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Biomedical subjects

M Groenink

Publications and source records attributed to M Groenink.

At least 19 recordsLinked to original sources

Aortic pressure-area relation in Marfan patients with and without beta blocking agents: a new non-invasive approach.

OBJECTIVE: To investigate the heterogeneous response to beta blockade in patients with Marfan syndrome by non-invasive assessment of the aortic pressure-area curve. DESIGN AND PATIENTS: 25 patients with the Marfan syndrome who used beta blocking agents (mean (SD) age, 29 (10) years; 20 men, five women), seven without beta blockade (34 (14) years; five men, two women), and 10 controls (29 (5) years; seven men, three women) underwent magnetic resonance imaging and non-invasive continuous blood pressure measurement. Pressure-area curves were constructed at the level of the descending thoracic aorta. A transition point was defined as the pressure at which the pressure-area relation deviated from its elastic (linear) to the collagen (exponential) course. SETTING: Tertiary referral centre for adult congenital heart disease. RESULTS: In six patients (five with and one without beta blockade), a transition point in the pressure-area curve was observed, indicating that the load bearing component was not only elastin but also collagen. In the remaining 26 Marfan patients and in the control subjects a linear pressure-area relation was observed. CONCLUSIONS: This new non-invasive method to derive aortic pressure-area curves showed that most patients with Marfan syndrome have a similar pressure-area curve to controls with similar blood pressures. Five patients on beta blockade showed a transition point in the pressure-area curve which could play a crucial role in the heterogeneous response to beta blocker treatment in Marfan patients. Patients with a transition at low blood pressures may not benefit from beta blocking agents.

Adrenergic beta-Antagonists↗

Magnetic resonance imaging of the main pulmonary artery: reliable assessment of dimensions in Marfan patients on a simple axial spin echo image.

OBJECTIVE: To investigate if a simple axial spin echo (SE) image can be used for reliable assessment of pulmonary artery dimensions in patients with Marfan syndrome. METHODS: Fifty Marfan patients (mean age 33 +/- 10 years; 34 men, 16 women) and 15 normal subjects (mean age 28 +/- 4 years; nine men, six women) underwent cardiac magnetic resonance imaging (MRI). Pulmonary artery dimensions were obtained on axial SE images at two different levels: (1) the level of the pulmonary artery root, and (2) the level of the pulmonary artery bifurcation. To evaluate the accuracy of axial plane measurements 10 Marfan patients also underwent contrast-enhanced MR angiography (CE-MRA). RESULTS: In the 10 Marfan patients who also underwent CE-MRA, the mean diameter at the pulmonary bifurcation assessed with CE-MRA (31.5 +/- 3.6 mm) was almost equal to mean diameter assessed with axial SE (30.7 +/- 3.6 mm). Agreement of methodology according to Bland and Altman analysis showed a 95% confidence interval ranging from -2.6 to + 4.4 mm for all distances of the pulmonary artery root. In Marfan patients the mean right-left diameter measured on both axial SE images and CE-MRA was approximately 2.5 mm larger than the anterior-right and anterior-left diameters (p < 0.001). CONCLUSIONS: Axial SE MRI is a reliable and easy acquisition to measure pulmonary artery dimensions in patients with Marfan syndrome, and could be used for follow-up, especially in patients with severe involvement of the cardiovascular system. Not only the pulmonary artery trunk but also the asymmetric pulmonary root should be measured, although the clinical relevance of the asymmetric root is not yet known.

Adult↗

Impact of current cryopreservation procedures on mechanical and functional properties of human aortic homografts.

