Biomedical subjects

E Bos

Publications and source records attributed to E Bos.

At least 19 recordsLinked to original sources

PubMed1998

Structure of an Fab fragment against a C-terminal peptide of hCG at 2.0 A resolution.

3A2 is an antibody raised against human chorionic gonadotropin and recognizes a linear epitope on the C-terminal peptide of the human chorionic gonadotropin beta-subunit. Its three-dimensional structure has been determined to 2-A resolution using molecular replacement and refined to a conventional R-factor of 18.2%. The protein exhibits the typical immunoglobulin fold, and the model contains 944 ordered water molecules and one sulfate ion. A comparison of the complementarity-determining regions of the Fab3A2 with those from the Protein Data Bank following the canonical structure method reveals a canonical main chain conformation. This antibody belongs to the canonical structure class (combination of canonical conformations of the complementarity determining loops) that shows a preference for haptens and not for peptides. However, the shape of the surface of the antigen binding loops resembles that of an anti-peptide antibody.

Amino Acid Sequence↗

PubMed1998

Crystallization of two hCG-specific monoclonal antibody fragments.

The Fab fragments of two monoclonal antibodies (Fab3A2, Fab6A) raised against epitopes of human chorionic gonadotrophin (hCG) have been crystallized using the vapour-diffusion technique. The Fab3A2 antibody recognises an epitope on the C-terminal peptide of the beta-subunit and the Fab6A a conformational epitope of hCG. Both Fab crystals grow as hexagonal rods from ammonium sulfate solutions. The Fab3A2 crystals belong to space group P3121 with a = b = 74.84, c = 198.2 A and diffract to 1.33 A at the ESRF. The Fab6A crystals are in the space group P3221 with a = b = 129.53, c = 74.40 A and diffract to 2.7 A at the Daresbury SRS. One Fab molecule per asymmetric unit is present in both crystals.

Animals↗

PubMed1998

Aortic allograft implantation techniques: pathomorphology and regurgitant jet patterns by Doppler echocardiographic studies.

BACKGROUND: The diagnosis of allograft-specific pathology by echocardiography has important consequences for patient counseling and research. This study describes the pathomorphologic findings and color Doppler jet patterns in a consecutive series of patients after allograft placement with either the subcoronary implantation or root replacement technique. METHODS: From 1987 to July 1996, the subcoronary allograft implantation technique and root replacement technique were used in 82 patients and 70 patients, respectively. These patients comprised the study group. RESULTS: The incidence of paravalvular leaks and eccentric regurgitant jets was higher with subcoronary implantation (41%) than with root replacement (11%). Patients with a subcoronary implanted allograft had a higher incidence of eccentric jets. CONCLUSIONS: These findings support the concept of preservation of valve geometry after root replacement, as allograft-specific pathomorphologic abnormalities and eccentric jets are more common after subcoronary implantation of allografts. Learning effects, however, cannot be excluded as the cause of these abnormalities.

Adolescent↗

PubMed1998

A comparison of adult pulmonary autograft diameter measurements with echocardiography and magnetic resonance imaging.

UNLABELLED: In 38 consecutive patients the pulmonary autograft was used in aortic root replacement. Investigations were performed with transthoracic echocardiography, transoesophageal echocardiography and magnetic resonance imaging in 31, 27 and 27 patients respectively. The mean age at operation was 28.7 years (range 19.0-52.0) and the follow-up period was 2.8 years (range 0.8-6.7). The pulmonary autograft diameter was measured at the subannular region (1), at the annulus at the hinge points of the valve leaflets (2), at the sinus (3), at the sino-tubular junction (4) and at the distal part of the autograft (5). With transoesophageal echocardiography the mean systolic measurements at levels 1 to 5 were 32, 31, 42, 35 and 34 mm, respectively. The corresponding diastolic measurements were smaller: 25, 28, 42, 35 and 34 mm respectively. There was no significant difference between transthoracic echocardiography and transoesophageal echocardiography measurements of the proximal autograft (levels 1-3). Diameters obtained with magnetic resonance imaging were 1 to 3 mm larger than those obtained with transthoracic echocardiography and transoesophageal echocardiography (P < 0.05), except the annulus at systole (P > 0.3). CONCLUSIONS: The mean pulmonary autograft diameters measured using transthoracic echocardiography, transoesophageal echocardiography and magnetic resonance imaging were larger than native aortic and pulmonary diameters of a normal population in the same age group. Diameters of the distal 2 levels could not be imaged reliably with transthoracic echocardiography. Magnetic resonance imaging diameter measurements were, in general, larger than with echocardiography.

