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Biomedical subjects

G Pettersson

Publications and source records attributed to G Pettersson.

At least 37 records · Page 2Linked to original sources

Effect of dynamic channelling on the transient-state kinetics of coupled enzyme reactions.

Evidence is presented to show that the presence of a channelled reaction branch in a coupled two-enzyme reaction leads to a slower overall relaxation of the system towards steady state following perturbations of the reaction conditions. A predominant part of the total reaction flux change resulting from perturbations may be governed by transients that are more rapid in the presence than in the absence of a channel, but only under specific conditions that are not likely to be of biological relevance.

Animals↗

Airway epithelium of transplanted lungs with and without direct bronchial artery revascularization.

OBJECTIVE: Normal systemic blood flow to the airways and lung parenchyma of transplanted lungs can only be re-established by direct bronchial artery revascularization. The purpose of the present study was to investigate whether such direct bronchial artery revascularization would preserve ciliary function, previously shown to be reduced in lungs transplanted without revascularization. METHODS: Twenty-five single lung transplanted patients were included in this study. Complete direct bronchial artery revascularization was achieved in eight patients. In 16 patients the procedure had either failed (n = 10) or was not attempted (n = 6). In one patient the result of the revascularization was unknown. Airway epithelium samples were obtained from the native and the transplanted lungs during bronchoscopic examinations. Airway erythema and excessive secretion were registered. The epithelium samples underwent histological examination and ciliary beat frequency was measured in vitro by video recording. Transbronchial biopsies from the transplanted lungs were examined for signs of rejection and bronchitis. RESULTS: No differences in ciliary beat frequency nor in the distribution of ciliated/de-ciliated columnar epithelium cells between native lungs and transplanted lungs with or without successful direct bronchial artery revascularization could be demonstrated. In 38% of the transplanted lungs without successful revascularization metaplastic or squamous epithelium was present, while lungs with successful revascularization had only normal columnar epithelium. Ongoing rejection or airway erythema did not influence ciliary beat frequency. Excessive secretion in the airways was the only finding associated with significantly increased ciliary beat frequency. CONCLUSIONS: Ciliary beat frequency of epithelium cells of transplanted lungs did not differ from that of native lungs and consequently direct bronchial artery revascularization did not have any demonstrable important influence. Excessive secretion in the airways was associated with increased ciliary beat frequency. The histological findings also showed that the abundance of ciliated cells was preserved in transplanted bronchi irrespective of bronchial artery revascularization. However, epithelium metaplasia was only seen in transplanted bronchi without revascularization.

Angiography↗

Twenty-to-thirty-seven-year follow-up after repair for Tetralogy of Fallot.

OBJECTIVE: To describe the long-term prognosis after repair of Tetralogy of Fallot with pulmonary stenosis beyond 20 years. METHODS: One hundred and eighty five patients underwent corrective repair of Tetralogy of Fallot at Rigshospitalet in Copenhagen between January 1960 and July 1977. Ninety seven patients had undergone a palliative operation prior to Tetralogy of Fallot repair. All the 125 patients who were discharged from the hospital were traced through the population register and the patients alive July 1997 were contacted by mail and/or telephone and questioned about use of medicine, professional status, family status and ability to perform sport activities. RESULTS: Sixty patients died in hospital and 125 patients, 78 males and 47 females, were discharged alive. Among operative survivors, median age at operation was 12.8 years (range 0.4-41 years). Thirteen patients required a reoperation, the main indication was failed VSD closure. There were 16 late cardiac deaths, out of which seven were sudden and unexpected and three were in immediate relation to reoperations. One hundred and nine patients were alive at follow-up. The mean follow-up time was 25.5 years (range 20-38 years). Sixteen percent used cardiac drugs, 89% were, or had been, working normally (all professions from academics to hard manual labors were represented), 53% (64% of women) had given birth after the repair and 51% performed sport activities regularly. No patients were lost to follow-up. CONCLUSIONS: The vast majority of the patients seemed to live normal lives 20-37 years after Tetralogy of Fallot repair. Late deaths were cardiac in origin, including sudden death from arrhythmias. The number of late reoperation has been low. Considering the natural history of the disease, Fallot repair has proven to be a beneficial procedure even including the very early experience short after introduction of open heart surgery.

Abnormalities, Multiple↗

Endoglucanase 28 (Cel12A), a new Phanerochaete chrysosporium cellulase.