We evaluated the impact f standard cryopreservation on mechanical and functional properties of human aortic homografts. From 14 human heart-valve donors, the thoracic descending aorta was obtained. Effects of cryopreservation on mechanical (elastic properties and breaking stress) and smooth muscle cell (SMC) and endothelium function were tested. Cryopreservation (cryo) did not significantly affect Young's modulus of elastin (fresh: 3.1 +/- 1.0, cryo: 2.7 +/- 0.9 x 10(5) Nm(-2)), collagen recruitment pressure (fresh: 1.1 +/- 0.3, cryo: 1.1 +/- 0.4 x 10(4) Nm(-2)), distensibility (fresh: 3.8 +/- 1.8, cryo: 3.6 +/- 1.6 x 10(5) N(-1)m2), or breaking stress (fresh: 2.4 +/- 1.0, cryo: 2.2 +/- 1.0 x 10(6) Nm(-2)). Following explantation, no endothelium-dependent relaxation was found. SMC function and endothelium-independent relaxation were mainly intact after explantation but significantly decreased after cryopreservation. Aortic mechanical properties are not influenced by cryopreservation. Following explantation, almost no endothelial cell function is present, and SMC contractility is strongly affected after cryopreservation.

Adolescent↗

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction.

OBJECTIVE: To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction. SETTING: Tertiary cardiovascular referral centre. METHODS: Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in 21 asymptomatic or minimally symptomatic patients with chronic right ventricular pressure overload caused by congenital heart disease, and in seven healthy volunteers. Right ventricular ejection fraction was determined using magnetic resonance imaging. RESULTS: Right ventricular ejection fraction in the volunteers was higher than in the patients (69.0 (8.2)% v 58.0(12.0)%, respectively; p < 0.006). Left ventricular ejection fraction was 72.3(7.8)% in volunteers and 68.1(11.0)% in patients (NS). There was a significant difference between patients and volunteers in the plasma concentrations of BNP (5.3 (3.5) v 2.3 (1.7) pmol/l, respectively; p < 0.009) and ANP (7.3 (4.5) v 3.6 (1.4) pmol/l; p < 0.05). In both patients and volunteers, mean plasma ANP was higher than mean plasma BNP. Right ventricular ejection fraction was inversely correlated with BNP and ANP (respectively, r = 0.65; p < 0.0002 and r = 0.61; p < 0.002). There was no correlation between left ventricular ejection fraction and BNP (r = 0.2; NS) or ANP (r = 0.52; NS). Similarly, no correlation was shown between the level of right ventricular systolic pressure and either plasma BNP (r = 0.20) or plasma ANP (r = 0.07). CONCLUSIONS: There was a significant inverse correlation between right ventricular ejection fraction and the plasma neurohormones BNP and ANP in asymptomatic or minimally symptomatic patients with right ventricular pressure overload and congenital heart disease. Monitoring changes in BNP and ANP may provide quantitative follow up of right ventricular dysfunction in these patients.

Adult↗

Biophysical properties of the normal-sized aorta in patients with Marfan syndrome: evaluation with MR flow mapping.

PURPOSE: To investigate the feasibility of magnetic resonance (MR) flow mapping in the assessment of aortic biophysical properties in patients with Marfan syndrome and to detect differences in biophysical properties in the normal-sized aorta distal to the aortic root between these patients and matched control subjects. MATERIALS AND METHODS: Seventy-eight patients with Marfan syndrome with aortic root dilatation and 23 matched control subjects underwent MR flow mapping in four locations in the normal-sized aorta (1, ascending aorta; 2, thoracic descending aorta; 3, descending aorta at the level of the diaphragm; and 4, abdominal descending aorta). Distensibility at each location and flow wave velocity between locations were calculated. RESULTS: Compared with the control subjects, patients with Marfan syndrome had decreased aortic distensibility at three of the four locations (levels 1, 2, and 4; P <.05) and increased flow wave velocity between all locations (P <.05) in the aorta. In patients with Marfan syndrome, flow wave velocity was also significantly increased along the entire aortic tract beyond the aortic root (from level 1 to level 4). CONCLUSION: MR imaging reveals abnormal biophysical properties of the normal-sized aorta in patients with Marfan syndrome. Monitoring of these properties is relevant for evaluating disease progression and treatment options.

Adolescent↗

Quantitative assessment of dural ectasia as a marker for Marfan syndrome.