Adult↗

PubMed1998

Child mortality patterns in rural areas of Anhui and Henan provinces in China, 1990.

County-based IMR and U5MR in Anhui and Henan provinces in China were estimated and analyzed by using the 1990 Census Data. Census was conducted on July 1, 1990, the number of deaths only occurred in the first half year of 1990 was collected. In order to obtain the total population and total number of deaths in the same year, the total number of deaths in each age-sex group for the whole 1990 was then estimated by taking the death number in the first half of 1990 as the base and multiplying a coefficient, which varied in different age-sex-region groups. Two major adjustments for some possible under-reporting cases in female birth and infant death were made. If the sex ratio at age 0 in some counties was beyond 1.2, then it was taken as 1.15 for rural counties and 1.10 for urban cities, which were the estimates of sex ratios for the children at age 5 in the national 1% Population Sampling Survey in 1995. The adjustment for IMR were made by comparing the segment of the county lift table from age 15 through 59 with that from the same age groups in the international and Chinese Model Life Tables. The IMR in the county life table would be substituted by the one in the closest Model Life Talbe, if it was less than in the latter. The findings of the analysis may be summarized as follows: (i) Total county-based IMR and U5MR were 33.4 per 1,000 and 41.4 per 1,000 respectively, with great variations between urban cities (25.4 per 1,000 for IMR and 31.4 per 1,000 for U5MR) and rural counties (35.1 per 1,000 for IMR and 43.6 per 1,000 for U5MR). There were also significant differences in child mortality between nationally identified poor counties and other counties in rural areas. In the poor counties the total IMR was 40.7 per 1,000 living births in average while in non-poor counties it was only 33.2 per 1,000 in average (P < 0.05). The U5MR in poor counties was 25 percent higher than in non-poor counties (51.5 vs 40.9 per 1,000 living births). (ii) Statistically significant correlation between child mortality and socio-economic variables was revealed from the data set, among which gross social economic products per capita was found to have the strongest relationship with child mortality. The negative correlation was found between child mortality and a set of so-called 'rich' variables including the gross social products, gross agricultural products, gross industrial products and the proportions of high-educated population at county level, whereas the positive correlation was found between child mortality and a set of 'poor' variables, such as proportions of residents with lower level of education and illiteracy rate. (iii) Differences in child mortality between these two provinces were found, which were identical to the trends of differences in socio-economic indicators between them. Lower child mortality proved to be associated with better socio-economic conditions (higher per capita products, higher proportions of residents with higher level of education, lower proportion of less educated people and illiteracy) in province Henan. (iv) A simple linear regression model was developed separately for Henan and Anhui to predict the IMR and U5MRs in each stage of economic development, where the dependent variables were the logarithm of IMR and U5MR, and the independent variables were the quintiles of the output value of gross products (GOP). It was found that at the first quintile, which was equivalent to 800 yuan of GOP in average, the predicted IMR and U5MR would reach 40 per 1,000 and 51 per 1,000 respectively. It would decline to 38 per 1,000 for IMR and 47 per 1,000 for U5MR in the second lowest quintile. Dramatic drop of child mortality was found between the second quintile and the third quintile, where 6 per 1,000 decline would occur for both IMR and U5MR. The decline would continue subsequently, but slower. The prediction of child mortality in rural counties could be used as a reference to assess counties at different stages of socio-

Adolescent↗

PubMed1997

Human cartilage glycoprotein-39 as a candidate autoantigen in rheumatoid arthritis.

OBJECTIVE: To identify a cartilage-derived autoantigen that is relevant to the rheumatoid arthritis (RA) disease process. METHODS: A DR4 (DRB1*0401) peptide binding motif was used for the selection of potential self reactive peptides within human cartilage glycoprotein-39 (HC gp-39), a protein that is differentially expressed at the site of chronic inflammation. Synthetic peptides accommodating the motif were tested for binding the RA-associated DR4 (DRB1*0401) molecules. High-affinity binders were then tested for their capacity to stimulate peripheral blood mononuclear cell responses in RA patients or healthy donors. To assess the arthritogenic nature of native HC gp-39, the protein was injected into BALB/c mice. RESULTS: HC gp-39-derived motif-based peptides were selectively recognized by peripheral blood T cells from RA patients. Injection of the intact protein into BALB/c mice resulted in immunity to HC gp-39, which was found to be associated with the development of a chronic, relapsing arthritis. Moreover, inhalation of the protein led to tolerization of antigen-specific T cells and to suppression of HC gp-39-induced arthritis. CONCLUSION: These data indicate that HC gp-39 is a target of the immune response in RA. Consequently, HC gp-39 is a candidate for antigen-specific immunotherapy.