A 28-kDa endoglucanase was isolated from the culture filtrate of Phanerochaete chrysosporium strain K3 and named EG 28. It degrades carboxymethylated cellulose and amorphous cellulose, and to a lesser degree xylan and mannan but not microcrystalline cellulose (Avicel). EG 28 is unusual among cellulases from aerobic fungi, in that it appears to lack a cellulose-binding domain and does not bind to crystalline cellulose. The enzyme is efficient at releasing short fibres from filter paper and mechanical pulp, and acts synergistically with cellobiohydrolases. Its mode of degrading filter paper appears to be different to that of endoglucanase I from Trichoderma reesei. Furthermore, EG 28 releases colour from stained cellulose beads faster than any other enzyme tested. Peptide mapping suggests that it is not a fragment of another known endoglucanases from P. chrysosporium and peptide sequences indicate that it belongs to family 12 of the glycosyl hydrolases. EG 28 is glycosylated. The biological function of the enzyme is discussed, and it is hypothesized that it is homologous to EG III in Trichoderma reesei and the role of the enzyme is to make the cellulose in wood more accessible to other cellulases.

Amino Acid Sequence↗

Mechanism of metabolite transfer in coupled two-enzyme reactions involving aldolase.

Transient-state kinetic experiments and analyses have been performed to examine the validity of hitherto unchallenged evidence proposed to be indicative of a channelled transfer of triose phosphates from aldolase to glyceraldehyde-3-phosphate dehydrogenase and glycerol-3-phosphate dehydrogenase. The results lend no support to such proposals, but show that the kinetic behaviour of the examined aldolase-dehydrogenase reactions is fully consistent with a free-diffusion mechanism of metabolite transfer.

Catalysis↗

Acid hydrolysis of bacterial cellulose reveals different modes of synergistic action between cellobiohydrolase I and endoglucanase I.

Intact and partially acid hydrolyzed cellulose from Acetobacter xylinum were used as model substrates for cellulose hydrolysis by 1,4-beta-D-glucan-cellobiohydrolase I (CBH I) and 1,4-beta-D-endoglucanase I (EG I) from Trichoderma reesei. A high synergy between CBH I and EG I in simultaneous action was observed with intact bacterial cellulose (BC), but this synergistic effect was rapidly reduced by acid pretreatment of the cellulose. Moreover, a distinct synergistic effect was observed upon sequential endo-exo action on BC, but not on bacterial microcrystalline cellulose (BMCC). A mechanism for endo-exo synergism on crystalline cellulose is proposed where the simultaneous action of the enzymes counteract the decrease of activity caused by undesirable changes in the cellulose surface microstructure.

Acetobacter↗

The porcine bronchial artery: surgical and angiographic anatomy.

The pig is often used in experimental studies on the significance of bronchial artery circulation, but the anatomy of this artery is only poorly described. The purpose of this study was to improve the anatomical basis for experimental studies on the porcine bronchial artery circulation. The origin of the artery from the aorta is described in 32 pigs. Heart-lung blocks were perfused with saline and removed in 16 pigs, and the broncho-oesophageal orifice was identified and cannulated. In these 16 specimens the intrapulmonary ramification was studied by angiography, and the extrapulmonary distribution and supply area by injection of Evans Blue. The broncho-oesophageal artery originated from the aorta as a single trunk in 91%. Angiography showed that each principal bronchus was accompanied by 2 bronchial artery branches far into the lung parenchyma. The central branching pattern of the artery between the aorta and the principal bronchi was divided into 3 subtypes. Evans Blue showed communication with the whole mediastinum. The anatomical relations are described. It is concluded that the broncho-oesophageal artery divides to follow each bronchus with 2 bronchial branches. A nomenclature for these branches is suggested. The pig anatomy is suited for experimental investigations on the bronchial circulation.

Animals↗

Predictors of chest pain after coronary artery bypass grafting.

To identify preoperative biopsychosocial factors characterizing patients who will experience chest pain (self-reported) one year after coronary artery bypass grafting (CABG), 111 patients under 61 years of age were evaluated by questionnaire before CABG and 12 months postoperatively. A "Coronary Health Profile" was evolved to study quality-of-life indicators, e.g. "Sense of Coherence" (SOC), emotional state (loneliness, depressed mood, stress, anxiety) and social support as well as experience of chest pain, and the results were correlated to biomedical data. Chest pain was experienced in the first postoperative year by 34% of the patients. These patients, who were younger than those without chest pain, generally had a body mass index >25, as well as lower preoperative values for SOC, poorer emotional state and social support. Independent predictors in a multivariate stepwise logistic regression analysis were moderate/weak SOC, ejection fraction <50%, and moderate/severe mood depression. We conclude that biomedical as well as psychosocial factors have a significant impact as predictors of chest pain (of any origin) after CABG, and must be considered in preoperative evaluation. The findings indicate the need for biopsychosocial support/intervention before as well as after CABG.

Adult↗

Human bronchial artery blood flow after lung Tx with direct bronchial artery revascularization.