PURPOSE: To establish normal values for lumbosacral dural sac dimensions with magnetic resonance (MR) imaging and to use these values to assess the sensitivity and specificity of dural ectasia as a marker for Marfan syndrome. MATERIALS AND METHODS: MR imaging was performed to measure dural sac diameter (DSD) from L1 through S1 in 44 adult patients with Marfan syndrome and in 44 matched control subjects. DSD values were corrected for vertebral body size, yielding dural sac ratios (DSRs). The control subjects served to establish the upper limit of normal DSR values at the L1 through S1 levels. RESULTS: Cutoff values for normal DSRs for L1 through S1 were 0.64, 0.55, 0.47, 0.48, 0.48, and 0.57. Significant DSR differences were shown at all levels between patients with Marfan syndrome and control subjects (P <.001 at all levels). At L1 through S1, the sensitivity of dural ectasia as a marker for Marfan syndrome was 45%-77%, and the specificity was 95% or greater. By combining levels L3 and S1, dural ectasia as a marker for Marfan syndrome yielded a sensitivity of 95% (42 of 44 patients) and a specificity of 98% (43 of 44). The presence of dural ectasia excelled, compared with the presence of other Marfan syndrome manifestations in the patient population. CONCLUSION: Abnormal DSR values at L3 or S1 can be used to identify Marfan syndrome with 95% sensitivity and 98% specificity.

Adolescent↗

Aortic root asymmetry in marfan patients; evaluation by magnetic resonance imaging and comparison with standard echocardiography.

BACKGROUND: Patients with Marfan syndrome may develop aortic root dissection despite only mild aortic root dilation as shown by standard echocardiography, which may be due to aortic root asymmetry. Purpose of the present study was to investigate aortic root asymmetry by magnetic resonance (MR) imaging in patients with Marfan syndrome and to compare these measurements with standardly performed echocardiography. METHODS: Eighty-seven Marfan patients (mean age 31 +/- 8 years) underwent MR imaging. From this population, 15 patients (mean age 29 +/- 3 years) were selected in whom both echocardiography and MR imaging had been performed within 3 months. With echocardiography, the aortic root was measured according to the recommendations of the American Society of Echocardiography. With MR imaging, a short axis view of the aortic root was obtained to measure distances between the noncoronary, right coronary and left coronary cusps and the aortic root area. Correlations between aortic root area and diameters were assessed, and 95% confidence intervals (95% CIs) calculated. RESULTS: No difference in the standardly measured noncoronary to right coronary cusp diameter between MR imaging and echocardiography was shown (42 +/- 6 mm). Largest aortic root diameter on the MR images was the right to left coronary cusp diameter (46 +/- 7 mm, p < 0.02). For a given noncoronary to right coronary cusp diameter, 95% confidence intervals revealed a variation of -20 to +20% in the aortic root area. CONCLUSIONS: The majority of Marfan patients show asymmetric dilation of the aortic root by MR imaging. This phenomenon may go unnoticed when standard echocardiography is performed. The asymmetry of the aortic root might be of clinical importance in unexpected aortic root dissection.

Adult↗

Dobutamine-induced increase of right ventricular contractility without increased stroke volume in adolescent patients with transposition of the great arteries: evaluation with magnetic resonance imaging.