Adipokines↗

PubMed1997

Selection of self-reactive peptides within human aggrecan by use of a HLA-DRB1*0401 peptide binding motif.

The pathogenesis of joint destruction in rheumatoid arthritis remains ill-defined. Joint destruction is thought to be the result of tissue damage mediated by T cells. The mere presence of articular cartilage appears responsible for sustaining chronic synovitis and thereby forwards a role for cartilage-responsive T cells in RA. Taking advantage of the positive DRB1*0401 association with RA susceptibility, we reasoned that T-cell recognition of autoantigens in RA would be restricted by DRB1*0401-encoded molecules. A DR4 (B1*0401) peptide binding motif was used for the identification of putative T-cell epitopes within human aggrecan, a candidate autoantigen. Thirteen peptides were synthesized and tested for binding DRB1*0401 or 0404-encoded molecules. Selected binders were tested for induction of proliferative responses in peripheral blood mononuclear cells from donors carrying the DR4 or DR1 specificity. Both healthy and RA donors responded to human aggrecan-derived peptides, thereby identifying these sequences as T-cell epitopes. Interestingly, responses to aggrecan-derived epitopes were significantly decreased in RA patients compared to controls. This was not due to an overall hyporesponsiveness of RA patients since responses to a recall antigen or mitogen did not differ from controls. The data suggest that in RA, aggrecan-specific T cells may exist in a different stage of activation or may have left the periphery to home to the joint.

Adult↗

PubMed1997

Clinical outcome and left ventricular function after pulmonary autograft implantation in children.

BACKGROUND: Aortic root replacement with a pulmonary autograft is an alternative treatment for children with aortic valve or root disease, or both. METHODS: Twenty-six patients (18 boys and 8 girls) with a mean age of 10.9 years (range, 0.3 to 16.9 years) underwent this procedures in a 7-year period. The mean follow-up period was 3.2 years (range, 0.2 to 7.5 years). RESULTS: During follow-up 3 patients died and one autograft was replaced with a mechanical valve. The actuarial survival and actuarial event-free survival rates were 87% and 79%, respectively, at both 5 and 7 years. None of the surviving patients had complaints, and all have done well and are living normal lives. Electrocardiographic signs of myocardial ischemia and left ventricular hypertrophy were not present. Echocardiography showed autograft valve regurgitation to be absent or trivial (n = 17) or mild (n = 5). Stenosis was not present. Increasing autograft annulus diameters were noted during follow-up, but this was not related to the severity of autograft regurgitation. Left ventricular dimensions and function were within normal limits later than 1 year after the operation. Only 2 patients had a moderate pulmonary stenosis without right ventricular hypertrophy. CONCLUSIONS: The surgical results, clinical outcome, valve function, and left ventricular function in our patients have been good. This procedure is recommended as a method of aortic valve replacement in children.

Actuarial Analysis↗

PubMed1997

Does the pulmonary autograft in the aortic position in adults increase in diameter? An echocardiographic study.