The inaccuracy of measuring human bronchial artery blood flow has previously been considerable. En bloc double-lung transplantation with bronchial artery revascularization (BAR) using a single conduit offers the unique opportunity of direct measurement of the total bronchial artery blood flow. In eight en bloc double-lung-transplanted patients with complete BAR, the basal blood flow was measured by using a 0.014-in. Doppler guide wire and arteriography. The average peak velocity in the conduit was 12-73 cm/s [+/-2.1 (SD) cm/s], and the conduit diameter was 1.7-3.1 mm [+/-0.10 (SD) mm], giving individual basal flow values between 19 and 67 ml/min [+/-5 (SD) ml/min], or 0.2-1.9% of estimated cardiac output. In three patients basal measurements were followed by injection of nitroglycerin and verapamil into the conduit. This increased the bronchial artery flow to 121-262% of basal values (31-89 ml/min). The measured values appear more physiologically plausible than previous bronchial artery blood flow measurements in humans.

Angiography↗

Vacuum assisted venous drainage (VAVD).

Poor venous drainage is a common problem in cardiac surgery, causing trouble for the surgeon and adverse effects to the patient. Smaller incisions for minimally invasive cardiac surgery require smaller venous catheters. In this study the function, safety and possible benefits of a system for vacuum assisted venous drainage has been tested experimentally and applied clinically. A vacuum regulator ('The Hamlet box') and safety procedures were developed. The system was characterized in vitro in regard to the relationship between vacuum, catheter size, and blood temperature and flow. The clinical study included 54 adult patients, coronary artery bypass graft surgery and valve operations. Venous cannulation was bi-caval with two 24 Fr catheters. All the perfusions were essentially event free, and the system was easy to manage and regulate. Venous drainage was totally adequate, irrespective of the position of the heart, and less fluid was added during the perfusions (a median of 250 ml/patient compared to a median of 1000 ml/patient in the control group). There has been no evidence of increased haemolysis or other adverse effects. All patients were hospital survivors and had uneventful postoperative courses. Vacuum assisted venous drainage is now used routinely, and further studies are under way to develop the system and clarify the physiological effects.

Cardiac Surgical Procedures↗

Bronchial artery perfusion scintigraphy to assess bronchial artery blood flow after lung transplantation.

UNLABELLED: The bronchial arterial system is inevitably interrupted in transplanted lungs when removing the organs from the donor, but it can be reestablished by direct bronchial artery revascularization (BAR) during implantation. The purpose of this study was to visualize and quantify the distribution of bronchial artery perfusion after en bloc double lung transplantation with BAR, by injecting radiolabeled macroaggregated albumin directly into the bronchial artery system. METHODS: BAR was performed using the internal mammary artery as conduit. Patients were imaged 1 mo (n = 13) or 2 y (n = 9) after en bloc double lung transplantation with BAR. Immediately after bronchial arteriography, 100 MBq macroaggregated albumin (45,000 particles) were injected through the arteriographic catheter. Gamma camera studies were then acquired in the anterior position. At the end of imaging, with the patient remaining in exactly the same position, 81mKr-ventilation scintigraphy or conventional intravenous pulmonary perfusion scintigraphy or both were performed. Images were evaluated by visual analysis, and a semiquantitative assessment of the bronchial arterial supply to the peripheral parts of the lungs was obtained with conventional pulmonary scintigraphy. RESULTS: The bronchial artery scintigraphic images showed that the major part of the bronchial arterial flow supplied central thoracic structures, but bronchial artery perfusion could also be demonstrated in the peripheral parts of the lungs when compared with conventional pulmonary scintigraphy. There were no differences between scintigrams obtained from patients studied 1 mo and 2 y post-transplantation. CONCLUSION: Total distribution of bronchial artery supply to the human lung has been visualized in lung transplant patients. This study demonstrates that this nutritive flow reaches even the most peripheral parts of the lungs and is present 1 mo as well as 2 y after lung transplantation. The results suggest that bronchial artery revascularization may be of significance for the long-term status of the lung transplant.

Adult↗

Recurrent endocarditis in silver-coated heart valve prosthesis.

BACKGROUND AND AIM OF THE STUDY: In order to prevent prosthetic valve endocarditis (PVE), the implantation of a new silver-coated sewing ring has been introduced to provide peri- and postoperative protection against microbial infection. METHODS: A 56-year-old woman with aortic stenosis had elective replacement with a St. Jude Medical mechanical valve fitted with a silver-coated sewing ring (Silzone). The patient developed early PVE, which necessitated reoperation after one month. Despite a second Silzone prosthesis being implanted, the endocarditis recurred. During a third operation an aortic homograft was implanted, and after six months a fourth operation was performed for a pseudoaneurysm at the base of the homograft, in proximity to the anterior mitral valve leaflet. RESULTS: The diagnosis of PVE was confirmed by the presence of continuous fever, transesophageal echocardiography and growth of penicillin-resistant Staphylococcus epidermidis from the valve prosthesis. CONCLUSION: The implantation of all prosthetic valves is encumbered with a risk of endocarditis. Although silver has bacteriostatic actions, the advantages of silver-coated prostheses in the treatment of this condition have yet to be assessed in clinical trials.