OBJECTIVE: Prognosis in patients with surgically corrected (Senning or Mustard) transposition of the great arteries (TGA) depends mainly on right ventricular (RV) function and RV functional reserve. We examined the role of dobutamine stress in the early detection of RV dysfunction in asymptomatic or slightly symptomatic patients with TGA using magnetic resonance imaging (MRI). DESIGN AND PATIENTS: Twelve asymptomatic or slightly symptomatic patients with chronic RV pressure overload, surgically corrected (Mustard or Senning) TGA (age 22.8 (+/- 3.4) years; New York Heart Association (NYHA) class I/II) and nine age matched healthy volunteers (age 27.3 (+/- 4.4) years) were included. MRI was applied both at baseline and during dobutamine stress (start dose 5 microg/kg/min to maximum dose 15 microg/kg/min) to determine RV and left ventricular (LV) stroke volumes (SV) and ejection fraction (EF). RESULTS: At baseline only RVEF was significantly higher in controls than in patients (71 (+/- 9) vs. 57 (+/- 10)%, p < 0.001), other RV parameters were not significantly different between the two examined groups: RVSV (86 (+/- 21) vs. 72 (+/- 27) ml, p = ns), RV end-diastolic volume (EDV) (123 (+/- 37) vs. 123 (+/- 33) ml, p = ns), and heart rate (61 (+/- 10) vs. 69 (+/- 14) bpm, p = ns), respectively. During dobutamine stress RVEF increased significantly both in controls and patients (20 (+/- 16) vs. 17 (+/- 18)%, p < 0.01 and p < 0.02 vs. rest, respectively), but stress RVEF was significantly higher in controls than in patients (85 (+/- 3) vs. 66 (+/- 7)%, p < 0.0001). RVSV increased significantly in controls (22 (+/- 19)%, p < 0.02), and there was no significant increase in RVSV in patients (-10 (+/- 28)%, p = ns). The controls showed no change in RVEDV (2 (+/- 17)%, p = ns), but in patients a significant decrease in RVEDV (-24 (+/- 15)%, p < 0.001) was observed. Maximal heart rate was significantly higher in patients than in controls (122 (+/- 20) vs. 101 (+/- 14) bpm, p < 0.02). CONCLUSION: In asymptomatic or slightly symptomatic patients with surgically corrected TGA dobutamine had a positive inotropic effect on RV, but the increased contractility was not accompanied by an appropriate increase in SV. Our data suggest inadequate RV filling in this category of patients, possibly due to rigid atrial baffles and compromised atrial function or decreased compliance due to RV hypertrophy.

Adolescent↗

The influence of aging and aortic stiffness on permanent dilation and breaking stress of the thoracic descending aorta.

OBJECTIVE: To assess the influence of aging and aortic stiffness on the extent of irreversible deformation and breaking stress of the human thoracic aorta. METHODS: From 14 human heart valve donors without aortic disease (mean age 35 years, range 8-59 years), 14 intact segments of the thoracic descending aorta were studied within 48 h after cardiac arrest. In an experimental setup, the segments were submitted to increasing hydrostatic pressure loads, both statically and dynamically, while radius and wall thickness were monitored echocardiographically. Pressure-radius curves were constructed. Radius and wall thickness were determined at a pressure of 100 mmHg. Radius at elastin resting length and collagen recruitment pressure (Pcol, mmHg) were derived from the pressure-radius relationship and stress-strain curves were constructed to yield Young's moduli of elastin and collagen. Distensibility (D, mmHg-1) was determined while loading the segment with a sinusoidal pressure wave of 120/50 mmHg at both 0.5 and 1 Hz. Subsequently increasing static pressure loads of 400, 800, 1200 and 1600 mmHg were applied. After each pressure load, the increase in aortic radius at a pressure of 100 mmHg (Rinc) was determined. The experiment continued until rupture occurred and breaking stress (sigma break, N m-2) was calculated, donor age and aortic stiffness were correlated with Rinc and sigma break of the aortic segments. RESULTS: Mean breaking stress of the 14 segments was 2.7 x 10(6) N m-2. Breaking stress was negatively correlated with age (r2 = 0.66) and positively with D (r2 = 0.44) and with Pcol (r2 = 0.18). Seven segments survived a pressure load of 800 mmHg, in these vessels, the extent of irreversible dilation was positively correlated with age (r2 = 0.42) and negatively with D (r2 = 0.40) and Pcol (r2 = 0.40). CONCLUSION: Permanent deformation and rupture of the human thoracic aorta following pressure overload are influenced by age, distensibility and collagen recruitment pressure.

Adolescent↗

Survival and complication free survival in Marfan's syndrome: implications of current guidelines.