OBJECTIVE: The objective of this study was to discern the fate of the pulmonary autograft diameter over time in adults and its relation to aortic regurgitation in the setting of aortic root replacement. METHODS: From January 1989 to May 1995, 36 consecutive adult patients underwent aortic root replacement with a pulmonary autograft for aortic valve disease. The mean age of 20 male and 16 female patients was 29.1 years (range 19.3 to 52.1 years). The mean follow-up was 2.3 years (range 0.3 to 6.0 years). Two patients died in the hospital. One other patient had a second operation for stenosis at the distal suture line of the allograft in the pulmonary position. Pulmonary autograft anulus and sinus diameters were measured with epicardial echocardiography before (only anulus) and after cardiopulmonary bypass, with transthoracic echocardiography at hospital discharge, and with transesophageal echocardiography during follow-up. RESULTS: The mean autograft anulus diameter did not increase immediately after cardiopulmonary bypass (mean diameter 26.2 mm before and 26.4 mm after cardiopulmonary bypass). The mean autograft sinus diameter after cardiopulmonary bypass was 36.5 mm. The mean autograft anulus diameter increased to 31.5 mm at follow-up, an increase of 5.1 mm (19%). The mean autograft sinus diameter increased to 43.9 mm at follow-up, an increase of 7.4 mm (20%). Fifty-nine percent of the anulus diameter increase and 40% of the sinus diameter increase was already reached at hospital discharge (7 to 10 days after the operation); the other part of the increase occurred during follow-up. Diameter increase was associated with neither the length of follow-up (follow-up less than 1 year compared with a longer follow-up) or severity of aortic regurgitation. CONCLUSION: Pulmonary autograft anulus and sinus diameters increase the first year after aortic root replacement with a pulmonary autograft. This occurs rapidly within 10 days after the operation, with a further increase during follow-up, without causing significant aortic regurgitation at medium-term follow-up.

Adult↗

PubMed1997

Effects of cryopreservation on contractile properties of porcine isolated aortic valve leaflets and aortic wall.

Human semilunar donor heart valves can be stored in banks, awaiting transplantation. To evaluate the result of the preservation protocols, a quantitative description of the tissue is necessary. In this study we investigated in a quantitative way the contractile properties of fresh and cryopreserved porcine isolated aortic heart valve leaflets in response to a number of endogenous vasoactive compounds. The responses of strips of the aortic wall were included for comparison. Contraction was measured isometrically in response to potassium (K+; 100 mmol/L), 5-hydroxytryptamine (1 nmol/L to 100 micromol/L), noradrenaline (1 nmol/L to 100 micromol/L), endothelin-1 (0.01 nmol/L to 0.3 micromol/L), and prostaglandin F(2alpha) (0.1 nmol/L to 10 micromol/L). The pharmacologic parameters E(MAX) (the maximal response expressed as a percentage of contraction to a 100 mmol/L dose of K+) and EC50 (the concentration that produces 50% of the maximal effect) were calculated for every compound (n = 6 to 7 each). We observed that all specimens contracted in response to potassium. Its magnitude in fresh leaflets equaled 1.6 +/- 0.14 mN compared with 26.6 +/- 2.6 mN in fresh aortic wall. Noradrenaline, endothelin-1, and prostaglandin F(2alpha) all caused contraction in valvular leaflets and aortic wall, whereas 5-hydroxytryptamine caused contraction in the valvular leaflets but relaxation in aortic wall. After cryopreservation, the response to K+ amounted to 24% of the response of the fresh specimens in valvular leaflets (n = 25) and 14% in aortic wall (n = 26). The values of E(MAX) and EC50 of the responses to noradrenaline, endothelin-1, and prostaglandin F(2alpha) remained unchanged. Although the physiologic relevance of contraction of valvular leaflets needs further study, its measurement may provide an additional model to verify the consequences of alternative methods of preservation.

Animals↗

PubMed1997

Poverty and mortality among the elderly: measurement of performance in 33 countries 1960-92.

This paper analyses the effect of income and education on life expectancy and mortality rates among the elderly in 33 countries for the period 1960-92 and assesses how that relationship has changed over time as a result of technical progress. Our outcome variables are life expectancy at age 60 and the probability of dying between age 60 and age 80 for both males and females. The data are from vital-registration based life tables published by national statistical offices for several years during this period. We estimate regressions with determinants that include GDP per capita (adjusted for purchasing power), education and time (as a proxy for technical progress). As the available measure of education failed to account for variation in life expectancy or mortality at age 60, our reported analyses focus on a simplified model with only income and time as predictors. The results indicate that, controlling for income, mortality rates among the elderly have declined considerably over the past three decades. We also find that poverty (as measured by low average income levels) explains some of the variation in both life expectancy at age 60 and mortality rates among the elderly across the countries in the sample. The explained amount of variation is more substantial for females than for males. While poverty does adversely affect mortality rates among the elderly (and the strength of this effect is estimated to be increasing over time), technical progress appears far more important in the period following 1960. Predicted female life expectancy (at age 60) in 1960 at the mean income level in 1960 was, for example 18.8 years; income growth to 1992 increased this by an estimated 0.7 years, whereas technical progress increased it by 2.0 years. We then use the estimated regression results to compare country performance on life expectancy of the elderly, controlling for levels of poverty (or income), and to assess how performance has varied over time. High performing countries, on female life expectancy at age 60, for the period around 1990, included Chile (1.0 years longer life expectancy), China (1.7 years longer), France (2.0 years longer), Japan (1.9 years longer), and Switzerland (1.3 years longer). Poorly performing countries included Denmark (1.1 years shorter life expectancy than predicted from income), Hungary (1.4 years shorter), Iceland (1.2 years shorter), Malaysia (1.6 years shorter), and Trinidad and Tobago (3.9 years shorter). Chile and Switzerland registered major improvements in relative performance over this period; Norway, Taiwan and the USA, in contrast showed major declines in performance between 1980 and the early 1990s.

