.8 (209.3) (control) to 470.5 (22.8) at 37.5 mg and 474.1 (296.6) at 75 mg (p < 0.05); and end diastolic pressure decreased from 16.5 (5.6) mm Hg (control) to 11.3 (5.0) at 37.5 mg and 11.4 (4.9) at 75 mg (p < 0. 05). CONCLUSIONS: In neonatal pigs 12 hours after cardiopulmonary bypass with ischaemic arrest, low dose l-NMMA improved left ventricular function, implying that there is a net deleterious cardiac action of nitric oxide at this time.
Animals↗
Molecular modeling and preclinical evaluation of the humanized NR-LU-13 antibody.
A mouse-human chimeric monoclonal antibody (chNR-LU-13), specific for the EGP40 pancarcinoma antigen, was humanized through three-dimensional molecular modeling. Humanization of the chNR-LU-13 antibody is expected to enhance its use for patients undergoing immunotherapy. On the basis of the observed amino acid sequence identity, chNR-LU-13 complementary determining regions (CDRs) of the V(L) and V(H) regions were grafted onto the human anti-DNA-associated idiotype immunoglobulin clone, R3.5H5G'CL. Ten amino acids residues within the humanized framework were back-mutated to their corresponding chNR-LU-13 sequence, because they were predicted to disrupt the canonical classification of the CDRs or were within 5 A of a CDR. Synthesis of the V(L) and V(H) regions was accomplished by recursive PCR, and the dual-chain expression vector p451.C4 was positioned under control of the CMV(P+E). We observed by competitive ELISA that the recombinant humanized NR-LU-13 (huNR-LU-13) IgG1 antibody exhibited an indistinguishable immunoreactivity profile when compared with the murine monoclonal antibody (muNR-LU-10). The huNR-LU-13 antibody was effective in mediating both antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity when assayed against either the breast carcinoma cell line, MCF-7, or the colon adenocarcinoma cell line, SW1222. Biodistribution studies using i.v. coinjected 131I-muNR-LU-10 and 125I-huNR-LU-13 confirmed that the huNR-LU-13 specifically targets to the tumor in athymic BALB/c mice bearing the SW1222 human tumor xenograft. Humanization of the chNR-LU-13 antibody is expected to eliminate an undesired human antimouse antibody response, allowing for repeated i.v. administration into humans.
Amino Acid Sequence↗
Inhibins, activins, and follistatins: expression of mRNAs and cellular localization in tissues from men with benign prostatic hyperplasia.
BACKGROUND: The transforming growth factor beta (TGF beta) superfamily of growth factors includes activins and inhibins, which have been shown to be present in the rat ventral prostate, and human prostate tumor cell lines, although their localization in benign prostatic hyperplasia (BPH) tissue is currently unknown. METHODS: BPH tissues were obtained at surgery, and the mRNA expression for the inhibin alpha, beta A, beta B subunits, the putative activin beta C subunit, the activin type II receptor (ActRII), and the activin binding protein, follistatin, was determined by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot analysis. Antibodies specific for alpha, beta A, beta B, activin A, and follistatin were used to determine the localization of these proteins in BPH tissue specimens. RESULTS: Southern blot analysis confirmed that mRNA for ActRII, beta C subunit, and follistatin was present in all biopsy samples assayed. However, alpha, beta A, and beta B subunit mRNA expression was variable between patient samples. Immunohistochemistry demonstrated the predominant localization of beta A, beta B, and activin A proteins to the epithelium of BPH tissues. No immunoreactivity for the inhibin alpha subunit was detected; follistatin immunoreactivity was localized to the fibroblastic stroma. CONCLUSIONS: The compartmentalization of activin subunit proteins to the epithelium, and of follistatin to the stroma, suggests that a paracrine interaction occurs between the activin ligands and follistatin-binding proteins in BPH tissue.
Activin Receptors↗
Active recombinant rat dipeptidyl aminopeptidase I (cathepsin C) produced using the baculovirus expression system.