OBJECTIVE: To evaluate survival and complication free survival in patients with Marfan's syndrome and to assess the possible influence of recently revised guidelines for prophylactic aortic root replacement in these patients. METHODS: 130 patients who had been attending one institution over 14 years were evaluated. Kaplan-Meier analysis was performed in 125 patients who did not present with aortic root dissection as the first sign of Marfan's syndrome, with the end points: death, aortic root dissection, and prophylactic aortic root replacement after diagnosis. In the patients developing aortic root dissection, current guidelines for prophylactic aortic root replacement were retrospectively applied to investigate the number of dissections that could theoretically have been prevented. The guidelines were: (1) aortic root diameter >/= 55 mm, (2) positive family history of aortic dissections and aortic root diameter >/= 50 mm, and (3) aortic root growth >/= 2 mm/year. Outcomes following emergency surgery (15 patients) and prophylactic surgery of the aortic root (30 patients) were compared. RESULTS: Five and 10 year survival after diagnosis was 95% and 88%, and the five and 10 year complication free survival was 78% and 66%, respectively. Thirteen patients developed dissection, 30 underwent prophylactic repair, and 82 had an uncomplicated course. Eleven dissections could theoretically have been prevented by application of the current guidelines. Five year survival following emergency and prophylactic repair of the aortic root was 51%, and 97%, respectively. CONCLUSIONS: Survival in the Marfan's syndrome in the past 14 years seems satisfactory; with application of current guidelines, it has probably even improved. However, because of the high fatality rate in Marfan patients developing aortic root dissection, more extensive screening for Marfan's syndrome and a search for additional risk factors are desirable.

Adolescent↗

Changes in aortic distensibility and pulse wave velocity assessed with magnetic resonance imaging following beta-blocker therapy in the Marfan syndrome.

It has been shown that beta-adrenergic blocking agents may reduce the rate of aortic root dilation and the development of aortic complications in patients with the Marfan syndrome. This may be due to beta-blocker-induced changes in aortic stiffness, of which distensibility and pulse wave velocity are in vivo measurable derivatives. We studied changes in distensibility at 4 levels of the aorta and pulse wave velocity along the entire aorta after 2 weeks of beta-blocker therapy in 6 Marfan syndrome patients and in 6 healthy volunteers, using magnetic resonance imaging (MRI) combined with brachial artery blood pressure measurements. In both groups, mean blood pressure decreased significantly (Marfan: 86 +/- 6 vs 78 +/- 5 mm Hg, p <0.05; control: 80 +/- 8 vs 73 +/- 3 mm Hg, p <0.05) (all data expressed as mean +/- 1 SD). At baseline, the Marfan syndrome patients exhibited decreased distensibility at the level of the ascending aorta (2 +/- 1 vs 6 +/- 2 10(-3)mm Hg(-1), p <0.01) and increased pulse wave velocity (6.2 +/- 0.4 vs 3.9 +/- 0.4 ms(-1), p <0.01) compared with control subjects. Only the Marfan syndrome patients had a significant increase in aortic distensibility at multiple levels and a significant decrease in pulse wave velocity after beta-blocker therapy (ascending aorta distensibility: 2 +/- 1 vs 4 +/- 1 10(-3)mm Hg(-1), p <0.05; abdominal aorta distensibility: 5 +/- 2 vs 8 +/- 3 10(-3)mm Hg(-1), p <0.05; pulse wave velocity: 6.2 +/- 0.4 vs 5.0 +/- 1.0 ms(-1), p <0.05). Thus, aortic stiffness in Marfan syndrome, together with mean blood pressure, is reduced by beta-blocker therapy, and MRI is well suited to detect these changes by measuring distensibility and pulse wave velocity.

Adolescent↗

Marfan syndrome in children and adolescents: an adjusted nomogram for screening aortic root dilatation.

OBJECTIVE: To construct an adjusted nomogram for the echocardiographic screening of aortic root diameter in children with possible Marfan disease. DESIGN: In 91 children (42 boys, 49 girls, age range 3.2 to 18.4 years) undergoing Marfan screening from 1983 until 1996, the diagnosis Marfan syndrome and any other aortic pathology was definitely ruled out. These served as a control population to set appropriate reference standards. RESULTS: Compared with a standard Dutch reference population, body surface area of the control subjects (mean (SD)) was above the 50th centile (boys 0.09 (0.20) m2, range -0.28 to 0.69 m2; girls 0.09 (0.17) m2, range -0.17 to 0.69 m2). Echocardiographically determined aortic root diameter and body surface area showed a linear relation and a greater variability of aortic root diameter in these relatively tall subjects (n = 91, R2 = 0.62) than in the standard nomogram (n = 56, R2 = 0.93). In 24% of cases (n = 22), the aortic root exceeded the upper limit of normal in the standard nomogram, by 2.2 (2.0) mm. An adjusted nomogram was constructed with a higher upper limit. CONCLUSIONS: A Marfan screening population differs from the unselected population in body surface area and aortic root size variability. An adjusted nomogram should therefore be used to detect a truly enlarged aortic root.