Aged↗

PubMed1997

25 years of aortic valve replacement using mechanical valves. Risk factors for early and late mortality.

This study describes the changes that have taken place in patient characteristics in 25 years of aortic valve replacement using mechanical valves, and looks for risk factors for early and late mortality. During this period, 1449 mechanical valves were implanted. Overall early mortality (< 30 days) was 5.3% and for aortic valve replacement without concomitant procedures 3.9%. Overall survival rates at 5, 10 and 15 years were 80%, 63% and 49%, respectively. Despite an increased proportion of higher risk patients (older age, more reoperations, more concomitant coronary bypass surgery) survival rates improved throughout the study period. Early mortality was related to an early year of operation, urgency, reoperation and concomitant surgery to the tricuspid valve or ascending aorta. Late mortality was higher for patients of older age, with an early year of operation, male gender, concomitant coronary bypass surgery, mitral valve surgery or replacement of the ascending aorta. Aortic regurgitation did not have a major influence on early nor late mortality. The improvement in early and late mortality in more recent years was largely the result of the introduction of cardioplegia. A changing, non-proportional effect was observed for several risk factors during the follow-up period. This study illustrates the changes and improvements in medical care that have taken place in patients requiring aortic valve replacement.

Aortic Valve↗

PubMed1997

Characterization of two temperature-sensitive mutants of coronavirus mouse hepatitis virus strain A59 with maturation defects in the spike protein.

Two temperature-sensitive (ts) mutants of mouse hepatitis virus strain A59, ts43 and ts379, have been described previously to be ts in infectivity but unaffected in RNA synthesis (M. J. M. Koolen, A. D. M. E. Osterhaus, G. van Steenis, M. C. Horzinek, and B. A. M. van der Zeijst, Virology 125:393-402, 1983). We present a detailed analysis of the protein synthesis of the mutant viruses at the permissive (31 degrees C) and nonpermissive (39.5 degrees C) temperatures. It was found that synthesis of the nucleocapsid protein N and the membrane protein M of both viruses was insensitive to temperature. However, the surface protein S of both viruses was retained in the endoplasmic reticulum at the nonpermissive temperature. This was shown first by analysis of endoglycosidase H-treated and immunoprecipitated labeled S proteins. The mature Golgi form of S was not present at the nonpermissive temperature for the ts viruses, in contrast to wild-type (wt) virus. Second, gradient purification of immunoprecipitated S after pulse-chase labeling showed that only wt virus S was oligomerized. We conclude that the lack of oligomerization causes the retention of the ts S proteins in the endoplasmic reticulum. As a result, ts virus particles that were devoid of S were produced at the nonpermissive temperature. This result could be confirmed by biochemical analysis of purified virus particles and by electron microscopy.

Animals↗

PubMed1996

Progressive accumulation of CTL with high avidity for donor antigens during the development of acute cardiac rejection.