An active form of rat dipeptidyl aminopeptidase I (DPPI, cathepsin C) was obtained by heterologous expression in insect cells. Baculoviruses carrying a cDNA sequence encoding the entire rat DPPI precursor was used to infect High Five cells in a serum-free medium. Recombinant DPPI (rDPPI) was secreted into the medium from which it was purified by a combination of ammonium sulfate fractionation, hydrophobic interaction chromatography (HIC), and ion-exchange chromatography. A polyhistidine-tagged form of the enzyme (HT-rDPPI) was purified from the medium by immobilized metal affinity chromatography (IMAC). In vivo activation of native rat DPPI involves at least three chain cleavages per subunit and the ability of the expression system to imitate this processing was investigated. Both rDPPI and HT-rDPPI were secreted into the medium as unprocessed and inactive proenzymes and gradually converted into their active forms in the medium. This process was not completed at the time of harvest but mature enzyme processed similarly to native rat and human DPPI could be obtained by incubating the eluates from the HIC and IMAC columns at pH 4.5 and 5 degrees C for 18-40 h. The yield of purified and matured enzyme was approximately 50 mg/liter, and it was shown that rDPPI and HT-rDPPI were active against both a dipeptide-p-nitroanilide substrate and human growth hormone N-terminally extended with an Ala-Glu dipeptide.
Animals↗
The information transmitted by ensembles of primary spindle afferents is diminished when ketamine is used as a pre-anaesthetic.
The effect of pre-anaesthetic ketamine on ensemble coding of different stimuli consisting of muscle stretches of various amplitudes was studied for ensembles of simultaneously recorded primary muscle spindle afferents (MSAs). The experiments were conducted on 8 alpha-chloralose anaesthetised cats. Three of the cats received a pre-anaesthetic dose of ketamine (25 mg/kg) injected subcutaneously (ketamine group), while the remaining five animals did not (non-ketamine group). Data for ensemble coding were collected both before and after cutting the ventral root. A method based on principal component analysis and algorithms was used to quantify stimulus discrimination and an ANOVA tested differences between groups as well as differences due to ventral root cutting. When the fusimotor supply was intact, a general trend of an increase in the ability to discriminate stimuli with increasing ensemble size was observed for both groups, however, this trend was significantly greater for the non-ketamine group as compared to the ketamine group. When the ventral root was cut, the discrimination pattern for the non-ketamine group decreased significantly (as compared to before ventral root cutting), however, no change occurred for the ketamine group. Consequently, no difference in discrimination pattern was detected between groups after ventral root cutting. The reduction in information transmitted by ensembles of primary MSAs when ketamine is used as a pre-anaesthetic may suggest that ketamine elicits an adverse affect on the fusimotor system.
Afferent Pathways↗
Bradykinin and muscle stretch alter contralateral cat neck muscle spindle output.
The objective of this study was to investigate the activity of primary and secondary muscle spindle afferents (MSAs) in neck muscles, when the contralateral splenius or trapezius muscles were (1) exposed to i.m. injection of bradykinin (BK) (6-86 microg/ml), (2) stretched, (3) stretched during exposure to BK or (4) stretched after exposure to BK. It was found that injection of BK, muscle stretch and the combination of the two stimuli significantly excited primary and secondary MSAs via reflex effects onto static fusimotor neurones. BK, alone, and in combination with muscle stretch, induced more frequent, potent and long lasting effects as compared to muscle stretch. The effects of muscle stretch was significantly increased after exposure of BK, indicating that stretch-sensitive nerve-endings within neck muscles are sensitised by BK. The results are discussed in relation to the disturbances in motor co-ordination and proprioception found in patients suffering from chronic muscle pain in the cervical region.
Animals↗
Alterations in information transmission in ensembles of primary muscle spindle afferents after muscle fatigue in heteronymous muscle.