Adolescent↗

Marfan syndrome in children and adolescents: predictive and prognostic value of aortic root growth for screening for aortic complications.

OBJECTIVE: To assess and measure the diagnostic and prognostic value of individual aortic root growth in children and adolescents with Marfan syndrome. DESIGN: From 1983 to 1996, 250 children were screened for Marfan syndrome. Serial echocardiographic aortic root measurements of 123 children (57 Marfan, 66 control) were available for evaluation of aortic root growth. Aortic root diameters were correlated with body surface area. Based on individual growth of the aortic root a discrimination formula was derived to distinguish Marfan patients from control subjects. RESULTS: Sensitivity and specificity of this method, which were dependent on the number of measurements, were 84% and 73%, respectively, for three serial measurements. The discrimination score also predicted a five year complication free survival in all patients. CONCLUSIONS: In children and adolescents with Marfan syndrome, aortic root growth differs significantly from subjects in whom Marfan syndrome was definitely ruled out during screening. Measurement of individual aortic root growth may serve to establish diagnosis at an early stage and is of prognostic value for occurrence of aortic complications.

Adolescent↗

Paracrine regulation of germinal center B cell adhesion through the c-met-hepatocyte growth factor/scatter factor pathway.

T cell-dependent humoral immune responses are initiated by the activation of naive B cells in the T cell areas of the secondary lymphoid tissues. This primary B cell activation leads to migration of germinal center (GC) cell precursors into B cell follicles where they engage follicular dendritic cells (FDC) and T cells, and differentiate into memory B cells or plasma cells. Both B cell migration and interaction with FDC critically depend on integrin-mediated adhesion. To date, the physiological regulators of this adhesion were unkown. In the present report, we have identified the c-met-encoded receptor tyrosine kinase and its ligand, the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF), as a novel paracrine signaling pathway regulating B cell adhesion. We observed that c-Met is predominantly expressed on CD38(+)CD77(+) tonsillar B cells localized in the dark zone of the GC (centroblasts). On tonsil B cells, ligation of CD40 by CD40-ligand, induces a transient strong upregulation of expression of the c-Met tyrosine kinase. Stimulation of c-Met with HGF/SF leads to receptor phosphorylation and, in addition, to enhanced integrin-mediated adhesion of B cells to both VCAM-1 and fibronectin. Importantly, the c-Met ligand HGF/SF is produced at high levels by tonsillar stromal cells thus providing signals for the regulation of adhesion and migration within the lymphoid microenvironment.

Animals↗

Correlation of repressed transcription of alpha-tocopherol transfer protein with serum alpha-tocopherol during hepatocarcinogenesis.

Using a subtraction-enhanced display technique, we identified a rodent alpha-tocopherol transfer protein (alpha-TTP) cDNA which exhibited markedly lower messenger RNA (mRNA) amounts in rat hepatocellular carcinoma (HCC) than in healthy controls. Several lines of evidence have substantiated that abnormal alpha-TTP results in isolated vitamin E deficiency. In this study, we investigated the hepatic mRNA amounts of alpha-TTP during rat hepatic carcinogenesis and liver regeneration on Northern blot, localization of alpha-TTP mRNA in HCC of rats and humans by in situ hybridization, and we analyzed the correlation between alpha-TTP mRNA and alpha-tocopherol. alpha-TTP mRNA concentrations of the rats were decreased at the early stage of hepatic carcinogenesis, and remained 3-5-fold reduced as the tumor progressed. In parallel, serum alpha-tocopherol concentrations were significantly decreased to 40% of those in the controls at the early stages of rat hepatic carcinogenesis (p < 0.01). The 2 data sets were strongly correlated (r = 0.834, p < 0.001). In situ hybridization revealed that a decrease of alpha-TTP mRNA was preferentially localized in the tumor nodules of rats and humans with HCC. Our data suggest that repressed transcription of alpha-TTP is associated with a decrease of serum alpha-tocopherol and with hepatic carcinogenesis.

Aged↗