To study the importance of cytotoxic T lymphocytes (CTL) with high avidity for donor antigens (Ag) in the development of acute cardiac allograft rejection, their appearance within the graft in relation to rejection was analyzed. For this study, donor directed CTL propagated from sequentially taken endomyocardial biopsies (EMB) were enumerated by limiting dilution analysis (LDA). Subsequentially, the fraction of these CTL having high avidity for donor Ag was determined by addition of a CD8 monoclonal antibody (mAb) to the cytotoxic phase of the LDA. Analysis of 37 EMB cultures obtained from 11 heart transplant (HTx) patients before, during, or after they experienced rejection, revealed the kinetics of donor specific CTL in relation to rejection for HTx patients in general. For 5 individual recipients, a more detailed analysis was performed. The kinetics found for individual patients confirmed the pattern found for the total group of HTx recipients tested. Frequencies of donor specific precursor CTL (pCTL) as well as of in vivo primed donor reactive CTL (committed CTL or cCTL) increased towards rejection and decreased after successful rejection therapy. More than 2 weeks before rejection was diagnosed, only a small fraction of the graft infiltrating donor specific pCTL and cCTL had high avidity for donor Ag (median = 35% and 11%, respectively). Within 2 weeks preceding rejection, this fraction increased gradually (median = 52% and 55%, respectively) and became dominant during rejection (median = 87% and 78%, respectively). After successful rejection therapy, a decrease to basal levels (median = 18% and 24%, respectively) was observed. Conclusively, intragraft accumulation of high avidity, donor specific pCTL and cCTL may cause transplant rejection.

Acute Disease↗

PubMed1996

Long-term follow-up (10 to 17 years) after Mustard repair for transposition of the great arteries.

BACKGROUND: The management strategies of patients who underwent Mustard repair for transposition (of the great arteries were changed in the 1970s: infants became eligible for direct surgical repair, so Blalock-Hanlon atrioseptostomy could be avoided, and cold cardioplegia was introduced for myocardial preservation. Data are lacking, however, regarding whether these changes have had positive effects on the long-term outcome. We therefore conducted a follow-up study on all 91 patients who underwent a Mustard repair for transposition of the great arteries in our institution between 1973 and 1980 to assess the incidence and clinical importance of sequelae as well as health-related quality of life for these patients. METHODS: Patients who were alive and could be traced through local registrar's offices received an invitation to participate in the follow-up study, which consisted of an interview, physical examination, echocardiography, exercise testing, and standard 12-lead and 24-hour electrocardiography. RESULTS: Patients operated on in the first 4 years had a significantly higher mortality rate and higher incidence of sinus node dysfunction than did patients operated on in the subsequent 4 years (25% vs 2% and 41% vs 3%, respectively). In contrast, the incidence of baffle obstruction necessitating reoperation was significantly higher in the second group. There were no significant differences in echocardiographic findings and exercise capacity between patients operated on in the first 4 years and in the subsequent 4 years. None of the patients had right ventricular failure; a mild degree of baffle leakage or obstruction was seen in 22% of the patients, and the mean exercise capacity was decreased to 84% +/- 16% of normal. CONCLUSION: The changes introduced between 1973 and 1980 have resulted in a considerable reduction of mortality and incidence of sinus node dysfunction but have also resulted in a more frequent need for reoperation.

Adolescent↗

PubMed1996

Donor-specific cellular immune response against human cardiac valve allografts.

We studied the presence of donor-specific T lymphocytes in explanted human cardiac valve allografts in vivo. From five of seven explants we propagated lymphocyte cultures in an interleukin-2 conditioned medium. Phenotyping revealed the presence of T-cell receptors in more than 95% of the lymphocytes obtained in each culture. Donor-specific cytotoxicity was demonstrated in three patients with known HLA status of the donor. Cytotoxicity was directed against only HLA class I in one patient, and against class I and/or class II in the others. These results indicate that donor-specific cellular reactivity can be induced by transplantation of human cardiac valve allografts.

Adult↗

PubMed1996

Allograft reconstruction of the right ventricular outflow tract.