This study showed that fatigue of the ipsilateral medial gastrocnemius muscle caused a clear-cut reduction in the ability of ensembles of primary muscle spindle afferents from the lateral gastrocnemius muscle to discriminate between muscle stretches of varying amplitude. The results were probably caused by reflex-mediated effects from chemosensitive group III and IV afferents onto the gamma-motoneurons projecting to lateral gastrocnemius muscle spindles. The experiments were conducted on seven cats anaesthetized with alpha-chloralose and a total of 41 primary muscle spindle afferents from the lateral gastrocnemius were registered. Afferents were simultaneously recorded in ensembles of three to 10 afferents. A method based on principal component analysis and algorithms for quantification of stimulus discrimination in ensembles of muscle afferents was used prior to, immediately following and five or more minutes after muscle fatigue had been induced to the ipsilateral medial gastrocnemius muscle. It is well established that the primary muscle spindle afferents play an important role in proprioception and kinaesthesia. Therefore the decrease in the accuracy of the information transmitted by ensembles of primary muscle spindle afferents caused by fatigue in an ipsilateral muscle implies concomitant effects on proprioception and kinaesthesia.
Animals↗
Convective warming blankets improve peroperative heat preservation in congenital heart surgery.
Peroperative heat preservation, following hypothermic cardiopulmonary bypass (CPB) in children, has always been a challenge to the anaesthetist. We studied the efficiency of a convective heating system on peroperative heat preservation in 50 children undergoing congenital heart surgery. Twenty-five children, rewarmed by CPB and heating mattress, were randomly selected (Group 1). Another 25 children, rewarmed by CPB, heating mattress and convective warming blankets in addition (Group 2), were selected so the two groups were comparable regarding age, weight and anaesthetic management. The central and peripheral temperatures were measured during bypass, at the end of bypass and at the end of operation. A retrospective evaluation showed that during bypass the peripheral temperature was significantly lower in Group 2 than in Group 1, with no significant difference in central temperature. At the end of bypass there was no significant difference between the two groups. At the end of operation the central and peripheral temperatures were significantly higher in Group 2. In conclusion convective warming blankets are effective in keeping or even raising the temperature following congenital heart surgery.
Body Temperature↗
Transurethral incision versus resection of the prostate for small to medium benign prostatic hyperplasia.
OBJECTIVE: To compare the effects of transurethral incision and resection of the prostate in patients with small to medium benign prostatic hyperplasia. PATIENTS AND METHODS: Patients were assessed preoperatively using the Madsen-Iversen symptom score, post- void residual urine volume, urinary flow and cystoscopy. Those eligible for the study were randomized to undergo either transurethral incision or resection of the prostate. Follow-up visits were scheduled at 2-3.6, 12, 24 and 60 months post-operatively with an assessment by symptom score and urinary flow rate; most patients also underwent cystoscopy at 24 and 60 months. RESULTS: The maximum urinary flow rate was significantly higher in those undergoing resection than incision at all but the last follow-up visits. Cystoscopy 24 months after surgery showed adhesions between the lateral lobes, closed incisions or obstructing prostatic lobes in most of the patients undergoing incision, but not in those resected (P < 0.001, chi-square test). During follow-up, a second transurethral procedure was carried out for persistent or recurrent symptoms, combined with a maximum urinary flow rate of < 10.0 mL/s, in 10 patients who underwent incision and in three who were resected (P = 0.039, chi-square test). CONCLUSION: Transurethral resection is preferable to transurethral incision of the prostate in the treatment of small to medium benign prostatic hyperplasia.
Aged↗
Percutaneous dilatational tracheostomy versus conventional surgical tracheostomy. A clinical randomised study.