Anti-Bacterial Agents↗

Arterial switch with internal pulmonary artery banding. A new palliation for TGA and VSD in complex cases.

In most cases, one stage repair by arterial switch operation (ASO) is the optimal treatment for neonates with transposition of the great arteries (TGA). Nevertheless, a ventricular septal defect (VSD) associated with TGA remains a major risk factor for early death and reoperation after complete repair in neonates with complex anatomy. A new palliative approach for such specific cases is proposed. An internal pulmonary artery banding (IPAB), as that already used to palliate other cardiac malformations, is performed in association with ASO instead of VSD closure. At the end of ASO, a circular polytetrafluorethylene (PTFE) patch with a 4-mm central hole is oversewn into the neo-pulmonary trunk. We adopted this method in a 17-day-old boy with TGA, VSD, hypoplastic tricuspid valve and diminutive right ventricle. After the operation the child thrived and was doing well without medication. Satisfactory growth of the right ventricle and tricuspid valve was observed by echocardiography during the following months. The patient successfully underwent VSD closure and IPAB removal 2 years after the first procedure. ASO with IPAB could be appropriate in all forms of TGA and VSD in which VSD closure appears too challenging in the neonatal period and in patients with uncertain suitability for biventricular repair. We preferred to use IPAB instead of classic PAB in order to reduce the risk of pulmonary valve damage, pulmonary artery distortion, and above all pulmonary artery dilatation and related coronary compression. In the presented case the strategy as well as IPAB worked according to our expectations.

Blood Vessel Prosthesis Implantation↗

Progress curves--a mean for functional classification of cellulases.

The chain-end preference and processivity of the cellulases 1,4-beta-D-glucan-cellobiohydrolase I (CBH I) and 1,4-beta-D-glucan-cellobiohydrolase II (CBH II) from Trichoderma reesei and 1,4-beta-D-glucan-cellobiohydrolase 50 (CBH 50) and 1,4-beta-D-glucan-cellobiohydrolase 58 (CBH 58) from Phanerochaete chrysosporium were studied by comparing experimental degradation data on reducing end-labelled bacterial microcrystalline cellulose with computer simulations of different models. Our results with T. reesei and P. chrysosporium cellulases show that there is a common pattern of hydrolysis for CBH-I-type enzymes and another clearly distinguishable pattern for CBH-II-type enzymes, especially in the initial part of the progress curve.

Cellulase↗

[Marfan syndrome and pregnancy].

Two cases of Marfan's syndrome with acute dissection in relation to labour are presented. One patient died of aortic rupture while the other was electively operated. The haemodynamic changes during pregnancy and labour can have catastrophic consequences. The Marfan patient must be well informed before pregnancy and carefully monitored during pregnancy and the peripartum period. Serial echocardiographic studies evaluating aortic root size and aortic valve function are essential. In case of severe cardiovascular manifestation the pregnancy should be interrupted.

Adult↗

Mechanism of NADH transfer among dehydrogenases.

Steady-state and transient-state kinetic experiments have been performed to test the proposal that there is a direct (channelled) transfer of NADH from one dehydrogenase to another if the two enzymes exhibit distinct chiral coenzyme specificity (A-side vs. B-side). The results lend no support to this proposal, but are fully consistent with a free-diffusion mechanism of NADH transfer irrespective of the chiral specificity of the enzymes.

Alcohol Dehydrogenase↗

The initial kinetics of hydrolysis by cellobiohydrolases I and II is consistent with a cellulose surface-erosion model.

Introduction of a novel method for the quantification of the cellobiose released made it possible to follow the initial stage of hydrolysis of bacterial microcrystalline cellulose (BMCC) by cellobiohydrolases 1,4-beta-D-glucan-cellobiohydrolase I (CBH I) and 1,4-beta-D-glucan-cellobiohydrolase II (CBH II) from Trichoderma reesei. A drastic retardation of the rate of the hydrolysis was observed already at a very low degree of conversion. Earlier-suggested retardation factors, such as product inhibition by cellobiose or enzyme inactivation, could be discounted as primary causes for the pattern. A model including steric hindrance by non-productive binding and erosion of the cellulose surface during the processive action of exoenzymes was proposed to describe the rate retardation observed. Simultaneous action of CBH I and CBH II on cellulose was not a prerequisite for synergy between them.

Binding, Competitive↗