OBJECTIVE: Evaluation of allograft reconstruction of the right ventricular outflow tract (RVOT). METHODS: From 1986 to April 1995, 201 allografts (146 pulmonary, 55 aortic) were implanted in 189 patients for conduit reconstruction of the RVOT in congenital heart disease or in the pulmonary autograft procedure. The mean age at allograft implantation was 16 years (range 2 weeks - 54 years). The primary diagnoses of these patients were truncus arterious (n = 19, 10%), transposition of the great arteries (TGA) with ventricular septal defect (VSD) and pulmonary atresia (PA) or stenosis (PS) (n = 14, 7%), PA with VSD (n = 26, 14%), PA or PS with intact septum (n = 7, 4%), tetralogy of Fallot (n = 44, 23%), corrected TGA with PA or PS (n = 11, 6%), tricuspid atresia (n = 9, 5%), aortic valve pathology for pulmonary autograft procedure (n = 55, 29%), and miscellaneous (n = 4, 2%). The allograft implantation was a reoperation in 54 patients (29%). RESULTS: The mean follow-up was 2.5 years (range 4 weeks-9 years). Six patients died in hospital (3.2%). Patient survival at 5 years was 91% (95% CL 86-95%). Freedom from all valve-related events (2 deaths, 17 reoperations, one endocarditis), as determined during reoperation or autopsy at 5 years was 78% (95% CL 65-86%). Freedom from structural allograft failure was 83% (2 deaths, 12 reoperations, 95% CL 70-90%). Allografts implanted for congenital right heart defects failed earlier than allografts used for pulmonary autograft procedures (P = 0.05). Aortic allografts showed structural failure more often than pulmonary allografts (P = 0.05). There were more valve-related events in patients of a younger age at implantation (P = 0.02) and in those allograft valves from younger donors (P = 0.004). CONCLUSIONS: Allograft RVOT reconstruction is an adequate surgical therapy. The allograft should preferably be pulmonary. A younger age at implantation is a risk factor for allograft failure. Donor age may be a thus-far underestimated risk factor for allograft degeneration.

Adolescent↗

PubMed1996

Augmented contraction of the human isolated coronary artery by sumatriptan: a possible role for endogenous thromboxane.

1. The antimigraine drug, sumatriptan, contracts the human coronary artery and, in some patients, elicits chest symptoms (e.g. pressure and pain), particularly after subcutaneous administration. We studied the effects of the thromboxane A2 (TxA2) analogue, U46619 and endothelin-1 on contractile responses to sumatriptan in the human isolated coronary artery as well as the role of endogenously produced TxA2 and endothelin-1 in contractions evoked by sumatriptan. 2. In the presence of U46619 (1 and 3 nM), mean concentration-response curves to sumatriptan in the human coronary artery were shifted vertically due to the initial contraction by U46619, but when this initial contraction was subtracted from the response to sumatriptan, no significant augmentation was observed. However, analysis of the degree of augmentation in individual arterial segments revealed that the augmentation was variable and related inversely to the Emax of sumatriptan in the absence of U46619 (r = 0.78 and 0.81 for 1 and 3 nM, respectively; P < 0.05). 3. Treatment with the TxA2 receptor antagonist, SQ30741 (100 nM), or incubation of vessel segments with aspirin (10 microM), significantly reduced responses to sumatriptan; in aspirin-treated vessel segments, SQ30741 failed to decrease further the contractions to sumatriptan. The decrease in Emax of sumatriptan by both SQ30741 and aspirin correlated significantly with the Emax of sumatriptan without SQ30741 (r = 0.74; P < 0.01) or aspirin (r = 0.94; P < 0.01). In aspirin-treated vessel segments, responses to sumatriptan were significantly augmented in the presence of U46619 (3 nM; P < 0.05). 4. The specificity of SQ30741 was demonstrated by its ability to antagonize coronary artery contractions to U46619 (pA2: 7.54 +/- 0.30), but not endothelin-1. Similarly, incubation with aspirin (10 microM) did not affect contractile responses to endothelin-1, but significantly reduced TxA2 production in coronary artery segments as judged by a decrease in thromboxane B2 (TxB2) from 4.77 +/- 0.98 to 1.38 +/- 0.36 ng g-1 2 h-1. 5. Endothelin-1 (1 nM) did not significantly augment contractions to sumatriptan; there was also no relationship between the degree of augmentation and the control Emax of sumatriptan in the absence of endothelin-1. Furthermore, unlike SQ30741 or aspirin, a high concentration (100 nM) of the non-selective ETA/ETB receptor antagonist, SB 209670, failed to affect contractile responses to sumatriptan. However, SB 209670 potently antagonized coronary artery contractions induced by endothelin-1 with a pA2 of 8.84 +/- 0.32. 6. Compared to control vascular segments, endothelial denudation did not reduce TxA2 production (with endothelium = 2.56 +/- 1.38 vs. without endothelium = 12.32 +/- 4.94 ng TxB2 g-1 2 h-1), suggesting that the production of TxA2 is not confined to the endothelium. The sumatriptan-induced contractions were also unaffected by endothelial denudation. 7. The results of the present study suggest that endogenously produced TxA2 enhances contractions to sumatriptan in the human isolated coronary artery. Such a mechanism may play a role in causing chest symptoms after sumatriptan by potentiating coronary vascular contraction by sumatriptan in vivo.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