BACKGROUND: As no clinical randomised studies have previously been performed comparing complications with the Ciaglia Percutaneous Dilatational Tracheostomy Introducer Set (PDT) and conventional surgical tracheostomy (TR), we designed a study with the aim of comparing the efficacy and safety of the two techniques. METHODS: Sixty patients selected for elective tracheostomy were randomised for either PDT (30 patients) or TR (30 patients). All patients had general anaesthesia and were ventilated with 100% oxygen. Furthermore, lidocaine with epinephrine 1% (3-5 ml) was used for local analgesia and to minimise bleeding during the procedure. RESULTS: The median time for insertion of the tracheostomy tube was 11.5 min (range 7-24 min) in the PDT group and 15 min (range 5-47 min) in the TR group (P<0.01). Complications during the procedure were cuff puncture of the endotracheal tube in 5 cases in the PDT group. Minor bleeding was encountered in 6 cases in the PDT group as opposed to 24 cases in the TR group (P<0.01), major bleeding in none versus 2 cases, respectively. In 8 cases in the PDT group, increased resistance to insertion of the tracheostomy tube was met by further dilatation. During the post-tracheostomy period, complications occurred with minor bleeding in 2 cases in the PDT group as opposed to 9 cases in the TR group (P<0.05), and major bleeding was encountered in 1 case in each group. Minor infections were encountered in 3 cases in the PDT group as opposed to 11 cases in the TR group (P<0.01). Major infection was encountered in none versus 8 cases, respectively (P<0.01). CONCLUSION: Our results indicate that the percutaneous dilatational tracheostomy technique performed with the Ciaglia Introducer Set is effective, safe and superior to conventional surgical tracheostomy as immediate complications as well as complications with the tracheostomy tube in situ are fewer and of less severity.
Adolescent↗
Modified ultrafiltration in paediatric cardiac surgery.
The effect of modified ultrafiltration (MUF) after cardiopulmonary bypass for paediatric cardiac surgery was evaluated in 138 children with moderate to severe congenital heart disease. The median age was 0.4 years (0 days to 6.5 years), and the weight 5.3 kg (2.2-20 kg). The operation was discontinued in six cases, three because of technical problems and three because of unstable circulation. One-hundred-and-thirty-four patients were ultrafiltrated for a median of 12 min (2-27 min) with an ultrafiltrate of median 44 ml/kg (6-118 ml/kg). Haematocrit was significantly increased from 28% (20-39%) to 36% (26-51%) and systolic arterial pressure from 56 mmHg (30-85 mmHg) to 74.0 mmHg (32-118 mmHg). Furthermore arterial oxygenation was significantly increased from 30.8 kPa (4.8-70.4 kPa) to 34.1 kPa (4.9-80.6 kPa), and arterial carbon dioxide tension from 4.8 kPa (3.1-7.3 kPa) to 5.1 kPa (3.1-7.6 kPa). Heart rate was significantly reduced from 145 beats/min (92-201 beats/min) to 136 beats/min (88-200 beats/min). There were no significant differences in central venous pressure, left atrial pressure and base excess before and after MUF. MUF increases systolic blood pressure, haematocrit, arterial oxygen and carbon dioxide tension coming off bypass in paediatric cardiac surgery and reduces heart rate and postoperative fluid overload.
Cardiac Surgical Procedures↗
Development of a new production system for weaned and growing pigs.
The design of modem housing systems for farm animals calls for cooperation between scientists within different disciplines. This article describes the design of a new production system for weaned and growing pigs, as well as the analyses and working processes behind its development. The aim of the study was to develop an economically competitive system that also provided better welfare for the animals and a healthier environment for the workers. Analyses were carried out with emphasis on behavioral needs and building design and economy. The resulting system, the "safari system," consists of a number of straw flow pens of increasing size. Pigs are moved to larger and larger pens each week until slaughter. The main advantage is that pigs are not mixed during the growth period and that they are given more space, especially toward the end of the growth period when their space demand is high. Furthermore, the provision of straw for comfort and exploration and of wallow basins for cooling in the pens for the larger pigs were considered significant welfare improvements. An analysis revealed that the safari system would be economically competitive in comparison to traditional intensive systems.
Journal Article↗